Early initiation of insulin attenuates histological and functional changes in the liver of streptozotocin-induced diabetic rats using 99mTc-sulfur colloid functional imaging.
This study aimed to investigate the effect of insulin on the reticuloendothelial system (RES) in the liver and spleen in diabetic rats. Sprague Dawley rats were divided into control, diabetic rats (DM) and diabetic rats treated with insulin (IDM) for 2 weeks. Rats were imaged with technetium-99m-sulfur colloid (99mTc-SC) tracer to determine regional distributions of the tracer for all groups by drawing regions of interest and then obtained the ratios as the cumulative counts of heart, liver, and spleen to the whole body (WB). Liver tissue from sacrificed rats from each group was examined by light and electron microscopy. 99mTc-SC uptake ratios showed a lower liver to WB uptake ratio in the DM rats compared to both controls and IDM rats. Electron microscopy showed severe vacuolization of the hepatocytes of DM rats. The IDM rats show complete resolution of the vacuolization. The early administration of insulin for 2 weeks to diabetic rats could significantly resolve the phagocytic RES function and histological changes in the liver.


A fatal neonatal case of medium-chain acyl-coenzyme A dehydrogenase deficiency with homozygous A-->G985 transition.
A term neonate became lethargic and hypotonic at 46 hours of age and died 10 hours later despite supportive therapy. Urinary organic acids indicated medium-chain acyl-coenzyme A dehydrogenase deficiency, and DNA studies confirmed this disorder. Neonatal symptoms in this enzyme deficiency have rarely been reported, and recent reviews have ignored or discounted this presentation.


Effect of ventilatory support on functional capacity in patients with heart failure: a pilot study.
Heart failure (HF) is an important public health problem, of which main clinical symptoms are dyspnea and fatigue. Noninvasive ventilatory support has been used as adjuvant therapy in cardiac rehabilitation in order to improve the functional capacity of patients. To evaluate the functional capacity of patients with HF submitted to ventilatory support. We evaluated the sociodemographic information, as well as data on quality of life, blood pressure (BP), peripheral oxygen saturation (SpO2), dyspnea, lactate concentration before and after the 6-minute walk test (6MWT) and the distance walked by patients of both sexes with chronic heart failure (CHF), with left ventricular ejection fraction (LVEF) < 45.0% , randomized in two groups: control and CPAP (the group used CPAP - 10 cmH2O for 30 minutes). A total of 12 patients, of which 8 were males, with CHF functional class II and III (NYHA) participated in the study. The patients had mean LVEF of 35.3 ± 8.7 and mean age was 46.3 ± 10.3 years. When comparing the control group with the CPAP group at the end of the 6th minute, there was a significant difference between the groups regarding SpO2 values ( 93.6 ± 1.5 % vs CPAP: 96.1±1.8%; p = 0.027), index of dyspnea ( 13.1 ± 1.16 vs CPAP: 11 ± 0.8; p = 0.009), lactate concentration ( 3.3 ± 0.7 mmol/l vs CPAP: 2.3 ± 0.5 mmol/l; p = 0.025) and distance walked at the 6MWT (CONTROL: 420.6 ± 73.8 m vs CPAP: 534 ± 89.91 m; p = 0.038). The previous use of the CPAP had beneficial effects on SpO2, index of dyspnea, lactate concentration, double product and the distance walked at the 6MWT in patients with CHF when performing the 6MWT.


Human colostrum and breast milk contain high levels of TNF-related apoptosis-inducing ligand (TRAIL).
TNF-related apoptosis inducing ligand (TRAIL) is a pleiotropic cytokine, which plays a key role in the immune system as well as in controlling the balance of apoptosis and proliferation in various organs and tissues. To investigate the presence and levels of soluble TRAIL in human colostrum and milk. The levels of soluble human TRAIL were measured in human colostrum (day 2 after delivery) and breast milk (day 5 after delivery). The presence of TRAIL was also measured in infant formula. Levels of soluble TRAIL in the colostrum and mature human milk were, respectively, at least 400 and 100 fold higher than those detected in human serum. No TRAIL was detected in formula. Human soluble TRAIL is present at extremely high levels in human colostrum and human milk and might have a significant role in mediating the anti-cancer activity of human milk.


Adrenal function in normal infants and in marasmus and kwashiorkor. Cortisol secretion, diurnal variation of plasma cortisol, and urinary excretion of 17-hydroxycorticoids, free corticoids, and cortisol.
Normal infants exhibited circadian rhythmicity of plasma F concentration. Infants from 2.1 to 3.2 months of age had CSR significantly higher than those of older infants. THF/THE urinary excretion ratios increased with age. The 17OHCS excretion was higher in the younger infants. Urinary excretions of free corticoids and cortisol were similar in all age groups. In marasmus, plasma F concentrations in the morning and evening were significantly elevated. Normal diurnal variation returned following therapy. CSR and 17OHCS excretions were not different from age controls, but were significantly lower than size controls, THF/THE ratios, urinary excretion of free corticoids and cortisol were normal. In marasmic kwashiorkor, plasma F concentrations were significantly elevated in the morning and evening. There was a suggestive decrease with therapy. CSR was low before and after treatment. THF/THE ratios, urinary 17OHCS excretion, and urinary free corticoids and cortisol were not significantly different from infants matched for size or patients with marasmus.


Controllable antibacterial and bacterially anti-adhesive surface fabricated by a bio-inspired beetle-like macromolecule.
Drug resistance to bacteria becomes an emerging intractable problem, therefore, developing novel antibacterial agents has become urgently needed. Herein, a bio-inspired design strategy was adopted to synthesize a series of beetle-like macromolecule of multiple quaternary ammonium salts (QASs), which was designed with different cationic charge densities and numbers of hexadecane chains by adjusting their different quaternization degree (QD). It was found that the fabricated fabric surface with them exhibited controllable and outstanding antibacterial and bacterially anti-adhesive properties. More importantly, the antibacterial efficiency was demonstrated to be enhanced with the increasing of QD, and related to the zeta potential, and surface tension. Additionally, the proposed bacterially anti-adhesive model of action revealed the "resisting effect" of hydration layer which greatly resisted the adhesion of bacteria.


Antipyretic effect of acetaminophen suppositories in rats.
An animal model used yeast-fevered rats to measure the relative antipyretic effects of different commercially available acetaminophen-containing suppositories. A laboratory-prepared acetaminophen-containing suppository and placebo suppositories also were investigated. Release from the suppositories was measured in vitro. All acetaminophen products containing 600 mg of drug elicited significant decreases in the rectal temperature of fever-induced rats.


[Changes gas and electrolyte structure of blood under influence terahertz radiations on frequencies nitrogen oxide 150,176-150,664 GHz in the conditions of stress].
Influence terahertz radiations nitrogen oxide frequencies of 150,176 - 150,664 GHz on gas and electrolyte structure of blood of white rats being in condition of sharp stress. It is shown that at 15 minute mode of influence terahertz waves on frequencies nitrogen oxide observe partial restoration of studied indicators gas and electrolyte structure of blood at stress animals. At 30 minute mode of influence the specified waves observe complete recovery of the broken indicators gas and electrolyte blood structure.


A retrospective case comparison study of the relationship between an Integrated Care Pathway for people diagnosed with schizophrenia in acute mental health care and service users' length of stay, readmission rates and follow-up within 7 days of discharge.
WHAT IS KNOWN ON THE SUBJECT?: There is some evidence reporting the value of diagnostic-driven Integrated Care Pathways (ICPs) in reducing service users' length of inpatient stay, readmission rates and follow-up within seven days of discharge, but this evidence is untested in studies comparing care using ICP with other forms of care planning. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE?: This study present findings from research comparing care in a Trust that uses an ICP with a Trust using another form of care planning to direct the care of people diagnosed with schizophrenia. We were interested particularly in whether using an ICP was linked to length of inpatient stay, readmission rates and follow-up care within seven days of discharge. The results compare ICP driven care with another form of care. This study adds to the international evidence by being among the first to compare empirically, outcomes in a mental health Trust using an ICP with a Trust not using an ICP to direct care. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health nurses are central to the delivery of the psychosocial aspects of ICPs in particular and judging by the link between psychosocial interventions and quality of mental health care, it is possible that nurse-led psychosocial interventions contributed to the reduced length of stay. Background Integrated Care Pathways (ICPs) are used to deliver mental health services, yet evidence relating to outcomes is mixed. Aim To compare service users' length of stay, readmission rates and follow-up within 7 days of discharge in a mental health Trust using an ICP to direct the care of people diagnosed with schizophrenia with a Trust using a nonICP method of care planning in England. A cohort study with a random sample of 400 service users with outcomes analysed retrospectively. Results The ICP Trust had a 13.5 day shorter average length of stay, this difference was statistically significant. No statistically significant differences were observed in rates of readmission or follow-up within 7 days of discharge. Discussion and implications Mental health nurses are central to the delivery of the psychosocial aspects of ICPs in particular and judging by the link between psychosocial interventions and quality of mental health care, it is possible that nurse-led psychosocial interventions contributed to the reduced length of stay.


Epidemiology and burden of rotavirus disease in Central Asia.
Rotavirus infection is the most common cause of severe gastroenteritis in children worldwide. New rotavirus vaccines are not currently used in the five countries that make up the Central Asian region. Three of these countries, Kazakhstan, Uzbekistan, and Kyrgyzstan, have a combined total population of 48 million and an estimated 1 million annual births. We conducted prospective hospital-based surveillance for rotavirus diarrhea in three Central Asian countries (Kazakhstan, Uzbekistan, and Kyrgyzstan) during 2005-2009 to estimate the burden of rotavirus. We calculated the proportion of rotavirus among children aged <5 years hospitalized with acute diarrhea and estimated numbers of rotavirus-associated deaths, hospitalizations, outpatient visits, and home care episodes. Of 20 780 children hospitalized with diarrhea and enrolled in the study, 26% (95% confidence interval (CI) 25-27) were positive for rotavirus antigen by ELISA. On an annual basis, 4007 (2.6 per 1000 child-years) rotavirus hospitalizations occur in Kazakhstan, 5491 (2.1 per 1000 child-years) in Uzbekistan, and 3883 (6.8 per 1000 child-years) in Kyrgyzstan. Rotavirus is also estimated to cause 68 (0.04 per 1000 child-years) deaths in children aged <5 years in Kazakhstan, 662 (0.25 per 1000 child-years) in Uzbekistan, and 156 (0.27 per 1000 child-years) in Kyrgyzstan. This study presents an epidemiological picture of rotavirus disease in Central Asia and illustrates a substantial rotavirus burden, which is preventable with rotavirus vaccination.


Evaluation of 4-bp insertion/deletion polymorphism within the 3'UTR of SGSM3 in bladder cancer using mismatch PCR-RFLP method: A preliminary report.
The small G protein signaling modulator 3 (SGSM3) has been shown to be associated with small G-protein-coupled receptor signaling. There is little data regarding the impact of SGSM3 polymorphisms on cancer risk. In the present study, we aimed to evaluate the impact of 4-bp insertion/deletion (rs56228771) polymorphism in the 3'UTR of SGSM3 and susceptibility to bladder cancer in a sample of the Iranian population. This case-control study included 143 pathologically confirmed bladder cancer patients and 144 healthy subjects. The SGSM3 4-bp ins/del (rs56228771) variant was determined by mismatch PCR-RFLP. The findings showed that ins/del genotype and ins allele of SGSM3 4-bp ins/del polymorphism significantly increased the risk of bladder cancer (OR = 3.11, 95%CI = 1.70-5.71, P < 0.0001 and OR = 2.11, 95%CI = 1.27-3.52, P = 0.004, respectively). Our findings support an association between 4-bp ins/del polymorphism in the 3'UTR of SGSM3 and the risk of bladder cancer in an Iranian population. Additional studies with larger sample sizes and diverse ethnicities are warranted to establish if such an association exists in general.


Polydispersity index of polymers revealed by DOSY NMR.
The polydispersity of a polymer chain is usually measured by its polydispersity index (PDI). In this study we present a method which allows to estimate the PDI of linear polymers from a simple diffusion experiment. The approach is based on the differential diffusion profile observed for the main polymer chain signal versus the extremity signal. From this difference, a statistical analysis of the DOSY spectrum allows the PDI to be estimated accurately, to the condition that the Flory coefficient of the polymer chain is known. Alternatively, the mass average molar mass Mw and the number average molar mass Mn can be extracted separately from the same spectrum. Results on PEO mixes reveal that, using this new method, PDI can be estimated with a very good accuracy. This method can easily be applied to almost any kind of linear polymers.


Long-term effects of early postnatal nutrition on subsequently body weight gain, emotionally and learning behaviour in male rats.
Male rats have been reared as litters of 2 pups (group A) or 12 pups (group B) during the first 3 weeks of life. Males of group A exhibited higher body weights from day 10 to day 430, reached puberty at earlier age and showed lower emotionality as well as diminished learning capability and decreased memory capacity in adulthood as compared to males of group B. Furthermore, adult males of group A developed an increased ratio of insulin to glucose serum concentration at 90 minutes after glucose administration.


Effects of histone methylation modification on low temperature seed germination and growth of maize.
Low temperature is a limiting factor of seed germination and plant growth. Although there is a lot information on the response of maize to low temperatures, there is still poorly description of how histone methylation affects maize germination and growth development at low temperatures. In this study, the germination rate and physiological indexes of wild-type maize inbred lines B73 (WT), SDG102 silencing lines (AS), SDG102 overexpressed lines (OE) at germination stage and seedling stage were measured under low temperature stress (4 ℃), and transcriptome sequencing was applied to analyze the differences of gene expression in panicle leaves among different materials. The results showed that the germination rate of WT and OE maize seeds at 4 ℃ was significantly lower than 25 ℃. The content of MDA, SOD and POD of 4 ℃ seeding leaves higher than contrast. Transcriptome sequencing results showed that there were 409 different expression genes (DEGs) between WT and AS, and the DEGs were mainly up-regulated expression in starch and sucrose metabolism and phenylpropanoid biosynthesis. There were 887 DEGs between WT and OE, which were mainly up-regulated in the pathways of plant hormone signal transduction, porphyrin and chlorophyll metabolism. This result could provide a theoretical basis for analyzing the growth and development of maize from the perspective of histone methylation modification.


Detection of the relatively slow-growing Propionibacterium acnes in seven matrices of blood components and advanced therapeutical medicinal products.
Relatively slow-growing bacteria like Propionibacterium acnes represent a challenge for quality control investigations in sterility release testing of blood components and advanced therapeutic medicinal products (ATMPs). A convenient validation with 7 matrices was performed using buffy coat, stem cells, islet cells, natural killer cells, red blood cells, platelets and plasma in the microbial detection system Bact/Alert®3D incubator. All matrix samples were spiked twofold with Propionibacterium acnes with approximately 50 colony forming units (CFUs) per bottle in iAST and iNST culture bottles for 14days using a multishot bioball. Additionally, the stem cell preparations were also incubated in iFAplus and iFNplus culture bottles, which include neutralizing polymers. The Bact/Alert®3D-System detected Propionibacterium acnes in anaerobic culture bottles in buffy coat [3.3 d (=positive signal day to detection as mean value)], red blood cells [3.2 d], platelets [3.3], plasma [3.7 d], natural killer cells [3.3 d] and islet cells [4.9 d], resp. No growth of Propionibacterium was found in autologous stem cells using iAST and iNST culture bottles. However, Propionibacterium was safely detected in the iFNplus culture bottle with polymers in the stem cell matrix. A successful validation of media was performed. Our study shows that Bact/Alert®3D-System safely detects the relatively slow-growing bacterium Propionibacterium acnes in different matrices in a practical way except stem cells. Using the iFNplus culture bottle for stem cell products positive signals were observed.


Perspectives on cardiovascular effects of incretin-based drugs: From bedside to bench, return trip.
Recently, cardiovascular outcome trials with glucose-lowering drugs used in type 2 diabetes mellitus, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), liraglutide and semaglutide, showed a reduction in cardiovascular events, which had not been observed in trials with other incretin-based drugs, such as lixisenatide or with dipeptidyl peptidase-4 inhibitors (DPP4i). Mechanisms underlying the observed cardiovascular differences between DPP4i and GLP1-RA, and across individual GLP1-RA are poorly understood. This review is aimed at collecting and summarizing available evidence from experimental and mechanistic studies on the action of GLP1-RA and DPP4i on the cardiovascular system, both deriving from clinical and pre-clinical sources. The results of cardiovascular outcome trials are interpreted on the basis of the experimental preclinical data available, paying particular attention to the heart failure results, and suggesting some novel intriguing hypotheses to explain some of the unexpected findings of cardioprotection of incretin-based drugs. In particular, we discuss the possible contribution to the incretin cardiovascular effects of a direct cardiac action of GLP-1 metabolites through GLP-1 receptor-independent pathways, and of DPP4 substrates other than GLP-1.


Reduction of Fusarium head blight and deoxynivalenol in wheat with early fungicide applications of prothioconazole.
Numerous studies have identified the benefit of fungicides applied at flowering (Zadoks Growth Stage (GS) 59-69) in the reduction of Fusarium head blight and the reduction of deoxynivalenol (DON) in harvested wheat grain. Two experiments were performed to identify the ability of prothioconazole (Proline) at three timings to reduce Fusarium head blight and resulting DON in harvested grain of wheat. Prothioconazole (150 g ha(-1)) was applied to plots of wheat at GS31, GS39, and GS65 in a full-factorial design. Plots were inoculated with Fusarium-infected oat grain at GS30 and mist-irrigated at GS65 to encourage head blight development. Plots were assessed for head blight symptoms at GS77 and harvested grain was analysed for yield, specific weight, thousand grain weight, and DON. Factorial analysis of variance (ANOVA) identified prothioconazole applications at each timing that resulted in significant reductions in Fusarium head blight and DON. The control achieved with combinations of spray timings was additive with no significant interactions. The control of Fusarium head blight at GS31, GS39, and GS65 was 50, 58 and 83%, respectively. The reduction in Fusarium head blight achieved by all three timings combined was 97% compared to the fully untreated control plots. The reduction of DON after application of prothioconazole at GS31, GS39, and GS65 was 27%, 49%, and 57%, respectively. The application of prothioconazole at all three timings achieved 83% reduction of DON compared with the fully untreated control plots. These experiments have determined, for the first time, significant additional head blight disease control and mycotoxin reduction with applications of a fungicide before flowering.


Synchronous double cancers of primary hepatic adenosquamous carcinoma and hepatocellular carcinoma: report of a case.
A 76-year-old male was referred for the treatment of liver tumors detected by abdominal computed tomography (CT). Dynamic CT revealed a low-density tumor with an irregularly enhanced rim in the left lateral sector, and a highly enhanced, well-circumscribed tumor in the caudate lobe, accompanied by dilation of the intrahepatic biliary ducts in the left lobe. Preoperative imaging studies led to the diagnosis of double cancers consisting of intrahepatic cholangiocarcinoma and hepatocellular carcinoma (HCC). Left hemihepatectomy with caudate lobectomy was performed. The postoperative course was uneventful. Microscopic evaluation revealed that the tumor in the left lateral sector was adenosquamous carcinoma (ASC), whereas that in the caudate lobe was HCC. This report presents the first case describing the resection of synchronous double cancers of primary hepatic ASC and HCC.


Inferred inactivation of the Cftr gene in the duodena of mice exposed to hexavalent chromium (Cr(VI)) in drinking water supports its tumor-suppressor status and implies its potential role in Cr(VI)-induced carcinogenesis of the small intestines.
Carcinogenicity of hexavalent chromium [Cr (VI)] has been supported by a number of epidemiological and animal studies; however, its carcinogenic mode of action is still incompletely understood. To identify mechanisms involved in cancer development, we analyzed gene expression data from duodena of mice exposed to Cr(VI) in drinking water. This analysis included (i) identification of upstream regulatory molecules that are likely responsible for the observed gene expression changes, (ii) identification of annotated gene expression data from public repositories that correlate with gene expression changes in duodena of Cr(VI)-exposed mice, and (iii) identification of hallmark and oncogenic signature gene sets relevant to these data. We identified the inactivated CFTR gene among the top scoring upstream regulators, and found positive correlations between the expression data from duodena of Cr(VI)-exposed mice and other datasets in public repositories associated with the inactivation of the CFTR gene. In addition, we found enrichment of signatures for oncogenic signaling, sustained cell proliferation, impaired apoptosis and tissue remodeling. Results of our computational study support the tumor-suppressor role of the CFTR gene. Furthermore, our results support human relevance of the Cr(VI)-mediated carcinogenesis observed in the small intestines of exposed mice and suggest possible groups that may be more vulnerable to the adverse outcomes associated with the inactivation of CFTR by hexavalent chromium or other agents. Lastly, our findings predict, for the first time, the role of CFTR inactivation in chemical carcinogenesis and expand the range of plausible mechanisms that may be operative in Cr(VI)-mediated carcinogenesis of intestinal and possibly other tissues.


Microwave-assisted synthesis of Co(II), Ni(II), Ti(III), and Ti (IV) complexes of iminochromeno-pyrido-pyrimidine and in vitro antiproliferative effect against H460, MCF-7, and HCT116.
The purpose of this paper is the synthesis of new metal complexes and their biological application. Four new transition metal complexes (2-5) were synthesized using conventional as well as microwave methods from 7-iminochromeno[4,3-d]pyrido[1,2-a]pyrimidin-6(7H)-one (1) and corresponding metal salts. Ligand 1 and metal complexes 2-5 were characterized by IR, 1H-NMR, 13 C-NMR, Mass spectroscopy and elemental analysis. The free ligand and the metal complexes have been tested for in vitro antiproliferative activity. The evaluation of the antiproliferative effects of compounds (1-5) on three tumor cell lines (H460, MCF-7, and HCT116) shows that all tested compounds have demonstrated moderate to pronounced antiproliferative and/or cytotoxic effect. The most active compounds were ligand 1 and metal complexes 3 and 5.


The Clinicopathological Correlations of hTERC Amplification with Esophageal Squamous Cell Precursor Lesions.
Esophageal squamous cell precursor lesions remain one of the most controversial topics in pathology and clinical management. To analyze the dysregulation of human telomerase RNA component (hTERC) in esophageal squamous cell precursor lesions and the clinicopathological correlations with the characteristics of esophageal squamous cell precursor lesions. Florescence in situ hybridization was performed to detect hTERC amplification in different gradings of esophageal squamous cell precursor lesions. With retrospective follow-up data, clinicopathological correlations between hTERC and esophageal squamous cell precursor lesions were subjected to logistic regression analysis. hTERC amplification gradually increased with upgrading of dysplasia, reaching the highest level in high-grade intraepithelial neoplasia, and there was a significant difference between the low-grade intraepithelial neoplasia group and the high-grade intraepithelial neoplasia group (P = 0.00). Logistic regression analysis showed that hTERC amplification was correlated with both dysplasia grading and ulcer characteristics of esophageal squamous cell precursor lesions (P < 0.05). hTERC amplification with increasing grading of esophageal squamous cell precursor lesions and the presence of ulcer characteristics might provide an important molecular and pathological marker for the diagnosis and clinical prognosis of esophageal squamous cell precursor lesions, especially for those ambiguous cases with more divergence in classification.


Scanning electron microscopy of an elastic fiber network which forms the internal elastic lamina in canine saphenous vein.
Scanning electron microscopy (SEM) was used to study the arrangement of elastic fibers in the canine saphenous vein as the basis for further studies of veins used in by-pass grafting operations. The elastic fiber arrangement in distended and non-distended veins was examined in both immersion-fixed and perfusion-fixed vessels. Transmission electron microscope (TEM) observation of the SEM samples confirmed the identity of these fibrillar structures as elastic fibers. In addition, specific stains for elastic fibers (Verhoeff's iron hematoxylin and orcein) were used. The elastic fibers forming the internal elastic lamina were arranged in a fishnet-like pattern. Large-diameter fibers, running longitudinally along the vascular wall, were interconnected by smaller oblique fibers. Together the fibers formed an elastic cylindrical network between the endothelium and the smooth muscle cells. The thicker longitudinal fibers were the same diameter in distended and non-distended veins. By contrast, the oblique fibers were thinner and more complexly branched in distended veins. The architecture of the elastic fiber network contributes to vascular flexibility and allows circumferential distension. The interconnecting oblique fibers presumably serve to distribute internal pressure equally around the venous wall.


Erratum: Genetic Evolution and Transmission Dynamics of Clade 126.96.36.199a Highly Pathogenic Avian Influenza A/H5N1 Viruses in Bangladesh.
[This corrects the article DOI: 10.1093/ve/veaa046.].


Three components of active membrane current in the C-neurons of rabbit cervical nodose ganglion under voltage clamp.
In the C-neurons of rabbit nodose ganglion there is a persistent slow outward current at Vm levels positive to -80 mV. This current was detectable in Na+-free Ringer and disappeared in Ca2+-free medium. Therefore it may be the Ca2+-activated K+ current. This K+ current shows a unique time and voltage dependency, suggesting that it may have a regulatory role on the excitability of C-neurons. Two other types of current also observed in C-neurons were IQ- and IA-like currents. In A-neurons, however, a Ca2+-activated K+ current was not observed at all.


The effects of chemotherapeutic drugs on PD-L1 gene expression in breast cancer cell lines.
Breast cancer is the most common cancer among women in terms of prevalence and mortality, and chemotherapy is one of the most effective treatments at higher stages. However, resistance to chemotherapy is the main obstacle in the treatment of this cancer. Accumulated evidence identified the PD-L1 protein as an essential protein in the development of different cancers. Abnormal expression of this protein in various tumor cells is linked to cancer development and inhibiting the function of immune cells, which correlated with reduced beneficial effects of chemotherapy drugs. In the present study, the effects of common chemotherapy drugs including doxorubicin, paclitaxel, and docetaxel on the expression of the PD-L1 gene were investigated by qRT-PCR before and after the treatment with these drugs in MD231, MD468, SKBR3 breast cancer cell lines. Also, the MTT test was applied to examine the effects of drugs on the growth and proliferation of cancer cells considering PD-L1 expression. The expression of the PD-L1 gene increased after 24 and 48 h of treatment with chemotherapy drugs. The obtained results indicate the enhancing effects of chemotherapy drugs on PD-L1 gene expression, which have a suppressive effect on the immune system against breast cancer. The use of these drugs as the first line of chemotherapy in triple-negative breast cancer is not recommended. However, there is still a need for further experimental and clinical research on the exact effects of these drugs on undesired immune cells exhaustion in breast cancer therapy.


A multicenter randomized comparison of paclitaxel-coated balloon with plain balloon angioplasty in patients with small vessel disease.
We investigated the efficacy and safety of using paclitaxel-coated balloon (PCB) to treat small vessel disease. In this multicenter, prospective, randomized controlled trial, one-hundred and thirty-five patients with native coronary lesions in small vessels were randomized into a PCB group and plain balloon angioplasty (POBA) group at a ratio of 2:1. There were no differences in target vessel failure (TVF) that was defined as cardiac death or target vessel-related myocardial infarction or target lesion revascularization (TLR), between the two groups (3.4 vs. 10.3%; P = 0.20), and TLR was slightly lower in the PCB group (2.3%) than that in the POBA group (10.3%) during 24 weeks follow-up. The late lumen loss (LLL) was significantly lower in the PCB group (0.01 ± 0.31 vs. 0.32 ± 0.34 mm; P < 0.01) and late lumen enlargement (LLE) was more frequently observed in the PCB group (48 vs. 15%; P < 0.01) by angiographic follow-up after 24 weeks. There were no cases of death, myocardial infarction, thrombosis and reocclusion in either group. This study was not able to demonstrate superiority of PCB compared with POBA.


Rapid and efficient microwave-assisted guanidine hydrochloride deep eutectic solvent pretreatment for biological conversion of castor stalk.
Microwave-assisted guanidine hydrochloride deep eutectic solvents (DESs) was developed for rapid and efficient pretreatment of castor stalk. The DES synthesized with guanidine hydrochloride and lactic acid showed a better delignification (92.02%) and enzymatic saccharification yield (96.3%) than choline chloride and lactic acid DES resulted. In addition, high-purity (up to 98%) lignin was recovered from the pretreatment liquor. The good recyclability of the guanidine hydrochloride-based DES was also proven with up to 90% cellulose hydrolysis with third-time recycled DES without post purification. The proposed microwave-assisted guanidine hydrochloride/lactic acid DES showed its great potentials as a highly effective and recyclable pretreatment solvent for future biorefinery strategies.


A new form of structural lipoprotein of outer membrane of Escherichia coli.
Among the membrane proteins synthesized in toluene-treated cells of Escherichia coli were two distinct membrane proteins of different molecular weights, which were cross-reactive with antiserum against a structural lipoprotein of the outer membrane. One was thought to be the known membrane lipoprotein since it migrated to the same position as that of the lipoprotein (Mr = 7,200) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, the other protein migrated slower than the lipoprotein. No protein corresponding to the slower-migrating species was detected in the membrane proteins synthesized in vivo. The apparent molecular weight of the protein at the new peak was estimated to be between 10,000 and 15,000. Both the new protein and the lipoprotein were found to be synthesized from stable mRNA(s) in the toluene-treated cells. The synthesis of the new protein as well as the lipoprotein was sensitive to chloramphenicol, indicating that both proteins were synthesized on ribosomes. Peptides mapping of the new protein revealed the same COOH-terminal sequence as in the lipoprotein. This indicates that the new protein has an extra sequence at the NH2-terminal end. This hypothesis is supported by the finding that the NH2 terminus of the new lipoprotein is methionine, while that of the lipoprotein is a substituted cysteine. From double label experiments with each of 17 different amino acids and arginine, the amino acid composition of the extra region was deduced. The new protein was found to contain at least 18 to 19 extra amino acid residues over the lipoprotein, if it is assumed that the new protein has no extra arginine residues. It was found that 4 out of the 5 amino acids which were deficient in the lipoprotein (phenylalanine, tryptophan, proline, and histidine) were also deficient in the new protein, but the fifth one, glycine, was present in the new protein. From these results, it seems possible that this new form of the lipoprotine is a precursor of the lipoprotein (prolipoprotein) in the process of biosynthesis and assembly of the lipoprotein in the outer membrane.


Tomographic findings are not always predictive of failed nonoperative management in blunt hepatic injury.
Nonoperative management (NOM) has become the standard treatment of blunt hepatic injury (BHI) for stable patients. Contrast extravasation (CE) on computed tomography (CT) scan had been reported as a sign that is associated with NOM failure. The goal of this study was to further investigate the risk factors of NOM failure in patients with CE on CT scan. From January 2005 to September 2009, patients with CE noted on a CT scan as a result of BHI were studied retrospectively. Physiological parameters, severity of injury, amount of transfusion, type of contrast extravasation, as well as treatment outcome were compared between patients with NOM failure and NOM success. A total of 130 patients were enrolled. Injury severity scores, amount of blood transfusion before hemostatic procedure, and grade of liver injury were significantly higher in NOM failure than in NOM success patients. There was no statistical difference in the NOM success rate between patients with contrast leakage into the peritoneum and those with contrast confined in the hepatic parenchyma. Higher injury severity score, more blood transfusion, and higher grade of liver injury are factors that correlate with NOM failure in patients with BHI. Contrast leakage into the peritoneum is not always a definite sign of NOM failure in BHI. Early and aggressive angioembolization is an effective adjunct of NOM in BHI patients, even with contrast leakage into peritoneum.


Investigation of a broad-spectrum PCR assay for human papillomaviruses in screening benign lesions of the upper aerodigestive tract.
A variety of different human papillomavirus (HPV) types can be found in benign and malignant lesions of the upper aerodigestive tract. Therefore a broad-spectrum assay is needed for screening reasons. A PCR system with degenerate consensus primers originating from a very conserved region (e.g. L1) of the HPV genome was applied. The sensitivity level was improved by combining PCR and nested PCR. A total of 27 biopsies from laryngeal papillomas (9), exophytic (3) and inverted (6) papillomas of the nasal cavity or paranasal sinuses, papillomas of the uvula or soft palate (5), leukoplakias of the larynx (2), seborrheic keratosis (1) and granulation tumor of the tongue (1) were analyzed by the broad-spectrum PCR system. Sixteen cases showed a positive result in either PCR or nested PCR or both. It was shown that the applied broad-spectrum PCR system is a reliable tool in the detection of HPV DNA in benign lesions of the upper aerodigestive tract.


Disentangling taxonomy of Biacetabulum (Cestoda, Caryophyllidea), parasites of catostomid fishes in North America: proposal of Megancestus gen. n. to accommodate B. carpiodi.
A new genus, Megancestus n. gen., is proposed to accommodate the caryophyllidean tapeworm Biacetabulum carpiodi Mackiewicz, 1969 from carpsuckers and quillback (Carpiodes spp.) in North America. This species is not closely related to other species of Biacetabulum Hunter, 1927 and is transferred to a newly erected genus. This new genus is typified by the possession of a small body (total length of 3.1-7.5 mm) with a scolex that bears a pair of large acetabulum-like loculi, two pairs of shallow lateral loculi, and a slightly convex apical disc, testes arranged in one or two layers, oval, thick-walled cirrus-sac, well-developed external seminal vesicle, separate gonopores, H-shaped ovary, few median vitelline follicles, and the uterus extending by a single loop anterior to the cirrus-sac. Megancestus differs from all Nearctic caryophyllidean genera (family Capingentidae), including Biacetabulum, by vitelline follicles dorsal to the ovary that connect the preovarian and postovarian vitelline fields. The most closely related Hunterella Mackiewicz et McCrae, 1962 differs by shape of the scolex (tholate, i.e., devoid of any loculi), dumbbell-shaped ovary and the uterus not extending anterior to the cirrus-sac. Megancestus carpiodi (Mackiewicz, 1969) n. comb. is the only species of the genus and it is a stenoxenous parasite, which has been found only in the river carpsucker (Carpiodes carpio-type host), quillback (Carpiodes cyprinus) and highfin carpsucker (Carpiodes velifer) (Catostomidae: Ictiobinae) in the lower and middle Mississippi basin.


Wood preservatives in children's wooden toys from China: Distribution, migration, oral exposure, and risk assessment.
A total of 90 wooden toys were collected, and six wood preservatives (chlorophenols and lindane) were analyzed by using gas chromatography-tandem mass spectrometry to assess the exposure risk of children to wood preservatives through oral contact with wooden toys. The detection rates of six preservatives ranged from 2.2% to 22.2%. The contents of the preservatives ranged from 0.6 µg/kg to 9.6 µg/kg. 2,4-Dichlorophenol (2,4-DCP) and 2,4,6-trichlorophenol (2,4,6-TCP) had higher detection rates and contents than other preservatives. Thus, their migration behaviors from toys to saliva were further investigated. In 11 positive samples, the max migration ratios of 2,4-DCP and 2,4,6-TCP ranged from 7.1% to 20.3% and from 11.1% to 24.8%, respectively. For children aged 3-36 months, the daily average 2,4-DCP exposure level associated with wooden toys ranged from 2.7 pg/(kg day) to 46.9 pg/(kg day), and the daily average 2,4,6-TCP exposure ranged from 3.6 pg/(kg day) to 69.4 pg/(kg day). The contribution to exposure provided by the saliva mobilization pathway was more than that provided by the ingestion of scraped-off toys, and the exposure level of 2,4,6-TCP was greater than that of 2,4-DCP. The max hazard quotient for 2,4-DCP was 1.9 × 10-4, and the max cancer risk for 2,4,6-TCP was 1.2 × 10-9. The above results indicated that although wood preservatives were distributed in wooden toys, exposure arising from directly mouthing these materials currently does not pose unacceptable risks to children.


Geographic Information System Analysis: Promoting the Organ Donation Process in Andalusia.
The objective is to study the geographic distribution of public awareness and acceptance of organ donation in Andalusian municipalities and determine its relationship with each population and the rate of aging. Data on organ donors from the Information System for Autonomous Regional Transplant Coordination in Andalusia were analyzed from 2006 to 2017. The geographic analysis was performed using free software from the Generalitat Valenciana Geographic Information System (gvGIS, Valencia, Spain). Data from the Spanish National Statistics Institute for the year 2017 were used as a reference for population estimates and calculating the rate of aging. From 2006 to 2017, a total of 3698 donors were registered in Andalusia, 28 of whom were residing in another autonomous community and 120 who were not censored as residents of their municipality, leaving a final total of 3550 donors. The rate of aging in 2017 was 1.02. Choropleth mapping was used to identify donors in each municipality. Population and aging rate in 2017 for these areas were also analyzed. Georeferenced data on organ donation not only reveals spatial differences in the distribution of public acceptance; it also provides insight into the relationship between this distribution and the sociodemographic characteristics of each community. In this study, areas with the least number of donors seem to coincide with difficult accessibility, higher aging index, and low population rates. These maps can assist transplant coordinators in targeting areas for public education and information campaigns to heighten awareness of the positive results of organ donation and potentiate its acceptance.


Left ventricular flow patterns in healthy subjects and patients with prosthetic mitral valves: an in vivo study using echocardiographic particle image velocimetry.
Echocardiographic particle image velocimetry is a new feature tracking-based approach to visualize and quantify left ventricular flow patterns in vivo. We investigated the potential role of this new technique by assessing vortex formations in healthy left ventricles and the effect of different types of prosthetic valves on intraventricular flow patterns and flow-mediated energy dissipation. We examined 19 patients (mean age, 57 +/- 19 years; 10 women). Nine were healthy, and 10 had prosthetic mitral valves (5 had bileaflet valves, 4 had bioprostheses, and 1 had a tilting-disc valve). Boluses of left heart contrast were administered intravenously. Echocardiographic apical views were analyzed offline by using prototype software that allowed intracavitary flow to be explored and enabled calculations of energy dissipation (relative pulsatile vorticity strength and vortex pulsation correlation) by means of particle image velocimetry. In healthy hearts a vortex filling the entire ventricle stores the kinetic energy of the blood and smoothly redirects the blood to the outflow tract. In patients with prosthetic valves, completely different flow patterns were identified depending on the type, orientation, and position of the valves, as well as left ventricular geometry. Patients with prosthetic valves showed significantly higher left ventricular energy dissipation than healthy subjects (relative pulsatile vorticity strength, 2.4 +/- 0.7 vs 1.6 +/- 0.4 [P < .001]; vortex pulsation correlation, 1.2 +/- 0.5 vs 0.7 +/- 0.2 [P < .001]). Echocardiographic particle image velocimetry is feasible. It clearly distinguishes flow patterns in healthy hearts from those in hearts with different types of prosthetic valves. Echocardiographic particle image velocimetry offers new insights into cardiac function and might be of importance to optimize valve replacement therapy.


Genetics of antiphospholipid syndrome.
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arterial or venous thrombosis or fetal loss and the presence of antiphospholipid antibodies (aPL). Genetic factors are thought to play a role in the susceptibility to APS. Similar to many other polygenic autoimmune diseases, human leukocyte antigen associations have been reported. The genetics of b(2)-glycoprotein I, one of the most representative target antigens of aPL, has been extensively studied. Additional genetic risk factors for the development of thrombosis in patients with aPL have also been discussed. However, the genes involved in APS have not been identified because antigen specificity of aPL and the pathophysiology of APS are highly heterogeneous and multifactorial. Genome-wide linkage analysis and larger cohort studies would lead to better understanding of the genes that might be involved in APS.


Confusion and its dynamics during device comprehension with breakdown scenarios.
The incidence and dynamics of confusion during complex learning and problem solving were investigated in an experiment where participants first read illustrated texts on everyday devices (e.g., an electric bell) followed by breakdown scenarios reflecting device malfunctions (e.g., "When a person rang the bell there was a short ding and then no sound was heard"). The breakdown scenarios were expected to trigger impasses and put participants in a state of cognitive disequilibrium where they would experience confusion and engage in effortful confusion resolution activities in order to restore equilibrium. The results confirmed that participants reported more confusion when presented with the breakdown scenarios compared to control scenarios that involved focusing on important device components in the absence of malfunctions. A second-by-second analysis of the dynamics of confusion yielded two characteristic trajectories that distinguished participants who partially resolved their confusion from those who remained confused. Participants who were successful in partial confusion resolution while processing the breakdowns outperformed their counterparts on knowledge assessments after controlling for scholastic aptitude, engagement, and frustration. This effect was amplified for those who were highly confused by the breakdowns. There was no direct breakdown vs. control effect on learning, but being actively engaged and partially resolving confusion during breakdown processing were positive predictors of increased learning with the breakdown compared to control scenarios. Implications of our findings for theories that highlight the role of impasses, cognitive disequilibrium, and confusion to learning are discussed.


Hazardous organic compounds in groundwater near Tehran automobile industry.
Potential of groundwater contamination by trichloroethylene (TCE) and other volatile organic compounds VOCs near car industry was conducted in this study. TCE, PCE, toluene, xylene, dichloromethane, cyclohexane, n-hexane and n-pentane were detected in all groundwaters. Mean TCE levels in groundwater ranged from 124.37 to 1,035.9 μg L⁻¹ with maximum level of 1,345.7 μg L⁻¹. Due to the data obtained from conventional wastewater treatment in car factory the TCE removal efficiency was only 24 percent which necessitates the TCE removal by advanced treatment processes before the use of well water.


Assessing long-term locoregional control of spinal osseous metastases after microwave ablation.
Osseous metastases to the spine result in significant pain and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of microwave ablation (MWA) for the treatment of spinal metastases regarding pain reduction and local control of disease progression. In this single center retrospective study, patients with osseous metastases to the spine undergoing MWA with vertebroplasty from 2013 to 2020 were included. Locoregional control of metabolic activity at the treated level was assessed using PET/CT scan both pre- and post-procedure. Pain reduction was measured using change in visual analog scale (VAS) pain score. Forty-eight spinal levels were treated with MWA in 28 patients (57 % male, mean age 68 ± 9 years). Median ablation time, energy, and temperature were 4 min and 13 s, 3.6 kJ, and 80 °C, respectively. Median pre-procedure maximum standard uptake value (SUVmax) was significantly reduced following ablation, from 4.55 (IQR 3.65-6.1) to 0 (IQR 0-1.8; p < 0.001), over an average of 29 ± 14.1 month follow up period. Pre-procedure VAS pain score was reduced from median (IQR) of 8 (6.5-9) to 1(1-2), 2(1-3) and 1(0.5-3) at 24 h, four weeks, and six months post-procedure, respectively (all p < 0.001 with respect to pre-procedure scores). In conclusion, this study supports microwave ablation as an effective technique for pain palliation and long-term locoregional tumor control of oligometastatic spinal disease as assessed by metabolic response.


Finding the clinical utility of 1,5-anhydroglucitol among primary care practitioners.
HbA1c is widely used as the standard measure to track glycemic control in patients with diabetes and pre-diabetes but measures average levels of glycated hemoglobin over two to three months, with limited utility in the presence of recent and/or short-term fluctuations in glycemic control, which are correlated with worse patient outcomes. We examined the clinical utility of 1-5-anhydroglucitol (1,5-AG) in six different, but common, case types of diabetes patients with short-term glycemic variability. We conducted a randomized controlled trial of simulated patients to examine the clinical practice patterns of primary care physicians before and after introducing 1,5-AG. The 145 participants were randomly assigned into standard care or standard care + 1,5-AG arms. Provider care was reviewed against explicit evidence-based care standards. At baseline, we saw no difference between the two study arms in clinical quality of care provided (p = 0.997). After introduction of 1,5-AG, standard care + 1,5-AG providers performed 3.2% better than controls (p = 0.025. In diagnosis and treatment, there was a slight, but nonsignificant trend toward better care (+1.1%, p = 0.507) for intervention providers. Upon disaggregation by case, almost all the improvement occurred in the medication-induced hyperglycemia patients (+8.1%, p = 0.047). A nationally representative sample of primary care physicians demonstrated that of six different cases used in this study, 1,5-AG was found to be most effective increasing awareness of poor glucose control in medication-induced hyperglycemia. If 1,5-AG is used in this particular circumstance, the overall savings to the healthcare system is estimated to be $28 million.


Ecdysis behaviors and circadian rhythm of ecdysis in the stick insect, Carausius morosus.
Successful ecdysis in insects depends on proper timing and sequential activation of an elaborate series of motor programs driven by a relatively conserved network of neuropeptides. The behaviors must be activated at the appropriate times to ensure successful loosening and shedding of the old cuticle, and can be influenced by environmental cues in the form of immediate sensory feedback and by circadian rhythms. We assessed the behaviors, components of the neural network and the circadian basis of ecdysis in the stick insect, Carausius morosus. C. morosus showed many of the characteristic pre-ecdysis and ecdysis behaviors previously described in crickets and locusts. Ecdysis was described in three phases, namely the (i) preparatory or pre-ecdysis phase, (ii) the ecdysial phase, and (iii) the post-ecdysis or exuvial phase. The frequencies of push-ups and sways during the preparatory phase were quantified as well as durations of all the phases. The regulation of ecdysis appeared to act via elevation of cGMP, as described in many other insects, although eclosion hormone-like immunoreactivity was not noted using a lepidopteran antiserum. Finally, C. morosus showed a circadian rhythm to the onset of ecdysis, with ecdysis occurring just prior to or at lights on. Ecdysis could be induced precociously with mechanical stimulation.


SIRT2-knockdown rescues GARS-induced Charcot-Marie-Tooth neuropathy.
Charcot-Marie-Tooth disease is the most common inherited peripheral neuropathy. Dominant mutations in the glycyl-tRNA synthetase (GARS) gene cause peripheral nerve degeneration and lead to CMT disease type 2D. The underlying mechanisms of mutations in GARS (GARSCMT2D ) in disease pathogenesis are not fully understood. In this study, we report that wild-type GARS binds the NAD+ -dependent deacetylase SIRT2 and inhibits its deacetylation activity, resulting in the acetylated α-tubulin, the major substrate of SIRT2. The catalytic domain of GARS tightly interacts with SIRT2, which is the most CMT2D mutation localization. However, CMT2D mutations in GARS cannot inhibit SIRT2 deacetylation, which leads to a decrease of acetylated α-tubulin. Genetic reduction of SIRT2 in the Drosophila model rescues the GARS-induced axonal CMT neuropathy and extends the life span. Our findings demonstrate the pathogenic role of SIRT2-dependent α-tubulin deacetylation in mutant GARS-induced neuropathies and provide new perspectives for targeting SIRT2 as a potential therapy against hereditary axonopathies.


ELISA Methods for the Detection of Ebolavirus Infection.
Ebola viruses are high-priority pathogens first discovered in rural Africa associated with sporadic outbreaks of severe hemorrhagic disease in humans and nonhuman primates. Little is known about the disease ecology or the prevalence of past exposure of human populations to any of the five species of the genus Ebolavirus. The use of immunologic means of detection for either virus antigens or the host's immune response to antigen associated with prior infections offers a powerful approach at understanding the epidemiology and epizootiology of these agents. Here we describe methods for preparing antigen detection sandwich enzyme-linked immunosorbent assays (ELISAs) as well as IgG and IgM ELISAs for the detection of ebolavirus antigens or antibodies in biological samples.


Tinnitus following COVID-19 vaccination: report of three cases.
To ensure the safety and quality of vaccines, especially the newest RNA-vaccines against COVID-19, is one of the World Health Organization's current highest priorities. Case description. We report three cases of sudden unilateral tinnitus following BNT162b2 mRNA-vaccine injection, which rapidly resolved in 2 out of 3 cases. The mechanism responsible for its development remains unclear. A hypersensitivity reaction with an abnormal autoimmune response or a vasculitic event may be implicated. Large-scale and well-designed studies are needed to improve surveillance of the COVID-19 vaccine and better define possible adverse reactions involving the cochleo-vestibular system and/or immunisation anxiety-related reactions.


Pretreatment with a novel Toll-like receptor 4 agonist attenuates renal ischemia-reperfusion injury.
Acute kidney injury (AKI) is common in surgical and critically ill patients. This study examined whether pretreatment with a novel Toll-like receptor 4 agonist attenuated ischemia-reperfusion injury (IRI)-induced AKI (IRI-AKI). We performed a blinded, randomized-controlled study in mice pretreated with 3-deacyl 6-acyl phosphorylated hexaacyl disaccharide (PHAD), a synthetic Toll-like receptor 4 agonist. Two cohorts of male BALB/c mice received intravenous vehicle or PHAD (2, 20, or 200 µg) at 48 and 24 h before unilateral renal pedicle clamping and simultaneous contralateral nephrectomy. A separate cohort of mice received intravenous vehicle or 200 µg PHAD followed by bilateral IRI-AKI. Mice were monitored for evidence of kidney injury for 3 days postreperfusion. Kidney function was assessed by serum blood urea nitrogen and creatinine measurements. Kidney tubular injury was assessed by semiquantitative analysis of tubular morphology on periodic acid-Schiff (PAS)-stained kidney sections and by kidney mRNA quantification of injury [neutrophil gelatinase-associated lipocalin (Ngal), kidney injury molecule-1 (Kim-1), and heme oxygenase-1 (Ho-1)] and inflammation [interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (Tnf-α)] using quantitative RT-PCR. Immunohistochemistry was used to quantify proximal tubular cell injury and renal macrophages by quantifying the areas stained with Kim-1 and F4/80 antibodies, respectively, and TUNEL staining to detect the apoptotic nuclei. PHAD pretreatment yielded dose-dependent kidney function preservation after unilateral IRI-AKI. Histological injury, apoptosis, Kim-1 staining, and Ngal mRNA were lower in PHAD-treated mice and IL-1β mRNA was higher in PHAD-treated mice. Similar pretreatment protection was noted with 200 mg PHAD after bilateral IRI-AKI, with significantly reduced Kim-1 immunostaining in the outer medulla of mice treated with PHAD after bilateral IRI-AKI. In conclusion, PHAD pretreatment leads to dose-dependent protection from renal injury after unilateral and bilateral IRI-AKI in mice.NEW & NOTEWORTHY Pretreatment with 3-deacyl 6-acyl phosphorylated hexaacyl disaccharide; a novel synthetic Toll-like receptor 4 agonist, preserves kidney function during ischemia-reperfusion injury-induced acute kidney injury.


Use of a quantitative point-of-care test for the detection of serum cardiac troponin T in patients with suspected acute coronary syndromes.
We compared a third generation quantitative cardiac troponin T (cTnT) point-of-care testing (POCT) from Roche Diagnostics with the laboratory assay (Roche Elecsys 2010 immunoassay analyser). Heparin-treated blood and serum were collected simultaneously in 133 unselected patients (mean age 62 +/- 14 years, 38% females) presenting to our hospital with possible cardiac chest pain. Results of the POCT were measured against the laboratory-based assay considered as the gold standard. There were 18 POCT positive versus 24 laboratory assay positive (> or = 0.03 ng/mL) patients. POCT was falsely negative in six patients, with values between 0.03 and 0.1 ng/mL. The POCT had a sensitivity of 75%, specificity of 100%, positive predictive value of 100%, negative predictive value of 95% and a total accuracy of 95%; kappa = 0.831 (P < 0.001). There was good correlation between the values of POCT and the laboratory assay: Y = 1.195X + 0.002, r2 = 0.94 (P < 0.0001). Whereas cTnT levels > 0.1 mg/mL were reliably detected with this current generation of POCT, cTnT levels between 0.03 and 0.10 ng/mL were not. Future generations of devices will need to improve sensitivity to reliably risk stratify patients with suspected acute coronary syndromes.


Evaluating the health effects of place-based slum upgrading physical environment interventions: A systematic review (2012-2018).
Rapid urbanization in low- and middle-income countries (LMIC) is associated with increasing population living in informal settlements. Inadequate infrastructure and disenfranchisement in settlements can create environments hazardous to health. Placed-based physical environment upgrading interventions have potential to improve environmental and economic conditions linked to health outcomes. Summarizing and assessing evidence of the impact of prior interventions is critical to motivating and selecting the most effective upgrading strategies moving forward. Scientific and grey literature were systematically reviewed to identify evaluations of physical environment slum upgrading interventions in LMICs published between 2012 and 2018. Thirteen evaluations that fulfilled inclusion criteria were reviewed. Quality of evaluations was assessed using an adapted Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Findings were then pooled with those published prior to 2012. Narrative analysis was performed. Of thirteen evaluations, eight used a longitudinal study design ("primary evaluations"). All primary evaluations were based in Latin America and included two housing, two transportation, and four comprehensive intervention evaluations. Three supporting evaluations assessed housing interventions in Argentina and South Africa; two assessed a comprehensive intervention in India. Effects by intervention-type included improvements in quality of life and communicable diseases after housing interventions, possible improvements in safety after transportation and comprehensive interventions, and possible non-statistically significant effects on social capital after comprehensive interventions. Effects due to interventions may vary by regional context and intervention scope. Limited strong evidence and the diffuse nature of comprehensive interventions suggests a need for attention to measurement of intervention exposure and analytic approaches to account for confounding and selection bias in evaluation. In addition to health improvements, evaluators should consider unintended health consequences and environmental impact. Understanding and isolating the effects of place-based interventions can inform necessary policy decisions to address inadequate living conditions as rapid urban growth continues across the globe.


tert-Butyl N-{(1S)-1-[(2,4-dihy-droxy-benzyl-idene)hydrazinecarbon-yl]-2-hy-droxy-eth-yl}carbamate ethanol monosolvate.
The mol-ecule of the title ethanol solvate, C(15)H(21)N(3)O(6)·C(2)H(6)O, adopts a curved shape; the conformation about the imine bond [N=N = 1.287 (3) Å] is E. The amide residues occupy positions almost orthogonal to each other [dihedral angle = 85.7 (2)°]. In the crystal, a network of O-H⋯O, O-H⋯N and N-H⋯O hydrogen bonds leads to the formation of supra-molecular arrays in the ab plane with the ethanol mol-ecules lying to the periphery on either side. Disorder in the solvent ethanol mol-ecule was evident with two positions being resolved for the C atoms [site occupancy of the major component = 0.612 (10)].


In-silico design and experimental validation of TiNbTaZrMoSn to assess accuracy of mechanical and biocompatibility predictive models.
Numerical design of TiNbTaZrMoSn alloy preceded its manufacture and mechanical, physico-chemical and in vitro characterisation. The specifications of the alloy required a multi-objective optimisation including lower modulus of elasticity than c.p.Ti, high strength, stabilised β crystal structure with a low martensitic start temperature, a narrow solidification range and high biocompatibility. The results reveal that there was a good match between the bulk mechanical properties exhibited by the alloy experimentally and those predicted. Regarding surface properties, independent of roughness effects, the oxide thickness and surface zeta-potential, measured in biologically relevant electrolytes and at physiological pH, arose as important factors in osteoblastic activity (i.e., cell proliferation, measured via DNA, protein and metabolite content, and differentiation, via ALP levels), but not in cell adhesion and viability. The thinner oxide layer and lower absolute value of surface zeta-potential on the TiNbTaZrMoSn alloy explain its lesser osteogenic properties (i.e., inhibition of ALP activity) compared to the c.p. Ti. This study demonstrates that the numerical models to predict microstructure and bulk mechanical properties of β-Ti alloys are robust, but that the prediction of cellular bioactivity lags behind and still requires parameterisation to account for features such as oxide layer composition and thickness, electro-chemical properties and surface charge, and topography to optimise cell response in silico before committing to the costly manufacture and deployment of these alloys in regenerative medicine.


Endothelin-1 induces changes in the expression levels of steroidogenic enzymes and increases androgen receptor and testosterone production in the PC3 prostate cancer cell line.
Endothelin‑1 (ET‑1) is involved in the regulation of steroidogenesis. Additionally, patients with castration‑resistant prostate cancer (PCa) have a higher ET‑1 plasma concentration than those with localized PCa and healthy individuals. The aim of the present study was to evaluate the effect of ET‑1 on steroidogenesis enzymes, androgen receptor (AR) and testosterone (T) production in PCa cells. The expression levels of endothelin receptors in prostate tissue from patients with localized PCa by immunohistochemistry, and those in LNCaP and PC3 cells were determined reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. Furthermore, the expression levels of ET‑1 were determined in LNCaP and PC3 cells by RT‑qPCR and western blotting. The ET‑1 receptor activation was evaluated by intracellular calcium measurement, the expression levels of AR and enzymes participating in steroidogenesis [cytochrome P450 family 11 subfamily A member 1 (CyP11A1), cytochrome P450 family 17 subfamily A member 1, aldo‑keto reductase family member C2 and 3β‑hydroxysteroid dehydrogenase/isomerase 2 (3β HSD2)] were determined by western blotting and T concentration was determined by ELISA using PC3 cells. The present results revealed higher expression levels of endothelin A receptor (ETAR) in tissues obtained from samples of patients with PCa with a low Gleason Score. No changes were identified for endothelin B receptor (ETBR). PC3 cells expressed higher levels of ET‑1 and ETAR, while LNCaP cells exhibited higher expression levels of ETBR. Blocking of ETAR and endothelin B receptor decreased the expression levels of CyP11A1 and 3β HSD2 enzymes and AR in PC3 cells, as well as T secretion. These findings suggested that ET‑1 has a potential role in modulating the intratumoral steroidogenesis pathway and might have relevance as a possible therapeutic target.


Accounting for variation in temperature and oxygen availability when quantifying marine ecosystem metabolism.
It is critical to understand how human modifications of Earth's ecosystems are influencing ecosystem functioning, including net and gross community production (NCP and GCP, respectively) and community respiration (CR). These responses are often estimated by measuring oxygen production in the light (NCP) and consumption in the dark (CR), which can then be combined to estimate GCP. However, the method used to create "dark" conditions-either experimental darkening during the day or taking measurements at night-could result in different estimates of respiration and production, potentially affecting our ability to make integrative predictions. We tested this possibility by measuring oxygen concentrations under daytime ambient light conditions, in darkened tide pools during the day, and during nighttime low tides. We made measurements every 1-3 months over one year in southeastern Alaska. Daytime respiration rates were substantially higher than those measured at night, associated with higher temperature and oxygen levels during the day and leading to major differences in estimates of GCP calculated using daytime versus nighttime measurements. Our results highlight the potential importance of measuring respiration rates during both day and night to account for effects of temperature and oxygen-especially in shallow-water, constrained systems-with implications for understanding the impacts of global change on ecosystem metabolism.


A GIS-based fuzzy classification for mapping the agricultural soils for N-fertilizers use.
Special attention should be paid to the choice of the proper N-fertilizer, in order to avoid a further acidification and degradation of acid soils and at the same time to improve nitrogen use efficiency and to limit the nitrate pollution of the ground waters. Therefore, the risk of leaching of the fertilizer and of the acidification of the soils must be considered prior to any N-fertilizer application. The application of N-fertilizers to the soil requires a good knowledge of the soil-fertilizer relationship, which those who are planning the fertilization policy and/or applying it might not have. In this study, a fuzzy classification methodology is presented for mapping the agricultural soils according to the kind and the rate of application of N-fertilizer that should be used. The values of pH, clay, sand and carbonates soil variables are estimated at each point of an area by applying geostatistical techniques. Using the pH values three fuzzy sets: "no-risk-acidification"; "low-risk-acidification"; and "high-risk-acidification" are produced and the memberships of each point to the three sets are estimated. Additionally, from the clay and sand values the membership grade to the fuzzy set "risk-of-leaching" is calculated. The parameters and their values, which are used for the construction of the fuzzy sets, are based on the literature, the existing knowledge and the experimentation, of the soil-fertilizer relationships and provide a consistent mechanism for mapping the soils according to the type of N-fertilizers that should be applied and the rate of applications. The maps produced can easily be interpreted and used by non-experts in the application of the fertilization policy at national, local and farm level. The methodology is presented through a case study using data from the Amfilochia area, west Greece.


[Problems posed by the interpretation of peroxidase labelling of various neurons in Cyprinidae].
The origin of a centrifugal visual pathway in Cyprinids could not be demonstrated with the technique involving the labelling of cell bodies by retrograde transport of Horseradish Peroxidase. The hypothalamic labelling following intraocular injection of HRP is localized in neurosecretory structures which take up the enzyme that has passed into the circulatory system. Identical results were obtained following direct intracardiac injection. Thus extreme caution must be taken in attempting to interpret HRP results.


High-performance liquid chromatographic determination of N-epsilon-(2-propenal)lysine in biological samples after derivatization with diethylethoxymethylenemalonate.
A recently reported methodology for amino acid analysis by HPLC has been adapted for quantification of N-epsilon-(2-propenal)lysine (a modified lysine by reaction with malondialdehyde that has been found in enzymatic digests of foods and in urine) in biological samples. We describe its use for investigating the in vitro degradation of N-epsilon-(2-propenal)lysine using rat tissue homogenates. Lysine dipeptide, used as a control in the incubation mixtures, and the lysine released by the hydrolytic action of the homogenates in the in vitro incubations are quantified in the same way. The samples are subjected to a cleanup prederivatization step using PD-10 disposable columns (Pharmacia). This allows precolumn derivatization with diethylethoxymethylenemalonate (50 min, 50 degrees C) and resolution of the derivatives of the compounds of interest by reversed-phase HPLC (binary gradient, 45 min) with quantification based on the uv absorption of the derivatives at 280 nm (detection limits below 1 pmol). The entire analysis takes 110 min. This method can be of general use for the determination of N-epsilon-(2-propenal)lysine in the context of research dealing with protein deterioration by reaction with malondialdehyde in biological systems and in foods. A method for the synthesis of N-epsilon-(2-propenal)lysine, used as external standard for the HPLC analysis, is described.


Consequences of Oviposition Site Choice for Geckos in Changing Environments.
Most lizards lay eggs inside nests where embryos experience daily fluctuations in temperature. As embryos are sensitive to exposure to high temperatures, increases in nest temperatures may pose a risk to lizards. In the velvet gecko Amalosia lesueurii, nest temperatures are positively correlated with air temperatures, so nests may get hotter in future. However, maternal variation in oviposition site choice might buffer populations from future warming. To evaluate the consequences of oviposition site choice, we incubated eggs under two fluctuating temperature regimes that mimicked temperatures experienced inside sun-exposed ("warm": mean = 25.4 °C; range = 16.5-35.5 °C) and shaded ("cold": mean = 23.3 °C; 17.5-30.5 °C) communal nests. We measured the phenotypic traits of hatchlings, released them to the wild, and monitored their survival over 6 months. Warm-incubated hatchlings hatched 15 days earlier, on average, and were smaller than their cold-incubated clutch mates. Incubation treatment did not influence the apparent survival of hatchlings. Hence, even if air temperatures increase by 2 °C in future, thermal regimes inside some currently used shaded nests will be suitable for embryo development. Maternal variation in nest site choice may therefore allow southern populations of the velvet gecko to persist in changing environments.


An automatic system for chromosomal analysis applied to prenatal diagnosis.
Computer-assisted metaphase analysis for prenatal diagnosis can be economically performed by a preexisting hardware-software system. The program can be run by technician-level (i.e. nonspecialist) personnel who can opt for the automatic operational mode for good quality metaphases or for the semimanual mode for problem metaphases (numerous superpositions, artifacts, etc.). The karyotype can be obtained in conversational mode. Hardcopy output is available for all modes.


Chest pain units: management of special populations.
Chest pain units provide an important alternative to traditional hospital admission for patients who present to the emergency department with symptoms compatible with acute coronary syndrome and a normal or inconclusive initial evaluation. Although patient subgroups such as women, diabetics, those with established coronary artery disease,and those with symptoms related to stimulant use present unique challenges,management in a chest pain unit appears to be appropriate in these populations. Judicious application of accelerated diagnostic protocols and current testing methods can promote safe, accurate, and cost-effective risk stratification of special populations to identify patients who can be safely discharged and patients who require hospital admission for further evaluation.


Effect of the ethnic, profession, gender, and social background on the perception of upper dental midline deviations in smile esthetics by Chinese and Black raters.
The purpose of this study was to compare the perception of upper dental midline deviation on the attractiveness of a smile among raters from different ethnicities, professions, genders, and ages and measure to what extent the presence or absence of the associated smiling structures influence the raters' evaluations. A male subject (26 years of age) with adequate smile characteristics was selected by 3 experienced orthodontists, and 561 raters from 2 different ethnic groups (281 Chinese raters and 280 Black raters) rated the subject's smile after the subject's upper dental midline was digitally altered from 0 to 5 mm using a 5-point Likert scale on 12 smile photographs divided into two groups: group 1, in the presence of smile related structures, two-thirds of the nose, lips, and chin (NLC), and group 2, in the absence of smile related structures, the lips only (L). There were statistically significant differences (p < 0.05) between the two ethnicities, in 2 mm and 4 mm in-group NLC and 5 mm in-group L, as well as the raters' profession to each midline shift of both groups (NLC) and (L) for both ethnicities except for 0 mm. Regarding the role of associated smile structures, the smile photos were observed in the presence of smile-associated structures, and in its absence (NLC × L), statistically significant differences (p < 0.05) were found when the deviation was 5 mm among the Chinese raters; in 1 mm, and 4 mm among the Black raters. Among different genders, statistical differences were only reported (p < 0.05) for Chinese raters for 5 mm in NLC, while statistical differences were observed for 2 mm and 3 mm in NLC for Black raters. For age categories, differences were observed (p < 0.05) for 4 mm, 5 mm in NLC and 4 mm, and 5 mm in L for Chinese raters, while 5 mm in NLC and 1 mm in L for Black raters. Perception of the upper dental midline deviations was influenced by the factors of ethnicity, profession, presence or absence of smile-associated structures, as well as the gender and age of the raters.


Pharmacokinetics of genistein distribution in blood and retinas of diabetic and non-diabetic rats.
Genistein, a natural tyrosine kinase inhibitor, may act as an intraocular antiangiogenic agent. Its therapeutical use, however, is limited by its nonlinear pharmacokinetics. We aimed to determine genistein's kinetics and retinal tissue distributions in normal and diabetic rats. We developed an isocratic, reverse-phase C18 HPLC system to measure genistein concentration in blood and retinas of streptozotocin (65 mg/kg IV)-diabetic and non-diabetic rats receiving two types of genistein-rich diet (150 and 300 mg/kg) for ten days. Genistein's decay exhibited a two-compartmental open model. Half-lives of distribution and elimination were 2.09 and 71.79 min, with no difference between groups. Genistein steady-state concentration in blood for 150 and 300 mg/kg diet did not differ between diabetic (0.259 ± 0.07 and 0.26 ± 0.06 μg/ml) and non-diabetic rats (0.192 ± 0.05 and 0.183 ± 0.09 μg/ml). In retina, genistein concentration was significantly higher in diabetic rats (1.05 ± 0.47 and 0.997 ± 0.47 μg/gm wt. vs. 0.087 ± 0.11 and 0.314 ± 0.18 μg/gm wt., p < 0.05). The study determined that increasing genistein dose did not change its bioavailability, perhaps due to the poor aqueous solubility. The retina's increased genistein could be due to increased permeability of blood-retinal barrier that occurs early in diabetes.


The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections.
A hallmark of the potent, multifaceted antimicrobial defence of Drosophila melanogaster is the challenge-induced synthesis of several families of antimicrobial peptides by cells in the fat body. The basic mechanisms of recognition of various types of microbial infections by the adult fly are now understood, often in great detail. We have further gained valuable insight into the infection-induced gene reprogramming by nuclear factor-kappaB (NF-kappaB) family members under the dependence of complex intracellular signalling cascades. The striking parallels between the adult fly response and mammalian innate immune defences described below point to a common ancestry and validate the relevance of the fly defence as a paradigm for innate immunity.


The heterogeneous pathogenesis of type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM) results from the destruction of pancreatic β-cells that is mediated by the immune system. Multiple genetic and environmental factors found in variable combinations in individual patients are involved in the development of T1DM. Genetic risk is defined by the presence of particular allele combinations, which in the major susceptibility locus (the HLA region) affect T cell recognition and tolerance to foreign and autologous molecules. Multiple other loci also regulate and affect features of specific immune responses and modify the vulnerability of β-cells to inflammatory mediators. Compared with the genetic factors, environmental factors that affect the development of T1DM are less well characterized but contact with particular microorganisms is emerging as an important factor. Certain infections might affect immune regulation, and the role of commensal microorganisms, such as the gut microbiota, are important in the education of the developing immune system. Some evidence also suggests that nutritional factors are important. Multiple islet-specific autoantibodies are found in the circulation from a few weeks to up to 20 years before the onset of clinical disease and this prediabetic phase provides a potential opportunity to manipulate the islet-specific immune response to prevent or postpone β-cell loss. The latest developments in understanding the heterogeneity of T1DM and characterization of major disease subtypes might help in the development of preventive treatments.


Diabetes is accompanied by changes in the levels of proteins involved in endosomal GLUT4 trafficking in obese human skeletal muscle.
The regulated delivery of the glucose transporter GLUT4 from intracellular stores to the plasma membrane underpins insulin-stimulated glucose transport. Insulin-stimulated glucose transport is impaired in skeletal muscle of patients with type-2 diabetes, and this may arise because of impaired intracellular trafficking of GLUT4. However, molecular details of any such impairment have not been described. We hypothesized that GLUT4 and/or levels of proteins involved in intracellular GLUT4 trafficking may be impaired in skeletal muscle in type-2 diabetes and tested this in obese individuals without and without type-2 diabetes. We recruited 12 participants with type-2 diabetes and 12 control participants. All were overweight or obese with BMI of 25-45 kg/m2 . Insulin sensitivity was measured using an insulin suppression test (IST), and vastus lateralis biopsies were taken in the fasted state. Cell extracts were immunoblotted to quantify levels of a range of proteins known to be involved in intracellular GLUT4 trafficking. Obese participants with type-2 diabetes exhibited elevated fasting blood glucose and increased steady state glucose infusion rates in the IST compared with controls. Consistent with this, skeletal muscle from those with type-2 diabetes expressed lower levels of GLUT4 (30%, p = .014). Levels of Syntaxin4, a key protein involved in GLUT4 vesicle fusion with the plasma membrane, were similar between groups. By contrast, we observed reductions in levels of Syntaxin16 (33.7%, p = 0.05), Sortilin (44%, p = .006) and Sorting Nexin-1 (21.5%, p = .039) and -27 (60%, p = .001), key proteins involved in the intracellular sorting of GLUT4, in participants with type-2 diabetes. We report significant reductions of proteins involved in the endosomal trafficking of GLUT4 in skeletal muscle in obese people with type 2 diabetes compared with age- and weight-matched controls. These abnormalities of intracellular GLUT4 trafficking may contribute to reduced whole body insulin sensitivity.


High-dose methotrexate does not affect the pharmacodynamics of phenobarbital hypnotic action but decreases the central nervous system (CNS) sensitivity to pentylenetetrazol-induced maximal seizures in rats.
Chemotherapy with high-dose methotrexate (HD-MTX) is often associated with acute neurotoxicity. We determined whether the altered neuronal function after HD-MTX [such as the reduced regional cerebral metabolic glucose rate (rCMRGlc) and slow electroencephalographic pattern] affects the sensitivity of the CNS to centrally acting drugs: the depressant phenobarbital, which reduces rCMRGlc, and the analeptic agent pentylenetetrazol (PTZ), which elevates rCMRGlc. Adult male Sabra rats received an i.v. infusion of MTX, 0.51 mg/min, to induce neurotoxicity or saline solution for 24 hr. Subsequently, MTX-treated and control groups were infused in one experiment with phenobarbital until loss of the righting reflex and in the second experiment with PTZ until the onset of maximal seizures. HD-MTX did not affect the infused hypnotic dose or serum, brain, and cerebrospinal fluid concentrations of phenobarbital at the onset of anesthesia. The convulsive dose and PTZ concentrations in the serum and brain at the onset of maximal seizures were significantly higher in the HD-MTX-treated animals. These outcomes indicate that HD-MTX and the reduced rCMRGlc that follows this treatment do not contribute to the hypnotic action of phenobarbital. On the other hand, treatment with HD-MTX exhibited anticonvulsant properties as evidenced by the reduced CNS sensitivity to PTZ-induced seizures.


Mutational signatures impact the evolution of anti-EGFR antibody resistance in colorectal cancer.
Anti-EGFR antibodies such as cetuximab are active against KRAS/NRAS wild-type colorectal cancers (CRCs), but acquired resistance invariably evolves. It is unknown which mutational mechanisms enable resistance evolution and whether adaptive mutagenesis (a transient cetuximab-induced increase in mutation generation) contributes in patients. Here, we investigate these questions in exome sequencing data from 42 baseline and progression biopsies from cetuximab-treated CRCs. Mutation loads did not increase from baseline to progression, and evidence for a contribution of adaptive mutagenesis was limited. However, the chemotherapy-induced mutational signature SBS17b was the main contributor of specific KRAS/NRAS and EGFR driver mutations that are enriched at acquired resistance. Detectable SBS17b activity before treatment predicted shorter progression-free survival and the evolution of these specific mutations during subsequent cetuximab treatment. This result suggests that chemotherapy mutagenesis can accelerate resistance evolution. Mutational signatures may be a new class of cancer evolution predictor.


EEG microstate D as psychosis-specific correlate in adolescents and young adults with clinical high risk for psychosis and first-episode psychosis.
Resting-state electroencephalography (EEG) microstates are brief periods (60-120 ms) of quasi-stable scalp field potentials, indicating simultaneous activity of large-scale networks. Microstates are assumed to reflect basic neuronal information processing. A common finding in psychosis spectrum disorders is that microstates classes C and D are altered. Whereas evidence in adults with schizophrenia is substantial, little is known about effects in underage patients, particularly in those at clinical high risk for psychosis (CHR) and first-episode psychosis (FEP). The present study used 74-channel EEG to investigate microstate effects in a large sample of patients with CHR (n = 100) and FEP (n = 33), clinical controls (CC, n = 18), as well as age-matched healthy controls (HC, n = 68). Subjects span an age range from 9 to 35 years, thus, covering underage patients as well as the most vulnerable period for the emergence of psychosis and its prodrome. Four EEG microstates classes were analyzed (A-D). In class D, CHR and FEP patients showed a decrease compared to HC, and CHR patients also to CC. An increase in class C was found in CHR and FEP compared to HC but not to CC. Results were independent of age and no differences were found between the psychosis spectrum groups. The findings suggest an age-independent decrease of microstate class D to be specific to the psychosis spectrum, whereas the increase in class C seems to reflect unspecific psychopathology. Overall, present data strengthens the role of microstate D as potential biomarker for psychosis, as early as in adolescence and already in CHR status.


Knowledge, beliefs, attitudes, and behaviors related to weight control, eating disorders, and body image in Australian trainee home economics and physical education teachers.
To examine the knowledge, beliefs, and attitudes about weight control and eating disorders among trainee home economics and physical education teachers and to assess their body image and weight control practices. The association between actual body weight and body image was also examined. Survey research was undertaken using a self-report questionnaire. Height and weight were measured. Trainee home economics and physical education teachers (N = 216, 96% participation rate) in their last month of training at three major state teacher training universities completed a questionnaire during their regular class times. Advice teachers give to overweight adolescents knowledge and beliefs about eating disorders, body image, desired weight, food habits, dieting, body appearance ratings, weight control practices, and diagnosed and self-reported eating disorders. Descriptive statistics, chi square, and analyses of variance compare gender and Body Mass Index differences. Males (85%) and females (87%) advised young overweight adolescents to diet to lose weight. Twenty percent of females and 13% of males regularly skipped breakfast. The advise given showed a lack of specific nutrition education about weight control, adolescent nutritional needs, and fad diets. Participants held misconceptions about eating disorders, and a range of 14% to 72% answered these questions incorrectly. Fourteen percent of females self-reported that they currently had an eating disorder, but only 6% had received treatment. Some females used potentially dangerous methods of weight loss, including 19% who abused laxatives and 10% who induced vomiting. Trainee home economics and physical education teachers need specific nutrition information and training about eating disorders, weight control, and suitable advice for overweight students. The female trainee teachers in our study had a poor body image and disordered eating similar to other young women in Western countries, and this should be taken into account by teacher training institutions.


Topography, ultrastructure and phagocytic capacity of avian lymph nodes.
The structure of the avian lymph node (ALN) is characterized by a thin capsule, thin lymphoreticular cords, and an absence of trabeculae. It is not possible to subdivide the ALN into cortex, paracortex and medulla, or to subdivide the system of sinuses into marginal, trabecular and medullary divisions. The lymphoreticular cords contain avian germinal centers (AGC) with B-lymphocytes and the area of T-lymphocytes. Postcapillary venules are responsible for the recirculation of lymphocytes. Sinus reticular cells do not exist in the ALN, but free macrophages are present. The phagocytic capacity of the macrophages was determined by injection of vital dyes (India ink, Berlin blue) and inoculation with Candida cells. Macrophages filled with markers migrate from the lymph sinuses into the lymphoreticular cords and further into the AGC. The mobility of the macrophages is remarkably lower after phagocytosis of Candida cells.


Everything is going to be all right. Psychopathology in the time of an epidemic in Italy.
Scopo del presente lavoro è descrivere alcune reazioni umane e alcuni elementi di psicopatologia durante la pandemia. La pandemia ha messo in luce diversi aspetti dell'animo umano negli operatori sanitari, nei pazienti e nelle altre persone. Vi sono medici, infermieri, operatori che lavorano 24 ore su 24 per curare e assistere i malati, accompagnare chi non ce la fa. Incuranti del rischio di contagio, della fatica, dei propri bisogni hanno un'unica priorità : aiutare, fare il proprio dovere. Molti di loro si sono ammalati, molti sono morti. Tra loro vi è un alto tasso di contagiati, malati, qualcuno muore. Tutti sono stremati. Sono stati chiamati eroi, ma non tutti sono eroi. I nostri pazienti psichiatrici, inizialmente, sono i più adeguati, prudenti, saggi, responsabili. Con poche, semplici parole esprimono tanta consapevolezza e sana umanità. Al contrario, altre persone, quelle che normalmente si sentono "al di sopra delle cose", entrano nel panico Questa pandemia ci ha fatto capire (se ancora lo ignoravamo) che la vita è fragile, che tutto ciò che ci circonda e su cui costruiamo le nostre sicurezze è precario e incerto.


Competency Standard Derivation for Point-of-Care Ultrasound Image Interpretation for Emergency Physicians.
Because number-based standards are increasingly controversial, the objective of this study was to derive a performance-based competency standard for the image interpretation task of point-of-care ultrasound (POCUS). This was a prospective study. Operating on a clinically-relevant sample of POCUS images, we adapted the Ebel standard-setting method to derive a performance benchmark in 4 diverse pediatric POCUS applications: soft tissue, lung, cardiac and focused assessment with sonography in trauma (FAST). In Phase I (difficulty calibration), cases were categorized into interpretation difficulty terciles (easy, intermediate, hard) using emergency physician-derived data. In Phase II (significance), a 4-person expert panel categorized cases as low, medium, or high clinical significance. In Phase III (standard setting), a 3x3 matrix was created, categorizing cases by difficulty and significance, and a 6-member panel determined acceptable accuracy for each of the 9 cells. An overall competency standard was derived from the weighted sum. We obtained data from 379 emergency physicians resulting in 67,093 interpretations and a median of 184 (interquartile range, 154, 190) interpretations per case. There were 78 (19.5%) easy, 272 (68.0%) medium, and 50 (12.5%) hard-to-interpret cases, and 237 (59.3%) low, 65 (16.3%) medium, and 98 (24.5%) cases of high clinical significance across the 4 POCUS applications. The panel determined an overall performance-based competency score of 85.0% for lung, 89.5% for cardiac, 90.5% for soft tissue, and 92.7% for FAST. This research provides a transparent chain of evidence that derived clinically relevant competency standards for POCUS image interpretation.


Optogenetic activation of SIFamide (SIFa) neurons induces a complex sleep-promoting effect in the fruit fly Drosophila melanogaster.
Sleep is a universal and extremely complicated function. Sleep is regulated by two systems-sleep homeostasis and circadian rhythms. In a wide range of species, neuropeptides have been found to play a crucial role in the communication and synchronization between different components of both systems. In the fruit fly Drosophila melanogaster, SIFamide (SIFa) is a neuropeptide that has been reported to be expressed in 4 neurons in the pars intercerebralis (PI) area of the brain. Previous work has shown that transgenic ablation of SIFa neurons, mutation of SIFa itself, or knockdown of SIFa receptors reduces sleep, suggesting that SIFa is sleep-promoting. However, those were all constitutive manipulations that could have affected development or resulted in compensation, so the role of SIFa signaling in sleep regulation during adulthood remains unclear. In the current study, we examined the sleep-promoting effect of SIFa through an optogenetic approach, which allowed for neuronal activation with high temporal resolution, while leaving development unaffected. We found that activation of the red-light sensor Chrimson in SIFa neurons promoted sleep in flies in a sexually dimorphic manner, where the magnitude of the sleep effect was greater in females than in males. Because neuropeptidergic neurons often also release other transmitters, we used RNA interference to knock down SIFa while also optogenetically activating SIFa neurons. SIFa knockdown only partially reduced the magnitude of the sleep effect, suggesting that release of other transmitters may contribute to the sleep induction when SIFa neurons are activated. Video-based analysis showed that activation of SIFa neurons for as brief a period as 1 second was able to decrease walking behavior for minutes after the stimulus. Future studies should aim to identify the transmitters that are utilized by SIFa neurons and characterize their upstream activators and downstream targets. It would also be of interest to determine how acute optogenetic activation of SIFa neurons alters other behaviors that have been linked to SIFa, such as mating and feeding.


Solitary meningeal plasmacytoma: Report of a case with electron microscopic and immunohistologic observations.
An unusual case of solitary extraskeletal plasmacytoma (SEP) arising from the meninges of the anterior fossa in a 58-year-old woman is presented. Despite an apparently complete surgical excision and 5000 rads to the tumor area given postoperatively, a recurrence ensued 5 years later. During the 5 years of clinical observation, repeated serum electrophoresis and immunoelectrophoresis, bone surveys, and bone marrow aspirations have ruled out the presence of underlying multiple myeloma. Immunofluorescence studies of the recurrent tumor showed the neoplastic cells to be producing a monoclonal immunoglobulin (IgA, kappa). Ultrastructural examination showed neoplastic plasma cells with marked nucleocytoplasmic asynchrony, frequent cytoplasmic electron-dense bodies, and rough endoplasmic reticulum dilated and filled with with electron-dense material. A critical evaluation of the eight cases of intracranial SEP published in the literature revealed that only three are well-documented examples of this tumor.


Peptide-specific antibody locates the COOH terminus of the lactose carrier of Escherichia coli on the cytoplasmic side of the plasma membrane.
The carboxyl-terminal decapeptide NH2-Leu-Leu-Arg-Arg-Gln-Val-Asn-Glu-Val-Ala-OH of the lactose carrier protein, the product of the lac Y gene of Escherichia coli, was synthesized, and specific anti-peptide antibodies were raised in rabbits. These antibodies bind to membrane-bound lactose carrier showing that the carboxyl terminus is accessible from the aqueous phase. The antibodies bind only to the surface of inverted cytoplasmic membrane vesicles (but not to closed, right-side-out membrane vesicles), demonstrating that the carboxyl terminus of the carrier protein is directed towards the cytoplasmic side of the plasma membrane in cells. The carboxyl terminus is a potent immunogenic epitope on the purified, detergent-solubilized carrier. Binding of peptide-specific antibodies to the carrier protein inhibits neither substrate binding nor translocation.