Neuroprotection of hypoxic postconditioning against global cerebral ischemia through influencing posttranslational regulations of heat shock protein 27 in adult rats.
We previously reported that hypoxic postconditioning (HPC) ameliorated hippocampal neuronal death induced by transient global cerebral ischemia (tGCI) in adult rats. However, the mechanism of HPC-induced neuroprotection is still elusive. Notably, heat shock protein 27 (Hsp27) has recently emerged as a potent neuroprotectant in cerebral ischemia. Although its robust protective effect on stroke has been recognized, the mechanism of Hsp27-mediated neuroprotection is largely unknown. Here, we investigated the potential molecular mechanism by which HPC modulates the posttranslational regulations of Hsp27 after tGCI. We found that HPC increased expression of Hsp27 in CA1 subregion after tGCI. Inhibition of Hsp27 expression with lentivirus-mediated short hairpin RNA (shRNA) abolished the neuroprotection induced by HPC in vivo. Furthermore, pretreatment with cycloheximide, a protein synthesis inhibitor, resulted in a significant decrease in the degradation rate of Hsp27 protein in postconditioned rats, suggesting that the increase in the expression of Hsp27 after HPC might result from its decreased degradation. Next, pretreatment with leupeptin, a lysosomal inhibitor, resulted in an accumulation of Hsp27 after tGCI, indicating that autophagic pathway may be responsible for the degradation of Hsp27. We further showed that the formation of LC3-II and autophagosomes increased after tGCI. Meanwhile, the degradation of Hsp27 was suppressed and neuronal damage was reduced when blocking autophagy with 3-Methyladenine, whereas activating autophagy with rapamycin showed an opposite tendency. Lastly, we confirmed that HPC increased the expression of phosphorylated MAPKAP kinase 2 (MK2) and Hsp27 after tGCI. Also, administration of SB203580, a p38 mitogen-activated protein kinase inhibitor, decreased the expressions of phosphorylated MK2 and Hsp27. Our results suggested that inhibition of Hsp27 degradation mediated by down-regulation of autophagy may induce ischemic tolerance after HPC. Additionally, phosphorylation of Hsp27 induced by MK2 might be associated with the neuroprotection of HPC.


Suppression of OKN and VOR by afterimages and imaginary objects.
Optokinetic nystagmus (OKN) is suppressed if attention is directed to a centrally placed afterimage superimposed on a moving display. Imagining a stationary object has little or no effect. An afterimage does not provide the retinal slip and misfoveation error signals provided by a stationary object and we have shown that an effective error signal does not arise from occlusion or masking of the display by the afterimage. Although a lack of relative motion between afterimage and moving display could indicate when OKN gain is one, there is no unique relative motion signal associated with a gain of zero. Subjects could partially inhibit the vestibulo-ocular reflex (VOR) in the dark when they imagined a head-fixed object. They could suppress the response more effectively by attending to an afterimage, but the suppression was still only partial. When OKN and VOR were evoked simultaneously, pursuit movements of the eyes could not be suppressed until the vestibular inputs had subsided. We conclude that signals associated with OKN, are fully available to the mechanism that assesses the headcentric motion of objects but that signals associated with VOR are only partially available to that mechanism.


Management of the Eye in Facial Paralysis.
The preoperative assessment of the eye in facial paralysis is a critical component of surgical management. The degree of facial nerve paralysis, lacrimal secretion, corneal sensation, and lower eyelid position must be assessed accurately. Upper eyelid loading procedures are standard management of lagophthalmos. Lower eyelid tightening repositions the lower eyelid and helps maintain the aqueous tear film. Eyelid reanimation allows an aesthetic symmetry with blinking and restores protective functions vital to ocular preservation. Patients often have multiple nervous deficits, including corneal anesthesia. Other procedures include tarsorrhaphy, spring implantation, and temporalis muscle transposition; associated complications have rendered them nearly obsolete.


Management of cutaneous vascular complications in systemic scleroderma: experience from the German network.
Major cutaneous vascular complications of systemic sclerosis (SSc) are secondary Raynaud's phenomenon (RP) and digital ulcers. Even though SSc is a rare disease, timely and appropriate management of its vascular complications is mandatory for reducing the rate of major impairment. It should therefore be aware to physicians from different specialties. We evaluated the diagnostic and therapeutic approach toward secondary RP and ulceration in SSc patients at 28 German clinical centers at the time of initiation of the German network for Systemic Scleroderma (DNSS). We retrieved data via questionnaires and from the DNSS patient registry. Management of RP and ulcerations in SSc were heterogeneous at initiation of the network, reflecting a sometimes insufficient use of the diagnostic and therapeutic possibilities. As such, (1) calcium channel blockers were the first line therapy in most centers; but often in insufficient dosages, and (2) only 21.2% of patients with acral ulceration had received prostacyclins when recruited into the network. The sometimes insufficient care of vascular complications of SSc in Germany revealed the need for their standardized management, e.g. within a network for SSc and for consensus on a diagnostic or therapeutic algorithm.


Decrease of the inhibition of lipid peroxidation by glutathione-dependent system in erythrocytes of non-insulin dependent diabetics.
The inhibition of lipid peroxidation of erythrocyte membranes by glutathione-dependent protection was studied in patients with non-insulin dependent diabetes mellitus. Incubation of red cells from diabetics with 1.5 mM t-butyl hydroperoxide resulted in a lipid peroxidation increase greater than that of normal controls. Glutathione-dependent and glutathione-independent protection against oxidative damage was examined using an artificial system, in which erythrocyte ghosts were incubated with t-butyl peroxide and dialysed hemolysate in the presence or the absence of 2 mM glutathione. The glutathione-dependent protection of hemolysate from diabetics was approximately 70% of that from normal controls. The results suggest that decrease in glutathione-dependent protection against lipid peroxidation, along with decrease in glutathione levels, increases oxidative damage in erythrocyte membranes taken from diabetic patients.


HGF and IGF-1 synergize with SDF-1α in promoting migration of myeloma cells by cooperative activation of p21-activated kinase.
Stromal-derived factor (SDF)-1α, insulin-like growth factor (IGF)-1 and hepatocyte growth factor (HGF) are potent mediators of cell migration. We studied the effect of combinations of these cytokines on the migration of myeloma cells. When SDF-1α was combined with either HGF or IGF-1, we found a striking synergy in the cytokines' ability to guide cells across a transwell membrane. Between HGF and IGF-1 there was no cooperativity. However, the effects of HGF and IGF-1 were not redundant. HGF and SDF-1 caused concentration gradient-directed migration, as opposed to IGF-1, which apparently caused randomly directed cell movement. The SDF-1α-driven migration of JJN-3 cells, a myeloma cell line secreting large amounts of HGF, was reduced when JJN-3 cells were given an inhibitor of the HGF receptor, demonstrating a cooperative activity between autocrine HGF and exogenous SDF-1α. There was a clear positive correlation between the degree of cytokine-induced migration and phosphorylation of p21-activated kinase (PAK) both in primary myeloma cells and in cell lines including INA-6 and IH-1. Downregulation of PAK with small interfering RNA in INA-6 cells resulted in decreased cytokine-driven migration. This study shows synergy between SDF-1α and HGF/IGF-1 in inducing migration of myeloma cells, yet each cytokine has distinct properties in the way it regulates cell migration. These findings are likely to be of clinical relevance because multiple myeloma cells are located in an environment containing HGF and IGF-1 and are exposed to an SDF-1α gradient between the bone marrow and peripheral blood.


Quantitative evaluation for cervical foraminal bony stenosis based on angled sagittal slices along a nerve root on computed tomography.
Cervical foraminal canal stenosis is a common disease, but any relationships between the measurement values of cervical foraminal canals and clinical symptoms have yet to be explored. We aim to determine a numerical cutoff point of cervical foraminal bony canal size that does not lead to radiculopathy so as to establish criteria for the surgical indication. We reconstructed angled sagittal slices along a nerve root on computed tomography (CT) on a workstation from pre-operative CT data and measured 1152 cervical foraminal canals (144 patients) from Cervical (C) 4/5 to C7/Thoracic (Th) 1. We evaluated the relationship between the size of foraminal canals and clinical manifestations. Receiver operating characteristic (ROC) analysis was used to calculate cutoff points of each foraminal canal size with positive neurologic manifestations. Of the 144 patients' 1152 nerve roots, 286 nerve roots (24.8%) were diagnosed as radiculopathy by neurological examinations. The mean measured value of all foraminal canals on angled sagittal CT imagery was 3.39 ± 1.37 mm. The cutoff point of foraminal canal sizes without radiculopathy was 2.7 mm (sensitivity 0.680, specificity 0.591) overall. A cutoff point ascertained by quantitative evaluation of cervical foraminal canal size is useful for making diagnosis of cervical foraminal canal bony stenosis.


Dose decision of HSK7653 oral immediate release tablets in specific populations clinical trials based on mechanistic physiologically-based pharmacokinetic model.
HSK7653, an oral dipeptidyl peptidase-4 inhibitor administered every 2 weeks, is a candidate for the treatment of type 2 diabetes mellitus. The major elimination pathway of HSK7653 in vivo is renal excretion, and hepatic metabolism and fecal excretion of unchanged compound contribute less to the systemic clearance of HSK7653. Considering the disposition characteristics and the potential indication population of HSK7653, evaluating the HSK7653 exposure in patients with renal impairment and geriatric populations is a prerequisite for bringing more benefits to the patients. Here, a PBPK model was developed based on in vitro experimental results, such as dissolution, permeability, and metabolism, and the in vivo renal clearance, to evaluate the effects of physiological factors and food on HSK7653 exposure in specific populations, including adult and elder individuals with renal impairment and geriatric populations. Simulation results showed that the AUC of HSK7653 increased by 46%, 82%, and 129% in adult patients with mild, moderate, and severe renal impairment, and by 56%, 78%, and 101% in patients aged 65-75, 75-85 and 85-95 years, respectively. The AUC increased in the range of 62%-83%, 98%-133%, and 153%-195% in elderly patients (65-95 years) with mild, moderate, and severe renal impairment, respectively. Moreover, two different absorption model development methods (dissolution profile method and the diffusion layer model method) predicted that food had no effect on the exposure of the same simulated population. Since the predicted AUC of HSK7653 at the 10 mg dose in various specific populations was still within the relatively flat results of the exposure-response analysis, the 10 mg dose of HSK7653 was first used to explore the exposure in the renal impairment population (CTR20221952).


Preschoolers favor the creator's label when reasoning about an artifact's function.
The creator of an artifact, by virtue of having made the object, has privileged knowledge about its intended function. Do children recognize that the label an artifact's creator uses can convey this privileged information? 3- and 4-year-olds were presented with an object that looked like a member of one familiar artifact category, but which the speaker referred to with the label of a different familiar category (e.g. a key-like object was called a "spoon"). Children who heard the speaker refer to the object as something she made were more likely to assign its function on the basis of the anomalous label she used than those who heard it referred to as something the speaker found. Thus, even very young children expect a unique connection between the label the creator of an artifact uses and the function she intends it to have.


Gut microbiota controlling radiation-induced enteritis and intestinal regeneration.
Cancer remains the second leading cause of mortality, with nearly 10 million deaths worldwide in 2020. In many cases, radiotherapy is used for its anticancer effects. However, radiation causes healthy tissue toxicity as a side effect. In intra-abdominal and pelvic malignancies, the healthy bowel is inevitably included in the radiation field, causing radiation-induced enteritis and dramatically affecting the gut microbiome. This condition is associated with significant morbidity and mortality that impairs cancer patients' and survivors' quality of life. This Review provides a critical overview of the main drivers in modulating the gut microenvironment in homeostasis, disease, and injury, focusing on gut microbial metabolites and microorganisms that influence epithelial regeneration upon radiation injury.


The effects of embryonic hypoxic programming on cardiovascular function and autonomic regulation in the American alligator (Alligator mississippiensis) at rest and during swimming.
Reptilian embryos naturally experience fluctuating oxygen levels in ovo, and developmental hypoxia has been established to have long-term impacts on cardiovascular function in vertebrates. In the present study, we investigated the impact of developmental 21% (normoxia) and 10% O2 (hypoxia) on juvenile (4-year-old) American alligator cardiovascular function in animals at rest and during swimming. In both experimental groups, combined right aortic and right subclavian blood flow approximately doubled during swimming. Carotid blood flow increased during swimming in the hypoxia-programmed animals only, and both carotid and left aortic blood flow reached higher values in swimming hypoxic-programmed animals compared to the normoxic group. However, pulmonary blood flow, which increased two to threefold during swimming (in both groups), was higher in normoxic-programmed animals at both rest and swimming. The differences between programming groups were preserved after cholinergic blockade (atropine), but reduced by adrenergic receptor antagonists (propranolol and phentolamine). Propranolol and phentolamine also blunted the incremental increases in blood flows during swimming, which was especially clear in the hypoxia-programmed animals. Alteration in adrenergic control and relative cardiac size (which was increased in hypoxic-programmed alligators) may account for the differences between the experimental groups.


The risk of post-pill amenorrhea: a preliminary report from the Menstruation and Reproduction History Research Program.
Menstrual cycle lengths prior to and after oral contraceptive use were prospectively recorded for 245 women. In this preliminary study, a difference in the distributions in the pre- and post-pill cycle lengths was observed. An increase of 5 days in the medial cycle length occurred after oral contraceptive use had been discontinued. Although there was an approximately twofold relative risk of amenorrhea of 90 days' duration or more after discontinuing pill use, the differences in the rates of amenorrhea between the pre-pill and post-pill cycles were not statistically significant.


Sensitive cells: enabling tools for static and dynamic control of microbial metabolic pathways.
Natural metabolic pathways are dynamically regulated at the transcriptional, translational, and protein levels. Despite this, traditional pathway engineering has relied on static control strategies to engender changes in metabolism, most likely due to ease of implementation and perceived predictability of design outcome. Increasingly in recent years, however, metabolic engineers have drawn inspiration from natural systems and have begun to harness dynamically controlled regulatory machinery to improve design of engineered microorganisms for production of specialty and commodity chemicals. Here, we review recent enabling technologies for engineering static control over pathway expression levels, and we discuss state-of-the-art dynamic control strategies that have yielded improved outcomes in the field of microbial metabolic engineering. Furthermore, we emphasize design of a novel class of genetically encoded controllers that will facilitate automatic, transient tuning of synthetic and endogenous pathways.


Giving Doctors' Daily Progress Notes to Hospitalized Patients and Families to Improve Patient Experience.
Hospital quality includes excellent physician-patient communication. The objective was to determine effects of distributing physicians' notes to patients. Hospitalized patients or family members on 6 wards at a university hospital received daily a printed copy of their medical team's progress note. Surveys were completed about the benefits and adverse effects of reading the physician notes. In all, 74% to 86% of patients or family members responded favorably that receiving doctors' notes improved understanding of their health condition or gave them more control over their hospital course. Patient concerns about privacy or offense were uncommon, although 16% thought notes were confusing or caused worry. Note distribution had minor effects on physician note writing practice. Having patients and family members read their physicians' progress notes is feasible and enhances patients' understanding of their diagnostic and treatment plan. Notes supplement traditional physician-patient verbal communication practice and have the potential to improve the hospitalized patient experience.


Bilateral Girdlestone Procedure as a Treatment Modality in a Case of Complicated Adult-Onset Osteopetrosis: A Case Report.
We describe a nonambulatory 39-year-old man who presented with a diagnosis of osteopetrosis and ankyloses, having experienced bilateral fractures of his proximal femora, undergone unsuccessful conventional surgical interventions, and having developed chronic osteomyelitis of his right proximal femur. Bilateral Girdlestone procedures were performed. Postoperative range of hip motion and Harris hip scores improved, and he became ambulatory, achieving optimal function considering the circumstances at 12 months postoperatively. Although the indications of the bilateral Girdlestone procedure remain undefined, these procedures may constitute acceptable treatment in patients with osteopetrosis with ankylosis and chronic osteomyelitis of the proximal femur.


Depressive symptoms among older adults: long-term reduction after a physical activity intervention.
We examined the effects of two physical activity modes on depressive symptoms over a 5-year period among older adults and change in physical self-esteem as a mediator of changes in depressive symptoms. Formerly sedentary, older adults (N = 174) were randomly assigned into 6-month conditions of either walking or low-intensity resistance/flexibility training. Depressive symptoms and physical self-esteem were measured before and after the 6-month intervention, and 12 and 60 months after intervention initiation. Depressive symptoms scores were decreased immediately after the intervention, followed by a sustained reduction for 12 and 60 months after intervention initiation; there was no differential pattern of change between the physical activity modes. Change in physical self-esteem predicted change in depressive symptoms. This study supports the effectiveness of an exercise intervention for the sustained reduction of depressive symptoms among sedentary older adults and physical self-esteem as a potential mediator of this effect.


Typical leptin fall is mitigated by breastfeeding in female infants.
Programming of the nutritional and hormonal status of offspring occurs mostly during the gestational and breastfeeding periods. Several studies have reported that breastfed children are more protected from developing obesity in adult life; however, the mechanism that explains this phenomenon is not clear. We undertook this study to evaluate if weight, gender or feeding mode (breastfed or formula-fed) affects leptin levels (during the first 3 months after birth) in a cohort of term newborns, the Breastfeeding Cohort. A cohort of 99 term newborns divided into four groups according to gender and feeding type: breastfed female, formula-fed female, breastfed male and formula-fed male were studied. Feeding mode was freely chosen by the parents. Blood sampling for glucose, insulin and leptin was performed at birth and after 3 months. No differences were found among the groups for maternal age, marital status, educational and socioeconomic level, maternal occupation, and prenatal care. No statistically significant differences were found for weight, length or body mass index at birth among the four groups. There were differences in leptin with a higher level in girls (0.907 ± 0.332) than boys (0.663 ± 0.351; p <0.001) at birth and at 3 months (0.618 ± 0.225, 0.464 ± 0.195; p <0.0001). A decrease in leptin levels from birth to 3 months was observed in all groups with the exception of breastfed females (0.849 ± 0.352-0.672 ± 0.222, p = NS). In our study, breastfed females were protected from this fall in serum leptin levels. Our findings support further studies on the long-term effects of breastfeeding.


Transition metal dichalcogenide electrodes with interface engineering for high-performance hybrid supercapacitors.
Transition metal dichalcogenides (TMDCs) have been explored in recent years to utilize in electronics due to their remarkable properties. This study reports the enhanced energy storage performance of tungsten disulfide (WS2) by introducing the conductive interfacial layer of Ag between the substrate and active material (WS2). The interfacial layers and WS2 were deposited through a binder free method of magnetron sputtering and three different prepared samples (WS2 and Ag-WS2) were scrutinize via electrochemical measurements. A hybrid supercapacitor was fabricated using Ag-WS2 and activated carbon (AC) since Ag-WS2 was observed to be the most proficient of all three samples. The Ag-WS2//AC devices have attained a specific capacity (Qs) of 224 C g-1, while delivering the maximum specific energy (Es) and specific power (Ps) of 50 W h kg-1 and 4003 W kg-1, respectively. The device was found to be stable enough as it retains 89% capacity and 97% coulombic efficiency after 1000 cycles. Additionally, the capacitive and diffusive currents were obtained through Dunn's model to observe the underlying charging phenomenon at each scan rate.


Psychometric Evaluation of the Moral Comfort Questionnaire.
Background and Purpose: The ethical challenges of the COVID-19 pandemic have contributed to an increase in moral distress (MD) in nurses-a long-standing, ubiquitous issue in nursing-highlighting its detrimental impact on nurses, patients, and healthcare organizations. MD is the negative outcome of a moral situation or dilemma in which a nurse is prevented from taking action on ethical decisions usually related to organizational constraints. On the opposite end of the spectrum, moral comfort (MC), an emerging concept in nursing, is an individual's feelings of ease with decisions and actions related to a moral dilemma or the positive outcome of a moral situation or dilemma. However, nursing literature on MC is sparse. While several instruments to measure MD exist, an instrument to measure MC was not found. The MC Questionnaire (MCQ) was theoretically developed. The purpose of this study was to conduct a psychometric evaluation of the new 35-item MCQ. Methods: Psychometric evaluation design was used. Reliability testing consisted of the examination of internal consistency (Cronbach's alpha values) and stability (test-retest reliability: Spearman's correlation coefficient, weighted Kappa, and Bland-Altman [B&A] analysis). Validity was examined using content validity (content expert evaluation) and discriminant validity (r < .30). Model fit of a proposed five-factor model was tested using confirmatory factor analysis (CFA). Results: Hospital-based direct-care (HB-DC) RNs (n = 466) participated from February 2019 to September 2019 in this Institutional Review Board-approved study. Participants completed demographic information, the MCQ, and the Moral Distress Scale-Revised (MDSR). The psychometric evaluation included a priori content validation and multiple statistical analyses: Cronbach's alpha, Spearman's correlation coefficient, weighted Kappa, B&A, discriminant validity, and CFA. Cronbach's alpha was .951, suggesting internal consistency. Spearman's correlation coefficient was 0.605 (p < .001), suggesting a strong correlation between Time 1 and Time 2. Weighted Kappa values for each item (range = .139-.559) suggested slight to moderate agreement between responses over time. The B&A plot suggested agreement of responses over time. Discriminant validity results suggested no correlation between the MCQ and MDSR (r = -.219), which was expected. CFA results suggest a poor model fit of the proposed five-factor model. A post hoc hierarchical cluster analysis showed the presence of two clusters. A subsequent two-factor exploratory factor analysis showed items loading onto one of the two factors (internal and external). Conclusions: MC in nurses is essential to promoting positive outcomes for nurses. An instrument to measure MC in nurses is needed to gain a further understanding of the concept. The MCQ was theoretically developed and psychometrically evaluated. Results suggest the validity and reliability of the MCQ with further testing of a two-factor model. Knowledge acquired from studies using the MCQ could potentially be used to develop strategies to promote MC in nurses, thereby promoting positive outcomes for nurses, patients, and healthcare organizations.


Use of a maternity support binder for relief of pregnancy-related back pain.
To examine the feasibility, acceptability, and effectiveness of a support binder for low back pain in pregnancy. Pilot study, using a prospective, two-group design with repeated measures. Ambulatory maternity clinic in a tertiary care teaching hospital. Women of at least 20 weeks gestation with low back pain, but no preexisting back or disc disease. Thirty women assigned to the intervention group and 10 to a comparison group. Participants completed a pain assessment at pretest. Intervention participants received a maternity support binder to wear while awake for 2 weeks. At an appointment 2 weeks later, a posttest questionnaire and a taped interview were administered. The comparison group participants received the support binder after the second appointment. Back pain intensity, duration, and effect on daily activities were assessed using a pain in pregnancy questionnaire. The intervention group had significant reduction in mean pain scores and effect of pain on daily activities, including family, house and yard, recreational, exercise, and sleep. Interaction of group by time was significant for change in pain and effect on family, house and yard, and exercise activities. The use of a support binder for pregnancy-related low back pain is a promising intervention and was well-accepted by the participants.


Discontinuity of care for mothers with chronic hepatitis B diagnosed during pregnancy.
Assiduous measures are taken to prevent perinatal transmission of hepatitis B virus (HBV) to infants; it is unclear whether the mothers receive appropriate care for their chronic HBV. We sought to assess the quality of HBV care in hepatitis B surface antigen (HBsAg)-positive mothers following pregnancy. HBsAg-positive women (n = 243) who had sought prenatal care at Massachusetts General Hospital were retrospectively identified and charts reviewed. The primary outcome was adherence to the American Association for the Study of Liver Diseases (AASLD) and American College of Obstetricians and Gynecologists guidelines. Over one-third (37%) of women were first diagnosed with HBV infection at a prenatal visit. One-third (32%) did not undergo timely liver function test measurements. HBV DNA was never measured in 26% and was untimely in 34% of patients. One-third (34%) of the women were at high-risk for HCC based on AASLD criteria, yet only 33% of these women underwent timely imaging. Nearly half (49%) never saw a liver specialist for their HBV care. In multivariate analysis, women were 3.7 times more likely to have a timely ALT and 8.1 times more likely to have a timely HBV DNA if they were followed by a liver specialist (P = 0.001, <0.001). We demonstrate remarkably inadequate and discontinuous HBV care for chronically infected mothers following pregnancy. As HBV infection is already being identified prenatally, quality improvement measures encompassing obstetricians, primary care providers and hepatologists are needed to ensure that HBV-infected women are linked to care postpregnancy.


Prenatal and Infancy Nurse Home Visiting and 18-Year Outcomes of a Randomized Trial.
Given earlier effects found in randomized clinical trials of the Nurse-Family Partnership, we examined whether this program would improve 18-year-old first-born youths' cognition, academic achievement, and behavior and whether effects on cognitive-related outcomes would be greater for youth born to mothers with limited psychological resources (LPR) and on arrests and convictions among females. We enrolled 742 pregnant, low-income women with no previous live births and randomly assigned them to receive either free transportation for prenatal care plus child development screening and referral (control; n = 514) or prenatal and infant home nurse visit (NV) plus transportation and screening (n = 228). Assessments were completed on 629 18-year-old first-born offspring to evaluate these primary outcomes: (1) cognitive-related abilities (nonverbal intelligence, receptive language, and math achievement) and (2) behavioral health (internalizing behavioral problems, substance use and abuse, sexually transmitted infections, HIV risk, arrests, convictions, and gang membership). Compared with control-group counterparts, NV youth born to mothers with LPR had better receptive language (effect size = 0.24; 95% confidence interval [CI]: 0.00 to 0.47; P = .05), math achievement (effect size = 0.38; 95% CI: 0.14 to 0.61; P = .002), and a number of secondary cognitive-related outcomes. NV females, as a trend, had fewer convictions (incidence ratio = 0.47; 95% CI: 0.20 to 1.11; P = .08). There were no intervention effects on other behaviors. The program improved the cognitive-related skills of 18-year-olds born to mothers with LPR and, as a trend, reduced female convictions but produced no other effects on youth behavioral health.


Acute hypoxia stress induced abundant differential expression genes and alternative splicing events in heart of tilapia.
Hypoxia is one of the critical environmental stressors for fish in aquatic environments. Although accumulating evidences indicate that gene expression is regulated by hypoxia stress in fish, how genes undergoing differential gene expression and/or alternative splicing (AS) in response to hypoxia stress in heart are not well understood. Using RNA-seq, we surveyed and detected 289 differential expressed genes (DEG) and 103 genes that undergo differential usage of exons and splice junctions events (DUES) in heart of a hypoxia tolerant fish, Nile tilapia, Oreochromis niloticus following 12h hypoxic treatment. The spatio-temporal expression analysis validated the significant association of differential exon usages in two randomly selected DUES genes (fam162a and ndrg2) in 5 tissues (heart, liver, brain, gill and spleen) sampled at three time points (6h, 12h, and 24h) under acute hypoxia treatment. Functional analysis significantly associated the differential expressed genes with the categories related to energy conservation, protein synthesis and immune response. Different enrichment categories were found between the DEG and DUES dataset. The Isomerase activity, Oxidoreductase activity, Glycolysis and Oxidative stress process were significantly enriched for the DEG gene dataset, but the Structural constituent of ribosome and Structural molecule activity, Ribosomal protein and RNA binding protein were significantly enriched only for the DUES genes. Our comparative transcriptomic analysis reveals abundant stress responsive genes and their differential regulation function in the heart tissues of Nile tilapia under acute hypoxia stress. Our findings will facilitate future investigation on transcriptome complexity and AS regulation during hypoxia stress in fish.


The associations between academic stress and depression among college students: A moderated chain mediation model of negative affect, sleep quality, and social support.
Growing competition in tight job market and academic excellence as a social norm in Asian culture have made Chinese college students burdened with immense academic stress. This study aimed to explore the associations between academic stress and depression, and the mediating roles of negative affect and sleep quality, as well as the moderating role of social support in the relationship between negative affect and sleep quality. A convenience sample of 221 male and 479 female college students aged between 17 and 25 completed questionnaires on academic stress, depression, negative affect, sleep quality and social support. Results indicated that academic stress could not only directly affect depression (b = 0.31, p < 001), but also affect depression through the mediation role of negative affect and sleep quality. The chain mediating effects includes three paths, namely, the mediating role of negative affect (indirect effect = 0.21, percentage of total effect = 69.58 %), the mediating role of sleep quality (indirect effect = 0.06, percentage of total effect = 21.03 %), and the chain mediating role of negative affect and sleep quality (indirect effect = 0.06, percentage of total effect = 19.86 %). Social support moderated the adverse influence of negative affect on sleep quality. Social support decreases the impact of negative affect on sleep quality. Specifically, the association between negative affect and sleep quality was stronger for college students with low (bsimple = 0.44, p < 0.001) social support than those with high (bsimple = 0.32, p < 0.001) social support. The results advanced our understanding of how academic stress affects college students' depression. These findings provide implications on the cultivation of stress coping strategies, promotion of emotion regulation skills, exaltation of sleep quality, and improvement of the social support level aiming for future depression preventions and interventions. Specific measures include setting up psychological health courses, teaching emotion management strategies, and establishing web-based programme steming from acceptance and commitment therapy. It should be noted that the cross-sectional design means the causal associations among the variables could not be determined.


[Perindopril and losartan attenuate intrahepatic Toll-like receptor 4 protein expression in rats with bile duct ligation-induced hepatic fibrosis].
To investigate the expression of Toll-like receptor 4 (TLR4) in the liver tissue of rats with bile duct ligation (BDL)-induced hepatic fibrosis and evaluate the inhibitory effects of perindopril and losartan on TLR4 expression. Male Wistar Rats were randomly divided into sham-operated group (n=6), BDL group, perindopril treatment group (2 mg/kg) and losartan treatment group (50 mg/kg) (n=12). Perindopril and losartan groups were further divided into two subgroups for corresponding treatments by gastric lavage once daily for 14 and 30 days. The protein level of TLR4 in the liver tissue was examined by Western blotting. In 14-day BDL group, the protein level of TLR4 significantly increased to 6.53∓1.11 folds of that in the sham group (P<0.05), and was lowered significantly to 1.71∓0.41 folds and 0.95∓0.38 folds following perindopril and losartan treatments for 14 days. TLR4 expression significantly increased to 6.51∓0.87 folds and 5.64∓0.87 folds of that of the sham group in perindopril and losartan groups after the 30-day treatments (P<0.05). TLR4 expression is up-regulated in the liver of rats with BDL-induced hepatic fibrosis, and can be lowered by perindopril and losartan treatmemts for 14 days.


Beneficial Effect of Carotid Artery Stenting on Cerebral Hemodynamic Impairment and Cognitive Function.
The aim of this study was to evaluate the effects of the carotid artery stenting (CAS) procedure on cerebral hemodynamics and cognitive performance in patients with internal carotid artery stenosis. In this prospective observational study, 16 consecutive patients in a single institute were treated with CAS from 2010 to 2011 (71.7 ± 7.3 years old, 12 males, and six left-sided procedures). Before and after the CAS procedure, all patients were evaluated with single photon emission computed tomography using 123I-iodoamphetamine and acetazolamide as well as the Weschler Adult Intelligent Scale (WAIS) to assess three intelligent quotients and four indexes. Patients with decreased preprocedural cerebral blood flow (CBF) and cerebrovascular reserve (CVR) experienced significant increases in CBF and CVR (P = 0.01 and 0.03). Twelve (75%) patients experienced a significant increase in one or more WAIS scores, while two (13%) showed a significant decrease. The most frequently improved scores were the Working Memory Index and Processing Speed Index (seven patients/44%). Preprocedural CBF was significantly correlated with the Full-scale and Performance Intelligent Quotients (r = 0.51-0.56, P = 0.02-0.04), and patients who experienced a significant increase in these scores had larger increases in CVR than patients with unchanged scores (P = 0.0097-0.019). These results indicate that the CAS procedure improved impaired cerebral hemodynamics and might benefit the cognitive function of patients with internal carotid artery stenosis related to impaired cerebral hemodynamics.


Anti-PF4 antibodies associated with disease severity in COVID-19.
Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)-polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.


Women's attitudes toward testing for fragile X carrier status: a qualitative analysis.
Fragile X syndrome (FXS) is primarily due to a repeat expansion mutation found in the FMR1 X-linked gene. We have conducted a qualitative analysis of responses from women concerning their attitudes toward testing for carrier status of the fragile X mutation among reproductive-age women. We obtained responses from focus groups including women with and without FXS in their families. We found the following themes: (1) mothers of children with FXS have difficulty formulating their opinions on population screening because of their unique experiences surrounding their own carrier diagnosis and their relationship with their children with FXS, (2) the motivation for carrier testing and need for information differ by family history of FXS and parental status, and (3) the timing of carrier testing with respect to a woman's life stage dictates whether carrier information will be viewed as beneficial or detrimental. There was evidence that non-carrier women from the general population would be wholly unprepared for positive carrier results. These findings have significant implications for genetic counseling as well as for population screening.


Remnants of normal tissue in polycystic disease of the liver. A cause for difficulty in the interpretation of indium-111 white blood cell study.
On In-111 WBC images, diffuse homogeneous uptake of the radiopharmaceutical should be present throughout the liver. The authors present a case of a febrile patient with polycystic liver disease in whom the normal diffuse uptake was not seen. Instead, the images demonstrated focal areas of uptake, which suggested infection. Tc-99m SC liver spleen scintigraphy demonstrated the In-111 WBC foci to correspond to areas of residual normal parenchyma. The patient underwent laparotomy and liver transplantation and no abscesses were found. Pathologic examination of the liver revealed multiple uninfected cysts and residual normal parenchyma in the caudate lobe, corresponding to the findings on scintigraphy.


Postnatal maturation of neurons in the cat's lateral geniculate nucleus.
The maturation of dendrites in the cat's dorsal lateral geniculate nucleus was studied in Golgi Kopsch preparations of kittens from 3 days to 8 weeks postnatal. During the first postnatal week, more than a month after their birthdate, cells are immature and lack dendrites, bearing only multiple somatic processes or a few short thick extensions. Cells enter an active phase of dendritic extension during the second postnatal week. Growth cone-like structures and filopodia occur at the ends of dendrites and also at dendritic branch points. Assignment to general cell classes based on dendritic disposition is possible only after this period, and characteristic grapelike appendages are obvious after the third week. Mature cells in the lateral geniculate nucleus are not considered spiny, yet spines and hairs are ubiquitous on most cells once dendrites elongate and remain numerous on peripheral dendrites even after the soma and proximal dendrites become smooth, by 4-6 weeks. The decline of spine levels continues after this period. All cells go through a similar but nonsynchronous sequence of maturation. Large cells may mature first, but no correlation was noted between rate of maturation and laminar location or retinal representation. In the second and third postnatal weeks, although the terminal arbors of retinal axons presynaptic to geniculate cells have already attained their final topography and laminar placement, the shape and synaptic relations of axon terminal swellings remain immature (Mason, '82a,b) through the most active phase of dendritic outgrowth. After 3 weeks, both retinal axons and target geniculate cell dendrites finalize the shapes of characteristics appendages and synaptic relations in tandem. Potential interactions between immature axon terminal arbors and dendrite-bare geniculate cells during dendrite outgrowth and subsequent remodeling of structural details are discussed.


Secondary metabolites isolated from Penicillium christenseniae SD.84 and their antimicrobial resistance effects.
A pair of new quinolone alkaloid enantiomers, (Ra)-(-)-viridicatol (1) and (Sa)-(+)-viridicatol (4), and seven known compounds, namely, 2, 3 and 5-9, were isolated from Penicillium christenseniae SD.84. The structures of 1 and 4 were determined using NMR and HRESIMS data. Theoretical calculations through CD and ECD confirmed 1 and 4 as a pair of enantiomers. The MIC values of 4 against Staphylococcus aureus and methicillin-resistant S. aureus were 12.4 and 24.7 μM, respectively, compound 1 had no inhibitory activity. Antimicrobial assays of 2, 3, and 5-7 showed a moderate activity against S. aureus and methicillin-resistant S. aureus. This study demonstrated the remarkable potential of Penicillium sp. to produce new drug-resistant leading compounds, thereby advancing the mining for new sources of antimicrobial agents.


Mindfulness mediates the relation between disordered eating-related cognitions and psychological distress.
The present study investigated whether mindfulness mediates the relation between disordered eating-related cognitions and negative psychological outcomes within a non-clinical college sample. Disordered eating-related cognitions were positively associated with general psychological ill-health and emotional distress in interpersonal contexts and inversely related to mindfulness. Mindfulness, which was also inversely related to general psychological ill-health and emotional distress, was found to partially mediate the relations between disordered eating-related cognitions and the two predicted variables.


Event-related potentials reflecting smoking cue reactivity and cognitive control as predictors of smoking relapse and resumption.
Given that most attempts to quit smoking fail, it is critical to increase knowledge about the mechanisms involved in smoking relapse and resumption (i.e., the increase in smoking over time after a quit attempt). Neurocognitive measures, such as event-related potentials (ERPs), may provide novel insights into smoking relapse and resumption. The objective of the present study is to investigate the association between smoking relapse and resumption and ERPs reflecting smoking cue reactivity (i.e., P300, LPP), inhibitory control (i.e., N2, P3), and error processing (i.e., error-related negativity (ERN), Pe). Seventy-two smokers viewed smoking and neutral pictures and performed a Go-NoGo and an Eriksen Flanker task, while ERPs were measured using electroencephalography. All smokers started a quit attempt in the week following the laboratory visit. Smoking behavior after the quit attempt was measured at 4, 8, and 12 weeks. Both relapse (i.e., 7-day point prevalence at 12 weeks) and smoking resumption (i.e., the number of cigarettes a day at 4, 8, and 12 weeks) were used as outcome measures. Logistic regression analyses showed that smaller P3 amplitudes, reflecting brain activation associated with inhibitory control, are related to an increased relapse risk. Latent growth curve analyses showed that reduced post-error slowing, the main behavioral measure reflecting error processing, is associated with stronger smoking resumption. ERPs reflecting smoking cue reactivity were unrelated to smoking relapse or resumption. The finding that smaller inhibitory control-related P3 amplitudes are associated with increased relapse risks suggests that strategies to increase inhibitory control in smokers are worth further investigation in the search for more effective smoking cessation interventions.


[Principles of medical and trace examinations in expert evaluation of transport accident traumas based on roentgenological methods].
Airtraffic and car traumas illustrate possibilities of x-ray methods in expert examination of transport trauma. X-ray data is most important in clarification of traumatic mechanisms and defects on the clothes of the victims which point to the accident details. Further accumulation of the material will allow introduction of more precise assays of the signs assessment.


Pharmacokinetics and effect of food after oral administration of prolonged-release tablets of ropinirole hydrochloride in Japanese patients with Parkinson's disease.
Ropinirole hydrochloride, a dopamine receptor agonist with a non-ergot alkaloid structure, is highly selective for the dopamine D(2) /D(3) receptors. This study was conducted to evaluate the steady-state pharmacokinetics, safety and efficacy after repeated oral administration of prolonged-release tablets of ropinirole hydrochloride in the absence of L-dopa preparations in Japanese patients with Parkinson's disease (PD). This was a multicenter, open-label, uncontrolled study. The total duration of participation in the study ranged from 56 to 63 weeks. In the study, the plasma concentrations of ropinirole, its major metabolite SK&F104557 (N-depropyl ropinirole) and another metabolite SK&F89124 (ropinirole hydroxylated at the seventh position of the indole ring) were assessed. Safety based on adverse events, haematology, biochemistry, urinalysis and electrocardiography (ECG) (standard 12-lead ECG) were evaluated, and vital signs (blood pressure/pulse rate) were measured. Efficacy based on the Japanese version of Unified Parkinson's Disease Rating Scale (UPDRS) Parts III (motor) and II [activities of daily living (ADL)] as well as tolerability was evaluated. After repeated oral administration of prolonged-release tablets of ropinirole hydrochloride in Japanese patients with PD, ropinirole, SK&F104557 and low levels of SK&F89124 were detected in plasma. The trough concentrations of ropinirole and the two metabolites increased in proportion to the dose when ropinirole hydrochloride prolonged-release tablets were administered at doses ranging from 2 to 16 mg/day. The plasma exposure to ropinirole and its two metabolites after intake of normal diet was comparable to that in the fasting state. The most common adverse events (10% or more) were somnolence, nausea, constipation, hallucination and nasopharyngitis. Most adverse events were mild or moderate in severity, and with no death. During the treatment period, serious adverse events were reported in five patients. Efficacy analysis (LOCF) at the final endpoint up to week 16 demonstrated a mean (SD) change from baseline in the Japanese UPDRS III (motor) and II (ADL) scores of -11·3 (8·21) and -3·9 (3·22), respectively, and thereafter remained at similar levels until week 52. After administration of prolonged-release tablets of ropinirole hydrochloride in the absence of L-dopa preparations in Japanese patients with PD, the plasma pharmacokinetics of ropinirole and its metabolites was linear and not affected by food. Compared with the immediate-release (IR) tablet, the prolonged-release tablet can be administered to Japanese patients with PD at a reduced daily dose frequency and adjusted to the maintenance dose after fewer dose changes with a smaller diurnal variation in the plasma ropinirole concentration.


Is HEADS in our heads? Health risk behavior is not routinely discussed with young people with chronic conditions.
Outpatient clinic visits are a window of opportunity to address health risk behaviors and promote a healthier lifestyle among young people. The HEADS (Home, Education, Eating, Activities, Drugs [i.e. substance use including tobacco, alcohol, and illegal drugs], Sexuality [including contraception], Safety, Self-harm) interview is a feasible way of exploring health risk behaviors and resilience. The purpose of this study was to evaluate how often HEADS topics were addressed according to young patients and staff in pediatric and adult outpatient clinics. We conducted a questionnaire survey among young patients and health care professionals at a tertiary university hospital. Young patients reported on their cumulative experience and staff reported on their usual practice. A total of 290 young patients aged 12-22 years (78% having a chronic condition) and 97 health care professionals participated. We found only small reported differences between staff and young patients regarding whether home, education, and activity were addressed. However, staff reported twice the rate of addressing smoking, alcohol, illegal drugs, sexuality, and contraception compared to young patients. Young patients reported that smoking, alcohol, illegal drugs, sexuality, and contraception were addressed significantly more at adult clinics in comparison to pediatric clinics. After controlling for age, gender and duration of illness, according to young patients, adjusted odds ratios for addressing smoking at adult vs. pediatric clinics was 2.47 (95% confidence interval [CI]: 1.26-4.83), alcohol 2.84 (95% CI:1.45-5.57), illegal drugs 4.20 (95% CI:1.69-10.44), sexuality 3.54 (95% CI: 1.67-7.50), contraception 3.68 (95% CI:1.61-8.41), and any of the above 2.95 (95% CI: 1.47-5.91). According to young patients, smoking, alcohol, illegal drugs, sexuality, and contraception were not routinely addressed at a tertiary hospital, and especially at paediatric clinics, these issues were seldom addressed.


No fever, no malaria ? A diagnostic challenge in an immunocompromised patient.
We describe the case of an immunosuppressed women with proven malaria tropicana. Fever was not reported with this patient. We conclude that the concept of using fever as a primary surrogate indicator for the presence of malaria should be used with caution in patients with complex immunosuppression.


Angiographic prostatic arterial anatomy in a Turkish population with benign prostatic hyperplasia
Prostatic artery embolization (PAE) is a minimally invasive effective method in the treatment of benign prostatic hyperplasia (BPH). The procedure is technically challenging, as pelvic vascular anatomy is highly prone to variations and the identification of the prostatic artery (PA) is the most time-consuming step, which can lead to increased procedure times. The aim of this study was to categorize the anatomic variations in the prostatic supply in patients with BPH treated with PAE. The digital subtraction angiography findings of 68 PAE procedures were reviewed retrospectively and the age, PA origin, number, and procedure of the patients were recorded. The origin of the PA was classified into 5 subtypes using the de Assis/ Carnavale classification. The incidence of each anatomic type was calculated. In the 68 PAE procedures, 119 pelvic sides were analyzed and a total of 119 PAs were classified. The most common origin was type 1 (n = 43, 36.1%), with the PA originating from the anterior division of the internal iliac artery (IIA), from a common trunk with the superior vesical artery. This was followed by type 4 (n = 34, 28.6%), with the PA originating from the internal pudendal artery; type 3 (n = 22, 18.5%), with the PA originating from the obturator artery; and type 2 (n = 13, 10.9%), with the PA originating from the anterior division of the IIA. Anatomic variations are common in the IIA and PA, showing racial and individual differences. Following a standard classification system to identify the origin of the PA is crucial and being aware of the most common types in each population will make PAE a faster and safer procedure.


Dealing with sand in the Arctic city of Nadym.
Sand plays an important role in the Arctic urban development as construction material and stable ground. Significance of its studies increases in face of permafrost degradation and coastal erosion and for understanding human capacities to restore natural landscapes after anthropogenic disturbances. This paper examines changing human interactions with sand in the city of Nadym, northwest of Siberia. The study utilizes an interdisciplinary approach which includes remote sensing and GIS analysis, field observations, and interviews with local residents and stakeholders. Analysis of spatial and social characteristics of sand demonstrates different roles of sand as part of the landscape, a resource, and as a mediator in urban and infrastructure development. Understanding the diversity of sand qualities, its uses, and perceptions is relevant for studies of landscape disturbances, resilience, vulnerability, and adaptive capacities of Arctic cities.


Modern scientific methods and their potential in wastewater science and technology.
Application of novel analytical and investigative methods such as fluorescence in situ hybridization, confocal laser scanning microscopy (CLSM), microelectrodes and advanced numerical simulation has led to new insights into micro- and macroscopic processes in bioreactors. However, the question is still open whether or not these new findings and the subsequent gain of knowledge are of significant practical relevance and if so, where and how. To find suitable answers it is necessary for engineers to know what can be expected by applying these modern analytical tools. Similarly, scientists could benefit significantly from an intensive dialogue with engineers in order to find out about practical problems and conditions existing in wastewater treatment systems. In this paper, an attempt is made to help bridge the gap between science and engineering in biological wastewater treatment. We provide an overview of recently developed methods in microbiology and in mathematical modeling and numerical simulation. A questionnaire is presented which may help generate a platform from which further technical and scientific developments can be accomplished. Both the paper and the questionnaire are aimed at encouraging scientists and engineers to enter into an intensive, mutually beneficial dialogue.


The potential in bioethanol production from waste fiber sludges in pulp mill-based biorefineries.
Industrial production of bioethanol from fibers that are unusable for pulp production in pulp mills offers an approach to product diversification and more efficient exploitation of the raw material. In an attempt to utilize fibers flowing to the biological waste treatment, selected fiber sludges from three different pulp mills were collected, chemically analyzed, enzymatically hydrolyzed, and fermented for bioethanol production. Another aim was to produce solid residues with higher heat values than those of the original fiber sludges to gain a better fuel for combustion. The glucan content ranged between 32 and 66% of the dry matter. The lignin content varied considerably (1-25%), as did the content of wood extractives (0.2-5.8%). Hydrolysates obtained using enzymatic hydrolysis were found to be readily fermentable using Saccharomyces cerevisiae. Hydrolysis resulted in improved heat values compared with corresponding untreated fiber sludges. Oligomeric xylan fragments in the solid residue obtained after enzymatic hydrolysis were identified using matrix-assisted laser desorption ionization-time of flight and their potential as a new product of a pulp mill-based biorefinery is discussed.


Sunitinib-induced nephrotic syndrome and irreversible renal dysfunction.
Sunitinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFRs), has become essential for treating imatinib-resistant malignant gastrointestinal stromal tumor. Recently, several cases have been reported that showed proteinuria and kidney dysfunction to be associated with anti-VEGF therapy. Although previous reports indicated that this side-effect is reversible, it is not well understood. We present here the case of a 72-year-old man who presented with nephrotic syndrome and renal dysfunction 6 months after administration of sunitinib. Sunitinib was discontinued, and nephrotic syndrome remitted spontaneously, but renal function recovery was limited. Nine months later, a renal biopsy was performed because sunitinib was again required and pathological examination was needed. The renal biopsy showed marked endothelial cell injury with focal segmental glomerulosclerosis and accelerated VEGF expression by podocytes. Sunitinib was then given at a reduced dose. Kidney dysfunction and nephrotic syndrome are rare but serious complications of sunitinib. The present case suggests that long-term treatment with a high dose of sunitinib can cause irreversible renal dysfunction, and that low-dose treatment makes these side-effects manageable.


Regulatory T cells stay on course.
Regulatory T (Treg) cells are thought to be susceptible to conversion into effector T cells. In this issue of Immunity, Miyao et al. (2012) provide evidence that the apparent plasticity of murine Foxp3(+) Treg cells is largely restricted to a defined subset of poorly committed Foxp3(+) cells.


Intraoral minor salivary gland tumors: a review of 75 cases in a Libyan population.
Minor salivary gland carcinomas are uncommon but most often occur in the oral cavity, particularly the hard palate. Dental examination may provide an opportunity for early detection. During the period of 1977-2000 a group of 75 patients (31 males and 44 females, median age 44.2 years and range 15-86 years) with minor salivary gland tumors were diagnosed, based on the 1991 WHO classification. The peak occurrence of the tumors was in the fifth decade for males and sixth decade for females. The frequency of benign tumors was 38.6% (n = 29) and malignant tumors 61.3% (n = 46). Pleomorphic adenoma was the most common histological type of benign tumor identified whereas mucoepidermoid carcinoma and adenoid cystic carcinoma were the most common malignant tumors. The most common primary location of the tumors was the palate followed by the cheek. A benign tumor usually presented as an asymptomatic swelling and ulceration, pain being more frequently associated with the malignant tumors. This study shows that intraoral tumors of minor salivary glands vary widely in presentation, and should be taking into account by medical and dental practitioners in any differential diagnosis when assessing intraoral pathology. Any lesion arising from the hard palate (the most common site in this series) should be considered as a possible minor salivary gland tumor. Referral to a multidisciplinary head and neck clinic following diagnosis is strongly recommended.


Assessing the relation of USDA conservation expenditures to suspended sediment reductions in an Iowa watershed.
From 1936 to 2010, U.S. Department of Agriculture (USDA) agencies spent $293.7 billion (value adjusted for inflation at the 2009 level) on conservation programs. Of these expenditures, $75.2 billion (26%) were allocated for technical assistance (TA; it is related to costs associated with USDA field staff providing their expert advice to farmers) and $218.5 billion (74%) for financial assistance (FA; monetary incentives for farmers to adopt conservation programs). A major environmental goal of these programs was to reduce soil erosion and sediment leaving the land. In this study, we correlate expenditures on FA and TA programs to a unique long (1937-2009) record of total suspended solids (TSS) and sediment load (SL) for the Raccoon River at Van Meter, Iowa. Study results suggest that three predictors (rainfall, TA and FA) are important in explaining the temporal changes in annual TSS and SL and provide evidence that USDA expenditures helped reduce TSS and SL in the Raccoon River. TA was more effective than FA in reducing TSS levels in the watershed. Our empirical model represents an initial, broad-scale attempt to correlate conservation expenditures to a specific water quality outcome, although more work is needed to disentangle the impacts associated with other unexplored factors.


Epigenetics of inflammation in hypothalamus pituitary gonadal and neuroendocrine disorders.
The hormone producing hypothalamus, pituitary and gonadal are arranged in hierarchy to form the hypothalamic-pituitary-gonadal axis (HPG axis). The axis is neuroendocrine in nature and releases hormones in response to the inputs from nervous systems. The axis maintains homeostasis and ensures smooth body functions, particularly those related to growth and reproduction. A deregulated HPG axis, such as observed under inflammation and other conditions, is therefore associated with several disorders such as polycystic ovary syndrome, functional hypothalamic amenorrhea etc. Several factors, both genetic as well as environmental, in addition to aging, obesity etc. affect HPG axis with resulting effects on puberty, sexual maturation and reproductive health. More research is now indicative of a role of epigenetics in mediating these HPG-affecting factors. Hypothalamus-secreted gonadotropin-releasing hormone is important for eventual release of sex hormones and it is subjected to several neuronal and epigenetic regulations. Gene promoter methylation as well as histone methylations and acetylations form the backbone of epigenetic regulation of HPG-axis, as the incoming reports suggest. Epigenetic events also mediate several feedback mechanisms within HPG axis and between HPG axis and the central nervous system. In addition, data is emerging for a role of non-coding RNAs, particularly the miRNAs, in regulation and normal functioning of HPG axis. Thus, the epigenetic interactions need better understanding to understand the functioning and regulation of HPG axis.


Divergent role of abiotic factors in shaping microbial community assembly of paocai brine during aging process.
Microbial communities in fermented food are shaped by a myriad of abiotic factors. The respective roles of abiotic factors in shaping the dynamic bacterial community of paocai during aging remain unclear. In the present study, 100 paocai samples (pH: 2.95-5.23; NaCl content: 0.13-15.41%; total acid: 6.61-18.33 mg/mL; total sugars: 7.96-487.90 μg/mL; total viable count: 3.55-8.99 LogCFU/mL; aging time: 5 day-15 year) were analyzed through high-throughput sequencing and the results revealed five dominant bacterial genera across different samples, including Lactobacillus, Pediococcus, Leuconostoc, Lactococcus and unclassified genera. Both NaCl and total acid (TA) were the major factors regulating bacterial community divergence in paocai. Based on these results, the microbial communities were reconstructed by manipulating the TA and NaCl contents in vitro to validate the effectiveness of these factors in shaping microbial communities during paocai fermentation. Results showed that roles of abiotic factors differentiated during fermentation. At the early stage, salt was the first abiotic filter, mainly working through promoting the abundance of Lactococcus and Leuconostoc. As the TA content increased, the selective role of salt weakened while acid became the dominant at the later stage, as evidenced by the increased abundance of Lactobacillus and Pediococcus following the increase of TA content.


Antagonistic co-limitation through ion promiscuity - On the metal sensitivity of Thalassiosira oceanica under phosphorus stress.
Nutrient limitation of primary producers is a fundamental principle in biogeochemical oceanography and has been used with great success in prescribing understanding to patterns of marine primary productivity. In recent years the paradigm of nutrient limitation has expanded from single nutrient limitation towards concepts of co-limitation by multiple resources. Interactive effects between multiple limiting resources are now thought commonplace in marine microbial communities. Here we investigate the response exhibited by phosphate-limited Thalassiosira oceanica to elevated concentrations of the phosphate analogs vanadate, arsenate and molybdate. Enrichments in external arsenate and vanadate to phosphate-limited cultures act to suppress growth rates entirely, an effect not seen in phosphate replete conditions. Retardation of growth rates is attributed to mistaken uptake through ion promiscuity as evidenced by observations of significant intracellular accumulation of both arsenic and vanadium under phosphate limited conditions. We describe this novel co-limitation scenario as dependent antagonistic co-limitation (DAC), and suggest that this phenomenon of non-deliberate intracellular accumulation could be used as both a proxy of phosphate stress in the modern ocean and a possible marker of phosphate depletion limiting the duration of oceanic anoxic events.


The landscape of contemporary clinical trials for untreated metastatic clear cell renal cell carcinoma.
Since the approval of immunotherapy checkpoint inhibitors for first-line treatment of metastatic renal cell carcinoma, new and clinically relevant questions have emerged that ongoing clinical trials and trials in development will address. These questions include how to integrate combination immunotherapy approaches like ipilimumab/nivolumab with targeted therapies against vascular endothelial growth factor (VEGF) receptors, which patients can discontinue treatment, and who needs ipilimumab to maximize clinical responses. Furthermore, with new approvals of treatment regimens combining checkpoint inhibitors with targeted therapies, new questions arise in the clinic regarding optimal treatment selection for first-line clear cell renal cell carcinoma. This review will highlight the contemporary clinical trials in metastatic clear cell renal cell carcinoma that try to address some of these knowledge gaps.


Horizontal transfer of a natterin-like toxin encoding gene within the holobiont of the reef building coral Acropora digitifera (Cnidaria: Anthozoa: Scleractinia) and across multiple animal linages.
Phylogenetic evidence is provided for horizontal transfer of a natterin-like toxin encoding gene from fungi into the genome of the coral Acropora digitifera. Sequencing analysis of the coral tissues supported that a fungal taxon predicted to be the most likely gene donor was represented in the coral microbiome. Further bioinformatics data suggested widespread recruitment of the natterin-like gene into venomous terrestrial invertebrates, and repositioning of this gene to non-toxic functions in non-venomous teleost fish.


Patient Selection for Hyperthermic Intraperitoneal Chemotherapy in Patients With Colorectal Cancer: Consensus on Decision Making Among International Experts.
Colorectal cancer (CRC) treatment for patients with peritoneal metastases is complex. The use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has continued to be debated. The aim of the present study was to assess the consensus among international experts for decision-making regarding the use of CRS and HIPEC for patients with CRC. Of 15 experts invited, 12 had provided their decision algorithms for CRS and HIPEC for patients with, or at high risk of, peritoneal metastases from CRC. Using the objective consensus method, the results were transformed into decision trees to provide information on the consensus and discordance. Only 1 scenario was found for which the consensus on performing HIPEC had reached 100%. The scenario was the treatment of young patients with complete cytoreduction and a peritoneal carcinomatosis index (PCI) of < 16 in the presence of certain risk factors. Five major decision criteria were identified: age, PCI, completeness of cytoreduction, extent of extraperitoneal metastases (EoMs), and, in the case of unverified EoMs, additional risk factors. Consensus was found regarding refraining from using HIPEC for older patients with a high PCI. The consensus further increased when addressing incomplete cytoreduction and an extensive extent of EoMs. A definite consensus concerning the use of HIPEC was only determined for very selected scenarios. These findings can be used for general guidance; however, owing to the heterogeneity of each individual situation, the impracticality of presenting the information through decision trees, and the unclear future of the role of HIPEC in the adjuvant setting, a one-on-one transfer to daily clinical practice could not be achieved.


Pulse gradient, large-volume injection, high-throughput ultra-performance liquid chromatographic/tandem mass spectrometry bioanalysis for measurement of plasma amrubicin and its metabolite amrubicinol.
In this communication, we report the development of a new ultra-performance liquid chromatographic/tandem mass spectrometry (UPLC-MS-MS) assay for measurement of amrubicin (an anthracycline anti-cancer agent) and its active metabolite, amrubicinol, in plasma. The enhanced electrospray ionization signal intensity of the analytes achieved by modifying the mobile phase with formic acid was associated with improvement in the lower limit of quantification. These favorable effects were electrolyte concentration-dependent. In order to maximize assay throughput, we used methanol protein precipitation to prepare the plasma samples, and simplified sample preparation by injecting 40 microL of the supernatant containing methanol at 87.5% (v/v) directly onto the UPLC column without any intermediary solvent evaporation step. The large-volume injection of highly organic supernatant sample increased matrix and elutropic effects, but these drawbacks were respectively overcome by using a 5mM formic acid-modified mobile phase and a new pulse gradient method. To our knowledge, this is the first report successfully using large-volume injection of strong organic samples with UPLC-MS-MS bioanalysis. The pulse gradient elution also resulted in band compression and enhanced the robustness of the chromatography. The promising new approach illustrated herein is extremely straightforward to optimize, and may be used for UPLC-MS-MS bioanalytical assay of other compounds.


Alleviation of dry mouth by saliva substitutes improved swallowing ability and clinical nutritional status of post-radiotherapy head and neck cancer patients: a randomized controlled trial.
The aim of this study is to investigate the effect of an edible saliva substitute, oral moisturizing jelly (OMJ), and a topical saliva gel (GC) on dry mouth, swallowing ability, and nutritional status in post-radiotherapy head and neck cancer patients. Sixty-two post-radiation head and neck cancer patients with xerostomia completed a blinded randomized controlled trial. They were advised to swallow OMJ (n = 31) or apply GC orally (n = 31) for 2 months. Outcome measures were assessed at baseline, 1, and 2 months, including subjective and objective dry mouth (Challcombe) scores, subjective swallowing problem scores (EAT-10), water swallowing time, clinical nutritional status (PG-SGA), body weight, and dietary intake. After 1 and 2 months of interventions, subjective and objective dry mouth scores, subjective swallowing problem scores, swallowing times, and clinical nutritional status in both groups were significantly improved (p < 0.0001). Compared to GC, OMJ group had higher percent improvement in all outcome measures (p < 0.001) except swallowing time and clinical nutritional status. Interestingly, subjective dry mouth scores were significantly correlated with subjective swallowing problem scores (r = 0.5321, p < 0.0001). Continuous uses of saliva substitutes (OMJ or GC) for at least a month improved signs and symptoms of dry mouth and enhanced swallowing ability. An edible saliva substitute was superior to a topical saliva gel for alleviating dry mouth and swallow problems. These lead to improved clinical nutritional status. Thus, palliation of dry mouth may be critical to support nutrition of post-radiotherapy head and neck cancer patients. Clinicaltrials.gov NCT03035825.


Lactobacillus reuteri F-9-35 Prevents DSS-Induced Colitis by Inhibiting Proinflammatory Gene Expression and Restoring the Gut Microbiota in Mice.
Probiotics are considered to be a potential treatment for ulcerative colitis (UC). The aim of this study was to compare the preventive effect of a space flight-induced mutant L. reuteri F-9-35 and its wild type on UC in vivo. Female mice were randomly assigned to five groups: one normal and four colitic. Mice from colitis groups were daily gavaged with 0.2 mL 12% (w/v) skim milk containing the mutant or wild type (1 × 1011 CFU/mL), skim milk alone or distilled water for the whole experiment period, starting 7 days before colitis induction. UC was induced by administrating mice with 3.5% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days, after which DSS was removed and maintained for 3 days as a recovery phase. The results showed that the mice fed with L. reuteri F-9-35 had less inflammatory phenotype according to macroscopic and histological analysis, reduced myeloperoxidase activity, and lower expression of proinflammatory genes (Tumor necrosis factor-α, cyclooxygenase-2 and interleukin-6) in colonic tissue compared with control. Furthermore, L. reuteri F-9-35 protected the mice from gut microbiota dysbiosis from DDS induced colitis. Neither wild type nor the milk alone had such beneficial effects. From above we conclude that L. reuteri F-9-35 has great potential in the prevention of UC as a dietary supplement. Ulcerative colitis (UC) is the most common inflammatory bowel diseases and there is still a lack of safe and effective treatments. Consumption of L. reuteri F-9-35 may effective in preventing human UC.


Healthcare, Responsibility and Golden Opportunities.
When it comes to determining how healthcare resources should be allocated, there are many factors that could-and perhaps should-be taken into account. One such factor is a patient's responsibility for his or her illness, or for the behavior that caused it. Policies that take responsibility for the unhealthy lifestyle or its outcomes into account-responsibility-sensitive policies-have faced a series of criticisms. One holds that agents often fail to meet either the control or epistemic conditions on responsibility with regard to their unhealthy lifestyles or their outcomes. Another holds that even if patients sometimes are responsible for these items, we cannot know whether a particular patient is responsible for them. In this article, we propose a type of responsibility-sensitive policy that may be able to surmount these difficulties. Under this type of policy, patients are empowered to change to a healthier lifestyle by being given what we call a 'Golden Opportunity' to change. Such a policy would not only avoid concerns about patients' fulfilment of conditions on responsibility for their lifestyles, it would also allow healthcare authorities to be justified in believing that a patient who does not change her lifestyle is responsible for the unhealthy lifestyle. We conclude with a discussion of avenues for further work, and place this policy in the broader context of the debate on responsibility for health.


Years After a Fire, Biocrust Microbial Communities are Similar to Unburned Communities in a Coastal Grassland.
Microbial communities are integral for ecosystem processes and their taxonomic composition and function may be altered by a disturbance such as fire. Biocrusts are composed of macroscopic and microscopic organisms and are important for a variety of ecosystem functions, such as nutrient cycling and erosion control. We sought to understand if biocrust community composition and function were altered 1 year after a prescribed fire and 6 years after a wildfire in a coastal California grassland on San Clemente Island. We used shotgun metagenomic sequencing and measurements of chlorophyll content, exopolysaccharide production related to soil stability, and nitrogen fixation. There were no differences in the community composition between unburned samples and the samples burned in the prescribed fire and wildfire. Chlorophyll content differed between the prescribed fire and the controls; however, there were no measured differences in exopolysaccharide production, and nitrogen fixation. However, the wildfire and their respective unburned samples had different functions based on the gene annotations. We compiled one Actinobacteria metagenome-assembled genome from the shotgun sequences which had genes for oxidative and heat stress tolerance. These results suggest that the biocrust community can reach a community composition and function similar to the unburned biocrusts within a year after a prescribed burn and 6 years after a wildfire. However, legacy effects of the wildfire may present themselves in the differences between functional gene sequences. Due to their ability to match the undisturbed community composition and function within years and without intervention, future restoration work should consider the biocrusts in their restoration plans as they may provide valuable ecosystem functions after a disturbance.


Tailoring the Atomic-Local Environment of Carbon Nanotube Tips for Selective H2 O2 Electrosynthesis at High Current Densities.
The atomic-local environment of catalytically active sites plays an important role in tuning the activity of carbon-based metal-free electrocatalysts (C-MFECs). However, the rational regulation of the environment is always impeded by synthetic limitations and insufficient understanding of the formation mechanism of the catalytic sites. Herein, the possible cleavage mechanism of carbon nanotubes (CNTs) through the crossing points during ball-milling is proposed, resulting in abundant CNT tips that are more susceptible to be modified by heteroatoms, achieving precise modulation of the atomic environment at the tips. The obtained CNTs with N,S-rich tips (N,S-TCNTs) exhibit a wide potential window of 0.59 V along with H2 O2 selectivity for over 90.0%. Even using air as the O2 source, the flow cell system with N,S-TCNTs catalyst attains high H2 O2 productivity up to 30.37 mol gcat. -1 h-1 @350 mA cm-2 , superior to most reported C-MFECs. From a practical point of view, a solid electrolyzer based on N,S-TCNTs is further employed to realize the in-situ continuous generation of pure H2 O2 solution with high productivity (up to 4.35 mmol cm-2 h-1 @300 mA cm-2 ; over 300 h). The CNTs with functionalized tips hold great promise for practical applications, even beyond H2 O2 generation.


Ocular surgery after herpes simplex and herpes zoster keratitis.
The recurrence of herpetic stromal keratitis (HSK) and herpes zoster ophthalmicus (HZO) has been reported after a variety of ocular surgeries. The aim of this study was to review the evidence on the preventive methods employed in the perioperative period in patients having undergone HSK/HZO. The PubMed and Web of Science databases were the main resources used to conduct the medical literature search. An extensive search was performed to identify relevant articles concerning the prophylaxis against and risk of HSK/HZO recurrence in patients undergoing ocular surgery up to December 31, 2019. The disturbance of the corneal nerve plexus occurs during several ocular surgeries including penetrating keratoplasty, lamellar keratoplasty, corneal cross-linking, cataract surgery, as well as photorefractive and phototherapeutic procedures. Such trauma, as well as modulation of the ocular immunological response caused by steroids applied postoperatively, might engender the HSK/HZO reactivation which is not uncommon. There is strong evidence that oral prophylaxis should be recommended just after surgery in patients undergoing penetrating keratoplasty and having suffered from HSK/HZO. For other types of surgeries, the evidence is less compelling; nevertheless, a period of disease quiescence and oral prophylaxis should still be considered. Within the article, we discuss the available evidence for HSK/HZO prophylaxis in ocular surgery. Additional studies would be required to define the real risk of HSK/HZO recurrence following eye surgeries, and particularly cataract surgery, and to confirm the utility of perioperative HSK/HZO prophylaxis.


Evaluation of deep learning-based auto-segmentation algorithms for delineating clinical target volume and organs at risk involving data for 125 cervical cancer patients.
To evaluate the accuracy of a deep learning-based auto-segmentation mode to that of manual contouring by one medical resident, where both entities tried to mimic the delineation "habits" of the same clinical senior physician. This study included 125 cervical cancer patients whose clinical target volumes (CTVs) and organs at risk (OARs) were delineated by the same senior physician. Of these 125 cases, 100 were used for model training and the remaining 25 for model testing. In addition, the medical resident instructed by the senior physician for approximately 8 months delineated the CTVs and OARs for the testing cases. The dice similarity coefficient (DSC) and the Hausdorff Distance (HD) were used to evaluate the delineation accuracy for CTV, bladder, rectum, small intestine, femoral-head-left, and femoral-head-right. The DSC values of the auto-segmentation model and manual contouring by the resident were, respectively, 0.86 and 0.83 for the CTV (P < 0.05), 0.91 and 0.91 for the bladder (P > 0.05), 0.88 and 0.84 for the femoral-head-right (P < 0.05), 0.88 and 0.84 for the femoral-head-left (P < 0.05), 0.86 and 0.81 for the small intestine (P < 0.05), and 0.81 and 0.84 for the rectum (P > 0.05). The HD (mm) values were, respectively, 14.84 and 18.37 for the CTV (P < 0.05), 7.82 and 7.63 for the bladder (P > 0.05), 6.18 and 6.75 for the femoral-head-right (P > 0.05), 6.17 and 6.31 for the femoral-head-left (P > 0.05), 22.21 and 26.70 for the small intestine (P > 0.05), and 7.04 and 6.13 for the rectum (P > 0.05). The auto-segmentation model took approximately 2 min to delineate the CTV and OARs while the resident took approximately 90 min to complete the same task. The auto-segmentation model was as accurate as the medical resident but with much better efficiency in this study. Furthermore, the auto-segmentation approach offers additional perceivable advantages of being consistent and ever improving when compared with manual approaches.


Developing and Validating a Prediction Model For Death or Critical Illness in Hospitalized Adults, an Opportunity for Human-Computer Collaboration.
Hospital early warning systems that use machine learning (ML) to predict clinical deterioration are increasingly being used to aid clinical decision-making. However, it is not known how ML predictions complement physician and nurse judgment. Our objective was to train and validate a ML model to predict patient deterioration and compare model predictions with real-world physician and nurse predictions. Retrospective and prospective cohort study. Academic tertiary care hospital. Adult general internal medicine hospitalizations. We developed and validated a neural network model to predict in-hospital death and ICU admission in 23,528 hospitalizations between April 2011 and April 2019. We then compared model predictions with 3,374 prospectively collected predictions from nurses, residents, and attending physicians about their own patients in 960 hospitalizations between April 30, and August 28, 2019. ML model predictions achieved clinician-level accuracy for predicting ICU admission or death (ML median F1 score 0.32 [interquartile range (IQR) 0.30-0.34], AUC 0.77 [IQ 0.76-0.78]; clinicians median F1-score 0.33 [IQR 0.30-0.35], AUC 0.64 [IQR 0.63-0.66]). ML predictions were more accurate than clinicians for ICU admission. Of all ICU admissions and deaths, 36% occurred in hospitalizations where the model and clinicians disagreed. Combining human and model predictions detected 49% of clinical deterioration events, improving sensitivity by 16% compared with clinicians alone and 24% compared with the model alone while maintaining a positive predictive value of 33%, thus keeping false alarms at a clinically acceptable level. ML models can complement clinician judgment to predict clinical deterioration in hospital. These findings demonstrate important opportunities for human-computer collaboration to improve prognostication and personalized medicine in hospital.


The tangle of space and time in human cognition.
Everyday concepts of duration, of sequence, and of past, present, and future are fundamental to how humans make sense of experience. In culture after culture, converging evidence from language, co-speech gesture, and behavioral tasks suggests that humans handle these elusive yet indispensable notions by construing them spatially. Where do these spatial construals come from and why do they take the particular, sometimes peculiar, spatial forms that they do? As researchers across the cognitive sciences pursue these questions on different levels--cultural, developmental--in diverse populations and with new methodologies, clear answers will depend upon a shared and nuanced set of theoretical distinctions. Time is not a monolith, but rather a mosaic of construals with distinct properties and origins.


One health: finding out what's happening on 'the other side'.
Alexander Stoll, a final-year student at the Royal Veterinary College, was awarded a bursary by the RCVS Charitable Trust to attend the first Veterinary, Biomedical and Pharma Sciences congress, which was held in Birmingham in the autumn. Here, he describes his experiences at the congress, which brought together delegates from a wide range of backgrounds under the theme of 'Two worlds, one health'


Proteolytic degradation of insulin and glucagon.
The degradation of insulin and glucagon by a highly purified enzyme isolated from rat skeletal muscle was investigated. A sensitive assay for proteolytic degradation of insulin and glucagon using fluorescamine to detect an increase in primary amine groups was established. As measured by an increase in fluorescamine reactive materials, insulin was rapidly degraded by this highly purified enzyme without requiring initial disulfide cleavage. Associated with the increase in fluorescamine reactive materials was a decrease in immunoassayable insulinmglucagon wal also proteolytically degraded by this enzyme but a number of other peptides and proteins including proinsulin, and A and B chains of insulin were not degraded. Thus, we have demonstrated that insulin (and glucagon) can be proteolytically degraded by an enzyme isolated from an insulin sensitive tissue, skeletal muscle. Proteolytic degradation by this enzyme requires the intact insulin molecule rather than separate A and B chains.


When residents work less, they feel better: Lessons learned from an unprecedent context of lockdown.
With the COVID-19 outbreak activities of urology departments have been limited to non-deferrable procedures impacting the daily program of residents in urology. We assessed the psychological impact of the lockdown on Belgian residents in urology and their resounding on the quality of the training. A self-administered anonymous questionnaire assessing the risk of burnout in a pandemic situation and its impact on the quality of the training was e-mailed to the members of the European Society of Residents in Urology of Belgium (ESRU-B). We used the Copenhagen Burnout Inventory score which assesses the different dimensions of burnout (personal (CBIP), professional (CBIPro), relational (CBIR)). Several questions evaluating impact on residents' health and apprehension of the future were included. The survey lasted for 5 days. Comparison of parameters before and during the coronavirus crisis was made using paired samples t-test or Chi2 test were. Fifty percent (62/126) of the ESRU-B members replied to the questionnaire. If 93% of the responders reported a negative impact on the quality of their practical training (CI95=[0.07-1.10]; P=0.83), 56% and 61.7% reported a positive impact of the crisis on their life and on their theoretical training respectively. Burnout risk scores were significantly reduced (P<0.001) for each dimension 7.26 to 3.40 (CBIP), 9.02 to 4.35 (CBIPro) and 4.42 to 3.03 (CBIR) respectively. Despite a negative impact on the daily work quality, the decrease in activity induced by the lockdown did not have a negative psychological impact on Belgian residents in urology but stress the opportunity to review the current training system to be better balanced between practice and theoretical formation.


Participation bias in postal surveys among older adults: the role played by self-reported health, physical functional decline and frailty.
Postal survey is a simple and efficient way to collect information in large study samples. The purpose of this study was to find out differences between older adults who responded to a postal survey on health outcomes and those who did not, and to examine the importance of frailty, physical functional decline and poor self-reported health in determining non-response. We mailed out a questionnaire on general health twice at a year's interval to 1000 individuals ≥60 years, and members of the medical insurance scheme of the French national education system. At Year1, 535 persons responded to the questionnaire (65% women, 70.9 ± 8.4 years). A year later (Year2), we obtained 384 responses (63.3% women, 70.5 ± 7.8 years). Compared to respondents, non-respondents at Year2 were more frequently categorized as frail, reported more often to be in bad health, and had more physical functional declines. Frailty, physical functional decline and poor self-reported health increased the likelihood of not responding to Year2 questionnaire, with poor self-reported health weakening the association of physical functional decline and non-response. Respondents of this postal survey are fitter and healthier than non-respondents. This participation bias precludes the generalization of postal surveys results.


Solid phase synthesis of benzylamine-derived sulfonamide library.
Using solid phase synthesis, a library has been constructed of benzylamine-derived sulfonamides which have strong inhibitory activity against the blood coagulant thrombin. The library compounds were obtained in good yield and high purity; four of these thrombin inhibitors showed nanomolar potency (Ki 600-10 nM).


Bonkers about biofuels.
Biofuels have been touted before, but failed to deliver. What's needed to get it right this time around?


Bilateral clear cell sarcoma of the kidney.
Clear cell sarcoma of the kidney (CCSK) accounts for 2-5% of all pediatric renal malignancies, and is known for its propensity to metastasize to bone and other sites. We are reporting two cases with bilateral CCSK that were diagnosed at our institution. One patient initially presented with bilateral renal masses, as well as pulmonary, hepatic and bone metastasis; while other present only with bilateral masses with no evident distant metastasis. Both patients received aggressive neo-adjuvant chemotherapy to decrease tumor size. One patient completed his designated treatment and initially showed complete remission (CR); eventually suffering from relapse. The other patient's tumor progressed during the course of chemotherapy. Both cases manifested brain dissemination at the time of relapse or progression. This emphasizes the importance of staging stratification in CCSK. This also illustrates CCSK's ability to metastasize to bone and other sites including the brain (a primary relapse site in our cases).


Future treatments in hypertension: Can we meet the unmet needs of patients?
The prevalence of arterial hypertension is approximately 47% in the United States and 55% in Europe. Multiple different medical therapies are used to treat hypertension including diuretics, beta blockers, calcium channel blockers, angiotensin receptor blockers, angiotensin converting enzyme inhibitors, alpha blockers, central acting alpha receptor agonists, neprilysin inhibitors and vasodilators. However, despite the numerous number of medications, the prevalence of hypertension is on the rise, a considerable proportion of the hypertensive population is resistant to these therapeutic modalities and a definitive cure is not possible with the current treatment approaches. Therefore, there is a need for novel therapeutic strategies to provide better treatment and control of hypertension. In this review, our aim is to describe the latest developments in the treatment of hypertension including novel medication classes, gene therapies and RNA-based modalities.


Money Affects Theory of Mind Differently by Gender.
Theory of Mind (ToM)--the ability to understand other's thoughts, intentions, and emotions--is important for navigating interpersonal relationships, avoiding conflict, and empathizing. Prior research has identified many factors that affect one's ToM ability, but little work has examined how different kinds of monetary incentives affect ToM ability. We ask: Does money affect ToM ability? If so, how does the effect depend on the structure of monetary incentives? How do the differences depend on gender? We hypothesize that money will affect ToM ability differently by gender: monetary rewards increase males' motivation to express ToM ability while simultaneously crowding out females' motivation. This prediction is confirmed in an experiment that varies the structure of monetary rewards for correct answers in the Reading the Mind in the Eyes Test (RMET). RMET scores decrease for females and increase for males with individual payments, and this effect is stronger with competitively-structured payments. RMET scores do not significantly change when monetary earnings go to a charity. Whether money improves or hinders ToM ability, and, hence, success in social interactions, thus depends on the interaction of gender and monetary incentive structure.


Synthesis of active firefly luciferase by in vitro translation of RNA obtained from adult lanterns.
Poly (A)+ RNA was isolated from the lanterns of adult fireflies, Photinus pyralis. The Poly (A)+ RNA was translated in a cell-free translation mixture from rabbit reticulocytes and the synthesis of enzymatically active firefly luciferase was demonstrated. The translation products were immunoprecipitated with anti-luciferase and then subjected to SDS gel electrophoresis. It was shown that a newly synthesized polypeptide exhibited an identical electrophoretic mobility as the purified enzyme.