Sarcopenia in Immune-Mediated Rheumatic Diseases-Review.
Sarcopenia is a condition characterized by decreased muscle strength and muscle mass, which can impact physical function. Sarcopenia develops as a consequence of age-related decline (primary sarcopenia) and has a major impact on physical, social, and emotional well-being. In addition, patients with rheumatic diseases may suffer from sarcopenia independently of aging (secondary sarcopenia). Exercise, pharmacological treatments, and nutritional supplementation are some of the strategies used for the management of sarcopenia in the general population. The aim of this review is to summarize the evidence around the prevalence and impact of sarcopenia in patients with rheumatic diseases. From our review, we can state that sarcopenia is a common and prevalent condition among the rheumatic diseases. Furthermore, the impacts of sarcopenia are not well-appreciated, and the implementation of treatment strategies has not been widespread. Strategies such as exercise and some pharmacological treatments are effective in improving physical and functional impairment related to these conditions. New pharmacological treatments are being actively studied and may contribute in the future to the management of sarcopenia.


Aqueous extract of Digitaria exilis grains ameliorate diabetes in streptozotocin-induced diabetic male Wistar rats.
The absence of scientific data on the age long folkloric use of Digitaria exilis grains by sufferers of diabetes prompted the present investigation. This study was aimed at evaluating the antidiabetic activity of aqueous extract of Digitaria exilis grains in streptozotocin (STZ)-induced diabetic rats. Forty two male rats (166.43 ± 3.32 g) were completely randomized into six groups (A-F) of 7 animals each. Animals in group A (control) were administered 0.5 ml of distilled water while those in groups B, C, D, E and F which were induced with diabetes mellitus (by intraperitoneal administration of 60 mg/kg body weight of STZ) were also administered distilled water, 50 mg/kg body weight of metformin (a reference antidiabetic drug), 50, 100 and 200 mg/kg body weight of aqueous extract of D. exilis grains respectively, twice daily for 14 days. Blood glucose levels and some relevant biomolecules were determined 14 days post-administration. Alkaloids, flavonoids, saponins, tannins, anthraquinones, terpenoids, cardiac glycosides, phlobatannins, phenolics and cardenolides were detected in the extract with alkaloids (30.20 mg/ml) occurring the most and phlobatannins (0.22 mg/ml) the least. Streptozotocin significantly (p < 0.05) increased the levels of blood glucose, serum albumin, urea, creatinine and cholesterol, activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver and intake of feed and water. Body weight, weight of pancreas, pancreatic insulin, liver glycogen content, red blood cell and white blood cell and their related indices, liver hexokinase and phosphofructokinase activities were significantly reduced by STZ. In contrast, the extract significantly reversed all those STZ-treatment induced changes with the 200 mg/kg body weight of the extract producing profound values that compared favourably with the distilled water treated non-diabetic animals and metformin treated diabetic animals. Overall, this study revealed that Digitaria exilis grains possess antidiabetic activity via increased insulin secretion, as plasma concentrations of insulin were not determined, enhanced activities of hexokinase and phosphofuctokinase and repletion of hepatic glycogen content.


Why are infant gerbils more resistant than adults to cerebral infarction after carotid ligation?
Younger gerbils have been found to be more resistant than adults to cerebral infarction after carotid ligation. In this study, the perfused cerebral area after bilateral common carotid occlusion was evaluated in infant, young, and adult Mongolian gerbils by the carbon black perfusion method to assess the existence and significance of collateral blood vessels between the vertebrobasilar and carotid circulations. Nineteen gerbils were divided into three groups (i.e., infant, young and adult gerbils aged 3-4, 5-7, and 10-17 weeks, respectively). After bilateral common carotid artery occlusion, carbon black was injected directly into the left ventricle by cardiac puncture through the closed thorax. In five of eight infant gerbils, the whole brain was perfused by carbon black, while in the remaining three, only the cerebellum and brainstem were stained well, and marked bilateral cerebral pallor was observed. On the other hand, carbon black did not perfuse the brain region supplied by the carotid arteries, both in young and adult gerbils (11 animals in total). These results suggest that infant gerbils might have a more highly developed network of collateral blood vessels between the vertebrobasilar and carotid circulations, and the existence of such a significant network might be the basis for the fact that infant gerbils are resistant to cerebral infarction following carotid ligation. We propose that gerbils should be used as a stroke model only when they are 5 weeks old or older.


Hip protectors for preventing hip fractures in older people.
Hip fracture in older people usually results from a fall on the hip. Hip protectors have been advocated as a means to reduce the risk of sustaining a hip fracture. To determine if external hip protectors reduce the incidence of hip fractures in older people following a fall. We searched the Cochrane Musculoskeletal Injuries Group trials register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to January Week 2, 2005), EMBASE (1988 to 2005 Week 02), CINAHL (1982 to December Week 2 2004), other databases and reference lists of relevant articles. We also contacted trialists. All randomised or quasi-randomised controlled trials comparing the use of hip protectors with a control group. Two authors independently assessed trial quality and extracted data. We sought additional information from trialists. Pooling of uncorrected data from cluster-randomised trials was only done on an exploratory basis. Fifteen included trials contributed data to this updated review. One trial, which was a study of compliance (adherence) lasting 12 weeks, contributed no fracture outcome data. Pooling of data from eleven trials conducted in nursing or residential care settings, including six cluster-randomised studies, showed evidence of a marginally statistically significant reduction in hip fracture incidence (relative risk (RR) 0.77, 95% confidence interval (CI) 0.62 to 0.97). This analysis showed significant statistical heterogeneity. Pooling of data from three individually randomised trials involving 5135 community dwelling participants, showed no reduction in hip fracture incidence from the provision of hip protectors (RR 1.16, 95% CI 0.85 to 1.59). There was no evidence of any significant effect of hip protectors on incidence of pelvic or other fractures. No important adverse effects of the hip protectors were reported but compliance, particularly in the long term, was poor. Accumulating evidence casts some doubt on the effectiveness of the provision of hip protectors in reducing the incidence of hip in older people. Acceptance and adherence by users of the protectors remain poor due to discomfort and practicality.


The use of a biotyping system to investigate an unusual clustering bacteraemias caused by Aeromonas species.
Aeromonas spp. were isolated from blood cultures taken from four clinically bacteraemic patients over an 18 day period on four separate wards. A common source was suspected and extensive environmental sampling revealed two more ward isolates of Aeromonas spp. A biotyping system was employed which distinguished the strains from each other and indicated that a common source was unlikely. This coincidental clustering occurred in the autumn, a period when isolates from water and faeces are normally at a peak. All patients were debilitated and it is postulated that their own gastrointestinal tracts acted as the most likely route for their bacteraemias.


Ecosystem services research in mountainous regions: A systematic literature review on current knowledge and research gaps.
Mountain ecosystem services (MES) can provide a wide range of benefits for human well-being, including provisioning, regulating, supporting and cultural services. This systematic review work analyzed existed knowledge and research gaps on MES at the global level. The study used databases of science direct, Scopus and google scholar using searching, appraisal, synthesis, and analysis (SALSA) framework. Using specific keywords for the searching engine, the number of publications linked with MES were about 1252 which published between 1992 and June 2019. But, only 74 publications fulfilled the inclusion criteria. The analysis highlighted the existence of gaps in the literature including case studies from a limited geographical areas, focus on regulating and provisioning services, and lack of studies that explore the kinds of interlink between ecosystem services, and occurrence of limitation linked with data and methodology. From the 74 publications used for analysis, only seven of them were addressed mainly trade-offs and synergies, but most of them focus on quantification, qualification and economic valuation of the services. From the total case studies, the services addressed were summed up to 317 services, and the services such as climate regulation, food and fodder, fresh water, recreation and ecotourism, and erosion regulation studied more. On the contrary, photosynthesis, ornamental resources, net primary production, disease regulation, genetic resources, water purification and waste treatments were the least studied. Therefore, future research works should focus on mountainous areas of no and least studied of its ecosystem services. Critical studies are also required that indicate the link between a human being with MES, the trade-offs and synergies between MES and the influence of human beings on the quality and accessibility of ecosystem services. Besides, priority should be given by researches for methodological development and proposing management option for the mountain ecosystem and resource.


Dutch primary schoolchildren's attitudes toward their dental appearance.
This study's purpose was to examine children's attitudes toward dental appearance and compare these with attitudes toward general health, body shape, grades in school, friends, money, and sports. The study also explored whether subjects reporting that they have attractive teeth believed themselves to have higher grades in school, more friends, a slim body shape, and better health than subjects reporting that they have unattractive teeth. A sample of 216 9- to 13-year-old Dutch children participated. The methods of paired comparisons and direct ranking were used to investigate children's judgments about the importance of dental appearance. The subjects were also asked to indicate how strongly they believed that they had high grades in school, a lot of friends, money, success in sports, attractive teeth, a slim body shape, and good health. High grades in school, a slim body shape, good health, a lot of friends, and more money were preferred to attractive teeth. Children reporting that they have attractive teeth believed themselves to have higher grades in school, a slimmer body shape, more friends, more money, and better health than children reporting that they have unattractive teeth. Although attractive teeth are highly valued in general, children give priority to other issues in their lives.


An Insight into Cotton Leaf Curl Multan Betasatellite, the Most Important Component of Cotton Leaf Curl Disease Complex.
Cotton leaf curl disease (CLCuD) is one of the most economically important diseases and is a constraint to cotton production in major producers, Pakistan and India. CLCuD is caused by monopartite plant viruses belonging to the family Geminiviridae (genus Begomovirus), in association with an essential, disease-specific satellite, Cotton leaf curl Multan betasatellite (CLCuMuB) belonging to a newly-established family Tolecusatellitidae (genus Betasatellite). CLCuMuB has a small genome (ca. 1350 nt) with a satellite conserved region, an adenine-rich region and a single gene that encodes for a multifunctional βC1 protein. CLCuMuB βC1 protein has a major role in pathogenicity and symptom determination, and alters several host cellular functions like autophagy, ubiquitination, and suppression of gene silencing, to assist CLCuD infectivity. Efficient trans-replication ability of CLCuMuB with several monopartite and bipartite begomoviruses, is also associated with the rapid evolution and spread of CLCuMuB. In this article we comprehensively reviewed the role of CLCuMuB in CLCuD, focusing on the βC1 functions and its interactions with host proteins.


Inter-observer reliability of digital vaginal examination using a four-grade scale in different patient positions.
This study aims to compare digital vaginal examination with the patient in supine and standing position and to correlate the degree of pelvic organ prolapse (POP) with a prolapse quality of life (P-QOL) questionnaire. Two hundred and seven women with POP symptoms were digitally examined in supine and standing positions using a four-grade scale (none, minimal, moderate, and severe). P-QOL was used to assess the severity of prolapse symptoms. Cohen's kappa coefficient was used to calculate the inter-observer agreement and Spearman rank correlation test to assess the correlation between examination findings and P-QOL scores. Only vaginal examination findings in standing position had a good inter-observer reliability (kappa value 0.76-0.91). The severity of P-QOL scores only correlated with the examination findings in the standing position (P < 0.001). Digital examination of POP is unreliable if woman is supine but is reliable and correlates with symptoms and QOL impairment when the examination is performed with the patient standing.


Metabolic studies of Hg-203 on Chlamydomonas reinhardi.
Sterile cultures of Chlamydomonas reinhardi, WT+, were treated with Hg-203 at 25 degrees C to identify probably formed volatile mercury compounds. Experiments were performed with living and dead cells under aerobic or anaerobic conditions, respectively, and the mercury concentration was measured in the system algae/nutrient medium. We found a timerelated decrease of mercury concentration in the cell suspension and the cell-free nutrient medium due to a reduction of Hg++ to Hg0, probably caused by extracellular enzymes; monomethyl or dimethyl mercury could not be detected.


Molecular taxonomic position of the elephant schistosome, Bivitellobilharzia nairi, newly discovered in Sri Lanka.
Bivitellobilharzia nairi (Mudaliar and Ramanujachar, 1945) Dutt and Srivastava, 1955 was first recorded in India. A number of adult worm specimens of this schistosome species were recovered from a domestic elephant, which died in 1999 in Sri Lanka. This is the first report of this schistosome from Sri Lanka. In the present study, in order to clarify the phylogenetic relationship with other species of schistosomes, sequences from the second internal transcribed spacer (ITS2) of the ribosomal gene repeat, part of the 28S ribosomal RNA gene (28S), and part of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene from B. nairi were analyzed. Two intraspecific variations were seen within 13 individuals in the ITS2 region. In the CO1 region of the mitochondrial DNA, there were four haplotypes in the nucleotide sequences and two haplotypes in the amino acid sequences. Phylogenetic analysis using the nuclear DNA showed that B. nairi was basal to all of species of the genus Schistosoma. The 28S tree also showed that the mammalian lineage was monophyletic. However, phylogenetic analysis using the mitochondrial DNA showed that B. nairi was nested within the genus Schistosoma. The taxonomical position for this species as well as the contradiction between the results from the nuclear and mitochondrial genes were discussed.


Cytoskeletal organization of bee ovarian follicles during oogenesis.
The germ cells in the germarium of the bee meroistic polytrophic ovarian cysts remain interconnected by cytoplasmic bridges as a result of incomplete cell division. These intercellular bridges form a distribution pathway for the substances that initially determine which of the cystocytes will become oocyte and later conduct the products synthesized by the nurse cells to the oocyte. In the present work, the presence and distribution of cytoskeleton components, actin and tubulin were studied in ovaries of queens of Apis mellifera and Scaptotrigona postica, two eusocial species, using antibody against α- and β-tubulin and FITC-phalloidin, aiming to shed light on the role of these cytoskeleton elements in oogenesis. The immunofluorescent preparations were analyzed by laser scanning confocal microscopy. F-actin was detected in the intercellular bridges of both species. The tubulin distribution in cell cytoplasm of A. mellifera and S. postica also displayed similar pattern. The role of these elements in the oogenetic events responsible for both cell support and motility is discussed.


In vitro analysis of the cellular proliferative response to 17-beta-estradiol of human breast cancer.
In human breast cancer the proliferating cells appear to differ from those containing estrogen receptors (ER) as shown by studies on isolated cellular subpopulations. In this paper the in vitro effect of 17-beta-estradiol on cell proliferation in 30 primary breast tumors was studied. The effect of several estradiol concentrations was assayed, and the influence of diethylstilbestrol, tamoxifen, and nafoxidine was also tested. The response to these compounds was measured through the thymidine labeling index (TLI). When exposed to 10(-9) mol/l and 10(-8) mol/l estradiol, 14 of 19 ER-positive tumors and six of 11 ER-negative tumors were induced to further proliferate. The TLI increase over the control was 219% (P less than 0.05) at 10(-9) mol/l E2 and 258% (P less than 0.05) at 10(-8) mol/l E2 for ER-positive tumors, and 233% (0.1 less than P less than 0.2) at 10(-9) mol/l E2 and 321% (0.1 less than P less than 0.2) at 10(-8) mol/l E2 for ER-negative tumors. The addition of diethylstilbestrol and antiestrogens in vitro inhibited, to varying degrees, the estradiol-induced increase in the TLI irrespective of the ER-status. The response to E2 was correlated with the expression of the ras p21 protein and carcinoembryonic antigen. It was found that the ras p21 protein is preferentially expressed in ER-negative tumors, the opposite being true for carcinoembryonic antigen. The ras p21 protein is preferentially expressed in those ER-positive tumors that do not respond to estradiol with an increase in the TLI.


Anterior tibial stress fractures treated with anterior tension band plating in high-performance athletes.
The non-surgical treatment of anterior tibial cortex stress fractures requires long periods of abstention from sports activities and often results in non-union. Many different surgical techniques have already been previously described to treat these fractures, but there is no consensus on the best treatment. We describe the outcome of treatment using anterior tibial tension band plating in three high-performance athletes (4 legs) with anterior tibial cortex stress fractures. Tibial osteosynthesis with a 3.5-mm locking compression plate in the anterolateral aspect of the tibia was performed in all patients diagnosed with anterior tibial stress fracture after September 2010 at Santa Casa Hospital. All of the fractures were consolidated within a period of 3 months after surgery, allowing for an early return to pre-injury levels of competitive sports activity. There were no infection, non-union, malunion or anterior knee pain complications. Anterior tibial tension band plating leads to prompt fracture consolidation and is a good alternative for the treatment of anterior tibial cortex stress fractures. Bone grafts were shown to be unnecessary.


Malignant peripheral nerve sheath tumor in spine: imaging manifestations.
Malignant peripheral nerve sheath tumor (MPNST) is a relatively rare soft tissue malignant tumor. Most of reports currently are pathological articles and clinical case reports and most of them are MPNST in the thorax, abdomen or extremities. Imaging report of spinal MPNST is very rare, and MPNST is easy to be misdiagnosed. In this study, we explored the computed tomography and magnetic resonance imaging manifestations of MPNST that occurred in the spine and to improve the preoperative diagnostic accuracy of MPNST.


Hemorrhagic tonsillitis in an infant: A case report.
This case report describes a case of severe hemorrhagic tonsillitis in a nine month-old child who suffered significant amount of blood loss and was emergently taken to operating room for control of hemorrhage. The child was brought to emergency room by mom after noticing blood around child's mouth and nose and a subsequent episode of hematemesis having awoken from sleep. Initial impression was bleeding secondary to epistaxis however a thorough bedside otolaryngology exam including flexible rhinolaryngoscopy ruled this out. Rapid pooling of blood in oropharynx, continued hemorrhage with significant blood loss and recent history of hematemesis prompted emergent intervention in operating room for endoscopy for control of hemorrhage including esophagogastroduodenoscopy (EGD). Bleeding was identified from a blood vessel at left lower tonsil pole. Although there is a description in literature of such cases, these are uncommon in the pediatric population and none has been described in a patient this young requiring emergent operative intervention. This case report discusses the diagnostic and decision making dilemma in an infant in setting of ongoing active hemorrhage and the role of multidisciplinary team management.


Fouling mitigation in membrane bioreactors using multivalent cations.
Several cations have been used to study the effect of mineral coagulants on activated sludge properties and membrane fouling in submerged membrane bioreactors (MBRs). The flocculability and settling properties of activated sludge were studied in various concentrations of sodium, potassium, magnesium, calcium, ferrum (in Fe(3+) form), and aluminum. Significant effect of cations and their concentrations on different parameters have been analyzed by 2-way ANOVA. Results showed that multivalent cations induce flocculation in bioreactors while monovalent cations have a detrimental effect on flocculability of activated sludge. The ratio of tight bound extracellular polymeric substances (TB-EPSs) to loosely bound (LB-EPSs) increased with concentration of multivalent cations that was in accordance with enhancement of biosorption in high concentration of multivalent cations. Moreover, these cations improved the settleability and dewatering properties of activated sludge. They also mitigated membrane fouling in the MBRs so that calcium and aluminum reduced membrane fouling to nearly 30%. Simple but useful correlations were developed for description of activated sludge properties based on easy measurable parameters that could be used also for estimation of membrane fouling. It was found that the ratio of TB-EPS to LB-EPS and also flocs size distribution are the main parameters affecting membrane fouling.


IgA vasculitis nephritis in children and adults: one or different entities?
The clinical features of the kidney involvement in immunoglobulin A (IgA) vasculitis (IgAVN) differ in children and adults for both clinical presentation and progression. IgAVN in children has mostly a self-limiting course and favorable resolution, while in adults the kidney involvement is frequently severe with unfavorable outcome. However, a subset of children is at risk of progression within the pediatric age or decades later in adulthood, particularly when the diagnosis and a prompt intervention are delayed. Factors predicting progression and outcome in the whole spectrum of age have been investigated in recent research, as well as the relationship between IgAVN and primary IgAN, which share the same pathology features, in the light of peculiar clinical differences and progression tendencies, and hence need for selective treatments. The search for a personalized treatment in children with IgAV and in different ages of life should rely on the identification of different risks for progression. This review will focus on recent studies which contribute to improve our knowledge in this still largely unclear area.


The Possible Effect of Dietary Fiber Intake on the Metabolic Patterns of Dyslipidemia Subjects: Cross-Sectional Research Using Nontargeted Metabolomics.
Dyslipidemia is important because of its association with various metabolic complications. Numerous studies have sought to obtain scientific evidence for managing dyslipidemia patients. This study aims to identify differences in the nutritional traits of dyslipidemia subjects based on metabolite patterns. Dyslipidemia (n = 73) and control (n = 80) subjects were included. Dyslipidemia was defined as triglycerides ≥200 mg/dL, total cholesterol ≥240 mg/dL, low density lipoprotein cholesterol ≥160 mg/dL, high-density lipoprotein cholesterol <40 mg/dL (men) or 50 mg/dL (women), or lipid-lowering medicine use. Nontargeted metabolomics based on ultra-high performance liquid chromatography-mass spectrometry identified plasma metabolites, and K-means clustering was used to reconstitute groups based on the similarity of metabolomic patterns across all subjects. Then, with eXtreme Gradient Boosting, metabolites significantly contributing to the new grouping were selected. Statistical analysis was conducted to analyze traits demonstrating appreciable differences between the groups. Dyslipidemia subjects were divided into 2 groups based on whether they were (n = 24) or were not (n = 56) in a similar metabolic state as the controls by K-means clustering. The considerable contribution of 4 metabolites (3-hydroxybutyrylcarnitine, 2-octenal, 1,3,5-heptatriene, and 5β-cholanic acid) to this new subset of dyslipidemia was confirmed by eXtreme Gradient Boosting. Furthermore, fiber intake was significantly higher in dyslipidemia subjects whose metabolic state was similar to that of the control than in the dissimilar group (P = 0.002). Moreover, significant correlations were observed between the 4 metabolites and fiber intake. Regression analysis determined that the ideal cutoff for fiber intake was 17.28 g/d. Dyslipidemia patients who consume 17.28 g/d or more of dietary fiber may maintain similar metabolic patterns to healthy individuals, with substantial effects on the changes in the concentrations of 4 metabolites. Our findings could be applied to developing dietary guidelines for dyslipidemia patients.


Fluorescence recovery after photobleaching (FRAP) to study nuclear protein dynamics in living cells.
Proteins involved in chromatin-interacting processes, like gene transcription, DNA replication, and DNA repair, bind directly or indirectly to DNA, leading to their immobilisation. However, to reach their target sites in the DNA the proteins have to somehow move through the nucleus. Fluorescence recovery after photobleaching (FRAP) has been shown to be a strong approach to study exactly these properties, i.e. mobility and (transient) immobilisation of the proteins under investigation. Here, we provide and discuss detailed protocols for some of the FRAP procedures that we have used to study protein behaviour in living cell nuclei. In addition, we provide examples of their application in the investigation of the androgen receptor (AR), a hormone-inducible transcription factor, and of two DNA-maintenance factors, the telomere binding proteins TRF1 and TRF2. We also provide protocols for qualitative FRAP analysis and a general scheme for computer modelling of the presented FRAP procedures that can be used to quantitatively analyse experimental FRAP curves.


Quantification and site-specification of the support practice factor when mapping soil erosion risk associated with olive plantations in the Mediterranean island of Crete.
Due to inappropriate agricultural management practices, soil erosion is becoming one of the most dangerous forms of soil degradation in many olive farming areas in the Mediterranean region, leading to significant decrease of soil fertility and yield. In order to prevent further soil degradation, proper measures are necessary to be locally implemented. In this perspective, an increase in the spatial accuracy of remote sensing datasets and advanced image analysis are significant tools necessary and efficient for mapping soil erosion risk on a fine scale. In this study, the Revised Universal Soil Loss Equation (RUSLE) was implemented in the spatial domain using GIS, while a very high resolution satellite image, namely a QuickBird image, was used for deriving cover management (C) and support practice (P) factors, in order to map the risk of soil erosion in Kolymvari, a typical olive farming area in the island of Crete, Greece. The results comprised a risk map of soil erosion when P factor was taken uniform (conventional approach) and a risk map when P factor was quantified site-specifically using object-oriented image analysis. The results showed that the QuickBird image was necessary in order to achieve site-specificity of the P factor and therefore to support fine scale mapping of soil erosion risk in an olive cultivation area, such as the one of Kolymvari in Crete. Increasing the accuracy of the QB image classification will further improve the resulted soil erosion mapping.


Quantifying citrate-enhanced phosphate root uptake using microdialysis.
Organic acid exudation by plant roots is thought to promote phosphate (P) solubilisation and bioavailability in soils with poorly available nutrients. Here we describe a new combined experimental (microdialysis) and modelling approach to quantify citrate-enhanced P desorption and its importance for root P uptake. To mimic the rhizosphere, microdialysis probes were placed in soil and perfused with citrate solutions (0.1, 1.0 and 10 mM) and the amount of P recovered from soil used to quantify rhizosphere P availability. Parameters in a mathematical model describing probe P uptake, citrate exudation, P movement and citrate-enhanced desorption were fit to the experimental data. These parameters were used in a model of a root which exuded citrate and absorbed P. The importance of soil citrate-P mobilisation for root P uptake was then quantified using this model. A plant needs to exude citrate at a rate of 0.73 μmol cm-1 of root h-1 to see a significant increase in P absorption. Microdialysis probes with citrate in the perfusate were shown to absorb similar quantities of P to an exuding root. A single root exuding citrate at a typical rate (4.3 × 10-5 μmol m-1 of root h-1) did not contribute significantly to P uptake. Microdialysis probes show promise for measuring rhizosphere processes when calibration experiments and mathematical modelling are used to decouple microdialysis and rhizosphere mechanisms.


Characterization of an extracellular protein, Rv1076 from M. tuberculosis with a potential role in humoral response.
Many mycobacterial proteins involved in lipid metabolism are reported to be essential for survival and pathogenesis of M. tuberculosis. Rv1076 of M. tuberculosis has been annotated as a putative esterase/lipase based on the consensus sequence 'GXSXG'. It is conserved in all the mycobacterial species. Therefore, in the present study we have characterized Rv1076 gene product in detail. The gene rv1076 was expressed in E. coli and purified from inclusion bodies with approx. 40% yield. The protein showed high specific activity with pNP- butyrate as preferred substrate. The enzyme was stable upto 50°C and in pH range of 6-8 i.e. under acidic conditions. Ser-140, Glu-239 and His-269 were confirmed as active site residues using site directed mutagenesis. The specific activity, Km and Vmax of enzyme was determined to be 177Umg-1 protein, 334μM and 262μmolml-1min-1, respectively. Western blot analysis established Rv1076 to be an extracellular protein. Several putative immunodominant epitopes were predicted in Rv1076. Rv1076 elicited strong humoral response in both extrapulmonary and relapsed cases of TB patients. Therefore, we conclude that Rv1076 is a novel secretory esterase of M. tuberculosis which could be a potential immunodominant antigen of M. tuberculosis.


5th generation millimeter wave wireless communication propagation losses dataset for indian metro cities based on corresponding weather conditions.
In this paper, we present 5th generation (5G) millimeter wave (mmWave) wireless communication propagation losses dataset for four Indian major urban cities like Delhi, Mumbai, Kolkata and Chennai based on corresponding weather conditions. Weather effect on mmWave is calculated in terms of mmWave path losses by considering various atmospheric weather conditions. Propagation of mmWave is affected by weather impairments (WIs) and due to that mmWave attenuation takes place and Indian metro cities have variety in weather variations. 5G mmWave propagation attenuation is calculated due to WIs like water vapour, oxygen, rain and fog for frequencies 28 GHz, 37 GHz and 39 GHz. Individual WI effects during the season are calculated and shown suing graphs and tables.


Protective effect of prolactin and placental lactogen on NO-induced Nb2 lymphoma cell apoptosis.
Nitric oxide (NO) is an important modulator involved in immune regulation. Here, we describe conditions under which NO-donors induce apoptosis on Nb2 lymphoma cells, as evidenced by decreased cell viability and increased hypodiploid DNA content determined by flow cytometry. In addition, DNA fragmentation typical of apoptosis was shown by agarose gel electrophoresis. This apoptosis was accompanied by a significant increase of caspase-3-like enzymatic activity. Both ovine prolactin (oPRL) and ovine placental lactogen (oPL) exerted a protective effect on the NO-donor-induced apoptosis. Furthermore, dexamethasone (Dex)-induced cell death was also associated with caspase-3-like activity and oPL had the same potency as oPRL in its protective effect on Dex-induced apoptosis of Nb2 cells.


Prolonged Video-EEG and Heart Rate Variability can Elucidate Autonomic Dysregulation in Infantile Apneic Seizures.
Infantile apneic seizures (IASs) are unexpected life-threatening events. We aimed to determine the utility of prolonged video-electroencephalography (vEEG) and heart rate variability (HRV) in IAS. The study included seven infants with apneic seizures captured by vEEG, percutaneous oxygen saturation (SpO2), and electrocardiography (ECG). Interictal, preictal, and postictal HRV of patients and N2 sleep HRV of 10 age-matched controls were determined. We analyzed seven vEEGs (duration = 17 to 87 hours) of seven patients aged three to 13 months (mean onset age of apneic event = 6.3 months). Fifteen apneic seizures (one to five per infant) were captured. The initial apneic seizure was captured at 7.5 to 76 hours (mean = 36.6 hours) after vEEG initiation. Ictal rhythmic delta/theta/fast waves were seen over temporal (five patients), central (one), and diffuse areas (one). Ictal SpO2 decreased between 1.5% and 90% (mean = 47.9%). Ictal decreased heart rate (HR) (six seizures) and ictal increased HR (14) was detected. Both decreased and increased HR was observed (five). The preictal low-frequency (LF)/high-frequency (HF) ratio was significantly higher than the interictal LF/HF ratio (P = 0.048). Preictal (P = 0.048), and postictal (P = 0.019) root mean square of successive differences (RMSSDs) of patients were lower than the sleep RMSSD of controls. These results indicated dominant sympathetic activity. RMSSD from interictal to preictal periods tended to be higher in IAS with decreased HR than in IAS with increased HR alone (P = 0.066). The postictal RMSSD showed tendency to be higher in IAS with decreased HR than in IAS with increased HR alone (P = 0.088). The decreased HR and increased RMSSD suggested not only sympathetic activity but also escalated parasympathetic activity in IAS. Infants with unexpected apneic events should be monitored with prolonged vEEG, SpO2, and ECG. Abnormal HRV in infants with apneic seizures might indicate additional autonomic dysregulation in IAS.


Dynamic effects of Fto in regulating the proliferation and differentiation of adult neural stem cells of mice.
N 6-methyladenosine (m6A) modification of RNA is deposited by the methyltransferase complex consisting of Mettl3 and Mettl14 and erased by demethylase Fto and Alkbh5 and is involved in diverse biological processes. However, it remains largely unknown the specific function and mechanism of Fto in regulating adult neural stem cells (aNSCs). In the present study, utilizing a conditional knockout (cKO) mouse model, we show that the specific ablation of Fto in aNSCs transiently increases the proliferation of aNSCs and promotes neuronal differentiation both in vitro and in vivo, but in a long term, the specific ablation of Fto inhibits adult neurogenesis and neuronal development. Mechanistically, Fto deficiency results in a significant increase in m6A modification in Pdgfra and Socs5. The increased expression of Pdgfra and decreased expression of Socs5 synergistically promote the phosphorylation of Stat3. The modulation of Pdgfra and Socs5 can rescue the neurogenic deficits induced by Fto depletion. Our results together reveal an important function of Fto in regulating aNSCs through modulating Pdgfra/Socs5-Stat3 pathway.


Anaphylaxis after ingestion of beignets contaminated with Dermatophagoides farinae.
A 48-year-old man was evaluated for anaphylaxis associated with ingestion of beignets prepared from a commercial mix. Microscopic examination of the patient's beignet mix revealed live Dermatophagoides farinae. Another unopened box from the same source was not infested. Skin test results to aeroallergens and foods, including all beignet mix ingredients, were positive only to D. farinae and D. pteronyssinus extracts. Skin prick test results to an infested mix extract (1:5 wt/vol) were also positive, but no reaction was observed with noninfested mix extract. ELISA inhibition studies demonstrated significant inhibition of the patient's serum binding to D. farinae strips by infected mix extract. Parallel inhibition curves were produced by the infested mix extract and a commercial D. farinae extract. Noninfested mix extract showed no inhibition. RAST analysis with beignet mix discs showed significant binding of the patient's serum IgE to infested mix discs but not to noninfested mix discs. RAST inhibition studies revealed more than 86% inhibition of binding of the patient's IgE to infested mix discs by infested mix extract and D. farinae extract. No inhibition was observed with noninfested mix or 5% fetal calf serum-phosphate-buffered saline. We conclude that the allergen to which the patient reacted was most likely D. farinae and that ingestion of D. farinae may cause anaphylaxis in sensitive persons.


Isolated ventricular myocytes from failing and non-failing human heart; the relation of age and clinical status of patients to isoproterenol response.
Single cardiac myocytes were isolated from the ventricles of failing and non-failing human hearts. The contraction amplitude, time-to-peak shortening and time to 50% and 90% relaxation were measured in cells stimulated at 0.2 Hz at 32 degrees C. The effects of increasing extracellular calcium and isoproterenol were investigated using cumulative concentration/response curves. Maximum contraction amplitude in high calcium or velocities of contraction or relaxation were not impaired in cells from failing hearts. Beta-adrenoceptor function in a single cell was assessed by the maximum contraction amplitude in the presence of isoproterenol relative to that with high calcium in the same cell (isoproterenol/calcium ratio). A decrease in the isoproterenol/calcium ratio correlated positively with an increase in the isoproterenol EC50 (concentration for half-maximal effect) for a cell (P less than 0.02, n = 39). The isoproterenol/calcium ratio in left ventricular myocytes decreased with increasing severity of disease, correlating with failure as defined by New York Heart Association class (P less than 0.001, n = 26 patients), left ventricular ejection fraction (P less than 0.001, n = 24), left ventricular end diastolic pressure (P less than 0.05, n = 21) and amount of diuretics prescribed (P less than 0.001, n = 26). In right ventricular myocytes, only increasing NYHA class correlated with decreasing isoproterenol/calcium ratios. There was a correlation of the isoproterenol/calcium ratio between right and left ventricular cells from patients with ischemic heart disease (P less than 0.05), n = 11). Beta-adrenoceptor subsensitivity occurred in mitral valve disease, ischemic heart disease, congenital abnormalities and congestive cardiomyopathy, but not in the right ventricle of patients with myocarditis. The isoproterenol/calcium ratio correlated negatively with the age of the patient (P less than 0.001, n = 26, left ventricle). Multiple regression indicated that the maximum contraction amplitudes in either high isoproterenol or high calcium declined significantly with age only, but that both age and severity of disease contributed to the decrease in isoproterenol/calcium ratio. Time-to-peak tension in isoproterenol, as well as relaxation times in high calcium also decreased with the age of the patient. Analysis of variance showed that between-patient variation was significantly greater than between-cell for most of the parameters measured. Beta-adrenoceptor desensitisation may be detected in individual myocytes from failing hearts, and this relates more to the severity of disease and the age of the patient rather than the etiology of heart failure. A decline in absolute contractility of muscle cells with age was detected.


Comparison between traditional strength training and complex contrast training on repeated sprint ability and muscle architecture in elite soccer players.
The purpose of this study was to compare traditional strength training (TST) and complex contrast training (CCT) on the repeated-shuttle-sprint ability (RSSA), the countermovement squat jump (CMJ) height, the one repetition maximum (1RM) at squat on the Smith machine, and on muscle architecture in young, male elite soccer players. Twenty-two soccer players (mean age 18.4±0.4 years; mean weight 70.2±9.1 kg; mean height 179.9±7.5 cm) who belonged to the under-20 age group were randomly assigned into two groups: CCT (N.=10) or TST (N.=12). During the study period, the soccer players trained with CCT through power exercises performed before high-velocity exercises and TST based on a set-repetition format through daily, undulatory periodization. After statistical analysis (P<0.05), the results demonstrated that the specific CCT regimen provided a significant improvement in the RSSA percent decrement (moderate effect size), CMJ (large effect size) and 1RM ability (large effect size). However, the TST promoted significant changes in 1RM (large effect size) and a significant increase in the muscle thickness of the vastus intermedius (moderate effect size). The CCT protocol could be used to improve the RSSA parameters, CMJ and 1RM, and the TST developed dynamic strength and muscle growth. Coaches can choose either CCT or TST protocols according to the needs of their soccer players.


Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes.
Drug induced liver injury (DILI), a major cause of pre- and post-approval failure, is challenging to predict pre-clinically due to varied underlying direct and indirect mechanisms. Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) and Ritonavir, a protease inhibitor, are antiviral drugs that cause clinical DILI with different phenotypes via different mechanisms. Assessing DILI in vitro in hepatocyte cultures typically requires drug exposures significantly higher than clinical plasma Cmax concentrations, making clinical interpretations of mechanistic pathway changes challenging. We previously described a system that uses liver-derived hemodynamic blood flow and transport parameters to restore primary human hepatocyte biology, and drug responses at concentrations relevant to in vivo or clinical exposure levels. Using this system, primary hepatocytes from 5 human donors were exposed to concentrations approximating clinical therapeutic and supra-therapeutic levels of Nevirapine (11.3 and 175.0 μM) and Ritonavir (3.5 and 62.4 μM) for 48 h. Whole genome transcriptomics was performed by RNAseq along with functional assays for metabolic activity and function. We observed effects at both doses, but a greater number of genes were differentially expressed with higher probability at the toxic concentrations. At the toxic doses, both drugs showed direct cholestatic potential with Nevirapine increasing bile synthesis and Ritonavir inhibiting bile acid transport. Clear differences in antigen presentation were noted, with marked activation of MHC Class I by Nevirapine and suppression by Ritonavir. This suggests CD8+ T cell involvement for Nevirapine and possibly NK Killer cells for Ritonavir. Both compounds induced several drug metabolizing genes (including CYP2B6, CYP3A4 and UGT1A1), mediated by CAR activation in Nevirapine and PXR in Ritonavir. Unlike Ritonavir, Nevirapine did not increase fatty acid synthesis or activate the respiratory electron chain with simultaneous mitochondrial uncoupling supporting clinical reports of a lower propensity for steatosis. This in vitro study offers insights into the disparate direct and immune-mediated toxicity mechanisms underlying Nevirapine and Ritonavir toxicity in the clinic.


[Study of hospitalizations for pneumococcal pneumoniae in Centre region, 2004-2008].
Streptococcus pneumoniae is a significant cause of morbidity-mortality: leading agent of community-acquired pneumonia and the first cause of death due to infectious diseases in France. Vaccines are available for children and adults, avoiding serious complications. We studied hospitalizations for pneumococcal pneumonia in Centre region in 2004-2008, using the 2004-2008 national hospital discharges database and assessed vaccine coverage of a sample population. Hospital discharges with diagnosis of pneumococcal pneumonia were selected, using the corresponding code (J13) in the French Diagnosis-Related Group coding system. We analysed hospitalization and patient data using linkage of the inpatient stays with their anonymous identification number. We analysed hospitalization and patient data: number and length of stay/patient, co-morbid factors and pneumococcal immunisation status. One thousand five hundred and forty-one hospitalisations were found for pneumococcal pneumonia in Centre Region, in 2004-2008. The time pattern showed an annual increase in hospital stays: winter hospitalisations were most frequent. The median age was 58 years, range: 2 months-106 years. The sex ratio M/F of the 1417 distinct inpatients was 1.43. The hospital impact was substantial, with prolonged length of stay (mean=9.9 days), frequent stays in intensive care unit (20%) and high death rate (6%). The vaccine coverage of the population with pneumococcal pneumonia was only 23%. Using the national hospital discharges database, this study presents a snapshot of pneumococcal pneumonia in one French region and demonstrates the local major clinical impact, as found in France. It shows that the hospital discharge database is a potential tool for epidemiology despite its possible bias. This type of study could be useful for organizing a regional vaccination campaing due to the better knowledge of the disease.


The treatment of hand burns.
In more than 80% of all burns, the hand is involved. Even if a burned hand does not play a major role for the survival of a patient, its function and aesthetic appearance are of utmost importance for the re-integration into society and professional life. Adequate treatment demands a number of major decisions: necessity of an escharotomy in the early post-traumatic phase, the timing of surgery and the type of wound coverage, as well as immobilization and rehabilitation. Rapid wound closure is of utmost importance, but infection control and the preservation of active and passive motion are also essential for optimal recovery of the injured hand. The treatment of hand burns requires the interdisciplinary teamwork of surgeons, physio- and occupational therapists, psychologists, motivated health care personnel and consequent treatment strategies.


Anaesthesia for video-assisted thoracoscopic patent ductus arteriosus ligation.
The case notes of children undergoing video-assisted thoracoscopic ligation of a patent ductus arteriosus were reviewed with particular emphasis on the anaesthetic management. All children were managed using one-lung ventilation with no serious adverse sequelae. The lungs could be isolated easily in all cases and no special equipment was required. We describe our initial series of 13 cases and discuss the anaesthetic implications arising from this surgical technique. We also discuss the different ways of monitoring duct closure.


Synapses with short-term plasticity are optimal estimators of presynaptic membrane potentials.
The trajectory of the somatic membrane potential of a cortical neuron exactly reflects the computations performed on its afferent inputs. However, the spikes of such a neuron are a very low-dimensional and discrete projection of this continually evolving signal. We explored the possibility that the neuron's efferent synapses perform the critical computational step of estimating the membrane potential trajectory from the spikes. We found that short-term changes in synaptic efficacy can be interpreted as implementing an optimal estimator of this trajectory. Short-term depression arose when presynaptic spiking was sufficiently intense as to reduce the uncertainty associated with the estimate; short-term facilitation reflected structural features of the statistics of the presynaptic neuron such as up and down states. Our analysis provides a unifying account of a powerful, but puzzling, form of plasticity.


Severe problem of macrolides resistance to common pathogens in China.
With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as Streptococcus pneumoniae, Streptococcus (including Group A streptococcus, Group B streptococcus), Staphylococcus aureus, Bordetella pertussis, and Mycoplasma pneumoniae, have shown varying degrees of drug resistance. In order to provide such problem and related evidence for rational use of antibiotics in clinic, we reviewed the drug resistance of common bacteria to macrolides in children recent 20 years.


A cross-sectional study of loss of muscle mass corresponding to sarcopenia in healthy Chinese men and women: reference values, prevalence, and association with bone mass.
A cross-sectional survey was conducted in Shanghai, eastern China, to evaluate the prevalence of loss of muscle mass corresponding to sarcopenia in Chinese men and women and compare the results with the prevalence in other populations. We also analyzed the differences between men and women, and assessed the effect of lean mass and fat mass of different regions on bone mass. A total of 1766 men and 1778 women aged 18-96 years participated in this study. Bone mineral density of spine and femur, and lean mass and fat mass of several body regions were measured by dual-energy X-ray absorptiometry. Class 1 and class 2 sarcopenia were defined as the appendicular lean mass (ALM) index (ALM/height(2)) 1 and 2 standard deviations below the sex-specific means for young adults. Mean values for ALM index were 7.93 for men and 6.04 kg/m(2) for women, aged 18-40 years. The reference values for classes 1 and 2 sarcopenia were 7.01 and 6.08 kg/m(2) in men and 5.42 and 4.79 kg/m(2) in women. The prevalence of sarcopenia was 4.8% in women and 13.2% in men aged 70 years and older, which is lower than that in Caucasian populations, but the same as that in Japanese and Koreans in Asia. Men demonstrated greater declines in muscle mass with aging than women, partly due to the protective effect of fat mass on lean mass in women. Leg lean mass was the strongest factor on femur bone mass; however, trunk lean mass was the strongest factor on spine bone mass. Maintaining a healthy weight is important for the elderly in order to avoid osteoporosis and sarcopenia.


Enzymatic synthesis of a modified phospholipid and its evaluation as a substrate for B. cereus phospholipase C.
The novel phospholipid 2, which bears a tert-butyl moiety in place of the natural trimethyl ammonium group of phosphatidylcholine, has been enzymatically synthesized via a transphosphatidylation reaction mediated by phospholipase D. The change from the choline headgroup in 1 to the tert-butyl group in 2 reduced the efficiency of hydrolysis by the phosphatidylcholine-preferring phospholipase C from Bacillus cereus by a factor of greater than 10(3).


Monte Carlo results for the Ising model with shear.
We study the kinetics of domain growth in the Ising model with nonconserved dynamics under the action of a stochastic driving field that mimics the action of a shear flow. At late times, we found multistriped configurations with constant transversal size and linear growth in the direction of the flow. In cases with weak shear, a regime characterized by the decreasing of the transversal size is found that could correspond to previous theoretical investigations. This behavior is confirmed by the analysis of the structure factor patterns.


Cellular cardiomyoplasty for a patient with heart failure.
A 73-year-old man with a history of myocardial infarction and hypertension for 5 years suffered heart failure (NYHA III-IV). 2D echo indicated hypokinesia at septal, left ventricular anterior wall and apical regions. Coronary angiograms demonstrated 60% stenosis in distal left main and 99% stenosis in proximal and distal left anterior descending coronary arteries (LAD). Both proximal artery and middle left circumflex coronary artery (LC) had 90% stenosis, and diffuse stenosis of right coronary artery (RC) was found. Myocardial perfusion imaging using 99mTc-MIBI indicated defective perfusion of left ventricular apex, anterior wall and septal region and severe reduced perfusion of posterior inferior wall. Myocardial metabolic activities (18F-deoxyglucose) also showed comparable reductions. After exposing the heart, LAD, LC, and RC were all completely occluded and bypass procedure could not be completed. Autologous satellite cells were implanted without any complication and the patient had an uneventful recovery. During the first 2 months, he remained in heart failure, and by the third month, he gradually improved and reached NYHA II. At fifth month after the procedure, significant increased ejection fraction (37.1-48.6%) and wall movement with modest reduction of left ventricular systolic diameter (48-45 mm) were observed. Imaging with 18F-deoxyglucose showed dramatic improvement in myocardial metabolic activity with similar improvement in myocardial perfusion (99mTc-MIBI). This is the first successful case of cellular cardiomyoplasty without any conjunctional procedure for patient with severe coronary heart disease and heart failure.


Effect of cyclosporine on colchicine partitioning in the rat liver.
Colchicine is secreted into bile as a major pathway of elimination. Cyclosporine (CsA) inhibits colchicine biliary secretion. In the present study, the effects of cyclosporine and its vehicle (cremophor) on the partitioning of colchicine across the liver were studied. CsA decreased the colchicine bile/plasma ratio from 484 +/- 39 to 53 +/- 3 (P < 0.001). This effect was due to both a decrease in bile/liver partitioning (control, 35.1 +/- 1.2, vs CsA treatment, 9.2 +/- 0.5; p < 0.001) as well as a decrease in liver/plasma partitioning (control, 13.7 +/- 0.8, vs CsA treatment, 5.7 +/- 0.4; P < 0.001). Cremophor also decreased the colchicine bile/plasma ratio (317 +/- 19, P < 0.02 vs control), but this effect was due to a decrease in the liver/plasma ratio (9.99 +/- 0.7, P < 0.02 vs control) rather than the bile/liver ratio (31.9 +/- 2.1, P > 0.2 vs control). Inhibition at the canalicular membrane is consistent with the location of gp-170, the presumed transporter of colchicine.


Weber number and the outcome of binary collisions between quantum droplets.
A theoretical analysis of binary collisions of quantum droplets under feasible experimental conditions is reported. Droplets formed from degenerate dilute Bose gases made up from binary mixtures of ultracold atoms are considered. Reliable expressions for the surface tension of the droplets are introduced based on a study of low energy excitations of their ground state within the random phase approximation. Their relevance is evaluated considering an estimation of the expected excitation energy having in mind the Thouless variational theorem. The surface tension expressions allow calculating the Weber number of the droplets involved in the collisions. Several regimes on the outcomes of the binary frontal collisions that range from the coalescence of the quantum droplets to their disintegration into smaller droplets are identified. Atoms losses of the droplets derived from self-evaporation and three-body scattering are quantified for both homo- and hetero-nuclear mixtures. Their control is mandatory for the observation of some interesting effects arising from droplets collisions.


Rapid comparative evaluation of SARS-CoV-2 rapid point-of-care antigen tests.
The objective of this study was to develop a scalable approach for direct comparison of the analytical sensitivities of commercially available SARS-CoV-2 antigen point-of-care tests (AgPOCTs) to rapidly identify poor-performing products. We present a methodology for quick assessment of the sensitivity of SARS-CoV-2 AgPOCTs suitable for quality evaluation of many different products. We established reference samples with high, medium, and low SARS-CoV-2 viral loads along with a SARS-CoV-2 negative control sample. Test samples were used to semi-quantitatively assess the analytical sensitivities of 32 different commercial AgPOCTs in a head-to-head comparison. Among 32 SARS-CoV-2 AgPOCTs tested, we observe sensitivity differences across a broad range of viral loads (9.8 × 108 to 1.8 × 105 SARS-CoV-2 genome copies per ml). 23 AgPOCTs detected the Ct25 test sample (1.6 × 106 copies/ml), while only five tests detected the Ct28 test sample (1.8 × 105 copies/ml). In the low-range of analytical sensitivity, we found three saliva spit tests only delivering positive results for the Ct21 sample (2.7 × 107 copies/ml). Comparison with published data supports our AgPOCT ranking. Importantly, we identified an AgPOCT widely offered, which did not reliably recognize the sample with the highest viral load (Ct16 test sample with 9.8 × 108 copies/ml) leading to serious doubts about its usefulness in SARS-CoV-2 diagnostics. The results show that the rapid sensitivity assessment procedure presented here provides useful estimations on the analytical sensitivities of 32 AgPOCTs and identified a widely-spread AgPOCT with concerningly low sensitivity.


Hypervascularization of the glans penis after a venous leakage and revascularisation procedure: a case report.
A patient, in which unsuccessful venous leakage procedure followed by revascularisation of the penis, lead to a hypervascularization of the glans and important oedema of the penis is presented. After embolization of the epigastric artery, these symptoms disappeared and the patient had normal erectile function.


Effectiveness of a Group-Based Lifestyle Change Program Versus Usual Care: An Electronic Health Record, Propensity Score-Matched Cohort Study.
Translational lifestyle change programs for community and clinical settings have been available for a decade, yet there are limited data on their comparative effectiveness. This study examines the effectiveness of a Centers for Disease Control and Prevention-aligned lifestyle change program relative to usual care in clinical practice. This was an electronic health record-based retrospective cohort study conducted in a community-based healthcare system. Investigators identified adult program participants and usual-care patients in the electronic health record between 2010 and 2018 and defined their index date (baseline) as the first lifestyle change program encounter or a random encounter date, respectively. Participants were matched 1:2 to usual-care patients on baseline demographics and clinical characteristics using propensity-score methods. Changes in body weight and blood pressure were examined from baseline through 24 months. The authors identified 2,833 program participants and 438,432 usual-care patients meeting study eligibility criteria. A total of 2,833 program participants were matched to 4,776 usual-care patients; the average age was 54 years, and 80% of the participants were female. Program participation was associated with a 1.9- and 1.6-fold higher prevalence of clinically meaningful (≥5%) weight loss at 12- and 24-month follow-up than usual care and a higher prevalence of blood pressure control at 12 months but not at 24 months. Patients without type 2 diabetes at baseline had more pronounced outcomes than those with type 2 diabetes. This study demonstrates the effectiveness of an evidence-based, Centers for Disease Control and Prevention-aligned lifestyle change program in reducing cardiometabolic risk factors compared with usual care in clinical practice, with long-term reductions in weight and transient reductions in blood pressure.


Optimizing Operating Room Scheduling.
This article reviews the management of an operating room (OR) schedule and use of the schedule to add value to an organization. We review the methodology of an OR block schedule, daily OR schedule management, and post anesthesia care unit patient flow. We discuss the importance of a well-managed OR schedule to ensure smooth patient care, not only in the OR, but throughout the entire hospital.


Identification of the promoter regions and sigma(s)-dependent regulation of the gadA and gadBC genes associated with glutamate-dependent acid resistance in Shigella flexneri.
Resistance to killing by low pH is a common feature of both Escherichia coli and Shigella flexneri. The most effective E. coli acid resistance system utilizes two isoforms of glutamate decarboxylase encoded by gadA and gadB, and a putative glutamate/gamma-amino butyric acid antiporter encoded by gadC. Expression of the gad system is dependent upon the alternate sigma factor, sigma(s). We confirm that gadA, gadB, and gadC are also all dependent upon sigma(s) for their expression in S. flexneri. -10 sequences similar to the sigma(s)-10 consensus sequence were identified by primer extension in the upstream promoters of all three genes and the transcriptional start points were identical in both E. coli and S. flexneri.


Potentiation of tonic GABAergic inhibition by activation of postsynaptic kainate receptors.
Presynaptic kainate-type glutamate ionotropic receptors (KARs) that mediate either the depression or the facilitation of GABA release have been intensively studied. Little attention has been given to the modulation of GABAA receptors (GABAARs) by postsynaptic KARs. Recent studies suggest that two GABAAR populations, synaptic (sGABAAR) and extrasynaptic (eGABAAR) GABAARs, mediate phasic and tonic forms of inhibition, respectively. Tonic inhibition plays an important role in the excitability of neuronal circuits and the occurrence of epileptic seizures. For this study, we are the first to report that the activation of postsynaptic KARs by the KAR agonist, Kainic acid (KA, 5 μM), enhanced tonic inhibition by potentiating eGABAARs. KA enhanced THIP-induced eGABAAR currents and prolonged the rise and decay time of muscimol-induced sGABAAR/eGABAAR currents, but also depressed the amplitude of evoked inhibitory postsynaptic currents (IPSCs), unitary IPSCs (uIPSCs), and muscimol-induced sGABAAR/eGABAAR currents. The PKC inhibitor, staurosporine (1 μM), in the patch pipette solution fully blocked the KA-induced potentiation of tonic inhibition, suggesting the involvement of an intracellular PKC pathway. Our study suggests that the activation of postsynaptic KARs potentiates eGABAARs but depresses sGABAARs. By activating postsynaptic KARs, synaptically released glutamate depresses phasic inhibition to facilitate neuronal plasticity, but potentiates tonic inhibition to protect neurons from over-excitation.


Value of pretreatment serum lactate dehydrogenase as a prognostic and predictive factor for small-cell lung cancer patients treated with first-line platinum-containing chemotherapy.
The current study aimed to evaluate the serum pretreatment lactate dehydrogenase (LDH) and overall survival (OS) in small cell lung cancer (SCLC) patients who received first-line platinum-containing chemotherapy. A total of 234 SCLC patients, who received first-line platinum-based chemotherapy between 2013 and 2018, were retrospectively analyzed. The data of hematological characteristics, age, gender, ECOG score, staging, metastatic site, smoking history, chemotherapy cycle, thoracic radiotherapy and hyponatremia were collected. Overall survival was calculated using the Kaplan-Meier method. The statistically significant factors in the univariate analysis were selected for the multivariate COX model analysis. Age, ECOG score, stage, thoracic radiotherapy, hyponatremia, liver metastasis, brain metastasis, bone metastasis, LDH, NSE and neutrophil-to-lymphocyte ratio (NLR) were closely correlated to OS in the univariate analysis. Furthermore, the multivariate analysis revealed that age (<65 years), ECOG score (<2 points), limited-stage (LD), thoracic radiotherapy and LDH <215.70 U/L were the independent prognostic factors for survival. The median OS time was worse for patients with LDH ≥215.70 U/L. In the subgroup analysis, LDH ≥215.70 U/L was significant for survival in both limited and extensive disease. Patients who achieved CR + PR in the first-line treatment had lower initial LDH levels. It was found that the pretreatment LDH increased the incidence of patients with liver metastasis. Positive independent prognostic factors for SCLC patients were age < 65 years old, ECOG score < 2 points, LD-SCLC, and pretreatment LDH <215.70 U/L. These factors may be useful for stratifying patients with SCLC for treatment approaches. SIGNIFICANT FINDINGS OF THE STUDY: Age < 65 years old, ECOG score < 2 points, LD-SCLC, and pretreatment LDH <215.70 U/L are the positive independent prognostic factors for SCLC patients. The current study provided more references for SCLC diagnosis and treatment and determined more factors for stratifying patients with SCLC for treatment approaches.


[Implementation of an EMG IPA in the emergency department].
An advanced practice nurse from the Bretonneau-Bichat (AP-HP) hospitals' mobile geriatric outpatient team works in the emergency department (SAU). Its mission is to facilitate the identification, evaluation and referral of frail elderly patients discharged home after a visit to the emergency department. Description of the implementation of this project, its progress, and one-year assessment.


Transfected rat cMOAT is functionally expressed on the apical membrane in Madin-Darby canine kidney (MDCK) cells.
The purpose of the present study is to investigate the expression of canalicular multispecific organic anion transporter (cMOAT) by its cDNA transfection in polarized Madin-Darby canine kidney cells (MDCK). MDCK cells were transfected with an expression vector (pCXN2) containing the rat cMOAT cDNA with lipofectamine to obtain the stable transfectant under G418. Cells from a single colony whose cMOAT expression was the highest were seeded to form a tight epithelial monolayer on microporous membrane filters. Export of glutathione S-bimane (GS-B) from monolayers was determined after preloading its precursor, monochloro bimane (MCB). A comparable amount of GS-B was excreted to the apical and basal compartments in the vector-transfected cells. In contrast, in cMOAT-transfected cells, the amount apically excreted was approximately twice that excreted into the basal compartment. Cyclosporin A (CsA) (30 microM), an inhibitor of cMOAT at higher concentrations, inhibited the preferential apical export of GS-B from cMOAT-transfected cells. Rat cMOAT is functionally expressed on the apical membrane of MDCK cells after transfection.


Contribution of TCR-beta locus and HLA to the shape of the mature human Vbeta repertoire.
T cells that survive thymic selection express a diverse array of unique heterodimeric alphabeta TCRs that mediate peptide-MHC Ag recognition. The proportion of the total T cell repertoire that expresses a particular Vbeta protein may be determined by a variety of factors: 1) germline preference for use of particular Vbeta genes; 2) allelic effects on the expression of different Vbeta genes; and 3) HLA effects on the expression of different Vbeta genes (acting via thymic selection and/or peripheral mechanisms). In this study, we show that Vbeta usage by human CD4(+) and CD8(+) T cells in neonatal and adult donors is highly correlated between unrelated individuals, suggesting that a large proportion of the observed pattern of Vbeta expression is determined by factors intrinsic to the TCR-beta locus. The presence of identical TCR alleles (within an individual) leads to a significantly better correlation between CD4(+) and CD8(+) T cells with respect to Vbeta expression; these effects are, however, relatively minor. The sharing of HLA alleles between individuals also leads to an increased correlation between their Vbeta expression patterns, although this did not reach statistical significance. We therefore conclude that the correlation in Vbeta expression patterns between CD4(+) and CD8(+) T cells can be explained predominantly by germline TCR-beta locus factors and not TCR-beta allelic or HLA effects.


Does dose of early intervention matter for preschoolers with externalizing behavior problems? A pilot randomized trial comparing intensive summer programming to school consultation.
The goals of this study were to (a) isolate the ideal length (i.e., 4 or 8 weeks) of the Summer Treatment Program for Kindergarteners (STP-PreK) for improving school readiness and kindergarten success outcomes of preschool children with externalizing behavior problems (EBPs) during the transition to kindergarten; and (b) compare the STP-PreK model to a more standard approach in school settings (i.e., behavioral school consultation). Forty-five preschool children (82% boys; Mage = 5.16 years; 93% Hispanic/Latino background) were randomized to one of three intervention conditions: 1) 8-week STP-PreK (8W); 2) 4-week STP-PreK (4W); or 3) school year behavioral consultation (SC). Both STP-PreK groups included an 8-week parent training component. Baseline, post-intervention, and 6-month follow-up data were collected on children's school readiness and kindergarten success outcomes including parent, teacher, and objective assessment measures. Analyses using linear mixed models indicated that children's behavioral, academic, social-emotional, and self-regulation functioning significantly improved across groups. Few significant differences were found between children receiving the 4W and 8W programs, suggesting that both programs have the potential to prepare preschool children with EBP for the transition to school. Both 4W and 8W groups experienced greater initial growth across time in most domains compared to children in the SC group. However, by the end of the kindergarten year, children in the SC group caught up to children in both 4W and 8W groups on most domains. Overall, these findings suggest that all three intervention doses are effective in improving kindergarten year functioning, with some important considerations for intervention timing in preparation for the transition to elementary school. Clinical implications for school personnel are discussed.


Microscopy ambient ionization top-down mass spectrometry reveals developmental patterning.
There is immense cellular and molecular heterogeneity in biological systems. Here, we demonstrate the utility of integrating an inverted light microscope with an ambient ionization source, nanospray electrospray desorption ionization, attached to a high-resolution mass spectrometer to characterize the molecular composition of mouse spinal cords. We detected a broad range of molecules, including peptides and proteins, as well as metabolites such as lipids, sugars, and other small molecules, including S-adenosyl methionine and glutathione, through top-down MS. Top-down analysis revealed variation in the expression of Hb, including the transition from fetal to adult Hb and heterogeneity in Hb subunits consistent with the genetic diversity of the mouse models. Similarly, temporal changes to actin-sequestering proteins β-thymosins during development were observed. These results demonstrate that interfacing microscopy with ambient ionization provides the means to perform targeted in situ ambient top-down mass spectral analysis to study the pattern of proteins, lipids, and sugars in biologically heterogeneous samples.


Modeling variability in treatment effects for cluster randomized controlled trials using by-variable smooth functions in a generalized additive mixed model.
Variability in treatment effects is common in intervention studies using cluster randomized controlled trial (C-RCT) designs. Such variability is often examined in multilevel modeling (MLM) to understand how treatment effects (TRT) differ based on the level of a covariate (COV), called TRT [Formula: see text] COV. In detecting TRT [Formula: see text] COV effects using MLM, relationships between covariates and outcomes are assumed to vary across clusters linearly. However, this linearity assumption may not hold in all applications and an incorrect assumption may lead to biased statistical inference about TRT [Formula: see text] COV effects. In this study, we present generalized additive mixed model (GAMM) specifications in which cluster-specific functional relationships between covariates and outcomes can be modeled using by-variable smooth functions. In addition, the implementation for GAMM specifications is explained using the mgcv R package (Wood, 2021). The usefulness of the GAMM specifications is illustrated using intervention data from a C-RCT. Results of simulation studies showed that parameters and by-variable smooth functions were recovered well in various multilevel designs and the misspecification of the relationship between covariates and outcomes led to biased estimates of TRT [Formula: see text] COV effects. Furthermore, this study evaluated the extent to which the GAMM can be treated as an alternative model to MLM in the presence of a linear relationship.


Long-term Outcome of Inflammatory Bowel Disease-Unclassified in Children.
To document the frequency at diagnosis and evolution over time of inflammatory bowel disease-unclassified in children. Analysis of case records (2004-2011) of patients diagnosed with inflammatory bowel disease-unclassified following upper-gastrointestinal endoscopy, ileocolonoscopy and small bowel imaging. Any subsequent diagnostic reclassification by 2016 was recorded. 344 children diagnosed as inflammatory bowel disease: 58% Crohn's disease, 34.5% ulcerative colitis, and 7.5% (n=26) inflammatory bowel disease-unclassified. 25/26 inflammatory bowel disease-unclassified patients were followed for 4.5-11.5 years. 17 of these patients needed endoscopic re-evaluation leading to changed diagnosis in ten (Crohn's disease 7, ulcerative colitis 3). 7.5% (25/344) of inflammatory bowel disease children had inflammatory bowel disease-unclassified at diagnosis; 10 (40%) evolved into Crohn's disease or ulcerative colitis.


[Subperiosteal hematoma of the orbits following forceps delivery--a case report].
Subperiosteal haematoma of the orbit is a rare event. It is a complication of a blunt cranial trauma. We describe a subperiosteal haematoma of the orbit in newborn after forceps delivery.


Does the Temporal Pattern of Moving to a Higher-Quality Neighborhood Across a 5-Year Period Predict Psychological Distress Among Adolescents? Results From a Federal Housing Experiment.
Using data from the Moving to Opportunity (MTO) experiment (1994-2002), this study examined how a multidimensional measure of neighborhood quality over time influenced adolescent psychological distress, using instrumental variable (IV) analysis. Neighborhood quality was operationalized with the independently validated 19-indicator Child Opportunity Index (COI), linked to MTO family addresses over 4-7 years. We examined whether being randomized to receive a housing subsidy (versus remaining in public housing) predicted neighborhood quality across time. Using IV analysis, we tested whether experimentally induced differences in COI across time predicted psychological distress on the Kessler Screening Scale for Psychological Distress (n = 2,829; mean β = -0.04 points (standard deviation, 1.12)). The MTO voucher treatment improved neighborhood quality for children as compared with in-place controls. A 1-standard-deviation change in COI since baseline predicted a 0.32-point lower psychological distress score for girls (β = -0.32, 95% confidence interval: -0.61, -0.03). Results were comparable but less precisely estimated when neighborhood quality was operationalized as simply average post-random-assignment COI (β = -0.36, 95% confidence interval: -0.74, 0.02). Effect estimates based on a COI excluding poverty and on the most recent COI measure were slightly larger than other operationalizations of neighborhood quality. Improving a multidimensional measure of neighborhood quality led to reductions in low-income girls' psychological distress, and this was estimated with high internal validity using IV methods.


Jmol SMILES and Jmol SMARTS: specifications and applications.
SMILES and SMARTS are two well-defined structure matching languages that have gained wide use in cheminformatics. Jmol is a widely used open-source molecular visualization and analysis tool written in Java and implemented in both Java and JavaScript. Over the past 10 years, from 2007 to 2016, work on Jmol has included the development of dialects of SMILES and SMARTS that incorporate novel aspects that allow new and powerful applications. The specifications of "Jmol SMILES" and "Jmol SMARTS" are described. The dialects most closely resemble OpenSMILES and OpenSMARTS. Jmol SMILES is a superset of OpenSMILES, allowing a freer format, including whitespace and comments, the addition of "processing directives" that modify the meaning of certain aspects of SMILES processing such as aromaticity and stereochemistry, a more extensive treatment of stereochemistry, and several minor additions. Jmol SMARTS similarly adds these same modifications to OpenSMARTS, but also adds a number of additional "primitives" and elements of syntax tuned to matching 3D molecular structures and selecting their atoms. The result is an expansion of the capabilities of SMILES and SMARTS primarily for use in 3D molecular analysis, allowing a broader range of matching involving any combination of 3D molecular structures, SMILES strings, and SMARTS patterns. While developed specifically for Jmol, these dialects of SMILES and SMARTS are independent of the Jmol application itself. Jmol SMILES and Jmol SMARTS add value to standard SMILES and SMARTS. Together they have proven exceptionally capable in extracting valuable information from 3D structural models, as demonstrated in Jmol. Capabilities in Jmol enabled by Jmol SMILES and Jmol SMARTS include efficient MMFF94 atom typing, conformational identification, SMILES comparisons without canonicalization, identification of stereochemical relationships, quantitative comparison of 3D structures from different sources (including differences in Kekulization), conformational flexible fitting, and atom mapping used to synchronize interactive displays of 2D structures, 3D structures, and spectral correlations, where data are being drawn from multiple sources.


Liver transcriptome analyses of acute poisoning and recovery of male ICR mice exposed to the mushroom toxin α-amanitin.
Approximately 70-90% of mushroom poisoning deaths are caused by α-amanitin-induced liver injury resulting from RNA polymerase II (RNAP II) inhibition. Liver regeneration ability may contribute greatly to individual survival after α-amanitin poisoning. However, it is unclear what cellular pathways are activated to stimulate regeneration. We conducted dose-effect and time-effect studies in mice that were intraperitoneally injected with 0.33-0.66 mg/kg α-amanitin to establish a poisoning model. The liver/body weight ratio, serological indices, and pathology were evaluated to characterize the liver injury. In the time-effect study, the liver transcriptome was analyzed to explore the mRNA changes resulting from RNAP II inhibition and the underlying pathways associated with recovery. Based on the two animal studies, we established a poisoning model with three sequential liver states: early injury, regulation, and recovery. The mRNA changes reflected by the differentially expressed genes (DEGs) in the transcriptome could be used to illustrate the inhibition of RNAP II by α-amanitin. DEGs at four key time points were well matched with the three liver states, including 8-h downregulated genes in the early injury state, 16-h and 72-h upregulated genes in the regulation state, and 96-h upregulated/downregulated genes in the recovery state. By clustering analysis, the mTOR signaling pathway was screened out as the most promising potential pathway promoting recovery. The results of our investigations of the pathways and events downstream of the mTOR pathway indicated that the activation of mTOR probably contributes crucially to liver regeneration, which could be a promising basis for drug development.


Ornamental morphology of ionic liquid functionalized ternary doped N, P, F and N, B, F-reduced graphene oxide and their prevention activities of bacterial biofilm-associated with orthopedic implantation.
The multifunctional biological active material design for bone tissue engineering is essential to induce osteoblast cell proliferation and attachment. Adhesion of bacteria on biomaterials to produce biofilms can be major contributors to the pathogenesis of implant material associated infections. This research work focuses on NPF& NBF elemental doping and functionalization of reduced graphene oxide using an imidazolium-based ionic liquid such as BMIM PF6 and BMIM BF4 by hydrothermal method. The resulting tri doped reduced graphene oxide (NPF-rGO and NBF-rGO) composite was further used as a scaffold for bone tissue engineering and anti-biofilm activities. The observation of the effect of NPF-rGO and NBF-rGO on the morphology, adhesion and cell proliferation of HOS cell was investigated. Moreover, the tri doped composite tested its antibiofilm properties against B. subtilis, E. coli, K. pneumoniae, and P. aeruginosa pathogenic bacteria. In-vitro studies clearly show the effectiveness of N, P, B, and F doping promoting the rGO mineralization, biocompatibility, and destruction of bacterial biofilm formation. The result of this study suggests that NPF-rGO and NBF-rGO hybrid material will be a promising scaffold for bone reaeration and implantation with a minimal bacterial infection.


Early efficacy of postoperative rehabilitation training for lumbar disc herniation.
To investigate the early clinical efficacy of rehabilitation training after unilateral biportal endoscopy for lumbar disc herniation and to analyze the prognostic factors. A total of 100 patients with lumbar disc herniation who underwent unilateral biportal endoscopy at The Sixth Affiliated Hospital of Nantong University from January 2019 to January 2021 were retrospectively analyzed. The control group was given a standard home-based exercise program, while the intervention group was given a substituted rehabilitation training opposed to a standard home-based exercise program. The early postoperative pain relief and quality of life values were compared between the two groups, and the independent risk factors affecting the prognosis of patients were analyzed. There were no significant differences in sex, age, smoking, drinking, BMI, course of disease, type of disc herniation, preoperative VAS, ODI or SF-36 between the two groups (P > 0.05). There was no significant difference in preoperative and postoperative VAS and ODI scores at 3 months between the two groups (P > 0.05), yet there were significant differences in postoperative VAS and ODI at 12 months (P < 0.05). The SF-36 score of the intervention group was lower than that of the control group at 12 months, and the difference was statistically significant (P < 0.05). The excellent rate of the Macnab standard modification used in the intervention group was 88.00% at 12 months, and that in the control group was 62.00%. The difference between the two groups was considered to indicate a statistically significant (P < 0.05). The results of logistic multivariate regression model analysis showed that rehabilitation training (95% CI: 1.360-12.122, P = 0.012), the type of intervertebral disc (95% CI: 0.010-0.676, P = 0.020), and age (95% CI: 1.056-8.244, P = 0.039) were independent risk factors affecting the prognosis of patients. Postoperative rehabilitation training can effectively relieve pain and improve quality of life; thus, it is highly recommended in the clinic. Postoperative rehabilitation training, intervertebral disc type and age are independent risk factors for the postoperative prognosis of lumbar intervertebral disc herniation.


A combination of semiquantitative telomerase assay and in-cell telomerase activity measurement using exfoliated urothelial cells for the detection of urothelial neoplasia.
Telomerase is a ribonucleoprotein that synthesizes telomeres. It is detected in more than 85% of samples obtained from cancer tissues, including urologic neoplasia. The authors determined telomerase activity semiquantatively and in-cell telomerase activity in exfoliated urothelial cells obtained from urologic neoplasia specimens. The goal of this study was to provide additional information regarding a noninvasive approach to the detection of urologic neoplasia. The authors used voided urine from 23 patients with urologic neoplasia, 2 patients with nonmalignant urologic disorders, and 10 normal individuals. Semiquantative determination of telomerase activity was performed using a fluorescence-based telomeric repeat amplification protocol (TRAP), and telomerase activity at the cellular level was determined by an in situ TRAP assay. The fluorescence-based TRAP assay detected urinary telomerase activity in samples from 10 of 13 patients with urologic neoplasia before treatment, whereas urinary cells obtained from 3 of 10 patients (including 1 patient with relapse) during or after treatment had detectable telomerase activity. In contrast, the in situ TRAP assay detected telomerase positive cells in samples from 11 of 13 patients before treatment and 6 of 10 patients during or after treatment. Of note was a dissociation of the results of the fluorescence-based TRAP assay and those of the in situ TRAP assay for some patients. Some patients for whom telomerase activity was not detected with the fluorescence-based TRAP assay had a low frequency of telomerase positive cells in their urine. A combination of semiquantative analysis and an in situ TRAP assay to detect telomerase positive cells might be a useful tool in the identification and monitoring of patients with urothelial neoplasia.


Gene design, cloning and protein-expression methods for high-value targets at the Seattle Structural Genomics Center for Infectious Disease.
Any structural genomics endeavor, particularly ambitious ones such as the NIAID-funded Seattle Structural Genomics Center for Infectious Disease (SSGCID) and Center for Structural Genomics of Infectious Disease (CSGID), face technical challenges at all points of the production pipeline. One salvage strategy employed by SSGCID is combined gene engineering and structure-guided construct design to overcome challenges at the levels of protein expression and protein crystallization. Multiple constructs of each target are cloned in parallel using Polymerase Incomplete Primer Extension cloning and small-scale expressions of these are rapidly analyzed by capillary electrophoresis. Using the methods reported here, which have proven particularly useful for high-value targets, otherwise intractable targets can be resolved.


Efficacy and safety of metronomic administration of paclitaxel for advanced recurrent non-small-cell lung cancer.
There are limited effective therapeutic options in the relapsed setting for non-small cell lung cancer (NSCLC) or in the first line for platinum-ineligible patients. To evaluate the safety and efficacy of a metronomic schedule of paclitaxel administered weekly in relapsed refractory NSCLC or upfront in patients not eligible for platinum-based chemotherapy. Retrospective analysis of a prospectively collected database from the medical oncology department at Tata Memorial Hospital in Mumbai, India. Patients with recurrent and treatment-naïve platinum-ineligible advanced NSCLC were treated with weekly paclitaxel at 80 mg/m 2 with palliative intent. Restaging scans were obtained every two months. Chemotherapy was continued until progressive disease, intolerable side effects, or decision of the patient. SPSS version 16 was used for analysis. Simple percentages were used for descriptive statistics. Progression-free survival (PFS) was calculated from date of start of paclitaxel till the date of progression, change of therapy due to any reason, or death due to any cause. Overall survival (OS) was calculated from date of start of paclitaxel to death. The Kaplan Meier method was used for estimation of survival. There were 37 patients over eight months. The median age was 59 years, with a male-to-female ratio of 5:1. Two patients received paclitaxel in the first line, 18 patients in second line, nine in third line, five in fourth line, and three were in fifth line. 73% patients had received prior platinum and 48.6% patients had Eastern Cooperative Oncology Group performance status (ECOG PS) >2. The median number of weekly cycles delivered was 14. The response rate was 35% [complete remission (CR): 2.7%, partial remission (PR): 32.4%, stable disease (SD): 32.4%, progressive disease (PD): 27%], the median PFS was four months, and the estimated median OS was seven months. Chemotherapy was well tolerated. The most frequent grade 3 toxicities included anemia: 8%, neutropenia: 5.4%, and sensory neuropathy: 8%. There were no grade 4 toxicities and no episodes of febrile neutropenia. Weekly low-dose continuous metronomic-type scheduling of paclitaxel is safe and effective for relapsed refractory NSCLC and in the first line in platinum-ineligible patients.


A case of tachydysrhythmia. Refractory to propranolol and responsive to neostigmine.
A case of atrial fibrillation, with a fast ventricular response, which developed under enflurane anaesthesia is described in a patient previously treated with digitalis and propranolol. The intravenous administration of propranolol was ineffective whereas that of neostigmine and atropine, 2 hours later, was successful and reduced the ventricular rate to normal values.


Toll-like receptor 4 can recognize SapC-DOPS to stimulate macrophages to express several cytokines.
SapC-DOPS is a newly combined compound consisting of saposin C and dioleoylphosphatidylserine (DOPS). Our recent study showed that SapC-DOPS exhibits anti-tumor activity. However, SapC-DOPS has recognition elements of Toll-like receptor (TLR) 2 and TLR4; therefore, we want to know whether SapC-DOPS can induce abnormal immunoreaction via identification TLRs. We investigated the capacity of SapC-DOPS to induce cytokines in vivo and in vitro and analyzed the involvement of TLR and NF-kB in these cytokines production. SapC-DOPS could activate the cytokine production by peripheral macrophages, enhance the expressions of TLR4 and stimulate the NF-κB nuclear translocation. PDTC, an NF-κB inhibitor, could decrease the SapC-DOPS inducible TNF-α and IL-1β production. SapC-DOPS was similar to LPS in the immune response and may induce the production of cytokines in macrophages via the TLR4 signaling pathway and, at least in part, the alteration of the NF-κB pathway.


Preoperative evaluation of the vertebral arteries and posterior portion of the circle of Willis for cervical spine surgery using 3-dimensional computed tomography angiography.
A retrospective analysis using prospectively collected data from 3-dimensional computed tomography angiography (3D-CTA). To investigate the frequency of anomalous vertebral arteries (VA) and variations of the posterior portion of the circle of Willis (PPCW) using 3D-CTA for preventing perioperative iatrogenic vascular complications. Some studies have reported that preoperative 3D-CTA is useful for determining the VA blood flow in the cervical spine. However, preoperative 3D-CTA has not been used for evaluating PPCW, which functions as vessels collateral to the basilar artery in the case of iatrogenic VA injury. The study included 100 consecutive patients (61 males and 39 females; mean age, 60.4 ± 15.4 yr; range, 11-86 yr) who underwent cervical decompression and/or instrumentation between April 2008 and May 2012. We measured the diameters of the VA (VAD), posterior communicating artery (PCOMD), first segment of the posterior cerebral artery (P1D), and basilar artery (BAD) twice and determined the frequency of anomalous VA and PPCW variations. Hypoplastic VA, hypoplastic PCOM, and hypoplastic P1 were detected in 11 (11.0%), 81 (81.0%), and 13 patients (13.0%), respectively. Hypoplastic PCOM-P1 and hypoplastic basilar artery were observed in 87 (87.0%) and 3 patients (3.0%), respectively. Overall, 47 patients (47.0%) possessed some degree of abnormal VA blood flow.There were 7 patients (7.0%) with both unilaterally hypoplastic VA and bilaterally hypoplastic PCOM-P1s, in whom iatrogenic VA injury on the dominant side could have caused lethal vascular complications. We termed the hypoplastic VA of the contralateral side without collateral vessels as "critical VA." The VAs and PPCW vary considerably. Preoperative 3D-CTA provides important information for preventing tragic vascular complications caused by iatrogenic VA injury. Taking the risk of radiation into consideration, we recommend this method for patients at the highest risk for iatrogenic VA injury.


Deletion of C-terminal 113 amino acids impairs processing and internalization of human insulin receptor: comparison of receptors expressed in CHO and NIH-3T3 cells.
We have studied the structure and the function of a truncated human insulin receptor in which 113 amino acids (aa 1231-1343) at the C-terminus of the beta-subunit were deleted. In this study, wild-type and truncated insulin receptors were expressed by stable transfection in NIH-3T3 cells and CHO cells. The mutation impairs post-translational processing of the insulin receptor; proteolytic cleavage is retarded, and degradation of the truncated receptor is accelerated. Furthermore, insulin-stimulated autophosphorylation of the mutant insulin receptor is impaired. This is associated with a defect in insulin-stimulated endocytosis. Finally, in NIH-3T3 cells, the mutant insulin receptor failed to mediate the mitogenic effects of insulin. In CHO cells, transfection of insulin receptor cDNA (either wild-type or mutant) did not alter mitogenic response to insulin. It has previously been shown that deletion of 43 amino acids at the C-terminus of the beta-subunit did not affect insulin receptor tyrosine kinase activity. Our data suggest that the structural domain located 43-113 amino acids from the C-terminus appears to have several functional roles. First, the domain appears to promote folding of receptor into the optimal conformation for post-translational processing. Second, the presence of this domain appears to promote the stability of the receptor beta-subunit in intact cells. Finally, perhaps as a consequence of the effects upon the stability of the receptor, this domain is required in intact cells for insulin-stimulated autophosphorylation and signal transmission.


[About a case of calcifying fibrous tumor of the pleura].
Calcifying fibrous tumor is a rare soft tissue benign tumor (OMS 2002). Some pleural localisations are described, which affect slightly older individuals than the other soft tissue forms. The calcifying fibrous tumor is included in the 2004 World Health Organization classification of pleural tumors. A pleural tumor located in the right inferior pulmonary lobe is diagnosed in a 59-year-old man. This pleural tumor is macroscopically well-circumscribed. Histologically, the rare spindle tumoral cells are located between bundles of a collagenous tissue, sometimes hyalinized, with psammomatous or dystrophic calcifications. The tumoral cells have a fibrohistiocytic origin. They stain positively for antibodies against vimentin, factor XIIIa, CD68, CD163, CD34. Antibodies against smooth muscle actin, desmin, PS100, ALK1 and EBV are negative. Main differencial diagnoses are other benign pleural tumors (solitary fibrous tumor, inflammatory myofibroblastique tumor), some malignant tumors (desmoplastic malignant pleural mesothelioma) and pleural pseudotumors (calcified pleural plaques, chronic fibrous pleuritis, amylose, hyalinizing granuloma). Our case is the 15th pleural calcifying fibrous tumor being reported.