A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder.
Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I. A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were reviewed for details of adverse effects, tolerability, and efficacy of medication. Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine. These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weight-gain effect of novel antipsychotics.


In vivo cholesterol synthesis by the rat digestive tract. I. A topological study.
Rats were fed a semi-purified diet containing 0.5% cholesterol; cholesterogenesis was measured in vivo 70 min after [1-14C]-acetate or tritiated water was incorporated into the gastrointestinal tract sterols. The results were qualitatively similar with the two precursors. Cholesterol synthesis was preponderant in the small intestine and mainly occurred in its mucosa with a decreasing biosynthetic gradient from the duodenum to the distal ileum. The gradient of cholesterogenesis decreased from the crypt cells to the apical cells in all segments of the intestine studied.


Cervical cancer risk factors among HIV-infected Nigerian women.
Cervical cancer is the third most common cancer among women worldwide, and in Nigeria it is the second most common female cancer. Cervical cancer is an AIDS-defining cancer; however, HIV only marginally increases the risk of cervical pre-cancer and cancer. In this study, we examine the risk factors for cervical pre-cancer and cancer among HIV-positive women screened for cervical cancer at two medical institutions in Abuja, Nigeria. A total of 2,501 HIV-positive women participating in the cervical cancer screen-and-treat program in Abuja, Nigeria consented to this study and provided socio-demographic and clinical information. Log-binomial models were used to calculate relative risk (RR) and 95% confidence intervals (95%CI) for the risk factors of cervical pre-cancer and cancer. There was a 6% prevalence of cervical pre-cancer and cancer in the study population of HIV-positive women. The risk of screening positivity or invasive cancer diagnosis reduced with increasing age, with women aged 40 years and older having the lowest risk (RR=0.4; 95%CI=0.2-0.7). Women with a CD4 count of 650 per mm3 or more also had lower risk of screening positivity or invasive cancer diagnosis (RR=0.3, 95%CI=0.2-0.6). Other factors such as having had 5 or more abortions (RR=1.8, 95%CI=1.0-3.6) and the presence of other vaginal wall abnormalities (RR=1.9, 95%CI=1.3-2.8) were associated with screening positivity or invasive cancer diagnosis. The prevalence of screening positive lesions or cervical cancer was lower than most previous reports from Africa. HIV-positive Nigerian women were at a marginally increased risk of cervical pre-cancer and cancer. These findings highlight the need for more epidemiological studies of cervical cancer and pre-cancerous lesions among HIV-positive women in Africa and an improved understanding of incidence and risk factors.


Health resource utilization and cost associated with myeloproliferative neoplasms in a large United States health plan.
Myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET) may lead to bone marrow fibrosis. Because the disease course of ET and PV are long and the disease course of MF may be fatal, healthcare resource utilization (HRU) associated costs of these neoplasms are especially important to understand. We used a large US health insurance claim database to describe the costs of these diseases. Compared to age-gender matched comparisons without myeloproliferative neoplasms (MPN), all aspects of HRU that we examined, including inpatient, outpatient and emergency room visits and pharmacy, as well as overall healthcare expenditures, were significantly higher in patients with MF, PV and ET (e.g. MF total costs = $54 168 vs. $10 203; PV = $14 903 vs. $7913; ET = $29 553 vs. $8026) than in matched comparisons. In order to reduce the burden of illness associated with these diseases, continued efforts in the development of more efficacious treatments for these disorders are needed.


Efficacy of House Dust Mite Sublingual Immunotherapy in Patients with Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Trial.
Sensitization to house dust mites (HDMs) is frequent in patients with atopic dermatitis. To investigate the efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides pteronyssinus extract in patients with atopic dermatitis sensitized to HDM. In this randomized, double-blind, placebo-controlled trial, we enrolled 91 patients 3 years or older, with SCORing Atopic Dermatitis (SCORAD) score greater than or equal to 15 and positive skin test result and/or IgE to D pteronyssinus. Patients were stratified according to age (<12 and ≥12 years) to receive HDM SLIT or placebo for 18 months. Primary outcome was a greater than or equal to 15-point decrease in SCORAD score. Secondary outcomes were decreases in SCORAD and objective SCORAD, Eczema Area and Severity Index, visual analog scale for symptoms, and pruritus scale scores; Investigator's Global Assessment 0/1; and decrease greater than or equal to 4 points in Dermatology Life Quality Index. Background therapy was maintained. A total of 66 patients completed the study (35 HDM SLIT, 31 placebo). After 18 months, 74.2% and 58% of patients in the HDM SLIT group and the placebo group, respectively, showed greater than or equal to 15-point decrease in SCORAD score (relative risk, 1.28; 95% CI, 0.89-1.83). Significant SCORAD score decreases from baseline of 55.6% and 34.5% in HDM SLIT and placebo groups (mean difference, 20.4; 95% CI, 3.89-37.3), significant objective SCORAD score decreases of 56.8% and 34.9% in HDM SLIT and placebo groups (mean difference, 21.3; 95% CI, 0.66-41.81), and more patients with Investigator's Global Assessment 0/1 in the HDM SLIT group as compared with the placebo group (14 of 35 vs 5 of 31; relative risk, 2.63; 95% CI, 1.09-6.39) were observed at 18 months. Our results suggest that HDM SLIT may be effective in HDM-sensitized patients as an add-on treatment for atopic dermatitis.


Evaluation of the toxic effects of aflatoxin B1 with a taste aversion paradigm in rats.
A taste aversion test was used to evaluate the toxic effects of aflatoxin (AF) B1 which is considered to be one of the most potent hepatocarcinogens known. Sixty male Fisher rats were randomly assigned to six treatment (injection) groups: Water (H2O); Dimethyl Sulphoxide (DMSO); Lithium Chloride (LiCl); 0.125 mg/kg AFB1 (AF-Low); 0.250 mg/kg AFB1 (AF-Medium) and 0.500 mg/kg AFB1 (AF-High). After adaption to a water-deprivation schedule which permitted 10-min access to water each day, the rats were given 10-min access to 0.1% saccharin solution which was followed by intraperitoneal injections of either H2O, DMSO, LiCl, or AF of varying doses according to group assignment. After a five-day recovery period, the rats were initially tested for a conditional taste aversion to the saccharin solution with a two-bottle test during the 10-min access period. Then, a series of two-bottle taste aversion tests were conducted in which H2O and saccharin solutions were available on an ad lib basis. The LiCl, AF-Low, AF-Medium, and AF-High groups developed strong aversions to the saccharin solution; whereas, the H2O and DMSO control groups did not. In addition, there was a dose-response relationship between the doses of aflatoxin and the level of aversion with the AF-High group demonstrating the most marked aversion throughout all saccharin tests. Retention tests showed that the taste aversion was still evident 30 days after the initial pairing of saccharin with AF.


Foxp1 in Forebrain Pyramidal Neurons Controls Gene Expression Required for Spatial Learning and Synaptic Plasticity.
Genetic perturbations of the transcription factor Forkhead Box P1 (FOXP1) are causative for severe forms of autism spectrum disorder that are often comorbid with intellectual disability. Recent work has begun to reveal an important role for FoxP1 in brain development, but the brain-region-specific contributions of Foxp1 to autism and intellectual disability phenotypes have yet to be determined fully. Here, we describe Foxp1 conditional knock-out (Foxp1cKO) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus. Foxp1cKO mice exhibit behavioral phenotypes that are of potential relevance to autism spectrum disorder, including hyperactivity, increased anxiety, communication impairments, and decreased sociability. In addition, Foxp1cKO mice have gross deficits in learning and memory tasks of relevance to intellectual disability. Using a genome-wide approach, we identified differentially expressed genes in the hippocampus of Foxp1cKO mice associated with synaptic function and development. Furthermore, using magnetic resonance imaging, we uncovered a significant reduction in the volumes of both the entire hippocampus as well as individual hippocampal subfields of Foxp1cKO mice. Finally, we observed reduced maintenance of LTP in area CA1 of the hippocampus in these mutant mice. Together, these data suggest that proper expression of Foxp1 in the pyramidal neurons of the forebrain is important for regulating gene expression pathways that contribute to specific behaviors reminiscent of those seen in autism and intellectual disability. In particular, Foxp1 regulation of gene expression appears to be crucial for normal hippocampal development, CA1 plasticity, and spatial learning.SIGNIFICANCE STATEMENT Loss-of-function mutations in the transcription factor Forkhead Box P1 (FOXP1) lead to autism spectrum disorder and intellectual disability. Understanding the potential brain-region-specific contributions of FOXP1 to disease-relevant phenotypes could be a critical first step in the management of patients with these mutations. Here, we report that Foxp1 conditional knock-out (Foxp1cKO) mice with loss of Foxp1 in the neocortex and hippocampus display autism and intellectual-disability-relevant behaviors. We also show that these phenotypes correlate with changes in both the genomic and physiological profiles of the hippocampus in Foxp1cKO mice. Our work demonstrates that brain-region-specific FOXP1 expression may relate to distinct, clinically relevant phenotypes.


Simple luminometric assay to detect phosphoinositol-linked receptor expression in Xenopus oocytes.
A simple and sensitive method to measure the expression of phosphoinositol-linked receptors in Xenopus laevis oocytes is described. Oocytes are co-injected with the calcium photoprotein aequorin and RNA, encoding the receptor of interest. The binding of ligand to the expressed receptor increases intracellular calcium that induces the aequorin to luminesce. With an autosampler-equipped luminometer, this provides a fully automated assay of receptor expression of oocytes. This method was applied to cloning the bombesin/GRP receptor expressed in Swiss 3T3 fibroblasts. Oocytes expressing the cloned BR showed up to a 10,000-fold increase in light emission in response to bombesin. The sensitivity of this procedure allowed detection of positive luminometer signals in single oocytes injected with RNA transcribed from cDNA pools as large as 25,000 clones. These findings show the potential value of this procedure for rapid screening of expression libraries, structure/function analysis of receptors and analysis of receptor antagonists or agonists.


Improving clinic- and neighborhood-based smoking cessation services within federally qualified health centers serving low-income, minority neighborhoods.
Within federally qualified health centers serving low-income, African American audiences, participatory approaches to system changes were organized through multidisciplinary committees that (a) drew on evidence-based guidelines, (b) guided system changes including the requirement of documenting smoking status and readiness to quit in encounter forms, (c) tested and refined practice improvements prior to their general adoption, and (d) guided development of neighborhood-based resources and supports for smoking cessation that were linked to clinic-based services. Documentation of smoking status or readiness to quit increased from 2% of encounter forms in the first 3 months to 94.3% in the last 3 months of the 24-month program. This rate remained over 90% throughout the following year. Exit interviews also indicated increased key clinic-based services, including "explained importance of quitting" (to 78% and 82% of interview respondents in the two intervention clinics in year 2), "tell you that you should quit" (to 80% in each), "tell you about nicotine gum...or other medications" (to 69% and 58%), "offer to help you quit" (to 61% and 64%), and "tell you about programs or help in your neighborhood" (to 51% and 56%). These rates exceeded those in one comparison clinic and equaled those in a second that also had launched a smoking cessation initiative. From exit interviews, improvements in neighborhood resources and support (e.g., people and activities that encourage nonsmoking) also exceeded those in comparison clinics. Thus, participatory approaches to system changes and quality improvement can enhance clinic- and neighborhood-based smoking cessation services within health centers serving low-income, minority populations.


A patch-clamp study of histamine-secreting cells.
The ionic conductances in rat basophilic leukemia cells (RBL-2H3) and rat peritoneal mast cells were investigated using the patch-clamp technique. These two cell types were found to have different electrophysiological properties in the resting state. The only significant conductance of RBL-2H3 cells was a K+-selective inward rectifier. The single channel conductance at room temperature increased from 2-3 pS at 2.8 mM external K+ to 26 pS at 130 mM K+. This conductance, which appeared to determine the resting potential, could be blocked by Na+ and Ba2+ in a voltage-dependent manner. Rat peritoneal mast cells had a whole-cell conductance of only 10-30 pS, and the resting potential was close to zero. Sometimes discrete openings of channels were observed in the whole-cell configuration. When the Ca2+ concentration on the cytoplasmic side of the membrane was elevated, two types of channels with poor ion specificity appeared. A cation channel, observed at a Ca2+ concentration of approximately 1 microM, had a unit conductance of 30 pS. The other channel, activated at several hundred micromolar Ca2+, was anion selective and had a unit conductance of approximately 380 pS in normal Ringer solution and a bell-shaped voltage dependence. Antigenic stimulation did not cause significant changes in the ionic conductances in either cell type, which suggests that these cells use a mechanism different from ionic currents in stimulus-secretion coupling.


CT angiography "spot sign" predicts hematoma expansion in acute intracerebral hemorrhage.
Morbidity and mortality in spontaneous intracerebral hemorrhage (ICH) are correlated with hematoma progression. We hypothesized that the presence of tiny, enhancing foci ("spot sign") within acute hematomas is associated with hematoma expansion. We prospectively studied 39 consecutive patients with spontaneous ICH by computed tomography angiography within 3 hours of symptom onset. Scans were reviewed by 3 readers. Patients were dichotomized according to the presence or absence of the spot sign. Clinical and radiological outcomes were compared between groups. The predictive value of this sign was assessed in a multivariate analysis. Thirteen patients (33%) demonstrated 31 enhancing foci. Baseline clinical variables were similar in both groups. Hematoma expansion occurred in 11 patients (28%) on follow-up. Seventy-seven percent of patients with and 4% without hematoma expansion demonstrated the spot sign (P<0.0001). Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio for expansion were 91%, 89%, 77%, 96%, and 8.5, respectively. Interobserver agreement was high (kappa=0.92 to 0.94). In patients with the spot sign, mean volume change was greater (P=0.008), extravasation more common (P=0.0005), and median hospital stay longer (P=0.04), and fewer patients achieved a good outcome (modified Rankin Scale score <2), although the latter was not significant (P=0.16). No differences in hydrocephalus (P=1.00), surgical intervention (P=1.00), or death (P=0.60) were noted between groups. In multiple regression, the spot sign independently predicted hematoma expansion (P=0.0003). The computed tomography angiography spot sign is associated with the presence and extent of hematoma progression. Fewer patients achieve a good clinical outcome and hospital stay was longer. Further studies are warranted to validate the ability of this sign to predict clinical outcomes.


P450-Mediated Non-natural Cyclopropanation of Dehydroalanine-Containing Thiopeptides.
Thiopeptides are a growing class of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products. Many biosynthetic enzymes for RiPPs, especially thiopeptides, are promiscuous and can accept a wide range of peptide substrates with different amino acid sequences; thus, these enzymes have been used as tools to generate new natural product derivatives. Here, we explore an alternative route to molecular complexity by engineering thiopeptide tailoring enzymes to do new or non-native chemistry. We explore cytochrome P450 enzymes as biocatalysts for cyclopropanation of dehydroalanines, chemical motifs found widely in thiopeptides and other RiPP-based natural products. We find that P450TbtJ1 and P450TbtJ2 selectively cyclopropanate dehydroalanines in a number of complex thiopeptide-based substrates and convert them into 1-amino-2-cyclopropane carboxylic acids (ACCAs), which are important pharmacophores. This chemistry takes advantage of the innate affinity of these biosynthetic enzymes for their substrates and enables incorporation of new pharmacophores into thiopeptide architectures. This work also presents a strategy for diversification of natural products through rationally repurposing biosynthetic enzymes as non-natural biocatalysts.


Sequence analysis of EBV DNA isolated from mouth washings and PBMCs of healthy individuals and blood of EBV-LPD patients.
Lymphoproliferative disorder (LPD) caused by Epstein-Barr virus (EBV) is a severe complication of bone marrow transplantation. The EBV strain causing LPD is of either donor or recipient origin, however, available data are limited to only a small number of cases. To obtain solid evidence, comparison of the EBV strain that caused the EBV-LPD with pre-stem cell transplantation (SCT) EBV strains of donor and recipient is imperative. Available techniques rely on the production of EBV transformed lymphoblastoid cell lines and lack sensitivity. The aim of this study was to develop a simple method for EBV sequence analysis on mouth washings (MWs) and peripheral blood mononuclear cells (PBMCs). EBV DNA was extracted from MWs and PBMCs that were collected from 20 healthy individuals. DNA was used for sequence analysis, using a polymerase chain reaction for the C-terminus of the LMP-1 gene. In seropositive individuals EBV DNA could be detected in 11/14 (79%) MWs and in 13/14 (93%) PBMC samples. Sequence analysis showed that in 11 out of 14 (79%) healthy individuals sequence patterns could be established. In these 11 healthy individuals 13 sequence patterns could be detected. Eleven of these 13 patterns (84.6%) were unique. These results encouraged us to explore the feasibility of this method on EBV DNA isolated from plasma from 9 EBV-LPD patients at time of EBV reactivation. In 7 EBV-LPD patients 8 sequence patterns were detected. Six out of 8 sequence patterns (75%) were unique. Our method is suitable for strain identification and we intend to use this technique to evaluate EBV origin in EBV-LPD patients.


Treatment of Upper Crossed Syndrome: A Narrative Systematic Review.
Upper crossed syndrome (UCS) is a common musculoskeletal condition that is characterized by tightness and weakness of the muscles of the neck, shoulders, and upper back. The aim of this current study is to summarize and provide an overview of the treatment in patients with UCS. A MEDLINE (PubMed), Cochrane library, Embase, Scopus, and Web of Science database search was conducted for English-language articles about upper crossed syndrome that were published until 19 January 2023. To identify potentially relevant articles, the following key search phrases were combined: "upper crossed syndrome", "upper cross syndrome", "diagnosis", and "treatment". A total of 233 articles were identified. After reading the titles and abstracts and assessing their eligibility based on the full-text articles, 11 articles were finally included in this review. The risk of bias (RoB) was assessed using RoB-2 and ROBINS-I for the randomized controlled trials (RCTs) and the non-randomized clinical trial (non-RCT), respectively. Among eleven studies that investigated the effect of treatment programs for UCS, five studies compared the therapeutic effect of exercise programs with controls, whereas six compared different rehabilitative treatment strategies, such as the muscle energy technique, soft-tissue mobilization, and stretching exercises. In addition, regarding the study design, ten studies were RCTs and only one study was a prospective observational study. Treatment programs including various types of exercises and techniques to correct an abnormal posture and restore neuromuscular imbalances are effective for decreasing pain and improving neck disabilities and postural deviations in patients with UCS.


Bilateral variations of brachial plexus involving the median nerve and lateral cord: An anatomical case study with clinical implications.
During the routine dissection of upper limbs of a Caucasian male cadaver, variations were observed in the brachial plexus. In the right extremity, the lateral cord was piercing the coracobrachialis muscle. The musculocutaneous nerve and lateral root of the median nerve were observed to be branching inferior to the lower attachment of coracobrachialis muscle. The left extremity exhibited the passage of the median nerve through the flat tendon of the coracobrachialis muscle near its distal insertion into the medial surface of the body of humerus. A variation in the course and branching of the nerve might lead to variant or dual innervation of a muscle and, if inappropriately compressed, could result in a distal neuropathy. Identification of these variants of brachial plexus plays an especially important role in both clinical diagnosis and surgical practice.


Survey of laboratory tests used in the diagnosis and evaluation of haemophilia A.
Although the incidence of haemophilia A is reportedly uniform across ethnic groups, the prevalence varies in different countries. This suggests variability in the effectiveness of diagnostic strategies which is of particular importance in the recognition of milder forms of the disease. To assess the different laboratory tests that are used in the diagnosis and subsequent management of haemophilia A we carried out a web-based survey of established haemophilia centres. This was sent to 13 haemophilia physicians from haemophilia-treatment centres in Germany, Italy, Spain, South Africa, Taiwan, Norway, Canada, UK and the USA. The survey asked for details of clotting tests, the use of genetic analysis and the use of global haemostatic assays in haemophilia A cases. The results show considerable variation in the laboratory methods used for the screening, diagnosis and monitoring of haemophilia A. There is variability in the techniques used even for long-standing, standardised assays such as the one-stage factor assay. There is marked regional variability in the use of molecular diagnosis. Assessment of haemophilia A requires accurate and sensitive assays. Some laboratories continue to rely on a single-factor assay in the diagnosis of non-severe disease, although cases with assay discrepancy may be missed by this strategy. Global assays are becoming important in the evaluation and management of patients. However, standardisation and the correlation with clinical outcomes require further study. Genetic diagnosis in patients with haemophilia remains underutilised in USA, possibly because of a lack of funding.


Tolerance in banana to Fusarium wilt is associated with early up-regulation of cell wall-strengthening genes in the roots.
SUMMARY Fusarium wilt, caused by the fungal pathogen Fusarium oxysporum f. sp. cubense (Foc), is one of the most destructive diseases of bananas. In the tropics and subtropics, Cavendish banana varieties are highly susceptible to Foc race 4 (VCG 0120). Cavendish selection GCTCV-218 was shown to have significantly lower disease severity and incidence compared with susceptible cultivar Williams in replicated greenhouse and field trials. Suppression subtractive hybridization (SSH) was previously carried out to identify genes induced in roots of GCTCV-218, but not in Williams, after infection with Foc'subtropical' race 4. Seventy-nine SSH clones were sequenced and revealed 13 non-redundant gene fragments, several of which showed homology to defence-associated genes, including cell wall-strengthening genes. Quantitative RT-PCR was used to confirm up-regulation and differential expression of a number of genes throughout a time-course, following Foc infection in the tolerant GCTCV-218 when compared with susceptible cv. Williams. Tolerance of GCTCV-218 was linked to significantly increased induction of cell wall-associated phenolic compounds.


[Incidence and the degree of compensation of diseases of the nervous system].
Based on the results of a clinicoepidemiological examination of the population of one of the medical districts of Leningrad and of the rural community (altogether 14,600 persons), marked differences were established in the general incidence of nervous system diseases (595.3% and 199.6%, respectively) as were 15 main patterns of neurological pathology. The incidence of nervous diseases was found to be fairly high, especially among women, which was supported by the data on 7 organized populations (overall 10.1 thousand persons). Factors of urbanization were shown to have an adverse effect on the population health status, manifesting, first of all, in a direct relationship between the incidence of initial signs of cerebral circulation failure and the number of the urban population. In the organized populations of the cities, the number of patients with the most unfavourable course of nervous system diseases (subcompensated and decompensated patterns) reached 21.5% of the total number of persons afflicted with chronic diseases of the nervous system. Meanwhile in the organized rural community, it was only 9.2%.


[Rheologic characteristics of blood in patients with chronic post-embolic pulmonary hypertension].
Examination of blood rheologic properties in 38 patients with chronic ++post-embolic pulmonary hypertension revealed an elevated blood viscosity at all shift rates and a reduced erythrocyte deformability. A close positive correlation was found between blood viscosity and perfusion deficit. Hemorheologic disorders in patients with chronic post-embolic + pulmonary hypertension are caused by pachyhemia and blood acid-base imbalance due to respiratory failure. They deteriorate pulmonary and systemic hemodynamic disturbances and contribute to progression of blood flow derangement.


Mental Health Conditions, Including Depression and Stress, Are Associated with Increased Odds of Gastric Cancer-Insights into the Role of Diet: A Case-Control Study.
Several risk factors, including nutritional/lifestyle ones, play a role in gastric cancer etiology. Further interactions with mental health have also been emphasized. We hypothesized that individuals with mental disorders would exhibit compromised nutrient intake, increasing their risk of gastric cancer. The state of mental health was evaluated in 82 patients with gastric cancer and 95 healthy controls using the 21-item Depression-Anxiety-Stress Scale. The participants' dietary intakes were evaluated by a 168-item food frequency questionnaire. Based on fully adjusted logistic regressions, there was a significant association between depression (OR = 1.938, CI 95%: 1.009-3.723) and stress (OR = 2.630, CI 95%: 1.014-6.819) with increased odds of gastric cancer. According to fully adjusted multinomial regressions, vitamins A and B6, beta-carotene, and black tea decreased the odds of depression, based on comparing the control group with cases of depression, while sugar and salt increased its odds. The highest significant association was found for salt intake and anxiety in cases with present anxiety (OR = 4.899, 95% CI: 2.218-10.819), and the highest significant protective effect was found for vitamin B6 and depression in cases with present depression (OR = 0.132, 95% CI: 0.055-0.320). However, considering causal relationships and clarifying the underlying mechanisms is imperative and requires further investigation. Advising healthy dietary patterns, e.g., a Mediterranean diet rich in vitamins, minerals, and phytochemicals such as vitamin A, B6, beta-carotene, and fiber, is expected to reduce the odds of gastric cancer, possibly related to lower levels of anxiety and depression.


Assessment of the Effectiveness of Extracorporeal Shock Wave Therapy (ESWT) For Soft Tissue Injuries (ASSERT): An Online Database Protocol.
Soft tissue injuries and tendinopathies account for large numbers of chronic musculoskeletal disorders. Extracorporeal shockwave therapy (ESWT) is popular, and effective in the management of chronic tendon conditions in the elbow, shoulder, and pain at and around the heel. Ethical approval was granted from the South East London Research Ethics Committee to implement a database for the Assessment of Effectiveness of Extracorporeal Shock Wave Therapy for Soft Tissue Injuries (ASSERT) to prospectively collect information on the effectiveness of ESWT across the UK. All participants will give informed consent. All clinicians follow a standardised method of administration of the ESWT. The primary outcome measures are validated outcome measures specific to the condition being treated. A Visual Analogue Score for pain and the EuroQol will be completed alongside the condition specific outcome tool at baseline, 3, 6, 12 and 24 months post treatment. The development of the ASSERT database will enable the evaluation of the effectiveness of ESWT for patients suffering from chronic conditions (plantar fasciopathy, tennis elbow, Achilles tendinopathy, greater trochanter pain syndrome and patellar tendinopathy). The results will aid the clinicians in the decision making process when managing these patients.


Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells.
Metformin, one of most commonly used antidiabetes drugs, is reported to exert its therapeutic effects by activating AMP-activated protein kinase (AMPK); however, the mechanism by which metformin activates AMPK is poorly defined. The objective of the present study was to determine how metformin activates AMPK in endothelial cells. Exposure of human umbilical vein endothelial cells or bovine aortic endothelial cells to metformin significantly increased AMPK activity and the phosphorylation of both AMPK at Thr172 and LKB1 at Ser428, an AMPK kinase, which was paralleled by increased activation of protein kinase C (PKC)-zeta, as evidenced by increased activity, phosphorylation (Thr410/403), and nuclear translocation of PKC-zeta. Consistently, either pharmacological or genetic inhibition of PKC-zeta ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-zeta might act as an upstream kinase for LKB1. Furthermore, adenoviral overexpression of LKB1 kinase-dead mutants abolished but LKB1 wild-type overexpression enhanced the effects of metformin on AMPK in bovine aortic endothelial cells. In addition, metformin increased the phosphorylation and nuclear export of LKB1 into the cytosols as well as the association of AMPK with LKB1 in bovine aortic endothelial cells. Similarly, overexpression of LKB1 wild-type but not LKB1 S428A mutants (serine replaced by alanine) restored the effects of metformin on AMPK in LKB1-deficient HeLa-S3 cells, suggesting that Ser428 phosphorylation of LKB1 is required for metformin-enhanced AMPK activation. Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells. Finally, inhibition of PKC-zeta abolished metformin-enhanced coimmunoprecipitation of LKB1 with both AMPKalpha1 and AMPKalpha2. We conclude that PKC-zeta phosphorylates LKB1 at Ser428, resulting in LKB1 nuclear export and hence AMPK activation.


New oral anticoagulants and perioperative management of anticoagulant/antiplatelet agents.
The strategy of whether to continue anticoagulation and antiplatelet agents during surgery depends on an evaluation of the thromboembolic risk and haemorrhagic risk of the individual patients. Procedures that carry a significant risk of bleeding may require temporary cessation of the medication. We briefly review the use of common oral anticoagulant and antiplatelet agents, including clinical indications and limitations associated with those agents. We also discuss the risks of thromboembolism, and balancing bleeding risk in patients receiving oral anticoagulation therapy, temporary interruption of such therapy and management of such patients undergoing an elective surgical procedure. Generally, patients at high risk of thromboembolism should be considered for a more aggressive perioperative management strategy with bridging therapy. Current recommendations for dual antiplatelet treatment range from 4 weeks in patients undergoing elective stenting with bare metal stents, up to 12 months in patients with drug-eluting stents or patients undergoing coronary stenting for acute coronary syndrome. If a patient is to undergo high-bleeding-risk surgery and an antiplatelet effect is not desired, clopidogrel, prasugrel and ticagrelor should be discontinued 5-7 days before the procedure. Early, effective communication between general practitioners and specialists is useful in managing high-risk patients on anticoagulation/antiplatelet agents during the perioperative periods.


Exosomes from bone marrow mesenchymal stem cells ameliorate glucocorticoid-induced osteonecrosis of femoral head by transferring microRNA-210 into bone microvascular endothelial cells.
Bone microvascular endothelial cells (BMECs) played an important role in the pathogenesis of glucocorticoid-induced osteonecrosis of femoral head (GCS-ONFH), and exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may provide an effective treatment. This study aimed to evaluate the effects of BMSC-Exos and internal microRNA-210-3p (miRNA-210) on GCS-ONFH in an in vitro hydrocortisone-induced BMECs injury model and an in vivo rat GCS-ONFH model. BMECs, BMSCs and BMSC-Exos were isolated and validated. BMECs after the treatment of hydrocortisone were cocultured with different concentrations of BMSC-Exos, then proliferation, migration, apoptosis and angiogenesis of BMECs were evaluated by CCK-8, Annexin V-FITC/PI, cell scratch and tube formation assays. BMSCs were transfected with miRNA-210 mimics and miRNA-210 inhibitors, then BMSC-ExosmiRNA-210 mimic and BMSC-ExosmiRNA-210 inhibitor secreted from such cells were collected. The differences between BMSC-Exos, BMSC-ExosmiRNA-210 mimic and BMSC-ExosmiRNA-210 inhibitor in protecting BMECs against GCS treatment were analyzed by methods mentioned above. Intramuscular injections of methylprednisolone were performed on Sprague-Dawley rats to establish an animal model of GCS-ONFH, then tail intravenous injections of BMSC-Exos, BMSC-ExosmiRNA-210 mimic or BMSC-ExosmiRNA-210 inhibitor were conducted after methylprednisolone injection. Histological and immunofluorescence staining and micro-CT were performed to evaluate the effects of BMSC-Exos and internal miRNA-210 on the in vivo GCS-ONFH model. Different concentrations of BMSC-Exos, especially high concentration of BMSC-Exos, could enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs treated with GCS. Compared with BMSC-Exos, BMSC-ExosmiRNA-210 mimic could further enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs, while BMECs in the GCS + BMSC-ExosmiRNA-210 inhibitor group showed reduced proliferation, migration and angiogenesis ability and higher apoptosis rates. In the rat GCS-ONFH model, BMSC-Exos, especially BMSC-ExosmiRNA-210 mimic, could increase microvascular density and enhance bone remodeling of femoral heads. BMSC-Exos containing miRNA-210 could serve as potential therapeutics for protecting BMECs and ameliorating the progression of GCS-ONFH.


RASSF1A inhibits gastric cancer cell proliferation by miR-711- mediated downregulation of CDK4 expression.
Although interaction with DNA repair proteins has demonstrated that RASSF1A is a tumour suppressor gene, much attention has been directed in recent years towards its roles in regulating the cell cycle. However, the precise mechanism remains unclear. Uncovering how RASSF1A participates in regulating the cell cycle is critical to exploring effective therapeutic targets for gastric cancer. Here we show that RASSF1A could regulate 14 miRNAs' expression in the typical human gastric cancer line SGC-7901, of which miR-711 was upregulated the most. Moreover, for SGC-7901 cells, miR-711 was found to downregulate CDK4 expression, and to arrest the cell cycle in the G1 phase. Our results suggest that RASSF1A inhibits the proliferation of gastric cancer cells by upregulating the expression of miR-711, which arrested gastric cancer cells in the G1 phase by downregulating expression of CDK4. This finding might provide us with a novel therapeutic target for gastric cancer by increasing RASSF1A expression via miR-711 regulation.


Enhancement of replication of RNA viruses by ADAR1 via RNA editing and inhibition of RNA-activated protein kinase.
Adenosine deaminase acting on RNA 1 (ADAR1) is a double-stranded RNA binding protein and RNA-editing enzyme that modifies cellular and viral RNAs, including coding and noncoding RNAs. This interferon (IFN)-induced protein was expected to have an antiviral role, but recent studies have demonstrated that it promotes the replication of many RNA viruses. The data from these experiments show that ADAR1 directly enhances replication of hepatitis delta virus, human immunodeficiency virus type 1, vesicular stomatitis virus, and measles virus. The proviral activity of ADAR1 occurs through two mechanisms: RNA editing and inhibition of RNA-activated protein kinase (PKR). While these pathways have been found independently, the two mechanisms can act in concert to increase viral replication and contribute to viral pathogenesis. This novel type of proviral regulation by an IFN-induced protein, combined with some antiviral effects of hyperediting, sheds new light on the importance of ADAR1 during viral infection and transforms our overall understanding of the innate immune response.


Discovering the Unclassified Suicide Cases Among Undetermined Drug Overdose Deaths Using Machine Learning Techniques.
The Centers for Disease Control and Prevention (CDC) monitor accidental and intentional deaths to answer questions that are critical for the development of effective prevention and resource allocation. CDC's National Violent Death Reporting System (NVDRS) is a major innovation in surveillance linking individual-level data from multiple sources. However, suicide underreporting is common, particularly from drug overdose deaths. This study sought to assess machine learning (ML) techniques in quantifying drug overdose suicide underreporting rates. Clinical, sociodemographic, toxicological, and proximal stressor data on overdose decedents (n = 2,665) were extracted from Utah's NVDRS from 2012 to 2015. The existing well-determined cases were used to train and test our ML models. We assessed and compared multiple machine learning methods including Logistic Regression, Random Forest Classifier, Support Vector Machines, and Artificial Neural Networks. We applied a majority voting methodology to classify undetermined drug overdose deaths. Overdose suicide rates were estimated to be underreported by 33% across all years, increasing yearly from 29% in 2012 to 37% in 2015. The overall test accuracies for all models ranged from 92.3% to 94.6%. This research identifies a cost-effective, replicable, and expandable ML-based methodology to estimate the true rates of suicide which may be partially masked during the opioid epidemic.


CT in the evaluation of pediatric abdominal abnormalities.
Space does not permit a discussion of the use of CT in the pelvis and chest, but obviously conditions such as lymphoma may involve these areas as well as the abdomen while pelvic masses may commonly present as abdominal abnormalities. In this review the author has tried to summarize the experiences of other and to combine this with his 4-year experience using an integrated imaging approach to arrive at some preliminary conclusions as to how CT may best be used in the care of children with abdominal abnormalities. As technology improves and experience widens, present thought and indications will undoubtedly be altered and probably be expanded. Even at this early stage it seems obvious to the author that CT should have great impact on traditional ways of studying abdominal pathology and that if properly used, it will result in better patients care at less cost in time and money to society and less trauma to the afflicted child.


Klebsiella pneumoniae capsule expression is necessary for colonization of large intestines of streptomycin-treated mice.
The role of the Klebsiella pneumoniae capsular polysaccharide (K antigen) during colonization of the mouse large intestine was assessed with wild-type K. pneumoniae LM21 and its isogenic capsule-defective mutant. When bacterial strains were fed alone to mice, the capsulated bacteria persisted in the intestinal tract at levels of 10(8) CFU/g of feces while the capsule-defective strain colonized at low levels, 10(4) CFU/g of feces. In mixed-infection experiments, the mutant was rapidly outcompeted by the wild type. In situ hybridization on colonic sections revealed that bacterial cells of both strains were evenly distributed in the mucus layer at day 1 after infection, while at day 20 the wild type remained dispersed and the capsule-defective strain was seen in clusters in the mucus layer. These results suggest that capsular polysaccharide plays an important role in the gut colonization ability of K. pneumoniae.


Endogenous digitalis-like factors.
Recent research has demonstrated the presence of endogenous compounds in blood and urine that crossreact with antibodies raised against digoxin. Given the widespread therapeutic use of digoxin and its being monitored clinically by immunoassay, such digoxin-like immunoreactive compounds pose significant diagnostic and interpretive problems. Serum levels of this factor(s) approaching therapeutic digoxin levels have been found in digoxin-free patients in renal failure, pregnant women, and newborns. The compound is incompletely characterized; however, existing data suggest that it is a small, neutral, nonpeptidic compound. In serum it is highly protein bound, and alterations in this binding appear to give rise to the false-positive assay results. The urinary form is probably conjugated. Digoxin-like immunoreactive substances may play a role in volume homeostasis and appear associated with essential and pregnancy-induced hypertension. If such roles are primary, measurement of digoxin-like immunoreactive substances may prove to be of value in and of itself.


Diagnostic delays in children with early onset epilepsy: impact, reasons, and opportunities to improve care.
Delayed diagnosis of early onset epilepsy is a potentially important and avoidable complication in epilepsy care. We examined the frequency of diagnostic delays in young children with newly presenting epilepsy, their developmental impact, and reasons for delays. Children who developed epilepsy before their third birthday were identified in a prospective community-based cohort. An interval ≥1 month from second seizure to diagnosis was considered a delay. Testing of development at baseline and for up to 3 years after and of intelligence quotient (IQ) 8-9 years later was performed. Detailed parental baseline interview accounts and medical records were reviewed to identify potential reasons for delays. Factors associated with delays included the parent, child, pediatrician, neurologist, and scheduling. Diagnostic delays occurred in 70 (41%) of 172 children. Delays occurred less often if children had received medical attention for the first seizure (p < 0.0001), previously had neonatal or febrile seizures (p = 0.02), had only convulsions before diagnosis (p = 0.005), or had a college-educated parent (p = 0.01). A ≥1 month diagnostic delay was associated with an average 7.4 point drop (p = 0.02) in the Vineland Scales of Adaptive Behavior motor score. The effect was present at diagnosis, persisted for at least 3 years, and was also apparent in IQ scores 8-9 years later, which were lower in association with a diagnostic delay by 8.4 points (p = 0.06) for processing speed up to 14.5 points (p = 0.004) for full scale IQ, after adjustment for parental education and other epilepsy-related clinical factors. Factors associated with delayed diagnosis included parents not recognizing events as seizures (N = 47), pediatricians missing or deferring diagnosis (N = 15), neurologists deferring diagnosis (N = 7), and scheduling problems (N = 11). Diagnostic delays occur in many young children with epilepsy. They are associated with substantial decrements in development and IQ later in childhood. Several factors influence diagnostic delays and may represent opportunities for intervention and improved care.


The Dynamics of Son Preference, Technology Diffusion, and Fertility Decline Underlying Distorted Sex Ratios at Birth: A Simulation Approach.
We present a micro-founded simulation model that formalizes the "ready, willing, and able" framework, originally used to explain historical fertility decline, to the practice of prenatal sex selection. The model generates sex ratio at birth (SRB) distortions from the bottom up and attempts to quantify plausible levels, trends, and interactions of son preference, technology diffusion, and fertility decline that underpin SRB trajectories at the macro level. Calibrating our model for South Korea, we show how even as the proportion with a preference for sons was declining, SRB distortions emerged due to rapid diffusion of prenatal sex determination technology combined with small but growing propensities to abort at low birth parities. Simulations reveal that relatively low levels of son preference (about 20 % to 30 % wanting one son) can result in skewed SRB levels if technology diffuses early and steadily, and if fertility falls rapidly to encourage sex-selective abortion at low parities. Model sensitivity analysis highlights how the shape of sex ratio trajectories is particularly sensitive to the timing and speed of prenatal sex-determination technology diffusion. The maximum SRB levels reached in a population are influenced by how the readiness to abort rises as a function of the fertility decline.


Development and Progress in Sensors and Technologies for Human Emotion Recognition.
With the advancement of human-computer interaction, robotics, and especially humanoid robots, there is an increasing trend for human-to-human communications over online platforms (e.g., zoom). This has become more significant in recent years due to the Covid-19 pandemic situation. The increased use of online platforms for communication signifies the need to build efficient and more interactive human emotion recognition systems. In a human emotion recognition system, the physiological signals of human beings are collected, analyzed, and processed with the help of dedicated learning techniques and algorithms. With the proliferation of emerging technologies, e.g., the Internet of Things (IoT), future Internet, and artificial intelligence, there is a high demand for building scalable, robust, efficient, and trustworthy human recognition systems. In this paper, we present the development and progress in sensors and technologies to detect human emotions. We review the state-of-the-art sensors used for human emotion recognition and different types of activity monitoring. We present the design challenges and provide practical references of such human emotion recognition systems in the real world. Finally, we discuss the current trends in applications and explore the future research directions to address issues, e.g., scalability, security, trust, privacy, transparency, and decentralization.


Bilateral pectoral musculature malformations with concomitant vascular anomaly.
We report on a unique combination of multiple variations concerning the pectoral muscles and the left external jugular vein. Specifically, a bilateral hypoplasia of the medial clavicular portion of the pectoralis major muscle was noticed along with the coexistence of total right pectoralis minor aplasia, substituted by loose connective and fatty tissue. Simultaneously, a supernumerary anterior-placed external jugular vein was found, which, after its supraclavicular course, pierced the interval between the left clavicular and the sternocostal head, and drained into the left jugular junction. The combination of the above anomalies constitutes an atypical pattern of Poland syndrome. We discuss the related embryological development and the relative literature. Attention was paid to the clinical importance for plastic surgeons, general surgeons, and radiologists, facilitating them with accurate interpretation of anterior thoracic wall findings.


Effectiveness of Pooled Platelet Transfusion in Concordant and Discordant Groups among Dengue Patients.
Dengue affects more than 50 million people per year and is one of the most common causes of severe thrombocytopaenia. Thrombocytopaenia is a common complication of dengue and other viral fevers apart from malaria, typhoid, leptospirosis, leukaemia and megaloblastic anaemia. A platelet count of <20,000/μl is characteristically seen in dengue haemorrhagic fever and dengue fever. It results from immune complex mediated platelet destruction or bone marrow suppression. Severe thrombocytopaenia <10,000/μl is one of the indications for prophylactic platelet transfusion therapy to prevent haemorrhage. To evaluate the effectiveness of transfusion of ABO compatible and ABO incompatible pooled platelet units in severe thrombocytopaenia cases. In this study ABO compatible and incompatible pooled platelet units were transfused to serologically confirmed dengue cases having thrombocytopaenia with or without bleeding manifestations. Each of the adult patients received 4-6 units of pooled platelet concentrates prepared from random donor whole blood suspended in plasma for severe thrombocytopaenia. Pre and post transfusion platelet counts were compared. Children aged less than 12 years, pregnant women and patients with splenomegaly those on ayurvedic and homeopathic therapy, recipients of packed red cells on the same day of platelet transfusion and recipients of multiple platelet transfusions within 24 hours were excluded from the study. The median post transfusion platelet increments (PPI) and corrected count increments (CCI) at 4hour post transfusion were 25,000/μL (5,000-80,000/μL) and 18,000/μL (range 8,000/μL- 47,500/μL) respectively among the responders. Median PPI and CCI at 24 hours were 45,000/μL and 28,863/μL among the responders. The median CCI at 4 hour post transfusion among the non-responders was 850/μL and at 24hours was 1,425/μL. At 24 hours responders showed significantly higher PPI as compared to non responders. The average platelets transfused were 4units in case of responders and 8 units in case of non-responders. ABO identical and compatible pooled platelet transfusions were more successful in increasing the post transfusion platelet counts as compared to ABO incompatible pooled platelets.


CD163+ tumor-associated macrophages correlated with poor prognosis and cancer stem cells in oral squamous cell carcinoma.
Tumor-associated macrophages (TAMs) play an important role in the progression and prognostication of numerous cancers. However, the role and clinical significance of TAM markers in oral squamous cell carcinoma (OSCC) has not been elucidated. The present study was designed to investigate the correlation between the expression of TAM markers and pathological features in OSCC by tissue microarray. Tissue microarrays containing 16 normal oral mucosa, 6 oral epithelial dysplasia, and 43 OSCC specimens were studied by immunohistochemistry. We observed that the protein expression of the TAM markers CD68 and CD163 as well as the cancer stem cell (CSC) markers ALDH1, CD44, and SOX2 increased successively from the normal oral mucosa to OSCC. The expressions of CD68 and CD163 were significantly associated with lymph node status, and SOX2 was significantly correlated with pathological grade and lymph node status, whereas ALDH1 was correlated with tumor stage. Furthermore, CD68 was significantly correlated with CD163, SOX2, and ALDH1 (P < 0.05). Kaplan-Meier analysis revealed that OSCC patients overexpressing CD163 had significantly worse overall survival (P < 0.05). TAM markers are associated with cancer stem cell marker and OSCC overall survival, suggesting their potential prognostic value in OSCC.


Radial versus femoral access for percutaneous coronary intervention in ST-elevation myocardial infarction patients treated with fibrinolysis: Results from the randomized routine early invasive clinical trials.
To investigate the relationship between arterial access site choice (radial versus femoral) and clinical outcomes among STEMI patients undergoing routine PCI after fibrinolysis. Patient-level data from trials of STEMI patients evaluating routine PCI after fibrinolysis were included. The primary endpoint was 30-day major bleeding; secondary endpoints included 30-day death and re-infarction. 1891 patients underwent PCI (trans-radial n=338, trans-femoral n=1553). Trans-radial PCI patients were less likely to be >75years (2% vs. 8%, p=0.0001), heavier (median weight 82 [72-90] vs. 80 [70-90] kg, p=0.0013) and more likely in Killip class I at presentation (87% vs. 82%, p=0.03). At 30days, trans-radial PCI was associated with a similar unadjusted risk for major bleeding (3.7% vs. 1.2%, Odds Ratio [OR] 0.43 [95% CI 0.13-1.48], p=0.18), mortality (3.4% vs. 1.2%, OR 0.34 [0.09-1.28], p=0.11) and re-infarction (3.9% vs. 4.7%, OR 1.25 [0.60-2.58], p=0.56). In multivariable analysis, radial access was associated with similar estimates for bleeding and death/reinfarction risk. In STEMI patients treated with fibrinolysis and undergoing an early routine invasive strategy, radial compared to femoral PCI is chosen in younger, less ill patients and is independently associated with similar risk of bleeding, re-infarction, and mortality. This study evaluated the relationship between arterial access choice (radial versus femoral) and in-hospital and 30-day outcomes in patients undergoing routine PCI after fibrinolysis for STEMI. We included patient-level data from trials evaluating a strategy of routine PCI after fibrinolysis for STEMI. Of 1891 patients undergoing PCI, trans-radial access (n=338) was chosen in younger, lower risk patients. At 30days, trans-radial access was associated with a similar unadjusted and adjusted risk of major bleeding, re-infarction and mortality.


IgE enhances Fc epsilon RI expression and IgE-dependent TNF-alpha release from canine skin mast cells.
The role of IgE on mast cell (MC) activation is well known. Recent studies have demonstrated that IgE also has the ability to up-regulate the high affinity IgE receptor (Fc epsilon RI) on the surface of human and murine MC, leading to an increased production of cytokines and chemokines. In the present study, we have examined the influence of IgE levels on Fc epsilon RI expression, and its consequences on TNF-alpha production from canine skin MC. Mature MC were enzymatically dispersed from the skin biopsies of 6-8 dogs and were cultured for up to 5 days in medium supplemented with recombinant canine stem cell factor (SCF) (6 ng/ml), in the presence of increasing serum IgE concentrations (ranging from 0 to 80 microg/ml). Subsequently, skin MC were activated with anti-IgE, and TNF-alpha concentration was assessed 5h post-activation by a cytotoxic bioassay. Fc epsilon RI receptors were identified in MC surface by flow cytometry. MC cultured for up to 5 days in the presence of high serum IgE concentration (8 microg/ml) produced twice the quantity of TNF-alpha than MC cultured in the absence of serum IgE, in response to stimulation with anti-IgE. Moreover, the percentage of Fc epsilon RI-positive skin cells was found to be approximately double in cells cultured with serum IgE compared to that cultured in the absence of IgE, following saturation of IgE receptors. These results suggest that, as found in human and murine MC, IgE may induce an up-regulation of the Fc epsilon RI density and an enhancement in the secretory activity of canine skin MC. This study could be of great interest in designing new therapeutic strategies for controlling MC activation in inflammatory and allergic processes.


Patients' perspectives on aerobic exercise early after stroke.
To describe patient perspectives of aerobic exercise during inpatient stroke rehabilitation, including their self-efficacy and beliefs towards exercise, as well as their perceptions of barriers. A survey was conducted at three Canadian rehabilitation centres to evaluate individuals' (N = 33) self-efficacy and outcome expectations for exercise. In addition, patient perceptions of other people recovering from stroke, social support, and aerobic exercise as part of rehabilitation were assessed. Thirty-two people completed the survey. Of these, 97% were willing to participate in aerobic exercise 5.9 ± 8.8 days after admission to inpatient rehabilitation. While outcome expectations for exercise were high, participants reported lower self-efficacy for exercise. Patients reported barriers related to the ability to perform exercise (other health problems (i.e., arthritis), not being able to follow instructions and physical impairments) more often than safety concerns (fear of falling). The lack of support from a spouse and family were commonly identified, as was a lack of information on how to perform aerobic exercise. Patients with stroke are willing to participate in aerobic exercise within a week after admission to inpatient rehabilitation. However, they perceive a lack of ability to perform aerobic exercise, social support from family and information as barriers. Implications for rehabilitation Aerobic exercise is recognized as part of comprehensive stroke rehabilitation. There is a need to better understand patient perspectives to develop and implement more effective interventions early after stroke. Patients lack confidence in their ability to overcome barriers early after stroke. Patients are concerned with their ability to perform exercise, fall risk, lack of support from a spouse and family, and limited information on aerobic exercise. There is a need to reinforce education with practical experience in structured aerobic exercise programs that show patients and caregivers how to manage disability and complex health needs.


EUS in the management of the patient with dysplasia in Barrett's esophagus.
Barrett's esophagus is the most important risk factor in the development of adenocarcinoma of the esophagus. Barrett's esophagus is generally regarded as the most significant complication of gastroesophageal reflux disease. Adenocarcinoma occurs more frequently in the setting of high-grade dysplasia. The prognosis of adenocarcinoma of the esophagus is strongly correlated with the stage of disease. The prognosis of late stage disease is extremely poor. Cure may be achieved when disease is found at an early stage. Esophagectomy has been the definitive treatment of limited stage adenocarcinoma of the esophagus. The morbidity and mortality rate for esophagectomy is high. Therefore, alternative endoscopic methods for curative treatments have gained popularity. The two main endoscopic therapies, photodynamic therapy and endoscopic mucosal resection, are both effective when applied to early-stage disease. Traditional evaluation of the patient with Barrett's esophagus with high-grade dysplasia includes esophago-gastro-duodenoscopy (EGD) with biopsy and computed tomography of the chest. Endoscopic ultrasound (EUS) has gained popularity in the evaluation of the patient with Barrett's esophagus and high-grade dysplasia because it is the only imaging technique capable of delineating the separate histologic layers of the gastrointestinal tract. The principal role of EUS in evaluating patients with Barrett's-associated dysplasia is to identify patients who may be candidates for endoscopic ablative (endoscopic mucosal resection, photodynamic therapy) therapies. EUS has been shown to be superior to computed tomography (including high resolution spiral CT) or magnetic resonance imaging for preoperative staging in patients with high-grade dysplasia and carcinoma. This review of the literature summarizes the ability of EUS to evaluate patients with Barrett's esophagus and high-grade dysplasia.


Multiresidue analysis of multiclass pesticides in lavandin essential oil by LC/MS/MS using the scheduled selected reaction monitoring mode.
In this paper we describe the development of the first multiclass pesticide residue method applied to essential oils. A total of 70 pesticides covering a wide range of polarity and currently used on essential oil crops have been included in the method. The procedure consists of a 10-fold dilution of lavandin essential oil followed by a direct injection analysis by liquid chromatography/tandem mass spectrometry. The system used is an API 4000 QTrap equipped with an electrospray ionization interface and operating in scheduled selected reaction monitoring acquisition mode. Matrix effects were evaluated by comparing the slopes of matrix-matched and solvent-based calibration curves. Weak signal suppression or enhancement (<20%) was observed for most of the compounds. Method sensitivity was determined statistically by the injection of five matrix-matched calibration curves with the distribution's normality and the variance's homogeneity checked before establishment of a suitable regression model. Limits of detection (LODs) and quantification (LOQs) were then determined using the blank standard's deviation and the slope of the mean curve. The analytical method has been validated for 67 of the 70 pesticides and meets the following LOQs: ≤1 μg/L for 9 pesticides, ≤5 μg/L for 44, ≤10 μg/L for 9, and ≤20 μg/L for 5.


Effect of N,N-dimethylglycine supplementation in parturition feed for sows on metabolism, nutrient digestibility and reproductive performance.
The current pilot study assessed the influence of N,N-dimethylglycine (DMG) on insulin sensitivity, glucose and fat metabolism, nutrient digestibility and reproductive performance of sows in the peripartal period. At day 105 of gestation, 25 sows were randomly assigned to the control (n = 13) or the DMG group (n = 12). Sows from the DMG group were supplemented with 1 g DMG/kg feed until day 3 of lactation. After an overnight fast 1 day after farrowing, a blood sample of each sow was drawn. The plasma was analyzed for insulin, glucose, fructosamine, leptin, thiobarbituric acid reactive substances (TBARS), ferric reducing ability of plasma (FRAP), non-esterified fatty acids (NEFA) and triglycerides (TG) and an oral glucose tolerance test was performed. A rectal feces sample was collected and the apparent fecal digestibility (AFD) of crude fat (CFAT), crude protein (CP) and nitrogen-free extract (NFE) was calculated after proximate analyses. Finally, a colostrum sample was collected from each sow and analyzed for the presence of DMG. Reproductive performance parameters were recorded. The results showed an improvement in the AFD of CFAT, CP and NFE when DMG was supplemented. This beneficial effect confirms the hypothesis that DMG acts as an emulsifying agent. The improvement in digestibility in the DMG group was accompanied by a numerical increase in plasma TG (P = 0.067). Plasma NEFA concentrations were not different between treatment groups. DMG supplementation neither affected glucose clearance nor influenced plasma insulin, glucose, fructosamine or leptin levels. TBARS and FRAP also remained unaffected, despite previously reported anti-oxidative properties of DMG. Furthermore, no significant impact on reproductive performance could be recorded. In conclusion, DMG supplementation significantly improved nutrient digestibility. Possible beneficial effects on energy metabolism and reproductive performance of sows should be tested when DMG is supplemented for a longer period of time or at a higher dose.


Treatment of prurigo nodularis with topical capsaicin.
Prurigo nodularis is an eruption of lichenified or excoriated nodules caused by intractable pruritus that is difficult to treat. Therefore the antipruritic efficacy of capsaicin seemed to be of particular interest because this alkaloid, extractable from red pepper, interferes with the perception of pruritus and pain by depletion of neuropeptides in small sensory cutaneous nerves. The aim of this concentration- and regimen-ranging study was to evaluate the efficacy, safety, and practicability of capsaicin in the topical treatment of prurigo nodularis in a large series of patients. A total of 33 patients with prurigo nodularis of various origins were selected to receive capsaicin (0.025% to 0.3%) 4 to 6 times daily for 2 weeks up to 10 months. The consecutive follow-up period was up to 6 months. In 7 patients, skin biopsy specimens were taken before, during, and after therapy and investigated histologically, immunohistochemically, and ultrastructurally. All 33 patients could be evaluated for efficacy. After cessation of the symptoms of neurogenic inflammation, such as burning sensations or erythema, all of them experienced a complete elimination of pruritus within 12 days. In addition, capsaicin largely contributed to the gradual healing of the skin lesions. After discontinuation of the therapy, pruritus returned in 16 of 33 patients within 2 months. At the ultrastructural level, no degenerative changes of cutaneous nerves could be found during or after capsaicin therapy. Depletion of substance P was demonstrated by confocal laser scanning microscopy thus confirming the specific effect of capsaicin in vivo. Topical treatment of prurigo nodularis with capsaicin proved to be an effective and safe regimen resulting in clearing of the skin lesions.


In vitro assessment of the efficacy of thermal therapy in human benign prostatic hyperplasia.
The successful management of BPH with minimally invasive thermal therapies requires a firm understanding of the temperature-time relationship for tissue destruction. In order to accomplish this objective, the present in vitro study assesses the cellular viability of human BPH tissue subjected to an experimental matrix of different temperature-time combinations. Hyperplastic prostate tissue was obtained from 10 radical prostatectomy specimens resected for adenocarcinoma. A portion of hyperplastic tissue from the lateral lobe of each prostate was sectioned into multiple 1 mm thick tissue strips, placed on a coverslip and thermally treated on a controlled temperature copper block with various temperatures (45-70 degrees C) for various times (1-60 min). After heat treatment, the tissue slices were cultured for 72 h and viability was assessed using two independent assays: histology and dye uptake for stromal tissue and using histology alone for the glandular tissue. The hyperplastic human prostate tissue showed a progressive histological increase in irreversible injury with increasing temperature-time severity. The dye uptake and histology results for stromal viability were similar for all temperature-time combinations. In vitro thermal injury showed 85-90% stromal destruction (raw data) of human BPH for temperature-time combinations of 45 degrees C for 60 min, 50 degrees C for 30 min, 55 degrees C for 5 min, 60 degrees C for 2 min and 70 degrees C for 1 min. Apoptosis was also identified in the control and milder treated tissues with the degree of glandular apoptosis (about 20%) more than that seen in the stromal regions (< 5%). The Arrhenius model of injury was fitted to the data for conditions leading to a 90% drop in viability (normalized to control) obtained for stromal tissue. The activation energies (E) were 40.1 and 38.4 kcal/mole for the dye uptake study and histology, respectively, and the corresponding frequency factors (A) were 1.1 x 10(24) and 7.78 x 10(22)/s. This study presents the first temperature-time versus tissue destruction relation for human BPH tissue. Moreover, it supports the concept that higher temperatures can be used for shorter durations to induce tissue injury comparable with the current clinically recommended lower temperature-longer time treatments (i.e. 45 degrees C for 60 min) for transurethral microwave thermotherapy of the prostate.


[Use of life quality indices in the rehabilitation therapy of inflammatory and degenerative rheumatic diseases].
To study whether life quality (LQ) indices may be used to evaluate the efficiency of structural resonance electromagnetic therapy (SREMT) and its correction in patients with rheumatoid arthritis (RA) and in those with osteoarthrosis (OA). One hundred and twenty patients with significant RA and 94 patients diagnosed as having OA were followed up. The SF-36 questionnaire was used to detect and assess objective data on health problems and changes. The patients with RA and those with OA were randomized to the groups matched for gender, age, and disease duration: a study group (n = 80) and a control one (n = 40) for RA; a study group (n = 56) and a control one (n = 38) for OA. Both group patients received the same medical and physiotherapeutic treatment (within each nosological entity, respectively). Furthermore, in the study groups, the patients with RA and those with OA had additionally 10-12 daily (43-min) sessions of SREMT on a Rematerp apparatus. The inclusion of SREMT into the multimodality treatment of patients with RA and those with OA has shown significant benefits. A wide spectrum of therapeutic action of SREMT exerts a positive impact on the basic LQ indices (the indicators of physical and role physical performance, somatic pain, general condition, and social and role emotional performance). SREMT may be recommended for use in rheumatological care as a technique that enhances the efficiency of performed therapy and medical rehabilitative measures in inflammatory and degenerative rheumatic diseases.


Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes.
Uncoupling protein (UCP)-1 expressed in brown adipose tissue plays an important role in thermogenesis. Recent data suggest that brown-like adipocytes in white adipose tissue (WAT) and skeletal muscle play a crucial role in the regulation of body weight. Understanding of the mechanism underlying the increase in UCP-1 expression level in these organs should, therefore, provide an approach to managing obesity. The thyroid hormone (TH) has profound effects on mitochondrial biogenesis and promotes the mRNA expression of UCP in skeletal muscle and brown adipose tissue. However, the action of TH on the induction of brown-like adipocytes in WAT has not been elucidated. Thus we investigate whether TH could regulate UCP-1 expression in WAT using multipotent cells isolated from human adipose tissue. In this study, triiodothyronine (T(3)) treatment induced UCP-1 expression and mitochondrial biogenesis, accompanied by the induction of the CCAAT/enhancer binding protein, peroxisome proliferator-activated receptor-γ coactivator-1α, and nuclear respiratory factor-1 in differentiated human multipotent adipose-derived stem cells. The effects of T(3) on UCP-1 induction were dependent on TH receptor-β. Moreover, T(3) treatment increased oxygen consumption rate. These findings indicate that T(3) is an active modulator, which induces energy utilization in white adipocytes through the regulation of UCP-1 expression and mitochondrial biogenesis. Our findings provide evidence that T(3) serves as a bipotential mediator of mitochondrial biogenesis.


A new thermal dose model based on Vogel-Tammann-Fulcher behaviour in thermal damage processes.
Thermal dose models are metrics that quantify the thermal effect on tissues based on the temperature and the time of exposure. These models are used to predict and control the outcome of hyperthermia (up to 45°C) treatments, and of thermal coagulation treatments at higher temperatures (>45°C). The validity and accuracy of the commonly used models (CEM43) are questionable when heating above the hyperthermia temperature range occurs, leading to an over-estimation of the accumulation of thermal damage. A new CEM43 dose model based on an Arrhenius-type, Vogel-Tammann-Fulcher, equation using published data, is introduced in this work. The new dose values for the same damage threshold that was produced at different in-vivo skin experiments were in the same order of magnitude, while the current dose values varied by two orders of magnitude. In addition, the dose values obtained using the new model for the same damage threshold in 6 lesions in ex-vivo liver experiments were more consistent than the current model dose values. The contribution of this work is to provide new modeling approaches to inform more robust thermal dosimetry for improved thermal therapy modeling, monitoring, and control.


The importance of the eosinophil in head and neck cancer.
In a previous study, we found tumor-associated tissue eosinophilia (TATE) to be a favorable prognostic indicator for squamous cell carcinoma of the head and neck (p less than 0.05). The present expanded study was undertaken to confirm this finding. The pathology of 120 head and neck tumors was examined for histologic features suggestive of poor prognosis. Ten descriptive histopathologic variables, including two malignancy grading scales, were correlated with DNA flow cytometric data and clinical outcome. No correlation was found between the malignancy grading scales and DNA flow cytometric data or clinical outcome. The present expanded study confirmed with greater statistical significance (p less than 0.001) that high-grade TATE is a favorable prognostic indicator for head and neck cancer. Furthermore, high-grade TATE was associated with the absence of distant metastasis (p less than 0.05). Using a stepwise logistic regression analysis of the clinicopathologic variables in the study, high-grade TATE was the most influential variable affecting clinical outcome, followed by border, stage, and perineural invasion. We conclude that the grade of TATE is a significant prognostic indicator for head and neck cancer. The significance and possible role of the eosinophil in the tumor-host interaction are discussed.


[The frequency of Streptococcus pneumoniae strains and sensitivity surveillance for several antibiotics in Gifu Prefecture].
The frequency and the antibacterial sensitivity of Streptococcus pneumoniae strains isolated from 6 key hospitals (in 5 areas) and 1 otorhinolaryngology clinic in Gifu Prefecture from February to March, 1999, were investigated with several antibiotics. A total of 128 strains of Streptococcus pneumoniae were isolated throughout the study: 47 strains (36.7%) of penicillin-susceptible S. pneumoniae (PSSP), 51 strains (39.8%) of penicillin-intermediate S. pneumoniae (PISP), and 30 strains (23.4%) of penicillin-resistant S. pneumoniae (PRSP); the resistant bacteria being relatively prominent. In these hospitals, PSSP was isolated by 38.8% in all the key hospitals and by 30% in the otolaryngology clinic with almost no discernible difference. PISP was isolated by 63.3%, higher in the otolaryngology clinic and PRSP by 28.6%, higher in the key hospitals conversely. The MIC90s in PISP and PRSP were determined with the antibiotics. In result, only cefditoren (CDTR) showed favorable antibacterial activities with the MIC90 of 0.78 microgram/ml among penicillins or oral cephems. The MIC90s of carbapenems such as imipenem (IPM), meropenem (MEPM), and panipenem (PAPM) were less than 0.39 microgram/ml; particularly, PAPM showed the highest antibacterial activities. Among new quinolones such as tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), and ciprofloxacin (CPFX), TFLX showed the highest antibacterial activities with the MIC90 of 0.39 microgram/ml. Other agents showed very low antibacterial activities as the MIC90s were 25 micrograms/ml in minocycline (MINO) and more than 100 micrograms/ml in clarithromycin (CAM) and clindamycin (CLDM).


Semen variables and hormone profiles after kidney transplantation during adolescence.
Our aim was to investigate the semen variables and hormone profiles among transplant patients who received kidneys during adolescence. Seven postpubertal transplant patients who underwent successful renal transplantation during adolescence (13-19 years; 3 were preemptive) were enrolled in our clinical follow-up. Serum levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were checked together with the semen analysis. The ages of the patients ranged from 18 to 25 years (median, 22 years). The median age was 15 years (range, 12-18 years) at initial presentation. The median time between initial diagnosis and transplantation was 12 months (range, 2-60 months). The median follow-up after transplantation was 51 months (range, 23-134 months). Three of the seven patients had unilateral low testicular volume. The renal function tests were within normal limits, as well as serum levels of prolactin, FSH, LH, and testosterone. Sperm counts ranged from 0.2 to 55 million/mL (median, 1.7 million/mL). Only 1 patient (14.2%) had normal sperm parameters. Oligoteratozoospermia (low sperm count and defects in morphology) was observed in 1/7 (14.2%), asthenoteratozoospermia (low levels of motility and defects in morphology) in 1/7 (14.2%), and all parameters were abnormal in 4/7 (57.1%) cases. Our data suggest that in contrast to adult patients, semen variables are severely affected and spermatogenesis does not improve after renal transplantation when the patient was subjected to uremia before or during adolescence, the crucial period for spermatogenesis.


Human donor liver and serum concentrations of perfluorooctanesulfonate and other perfluorochemicals.
Perfluorooctanesulfonate (PFOS, CaF17SO3-) has been identified in the serum of nonoccupationally exposed humans and in serum and liver tissue in wildlife. The purpose of this investigation was to determine whether PFOS liver concentrations in humans are comparable to the approximate 30 ng/mL average serum concentrations reported in nonoccupationally exposed subjects. Thirty-one donors (16 male and 15 female, age range 5-74) provided serum and/or liver samples for analysis of PFOS and three other fluorochemicals: perfluorosulfonamide (PFOSA, C8F17SO2NH2), perfluorooctanoate (PFOA, C7F15CO2-), and perfluorohexanesulfonate (PFHxS, C6F13SO3-). Both sera and liver samples were extracted by ion-pair extraction and quantitatively assayed using high-performance liquid chromatography electrospray tandem mass spectrometry. Liver PFOS concentrations ranged from <4.5 ng/g (limit of quantitation, LOQ)to 57.0 ng/g. Serum PFOS concentrations ranged from <6.1 ng/mL (LOQ) to 58.3 ng/mL. Among the 23 paired samples, the mean liver to serum ratio was 1.3:1 (95% confidence interval 0.9:1-1.7:1). This liver to serum ratio is comparable to that reported in a toxicological study of cynomolgus monkeys, which had liver and serum concentrations 2-3 orders of magnitude higher than observed in these human donors. This information may be useful in human risk characterization for PFOS. Liver to serum ratios were not estimated for PFOA, PFHxS, and PFOSA as 90% of the human donor liver samples were determined to be less than the LOQ.


Association between clinical frailty, illness severity and post-discharge survival: a prospective cohort study of older medical inpatients in Norway.
Study associations between frailty, illness severity and post-discharge survival in older adults admitted to medical wards with acute clinical conditions. Prospective cohort study of 195 individuals (mean age 86; 63% females) admitted to two medical wards with acute illness, followed up for all-cause mortality for 20 months after discharge. Ward physicians screened for frailty and quantified its degree from one to eight using Clinical Frailty Scale (CFS), while clinical illness severity was estimated by New Early Warning Score 2 (NEWS2) and laboratory illness severity was calculated by a frailty index (FI-lab) using routine blood tests. CFS, NEWS2 and FI-lab scores were independently associated with post-discharge survival in an adjusted Cox proportional hazards model with age, ward category (acute geriatric and general medical) and comorbidity as covariates. Adjusted hazard ratios and 95% confidence intervals were 1.54 (1.24-1.91) for CFS, 1.12 (1.03-1.23) for NEWS2, and 1.02 (1.00-1.05) for FI-lab. A frailty × illness severity category interaction effect (p = 0.003), suggested that the impact of frailty on survival was greater in those experiencing higher levels of illness severity. Among patients with at least moderate frailty (CFS six to eight) and high illness severity according to both NEWS2 and FI-lab, two (13%) were alive at follow-up. Frailty screening aided prognostication of survival following discharge in older acutely ill persons admitted to medical wards. The prognostic value of frailty increased when combined with readily available illness severity markers acquired during admission.


A poliovirus-induced cytoplasmic membrane complex is exploited by the RNA polymerase of superinfecting Mouse Elberfeld (ME) virus.
The preexistence of a cytoplasmic membrane complex in HEp-2 cells, induced by poliovirus when inhibited in its reproduction by guanidine, was a prerequisite for accelerated reproduction of superinfecting Mouse Elberfeld (ME) virus. Guanidine-inhibited poliovirus induced a membrane complex of 470S that was successively modified into a faster sedimenting membrane complex (up to 700S) by superinfecting ME virus and exploited for ME virus reproduction. The modified membrane complex was the site for ME virus-specific RNA polymerization characterized by the existence of in vivo and in vitro activity of ME virus RNA polymerase associated with the modified membrane complex. Proof of membrane-bound RNA polymerase and newly synthesized ME virus RNA including replicative intermediate led to the conclusion that superinfecting ME virus exploits the 'poliovirus/guanidine'-induced complex as the site of action of its replication complex.


Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications.
Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one. The objective of this report was to systematically review scientific data from studies conducted in the tropics on concurrent malaria and typhoid fever within the last two decades (1987-2007), to highlight the diagnostic challenges and the public health implications. Using the MedLine Entrez-PubMed search, relevant publications were identified for the review via the key words Malaria and Typhoid fever, which yielded 287 entries as of January 2008. Most of the studies reviewed expressed concern that poor diagnosis continues to hinder effective control of concurrent malaria and typhoid fever in the tropics due to: non-specific clinical presentation of the diseases; high prevalence of asymptomatic infections; lack of resources and insufficient access to trained health care providers and facilities; and widespread practice of self-treatment for clinically suspected malaria or typhoid fever. There were considerably higher rates of concurrent malaria and typhoid fever by Widal test compared to the bacteriological culture technique. Although culture technique remains the gold standard in typhoid fever diagnosis, Widal test is still of significant diagnostic value provided judicious interpretation of the test is made against a background of pertinent information. Malaria could be controlled through interventions to minimize human-vector contact, while improved personal hygiene, targeted vaccination campaigns and intensive community health education could help to control typhoid fever in the tropics.


Pulmonary Tumor Thrombotic Microangiopathy Mimicking Inhalation Lung Injury.
Pulmonary tumor thrombotic microangiopathy (PTTM) is a complication characterized by dyspnea, pulmonary hypertension, and occasionally sudden death. We encountered a man who developed PTTM and had an inhalation history of chemical herbicides and abnormal findings on chest computed tomography, mimicking chemical inhalation lung injury. He was diagnosed with PTTM with adenocarcinoma by a transbronchial lung biopsy and received chemotherapy and anticoagulant therapy. He survived for one month. An autopsy revealed primary gastric cancer with PTTM that can have a presentation similar to diffuse pulmonary diseases, including chemical inhalation lung injury. The examination of a biopsy specimen is crucial in such patients.


Ambulatory hand emergency: 2 years-experience in an public university hospital center.
Hand emergencies represent the most frequent traumatic injuries and outpatient surgery is still improving. It will achieve 70% of total surgeries by 2022. Our hand trauma center has been able to set up an emergency day surgery department in a university hospital center. With this article, we would like to report the ambula- tory care management and practice for hand emer- gencies in our university hospital center over 2 years. 892 patients suffering from hand traumas and managed in our day surgery department, were retro-spectively reviewed between January 2016 and December 2017. Patients' demographic data, anesthe- tic data, trauma's circumstances, medical care and surgical outcomes have been disclosed. A descriptive analysis and a statistical assessment was realized. Cut injury was the most recorded case, followed by impactions. Tendon injuries were the most frequent (32%), followed by fractures (26%), and exposed joints (18%). 13% of injuries were nil findings. Average patient care delay was 1.16 days. Mean of hospitalization was 7.5 hours. 16/892 patients needing intravenous antibiotics required hospitalization. 41 complications including 27 secondary surgeries were reported. Hospital facilities are forced to reassess their entire procedures to achieve efficiency and improvement for healthcare. Progress in outpatient surgery permits emergency management in hand surgery, improving patient cares both medically and economically.


Highly selective and sensitive detection of neurotransmitters using receptor-modified single-walled carbon nanotube sensors.
We present receptor-modified carbon nanotube sensors for the highly selective and sensitive detection of acetylcholine (ACh), one kind of neurotransmitter. Here, we successfully expressed the M1 muscarinic acetylcholine receptor (M1 mAChR), a family of G protein-coupled receptors (GPCRs), in E. coli and coated single-walled carbon nanotube (swCNT)-field effect transistors (FETs) with lipid membrane including the receptor, enabling highly selective and sensitive ACh detection. Using this sensor, we could detect ACh at 100 pM concentration. Moreover, we showed that this sensor could selectively detect ACh among other neurotransmitters. This is the first demonstration of the real-time detection of ACh using specific binding between ACh and M1 mAChR, and it may lead to breakthroughs for various applications such as disease diagnosis and drug screening.


Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar.
PPAR (peroxisome proliferator-activated receptor) pan agonists play a critical role in treating metabolic diseases, especially the Type-2 diabetes mellitus (T2DM). GlaxoSmithKline's sodelglitazar (GW677954) is one of the potent PPAR pan agonists, which is currently being investigated in Phase II clinical trials for the treatment of T2DM and its complications. The present study was aimed at investigation into the effect of sodelglitazar at the binding pockets of PPARs. The Schrodinger Suite program (2009) was used for the molecular docking, while the GROMACS program used for the molecular dynamics (MD) simulations. The results thus obtained showed that sodelglitazar being docked well in the active site of PPARs. It was revealed by the MD simulations that the structures of the receptors remained quite stable during the simulations and that the important AF-2 helix showed less flexibility after binding with sodelglitazar. Also, it was observed that sodelglitazar could periodically form hydrogen bonds with the AF-2 helix of PPARs to stabilize the AF-2 helix in an active conformation. Our findings have confirmed that GlaxoSmithKline's sodelglitazar can activate the PPARs, which is quite consistent with the previous biological studies.


Fast Detection of SARS-CoV-2 RNA Directly from Respiratory Samples Using a Loop-Mediated Isothermal Amplification (LAMP) Test.
The availability of simple SARS-CoV-2 detection methods is crucial to contain the COVID-19 pandemic. This study examined whether a commercial LAMP assay can reliably detect SARS-CoV-2 genomes directly in respiratory samples without having to extract nucleic acids (NA) beforehand. Nasopharyngeal swabs (NPS, n = 220) were tested by real-time reverse transcription (RT)-PCR and with the LAMP assay. For RT-PCR, NA were investigated. For LAMP, NA from 26 NPS in viral transport medium (VTM) were tested. The other 194 NPS were analyzed directly without prior NA extraction (140 samples in VTM; 54 dry swab samples stirred in phosphate buffered saline). Ten NPS were tested directly by LAMP using a sous-vide cooking unit. The isothermal assay demonstrated excellent specificity (100%) but moderate sensitivity (68.8%), with a positive predictive value of 1 and a negative predictive value of 0.65 for direct testing of NPS in VTM. The use of dry swabs, even without NA extraction, improved the analytical sensitivity; up to 6% of samples showed signs of inhibition. LAMP could be performed successfully with a sous-vide cooking unit. This technique is very fast, requires little laboratory resources, and can replace rapid antigen tests or verify reactive rapid tests on-site.


Cannabinoid 1 receptor blockade reduces atherosclerosis with enhances reverse cholesterol transport.
A recent clinical study using coronary intravascular ultrasound showed that rimonabant, a cannabinoid 1 (CB1) receptor antagonist, significantly reduced total atheroma volume, suggesting that CB1 receptor blockade could be beneficial in anti-atherogenic therapy. The reverse cholesterol transport (RCT) system plays important roles in atherogenesis. We investigated whether CB1 receptor blockade could modulate atherogenesis in mice. Oral administration of rimonabant (8 mg/kg/day) to apolipoprotein E-deficient mice for 3 months significantly reduced the relative area of atherosclerotic lesions in the aorta (vehicle; 12.6+/-4.0% vs. rimonabant; 9.7+/-2.3, n=12 each, p<0.05) with an increase in serum adiponectin levels (15.6+/-2.3 microg/mL vs. 12.2+/-2.1, n=12 each, p<0.001), without affecting body weight or serum cholesterol levels. Rimonabant tended to increase serum high-density lipoprotein cholesterol (HDL-C) (p=0.05). The relative area of atherosclerotic lesions in the aorta correlated inversely with serum HDL-C levels (r=-0.45, n=24, p<0.05). Rimonabant upregulated the mRNA expression levels of various components of the RCT system on THP-1 cell-derived macrophages (scavenger receptor B1: 1.15+/-0.12 fold, n=6; p<0.05, ATP-binding cassette [ABC] transporter G1: 1.23+/-0.11 fold, n=6; p<0.01), but not ABCA1 (1.13+/-0.20 fold, n=6; p=0.13). CB1 receptor blockade reduced atherosclerosis in apoE-deficient mice through an increase in serum adiponectin levels and activation of the RCT system. CB1 receptor blockade may be therapeutically beneficial for atherogenesis by increasing the serum adiponectin level and enhancing of the RCT system.


Characterization of the altered form of the c-src gene product in neuronal cells.
The pp60c-src protein that is expressed at high levels in cultures of neurons from rat embryos displays an altered mobility on SDS-polyacrylamide gels due to a structural difference in the amino-terminal region of the molecule. In this report we show that the expression of this unique form of pp60c-src, designated pp60c-src(+), is not restricted to cultured neuronal cells since the pp60c-src molecules expressed in tissues from avian and rat neural tissues also display a retarded electrophoretic mobility. The amino-terminal region from pp60c-src(+) was found to contain a novel phosphorylated tryptic peptide that contains phosphoserine. However, this phosphorylation does not appear to be responsible for the retarded electrophoretic mobility of pp60c-src(+), since the mobility of this protein is not altered by phosphatase treatment under conditions that remove greater than 95% of the radiolabeled phosphate on pp60c-src(+). The altered electrophoretic form of pp60c-src was also shown to be radiolabeled with [3H]myristate, indicating that pp60c-src is fatty-acylated in neurons, as is pp60c-src in fibroblasts. The pp60c-src molecules synthesized in vitro using rabbit reticulocyte lysates programmed with mRNA from embryonic brain migrated more slowly on SDS-polyacrylamide gels than the pp60c-src protein that was translated in vitro using RNA from embryonic limb tissue. These results suggest the possibility that the c-src mRNA expressed in neurons may undergo a unique form of processing to generate the structurally distinct form of neuronal pp60c-src(+).


A single-domain rhodanese homologue MnRDH1 helps to maintain redox balance in Macrobrachium nipponense.
Rhodaneses are known to catalyze in vitro the transfer of a sulfane sulfur atom from thiosulfate to cyanide with concomitant formation of thiocyanate, however, their biological functions remain speculative despite the main role is considered as detoxifying cyanide especially in animal livers. In this study, we characterized a single-domain rhodanese homologue, MnRDH1, from Macrobrachium nipponense. We found MnRDH1 with the highest expression in hemocytes. Upon Aeromonas hydrophila challenge, expression of MnRDH1 was up-regulated in various tissues, including hepatopancreas, gill, intestine and hemocytes. RNAi knockdown of MnRDH1 led to rapid increases of malondialdehyde content, which reveals that MnRDH1 deficiency causes oxidative stress. The expression of MnRDH1 in hepatopancreas was significantly increased in response to the doxorubicin-induced oxidative stress, indicating the gene is oxidative stress inducible. We transformed E. coli with MnRDH1 and the mutant MnRDH1C75A, and found significant rhodanese activity of the recombinant protein of MnRDH1 in vitro, but detected no enzyme activity of the mutant MnRDH1C75A. When under the oxidative insult by H2O2, the MnRDH1 transformed E. coli had significantly enhanced survival rates compared to those bacteria transformed with MnRDH1C75A. In conclusion, our study demonstrates that rhodanese in M. nipponense confers oxidative stress tolerance, and thus renders an evidence for the notion that rhodanese family genes act a critical role in antioxidant defenses.