Atypical TRAV1-2- T cell receptor recognition of the antigen-presenting molecule MR1.
MR1 presents vitamin B-related metabolites to mucosal associated invariant T (MAIT) cells, which are characterized, in part, by the TRAV1-2+ αβ T cell receptor (TCR). In addition, a more diverse TRAV1-2- MR1-restricted T cell repertoire exists that can possess altered specificity for MR1 antigens. However, the molecular basis of how such TRAV1-2- TCRs interact with MR1-antigen complexes remains unclear. Here, we describe how a TRAV12-2+ TCR (termed D462-E4) recognizes an MR1-antigen complex. We report the crystal structures of the unliganded D462-E4 TCR and its complex with MR1 presenting the riboflavin-based antigen 5-OP-RU. Here, the TRBV29-1 β-chain of the D462-E4 TCR binds over the F'-pocket of MR1, whereby the complementarity-determining region (CDR) 3β loop surrounded and projected into the F'-pocket. Nevertheless, the CDR3β loop anchored proximal to the MR1 A'-pocket and mediated direct contact with the 5-OP-RU antigen. The D462-E4 TCR footprint on MR1 contrasted that of the TRAV1-2+ and TRAV36+ TCRs' docking topologies on MR1. Accordingly, diverse MR1-restricted T cell repertoire reveals differential docking modalities on MR1, thus providing greater scope for differing antigen specificities.


Electrophysiological changes in the primary sensory neuron following subchronic soman and sarin: alterations in sensory receptor function.
Cats were administered soman or sarin either in a single high dose (1 mg/kg) with pretreatment or in multiple sublethal doses to determine whether these potent organophosphorus agents could produce a delayed neurotoxicity and what, if any, pathophysiological changes occurred in peripheral sensory receptors. Neither soman nor sarin, when administered as a single high dose, produced a delayed neurotoxicity as observed behaviorally for up to 60 days. There were also no observable signs of delayed neurotoxicity when these agents were administered in multiple doses. Functional tests of proprioceptors and mechanoreceptors were performed on the cats which received multiple sublethal doses of either soman or sarin. It was found that the discharge rates of muscle spindle primary endings were depressed while the discharge rates of secondary endings were facilitated following the administration of either soman or sarin. The discharge rates of slowly adapting type 1 mechanoreceptors were also depressed. The total number of identified mechanoreceptors was reduced in both the soman- and sarin-treated animals. Conduction velocities of several of the muscle spindle and mechanoreceptor afferents were significantly decreased. The alterations in muscle spindle function may be due to changes in the muscle resulting from acetylcholinesterase inhibition. Another explanation for the changes in both muscle spindle and mechanoreceptor function may be the direct effect of the organophosphorus agents on the afferents themselves, thus altering their excitability.


Thermo- and pH-responsive polymer brushes-grafted gigaporous polystyrene microspheres as a high-speed protein chromatography matrix.
Dual thermo- and pH-responsive chromatography has been proposed using poly(N-isopropylacrylamide-co-butyl methacrylate-co-N,N-dimethylaminopropyl acrylamide) (P(NIPAM-co-BMA-co-DMAPAAM)) brushes grafted gigaporous polystyrene microspheres (GPM) as matrix. Atom transfer radical polymerization (ATRP) initiator was first coupled onto GPM through Friedel-Crafts acylation with 2-bromoisobutyryl bromide. The dual-responsive polymer brushes were then grafted onto GPM via surface-initiated ATRP. The surface composition, gigaporous structure, protein adsorption and dual-responsive chromatographic properties of the matrix (GPM-P(NIPAM-co-BMA-co-DMAPAAM) were characterized in detail. Results showed that GPM were successfully grafted with thermoresponsive cationic polymer brushes and that the gigaporous structure was well maintained. A column packed with GPM-P(NIPAM-co-BMA-co-DMAPAAM presented low backpressure, good permeability and appreciable thermo-responsibility. By changing pH of the mobile phase and temperature of the column in turn, the column can separate three model proteins at the mobile phase velocity up to 2528cmh(-1). A separation mechanism of this matrix was also proposed. All results indicate that the dual thermo- and pH-responsive chromatography matrix has great potentials in 'green' high-speed protein chromatography.


Congenital absence of a pedicle in the cervical spine: a new approach with CT scan.
After complete review of the literature concerning the congenital absent pedicle syndrome, another typical case is presented. In the opinion of the authors, the diagnostic importance of the associated clinical symptoms is doubtful. Furthermore they demonstrate the great value of CT in the differential diagnosis of this lesion.


[Stomach ulcer as a problem of energy balance: design of a cellular automatic simulation of disorders of blood flow distribution in the stomach wall].
A cellular automaton is described, which allows a simple simulation of patterns of gastric blood flow distribution. Effects of redistribution, which can be simulated on the basis of the energy requirements of acid secretion and the morphology of the gastric vascular bed, are isomorph to form and site of gastric ulcer in man. Special forms of the 'peptic' lesion as linear ulcers or 'peptic' stenoses of the oesophagus are consistent with the theory of a submucous steal-phenomenon.


Selection of lethal genes for ingestion RNA interference against western flower thrips, Frankliniella occidentalis, via leaf disc-mediated dsRNA delivery.
The western flower thrips, Frankliniella occidentalis, is a major pest that damages a wide variety of crops and vegetables. Following extensive use of insecticides, it has developed high levels of resistance to almost all groups of insecticides due to its high reproduction rate and short generation time. Therefore, an alternative pest control strategy, such as RNA interference (RNAi)-based control, is essential. To establish an ingestion RNAi-based control, a total of 57 genes involved in various biological processes were selected, and their double-stranded RNAs (dsRNA) were delivered to an insecticide-susceptible strain of F. occidentalis via the leaf disc-feeding method using a bioassay chamber optimized by 3D printing. The mortality of dsRNA-ingested thrips was examined every 24 h until 120 h post-treatment. Of the 57 genes screened, dsRNAs of the Toll-like receptor 6, apolipophorin, coatomer protein subunit epsilon and sorting and assembly machinery component were most lethal when ingested by thrips. The dsRNA-fed thrips showed substantially reduced transcription levels of target genes, demonstrating that the observed mortality was likely due to RNAi. When these genes were tested for ingestion RNAi against an insecticide-resistant strain of F. occidentalis, bioassay results were similar. In conclusion, this study provides the first evidence that ingestion RNAi can be lethal to F. occidentalis, a mesophyll sucking pest, and further suggests that transgenic plants expressing hairpin RNA of these essential genes can be employed to control insecticide-resistant thrips.


Community-acquired Haemophilus influenzae pneumonia--New insights from the CAPNETZ study.
We aimed to identify clinical characteristics and to assess effectiveness of different initial antibiotic regimens in adult patients with community-acquired pneumonia (CAP) caused by Haemophilus influenzae. Characteristics were compared between patients with H. influenzae monoinfection versus CAP of other and unknown aetiology enrolled by the German prospective cohort study CAPNETZ. Impact of initial antibiotic treatment on "early clinical response" according to FDA criteria and overall clinical cure were analysed. H. influenzae was found in 176 out of 2790 patients with pathogen detection (6.3%). Characteristics significantly associated with a H. influenzae CAP (p < 0.017) included purulent sputum, prior pneumococcal vaccination and respiratory co-morbidities. Early clinical response rates on day 4 did not differ between patients receiving any mono- versus combination therapy (85.9% versus 88%), but were numerically higher for regimens including any fluoroquinolone (96.7%) and lower under macrolide monotherapy (70%). Initial CURB-65 score and chronic liver disease were identified as negative predictors for "early clinical response". At day 14, overall clinical cure was 91.9%. H. influenzae was a common CAP pathogen, particularly in patients with previous pneumococcal vaccination and respiratory co-morbidities. Severity of illness and chronic liver disease were associated with a lower rate of "early clinical response".


The inexorable rise of automated food deliveries and potential anticipatory policy actions.
Food deliveries to consumers using autonomous vehicles are forecast to become commonplace in Australia and globally. The aims of this study were to (i) explore the anticipated nature of AV food delivery services in Australia and (ii) identify available policy options to optimise positive outcomes and minimise any negative consequences for health and well-being. In total, 36 interviews were conducted with 40 expert stakeholders across a range of relevant sectors including transport, urban planning, health and telecommunications. Interviewees discussed the ways in which automated food deliveries are likely to be implemented and the potential implications for lifestyles and health. The interviewees expected automated food deliveries to constitute an extension of current trends towards online food ordering and rapid home deliveries, with potential adverse implications for diet quality at the population level. Effective regulation of automated food and beverage delivery services will be needed to anticipate and address this emerging phenomenon. There is the opportunity to optimise the public health outcomes associated with automated food deliveries while minimising potential negative consequences through proactive anticipatory action. Delays could result in undesirable and irreversible changes to the food environment.


Barriers to quality of life in patients with multiple sclerosis: a qualitative study.
Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system that affects the patients' quality of life. This research was conducted with the aim of identifying the barriers of quality of life in patients with MS. This qualitative study was conducted through a conventional content analysis approach. We used the purposeful sampling with maximum diversity in terms of gender, age, education, marital status and employment. Data were collected through semi-structured interviews with 18 patients with multiple sclerosis referred to the MS Association of Isfahan. Interviews were conducted to the point of information saturation. Through the content analysis of the interviews, we identified 2 main categories and 11 sub-categories. The main categories include intrapersonal problems (physical problems, psychological disorders, turbulent future, functional limitations, job loss and pennilessness), and environmental barriers (disease and treatment process, fatigue of caregivers, information deficiency about MS, family tensions, lack of social support and fun and entertainment). In order to improve the quality of life in these patients, there is a need for attention and practical measures in the field of identified factors. By removing barriers such as providing educational and counseling services to the patients and their families, adapting the urban structure, providing financial support and adequate insurance coverage, the authorities can take measures to ensure patients' health and improve their quality of life.


Treatment and outcome of destructive tuberculosis of the talus.
We describe a case of isolated destructive talar tuberculosis that is, to the best of our knowledge, the first reported case in Germany. Caseous talar necrosis was finally detected after repeated surgical debridements of an infection eight months after subtalar screw arthrodesis. Following the diagnosis of TB, we performed a total of three additional surgical revisions within a three-month period; these revisions included a talectomy and an induction of a septic tibiocalcaneal arthrodesis with an external fixator that was removed after solid fusion six months later. Following this treatment regime, which included pharmaceutical anti-tuberculosis therapy, the 50-year-old male patient was fitted with orthopaedic shoes. He resumed work as a professional farmer with a number of restrictions 12 months after the diagnosis and treatment of destructive talar tuberculosis.


Diagnostic tool for Glanzmann's thrombasthenia clinicopathologic spectrum.
To platelet aggregometry and describe the clinical spectrum of Glanzmann's thrombasthenia diagnosed by platelet aggregometry. A case-series. This study was carried out at the clinical laboratories at the Aga Khan University Hospital, Karachi from January 2003 to January 2006. All patients irrespective of age and gender presenting with bleeding symptoms and having normal platelet count were evaluated. Demographic details, relevant clinical history along with results of complete blood count, bleeding time and platelet aggregation studies were retrieved through computerized data base and evaluated for the diagnosis of Glanzmann's thrombasthenia. During the study period, 50 out of 2317 patients (2.2%) were diagnosed as Glanzmann's thrombasthenia by platelet aggregometry with male to female ratio of 0.85:1 and median age of 10.2 years (ranging from 3 months to 27 years). Common symptoms were epistaxis, oral and gingival bleed, bleeding from minor cuts and trauma that were observed in 46% of the patients; while 18%, 8% and 10% of them also complained of bruising, hematuria and bleeding per rectum respectively. Majority i.e. 86% had a bleeding time greater than 10 minutes. All patients had received blood or blood products for their bleeding episodes. Platelet aggregometry is a useful diagnostic modality for the assessment of Glanzmann's thrombasthenia. The disorder presents with muco-cutaneous bleeding and was found to be a common cause of bleeding in our setup.


Prevalence of obesity and the relationship between the body mass index and body fat: cross-sectional, population-based data.
Anthropometric measures such as the body mass index (BMI) and waist circumference are widely used as convenient indices of adiposity, yet there are limitations in their estimates of body fat. We aimed to determine the prevalence of obesity using criteria based on the BMI and waist circumference, and to examine the relationship between the BMI and body fat. This population-based, cross-sectional study was conducted as part of the Geelong Osteoporosis Study. A random sample of 1,467 men and 1,076 women aged 20-96 years was assessed 2001-2008. Overweight and obesity were identified according to BMI (overweight 25.0-29.9 kg/m²; obesity ≥30.0 kg/m²) and waist circumference (overweight men 94.0-101.9 cm; women 80.0-87.9 cm; obesity men ≥102.0 cm, women ≥88.0 cm); body fat mass was assessed using dual energy X-ray absorptiometry; height and weight were measured and lifestyle factors documented by self-report. According to the BMI, 45.1% (95%CI 42.4-47.9) of men and 30.2% (95%CI 27.4-33.0) of women were overweight and a further 20.2% (95%CI 18.0-22.4) of men and 28.6% (95%CI 25.8-31.3) of women were obese. Using waist circumference, 27.5% (95%CI 25.1-30.0) of men and 23.3% (95%CI 20.8-25.9) of women were overweight, and 29.3% (95%CI 26.9-31.7) of men and 44.1% (95%CI 41.2-47.1) of women, obese. Both criteria indicate that approximately 60% of the population exceeded recommended thresholds for healthy body habitus. There was no consistent pattern apparent between BMI and energy intake. Compared with women, BMI overestimated adiposity in men, whose excess weight was largely attributable to muscular body builds and greater bone mass. BMI also underestimated adiposity in the elderly. Regression models including gender, age and BMI explained 0.825 of the variance in percent body fat. As the BMI does not account for differences in body composition, we suggest that gender- and age-specific thresholds should be considered when the BMI is used to indicate adiposity.


Risk of subsequent cutaneous malignancy in patients with prior keratinocyte carcinoma: a systematic review and meta-analysis.
In this systematic review and meta-analysis the risk of a subsequent basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or melanoma in patients with a previous keratinocyte carcinoma (KC) was investigated. PubMed, Embase, Web of Science and the Cochrane library were searched for studies published before 1st January 2012 that reported risks (i.e. proportions, cumulative risks or standardised incidence ratios [SIR]) of developing a subsequent BCC, SCC or melanoma in patients with prior KC. 45 articles fulfilled the inclusion criteria. In BCC patients, the pooled proportion for a subsequent BCC, SCC or melanoma was respectively 29.2% (95% confidence interval (CI) 24.6-34.3%), 4.3% (1.7-10.1%) and 0.5% (0.4-0.8%). The pooled proportion of a subsequent SCC, BCC or melanoma in SCC patients was respectively 13.3% (95% CI 7.4-22.8%), 15.9% (5.6-37.6%) and 0.5% (0.3-0.6%). The pooled SIRs for a subsequent BCC, SCC or melanoma were respectively 17.4 (95% CI 0.0-37.4), 3.2 (0.0-6.5) and 2.4 (2.3-2.6) in BCC and 4.2 (95% CI 2.0-6.5), 15.0 (14.0-16.0) and 2.7 (2.3-3.2) in SCC patients. In the subgroup analyses, strongest differences in risks were found in the continent strata (risks Australia>North America>Europe).


Classification of dangerous substances and pesticides in the European economic community directives: a proposed revision of criteria for inhalation toxicity.
Criteria for the classification of dangerous substances with respect to their inhalation toxicity were originally proposed by the European Economic Community (EEC) on the basis of a 1-hr LC50, as were the similar United Nations (UN) "transport" criteria. Both sets of criteria have since been amended for a 4-hr LC50, but whereas the UN criteria limits have been decreased to compensate for the increased exposure time, the EEC limits have not. This has introduced an anomaly into the EEC classification scheme whereby substances are classified more severely than they were previously. The EEC scheme is now out of line with the UN criteria and other international guidelines and gives a much more stringent toxicity classification for individual substances by inhalation than by the oral route, as well as causing an unjustifiable duplication of animal tests. This anomaly has led to a proposal by the Federal Republic of Germany for revised criteria. This paper examines the scientific basis for the relationship between inhalation exposure duration and toxicity, and for a comparison of the LD50 and LC50 classifications for individual substances. It is concluded that the proposed German revised classification scheme is more in line with the UN transport criteria and international guidelines and provides a rational basis for a classification scheme for inhalation toxicity. The classification criteria therefore should be harmonized by a revision of the EEC classification limits for inhalation toxicity.


Delivery of cell-penetrating peptide-peptide nucleic acid conjugates by assembly on an oligonucleotide scaffold.
Delivery to intracellular target sites is still one of the main obstacles in the development of peptide nucleic acids (PNAs) as antisense-antigene therapeutics. Here, we designed a self-assembled oligonucleotide scaffold that included a central complementary region for self-assembly and lateral regions complementing the PNAs. Assembly of cell-penetrating peptide (CPP)-PNAs on the scaffold significantly promoted endocytosis of PNAs by at least 10-fold in cell cultures, particularly for scaffolds in which the central complementary region was assembled by poly(guanine) and poly(cytosine). The antisense activity of CPP-PNAs increased by assembly on the scaffold and was further enhanced after co-assembly with endosomolytic peptide (EP)-PNA. This synergistic effect was also observed following the assembly of antigene CPP-PNAs\EP-PNAs on the scaffold. However, antigene activity was only observed by targeting episomal viral DNA or transfected plasmids, but not the chromosome in the cell cultures. In conclusion, assembly on oligonucleotide scaffolds significantly enhanced the antisense-antigene activity of PNAs by promoting endocytosis and endosomal escape. This oligonucleotide scaffold provided a simple strategy for assembly of multiple functional peptide-PNA conjugates, expanding the applications of PNAs and demonstrating the potential of PNAs as antiviral therapeutics.


Reconfiguration of respiratory-related population activity in a rostrally tilted transversal slice preparation following blockade of inhibitory neurotransmission in neonatal rats.
Recent studies showed that respiratory rhythm generation depends on oscillators located in the pre-Bötzinger complex (pre-BötC) and the parafacial respiratory group (pFRG). To study inhibitory synaptic interactions between these two oscillators, we developed a rostrally tilted transversal slice preparation, which preserves these regions. The onset of rhythmic mass activity in the retrotrapezoid nucleus (RTN)/pFRG preceded that of the pre-BötC. Blockade of glycinergic and gamma-aminobutyric acidic inhibition synchronized pre-BötC and RTN/pFRG activity and significantly increased pre-BötC burst frequency, amplitude, and duration. Population imaging revealed recruitment of inspiratory-like neurones, while expiratory-like neurones lost their phasic activity. The reconfiguration after disinhibition reveals: (1) synaptic inhibition of the pre-BötC arising from the RTN/pFRG, (2) excitatory drive from the RTN/pFRG that triggers the pre-BötC burst. Our findings support the view that these synaptic interactions in vitro relate to the initiation of the inspiratory phase or to the steering of the expiratory-inspiratory phase transition in vivo.


Increased Healthcare Resource Utilization and Direct and Indirect Costs in Patients with Depression and Comorbid Overactive Bladder: Evidence From a Retrospective, Matched Case-Control Cohort Analysis.
This study sought to compare healthcare resource utilization (HCRU), costs, and workplace productivity among patients with depression, with and without overactive bladder (OAB). This retrospective, case-control cohort analysis compares HCRU, costs, and workplace productivity among propensity score matched patients with depression and OAB (case cohort) and patients with depression without OAB (control cohort). Patients were aged 18 years or older, insured/on Medicare, and had diagnosed depression and an antidepressant medication claim pre index. First OAB-related event was index for cases; controls were assigned a proxy (study period 12 months). Comparisons of HCRU and costs and regression models assessed the relationship between OAB and costs. For the workplace productivity subset analyses cases and controls were balanced on baseline covariates for the short-term disability analyses but as they were unbalanced for the absentee analyses, multivariate regression analyses were used for this subset. The study criteria were met by 39,085 cases and 308,736 controls, from which, 37,997 patients were successfully matched 1:1 (mean age 55 years; 81% female). Most depression-related HCRU measures were similar across cohorts; however, outpatient visits, ER visits, and number of unique depression medications were significantly higher (all p < 0.05) among cases. Cases also had 13% higher total depression-related costs (p < 0.0001). Total mean (standard deviation [SD]) depression-related costs were $1796 ($4235) for cases versus $1597 ($3863) for controls (p < 0.0001). For workplace productivity (absentee data: cases [n = 686], controls [n = 642]; short-term disability data: cases [n = 4395], controls [n = 4433]) absentee outcomes were similar across cohorts. However, a higher percentage of cases used short-term disability benefits compared to controls (21.3% versus 16.9%; p < 0.0001) and cases experienced more case days (11.0 versus 8.6 mean days) and received higher mean payments than controls ($1226 versus $1033; p < 0.0001) in this subset. OAB was associated with 13% higher depression-related costs and 4.4% more cases used short-term disability benefits.


Morphological changes in the liver, thymus, spleen, and small intestine of animals after leucine treatment.
Leucine treatment (100 mg/kg daily for 5 days) leads to activation of the hepatocyte nuclear system and granular endoplasmic reticulum and to a drastic increase in the number of mitochondria, characterized by polymorphism. In the spleen, Malpighian bodies and periarterial lymphoid sheaths are enlarged, lymphocytes infiltrate the periarterial zone, and the mantle zone is enlarged. In the thymus, the width of the cortical matter shrinks, while that of the medulla increases. The content of lymphocytes in the medulla decreases, while that of Hassal's bodies increases. Unambiguous effects of leucine on the small intestinal morphology (mainly on the villous epithelium) were shown. Goblet cells in the villous epithelium were sharply stenosed because of decreased secretory granules in them.


Vegetation Composition Determines Microbial Activities in a Boreal Forest Soil.
Abstract Forest soil ecology was studied in Fennoscandinavian dry Scots pine forests grazed by reindeer to varying extents (ungrazed, lichen-dominated-sites; grazed sites; and bryophyte-dominated sites). We hypothesized that the productivity parameters of the site (i.e., tree growth and soil nutrient concentrations), the vegetation composition, and the microbial activities are directly correlated. Since the productivity of the lichen-dominated ecosystem is low, microbial activities are assumed to be naturally low. Grazing was expected to decrease both the amount of Scots pine fine roots and the soil microbial activities. Several variables on the characteristics of the soil microbial community, Scots pine fine roots, soil nutrients, and tree growth were studied in relation to vegetation composition by using non-metric multidimensional scaling (NMDS). Basal respiration (Bas), metabolic quotient of the microbial community (qCO2), and pine fine root parameters increased toward the ungrazed, nutrient-poor, lichen-dominated sites, which were grouped at one end of the first axis in the NMDS ordination. Soil nutrient and tree growth parameters and thickness of the humus layer increased toward bryophyte-dominated sites, which were grouped at the other end of the first axis in the ordination. The grazed sites fell between them. These were characterized by lower Bas and qCO2 values and longer lag, compared to ungrazed lichen- or bryophyte-dominated sites, probably due to decreased carbon input and microclimatic change (the soil without lichen carpet is exposed to direct sunlight and wind). Microbial biomass (Cmic), fungal biomass (ergosterol concentration), and the specific growth rate (µCO2) were not related to vegetation ordination. The high fine root production is the most plausible explanation for the high microbial activities at nutrient-poor, lichen-dominated sites, which produce qualitatively poor and slowly decomposing litter, as fine roots secrete considerable amounts of organic substances. At bryophyte-dominated sites, the higher soil nutrient concentrations and the higher production of easily decomposable substrates are likely to maintain the microbial activities.


The Sea Empress oil spill (Wales, UK): effects on Common Scoter Melanitta nigra in Carmarthen Bay and status ten years later.
Carmarthen Bay, UK, regularly supports internationally important numbers (>16,000) of non-breeding Common Scoters Melanitta nigra. The spill of 72,000 tonnes of crude oil from the Sea Empress in 1996 affected birds both through direct mortality and likely pollution of key food resources. Numbers were greatly reduced following the spill, whilst changes in the distribution of birds within Carmarthen Bay suggested that potentially sub-optimal foraging zones were used. However, ten years after the incident, numbers of Common Scoter were no different to those recorded immediately before the spill. Compared to some other spills, rapid revival is evident. Numbers increased to pre-spill levels within three winters and distributional changes suggested a concurrent return to previously contaminated feeding areas, implying that the ecosystem had regenerated sufficiently to support its top predator. The importance of prolonged, standardised monitoring of bird numbers and distribution as indicators of ecological recovery from environmental damage is emphasised.


Can we consider the right hepatic lobe size/albumin ratio a noninvasive predictor of oesophageal varices in hepatitis C virus-related liver cirrhotic Egyptian patients?
The current guidelines recommend the screening of all cirrhotic patients by endoscopy, but repeated endoscopic examinations are unpleasant for patients and have a high cost impact and burden on endoscopic units. The aim of this study is to evaluate the optimal liver lobe size/albumin ratio and to compare this ratio with spleen size, platelet count and platelet count/spleen diameter ratio as potential noninvasive predictors of oesophageal varices in hepatitis C virus (HCV)-related liver cirrhosis in Egyptian patients. This prospective study included one hundred patients with HCV-related liver cirrhosis. All studied subjects underwent a detailed clinical examination, biochemical workup, upper gastrointestinal endoscopy and abdominal ultrasound. The platelet count/spleen diameter ratio and the right liver lobe/albumin concentration ratio for all patients were calculated. The 4 predictors demonstrated a high statistically significant correlation with the presence and grade of oesophageal varices (P values<0.001). The platelet count/spleen diameter ratio had the highest accuracy, followed by the right liver lobe/albumin concentration ratio, spleen size and then platelet count. The use of the studied noninvasive predictors, especially the platelet count/spleen diameter ratio and the right liver lobe/albumin concentration ratio, can help physicians by restricting the use of endoscopic screening only to patients presenting a high probability of oesophageal varices. This is especially useful in clinical settings where resources are limited and endoscopic facilities are not present in all areas. Such is the case in Egypt, where there is a large number of patients who require oesophageal screening for oesophageal varices.


Toxicological effects of microplastics in Litopenaeus vannamei as indicated by an integrated microbiome, proteomic and metabolomic approach.
Microplastics (MPs) are a hazardous pollutant of world concern that threaten aquatic organisms and ecosystems. In this study, we chose the worldwide-distributed shrimp Litopenaeus vannamei as a model and investigated the toxicological effects of five types of MPs on L. vannamei using several omics approaches. After 14 days of exposure to MPs, obvious intestinal microbiota variation was observed, such as increased abundances of Bacteroidetes and Proteobacteria and a decreased abundance of Firmicutes. Specifically, MPs induced several putative opportunistic pathogens and reduced lactic acid- and short-chain fatty acid-producing bacteria. Alternatively, MPs altered haemolymph proteome profiles, but the five types of MPs had different effects on the enriched pathways and the expression of immune-related proteins. Furthermore, MPs also caused haemolymph metabolite variation, especially in amino acid and alpha-linolenic acid metabolism, and 28 differential metabolites were altered in the five MP-treated groups. Changes in intestinal bacteria were correlated with the haemolymph proteins and metabolites of the shrimp. Overall, these results reveal the toxicological effects of MPs on the intestinal microbiota and the host's immunity and metabolism in shrimp.


[Sleep apnea syndrome combined with an anatomical obstruction of the upper airways].
In patients with sleep apnoea syndrome abnormalities of the upper airways may play a major role in the genesis of apnoea. Three cases are presented which illustrate the part played by hypertrophy of the tonsils in a child and by stenosis of the pharynx in an adult and of the larynx in another adult. All three patients were cured by surgical correction of these abnormalities. The physiopathology of alveolar hypoventilation, present in one of the three patients, is discussed in relation to the effects of pure oxygen inhalation on the patient's ventilation.


Poly[mu-2-aminopyrazine-kappa2N1:N4-mu-cyanido-copper(I)]: a three-dimensional network from laboratory powder diffraction data.
In the title compound, [Cu(CN)(C(4)H(5)N(3))](n) or [Cu(mu-CN)(mu-PyzNH(2))](n) (PyzNH(2) is 2-aminopyrazine), the Cu(I) center is tetrahedrally coordinated by two cyanide and two PyzNH(2) ligands. The Cu(I)-cyano links give rise to [Cu-CN](infinity) chains running along the c axis, which are bridged by bidentate PyzNH(2) ligands. The three-dimensional framework can be described as being formed by two interpenetrated three-dimensional honeycomb-like networks, both made of 26-membered rings of composition [Cu(6)(mu-CN)(2)(mu-PyzNH(2))(4)].


Prognostic Implications of Post-Intervention Resting Pd/Pa and Fractional Flow Reserve in Patients With Stent Implantation.
This study sought to investigate the prognostic implications of post-percutaneous coronary intervention (PCI) nonhyperemic pressure ratios compared with that of post-PCI fractional flow reserve (FFR). FFR measured after PCI has been shown to possess prognostic implications. However, the prognostic value of post-PCI nonhyperemic pressure ratios has not yet been clarified. A total of 588 patients who underwent PCI with available both post-PCI FFR and resting distal coronary pressure-to-aortic pressure ratio (Pd/Pa) were analyzed. Post-PCI FFR and Pd/Pa were measured after successful angiographic stent implantation. The primary outcome was target vessel failure (TVF) up to 2 years, defined as a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization. Prognosis of patients according to post-PCI Pd/Pa was compared with that of post-PCI FFR. Despite angiographically successful PCI, 18.5% had post-PCI FFR ≤0.80 and 36.9% showed post-PCI Pd/Pa ≤0.92. In post-PCI Pd/Pa >0.92 group, 93.8% of patients showed post-PCI FFR >0.80. Conversely, 60.4% of patients showed post-PCI FFR >0.80 in post-PCI Pd/Pa ≤0.92 group. Although there was significant difference in TVF according to post-PCI FFR (≤0.80 vs. >0.80: 10.3% vs. 2.5%; p < 0.001) and Pd/Pa (≤0.92 vs. >0.92: 6.2% vs. 2.5%; p = 0.029), the reclassification ability of model for TVF was increased only with post-PCI FFR (net reclassification index 0.627; p = 0.003; integrated discrimination index 0.019; p = 0.015), but not with post-PCI Pd/Pa, compared with model including clinical factors. Compared with patients with post-PCI Pd/Pa >0.92, patients with post-PCI Pd/Pa ≤0.92 and FFR ≤0.80 had significantly higher risk of TVF (10.4% vs. 2.5%; adjusted hazard ratio: 4.204; 95% confidence interval: 1.521 to 11.618; p = 0.006); however, those with post-PCI Pd/Pa ≤0.92 but FFR >0.80 showed similar risk of TVF (3.5% vs. 2.5%; adjusted hazard ratio: 1.327; 95% confidence interval: 0.398 to 4.428; p = 0.645). Over one-half of the patients with abnormal post-PCI Pd/Pa ≤0.92 showed post-PCI FFR >0.80. Compared with post-PCI FFR, post-PCI Pd/Pa showed limited reclassification ability for the occurrence of TVF. Among patients with abnormal post-PCI Pd/Pa, only patients with positive post-PCI FFR showed significantly higher risk of TVF than did those with post-PCI Pd/Pa >0.92. (Prognostic Perspective of Invasive Hyperemic and Non-Hyperemic Physiologic Indices Measured After Percutaneous Coronary Intervention [PERSPECTIVEPCI]; NCT04265443).


Psychiatric hospitalization and community-based program attendance.
The psychiatric rehabilitation model of community-based treatment programs for chronic psychiatric patients advocates the teaching of community living skills. Learning these skills requires program attendance, and there is some evidence that consistent attenders are less likely to be hospitalized. This study describes a psychiatric rehabilitation program that resulted in a decrease in number of subsequent psychiatric hospitalizations. However, this decrease was unrelated to program attendance; the number of hospitalizations in the year prior to enrollment was by far the best predictor of hospitalization. Changes in perception of the patient's support network by persons making hospitalization decisions was offered as one possible explanation for the effectiveness of some community-based programs.


Fibrin and the vessel wall.
Fibrin is a major component of atherosclerotic plaques, and there may also be situations in which intravascular fibrin is formed in contact with the endothelium. The studies to be presented describe the distribution of fibrinogen/fibrin I, fibrin II, and fragments D and D-dimer in normal vessels and atherosclerotic plaques of increasing severity and also describe some functional effects of fibrin on normal endothelium. Immunohistochemical studies using three specific monoclonal antibodies with the avidin-biotin complex immunoperoxidase technique demonstrated that little fibrinogen/fibrin I or fibrin II and no D/D-dimer were detected in normal aortas. In early lesions and in fibrous plaques, fibrinogen/fibrin I and fibrin II were distributed in long threads and around vessel wall cells. D/D-dimer was not seen in early lesions. In advanced plaques all three molecular forms were detected in areas of loose connective tissue, in thrombi, and around cholesterol crystals. Thus increased fibrin formation and degradation may be associated with progression of atherosclerotic disease. Additionally, the presence of fibrin II around vessel wall cells suggests that these cells may be involved in the fbgn to fibrin transition within the vessel wall. The second aspect of the work to be presented concerns effects of fibrin on vascular endothelium. Fibrin formed on the surface of cultured human umbilical vein endothelial cells stimulated production of prostacyclin and tissue plasminogen activator by the cells in a time- and dose-dependent manner. Stimulation of prostacyclin was completely inhibited by indomethacin and partially inhibited by actinomycin D, cycloheximide, and trifluoperazine, while stimulation of t-PA synthesis was completely inhibited by actinomycin D and cycloheximide and partially inhibited by cytochalasin D, vinblastine, and trifluoperazine.(ABSTRACT TRUNCATED AT 250 WORDS)


Preoperative selection of patients for lumbar sympathectomy by use of the Doppler index.
Yao and Bergan [8] have shown that an ankle systolic index of more than 0.25 is associated with a high rate of success from lumbar sympathectomy. This association has been borne out in our small series. We have also suggested that diseases that obviously compromise collateral circulation might be a relative contraindication to sympathectomy. Although incomplete, literature on collateral flow in relation to sympathectomy tends to confirm this idea. Consideration of such diseases as a contraindication to sympathectomy might further increase the success rate after sympathectomy. Regardless, ankle systolic index alone appears to be a reliable objective, non-invasive method of selecting patients with an increased chance of success from lumbar sympathectomy.


The influence of pet ownership on self-compassion among nurses: a cross-sectional study.
The modern lifestyle trend of pet ownership is undoubtedly beneficial for both physical and mental health. Research has shown a connection between pet ownership and staff self-compassion. However, there has not been any evidence linking pet ownership to self-compassion in the nurse population. To investigate the current status of pet ownership among nurses and explore the influence of pet ownership on self-compassion among nurses. An online survey was conducted in July 2022 with 1,308 nurses in China. Data were collected using a general information questionnaire and a self-compassion scale. To compare categorical variables, the independent t test, one-way ANOVA, and multiple linear regression analysis were utilized. SPSS software was used for the statistical analysis. We found that 16.9% of nurses owned at least one pet, and dogs and cats were the primary pets. The t test for independent samples showed that pet owners and non-pet owners scored differently on self-compassion (t = 3.286, p = 0.001), self-kindness (t = 3.378, p = 0.001), common humanity (t = 2.419, p = 0.016), and mindfulness (t = 2.246, p = 0.025). One-way ANOVA revealed that the highest degree was an influencing factor of self-compassion (χ 2 = 1.386, p = 0.019). Multiple linear regression showed that average monthly income, pet ownership, and highest degree were the factors that influenced self-compassion most significantly (F = 8.335, p < 0.001). The results revealed that nurses actually own pets as part of their modern lifestyle, which provides them with social support and potentially enhances their self-compassion. More efforts should be focused on the impact of pet ownership on nurses' physical and mental health, and pet-based interventions should also be developed.


Psychological Distress in Women With Abnormal Pap Smear Results Attending Cervical Cancer Screening.
Women often experience psychological distress upon receipt of an abnormal Pap test result. This study aimed to evaluate psychological distress and its correlates among women who received an abnormal Pap screening test result. A cross-sectional study was performed in a cohort of 172 consecutive women who had attended screening for cervical cancer and who received abnormal Pap smear results and underwent additional diagnostic procedures (colposcopy/biopsy/endocervical curettage). The participants filled out a questionnaire on sociodemographic variables and the Cervical Dysplasia Distress Questionnaire. Multivariate linear regression was used for the analysis of the data. For multiple comparisons, the Bonferroni correction was applied to adjust the level of significance. In women who received an abnormal Pap smear result, the independent correlate of higher psychological distress (by Cervical Dysplasia Distress Questionnaire score) before diagnostic procedures was lower satisfaction with information/support received from other people ( p = .002). Correlates of psychological distress in women older than 40 years with abnormal Pap smear were anxiety ( p = .042) and worry about having cervical cancer, general health and having sex ( p = .044). The authors' findings could enable control of factors predictive of psychological distress in women who received a positive Pap smear screening test before undergoing diagnostic procedures, primarily via active provision of targeted information.


Neto1 associates with the NMDA receptor/amyloid precursor protein complex.
Neuropilin tolloid-like 1 (Neto1), is a CUB domain-containing transmembrane protein that was recently identified as a novel component of the NMDA receptor complex. Here, we have investigated the possible association of Neto1 with the amyloid precursor protein (APP)695/GluN1/GluN2A and APP695/GluN1/GluN2B NMDA receptor trafficking complexes that we have previously identified. Neto1(HA) was shown to co-immunoprecipitate with assembled NMDA receptors via GluN2A or GluN2B subunits; Neto1(HA) did not co-immunoprecipitate APP695(FLAG) . Co-immunoprecipitations from mammalian cells co-transfected with APP695(FLAG) , Neto1(HA) and GluN1/GluN2A or GluN1/GluN2B revealed that all four proteins co-exist within one macromolecular complex. Immunoprecipitations from native brain tissue similarly revealed the existence of a GluN1/GluN2A or GluN2B/APP/Neto1 complex. Neto1(HA) caused a reduction in the surface expression of both NMDA receptor subtypes, but had no effect on APP695(FLAG) - or PSD-95α(c-Myc) enhanced surface receptor expression. The Neto1 binding domain of GluN2A was mapped using GluN1/GluN2A chimeras and GluN2A truncation constructs. The extracellular GluN2A domain does not contribute to association with Neto1(HA) but deletion of the intracellular tail resulted in a loss of Neto-1(HA) co-immunoprecipitation which was paralleled by a loss of association between GluN2A and SAP102. Thus, Neto1 is concluded to be a component of APP/NMDA receptor trafficking complexes.


Abdominal actinomycosis: a rare complication after cholecystectomy.
We present a single case of abdominal actinomycosis occurring in a 74-year-old female with a history of cholecystectomy 42 months before presentation. In a review of the literature, we present risk factors, clinical characteristics, diagnosis, and treatment of this infection. Abdominal actinomycosis is a rare, chronic, granulomatous infection characterized by the release of 'sulphur granules'. Actinomyces species should always be part of the differential diagnosis of patients presenting with a history of surgical or invasive procedures, presenting with an abdominal mass. Computed tomography (CT)-guided aspiration with or without core biopsy of this mass is a useful investigation. Diagnosis is often difficult: In less than 10% of cases, the diagnosis is made pre-operatively. Definitive diagnosis is often based on histochemical, macroscopic, and microscopic examination of tissue specimens. The disease should be treated with high doses of intravenous penicillin for 2-6 weeks followed by oral therapy for at least 6-12 months.


Recovery of adenine nucleotide pool in the brain after craniocerebral trauma in rats: comparison of biochemical data with mathematical model.
A mathematical model is developed, which predicts the maximum deviation of adenine nucleotide content from the normal and the period of its restoration in the brain of animals. This model diminishes labor expenditures and duration of experimental studies. Moreover, it significantly increases the accuracy and reliability of the data. This model can assess the efficiency of pharmacotherapy of craniocerebral trauma aftereffects.


Activation and stabilization of chymotrypsin in microdomains of poly(ethylenimine) derivatives. A model of in vivo environment.
Both activity and stability of alpha-Chymotrypsin (ChT) are substantially enhanced in the microdomains of laurylated or benzylated derivatives of poly(ethylenimine). EPR data revealed that the enhancement in activity of ChT is due to increase in the polarity of the microenvironment of Ser-195 caused by complexation of ChT to the polymer derivatives.


Functional testing of tranexamic acid effects in patients undergoing elective orthopaedic surgery.
Tranexamic acid (TXA) can reduce blood loss and transfusion rates in orthopaedic surgery. In this regard, a new viscoelastometric test (TPA-test, ClotPro), enables the monitoring of TXA effects. This prospective observational study evaluated and correlated TXA plasma concentrations (cTXA) following intravenous and oral administration in patients undergoing elective orthopaedic surgery with lysis variables of TPA-test. Blood samples of 42 patients were evaluated before TXA application and 2, 6, 12, 24 and 48 h afterwards. TPA-test was used to determine lysis time (LT) as well as maximum lysis (ML) and cTXA was measured using Ultra-High-Performance-Liquid-Chromatography/Mass-Spectrometry. Data are presented as median (min-max). LTTPA-test and MLTPA-test correlated with cTXA (r = 0.9456/r = 0.5362; p < 0.0001). 2 h after intravenous TXA administration all samples showed complete lysis inhibition (LTTPA-test prolongation: T1: 217 s (161-529) vs. T2: 4500 s (4500-4500);p < 0.0001), whereas after oral application high intraindividual variability was observed as some samples showed only moderate changes in LTTPA-test (T1: 236 s (180-360) vs. T2: 4500 s (460-4500); p < 0.0001). Nevertheless, statistically LTTPA-test did not differ between groups. MLTPA-test differed 2 h after application (i.v.: 9.0% (5-14) vs. oral: 31% (8-97); p = 0.0081). In 17/21 samples after oral and 0/21 samples after intravenous administration cTXA was < 10 µg ml-1 2 h after application. TPA-test correlated with cTXA. MLTPA-test differed between intravenous and oral application 2 h after application. Most patients with oral application had TXA plasma concentration < 10 µg ml-1. The duration of action did not differ between intravenous and oral application. Additional studies evaluating clinical outcomes and side-effects based on individualized TXA prophylaxis/therapy are required.


Neurological outcomes following preterm birth.
Neonatal survival continues to improve; for many years, including throughout the 1990s there have been anxieties that this was at the cost of additional morbidity, most particularly in terms of neurosensory impairments. Recent evidence suggests that rates of neuromotor morbidity, in particular cerebral palsy, may be declining for all but the most immature babies. Severe sensory impairment has a low, but relatively static incidence. High prevalence, low severity motor problems and their inter-relationship with developmental co-ordination disorder, executive dysfunction and cognitive impairment are increasingly recognised and correlated with reduced school performance. Because of difficulties in comparing outcomes across different populations, validated motor and manual function classifications have been developed for children with cerebral palsy and can help to standardise outcome measures. Improved neuro-imaging is helping us understand the types and consequences of neonatal brain injury. The possibility of using composite measures of early motor movement quality, longitudinal use of motor classification systems and volumetric magnetic resonance imaging (MRI) imaging to understand developmental processes needs to be explored.


Spatial association of prolyl oligopeptidase, inositol 1,4,5-triphosphate type 1 receptor, substance P and its neurokinin-1 receptor in the rat brain: an immunohistochemical colocalization study.
Prolyl oligopeptidase (POP) is a serine endopeptidase which hydrolyzes proline-containing peptides shorter than 30 amino acids. It has been suggested that POP is associated with cognitive functions, possibly via the cleavage of neuropeptides such as substance P (SP). Recently, several studies have also linked POP to the inositol 1,4,5-triphosphate (IP(3)) signaling. However, the neuroanatomical interactions between these substances are not known. We used double-labeled immunofluorescence to determine the POP colocalization with SP, SP receptor (neurokinin-1 receptor, NK-1R) and IP(3) type 1 receptor (IP(3)R1) in the rat brain. Furthermore, since striatal and cortical GABAergic neurons are involved in SP neurotransmission, we studied the coexpression of POP, SP and GABA by triple-labeled immunofluorescence. POP was moderately present in IP(3)R1-containing cells in cortex; the colocalization was particularly high in the thalamus, hippocampal CA1 field and cerebellar Purkinje cells. Colocalization of POP with SP and NK1-receptor was infrequent throughout the brain, though some POP and SP coexpression was observed in cerebellar Purkinje cells. We also found that POP partially colocalized with SP-containing GABAergic neurons in striatum and cortex. Our findings support the view that POP is at least spatially associated with the IP(3)-signaling in the thalamus, hippocampus and cerebellar Purkinje cells. This might point to a role for POP in the regulation of long-term potentiation and/or depression. Moreover, the low degree of colocalization of POP, SP and its NK-1R suggests that a transport system is needed either for POP or SP to make hydrolysis possible and that POP may act both intra- and extracellularly.


Measuring transmembrane helix interaction strengths in lipid bilayers using steric trapping.
We have developed a method to measure strong transmembrane (TM) helix interaction affinities in lipid bilayers that are difficult to measure by traditional dilution methods. The method, called steric trapping, couples dissociation of biotinylated TM helices to a competitive binding by monovalent streptavidin (mSA), so that dissociation is driven by the affinity of mSA for biotin and mSA concentration. By adjusting the binding affinity of mSA through mutation, the method can obtain dissociation constants of TM helix dimers (K d,dimer) over a range of six orders of magnitudes. The K d,dimer limit of measurable target interaction is extended 3-4 orders of magnitude lower than possible by dilution methods. Thus, steric trapping opens up new opportunities to study the folding and assembly of α-helical membrane proteins in lipid bilayer environments. Here we provide detailed methods for applying steric trapping to a TM helix dimer.


The crossroads: divergent roles of virus-specific CD4+ T lymphocytes in determining the outcome for human papillomavirus infection.
Despite the widespread availability of effective prophylactic vaccines to prevent human papillomavirus (HPV) infection, HPV remains a major health burden. For health care systems in countries with the capacity for vaccine roll out, incomplete strategies result in citizens with naturally occurring infection, who are at an a posteriori risk of HPV-driven disease. Genital HPV infection is the most common sexually transmitted virus globally. Those classified as high-risk HPV strains are more likely to generate persistent disease. Within this group, HPV16 and 18 are the most prevalent and likely to induce persistent high-grade squamous intraepithelial neoplasia; neoplasia is a large step toward cancerous growth known as a squamous cell carcinoma which contribute to all cervical, 70% of oropharyngeal, 78% of vaginal and 88% of anal cancers. This review will illuminate the relevance of CD4+ T lymphocytes in determining the outcome of papillomavirus infection from the perspective of oropharyngeal and anogenital HPV-driven disease in the immune competent and immunocompromised. The focus is on recent investigations for this "silent" pandemic among current global health crises that should not be forgotten. Informing effective strategies that control viral infection through naturally acquired or induced immunity will identify aspects of scientific and clinical practice that may improve outcome.


Microplastic contamination in the digestive tract of sea urchins (Echinodermata: Echinoidea) in Kepulauan Seribu, Indonesia.
The accumulation of microplastics on sediment surfaces contributed to the digestive tract of sea urchins contamination during foraging. Therefore, the aim of this study was to investigate the potential relationship between the accumulation of microplastics on sediment surfaces and the contamination of sea urchins' digestive tracts during their foraging activities. Sediment and sea urchins' samples were collected from Pari and Harapan Islands, in Kepulauan Seribu, DKI Jakarta, Indonesia. Microplastics were extracted and observed in sediment and the digestive tract of sea urchins' samples. Fourier transform infrared (FTIR) spectroscopy identified microplastic polymers. The average microplastic concentration on Pari Island was 160 ± 158.75 particles/kg dry weight sediment and 3.93 ± 2.25 particles/g dry weight in the digestive tract of sea urchins. Correspondingly, on Harapan Island, the values were 113 ± 41.63 particles/kg dry weight and 0.27 ± 0.28 particles/g dry weight. Fragment-type microplastics (75%) were predominantly detected in the digestive tract of sea urchins, while fiber-type microplastics (59%) were more common in sediments on Pari Island. Conversely, on Harapan Island fragment types were more prevalent (53%). Microplastics larger than 1000 µm were identified in both sediment and the digestive tract of sea urchins. The observed plastic polymers, such as polyethylene, polyester, and polypropylene were dominant at both study sites. This study postulated that microplastics in sediments may be ingested during sea urchins digestion, supported by a significant correlation of 0.016. Consequently, the presence of microplastics in sea urchins from Pari Island and Harapan Island in Kepulauan Seribu was confirmed. Future investigations should explore the toxic effects of absorbed microplastics on sea urchins' physiology, requiring further analysis.


Optimizations to achieve high-level expression of cytochrome P450 proteins using Escherichia coli expression systems.
Recombinant expression of membrane-bound cytochrome P450s in bacterial expression systems provide a well-established system capable of producing large yields of catalytically active protein. As the biochemical knowledge regarding cytochrome P450s increases, so does the efficiency of protein expression through various modifications that do not disrupt the functional properties of the protein of interest. Changes such as N-terminal modifications, reduction of secondary mRNA structure, bacterial codon usage, selection of vector and host strain, as well as varying external growth conditions all appear to influence protein expression. Several optimizations are often required for sufficient expression of cytochrome P450s at the desired cellular localization. This review aims to comprehensively summarize and update the significant advances made in membrane protein P450 expression in bacterial expression systems.


Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains.
The tumour necrosis factor (TNF) family is crucial for immune homeostasis, cell death and inflammation. These cytokines are recognized by members of the TNF receptor (TNFR) family of death receptors, including TNFR1 and TNFR2, and FAS and TNF-related apoptosis-inducing ligand (TRAIL) receptors. Death receptor signalling requires death-domain-mediated homotypic/heterotypic interactions between the receptor and its downstream adaptors, including TNFR1-associated death domain protein (TRADD) and FAS-associated death domain protein (FADD). Here we discover that death domains in several proteins, including TRADD, FADD, RIPK1 and TNFR1, were directly inactivated by NleB, an enteropathogenic Escherichia coli (EPEC) type III secretion system effector known to inhibit host nuclear factor-κB (NF-κB) signalling. NleB contained an unprecedented N-acetylglucosamine (GlcNAc) transferase activity that specifically modified a conserved arginine in these death domains (Arg 235 in the TRADD death domain). NleB GlcNAcylation (the addition of GlcNAc onto a protein side chain) of death domains blocked homotypic/heterotypic death domain interactions and assembly of the oligomeric TNFR1 complex, thereby disrupting TNF signalling in EPEC-infected cells, including NF-κB signalling, apoptosis and necroptosis. Type-III-delivered NleB also blocked FAS ligand and TRAIL-induced cell death by preventing formation of a FADD-mediated death-inducing signalling complex (DISC). The arginine GlcNAc transferase activity of NleB was required for bacterial colonization in the mouse model of EPEC infection. The mechanism of action of NleB represents a new model by which bacteria counteract host defences, and also a previously unappreciated post-translational modification.


Next generation planar waveguide detection of microcystins in freshwater and cyanobacterial extracts, utilising a novel lysis method for portable sample preparation and analysis.
The study details the development of a fully validated, rapid and portable sensor based method for the on-site analysis of microcystins in freshwater samples. The process employs a novel lysis method for the mechanical lysis of cyanobacterial cells, with glass beads and a handheld frother in only 10 min. The assay utilises an innovative planar waveguide device that, via an evanescent wave excites fluorescent probes, for amplification of signal in a competitive immunoassay, using an anti-microcystin monoclonal with cross-reactivity against the most common, and toxic variants. Validation of the assay showed the limit of detection (LOD) to be 0.78 ng mL(-1) and the CCβ to be 1 ng mL(-1). Robustness of the assay was demonstrated by intra- and inter-assay testing. Intra-assay analysis had % C.V.s between 8 and 26% and recoveries between 73 and 101%, with inter-assay analysis demonstrating % C.V.s between 5 and 14% and recoveries between 78 and 91%. Comparison with LC-MS/MS showed a high correlation (R(2)=0.9954) between the calculated concentrations of 5 different Microcystis aeruginosa cultures for total microcystin content. Total microcystin content was ascertained by the individual measurement of free and cell-bound microcystins. Free microcystins can be measured to 1 ng mL(-1), and with a 10-fold concentration step in the intracellular microcystin protocol (which brings the sample within the range of the calibration curve), intracellular pools may be determined to 0.1 ng mL(-1). This allows the determination of microcystins at and below the World Health Organisation (WHO) guideline value of 1 μg L(-1). This sensor represents a major advancement in portable analysis capabilities and has the potential for numerous other applications.


Alternative diagnoses in the colic patient.
Despite clinical signs compatible with obstruction or ischemia of the gastrointestinal tract, the clinician occasionally is unable to identify a gastrointestinal cause for colic. In this article, disorders not originating from obstruction or ischemia of the gastrointestinal tract but causing real or apparent abdominal pain are presented as alternative causes of colic. In addition, colic of gastrointestinal origin may be the primary inciting factor or a secondary complication of an alternative disorder, causing colic-like signs. Recognition of alternative diagnoses relies on a thorough and consistent approach to the clinical assessment of the equine colic patient and helps to ensure appropriate patient management.


[A study of the engraftment, expansion and differentiation of human hematopoietic stem cells in goats].
To establish a human/goat hematopoietic stem cell (HSC) xenogeneic transplant model and to probe the engraftment, expansion and differentiation of human HSC in vivo. Human HSCs were isolated from human umbilical cord blood and 1 x 10(5) human HSCs were in utero transplanted into 50 fetal goats at the 55 - 65 the gestation days. The engraftment, expansion and differentiation of human HSCs in goats were determined by FACS analysis, PCR and PCR-Southern blot hybridization at various intervals after birth. Hematopoietic chimerism occurred certainly in 35 of 39 live-born recipients. On average, The proportion of human hematopoietic cells in goat blood was 1% approximately 3% and remained phenotypically stable for at least 10 months. The human hematopoietic cells circulated in goat blood expressed CD34, CD14, CD20 and glycophorin A (GPA) but did not express CD3, CD4, CD7, CD8 and CD56 or expressed them at a very low level. The number of human HSC can be effectively expanded 1 000 - 10 000 fold. Human HSCs in goats undergo a limited differentiation. Our human/goat HSC xenogeneic model provides a useful way for the investigation of HSC transplantation, expansion and differentiation in vivo.


Inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel sulfated polysaccharide derived from a blue-green alga, Spirulina platensis.
We have investigated the effect of calcium spirulan (Ca-SP) isolated from a blue-green alga, Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose, on invasion of B16-BL6 melanoma, Colon 26 M3.1 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no effect on that to fibronectin. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel and laminin substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin, while the pretreatment of laminin substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contrast, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP. Seven intermittent i.v. injections of 100 microg of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung metastasis of B16-BL6 melanoma cells, by inhibiting the tumor invasion of basement membrane probably through the prevention of the adhesion and migration of tumor cells to laminin substrate and of the heparanase activity.


Efficacy of different chemotherapeutic schemes for hookworm-infected villagers in China.
A comparative analysis has been made of the efficacy of different chemotherapeutic schemes against hookworm infections in China. Hookworm eggs were detected by the improved Kato's thick smear method. Benzimidazole was offered to residents in the tested villages, while NaHCO3 was used as placebo in control villages. Data were analysed by negative binomial distribution with statistic software R2.2.1. In the tested village as a result of the application of selective chemotherapy, hookworm infection rate decreased from 58.79% to 1.08%, while the average of eggs per gram (EPG) reduced from 526.29 to 56.91. The infection rates in the target chemotherapy village and in the mass chemotherapy village declined from 6.90% to 1.92% and 10.10% to 0.65% respectively. It was concluded that the consecutive selective chemotherapy could rapidly decrease the infection rate and EPG of hookworm and maintain the infection rate at low level. The curative effect of the target chemotherapy was similar to that of the mass chemotherapy in the low hookworm endemic area.


Development of the Chinese Haemovigilance Network and reporting of adverse transfusion reactions from 2018 to 2020.
To advance blood transfusion safety, the Chinese Haemovigilance Network (CHN) was put into operation in 2018. This report describes the development of the CHN and evaluates its role by analysing reported adverse transfusion reactions (ATRs) from 2018 to 2020. All data in this study were obtained from the CHN online reporting platform. A timeline of CHN development is presented, and the activities of CHN-enrolled facilities are analysed by year. The reported ATRs were analysed in detail for ATR types, blood components involved and adherence to case definition, severity and imputability criteria. Incidence rates were calculated and compared with international examples. During 2018-2020, a total of 3061 ATRs were reported through the CHN online reporting system. The rate of reported ATRs in all facilities and the 10 highest reporting facilities was 0.7‰ and 1.8‰, respectively. When analysed by year, the incidence rate showed an increasing trend from 2018 to 2020. Allergic (68.2%) and febrile non-haemolytic transfusion reaction (27.1%) were the most common. The vast majority of ATRs (92.0%) were not serious, but serious cases of transfusion-associated circulatory overload, transfusion-associated dyspnoea and hypotensive reaction were common. Most (86.0%) of reported cases were definitely or probably associated with transfusion. Under-reporting of ATRs occurs in many Chinese hospitals, but the establishment of CHN has increased ATR recognition and management. More effort will be needed in the future to detect transfusion problems and improve transfusion practice in China.


Colorimetric aptasensor for fumonisin B1 detection based on the DNA tetrahedra-functionalized magnetic beads and DNA hydrogel-coated bimetallic MOFzyme.
The toxicity and incidence of fumonisin B1 (FB1) pose a major challenge to public health and the environment, prompting the development of alternative quantitative strategies for FB1. Herein, a colorimetric aptasensor was constructed based on DNA tetrahedra-functionalized magnetic beads (MBs) and DNA hydrogel-coated Mn-Zr bimetallic metal-organic frameworks-based nanozyme (MOFzyme). Initially, MBs functionalized by DNA tetrahedra demonstrated excellent capturing capability for FB1. Along with the capture of FB1, catalyst DNA (C) was released into the supernatant. Aided by fuel DNA (F), C can trigger continuous cleavage of the main chains and cross-linking points of the DNA hydrogel through an entropy-driven DNA circuit integrated into the hydrogel coating. Subsequently, the bimetallic MOFzyme encapsulated inside the DNA hydrogel was exposed and exerted its superb peroxidase-like activity, producing a colorimetric signal whose intensity was positively dependent on the amount of FB1. The developed aptasensor exhibited good linearity in the range of 5 × 10-4 to 50 ng mL-1 with a limit of detection (LOD) of 0.38 pg mL-1, and reasonable specificity in different matrices. Furthermore, the aptasensor was successfully applied to quantify FB1 in actual samples with recoveries fell within 92.25 %- 108.00 %, showing its great potential in environmental monitoring and food safety.


Exploring Reasons for Delayed Start-of-Care Nursing Visits in Home Health Care: Algorithm Development and Data Science Study.
Delayed start-of-care nursing visits in home health care (HHC) can result in negative outcomes, such as hospitalization. No previous studies have investigated why start-of-care HHC nursing visits are delayed, in part because most reasons for delayed visits are documented in free-text HHC nursing notes. The aims of this study were to (1) develop and test a natural language processing (NLP) algorithm that automatically identifies reasons for delayed visits in HHC free-text clinical notes and (2) describe reasons for delayed visits in a large patient sample. This study was conducted at the Visiting Nurse Service of New York (VNSNY). We examined data available at the VNSNY on all new episodes of care started in 2019 (N=48,497). An NLP algorithm was developed and tested to automatically identify and classify reasons for delayed visits. The performance of the NLP algorithm was 0.8, 0.75, and 0.77 for precision, recall, and F-score, respectively. A total of one-third of HHC episodes (n=16,244) had delayed start-of-care HHC nursing visits. The most prevalent identified category of reasons for delayed start-of-care nursing visits was no answer at the door or phone (3728/8051, 46.3%), followed by patient/family request to postpone or refuse some HHC services (n=2858, 35.5%), and administrative or scheduling issues (n=1465, 18.2%). In 40% (n=16,244) of HHC episodes, 2 or more reasons were documented. To avoid critical delays in start-of-care nursing visits, HHC organizations might examine and improve ways to effectively address the reasons for delayed visits, using effective interventions, such as educating patients or caregivers on the importance of a timely nursing visit and improving patients' intake procedures.


Combining Metabolic ¹⁵N Labeling with Improved Tandem MOAC for Enhanced Probing of the Phosphoproteome.
In eukaryotic cells many diverse cellular functions are regulated by reversible protein phosphorylation. In recent years, phosphoproteomics has become a powerful tool for studying protein phosphorylation because it enables unbiased localization, and site-specific quantification of in vivo phosphorylation of hundreds of proteins in a single experiment. A common strategy for identifying phosphoproteins and their phosphorylation sites from complex biological samples is the enrichment of phosphopeptides from digested cellular lysates followed by mass spectrometry. However, despite high sensitivity of modern mass spectrometers the large dynamic range of protein abundance and the transient nature of protein phosphorylation remained major pitfalls in MS-based phosphoproteomics. This is particularly true for plants in which the presence of secondary metabolites and endogenous compounds, the overabundance of ribulose-1,5-bisphosphate carboxylase and other components of the photosynthetic apparatus, and the concurrent difficulties in protein extraction necessitate two-step phosphoprotein/phosphopeptide enrichment strategies (Nakagami et al., Plant Cell Physiol 53:118-124, 2012).Approaches for label-free peptide quantification are advantageous due to their low cost and experimental simplicity, but they lack precision. These drawbacks can be overcome by metabolic labeling of whole plants with heavy nitrogen ((15)N) which allows combining two samples very early in the phosphoprotein enrichment workflow. This avoids sample-to-sample variation introduced by the analytical procedures and it results in robust relative quantification values that need no further standardization. The integration of (15)N metabolic labeling into tandem metal-oxide affinity chromatography (MOAC) (Hoehenwarter et al., Mol Cell Proteomics 12:369-380, 2013) presents an improved and highly selective approach for the identification and accurate site-specific quantification of low-abundance phosphoproteins that is based on the successive enrichment of light and heavy nitrogen-labeled phosphoproteins and peptides. This improved strategy combines metabolic labeling of whole plants with the stable heavy nitrogen isotope ((15)N), protein extraction under denaturing conditions, phosphoprotein enrichment using Al(OH)3-based MOAC, and tryptic digest of enriched phosphoproteins followed by TiO2-based MOAC of phosphopeptides and quantitative phosphopeptide measurement by liquid chromatography (LC) and high-resolution accurate mass (HR/AM) mass spectrometry (MS). Thus, tandem MOAC effectively targets the phosphate moiety of phosphoproteins and phosphopeptides and allows probing of the phosphoproteome to unprecedented depth, while (15)N metabolic labeling enables accurate relative quantification of measured peptides and direct comparison between samples.


Ring-testing and field-validation of a terrestrial model ecosystem (TME)--an instrument for testing potentially harmful substances: effects of carbendazim on organic matter breakdown and soil fauna feeding activity.
Organic matter (OM) decomposition and soil fauna feeding activity were integrated as functional endpoints into ecotoxicological tests with intact-soil-core Terrestrial Model Ecosystems (TMEs). Cellulose filter paper served as standardized OM and was either inserted into the top soil or placed on the soil surface for a period of up to 16 weeks. Faunal feeding activity was assessed by the bait-lamina method. The fungicide carbendazim, applied at six dosages ranging from 0.36 kg/ha to 87.5 kg a.i./ha, served as a model chemical. To validate the results from the TME test, a field study was run in parallel. In TMEs the cellulose paper inserted into the soil was decomposed faster than under field conditions. The carbendazim-induced effects on OM decomposition in TMEs and in the field were comparable and followed a clear dose-response relationship. The calculated EC50 values after 8 weeks of incubation were 9.5, 7.1 and 2.1 kg carbendazim/ha for grassland TMEs, grassland field and arable TMEs, respectively. The feeding activity of the soil fauna showed a large variability. The EC50 values for the effect of carbendazim on bait-lamina consumption ranged between 2.0 and 56 kg a.i./ha. Effects on decomposition were correlated with effects on enchytraeids and earthworms but not with effects on bait-lamina consumption.


Pediculosis capitis: new insights into epidemiology, diagnosis and treatment.
Pediculosis capitis is a ubiquitous parasitic skin disease caused by Pediculus humanus capitis. Head lice are highly specialised parasites which can propagate only on human scalp and hair. Transmission occurs by direct head-to-head contact. Head lice are vectors of important bacterial pathogens. Pediculosis capitis usually occurs in small epidemics in play groups, kindergartens and schools. Population-based studies in European countries show highly diverging prevalences, ranging from 1% to 20%. The diagnosis of head lice infestation is made through the visual inspection of hair and scalp or dry/wet combing. The optimal method for the diagnosis of active head lice infestation is dry/wet combing. Topical application of a pediculicide is the most common treatment. Compounds with a neurotoxic mode of action are widely used but are becoming less effective due to resistant parasite populations. Besides, their use is restricted by safety concerns. Dimeticones, silicone oils with a low surface tension and the propensity to perfectly coat surfaces, have a purely physical mode of action. This group of compounds is highly effective and safe, and there is no risk that head lice become resistant. The control of epidemics requires active contact tracing and synchronised treatment with an effective and safe pediculicide.


Recent trends, challenges and future outlook of transdermal drug delivery systems for rheumatoid arthritis therapy.
At present, several drug molecules have been used for the treatment of rheumatoid arthritis (RA). However, the utilization of these compounds through the oral and parenteral route is limited due to low bioavailability, rapid metabolism, poor absorption, first-pass effect, and serious adverse effects. A transdermal delivery system is an appealing option in this scenario, as it possesses the proficiency to overcome drawbacks associated with the oral and parenteral route. With the innovation of several enhancement strategies, many therapeutic agents have been administered transdermally, proposing an exceptional approach to treat RA. The present article provides an insight into the etiology and pathophysiology of RA. The challenges of the transdermal route and the strategies to improve those problems are described. The current advances in increasing the transdermal efficiency of the therapeutics against RA are discussed. Limitations and advantages regarding the state of the art transdermal delivery system and future outlook are also summarized.


Influence of baseline hemodynamic status and sympathetic activity on the response to nicardipine, a new dihydropyridine, in patients with hypertension or chronic congestive heart failure.
We evaluated the immediate hemodynamic response to nicardipine, administered as an intravenous bolus and 30-minute sustaining infusion, in 10 patients with systemic hypertension (HTN) and 10 patients with chronic congestive heart failure (CHF). Baseline systemic vascular resistance and the response to nicardipine for HTN (1968 +/- 657 to 905 +/- 256 dynes X sec X cm-5) and CHF (2002 +/- 988 to 1089 +/- 216 +/- 99 dynes X sec X cm-5) were virtually identical (P less than 0.01). In both groups there was a significant increase of cardiac index in response to afterload reduction: HTN, 2.70 +/- 0.46 to 4.47 +/- 1.01; CHF, 1.90 +/- 0.33 to 2.88 +/- 0.80 L/min/m2 (P less than 0.01), so that a negative inotropic effect was not evident. In HTN the increase in cardiac index was primarily the result of reflex increase of heart rate (67 +/- 16 to 95 +/- 25 bpm [P less than 0.05]), associated with norepinephrine increase from 402 +/- 243 to 744 +/- 364 pg/ml (P less than 0.001). In CHF the cardiac index increase was caused by a stroke volume index increase (23 +/- 4 to 33 +/- 9 ml/min; P less than 0.01), with no significant change in heart rate or norepinephrine. Thus nicardipine, by means of calcium channel antagonism, induced reversal of vasoconstriction. Differences in the cardiac response identify the importance of characterizing the pathophysiologic status of cardiac impairment to more accurately interpret pharmacologic interventions.


Predictors of guideline concordance for surveillance colonoscopy recommendations in patients at a safety-net health system.
Appropriate surveillance intervals for colorectal cancer (CRC) screening is one of the Centers for Medicare and Medicaid Services 2014 physician quality reporting system measures. Appropriateness of surveillance intervals will continue to be monitored closely, particularly as reimbursements become tied to quality measures. Quantify and identify predictors for guideline-concordant surveillance recommendations after adenoma polypectomy. We conducted a retrospective cohort study of patients who had colonoscopy with polypectomy at a safety-net health system between June 2011 and December 2013. Surveillance recommendations shorter and longer than guideline recommendations were defined as potential overuse and underuse. We used multivariate logistic regression to identify correlates of guideline-concordant surveillance recommendations, overuse, and underuse. Among 1,822 patients with polypectomy, 1,329 had ≥1 adenoma. Surveillance interval recommendations were guideline-concordant in 1,410 (77.4%) patients, potential overuse in 263 (14.4%), potential underuse in 85 (4.7%), and missing in 64 (3.5%) patients. Predictors of guideline-concordant recommendations in multivariate analyses included age >65 years (OR 1.36, 95% CI 1.02-1.80), incomplete resection (OR 3.58, 95% CI 1.41-9.09), and good/excellent prep quality (OR 2.22, 95% CI 1.72-2.86). Underuse recommendations were more likely in patients with ≥3 adenomas; overuse recommendations were more likely in patients with high-grade dysplasia or fair prep quality and less likely in those with piecemeal resection, ≥3 adenomas, age >65, or Hispanic ethnicity. Surveillance recommendations are not concordant with guidelines in one of four cases. Interventions to improve prep quality and guideline concordance of surveillance recommendations can improve cost-effectiveness of CRC screening.


Reversed-J inferior versus full median sternotomy: which is better for awake coronary bypass surgery.
The aim of this study was to ascertain whether the approach with a less invasive reversed-J inferior sternotomy could improve intraoperative patient compliance and postoperative recovery than the standard median sternotomy. Seventeen patients underwent elective single coronary artery bypass graft operation under high thoracic epidural anesthesia without endotracheal intubation. The reversed-J sternotomy was performed in 10 patients (Group A) and full sternotomy in 7 patients (Group B). The technical and surgical difficulties, pulmonary functions (by spirometric tests) and hospital stay were assessed. Through the reversed-J sternotomy coronary revascularization was accomplished without any additional technical difficulties and with a good exposure of both the left anterior descending artery and the left internal thoracic artery. No conversion to standard sternotomy and no intubation were observed. Additional doses of local anesthetic at jugular notch was not required in Group A. Pleura was opened more in Group B (57% vs. 20%; p = 0.14). Oxygen saturation was better in Group A during the surgical procedure (98.8 +/- 0.7% vs. 97.1 +/- 2.1%; p = 0.033), however, intraoperative PaCO2 was similar in both the groups. The patients in Group A were discharged from the hospital earlier (3.2 +/- 1.5 vs. 7.3 +/- 3.5 days; p = 0.004). Less invasive approach to coronary artery bypass graft operations is possible through combination of the high thoracic epidural anesthesia and a reversed-J sternotomy. This technique is less traumatic for patient and provides practical better oxygenation and shorter hospital stay.


Examination of the brain natriuretic peptide rs198389 single-nucleotide polymorphism on type 2 diabetes mellitus and related phenotypes in an Algerian population.
In European populations, the NPPB rs198389 single nucleotide polymorphism (SNP) is associated with a reduced risk of type 2 diabetes mellitus (T2DM). We investigated the putative associations between NPPB rs198389, the T2DM risk and quantitative metabolic traits in an Algerian population. The association analysis was performed as a T2DM case-control study (with 78 cases and 645 controls) nested into the ISOR population-based study. The NPPB rs198389 SNP was not associated with T2DM (odds ratio (OR) [95% confidence interval (CI)]=0.73 [0.51-1.04], p=0.08). However, the C allele was associated with lower fasting plasma insulin levels (p=0.05) and a lower homeostatic model assessment insulin resistance index (p=0.05) in non-diabetic individuals. The NPPB rs198389 SNP might modulate fasting insulin levels in an Algerian population.


Interleukin-1 production by a cloned line of human monocyte-like cells (CM-SM). Correlation with state of differentiation.
Interleukin-1 (IL-1) production by the human monocyte-like cloned cell line CM-SM has been investigated as a function of the state of cell differentiation. CM-SM cells were induced to differentiate along the monocyte-macrophage lineage by bacterial lipopolysaccharides (LPS) or by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Cell differentiation was studied by various morphological, functional, cytochemical, and immunological variables, whereas IL-1 activity in the supernatants was measured by the lectin-primed thymocyte proliferation assay. Unstimulated CM-SM cells constitutively produced small amounts of IL-1, and most of the cells appeared relatively undifferentiated. LPS induced cell differentiation, but the effect was reversible, and the cells, in general, did not acquire a capacity for phagocytosis. IL-1 levels were increased about 10-fold over the controls. TPA induced further cell differentiation to macrophage-like cells capable of phagocytosis. IL-1 activity could not be measured directly in the supernatants owing to the synergistic effect of TPA in the assay system. Unequivocal removal of the phorbol was not achieved, but the data indicated that the 'real' levels of IL-1 in the TPA-induced cultures were not significantly higher than those from LPS-induced cultures.


The impact of hepatitis screening on diagnosis and treatment in rheumatoid arthritis.
Identification of patients with exposure to viral hepatitis is an important part of the care of patients with inflammatory arthritis. This study was conducted to assess the extent of hepatitis B and C screening, and the prevalence of viral hepatitis in a cohort of patients with established rheumatoid arthritis (RA). The medical records of 100 consecutive RA patients were retrospectively analysed for screening of hepatitis B surface antigen, surface antibody and core antibody and hepatitis C antibody. A teaching session was then conducted with the rheumatology team, emphasising the rationale for viral hepatitis testing. We then prospectively analysed 100 more RA patients to see if hepatitis screening improved. In the initial 100 patients (21 % male, mean age 65 years), 85 % were taking methotrexate and 22 % biologic treatments. A complete hepatitis screen was present in 8 %, while 12 % had hepatitis B core antibody checked and 53 % had been tested for hepatitis C.The second cohort of patients was similar to the first in terms of demographics and treatment. A complete hepatitis screen was available in 63 %, while 65 % had hepatitis B core antibody checked and 81 % had been tested for hepatitis C.In total, we identified 4 new cases of positive hepatitis B core antibody, 11 cases of positive hepatitis B surface antibody and 1 case of positive hepatitis C antibody. Even in populations where hepatitis B or C is non-endemic, screening will reveal new cases. Educational initiatives are helpful in teaching staff to screen patients.


A note on the antitubercular activities of 1-aryl-5-benzylsulfanyltetrazoles.
A set of 32 1-phenyl-5-benzylsulfanyltetrazoles substituted on the phenyl ring as well as on the benzyl moiety was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis. The activity against M. tuberculosis becomes higher with increasing electron-accepting properties of the substituents on the phenyl ring. On the other hand, any substitution on the benzylic moiety decreases the activity.


[The clinical characteristics and the diagnosis and treatment of tumors of duodenal papilla].
To assess the clinical features, diagnosis, treatment and prognosis of duodenal papilla tumors. The clinical data of 76 patients diagnosed as tumor of duodenal papilla for endoscopic or surgical treatment, in the Second Affiliated Hospital of Zhejiang University, School of Medicine since April 2004 to April 2015 were collected and analyzed retrospectively. There were 50 male and 26 female patients aging from 38 to 83 years with a median age of 62 years. All patients were diagnosed by ultrasound, CT or endoscopic retrograde cholangiopancreatography. All the 76 patients accepted surgical treatment, among which 61 cases accepted pancreaticoduodenectomy, 6 cases accepted trans-duodenum papillae resection and reconstruction, 5 cases accepted endoscopic duodenal papilla tumor resection and 4 cases accepted palliative operations. Kaplan-Meier method was used to analyze the survival rate. Among the 76 cases of patients, the pathological diagnosis included 10 cases of benign tumors, 8 cases of precancerous lesions, 58 cases of malignant tumor. Death cases were not caused by postoperative complications. Coincidence rate of preoperative biopsy and postoperative pathological diagnosis was 77.6%. Postoperative follow-up was 2 to 120 months, the results showed that the 1, 3, 5 year survival rates were 73.2%, 51.8%, 32.1% for 53 patients with duodenal papillary carcinoma. Duodenal papilla tumors had varied clinical manifestations, ultrasound, CT and endoscopic examination and ERCP can improve the diagnostic rate of duodenal papilla tumors. For benign tumors and early stage malignant tumors, local excision or endoscopic resection was safe and effective. For advanced malignancies, radical pancreaticoduodenectomy was essential.


Outcome of TiNi stent treatments in symptomatic central airway stenoses caused by Aspergillus fumigatus infections after lung transplantation.
Central airway stenoses due to Aspergillus fumigatus infections have been a significant cause of morbidity and mortality after lung transplantation. We reviewed our experience using self-expandable braided TiNi-metallic stents in the management of 4 single-lung transplant recipients with central airways stenoses between January 2003 and June 2010. Thirty-six single-lung transplant recipients were subjected to pulmonary function testing and surveillance bronchoscopy with biopsy at predetermined intervals and when clinically indicated. Bronchial wash fluid and biopsy material were examined by appropriate fungal stain and culture techniques. Nine of 36 patients (25%) were diagnosed with Aspergillus fumigatus infections; 4 (11.1%) showed rapid decrease in pulmonary function and developed severe upper airway narrowings with about 80% of the central airway obstructed by thick plugs of mucus, heavily laden with Aspergillus species. All 4 patients were managed with stent placement as well as antifungal treatments and showed a forced vital capacity and forced expiratory volume in 1 second improvement of 11.3% and 25.9%, respectively after 1 month. TiNi stent applications in combination with antifungal drugs are sufficient to treat central airway stenoses after lung transplantation.


Primary vitrectomy for rhegmatogenous retinal detachment associated with choroidal detachment.
This study aimed to report the success rate of primary vitrectomy, scleral buckling, and oral steroids in eyes with combined rhegmatogenous retinal detachment (RRD) and choroidal detachment (CD) and to compare these results with those reported in the literature for similar cases managed by scleral buckling alone. Consecutive case series. Twenty-one eyes of 21 consecutive patients with primary RRD associated with CD were examined. All patients were treated with systemic corticosteroids before surgery. Pars plana vitrectomy with scleral buckling or encircling or both were performed. Retinal reattachment rate and resolution of choroidal detachment were measured. At mean follow-up of 11.4 months, retinal reattachment was attained in 19 eyes (90.5%) compared to less than 53% reported in the literature for scleral buckling alone. With preoperative oral steroids, choroidal detachment regressed completely in 13 eyes (61.9%). In the remaining eyes with persistent choroidal detachment, suprachoroidal fluid was drained during vitrectomy. Aggressive treatment with oral steroids followed by pars plana vitrectomy and scleral buckling or encircling is recommended instead of scleral buckling alone in the management of combined primary rhegmatogenous retinal detachment and choroidal detachment.


Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications.
Nanoparticles with controlled physical properties have been widely used for controlled release applications. In addition to shape, the anisotropic nature of the particles can be an important design criterion to ensure selective surface modification or independent release of combinations of drugs. Electrohydrodynamic (EHD) co-jetting is used for the fabrication of uniform anisotropic nanoparticles with individual compartments and initial physicochemical and biological characterization is reported. EHD co-jetting is used to create nanoparticles, which are characterized at each stage with scanning electron microscopy (SEM), structured illumination microscopy (SIM), dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Surface immobilization techniques are used to incorporate polyethylene glycol (PEG) and I(125) radiolabels into the nanoparticles. Particles are injected in mice and the particle distribution after 1, 4 and 24 hours is assessed. Nanoparticles with an average diameter of 105.7 nm are prepared by EHD co-jetting. The particles contain functional chemical groups for further surface modification and radiolabeling. The density of PEG molecules attached to the surface of nanoparticles is determined to range between 0.02 and 6.04 ligands per square nanometer. A significant fraction of the nanoparticles (1.2% injected dose per mass of organ) circulates in the blood after 24 h. EHD co-jetting is a versatile method for the fabrication of nanoparticles for drug delivery. Circulation of the nanoparticles for 24 h is a pre-requisite for subsequent studies to explore defined targeting of the nanoparticles to a specific anatomic site.


Metabolism and Anticancer Mechanisms of Selocompounds: Comprehensive Review.
Selenium (Se) is an essential micronutrient with several functions in cellular and molecular anticancer processes. There is evidence that Se depending on its chemical form and the dosage use could act as a modulator in some anticancer mechanisms. However, the metabolism of organic and inorganic forms of dietary selenium converges on the main pathways. Different selenocompounds have been reported to have crucial roles as chemopreventive agents, such as antioxidant activity, activation of apoptotic pathways, selective cytotoxicity, antiangiogenic effect, and cell cycle modulation. Nowadays, great interest has arisen to find therapies that could enhance the antitumor effects of different Se sources. Herein, different studies are reported related to the effects of combinatorial therapies, where Se is used in combination with proteins, polysaccharides, chemotherapeutic agents or as nanoparticles. Another important factor is the presence of single nucleotide polymorphisms in genes related to Se metabolism or selenoprotein synthesis which could prevent cancer. These studies and mechanisms show promising results in cancer therapies. This review aims to compile studies that have demonstrated the anticancer effects of Se at molecular levels and its potential to be used as chemopreventive and in cancer treatment.


Full size microplastics in crab and fish collected from the mangrove wetland of Beibu Gulf: Evidences from Raman Tweezers (1-20 μm) and spectroscopy (20-5000 μm).
Microplastic pollution in organisms is a growing environmental concern worldwide. Current methods to identify microplastics (MPs) are subject to the limitations of analytical techniques, and there is no full-scale method to measure MPs in organisms. In this study, Raman Tweezers and spectroscopy methods were combined and applied to identify MPs in organisms within the size range of 1-5000 μm. The abundance of small MPs (1-20 μm) was measured in crab (0.39-2.83 items/individual) and fish (0.35-3.22 items/individual). Most MPs were transparent in color and pellet shape. The proportion of small MPs (1-20 μm) was 35.77%, and analysis revealed the non-inclusion of this fraction will induce large deviations in the overall measurement. The large MPs (20-5000 μm) were identified in crab and fish with abundances ranging from 0.74-4.96 items/individual and 0.72-5.39 items/individual, respectively. Mainly fiber shape items were detected, the dominant particle size ranged from 20 to 100 μm, and most MPs were white. Polyethylene (PE) and polyethylene terephthalate (PET) were the main types of MPs polymers detected. Our study fills the gap to provide a new method to detect MPs in organisms below 20 μm, facilitating study of the migration and transformation of small MPs in the environment.