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Ten advanced cancer patients (both with hormone-sensitive and non-hormone sensitive tumors) were treated with high dose medroxyprogesterone acetate (MAP, greater than 500 mg/day). We determined body weight, lean body mass, blood pressure, sodium blood level, urinary excretion, and exchangeable sodium pool by the 22Na method before and after treatment. These data seem to exclude a fluid retentive effect for high-dose MAP. | Hydroxyprogesterones |
BACKGROUND: Involution of neonatal ovarian cysts occurs usually by 12 months. Persisting cysts larger than 4 cm are prone to torsion. Two modes of therapy are advocated: surgery and percutaneous US-guided cyst aspiration. OBJECTIVE: To compare ovarian preservation following the use of US-guided aspiration or conventional surgery for the treatment of large asymptomatic neonatal ovarian cysts, and to suggest alternative treatment when intrauterine ovarian torsion occurs. MATERIALS AND METHODS: The study population comprised 25 baby girls with an ovarian cyst, 5 with a simple cyst and 20 with a complex cyst. Of these 25 infants, 8 had surgery and 17 had US-guided cyst aspiration. RESULTS: In the surgical group of 8, 6 underwent oophorectomy, and in 2 the ovary was saved. In the aspirated group of 17, the ovary was saved in 10, and was lost in 5. At the time of this report one patient was still in the follow-up period, and one was lost to follow-up. CONCLUSION: US-guided aspiration of large neonatal cysts preserves ovarian tissue in a higher percentage of patients than surgery. It is safe, effective, and repeatable. We recommend US-guided aspiration of asymptomatic large ovarian cysts for salvage or for decompression if intrauterine ovarian torsion occurs. Surgery should be reserved for patients with acute torsion, intestinal obstruction and intestinal volvulus. | Ovarian Cysts |
INTRODUCTION: The literature describes advantages for mothers giving birth in water, but waterbirth is controversial in Sweden and has not been offered at hospitals until recently. This study aimed to describe and compare the characteristics and outcome of waterbirths with those of spontaneous vaginal births at the same clinics. MATERIAL AND METHODS: A retrospective cohort study was conducted on all waterbirths at two maternity units in Sweden from March 2014 to November 2015 (n = 306), and a consecutively selected comparison group of 306 women having conventional spontaneous vaginal births. Logistic regression was used to analyze the primary outcome; second-degree perineal tears. RESULTS: Women giving birth in water had a lower risk of second-degree perineal tears [adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.4-0.9]). Their labor was shorter (6 h 3 min vs. 7 h 52 min) and there were significantly fewer interventions than in the comparison group; amniotomy (13.7 vs. 35.3%), internal cardiotocography (11.1 vs. 56.8%), and augmentation with oxytocin (5.2 vs. 31.3%). There were no differences in Apgar scores or admissions to neonatal intensive care unit. The experience of childbirth, measured with a numeric rating scale, was higher in the waterbirth group indicating a more positive birth experience. Three newborns born in water had an umbilical cord avulsion. CONCLUSIONS: In this low-risk population, waterbirth is associated with positive effects on perineal tears, the frequency of interventions, the duration of labor and women's birth experience. Midwives handling waterbirth should be aware of the risk of umbilical cord avulsion. | Natural Childbirth |
The virulence of Marek's disease virus (MDV) is continuously evolving, and more virulent MDV pathotypes are emerging, thereby reducing the effectiveness of the existing vaccines. In this study, feather pulps were collected from diseased chickens in commercial chicken flocks in China that presented significant MD visceral tumors in 2011 and were inoculated into a monolayer of duck embryo fibroblasts (DEFs). Three field isolates of MDV were obtained by plaque cloning and identified as MDV via PCR and designated strains LCC, LLY, and LTS. Unvaccinated and CVI988 vaccine-vaccinated specific pathogen-free chickens were challenged at 7 days post vaccination (dpv) with 1000 plaque forming units of each of the respective MDV isolates. These strains induced gross MD lesions in all (100%) of the unvaccinated chickens, and the mortality rates of the unvaccinated chickens were 42.9%, 46.7%, and 23.1% by 60 days post challenge (dpc), respectively. The CVI988 vaccine induced protective indices (PIs) of 85.7, 92.3, and 66.7, respectively. These results showed that the pathogenic characteristics of the Chinese isolates were diverse and that vaccine CVI988 provided different levels of protection against them. These data indicated that the existence of variant MDV strains was a possible reason of immunity failure in China. | Marek Disease Vaccines |
Characterization of EOF mobility for Tris and TBE buffer solutions is performed in nanoporous arrays using the fluorescent marker method to examine the magnitude of EOFs through nanopores with mean diameters close to electric double layer thickness (Debye length). Structures made from solid silica nanospheres with effective pore sizes from 104 nm down to 8 nm are produced within the microchannel using an evaporation self-assembly method. EOF results in nanoporous matrices show higher EOF mobilities for stronger electrolyte solutions, which are drastically different compared to microchannel EOF. The effects of scaling are also examined by comparing the EOF mobility for varying ratios of pore diameters to the Debye length, which shows a surprising consistency across all particle sizes examined. This work demonstrates various factors which must be considered when designing nanofluidic devices, and discusses the causes of these small scale effects. | Electroosmosis |
The adrenal gland is one of the most common endocrine organs affected by chemically induced lesions. In the adrenal cortex, lesions are more frequent in the zona fasciculata and reticularis than in the zona glomerulosa. The adrenal cortex produces steroid hormones with a 17-carbon nucleus following a series of hydroxylation reactions that occur in the mitochondria and endoplasmic reticulum. Toxic agents for the adrenal cortex include short-chain aliphatic compounds, lipidosis inducers, amphiphilic compounds, natural and synthetic steroids, and chemicals that affect hydroxylation. Morphologic evaluation of cortical lesions provides insight into the sites of inhibition of steroidogenesis. The adrenal cortex response to injury is varied. Degeneration (vacuolar and granular), necrosis, and hemorrhage are common findings of acute injury. In contrast, chronic reparative processes are typically atrophy, fibrosis, and nodular hyperplasia. Chemically induced proliferative lesions are uncommon in the adrenal cortex. The adrenal medulla contains chromaffin cells (that produce epinephrine, norepinephrine, chromogranin, and neuropeptides) and ganglion cells. Proliferative lesions of the medulla are common in the rat and include diffuse or nodular hyperplasia and benign and malignant pheochromocytoma. Mechanisms of chromaffin cell proliferation in rats include excess growth hormone or prolactin, stimulation of cholinergic nerves, and diet-induced hypercalcemia. There often are species specificity and age dependence in the development of chemically induced adrenal lesions that should be considered when interpreting toxicity data. | Adrenal Gland Diseases |
Synaptic adhesion organizes synapses, yet the signaling pathways that drive and integrate synapse development remain incompletely understood. We screened for regulators of these processes by proteomically analyzing synaptic membranes lacking the synaptogenic adhesion molecule SynCAM 1. This identified FERM, Rho/ArhGEF, and Pleckstrin domain protein 1 (Farp1) as strongly reduced in SynCAM 1 knockout mice. Farp1 regulates dendritic filopodial dynamics in immature neurons, indicating roles in synapse formation. Later in development, Farp1 is postsynaptic and its 4.1 protein/ezrin/radixin/moesin (FERM) domain binds SynCAM 1, assembling a synaptic complex. Farp1 increases synapse number and modulates spine morphology, and SynCAM 1 requires Farp1 for promoting spines. In turn, SynCAM 1 loss reduces the ability of Farp1 to elevate spine density. Mechanistically, Farp1 activates the GTPase Rac1 in spines downstream of SynCAM 1 clustering, and promotes F-actin assembly. Farp1 furthermore triggers a retrograde signal regulating active zone composition via SynCAM 1. These results reveal a postsynaptic signaling pathway that engages transsynaptic interactions to coordinate synapse development. | Cell Adhesion Molecule-1 |
TRK fusions are oncogenic drivers of various adult and paediatric cancers. The first-generation TRK inhibitors, larotrectinib and entrectinib, were granted landmark, tumour-agnostic regulatory approvals for the treatment of these cancers in 2018 and 2019, respectively. Brisk and durable responses are achieved with these drugs in patients, including those with locally advanced or metastatic disease. In addition, intracranial activity has been observed with both agents in TRK fusion-positive solid tumours with brain metastases and primary brain tumours. While resistance to first-generation TRK inhibition can eventually occur, next-generation agents such as selitrectinib (BAY 2731954, LOXO-195) and repotrectinib were designed to address on-target resistance, which is mediated by emergent kinase domain mutations, such as those that result in substitutions at solvent front or gatekeeper residues. These next-generation drugs are currently available in the clinic and proof-of-concept responses have been reported. This underscores the utility of sequential TRK inhibitor use in select patients, a paradigm that parallels the use of targeted therapies in other oncogenic driver-positive cancers, such as ALK fusion-positive lung cancers. While TRK inhibitors have a favourable overall safety profile, select on-target adverse events, including weight gain, dizziness/ataxia and paraesthesias, are occasionally observed and should be monitored in the clinic. These side-effects are likely consequences of the inhibition of the TRK pathway that is involved in the development and maintenance of the nervous system. | Receptor, trkA |
BACKGROUND: In South Africa, Calpurnia aurea (Ait.) Benth is used to destroy lice and to relieve itches, to destroy maggots and to treat allergic rashes, particularly those caused by caterpillars. Antioxidants play an important role protecting against damage by reactive oxygen species. Plants containing flavonoids have been reported to possess strong antioxidant properties. METHODS: The antibacterial, antioxidant activities and phenolic contents of the methanol extracts of the leaves and stems of Calpurnia aurea were evaluated using in vitro standard methods. Spectrophotometry was the basis for the determinations of total phenol, total flavonoids, flavonols, and proanthocyanidins. Tannins, quercetin and catechin equivalents were used for these parameters. The antioxidant activities of the stem extract of Calpurnia aurea were determined by ABTS, DPPH, and ferrous reducing antioxidant property (FRAP) methods. Laboratory isolates of 10 bacteria species which included five Gram-positive and five Gram-negative strains were used to assay for antibacterial activity of this plant. RESULTS: The results from this study showed that the antioxidant activities of the stem extract of Calpurnia aurea as determined by the total phenol, flavonoids, and FRAP methods were higher than that of the leaves. On the other hand, the leaf extract of the plant has higher level of total flavonols and proanthocyanidins. The leaf extract also has higher radical scavenging activity as shown in 1, 1-Diphenyl-2-picrylhydrazyl (DPPH), and 2,2 inverted question mark-azinobis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS) assay. The leaf extract showed activity against seven of the bacterial organisms. CONCLUSION: The results from this study indicate that the leaves and stem extracts of Calpurnia aurea possess antioxidant properties and could serve as free radical inhibitors or scavenger or, acting possibly as primary antioxidants. Although, the antibacterial properties of Calpurnia aurea are not as effective as the standard drugs- Chloramphenicol and Streptomycin, they still possess some activity against bacterial strains used in this study. Calpurnia aurea may therefore be a good candidate for functional foods as well as pharmaceutical plant-based products. | Laburnum |
A propeller-shaped perylene diimide trimer was synthesized and a simple evaporation method was used for the self-organization of trimer molecules into fluorescent nanofibers. The sizes of these fibers-from 4 to 150 nm in diameter-were measured by atomic force microscopy and can be controlled by adjusting the concentration of the initial solution. The aspect ratios (length/height) are around 500. The plane of the trimer was determined by polarized scanning confocal microscopy to be perpendicular to the axis of the fibers, in agreement with molecular mechanics calculations. UV/vis and NMR spectroscopies were used to monitor concentration-dependent pi-pi stacking in solution. Single-fiber fluorescence imaging and spectroscopy were performed using a total internal reflection fluorescence microscope equipped with a digital color camera and imaging CCD spectrometer. Strongly red-shifted fluorescence from these fibers indicates a high degree of electronic delocalization, and breaking up this delocalization by photobleaching blue-shifts the emission toward that of an isolated noninteracting molecule. The delocalization along these nanofibers and the ability to study the electronic structure using fluorescence make them potentially useful in nanoscale devices, such as field effect transistors and photoconductors. | Phenalenes |
The advent of single-cell RNA-sequencing (scRNA-seq) provides an unprecedented opportunity to explore gene expression profiles at the single-cell level. However, gene expression values vary over time and under different conditions even within the same cell. There is an urgent need for more stable and reliable feature variables at the single-cell level to depict cell heterogeneity. Thus, we construct a new feature matrix called the delta rank matrix (DRM) from scRNA-seq data by integrating an a priori gene interaction network, which transforms the unreliable gene expression value into a stable gene interaction/edge value on a single-cell basis. This is the first time that a gene-level feature has been transformed into an interaction/edge-level for scRNA-seq data analysis based on relative expression orderings. Experiments on various scRNA-seq datasets have demonstrated that DRM performs better than the original gene expression matrix in cell clustering, cell identification and pseudo-trajectory reconstruction. More importantly, the DRM really achieves the fusion of gene expressions and gene interactions and provides a method of measuring gene interactions at the single-cell level. Thus, the DRM can be used to find changes in gene interactions among different cell types, which may open up a new way to analyze scRNA-seq data from an interaction perspective. In addition, DRM provides a new method to construct a cell-specific network for each single cell instead of a group of cells as in traditional network construction methods. DRM's exceptional performance is due to its extraction of rich gene-association information on biological systems and stable characterization of cells." | Single-Cell Gene Expression Analysis |
In a population of 2,372 consecutive cases of breast carcinomas, 114 cases of clinically occult non palpable breast lesions have been diagnosed (4.8%). 51% of them can be considered as minimal breast carcinomas (MBC) by Gallager's definition and 72% by that of the American College of Surgeons; whatever the definition this category has an excellent prognosis with 11% of axillary invasion for the infiltrating tumors under 5 mm and 7% for these under 10 mm and 100% 5-year survival rate in both cases. The category of infiltrating tumors of over 5 mm and 10 mm also has a good prognosis with 21% and 26% of axillary lymph node invasion respectively, with a survival rate of 83.82% and 77.92%. The comparative histological analysis shows at this stage an increase in the intraductal carcinomas (IC) (35% instead of 6% for the palpable carcinomas), the infiltrating ductal carcinomas with predominant intraductal component (IDCPIC) (19% instead of 12%) and the tubular carcinomas (11% instead of 3%). The study of the peritumoral and environmental mastopathy and the histological repartition, confirms the classical histogenetic arguments regarding breast carcinomas. | Adenocarcinoma |
Kaposi-sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) is the causative agent of several malignancies, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). Active KSHV replication has also been associated with a pathological condition called KSHV inflammatory cytokine syndrome (KICS), and KSHV may play a role in rare cases of post-transplant polyclonal lymphoproliferative disorders. Several commonly used herpesviral DNA polymerase inhibitors are active against KSHV in tissue culture. Unfortunately, they are not always efficacious against KSHV-induced diseases. To improve the outcome for the patients, new therapeutics need to be developed, including treatment strategies that target either viral proteins or cellular pathways involved in tumor growth and/or supporting the viral life cycle. In this review, we summarize the most commonly established treatments against KSHV-related diseases and review recent developments and promising new compounds that are currently under investigation or on the way to clinical use. | Lymphoma, Primary Effusion |
Dicoumarols and coumarin derivatives have shown a variety of pharmaceutical activities and have been found to be potent inhibitor for the NAD(P)H-dependent flavoproteins. In this report, dicoumarol and its derivatives containing the substituted benzene ring at the methylenebis position were synthesized and evaluated for their antibacterial activity against gram-positive bacteria: Staphylococcus aureus and Bacillus subtilis, and gram-negative bacteria: Escherichia coli and Klebsiella sp. The results showed that the synthesized dicoumarols affect cell growth but are selective against gram-positive over gram-negative bacterial cells. However, for most derivatives, the substitution of steric bulky benzene group on the methylenebis position appears to decrease in the efficacy of antibacterial effect. This finding is roughly described by the predicted poorer docked structure of the derivatives to a homology model of S. aureus flavoprotein. 3D-QSAR study highlighted structural features around the substituted benzene ring of dicoumarols as the antibacterial activity. CoMFA and CoMSIA contour maps support the idea that steric repulsion at the para position could diminish the antibacterial activity. The results of this study provide a better understanding of the molecular basis for the antibacterial activity of dicoumarols. | 4-Hydroxycoumarins |
Brassinosteroid signaling kinases (BSKs) are plant-specific receptor-like cytoplasmic protein kinases involved in the brassinosteroid signaling pathway. Unlike common protein kinases, they possess a naturally occurring alanine residue at the gatekeeper" position, as well as other sequence variations. How BSKs activate downstream proteins such as BSU1, as well as the structural consequences of their unusual sequential features, was unclear. We crystallized the catalytic domain of BSK8 and solved its structure by multiple-wavelength anomalous dispersion phasing methods to a resolution of 1.5A. In addition, a co-crystal structure of BSK8 with 5-adenylyl imidodiphosphate (AMP-PNP) revealed unusual conformational arrangements of the nucleotide phosphate groups and catalytic key motifs, typically not observed for active protein kinases. Sequential analysis and comparisons with known pseudokinase structures suggest that BSKs represent constitutively inactive protein kinases that regulate brassinosteroid signal transfer through an allosteric mechanism." | Molecular Structure |
BACKGROUND: In asthma exacerbations, higher doses of inhaled beta-agonists are used to overcome acute bronchoconstriction. Traditionally, wet nebulisation has been used, but metered-dose inhaler with a spacer device is an alternative delivery method. OBJECTIVE: To compare the clinical outcomes in adults and children with acute asthma, presenting in emergency departments or in the community, who have been randomised to beta-agonists given by two different delivery. METHODS: a metered-dose inhaler with spacer or a nebuliser. RESULTS: A Cochrane review has found no important differences between the two delivery methods in adults. Children may suffer fewer side effects with spacer delivery. CONCLUSIONS: Individual response to treatment cannot be predicted, but many studies overcame this problem by using frequent repeated doses of beta-agonists (one respule via nebuliser or four separate actuations of a metered-dose inhaler through a spacer) every 10-15 min, titrated against the clinical response of the patients. This approach is advocated in clinical practice. | Inhalation Spacers |
Because osteoporotic fractures may be prevented, diagnostic techniques are essential in the assessment of osteoporosis. Conventional radiographs of the spine are not suited for diagnosing early osteoporosis, but they show fractures that may have no clinical symptoms. The radiologist should be aware of the enormous significance of these fractures for future osteoporotic fractures. Bone mass measurements are standard techniques in the diagnosis of osteoporosis, which are the basis of the WHO definition of osteoporosis. In this article the authors presented these standard techniques and newer diagnostic techniques that provide insights in the structure of trabecular bone. | Osteoporosis, Postmenopausal |
In mammalian ovaries, most of the oocytes are in early stages of development and only a small number of these will complete their development, ovulate, and be available for fertilization. Systems for the culture of oocytes at these early stages, when they are present in preantral follicles, are described herein. Results show that oocytes can undergo a major part of their development in vitro. As methods for oocyte development in vitro improve, these culture systems will allow the efficient use of the large available pool of preantral follicles for clinical, agricultural, or zoological purposes. | Oocytes |
We report the case of a 61-year-old man who presented with ankle pain of unknown etiology. The actual cause for his pain was missed during his two initial visits when only ankle radiographs were taken. During his third visit, a full-length tibia film revealed a proximal tibiofibular synostosis. He successfully underwent a fibular osteotomy with complete symptomatic relief. A literature review of this topic is presented. | Synostosis |
Costosternal chondrodynia (Tietze's syndrome variant) should be considered in those rare patients who present with severe breast pain several months after reconstructive breast surgery. The authors treated 25 cases, 3 of which are discussed in detail, where the origin of the pain was traced to the costosternal cartilages. The differential diagnosis and management of this hitherto undescribed problem after breast surgery are discussed. | Tietze's Syndrome |
Adult neurogenesis is the process of generating new neurons throughout life in the olfactory bulb and hippocampus of most mammalian species, which is closely related to aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, is the rate-limiting enzyme for mammalian nicotinamide adenine dinucleotide (NAD) salvage synthesis by generating nicotinamide mononucleotide (NMN) from nicotinamide. Recent findings from our laboratory and other laboratories have provided much evidence that NAMPT might serve as a therapeutic target to restore adult neurogenesis. NAMPT-mediated NAD biosynthesis in neural stem/progenitor cells is important for their proliferation, self-renewal, and formation of oligodendrocytes in vivo and in vitro. Therapeutic interventions by the administration of NMN, NAD, or recombinant NAMPT are effective for restoring adult neurogenesis in several neurological diseases. We summarize adult neurogenesis in aging, ischemic stroke, traumatic brain injury, and neurodegenerative disease and review the advances of targeting NAMPT in restoring neurogenesis. Specifically, we provide emphasis on the P7C3 family, a class of proneurogenic compounds that are potential NAMPT activators, which might shed light on future drug development in neurogenesis restoration." | Nicotinamide Phosphoribosyltransferase |
By means of an electronic computer various standard technics of irradiation for cancer of the middle esophagus are compared as to the basic dosimetry range with the schedule of irradiation, calculated according to the program of the optimum dosimetry level. The criterion of the optimum dosimetry level was the requirement of a minimum integral dose in patient's body under even irradiation of the tumor zone (circular area with a diameter of 6 cm) but not less than 80% of the dosage in the esophagus center. The technics under stude show that rotation irradiation through 360 degrees provide the nearest approximation to the optimum regime. | Radioisotope Teletherapy |
Plant nuclear factor (NF-Y) is a transcriptional activating factor composed of three subfamilies: NF-YA, NF-YB, and NF-YC. These transcriptional factors are reported to function as activators, suppressors, and regulators under different developmental and stress conditions in plants. However, there is a lack of systematic research on the NF-Y gene subfamily in sugarcane. In this study, 51 NF-Y genes (ShNF-Y), composed of 9 NF-YA, 18 NF-YB, and 24 NF-YC genes, were identified in sugarcane (Saccharum spp.). Chromosomal distribution analysis of ShNF-Ys in a Saccharum hybrid located the NF-Y genes on all 10 chromosomes. Multiple sequence alignment (MSA) of ShNF-Y proteins revealed conservation of core functional domains. Sixteen orthologous gene pairs were identified between sugarcane and sorghum. Phylogenetic analysis of NF-Y subunits of sugarcane, sorghum, and Arabidopsis showed that ShNF-YA subunits were equidistant while ShNF-YB and ShNF-YC subunits clustered distinctly, forming closely related and divergent groups. Expression profiling under drought treatment showed that NF-Y gene members were involved in drought tolerance in a Saccharum hybrid and its drought-tolerant wild relative, Erianthus arundinaceus. ShNF-YA5 and ShNF-YB2 genes had significantly higher expression in the root and leaf tissues of both plant species. Similarly, ShNF-YC9 had elevated expression in the leaf and root of E. arundinaceus and in the leaf of a Saccharum hybrid. These results provide valuable genetic resources for further sugarcane crop improvement programs. | Saccharum |
Human asexuality has been defined as a lack of sexual attraction to others, although its nature is not well understood. Asexual men's genital and subjective sexual arousal patterns were compared to sexual men's to better understand asexual men's sexual response patterns. Using a penile plethysmograph to measure genital arousal, 20 asexual, 27 heterosexual, and 22 gay cisgender men (M age = 28.28, SD = 9.41) viewed erotic films depicting sexual activity or masturbation, and a subsample engaged in sexual fantasy of their choosing. Questionnaires assessing sexual function and behavior were also completed. Asexual men scored lower on sexual desire and orgasmic function, higher on sexual aversion, and did not differ on overall sexual satisfaction. Compared with gay and heterosexual men, asexual men demonstrated lower genital and subjective sexual arousal to the erotic films but displayed similar sexual arousal when engaging in sexual fantasy. Asexual men's lower levels of sexual excitation rather than their higher levels of sexual inhibition were associated with lower responses to the erotic films. These findings suggest asexual men have preferred sexual stimuli that differ from sexual men and have a similar capacity for sexual arousal as sexual men. Collectively these findings add to a growing literature aiming to understand the nature of asexuality. | Sexual Arousal |
The light-induced global conformational change of photoactive yellow protein was directly observed by small-angle X-ray scattering (SAXS). The N-terminal 6, 15, or 23 amino acid residues were enzymatically truncated (T6, T15, or T23, respectively), and their near-UV intermediates were accumulated under continuous illumination for SAXS measurements. The Kratky plot demonstrated that illumination induced partial loss of globularity. The change in globularity was marked in T6 but very small in T15 and T23, suggesting that structural change in positions 7-15 mainly reduces the globularity. The radius of gyration (R(g)) estimated by Guinier plot was increased by 1.1 A for T6 and 0.7 A for T15 and T23 upon illumination. As T23 lacks most of the N-terminal loop, structural change in the main part composed of the PAS core, helical connector, and beta-scaffold caused an increase of R(g) by 0.7 A. The structural change of positions 7-15 caused an additional increase by 0.4 A. The decrease of R(g) upon truncation of positions 7-15 for dark state was 0.3 A, while that for the intermediate was 0.7 A, suggesting that this region moves outward on formation of the intermediate. These results indicate that a light-induced structural change of PYP takes place in the main part and N-terminal 15 amino acid residues. The former induces only dimensional increase, but the latter results in additional change in shape. | Halorhodospira halophila |
In order to evaluate the influence of route and dose of inoculation on interleukin 2 (IL2) production, C57BL/6 mice were infected either intravenously (I.V.) or subcutaneously (S.C.) with 10(5) or 10(8) Mycobacterium lepraemurium. The role of genetic factors on the production of IL2 during M. lepraemurium infection, was investigated in 7 inbred mouse strains (C57BL/6, DBA/2, F1 (C57BL/6 X DBA/2), DBA/1, BALB/c, CBA and A/J) after I.V. infection with 10(7) M. lepraemurium. At different times after M. lepraemurium inoculation, the number of AFB within the spleens of infected mice was counted and the ability of Con A-activated spleen cells to produce IL2 was studied. In S.C. inoculated C57BL/6 mice the increase in footpad thickness was measured during the progression of infection. After one month of infection heavily infected C57BL/6 mice (10(8) bacilli) showed an early and strong deficiency of IL2 production, regardless of the route of inoculation, whereas mice infected with a lower dose (10(5) bacilli) did not. In S.C. infected mice the decrease of IL2 production was observed when the footpad enlargement reached to the plateau phase. The data obtained from the numeration of AFB within the spleens of infected mice allowed to rank the infected mouse strains into 2 separated groups according to the pattern of the Bcg gene expression. An IL2 deficiency was only observed in C57BL/6, DBA/1, (C57BL/6 X DBA/2)F1 and DBA/2 infected mouse strains. No evident correlation could be shown between splenic IL2 activity upon Con A stimulation and the number of AFB recovered from the spleens of these 7 inbred mouse strains. | Mycobacterium lepraemurium |
Mouse Twist is essential for cranial neural tube, limb and somite development. [Genes Dev. 9 (1995) 686]. To identify the molecular defects disrupting limb morphogenesis, we have analysed expression of mesenchymal transcription factors involved in patterning and the cell-cell signalling cascades controlling limb bud development. These studies establish that Twist is essential for maintenance and progression of limb bud morphogenesis. In particular, the SHH/FGF signalling feedback loop operating between the polarizing region and the apical ectodermal ridge (AER) is disrupted. These defects in epithelial-mesenchymal signalling are most likely a direct consequence of disrupted fibroblast growth factor (FGF) signalling in Twist-deficient limb buds. In early limb buds, down-regulation of Fgf receptor 1 and Fgf10 expression in the mesenchyme occurs concurrent with loss of Fgf4 and Fgf8 expression in the AER. Finally, Twist function, most likely by regulating FGF signalling, is required for cell survival as apoptotic cells are detected in posterior and distal limb bud mesenchyme. | Fibroblast Growth Factor 4 |
The riparian zone supports important ecological functions and acts as an ecotone connecting terrestrial and aquatic areas. Soil microbes under the revegetation of woody species are crucial to the biogeochemical cycle of nutrients. Here, soil samples were collected to examine the soil microbes during different emergence phases in 2019 (May:T1, July:T2, and September:T3) in the riparian zone of the Three Gorges Reservoir, China. The variations in the bacterial community were evaluated using high-throughput sequencing. The results showed that:during the emergence phases, soil properties such as pH value (pH), ammonium nitrogen (NH(4)(+)-N), and nitrate-nitrogen (NO(3)(-)-N) and soil enzymes changed significantly(P<0.05), and soil bacterial alpha diversity also changed with time. Except for the Chao1 index, the richness of rhizosphere soil bacteria showed T1>T2>T3, whereas the alpha diversity of non-rhizosphere soil bacteria showed T3>T1>T2. The redundancy analysis (RDA) test implied that soil urease, NH(4)(+)-N, pH, and NO(3)(-)-N were the key factors structuring the microbial community. Proteobacteria and Acidobacteria were the two dominant components among the 60 phyla that were detected in the soil. Based on phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) prediction, metabolism was the basic function of soil bacterial communities of Taxodium distichum; in the secondary functional layer, the metabolic pathways related to carbon, nitrogen, and phosphorus mainly included amino acid metabolism, carbohydrate metabolism, lipid compound metabolism, and energy metabolism, and the relative abundance of each metabolic function had a certain time difference in different periods. These findings could help us better understand how soil microbes change after restoring vegetation in the Three Gorges Reservoir area. | Taxodium |
First metatarsophalangeal joint arthrodesis is a reliable procedure with predictable outcomes in the treatment of moderate-to-severe hallux valgus with degenerative changes of the joint. It offers better functional outcome compared to arthroplasty with or without prosthesis in appropriate patient populations. Recent studies have shown that with appropriate fixation, early weight bearing may be initiated without an increase in nonunion. | Arthrodesis |
We report a patient with alexia with agraphia accompanied by letter-by-letter reading after hemorrhage in the left middle and inferior occipital gyri that spared the angular gyrus and the fusiform gyrus. Kanji (Japanese morphograms) and kana (Japanese phonetic writing) reading and writing tests revealed that alexia with agraphia was characterized by kana-predominant alexia and kanji-predominant agraphia. This type of dorsal" letter-by-letter reading is discernable from conventional ventral type letter-by-letter reading that is observed in pure alexia in that (1) kinesthetic reading is less effective, (2) kana or literal agraphia coexists, and (3) fundamental visual discrimination is nearly normal." | Agraphia |
The observation of twisted microfibrils in cellulose Ibeta both in imaging and in molecular simulations has been reported and studied for years. This article reports a computational modeling study of cellulose Ibeta twist showing its strong dependence on fibril diameter and no dependence on fibril length. We report that an important contribution to the twist in the model, empirically and analytically, is the hydrogen bonding that spans the glycosidic linkage, and that the characteristics of the chiral centers involved in the trans-glycosidic-linkage hydrogen bonding determine the directions if those interactions and cause observed right-handed twist. Other crystalline forms of cellulose show evidence of twisting at the microfibril scale, but less than Ibeta. The minimal twist in other forms of cellulose was shown previously to be due to inter-layer hydrogen bonds; this study shows it is also partially due to the primary alcohol not occurring in the TG orientation in those forms. Thus, only cellulose I has the primary alcohol in TG orientation, which leads to formation of the twist-causing hydrogen bonds. | Cellulose |
Demand is increasing for safer inhalational anesthetics for use in pediatric anesthesia. In this regard, researchers have debated whether isoflurane is more toxic to the developing brain than desflurane. In the present study, we compared the effects of postnatal exposure to isoflurane with those of desflurane on long-term cognitive performance and investigated the role of the Akt/GSK3beta signaling pathway. Postnatal day 6 (P6) mice were exposed to either isoflurane or desflurane, after which the phosphorylation levels of Akt/GSK3beta and learning and memory were assessed at P8 or P31. The phosphorylation levels of Akt/GSK3beta and learning and memory were examined after intervention with lithium. We found that isoflurane, but not desflurane, impaired spatial learning and memory at P31. Accompanied by behavioral change, only isoflurane decreased p-Akt (ser473) and p-GSK3beta (ser9) expressions, which led to GSK3beta overactivation. Lithium prevented GSK3beta overactivation and alleviated isoflurane-induced cognitive deficits. These results suggest that isoflurane is more likely to induce developmental neurotoxicity than desflurane in context of multiple exposures and that the Akt/GSK3beta signaling pathway partly participates in this process. GSK3beta inhibition might be an effective way to protect against developmental neurotoxicity. | Isoflurane |
Leptospirosis in humans is a common zoonotic disease. It is often under-diagnosed, especially when associated with neurological features, resulting in significant morbidity and mortality. This subgroup of patients with neurological manifestations is often empirically treated for cerebral malaria, dengue fever, tuberculous meningitis, hepatic encephalopathy, viral encephalitis, etc. Hence it is important to be aware of uncommon manifestations of this disease. We report one such patient, which highlights the importance of considering leptospirosis as the diagnostic possibility with hepato-renal, pulmonary and nervous system involvement, particularly where diagnostic supports and resources are limited." | Leptospira interrogans serovar icterohaemorrhagiae |
Five pediatric patients who presented with hip contractures are described. There were 3 boys and 2 girls ranging in age from 7 to 14. None had morning stiffness and one complained of no pain at all. Each had undergone several diagnostic procedures and had seen an average of 2.5 doctors before receiving the diagnosis of arthritis. All were antinuclear antibody negative and HLA-B27 positive, and they had excellent responses to treatment with nonsteroidals and physical therapy. HLA-B27 positive arthritis should be considered in the differential diagnosis of otherwise unexplained hip contractures in children. | Hip Contracture |
Among the physiological reactions to climate, the haematocrit value had a tendency to increase in the hotter months, though the increase observed was within physiological limits. Rectal temperature did not change to significantly higher levels, during the months with average ambient temperatures in the region of 25.1-31.6 degrees C. Similarly, pulse rates, too, increased in parallel to rising ambient temperatures. | Hematocrit |
Cefdinir, a so-called third-generation oral cephalosporin was tested in vitro against over 700 pathogens from patients with bacteremia. Cefdinir was very active against the Enterobacteriaceae with a 50% minimum inhibitory concentration (MIC50) value range of less than or equal to 0.03-8 micrograms/ml. The enteric species having the highest MIC90S (greater than or equal to 16 micrograms/ml) were Citrobacter freundii, and the enterobacters, Morganella morganii, Proteus vulgaris, and Serratia marcescens. Cefdinir was generally two- to fourfold less active than cefixime, but markedly more potent with a wider spectrum compared with older oral cephalosporins, cefaclor or cefuroxime. In contrast to cefixime, cefdinir inhibited Staphylococcus aureus (MIC90, 1 micrograms/ml) and other staphylococci. Pneumococci, beta-hemolytic streptococci, Haemophilus influenzae, Moraxella catarrhalis, and pathogenic Neisseria spp. (MIC90S, 0.12-0.5 micrograms/ml) were cefdinir susceptible, but Pseudomonas aeruginosa, oxacillin-resistant staphylococci and Bacteroides fragilis gr. strains were resistant. Cefdinir was generally bactericidal with a minimal inoculum effect at 10(6) colony-forming units per spot. Cefdinir beta-lactamase hydrolysis by some recently described extended broad spectrum beta-lactamases was suspected. Cefdinir exhibited a wide, balanced spectrum for an oral cephalosporin indicating possible clinical use against susceptible pathogens in respiratory tract, urinary tract, genital and cutaneous infections. | Cefdinir |
Azulene, acenaphthylene and fulvene derivatives exhibit important physical properties useful in materials chemistry as well as valuable biological properties. Since about two decades ago, the metal-catalyzed functionalization of such compounds, via C-H bond activation of their 5-membered carbocyclic ring, proved to be a very convenient method for the synthesis of a wide variety of azulene, acenaphthylene and fulvene derivatives. For such reactions, there is no need to prefunctionalize the 5-membered carbocyclic rings. In this review, the progress in the synthesis of azulene, acenaphthylene and fulvene derivatives via metal-catalyzed C-H bond activation of their 5-membered carbocyclic ring are summarized. | Acenaphthenes |
Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype - phenotype correlation in this syndrome. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. Treatment depends on the phenotype and social sex of the individual. Open issues in the management of androgen insensitivity syndromes includes decisions on sex assignment, timing of gonadectomy, fertility, physcological outcomes and genetic counseling." | Disorder of Sex Development, 46,XY |
Primary immunodeficiency diseases are not common in children. The possibility of an immunological defect should be considered in any individual with repeated infections. A definite diagnosis for immodeficiency is sometimes difficult to achieve because of overlapping clinical manifestations. Immunoglobulin subclass deficiency is an immunological deficiency disease with which, one or more IgG subclasses are deficient. T cell immunity is normal. Patients may develop recurrent bacterial and respiratory infections or could remain asymptomatic. OBJECTIVE: The authors report a case of immunoglobulin G subclass deficiency presenting initially as transient hypogammaglobulinemia of infancy. CASE REPORT: A 2 month-old boy presented to Siriraj Hospital with a history of chronic protracted diarrhea, disseminated scabies and sepsis. On presentation, he had generalized scaly and maculopapular rash with no palpable lymph nodes. CBC revealed WBC 22,100 cells/cm3 with PMN 42 per cent, lymphocytes 38 per cent, Eosinophils 4 per cent, Basophil 2 per cent and platelets 254,000/cm3. The immunoglobulin levels were as follows: IgG 181 mg/dl, IgA < 6.6 mg/dl, IgM 26.3 mg/dl. Lymphocyte enumerations revealed CD4 of 2,433 cells/cm3 (N 1,460-5,160); CD8 4,682 cells/cm3 (N 650-2,450); CD19 1,588 cell/cm3 (N 500-1,500); CD16 230 cell/cm3 (N 573 +/- 264). The initial diagnosis was X-linked agammaglobulinemia vs common variable immunodeficiency disease. His diarrhea and five courses of sepsis responded well to antibiotics administration and courses of intravenous immunoglobulin (IVIG) replacement. His through IgG became normal at 2 years of age (after 12 months of IVIG). IVIG was stopped and the diagnosis was changed to transient hypogammaglobulinemia of infancy (THI). Nevertheless, during his 4 month follow-up he developed recurrent sinopulmonary infections (i.e, otitis media and pneumonia). Repeated immunoglobulin profile showed IgG 1,200 mg/dl, IgA 135 mg/dl, IgM 26 mg/dl, IgG subclass were IgG, 1,030 mg/dl (N 280-830), IgG2 30 mg/dl (N 40-2,400), IgG3 22 mg/dl (N 6-130), IgG4 3 mg/dl (N 3-120). A diagnosis of IgG2 subclass deficiency presenting early as transient hypogammaglobulinemia of infancy was then made. Treatment with monthly IVIG was reinitiated and the patient is currently doing well. CONCLUSION: The authors present a case of IgG subclass deficiency presenting as transient hypogammaglbulinemia of infancy. Follow-up of the immune profile and clinical manifestation is necessary for a definite diagnosis. | Blood Protein Disorders |
Most environmental exposures involve concurrent or sequential exposure to multiple chemicals in air, water, and food. Interactive effects in carcinogenesis have been described for certain combinations of agents. They are described in terms of enhancement or inhibition of carcinogenesis. Enhancement effects have been documented for cigarette smoking in combination with exposure to asbestos, radon, alcohol, or other exposures. A variety of inhibitors of carcinogenesis have also been described. They are classified into agents preventing formation of carcinogens; blocking agents; and suppressing agents. Assessment of risk from exposure to multiple agents can be derived either from epidemiological studies in relation to actual exposure or from laboratory studies after controlled exposure to different agents. Prediction of how toxic components of mixtures will interact should be based on an understanding of the mechanisms of such interactions. Compounds may interact chemically, yielding new toxic components or causing a change in the biological availability of the existing components or metabolites. In humans, great individual variability in response is to be expected because of genetic heterogeneity or acquired host susceptibility factors. Interaction is thus a key component in the risk assessment process. In this paper, the definition of interaction and the theoretical basis for different types of interaction in cancer causation are reviewed. Epidemiological and experimental studies showing interactive effects of two chemical carcinogens are also presented. | Drug Interactions |
Despite the fact that cholinergic interneurons are a key cell type within the nucleus accumbens, a relationship between synaptic plasticity and the in vivo activity of cholinergic interneurons remains to be established. Here, we identify a three-way link between the activity of cholinergic interneurons, synaptic plasticity, and learning in mice undergoing the extinction of a cocaine-context association. We found that activity of cholinergic interneurons regulates extinction learning for a cocaine-context association and generates a sustained reduction in glutamatergic presynaptic strength onto medium spiny neurons. Interestingly, activation of cholinergic interneurons does not support reinforcement learning or plasticity by itself, suggesting that these neurons have a modulatory rather than a reinforcing function. | Cholinergic Neurons |
AIM: The aim of this study was to evaluate how simple it is to build a homemade low-cost simulator using a simple 5-step scheme. METHODS: A scheme explaining how to build an endoscopic surgery simulator in 5 easy steps was presented to 26 surgeons. The simulator required a pair of scissors and easy-to-find materials. Its total cost was less than euro35. The participants assessed the simulator using common endoscopic training toys or ex vivo tissue and completed an anonymous query comparing it with other commercial simulators that they had experienced before. RESULTS: In all, 84.6% found the simulator really easy to build. Every participant felt that he or she could do the same simulator themselves. Comparing with other commercial available box simulators, the majority of participants found the homemade simulator easier to (a) mount and dismount, (b) transport, (c) clean, and (d) use when practicing alone. CONCLUSIONS: Anyone can build its own simulator for a small amount of money. | Endoscopy |
OBJECTIVE: To evaluate the influence of elite-level alpine skiing on athletes' skeleton. METHODS: Thirteen professional alpine skiers (9 males and 4 females with mean age of 22.6 years) and their age- and height matched control subjects were measured with dual energy X-ray absorptiometry (total body, lumbar spine, proximal femur, forearm) and quantitative ultrasound (hand). RESULTS: After adjusting for sex, age, weight and height, between-group differences were 15% (p=0.012) for the lumbar spine, 14% (p=0.022) for the femoral neck, 10% (p=0.051) for the total hip, and 11% (p=0.001) for the total body favoring the alpine skiers. However, after controlling for total body lean mass (~muscle mass), the group-differences lost their statistical significance, the borderline 10% difference (p=0.051) in femoral neck BMD excluded. CONCLUSION: Factors contributing to the alpine skiers' higher BMD may not only include the greater muscle mass (~stronger muscles) of these athletes but also a large number of impacts and possibly other high-frequency features in external loading generated by the high-speed skiing performance. | Femur Neck |
The trading of illicit and falsified pharmaceuticals is a growth market. Factors influencing this illegal market are high profit margins, a low risk of detection, low control density, an obscure legal situation, and lastly, the easy and anonymous ways of selling over the Internet, usually across national borders. This situation was the background for the research project on the impact of European eâÂÂcommerce liberalisation on pharmaceutical crime (ALPhA). The goal of the project was to develop concrete recommendations for action regarding the improved prosecution of internet-based pharmaceutical crime and to create a broad body of data for effective law-making by legislators.In this article the initial situation regarding pharmaceutical crime and its risk potential is described and some of the results from the comparative-law investigation of the ALPhA research project are presented along with its final recommendations. The latter are directed at policy-makers and law enforcement agencies in addition to industry and science and demonstrate the type of framework to be designed to increase safety for the public and to minimize risks when purchasing pharmaceuticals. | Substandard Drugs |
The efficacy of coupling between the benzodiazepine receptor and chloride channel as well as the coupling to the GABA receptor is differentially affected by different benzodiazepine ligands. In general, the order of efficacy with regard to allosteric effects of benzodiazepine ligands on the chloride channel ([35S]TBPS) and GABA receptor ([3H]muscimol), is: agonist greater than agonist/antagonist greater than partial agonist greater than antagonist; with inverse agonists acting in a manner opposite to the classical benzodiazepine agonists. The chloride ionophore is allosterically modulated both by benzodiazepine and GABA receptors. | Etazolate |
The authors investigated the effect of group discussion, such as may occur formally in panel interview scenarios, assessment centers, or 360-degree feedback situations, on judgments of performance. Research on group polarization suggests that the effect of group discussion combined with raters' preexisting impressions of ratees or interviewees should result in an extremitization of impressions. Thus, the authors hypothesized that group discussion would (a) make ratings less accurate, (b) polarize impressions that were already good or poor as reflected by greater contrast effects, and (c) increase positive halo. Results indicated that group discussion resulted in less accurate ratings and greater contrast effects. Additional analyses suggested that group discussion increased positive halo. The authors discuss implications for research on group or panel judgments." | Employee Performance Appraisal |
A patient with Rotor syndrome has been followed up for 28 years. The subject was in good health and exhibited marked jaundice due to a hyperbilirubinemia ranging between 5 and 8 mg bilirubin per 100 ml, about 70% of the bilirubin giving direct van den Berg reaction. The liver was slightly enlarged and of normal color. Histologically it showed traces of a brown pigment and marked siderosis in the hepatocytes. In addition, mild hypersideremia and hypercholesteremia were observed together with increased amounts of bilirubin and urobilinogen in urine. Menthol glucuronide formation was normal. Hepatic excretion of bilirubin, sulfobromophthalein and radio-opaque dyes was impaired. There was no change in liver histology of biopsies taken at an interval of 6 years, the siderosis in particular remaining constant. During the observation a moderate increase in the activities of serum transaminases occurred but no longer recurred when physical and dietetic stress was avoided. | Urobilinogen |
Gamma-glutamyl hydrolase, a cysteine peptidase, catalyzes the hydrolysis of poly-gamma-glutamate derivatives of folate cofactors and many antifolate drugs. We have used internally quenched fluorogenic derivatives of glutamyl-gamma-glutamate and (4,4-difluoro)glutamyl-gamma-glutamate to examine the effect of fluorine substitution adjacent to the scissile isopeptide bond. Using a newly developed continuous fluorescence assay, the hydrolysis of both substrates could be described by Michaelis-Menten kinetics. Fluorine substitution resulted in a significant decrease in observed rates of hydrolysis under steady-state conditions due primarily to a approximately 15-fold increase in Km. Using stopped-flow techniques, hydrolysis of the non-fluorinated isopeptide was characterized by a burst phase followed by a steady-state rate, indicating that formation of the acyl enzyme is not rate-limiting for hydrolysis of this isopeptide. This conclusion was confirmed by analysis of the progress curves over a wide range of substrate concentration, which demonstrated that the acylation rate (k2) is approximately 10-fold higher than the deacylation rate (k3). The increased value of Km associated with the difluoro derivative limited the ability to obtain comparable pre-steady-state kinetics data at saturating concentration of substrate due to inner filter effects. However, even under nonsaturating conditions, a modest burst was observed for the difluoro derivative. These data indicate that either deacylation or rearrangement of the enzyme-product complex is rate-limiting in this isopeptide hydrolysis reaction. | gamma-Glutamyl Hydrolase |
For the first time, a plant (rice) translin was characterized. The rice translin protein, which was octameric in native state, bound efficiently to single-stranded DNA and RNA. Translin, a DNA-/RNA-binding protein, is expressed in brain, testis and in certain malignancies. It is involved in chromosomal translocation, mRNA metabolism, transcriptional regulation and telomere protection. Studies from human, mice, drosophila and yeast have revealed that it forms an octameric ring, which is important for its function. In spite of the absence of neuronal functions and cancer processes, translin is present in plant systems, but information on plant translin is lacking. Here we report the characterization of a plant (rice) translin. Translin cDNA from O. sativa was cloned into an expression vector; protein was over-expressed in E. coli and subsequently purified to homogeneity. Circular dichroism and homology-based modeling showed that the rice translin protein was similar to the other translin proteins. Native PAGE and gel-filtration analyses showed rice translin to form an octamer and this octameric assembly was independent of disulphide bonds. Rice translin bound to single-stranded DNA sequences like human translin, but not to the double-stranded DNA. Rice translin bound more efficiently to linear DNA (with staggered ends) than open or closed circular DNA. Rice translin also bound to RNA, like its human counterpart. Rice translin displays all the characteristic properties of the translin group of proteins and does indeed qualify as a bonafide translin" protein. To our knowledge, this is the first report wherein the translin protein from a plant source has been functionally characterized. Understanding the translin biology from plant systems will give the new insights into its functional role during plant development." | Plant Proteins |
Femoral mononeuropathy (FMN) as an extraarticular finding of rheumatoid arthritis (RA) is a phenomenon which has not been reported previously. We report a 53-year-old female patient with RA, presenting FMN findings during the course of the disease. On examination, right quadriceps and iliopsoas muscles showed grade 3 weakness on the Medical Research Council (MRC) scale. Sensory examination revealed sensory loss in the right medial leg and thigh. Patellar tendon reflex was absent in the right side. A diagnosis of a partial right femoral neuropathy was confirmed using nerve conduction study and electromyography. The probable mechanism of FMN was thought to be vasculitis. | Femoral Neuropathy |
Four proteases differing in their specificity, i.e. subtilisin, trypsin, alpha-chymotrypsin and V8 staphylococcal protease, cleave the bifunctional protein Escherichia coli aspartokinase I-homoserine dehydrogenase I (composed of 820 residues) producing an active homoserine dehydrogenase fragment. This cleavage occurs within a short segment of the polypeptide chain extending from residue 293 to residue 300." | Aspartokinase Homoserine Dehydrogenase |
The early gene expression changes mediating carcinogen enhancement of viral transformation (CET) remain to be elucidated. A model cell culture system has been developed that is now permitting a molecular analysis of CET. Pretreatment of cloned rat embryo fibroblast (CREF) cells with methyl methanesulfonate (MMS) prior to infection with the cold-sensitive host-range type 5 adenovirus mutant, H5hr1, results in a dose-dependent increase in viral transformation. The present study investigates the role of immediate-early response genes, specifically c-fos, in the CET process. MMS pretreatment, alone or in combination with infection with H5hr1 temporally and differentially increases c-fos, c-jun, jun-B, jun-D and c-myc steady-state mRNA levels. Maximum induction occurs with c-fos and c-jun 8 to 12 h posttreatment and the magnitude of response is generally greatest in CREF cells pretreated with MMS and then infected with H5hr1. Enhancement in RNA levels is observed in the presence of cycloheximide indicating that ongoing protein synthesis is not required for induction of c-fos, c-jun, jun-B or c-myc expression. Nuclear run-on analysis indicates an enhancement in transcriptional rates for c-fos, c-jun, jun-B and c-myc in CREF cells treated with MMS or MMS plus infection with H5hr1. A requirement for elevated c-fos in the early stages of CET is indicated by the ability of c-fos antisense oligonucleotides to prevent the CET process. Direct evidence implicating early increases in c-fos as a mediator of the CET process is demonstrated by stably expressing mouse mammary tumor virus promoter-regulated human sense and antisense c-fos genes in CREF cells. Induction of c-fos sense expression by dexamethasone (DEX) in the absence of MMS treatment results in enhanced c-fos mRNA, Fos protein, AP-1 DNA-binding activity and H5hr1-induced transformation and CET. Induction of c-fos expression by DEX in stable c-fos-sense CREF constructs also results in elevated levels of c-jun, jun-B and c-myc mRNA and protein. Conversely, induction of c-fos antisense expression prevents the increase in c-fos mRNA, Fos protein and AP-1 DNA-binding activity and eliminates CET. In the antisense-c-fos constructs, increases in c-jun, jun-B and c-myc mRNA and protein normally induced by MMS also are not apparent. Thus, induction or inhibition in c-fos expression affects the level of expression of additional immediate-early response genes, including c-jun, jun-B and c-myc.(ABSTRACT TRUNCATED AT 400 WORDS) | Genes, fos |
European and African natural populations of Drosophila melanogaster have been the focus of several studies aiming at inferring demographic and adaptive processes based on genetic variation data. However, in these analyses little attention has been given to gene flow between African and European samples. Here we present a dataset consisting of 14 fully sequenced haploid genomes sampled from a natural population from the northern species range (Umea, Sweden). We co-analyzed this new data with an African population to compare the likelihood of several competing demographic scenarios for European and African populations and show that gene flow improves the fit of demographic models to data. | Haploidy |
The study was to investigate the effect of gestrinone on the growth of human uterine leiomyoma cells and on the levels and activity of p38, Src and estrogen receptor alpha (ERalpha). Human uterine leiomyoma cells were cultured and treated with dimethylsulfoxide (DMSO) or a gestrinone concentration gradient. Morphological changes were observed and apoptosis was evaluated. Levels of p38 and phosphorylated-p38 (pp38) were assayed by enzyme-linked immunosorbent assay (ELISA). Levels of ERalpha and Src were analyzed using real-time RT-PCR and Western blotting. The result showed that gestrinone significantly inhibited the growth of cultured human uterine leiomyoma cells in a concentration- and time-dependent manner, with a 50% inhibitory concentration (IC(50)) value and corresponding 95% confidence intervals (CI) of 43.67 (23.46 approximately 81.32), 27.78 (12.51 approximately 61.68) and 15.25 (7.17 approximately 32.43) mumol/L at 20, 40 and 60h, respectively. Compared with control-treated leiomyoma cells, gestrinone significantly reduced both the expression of ERalpha (P<0.05) and the levels of phospho-Ser167-ERalpha (P<0.05). Gestrinone also markedly suppressed the level of phospho-Tyr416-Src (P<0.05). Moreover, gestrinone significantly increased the ratio of phospho-p38/p38 mitogen-activated protein kinase (MAPK) (P<0.05). However, no significant increase in apoptosis or cell cycle arrest was observed (P>0.05) in response to the tested concentrations of 0.1 to 3.0mumol/L. As a conclusion, gestrinone suppresses the proliferation of uterine leiomyoma cells mainly by regulating the activity of ERalpha/Src/p38 MAPK in a concentration-dependent manner at a low concentration of 0.1 approximately 3.0muM, but not significantly regulating apoptosis. Gestrinone opposes the growth of uterine leiomyoma through multiple genes. | Norgestrienone |
Alongside the kidneys and lungs, the liver has been recognised as an important regulator of acid-base homeostasis. While respiratory alkalosis is the most common acid-base disorder in chronic liver disease, various complex metabolic acid-base disorders may occur with liver dysfunction. While the standard variables of acid-base equilibrium, such as pH and overall base excess, often fail to unmask the underlying cause of acid-base disorders, the physical-chemical acid-base model provides a more in-depth pathophysiological assessment for clinical judgement of acid-base disorders, in patients with liver diseases. Patients with stable chronic liver disease have several offsetting acidifying and alkalinising metabolic acid-base disorders. Hypoalbuminaemic alkalosis is counteracted by hyperchloraemic and dilutional acidosis, resulting in a normal overall base excess. When patients with liver cirrhosis become critically ill (e.g., because of sepsis or bleeding), this fragile equilibrium often tilts towards metabolic acidosis, which is attributed to lactic acidosis and acidosis due to a rise in unmeasured anions. Interestingly, even though patients with acute liver failure show significantly elevated lactate levels, often, no overt acid-base disorder can be found because of the offsetting hypoalbuminaemic alkalosis. In conclusion, patients with liver diseases may have multiple co-existing metabolic acid-base abnormalities. Thus, knowledge of the pathophysiological and diagnostic concepts of acid-base disturbances in patients with liver disease is critical for therapeutic decision making. | Liver Function Tests |
Powdery mildews are major diseases for a range of crops. The loss of function of specific Mildew Locus O (MLO) genes has long been associated with pre-haustorial plant resistance to powdery mildew and has proven to be durable in several species. Erysiphe pisi is the major causal agent of powdery mildew in pea (Pisum sativum L.) and in the closely related Lathyrus sativus L. and Lathyrus cicera L. PsMLO1 has been extensively studied in pea. However, no MLO gene family members have been isolated and characterized in Lathyrus species so far. In this study, MLO1 genes were isolated and characterized in L. sativus and L. cicera genotypes with varied levels of partial resistance against powdery mildew. Phylogenetic analyses confirmed that Lathyrus MLO1 belongs to Clade V, like all dicot MLO proteins associated with powdery mildew susceptibility. A L. sativus recombinant inbred line population (RIL) was genotyped by sequencing to develop a high-density L. sativus genetic linkage map. DNA sequence polymorphisms between the analyzed genotypes allowed the location of MLO1 in the newly developed L. sativus RIL genetic linkage map. Subsequent comparative mapping between L. sativus and L. cicera genetic maps and P. sativum, Lens culinaris Medik., and Medicago truncatula Gaertn. reference genomes revealed important aspects of the conservation of the MLO1 locus position and of the overall chromosomal rearrangements occurring during legume evolution, with relevance to legume disease resistance breeding programs. | Lathyrus |
AIMS AND OBJECTIVES: To explore how Philippine-educated nurses explain their choice of Norway as their migration destination and their experience with the credential assessment process in Norway. BACKGROUND: Norway has an increasing need for nurses, and nurses educated in non-EU countries are an important resource for the Norwegian health service. Philippine nurses compose the largest group of internationally educated nurses from outside the EU, but their Philippine nursing education is only credited as equivalent to 2 years in Norway. Migration is known to engender stressful experiences amongst migrant nurses, which may affect their health. However, studies on Philippine nurses' experiences of migrating to and working in Norway are lacking. DESIGN AND METHODS: The study used a hermeneutic design, conducting qualitative research interviews with ten Philippine nurses. All of them had a certification as auxiliary nurses, but not as registered nurses. The Consolidated Criteria for Reporting Qualitative Research is used. RESULTS: The nurses' choice of a migration country appeared to be both random and based on the opportunity to find well-paid work, as well as having acquaintances who had already migrated to Norway. The migrated Philippine nurses seemed experienced and competent. In Norway, they were disappointed as they felt undervalued. The nurses struggled to learn Norwegian, while striving for survival when acquiring jobs or accommodations. They were excluded from acting as legal nurses in the Norwegian healthcare system; they fulfilled the governmental requirements, but they were repeatedly rejected. The informants saw this as harsh, but still hoped to be successful. CONCLUSIONS: There is a need to facilitate effective language training and a well-founded, predictable system of credentialing. RELEVANCE TO CLINICAL PRACTICE: Attention should be paid to the integration of immigrants and safeguarding and strengthening the professional competence the nurses bring with them. | Nurses, International |
Here, we examined the effects of phosphatidylserine (PS) and cholesterol on the fibril-forming properties of the N-terminal 1âÂÂ83 fragment of an amyloidogenic G26R variant of apoA-I bound to small unilamellar vesicles. A thioflavin T fluorescence assay together with microscopic observations showed that PS significantly retards the nucleation step in fibril formation by apoA-I 1âÂÂ83/G26R, whereas cholesterol slightly enhances fibril formation. Circular dichroism analyses demonstrated that PS facilitates a structural transition from random coil to alpha-helix in apoA-I 1âÂÂ83/G26R with great stabilization of the alpha-helical structure upon lipid binding. Isothermal titration calorimetry measurements revealed that PS induces a marked increase in capacity for binding of apoA-I 1âÂÂ83/G26R to the membrane surface, perhaps due to electrostatic interactions of positively charged amino acids in apoA-I with PS. Such effects of PS to enhance lipid interactions and inhibit fibril formation of apoA-I were also observed for the amyloidogenic region-containing apoA-I 8âÂÂ33/G26R peptide. Fluorescence measurements using environment-sensitive probes indicated that PS induces a more solvent-exposed, membrane-bound conformation in the amyloidogenic region of apoA-I without affecting membrane fluidity. Since cell membranes have highly heterogeneous lipid compositions, our findings may provide a molecular basis for the preferential deposition of apoA-I amyloid fibrils in tissues and organs. | Apolipoprotein A-I |
A survey of the practice styles and preferences of members of the American Society of Cataract and Refractive Surgery with United States ZIP codes was performed in September 1999. Approximately 27% (1342) of 4932 questionnaires mailed were returned before the November cutoff. Three profile questions were used to cross-tabulate: age of the opthalmologist, geographic location, and volume of cataract surgery per month. Current data were compared with data of previous surveys." | Refractive Surgical Procedures |
A case of penile Mondor's disease associated with syphilitic chancre is reported. The aetiology and management of Mondor's disease is also discussed. | Chancre |
Different kinds of postoperative analgesia were used in 106 patients after urgent proctological operations. A comparative analysis of the objective and subjective data obtained have shown that epidural anesthesia is the most effective method of postoperative analgesia in urgent proctology. | Promedol |
Nineteen virulent bacteriophages for fast- and slow-growing rhizobia were isolated. Most of the phage isolates were of two morphological types, and these showed specificity for either the fast- or the slow-growing rhizobia. The ecological distribution, morphology, and host range of the phages is presented. Classification of lotus rhizobia is discussed on the basis of phage typing. | Rhizobium |
Denaturation of recombinant sarcosine oxidase or the natural enzyme isolated from Corynebacterium sp. P-1 with guanidine hydrochloride releases noncovalently bound FAD and a second UV-absorbing component (peak 2) which comigrates with NAD+ during reversed-phase HPLC. Both FAD and peak 2 are also found in extracts prepared by incubating sarcosine oxidase at 37 degrees C for 30 min, a procedure which causes partial (approximately 50%) release of the enzyme's noncovalently bound FAD. Peak 2 in the 37 degrees C extract is heat labile and decomposes upon boiling for 5 min at pH 8.0. A similar instability was observed with NAD+. Reaction of the 37 degrees C extract from sarcosine oxidase with phosphodiesterase yields nicotinamide mononucleotide, AMP, and FMN, as expected for a mixture containing NAD+ and FAD. Peak 2 was converted to NADH upon reaction of the 37 degrees C extract with yeast alcohol dehydrogenase in the presence of ethanol. Guanidine hydrochloride extracts, prepared from recombinant or natural enzyme, contain 1 mol of NAD+/mol of FAD. Since sarcosine oxidase contains 1 mol of noncovalently bound FAD, the results show that the enzyme also contains 1 mol of NAD+. The NAD+ is tightly bound and is not lost during enzyme purification. It is not susceptible toward hydrolysis by NADase, reduction by alcohol dehydrogenase, or nucleophilic attack by cyanide. Unlike the flavins in sarcosine oxidase, NAD+ is not reduced by sarcosine and is not in redox equilibrium with the flavins. | Sarcosine Oxidase |
BACKGROUND: Although there is much consensus, certain controversies exist regarding the management of Fournier's gangrene. METHOD: Publications in English on Fournier's gangrene from January 1950 to September 1999 were obtained through the Medline database and relevant reference lists in publications. It was possible to identify 1726 cases for study. Data extracted for review included country of reported cases, number of patients in each report and relevant clinical features. RESULTS: Fournier's gangrene occurs worldwide. However, its definition has generated considerable controversy as efforts are made to refine the original description in the light of increasingly understood aetiological factors. Attempts to classify the disease into primary and secondary forms have not been successful. The basic pathological process, necrotizing fasciitis, has been identified in the perineum of women and children, although the disease afflicts the male more often than the female. Most reported cases have occurred in the USA and Canada. The major sources of sepsis are the local skin, colon, anus and rectum, and the lower urinary tract. Colonic, anal and rectal sources carry the worst prognosis. Diabetes mellitus is important in aetiological terms. Rare causes include vasectomy and circumcision. Investigations are essential to define the cause of an episode but not for the diagnosis of the disease. Early aggressive treatment of Fournier's gangrene and underlying conditions is essential. Hyperbaric oxygen and honey are treatment modalities yet to be universally adopted. Risk of death, 16 per cent overall in this series, is related to the patient's condition at presentation. CONCLUSION: Controversies over the definition of Fournier's gangrene persist but these do not affect the treatment options. The diagnosis is made on clinical grounds. The occurrence of the disease in women is under-reported and may go unrecognized by some clinicians. Some treatment options, such as hyperbaric oxygenation and radical excision, remain controversial. | Fournier Gangrene |
Total parenteral nutrition (TPN) can be a lifesaving intervention for premature neonates and it is often delivered through peripheral access in this unique population. However, extravasation and tissue damage can result. Current literature lacks strong evidence regarding the treatment and reconstruction of such injuries in this age group. The authors present a patient with a 30-week gestational age premature newborn whom suffered an extravasation injury with peripherally administered TPN leading to full thickness skin and soft tissue necrosis of the dorsum of the right hand. This was serially debrided and ultimately repaired using Apligraf (Graftskin, Living Skin Equivalent, LSE; Organogenesis Inc, Canton, MA), which rapidly facilitated secondary healing. | Soft Tissue Injuries |
CONCLUSION: The permeability of the blood-labyrinth barrier for radioactive mannitol was unchanged after impulse noise trauma. The present findings are contradictory to the theory of an increased permeability in the blood-labyrinth barrier as a result of extensive noise exposure. OBJECTIVE: Noise trauma is reported to cause multiple effects on the cochlea including mechanical and metabolic damage. The aim of the study was to observe the effects of impulse noise on cochlear homeostasis. MATERIALS AND METHODS: A well-established rat model was used for evaluation of the early effects of impulse noise trauma on the integrity of the blood-perilymph barrier. To evaluate whether a blood-perilymph barrier disruption contributes to cochlear injury after impulse noise, the paracellular transport of radioactive mannitol into scala vestibuli perilymph (PLV) and electrolyte concentration in perilymph were estimated. Thirteen animals exposed to synthesized impulses of 160 dB SPL peak value, at a rate of 100 pulses, were designed as the study group and 15 rats not exposed to noise were designed as the control group. After mannitol infusion each ear of the animal in the study group was separately exposed to impulse noise and PLV samples were taken during 2 h post-infusion. In the control group, corresponding PLV samples were taken after mannitol injection. RESULTS: At 2 h after mannitol infusion there was no difference in PLV mannitol concentration in the study group and control group (21.5%+/-2.2 and 20.5%+/-2.1, respectively). Impulse noise had no effect on the electrochemical composition of PLV. | Perilymph |
Holtzman male Sprague-Dawley rats were given four injections of saline or soman at 31 micrograms/kg or 46 micrograms/kg. The injections were given every 3 days during a 2-week period. Tail vein blood samples, drawn 24 hr before the first injection and 24 hr after the last injection, were analyzed for acetylcholinesterase (AChE) inhibition. For the low and high soman groups, whole blood AChE was inhibited 20 and 24%, respectively, while plasma AChE was inhibited 17 and 25%, respectively. Parallel saline injections produced a small inhibition of whole blood AChE and an increase in activity (negative inhibition) of plasma AChE. During the second week of soman administration rats began training on a discriminated shock avoidance task. The seven animals administered 46 micrograms/kg soman did not learn the lever-pressing avoidance response during a period of 120 days. Five of eight saline rats and four of seven 31 micrograms/kg soman rats learned the avoidance response. There was no significant difference between learners relative to rate of learning of the avoidance task. All of the rats learned to escape the shocks. These data indicate that subchronic soman inhibits learning of new behaviors by laboratory rats. | Soman |
Two siblings with Refsum's disease, an inherited disorder of lipid metabolism, oxidized intravenously injected uniformly labeled phytanic acid-C(14) at rates less than 5 percent of those found in normal subjects. The defect in oxidation of phytanic acid persisted in cultures of fibroblasts from the patients' skin. The rate of oxidation of the phytanic acid-C(14) was less than 1 percent of that found in cultures of fibroblasts from normal skin. However, pristanic acid, previously shown to be the first product of phytanic acid degradation, was oxidized at a normal rate in the patients' cultures. These results indicate that the enzymatic defect in Refsum's disease is in the first step of the pathway for degradation of phytanic acid, that is, in the unusual alpha-oxidative process that leads to a shortening of phytanic acid by one carbon atom. | Refsum Disease |
Diagnosing Sezary syndrome (SS) on clinicopathological grounds alone is far from straightforward, particularly in the early stages of the disease. Atypical lymphocytes may be seen in the peripheral blood of patients with reactive forms of erythroderma, so additional criteria are needed to establish the diagnosis of a T-cell leukemia/lymphoma. A wide variety of confirmatory tests have been proposed in the literature, but there has been no systematic attempt to compare the specificity and sensitivity of these different methods. Recent data indicate that T-cell receptor (TCR) gene analysis is the most useful test currently available and that methods based on polymerase chain reaction are more sensitive than Southern blot analysis. We propose that the diagnostic criteria for SS should include erythroderma, atypical circulating mononuclear cells, and evidence of a clonal T-cell population in the peripheral blood. Clonality can be established with certainty by cytogenetic or TCR gene analysis, but only the latter is sufficiently sensitive to be of value in routine diagnosis. Immunophenotypic data showing an expanded CD4(+)/CD7(-) population, an elevated CD4/CD8 ratio, or restricted V beta expression are not specific to T-cell malignancy and should not be used as a sole diagnostic criteria in SS. Entry criteria for future clinical studies will need to be more rigorous if meaningful comparisons are to be made between different treatment options. | Sezary Syndrome |
Immunoelectrophoresis (IEP) was the first practical method that combined electrophoresis and -immunoprecipitation for identifying and characterizing proteins within complex mixtures. Over the years, IEP has been extended to include a variety of techniques and, as a general name, has been applied to virtually any technique that involves electrophoresis and antigen-antibody precipitin reaction for proteins. Because of the diversity in technical details of different IEP versions, the method described here deals only with classic IEP. Although it requires some manual expertise, IEP is versatile, relatively easy to customize, and economical with no need for expensive instrumentation. Further, it can discern identity, partial identity, and nonidentity of the proteins. Any low-viscosity body fluid specimen or, possibly, culture fluid and tissue extract could be tested with IEP if proper antibodies are available. With these attributes, classic IEP remains a valuable tool for clinical diagnostic testing, purity checking of biochemical and pharmaceutical products, and research. | Amido Black |
In 1956, secretory granules were detected via electron microscopy in the mammalian atria by Kisch. This remarkable discovery signaled the beginning of a new field of research that decades later has lead to the concept of the heart as an endocrine organ and the establishment of the natriuretic peptide (NP) system. In 1981, deBold and colleagues identified from the atrial myocardium the first member of the NP family, atrial NP. Thereafter, new members of this growing family of cardiac hormones were identified and investigated. The successful story of B-type or brain NP (BNP), from its discovery to its use in the diagnosis and prognosis of cardiovascular diseases and later as a tool in the treatment of acute congestive heart failure, have since taken place. However, the use of peptides as chronic therapies has been limited by enzymatic degradation. Chronic administration of BNP, particularly in disease states like hypertension and early heart failure, could be effective as an antihypertensive therapy and in delaying progression of cardiac disease. To date, the use of BNP is limited to patients with acute decompensated heart failure, but new strategies are under investigation to extend the use of chronic BNP in less severe stages of cardiovascular diseases. Innovative technologies have been recently developed that allow protection of proteins from enzymatic degradation, making feasible oral administration of small proteins such as BNP. This review will focus on the potential role of BNP as a new chronic therapeutic strategy in the treatment of cardiovascular diseases and will summarize our recent report of the development and in vivo evaluation of orally active human BNP. | Natriuretic Peptide, Brain |
Identifying and monitoring coastlines and shorelines play an important role in coastal erosion assessment around the world. The application of deep learning models was used in this study to detect coastlines and shorelines in Vietnam using high-resolution satellite images and different object segmentation methods. The aims are to (1) propose indicators to identify coastlines and shorelines; (2) build deep learning (DL) models to automatically interpret coastlines and shorelines from high-resolution remote sensing images; and (3) apply DL-trained models to monitor coastal erosion in Vietnam. Eight DL models were trained based on four artificial-intelligent-network structures, including U-Net, U2-Net, U-Net3+, and DexiNed. The high-resolution images collected from Google Earth Pro software were used as input data for training all models. As a result, the U-Net using an input-image size of 512 x 512 provides the highest performance of 98% with a loss function of 0.16. The interpretation results of this model were used effectively for the coastline and shoreline identification in assessing coastal erosion in Vietnam due to sea-level rise in storm events over 20 years. The outcomes proved that while the shoreline is ideal for observing seasonal tidal changes or the immediate motions of current waves, the coastline is suitable to assess coastal erosion caused by the influence of sea-level rise during storms. This paper has provided a broad scope of how the U-Net model can be used to predict the coastal changes over vietnam and the world. | Deep Learning |
The interior barrel of the prefilled syringe is often lubricated/siliconized by the syringe supplier or at the syringe filling site. Syringe siliconization is a complex process demanding automation with a high degree of precision; this information is often deemed know-how" and is rarely published. The purpose of this study is to give a detailed account of developing and optimizing a bench-top siliconization unit with nozzle diving capabilities. This unit comprises a liquid dispense pump unit and a nozzle integrated with a Robo-cylinder linear actuator. The amount of coated silicone was determined by weighing the syringe before and after siliconization, and silicone distribution was visually inspected by glass powder coating or characterized by glide force testing. Nozzle spray range, nozzle retraction speed, silicone-coated amount, and air-to-nozzle pressure were found to be the key parameters affecting silicone distribution uniformity. Distribution uniformity is particularly sensitive to low-target silicone amount where the lack of silicone coating on the barrel near the needle side often caused the syringes to fail the glide force test or stall when using an autoinjector. In this bench-top unit we identified optimum coating conditions for a low silicone dose, which were also applicable to a pilot-scale siliconization system. The pilot unit outperformed the bench-top unit in a tighter control (standard deviation) in coated silicone amount due to the elimination of tubing flex. Tubing flex caused random nozzle mis-sprays and was prominent in the bench-top unit, while the inherent design of the pilot system substantially limited tubing flux. In summary, this bench-top coating unit demonstrated successful siliconization of the 1 mL long syringe with approximately 0.2 mg of silicone oil using a spraying cycle also applicable to larger-scale siliconization. LAY ABSTRACT: Syringe siliconization can be considered a well-established manufacturing process and has been implemented by numerous syringe providers. However, its technical details and associated critical process parameters are rarely published. The purpose of this study is three-fold: (1) to reveal design details of a bench-top siliconization unit, (2) to identify critical process parameters and determine their optimum range to provide consistent and even silicone coating, and (3) to demonstrate the applicability of the optimum process condition derived from the bench-top unit to a pilot siliconization unit. The outcomes of this study will benefit scientists and engineers developing pre-filled syringe products by helping them to better understanding silicone spray coating principles and their relationship to siliconization processes in a large-scale manufacturing setting." | Silicones |
Since the first use of streptomycin as an effective antibiotic drug in the treatment of tuberculosis, aminoglycoside antibiotics have been widely used against a variety of bacterial infections for over six decades. However, the pathways for aminoglycoside biosynthesis still remain unclear, mainly because of difficulty in genetic manipulation of actinomycetes producing this class of antibiotics. Gentamicin belongs to the group of 4,6-disubstituted aminoglycosides containing a characteristic core aminocyclitol moiety, 2-deoxystreptamine (2-DOS), and the recent discovery of its biosynthetic gene cluster in Micromonospora echinospora has enabled us to decipher its biosynthetic pathway. To determine the minimal set of genes and their functions for the generation of gentamicin A(2), the first pseudotrisaccharide intermediate in the biosynthetic pathway for the gentamicin complex, various sets of candidate genes from M. echinospora and other related aminoglycoside-producing strains were introduced into a nonaminoglycoside producing strain of Streptomyces venezuelae. Heterologous expression of different combinations of putative 2-DOS biosynthetic genes revealed that a subset, gtmB-gtmA-gacH, is responsible for the biosynthesis of this core aminocyclitol moiety of gentamicin. Expression of gtmG together with gtmB-gtmA-gacH led to production of 2'-N-acetylparomamine, demonstrating that GtmG acts as a glycosyltransferase that adds N-acetyl-d-glucosamine (GLcNA) to 2-DOS. Expression of gtmM in a 2'-N-acetylparomamine-producing recombinant S. venezuelae strain generated paromamine. Expression of gtmE in an engineered paromamine-producing strain of S. venezuelae successfully generated gentamicin A(2), indicating that GtmE is another glycosyltransferase that attaches d-xylose to paromamine. These results represent in vivo evidence elucidating the complete biosynthetic pathway of the pseudotrisaccharide aminoglycoside." | N-Acylsphingosine Galactosyltransferase |
BACKGROUND: Microphthalmia, anophthalmia, coloboma (MAC) complex is a spectrum of ocular abnormalities that occur in isolation or as part of a syndrome. Genetic abnormalities have been shown to account for 80% of cases in bilateral anophthalmia or severe microphthalmia, where 25-30% were attributed to chromosomal defects in this subset of MAC patients. To date, chromosome 9 short arm (9p) abnormalities have not been shown to associate with development of MAC. PURPOSE: To report a case of MAC spectrum disorder that is related to 9p deletion and duplication. MATERIALS AND METHODS: A child who exhibited signs of MAC was evaluated retrospectively. Genetic analysis with comparative genomic hybridization (CGH) and a family pedigree was obtained from the proband. RESULTS: A 3-year-old girl with a history of an atrial septal defect, a horseshoe kidney and global developmental delay was presented. Ophthalmic examination revealed bilateral iris coloboma, bilateral choroidal-retinal coloboma, and left-sided microphthalmia. Subsequent oligonucleotide-based array CGH revealed two different sites of duplication and deletion on 9p (9p24.3 (209020_1143516)x1, 9p24.3p24.1 (1158662_6395264)x3). CONCLUSION: We present the first case of MAC spectrum disorder that is related to 9p deletion and duplication. The link between the associated genetic abnormality and the phenotypic features is yet to be established. Duplication of JAK2 gene, which is within the same region of abnormalities, may have potentiated the development of MAC spectrum disease. | Coloboma |
A patient presenting with cutaneous vasculitis was noted to be pancytopenic. Subsequent investigation showed a myelodysplastic syndrome (MDS)--refractory anaemia with excess of blasts. Within 3 months her MDS progressed to acute myeloid leukaemia. | Preleukemia |
Transplantation has now become the treatment of choice for end-stage organ failure. However, acute rejection still occurs in approximately 20-50% of cadaver or living donor kidney recipients during the first year post-transplantation and lead to permanent damage of graft function or loss. Recently chimeric(basiliximab) and the humanized(daclizumab) monoclonal antibodies against the alpha chain(CD25) of the interleukin 2 receptor(IL-2R) introduced in the late 1990s. Induction therapy with these antibodies results in a 15-20% reduction in acute rejection episodes after renal transplantation. The availability of anti-IL-2R monoclonal antibodies offers a further opportunity for graft-specific induction therapy. | Daclizumab |
Clinical signs of botulism were observed in a group of eight cats, four of which died, after being fed pelican carrion. Clostridium botulinum type C was isolated from one cat. The microorganism and its toxin were found in the pelican. This is apparently the first report of natural botulism in cats. | Clostridium botulinum type C |
Previous gene-targeting studies indicated that Bim, a BH3-only death activator, regulates total blood cell number. Cytokines contribute to this process by negatively regulating steady-state levels of Bim mRNA. Here we present a molecular mechanism for cytokine-mediated posttranscriptional regulation of Bim mRNA by heat-shock cognate protein 70 (Hsc70), which binds to AU-rich elements (AREs) in the 3'-untranslated region of specific mRNAs and enhances their stability. The RNA binding potential of Hsc70 is regulated by cochaperones including Bag-4 (also SODD), CHIP, Hip, and Hsp40. Cytokines regulate the expression or function of these cochaperones by activating Ras pathways. Thus, exposure of cells to cytokines ultimately leads to destabilization of Bim mRNA and promotion of cell survival. This unanticipated role of a chaperone/cochaperone complex in mRNA stability appears to be critical for hematopoiesis and leukemogenesis." | Heterogeneous-Nuclear Ribonucleoprotein D |
The diversity and importance of Echinococcus species in domesticated animals in Kazakhstan are poorly understood. In this study, 17 cysts of Echinococcus were collected from cattle and a further 17 cysts from sheep. DNA was extracted from the individual cysts and used for polymerase chain reaction amplification of mitochondrial subunit 1 of the cox1 and nadh1 gene. Amplicon sequencing results revealed the presence of Echinococcus granulosus sensu stricto G1 in 15 cattle and 15 sheep, and G3 genotype from two cattle. Echinococcus canadensis (G6/G7 strain) was found in two cysts originating from sheep. | Echinococcus |
Curcumin has been reported to have a therapeutic effect on Alzheimer's disease (AD), but the specific mechanism remains to be elucidated. In the present research, we aimed to investigate the effect and molecular mechanism of curcumin on AD. Mouse primary hippocampal neuron cells were treated with various concentrations of beta-amyloid 42 (Abeta(42)) and the results found that Abeta(42) inhibited cell viability in a dose-dependent manner. Compared with 50 ng/mL Abeta(42), 500 ng/mL Abeta(42) could further promote cell apoptosis, reduce the ratio of Nicotinamide adenine dinucleotide (NAD(+))/Nicotinamide adenine diphosphate hydride (NADH) and Adenosine 5'-triphosphate (ATP) level, and inhibit Sirtuins 3 (SIRT3) deacetylation activity and protein expression of Thyroid hormone receptor beta (Thrb) and SIRT3. Hence, 500 ng/mL Abeta(42) was used to establish a cell model of AD. Curcumin significantly reversed the inhibitory effects of Abeta(42) on cell viability, SIRT3 deacetylation activity, the ratio of NAD(+)/NADH, ATP level and the protein expression of Thrb and SIRT3, and the promotive effect on apoptosis. ChIPBase was used to predict the binding region of Thrb and SIRT3. Dual luciferase reporter gene and Chromatin immune precipitation (ChIP) assays were employed to verify the relationship between Thrb and promoter of SIRT3 mRNA. Overexpression of Thrb recovered Abeta(42) induced metabolic dysfunction, while Thrb silence aggravated Abeta(42) induced metabolic dysfunction. Moreover, Thrb silence or 3-TYP (a selective inhibitor of SIRT3) treatment abolished the amelioration of curcumin on Abeta(42) induced metabolic dysfunction. Additionally, curcumin attenuated memory deficits in Amyloid precursor protein transgenic (APP(TG)) mice. Collectively, curcumin alleviated Abeta(42)-induced neuronal metabolic dysfunction through increasing Thrb expression and SIRT3 activity and improved cognition in APP(TG) mice." | Thyroid Hormone Receptors beta |
The kynurenine pathway intermediate 3-hydroxyanthranilic acid (3-HANA) is converted by 3-HANA 3,4-dioxygenase (3-HAO) to the putative neuropathogen quinolinic acid (QUIN). In the present study, the neuroprotective effects of the 3-HANA analogue and 3-HAO inhibitor NCR-631 was investigated using organotypic cultures of rat hippocampus. An anoxic lesion was induced by exposing the cultures to 100% N2 for 150 min, resulting in a pronounced loss of pyramidal neurons, as identified using NMDA-R1 receptor subunit immunohistochemistry. NCR-631 provided a concentration-dependent protective effect against the anoxia. NCR-631 was also found to counteract the loss of pyramidal neurons in two models of neuroinflammatory-related damage; incubation with either LPS (10 ng/ml) or IL-1 beta (10 IU/ml). The findings suggest that NCR-631 has neuroprotective properties and that it may be a useful tool to study the role of kynurenines in neurodegeneration. | 3-Hydroxyanthranilic Acid |
3-Keto-L-gulonate 6-phosphate decarboxylase (KGPDC) and D-arabino-hex-3-ulose 6-phosphate synthase (HPS), members of the orotidine 5'-monophosphate decarboxylase (OMPDC) suprafamily, catalyze reactions that involve the formation of Mg(2+)-ion stabilized 1,2-enediolate intermediates. The active sites of KGPDC and HPS share several conserved residues, including the presumed ligands for the Mg(2+) and a catalytic histidine residue that has been implicated in protonation of the intermediate in the KGPDC-catalyzed reaction. As reported in the previous manuscript, both enzymes are naturally promiscuous, with KGPDC from Escherichia coli catalyzing a low level of the HPS reaction and the HPS from Methylomonas aminofaciens catalyzing a significant level of the KGPDC reaction. Interestingly, the promiscuous HPS reaction catalyzed by KGPDC can be significantly enhanced by replacing no more than four active site residues from KGPDC reaction with residues from HPS. In this manuscript, we report structural studies of wild-type and mutant KDGPC's that provide a structural explanation for both the natural promiscuity for the HPS reaction and the enhanced HPS activity and diminished KGPDC activity catalyzed by active site mutants." | Orotidine-5'-Phosphate Decarboxylase |
Fertilization of an egg by multiple sperm (polyspermy) leads to lethal genome imbalance and chromosome segregation defects. In Arabidopsis thaliana, the block to polyspermy is facilitated by a mechanism that prevents polytubey (the arrival of multiple pollen tubes to one ovule). We show here that FERONIA, ANJEA, and HERCULES RECEPTOR KINASE 1 receptor-like kinases located at the septum interact with pollen tube-specific RALF6, 7, 16, 36, and 37 peptide ligands to establish this polytubey block. The same combination of RALF (rapid alkalinization factor) peptides and receptor complexes controls pollen tube reception and rupture inside the targeted ovule. Pollen tube rupture releases the polytubey block at the septum, which allows the emergence of secondary pollen tubes upon fertilization failure. Thus, orchestrated steps in the fertilization process in Arabidopsis are coordinated by the same signaling components to guarantee and optimize reproductive success. | Germ Cells, Plant |
AIM: the concept of 'advanced midwifery practice' is explored to a limited extent in the international literature. However, a clear conception of advanced midwifery practice is vital to advance the discipline and to achieve both internal and external legitimacy. This concept analysis aims to clarify advanced midwifery practice and identify its components. METHODS: a review of the literature was executed using Rodgers' evolutionary method of concept analysis to analyze the attributes, references, related terms, antecedents and consequences of advanced midwifery practice. RESULTS: an international consensus definition of advanced midwifery practice is currently lacking. Four major attributes of advanced midwife practitioners (AMPs) are identified: autonomy in practice, leadership, expertise, and research skills. A consensus was found on the need of preparation at master's level for AMPs. Such midwives have a broad and internationally varied scope of practice, fulfilling different roles such as clinicians, clinical and professional leaders, educators, consultants, managers, change agents, researchers, and auditors. Evidence illustrating the important part AMPs play on a clinical and strategic level is mounting. KEY CONCLUSIONS: the findings of this concept analysis support a wide variety in the emergence, titles, roles, and scope of practice of AMPs. Research on clinical and strategic outcomes of care provided by AMPs supports further implementation of these roles. As the indistinctness of AMPs' titles and roles is one of the barriers for implementation, a clear conceptualization of advanced midwifery practice seems essential for successful implementation. IMPLICATIONS FOR PRACTICE: an international debate and consensus on the defining elements of advanced midwifery practice could enhance the further development of midwifery as a profession and is a prerequisite for its successful implementation. Due to rising numbers of AMPs, extension of practice and elevated quality requirements in healthcare, more outcomes research exclusively evaluating the contribution of AMPs to healthcare becomes possible and desirable. | Midwifery |
Niemann-Pick disease type C (NPC) is an autosomal recessive disease most commonly caused by a mutation of NPC1, resulting in the accumulation of cholesterol in late endosomes or lysosomes. In this study, we examined whether an abnormality of autophagy is involved in the pathogenesis of NPC and how cholesterol accumulation participates in this process, using both a U18666A-induced NPC model and NPC1-deficient Chinese hamster ovary cells. In these cells, an increase in the level of the microtubule-associated protein 1 light chain 3 (LC3-II) was demonstrated by Western blotting. An increase in the number of granular LC3-positive structures that colocalized with filipin-labeled accumulated cholesterol was also observed in morphological studies. Cholesterol depletion inhibited the formation of granular LC3-positive structures that colocalized with filipin-labeled cholesterol, and instead promoted the formation of ring-shaped LC3-positive filipin-negative structures in U18666A-treated cells. These results demonstrate the close association of the accumulation of LC3 with accumulated cholesterol in NPC cells. | Filipin |
The transient receptor potential (TRP) channel TRPV4 is a calcium-permeable cation channel protein which plays a mechanosensory and osmosensory role in several musculoskeletal tissues. Previous studies have shown that some specific mutations in the ankyrin repeat domain (ARD) of TRPV4 can reduce channel activity and further cause the osteoarthropathy related disease. Mutations in this region probably influence the constitutive activity of the channel, which mainly regulated by the binding of a small ligand such as adenosine triphosphate (ATP). These findings suggest that it is crucial to understand the fundamental mechanisms regulated by chemical ligands such as ATP binding with the ankyrin repeat domain (ARD) of TRPV4. However, how these mutations at the molecular level resulting in the related diseases are still unclear. Here we use full atomistic simulations to investigate the mutation induced conformational changes and ATP binding ability differences of TRPV4-ARD. Conformation characteristics of different mutations of TRPV4-ARD are explored. Optimal communication paths are studied to explain how a point mutation away from aim region (Finger 3) can cause a significant alteration on the conformation. We identify two molecular mechanisms through the conformation of Finger 3 and through alter the ATP binding mechanism correspondently to explain these unknowns. Our study provides fundamental insights into the mutation induced structural changes of the TRPV4-ARD and helps to explain how the mutations alter the ATP binding ability of the TRPV4-ARD. | Ankyrin Repeat |
Most organs are currently preserved by cold storage (CS) prior to transplantation. However, as more so called marginal donor organs are utilized, machine perfusion has regained clinical interest. Recent studies have demonstrated advantages of pulsatile perfusion over CS preservation for kidney transplantation. However, it remains unclear whether there is a significant benefit of one preservation method over the other in general, or, whether the utilization of particular preservation approaches needs to be linked to organ characteristics. Proposed protective mechanisms of pulsatile perfusion remain largely obscure. It can be speculated that pulsatile perfusion may not only provide nutrition and facilitate the elimination of toxins but also trigger protective mechanisms leading to the amelioration of innate immune responses. Those aspects may be of particular relevance when utilizing grafts with suboptimal quality which may have an increased vulnerability to ischemia/reperfusion injury and compromised repair mechanisms. This review aims to enunciate the principles of organ perfusion and preservation as they relate to indication, aspects of organ protection and to highlight future developments. | Organ Preservation |
BACKGROUND: Lithium, mainstay treatment for bipolar disorder, causes nephrogenic diabetes insipidus and hypercalcemia in about 20% and 10% of patients, respectively, and may lead to acidosis. These adverse effects develop in only a subset of patients treated with lithium, suggesting genetic factors play a role. METHODS: To identify susceptibility genes for lithium-induced adverse effects, we performed a genome-wide association study in mice, which develop such effects faster than humans. On day 8 and 10 after assigning female mice from 29 different inbred strains to normal chow or lithium diet (40 mmol/kg), we housed the animals for 48 hours in metabolic cages for urine collection. We also collected blood samples. RESULTS: In 17 strains, lithium treatment significantly elevated urine production, whereas the other 12 strains were not affected. Increased urine production strongly correlated with lower urine osmolality and elevated water intake. Lithium caused acidosis only in one mouse strain, whereas hypercalcemia was found in four strains. Lithium effects on blood pH or ionized calcium did not correlate with effects on urine production. Using genome-wide association analyses, we identified eight gene-containing loci, including a locus containing Acer2, which encodes a ceramidase and is specifically expressed in the collecting duct. Knockout of Acer2 led to increased susceptibility for lithium-induced diabetes insipidus development. CONCLUSIONS: We demonstrate that genome-wide association studies in mice can be used successfully to identify susceptibility genes for development of lithium-induced adverse effects. We identified Acer2 as a first susceptibility gene for lithium-induced diabetes insipidus in mice. | Alkaline Ceramidase |
Relationship between family-3A cytochrome P-450-dependent (troleandomycin inhibitable) and maternal environmental-dependent systolic blood pressure (SBP) was investigated in spontaneously hypertensive rats (SHR). Adult SHR nursed by foster or natural SHR mothers had indistinguishable SBP. Troleandomycin reduced 50% of Wistar-Kyoto (WKY)-SHR strain difference in SBP. SHR having WKY foster mothers had SBP similar to troleandomycin-reduced SHR levels, which was unaffected by troleandomycin. The two components of SBP elevation appear identical. Because observations of others demonstrated that WKY fostered to SHR show no SBP increase, the maternally dependent/troleandomycin-sensitive component of SBP elevation may reflect epistatic interaction between genes determining maternal differences and offspring sensitivity, respectively. | Troleandomycin |
According to present knowledge, blood derived endothelial progenitor cells (EPC) might act as proangiogenic myeloid cells, which play a fundamental role in the regulation of angiogenesis and blood vessel reorganisation. In this context, we have evaluated the contribution of endogenous myeloid cells in co-cultures of blood derived outgrowth endothelial cells (OEC) and osteogenic cells. In addition, we investigated the role of EPC as a potential source of myeloid cells in the formation of vascular structures in an in vitro model consisting of mesenchymal stem cells (MSC) and OEC. For this purpose, we added EPCs to co-cultures of MSC and OECs. Vascular structures and the co-localisation of myeloid cells were analysed by confocal laser microscopy (CLSM) for endothelial and myeloid markers and quantitative image analysis. The molecular effects of myeloid cells were evaluated by quantitative real time PCR, ELISA and protein arrays from cell culture supernatants and lysates. Endogenous myeloid cells were significantly co-localised with angiogenic structures in co-cultures of OEC and osteogenic cells. The active addition of EPC to co-cultures of OEC and MSC resulted in a statistically approved increase in the formation of prevascular structures at early stages of the co-culture process. In addition, we observed an increase of endothelial markers, indicating beneficial effects of EPC or myeloid cells on endothelial cell growth. Furthermore, real time PCR indicated high expression levels of CD68, CD11b and CD163 in co-cultures of EPC and MSC indicating that EPC act at least partly as macrophage like-cells. | Myeloid Progenitor Cells |
We have prospectively studied changes in serum postprandial cholylglycine (CG) concentration during 297 pregnancies. We found an increase in CG concentration from 0.3 mumol/L at 15 weeks' pregnancy to 0.6 mumol/L at 40 weeks' pregnancy. Although this increase was statistically significant (p less than 0.005), median concentrations of CG remained well within the normal range (0-1.5 mumol/L). However, 10% of the group showed markedly elevated serum CG concentrations at 30 weeks' pregnancy, and the CG level in this group continued to rise during the third trimester. Pruritus was significantly more common in the group with elevated CG concentrations (48%) than in the group with normal CG levels (20%) (p less than 0.005). Serum CG was a much more sensitive predictor of pruritus during pregnancy than other biochemical liver tests. Elevated CG levels were found more commonly in Mediterranean and Asian patients than patients of other ethnic origins (p less than 0.025). No statistically significant associations were found between elevated CG concentrations and maternal age, number of previous pregnancies, pruritus during previous pregnancies, contraceptive-induced cholestasis, and fetal maturity. We conclude that obstetric cholestasis is probably much more common than previously suspected and that consideration should be given to the measurement of serum bile acids in all pregnant individuals with unexplained pruritus. | Glycocholic Acid |
BACKGROUND AND PURPOSE: Hemodynamics are thought to play a role in intracranial aneurysm growth and rupture. Computational fluid dynamics is frequently performed to assess intra-aneurysmal hemodynamics, using generalized flow waveforms of healthy volunteers as inflow boundary conditions. The purpose of this study was to assess differences in inflow conditions for different aneurysmal parent artery locations and variations of circle of Willis configurations. MATERIALS AND METHODS: In a series of 96 patients with 103 aneurysms, velocity measurements were acquired using 2D phase-contrast MR imaging perpendicular to the aneurysmal parent arteries in the circle of Willis. Circle of Willis configurations were inspected for variations using multiple overlapping thin-slab-acquisition MRAs. Flow rates, velocity magnitudes, and pulsatility indices were calculated for each parent artery location in subgroups of complete and incomplete circle of Willis configurations. RESULTS: Flow rates, velocity magnitudes, and pulsatility indices were significantly different among aneurysmal parent arteries. Incomplete circle of Willis configurations were observed in 24% of the cases. Significantly lower basilar artery flow rates were observed in configurations with hypoplastic P1 segments. Significantly higher A1 flow rates were observed in configurations with a hypoplastic contralateral A1 segment. CONCLUSIONS: Inflow conditions vary substantially between aneurysmal parent arteries and circle of Willis configurations. We have created a collection of parent artery-specific inflow conditions tailored to the patient-specific circle of Willis configuration that can be used in future computational fluid dynamics studies analyzing intra-aneurysmal hemodynamics. | Circle of Willis |
BACKGROUND: Although anxiety disorders are more prevalent during the perinatal period, little attention has been given so far to the influence that pregnancy and the post-partum period can have on anxiety disorders. AIM: To review the literature concerning the prevalence, presentation and treatment of anxiety disorders during pregnancy and the post-partum period and to identify the risk factors involved. METHOD: We reviewed the literature in order to find articles concerning the influence of the post-partum period on various types of anxiety disorders. RESULTS: Having selected the most relevant articles, we discuss the findings in relation to specific types of anxiety disorder. CONCLUSION: Women are more vulnerable to anxiety disorders during the perinatal period. Because anxiety disorders can have a significant impact on the mother and her foetus/infant it is important that anxiety disorders are identified and treated at the earliest opportunity. | Puerperal Disorders |
The present work reports the alternate synthesis of amido-amine derivative of alginic acid (AmAA) with high degree of functionalization. The AmAA have been characterized for percentage functionalization, functional group change, surface morphology and thermal decomposition behavior. The results indicate that the amido-amine derivatisation of alginic acid (AA) with >95% functionalization, significantly improves its Pb(II) adsorption efficiency (395.72 mg/g to 535.87 mg/g) over the AA. The equilibrium and kinetic studies showed that Langmuir and Freundlich adsorption isotherm models fitted well to the experimental data, and these followed pseudo-second order kinetic model. The FTIR (Fourier transform infrared spectroscopy) and (13)C CP-MAS NMR (Cross-polarization magic angle spinning carbon-13 solid state nuclear magnetic resonance spectroscopy) analysis revealed that Pb(II) binds to the carboxyl group in case of AA and to the carbonyl & amine group in case of AmAA, which leads to increase in its adsorption efficiency. The study concludes that the functionalization of amido-amine on AA improves its adsorptive efficiency for Pb(II) from aqueous medium. | Alginic Acid |
Core P(MAOETIB-GMA) microparticles of 40-200 microm were prepared by suspension copolymerization of the iodinated monomer 2-methacryloyloxyethyl (2,3,5-triiodobenzoate), MAOETIB, with a low concentration of the monomer glycidyl methacrylate, GMA, which formed hydrophilic surfaces on the particles. Magnetic gamma-Fe(2)O(3)/P(MAOETIB-GMA) core-shell microparticles were prepared by coating the aforementioned core particles through nucleation of iron oxide nanoparticles on the surfaces of the P(MAOETIB-GMA) particles. This was followed by stepwise growth of thin iron oxide layers. The radiopacity and magnetism of these particles were demonstrated in vitro by CT and MRI. In vivo embolization capabilities of these first multimodal visible embolization particles were demonstrated in a rat's kidney tumor embolization model. | Polymethacrylic Acids |
INTRODUCTION: The rapidly growing imbalance of the sex ratio at birth (SRB) in China since the late 1980s demonstrates that, despite an extensive official prohibition, sex-selective abortion has been widely practised there in the past two or three decades. Given the reality of 30-40 million missing females, China has a more challenging set of ethical and social policy issues to be addressed regarding sex-selective abortion than is the case in Western and many other countries. SOURCES OF DATA: This article is based on a search and review of Chinese and English-language literature, including several very recent books in Chinese on the imbalance of the sex ratio at birth in China. It also draws on first-hand information gathered from the author's extensive fieldwork on Chinese views and experiences of abortion. AREAS OF AGREEMENT: The current female deficit is a real and serious problem in China-not a 'false alarm' as earlier alleged. It is a direct consequence of the widespread practice of sex-selective abortion and is chiefly caused by the strong socio-cultural preference for sons in China. Chinese academics-demographers and medical ethicists-in general agree with the official position that sex-selective abortion is morally wrong and should be legally prohibited. AREAS OF CONTROVERSY: Some critical voices, mainly in the English-language literature, have asked whether coercive state intervention in this area is ethically justifiable. Another controversial question is whether and to what degree China's ambitious and rigorous population control programme, widely known as the 'one child' policy, is a contributing factor to the phenomenon of millions of missing females. AREAS TIMELY FOR DEVELOPING RESEARCH: Much further research on the ethical and social policy issues surrounding sex-selective abortion in the Chinese context needs to be done. Systematic quantitative and in-depth qualitative sociological investigations into Chinese people's attitudes toward the subject, and the role of medical professionals, are long overdue. | Sex Preselection |
Several amino acids (AA) are known to regulate key metabolic pathways that are crucial for immune responses. In particular, arginine (ARG) appears to have important roles regarding immune modulation since it is required for macrophage responses and lymphocyte development. Moreover, citrulline (CIT) is a precursor of arginine, and it was reported as an alternative to ARG for improving macrophage function in mammals. The present study aimed to explore the effects of dietary ARG and CIT supplementation on the gilthead seabream (Sparus aurata) immune status. Triplicate groups of fish (23.1 +/- 0.4 g) were either fed a control diet (CTRL) with a balanced AA profile, or the CTRL diet supplemented with graded levels of ARG or CIT (i.e., 0.5 and 1% of feed; ARG1, CIT1, ARG2, and CIT2, respectively). After 2 and 4 weeks of feeding, fish were euthanized and blood was collected for blood smears, plasma for humoral immune parameters and shotgun proteomics, and head-kidney tissue for the measurement of health-related transcripts. A total of 94 proteins were identified in the plasma of all treatments. Among them, components of the complement system, apolipoproteins, as well as some glycoproteins were found to be highly abundant. After performing a PLS of the expressed proteins, differences between the two sampling points were observed. In this regard, component 1 (61%) was correlated with the effect of sampling time, whereas component 2 (18%) seemed associated to individual variability within diet. Gilthead seabream fed ARG2 and CIT2 at 4 weeks were more distant than fish fed all dietary treatments at 2 weeks and fish fed the CTRL diet at 4 weeks. Therefore, data suggest that the modulatory effects of AA supplementation at the proteome level were more effective after 4 weeks of feeding and at the higher inclusion level (i.e., 1% of feed). The bactericidal activity increased in fish fed the highest supplementation level of both AAs after 4 weeks. Peripheral monocyte numbers correlated positively with nitric oxide, which showed an increasing trend in a dose-dependent manner. The colony-stimulating factor 1 receptor tended to be up-regulated at the final sampling point regardless of dietary treatments. Data from this study point to an immunostimulatory effect of dietary ARG or CIT supplementation after 4 weeks of feeding in the gilthead seabream, particularly when supplemented at a 1% inclusion level. | Sea Bream |
Machado-Joseph disease is a progressive neurodegenerative disorder associated with the polyQ-expanded ataxin-3 (encoded by ATXN3), for which no therapy is available. With the aim of clarifying the mechanism of neurodegeneration, we hypothesized that the abnormally long polyQ tract would interact aberrantly with ataxin-2 (encoded by ATXN2), another polyQ protein whose function has recently been linked to translational regulation. Using patient's samples and cellular and animal's models we found that in Machado-Joseph disease: (i) ataxin-2 levels are reduced; and (ii) its subcellular localization is changed towards the nucleus. Restoring ataxin-2 levels by lentiviral-mediated overexpression: (i) reduced mutant ataxin-3 levels; and (ii) rescued behaviour defects and neuropathology in a transgenic mouse model of Machado-Joseph disease. Conversely (i) mutating the ataxin-2 motif that enables binding to its natural interactor and translation activator poly(A)-binding protein; or (ii) overexpressing poly(A)-binding protein, had opposite effects, increasing mutant ataxin-3 translation and aggregation. This work suggests that in Machado-Joseph disease, mutant ataxin-3 drives an abnormal reduction of ataxin-2 levels, which overactivates poly(A)-binding protein, increases translation of mutant ataxin-3 and other proteins and aggravates Machado-Joseph disease. Re-establishment of ataxin-2 levels reduces mutant ataxin-3 and alleviates Machado-Joseph disease pathogenesis opening a new avenue for therapeutic intervention in this and potentially other polyQ disorders. | Ataxin-3 |
Conventional targeted sequencing methods eliminate many of the benefits of nanopore sequencing, such as the ability to accurately detect structural variants or epigenetic modifications. The ReadUntil method allows nanopore devices to selectively eject reads from pores in real time, which could enable purely computational targeted sequencing. However, this requires rapid identification of on-target reads while most mapping methods require computationally intensive basecalling. We present UNCALLED ( https://github.com/skovaka/UNCALLED ), an open source mapper that rapidly matches streaming of nanopore current signals to a reference sequence. UNCALLED probabilistically considers k-mers that could be represented by the signal and then prunes the candidates based on the reference encoded within a Ferragina-Manzini index. We used UNCALLED to deplete sequencing of known bacterial genomes within a metagenomics community, enriching the remaining species 4.46-fold. UNCALLED also enriched 148 human genes associated with hereditary cancers to 29.6x coverage using one MinION flowcell, enabling accurate detection of single-nucleotide polymorphisms, insertions and deletions, structural variants and methylation in these genes. | Nanopore Sequencing |
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