Mechanisms underlying hyperpolarization evoked by P2Y receptor activation in mouse distal colon.
In murine colonic circular muscle, ATP mediates fast component of the nerve-evoked inhibitory junction potentials, via activation of P2Y receptors and opening of apamin-sensitive Ca2+-dependent K+ channels. We investigated, using microelectrode recordings, the intracellular events following P2Y-receptor activation by electrical field stimulation or by adenosine 5'-O-2-thiodiphosphate (ADPbetaS), ATP stable analogue. The fast-inhibitory junction potential amplitude was reduced by thapsigargin or ciclopiazonic acid (CPA), sarcoplasmic reticulum Ca2+-ATPase inhibitors, by ryanodine, which inhibits Ca2+ release from ryanodine-sensitive stores, and by 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536), an adenylyl cyclase inhibitor. Fast-inhibitory junction potentials were enhanced by 2-aminoethoxy-diphenylborate (2-APB), an IP3 receptor inhibitor or by {1-[6((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione} (U-73122), a phospholipase C inhibitor. ADPbetaS induced hyperpolarization that was significantly reduced by apamin, thapsigargin, CPA, ryanodine, 2-APB and SQ 22,536, but it was not modified by U-73122. Forskolin, an adenylyl cyclase activator, induced hyperpolarization that was inhibited by SQ 22,536, apamin or ryanodine. In conclusion, in murine colon, apamin-sensitive hyperpolarization induced by activation of P2Y receptors is mainly mediated by release of Ca2+ from intracellular ryanodine-dependent stores via a mechanism involving adenylyl cyclase.


Microsatellite instability in human prostate cancer.
Microsatellite instability (MSI) was examined at 36 loci, and found in 9 (43%) of the 21 prostatic cancers. A loss of heterozygosity had occurred in five cases (24%). MSI did not correlate with clinical stage, but might play a role in the development of a subset of prostate cancers.


Determination of the structure of a novel acidic oligosaccharide with blood-group activity isolated from bovine submaxillary-gland mucin.
In this study we investigated the structure of an acidic fucose-containing pentasaccharide released from bovine submaxillary-gland mucin by alkaline-borohydride treatment. The structure, determined by a combination of one-dimensional and two-dimensional 1H-n.m.r. spectroscopy at 270 MHz and methylation analysis involving g.l.c.-m.s., was as follows: Fuc alpha(1----2)Gal beta(1----4)GlcNAc beta(1----3)[NeuAc alpha(2----6)]GalNAcol This pentasaccharide is a novel structure and is the first report of a blood-group-H type 2 determinant on a submaxillary-gland mucin.


Cost and cost-effectiveness of point-of-care testing and treatment for sexually transmitted and genital infections in pregnancy in low-income and middle-income countries: a systematic review protocol.
The economic and health burden of sexually transmitted and genital infections (henceforth, STIs) in low-income and middle-income countries (LMICs) is substantial. Left untreated, STIs during pregnancy may result in several adverse pregnancy and birth outcomes. Timely diagnosis and treatment at point-of-care (POC) can potentially improve these outcomes. Despite the availability and promotion of POC diagnostics for STIs as a key component of antenatal care in LMICs, their widespread use has been limited, owing to the high economic costs faced by individuals and health systems. To date, there have been no systematic reviews which explore the cost or cost-effectiveness of POC testing and treatment of STIs in pregnancy in LMICs. The objective of this protocol is to outline the methods that will compare, synthesise and appraise the existing literature in this domain. We will conduct literature searches in MEDLINE, Embase and Web of Science. To find additional literature, we will search Google Scholar and hand search reference lists of included papers. Two reviewers will independently search databases, screen titles, abstracts and full texts; when necessary a third reviewer will resolve disputes. Only cost and cost-effectiveness studies of POC testing and treatment of STIs, including syphilis, chlamydia, trichomonas, gonorrhoea and bacterial vaginosis, in pregnancy in LMICs will be included. Published checklists will be used to assess quality of reporting practices and methodological approaches. We will also assess risk of publication bias. Interstudy heterogeneity will be assessed and depending on variation between studies, a meta-analysis or narrative synthesis will be conducted. Ethical approval is not required as the review will use published literature. The results will be published in a peer-reviewed open source journal and presented at an international conference. CRD42018109072.


Divalent Cations and Lipid Composition Modulate Membrane Insertion and Cancer-Targeting Action of pHLIP.
The pH-Low Insertion Peptide (pHLIP) has emerged as an important tool for targeting cancer cells; it has been assumed that its targeting mechanism depends solely on the mild acidic environment surrounding tumors. Here, we examine the role of Ca2+ and Mg2+ on pHLIP's insertion, cellular targeting, and drug delivery. We demonstrate that physiologically relevant concentrations of either cation can shift the protonation-dependent transition by up to several pH units toward basic pH and induce substantial protonation-independent transmembrane insertion of pHLIP at pH as high as 10. Consistent with these results, the ability of pHLIP to deliver the cytotoxic compound monomethyl-auristatin-F to HeLa cells is increased several fold in presence of Ca2+. Complementary measurements with model membranes confirmed this Ca2+/Mg2+-dependent membrane-insertion mechanism. The magnitude of this alternative Ca2+/Mg2+-dependent effect is also modulated by lipid composition-specifically by the presence of phosphatidylserine-providing new clues to pHLIP's unique tumor-targeting ability in vivo. These results exemplify the complex coupling between protonation of anionic residues and lipid-selective targeting by divalent cations, which is relevant to the general signaling on membrane interfaces.


MELAS: clinical phenotype and morphological brain abnormalities.
We describe the clinical and neuropathological findings of three unrelated autopsy cases of MELAS harboring the A3243G transition in the mitochondrial DNA (mtDNA). Using immunohistochemical techniques, we studied the expression of several subunits of the respiratory chain in various brain regions from the same cases. In all three cases there was a reduced immunocytochemical staining for mtDNA-encoded subunits of the respiratory chain, confirming the presence of a defective mitochondrial protein synthesis in this disease. Mitochondrial abnormalities were mostly confined to multiple areas of different size and shape, in agreement with the focal character of the brain pathology in MELAS, and were most prominent in the cerebral cortex, providing a morphological contribution to the explanation of the cognitive regression of the patients. Immunoreactivity for mtDNA-encoded subunits was reduced in the walls of many pial and intracerebral arterioles of different brain regions but there was no clear correlation between territories of affected vessels and distribution of the histological and immunohistochemical lesions. Cerebral focal lesions in MELAS might have a metabolic nature and several pathogenetic mechanisms might be involved in the genesis of stroke-like episodes when there is a local increased ATP demand.


Detection of the bunyavirus Germiston in VERO and Aedes albopictus C6/36 cells by in situ hybridization using cDNA and asymmetric RNA probes.
Using Germiston virus infected vertebrate (VERO) and invertebrate (Aedes albopictus C6/36) cells, paraformaldehyde-glutaraldehyde fixative allowed the best preservation of cellular morphology and the highest hybridization signals with cDNA and asymmetric RNA probes against the viral S segment. Asymmetric RNA probes always gave higher sensitivity and better specificity of in situ hybridization than the nick-translated symmetric DNA probe in both vertebrate and invertebrate cells. The study of Aedes albopictus C6/36 cells persistently infected with Germiston virus showed that only a small number of cells contained the S segment, and that the replication and transcription of the S segment took place in the cytoplasm of acutely and persistently infected cells.


Endovascular therapy for acute stroke is a safe and efficient evolving method: a single-center retrospective analysis.
To determine the clinical outcome in patients undergoing endovascular therapy for acute stroke. During the period 2009-2012, 134 patients with acute stroke and normal computed tomography (CT) findings were treated with endovascular therapy at a single center. Based on CT perfusion and CT angiography findings, all patients had large vessel occlusions. Intravenous thrombolysis was used in eligible patients. The recanalization rate, time to recanalization, periprocedural complications, and clinical outcome at discharge from the hospital (National Institutes of Health score, modified Rankin Scale [mRS]) were analyzed. The recanalization rate during the study interval increased from 70% (2008-2009) to 94% (2011-2012) (P ≤ .01). The procedure time was reduced from 124 minutes (2009) to 43 minutes (2012) (P ≤ .01), and the periprocedural complication rate decreased from 21% (2009) to 2% (2012) (P ≤ .01). Patients in 2009-2010 had a 2.21 times greater probability for an mRS score ≥ 2 after the procedure compared with patients in 2011-2012 (95% confidence interval, 1.0-5.0). If the procedure lasted 15 minutes longer, the prospect for an mRS score ≥2 after the procedure was 1.30 times greater (P = .02). High recanalization rates, low procedural complications, and improved clinical outcomes were achieved using endovascular therapy in selected patients with acute stroke during a 4-year period. Endovascular therapy is an evolving safe and effective treatment for intracranial large vessel occlusion.


GGA3 mediates TrkA endocytic recycling to promote sustained Akt phosphorylation and cell survival.
Although TrkA postendocytic sorting significantly influences neuronal cell survival and differentiation, the molecular mechanism underlying TrkA receptor sorting in the recycling or degradation pathways remains poorly understood. Here we demonstrate that Golgi-localized, γ adaptin-ear-containing ADP ribosylation factor-binding protein 3 (GGA3) interacts directly with the TrkA cytoplasmic tail through an internal DXXLL motif and mediates the functional recycling of TrkA to the plasma membrane. We find that GGA3 depletion by siRNA delays TrkA recycling, accelerates TrkA degradation, attenuates sustained NGF-induced Akt activation, and reduces cell survival. We also show that GGA3's effect on TrkA recycling is dependent on the activation of Arf6. This work identifies GGA3 as a key player in a novel DXXLL-mediated endosomal sorting machinery that targets TrkA to the plasma membrane, where it prolongs the activation of Akt signaling and survival responses.


Multiscale Anisotropic Scaffold Integrating 3D Printing and Electrospinning Techniques as a Heart-on-a-Chip Platform for Evaluating Drug-Induced Cardiotoxicity.
Cardiac safety assessments are significant in drug discovery, as drug-induced cardiotoxicity (DIC) is the primary cause of drug attrition. Despite heart-on-a-chip (HoC) technology becoming an increasingly popular tool for evaluating DIC, its development remains a challenge owing to the anisotropic cardiac structure of the native myocardium. Herein, an anisotropic multiscale cardiac scaffold is presented via a hybrid biofabrication method by combining 3D printing with electrospinning technology, where the 3D-printed micrometer-scale scaffold frames enable mimicking the interwoven myocardium anatomical structure and the branched-aligned electrospun nanofibers network is able to directionally guide cellular arrangements. The in vitro 3D bioengineered cardiac tissues are then fabricated by encapsulating three-layer multiscale scaffolds within a photocurable methacrylated gelatin hydrogel shell. It is demonstrated that such an anisotropic multiscale structure could contribute to enhancing cardiomyocyte maturation and synchronous beating behavior. More attractively, with the integration of 3D bioengineered cardiac tissues and a self-designed microfluidic perfusion system, a 3D anisotropic HoC platform is established for evaluating DIC and cardioprotective efficacy. Collectively, these results indicate that the HoC model developed by integrating the 3D bioengineered cardiac tissues could effectively recapitulate the clinical manifestations, thereby highlighting their efficacy as a valuable preclinical platform for testing drug efficacy and cardiotoxicity.


Development, Characterization, and In Vitro Biological Performance of Amphotericin B and Terbinafine Microemulsions Against Leishmania major.
This study evaluated the effect of microemulsion (ME) containing Amphotericin B (AmB) alone and associated with Terbinafine (Tbf) on Leishmania major (L. major) using in vitro models. The ME formulations of these drugs were formulated and described. After evaluating their cytotoxicity on the J774A1 macrophage (MΦ), their potency against promastigotes and intracellular amastigotes models was evaluated using an in vitro MTT assay and Giemsa stain, respectively. Based on pseudo ternary phase diagrams, unloaded ME, Tbf-loaded ME (ME-Tbf), and, AmB-loaded ME (ME-AmB) with mean droplet sizes 3.4 ± 0.81, 10.05 ± 0.21, and 8.21 ± 0.46 were successfully prepared, respectively. Concerning toxicity, ME-AmB and ME-Tbf indicated lower toxicity on MΦs compared to the free drugs. The ME formulations showed considerably inhibitory effects compared to the free drug forms when the IC50 was examined. The IC50 values of AmB (59.19 ± 1.74 and 36.4 ± 3.2 μg/mL), ME-AmB (7.5 ± 0.9 and 0.8 ± 0.05 μg/mL), Tbf (234.5 ± 9 and 128.8 ± 0.28 μg/mL), ME-Tbf (26.27 ± 0.2 and 11.97 ± 0.6 μg/mL), AmB + Tbf (30.18 and 24.93 μg/mL), and ME-AmB + ME-Tbf (4.79 and 0.37 μg/mL) were estimated after 48 and 72 h, respectively.


A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes.
Variants in the gene encoding NACHT leucine-rich-repeat protein 1 (NALP1), an important molecule in innate immunity, have recently been shown to confer risk for vitiligo and associated autoimmunity. We hypothesized that sequence variants in this gene may be involved in susceptibility to a wider spectrum of autoimmune diseases. Investigating large patient cohorts from six different autoimmune diseases, that is autoimmune Addison's disease (n=333), type 1 diabetes (n=1086), multiple sclerosis (n=502), rheumatoid arthritis (n=945), systemic lupus erythematosus (n=156) and juvenile idiopathic arthritis (n=505), against 3273 healthy controls, we analyzed four single nucleotide polymorphisms (SNPs) in NALP1. The major allele of the coding SNP rs12150220 revealed significant association with autoimmune Addison's disease compared with controls (OR=1.25, 95% CI: 1.06-1.49, P=0.007), and with type 1 diabetes (OR=1.15, 95% CI: 1.04-1.27, P=0.005). Trends toward the same associations were seen in rheumatoid arthritis, systemic lupus erythematosus and, although less obvious, multiple sclerosis. Patients with juvenile idiopathic arthritis did not show association with NALP1 gene variants. The results indicate that NALP1 and the innate immune system may be implicated in the pathogenesis of many autoimmune disorders, particularly organ-specific autoimmune diseases.


The effect of accessing medical records by date of death on estimates of survival.
An inefficient, but quickly and easily calculated, estimate of a survival-time distribution is described. Conditions for the estimate to be unbiased specify bounds on the length of time a study has been in progress and the way in which people must enter a study. These appear to be frequently met when a large medical registry is examined with a view to establishing base line survival experience for a selected class of patients.


Put your FTSE down: Wealth shocks and road traffic collisions.
This paper examines the impact of a key source of wealth (the stock market) on road traffic collisions. Using data on over 2 million road accidents we do not find a linear relationship between stock prices and road crashes (fatal or otherwise) in Great Britain. However, we do find a V-shaped effect - collisions respond to the absolute change in stock market returns. The results are robust to a series of falsification exercises that potentially support a causal interpretation. We also examine another source of wealth that has not previously been examined - house prices. Similarly, we do not find that changes in monthly house prices have an impact on accidents, but a symmetric V-shaped is also shown for slight and serious accidents.


The kidney antifibrotic effects of 5,7,3',4',5'-pentamethoxyflavone from Bauhinia championii in streptozotocin-induced diabetic rats: in vivo and in vitro experiments.
The antidiabetic effects of flavonoids have been reported, but it is still unclear whether 5,7,3',4',5'-pentamethoxyflavone, isolated from Bauhinia championii Benth. (Fabaceae), also exhibits such properties. To isolate 5,7,3',4',5'-pentamethoxyflavone from B. championii using high-speed countercurrent chromatography and examine its potential in treating diabetic nephropathy. The phytochemical constituents from the stems of B. championii were separated and purified with high-speed countercurrent chromatography; 5,7,3',4',5'-pentamethoxyflavone (PMF) was identified by mass spectrum, 1H-NMR, and 13C-NMR. After exposing mesangial cells to 30 mM glucose and either 5 μM or 10 μM PMF for 6 h, the levels of fibronectin (FN) and p-Smad2/3 were analyzed using Western blotting. Male Sprague-Dawley rats were injected intraperitoneally with 55 mg/kg streptozotocin to induce diabetes and then were randomized into three groups (n = 10): vehicle administration, low-dose (5 mg/kg) PMF, and high-dose (25 mg/kg) PMF by intragastric gavage for 3 months. A healthy group was included as the control. Compared to the diabetic group, low-dose and high-dose PMF treatment decreased the phosphorylation of Smad2/3 by 0.54- and 0.52-fold, and the accumulation of FN decreased by 0.82- and 0.77-fold in vitro; the phosphorylation of Smad2/3 was decreased by 0.39- and 0.37-fold, and the accumulation of FN decreased by 0.47- and 0.40-fold in vivo, respectively. Furthermore, PMF alleviated the glomerular basement membrane thickness and foot process fusion. The findings suggest for the first time that PMF may be a promising treatment option for diabetic kidney fibrosis, which warrants additional clinical investigation.


The missing link: implementation of morphogenetic growth control on the cellular and molecular level.
In the wing imaginal disc of Drosophila melanogaster, the morphogen Dpp controls growth, probably in an instructive manner. Many models for growth control by Dpp have been proposed and have been extensively discussed elsewhere. In this review, we speculate on how instructive growth control could provide a link between Dpp signaling and cell growth and/or cell cycle progression and so implement morphogenetic growth control on the cellular and molecular levels.


Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy.
We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks. Treatment effects on DXA measures for domagrozumab versus placebo were assessed at Week 49. At Week 49, domagrozumab statistically significantly increased lean body mass versus placebo in the appendicular skeleton (p = 0.050) and arms (p < 0.001). The relationship between lean body mass at Week 49 and functional endpoints at Week 97 was evaluated. Changes in lean body mass at Week 49 in all regions except arms were significantly correlated with percent change from baseline in 4-stair climb (4SC) at Week 97. DXA-derived percent lean mass at Week 49 also correlated with 4SC and North Star Ambulatory Assessment at Week 97. These data indicate that whole-body DXA measures can be used as biomarkers for treatment effects and disease progression in patients with DMD, and warrant further investigation.Trial registration: ClinicalTrials.gov, NCT02310763; registered 8 December 2014.


Non-COVID-19 UK clinical trials and the COVID-19 pandemic: impact, challenges and possible solutions.
The COVID-19 pandemic impacted the operationalisation of non-COVID-19 clinical trials globally, particularly site and participant recruitment and trial success/stoppage. Trials which anticipate recruitment challenges may embed methods such as the QuinteT Recruitment Intervention (QRI) to help identify and understand the sources of challenges. Such interventions can help shed light on pandemic-related challenges. This paper reports our experience of the impact of the COVID-19 pandemic on conducting clinical trials with an embedded QRI, highlighting how the QRI aided in identifying challenges and potential solutions, particularly related to the site set-up and participant recruitment. We report on 13 UK clinical trials which included a QRI. Information is from QRI data and researchers' experience and reflections. In most trials, recruitment was lower than even the lowest anticipated rates. The flexibility of the QRI facilitated rapid data collection to understand and document, and in some instances respond to, operational challenges. Challenges were mostly logistical, pandemic-related and beyond the control of the site or central trial teams. Specifically: disrupted and variable site opening timelines -often due to local research and development (R&D) delays- shortages of staff to recruit patients; fewer eligible patients or limited access to patients; and intervention-related factors. Almost all trials were affected by pandemic-related staffing issues including redeployment, prioritisation of COVID-19 care and research, and COVID-19-related staff illness and absence. Trials of elective procedures were particularly impacted by the pandemic, which caused changes to care/recruitment pathways, deprioritisation of services, reduced clinical and surgical capacity and longer waiting lists. Attempted solutions included extra engagement with staff and R&D departments, trial protocol changes (primarily moving online) and seeking additional resourcing. We have highlighted wide-ranging, extensive and consistent pandemic-related challenges faced by UK clinical trials, which the QRI helped to identify and, in some cases, address. Many challenges were insurmountable at individual trials or trials unit level. This overview highlights the need to streamline trial regulatory processes, address staffing crises, improve recognition of NHS research staff and for clearer, more nuanced central guidance on the prioritisation of studies and how to deal with the backlog. Pre-emptively embedding qualitative work and stakeholder consultation into trials with anticipated difficulties, moving some processes online, and flexible trial protocols may improve the resilience of trials in the current challenging context.


Dietary glycemic index, glycemic load and risk of bladder cancer: a prospective study.
Previous studies have provided limited evidence for an adverse effect of high glycemic index (GI) and glycemic load (GL) on bladder cancer risk. This study aimed to examine the association between GI, GL and bladder cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. GI and GL scores were computed among 101,721 participants in the PLCO study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression model adjusting for confounders. After a median of 12.5 years of follow-up, 776 incident bladder cancer cases occurred. There was no significant association between bladder cancer risk and GI (HRQ5vsQ1 = 1.18, 95% CI 0.94-1.48, p for trend = 0.177) or GL (HRQ5vsQ1 = 0.92, 95% CI 0.65-1.30, p for trend = 0.826). The associations did not differ by continuous analyses. Spline regression plots revealed a lower risk of bladder cancer with higher GI or GL, but the difference was not statistically significant. There was no statistical evidence for nonlinearity (P for nonlinearity > 0.05). In summary, analysis of the PLCO cohort did not provide evidence that higher GI or GL diets were associated with greater bladder cancer risk.


Assessment of signs of influenza illness in the ferret model.
The ferret model of influenza A infection was evaluated to determine whether physical signs of influenza illness in addition to fever could be adequately followed. Ferrets were evaluated for nasal and systemic signs of influenza infection in a blinded, randomized protocol. Nasal signs were scored depending on the degree of nasal discharge and congestion. Systemic signs were evaluated on the basis of the activity level of ferrets. Nasal and systemic signs in ferrets challenged with influenza began to rise at peak virus shedding. This rise was coincident with the onset of the nasal inflammatory cell response. Nasal and systemic signs were statistically higher in challenged ferrets as compared with controls from 28 to 52 h after infection [P = 0.002 except at 28 h (P = 0.01)]. Despite precautions against influenza transmission, controls shed influenza virus associated with mild increases in nasal and systemic signs late in the course of the study. Our results suggest that severity of influenza illness can be adequately assessed in the ferret model using collective measurements of nasal and systemic signs, temperatures, and nasal cellular infiltration.


Amino acids as determinants of host preference for the xylem feeding leafhopper, Homalodisca coagulata (Homoptera: Cicadellidae).
Homalodisca coagulata is a highly polyphagous xylem feeder with distinct seasonal patterns in it's selection of host plants. These patterns were examined in relation to the amino acid content of the xylem for four common host species; Lagerstroemia indica, Baccharis halimifolia, Prunus persica, and Prunus salicina. Xylem fluid was collected from each host species at times when numbers of feeding leafhoppers were both low and high. In each case, concentrations of amino acids were greatest when numbers were high. Similarly, comparisons between host species at given times showed that concentrations of amino acids were positively correlated with host selection. In a second study, amino acids of xylem were manipulated by budding scions of a non-preferred host (P. persica) on rootstocks of preferred (P. salinica) and non-preferred (P. persica) hosts. Morphology and phenology of the budded trees were similar to that of the scion species yet the xylem composition of amino acids was primarily dependent on the rootstock. Concentrations of amino acids and the preference of leafhoppers were roughly two-fold greater for scions of the preferred than the non-preferred rootstock. In both studies, amides (glutamine plus asparagine) were the amino acids most highly correlated with host selection. These compounds are the predominant amino acids in xylem fluid, have high nitrogen to carbon ratios, and account for a high percentage of the caloric value in xylem fluid. Many of the less abundant amino acids were positively correlated with host preference, but the correlations were less consistent and correlation coefficients were generally lower.


[Knowledge of hepatitis B virus among outpatients consulting in the hepatogastroenterology department at the Lome Campus University Hospital].
To evaluate the knowledge abouthepatitis B virus (HBV) infection of patientsconsulting in the hepatogastroenterology department. This prospective, descriptive, and analytic study took place over a two-month period among outpatients in this department of the Lome Campus University Hospital. The study included 276 patients, predominantly male. Participants' mean age was 36.7 years (range: 17 to 75 years). In all, 190 patients (around 68.8%) confirmed that they had heard of this disease at least once, mainly via the media or the hospital. Twenty patients (10.5%) mentioned as the main means of infection sexual intercourse, body fluids (blood), and maternalfetal transmission. Overall, 28 participants reported having been vaccinated against HBV. Of those who had ever heard of this disease, only 58 (30.5%) knew that it exists in an acute form and 69 patients (36.3%) about its chronic form. Thirty (15.8%) patients knew that cirrhosis and liver cancer are its main complications, and 68 (35.8%) were unaware that HBV treatment is available in Togo. This study revealed that participants had a poor level of knowledge about HBV.


Biochemical studies of immune complexes. II. Purification of immune complexes from sera of patients with malignant melanoma.
Circulating immune complexes (CICs) from serum samples of patients with malignant melanoma were isolated in high yield utilizing a bifunctional chromatography matrix that binds all normal serum proteins except IgG-containing immune complexes (ICs), IgG, and transferrin. Protein fractions were subsequently analyzed by polyacrylamide gel electrophoresis (PAGE) and characterized by molecular weight. By this method, one common and several unique component nonimmunoglobulin proteins of the ICs were identified. These proteins possess similar molecular weights to several previously described human melanoma antigens. This technique should permit biochemical and immunological characterization of the component antigens of CICs in melanoma and other malignancies.


Evaluation of the prevalence of herpes simplex-1 infection in oral squamous cell carcinoma specimens in Alzahra and Kashani Hospitals with polymerase chain reaction method in 2012-2013.
Although tobacco, alcohol abuse are well-recognized risk factors for oral squamous cell carcinoma (OSCC), there is evidence to indicate that herpes simplex virus (HSV) may also play some inducing role. The purpose of this study was to investigate the presence of HSV in Iranian patients with OSCC using the polymerase chain reaction (PCR). Biopsies of OSCC were obtained from 60 patients, 54 males and 6 females, aged between 36 and 80 years old. Paraffin-embedded, histologically confirmed specimens were analyzed for the presence of HSV DNA using PCR. Only three samples (5%) was positive, suggesting that HSV may not play an important role in this group of patients. The prevalence of HSV-1 positive sample in this study was 5%. It shows that HSV-1 has no important role in OSCC.


A pseudoknotted RNA oligonucleotide.
The diverse functions of RNA, which include enzymatic activities, regulatory roles in transcription and translation, are made possible by tertiary structure. Computer algorithms can predict the secondary structure of an RNA molecule using free-energy parameters for base pairing and stacking, loops and bulges. However, with the exception of transfer RNA, little is known about the structures and thermodynamics of interactions involved in the tertiary structure of RNA. Recently, it has been proposed that a novel form of RNA folding called pseudoknotting occurs at the 3' end of certain viral RNAs from plants. A pseudoknot involves intramolecular pairing of bases in a hairpin loop with a few bases outside the stem of the loop to form an additional stem and loop region (Fig. 1). If each stem contained a full helical turn, a true knot would be formed. We present evidence from single-strand specific (S1) and double-strand specific (V1) nuclease digestion, that a short RNA oligonucleotide (19 nucleotides long) adopts a stable pseudoknotted structure. The nuclease digestion and thermodynamic properties of this oligonucleotide were compared with those of oligonucleotides which form hairpin structures containing the two possible stem regions in the pseudoknot. These results show that appropriate sequences can form pseudoknots and indicate that pseudoknots are a significant type of local tertiary structure which must be considered in the folding of complex RNA molecules.


Protection of mice against virulent virus infection by a temperature-sensitive mutant derived from an HVJ (Sendai virus) carrier culture.
Experimental infection with HVJ (haemagglutinating virus of Japan-the Sendai strain of parainfluenza 1 virus) in mice was studied. Aerosol infection of newborn mice with the wild-type virus (HVJ-W) retarded the development of body weight and killed the animals within a few weeks. Large amounts of virus were isolated from both the lungs and the nasal turbinates of infected mice. In contrast, newborn mice exposed by inhalation to a temperature-sensitive (ts) mutant (HVJ-pB) derived from an HVJ carrier culture showed no clinical signs and grew equally well as mock-infected animals. No infectious virus could be recovered from the lungs although the ts mutant grew to moderate titre in the nasal turbinates. The prior inoculation of newborn mice with the ts mutant virus induced a state of significant resistance to subsequent challenge with the virulent wild-type virus. No replication of challenge virus in both lungs and nasal turbinates could be detected and the animals were protected a lethal infection. It is suggested that an avirulent temperature-sensitive mutant which has lost the capacity to replicate in the lower respiratory tract but is still capable of multiplying in the nasal turbinates may be a promising candidate for use in live vaccines especially against the infectious disease of the lower respiratory tract.


[The chemical and radiation effects of uranium solutions on the developing roe of the loach (Misgurnus fossilis L.)].
A study was made of the effect of alpha-radiation of 238U solutions and enriched uranium (9.9 X 10(7) Bq/g) on developing Misgurnus fossilis eggs. The incidence of abnormal larvae and the death rate of eggs increased when the latter were incubated in 138 mg/l solution of uranium 238: this was not accompanied by the increase in the yield of the aberrant ana- and telophases in the epithelium cells of 1-day larvae.


Neurotoxic character of thimerosal and the allometric extrapolation of adult clearance half-time to infants.
The decomposition rate of organomercurials and the potency of the blood-brain barrier increase with the size of the organic radical. Thus methylmercury damages the brain more than thimerosal does, and when intake limits set for methylmercury are applied to thimerosal the safety margin is increased even if the clearances were the same. However, the clearance half-time of ethylmercury in adults is about one-third of the 50 days' clearance half-time of methylmercury given for 60 kg body weight. Moreover, because metabolic rates (e.g. basal metabolism, daily loss of mercury in per cent of body burden) in different weight groups are related to the fractional power of body weight (rule of allometry), mercury clears from the infant body faster than from the adult body. Blood mercury concentrations observed after vaccination showed agreement with allometrically extrapolated concentrations.


Optimal positioning of self-expanding valves before deployment decreases paravalvular regurgitation following transcatheter aortic valve replacement.
To evaluate the association between measurements performed during Medtronic CoreValve (MCV) deployment and paravalvular leak (PVL). The MCV can be recaptured and repositioned, allowing the TAVR operator to implant at a more favorable position. The association between angiographic measurements of MCV position while the valve is recapturable and PVL post deployment has not been investigated. 493 patients undergoing TAVR with MCV (January 2011-July 2017) were included. PVL was defined as intraprocedural aortic regurgitation that was judged clinically to require balloon postdilation. Depth of the valve at the left coronary cusp (LCC) and noncoronary cusp (NCC) were measured when the valve was 80% deployed. An optimal cutoff value for the ratio LCC/NCC for PVL was identified in 40 patients. Using this cutoff value, the association between LCC/NCC and PVL was then validated in 453 patients. The median LCC/NCC was 1.51 (interquartile range 1.06-1.89).The optimal cutoff value for LCC/NCC was 1.48 (93% sensitivity, 77% specificity, AUC0.85). In the validation group 112 (24.7%) patients had PVL. For LCC/NCC ≥ 1.48, the incidence of PVL was lower compared to LCC/NCC < 1.48 (9.58% vs. 41.78%, P < 0.0001). LCC/NCC of 1.48 had a sensitivity of 79.5% and specificity of 63.6% for PVL (AUC0.72). In a multivariate model, LCC/NCC < 1.48 independently predicted PVL (OR = 6.67, 95% CI 3.96-11.23, P < 0.0001). Positioning the MCV such that the LCC/NCC is ≥1.48 may result in less PVL.


Polymerase chain reaction to detect human cytomegalovirus in livers of infants with neonatal hepatitis.
Neonatal hepatitis is closely related to human cytomegalovirus infection in Taiwan, a conclusion based on serological and urine culture studies. To obtain more direct evidence further relating cytomegalovirus to the pathogenesis of neonatal hepatitis, the cytomegalovirus genome was studied in the liver tissues of 50 infants with neonatal hepatitis using the polymerase chain reaction (PCR). Liver tissues from 26 infants with biliary atresia and another 30 infants and children with diagnoses other than neonatal hepatitis, cholestasis, or hepatitis were also studied for comparison. Sequences from the immediate early gene 1 and 2 regions were used as primers. The liver tissues from 23 (46%) of the 50 infants with neonatal hepatitis were positive for cytomegalovirus genome, whereas those of 2 of the 26 infants with biliary atresia and none of the liver tissues from 30 infants and children without neonatal hepatitis were positive for cytomegalovirus genome, by PCR. The results of PCR correlated well with that of serology and urine culture. This study provides further evidence of cytomegalovirus in the pathogenesis of neonatal hepatitis.


Sex-specific interaction between APOE and APOA5 variants and determination of plasma lipid levels.
The APOA5 and APOE genes play an important role in determination of plasma levels of triglycerides (TG) and total cholesterol (TC). We have analyzed APOA5 (T-1131>C and Ser19>Trp) and APOE (e2/e3/e4) variants in 2500 representatively selected Caucasians (1168 men, 1332 women). In female subjects (but not in male) an association between APOE polymorphism and TC was observed on the background of the common APOA5 haplotype (TT-1131/SerSer19) - APOE2 carriers have the lowest (5.12 (1.15) mmol/l) and the APOE4 carriers have the highest (6.05 (1.06) mmol/l) levels of plasma TC (P<0.001). If at least one APOA5 C-1131 or Trp19 allele was present, APOE exhibits no significant effect on plasma TC. APOA5 did not affect plasma TG levels, if APOE4 allele was present. In the presence of APOE2 or APOE3, carriers of the APOA5 alleles, C-1131 and/or Trp19, have higher TG levels (1.64 (1.05) mmol/l) than others (1.37 (0.75) mmol/l) (P<0.01). In male subjects, the same, but non-significant trend was observed. In female subjects, we have detected an interaction between APOE and APOA5 variants and plasma lipid levels.


Laparoscopic versus open colorectal surgery in the acute setting (LaCeS trial): a multicentre randomized feasibility trial.
Approximately 30 000 people undergo major emergency abdominal gastrointestinal surgery annually, and 36 per cent of these procedures (around 10 800) are carried out for emergency colorectal pathology. Some 14 per cent of all patients requiring emergency surgery have a laparoscopic procedure. The aims of the LaCeS (laparoscopic versus open colorectal surgery in the acute setting) feasibility trial were to assess the feasibility, safety and acceptability of performing a large-scale definitive phase III RCT, with a comparison of emergency laparoscopic versus open surgery for acute colorectal pathology. LaCeS was designed as a prospective, multicentre, single-blind, parallel-group, pragmatic feasibility RCT with an integrated qualitative study. Randomization was undertaken centrally, with patients randomized on a 1 : 1 basis between laparoscopic or open surgery. A total of 64 patients were recruited across five centres. The overall mean steady-state recruitment rate was 1·2 patients per month per site. Baseline compliance for clinical and health-related quality-of-life data was 99·8 and 93·8 per cent respectively. The conversion rate from laparoscopic to open surgery was 39 (95 per cent c.i. 23 to 58) per cent. The 30-day postoperative complication rate was 27 (13 to 46) per cent in the laparoscopic arm and 42 (25 to 61) per cent in the open arm. Laparoscopic emergency colorectal surgery may have an acceptable safety profile. Registration number: ISRCTN15681041 ( http://www.controlled-trials.com).


Meckel's diverticulum.
Meckel's diverticulum is a cause of significant morbidity and mortality. Often this is related to the delay in diagnosis. Based on a US population of 200 million people and a 2% incidence, there are 4 million Meckel's diverticula present waiting to cause symptoms. Considering that most Meckel's diverticula are asymptomatic and that many authors have described the condition as a great mimic, the diagnosis is often quite elusive. Therefore, a high index of suspicion is needed to diagnose Meckel's diverticulum correctly and expeditiously as the source of disease in the patient with an often unclear abdominal presentation. The difficulty with diagnosis should be lessened if one considers that Meckel's diverticulum presents largely in the male and younger age groups with the three major symptom complexes of bowel obstruction, gastrointestinal bleeding, and inflammation. Use of 99mTc pertechnetate scintigraphy appears to be the diagnostic study of choice if Meckel's diverticulum is suspected and the patient is clinically stable. When one considers the potential for bad outcome if Meckel's diverticulum is missed in the setting of possible obstruction or hemorrhage (i.e., bowel infarction or exsanguination), a high index of suspicion and diagnostic aggressiveness is warranted. Lastly, if one thought is to be left behind, it should be: "Meckel's is a great mimic that must be considered in all cases of intra-abdominal disease in which the cause is not readily apparent."


[Complex treatment of postoperative peritonitis as a method of prophylaxis of commissural disease in children].
This work dedicate to study of the use liposome drugs for treatment an complete abdominal pathology--child's postoperative peritonitis. Clinical-instrumental rates for two surgical methods (laparotomy and laparoscopy with liposome drugs) were used. The advantages of the using of the laparoscopy versus open operative treatment for this pathology are shown.


Estrogen control of progesterone receptor induction in human breast cancer: role of nuclear estrogen receptor.
We have provocative data which suggest that the nuclear estrogen-receptor complex interacts with DNA, that this interaction is required for appropriate receptor turnover or processing, and that processing may be essential for induction of a specific protein by estrogen. If the receptor is improperly inserted into DNA, as for instance when it is bound by nafoxidine, processing fails and the biological effect is blunted.


Acid survival of Helicobacter pylori: how does urease activity trigger cytoplasmic pH homeostasis?
Helicobacter pylori can survive for several hours at pH 1 in the presence of urea. Under these conditions, the organism maintains its cytoplasmic pH at a value close to neutral. The role of the cytoplasmically located urease enzyme in this process is a matter of debate. We propose that cytoplasmic ammonia generated by the action of urease is protonated by H(+) ions leaking in from the acidic medium and that the NH(4)(+) formed is extruded from the cytoplasm via an as-yet-unidentified transport system. This mechanism is compared with the general mechanism of cytoplasmic pH homeostasis in microorganisms.


Estimation of regional lung function in interstitial pulmonary disease using 99mTc-technegas and 99mTc-macroaggregated albumin single-photon emission tomography.
For quantitative evaluation of the regional lung function in patients with interstitial pulmonary disease (IP) in the sitting position, 99mTc-Technegas and 99mTc-macroaggregated albumin (MAA) single-photon emission tomography (SPET) studies were performed in 12 healthy controls (HC) and 42 IP patients. Four transverse images were prepared from the data obtained and designated as slices no. 1-4 from the top downward. Regions of interest (ROIs) were determined in the anterior and posterior parts of the lung in each slice, and the ratio of the count per voxel in the ROIs to the count in the entire lung was calculated as the regional Technegas index (T). The regional perfusion index (Q) was calculated by a similar procedure using the data of 99mTc-MAA SPET. The ratios between T and Q (T/Q) in the anterior and posterior regions of the lung, and the ratios of T and Q between the anterior and posterior regions of the lung (Tp/Ta and Qp/Qa) were examined. In the HC group, T/Q decreased but Tp/Ta and Qp/Qa increased from the upper to the lower lung fields. When IP patients were classified into (I) those in whom T/Q decreased from the upper to the lower lung fields, (II) those in whom it was similar in all slices, (III) those in whom it increased from slice 3 to slice 4, and (IV) those in whom it increased from slice 2 to slices 3 and 4, this classification was more closely correlated with %VC than with %DLCO or PaO2. When the patients were classified according to Tp/Ta and Qp/Qa into (A) those in whom the values were greater in the lower than the upper lung field, (B) those in whom the values were similar in all slices, and (C) those in whom the values were smaller in lower than in upper lung fields, categories B and C were observed frequently even in patients whose %VC was in the normal range. This method is considered to be an effective means to evaluate the progression and pathology of IP and to detect early impairment of lung function.


Prognostic factors for and pattern of lymph-node involvement in patients with operable cervical cancer.
Lymph node metastases significantly worsen the prognosis in cervical carcinoma. Risk factors-pathological and patient related-could select patients at high risk for lymph node involvement. This retrospective analysis was performed by analyzing data from patients with cervical carcinoma treated between 2000 and 2017 at the Department of Obstetrics and Gynecology of the University Hospital Ulm. In total, 261 patients with cervical carcinoma (International Federation of Gynecology and Obstetrics (FIGO) stage IA-IIB) and lymphadenectomy with at least 10 removed lymph nodes were available for analysis. Overall, 86 (33.0%) patients had lymph node metastases; 73 patients had pelvic lymph node metastases only and 13 patients had both pelvic and paraaortic lymph node metastases. Lymph node metastases were found most often in the region of the external iliac artery and obturator fossa, with 57.0% and 54.7% of all 86 node-positive patients, respectively. Univariable analyses showed that presence of lymph node metastases was significantly associated with both preoperative FIGO stage (p = 0.001) and final pathological tumor stage (p < 0.001), status of resection margin (p = 0.002), lymphovascular space invasion (LVSI), (p < 0.001) and vascular space invasion, (p < 0.001). In a multivariable logistic regression model with presence of lymph node metastases (yes/no) as binary response variable, only LVSI (p < 0.001) and body mass index (BMI), (p = 0.035) remained as significant independent predictors of lymph node involvement. Subgroup analyses showed that LVSI was a significant predictive factor for lymph node involvement in patients with a preoperatively assessed FIGO stage < IIB (p < 0.001), but not for patients with a preoperatively assessed FIGO stage ≥ IIB (p = 0.122). The risk factor LVSI should play an important role in deciding whether an individualized therapy concept is based on escalating or deescalating treatment. In future, the sentinel concept could reduce morbidity and at the same time provide an important prognostic assessment for a subset of cervical cancer patients.


A randomized controlled trial comparing two types of pneumatic compression for breast cancer-related lymphedema treatment in the home.
Pneumatic compression devices (PCDs) are used in the home setting as adjunctive treatment for lymphedema after acute treatment in a clinical setting. PCDs range in complexity from simple to technologically advanced. The objective of this prospective, randomized study was to determine whether an advanced PCD (APCD) provides better outcomes as measured by arm edema and tissue water reductions compared to a standard PCD (SPCD) in patients with arm lymphedema after breast cancer treatment. Subjects were randomized to an APCD (Flexitouch system, HCPCS E0652) or SPCD (Bio Compression 2004, HCPCS E0651) used for home treatment 1 h/day for 12 weeks. Pressure settings were 30 mmHg for the SPCD and upper extremity treatment program (UE01) with standard pressure for the APCD. Thirty-six subjects (18 per group) with unilateral upper extremity lymphedema with at least 5% arm edema volume at the time of enrollment, completed treatments over the 12-week period. Arm volumes were determined from arm girth measurements and suitable model calculations, and tissue water was determined based on measurements of the arm tissue dielectric constant (TDC). The APCD-treated group experienced an average of 29% reduction in edema compared to a 16% increase in the SPCD group. Mean changes in TDC values were a 5.8% reduction for the APCD group and a 1.9% increase for the SPCD group. This study suggests that for the home maintenance phase of treatment of arm lymphedema secondary to breast cancer therapy, the adjuvant treatment with an APCD provides better outcomes than with a SPCD.


Causal associations between prodromal infection and neuromyelitis optica spectrum disorder: A Mendelian randomization study.
Prodromal infections are associated with neuromyelitis optica spectrum disorder (NMOSD), but it remains unclear which type of infection has a causal association with NMOSD. We aimed to explore the causal associations between four herpesvirus infections (chickenpox, cold sores, mononucleosis and shingles) and NMOSD, as well as between other types of infections and NMOSD. For data on infections, we used the genome-wide association study (GWAS) summary statistics from the 23andMe cohort. For outcomes, we used the GWAS data of participants of European ancestry, including 215 NMOSD patients (132 anti-aquaporin-4 antibody [AQP4-ab]-positive patients and 83 AQP4-ab-negative patients) and 1244 normal controls. Single-nucleotide polymorphism (SNP) identification and two-sample Mendelian randomization (MR) analyses were then performed. In the 23andMe cohort, we identified one SNP for chickenpox (rs9266089 in HLA-B gene), one SNP for cold scores (rs885950 in the POU5F1 gene), one SNP for mononucleosis (rs2596465 in the HCP5 gene), and three SNPs for shingles (rs2523591 in the HLA-B gene; rs7047299 in the IFNA21 gene; rs9260809 in the MICD gene). The association between cold sores and AQP4-ab-positive NMOSD reached statistical significance (odds ratio [OR] 745.318; 95% confidence interval [CI] 22.176, 25,049.53 [p < 0.001, Q < 0.001]). The association between shingles and AQP4-ab-positive NMOSD was also statistically significant (OR 21.073; 95% CI 4.271, 103.974 [p < 0.001, Q < 0.001]). No significant association was observed between other infections and AQP4-ab-positive or AQP4-ab-negative NMOSD. These findings suggest there are positive associations between cold sores and shingles and AQP4-ab-positive NMOSD, indicating there may be causal links between herpes simplex virus and varicella-zoster virus infection and AQP4-ab-positive NMOSD.


Purification and characterization of the parvalbumin from monkey skeletal muscle.
1. A high affinity Ca2+ binding and low mol. wt protein, parvalbumin, was purified from monkey skeletal muscle. 2. As compared with other animals, only one component and a lower content of monkey parvalbumin were found. 3. This may suggest that both the component and the content of parvalbumin decreases with biological evolution. 4. The parvalbumin was found to have a mol. wt of 11,400, a pI of 5.1, a high aspartic acid and lysine content, maximum absorption at around 260 nm, a blocked amino-terminal, an immunological distinction, 2 mol Ca2+ binding/mol, and a conformational change by Ca2+ binding. 5. Parvalbumin was shown to have alpha type properties.


[Hereditary spherocytic hemolytic anemia in an adult with the formation of ectopic foci of extramedullary hemopoiesis in the chest].
The paper describes a rare case of formation of paravertebral extramedullary hemopoietic foci in microspherocytic anemia or Minkovsky-Shoffar disease in an adult. Therapeutic splenectomy has led to regression of extramedullary hemopoietic foci, which supports that there is a direct relationship of the above formations to the specific features of the etiology and pathogenesis of microspherocytic anemia.


Emotional Health and Self-esteem Among Adolescents in Malaysian Orphanages.
This study aimed to assess the prevalence and risk factors of depression, anxiety, stress and low self-esteem among institutional Malaysian adolescents. This cross-sectional descriptive study included 287 adolescents aged 12-18 years living in six selected orphan homes. Study's instruments included Socio-demographic questionnaire, validated Malay version of Depression Anxiety Stress Scale-21 and Rosenberg Self-Esteem Scale. The findings revealed that 85.2, 80.1 and 84.7% of participants had depression, anxiety and stress respectively. Females were more likely to be depressed. Furthermore, anxiety was significantly associated with race and age but no significant associations between stress and the demographic factors were found. The study also showed that 70.8% of males and 69.2% of females had low self-esteem and the self-esteem was associated with depression, anxiety and stress.Therefore, mental health problems are very common among adolescents in Malaysian orphanages. Results reveal the urgency of immediate actions to reduce the mental health problems among Malaysian institutional adolescents.


Determination of the intracellular free chloride concentration in rat brain synaptoneurosomes using a chloride-sensitive fluorescent indicator.
The chloride-sensitive fluorescent indicator MQAE (N-(6-methoxyquinolyl) acetoacetyl ester) has been used for determination of the intracellular free chloride concentration in rat brain synaptoneurosomes. Loading of the synaptoneurosomes with MQAE occurs by transmembrane diffusion. Calibration of the intracellular MQAE was done by determining the correlation between fluorescence intensity and intrasynaptoneurosomal Cl- concentration in the presence of the Cl-/OH- exchanger tributyltin and the K+/H+ exchanger nigericin, starting from zero Cl- concentration. The total quenchable signal of MQAE was determined by adding KSCN in the presence of the K+ ionophore valinomycin. The correlation between the reciprocal of the fluorescence intensity and the chloride concentration was linear at least up to 50 mM Cl-. The fluorescence of freshly prepared synaptoneurosomes was then measured and the obtained value was plotted into the calibration curve and the corresponding Cl- was read. The mean intrasynaptoneurosomal chloride concentration was 14 +/- 4 mM. We also quantitatively estimated the Cl- flux after addition of the barbiturate, pentobarbitone that opens GABAA receptor-Cl(-)-channels, to the synaptoneurosomes. An addition of 1 mM pentobarbitone corresponded to an approx. 0.59 mM change in the intrasynaptoneurosomal free chloride concentration. The results show that the chloride-sensitive fluorescent indicator MQAE is a useful tool when determining intracellular chloride activity, and in quantitative determination of chloride fluxes in living cells and subcellular preparations.


Heterotopic activation of A delta and C fibres triggers inhibition of trigeminal and spinal convergent neurones in the rat.
1. Extracellular recordings were made from fourteen non-noxious only and nineteen convergent neurones in trigeminal nucleus caudalis of halothane-anaesthetized rats. All the neurones studied were excited by the continuous micro-electrophoretic ejection of an excitatory amino acid, DL-homocysteic acid (DLH), with mean currents of 38.0 +/- 7.2 and 39.8 + 6.5 nA producing steady discharges of 35.0 +/- 3.3 and 31.8 +/- 1.3 spikes/s from the non-noxious only and convergent neurones respectively. 2. The repeated percutaneous application (100 trials; 0.66 Hz) of single square-wave stimuli (10 mA; 2 ms) to the tail always induced a biphasic depression of the activity of the convergent, but never of the non-noxious only, neurones. Both the early and late components of this inhibition occurred at shorter latencies when the base rather than the tip of the tail was stimulated. Differences in latencies from the two sites of stimulation (100 mm apart) were used to estimate the conduction velocities of the peripheral fibres which were triggering the inhibitions. 3. The cumulated results showed that, for the onset of the earlier component of the inhibition, the mean difference between the latencies from the two sites of stimulation was 13.6 +/- 1.9 ms, corresponding to a peripheral conduction velocity of 7.3 +/- 0.3 m/s, which is in the A delta-fibre range. For the onset of the late component of inhibition, the mean difference was 147.7 +/- 14.9 ms, corresponding to a peripheral conduction velocity of 0.68 +/- 0.07 m/s, which is in the C-fibre range. 4. When currents of different intensities were applied percutaneously to the two stimulation sites, the thresholds for obtaining the A delta component were in the range 0.25-0.5 mA whereas the C component appeared with currents 1-2 mA. A clear relationship between current intensity and magnitude of inhibition was observed in the 0.25-2 mA range for the A delta component and in the 1-5 mA range for the C component. 5. In an additional series of experiments recordings were made from eleven convergent neurones in the dorsal horn of the lumbar spinal cord. By using essentially the same experimental procedure the effects of repetitive application (100 trials, 0.66 Hz) of percutaneous electrical stimuli (1 or 10 mA, 2 ms) applied to the muzzle, were studied on the steady discharges (42.3 +/- 5.4 spikes/s) induced by DLH. The application of the 10 mA stimuli induced a biphasic depression of activity, whereas only an early component was observed following 1 mA stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)


Formamide-Free Genomic In Situ Hybridization (ff-GISH).
Fluorescence in situ hybridization allows for the mapping of various sequence types in the genomes and is thus widely used in structural, functional, and evolutionary studies. One particular type of in situ hybridization that specifically allows to map whole parental genomes in diploid and polyploid hybrids is genomic in situ hybridization (GISH). The efficiency of GISH, i.e., the specificity of hybridization of genomic DNA probes to the parental subgenomes in hybrids depends, among others, on the age of the polyploids and the similarity of the parental genomes, specifically their repetitive DNA fractions. Typically, high levels of overall repeat similarity between the parental genomes result in lower efficiency of GISH. Here, we present the formamide-free GISH (ff-GISH) protocol that can be applied to diploid and polyploid hybrids of both monocots and dicots. ff-GISH allows higher efficiency of the labeling of the putative parental genomes compared to the standard GISH protocol and allows discrimination of parental chromosome sets that share up to 80-90% repeat similarity. This modified method is nontoxic, is simple, and lends itself to modifications. It can also be used for standard FISH and mapping of individual sequence types in chromosomes/genomes.


Comparison of ultrasound versus fluoroscopic guided rotator cuff interval approach for MR arthrography.
Our purpose is to compare ultrasound and fluoroscopic-guided approaches to the glenohumeral joint at the rotator cuff interval for magnetic resonance (MR) arthrography of the shoulder. Forty consecutive patients were prospectively studied. 20 patients underwent ultrasound-guided and 20 patients underwent fluoroscopic guided injection. Successful rate of ultrasound guidance is 95%. No significant difference in pain score and duration of injection between two methods (P>.05). Ultrasound-guided rotator cuff interval injection of the glenohumeral joint for MR arthrography is comparable with fluoroscopic-guided injection. Ultrasound is the preferred method as there is no ionizing radiation.


Systemic anaphylaxis secondary to the use of 5 per cent plasma protein fractions.
A severe anaphylactic reaction developed in a twenty-six year old female after the administration of only 40 ml of 5 per cent plasma protein fractions (Plasmanate). The reaction was characterized by generalized tingling, chest pain, sudden severe hypotension, and urticaria. The patient responded to intravenous fluid, epinephrine, diphenylhydramine, and steroid administration.


[Potential endocrine disrupting effects of bifenthrin in rats].
To study the potential endocrine disrupting effects of bifenthrin (BIF) by using uterotrophic assay and Hershberger assay. In uterotrophic assay, 60 female SD rats were randomly divided into 6 groups, 10 rats per group. Rats in bifenthrin-treated groups were given different doses of bifenthrin (1.47, 4.41 and 13.23 mg/kg BW by gavage for 3 consecutive days). Rats in negative control groups were given corn oil by gavage. Rats in ethinyl estradiol (EE) oral positive control groups were given EE 1.0 microg/kg BW by gavage. Rats in EE injected positive groups were given 0.6 microg/kg BW EE by subcutaneously injection while given corn oil by gavage. At necropsy, the wet and blotted uteri were weighed. The relative uteri weights were calculated, and the histology of uteri was observed. In Hershberger assay, 60 castrated male SD rats were randomly divided into 6 groups, with 10 rats in each group. Rats in BIF-treated groups were given different doses of BIF (1.4, 4.2 and 12.6 mg/kg BW) by gavage. Flutamide (3.0 mg/kg BW) were given to animals in the positive control group by gavage. Rats in the negative control group and testosterone propionate group were given corn oil by gavage for 10 consecutive days. Rats in all groups except the negative control group were also treated with testosterone propionate (TP, 0.2 mg/kg BW) by subcutaneous injection. At necropsy, ventral prostate (VP), seminal vesicle plus fluids and coagulating glands (SVCG), levator ani-bulbocavernosus muscle (LABC), paired Cowper's glands (COW) and the glands penis (GP), liver, kidneys, adrenals were weighed. Serum triiodothyronine (T3) and thyroxine (T4) were determined. In uterotrophic assay, compared with the negative control group, the mean relative wet weight and relative blotted weight of uterine were increased significantly in the female rats given by BIF at 13.23 mg/kg BW for 3 days (P < 0.05). BIF resulted in a significant increase of epithelial cell heights of uteri at 4.41 and 13.23 mg/kg BW, as compared with control group. In Hershberger assay, compared with the TP group, mean absolute weight and relative weight of VP and LABC in BIF high dose group were significant decreased. Moreover, total T3 and T4 level were decreased also (P < 0.05). Uterotrophic assay and Hershberger assay used in this study showed that BIF may have endocrine disrupting properties.


Total synthesis of the Aspidosperma alkaloid (±)-subincanadine F via a titanium-mediated intramolecular nucleophilic acyl substitution strategy.
The total synthesis of the bridge-fused Aspidosperma indole alkaloid (±)-subincanadine F has been accomplished in seven steps. The synthetic utility of a titanium-mediated intramolecular nucleophilic acyl substitution (INAS) reaction for the construction of the bridge-fused ring system was demonstrated.


Asymmetrical vertebral column decancellation for the management of rigid congenital kyphoscoliosis.
Congenital kyphoscoliosis is a disease that often requires surgical treatment. Wedge osteotomies, such as pedicle subtraction osteotomy, are insufficient to correct this complicated rigid deformity. Vertebral column resection yields sufficient correction, but it is an exhaustively lengthy operation with a high risk of major complications. There are few effective and safe techniques for treating rigid congenital kyphoscoliosis. We aimed to investigate the technique of asymmetrical vertebral column decancellation (AVCD) for the treatment of rigid congenital kyphoscoliosis and evaluate the clinical and radiographic results of patients treated with the technique. Between January 2013 to June 2017, the data of 31 patients with congenital kyphoscoliosis who underwent single level AVCD were reviewed. Preoperative and postoperative radiographical parameters and the visual analogue scale, Asia Spinal Injury Association, and Scoliosis Research Society-22 scores were documented. The patients were followed up for an average period of 29 months. The average operative time was 273.9 ± 46.1 min. The average volume of blood loss was 782.3 ± 162.6 ml. The main coronal curve improved from a mean of 81.4° preoperatively to 24.7° at the final follow-up, and the coronal balance improved from 28.9 to 7.6 mm. The degree of local kyphosis improved from a mean of 86.5° to 29.2°, and the sagittal balance improved from 72.3 to 16.9 mm. All clinical outcomes also improved significantly from preoperatively to the final follow-up. No permanent postoperative neurologic complications occurred. The AVCD surgical procedure corrects spinal deformities in both the coronal and sagittal planes by way of a convex-sided Y shape osteotomy, achieves satisfactory realignment without additional neurological complications, and can be considered an alternative treatment for rigid congenital kyphoscoliosis.


Sequence analysis of cDNA coding for a major house dust mite allergen, Der p 1. Homology with cysteine proteases.
A cDNA clone coding for Der p 1, a major allergen from the house dust mite Dermatophagoides pteronyssinus, has been sequenced. It codes for a 222 residue mature protein with a derived molecular weight of 25,371 and contains 1 potential N-glycosylation site. In addition, the cDNA appears to code for a 13 residue proregion, and an incomplete signal peptide. The deduced sequence shows a high degree of homology with animal and plant cysteine proteases, particularly in the region of the contact residues making up the active site. Southern analysis of genomic DNA indicates that the allergen is coded by a noncontiguous gene. These data will now facilitate epitope mapping studies.


Magnesium sulfate diminishes the effects of amide local anesthetics in rat sciatic-nerve block.
Magnesium sulfate (MgSO(4)) is well known as an antagonist of N-methyl-d-aspartate receptors and was used for intrathecal analgesia a century ago. However, the effects of MgSO(4) combined with local anesthetics (LAs) on peripheral nerves are unclear. We tested the hypothesis that MgSO(4) could be used as an adjuvant to prolong and intensify conduction block by amide-type LAs in a rat sciatic-nerve block model. Further, the mechanism of possible synergy between LAs and MgSO(4) was investigated in whole-cell mode patch-clamp experiments. Sciatic nerves were exposed to 2%/73.9 mM lidocaine, 0.25%/7.7 mM bupivacaine, and 0.5%/15.4 mM ropivacaine, with or without addition of 1.25%, 2.5%, or 5% MgSO(4)/50.7 mM, and nerve block characteristics were assessed. To elucidate the LA-MgSO(4) interaction, voltage-dependent inactivation curves were determined in cultured rat GH(3) cells that expressed neuronal Na(+) channels. Unexpectedly, the addition of MgSO(4) overall significantly shortened the duration of block by lidocaine, bupivacaine, and ropivacaine. The steady-state inactivation of Na(+) channels in the presence of 300 muM lidocaine was almost unchanged by the addition of 10 mM MgSO(4), indicating that MgSO(4) does not affect the potency of lidocaine toward the inactivated Na(+) channel. MgSO(4) coadministered with amide-type LAs shortened the duration of sciatic-nerve block in rats. Therefore, it does not seem to be useful as an adjuvant for peripheral-nerve block. The mechanism of this observed antagonism is unclear but appears to be independent of the action of LAs and MgSO(4) at the LA receptor within the Na(+) channel.


Long-term fine caliber hair removal with an electro-optic Q-switched Nd:YAG Laser.
In spite of major advances in hair removal therapy, fine caliber hair remains a significant challenge for laser- and light-based devices. Evaluate a novel Electro-Optic (EO) Q-switched Nd:YAG laser for pigmented fine caliber hair removal in the Standard Single and a double pulse (DP) mode. Eleven patients underwent four laser treatments at monthly intervals. Bilateral anatomical regions received to one side the standard single pulse (SSP) while the other side the DP option. Blinded investigators conducted hair counts at 6 months post-treatment and after 24 months. Patients assessed hair loss and discomfort. Six patients rated their satisfaction at 6 months. At 6 months, investigators found a reduction of 50% in hair counts with the DP and 46% with standard pulse. Ninety percent in DP and 50% in SSP reported none to mild discomfort. Transient erythema and edema was observed with a lower severity rating with the DP. There were no other untoward effects. 83.3% of patients who completed the study at 6 months expressed satisfaction with the results. At 24 months hair loss was maintained at the same rate. The EO Q-switched Nd:YAG laser is an effective option for the permanent treatment of unwanted fine hair and has a high-patient satisfaction rate. There is less therapeutic discomfort in the DP mode.


Social and Built Environmental Correlates of Predicted Blood Lead Levels in the Flint Water Crisis.
To highlight contextual factors tied to increased blood lead level (BLL) risk following the lead-in-water contamination in Flint, Michigan. Using geocoded BLL data collected in 2013 and 2015 and areal interpolation, we predicted BLLs at every residential parcel in the city. We then spatially joined social and built environmental variables to link the parcels with neighborhood-level factors that may influence BLLs. When we compared levels before and during the water crisis, we saw the highest estimates of predicted BLLs during the water crisis and the greatest changes in BLLs in neighborhoods with the longest water residence time in pipes (μ = 2.30 µg/dL; Δ = 0.45 µg/dL), oldest house age (μ = 2.22 µg/dL; Δ = 0.37 µg/dL), and poorest average neighborhood housing condition (μ = 2.18 µg/dL; Δ = 0.44 µg/dL). Key social and built environmental variables correlate with BLL; such information can continue to guide response by prioritizing older, deteriorating neighborhoods with the longest water residence time in pipes.


Characteristics of indoor and outdoor Polycyclic Aromatic Hydrocarbons (PAHs) pollution in TSP in rural Northeast China: A case study of heating and non-heating periods.
Approximately 91% of the world's population lives in an air-polluted environment, and environmental pollution has become a widespread concern. Urban indoor and outdoor air pollution has been fully researched and effective control measures have been proposed. However, the issue of air pollution in rural areas has not been explored in depth. Compared to urban air pollution, the rural air pollution problem is more complex and urgent. Due to climatic factors and economic conditions in rural Northeast China, most households use solid fuels such as biomass straw and coal as domestic energy during the heating period, which will cause serious pollution problems of Total Suspended Particulate (TSP) and Polycyclic Aromatic Hydrocarbons (PAHs). To investigate the pollution characteristics of PAHs in indoor and outdoor TSP in rural Northeast China during the heating and non-heating periods, a medium-sized particulate matter collector 1108A was used to collect TSP for 7 days, and GC-MS was used to detect PAHs. The results showed that indoor TSP and PAHs pollution levels were the highest during the heating period. PAHs source analysis by Diagnostic Ratio (DR) and Principal Component Analysis (PCA) indicated that the main sources were biomass and coal combustion, vehicle emissions, and domestic waste incineration. According to the results of carcinogenic risk model calculations, there is a potential carcinogenic risk to the population in the Northeast rural living area. This study reflects the pollution characteristics and sources of indoor and outdoor TSP and PAHs in rural Northeast China during heating and non-heating periods, and provides a reference for further prevention and control of air pollution in rural areas, which is conducive to improving the living environment and improving human health.


Different tumours induced by benzo(a)pyrene and its 7,8-dihydrodiol injected into adult mouse salivary gland.
A comparison has been made between the carcinogenic activities of benzo(a)pyrene and the proposed proximate carcinogen, benzo(a)pyrene 7,8-dihydrodiol, in the adult C57BL mouse submandibular salivary gland. In preliminary studies using a range of doses, the dihydrodiol was slightly less active than the parent hydrocarbon in this system. There was a difference in the type of tumour induced by the 2 compounds. Benzo(a)pyrene induced tumours of the salivary glands at the site of injection, whereas the dihydrodiol induced malignant lymphosarcomas, particularly of the thymus, which were often metastatic to other orgnas. Possible reasons for the different sites of action of the 2 compounds are discussed.


Becoming a limpet: An 'intermittent limpetization' process driven by host features in the kleptoparasitic gastropod family Capulidae.
A coiled shell is the most evident feature of the typical Bauplan of a gastropod mollusc. However, at least 54 families independently evolved an apparently simplified shell morphology: the limpet. Species with this largely uncoiled, depressed shell morphology occur in almost every aquatic habitat and are associated to a number of different lifestyles and diets. The marine gastropod family Capulidae includes 18 recognised genera, the large majority of which are coiled, but with a number of limpet-like species. Capulid shell plasticity is also associated to a broad range of feeding ecologies, from obligate suspension feeders to kleptoparasites. To investigate the evolution of the limpet-like shell in the family Capulidae we performed an ancestral state reconstruction analysis on a time-calibrated phylogenetic tree (COI, 16S, and ITS2) including 16 species representing a good deal of its morphological diversity. Our results identified at least three capulid lineages that independently evolved limpet-like shells, suggesting that a recurrent limpetization process characterizes this family. One of the limpet-like genera was undescribed and was here named Cryocapulus n. gen. We suggest that capulids evolved from a coiled suspension feeder lineage and that the shift to kleptoparasitism, which occurred in the family ancestor, may have represented a strategy to save energy through the exploitation of the water current produced by the host. Probably the major drivers of shell evolution in capulids are related to their ecology, most of them being kleptoparasites, include the shape and the kind of host substrate, and lead to the repeated acquisition of a limpet-like shape.


Comparison of oestrus synchronisation programmes in dairy cattle using oestradiol benzoate, short-acting progesterone and cloprostenol, or buserelin and cloprostenol.
To evaluate the efficacy of a programme using oestradiol benzoate, progesterone and the prostaglandin-F2 (PG) analogue, cloprostenol, to synchronise oestrus and ovulation in dairy cows, compared with a programme using a gonadotropinreleasing hormone (GnRH) agonist, buserelin, and cloprostenol. Twenty non-lactating dairy cows, at random stages of the oestrus cycle, were randomly assigned to 1 of 2 treatments. In Treatment 1 ( OPPG; n=10), cows were injected with 2 mg oestradiol benzoate intramuscularly (IM) plus 200 mg progesterone subcutaneously (SC) on Day 0, followed by 500 microg cloprostenol IM on Day 9 and 1 mg oestradiol benzoate on Day 10. In Treatment 2 (GPG; n=10), cows were injected with 10 microg buserelin IM on Day 0, 500 microg cloprostenol IM on Day 7 and 10 microg buserelin on Day 9. The ovaries of all cows were examined by ultrasonography, using an 8 MHz probe, from 5 days before the initial treatment until ovulation. Cows were observed for oestrus 3 times daily for 7 days after cloprostenol treatment. Blood samples were collected daily for determination of progesterone, and 6-hourly for 36 h after the second oestradiol or buserelin injection for the determination of follicle stimulating hormone (FSH) and luteinising hormone (LH) concentrations. The percentage of cows observed in oestrus was higher in the OPPG group than in the GPG group (100% vs 55.6%, p=0.018). Treatment with either short-acting progesterone plus oestradiol benzoate or buserelin was followed by atresia or ovulation of the dominant follicle. Emergence of a new follicular wave occurred earlier (p>0.001) in the GPG group (2.2+/-0.2 days) than in the OPPG group (3.6+/-0.2 days). There was no significant difference between treatment groups in the variation of time of follicular wave emergence or size of the largest follicles at either the time of initial treatment (10.8+/-1.4 mm vs 11.1+/-0.8 mm), cloprostenol treatment (13.8+/-0.7 mm vs 14.0+/-1.3 mm) or of ovulation (15.4+/-0.7 mm vs 17.6+/-1.1 mm; p=0.10). The LH surge occurred sooner after the second injection of buserelin (4.0+/-1.0 h) than after the second injection of oestradiol benzoate (22.8+/-1.2 h; p>0.001). The interval between the second injection of oestradiol benzoate or buserelin and ovulation did not differ significantly between treatment groups (1.7+/-0.3 days vs 1.6+/-0.2 days; p=0.69). The use of short-term progesterone treatment, combined with oestradiol benzoate for follicular wave synchronisation, and cloprostenol to cause lysis of residual luteal tissue, is a promising alternative to established methods of oestrus synchronisation in cows.


Heart rate turbulence and other autonomic risk markers for arrhythmia risk stratification in dilated cardiomyopathy.
Noninvasive arrhythmia risk stratification in patients with nonischemic dilated cardiomyopathy (DCM) using autonomic markers have yielded disappointing results. Heart rate turbulence is a new method to assess cardiac autonomic function. The aim of the study was to compare the predictive value of heart rate turbulence with those of conventional autonomic risk markers for ventricular tachyarrhythmic events in patients with DCM. The predictive value of heart rate turbulence, baroreflex sensitivity (phenylephrine method), and heart rate variability was assessed in patients with symptomatic congestive heart failure due to DCM who were in sinus rhythm and had a 24-hour Holter recording. Patients were followed for a combined end point of ventricular tachyarrhythmic events. A total of 114 patients (mean left ventricular ejection fraction, 28 +/- 11%), included in the Frankfurt DCM database between 1996 and 2000, fulfilled the criteria for inclusion in this study. Determinate test results were obtained for heart rate variability in 98%, for baroreflex sensitivity in 90%, and for heart rate turbulence in 75% of patients (P = .008). Correlation between the different autonomic markers were only modest (r values, 0.36-0.43). During a follow-up of 22 +/- 17 months, an end point event occurred in 15 patients. On univariate analysis, left ventricular ejection fraction and baroreflex sensitivity were significant predictors of arrhythmic events. On multivariate analysis, only baroreflex sensitivity remained an independent predictor (chi(2) = 3.17; P = .07). Reliable analysis of heart rate turbulence is possible in approximately 75% of eligible patients with DCM. Whereas blunted baroreflex sensitivity is a predictor of arrhythmic events, heart rate variability and turbulence do not yield predictive power in these patients.


The effects of electrolysis on operational solutions in electromembrane extraction: The role of acceptor solution.
Fundamental operational principle and instrumental set-up of electromembrane extraction (EME) suggest that electrolysis may play an important role in this recently developed micro-extraction technique. In the present study, the effect of electrolysis in EME is described comprehensively for the first time and it is demonstrated that electrolysis considerably influences EME performance. Micro-electromembrane extraction (μ-EME) across free liquid membrane formed by 1-pentanol was utilized for real-time monitoring of the electrolytically induced changes in composition of μ-EME solutions. These changes were visualized with a set of acid-base indicators. Changes in colours of their aqueous solutions revealed serious variations in their pH values, which occurred within seconds to minutes of the μ-EME process. Variations of up to eight pH units were observed for indicator solutions initially prepared in 1, 5 and 10mM hydrochloric acid. No or only negligible pH changes (less than 0.15 pH unit) were observed for indicator solutions prepared in 50 and 100mM acetic acid demonstrating that initial composition of the aqueous solutions was the crucial parameter. These results were also confirmed by theoretical calculations of maximum pH variations in the solutions, which were based on total electric charge transfers measured in the μ-EME systems, and by exact measurements of their pH values after μ-EMEs. Acceptor solutions that, in the current practice, consist predominantly of low concentrations of strong mineral acids or alkali hydroxides may thus not always ensure adequate EME performance, which was manifested by decrease in extraction recoveries of a basic drug papaverine. A suitable remedy to the observed effects is the application of acceptor solutions containing high concentrations of weak acids or bases. These solutions not only eliminate the decrease in recoveries but also serve well as matrices of extracted samples for subsequent analysis by capillary electrophoresis.


Working from home: mismatch between access and need in relation to work-home interference and fatigue.
Working from home (WfH) is a promising practice that may enable employees to successfully and sustainably combine work and private life. Yet, not every employer facilitates WfH and not every employee has similar needs concerning the practice. The current study aims to examine the association of a WfH mismatch with work-home interference (WHI) and fatigue. Data on WfH, WHI, and fatigue of a quasi-representative sample of 2374 Dutch employees in 2012/13 and a follow-up measurement one year later were used. Cross-sectional and longitudinal regression analyses were conducted to investigate the cross-sectional and temporal associations between WfH mismatch on the one hand and (changes in) time-based and strain-based WHI and fatigue on the other hand. In the cross-sectional analyses, WfH mismatch was significantly associated with higher time-based WHI (B=0.13), strain-based WHI (B=0.17) and more fatigue (B=0.32). WfH mismatch was not associated with changes in these outcomes after one year of follow-up. A tailored WfH organizational policy, in which employees' need for working from home is taken into account, may be a fruitful approach to utilize WfH as a way for employees to successfully and sustainably combine work and private life to its full potential.


Obstacles on the way to the clinical visualisation of beta cells: looking for the Aeneas of molecular imaging to navigate between Scylla and Charybdis.
For more than a decade, researchers have been trying to develop non-invasive imaging techniques for the in vivo measurement of viable pancreatic beta cells. However, in spite of intense research efforts, only one tracer for positron emission tomography (PET) imaging is currently under clinical evaluation. To many diabetologists it may remain unclear why the imaging world struggles to develop an effective method for non-invasive beta cell imaging (BCI), which could be useful for both research and clinical purposes. Here, we provide a concise overview of the obstacles and challenges encountered on the way to such BCI, in both native and transplanted islets. We discuss the major difficulties posed by the anatomical and cell biological features of pancreatic islets, as well as the chemical and physical limits of the main imaging modalities, with special focus on PET, SPECT and MRI. We conclude by indicating new avenues for future research in the field, based on several remarkable recent results.


Performance Indicators for Colposcopy in Ontario.
This study sought to evaluate the delivery of colposcopy assessments and treatments in Ontario from 2009 to 2017 according to specific performance measures, derived from guidelines on colposcopy use. This population-based descriptive analysis included screen-eligible women ages 21 to 69 in Ontario who underwent cervical screening between 2009 and 2017. Performance measures that describe the quality of colposcopy services in the province were calculated. Five performance measures were used to assess the use of colposcopy in Ontario from 2009 to 2017. From 2013 to 2017, the percentage of women seen for colposcopy after a first diagnosis of atypical squamous cells of undetermined significance (ASCUS), without evidence of repeat cytology, remained stable, ranging from 5.9% to 6.3%. The median wait time to colposcopy for atypical glandular cells (AGC), atypical squamous cells (ASC-H), cannot rule out high-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions (HSIL), remained relatively stable from 2013 to 2017. In addition, the percentage of women with high-grade Pap test results who were seen in colposcopy within 6 months increased from 74.7% to 83.5%. The percentage of women who were not seen in follow-up within 12 months after treatment for cervical dysplasia remained stable, as did the percentage of women who discontinued colposcopy after three normal Pap test results following treatment for cervical dysplasia. This study developed five performance indicators and used them to assess the delivery of colposcopic services in Ontario from 2009 to 2017. Performance indicators have previously been used effectively in the field of colorectal cancer screening to identify strengths and weaknesses in the delivery of healthcare services. This had never previously been done in colposcopy.


[On neurogenic granular cells and their relationships to the so-called granular cell myoblastoma (author's transl)].
A report on granular cells found in biopsy material is presented. Morphologically identical patterns were seen in a pigmentated granular 'rankenneuroma' and in a patient with a morphea of the tongue. The independent development of granular cells in tumorous and nontumorous tissue supports the idea that the so-called granular cell myoblastoma originates from degenerative alterations of Schwann cells.


Conduction disturbances in patients with mitral valve prolapse.
The electrocardiograms (ECGs) of 55 patients with mitral valve prolapse were analyzed. Twelve of these demonstrated conduction abnormalities. Five patients had first degree heart block. Three had the classic ECG changes of the Wolff-Parkinson-White syndrome. Two patients had left anterior hemiblock, one of whom also had incomplete right bundle branch block. One patient had episodes of advanced atrioventricular block and periods of sinus arrest, which resulted in recurrent syncopal attacks. One patient had incomplete left bundle branch block. The presence of conduction disturbances points to the diffuse nature of the myocardial abnormality in mitral valve prolapse.


Calcium3D: a visual software package for the simulation of calcium buffered diffusion in neuroendocrine cells.
We present Calcium3D, a user-friendly software package for simulating calcium triggered processes in neuroendocrine cells. We use Monte Carlo methods for the simulation of the basic processes involved: entry of calcium into the cytoplasm, the diffusion of ions and mobile intracellular calcium buffers inside the intracellular medium, and the kinetics of the reaction of calcium with these buffers. The outputs of the simulation are calcium and buffer concentrations as a function of time and for different depths from the cellular membrane.


Formation of the 680 nm-absorbing form of the cytochrome bd oxidase complex of Escherichia coli by reaction of hydrogen peroxide with the ferric form.
Reduced minus aerated difference spectra of membranes from Escherichia coli (grown under oxygen-limited conditions) show, in addition to the 650 nm trough attributed to the oxygenated form of cytochrome d, a smaller trough centred at about 680 nm of unknown origin. When the reference spectrum is that of a sample oxidized with ferricyanide and to which hydrogen peroxide was added, the trough proportions changed, the 680 nm species being more dominant. Similarly, when 8.8 mM hydrogen peroxide is added to a persulphate-oxidized sample, a peak at 680 nm is immediately formed. No such compound is observed when peroxide is added to persulphate-oxidized membranes from a cytochrome d-deficient mutant. It is concluded that the 680 nm species represents a peroxy form of haem d, which is stable at room temperature and is probably an intermediate in the reaction mechanism of this oxidase.


Mitochondrial DNA diversity and PCR-based sex determination of Irrawaddy dolphin (Orcaella brevirostris) from Chilika Lagoon, India.
Of the only known two Lagoon populations of Irrawaddy dolphins (Orcaella) in the world, one is residing in the Chilika Lagoon in Orissa state, India. In addition to accidental deaths in gill net fishery and mechanized boat operations, there has been exploitation of the species for their oil. Extreme patchy distribution and vulnerability to becoming entangled in fishing gear has made it a focus of conservation concern. Information on genetic diversity of populations has considerable potential for informing conservation plans. The present paper reports the first genetic study of O. brevirostris from Chilika Lagoon based on mtDNA sequencing and PCR-based sex identification from 11 individuals. Control region sequence comparison showed two haplotypes and cytochrome b a single haplotype in the Chilika population of the species. Phylogenetic analysis indicated distinct clades within the Asian samples, with the Indian population showing closest genetic proximity to the haplotypes from Thailand. Sex of the animal was determined by PCR-based method. It is important to continue to examine the population discreteness and genetic variation of Irrawaddy dolphin in Chilika Lagoon vis-à-vis its global geographic distribution for formulating the conservation plans of the species.


Muscle mass gain is positively associated with functional recovery in patients with sarcopenia after stroke.
Intervention for treating sarcopenia is of great concern in clinical settings. The aim of this study was to investigate the relationship between changes in skeletal muscle mass and functional outcomes in patients with sarcopenia after stroke. A retrospective cohort study of stroke patients with sarcopenia consecutively admitted to a single center's convalescent rehabilitation wards was conducted from 2015 to 2018. Sarcopenia was defined as a loss of skeletal muscle mass index (SMI) with bioelectrical impedance and decreased muscle strength as measured by handgrip strength; cut-off values were adopted from the 2019 Asian Working Group for Sarcopenia. Changes in SMI during hospitalization were measured. Outcomes included the motor domain of Functional Independence Measure at discharge and its gain. Multivariate analysis determined whether the changes in SMI were associated with these outcomes. During the study period, 272 stroke patients were enrolled. Of those, 120 patients (44%) (mean age 79 years, 70 females) were diagnosed with sarcopenia. The mean (SD) for changes in SMI was 0.2 (0.5) kg/m2. Multiple linear regression analysis showed that changes in SMI were significantly associated with Functional Independence Measure - motor at discharge (β=0.175, P=0.003) and Functional Independence Measure - motor gain (β=0.247, P=0.003). Muscle mass gain may be positively associated with functional recovery in patients with sarcopenia after stroke. Exercise and nutritional therapy to increase skeletal muscle mass, in addition to conventional stroke rehabilitation, is needed for these patients.


American canine hepatozoonosis.
Hepatozoon americanum infection is an emerging tickborne disease in the southern United States. This organism causes a very different and much more severe disease than does Hepatozoon canis, the etiologic agent of canine hepatozoonosis in the rest of the world. H americanum is transmitted through ingestion of the definitive host, Amblyomma maculatum (the Gulf Coast tick). Clinical signs of American canine hepatozoonosis tend to wax and wane over time and may include lameness, weakness, pain, muscle atrophy, fever, and mucopurulent ocular discharge. Radiographs typically reveal periosteal proliferation of various bones. Extreme leukocytosis is the most common laboratory finding, along with a mild elevation of serum alkaline phosphatase. Diagnosis is made by visualization of gamont-containing neutrophils or monocytes on examination of blood smears; observation of typical cysts, meronts or pyogranulomas on muscle biopsy; or detection of serum antibodies against H americanum sporozoites. Common complications of chronic infection include glomerulopathies, amyloidosis, and vasculitis. Although the prognosis for this disease in the past was guarded to poor, recent advances in treatment have increased the long-term survival rate of infected dogs.


A cytochemical study of the effect of cholinergic and beta-adrenergic stimulation on calcium fluxes of rat parotid gland.
Parotid gland tissue from carbachol-treated and isoproterenol-treated rats was studied cytochemically by pyroantimonate precipitation and x-ray microanalysis in an effort to identify any intracellular calcium reservoirs that might be available for use in a stimulus-secretion coupling mechanism, and to determine any differences that might exist in terms of calcium utilization due to the cholinergic or beta-adrenergic receptor mechanisms. Stimulation by either secretagogue results in a reduction of mitochondrial and plasma membrane calcium, but the reduction in mitochondrial calcium deposits of carbachol-treated animals is only one-half that of the beta-adrenergic-treated animals. This could possibly suggest a greater dependency on mitochondrial calcium for beta-adrenergic stimulated animals.


Reduction in nevus biopsies in patients monitored by total body photography.
Total body photography (TBP) can facilitate identification of new and changing lesions. By confirming that particular nevi are stable, TBP may reduce nevus biopsies. We sought to determine the number and rate of nevus biopsies before and after TBP, and the factors associated with increased biopsy rate during monitoring by TBP. We reviewed records of all patients in 2 pigmented lesion clinics (PLCs) who received TBP and had 2 or more follow-up visits over a period of 2 years or longer. Before PLCs and TBP, the mean number of nevus biopsies per patient was 5.92 (589 patients) at a mean rate of 1.62 per year (160 patients). After TBP in PLCs, the same patients averaged 1.56 biopsies at a mean rate of 0.34 per year (P < 2 × 10(-16)). The entire cohort (926 patients) averaged similarly low post-TBP biopsy rates of less than 0.2 per year and per visit. Biopsy rates after TBP were positively correlated with decreased age, male gender, and family history of melanoma, but not nevus number. Some information was not available for some patients. Patients at risk for melanoma experienced a 3.8-fold reduction in nevus biopsies after TBP. Younger male patients with family history of melanoma had higher biopsy rates after TBP.


Immune response induced by a single or several syngeneic monoclonal antiABPC48 antiidiotypic antibodies: no predominant coexpression of ABPC48 idiotopes.
BALB/c mice were immunized with monoclonal BALB/c antibodies IDA10, IDA16 and IDA17 raised against the BALB/c ABPC48 myeloma protein. Several procedures of immunization--copolymers with lipopolysaccharide or keyhole limpet hemocyanin, simultaneous or sequential injections of different IDAs--were performed in an attempt to orient the immune response towards the production of ABPC48-like idiotypes. We used a binding assay which identifies two idiotopes on the same molecule to measure the population of antibodies induced in these responses. The expression of ABPC48 cross-reactive idiotypes in immune sera was analyzed. The results show that, with all immunization protocols, immune responses to different monoclonal antiidiotypic antibodies are mostly independent of each other: the coexpression of ABPC48 idiotopes, either private or recurrent on the induced antibodies, is rarely found; it makes it difficult to discriminate by a serological approach between cross-reactive idiotypes and anti-antiidiotypic antibodies. We discuss the interest of combining molecular and serological approaches to identify these two populations of antibodies.