Treating dyspareunia caused by vaginal atrophy: a review of treatment options using vaginal estrogen therapy.
Vulvovaginal atrophy (VVA) and dryness are common symptoms of the decline in endogenous production of estrogen at menopause and often result in dyspareunia. Yet while 10% to 40% of women experience discomfort due to VVA, it is estimated that only 25% seek medical help. The main goals of treatment for vaginal atrophy are to improve symptoms and to restore vaginal and vulvar anatomic changes. Treatment choices for postmenopausal dyspareunia resulting from vulvovaginal atrophy will depend on the underlying etiology and might include individualized treatment. A number of forms of vaginal estrogen and manner of delivery are currently available to treat moderate to severe dyspareunia caused by VVA. They all have been shown to be effective and are often the preferred treatment due to the targeted efficacy for urogenital tissues while resulting in only minimal systemic absorption. Both healthcare professionals and patients often find it difficult to broach the subject of sexual problems associated with VVA. However, with minimal effort to initiate a conversation about these problems, healthcare providers can provide useful information to their postmenopausal patients in order to help them each choose the optimal treatment for their needs and symptoms.


Sex differences in iron status and hepcidin expression in rats.
Studies have shown that men and women exhibit significant differences regarding iron status. However, the effects of sex on iron accumulation and distribution are not well established. In this study, female and male Sprague-Dawley rats were killed at 4 months of age. Blood samples were analyzed to determine the red blood cell (RBC) count, hemoglobin (Hb) concentration, hematocrit (Hct), and mean red blood cell volume (MCV). The serum samples were analyzed to determine the concentrations of serum iron (SI), transferrin saturation (TS), ferritin, soluble transferrin receptor (sTfR), and erythropoietin (EPO). The tissue nonheme iron concentrations were measured in the liver, spleen, bone marrow, kidney, heart, gastrocnemius, duodenal epithelium, lung, pallium, cerebellum, hippocampus, and striatum. Hepatic hepcidin expression was detected by real-time PCR analysis. The synthesis of ferroportin 1 (FPN1) in the liver, spleen, kidney, and bone marrow was determined by Western blot analysis. The synthesis of duodenal cytochrome B561 (DcytB), divalent metal transporter 1 (DMT1), FPN1, hephaestin (HP) in the duodenal epithelium was also measured by Western blot analysis. The results showed that the RBC, Hb, and Hct in male rats were higher than those in female rats. The SI and plasma TS levels were lower in male rats than in female rats. The levels of serum ferritin and sTfR were higher in male rats than in female rats. The EPO levels in male rats were lower than that in female rats. The nonheme iron contents in the liver, spleen, bone marrow, and kidney in male rats were also lower (56.7, 73.2, 60.6, and 61.4 % of female rats, respectively). Nonheme iron concentrations in the heart, gastrocnemius, duodenal epithelium, lung, and brain were similar in rats of both sexes. A moderate decrease in hepatic hepcidin mRNA content was also observed in male rats (to 56.0 % of female rats). The levels of FPN1 protein in the liver, spleen, and kidney were higher in male rats than in female rats. There was no significant change in FPN1 expression in bone marrow. Significant difference was also not found in DcytB, DMT1, FPN1, and HP protein levels in the duodenal epithelium between male and female rats. These data suggest that iron is distributed differently in male and female rats. This difference in iron distribution may be associated with the difference in the hepcidin level.


Reversal of severe mitral regurgitation by device closure of a large patent ductus arteriosus in a premature infant.
We report a critically ill premature infant with severe mitral valve regurgitation associated with pulmonary hypertension and a severely dilated left atrium from a large patent ductus arteriosus. The mitral valve regurgitation improved significantly with normalisation of left atrial size 4 weeks after percutaneous closure of the patent ductus arteriosus. This case highlights the potential reversibility of severe mitral valve regurgitation with treatment of an underlying cardiac shunt.


PD-L1 expression and association with malignant behavior in pheochromocytomas/paragangliomas.
The immunosuppressive effect of the programmed death (PD)-1/PD-L1 pathway plays an important role in the treatment of a variety of tumors, such as lung and breast cancer, but there is little literature about PD-1/PD-L1 in pheochromocytomas/paragangliomas (PCCs/PGLs). We explored the relationship of PD-L1 and malignant behavior in 77 cases of PCC/PGL using immunohistochemistry (IHC) to assess protein expression and RNAscope to detect mRNA expression in 20 cases. The IHC data showed that 59.74% of the PCCs/PGLs expressed PD-L1, and the extent of expression was highly correlated with Ki-67 (P = .019) and hypertension (P = .013) but not with age, sex, tumor size, capsular invasion, tumor necrosis, relapse/distant metastasis, secretion of noradrenaline/adrenaline/dopamine, or diabetes mellitus. In addition, we found an excellent correlation of PD-L1 mRNA and protein expression with a κ coefficient of 0.828, and further stratification of the IHC and RNAscope findings showed high consistency (Pearson coefficient 0.753). The correlation of PD-L1 and Ki-67 indicated that PD-L1 could be considered a malignant proliferation biomarker for PCCs/PGLs, which would be a putative biomarker for anti-PD-L1 therapies.


Type I hyperlipoproteinemia caused by lipoprotein lipase defect in lipid-interface recognition was relieved by administration of medium-chain triglyceride.
We have previously reported lipoprotein lipase with a defect of lipid-interface recognition in a patient with type I hyperlipoproteinemia. In this patient, lipoprotein lipase from post-heparin plasma (PHP) hydrolyzed monomeric substrate tributyrin, but scarcely hydrolyzed triolein emulsified with Triton X-100 and that in very-low-density lipoproteins ([VLDL] d < 1.006 g/mL), and did not bind to VLDL. The triglyceride (TG) level of this patient did not decrease to less than 1,000 mg/dL with a low-fat diet (1,400 kcal containing 10 g fat/d). When the patient took 30 g medium-chain TG (MCT) in addition to the 1,400-kcal diet, her serum TG level decreased to 250 mg/dL and her clinical signs improved. The low clearance rate of serum TG with heparin injection improved after intake of MCT. Caproic acid levels were maintained at 1.4% and 2.6% in chylomicrons and VLDL after MCT intake, respectively. The patient's lipoprotein lipase hydrolyzed triolein emulsified with 2% tricaprin at the same rate as that of control lipoprotein lipase. The patient's lipoprotein lipase-catalyzed hydrolyzing rate of triolein in chylomicrons obtained after MCT administration was also enhanced up to 70% of that of control lipoprotein lipase. These findings suggest that hypertriglyceridemia caused by lipoprotein lipase with a defect in lipid-interface recognition could be relieved with the administration of medium-chain TG, and that one of the mechanisms of this effect might be a modification of TG-rich lipoproteins by MCT.


Pinpointing miRNA and genes enrichment over trait-relevant tissue network in Genome-Wide Association Studies.
Understanding gene regulation is important but difficult. Elucidating tissue-specific gene regulation mechanism is even more challenging and requires gene co-expression network assembled from protein-protein interaction, transcription factor and gene binding, and post-transcriptional regulation (e.g., miRNA targeting) information. The miRNA binding affinity could therefore be changed by SNP(s) located at the 3' untranslated regions (3'UTR) of the target messenger RNA (mRNA) which miRNA(s) interacts with. Genome-wide association study (GWAS) has reported significant numbers of loci hosting SNPs associated with many traits. The goal of this study is to pinpoint GWAS functional variants located in 3'UTRs and elucidate if the genes harboring these variants along with their targeting miRNAs are associated with genetic traits relevant to certain tissues. By applying MIGWAS, CoCoNet, ANNOVAR, and DAVID bioinformatics software and utilizing the gene expression database (e.g. GTEx data) to study GWAS summary statistics for 43 traits from 28 GWAS studies, we have identified a list of miRNAs and targeted genes harboring 3'UTR variants, which could contribute to trait-relevant tissue over miRNA-target gene network. Our result demonstrated that strong association between traits and tissues exists, and in particular, the Primary Biliary Cirrhosis (PBC) trait has the most significant p-value for all 180 tissues among all 43 traits used for this study. We reported SNPs located in 3'UTR regions of genes (SFMBT2, ZC3HAV1, and UGT3A1) targeted by miRNAs for PBC trait and its tissue association network. After employing Gene Ontology (GO) analysis for PBC trait, we have also identified a very important miRNA targeted gene over miRNA-target gene network, PFKL, which encodes the liver subunit of an enzyme. The non-coding variants identified from GWAS studies are casually assumed to be not critical to translated protein product. However, 3' untranslated regions (3'UTRs) of genes harbor variants can often change the binding affinity of targeting miRNAs playing important roles in protein translation degree. Our study has shown that GWAS variants could play important roles on miRNA-target gene networks by contributing the association between traits and tissues. Our analysis expands our knowledge on trait-relevant tissue network and paves way for future human disease studies.


A biological method to monitor early effects of the air pollution caused by the industrial exploitation of geothermal energy.
The suitability of a set of ecophysiological parameters, to be used as early warning indicator to detect signs of a worsening environment around geothermal power plants, was tested by comparison with the diversity of epiphytic lichens, a well-established indicator of geothermal air pollution. Samples of the lichen Evernia prunastri were transplanted around a geothermal power plant at Larderello (Tuscany, Italy) and at a control site, and integrity of cell membranes, concentration of chlorophyll a, b and carotenoids, chlorophyll integrity and variations in pH of thalli were measured. The results showed that cell membrane damage, expressed by changes in electrical conductivity, could be used to detect early (exposure periods as short as 1 month) deleterious effects of geothermal air pollution.


Feature-based attention processes in primate prefrontal cortex do not rely on feature similarity.
Feature-based attention enables privileged processing of specific visual properties. During feature-based attention, neurons in visual cortices show "gain modulation" by enhancing neuronal responses to the features of attended stimuli due to top-down signals originating from prefrontal cortex (PFC). Attentional modulation in visual cortices requires "feature similarity:" neurons only increase their responses when the attended feature variable and the neurons' preferred feature coincide. However, whether gain modulation based on feature similarity is a general attentional mechanism is currently unknown. To address this issue, we record single-unit activity from PFC of macaques trained to switch attention between two conjunctive feature parameters. We find that PFC neurons experience gain modulation in response to attentional demands. However, this attentional gain modulation in PFC is independent of the feature-tuning preferences of neurons. These findings suggest that feature similarity is not a general mechanism in feature-based attention throughout the cortical processing hierarchy.


Effect of posaconazole on cyclosporine blood levels and dose adjustment in allogeneic blood and marrow transplant recipients.
The posaconazole prescribing information recommends an upfront cyclosporine dose reduction upon initiation of posaconazole prophylaxis. We examined this recommendation in the early phase of allogeneic transplantation, where cyclosporine levels potentially becoming subtherapeutic following upfront dose reduction would be deleterious to transplant outcome. Our data show that while posaconazole leads to an increase in cyclosporine levels, subsequent cyclosporine dose reduction can be safely guided by therapeutic drug monitoring and is not required upfront. Therefore, the current recommendation may be modified.


Precision of single vs bilateral hip bone mineral density scans.
This study was performed to determine and compare the precision of single and bilateral hip bone mineral density (BMD) measurements and to determine the precision of spinal and total body measurements by dual-energy X-ray absorptiometry (DXA). Precision (group root-mean-square average coefficient of variation) was determined in 6 subjects scanned six times each at the spine, both hips, and total body, with repositioning after each scan. Mean percentage coefficients of variance (%CVs) in BMD for single and bilateral hip scans were, respectively: 0.65% and 0.67% for the total hip, 1.16% and 1.03% for the trochanter, and 1.66% and 1.31% for the femoral neck, respectively. Mean %CV was 1.04% for spine BMD (L2-L4), 0.67% for total body BMD, 1.12% for total body bone mineral content (BMC), 0.94% for total body fat tissue, and 0.77% for total body nonfat soft tissue. We conclude that precision overall is excellent and that femoral neck precision can be improved with bilateral compared with the traditional single hip scans.


Dopamine D4 receptor gene polymorphisms: relation to ethnicity, no association with schizophrenia and response to clozapine in Israeli subjects.
The dopamine D4 receptor (DRD4) is a candidate gene in the search for a genetic etiology of schizophrenia and for pharmacogenetic factors in the response to antipsychotic treatment. Previous work has not found linkage or association of a polymorphism in exon 3 of this gene with diagnosis of schizophrenia or response to clozapine. In this study we examined this association in Israeli schizophrenic subjects treated with clozapine, compared to ethnically matched controls. Another polymorphism of this gene, in exon 1, was also studied. Both polymorphisms showed no association with schizophrenia or treatment response. A significant difference in allelic distribution of DRD/ exon 3 polymorphism was found between Ashkenazi and non-Ashkenazi control subjects.


Gene expression of biomarkers of nephrotoxicity in F344 rats co-exposed to melamine and cyanuric acid for seven days.
A number of studies have demonstrated that co-exposure to low levels of melamine and cyanuric acid elicits renal toxicity due to the formation of melamine cyanurate crystals in the kidney nephrons. In this work, we investigated if co-exposure of rats to these compounds leads to alterations in the expression of the genes encoding kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), clusterin, osteopontin, and neutrophil gelatinase-associated lipocalin/lipocalin 2 (NGAL), which have been proposed as urinary biomarkers for nephrotoxicity. Six-week-old male and female F344 rats were fed ad libitum a diet fortified with 0 (control), 7, 23, 69, 229, or 694 ppm melamine and cyanuric acid (co-exposure groups), 1388 ppm melamine, or 1388 ppm cyanuric acid for seven days. Histopathology and clinical chemistry examination indicated marked toxicity only in the animals exposed to the two highest combined doses of melamine and cyanuric acid. Consistent with these observations, quantitative real-time polymerase chain reaction analysis of kidney tissue indicated increased expression of all genes analyzed relative to the control in both male and female rats fed daily with 229 or 694 ppm melamine and cyanuric acid. Exposure to lower levels of both compounds or to the individual compounds did not induce gene expression changes. These data indicate that quantifying the expression levels of the selected biomarker genes constitutes a useful endpoint to assess the combined toxicity of melamine and cyanuric acid in both male and female rats.


Enzymatic heterogeneity of seminomas.
Heterogeneity of placental-like alkaline phosphatase (PLAP-like enzyme) in seminoma was studied. PLAP-like enzyme from seminoma tissues was separated into three areas with different proportions between tumors, while PLAP and PLAP-like enzymes in normal testes were separated into two areas on the basis of hydrophobicity. By use of lectin affinity chromatography, PLAP-like enzyme in seminoma revealed extra sugar chains compared to PLAP, indicating heterogeneity of the carbohydrate moiety. However, the glycosylation patterns were found to be essentially similar between seminoma and normal testis. On isoelectric focusing, differences in migration patterns of PLAP-like enzyme were revealed between seminoma and normal testis as well as between PLAP-like enzyme and PLAP. The differences in charge were mainly due to differences in sialylation of the molecules. The complex pattern on isoelectric focusing was not altered by neuraminidase treatment, indicating a considerable charge heterogeneity within the population of PLAP-like enzyme molecules from seminoma.


New insights into chemical compositions and health promoting effects of edible oils from new resources.
This paper discusses the chemical compositions and health benefits of several kinds of oils which are extracted from new resources, including avocado seed oil, jackfruit seed oil, papaya seed oil, custard-apple seed oil, pomegranate seed oil, cherry seed oil, and pumpkin seed oil. In addition, the beneficial components found in these oils provide a future trend towards the utilization of seed oils as functional foods in the prevention and management of various chronic diseases. Nevertheless, the development prospects of some seed oils, such as papaya seed oil or custard-apple seed oil, need to be further studied and reconsidered due to the unconfirmed edibility. Furthermore, some other hindrances need to be solved to make better use of these valuable food industry by-products.


Pertuzumab plus trastuzumab and chemotherapy for Japanese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subgroup analysis of the JACOB trial.
The phase III JACOB trial (NCT01774786) compared the efficacy and safety of pertuzumab and trastuzumab plus chemotherapy with placebo and trastuzumab plus chemotherapy in patients with previously untreated human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric or gastroesophageal junction cancer. We conducted a subgroup analysis in Japanese patients. Patients were randomized 1:1 to pertuzumab 840 mg or placebo, plus trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) and chemotherapy (cisplatin 80 mg/m2, and capecitabine 1000 mg/m2 twice daily for 28 doses or 5-fluorouracil 800 mg/m2 every 24 h for 120 h), every 3 weeks. Continuation of chemotherapy after 6 cycles was at the discretion of the patient and the treating physician. A total of 40 Japanese patients were included in each arm. Median overall survival was 22.0 months (95% confidence interval [CI] 13.8-not evaluable) and 15.6 months (95% CI 9.7-19.2) in the pertuzumab and placebo arms, respectively (hazard ratio [HR] 0.64 [95% CI 0.37-1.10]). Median progression-free survival was 12.4 months (95% CI 6.1-14.1) in the pertuzumab arm and 6.3 months (95% CI 4.3-8.1) in the placebo arm (HR 0.50 [95% CI 0.30-0.82]). Grade ≥ 3 adverse events and serious adverse events were more frequent in the pertuzumab arm than the placebo arm. Results from this subgroup analysis of the JACOB trial suggest similar efficacy of pertuzumab in Japanese patients and patients in the overall population, encouraging continued investigation of new agents for gastric cancer in Japanese patients.


"Missing minorities" in blood donation: Rethinking blood procurement in Europe as a citizenship regime.
Although European blood collection organizations are currently obtaining sufficient and safe blood from the majority population, they report having difficulty recruiting first and second-generation immigrants from non-European countries. Most existing studies on these underrepresented groups, who have been coined the "missing minorities" in blood donation, have adopted an instrumental approach that focuses on the development of targeted recruitment strategies to overcome specific barriers to donation faced by members of these minorities. Although this approach does offer several short-term benefits, our central argument is that it is one-sided in its questioning of the non-participation of ethnic minorities. The literature currently lacks research on how the blood procurement system is failing to include minorities. Drawing on recent social theory, we seek a broader sociological understanding of minority under-representation in blood donor populations by shifting the analytic focus toward a critical examination of the main pillars of the procurement system within the European context. This paper advances a novel analytical framework based on two general propositions. First, we apply the literature on "citizenship regimes" to argue that blood donation is part of one specific institutionalization of citizenship and solidarity. We then reconceptualize the "problem" of missing minorities in European blood donation as an application for social change, suggesting avenues related to blood collection as a way of renegotiating minority-majority relations of solidarity.


Histological evaluation of polyesterimide-insulated gold wires in brain.
Polyesterimide-coated gold wires were implanted subdurally on the parietal cortex of rabbits for 16 weeks. Light microscope examination of the implant sites showed no evidence of toxicity. There was no inflammatory response of the adjacent parenchyma. Gliosis in the molecular or neuronal layers was only slight to moderate. Overall, the polymer demonstrated good biocompatibility at 16 weeks after implantation. Future, long-term biocompatibility studies of this material are indicated, including evaluation of tumourigenic properties.


Hyaluronic acid and human/bovine serum albumin shelled nanocapsules: Interaction with mucins and in vitro digestibility of interfacial films.
Liquid lipid nanocapsules are oil droplets surrounded by a protective shell, which enable high load and allow controlled delivery of lipophilic compounds. However, their use in food formulations requires analysing their digestibility and interaction with mucin. Here, serum albumins and hyaluronic acid shelled olive oil nanocapsules are analysed to discern differences between human and bovine variants, the latter usually used as model system. Interfacial interaction of albumins and hyaluronic acid reveals that human albumin presents limited conformational changes upon adsorption, which increase by complexation with the polysaccharide present at the interface. The latter also promotes hydrophobic interactions with mucin, especially at pH 3 and protects albumin interfacial layer under in vitro gastric digestion. The interfacial unfolding induced in human albumin by hyaluronic acid facilitates in vitro lipolysis while its limited conformational changes provide the largest protection against in vitro lipolysis.


The effects of adalimumab on the rat autotransplantation endometriosis model: A placebo-controlled randomized study.
Endometriosis is a chronic inflammatory pathology that can cause persistent pelvic pain and infertility by affecting women of reproductive age. It is defined as the placement of endometrial tissue outside the uterine cavity. Hormonal, genetic and immunological factors have an effect on the development of endometriotic implants. Adalimumab is a monoclonal antibody specific for tumor necrosis factor alpha (TNF-á), used in the treatment of autoimmune diseases. To investigate the effectiveness of adalimumab on histopathological and biochemical values in rats with experimental endometriosis. This study is a comparative, prospective, experimental rat study. Wistar albino female rats were divided into 4 groups. Group 1 was separated as the control group. Endometriotic implants were simultaneously induced in group 2 and group 3. After 4 weeks, developing endometriotic foci were measured. Adalimumab (5 mg/kg) was simultaneously intraperitoneally (ip.) administered to group 3 and group 4 for 4 weeks. At the end of the study, histopathological scoring and fibrillin-1 scoring were performed. Total antioxidant status (TAS), total oxidant status (TOS) and malondialdehyde (MDA) values were measured. Findings in all groups were compared. When group 1 and group 2 were compared, the histopathological score, as well as MDA and TOS levels increased, while TAS levels decreased in group 2 (p < 0.001). After adalimumab treatment, the average endometriotic implant size in group 3 (0.32 ±0.002 mm) decreased compared to group 2 (0.77 ±0.04 mm) (p = 0.032). While fibrillin-1 score increased in group 2 and group 3 compared to group 1, it decreased in group 3 compared to group 2 (p < 0.001). Histopathological score decreased, TAS levels increased and MDA levels decreased in group 3 compared to group 2 (p < 0.001). Adalimumab may play a role in the regression of endometrial implants by showing antioxidant and anti-inflammatory effects on histopathological damage and fibrosis.


Employment Status and Work Functioning among Kidney Transplant Recipients.
To date, employment figures of kidney transplant recipients in Europe are inconsistent. Additionally, little is known about work functioning of employed kidney transplant recipients and work functioning trajectories before and after transplantation. Data from the ongoing TransplantLines Biobank and Cohort study and from community-dwelling employed adults were used. Health-related work functioning of kidney transplant recipients was assessed with the Work Role Functioning Questionnaire 2.0 and compared with potential kidney donors and community-dwelling employed adults. We included 668 kidney transplant recipients of working age (59% men, age 51±11 years) at median 3 (interquartile range, 2-10) years after transplantation, 246 potential kidney donors of working age (43% men, age 53±9 years), and 553 community-dwelling employed adults (70% men, age 45±11 years). The proportion of employed kidney transplant recipients was lower compared with potential kidney donors (56% versus 79%). If employed, the work functioning score of kidney transplant recipients was slightly lower compared with employed potential kidney donors yet higher compared with community-dwelling employed adults (medians 91 [interquartile range, 76-98], 94 [interquartile range, 85-99], and 88 [interquartile range, 79-95], respectively). Backward linear regression analyses revealed that lower educational level, having a kidney from a deceased donor, presence of tingling or numbness of hands or feet, presence of concentration/memory problems, presence of anxiety, and presence of severe fatigue were independently associated with lower work functioning among kidney transplant recipients. Additional subgroup analyses showed that work functioning scores were lower before transplantation than at 12 months after transplantation (83 [interquartile range, 66-93] versus 92 [interquartile range, 88-98], respectively; P=0.002). Stable employed kidney transplant recipients report to function well at work. In addition, this study shows that self-reported work functioning is higher after successful kidney transplantation compared with before transplantation. TransplantLines Biobank and Cohort study, NCT03272841 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_09_26_CJN05560522.mp3.


Pharmacologic rescue of motivational deficit in an animal model of the negative symptoms of schizophrenia.
Deficits in incentive motivation, the energizing of behavior in pursuit of a goal, occur in many psychiatric disorders including schizophrenia. We previously reported deficits in both cognition and incentive motivation in a transgenic mouse model of increased striatal-specific dopamine D2 receptor (D2R) density (D2R-OE mice). This molecular alteration is observed in patients with schizophrenia, making D2R-OE mice a suitable system to study the cellular and molecular mechanisms of motivation and avolition, as well as a tool for testing potential therapies against motivational deficits. Behavioral studies using operant conditioning methods were performed both to further characterize the incentive motivation deficit in D2R-OE mice and test a novel pharmacological treatment target that arose from an unbiased expression study performed using gene chips and was validated by quantitative reverse transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry. The reluctance of D2R-OE mice to work is due neither to intolerance for low rates of reward, decreased reactivity to reward, nor increased sensitivity to satiety or fatigue but to a difference in willingness to work for reward. As in patients with schizophrenia, this deficit was not ameliorated by D2R blockade, suggesting that reversal of the motivational deficit by switching off the transgene results from molecular changes downstream of D2R overexpression. We observed a reversible increase in serotonin subtype 2C (5-HT2C) receptor expression in D2R-OE mice. Systemic injection of a 5-HT2C receptor antagonist increased incentive motivation in D2R-OE and control mice. We propose that targeting 5-HT2C receptors may be a useful approach to modulate incentive motivation in psychiatric illness.


Deadly teamwork: neural cancer stem cells and the tumor microenvironment.
Neural cancers display cellular hierarchies with self-renewing tumorigenic cancer stem cells (CSCs) at the apex. Instructive cues to maintain CSCs are generated by both intrinsic networks and the niche microenvironment. The CSC-microenvironment relationship is complex, as CSCs can modify their environment and extrinsic forces induce plasticity in the cellular hierarchy.


Early intervention in schizophrenia.
The management of schizophrenia may be characterised by two paradigms. The first approaches the schizophrenias as episodic relapsing disorders, where treatment is provided through both acute (crisis) care and to achieve prophylaxis. The second paradigm, sometimes arising from a failure of the first, is of "rehabilitation", involving amelioration of disabilities, occasionally within a framework of relative asylum. We would propose a third paradigm of "early intervention", involving a combination of medical and psychosocial interventions targeted at young, vulnerable people with the aim of preventing or limiting likely social, psychological and mental deterioration. Vigorous intervention early in the course of illness, early recognition and treatment of relapse and the promotion of psychological adjustment to psychotic illness are proposed as key elements of this third paradigm.


Feeding and Growth Outcomes in Infants with Type C Esophageal Atresia Who Undergo Early Primary Repair.
To describe growth and feeding outcomes in patients with type C esophageal atresia who underwent early primary repair and to identify predictors for poor growth. This single-center, retrospective, cohort study included all patients with type C esophageal atresia who underwent early primary repair from 2013 to 2019. Weight-for-age z score (WAZ) was calculated at birth, and every 6 months until 3 years postoperatively. Longitudinal median regression was used to evaluate WAZ over time. A multivariable logistic regression model explored predictors of growth outcomes. Of 46 infants who met the inclusion criteria, 72% were term. The median age at repair was 1.5 days of life (IQR, 1-2 days of life) and the hospital length of stay was 20 days (IQR-14, 30 days). Two patients had esophageal leak (4.3%). The median WAZ at birth was below average (-0.72; IQR, -1.37 to -0.40), but improved to reach average by 3 years (-0.025; IQR, -0.85 to 0.97, P < .001). At discharge, 72% of patients were receiving full oral nutrition, which improved to 95% by 3 years. The only independent predictor of poor growth at 1 year (WAZ < -1 [33%]) was WAZ at discharge (P = .02). Infants with esophageal atresia who undergo early primary repair are capable of achieving standard growth curves by 3 years of age. However, poor discharge WAZ score was predictive of poor WAZ score at 1 year. Efforts to identify at-risk patients and institute targeted inpatient and outpatient nutrition interventions are needed to improve their growth trajectory.


Mitochondrial aberrations during the progression of disuse atrophy differentially affect male and female mice.
Disuse decreases muscle size and is predictive of mortality across multiple pathologies. Detriments to mitochondrial function are hypothesized to underlie disuse-induced muscle atrophy. Little data exist on early mechanisms contributing to onset of these pathologies, nor is it known how they differ between sexes. The purpose of this study was to examine differential and conserved responses to mitochondrial quality control in male and female mice during the development and progression of disuse-induced atrophy. One hundred C57BL/6J mice (50 male and 50 female) were hindlimb unloaded to induce disuse atrophy for 0 (con), 24, 48, 72, or 168 h. At designated time-points, extensor digitorum longus, gastrocnemius, and soleus muscles were collected for analysis of mitochondrial quality control markers. One hundred sixty-eight hours of disuse resulted in ~25% lower oxidative muscle fibre CSA in both male (P = 0.003) and female (P = 0.02) mice without any differences due to disuse in glycolytic fibres. In male mice, 48 h of unloading was sufficient to result in ~67% greater mitochondrial oxidative stress as assessed by the reporter gene pMitoTimer compared with 0 h (P = 0.002), this mitochondrial stress preceded detectable muscle loss. However in female mice, mitochondrial oxidative stress did not occur until 168 h of disuse (~40% greater mitochondrial oxidative stress in 168 h compared with 0 h of disuse, P < 0.0001). Blunted oxidative stress in female mice appeared to coincide with greater inductions of autophagy and mitophagy in female mice (~3-fold greater BNIP3 and ~6-fold greater LC3II/I ratio P < 0.0001 and P = 0.038 respectively). Male mice overall had greater reactive oxygen species (ROS) production compared with female mice. Female mice had a greater induction of ROS within 24 h of disuse (~4-fold greater compared with 0 h, P < 0.0001); whereas male mice did not have greater ROS production until 168 h of disuse (~2-fold greater, P < 0.0001). Although all muscle types exhibited some alterations to mitochondrial quality control, such as increased markers of mitophagy and fission, the soleus muscle in both male and female mice exhibited consistent alterations to various markers of mitochondrial quality. Markers of mitochondrial translation were approximately 30-50% lower within 24 h of unloading in both male and female soleus muscle (P value ranges: <0.0001-0.03). Disuse negatively affects mitochondria differentially between sexes during development of muscle wasting. Acutely, female mice may forgo muscle mass to maintain mitochondrial quality compared with male mice. These differences may contribute to divergent clinical manifestations of atrophy.


Effects of N-terminal deletions on 1-aminocyclopropane-1-carboxylate synthase activity.
A series of nested N-terminal deletions were made on the full-length (wt) and C-terminal deleted (Cdel) 1-aminocyclopropane-1-carboxylate synthase cDNAs. These wt and mutant ACC synthases were over-expressed in a heterologous E. coli expression system. It was found that removal of an amino acid region (residues 2-12) from the non-conserved N-termini of wt and Cdel ACC synthases led to a slight increase in both in vivo ACC production and in vitro ACC synthase activity. Further deletion of 11 amino acids through Glu-23 from the N-termini of both wt and Cdel ACC synthases resulted in a substantial reduction in both in vivo ACC production and in vitro enzyme activity. Deletion of an amino acid region, residues 3 through 27, from the N-terminus of ACC synthase abolished enzyme activity completely. Kinetic analysis of a highly purified double-deletion mutant (NCdel-1) of ACC synthase demonstrated that the Km of this mutant is 42 microM, which is much smaller than that of the corresponding Cdel (280 microM) and closer to that of wt (22 microM) reported previously, suggesting a clear effect of the non-conserved N-terminal region on its ACC synthase function.


Prevalence of age-related maculopathy at two points in time in an elderly British population.
As the demography of Western society changes, the population prevalence of diseases such as age-related macular degeneration (AMD) is expected to rise. Despite this, there remains a paucity of quality data concerning the population prevalence of AMD, the commonest cause of blindness in the elderly. To report the prevalence of AMD at two points in time in an elderly population. A geographically defined random population sample of elderly people was defined in 1980, and studied in 1982-4. In 1990, a cohort of survivors was identified. Participants underwent full ophthalmic examination with fundus photography using the same camera on each occasion. Photographs were randomly encoded and graded by two independent masked observers using the Wisconsin Age-related Maculopathy Grading System. Disagreements were resolved by consensus. Eighty-eight survivors participated in the follow-up examinations. Of these, 82 subjects had gradable retinal photographs for both examination points in at least one eye. There were 158 pairs of images (initial and subsequent) available for analysis. The mean age was 80 years (range 77-90 years) at the initial examination, and 87 years (range 84-97 years) at the subsequent examination; 70.7% of subjects were female. Prevalence rates for the initial examination were: drusen 72.8%, drusen confluence 37.3%, degeneration of the retinal pigment epithelium (RPE) 51.3%, increased pigment 22.2%, exudative AMD 1.9% and geographic atrophy 1.9%. Rates at second examination were: drusen 62.7% drusen confluence 41.8%, RPE degeneration 72.8%, increased pigment 16.5%, exudative AMD 3.8% and geographic atrophy 3.2%. This 'double' prevalence study provides detailed data on AMD lesions at two points in time in a population-based group of elderly people.


Energy Metabolism of Osteocytes.
In this review, we provide a recent update on bioenergetic pathways in osteocytes and identify potential future areas of research interest. Studies have identified a role for regulation of bone formation and bone resorption through osteocyte mechanosensing and osteocyte secreted factors. Nevertheless, there is a paucity of studies on the bioenergetics and energy metabolism of osteocytes, which are required for the regulation of bone remodeling. Osteocytes are cells of the osteoblast lineage embedded in bone. The osteocyte lacunocanalicular network within the skeletal matrix is exposed to a unique hypoxic environment. Therefore, the bioenergetic requirements of these cells could differ from other bone cells due to its location in the ossified matrix and its role in bone regulation transduced by mechanical signals. Recent findings highlighted in this review provide some evidence that metabolism of these cells is dependent on their location due to the substrates present in the microenvironment and metabolic cues from stress pathways. Both glycolysis (glucose metabolism) and oxidative phosphorylation (mitochondrial dynamics, ROS generation) affect osteocyte function and viability. In this review, we provide evidence that is currently available about information regarding bioenergetics pathways in osteocytes. We discuss published studies showing a role for hypoxia-driven glucose metabolism in regulating osteocyte bioenergetics. We also provide information on various substrates that osteocytes could utilize to fuel energetic needs, namely pyruvate, amino acids, and fatty acids. This is based on some preliminary experimental evidence that is available in literature. The role of parathyroid hormone PTH and parathryoid hormone-related peptide PTHrP in bone anabolism and resorption, along with regulation of metabolic pathways in the cells of the skeletal niche, needs to be explored further. Mitochondrial metabolism has a role in osteocyte bioenergetics through substrate utilization, location of the osteocyte in the bone cortex, and mitochondrial biogenesis. While there are limitations in studying metabolic flux in traditional cell lines, there are now novel cell lines and sophisticated tools available to study osteocyte bioenergetics to help harness its potential in vivo in the future.


Development of Thermotolerant Lactobacilli Cultures with Improved Probiotic Properties Using Adaptive Laboratory Evolution Method.
Probiotics play a significant role in functional foods. Heat stress and dehydration are the two principal mechanisms leading to inactivation and loss of probiotics viability in its production. There is a need to develop an industrial organism to withstand higher temperatures during its processing and storage. This current study aims to develop thermotolerant strains of Lacticaseibacillus casei N (N) and Lactobacillus helveticus NRRL B-4526 (H) by acclimatizing the wild-type strains to the higher temperature of 45 °C by adaptive laboratory evolution. A two-fold increase in biomass was observed in both acclimatized strains up to the 200th generation, which subsequently remained stable after 500 generations. The morphological change of these acclimatized strains was observed under scanning electron microscopy. Also, there was an increase in probiotic attributes of these acclimatized strains compared to their wild-types. Among two acclimatized strains, L. casei N-45 had shown higher tolerance in the acidic pH 3.0 (89.31%), the bile of 0.3% (84.45%), simulated gastric juice (79.12%), and simulated intestinal juice (73.86%). There was also an increase in salt tolerance (NaCl), radical scavenging activity, autoaggregation, coaggregation, and hydrophobicity of these adapted strains. The total protein profiling using 2D gel electrophoresis reveals the differences in protein expressions between wild-type and acclimatized strains. Specific protein spots from acclimatized strains of H-45 and N-45 were further subjected to MALDI-TOF MS/MS. Some of the identified proteins were recognized to play a role in RNA chaperones and protein synthesis during stress conditions.


Improvement of transformation and electroduction in avermectin high-producer, Streptomyces avermitilis.
Factors affecting the PEG-mediated transformation and electrotransformation of Streptomyces avermitilis protoplasts, an industrial avermectin high-producer, were evaluated. The maximum protoplast transformation efficiency under optimum conditions with PEG was 3 x 106 transformants per microg plasmid pIJ702 DNA. The efficiency of electrotransformation with the same plasmid the intact cells grown in medium with 0.5 mmol/L CaCl2, suspended in buffer with 0.5 mol/L sucrose +1 mmol/L MgCl2, and pulsed at an electric field strength of 10 kV/cm, 800 ohms, 25 microF, was of 2 x 10(3) transformants per microg DNA. When the cells were electroporated after mild lysozyme-treatment, the efficiency was up to 10(4) transformants per microg DNA. Electroporation of protoplasts and germlings had a lower efficiency (10(2) transformants per microg DNA). We report that electroporation under optimum conditions can be used for direct transfer of nonconjugative plasmid pIJ699 between two different Streptomyces species, S. avermitilis and S. lividans.


Biophysical characterization of antibacterial compounds derived from pathogenic fungi Ganoderma boninense.
There have been relatively few studies which support a link between Ganoderma boninense, a phytopathogenic fungus that is particularly cytotoxic and pathogenic to plant tissues and roots, and antimicrobial compounds. We previously observed that liquid-liquid extraction (LLE) using chloroformmethanol-water at a ratio (1:1:1) was superior at detecting antibacterial activities and significant quantities of antibacterial compounds. Herein, we demonstrate that antibacterial secondary metabolites are produced from G. boninense mycelia. Antibacterial compounds were monitored in concurrent biochemical and biophysical experiments. The combined methods included high performance thin-layer chromatography (HPTLC), gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), fourier transform infrared (FTIR), and nuclear magnetic resonance (NMR) spectroscopy. The antibacterial compounds derived from mycelia with chloroform-methanol extraction through LLE were isolated via a gradient solvent elution system using HPTLC. The antibacterial activity of the isolated compounds was observed to be the most potent against Staphylococcus aureus ATCC 25923 and multidrug-resistant S. aureus NCTC 11939. GC-MS, HPLC, and FTIR analysis confirmed two antibacterial compounds, which were identified as 4,4,14α-trimethylcholestane (m/z = 414.75; lanostane, C30H54) and ergosta-5,7,22-trien-3β-ol (m/z = 396.65; ergosterol, C28H44O). With the aid of spectroscopic evaluations, ganoboninketal (m/z = 498.66, C30H42O6), which belongs to the 3,4-seco-27-norlanostane triterpene family, was additionally characterized by 2D-NMR analysis. Despite the lack of antibacterial potential exhibited by lanostane; both ergosterol and ganoboninketal displayed significant antibacterial activities against bacterial pathogens. Results provide evidence for the existence of bioactive compounds in the mycelia of the relatively unexplored phytopathogenic G. boninense, together with a robust method for estimating the corresponding potent antibacterial secondary metabolites.


Long Acting Polycaprolactone Based Parenteral Formulation of Aripiprazole Targeting Behavioural and Biochemical Deficit in Schizophrenia.
Schizophrenia is a neurodevelopmental disorder which is expressed in the form of disturbed behaviour and abnormal mental functions. Patient's non-adherence to the medicine is the main cause of failure of drug therapy and increases incidence of relapses. Thus, for successful management of disease long acting parenteral formulations were developed. Aripiprazole was encapsulated in biocompatible polycaprolactone microsphere by o/w emulsion solvent-evaporation method in order to achieve sustained release of the drug for several weeks after single subcutaneous administration. They were optimised on the basis of various parameters such as physical appearance, particle size (49.4 μm-387.1 μm), encapsulation efficiency (70%-95%), percentage yield (33%-75%) and drug loading (25.9%-47.5%). The surface topography and sphericity of the microspheres was determined by scanning electron microscopy which revealed that the microspheres formed were spherical and non-porous in nature. The in vitro releases from the selected formulations were found to be 87% and 95% respectively after 45 days of dissolution. In vivo efficacy of optimised formulation showed significantly (p < 0.05) amelioration of various positive, negative and cognitive symptoms associated with schizophrenia and oxidative stress markers in ketamine-induced schizophrenia model in rats for 30 days.


Purification by cibacron blue F3GA dye affinity chromatography and comparison of NAD(P)H:quinone reductase (E.C.18.104.22.168) from rat liver cytosol and microsomes.
The dicoumarol-sensitive NAD(P)H:quinone reductase (E.C.220.127.116.11), often referred to as DT-diaphorase, has been purified from both the cytosolic and microsomal fractions from rat liver using a novel, highly efficient, two-step purification procedure utilizing immobilized Cibacron Blue F3GA dye affinity chromatography as the principal step. Under the conditions reported here, this dye affinity resin, generally recognized as preferentially binding nucleotide-dependent proteins, was highly selective in the recovery of up to 95% of the NAD(P)H:quinone reductase directly from the cytosol as a preparation which was often greater than 90% pure. Further purification by gel exclusion chromatography resulted in pure protein preparations with final recoveries approaching 80%. Similar results were obtained during the purification of this quinone reductase activity from microsomal extracts. Evidence is presented which suggests that the enzyme isolated from each cellular fraction are highly homologous, if not identical; data are consistent with genetic evidence.


Laparoscopic surgery versus radiofrequency ablation for the treatment of single hepatocellular carcinoma ≤3 cm in the elderly: a propensity score matching analysis.
Laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) represented potential treatments for patients with a single hepatocellular carcinoma (HCC) smaller than 3 cm. As the aging population soared, our study aimed to examine the advantage/drawback balance for these treatments, which should be reassessed in elderly patients. A multicentric retrospective study compared 184 elderly patients (aged >70 years) (86 patients underwent LLR and 98 had RFA) with single ≤3 cm HCC, observed from January 2009 to January 2019. After propensity score matching (PSM), the estimated 1- and 3-year overall survival rates were 96.5 and 87.9% for the LLR group, and 94.6 and 68.1% for the RFA group (p = 0.001) respectively. The estimated 1- and 3-year disease-free survival rates were 92.5 and 67.4% for the LLR group, and 68.5 and 36.9% for the RFA group (p = 0.001). Patients with HCC of anterolateral segments were more often treated with laparoscopic resection (47 vs. 36, p = 0.04). The median operative time in the resection group was 205 min and 25 min in the RFA group (p = 0.01). Length of hospital stay was 5 days in the resection group and 3 days in the RFA group (p = 0.03). Despite a longer length of hospital stay and operative time, LLR guarantees a comparable postoperative course and a better overall and disease-free survival in elderly patients with single HCC (≤3 cm), located in anterolateral segments.


Accessibility of drug databases and resources with assistive technology.
Pharmacy programs are responsible for providing appropriate academic accommodations to student learners in the classroom including individuals with disabilities according to Accreditation Council for Pharmacy Education Accreditation Standards. In the literature, faculty have published methods on teaching strategies and assistive technologies to increase accessibility in a laboratory setting and implementation of resources for learners with visual or hearing impairment. An area that has not been highlighted in the literature is the accessibility of drug databases and resources often utilized in pharmacy practice and is an integral part of pharmacy curricula. This commentary provides information about the accessibility of the content and features within drug databases and resources using assistive technology for individuals with visual impairment. Pharmacy programs must conduct testing of software and drug resources commonly used to ensure appropriate accommodations are provided for learners with disabilities. In addition, external stakeholders who develop drug information resources may need to consider accessibility of content for student learners with visual impairment and other forms of disability.


Cope with copper: From copper linked mechanisms to copper-based clinical cancer therapies.
Recent studies have established a strong link between copper and cancer biology, as copper is necessary for cancer growth and metastasis. Beyond the conventional concept of copper serving as a catalytic cofactor of metalloenzymes, emerging evidence demonstrates copper as a regulator for signaling transduction and gene expression, which are vital for tumorigenesis and cancer progression. Interestingly, strong redox-active properties make copper both beneficial and detrimental to cancer cells. Cuproplasia is copper-dependent cell growth and proliferation, whereas cuproptosis is copper-dependent cell death. Both mechanisms act in cancer cells, suggesting that copper depletion and copper supplementation may be viable approaches for developing novel anticancer therapies. In this review, we summarized the current understanding of copper's biological role and related molecular mechanisms in cancer proliferation, angiogenesis, metastasis, autophagy, immunosuppressive microenvironment development, and copper-mediated cancer cell death. We also highlighted copper-based strategies for cancer treatment. The current challenges of copper in cancer biology and therapy and their potential solutions were also discussed. Further investigation in this field will yield a more comprehensive molecular explanation for the causal relationship between copper and cancers. It will reveal a series of key regulators governing copper-dependent signaling pathways, thereby providing potential targets for developing copper-related anticancer drugs.


Donors who react may not come back: analysis of repeat donation as a function of phlebotomist ratings of vasovagal reactions.
Previous studies using small or restricted samples suggest that vasovagal reactions to blood donation are associated with a decreased likelihood of repeat donation. In the present study, we examined data for all allogeneic whole blood donors (n=89,587) in the American Red Cross Blood Services, Central Ohio Region during an entire year. Results of a one-year follow-up revealed that moderate and severe vasovagal reactions reduced the likelihood of repeat donation by 50% or more. Light vasovagal reactions, which represented 97% of all reactions recorded, significantly reduced return rates by 20% for first-time donors and 33% for experienced donors.


Expanded health belief model predicts diabetes self-management in college students.
An instrument was designed to determine relationships between constructs of the Expanded Health Belief Model and to identify characteristics of college students who successfully manage their diabetes. The Diabetes College Scale was developed to measure attitudes and behaviors pertinent to diabetes management and college life. It was tested for content validity, test-retest reliability, and internal consistency. Data were collected from college students using a cross-sectional design. Campus health care providers were invited via electronic mail to administer the survey to students with Type I diabetes. Ninety-eight questionnaires were mailed to interested providers, of which 86 (88%) were returned. Mean scores for attitude constructs, seven behaviors, and two outcomes were measured. Twenty-six experts established content validity. Instrument reliability was evaluated using paired t-tests, Cronbach's alpha, and correlation coefficients. Correlation coefficients and stepwise multiple regression analysis evaluated relationships among variables measured. Intention and emotional response were strong predictors of exercise, whereas health importance and intention were predictive of testing blood sugar. Situational factors and emotional response were substantial barriers to optimal diabetes self-care. College health care providers should address these areas in providing services to this population. Additional testing of the instrument is also recommended.


Identification of promising high-affinity inhibitors of SARS-CoV-2 main protease from African Natural Products Databases by Virtual Screening.
With the rapid spread of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen agent of COVID-19 pandemic created a serious threat to global public health, requiring the most urgent research for potential therapeutic agents. The availability of genomic data of SARS-CoV-2 and efforts to determine the protein structure of the virus facilitated the identification of potent inhibitors by using structure-based approach and bioinformatics tools. Many pharmaceuticals have been proposed for the treatment of COVID-19, although their effectiveness has not been assessed yet. However, it is important to find out new-targeted drugs to overcome the resistance concern. Several viral proteins such as proteases, polymerases or structural proteins have been considered as potential therapeutic targets. But the virus target must be essential for host invasion match some drugability criterion. In this Work, we selected the highly validated pharmacological target main protease Mpro and we performed high throughput virtual screening of African Natural Products Databases such as NANPDB, EANPDB, AfroDb, and SANCDB to identify the most potent inhibitors with the best pharmacological properties. In total, 8753 natural compounds were virtually screened by AutoDock vina against the main protease of SARS-CoV-2. Two hundred and five (205) compounds showed high-affinity scores (less than - 10.0 Kcal/mol), while fifty-eight (58) filtered through Lipinski's rules showed better affinity than known Mpro inhibitors (i.e., ABBV-744, Onalespib, Daunorubicin, Alpha-ketoamide, Perampanel, Carprefen, Celecoxib, Alprazolam, Trovafloxacin, Sarafloxacin, Ethyl biscoumacetate…). Those promising compounds could be considered for further investigations toward the developpement of SARS-CoV-2 drug development.


Immunoglobulin classes in the garden lizard, Calotes versicolor.
Two classes of immunoglobulins have been purified from lizard serum using a combination of ion-exchange chromatography on DEAE-cellulose and gel filtration on Sephadex G-200 or on Sepharose 6B. Lizard IgM is 2-ME sensitive and has an intact molecular weight similar to human IgM. On SDS-PAGE, reduced IgM dissociates into heavy and light chains of molecular weight 70,000 and 23,500 daltons respectively. Lizards also possess a 2-ME resistant, low molecular weight immunoglobulin designated as IgY similar to avian and amphibian IgY. IgY dissociates on SDS-PAGE to yield 59,500 dalton heavy and 26,000 dalton light chains. Antisera raised in rabbits to each of the two Ig classes could be made class-specific by cross-absorption, thus indicating that IgM and IgY represent distinct isotypes.


Strategies for routine biopsies in heart transplantation based on 8-year results with more than 13,000 biopsies.
The endomyocardial biopsy (EMB) in heart transplant recipients has been considered the "gold standard" for diagnosis of graft rejection (REJ). The purpose of this retrospective study is to develop long-term strategies (frequency and postoperative duration of EMB) for REJ monitoring. Between 1985 and 1992, 346 patients (mean age 44.5 years, female patients = 14%) received 382 heart grafts. For graft surveillance EMBs were performed according to a fixed schedule depending on postoperative day and the results of previous biopsies. In the first year the average number (no.) of EMBs/patient was 20 with 19% positive for REJ in the first quarter, dropping to 7% REJ/EMB by the end of the first year. The percentage of REJ/EMB declined annually from 4.7% to 4.5%, 2.2% and less than 1% after the fifth year. Individual biopsy results in the first 3 postoperative months had little predictive value. Patients with fewer than two REJ (group 1), vs patients with two or more REJ in the first 6 postoperative months (group 2), were significantly less likely to reject in the second half of the first year (group 1: 0.29 +/- 0.6 REJ/patient; group 2:0.83 +/- 1.3 REJ/patient; P < 0.001) and third postoperative year (group 1:0.12 +/- 0.33 REJ/patients; group 2:0.46 +/- 0.93 REJ/patient; P < 0.05). In conclusion, routine EMBs in the first 3 postoperative months have only limited predictive value, however the number of routine EMBs can be drastically reduced later depending on the intermediate postoperative REJ pattern.


Flow cytometric analysis for reproductive biology.
Flow cytometric studies of spermatogenesis have been advanced by the need for: i) rapid, sensitive, objective and multiparameter measurements of reproductive effects due to environmental, occupational, and therapeutic exposure to toxicants; and ii) assessment of fertility potential of human and animal sperm. As a consequence, various flow cytometric techniques are already available to identify germ cell subpopulations undergoing both proliferative and maturative processes in normal and perturbed conditions. Significant improvements have been introduced in order to investigate the spermatogenic complex differentiation pathway and the apparent uniformity of mature sperm. Flow cytometry (FCM) has been applied to the measurement of both testis and sperm cells in a variety of species, including man. End points considered in toxicology studies are: altered testicular germ cell ratios, DNA and RNA content, increase of the coefficient of variation, induction of diploid elongated spermatids and diploid sperm, altered nuclear morphology, sperm cell viability, mitochondrial function and sperm chromatin structure. Precise DNA content measurements allow accurate analysis to determine the proportion of X- and Y-chromosome bearing sperm and sorting of these subpopulations for gender preselection. FCM technology has reached a maturation level that allows its inclusion in the list of available and routine methods for reproductive studies in human and animal populations.


Determination of pyronaridine in blood plasma by high-performance liquid chromatography for application in clinical pharmacological studies.
A method is described for the determination of pyronaridine in plasma using high-performance liquid chromatography with fluorescence detection. The method involves liquid-liquid extraction with phosphate buffer (pH 6.0, 0.05 M) and diethyl ether-hexane (70:30%, v/v) and chromatographic separation on a C18 column (Nucleosil, 250 x 4.6 mm I.D., 5 microns particle size) with acetonitrile-0.05 M phosphate buffer pH 6.0 (60:40%, v/v) as the mobile phase (1 ml/min) and detection by fluorescence (lambda ex = 267 nm, lambda em = 443 nm). The detector response is linear up to 1000 ng and the overall recoveries of pyronaridine and quinine were 90.0 and 60.3%, respectively. The assay procedure was adequately sensitive to measure 10 ng/ml pyronaridine in plasma samples with acceptable precision (< 15% C.V.). The method was found to be suitable for use in clinical pharmacological studies.


MicroRNA-21 inhibits ovarian granulosa cell proliferation by targeting SNHG7 in premature ovarian failure with polycystic ovary syndrome.
microRNA (miRs or miRNAs) is a type of non-coding RNA which plays the role of a regulator in gene expression. A number of miRNAs has been found by the researchers for its critical role in the pathogenesis of polycystic ovary syndrome (PCOS). But there is a no clear information available about the biological role played by miR-21 in PCOS prognosis. So, the aim of the current study is to determine the role played by miR-21 in the progression of PCOS. In order to achieve this aim, the researcher examined miR-21 expression levels in ovarian tissue samples collected from PCOS patients as well as their KGN cells (human granulosa-like tumor cell line). The study results inferred downregulation in the expression levels of miR-21 in ovarian tissues of PCOS patients and KGN cells, when compared with unaffected ovarian tissues and IOSE80 (human ovarian surface epithelial cell line). With the overexpression of miR-21, the proliferation of KGN cells was prevented and apoptosis was induced among these cells. The authors used StarBase analysis for predicting the direct binding target of miR-21. As per the assay results attained from luciferase reporter assay and western blot analysis, it was found that SNHG7 acted as a target gene for miR-21 while the latter downregulated the former. To conclude, the current study revealed the contribution of miR-21/SNHG7 axis in the regulation of Granulosa Cell (GC) proliferation and apoptosis. It further suggested a new molecular mechanism for GC dysregulation while the finding presents a new promising target for PCOS treatment procedure.


[Acute nonalcoholic nonbiliary pancreatitis. Difficulties in diagnosis and possibility of nicotine toxicity].
The possibility of nicotine toxicity, although rare, should be considered in cases of acute edematous pancreatitis. A 30-year-old woman was hospitalized to identify the cause of an initial episode of acute edematous pancreatitis. The observation of native anti-DNA and antiphospholipid antibodies suggested lupus pancreatitis and/or an antiphospholipid syndrome, both subsequently ruled out. The final diagnosis was nicotine poisoning induced by the combination of a nicotine patch and tobacco smoking. Although a nicotine patch has never been reported in connection with an episode of acute pancreatitis before, this case suggests that such an event might be a rare complication of an overdose of nicotine.


Induction of obliterative airway disease by anti-HLA class I antibodies.
Anti-HLA class I Abs are associated with the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. BOS is characterized histologically by fibrosis and airway epithelial cell apoptosis. We have previously shown that anti-HLA class I Abs induce proliferation, growth factor production and apoptosis in airway epithelial cells in vitro. Thus, this study was designed to determine whether anti-HLA class I Abs alone could induce obliterative airway disease (OAD) in heterotopic murine tracheal allografts. Toward this, HLA-A*0201-transgenic tracheal allografts were transplanted into Rag1-deficient mice treated with the W6/32 anti-HLA class I mAb. Allografts were harvested at days +30, +45, +60 and +90. Allografts displayed epithelial metaplasia by day +45, epithelial destruction and mild cellular infiltration by day +60 and complete lumen obliteration and moderate cellular infiltration by day +90. Anti-HLA class I Abs induced the production of several growth factors and growth factor receptors and apoptosis of parenchymal cells in the allograft. In addition, anti-HLA class I Abs induced macrophages and granulocytes infiltration. The results from this study demonstrate that anti-HLA class I Abs play an important role in the pathogenesis of OAD by inducing growth factor production, apoptosis and chemotaxis of inflammatory cells.


Molecular beacons: Fluorescent probes for detection of endogenous mRNAs in living cells.
A novel approach for detecting nucleic acid in solution has been adopted for real-time imaging of native mRNAs in living cells. This method utilizes hybridization probes, called "molecular beacons", that generate fluorescent signals only when they are hybridized to a complementary target sequence. Nuclease-resistant molecular beacons are designed to efficiently hybridize to accessible regions within RNAs and then be detected via fluorescence microscopy. The target regions chosen for probe binding are selected using two computer algorithms, mfold and OligoWalk, that predict the secondary structure of RNAs and help narrow down sequence stretches to which the probes should bind with high affinity in vivo. As an example, molecular beacons were designed against regions of oskar mRNA, microinjected into living Drosophila melanogaster oocytes and imaged via confocal microscopy.


Capacity differences in working memory based on resting state brain networks.
Herein, we compared the connectivity of resting-state networks between participants with high and low working memory capacity groups. Brain network connectivity was assessed under both resting and working memory task conditions. Task scans comprised dual-task (reading sentences while memorizing target words) and single-task (reading sentences) conditions. The low capacity group showed relatively stronger connectivity during resting-state in most brain regions, and the high capacity group showed a stronger connectivity between the medial prefrontal and posterior parietal cortices. During task performance, the dorsal attention and salience networks were relatively strongly connected in the high capacity group. In the comparison between dual- and single-task conditions, increased coupling between the anterior cingulate cortex and other attentional control-related areas were noted in the high capacity group. These findings suggest that working memory differences are related with network connectivity variations in attentional control-associated regions during both resting and task performance conditions.


Analysis of Neonatal Outcome with Supplemental Oxygen to Mother during Elective Cesarean Section under Spinal Anesthesia: A Prospective Randomized Controlled Trial.
Many questions have arisen on benefits of routine use of supplemental oxygen during elective cesarean section (CS) under spinal anesthesia. The aim of this randomized controlled study was to evaluate neonatal outcome in immediate postpartum period with or without supplemental oxygen to mother, undergoing elective CS under spinal anesthesia. One hundred and thirty-four nonlaboring term pregnant women were allocated randomly into two groups to breathe room air (air group) or oxygen (oxygen group). Times from starting oxygen supplementation to delivery interval, skin incision to delivery (I-D) interval, and uterine incision to delivery (U-D) interval were recorded. APGAR scores were assessed at 1 min and 5 min after delivery. Umbilical cord blood gas analysis was done immediately to measure pH, oxygen partial pressure, carbon dioxide partial pressure (PCO2), and bicarbonate. Statistical comparisons were performed using either Student's t-test or Mann-Whitney U-test. For oxygen group versus air group, In Oxygen group, proportion of fetal acidosis was significantly less; umbilical arterial (UA) blood pH (7.22 ± 0.05 vs. 7.19 ± 0.05, P = 0.001) as well as umbilical venous (UV) blood pH (7.26 ± 0.05 vs. 7.22 ± 0.06, P < 0.001) were significantly higher and UA PCO2 (55.4 ± 9.9 vs. 62.9 ± 6.9, P = 0.001) and UV PCO2 (51.4 ± 8.2 vs. 54.3 ± 7.2, P = 0.036) were significantly lower compared to air group. APGAR scores were similar between the groups. Supplemental oxygen has potential benefits as demonstrated by less proportion of FA in mothers receiving supplemental oxygen.


Water recreation-related spinal injuries: risk factors in natural bodies of water.
Spinal cord injuries are a major public health problem, and costs to society may total $6.2 billion per year. Using a case-control design, we investigated risk factors for spinal injury in male Wisconsin residents who sustained their injuries during water recreational activity. Compared with the controls, the people who sustained spinal injury were more likely to have entered the water from a pier or dock; to have dived into water; and to have used alcohol. Injury prevention programs for water recreation enthusiasts should address the topics of the hazards of combining alcohol with these activities, how to enter natural bodies of water safely, and safe water levels for diving.


Further studies on collagen mRNA: partial chemical characterization and polyadenylic acid sequence.
Collagen mRNA has already been purified and characterized by us. Its purity has now been enhanced by two different methods. Gel electrophoresis shows in either method, a single peak with the same mobility already reported: 1.05 X 10(6) daltons. Base composition analyses of collagen mRNA purified by either method were almost identical. Chemical analyses of the isolated polyadenylic acid stretch show that it is, 0.48 X 10(5) daltons-long, (about 140 nucleotides-long), contains 75% AMP, and is located at the 3' end of the polymer.


Modified obstetric early warning scoring systems (MOEWS): validating the diagnostic performance for severe sepsis in women with chorioamnionitis.
We sought to compare the predictive power of published modified obstetric early warning scoring systems (MOEWS) for the development of severe sepsis in women with chorioamnionitis. This was a retrospective cohort study using prospectively collected clinical observations at a single tertiary unit (Chicago, IL). Hospital databases and patient records were searched to identify and verify cases with clinically diagnosed chorioamnionitis during the study period (June 2006 through November 2007). Vital sign data (heart rate, respiratory rate, blood pressure, temperature, mental state) for these cases were extracted from an electronic database and the single worst composite recording was identified for analysis. Global literature databases were searched (2014) to identify examples of MOEWS. Scores for each identified MOEWS were derived from each set of vital sign recordings during the presentation with chorioamnionitis. The performance of these MOEWS (the primary outcome) was then analyzed and compared using their sensitivity, specificity, positive and negative predictive values, and receiver-operating characteristic curve for severe sepsis. Six MOEWS were identified. There was wide variation in design and pathophysiological thresholds used for clinical alerts. In all, 913 women with chorioamnionitis were identified from the clinical database. In all, 364 cases with complete data for all physiological indicators were included in analysis. Five women developed severe sepsis, including 1 woman who died. The sensitivities of the MOEWS in predicting the severe deterioration ranged from 40-100% and the specificities varied even more ranging from 4-97%. The positive predictive values were low for all MOEWS ranging from <2-15%. The MOEWS with simpler designs tended to be more sensitive, whereas the more complex MOEWS were more specific, but failed to identify some of the women who developed severe sepsis. Currently used MOEWS vary widely in terms of alert thresholds, format, and accuracy. Most MOEWS have not been validated. The MOEWS generally performed poorly in predicting severe sepsis in obstetric patients; in general severe sepsis was overdetected. Simple MOEWS with high sensitivity followed with more specific secondary testing is likely to be the best way forward. Further research is required to develop early warning systems for use in this setting.


NADPH-diaphorase distribution in the rabbit superior colliculus and co-localization with calcium-binding proteins.
Nitric oxide (NO) and calcium-binding proteins (CaBP) are important neuromodulators implicated in brain plasticity and brain disease. In addition, the mammalian superior colliculus (SC) has one of the highest concentrations of NO within the brain. The present study was designed to determine the distribution of nitric oxide-synthesizing neurons in the SC of the rabbit by enzyme histochemistry for reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), and its degree of co-localization with CaBP, parvalbumin (PV) and calbindin (CB). NADPH-d-labelled fibres formed dense patches of terminal buttons within the intermediate grey layer and streams of fibres within the deepest layers of SC. Cells expressing NOS constitute a subpopulation of neurons in which practically all cell types are represented. Combined PV/NADPH-d experiments showed a complete lack of co-localization within individual neurons and fibres. On the contrary, double-labelled neurons appeared in CB/NADPH-d-stained sections, only in the superficial layers, and mostly in the SGS and SO. These cells, which were intermingled with other neurons containing either NADPH-d or CB, appear to be a subtype of narrow-field and wide-field vertical cells, and display an anterior-posterior gradient of density. Owing to the involvement of the superficial layers of the SC in the organization and integration of the visual information, it is suggested that these neurons may play a concrete role within the visual circuits. Our data indicate a clear selectivity in the expression of NADPH-d, PV and CB in the SC, and that NO and CB probably serve as co-modulators and/or co-transmitters in the connectivity of the superficial layers of this midbrain structure.


Impact of obesity on ureteroscopic laser lithotripsy of urinary tract calculi.
The treatment of urinary tract stones in obese patients may differ from the treatment of non-obese patients and their success rate varies. Our objective was to compare ureteroscopic treatment outcomes of ureteral and renal stones, stratified for stone size and location, between overweight, obese and non-obese patients. Charts were reviewed for 500 consecutive patients presenting at our institution for renal and ureteral stones. A total of 107 patients underwent flexible or semi-rigid ureteroscopy with Ho:YAG laser lithotripsy and met criteria for review and analysis. Overall, initial stone-free rates were 91%, 97%, and 94% in normal, overweight and obese individuals respectively. When compared to non-obese patients, there were no significant differences (p value = 0.26; 0.50). For renal and proximal ureteral stones, the stone-free rate in overweight and obese individuals was 94% in both groups; and a stone-free rate of 100% was found for distal stones, also in both groups. Ureteroscopic treatment of stones in obese and overweight patients is an acceptable treatment modality, with success rates similar to non-obese patients.


Driver-passenger communicative stress and psychological distress among Chinese bus drivers: the mediating effect of job burnout.
This study aimed to investigate the relationship between driver-passenger communicative stress and psychological distress among bus drivers, as well as whether job burnout mediates the effect of driver-passenger communicative stress on psychological distress. A questionnaire consisting of a 12-item version of the General Health Questionnaire (GHQ-12), a one-item driver-passenger communicative stress scale, the Maslach Burnout Inventory-General Survey (MBI-GS), as well as sociodemographic and work factors, was distributed to 310 bus drivers in Shanghai, of which 307 completed it (99.0% response rate). A parallel multiple mediation model with bootstrap approach, was calculated to test the mediating effect. Driver-passenger communicative stress, emotional exhaustion and cynicism were positively associated with psychological distress. Communicative stress was significantly positively linked with two of the three dimensions of burnout (emotional exhaustion and cynicism) and dependent variable. Emotional exhaustion and cynicism were positively associated with the dependent variable. The results indicate that emotional exhaustion and cynicism partially mediated the effect of communicative stress on psychological health, and that 60.0% of this effect can be explained by mediating effects, in which emotional exhaustion and cynicism weighed 63.2% and 36.8%, respectively. Communicative stress had effects on psychological distress among Chinese bus drivers, and job burnout was a mediator in this relationship.


The influence of physical activity level and cytomegalovirus serostatus on the cytokine levels of young individuals.
The practice of physical activity (PA) is a non-pharmacological variable that alters the immune response through changes in cytokines and cellular immunity. Inversely latent cytomegalovirus (CMV) infection prematurely ages the immune system and contributes to the chronic inflammatory condition in several diseases and in aging. This study aimed to compare the association of the PA level and CMV serostatus on whole blood mitogen-stimulated cytokine production of young individuals. The resting blood samples were collected from 100 volunteers of both sexes assigned to one of six groups according to the degree of PA and CMV serostatus: sedentary CMV- (n = 15), moderate physical activity CMV- (moderate PA CMV -, n = 15), high physical activity CMV- (high PA CMV-, n = 15), sedentary CMV+ (n = 20), moderate physical activity CMV + (moderate PA CMV+, n = 20) and high physical activity CMV + (high PA CMV +, n = 20). The collected peripheral blood got diluted in supplemented RPMI-1640 culture medium and incubated for 48 h with a 2% concentration of phytohemagglutinin at 37ºC and CO2 at 5%. The supernatants were collected and used for the IL-6, IL-10, TNF-α, and INF-γ analysis by the ELISA method. The IL-10 concentration was higher in the Moderate PA and High PA groups when compared to the sedentary group, regardless of CMV status. The physically active (moderate and high PA) CMV+ individuals presented lower concentrations of IL-6 and TNF-α compared to CMV+ sedentary individuals, and the sedentary CMV+ subjects had a higher concentration of INF-γ compared to Sedentary CMV- subjects (p < 0.05). In summary, it is possible to infer that PA is key to controlling inflammation related to CMV infection. The stimulation of physical exercise is an important factor in controlling many diseases at the populational level.


A novel heterozygous ERCC6 variant identified in a Chinese family with non-syndromic primary ovarian insufficiency.
Premature ovarian insufficiency (POI) is a clinical syndrome occurring in women before 40 with decreased ovarian function. Up to 25% of POI cases result from genetic factors that remain largely unknown. The Excision repair cross-complementing, group 6 (ERCC6) variant has been found to cause POI, which is hardly ever diagnosed in adolescents. Whole-exome sequencing was performed on a 19-year-old proband with non-syndromic POI and her parents. Sanger sequencing was used to confirm the identified variant. The effect of the variant on the protein was analyzed in silico and Swiss-MODEL. A novel heterozygous missense variant, c.2444G > A (p. GLy815Asp) of ERCC6 was identified in the proband who inherited the variant from her father. The variant was confirmed in another POI patient from the pedigree and was absent in the proband's mother and sister who presented normally. In silico analysis predicted this variant was deleterious. Swiss-Model revealed that the mutant amino acid formed multiple H-bonds with adjacent residues, which may lead to a dysfunction of ERCC6 protein. We firstly diagnosed an adolescent POI case associated with a novel heterozygous ERCC6 variant. The results expanded the variants spectrum of ERCC6 and provided guidance for POI diagnosis and genetic counselling.


Cognitive functions: evaluation and changes after transcatheter aortic valve implantation in elderly patients.
To assess the prevalence and postprocedural evolution of cognitive impairment (CI) in patients undergoing transcatheter aortic valve implantation. 62 patients were enrolled. Mini Mental state examination (MMSE), verbal memory test (VMT), visual search test (VST) and phonemic verbal fluency (PVF) were used to evaluate the cognitive status. CI was considered when a pathological result of MMSE was confirmed by VMT, VST and PVF. A total of 26.2% patients had CI at baseline. MMSE, VMT, VST and PVF were pathologic in 39, 16.1, 8.1 and 22.6% of the patients, respectively. Overall, no significant differences in cognitive function in any dimension were observed from baseline up to 1-year follow-up. CI is frequent in patients undergoing transcatheter aortic valve implantation, though the procedure does not forge cognitive status.


Which workers bear the burden of social distancing?
Using data from O∗NET, we construct two measures of an occupation's potential exposure to social distancing measures: (i) the ability to conduct that job from home and (ii) the degree of physical proximity to others the job requires. After validating these measures with comparable measures from ATUS as well as realized work-from-home rates during the pandemic, we employ the measures to study the characteristics of workers in these types of jobs. Our results show that workers in low-work-from-home and high-physical-proximity jobs are more economically vulnerable across various measures constructed from the CPS and PSID: they are less educated, of lower income, have fewer liquid assets relative to income, and are more likely renters. Consistent with the idea that high physical proximity or low work-from-home occupations were more exposed to the Coronavirus shock, we show that the types of workers predicted to be employed in them experienced greater declines in employment during the pandemic. We conclude by comparing the aggregate employment losses in these occupations to their employment losses in the 2008 recession, and find evidence that these occupations were disproportionately exposed to the pandemic shock, and not just comprised of more cyclically sensitive workers. The online version contains supplementary material available at 10.1007/s10888-021-09487-6.


Intrathecal injection of a therapeutic gene-containing polyplex to treat spinal cord injury.
Spinal cord injury (SCI) is a serious clinical problem that suddenly deprives patients of neurologic function and drastically diminishes their quality of life. Gene introduction has the potential to be effective for various pathological states of SCI because various proteins can be produced just by modifying nucleic acid sequences. In addition, the sustainable protein expression allows to maintain its concentration at an effective level at the target site in the spinal cord. Here we propose an approach using a polyplex system composed of plasmid DNA (pDNA) and a cationic polymer, poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)], that has high capacity to promote endosome escape and the long-term safety by self-catalytically degrading within a few days. We applied brain-derived neurotrophic factor (BDNF)-expressing pDNA for SCI treatment by intrathecal injection of PAsp(DET)/pDNA polyplex. A single administration of polyplex for experimental SCI provided sufficient therapeutic effects including prevention of neural cell death and enhancement of motor function recovery. This lasted for a few weeks after SCI, demonstrating the capability of this system to express BDNF in a safe and responsible manner for treatment of various pathological states in SCI.


Electronic weaponry--a question of safety.
Electronic weapons represent a new class of weapon available to law enforcement and the lay public. Although these weapons have been available for several years, there is inadequate research to document their safety or efficacy. Two of the most common, the TASER and the stun gun, are reviewed. The electronic weapon was initially and still is approved by the US Consumer Product Safety Commission; its approval was based on theoretical calculations of the physical effects of damped sinusoidal pulses, not on the basis of animal or human studies. These devices are widely available and heavily promoted, despite limited research into their safety or efficiency and despite recent animal studies documenting their potential for lethality.


Intravenous Acetaminophen in Multimodal Pain Management for Patients Undergoing Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.
Although multimodal pain management including periarticular multidrug injection can provide excellent pain relief in the early postoperative period after total knee arthroplasty (TKA), rebounding pain remains an important challenge. A randomized, double-blind, placebo-controlled trial was performed to investigate the efficacy of adding intravenous acetaminophen to multimodal pain management for TKA. We enrolled 67 patients scheduled for unilateral TKA. Patients were randomly assigned to receive either 1000 mg of intravenous acetaminophen at 6-hour intervals or normal saline at the same intervals. All patients were treated with intraoperative periarticular multidrug injection and intravenous and oral nonsteroidal anti-inflammatory drugs. The primary outcome was the postoperative 100-mm visual analog pain scale at the time of administration of study drugs. In the intention-to-treat analysis, the pain score was significantly better in the intravenous acetaminophen group than the placebo group at 17:00 one day after TKA (15.3 ± 17.0 mm vs 26.8 ± 19.0 mm; P = .013). There were no significant differences in terms of the rate of complications between groups. Even in the setting of multimodal pain management including periarticular multidrug injection, intravenous acetaminophen provided better pain relief for patients undergoing unilateral TKA.


Application of expert system and LSTM in extracting index of synaptic plasticity.
The indexes of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), can usually be measured by evaluating the slope and/or magnitude of field excitatory postsynaptic potentials (fEPSPs). So far, the process depends on manually labeling the linear portion of fEPSPs one by one, which is not only a subjective procedure but also a time-consuming job. In the present study, a novel approach has been developed in order to objectively and effectively evaluate the index of synaptic plasticity. Firstly, we introduced an expert system applying symbolic rules to discard the contaminated waveform in an interpretable way, and further generate supervisory signals for subsequent seq 2seq model based on neural networks. For the propose of enhancing the system generalization ability to deal with the contaminated data of fEPSPs, we employed long short-term memory (LSTM) networks. Finally, the comparison was performed between the automatically labeling system and manually labeling system. These results show that the expert system achieves an accuracy of 96.22% on Type-I labels, and the LSTM supervised by the expert system obtains an accuracy of 96.73% on Type-II labels. Compared to the manually labeling system, the hybrids system is able to measure the index of synaptic plasticity more objectively and efficiently. The new system can reach the level of the human expert ability, and accurately produce the index of synaptic plasticity in a fast way.


A possible role for intracellular GSH in spontaneous reaction of a cysteine (T338C) engineered into the Cystic Fibrosis Transmembrane Conductance Regulator.
The conductance of oocytes expressing T338C CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) exhibits variable responses to dithiothreitol (DTT) and 2-mercaptoethanol (2-ME) that we proposed might be due to the extraction of copper from an adventitious binding site (Liu et al. J Biol Chem 281(12):8275-8285, 2006). In order to study the origins of variability in chemical reactivity of T338C CFTR channels, oocytes expressing T338C CFTR were exposed to BCNU (bischloroethylnitrosourea), an inhibitor of glutathione reductase. BCNU treatment caused a significant reduction of initial conductance and an increase in the response to 2-ME or DTT, suggesting a direct or indirect influence of intracellular glutathione (GSH), a major determinant of the disposition of intracellular copper. Single-channel recordings indicated that T338C CFTR channels not exposed to 2-ME or DTT exhibited multiple conductance levels not seen in T338A CFTR channels. Exposure to BCNU shifted the distribution of single-channel current amplitudes towards lower values, whereas exposure to DTT favored higher amplitudes. These results suggest that the altered chemical state of T338C channels is associated with a decreased single-channel conductance and that intracellular factors (most likely GSH) may modulate the propensity of the channel to form these altered states.


The karyotype of Phlebotomus perniciosus with some observations on cytogenetics of Phlebotominae in relation to the other Psychodidae.
The karyotype of Phlebotomus perniciosus has been described. This consists of five pairs of chromosomes and includes a pair of heterosomes of XY type. Some observations on the karyotypic structure of Phlebotominae based on the comparison between Phlebotomus and Lutzomyia and between Phlebotominae and Psychodinae have been made, taking into account the taxonomical and karyological situation of the two groups.


The relationship of insulin resistance and extracoronary calcification in the multi-ethnic study of atherosclerosis.
We hypothesized that insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA), is independently associated with prevalent and incident extra-coronary calcification (ECC). We studied calcium scores of the aortic valve calcification (AVC), mitral valve calcification (MVC), thoracic aorta calcification (TAC) and aortic valve root calcification (AVR) in 6104 MESA participants not on diabetes medication who had baseline cardiac CT scans; 5312 had follow-up scans (mean 2.4 years). Relative-risk regression modeled prevalent and incident ECC adjusted for baseline demographics (model 1), and additionally for CVD risk factors (model 2). In model 1, prevalence and incidence risk-ratios for the highest versus lowest quartile of HOMA were 20-30% higher in all ECC locations (p-value for trend ≤0.05 for all but incident-AVC). In model 2, all associations were attenuated, primarily by adjustment for metabolic syndrome components. HOMA has a positive and graded association with ECC, but not independently of cardiovascular risk factors-particularly metabolic syndrome components.


Obese male mice (ob/ob) are normally sensitive to the satiating effect of CCK-8.
The ob/ob mouse has a defect in short-term satiety mechanisms because ob/ob mice eat larger meals than leans and have abnormal postprandial behaviors. We suggested that this defect involved a failure to release CCK normally in response to ingested nutrients and/or decreased receptor sensitivity to CCK. McLaughlin and Baile reported that female obese mice were less sensitive to the satiating effect of CCK-8, a result consistent with the hypothesis of decreased receptor sensitivity. To investigate this possibility further, we determined the sensitivity to exogenous CCK-8 of obese and lean male mice. Adult male C57Bl/6J ob/ob and male +/+ controls were injected with CCK-8 (1, 2, 4, and 8 micrograms/kg, IP) 15 min prior to the presentation of solid food (Noyes pellets) after 4.5 hr food deprivation in the dark. Food intake (FI) was measured at 30 min and 150 min. CCK-8 decreased FI during the first 30 min in both obese and lean mice (p less than 0.01). The threshold dose for inhibition of FI was 2 micrograms/kg in obese and 4 micrograms/kg in lean. Since obese mice weighed approximately twice as much as lean mice, their total dose of CCK-8 was equal to that of lean mice. Thus, obese male mice were at least as sensitive to the satiating effect of CCK-8 as lean male mice. These results do not confirm McLaughlin and Baile's result in female mice eating in the light and they suggest that the defect in satiety in obese male mice is not the result of decreased sensitivity of CCK receptors.


Dysfunctional Eating Behaviors and Dietary Intake in Puerto Rico.
Dysfunctional eating behaviors (DEB: emotional eating (EE), uncontrolled eating (UE) and cognitive restraint (CR)) are prevalent in U.S. Latinos and may influence diet. However, this has not been studied in Puerto Rico (PR). This study documents DEB in PR, and explores associations with diet. Cross-sectional study of adults (n = 92) in Ponce, PR. DEB were measured with the TFEQ-R18-V2. The Block Fat and Fruits and Vegetables Screener measured dietary intake. Analysis included adjusted proportions, means and linear regressions. 76%, 88%, and 87% of participants experienced EE, UE and CR, respectively. EE was associated with calories from fats (β = 1.95, 95% CI 0.40, 3.51) and saturated fats (β = 3.26, 95% CI 0.67, 5.85), and CR with fruits and vegetables (β = 0.69, 95% CI 0.20, 1.19). A large percentage of the sample experienced DEB. EE and CR were associated with dietary intake. Studies are needed to understand associations between DEB, diet and health in PR.


Life cycle impact assessment of biofuels derived from sweet sorghum in the U.S.
The objective of this study was to evaluate the environmental impact of the production of a range of liquid biofuels produced from the combination of fermenting sorghum stalk juice (bioethanol) and the pyrolysis/hydrotreatment of residual bagasse (renewable gasoline and diesel). Life cycle impact assessment (LCIA) was performed on a farm-to-wheels system that included: (i) sorghum farming, (ii) juice extraction, (iii) juice fermenting, (iv) bagasse pretreatment, (v) bagasse thermochemical treatment (pyrolysis, hydroprocessing, and steam reforming), and (vi) typical passenger vehicle operation. LCIA results were compared to those of petroleum fuels providing the equivalent functional unit-cumulative kilometers driven by spark ignition direct injection (SIDI) vehicles utilizing either renewable gasoline or 'bioE85-a blend of bioethanol and renewable gasoline,' and a compression ignition direct injection (CIDI) vehicle utilizing renewable diesel produced from 76 tons of harvested sweet sorghum (1 ha). Sweet sorghum biofuels resulted in a 48% reduction climate change impact and a 52% reduction in fossil fuel depletion. Additionally, reduced impacts in ozone depletion and eutrophication were found (67% and 47%, respectively). Petroleum fuels had lower impacts for the categories of non-carcinogenic health impact, smog, respiratory effects, and ecotoxicity, showing tradeoffs between sorghum and petroleum fuels. Overall, sorghum biofuels provide advantages in environmental impact categories including global warming potential, fossil fuel depletion and eutrophication, showing potential for sorghum as a promising second-generation feedstock for fuel.