Efficacy of intraductal placement of nonflared fully-covered metal stent for refractory perihilar benign biliary strictures: A multicenter prospective study with long-term observation.
Endoscopic fully-covered self-expandable metal stents (FCSEMSs) are used to treat benign biliary strictures (BBSs); however, treatment for perihilar BBSs is technically challenging. The aim of this study was to evaluate the usefulness of an unflared FCSEMS designed for intraductal placement in patients with refractory perihilar BBS. Twenty-two consecutive patients with perihilar BBS unresolved by endoscopic plastic stent placement at 13 tertiary medical centers were prospectively enrolled. The FCSEMS was placed above the papilla and removed after 4 months. The primary outcome was stricture resolution at 4 months, and the secondary outcomes were technical success, stent removal, adverse events, and recurrence. The technical success rate of intraductal FCSEMS placement was 100%, and plastic stent placement at contralateral or side branch was performed in 86% of patients. The rate of successful stent removal at 4 months was 100%, and stricture resolution was observed in 91% of patients. Stent migration or stent-induced de novo stricture did not occur in any patient. The stricture recurrence rate was 16%, and the median (interquartile range) follow-up duration was 2.8 (1.6-3.3) years. Intraductal placement of unflared FCSEMS is effective treatment for refractory perihilar BBS.


Cross-sectional study to investigate the health-related quality of life in children with severe lower limb trauma in Victoria.
The aim of this study is to investigate the health-related quality of life in children with severe lower limb trauma after at least 12 months post-injury and to assess patient and injury characteristics in association with the health-related quality of life scores. All children in the state of Victoria, who were 18 years of age or younger, suffering from severe lower limb injury before 2006 were studied. Patient and injury characteristics were abstracted from medical records. The health-related quality of life (HRQOL) scores were obtained using the Paediatric Quality of Life Inventory. Thirty-two out of 64 eligible patients participated in this study. All aspects of health-related quality of life in children with severe lower limb trauma after at least 12 months post-injury were significantly poorer compared with non-affected children, particularly in the physical health domain (difference: -12.51 ± 7.43: P < 0.05). It was observed that bilateral limb involvement and the need for soft tissue management were related to poor physical functioning (P < 0.05). Other characteristics such as traumatic amputation, gender, growth plate injury, joint bony injury and accident mechanism did not affect the overall HRQOL scores (P > 0.05). The HRQOL in children with severe lower limb trauma was significantly impaired even after 12 months post-injury, notably in patient group with bilateral limb involvement and need for soft tissue management. Traumatic amputation, gender, growth plate injury, joint bony injury and accident mechanism did not have an impact on quality of life.


Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR-124 and reduced AMPA receptors.
Hippocampal demyelination, a common feature of postmortem multiple sclerosis (MS) brains, reduces neuronal gene expression and is a likely contributor to the memory impairment that is found in >40% of individuals with MS. How demyelination alters neuronal gene expression is unknown. To explore whether loss of hippocampal myelin alters expression of neuronal microRNAs (miRNAs), we compared miRNA profiles from myelinated and demyelinated hippocampi from postmortem MS brains and performed validation studies. A network-based interaction analysis depicts a correlation between increased neuronal miRNAs and decreased neuronal genes identified in our previous study. The neuronal miRNA miR-124 was increased in demyelinated MS hippocampi and targets mRNAs encoding 26 neuronal proteins that were decreased in demyelinated hippocampus, including the ionotrophic glutamate receptors AMPA2 and AMPA3. Hippocampal demyelination in mice also increased miR-124, reduced expression of AMPA receptors, and decreased memory performance in water maze tests. Remyelination of the mouse hippocampus reversed these changes. We establish here that myelin alters neuronal gene expression and function by modulating the levels of the neuronal miRNA miR-124. Inhibition of miR-124 in hippocampal neurons may provide a therapeutic approach to improve memory performance in MS patients.


Fetal cardiac rhabdomyomas treated with maternal sirolimus.
To review the pathophysiology of rhabdomyomas and the emerging option of prenatal treatment of fetal cardiac rhabdomyomas. We present a case of fetal rhabdomyomas causing significant hemodynamic compromise that received in utero treatment of maternal sirolimus. Genetic amniocentesis confirmed a TSC2 mutation. A treatment program was initiated with a 10-mg loading dose titrated to a goal maternal trough of 10 to 15 ng/dL. In order to follow fetal cardiac function, a sophisticated method of speckle tracking echocardiography was used before and after treatment. Obstetric ultrasound was used to monitor fetal growth, and clinical surveillance, echocardiography, and brain MRI were used to monitor postnatal growth and development through 6 months of neonatal life. Sirolimus was initiated from 28 to 36 weeks of gestation with improvement of cardiac status. During this period, intrauterine growth restriction developed. Postnatally, the infant has had stable rhabdomyomas and cardiac function without reinitiating sirolimus. Brain MRI demonstrated scattered cortical tubers and subependymal nodules, and the infant has not had seizure-like activity. At 6 months of age, the infant has achieved appropriate developmental milestones. In counseling cases of prenatal onset large obstructing rhabdomyomas and cardiac compromise, in utero sirolimus treatment can be considered.


"Silent" post-menopausal genital tuberculosis with lethal outcome.
Female genital Tuberculosis (TB) is a rare disease, that usually affects female patients of reproductive age living in developing countries. The diagnosis of the disease is quite difficult since there is no consensus on the appropriate screening and management needed. Female genital TB can mimic many other pathologies including advanced ovarian cancer. Laboratory findings or blood serum tests usually are not suggestive of the disease. Imaging findings can be misleading. The incidence of the disease in Greece is rare. We present a rare case report of a post-menopausal patient with female genital TB, mimicking malignancy and resulting to a lethal outcome. Laboratory and imaging findings were non-specific for the disease, leading to a false diagnosis of disseminated peritoneal carcinomatosis.


The role of family conflict in mediating impulsivity to early substance exposure among preteens.
Preadolescence substance exposure, which increases the risk of regular substance use, has been a public health concern. Although studies found that impulsivity is a predisposing factor of early substance exposure, the pathways through which impulsivity is associated with early substance exposure remain unclear. This study examined how family conflict mediates this association among U.S. preteens as family environment plays an essential role in pre-adolescent development. Respondents (N = 11,800, 9-10 years old) from the Adolescent Brain Cognitive Development (ABCD) Study Release 2.01 (July 2019) were included in this study. Generalized structural equation modeling was performed to investigate the mediation effects of family conflict on the associations between childhood impulsivity and early exposure to alcohol and tobacco use, controlling for covariates based on the Problem Behavior Theory. Pre-adolescents with high impulsivity levels (≥90th percentile) were more likely to report early alcohol and tobacco exposure (total effect: ORs = 1.49 and 1.70, respectively), where 4.13% and 12.41% of the associations, respectively, were meditated by family conflict (indirect effect: ORs = 1.02 and 1.07; Sobel test ps = 0.022 and 0.005, respectively). Family conflict mediates the associations between childhood impulsivity and early substance exposure among preteens, with higher impulsivity leading to more severe family conflicts that are, in turn, associated with a higher likelihood of early substance exposure. To prevent preteens with high impulsivity level from early use of substances, interventions may focus on reducing family conflicts such as parenting counseling that guides parents to strengthen conflict-resolution skills and create a stable home environment for preteens.


Astragalus polysaccharide enhances the immune function of RAW264.7 macrophages via the NF-κB p65/MAPK signaling pathway.
The aim of the present study was to investigate the immunoregulatory effects of Astragalus polysaccharide (APS) on RAW264.7 cells. The production of cytokines by RAW264.7 cells was analyzed using ELISA, while cell viability and optimal concentration of APS were assessed using the Cell Counting Kit-8 assay. In addition, the mRNA levels of IL-6, inducible nitric oxide synthase (iNOS) and TNF-α were determined by reverse transcription-quantitative PCR analysis. The levels of co-stimulatory molecules and cell cycle distribution were assessed by flow cytometry. Electrophoretic mobility shift assay was used to determine the effects of APS on p65 expression. Compared with controls, APS enhanced the production of NO, the gene expression of TNF-α, IL-6 and iNOS and the protein levels of phosphorylated p65, p38, Jun N-terminal kinase and extracellular signal regulated kinase in RAW264.7 cells, whereas these effects of APS were alleviated by pyrrolidine dithiocarbamate. The results of the present study indicated that the immunoregulatory effects of APS are mediated, at least in part, via the activation of the NF-κB p65/MAPK signaling pathway.


Experimental evaluation of portal venous pulsatile flow synchronized with heartbeat intervals: effects of vascular clamping on portal hemodynamics.
We previously showed that blood flow in the portal vein was pulsatile and influenced by both the inferior vena cava and the arterial system in a complex manner (Nihei et al., 38:141-149, 2011). The objective of the present study is to identify determinants of blood flow and to clarify the source of pulsatile flow in the portal vein. Three-breed terminal crossbreed mini-pigs underwent general anesthesia. Pressure and flow in the portal vein, inferior vena cava, hepatic artery, and mesenteric artery were measured simultaneously. Vascular occluders were placed in the inferior vena cava, hepatic artery, and mesenteric artery to examine the effects of clamping on portal venous flow. Clamping of the mesenteric artery altered pressure and flow waves in the portal vein to waveforms similar to those in the inferior vena cava. Waves resembling those of the inferior vena cava superimposed on portal venous flow appeared later than waves of the inferior vena cava. Clamping of the inferior vena cava promptly altered portal venous pressure and flow. Because clamping of the inferior vena cava led to a sharp rise in portal venous pressure, detailed evaluations were not feasible. Clamping of the hepatic artery had no effect on flow-wave pulsation in the portal vein. In the hepatic circulation, flow-wave pulsation in the portal vein is influenced by flow in the inferior vena cava via the sinusoids and by flow in the mesenteric artery via the capillary vessels of the intestine.


YAP1 induces marrow derived suppressor cell recruitment in Chlamydia trachomatis infection.
Chlamydia trachomatis (C. trachomatis) is the most commonly diagnosed bacterial sexually transmitted infection (STI) worldwide. Marrow derived suppressor cells (MDSCs) are a heterogeneous population of immature monocytes and granulocytes, which are effective inhibitors for T cell activation. This study explores the role of MDSCs in the immune escape mechanism of C. trachomatis. We established a vaginal infection model of a BALB/c-Chlamydia trachomatis mouse pneumonia strain (MoPn), and compared the percentages of MDSCs, CD4+T, and CD8+T cells in the spleen and cervix of mice before and after infection. The expression levels of arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS) in MDSCs, and the expression level of transcriptional co-activator yes-associated protein 1 (YAP1) in the cervix were also compared. The results show that the proportion of MDSCs increases, while the proportion of CD4+T and CD8+T cells decreases after C. trachomatis-infection. The expression of Arg-1 and iNOS in MDSCs and YAP1 in host cells is up-regulated. C. trachomatis growth is inhibited after the inhibition of YAP1 in host cells. The proportion of MDSCs decreases after in vivo pharmacological inhibition of YAP1 in the C. trachomatis-infected mouse model. These results demonstrate, for the first time, the participation of MDSC in the immune escape of C. trachomatis under the action of YAP1.


Functional brain imaging of symptoms and cognition in schizophrenia.
The advent of functional magnetic resonance imaging and positron emission tomography has provided novel insights into the neural correlates of cognitive function and psychopathological symptoms. In patients with mental disorders, cognitive and emotional processes are disrupted. In this chapter, we review the basic methodological and conceptual principles for neuroimaging studies in these patients. By taking schizophrenia as an example, we outline the cerebral processes involved in the symptoms of this disorder, such as auditory hallucinations and formal thought disorder. We also characterize the neural networks involved in their emotional and cognitive dysfunction.


Monoamine neurotransmitter deficiencies.
Pediatric neurotransmitter disorders refer to a constellation of inherited neurometabolic syndromes attributable to disturbances of neurotransmitter synthesis, degradation, or transport. Monoamine deficiencies represent defects in synthesis of dopamine, serotonin, norepinephrine, and epinephrine or in availability of tetrahydrobiopterin, an important cofactor for monoamine synthesis. Some disorders do not manifest peripheral hyperphenyalaninemia and require CSF neurotransmitter metabolite assay for diagnosis. These include Segawa dopa-responsive dystonia and enzymatic deficiencies of aromatic amino acid decarboxylase, tyrosine hydroxylase, and sepiapterin reductase. The first, autosomal dominantly inherited GTP cyclohydrolase deficiency, has a satisfying response to therapy at any age with benefits maintained over time. The others have more severe and treatment-refractory phenotypes, typically with manifestations well beyond movement disorders. Disorders detectable by elevated serum phenylalanine are deficiencies of GTP cyclohydrolase (homozygous), pterin-carbinolamine dehydratase, dihydropteridine reductase, and pyruvoyl-tetrahydropterin synthase. The latter is the most prevalent and heterogeneous but typically has infantile onset with extrapyramidal as well as bulbar, hypothalamic, limbic, and epileptic manifestations. There are therapeutic roles for neurotransmitter supplementation, and dopaminergic agonists. Basal ganglia calcifications in dihydropteridine reductase deficiency are reversible with folinic acid. Deficiencies of monoamine degradation lead to cognitive, behavioral, and autonomic disorders.


Dependence of the minority-carrier lifetime on the stoichiometry of CdTe using time-resolved photoluminescence and first-principles calculations.
CdTe is one of the most promising materials for thin-film solar cells. However, further improvement of its performance is hindered by its relatively short minority-carrier lifetime. Combining theoretical calculations and experimental measurements, we find that for both intrinsic CdTe and CdTe solar cell devices, longer minority-carrier lifetimes can be achieved under Cd-rich conditions, in contrast to the previous belief that Te-rich conditions are more beneficial. First-principles calculations suggest that the dominant recombination centers limiting the minority-carrier lifetime are the Te antisite and Te interstitial. Therefore, we propose that to optimize the solar cell performance, extrinsic p-type doping (e.g., N, P, or As substitution on Te sites) in CdTe under Cd-rich conditions should be a good approach to simultaneously increase both the minority-carrier lifetime and hole concentration.


Glycemic Measures and Risk of Mortality in Older Chinese: The Guangzhou Biobank Cohort Study.
China has the largest number of people with type 2 diabetes mellitus (T2DM) in the world. Data from previous studies have suggested that up to one-fifth of individuals with diabetes would be missed without an oral glucose tolerance test (OGTT). To date, there is little information on the mortality risk of these individuals. We estimated the association of different indicators of hyperglycemia with mortality in the general Chinese population. Prospective cohort study. China. A total of 17 939 participants aged 50+ years. Previously diagnosed diabetes and newly detected diabetes defined by fasting glucose (≥7.0 mmol/L), 2-hour postload glucose (≥11.1 mmol/L), or hemoglobin A1c (HbA1c, ≥6.5%). Deaths from all-cause, cardiovascular disease, and cancer were identified by record linkage with death registration. During 7.8 (SD, 1.5) years' follow-up, 1439 deaths were recorded. Of 3706 participants with T2DM, 2126 (57%) had known T2DM, 118 (3%) were identified by isolated elevated fasting glucose, 1022 (28%) had isolated elevated postload glucose, and 440 (12%) had both elevated fasting and postload glucose. Compared with normoglycemia, the hazard ratio (95% confidence interval) of all-cause mortality was 1.71 (1.46-2.00), 0.96 (0.47-1.93), 1.43 (1.15-1.78), and 1.82 (1.35-2.45) for the 4 groups, respectively. T2DM defined by elevated HbA1c was not significantly associated with all-cause mortality (hazard ratio, 1.17; 95% confidence interval, 0.81-1.69). Individuals with isolated higher 2-h postload glucose had a higher risk of mortality by 43% than those with normoglycemia. Underuse of OGTT leads to substantial underdetection of individuals with a higher mortality risk and lost opportunities for early intervention.


Mice Deficient in Proglucagon-Derived Peptides Exhibit Glucose Intolerance on a High-Fat Diet but Are Resistant to Obesity.
Homozygous glucagon-GFP knock-in mice (Gcggfp/gfp) lack proglucagon derived-peptides including glucagon and GLP-1, and are normoglycemic. We have previously shown that Gcggfp/gfp show improved glucose tolerance with enhanced insulin secretion. Here, we studied glucose and energy metabolism in Gcggfp/gfp mice fed a high-fat diet (HFD). Male Gcggfp/gfp and Gcggfp/+ mice were fed either a normal chow diet (NCD) or an HFD for 15-20 weeks. Regardless of the genotype, mice on an HFD showed glucose intolerance, and Gcggfp/gfp mice on HFD exhibited impaired insulin secretion whereas Gcggfp/+ mice on HFD exhibited increased insulin secretion. A compensatory increase in β-cell mass was observed in Gcggfp/+mice on HFD, but not in Gcggfp/gfp mice on the same diet. Weight gain was significantly lower in Gcggfp/gfp mice than in Gcggfp/+mice. Oxygen consumption was enhanced in Gcggfp/gfp mice compared to Gcggfp/+ mice on an HFD. HFD feeding significantly increased uncoupling protein 1 mRNA expression in brown adipose and inguinal white adipose tissues of Gcggfp/gfp mice, but not of Gcggfp/+mice. Treatment with the glucagon-like peptide-1 receptor agonist liraglutide (200 mg/kg) improved glucose tolerance in Gcggfp/gfp mice and insulin content in Gcggfp/gfp and Gcggfp/+ mice was similar after liraglutide treatment. Our findings demonstrate that Gcggfp/gfp mice develop diabetes upon HFD-feeding in the absence of proglucagon-derived peptides, although they are resistant to diet-induced obesity.


Efficient intramolecular beta-mannoside formation using m-xylylene and isophthaloyl derivatives as rigid spacers.
A series of mannosyl donors linked via position 2 to an m-xylylene or an isophthaloyl spacer which was connected to the position 6 of a glucoside acceptor afforded, via intramolecular glycosylation, the corresponding disaccharides with high beta anomeric ratio.


Acute Generalized Exanthematous Pustulosis: Clinical Features, Differential Diagnosis, and Management.
Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP.


Feasibility study of intraoperative pericardial fluid biomarkers and length of stay after cardiac surgery.
Pericardial fluid biomarkers reflect the physiologic state of the myocardium. Previously, we showed a sustained increase in pericardial fluid biomarkers compared with blood in the 48 hours after cardiac surgery. We assess the feasibility of analyzing 9 common cardiac biomarkers from pericardial fluid collected during cardiac surgery and test a preliminary hypothesis of association between the most common biomarkers, troponin and brain natriuretic peptide, and length of stay after surgery. We prospectively enrolled 30 patients aged 18 years or more undergoing coronary artery or valvular surgery. Patients with ventricular assist devices, atrial fibrillation surgery, thoracic aorta surgery, redo surgery, concomitant noncardiac surgery, and preoperative inotropic support were excluded. Before pericardial excision during surgery, a 1-cm pericardial incision was made to insert an 18-gauge catheter and collect 10 mL of pericardial fluid. Concentrations of 9 established biomarkers of cardiac injury or inflammation including brain natriuretic peptide and troponin were measured. Zero truncated Poisson regression adjusted for Society of Thoracic Surgery Preoperative Risk of Mortality tested for a preliminary association between pericardial fluid biomarkers and length of stay. Pericardial fluid was collected and pericardial fluid biomarkers resulted for all patients. Adjusted for Society of Thoracic Surgery risk, brain natriuretic peptide, and troponin were associated with increased intensive care unit and overall hospital length of stay. In 30 patients, pericardial fluid was obtained and analyzed for cardiac biomarkers. Adjusting for Society of Thoracic Surgery risk, pericardial fluid troponin and brain natriuretic peptide were preliminarily associated with increased length of stay. Further investigation is needed to validate this finding and to investigate the potential clinical utility of pericardial fluid biomarkers.


Water-based lubricant as an adjunct to wound toilet: Validation of a technique by experiment.
Metal debris can produce a foreign body inflammatory reaction or as third body wear in the situation of joint arthroplasty. We evaluate a simple method for reducing this debris using a sterile water-based lubricating gel. Eight experimental surgical models consisting of porcine muscle overlying a polyethylene tube with a titanium locking plate and screws secured were constructed. Four models had water based lubricating gel applied to the wound edges, four were left without as controls. Image were then captured before and after irrigation from which the amount of debris could be quantified. The reduction of surface area covered by debris for models with water-based gel was greater (p=0.001). The average reduction in surface area was 27.2% for the control group and 94.1% for the models covered with lubricating gel. We show that using a safe, inexpensive and easily available water-based lubricating gel reduces the amount of embedded debris when burring metal implants using a high-speed burr.


Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors.
Selective delivery of therapeutic molecules to primary and metastatic tumors is optimal for effective cancer therapy. A liposomal nanodelivery complex (scL) for systemic, tumor-targeting delivery of anticancer therapeutics has been developed. scL employs an anti-transferrin receptor (TfR), scFv as the targeting molecule. Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, is present in most human cancers. Rather than being transiently permissive for tumor initiation, persistence of p53 dysfunction is a continuing requirement for maintaining tumor growth. Herein, we report results of a first-in-man Phase I clinical trial of restoration of the normal human tumor suppressor gene p53 using the scL nanocomplex (SGT-53). Minimal side effects were observed in this trial in patients with advanced solid tumors. Furthermore, the majority of patients demonstrated stable disease. One patient with adenoid cystic carcinoma had his status changed from unresectable to resectable after one treatment cycle. More significantly, we observed an accumulation of the transgene in metastatic tumors, but not in normal skin tissue, in a dose-related manner. These results show not only that systemically delivered SGT-53 is well tolerated and exhibits anticancer activity, but also supply evidence of targeted tumor delivery of SGT-53 to metastatic lesions.


Chronic in vivo morphine administration facilitates primed-bursts-induced long-term potentiation of Schaffer collateral-CA1 synapses in hippocampal slices in vitro.
In this study, the effects of chronic morphine administration (20-30 days) on long-term potentiation (LTP) were investigated at the Schaffer collateral-CA1 pyramidal cell synapses of the rat hippocampal slices. Orthodromic population spike (OPS) amplitude and delay (peak latency) were measured as indices of increase in synaptic efficacy. The amounts of LTP of OPS delay and LTP of OPS amplitude were higher in slices from dependent rats. Perfusion of slices from control and dependent rats with morphine containing ACSF and delivering tetanic stimulation, showed that short-term presence of morphine could not mimic the LTP enhancing effects of chronic morphine administration, however, attenuated the amount of LTP of OPS amplitude in slices of dependent rats. This study supports the hypothesis that the susceptibility of CA1 synapses to plastic changes increases by chronic, not acute exposure to morphine and suggests that a withdrawal phenomenon might be an underlying mechanism for the observed augmented LTP of OPS amplitude in slices of dependent rats.


Plasma EFEMP1 Is Associated with Brain Aging and Dementia: The Framingham Heart Study.
Epidermal growth factor containing fibulin extracellular matrix protein-1 (EFEMP1) has been associated with increased white matter hyperintensities (WMH) burden and disorders of premature aging and may have a shared pathophysiological role in the development of WMH and dementia. To determine the association between plasma EFEMP1 levels and MRI markers of vascular brain injury and incident all-cause and Alzheimer's disease (AD) dementia. We measured plasma EFEMP1 levels in 1597 [53% women, mean age 68.7 (SD 5.7) years] dementia-free Framingham Offspring cohort participants between 1998-2001 and subsequently followed them for incident dementia. Secondary outcomes included stroke, structural MRI brain measures and neurocognitive test performance. During a median 11.8 [Q1, Q3 : 7.1, 13.3] year follow-up, 131 participants developed dementia. The highest quintile of plasma EFEMP1, compared to the bottom four quintiles, was associated with an increased risk of time to incident all-cause dementia (HR 1.77, 95% CI 1.18-2.64) and AD dementia (HR 1.76, 95% CI 1.11-2.81) but not with markers of vascular brain injury (WMH, covert brain infarcts or stroke). Higher circulating EFEMP1 concentrations were also cross-sectionally associated with lower total brain (β±SE, -0.28±0.11, p = 0.01) and hippocampal volumes (-0.006±0.003, p = 0.04) and impaired abstract reasoning (Similarities test, -0.18±0.08, p = 0.018 per standard deviation increment in EFEMP1). Elevated circulating EFEMP1 is associated with an increased risk of all-cause and AD dementia, smaller hippocampal and total brain volumes, and poorer cognitive performance. EFEMP1 may play an important biological role in the development of AD dementia. Further studies to validate these findings are warranted.


Quantification of fluids injection in a glass-bead matrix using X-ray microtomography.
Several daily activities involve the accumulation or percolation of fluids through porous media. X-ray microtomography is a non-invasive technique capable of providing images of the internal microstructure of materials showing the different phases of fluid distribution present in the sample directly or at the pore-scale. This methodology was used to qualitatively and quantitatively assess samples consisting with glass beads of standard size, which contained fluid filling a porous region. Three samples were prepared with 0.6 mm or 0.8 mm diameter glass beads inserted into a glass tube with an inner diameter of 6.7 mm and 1.0 mm wall thickness. The fluids injected were dopant salt-water solution, industrial oil and commercial oil. The samples were scanned using a Skyscan-1172 microtomographic system. All phases present in the sample were differentiated. The values of injected fluids were determined through 2D and 3D analyses. Two types of solutions were used, one doped with KI, and the other with BaCl(2)·(2)H(2)O. The percentage of KI used allowed the individualization of the solution and, therefore, the direct quantification of this phase through 2D and 3D images.


Ultrasound of the traumatized spleen: left butterfly sign in lesions masked by echogenic blood clots.
Ultrasonic display of blood on both sides of the splenogastric ligament (left butterfly sign) in the left traumatized patient indicates hemoperitoneum within the lesser sac. Particular attention must be paid then to the splenic parenchyma, where isoechogenic blood clots can mask a hematoma. The association of subtile parenchymal changes and of a left butterfly sign are relevant of frank splenic lesions.


Community Perspectives on Men's Role in the Utilisation of Maternal Health Services Among Saharia Tribes in Gwalior, Madhya Pradesh, India: Insights from a Qualitative Study.
Utilization of maternal health care services by tribal population could be detrimental in reducing high maternal mortality in Madhya Pradesh, India. A growing body of evidence indicates the positive association between male involvement and increased use of antenatal care services. Further research is required to understand barriers and possible solutions to develop culturally appropriate interventions to engage men to promote the utilization of maternal health care services. The study used qualitative data collected through 8 focus group discussions with men and women and 8 key informant interviews with either a community representative or health worker in two blocks dominated by Saharia tribes in Gwalior district, Madhya Pradesh, India in 2018. Information on the perception of utilization of maternal and child health services, male involvement, challenges and opportunities were elicited using a structured guide. Framework analysis was used to analyse the data. Findings document barriers at the individual (poor knowledge, fear of loss of wage, choice of home as a place of delivery), community (practices that reinforced the prevailing gender norms) and health care facility level (quality and attitude of health care providers) to male engagement in utilization of maternal health services. Community perceptions on possible solutions to address these were more likely to be gender exploitative interventions. To promote utilization of maternal health care services among Saharia tribes, this study highlights the importance of developing gender sensitive interventions that addresses the individual, community and health care facility level barriers of male involvement and do not reinforce existing gender norms.


Monitoring surgical and medical outcomes: the Bernoulli cumulative SUM chart. A novel application to assess clinical interventions.
Monitoring clinical interventions is an increasing requirement in current clinical practice. The standard CUSUM (cumulative sum) charts are used for this purpose. However, they are difficult to use in terms of identifying the point at which outcomes begin to be outside recommended limits. To assess the Bernoulli CUSUM chart that permits not only a 100% inspection rate, but also the setting of average expected outcomes, maximum deviations from these, and false positive rates for the alarm signal to trigger. As a working example this study used 674 consecutive first liver transplant recipients. The expected one year mortality set at 24% from the European Liver Transplant Registry average. A standard CUSUM was compared with Bernoulli CUSUM: the control value mortality was therefore 24%, maximum accepted mortality 30%, and average number of observations to signal was 500-that is, likelihood of false positive alarm was 1:500. The standard CUSUM showed an initial descending curve (nadir at patient 215) then progressively ascended indicating better performance. The Bernoulli CUSUM gave three alarm signals initially, with easily recognised breaks in the curve. There were no alarms signals after patient 143 indicating satisfactory performance within the criteria set. The Bernoulli CUSUM is more easily interpretable graphically and is more suitable for monitoring outcomes than the standard CUSUM chart. It only requires three parameters to be set to monitor any clinical. the average expected outcome, the maximum deviation from this, and the rate of false positive alarm triggers.


Paradigm confirmed: the first use of ionic liquids to dramatically influence the outcome of chemical reactions.
It has been an unproven paradigm that the choice of which ionic liquid to use in a chemical reaction can have a dramatic effect on the outcome of that chemical reaction. We demonstrate, for the first time, that the reaction of toluene and nitric acid in three different ionic liquids gives rise to three completely different products in high yield. Furthermore, ionic liquids can catalyze these reactions with the only byproduct being water. [reaction: see text]


Image brightening in samples of high dielectric constant.
An analytic solution is given for the electromagnetic problem of a lossy dielectric cylinder of infinite length, irradiated by a circularly polarized radiofrequency (RF) magnetic field; the NMR-active components of the field inside the cylinder are projected out by transforming the RF Hamiltonian to the rotating frame and retaining only those terms independent of time; it is noted that the resulting cartesian field components are required to be real. The squared magnitude of the NMR-active fields are then used to calculate the gradient-recalled images of the cylinder, for small tip angles of the magnetization; and the result is shown to predict almost quantitatively the intensity patterns of experimental proton images at 3.0 and 4.0T, in a cylindrical phantom of radius 9.25cm, filled with 0.05M aqueous NaCl. In particular, the artifactual brightening at the center of the recorded image is convincingly reproduced in a simulation, whose underlying model excludes wave propagation along the direction of the cylinder axis. Formation of the artifact is explained in terms of the focussing of the RF magnetic field at the center of the cylinder, as illustrated by contour plots showing the time evolution of the rotating flux. An extended electromagnetic model--having the dielectric cylinder enclosed in a long, shielded volume resonator (e.g., of bird cage type)--is then sketched. The mathematical details appear in Appendix A; and the simulated images are shown to be virtually indistinguishable from those of the simpler original model. The theory of the Q, or quality factor, of the dielectric cylinder--considered itself as a resonant object--is developed for the enclosed cylinder model, where flux containment by the shield permits an unambiguous treatment of both the stored energy and the radiative losses. This is extended to treat the Q of a lossy dielectric sphere without shielding. Further plots of flux contours are given for the sphere, excited at 208 MHz with a uniform circularly polarized field, as well as by a surface coil, and for the enclosed cylinder in the range 140-160 MHz. It is then argued that the center brightening artifacts in magnetic resonance images are due to the underdamped dielectric resonance of the sample, i.e., at Q >0.5, while the overdamped condition, Q < 0.5, leads to exclusion of flux from the center, i.e., to the classic skin effect. The term "dielectric resonance" is shown to require careful interpretation for mixed-mode excitation, such as occurs with a surface coil. An extended reciprocity formula for NMR reception, valid for an arbitrary electromagnetic Green's function, is also given in Appendix B.


Determinants of recycling common types of plastic product waste in environmental horticulture industry: The case of Georgia.
Environmental horticulture firms provide a variety of commercial/residential landscape products and services encompassing ornamental plant production, design, installation, and maintenance. The companies generate tons of waste including plastic containers, trays, and greenhouse/field covers, creating the need to reduce and utilize plastic waste. Based on survey data collected in Georgia in 2013, this paper investigates determinants of the environmental horticulture firms' recycling decision (plastic containers, flats, and greenhouse poly). Our findings indicate that the decision to discard vs. recycle plastic containers, flats, and greenhouse poly is significantly influenced by firm scope, size, location, and partnership with recycling providers, as well as whether recycling providers offer additional waste pickup services. Insights from this study are of use to local governments and environmental organizations interested in increasing horticultural firm participation in recycling programs and lowering the volume of plastic destined for landfills.


Changes in electromechanical delay during fatiguing dynamic muscle actions.
The onsets of the electromyographic (EMG) signal, mechanomyographic (MMG) signal, and force production were used to identify voluntary electromechanical delay (EMD) during maximal and submaximal leg extensions. Twelve men performed 30% 1-repetition-maximum concentric, dynamic constant external resistance leg extensions to failure. The time periods for the onsets of EMG to MMG (EMDE-M ), MMG to force (EMDM-F ), and EMG to force (EMDE-F ) were assessed before, during, and after testing. Pretest vs. posttest assessments indicated approximately equal contributions from excitation-contraction coupling (EMDE-M ) and series elastic component (EMDM-F ) to the overall EMDE-F . During the workbout, excitation-contraction coupling failure and increases in the compliance of the series elastic component began at 40% and 30% of the repetitions to failure, respectively, and continued to failure. Increases in the series elastic component (EMDM-F ) began to affect EMDE-F before excitation-contraction coupling failure (EMDE-M ), and both contributed to EMDE-F throughout the remainder of the fatiguing workbout. Muscle Nerve 56: 315-320, 2017.


First Demonstration of Positive Allosteric-like Modulation at the Human Wild Type Translocator Protein (TSPO).
We show that changing the number and position of nitrogen atoms in the heteroatomic core of a pyrazolopyrimidine acetamide is sufficient to induce complex binding to wild type human TSPO. Only compounds with this complex binding profile lacked intrinsic effect on glioblastoma proliferation but positively modulated the antiproliferative effects of a synthetic TSPO ligand. To the best of our knowledge this is the first demonstration of allosteric-like interaction at the wild type human TSPO.


Pressed ceramics onto zirconia. Part 1: Comparison of crystalline phases present, adhesion to a zirconia system and flexural strength.
To compare the crystalline phases present, quantify the adhesion to zirconia and measure the mechanical properties of four commercially available pressed ceramics suitable for zirconia substructures. This study compares the X-ray diffraction response and the mechanical properties of four different pressed ceramics (Noritake CZR Press, Vita PM9, Wieland PressXzr and IPS e.max ZirPress) to Vita In-Ceram YZ zirconia substrate. The adhesion was determined using the interfacial strain energy release rate fracture mechanics approach; in addition biaxial flexural strength values of each material was determined. X-ray diffraction analysis revealed that Noritake CZR Press and Vita PM9 contain leucite whereas IPS e.max ZirPress and Wieland PressXzr are non-leucite amorphous materials. The strain energy release rate results revealed that the pressed ceramics with leucite have better adhesion than non-leucite ceramics to zirconia. Differences were observed between biaxial strength results for the pressed ceramics from bilayer compared with monolayer specimens. Pressed ceramics compatible with zirconia tested in this study were of two types; leucite containing and non-leucite containing essentially glass ceramics. Leucite containing pressable ceramics appears to have better adhesion to zirconia.


Antibiotic identification, use, and self-medication for respiratory illnesses among urban Latinos.
The purpose of this study was to describe the extent to which antibiotic and nonantibiotic medications commonly used for upper respiratory infections (URIs) were correctly identified by a sample of urban dwelling Latinas and the association of medication identification with antibiotic use and self-medication. One hundred women completed an interview and were asked to identify whether a list of 39 medications (17 antibiotics, 22 nonantibiotics) were antibiotics or not, whether anyone in the household had used the medication, their ages, and the source of the medication. Overall, participants correctly identified 62% of nonantibiotics and 34% of antibiotics. Seventy three (73%) women in the study reported antibiotic use by at least one member of the household in the past year. Among users, self-medication was reported in 67.2% of antibiotics for adults, but in only 2.4% of children. There was no difference in antibiotic recognition between those who self-medicated and those who did not, but antibiotic self-medication was associated with a significantly lower recognition of nonantibiotics (p= .01). Measures to improve antibiotic utilization should address self-medication and consider the cultural and social context in which antibiotic use occurs.


An overview of global GBS epidemiology.
Streptococcus agalactiae (group B streptococcus (GBS)), remains the leading cause of neonatal sepsis and meningitis in many countries and an important cause of disease in pregnant women, immunocompromised adults and the elderly. Intrapartum antibiotic strategies have reduced the incidence of early-onset neonatal GBS where applied, but have had no impact on late onset GBS infection and only a limited impact on disease in pregnant women. In low/middle income settings, the disease burden remains uncertain although in several countries of Southern Africa appears comparable to that of high-income countries. Disease may be rapidly fulminating and cases therefore missed before appropriate samples are obtained. This may lead to significant underestimation of the true burden and be a particular issue in many African and Asian countries; comprehensive epidemiological data from such countries are urgently required. The available data suggest that the serotype distribution of GBS isolates is similar in Africa, Western Pacific, Europe, the Americas and the Eastern Mediterranean regions and has not changed over the past 30 years. Five serotypes (Ia, Ib, II, III, V) account for the majority of disease; conjugate vaccines including some or all of these serotypes therefore hold great promise for preventing this important disease.


Facile and Ultraclean Graphene-on-Glass Nanopores by Controlled Electrochemical Etching.
A wide range of approaches have been explored to meet the challenges of graphene nanostructure fabrication, all requiring complex and high-end nanofabrication platform and suffering from surface contaminations, potentially giving electrical noise and increasing the thickness of the atomically thin graphene membrane. Here, with the use of an electrical pulse on a low-capacitance graphene-on-glass (GOG) membrane, we fabricated clean graphene nanopores on commercially available glass substrates with exceptionally low electrical noise. In situ liquid AFM studies and electrochemical measurements revealed that both graphene nanopore nucleation and growth stem from the electrochemical attack on carbon atoms at defect sites, ensuring the creation of a graphene nanopore. Strikingly, compared to conventional TEM drilled graphene nanopores on SiN supporting membranes, GOG nanopores featured an order-of-magnitude reduced broadband noise, which we ascribed to the electrochemical refreshing of graphene nanopore on mechanically stable glass chips with negligible parasitic capacitance (∼1 pF). Further experiments on double-stranded DNA translocations demonstrated a greatly reduced current noise, and also confirmed the activation of single nanopores. Therefore, the exceptionally low noise and ease of fabrication will facilitate the understanding of the fundamental property and the application of such atomically thin nanopore sensors.


[Assessment of the degree of severity in acute pneumonia and diagnostic accuracy].
Efficiency analysis of application of the machine independent programme for identification of critical degree of acute pneumonia on 41 patients is presented. The following benefits as perception visibility of the monitoring results, decrease of the "error omission", possibilities to prognosis the course of the disease were exposed.


New viruses of Cladosporium sp. expand considerably the taxonomic structure of Gammapartitivirus genus.
Despite the fact that Cladosporium sp. are ubiquitous fungi, their viromes have been little studied. By analysing a collection of Cladosporium fungi, two new partitiviruses named Cladosporium cladosporioides partitivirus 1 (CcPV1) and Cladosporium cladosporioides partitivirus 2 (CcPV2) co-infecting a strain of Cladosporium cladosporioides were identified. Their complete genome consists of two monocistronic dsRNA segments (RNA1 and RNA2) with a high percentage of pairwise identity on 5' and 3' end. The RNA directed RNA polymerase (RdRp) of both viruses and the capsid protein (CP) of CcPV1 display the classic characteristics required for their assignment to the Gammapartitivirus genus. In contrast, CcPV2 RNA2 encodes for a 41 KDa CP that is unusually smaller when aligned to CPs of other viruses classified in this genus. The structural role of this protein is confirmed by electrophoresis on acrylamide gel of purified viral particles. Despite the low percentage of identity between the capsid proteins of CcPV1 and CcPV2, their three-dimensional structures predicted by AlphaFold2 show strong similarities and confirm functional proximity. Fifteen similar viral sequences of unknown function were annotated using the CcPV2 CP sequence. The phylogeny of the CP was highly consistent with the phylogeny of their corresponding RdRp, supporting the organization of Gammapartitiviruses into three distinct clades despite stretching the current demarcation criteria. It is proposed that a new subgenus be created within the genus Gammapartitivirus for this new group.


Adsorption of p-chlorophenol by biofilm components.
Through batch equilibrium experiments under the conditions of temperature 25 degrees C, pH values of 2.7, 5.3 and 6.1, the p-chlorophenol (4-cp) adsorption to biofilm components was investigated in this study. The contributions of biofilm components to 4-cp adsorption were discussed by comparing four adsorption systems, i.e. 4-cp adsorbed by model suspended particulate matter (kaolin) with biofilm coating, bacteria, bacterial exopolysaccharide (EPS) and kaolin, respectively. Langmuir and Freundlich isotherm equations were used to evaluate the experiment data. All the four adsorptions fitted for the two equations. Equilibrium isotherms were obtained for 4-cp adsorption on different adsorbents. The kinetic characteristics of 4-cp adsorption by biofilm components and the effect of pH on the kinetic process were investigated. The time to reach the highest adsorption amount and near equilibrium state in the four systems was different. The 4-cp adsorption by kaolin with biofilm coating reached near equilibrium at 60 min at pH 6.1. The 4-cp adsorption by EPS and kaolin reached near equilibrium at 150 and 180 min, respectively. But the 4-cp adsorption by bacteria showed no evident near equilibrium during 3 h in the experiment. The impact of pH value on the adsorption was also examined. The adsorption amount slightly increased with increasing pH from 2.7 to 6.1 for the adsorption systems of bacterial EPS and kaolin, but it slightly decreased in the systems of kaolin with biofilm coating and bacteria.


Dealcoholization of Korean traditional rice wine, takju, combining thermal, bentonite clarification or reverse osmosis treatment.
The objective of this study was to prepare low-alcoholic takju. Low-alcohol (3.06%) and dealcoholized (0.04-0.28%) takju samples were prepared by adopting bentonite clarification, heat and reverse osmosis treatments. The dealcoholization of takju, in most cases, significantly (p < 0.05) reduced the total mineral (from 505.80 to 258.61 mg/L), free amino acid (from 989.81 to 293.58 mg/mL), antioxidant potentials and total phenolic (from 345.30 to 156.30 µg GAE/mL) contents remained in the control to RO-3 (takju sample obtained from 3-time reverse osmosis and heat treatment). Similarly, the content of volatile compounds was also significantly (p < 0.05) decreased with the dealcoholization treatments. The finding of this study clearly showed that dealcoholized takju could be prepared but at the expense of reduced nutritional and antioxidant potentials. This study could be an exemplary in promoting traditional beverages in different countries by producing low or alcohol-free drinks.


Chitosan beads coated with almond and walnut shells for the adsorption of gatifloxacin antibiotic compound from aqueous solutions.
In the present study, chitosan (C), walnut (W), and almond shell (A) powder adsorbent (in different combinations as almond shells:walnut:chitosan 2:1:1 (AWC), chitosan:almond shell:walnut 2:1:1 (CAW), and walnut:almond shells:chitosan 2:1:1 (WAC)) powder were combined in different ratios to produce low-cost composite adsorbent beads for the removal of antibiotics gatifloxacin (GAT) from synthetic wastewater. The beads were characterized by a scanning electron microscope, Fourier transform infrared spectrum spectrophotometer, and energy-dispersive X-ray spectroscopy. The batch adsorption approach was employed to remove the antibiotic from the water. Moreover, isotherm and kinetics were conducted to illustrate the adsorption mechanism. Parameters like the effect of the adsorbent's dosage, pH, initial concentration, and contact time on antibiotic adsorption were evaluated. Adsorption percentage increased slightly with the increase in adsorbent dosage. The optimum pH for GAT adsorption on beads was 5-7. In addition, adsorption increased with initial antibiotic concentration and time rise. The adsorption isotherm data were successfully fitted to Langmuir isotherm for AWC and CAW beads, while WAC beads followed the Freundlich isotherm. The highest adsorption was attained at pH 5 on CAW beads and pH 7 on AWC and WAC beads. The optimal contact time for equilibrium studies was 120 min for all types of beads. The adsorption isotherm data in AWC beads fit well with the Langmuir model and Freundlich adsorption for CAW and WAC beads. The rate of adsorption on beads follows Lagergren pseudo-second-order kinetics. The results indicate that prepared combination beads can be used to remove antibiotics from wastewater.


Onion (Allium cepa L.) peels: A review on bioactive compounds and biomedical activities.
Huge quantities of byproducts/wastes generated in onion processing are usually discarded, but they are excellent sources of bioactive compounds and phytochemicals. However, with growing interest in the sustainable use of resources and the circular economy to reduce adverse impacts on the environment, food processing wastes such as onion peel/skin can be extracted and employed as inputs in developing or reformulating nutrient supplements, and pharmacological drugs. This review highlights major bioactive components, especially total phenolics, total flavonoid, quercetin and its derivatives present in onion peel/skin and their therapeutic applications as cardioprotective, neuroprotective, antiobesity, antidiabetic, anticancer and antimicrobial agents. The present review emphasized that onion peel is one of the important agricultural by-products which is rich in bioactive compounds and can be utilized as health promoting ingredient especially in pharmacological and biomedical fields. Thus, with increasing burden of life style disorders/non-communicable diseases, finding suitable natural alternative for their treatment is one major concern of the researchers and onion peel and its extract can be exploited as a prime ingredient.


The effects of cadmium in vitro on adenosine triphosphatase system and protection by thiol reagents in rat brain microsomes.
Cadmium (Cd) inhibited the activities of Na(+)-K+ ATPase (IC50 = 5.0 x 10(-5) M), K(+)-p-nitrophenyl phosphatase (PNPPase) (IC50 = 4.0 x 10(-5) M) and 3H-ouabain binding (IC50 = 7.5 x 10(-5) M) in rat brain microsomes. Monothiols (cysteine but not glutathione and D-penicillamine) and dithiols (dimercaprol, dimercaptosuccinic acid and dithiothreitol) offered varied levels of protection against Cd-inhibition of Na(+)-K+ ATPase. Protection of Na(+)-K+ ATPase by these sulfhydryl (SH) agents was higher at 7.5 as compared to 8.5 pH. The present data suggest that Cd-inhibited Na(+)-K+ ATPase, by interfering with phosphorylation of enzyme molecule and dephosphorylation of the enzyme-phosphoryl complex and exerts a similar effect to that of SH-blocking agents.


C. elegans homologue of the Caf1 gene, which encodes a subunit of the CCR4-NOT complex, is essential for embryonic and larval development and for meiotic progression.
The evolutionary conserved CCR4-NOT multi subunit complex is involved in different aspects of mRNA metabolism, including mRNA synthesis initiation and mRNA deadenylation (shortening of the poly(A) tail) in yeast and higher eukaryotes. Here we report the characterization of the gene encoding the Caf1 subunit of this complex in Caenorhabditis elegans, ccf-1, and the phenotypes associated with its inactivation. Use of staged populations and of mutants strains with altered germline showed that ccf-1 is predominantly expressed in embryos and adults. Loss of ccf-1 function, by both RNAi and a deletion allele, caused early embryonic and larval lethality. It also resulted in sterility in both males and hermaphrodites by blocking germ cell development at the pachytene stage of meiosis I. These results reveal that ccf-1 is an essential factor for both somatic and germline development in C. elegans. Functional analysis of ccf-1 may contribute to the understanding of the molecular role of the CCR4-NOT complex.


The structure of a serotonin and LSD binding site of myelin basic protein.
Experiments have established the presence of a serotonin binding site in the tryptophan region of myelin basic protein. LSD competes for this binding site in vivo and in vitro. Although previous models have been suggested for the site, these models failed to explain the results of serotonin modification studies or the mode of LSD binding to the site. A new model of the site is proposed to rectify these problems. Means of testing the model are suggested. Implications for understanding neuroreceptor physiology, specificity, and disease are discussed. The name "molecular sandwiching" is suggested to describe the binding process.


Polyamide thin-layer chromatography of phosphorylated tyrosine, threonine, and serine.
One-dimensional thin-layer chromatography on polyamide plates offers an easy and rapid identification of O-phosphotyrosine. The thin-layer plate is developed for 30 min in 5% propionic acid containing 0.013%-0.025% sodium dodecyl sulfate. O-Phosphotyrosine, with Rf = 0.54, can be well separated from O-phosphothreonine and O-phosphoserine, which comigrate at Rf = 0.72.


Effect of tracheal tube cuff inflation with alkalinized lidocaine versus air on hemodynamic responses during extubation and post-operative airway morbidities in children: prospective observational cohort study, Ethiopia.
Endotracheal tube with an inflated cuff was used to manage and maintain the airway during general anesthesia in children. When the lateral pressure exerted by an inflated Endotracheal tube cuff on tracheal mucosa exceeds capillary perfusion pressure, patients may complain of cough, sore throat, and hoarseness in the postoperative period. This study aimed to assess the effect of a tracheal tube cuff filled with alkalinized lidocaine versus air on hemodynamic parameter changes during extubation and post-operative airway morbidity in children. Institutional based observational prospective cohort study was conducted among 56 elective children; aged 3-13 years, who underwent operation under general anesthesia with cuffed endotracheal intubation for greater than one hour by grouping into the air (group1) and alkalinized Lidocaine (group2) at Tikur Anbessa specialized Hospital. Hemodynamic parameters (Heart rate and Blood pressure) and other variables were measured starting from 5 min before extubation to 24th hours after extubation of the endotracheal tube. A Comparison of numerical variables between study group was done with an independent t-test. Data were expressed in terms of mean ± standard deviation. Categorical data were assessed by Chi-square tests. Postoperative Sore throat was lower in alkalinized lidocaine group compared to the air group. The mean heart rate at five minutes after extubation was significantly lower in alkalinized lidocaine group (107.29 ± 6.457 beat per minute (bpm)) compared to the air group (122.04 ± 8.809 bpm), with P ≤ 0.001. Systolic blood pressure was also significantly lower in alkalinized lidocaine group (99.64 ± 8.434 millimeters of mercury (mmHg)) compared to the air group (108.21 ± 11.902 mmHg), p = 0.016 at five minutes after extubation. Alkalinized lidocaine inflated tracheal tubes have shown improved hemodynamic and laryngotracheal morbidities in children.


Semliki Forest virus-induced polykaryocyte formation is an ATP-dependent event.
Infection of Aedes albopictus cells with Semliki Forest virus (SFV) leads to polykaryocyte formation below pH 6.2. This syncytium formation is accompanied by a decrease of the cellular ATP level. Addition of inhibitors of oxidative phosphorylation leads to a rapid, total depletion of ATP in infected cells at pH 6 and results in an inhibition of polykaryocyte formation. However, when cells were exposed for only a few minutes to pH 6 in the presence of the inhibitors and then kept at pH 7.2, the ATP level partially recovered to values sufficient for syncytium formation. Similar results were obtained after ATP depletion induced by 2-deoxyglucose. Thus, it can be concluded that SFV-induced syncytium formation is an ATP-dependent event.


Strand-specific in vivo screen of cancer-associated miRNAs unveils a role for miR-21(∗) in SCC progression.
MicroRNAs play diverse roles in both normal and malignant stem cells. Focusing on miRs and/or miR(∗)s abundant in squamous cell carcinoma (SCC) stem cells, we engineer an efficient, strand-specific expression library, and apply functional genomics screening in mice to identify which of 169 cancer-associated miRs are key drivers in malignant progression. Not previously linked functionally to cancer, miR-21(∗) was the second top hit, surfacing in >12% of tumours. miR-21(∗) also correlates with poor prognosis in human SCCs and enhances tumour progression in xenografts. On deleting the miR-21 gene and rescuing each strand separately, we document the dual, but independent, oncogenicity of miR-21 and miR-21(∗). A cohort of predicted miR-21(∗) targets inversely correlate with miR-21(∗) in SCCs. Of particular interest is Phactr4, which we show is a miR-21(∗) target in SCCs, acting through the Rb/E2F cell cycle axis. Through in vivo physiological miR screens, our findings add an interesting twist to an increasingly important oncomiR locus.


[Acute erosive-ulcerous lesions of the digestive tract in patients with acute appendicitis].
Examined were 98 patients with different forms of acute appendicitis. In acute common appendicitis, the stress lesions were diagnosed in 8.3%, in phlegmonous--in 15.4%, gangrenous--in 24.1%, gangrenous perforative--in 36.8% of the patients.


Feasibility of early removal of chest tube in the operating room for spontaneous pneumothorax: A prospective randomized controlled study.
Chest drainage tube after surgery causes pain and prolonged length of hospital stay. Especially, young patients tend to experience greater postoperative pain than elderly patients. Therefore, we needed to discuss the indication of chest tube placement. The purpose of this study was to demonstrate the safety and advantages of post-operative management without drainage tube placement, by comparing cases with and without drainage tube placement. Patients who underwent bullectomy for spontaneous pneumothorax were enrolled in this prospective randomized controlled study and randomized into two groups: group with a post-operative chest tube and group without a chest tube. Surgery and post-operative management were performed according to our protocol. Among the 42 patients, pneumothorax occurred in 1 patient with a chest tube a day after tube removal. Patients without chest tube had significantly lower post-operative pain (P = 0.107∼P < 0.001), despite their reduced use of rescue drugs. The mean length of post-operative hospital stay was 2.5 days in patients with chest tube, which was significantly longer than that of patients without chest tube (1.2 days; P < 0.001). Our patient selection and surgical protocols may be feasible and contribute to post-operative pain control.


Evidence for asymmetric distribution of sciatic nerve endometriosis.
To investigate if a lateral asymmetry exists in the distribution of endometriotic lesions of the sciatic nerve. All articles on sciatic nerve endometriosis identified by MEDLINE and EMBASE database searches were retrieved, and additional reports were collected by systematically reviewing all references. Monographs on endometriosis published in the last 15 years were consulted. We considered articles in which the presence of an endometriotic lesion of the sciatic nerve and the affected side were assessed. We also included reports lacking histological examination of sciatic nerve specimens but with a surgical diagnosis of pelvic endometriosis. Two authors abstracted data independently on standardized forms. The number of women and the side of the lesion were obtained from individual studies, and the combined frequency of left- and right-side sciatic nerve endometriosis in published reports was computed. Thirty-two reports including 63 subjects were selected. Endometriosis of the sciatic nerve was on the right side in 41 patients, on the left in 20, and bilateral in two. Considering only patients with unilateral sciatic nerve endometriosis, the observed proportion of right-side lesions (41 of 61 [67.2%]; 95% confidence interval 54.0%, 78.7%) significantly differed from the expected proportion of 50% (chi(2)(1) 7.23, P =.007). Among the 16 cases of histological demonstration of endometriosis infiltrating sciatic nerve roots or fibers, ten had it on the right side (62.5%) and six on the left. Twenty-six of the 38 subjects (68.4%) with surgical demonstration of pelvic endometriosis but without histopathologic evidence of direct sciatic nerve involvement were affected by right cyclic sciatica. The finding that two thirds of patients with sciatic nerve endometriosis had right-side lesions constitutes further evidence against the coelomic metaplasia theory. The interposition of the sigmoid colon between the regurgitated endometrial cells implanted on the left posterolateral pelvic peritoneum seems to protect the left lumbosacral plexus and sciatic nerve.


[The cost-effectiveness analysis of gefitinib or erlotinib in the treatment of advanced EGFR mutant non-small cell lung cancer patients].
Targeted therapy in non-small cell lung cancer (NSCLC) had become a research hotspot. Both of gefitinib and erlotinib had already been recommended as first line treatment in epidermal growth factor receptor (EGFR) mutant advanced NSCLC patients. The study aimed to compare the effectiveness and prognosis of advanced NSCLC with gefitinib or erlotinib, as well as the cost-effectiveness ratio of the two drugs. Data of 66 EGFR mutant NSCLC patients who were included in Guangzhou medical insurance were analyzed. The efficacy and adverse reactions were evaluated. All the patients were followed-up regularly and the cost of the treatment was recorded. The median progression free survival (PFS) of all patients was 15.0 months. 49 patients received gefintib and 17 patients had erlotinib. The PFS for the two groups of patients was 17.5 month and 13 months, respectively (P=0.459). 31 (62.3%) patients had rash in gefitinib group, 16 (94.1%) in erlotinib group. Cost-effectiveness ratio (CER) in gefitinib group was 3,027 RMB per month, while 6,800 RMB in erlotinib group. The incremental cost-effectiveness ratio (ICEA) of erlotinib was 2.25 times of gefitinib. For EGFR mutant advanced NSCLC patients, equal efficacy and survival benefit were observed in patients with gefitinib and erlotinib. The adverse reaction was milder in gefitinib group than that of erlotinib group. And with Guangzhou medical insurance, gefitinib had a superior cost-effectiveness ratio.


Quantitative investigation of the changes in the cell composition of the spleen during the growth of Worker's carcinosarcoma.
The weight of the spleen and its cell composition as a function of the weight of the tumor was studied during the development of Worker's carcinosarcoma. The progression of the dependence is presented in the appropriate mathematical form. It is shown that with development of the process of tumor enlargement, erythro- and myelopoiesis are intensified in the spleen. The overall quantity of erythroblastic elements reaches a maximum value when the weight of the tumor reaches 30 g and subsequently remains at the same level. The kinetic curves of the changes in the number of lymphocytes in the spleen and also their graphical dependence on the weight of the tumor are of an extreme character. At late stages in the development of the tumor, the number of cells of the granulocyte type begins to increase.


The levels of metallothionein-like proteins in animal tissues.
The level of metallothionein-like proteins was determined in different tissues of 6 animal species. The highest concentrations were found in pig and rat tissues. The organs richest in metallothionein-like proteins included: kidneys (101-305 microgram/g), intestine (127-257 microgram/g) and liver (54-496 microgram/g).


Total antioxidant capacity of new natural powdered seasonings after gastrointestinal and colonic digestion.
New powdered seasonings, rich in natural antioxidant compounds, have successfully been applied recently in different food matrices. Once ingested, the antioxidants contained in these seasonings may exert protective effects against oxidative stress along the gastrointestinal tract. This fact was evaluated by submitting the different seasonings under study to simulated digestion followed by assessing the reducing and antiradical capacities of the digested fractions. Enzymatic gastrointestinal digestion enhanced 2-3 times both antioxidant activities and colonic fermentation increased more than 10-fold the radical scavenging ability of digested fractions compared with undigested seasonings. Digested fractions derived from the seedless wine pomace seasoning presented generally the highest antioxidant properties. The results were evaluated considering bioaccessibility factors to have a more realistic overview of the potential antioxidant capacities of the seasonings and of the probable beneficial effects of their consumption on the prevention of oxidative damage along the gut.


The de novo design and synthesis of cyclic urea inhibitors of factor Xa: initial SAR studies.
In this report we discuss the design, synthesis, and validation of a novel series of cyclic urea inhibitors of the blood coagulation protein Factor Xa. This work culminates in compound 11, a monoamidine inhibitor of fXa employing a new S4 ligand that reduces the cationic character of these analogs. Compound 11 represents a lead for a series of more potent and selective inhibitors.


Carbamylation-induced alterations in low-density lipoprotein metabolism.
Low-density lipoprotein was derived from carbamyl (carbamyl-LDL) by incubating LDL in potassium cyanate (KCNO). The proportion of free amino groups in the carbamyl-LDL was negatively correlated (r = -0.95) with the time of incubation in potassium cyanate (ranged from 5 to 360 min). The carbamylation did not change the chemical composition or the flotation characteristics of the LDL particles. However, the electrophoretic mobility of carbamyl-LDL was distinctly increased with the extent of carbamylation. The carbamyl-LDL had substantially decreased binding to the LDL apoB/E receptors of the bovine adrenocortical membranes when compared to the control-LDL. The reduced binding was already observed when only 9% of the free amino groups were derived from carbamyl. A minor carbamylation of LDL (less than 20% of the free amino groups) decreased the in vivo clearance of LDL from rabbit plasma. However, when more than 20% of the free amino groups were derived the carbamyl-LDL had accelerated clearance compared to the control-LDL. LDL isolated from uremic patients was cleared in rabbits at a slower rate than LDL isolated from a control subject. Providing that carbamylation of LDL could also occur in vivo resulting in similar alterations of the LDL binding to the LDL B/E receptors, as observed in the present study, the uremia-related accelerated atherosclerosis could have one additional mechanistic explanation.


The use of a vasoconstrictor to improve tumour blood flow in intra-arterial chemotherapy: preliminary report.
The effectiveness of intra-arterial chemotherapy is dependent on a high tumour to normal blood flow ratio (T/NT). This report demonstrates the use of a vasoconstrictor (NE) to improve the relative blood flow to head and neck tumours by causing vasoconstriction and decreased blood flow to normal soft tissue. Five quantitative planar Tc-MAA perfusion studies were performed on three patients with increasing dose rates of norepinephrine (NE) to determine the optimal dose in each patient that would produce the best T/NT. All patients demonstrated a change in perfusion pattern with increasing dose rates (0.1 to 15 micrograms min-1), although there was considerable variation between patients. Quantitative SPECT was performed on two patients. In one, there was a 35% increase in the T/NT and a 16% decrease in arteriovenous (A-V) shunting to the lung.


Purification and characterization of a novel recombinant highly enantioselective short-chain NAD(H)-dependent alcohol dehydrogenase from Thermus thermophilus.
The gene encoding a novel alcohol dehydrogenase (ADH) that belongs to the short-chain dehydrogenase/reductase (SDR) superfamily was identified in the extremely thermophilic, halotolerant gram-negative eubacterium Thermus thermophilus HB27. The T. thermophilus ADH gene (adh(Tt)) was heterologously overexpressed in Escherichia coli, and the protein (ADH(Tt)) was purified to homogeneity and characterized. ADH(Tt) is a tetrameric enzyme consisting of identical 26,961-Da subunits composed of 256 amino acids. The enzyme has remarkable thermophilicity and thermal stability, displaying activity at temperatures up to approximately 73 degrees C and a 30-min half-inactivation temperature of approximately 90 degrees C, as well as good tolerance to common organic solvents. ADH(Tt) has a strict requirement for NAD(H) as the coenzyme, a preference for reduction of aromatic ketones and alpha-keto esters, and poor activity on aromatic alcohols and aldehydes. This thermophilic enzyme catalyzes the following reactions with Prelog specificity: the reduction of acetophenone, 2,2,2-trifluoroacetophenone, alpha-tetralone, and alpha-methyl and alpha-ethyl benzoylformates to (S)-(-)-1-phenylethanol (>99% enantiomeric excess [ee]), (R)-alpha-(trifluoromethyl)benzyl alcohol (93% ee), (S)-alpha-tetralol (>99% ee), methyl (R)-(-)-mandelate (92% ee), and ethyl (R)-(-)-mandelate (95% ee), respectively, by way of an efficient in situ NADH-recycling system involving 2-propanol and a second thermophilic ADH. This study further supports the critical role of the D37 residue in discriminating NAD(H) from NADP(H) in members of the SDR superfamily.


Somatostatin modulates Ca2+ currents in neostriatal neurons.
Somatostatin is synthesized and released by aspiny interneurons of the neostriatum. This work investigates the actions of somatostatin on rat neostriatal neurons of medium size (ca. 6 pF). Somatostatin (1 microM) reduces both calcium action potentials (20 mM tetraethylammonium) by ca. 24% and calcium currents by ca. 35%, in all cells tested. This action was produced in the presence of tetrodotoxin and in dissociated cells and was blocked by cyclo(-7-aminoheptanoyl-phe-d-try-lys-O-benzyl-thr) acetate (CPP-1), a somatostatin receptor antagonist. Except for nitrendipine (5 microM), several calcium channel antagonists, 1 microM omega-conotoxin GVIA, 400 nM omega-agatoxin TK, and 1 microM omega-conotoxin MVIIC, partially occluded somatostatin action. According to the calcium channel types known to be blocked by these antagonists, P/Q-type channels appeared to be the channels mainly modulated by somatostatin, followed by N-type channels. Since these channel types generate the afterhyperpolarizing potential in spiny neurons, we investigated the action of somatostatin on this event. Somatostatin reduces the amplitude of the afterhyperpolarizing potential by ca. 39%. This action is occluded by omega-agatoxin TK and omega-conotoxin MVIIC but not by omega-conotoxin GVIA or nicardipine. Thus, the action of somatostatin on the afterhyperpolarizing potential is mainly mediated by P/Q-type calcium channels. The block of the slow afterhyperpolarizing potential made most neurons exhibit an irregular firing mode, suggesting that ion currents other than calcium may also be affected by somatostatin. We conclude that somatostatin exerts a direct postsynaptic effect on neostriatal neurons via the activation of somatostatin receptors. This action affects non-L-type calcium channels and therefore modifies the afterhyperpolarizing potential and the firing pattern. It is proposed that somatostatin and its analogues may have profound effects on the motor functions controlled by the basal ganglia.


Lysophosphatidic acid induces glycodelin gene expression in cancer cells.
Glycodelin is a glycoprotein that has been suggested to be important in normal pregnancy and in malignancy. The regulation of its synthesis has not been studied. In this study, we report the induction of glycodelin gene expression by lysophosphatidic acid (LPA). We studied the effect of LPA (5, 10 and 25 microM) on glycodelin production in breast (MDA-MB-231), cervical (Hela), endometrial (RL-95), ovarian cancer (OVCAR-3) and erythroleukemia (K562) cells. There was a dose-dependent (5-25 microM) induction of glycodelin gene and protein expression in these cell types. LPA is a mimic of phorbol myristate acetate (PMA) action and is found to be elevated in high concentrations in the serum of cancer subjects. As glycodelin is an angiogenic protein with a potential immunosuppressive role, control of LPA synthesis might offer a potential target for intervention.


The hERG K+ channel: target and antitarget strategies in drug development.
The human ether-à-go-go related gene (hERG) K+ channel is of great interest for both basic researchers and clinicians because its blockade by drugs can lead to QT prolongation, which is a risk factor for torsades de pointes, a potentially life-threatening arrhythmia. A growing list of agents with "QT liability" have been withdrawn from the market or restricted in their use, whereas others did not even receive regulatory approval for this reason. Thus, hERG K+ channels have become a primary antitarget (i.e. an unwanted target) in drug development because their blockade causes potentially serious side effects. On the other hand, the recent identification and functional characterization of hERG K+ channels not only in the heart, but also in several other tissues (e.g. neurons, smooth muscle and cancer cells) may have far reaching implications for drug development for a possible exploitation of hERG as a target, especially in oncology and cardiology.


Zeroing out on zero-COVID.
There is no such thing as "zero-COVID." As the Omicron variant spreads to China's capital city, Beijing, the question is not if, but when and how, China will begin to "live with COVID-19" rather than continue to impose endless lockdowns. The problem is that under China's stifling political climate, this notion cannot be uttered, let alone debated. How did a country with a history of deep respect for science and a laser focus on becoming a global powerhouse in technology and innovation fall into such isolation from the rest of the world?


Ribonuclease H from chick embryos cleaves precisely at the junction between the RNA and DNA portion of the hybrid helix.
DNA polymerase from Micrococcus luteus and RNA polymerase from E. coli catalyze the synthesis of poly(dA) with poly(dT) template, in the presence of ATP and [alpha-32P]dATP. The reaction is completely dependent on poly(A) primer synthesis. Poly(A) chains are covalently extended by DNA polymerase. Primer poly(A) is linked to the product poly(dA) via a 3':5'-phosphodiester bond, and can be specifically removed by ribonuclease H from chick embryos, leaving a 5'-phosphate end of poly(dA). The length of RNA and DNA products appears to be relatively variable. The size of the DNA is less than 3 000 nucleotides.


Metastatic renal cell carcinoma presenting as a circumscribed orbital mass.
To report a case of renal cell carcinoma presenting as a well-circumscribed orbital tumor. Retrospective interventional case report. A 60-year-old woman presented with proptosis of the left eye. Imaging showed a well circumscribed tumor in the region of the medial rectus muscle. Excision biopsy revealed a diagnosis of metastatic renal cell carcinoma that was confirmed on abdominal imaging. Renal cell carcinoma can rarely present as a well-circumscribed orbital mass and should be included in the differential diagnosis of such lesions.


Antibiotic prophylaxis against postpartum endometritis after vaginal delivery: a prospective randomized comparison between Amox-CA (Augmentin) and abstention.
The most common adverse outcome associated with vaginal delivery is endometritis. It plays a significant role in postpartum morbidity and mortality. There is considerable evidence to support the idea that a single dose of antibiotic after vaginal delivery might decrease the incidence of postpartum endometritis. In this study the evaluation of the efficacy of antibiotic prophylaxis was based upon comparison of a group of patients given a single dose of Amox-CA (Augmentin) with a group of patients without treatment. The study was performed in the Department of Obstetrics and Gynecology of the A. Béclère Public Hospital, Clamart, France (Paris-Sud University). The patients who were the subject of the study had delivered vaginally during the period of 1 year, and were free of any clinical diagnosis of chorioamnionitis or other extragenital infection, had a maternal temperature of less than 38 degrees C during labor and 1 h after delivery, and had no history of allergy to penicillins or cephalosporins. After application of exclusion criteria, 1373 patients were randomized and 1291 included 610 in Group I given Amox-CA and 681 in Group II without any antibiotic. A single dose of 1.2 g of Amox-CA was given by intravenous injection, 1 h after delivery, in Group I. Patients of Group II received no injection. Postpartum status was evaluated before the patient left hospital and 2 weeks later. The two groups were similar in terms of demographic and clinical parameters. Four patients developed endometritis in Group I (4/610, 0.66%). Sixteen patients in Group II developed endometritis (16/680, 2.38%) (P = 0.013; 95% confidence interval (CI), 0.36-3.08%).(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of homology models and X-ray structures of the nuclear receptor CAR: assessing the structural basis of constitutive activity.
The constitutive androstane receptor (CAR) possesses an intrinsic basal activity whose structural basis has been analysed during the last decade. Recently, we published a homology model of the CAR ligand binding domain (LBD) based on the X-ray structures of the closely related pregnane X (PXR) and vitamin D (VDR) receptor. A detailed analysis of the homology model and molecular dynamics (MD) simulations afforded us to propose a potential mechanism underlying the constitutive activity of CAR. Almost simultaneously, X-ray structures of human and mouse CAR LBD were released. In the present study, a detailed analysis and comparison of homology model and X-ray structures is carried out in order to evaluate the quality and reliability of our homology modelling procedure. The hypothesis of the constitutive activity which we proposed on the basis of our modelling results was tested for consistency with the crystal structures. In addition, the features stated to be essential for the basal activity based on the X-ray data were investigated by means of molecular dynamics simulations. Our results show that the homology modelling procedure was able to predict the CAR LBD structure with high accuracy. Structural features that have been revealed as critical for constitutive activity in the model are also observed in the X-ray structures. Furthermore, the MD simulations of the CAR X-ray structures and a detailed analysis of other NRs clarify the role of distinct structural features that have been assigned an important role for the constitutive activity.


EXAFS studies of the calcium salts of natural DNA and polydA:polydT.
Preliminary EXAFS experiments were carried out on film of the Ca salts of the synthetic polynucleotide polydA:polydT at 95%, 81%, and 76% relative humidity (r.h.) and for the Ca salt of chicken erythrocyte DNA at 81% r.h. (approximately 43% GC pairs). Detailed analysis of EXAFS data shows that the Ca2+ ion is in fairly close proximity (within 4 A) to a number of phosphorous atoms. This is in contradiction with the recently proposed model, which assumes a close coordination between the cations and the purine and pyrimidine bases deep inside the polynucleotide molecule, so that the distance to the nearest phosphorous atoms must not be less than 5 A. Instead, the EXAFS results suggest that the Ca2+ ions are, for the most part, located at the periphery of individual polydA:polydT (or DNA) molecules, possibly serving as intermolecular links.


DNA typing in hereditary disease.
An increasing number of hereditary diseases are becoming amenable to diagnosis by analysis of DNA as the responsible genes are located and identified. Gel electrophoresis of DNA fragments plays a central role in the diagnosis of hereditary disease. Electrophoretic separation of differently sized fragments enables the characterization or typing of normal variants which are known to be genetically linked to disease genes. For some diseases it is possible to directly detect mutations by DNA electrophoresis. Deletion mutants may be detected by a restriction fragment of altered size or by a failure to amplify a coding region with the polymerase chain reaction. Carriers of small deletions, involving a few base pairs, may be identified by DNA amplification which produces heteroduplexes that show characteristic, anomalous electrophoretic migration. Mutations that alter restriction sites also alter the sizes of restriction fragments. Common disease mutations that alter a single base pair may be detected using a pair of reactions with normal and mutant oligonucleotides under conditions where a perfect match is necessary for hybridization, amplification or ligation. Alternatively a mismatched oligonucleotide primer may be designed to generate a restriction site with either the normal or mutant allele, following DNA amplification. Finally a number of techniques are available that are useful as screening tools for novel mutations.


Neural transplantation.
Neural transplantation has recently emerged as an exciting extension of neural regeneration and plasticity studies. In this review, the roots of current attempts at autologous and heterologous grafting of neural tissue are traced. Grafts of peripheral and central nervous tissue have been shown to be viable after implantation in a variety of locations in adult animals' brain and spinal cord, and survival data are impressive. Donor tissue is optimal when harvested from fetuses, and successful growth and differentiation of neural grafts have been demonstrated in host animals in a broad age range. A variety of morphologic, physiologic, and behavioral parameters suggest a certain degree of integration of graft tissue into the host central nervous system, although technical limitations do not yet allow definitive statements regarding the extent of functional reinnervation. Perhaps the most promising and innovative of current studies are those that utilize a combination of peripheral and central neural tissue as transplant material. There are a number of possible applications of neural transplantation to clinical neurology and neurosurgery, some of which are discussed.


Cytogenetics of trophoblasts from complete hydatidiform moles.
The risk of developing choriocarcinoma following a complete hydatidiform mole (CHM) is 2000-4000 times greater than the risk following a normal pregnancy. To understand more fully the increased susceptibility of the molar trophoblast to malignant transformation, we separated the trophoblastic cells from the stromal cells in 14 complete moles and cultured them for cytogenetic analysis. The numerical and structural abnormalities found were compared with those found in the trophoblasts from normal pregnancy and malignant choriocarcinoma cell lines. The percentage of polyploid cells was 2.8 times greater in molar trophoblasts than in normal trophoblasts. Although we found no consistent chromosomal abnormality in the molar trophoblasts, these cells were significantly more vulnerable to chromosomal breakage than the molar fibroblasts, normal trophoblasts, normal fibroblasts, and maternal decidual cells. Out of a total of 103 breakpoints observed in 338 cells, 42 coincided with known fragile sites, 18 with the location of protooncogenes, 27 with breakpoints reported in other neoplasia, and 18 with breakpoints found in four choriocarcinoma cell lines. The chromosomes in choriocarcinoma cell lines have hypotetraploid mode and many structural rearrangements. Our results suggest that the genetic instability found in the molar trophoblasts may be responsible for progressive karyotypic changes and greater susceptibility to malignant transformation.


Applications of fluorine-containing amino acids for drug design.
Fluorine-containing amino acids are becoming increasingly prominent in new drugs due to two general trends in the modern pharmaceutical industry. Firstly, the growing acceptance of peptides and modified peptides as drugs; and secondly, fluorine editing has become a prevalent protocol in drug-candidate optimization. Accordingly, fluorine-containing amino acids represent one of the more promising and rapidly developing areas of research in organic, bio-organic and medicinal chemistry. The goal of this Review article is to highlight the current state-of-the-art in this area by profiling 42 selected compounds that combine fluorine and amino acid structural elements. The compounds under discussion represent pharmaceutical drugs currently on the market, or in clinical trials as well as examples of drug-candidates that although withdrawn from development had a significant impact on the progress of medicinal chemistry and/or provided a deeper understanding of the nature and mechanism of biological action. For each compound, we present features of biological activity, a brief history of the design principles and the development of the synthetic approach, focusing on the source of tailor-made amino acid structures and fluorination methods. General aspects of the medicinal chemistry of fluorine-containing amino acids and synthetic methodology are briefly discussed.


A micro-electrode amplifier with an infinite resistance current source for intracellular measurements of membrane potential and resistance changes under current clamp.
A microelectrode amplifier for intracellular electrophysiological research is described. It is equipped with an electronic infinite resistance constant current source for the injection of current into biological cells. With this amplifier the potential changes, the resistance changes and the dependence on extrinsic current of single cells can be measured independently and simultaneously.


Chronic axonal neuropathy with triosephosphate isomerase deficiency.
A patient with triosephosphate isomerase deficiency resulting from compound heterozygote mutation is described. Chronic axonal neuropathy was identified on clinical and neurophysiologic grounds and confirmed by sural nerve biopsy. This report describes the first biopsy-proven case confirming that peripheral neuropathy can occur with triosephosphate isomerase deficiency.


Emergency contraception in South Africa: knowledge, attitudes, and use among public sector primary healthcare clients.
To determine knowledge of, attitudes toward, and use of emergency contraception (EC), interviews were held with 1068 clients of 89 public sector primary healthcare facilities in two urban and two rural areas of South Africa. Only 22.8% of the clients had heard of EC. Awareness was significantly lower in the most rural area and among older, less educated women. Knowledge of EC was superficial, with 47.1% unsure of the appropriate interval between unprotected intercourse and starting EC and 56.6% not knowing whether it was available at the clinic. Few (9.1%) of those who knew of EC had used it. After explaining EC, attitudes toward its use were found to be positive, with 90.3% indicating that they would use it if needed. Awareness was lower than in developed countries, but higher than in other developing countries. Findings indicate that if women know of EC, where to get it, and how soon to take it, they would use it if needed.


Dendrite plasticity: branching out for greener pastures.
Environmental stress triggers substantial alterations in animal physiology and, in some cases, brain structure. Using the nematode Caenorhabditis elegans, a new study reports that unfavorable conditions lead to dramatic dendrite remodeling in neurons that mediate an adaptive dispersal behavior.


Association of the Mediterranean Diet With Onset of Diabetes in the Women's Health Study.
Higher Mediterranean diet (MED) intake has been associated with reduced risk of type 2 diabetes, but underlying biological mechanisms are unclear. To characterize the relative contribution of conventional and novel biomarkers in MED-associated type 2 diabetes risk reduction in a US population. This cohort study was conducted among 25 317 apparently healthy women. The participants with missing information regarding all traditional and novel metabolic biomarkers or those with baseline diabetes were excluded. Participants were invited for baseline assessment between September 1992 and May 1995. Data were collected from November 1992 to December 2017 and analyzed from December 2018 to December 2019. MED intake score (range, 0 to 9) was computed from self-reported dietary intake, representing adherence to Mediterranean diet intake. Incident cases of type 2 diabetes, identified through annual questionnaires; reported cases were confirmed by either telephone interview or supplemental questionnaire. Proportion of reduced risk of type 2 diabetes explained by clinical risk factors and a panel of 40 biomarkers that represent different physiological pathways was estimated. The mean (SD) age of the 25 317 female participants was 52.9 (9.9) years, and they were followed up for a mean (SD) of 19.8 (5.8) years. Higher baseline MED intake (score ≥6 vs ≤3) was associated with as much as a 30% lower type 2 diabetes risk (age-adjusted and energy-adjusted hazard ratio, 0.70; 95% CI, 0.62-0.79; when regression models were additionally adjusted with body mass index [BMI]: hazard ratio, 0.85; 95% CI, 0.76-0.96). Biomarkers of insulin resistance made the largest contribution to lower risk (accounting for 65.5% of the MED-type 2 diabetes association), followed by BMI (55.5%), high-density lipoprotein measures (53.0%), and inflammation (52.5%), with lesser contributions from branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%), and minimal contribution (≤2%) from hemoglobin A1c. In post hoc subgroup analyses, the inverse association of MED diet with type 2 diabetes was seen only among women who had BMI of at least 25 at baseline but not those who had BMI of less than 25 (eg, women with BMI <25, age- and energy-adjusted HR for MED score ≥6 vs ≤3, 1.01; 95% CI, 0.77-1.33; P for trend = .92; women with BMI ≥25: HR, 0.76; 95% CI, 0.67-0.87; P for trend < .001). In this cohort study, higher MED intake scores were associated with a 30% relative risk reduction in type 2 diabetes during a 20-year period, which could be explained in large part by biomarkers of insulin resistance, BMI, lipoprotein metabolism, and inflammation.


Contribution of silver nanoparticles to extend Salmonella typhimurium growth under various respiration regimes.
Living cells interact with different forms of metal; the resulted biochemical alteration depends on the dose. Over an average dose in ionic form, metals interact with respiration processes at various levels, and it induces oxidative stress by shifting the whole oxydoreduction equilibrium. To correct the toxicity, cell develops different ways to cancel the effect of the exceeded charges, and it reduces the ion to get a more stable form. In the case of nanoparticles, the reactivity of surface has been enhanced that can alter the biological mechanisms; the cell may develop different strategies to minimize this reactivity. The current study is focused on the pursuing of cell behavior regarding the presence of nanoparticles and their associated metals. Nanoparticles have been synthesized using bio-reducing agents and then were structurally characterized using X-ray diffraction, UV-Vis, and infra-red spectroscopy. The oxydoreduction flexibility of the post-synthesis modified nanoparticles was tested in vitro. Interactions with cells were done using Salmonella under various respiration conditions. The final results show the possible correction of oxidative stress effects and the recuperation of respiration.


Economic and financial risks of commercial tilapia cage culture in a neotropical reservoir.
The aim of this study was to analyze the financial and economic risks of tilapia cage culture across different production water volumes (m³). The production water volumes evaluated were 10 to 50 thousand m³ (Small Volume, SV), 51 to 150 thousand m³ (Medium Volume, MV), 151 to 300 thousand m³ (Large Volume, LV), and >301 thousand m³ (Extra-Large Volume, ELV). Productivity and economic data were obtained from a commercial Nile tilapia cage farm with 232 net cages installed in a neotropical reservoir, in Brazil, from 2017 to 2019. Cost and profitability analyses, economic feasibility, and risk and sensitivity analyses were performed using a Monte Carlo simulation. The implementation of commercial tilapia cage farming relies mainly on feed prices. The initial investment demand is proportional to the size of the farms. On the other hand, MV, LV, and ELV tilapia farms showed the lowest financial risks despite the higher investments. These farms presented a medium-low risk at ≈39% probability, whereas the SV farm presented a medium to medium-high risk at 51.17% probability. Thus, fish farms with a production volume above 51 thousand m³ tend to be more profitable and have a ≈36% probability of low financial and economic risk with a Payback period of fewer than 10 years, mainly due to the lower feed costs per mass of fish produced. This study assists investors in choosing a better path toward a more viable and profitable activity.