Dietary lipids influence insulin action.
Insulin binding and insulin responsiveness are altered by dietary fat-induced changes in the fatty acid composition of the adipocyte plasma membrane. Feeding a high P/S diet increased polyunsaturated fatty acid content of major membrane phospholipids of adipocyte plasma membrane in normal and diabetic animals, increased membrane linoleic acid content, and prevented a decrease in arachidonic acid level in diabetic animals. The high P/S diet increased insulin binding in control animals. Animals fed the high P/S diet had significantly higher rates of insulin-stimulated glucose transport and lipogenesis than did animals fed the low P/S diet. Feeding a high P/S diet significantly increased the amount of glucose transported when expressed as a function of the specific amount of insulin bound. To determine if dietary fat-induced alterations in the fatty acid composition of skeletal muscle lipid alter insulin-dependent and basal muscle metabolism, contralateral epitrochlearis and extensor digitorum longus muscles were isolated and incubated in vitro. High levels of dietary omega-3 fatty acids reduced PGE2 and PGF2 alpha synthesis in extensor digitorum longus and epitrochlearis muscle. Insulin increased glucose and amino acid transport; the increase in glucose transport by insulin was significantly greater after consumption of the high omega-3 fatty acid diet. Rats fed high levels of omega-3 fatty acids showed reduced net protein degradation in the presence and absence of insulin due to decreased rates of protein degradation and synthesis. These experiments indicate that high levels of dietary omega-3 fatty acids alter muscle membrane composition, glucose transport, and metabolism of muscle protein. To determine if dietary fatty acids alter the onset of diabetes and insulin binding to liver nuclei in spontaneously diabetic rats, weanling rats were fed chow or semipurified diets containing 20% (w/w) fat of either high or low P/S ratio. Feeding a high P/S diet increased insulin binding to liver nuclei of control and diabetic animals. Although diet did not alter the onset of diabetes, insulin binding to liver nuclei is higher in animals at the onset of diabetes than in highly diabetic animals. Eight-week-old female C57 B 6J lean and ob/ob mice were fed semipurified diets containing 20% (w/w) fat of either high or low P/S ratio to investigate the effect of diet on specific binding of insulin to liver nuclei. Insulin binding was highest in nuclei from lean mice fed a high P/S diet. Specific binding of insulin to nuclei from obese mice was also increased by the high P/S diet, but to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)


Adaptive radiation along a thermal gradient: preliminary results of habitat use and respiration rate divergence among whitefish morphs.
Adaptive radiation is considered an important mechanism for the development of new species, but very little is known about the role of thermal adaptation during this process. Such adaptation should be especially important in poikilothermic animals that are often subjected to pronounced seasonal temperature variation that directly affects metabolic function. We conducted a preliminary study of individual lifetime thermal habitat use and respiration rates of four whitefish (Coregonus lavaretus (L.)) morphs (two pelagic, one littoral and one profundal) using stable carbon and oxygen isotope values of otolith carbonate. These morphs, two of which utilized pelagic habitats, one littoral and one profundal recently diverged via adaptive radiation to exploit different major niches in a deep and thermally stratified subarctic lake. We found evidence that the morphs used different thermal niches. The profundal morph had the most distinct thermal niche and consistently occupied the coldest thermal habitat of the lake, whereas differences were less pronounced among the shallow water pelagic and littoral morphs. Our results indicated ontogenetic shifts in thermal niches: juveniles of all whitefish morphs inhabited warmer ambient temperatures than adults. According to sampling of the otolith nucleus, hatching temperatures were higher for benthic compared to pelagic morphs. Estimated respiration rate was the lowest for benthivorous profundal morph, contrasting with the higher values estimated for the other morphs that inhabited shallower and warmer water. These preliminary results suggest that physiological adaptation to different thermal habitats shown by the sympatric morphs may play a significant role in maintaining or strengthening niche segregation and divergence in life-history traits, potentially contributing to reproductive isolation and incipient speciation.


Characteristics of Pediatric Emergency Revisits After an Asthma-Related Hospitalization.
We identify and characterize factors related to subsequent emergency revisits among children hospitalized for asthma. This population-based, prospective, observational cohort included children aged 2 to 16 years, hospitalized for asthma at an urban pediatric facility and followed for greater than or equal to 12 months. The primary outcome was asthma-related emergency revisit within 12 months of discharge. Revisits were identified by billing codes, respiratory chief complaints, and medications administered (eg, albuterol, systemic corticosteroids), dispensed, or prescribed. Predictors and covariates include demographic, socioeconomic, access, and environmental exposure variables collected during index admission. Multivariable logistic regression was used to evaluate the association between predictors and odds of asthma-related revisit. A total of 671 children were enrolled; the majority were boys (65%), aged 4 to 11 years (59%), black (59%), and publicly insured (73%). There were 274 patients (41%) who were treated for asthma-related emergency revisits within 12 months of the index admission. In adjusted models, younger children, black children, children with excellent reported access to primary care, and children with a history of inhaled steroids were more likely to experience emergency revisits. Low income, detectable cotinine levels, and traffic exposure did not independently predict revisit. Asthma-related emergency revisit is common after hospitalization, with more than 40% of children returning within 12 months. Socioeconomic and exposure-related risk factors typically predictive of asthma morbidity were not independently associated with emergency revisit among children in this cohort.


The Crucial Questions on Synovial Biopsy: When, Why, Who, What, Where, and How?
In the majority of joint diseases, changes in the organization of the synovial architecture appear early. Synovial tissue analysis might provide useful information for the diagnosis, especially in atypical and rare joint disorders, and might have a value in case of undifferentiated inflammatory arthritis, by improving disease classification. After patient selection, it is crucial to address the dialogue between the clinician and the pathologist for adequately handling the sample, allowing identifying histological patterns depending on the clinical suspicion. Moreover, synovial tissue analysis gives insight into disease progression helping patient stratification, by working as an actionable and mechanistic biomarker. Finally, it contributes to an understanding of joint disease pathogenesis holding promise for identifying new synovial biomarkers and developing new therapeutic strategies. All of the indications mentioned above are not so far from being investigated in everyday clinical practice in tertiary referral hospitals, thanks to the great feasibility and safety of old and more recent techniques such as ultrasound-guided needle biopsy and needle arthroscopy. Thus, even in rheumatology clinical practice, pathobiology might be a key component in the management and treatment decision-making process. This review aims to examine some essential and crucial points regarding why, when, where, and how to perform a synovial biopsy in clinical practice and research settings and what information you might expect after a proper patient selection.


Hiatal hernial ulcers: clinical features and follow-up.
We describe the clinical features and therapeutic outcome in 49 patients in whom benign gastric ulceration of an hiatal hernia was demonstrated endoscopically. Hiatal hernia ulcers accounted for 10% of all benign gastric ulcers. The typical patient was an elderly female with a history of dyspepsia who was receiving non-steroidal anti-inflammatory drugs. Twenty-seven (55%) patients had evidence of haemorrhage (acute in 15; chronic in 12) from the hiatal hernial ulcer at presentation. In 16 (33%) patients, symptoms attributable to haemorrhage constituted the sole clinical evidence of the hiatal hernial ulcer. Acute haemorrhage from hiatal hernial ulcers was associated with non-steroidal anti-inflammatory drug (NSAID) treatment (P less than 0.05). Chronic blood loss from hiatal hernial ulcers was associated with female gender (P less than 0.005) but not with NSAID treatment. Hiatal hernial ulcers healed slowly in response to medical treatment with H2-receptor antagonists (median time to healing 12 weeks). Surgical treatment may be the therapy of choice for hiatal hernial ulcers because of the high complication rate, poor response to medical therapy, and the apparent predominance of mechanical aetiological factors.


Community-acquired pneumonia in children in Lambarene, Gabon.
Community-acquired pneumonia (CAP) accounts for more than two million deaths per year in children < 5 years of age. Recognition of pathogens is vital for guiding antibiotic treatment. In Gabon, no epidemiologic data on childhood CAP were available to help guide antibiotic therapy. We conducted a prospective, hospital-based, cross-sectional survey at the Albert Schweitzer Hospital, Lambarene, Gabon, to assess the importance of atypical organisms (Chlamydia pneumoniae, Mycoplasma pneumoniae, Bordetella pertussis, and Legionella pneumophila) and Streptococcus pneumoniae in the etiology of CAP in children by means of real-time polymerase chain reaction, cell culture, and serology. Collectively, atypical bacteria accounted for 11% of cases with a special emphasis on B. pertussis, accounting for 6% of cases. Clinical differentiation of atypical from typical pneumonia in children remains challenging. Molecular diagnostic methods offer fast and highly sensitive diagnostic tools and would be able to help guide antimicrobial therapy in rural areas where follow-up is difficult.


Anti-inflammatory effect of yoghurt in an experimental inflammatory bowel disease in mouse.
Inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) is the clinical outcome of three interactive pathogenic factors: genetic susceptibility, environmental triggers and immune dis-regulation. At present, only the immune response is targeted by most therapeutic or preventive strategies. The beneficial effect of yoghurt on health as well as its immunomodulator effect on the gut immune system is well documented. The aim of this work was to study the possible beneficial effects of yoghurt consumption on an experimental model of IBD in mice. Balb/c mice were fed with yoghurt for 10 consecutive days. At the end of the feeding period the mice received three inoculations of 2, 4, 6-trinitrobenzene sulphonic acid (TNBS) solutions once a week for 3 consecutive weeks. After TNBS instillation the mice received yoghurt again for 10 consecutive days. IBD control received only TNBS. After treatments we analysed the number of IgA-secreting cells, CD4+, CD8+ T cells population and the number of apoptotic cells in the large intestine. The number of erythrocytes and leucocytes in peripheral blood mononuclear cells (PBMCs) was also determined. We demonstrated the antinflammatory effect of yoghurt in an experimental model of IBD induced by TNBS. The effect was mediated by an increase in the number of the IgA+cells, a decrease in CD8+ population and by the induction of apoptosis of the infiltrative cells in the large intestine.


The De Hemptinne inhaler.
The De Hemptinne ether inhaler was presented to the Royal Academy of Medicine of Belgium in February, 1847 by Auguste De Hemptinne, a pharmacist. This article outlines the details of construction and use of this device. A comparison to contemporary inhalers is also made.


Likelihood of Lung Cancer Screening by Poor Health Status and Race and Ethnicity in US Adults, 2017 to 2020.
Lung cancer screening (LCS) via low-dose chest computed tomography can prevent mortality through surgical resection of early-stage cancers, but it is unknown whether poor health is associated with screening. Though LCS may be associated with better outcomes for non-Hispanic Black individuals, it is unknown whether racial or ethnic disparities exist in LCS use. To determine whether health status is associated with LCS and whether racial or ethnic disparities are associated with LCS independently of health status. This cross-sectional, population-based study of community-dwelling US adults used data from Behavioral Risk Factor Surveillance System annual surveys, 2017 to 2020. Participants were aged 55 to 79 years, with a less than 30 pack-year smoking history, and were current smokers or those who quit within 15 years. Data were analyzed from August to November 2021. Self-reported health status and race and ethnicity. Self-reported LCS in the last 12 months. Of 14 550 individuals (7802 men [55.5%]; 7527 [55.0%] aged 65-79 years [percentages are weighted]), representing 3.68 million US residents, 17.0% (95% CI, 15.1%-18.9%) reported undergoing LCS. The prevalence of LCS was lower among non-Hispanic Black than non-Hispanic White individuals but not to a significant degree (12.0% [95% CI, 4.3%-19.7%] vs 17.5% [95% CI, 15.6%-19.5%]; P = .57). Health status was associated with LCS: 468 individuals in poor health vs 96 individuals in excellent health reported LCS (25.2% [95% CI, 20.6%-29.9%] vs 7.6% [95% CI, 5.0%-10.3%]; P < .001), and those with difficulty climbing stairs were more likely to report LCS than those without this functional limitation. Adjusting for sociodemographic factors, functional status, and comorbidities, self-rated health status remained associated with LCS (adjusted odds ratio, 1.19 per each 1-step decline in health; 95% CI, 1.03-1.38), and non-Hispanic Black individuals were 53% less likely to report LCS than non-Hispanic White individuals (adjusted odds ratio, 0.47; 95% CI, 0.24-0.90). Results were robust in sensitivity analyses in which health was alternatively quantified as number of comorbidities. LCS in the US is more common among those who may be less likely to benefit from screening because of poor underlying health. Furthermore, racial or ethnic disparities were evident after accounting for health status, with non-Hispanic Black individuals nearly half as likely as non-Hispanic White individuals to report LCS despite the potential for greater benefit of screening this population.


Lymphangiogenesis in kidney and lymph node mediates renal inflammation and fibrosis.
Lymphangiogenesis is associated with chronic kidney disease (CKD) and occurs following kidney transplant. Here, we demonstrate that expanding lymphatic vessels (LVs) in kidneys and corresponding renal draining lymph nodes (RDLNs) play critical roles in promoting intrarenal inflammation and fibrosis following renal injury. Our studies show that lymphangiogenesis in the kidney and RDLN is driven by proliferation of preexisting lymphatic endothelium expressing the essential C-C chemokine ligand 21 (CCL21). New injury-induced LVs also express CCL21, stimulating recruitment of more CCR7+ dendritic cells (DCs) and lymphocytes into both RDLNs and spleen, resulting in a systemic lymphocyte expansion. Injury-induced intrarenal inflammation and fibrosis could be attenuated by blocking the recruitment of CCR7+ cells into RDLN and spleen or inhibiting lymphangiogenesis. Elucidating the role of lymphangiogenesis in promoting intrarenal inflammation and fibrosis provides a key insight that can facilitate the development of novel therapeutic strategies to prevent progression of CKD-associated fibrosis.


Changes in dural sac caliber with standing MRI improve correlation with symptoms of lumbar spinal stenosis.
Weight bearing does alter the dimension of lumbar spinal canal, but no study has analyzed its clinical correlation. This study aims to evaluate whether the changes in dural sac cross-sectional area (DSCA) and sagittal anteroposterior (AP) diameter on standing magnetic resonance imaging (MRI) correlate better with clinical symptoms of lumbar spinal stenosis. Seventy consecutive patients with neurogenic claudication were prospectively recruited to undergo a 0.25-T MRI examination performed in supine and standing positions. Clinical symptoms including the walking distance, Visual Analogue Score of leg pain, Chinese Oswestry Disability Index, and short form-12 were assessed. DSCA and sagittal AP diameter at the most constricted spinal level on supine and standing positions were measured and correlated with each clinical symptom by Pearson correlation coefficients (r). DSCA and AP diameter on standing MRI and their % changes from supine to standing showed significant (r = 0.55, 0.53, -0.44, -0.43; p < 0.001) and better correlations than those on supine MRI (r = 0.39, 0.42; p < 0.001) with walking distance. Significant correlations were also found between dural sac calibers on standing MRI and leg pain scores (r = -0.20, r = -0.25; p < 0.05). Patients walking ≤500 m had a significantly smaller DSCA, narrower AP diameter and greater % change in dural sac calibers (p < 0.01) than those walking >500 m. A >30% reduction of DSCA and AP diameter was observed in patients with worse claudication distance (p < 0.05). DSCA and sagittal AP diameter on standing MRI correlate significantly and better than findings on supine MRI with claudication symptoms. Standing MRI demonstrates dynamic changes of dural sac and provides an additional value to supine MRI in correlating clinical symptoms of lumbar spinal stenosis.


A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC.
The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.


Determinants of spontaneous activity in networks of cultured hippocampus.
The brain generates extensive spontaneous network activity patterns, even in the absence of extrinsic afferents. While the cognitive correlates of these complex activities are being unraveled, the rules that govern the generation, synchronization and spread of different patterns of intrinsic network activity in the brain are still enigmatic. Using hippocampal neurons grown in dissociated cultures, we are able to study these rules. Network activity emerges at 3-7 days in-vitro (DIV) independent of either ongoing excitatory or inhibitory synaptic activity. Network activity matures over the following several weeks in culture, when it becomes sensitive to chronic drug treatment. The size of the network determines its properties, such that dense networks have higher rates of less synchronized activity than that of sparse networks, which are more synchronized but rhythm at lower rates. Large networks cannot be triggered to fire by activating a single neuron. Small networks, on the other hand, do not burst spontaneously, but can be made to discharge a network burst by stimulating a single neuron. Thus, the strength of connectivity is inversely correlated with spontaneous activity and synchronicity. In the absence of confirmed 'leader' neurons, synchronous bursting network activity appears to be triggered by at least several local subthreshold synaptic events. We conclude that networks of neurons in culture can produce spontaneous synchronized activity and serve as a viable model system for the analysis of the rules that govern network activity in the brain.


Biallelic PI4KA variants cause neurological, intestinal and immunological disease.
Phosphatidylinositol 4-kinase IIIα (PI4KIIIα/PI4KA/OMIM:600286) is a lipid kinase generating phosphatidylinositol 4-phosphate (PI4P), a membrane phospholipid with critical roles in the physiology of multiple cell types. PI4KIIIα's role in PI4P generation requires its assembly into a heterotetrameric complex with EFR3, TTC7 and FAM126. Sequence alterations in two of these molecular partners, TTC7 (encoded by TTC7A or TCC7B) and FAM126, have been associated with a heterogeneous group of either neurological (FAM126A) or intestinal and immunological (TTC7A) conditions. Here we show that biallelic PI4KA sequence alterations in humans are associated with neurological disease, in particular hypomyelinating leukodystrophy. In addition, affected individuals may present with inflammatory bowel disease, multiple intestinal atresia and combined immunodeficiency. Our cellular, biochemical and structural modelling studies indicate that PI4KA-associated phenotypical outcomes probably stem from impairment of PI4KIIIα-TTC7-FAM126's organ-specific functions, due to defective catalytic activity or altered intra-complex functional interactions. Together, these data define PI4KA gene alteration as a cause of a variable phenotypical spectrum and provide fundamental new insight into the combinatorial biology of the PI4KIIIα-FAM126-TTC7-EFR3 molecular complex.


HLA-B*15:21 and carbamazepine-induced Stevens-Johnson syndrome: pooled-data and in silico analysis.
HLA-B*15:02 screening before carbamazepine (CBZ) prescription in Asian populations is the recommended practice to prevent CBZ-induced Stevens-Johnson syndrome (CBZ-SJS). However, a number of patients have developed CBZ-SJS even having no HLA-B*15:02. Herein, we present the case of a Thai patient who had a negative HLA-B*15:02 screening result but later developed CBZ-SJS. Further HLA typing revealed HLA-B*15:21/B*13:01. HLA-B*15:21 is a member of the HLA-B75 serotype and is commonly found in Southeast Asian populations. Based on this case, we hypothesised that if all HLA-B*15:02 carriers were prevented from CBZ prescription, another common HLA-B75 serotype marker would show its association with CBZ-SJS. To test this hypothesis, we pooled data from previous association studies in Asian populations, excluded all cases with HLA-B*15:02, and analysed the association significance of HLA-B75 serotype markers. A significant association was found between CBZ-SJS and HLA-B*15:21 and HLA-B*15:11. We also applied an in silico analysis and found that all HLA-B75 serotype molecules shared similar capability in binding the CBZ molecule. In summary, this report provides the first evidence of a positive association between HLA-B*15:21 and CBZ-SJS and the first in silico analysis of CBZ binding sites and details of the molecular behaviour of HLA-B75 molecule to explain its molecular action.


FADD phosphorylation contributes to development of renal fibrosis by accelerating epithelial-mesenchymal transition.
FADD, a classical apoptotic signaling adaptor, has recently been reported to exhibit a series of non-apoptotic functions. Here, we report that FADD may play a critical role in the development of renal fibrosis. Neutrophil infiltration in the renal interstitial part, glomerular mesangial cell proliferation, and base-membrane thickening were observed in FADD-D mice by H&E, PAS, and PASM staining. Immunofluorescence analysis revealed that macrophage infiltration was significantly enhanced in FADD-D mice. Renal fibrosis might be induced by IgA nephritis in FADD-D mice as evidenced by increased Ki67 and type IV collagen. Additionally, the levels of α-SMA, Fibronectin, and Vimentin were also found to be elevated. Mechanism study indicated that the TLR4/myD88/NF-κB signaling pathway was activated in FADD-D mice. Moreover, FADD phosphorylation activated the mTOR and TGF-β/Smad pathway and accelerated the process of epithelial mesenchymal transition. Further studies indicated that the TGF-β1 pathway was also activated and the process of EMT was accelerated in both FADD-disrupted HEK293 cells and FADD-deficient MES cells. Thus, we concluded that FADD phosphorylation could lead to IgA nephritis and eventually result in renal fibrosis. Taken together, our study provides evidence, for the first time, that FADD, especially in its phosphorylated form, has an effect on the development of renal fibrosis.Abbreviations: FADD: FAS-associated protein with death domain; DED: death effector domain; DD: death domain; CKD: chronic kidney disease; ECM: extracellular matrix; ESRD: end-stage renal disease; RRT: renal replacement therapy; H&E: hematoxylin and eosin; PASM: periodic acid silver methenamine.


Orphan Three-Finger Toxins Bind at Tissue Factor-Factor VIIa Interface to Inhibit Factor X Activation: Identification of Functional Site by Docking.
Three-finger toxins (3FTxs) contribute to toxicity of venomous snakes belonging to the family Elapidae. Currently, functions of a considerable proportion of 3FTxs are still unknown. Here, we describe the function of orphan group I 3FTxs consisting of four members. We also identified a new member of this group by sequencing a transcript isolated from Naja naja venom. This transcript, named najalexin, is identical to that previously described 3FTx from Naja atra venom gland, and shared high sequence identity with ringhalexin from Hemachatus haemachatus and a hypothetical protein from Ophiophagus hannah (here named as ophiolexin). The three-dimensional structure, as predicted by molecular modeling, showed that najalexin and ophiolexin share the same conserved structural organization as ringhalexin and other 3FTxs. Since ringhalexin inhibits the activation of factor X by the tissue factor-factor VIIa complex (TF-FVIIa), we evaluated the interaction of this group of 3FTxs with all components using in silico protein-protein docking studies. The binding of orphan group I 3FTxs to TF-FVIIa complex appears to be driven by their interaction with TF. They bind to fibronectin domain closer to the 170-loop of the FVIIa heavy chain to inhibit factor X activation. The docking studies reveal that functional site residues Tyr7, Lys9, Glu12, Lys26, Arg34, Leu35, Arg40, Val55, Asp56, Cys57, Cys58, and Arg65 on these 3FTxs are crucial for interaction. In silico replacement of these residues by Ala resulted in significant effects in the binding energies. Furthermore, these functional residues are not found in other groups of 3FTxs, which exhibit distinct pharmacological properties.


A reinvestigation of seroconversion rates in hepatits B-vaccinated individuals.
The purpose of this study was to examine whether the hepatitis B seroconversion rates in a small sample of subjects reflected that of the published rates, regardless of HIV status, after a hepatitis B vaccination series was completed while following strict vaccine protocols. The study, which had a nonexperimental, correlational cross-sectional design, took place at a community clinic in Laguna Beach, CA. Participants comprised 100, predominantly White, men aged 18-65 years (mean 39.2 years) who were hepatitis B naive, regardless of immune status. After receiving a primary vaccine series for hepatitis B, participants were tested for seroconversion to immune status. Seroconversion to the immune state occurred in 78.6% of the non-immunocompromised, HIV-negative participants (n = 50), who had received the standard three-dose regimen of the vaccine, and in 77% of the immunocompromised, HIV-positive participants (n = 48), who had received the recommended modified three-double-dose regimen. The manufacturer-published rates of seroconversion are 90-100%, depending upon the population. These findings highlight a need for further study to validate or reveal deficits in current vaccine protocols for individuals who are vaccinated against hepatitis B, including health care workers, the immune-compromised and other high-risk populations.


Biodegradation of methyl tert-butyl ether and other fuel oxygenates by a new strain, Mycobacterium austroafricanum IFP 2012.
A strain that efficiently degraded methyl tert-butyl ether (MTBE) was obtained by initial selection on the recalcitrant compound tert-butyl alcohol (TBA). This strain, a gram-positive methylotrophic bacterium identified as Mycobacterium austroafricanum IFP 2012, was also able to degrade tert-amyl methyl ether and tert-amyl alcohol. Ethyl tert-butyl ether was weakly degraded. tert-Butyl formate and 2-hydroxy isobutyrate (HIBA), two intermediates in the MTBE catabolism pathway, were detected during growth on MTBE. A positive effect of Co2+ during growth of M. austroafricanum IFP 2012 on HIBA was demonstrated. The specific rate of MTBE degradation was 0.6 mmol/h/g (dry weight) of cells, and the biomass yield on MTBE was 0.44 g (dry weight) per g of MTBE. MTBE, TBA, and HIBA degradation activities were induced by MTBE and TBA, and TBA was a good inducer. Involvement of at least one monooxygenase during degradation of MTBE and TBA was shown by (i) the requirement for oxygen, (ii) the production of propylene epoxide from propylene by MTBE- or TBA- grown cells, and (iii) the inhibition of MTBE or TBA degradation and of propylene epoxide production by acetylene. No cytochrome P-450 was detected in MTBE- or TBA-grown cells. Similar protein profiles were obtained after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of crude extracts from MTBE- and TBA-grown cells. Among the polypeptides induced by these substrates, two polypeptides (66 and 27 kDa) exhibited strong similarities with known oxidoreductases.


Isolation and characterization of the centromere from chromosome V (CEN5) of Saccharomyces cerevisiae.
We have cloned a functional centromeric DNA sequence from Saccharomyces cerevisiae. Using the 2 mu chromosome-loss mapping technique and meiotic tetrad analysis, we have identified this DNA sequence as the centromere of chromosome V (CEN5). The CEN5 sequence has been localized on an 1,100-base-pair BamHI-BglII restriction fragment. Plasmids containing CEN5 and an autonomously replicating sequence are mitotically stable in S. cerevisiae and segregate in a Mendelian fashion during meiosis.


Clinical outcomes of platinum-based chemotherapy according to T790M mutation status in EGFR-positive non-small cell lung cancer patients after initial EGFR-TKI failure.
Emergence of the T790M point mutation in exon 20 of epidermal growth factor receptor (EGFR) is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). It remains unclear whether the efficacy of platinum-doublet chemotherapy is impacted by the presence of the T790M mutation. The aim of this study is to evaluate the efficacy of platinum-doublet chemotherapy after initial EGFR-TKI failure according to the EGFR T790M in patients with advanced EGFR-mutation-positive non-small cell lung cancer (NSCLC). We retrospectively reviewed 50 patients with advanced NSCLC harboring EGFR mutations who underwent rebiopsy to evaluate their T790M mutation status after development of resistance to first-line EGFR-TKIs (gefitinib, erlotinib, or afatinib) and were subsequently treated with second-line platinum-based chemotherapy. The median age of patients was 63 years (range, 35-77 years), and 15 (30%) patients were male. Histological examination revealed that all patients had adenocarcinoma, 39 (78%) had stage IV disease, and 11 (22%) patients had postoperative recurrence. Of all, 17 patients (34%) had the T790M mutation by rebiopsy after initial EGFR-TKI failure. The overall response rate (ORR) of platinum-doublet chemotherapy was 24% for both T790M-positive and T790M-negative patients. There was no significant difference in the progression-free survival (PFS) in T790M-positive and T790M-negative patients (median PFS, 6.0 months vs. 5.1 months; 95% confidence interval [CI], 0.1-11.9 vs. 4.4-5.8; hazard ratio [HR], 0.90 [95%CI, 0.49-1.66]; P=0.7210). None of the factors were predictive of platinum-doublet chemotherapy efficacy by the multivariate analysis. There were no differences in clinical outcomes of platinum-based chemotherapy according to the T790M status of NSCLC patients.


Rapid syncytium formation induced by Moloney murine sarcoma virus in 3T3/NIH cells and its delay by mouse interferon.
Moloney murine sarcoma virus (MSV) clone 124 was found to induce rapid syncytium formation upon infection of 3T3/NIH at a high multiplicity of infection. This effect became apparent, by light microscopy, within 1 to 2 hours, whereas by scanning electron microscopy, clusters of 4 to 25 cells were seen in their initial steps of syncytium formation within 20 to 30 minutes after virus addition. It appeared that the cell fusion was initiated by connection between the cells through virus bound to their surface. After a few more hours several neighbouring syncytia fused into giant cells containing over a hundred nuclei. Though MSV (124) stocks contained also some MLV it appeared that the syncytium inducing activity was related to the MSV particles. MLV particles were not only incapable to induce syncytium formation, they even interfered with this activity of MSV. The MSV-induced cell fusion required the adsorption of intact virions, but was independent on protein synthesis. Mouse interferon remarkably reduced the rate of syncytium development.


Different stabilities of two AMP-forming acetyl-CoA synthetases from Phycomyces blakesleeanus expressed under different environmental conditions.
The stability of acetyl-CoA synthetases (ACS1 and ACS2) from P. blakesleeanus against temperature, urea and trypsin was studied and compared. Thermal inactivation of ACS1 was biphasic, while that of ACS2 was monophasic. The thermodynamic parameters calculated from the inactivation profiles show ACS2 to be a more thermostable enzyme than ACS1. The presence of ATP and Mg(2+) exerted a protective effect on both enzymes, and led to a marked increase in the E(a), DeltaH(not =), DeltaS(not =) and DeltaG(not =) values. ACS2 is also much more stable against denaturation with urea; the estimates of DeltaG(w) (free energy change for protein unfolding at zero denaturant concentration) were 9.4 kJ mol(-1) and 18.1 kJ mol(-1) for ACS1 and ACS2, respectively. Finally, a half-life of 44.5 min for ACS2 versus the 21 min for ACS1 indicates that ACS2 is more stable than ACS1 against digestion by trypsin. These results seem to show that ACS2 is more rigid overall than ACS1, which may be essential for preserving its catalytic activity in the stress situation in which it is expressed.


The development of pulmonary lesions associated with dead adult D. immitis in naive dogs.
The sequential response of the lung to the death of adult D. immitis has not been reported. To determine the time sequence and severity of pulmonary lesions following the death of D. immitis, light microscopy was used to follow 36 dogs, detailing the respective lesions 1-35 days after insertion of dead D. immitis or of control polyvinyl chloride threads. Results showed that dogs exposed to dead filariae developed more severe pulmonary arterial disease than did those exposed to inert threads. Severe pulmonary lesions occurred at 5-9 days post insertion with the right caudal lobes being the most affected, both macro and microscopically. These findings suggest that this was a suitable model for the study of this parasite-host interaction and that 5-9 days following insertion of dead D. immitis was the most intensive period of host reactivity.


Endoscopic treatment of nonstricture-related benign biliary diseases using covered self-expandable metal stents.
Nonstricture benign biliary diseases (BBDs) such as leaks, perforations, and bleeding, have been traditionally managed by placement of one or more plastic stents. Emerging data support the use of covered, self-expandable, metal stents (CSEMSs). The aim of this study was to assess the outcomes of endoscopic temporary placement of CSEMS in patients with nonstricture BBD. This was a retrospective study of CSEMS placement for BBD between May 2005 and August 2013 at two tertiary care centers. The main outcome measures were resolution of perforation, bleeding, leak, and adverse events related to CSEMS treatment. A total of 87 patients were included (median age 62 years [range 18 - 86]). Indications for stent placement were bile leaks (n = 35, 40 %), bleeding (n = 27, 31 %), perforation (n = 18, 21 %), and other conditions (n = 7, 8 %). Fully and partially covered 8 - 10-mm diameter CSEMS were placed and subsequently removed in all 87 patients (100 %). Resolution of the underlying problem was achieved for 33 bile leaks (94 %), 25 bleedings (93 %), 18 perforations (100 %), and for 3 cases with other indications (43 %). The median duration of stenting was 9 weeks in patients with biliary leaks, 3 weeks for bleeding, and 9.5 weeks for perforations. Median follow-up was 82 weeks after stent removal. Seven adverse events occurred, including cholangitis in six patients (7 %), and tissue hyperplasia leading to difficulty in the removal of a partially covered SEMS in one patient. Nonstricture BBD can be effectively and safely treated with the short term placement of CSEMS. .


Gender-Specific Differences in Peritoneal Dialysis.
Gender-specific differences between patients on renal replacement therapy have so far rarely been investigated. In the present study we aimed to describe gender-specific differences in a large cohort of peritoneal dialysis (PD) patients. Clinical information for all patients who started PD at our center has been collected since the start of the PD-program in 1979. We used Cox regression to examine associations between technique failure and gender. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs). A total of 745 patients (315 women and 430 men with a median age of 57 years; IQR 43-67) started PD between 1979 and 2015 in our center. Women were significantly younger at PD start 54 (40-65) years vs. 58 (47-68) years, p<0.001. Within the last almost 15 years, more man than women started PD, but technical survival rates were significantly better in female compared to men (HR=0.662, CI 95% (0.496-0.885) P=0.005). Cardiovascular events were the main cause of death over the study period in both sexes, but decreased over time. Additionally, death due to PD-associated peritonitis decreased significantly over the three decades in both sexes. Our data suggest that technical survival rates were significantly better in female compared to men over three decades and death due to cardiovascular events and PD-associated peritonitis decreased significantly over the three decades in both sexes.


Foundations of immunohistochemistry. A practical review.
In this review of immunohistochemical methods, an emphasis is placed on the historic development of enzyme-linked procedures that are applicable to antigen localization in routinely processed tissues. As the technology of immunohistochemistry has improved, a bewildering montage of antibodies, bridges, labels, and chromogens has evolved. Each has its apparent advantages, yet each also has certain limitations. Admittedly, a comprehensive review of these different methods is beyond the scope of this forum, and several immunohistochemical techniques in current use will not be discussed in detail. Still, the principles of horseradish peroxidase-linked procedures, as described in this review, form the foundation of contemporary diagnostic immunohistology. They provide not only a powerful method of antigen detection, but also a model with which to compare recent and future innovations.


Regulating the marketing of foods for infants and young children: Lessons from assessment of gaps in monitoring and enforcement in Thailand.
Breast milk substitute (BMS) marketing harms breastfeeding and public health. To control BMS marketing, the Member States of the World Health Organization is called upon to adopt all provisions of the International Code of Marketing of Breastmilk Substitutes (the Code) into national law. In 2017, Thailand adopted many provisions of the Code through the Control of Marketing Promotion of Infant and Young Child Food Act B.E. 2560 (the Act), including the establishment of a compliance monitoring system and enforcement mechanisms. Nevertheless, recent research showed widespread violations. This study aims to assess gaps in the monitoring system and the Act's enforcement in its first three years of operation. This qualitative research study employed in-depth interviews between April and June 2020 with 34 key informants (KIs) from the Thai government, academia and civil society organisations. KIs identified gaps in six areas that could be mitigated to increase compliance with the Act. These gaps are unclear provisions on coverage of the Act; communications with retailers and the public; lack of strong direction and processes; inadequate budget allocations; skilled and confident human resources; and external factors which facilitate BMS marketing. Recommendations may be relevant for other countries and include revising and clarifying the Act, developing targeted communication strategies; providing clear monitoring direction including through setting key performance indicators related to the Act; and providing sufficient budget and training for authorised and support officers. Strengthening the health system and workplace support for breastfeeding and social marketing would also help address wider structural factors.


Burnout and Engagement: Relative Importance of Predictors and Outcomes in Two Health Care Worker Samples.
This study's purpose was twofold: first, to examine the relative importance of job demands and resources as predictors of burnout and engagement, and second, the relative importance of engagement and burnout related to health, depressive symptoms, work ability, organizational commitment, and turnover intentions in two samples of health care workers. Nurse leaders ( n = 162) and licensed emergency medical technicians (EMTs; n = 102) completed surveys. In both samples, job demands predicted burnout more strongly than job resources, and job resources predicted engagement more strongly than job demands. Engagement held more weight than burnout for predicting commitment, and burnout held more weight for predicting health outcomes, depressive symptoms, and work ability. Results have implications for the design, evaluation, and effectiveness of workplace interventions to reduce burnout and improve engagement among health care workers. Actionable recommendations for increasing engagement and decreasing burnout in health care organizations are provided.


Association of age, race, and obstetric history with urinary symptoms among women in the Nurses' Health Study.
The purpose of this study was to better understand associations among age, race, obstetric history, and urinary incontinence in women. Race and obstetric history were assessed through the use of biennial mailed questionnaires from 1976 to 1996 among participants of the Nurses' Health Study. In 1996, 83,168 women aged 50 to 75 years reported their frequency of leaking urine and quantity leaked. We used logistic regression to calculate multivariate-adjusted odds ratios and 95% CIs for the relation of risk factors to leaking urine. Overall, 34.1% of the women reported leaking urine at least once per month during the previous 12 months; this prevalence was lowest in the black women (21.2%). After potential confounders were controlled, there were strong trends of increasing prevalence of occasional and frequent leaking with increasing age (P trend <.0001). There was also increasing prevalence of leaking urine with increasing parity; for example, compared with nulliparous women, the odds ratio for frequent leaking was 1.72 (95% CI, 1.55-1.90) among those with >/=5 births. Odds ratios that were associated with parity were higher in women aged <60 years than in women aged >/=60 years. Age at first birth of >35 years was associated with a slight elevation in frequent leaking compared with women with age at first birth from 21 to 25 years but was stronger for women with age at first birth of <21 years (OR, 1.27; 95% CI, 1.13-1.42). In these women, leaking urine is common; this condition is most prevalent in white women, in older women, in parous women, and in women with a younger age at first birth.


Erupted composite odontoma associated with malformed teeth - unusual dental aberrations following maxillofacial trauma.
Tooth development may be hampered following traumatic injuries to maxilla or mandible. The developmental deviations that occur in a tooth bud in the line of a jaw fracture range from agenesis to hamartomatous proliferation. Odontomas are benign odontogenic hard tissue tumors, which are hamartomas characterized by slow growth and non-aggressive behavior. 'Erupted odontoma' is a term used to specifically denote odontomas, which are exposed into the oral cavity. These are rare entities with only 25-30 cases being reported so far in the dental literature. This clinical report is pertaining to a rare case of an erupted odontoma in an adolescent patient which was presenting as a hard tissue outgrowth along with an extra-oral sinus in the posterior mandibular region. The surgical excision of the odontoma along with the associated malformed teeth resulted in resolution of pain and sinus discharge associated with this lesion. Erupted odontomas need to be considered in the differential diagnosis of hard tissue projections or outgrowths in the site of past maxillofacial injuries. Surgical excision of these lesions enable resolution of patient symptoms associated with this condition as evidenced in the present case and in other cases cited in the literature. The erupted odontoma attached to malformed molars and presenting with signs and symptoms suggestive of osteomyelitis is a rare combination of developmental aberrations following maxillofacial injury.


[Automatic analysis of the electromyogram: technique and results in healthy and ill subjects].
The EMG signal was recorded from the brachial biceps in 12 different needle positions, in control subjects and patients, all the subjects exerting a standard effort. The signal was automatically analysed, off-line, and 18 parameters were computed from the signal waves. These parameters described the electrical activity of the muscle. The comparison between results from control subjects and patients showed significant differences for 13 parameters. Eight of them allowed one to separate neurogenic and myogenic patients. For each parameter, the observed variations from the normal exhibited opposite values for neurogenic and myogenic subjects. Some neurogenic patients with apparently normal biceps had a pathological quantitative analysis. The method could thus be used to reveal early disturbances.


Immunomodulatory Strategies Targeting Dendritic Cells to Improve Corneal Graft Survival.
Even though the cornea is regarded as an immune-privileged tissue, transplantation always comes with the risk of rejection due to mismatches between donor and recipient. It is common sense that an alternative to corticosteroids as the current gold standard for treatment of corneal transplantation is needed. Since blood and lymphatic vessels have been identified as a severe risk factor for corneal allograft survival, much research has focused on vessel regression or inhibition of hem- and lymphangiogenesis in general. However, lymphatic vessels have been identified as required for the inflammation's resolution. Therefore, targeting other players of corneal engraftment could reveal new therapeutic strategies. The establishment of a tolerogenic microenvironment at the graft site would leave the recipient with the ability to manage pathogenic conditions independent from transplantation. Dendritic cells (DCs) as the central player of the immune system represent a target that allows the induction of tolerogenic mechanisms by many different strategies. These strategies are reviewed in this article with regard to their success in corneal transplantation.


Joint trajectories of cigarette smoking and depressive symptoms from the mid-20s to the mid-30s predicting generalized anxiety disorder.
The current study examines longitudinal patterns of cigarette smoking and depressive symptoms as predictors of generalized anxiety disorder using data from the Harlem Longitudinal Development Study. There were 674 African American (53%) and Puerto Rican (47%) participants. Among the 674 participants, 60% were females. In the logistic regression analyses, the indicators of membership in each of the joint trajectories of cigarette smoking and depressive symptoms from the mid-20s to the mid-30s were used as the independent variables, and the diagnosis of generalized anxiety disorder in the mid-30s was used as the dependent variable. The high cigarette smoking with high depressive symptoms group and the low cigarette smoking with high depressive symptoms group were associated with an increased likelihood of having generalized anxiety disorder as compared to the no cigarette smoking with low depressive symptoms group. The findings shed light on the prevention and treatment of generalized anxiety disorder.


The importance of bidirectional block during pulmonary vein isolation.
The definition of a successful ablation of atrial fibrillation can vary among electrophysiologists. A commonly described endpoint is bidirectional block of the four pulmonary veins. A case is described in which entrance block into a pulmonary vein was achieved early during pulmonary vein isolation. However, triggers from the pulmonary vein continued to conduct into the atrium, revealing the block was only unidirectional. Further ablation resulted in true electrical isolation and highlights the importance of achieving bidirectional block.


Advances in anticoagulation management of patients undergoing cardioversion of nonvalvular atrial fibrillation.
Atrial fibrillation (AF) is a major cause of stroke. The restoration of sinus rhythm through cardioversion, either chemical or electrical is a common practice. Interestingly, there is an incremental increase from the baseline risk for embolisation in the immediate post-cardioversion period, with most events occurring within 10 days from cardioversion. Especially patients with recent onset AF show the lowest rates of antithrombotic therapy, while having a high stroke risk. Despite the increased risk for embolisation, anticoagulation in patients undergoing cardioversion of atrial fibrillation is often inadequate. Moreover, since the implementation of non-vitamin K antagonists oral anticoagulants (DOACs) there are several therapeutic approaches for pericardioversion anticoagulant therapy and not all suits to all patients. In addition, the extensive use of transesophageal echocardiography provides an alternative strategy, especially useful for patients of high haemorrhagic risk. In this review article, we aim to provide an update on the anticoagulation strategies for patients undergoing cardioversion of non-valvular atrial fibrillation in the advent of the use of DOACs.


Pharmacology on microfluidics: multimodal analysis for studying cell-cell interaction.
Understanding the mechanisms of cell-cell interaction is a key unanswered question in modern pharmacology, given crosstalk defects are at the basis of many pathologies. Microfluidics represents a valuable tool for analyzing intercellular communication mediated by transmission of soluble signals, as occurring for example between neurons and glial cells in neuroinflammation, or between tumor and surrounding cells in cancer. However, the use of microfluidics for studying cell behavior still encompasses many technical and biological challenges. In this review, a state of the art of successes, potentials and limitations of microfluidics applied to key biological questions in modern pharmacology is analyzed and commented.


Review of a pilot quality-assessment program for interpretative comments.
Interpretative commenting constitutes an important aspect of the post-analytical phase in chemical pathology, but has only recently been the subject of quality assessment. The Royal College of Pathologists of Australasia (RCPA)-Australasian Association of Clinical Biochemists (AACB) Chemical Pathology Patient Report Comments Program is currently in its third year, having started in 2000 as a pilot program. We present a review of the pilot program. The program is aimed at individuals rather than laboratories. Two cases were circulated to participants of the Chemical Pathology Quality Assurance Program every month over a 6-month period. The case report contained the age and sex of the patient, together with brief clinical notes, the biochemistry results for commenting and other information of relevance. Three lines of space were given for the comment. The comments received from participants were broken down into their components and translated into common key phrases for the purpose of summarization and analysis. A histogram of the frequency of use of the common key phrases was generated. The comments or the key phrases were not given scores or marks, nor was any other indication given as to the appropriateness of their comments. This approach of simple peer-group comparison of comments without any assessment of the appropriateness of the comments was found to be inadequate; thus, when the program continues, key phrases will be classified according to degree of appropriateness and a suggested comment for each case will be proposed by an 'expert' panel. The program can serve a useful role in continuing education. Clinical biochemists and trainees who add interpretative comments to results produced by their laboratory, or give interpretative advice over the telephone, may potentially benefit from participating in this program.


Shed GP of Ebola virus triggers immune activation and increased vascular permeability.
During Ebola virus (EBOV) infection a significant amount of surface glycoprotein GP is shed from infected cells in a soluble form due to cleavage by cellular metalloprotease TACE. Shed GP and non-structural secreted glycoprotein sGP, both expressed from the same GP gene, have been detected in the blood of human patients and experimentally infected animals. In this study we demonstrate that shed GP could play a particular role during EBOV infection. In effect it binds and activates non-infected dendritic cells and macrophages inducing the secretion of pro- and anti-inflammatory cytokines (TNFα, IL1β, IL6, IL8, IL12p40, and IL1-RA, IL10). Activation of these cells by shed GP correlates with the increase in surface expression of co-stimulatory molecules CD40, CD80, CD83 and CD86. Contrary to shed GP, secreted sGP activates neither DC nor macrophages while it could bind DCs. In this study, we show that shed GP activity is likely mediated through cellular toll-like receptor 4 (TLR4) and is dependent on GP glycosylation. Treatment of cells with anti-TLR4 antibody completely abolishes shed GP-induced activation of cells. We also demonstrate that shed GP activity is negated upon addition of mannose-binding sera lectin MBL, a molecule known to interact with sugar arrays present on the surface of different microorganisms. Furthermore, we highlight the ability of shed GP to affect endothelial cell function both directly and indirectly, demonstrating the interplay between shed GP, systemic cytokine release and increased vascular permeability. In conclusion, shed GP released from virus-infected cells could activate non-infected DCs and macrophages causing the massive release of pro- and anti-inflammatory cytokines and effect vascular permeability. These activities could be at the heart of the excessive and dysregulated inflammatory host reactions to infection and thus contribute to high virus pathogenicity.


MicroRNA-379 acts as a tumor suppressor in non-small cell lung cancer by targeting the IGF‑1R-mediated AKT and ERK pathways.
Lung cancer is one of the most common types of malignancy in humans and is a leading cause of cancer-related deaths among men and women worldwide. Aberrantly expressed microRNAs in non-small cell lung cancer (NSCLC) contribute to tumor occurrence and development as either tumor suppressors or promoters. MicroRNA-379 (miR‑379) is dysregulated in several types of human cancer. However, its expression pattern, role and underlying mechanism in NSCLC progression and metastasis are poorly understood. In this study, assay of reverse transcription-quantitative polymerase chain reaction showed that miR‑379 was downregulated in both NSCLC tissue and cell lines. Low miR‑379 expression in NSCLC tissues was significantly correlated with TNM stage and lymph node metastasis. In addition, functional experiments revealed that restoring the expression of miR‑379 inhibited cell proliferation, migration and invasion of NSCLC. The insulin-like growth factor receptor-1 (IGF‑1R) was identified as a direct target of miR‑379 in NSCLC. IGF‑1R was highly expressed in NSCLC tissues and inversely correlated with miR‑379 expression. Downregulation of IGF‑1R had tumor suppressive roles similar to that of miR‑379 overexpression on NSCLC cell proliferation, migration and invasion. Moreover, the upregulation of IGF‑1R effectively rescued the tumor suppressive roles induced by miR‑379 overexpression in NSCLC. The resumption of the expression of miR‑379 inhibited the activation of AKT and ERK signaling pathways in NSCLC. These findings suggested that miR‑379 acts as a tumor suppressor in NSCLC by directly targeting IGF‑1R and indirectly regulating AKT and ERK signaling pathways. miR‑379 provides novel therapeutic targets for the treatment of patients with this disease.


[The influence of memory disorders on self-evaluation of subjective quality of life among schizophrenic patients].
For the past few years, in the field of psychiatric disorders, measurements of subjective quality of life are integrated as an important criterion of judgment. The use of standardized questionnaires, based on the patients point of view has become widespread. However, in schizophrenic patients, cognitive impairement, and notably memory, is often advanced as a limit to the use of the self-reported questionnaires. In this preliminary study, we investigated in 53 schizophrenic patients, the impact of memory impairment, specifically the episodic memory, on quality of life, taking into account confounding socio-demographic and clinical factors. The memory was assessed using the BEM 84. The patient's subjective quality of life was assessed by the self-reported questionnaire S-QoL. No correlation was found between memory efficiency and quality of life level: patients with severe and non-severe impairment scored all the S-QoL domains similarly. However, the majority of schizophrenic patients could be considered as deficient on a wide assortment of neuropsychological evaluations, in particular in the attention and executive functions. The influence of the whole cognitive impairment of life must be confirmed.


Long-term safety and tolerability of oral tofacitinib in patients with Crohn's disease: results from a phase 2, open-label, 48-week extension study.
Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease. This 48-week open-label extension study primarily investigated long-term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as maintenance therapy in patients with Crohn's disease. Patients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled. Patients in remission (Crohn's disease activity index <150) at baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. A single dose adjustment was allowed after 8 weeks' fixed, open-label treatment. Sixty-two patients received tofacitinib 5 mg b.d.; 88 received 10 mg b.d. Both groups had similar rates of adverse events and serious infections. Crohn's disease worsening was the most frequent adverse event for tofacitinib 5 (33.9%) and 10 mg b.d. (19.3%). Patients not in remission at baseline, receiving 10 mg b.d., had higher rates of serious adverse events (19.3%) and discontinuation attributed to insufficient clinical response (30.7%) vs 5 mg b.d. (8.1% and 9.7%, respectively). At week 48, of patients with baseline remission receiving 5 mg b.d., 87.9% maintained remission and 75.0% sustained remission as observed (46.8% and 38.7%, respectively, by non-responder imputation). Study design prevented between-dose efficacy comparisons. No new safety signals emerged. Although both doses showed generally similar safety outcomes for overall adverse events, serious adverse events were more frequent for tofacitinib 10 than 5 mg b.d. Discontinuation due to insufficient clinical response was lower among patients in remission at baseline. ClinicalTrials.gov: NCT01470599.


Low-Cost Synthesis of Smart Biocompatible Graphene Oxide Reduced Species by Means of GFP.
The aim of this work is focused on the engineering of biocompatible complex systems composed of an inorganic and bio part. Graphene oxide (GO) and/or graphite oxide (GtO) were taken into account as potential substrates to the linkage of the protein such as Anemonia sulcata recombinant green fluorescent protein (rAsGFP). The complex system is obtained through a reduction process between GO/GtO and rAsGFP archiving an environmentally friendly biosynthesis. Spectroscopic measurements support the formation of reduced species. In particular, photoluminescence shows a change in the activity of the protein when a bond is formed, highlighted by a loss of the maximum emission signal of rAsGFP and a redshift of the maximum absorption peak of the GO/GtO species. Moreover, the hemolysis assay reveals a lower value in the presence of less oxidized graphene species providing evidence for a biocompatible material. This singular aspect can be approached as a promising method for circulating pharmaceutical preparations via intravenous administration in the field of drug delivery.


BMI is Associated with the Willingness to Record Diet with a Mobile Food Record among Adults Participating in Dietary Interventions.
Image-based dietary assessment methods have the potential to address respondent burden and improve engagement in the task of recording for dietary interventions. The aim of this study was to assess factors associated with the willingness of adults to take images of food and beverages using a mobile food record (mFR) application. A combined sample of 212 young adults and 73 overweight and obese adults completed a 4-day mobile food record on two occasions and a follow-up usability questionnaire. About 74% of participants stated they would record using the mFR for a longer period compared with a written record (29.4 ± 69.3 vs. 16.1 ± 42.6 days respectively; p < 0.0005). Multivariable logistic regression was used to identify those who were more likely to record mFR in the top tertile (≥14 days). After adjusting for age and gender, those with a BMI ≥ 25 were 1.68 times more likely (Odds Ratio 95% Confidence Interval: 1.02-2.77) than those with BMI < 25 to state a willingness to record with the mFR for ≥ 14 days. The greater willingness of overweight and obese individuals to record dietary intake using an mFR needs further examination to determine if this translates to more accurate estimates of energy intake.


Surgery alone, adjuvant tegafur/gimeracil/octeracil (S-1), or platinum-based chemotherapies for resectable gastric cancer: real-world experience and a propensity score matching analysis.
Adjuvant chemotherapy has changed the paradigm in resectable gastric cancer. S-1 is an oral chemotherapeutic with promising efficacy in Asia. However, comparisons with close observation or platinum-based doublets post D2 gastrectomy have been less reported, notably on real-world experiences. We retrospectively evaluated patients with D2-dissected stage IB-III gastric cancer who received S-1 (S-1, n = 67), platinum-based doublets (P, n = 145) and surgery with close observation (OBS, n = 221) from Jan 2008 to Oct 2018. A propensity score matching was used to compare for recurrence-free (RFS) and overall survivals (OS) in patients who had a locally-advanced disease (T3-4 or lymph node-positive). Adverse reactions, dosage, and associated factors for S-1 are also discussed. In a median follow-up time of 51.9 months, adjuvant S-1 monotherapy was associated with an intermediate survival as compared with P and OBS (median RFS/OS: S-1 vs. P, 20.9/35.8 vs. 31.2/50.5 months, HR = 1.76/2.14, p = 0.021/0.008; S-1 vs. OBS, 24.4/40.2 vs. 20.7/27.0 months, HR = 0.62/0.55, p = 0.041/0.024). The survival differences were more prominent in patients with N2-3 diseases. S-1 was well-tolerated with a relative dose intensity of 73.6%, a median duration of 8.3 months and associated with less adverse reactions as compared with P. S-1 monotherapy was selected by physicians based on age, lymph node stage, serum carcinoembryonic antigen and disease stage. Adjuvant S-1 correlated with intermediate survival outcomes between OBS and P but conferred fewer adverse reactions as compared with P. Patients with a moderate risk of recurrence had comparable survivals when treated with S-1 while platinum-based doublets were favored in advanced cases. The study provides additional information about adjuvant S-1 in patients with selected risk of recurrence.


Enteral Nutrition in Pediatric Patients.
Pediatric patients require specialized attention and have diverse demands for proper growth and development, and thus need a different approach and interest in nutritional assessment and supply. Enteral nutrition is the most basic and important method of nutritional intervention, and its indications should be identified. Also, the sites, modes, types, and timing of nutritional intervention according to the patient's condition should be determined. In addition, various complications associated with enteral nutrition supply should be identified, and prevention and treatment are required. This approach to enteral nutrition and proper administration can help in the proper growth and recovery of pediatric patients with nutritional imbalances or nutritional needs.


Effect of mesenchymal stem cells on Sjögren-like mice and the microRNA expression profiles of splenic CD4+ T cells.
Mesenchymal stem cells (MSCs) serve immuno-regulatory functions and offer a promising novel treatment for certain autoimmune diseases. The present study investigated the therapeutic effect of mice bone marrow (BM)-MSCs on mice with relatively late stage of Sjögren-like disease and the impact of BM-MSCs on the microRNA (miRNA) expression profiles of splenic CD4+ T cells. Female NOD/Ltj mice were randomized into two groups: The disease group (n=8) and the MSC-treated group (n=8). Female ICR mice served as the healthy control group (n=8). The MSC-treated group received an injection of MSCs when they were 26 weeks old. Water intake, blood glucose and salivary flow rate were measured and submandibular glands were resected and stained with hematoxylin and eosin to calculate the focus score. The concentrations of interleukin (IL)-2, IL-6, hepatocyte growth factor, interferon γ, IL-10, prostaglandin E2, transforming growth factor β1 and tumor necrosis factor-α in serum were measured using ELISA. The expression of miRNAs in splenic CD4+ T cells were measured using deep sequencing. The results demonstrated that treatment with BM-MSCs prevented a decline in the salivary flow rate and lymphocyte infiltration in the salivary glands of NOD mice, indicating that MSC-treatment had a therapeutic effect on NOD mice with relatively late stage of Sjögren-like disease. ELISA and deep sequencing results showed that the three groups of mice had different serum concentrations of cytokines/growth factors and different miRNA expression profiles of splenic CD4+ T cells. This implies that the alteration in serum levels of cytokines/growth factors and miRNA expression profiles of splenic CD4+ T cells may explain the therapeutic effect MSCs have on Sjögren's syndrome.


Transportation of nanoscale cargoes by myosin propelled actin filaments.
Myosin II propelled actin filaments move ten times faster than kinesin driven microtubules and are thus attractive candidates as cargo-transporting shuttles in motor driven lab-on-a-chip devices. In addition, actomyosin-based transportation of nanoparticles is useful in various fundamental studies. However, it is poorly understood how actomyosin function is affected by different number of nanoscale cargoes, by cargo size, and by the mode of cargo-attachment to the actin filament. This is studied here using biotin/fluorophores, streptavidin, streptavidin-coated quantum dots, and liposomes as model cargoes attached to monomers along the actin filaments ("side-attached") or to the trailing filament end via the plus end capping protein CapZ. Long-distance transportation (>100 µm) could be seen for all cargoes independently of attachment mode but the fraction of motile filaments decreased with increasing number of side-attached cargoes, a reduction that occurred within a range of 10-50 streptavidin molecules, 1-10 quantum dots or with just 1 liposome. However, as observed by monitoring these motile filaments with the attached cargo, the velocity was little affected. This also applied for end-attached cargoes where the attachment was mediated by CapZ. The results with side-attached cargoes argue against certain models for chemomechanical energy transduction in actomyosin and give important insights of relevance for effective exploitation of actomyosin-based cargo-transportation in molecular diagnostics and other nanotechnological applications. The attachment of quantum dots via CapZ, without appreciable modulation of actomyosin function, is useful in fundamental studies as exemplified here by tracking with nanometer accuracy.


An iatrogenically unmasked life threatening disease: brugada syndrome.
Brugada syndrome is a life threatening disease that is usually overlooked during emergency service admissions. It is characterized by typical electrocardiography resembling right bundle branch block, static or dynamic ST-segment elevation in leads V 1-3. There is familial tendency in some cases. A majority of patients have a structurally normal heart and are likely to remain asymptomatic, however they may present to emergency departments with syncope and various serious arrhythmias. Therefore it is crucially important for emergency medicine physicians not to omit this potential diagnosis. Herein we report a case with Brugada syndrome which was iatrogenically unmasked after propafenone administration for atrial fibrillation.


The tumour suppressor p33ING1 does not enhance camptothecin-induced cell death in melanoma cells.
The tumour suppressor ING1 shares many biological functions with p53, such as cell cycle arrest, DNA repair, apoptosis, and chemosensitivity. Previous findings indicate that the isoform p24ING1 is capable of enhancing chemosensitivity in human fibroblasts. To investigate if the p33ING1 isoform is also involved in chemosensitivity, we overexpressed p33ING1 in melanoma cells and assessed for cell death after treatment with camptothecin. Results from the sulforhodamine B cell survival assay and flow cytometry analysis show no significant difference among cells transfected with vector, p33ING1, and antisense p33ING1. Furthermore, co-transfection of the p33ING1 and p53 constructs had no effect on the frequency of cell death, indicating that there is no synergistic effect between the two tumour suppressors in camptothecin-induced cell death in melanoma cells. This is in contrast to previously observed collaboration between p33ING1 and p53 in DNA repair and apoptosis. Taken together, we demonstrate that p33ING1 does not enhance camptothecin-induced cell death in melanoma cells.


Why do nurses neglect to report violent incidents?
Violent incidents have increased in psychiatric hospitals, with 75% of mental health nurses and 85% of nurses generally being threatened. Anecdotal evidence suggests that inconsistent reporting contributes to poor implementation of proactive policies for preventing violent incidents. Using questionnaires to generate data, this study tested three hypotheses to determine the factors that influence nurses' reporting behaviour. The key finding was that the most likely predictor of reporting behaviour is the level of violence and the consequences of the incident.


Role of muscarinic receptors in the contraction of jejunal smooth muscle in the horse: An in vitro study.
Nonselective antimuscarinic drugs are clinically useful in several pathologic conditions of horses, but, blocking all muscarinic receptor (MR) subtypes, may cause several side effects. The availability of selective antimuscarinic drugs could improve therapeutic efficacy and safety. We aimed to enlighten the role of different MR subtypes by evaluating the effects of nonselective, and selective M1, M2 and M3 MR antagonists on the contractions of horse jejunum. Segments of circular muscle of equine jejunum, were put into organ baths, connected to isotonic transducers, and the effects on ACh concentration-response curves, and on electrical field stimulation (EFS)-evoked contractions of intestinal preparations, induced by nonselective or selective MR antagonists, compared to pre-drug level, were studied. Atropine (nonselective MR antagonist), pirenzepine (selective M1 antagonist), and p-FHHSiD (selective M3 antagonist) competitively antagonized ACh (pA2=9.78±0.21; 7.14±0.25 and 7.56±0.17, respectively). Methoctramine (selective M2 antagonist) antagonized ACh in a concentration-unrelated fashion; however, it competitively antagonized carbachol, a nonselective muscarinic agonist (pA2=6.42±0.23). Atropine dose-dependently reduced EFS-evoked contractions, reaching a maximal effect of -45.64±6.54%; the simultaneous block of neurokinin receptors, almost completely abolished the atropine-insensitive contractions. p-FHHSiD dose-dependently reduced EFS-induced contractions, while pirenzepine caused a minor decrease. Methoctramine, ineffective up to 10-7M, enhanced the contractions at 10-6M; the block of neurokinin receptors abolished the increase of contraction. Cholinergic contractions of horse jejunum are mainly mediated by M3 receptors; M2 selective antagonists seem to scarcely affect cholinergic, and to enhance neurokininergic contractions of equine jejunum, thus their use entails a lower risk of causing intestinal hypomotility, compared to nonselective drugs.


Review: HPLC determination of fumonisin mycotoxins.
An overview of liquid chromatographic methods, mainly employing fluorescence detection together with sample pre-treatment methods, is presented for the determination of the toxic group of fumonisin mycotoxins in various matrices.


Thyroid hemiagenesis accompanying a thyroglossal duct cyst: a case report.
A case of thyroid hemiagenesis discovered incidentally in a patient presenting with a thyroglossal duct cyst is reported. Thyroid embryology is briefly reviewed. Various characteristics of thyroid hemiagenesis and thyroglossal duct cysts are explored.


Visual evoked-response components related to speechreading and spatial skills in hearing and hearing-impaired adults.
Averaged visual evoked responses (VER) to light flashes which varied systematically in brightness and predictability were collected from 24 hearing and 24 hearing-impaired adults. In addition, speechreading, abstract reasoning, and spatial relations tests were administered. Separate principal components analyses of the VERs were conducted on each group to replicate and extend our previous report of an early VER component (VF16) which reflected individual differences in the speechreading skills of hearing subjects. VF16 appeared in both analyses, confirming its replicability as a latent VER component. VF16 correlated with speechreading skill in hearing-impaired males (r = -.73), under stimulus conditions identical to those in our previous study. However, its correlations with speechreading skills in hearing subjects were not significant. VF16 also varied systematically with stimulus predictability and correlated with spatial ability in both groups only when the time of occurrence of the light flashes was predictable. These data tentatively suggest that VF16 is a VER correlate of individual differences in a psychologically dynamic process, perhaps involving expectancy, which may relate to the performance of hearing-impaired and hearing people in visually based communication or cognitive processing situations.


Scarless wound healing: finding the right cells and signals.
From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. However, effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and the oral mucosa. However, many new advances have occurred in recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have previously demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches for diminishing scar formation. Particular attention will also be paid to the canonical Wnt/β-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be re-directed to a more fetal scarless phenotype. Graphical abstract Recent approaches to reducing scar formation. Representation showing novel scientific approaches for decreasing scar formation, including the targeting of pro-fibrotic cell populations based on surface molecule expression (e.g. DPP4(+) fibroblasts, ADAM12(+) pericytes). Modulation of cellular mechanotransduction pathways are another means to reduce scar formation, both at the molecular level or, macroscopically with dressings designed to offload tension, at cutaneous wound sites (ADAM12 a disintegrin and metalloprotease 12, DPP4 dipeptidyl peptidase-4, FAK focal adhesion kinase).


Career and Family - Are They Compatible?: Results of a Survey of Male and Female Gynaecologists in Germany.
Purpose: Nowadays, most gynaecologists are female and the compatibility of job-related career and family life is an upcoming issue. The working group "Gender and Career" of the German Society for Gynaecology and Obstetrics (DGGG) designed a survey to reflect the present situation with a focus on the compatibility of career and family. Material and Methods: A web-based 74-item survey was filled out by members of the DGGG. In total, there were 1037 replies, 75 % female (n = 775) and 25 % male (n = 261) gynaecologists. Results: 62 % of the female and 80 % of the male respondents had already finished their doctoral theses and 2 % female and 13 % male had finished their PhD. Mean number of children was 1.06 (SD 1.08) in female and 1.68 (SD 1.34) in male gynaecologists. The majority of females desired day care for their children, but only 5 to 13 % of employers offer any day care. 88 % of the female and 72 % of the male physicians think that job-related career and family are not compatible. Conclusion: The majority of female gynaecologists wished to have professional child care, but most employers or other institutions do not offer this. This might be one of the reasons why career and family appear incompatible.


NADPH Oxidase-Derived Superoxide Provides a Third Signal for CD4 T Cell Effector Responses.
Originally recognized for their direct induced toxicity as a component of the innate immune response, reactive oxygen species (ROS) can profoundly modulate T cell adaptive immune responses. Efficient T cell activation requires: signal 1, consisting of an antigenic peptide-MHC complex binding with the TCR; signal 2, the interaction of costimulatory molecules on T cells and APCs; and signal 3, the generation of innate immune-derived ROS and proinflammatory cytokines. This third signal, in particular, has proven essential in generating productive and long-lasting immune responses. Our laboratory previously demonstrated profound Ag-specific hyporesponsiveness in the absence of NADPH oxidase-derived superoxide. To further examine the consequences of ROS deficiency on Ag-specific T cell responses, our laboratory generated the OT-II.Ncf1(m1J) mouse, possessing superoxide-deficient T cells recognizing the nominal Ag OVA323-339 In this study, we demonstrate that OT-II.Ncf1(m1J) CD4 T cells displayed a severe reduction in Th1 T cell responses, in addition to blunted IL-12R expression and severely attenuated proinflammatory chemokine ligands. Conversely, IFN-γ synthesis and IL-12R synthesis were rescued by the addition of exogenous superoxide via the paramagnetic superoxide donor potassium dioxide or superoxide-sufficient dendritic cells. Ultimately, these data highlight the importance of NADPH oxidase-derived ROS in providing a third signal for adaptive immune maturation by modulating the IL-12/IL-12R pathway and the novelty of the OT-II.Ncf1(m1J) mouse model to determine the role of redox-dependent signaling on effector responses. Thus, targeting ROS represents a promising therapeutic strategy in dampening Ag-specific T cell responses and T cell-mediated autoimmune diseases, such as type 1 diabetes.


Alcohol Use Disorder Moderates the Effect of Age on Heart Rate Variability in Veterans With Posttraumatic Stress Disorder.
Research on heart rate variability (HRV) in posttraumatic stress disorder (PTSD) and comorbid alcohol use disorder (AUD) is limited despite its use as a biomarker of both disorders. This study examined whether AUD comorbidity contributes an additive effect on HRV for veterans with PTSD. HRV was assessed in 70 male Operation Enduring Freedom/Operation Iraqi Freedom veterans with PTSD, including 32 with co-occurring AUD. Mean HRV values for both groups were below the mean for healthy adults, but additive effects of PTSD and AUD on HRV were not observed. Consistent with prior studies, hierarchical regressions showed that HRV decreased with age in the PTSD-only group. However, HRV increased slightly with age among veterans with both PTSD and AUD. This interaction remained significant after controlling for common HRV covariates. These findings support HRV as a biomarker of PTSD and extend research by demonstrating the complex relationship between PTSD and HRV in the context of co-occurring AUD.


Quality assurance and risk management: a survey of dental schools and recommendations for integrated program management.
Quality assurance (QA) and risk management (RM) programs are intended to improve patient care, meet accreditation standards, and ensure compliance with liability insurance policies. The purpose of this project was to obtain and disseminate information on whether dental schools integrate QA and RM and what mechanisms have been most effective in measuring accomplishments in these programs. All sixty-five U.S. and Canadian dental schools were sent a twenty-nine-item survey, and forty-six (71 percent) schools responded. The main findings are as follows: 66 percent had a written QA program combined with a QA committee; 95 percent received administrative support; there was wide variation in the makeup of the QA committee; many institutions reported significant changes resulting from the QA program; and over half of the respondents merged QA and RM in some fashion. To develop or maintain an effective QA/RM program, the authors propose the following: obtain active support from the dean; develop goals and mission/vision statements; include trained personnel on the committee; establish wide levels of involvement in the QA program; develop QA measurements to ensure compliance with institutionally developed standards of patient care; and establish continuous cycles of improvement.


[Report of a patient with spontaneous aggregation of his giant and morphologically abnormal platelets].
To study the pathological and clinical characteristics of a patient with spontaneous platelet aggregation of his giant and morphologically abnormal platelets. Platelet size and structure were observed under light microscope and electron microscope. Platelet aggregation was measured turbidometrically. Platelet glycoproteins (GP) were analyzed using flow cytometry. PCR and DNA sequencing were performed to identify the gene abnormality. The patient had spontaneous platelet aggregation of giant platelets with thickened plasma membrane and increased number of granules in various shapes. Aspirin and ticlopidine did not affect the spontaneous aggregation. The expression of GP I b, GP II b, GP III a and P-selectin in the platelet membrane were in normal range. Results of gene analyses for GP I balpha, GP I bbeta and GPIX were also normal. Both morphological and functional abnormalities of the platelets from the patient were clearly distinguishable from that of other hereditary giant platelet disorders. It would probably represent a novel platelet disorder which had not been reported to date.


CHANGES OF CONE PHOTORECEPTOR MOSAIC IN AUTOSOMAL RECESSIVE BESTROPHINOPATHY.
To assess the morphological changes of cone photoreceptors in eyes with autosomal recessive bestrophinopathy. Both eyes of five patients with autosomal recessive bestrophinopathyunderwent spectral domain optical coherence tomography and adaptive optics fundus imaging. The cone photoreceptor densities were measured at intervals of 100 μm between 500 μm nasal and temporal eccentricities from the foveal center. The median age of the patients was 30 years (range, 23-45 years), and the best-corrected visual acuity ranged from 20/20 to 20/80. Adaptive optics fundus images showed reduced cone photoreceptor densities corresponding to the damages of the photoreceptor layer in the spectral domain optical coherence tomography images in four patients with relatively good best-corrected visual acuity. The cone photoreceptor densities at the center of the fovea were less than one-third of the normal cone densities (range 11,600-30,400 cells/mm). Cone photoreceptor mosaics were visible over the lesions with serous retinal detachment and retinal edema, although they were partially hyporeflective. There is a significant cone photoreceptor loss in the macular region of patients with autosomal recessive bestrophinopathy, although they had relatively good visual acuity. Monitoring cone photoreceptors by adaptive optics fundus imaging should provide accurate assessments of the disease status and indications for future therapeutic interventions.


Phenotypic and genotypic variation in methylases involved in type II restriction-modification systems in Helicobacter pylori.
To determine relationships between Helicobacter pylori geographical origin and type II methylase activity, we examined 122 strains from various locations around the world for methylase expression. Most geographic regions possessed at least one strain resistant to digestion by each of 14 restriction endonucleases studied. Across all of the strains studied, the average number of active methylases was 8.2 +/- 1.9 with no significant variation between the major geographic regions. Although seven pairs of isolates showed the same susceptibility patterns, their cagA/vacA status differed, and the remaining 108 strains each possessed unique patterns of susceptibility. From a single clonal group, 15 of 18 strains showed identical patterns of resistance, but diverged with respect to M.MboII activity. All of the methylases studied were present in all major human population groupings, suggesting that their horizontal acquisition pre-dated the separation of these populations. For the hpyV and hpyAIV restriction-modification systems, an in-depth analysis of genotype, indicating extensive diversity of cassette size and chromosomal locations regardless of the susceptibility phenotype, points toward substantial strain-specific selection involving these loci.


Bistability and biasing effects in the perception of ambiguous point-light walkers.
The perceptually bistable character of point-light walkers has been examined in three experiments. A point-light figure without explicit depth cues constitutes a perfectly ambiguous stimulus: from all viewpoints, multiple interpretations are possible concerning the depth orientation of the figure. In the first experiment, it is shown that non-lateral views of the walker are indeed interpreted in two orientations, either as facing towards the viewer or as facing away from the viewer, but that the interpretation in which the walker is oriented towards the viewer is reported more frequently. In the second experiment the point-light figure was walking backwards, making the global orientation of the point-light figure opposite to the direction of global motion. The interpretation in which the walker was facing the viewer was again reported more frequently. The robustness of these findings was examined in the final experiment, in which the effects of disambiguating the stimulus by introducing a local depth cue (occlusion) or a more global depth cue (applying perspective projection) were explored.


Porphyrin-kaolinite as efficient catalyst for oxidation reactions.
The preparation, characterization, and application in oxidation reactions of new biomimetic catalysts are reported. Brazilian Sao Simao kaolinite clay has been functionalized with [meso-tetrakis(pentafluorophenyl)porphinato]iron(III), Fe(TPFPP). To obtain the functionalized clay, the natural clay was purified by dispersion-sedimentation, expanded by insertion of dimethyl sulfoxide (DMSO), and functionalized with amino groups by substitution of DMSO with ethanolamine. These previous steps allowed clay functionalization with Fe(TPFPP), leading to a layered material with a basal spacing of 10.73 A. Clay functionalization with the porphyrin was confirmed by formation of the secondary amine, as demonstrated by FTIR bands at 3500-3700 cm(-1). UV-vis spectroscopy revealed a red shift in the Soret band of the iron porphyrin in the functionalized material as compared to the parent iron porphyrin catalyst in solution, indicating Fe(III)P --> Fe(II)P reduction. The catalytic performance of the functionalized clay was evaluated in the epoxidation of cyclooctene, with complete selectivity for the epoxide (100% epoxide yield), and ketonization of cyclohexane, cyclohexanone being the major product. The novel catalyst was also evaluated in the Baeyer-Villiger (BV) oxidation of cyclohexanone, with 85% conversion of cyclohexanone in epsilon-caprolactone, with total selectivity to epsilon-caprolactone.


Lymphangitic carcinomatosis as the initial manifestation of primary signet-ring cell adenocarcinoma of the lung: A case report.
Signet-ring cell carcinomas are an aggressive, poorly differentiated, and highly invasive adenocarcinoma carrying a poor prognosis. Most of these tumors originate in gastrointestinal organs; however, primary lung signet-ring cell adenocarcinomas can rarely occur. Tumoral lymphatic infiltration is a complication of these tumors and can cause phenomena such as lymphangitic carcinomatosis, characterized by a nodular thickening of the pleura, pleural effusions, and mediastinal lymphadenopathies. We report a case of a 63-year-old ex-smoker with a 2-week clinical course of dyspnea and pleuritic chest pain in which a nodular thickening of the pleura and pleural effusion were documented and led to the diagnosis of a primary signet-ring cell adenocarcinoma of the lung with lymphangitic carcinomatosis. This complication has never been described in the context of a primary lung tumor of this subtype. Both entities carry a high mortality and have no therapeutical options. This report adds to the information available about them.


[Illness caused by work: a convincing clinical picture or chiefly a diminished feeling of well-being?].
Cooperation between occupational-health physicians and treating physicians can lead to a mutually convincing result. The input from the occupational-health physician consists of a careful and critical examination into the social and personal background of the employee on sick leave. The benefit of the doubt in the case of any remaining questions in the assessment of the degree of unfitness for work would then lean towards possibilities and not limitations. The degree of disability is then assessed by a convincing clinical picture and not by the diminished feeling of well-being of the patient.


Work-related musculoskeletal disorders among physical therapists in Taiwan.
Work-related musculoskeletal disorders (WMSD) refer to musculoskeletal injuries caused by the occupation. Physical therapists (PTs) suffer from a high risk of WMSD despite their extensive knowledge in ergometrics and injury prevention. This study aims to discover the incidence and prevalence of WMSD among PTs using Taiwan's nationwide claims database. The trend of annual patients seeking rehabilitation and the prevalence of WMSD among PTs were presented. The age- and gender-specific incidence of WMSD were also calculated. The prevalence of WMSD in PTs varied from 6.1% to 75.2%, and the incidence ranged from 6.1 to 29.1 per 100 person-years during 1997 and 2012. For those aged ≤30 years, the incidence was higher in females than males (incidence rate ratio = 1.08, 95% confidence interval [CI]: 1.02-1.14, P = .011), whereas for those aged from 31 to40 years, females had lower incidence of WMSD than males (incidence rate ratio = 0.88, 95% CI: 0.80-0.96, P = .007). The patients/PTs ratio was higher (270.56-337.74) in 1998 and 2004 to 2007 and became stable (245.93-252.82) in 2008 to 2012, correlating with a rise in the WMSD prevalence in 1999 to 2007 and a steady prevalence after 2008 (63.5%-66.3%) in PTs. In conclusion, the risk of WMSD among PTs was positively correlated to the frequency of patients seeking rehabilitation service. In addition, age and gender were important risk factors for developing WMSD among PTs.


Management of Erythrodermic Psoriasis through Ayurveda - A Case Report.
Psoriasis is a noninfectious chronic inflammatory skin disorder, characterized by well-defined erythematous plaques with silvery scales. In an ayurvedic perspective, we can compare this disease with Kitibha Kushta (a type of skin lesion) because most of its signs and symptoms mimic that of erythrodermic psoriasis. A 23-year-old patient diagnosed with psoriasis presented with erythematous overlapped patches all over the body, Auspitz sign, and pain associated with occasional itching sensation. After assessing the dosha involvement, proper Shodhana (purification therapy), Shamana (pacifying therapy), and Rasayana (rejuvenation therapy) were adopted and a reduction in erythema, itching, scaling, pain, and lesions were seen, along with a swingeing decrease of PASI, DLQI, and VAS scores from 37.4, 11, and 07 to absolute zero. Even though erythrodermic psoriasis is very difficult to treat, a thorough assessment of pathogenesis, proper shodhana (purification) and rasayana (rejuvenation therapy) proves to be effective. This gives further scope, similar to a structured clinical trial in the disease.


Beta-arrestin1 mediates insulin-like growth factor 1 (IGF-1) activation of phosphatidylinositol 3-kinase (PI3K) and anti-apoptosis.
beta-arrestins (1 and 2) are widely expressed cytosolic proteins that play central roles in G protein-coupled receptor signaling. beta-arrestin1 is also recruited to the insulin-like growth factor 1 (IGF-1) receptor, a receptor tyrosine kinase, upon agonist binding. Here we report that, in response to IGF-1 stimulation, beta-arrestin1 mediates activation of phosphatidylinositol 3-kinase in a pathway that leads to the subsequent activation of Akt and anti-apoptosis. This process is independent of both Gi and ERK activity. The pathway fails in mouse embryo fibroblasts lacking both beta-arrestins and is restored by stable transfection of beta-arrestin1. Remarkably, this pathway is insensitive to chemical inhibition of IGF-1 receptor tyrosine kinase activity. These results suggest that, in addition to their roles in G protein-coupled receptor signaling, beta-arrestins couple the IGF-1 receptor tyrosine kinase to the phosphatidylinositol 3-kinase system and suggest that this mechanism is operative independently of the tyrosine kinase activity of the receptor.


Analysis of the sesquiterpenoids in processed Atractylodis Rhizoma.
In Asia, processed Atractylodis Rhizoma, the dried rhizome of Atractylodes ovata De Candolle (Compositae), is widely used as a tonic agent in herbal diets; stir-frying with soil is the most common processing method. In this study, we focused on determining variations in the function and concentrations of sesquiterpenoids in processed Atractylodis Rhizoma. Raw Atractylodis Rhizoma was processed by stir-frying it with different assistant substrates (i.e., red soil and burnt clay). The results indicated that there was less atractylon in stir-fried materials than in raw materials. However, there were higher levels of atractylenolides II and III in stir-fried materials than in raw materials. We also found that the heavy-metal content in burnt clay exceeded regulations set by the Taiwanese government. Moreover, commercial Atractylodis Rhizoma in Taiwan exhibited great differences in concentrations of the active components. In addition, atractylon showed stronger cytotoxicity than atractylenolides II and III in various cell lines. Therefore, we suggest that the toxic effects of atractylon are reduced following atractylon degradation to atractylenolides II and III. In conclusion, the toxicity of Atractylodis Rhizoma is reduced through processing.