Fast and reversible trapping of surface glycine receptors by gephyrin.
Variations in receptor number at a given synapse are known to contribute to synaptic plasticity, but methods used to establish this idea usually do not allow for the determination of the dynamics of these phenomena. We used single-particle tracking to follow in real time, on the cell surface, movements of the glycine receptor (GlyR) with or without the GlyR stabilizing protein gephyrin. GlyR alternated within seconds between diffusive and confined states. In the absence of gephyrin, GlyR were mostly freely diffusing. Gephyrin induced long confinement periods spatially associated with submembranous clusters of gephyrin. However, even when most receptors were stabilized, they still frequently made transitions through the diffusive state. These data show that receptor number in a cluster results from a dynamic equilibrium between the pools of stabilized and freely mobile receptors. Modification of this equilibrium could be involved in regulation of the number of receptors at synapses.


SMB-1, a novel subclass B3 metallo-beta-lactamase, associated with ISCR1 and a class 1 integron, from a carbapenem-resistant Serratia marcescens clinical isolate.
A carbapenem-resistant Serratia marcescens strain, 10mdr148, was identified in a Japanese hospital in 2010. The carbapenem resistance of this strain was attributed to the production of a novel metallo-β-lactamase (MBL), named SMB-1 (Serratia metallo-β-lactamase). SMB-1 possessed a zinc binding motif, H(Q)XHXDH (residues 116 to 121), H196, and H263 and was categorized as a member of subclass B3 MBL. SMB-1 has 75% amino acid identity with the most closely related MBL, AMO1, of uncultured bacterium, recently identified through the metagenomic analysis of apple orchard soil. The introduction of bla(SMB-1) into Escherichia coli conferred resistance to a variety of β-lactam antibiotics, penicillins, cephalosporins, and carbapenems, but not aztreonam, a resistance pattern consistent with those of other MBLs. SMB-1 demonstrated high k(cat) values of >500 s(-1) for carbapenems, resulting in the highest hydrolyzing efficiency (k(cat)/K(m)) among the agents tested. The hydrolyzing activity of SMB-1 was well inhibited by chelating agents. The bla(SMB-1) gene was located on the chromosome of S. marcescens strain 10mdr148 and at the 3' end of the ISCR1 element in complex with a typical class 1 integron carrying aac(6')-Ib and catB3 gene cassettes. Downstream of bla(SMB-1), the second copy of the 3'conserved segment and ISCR1 were found. To our knowledge, this is the first subclass B3 MBL gene associated with an ISCR1 element identified in an Enterobacteriaceae clinical isolate. A variety of antibiotic resistance genes embedded with ISCR1 have been widely spread among Enterobacteriaceae clinical isolates, thus the further dissemination of bla(SMB-1) mediated by ISCR1 transposition activity may become a future concern.


Antiepileptogenic effects of glutathione against increased brain ADA in PTZ-induced epilepsy.
Adenosine has been shown to play a significant role as a modulator of neuronal activity in convulsive disorders, acting as an endogenous anticonvulsant agent. Any change in adenosine deaminase (ADA) levels will reflect to adenosine levels. In the present study, we have investigated the effect of glutathione on brain tissue ADA levels due to seizures induced by convulsive and subconvulsive dose of pentylenetetrazol (PTZ) in mice. ADA levels due to seizures induced by convulsive and subconvulsive pentylenetetrazol were measured using the Giusti method. ADA levels were higher in the experimental epilepsy groups than in the control and sham groups. ADA levels significantly decreased in the glutathione groups, which may have antiseizure effects. Decreased levels of ADA would be due to increased adenosine levels, protecting against oxidative stress.


Why do patients with postsurgical acute tubular necrosis die?
We compared early (less than 70 days) cumulative survival, cause of death, and morbidity (defined as the number of organ system failures and reoperations) of 236 patients who needed dialysis for acute tubular necrosis (ATN) after transplantation with that of a control group of 215 transplant patients who had immediate renal function after transplantation. The patients were matched for age, number of transplants, time of transplantation, diabetic status, living-related vs cadaveric donor, and number of HLA matches. There were no differences in cumulative survival after transplantation, causes of death, organ system failure, or surgical complications as evident from the number of reoperations. The ATN patients' overall clinical course was similar to that described for other postsurgical patients with ATN in their native kidneys. We conclude that the poor survival and the surgical complications in patients with postoperative ATN are due to the basic disease and not to acute renal failure or to dialysis. To improve survival, research should be focused on the basic disease and the surgical procedures rather than on dialysis technique.


Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19.
After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19. Here, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection. We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets. By exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.


Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma.
Immune checkpoint inhibitors targeting programmed cell death 1 (PD1) or its ligand (PD-L1) showed activity in several cancer types. We performed immunohistochemistry for CD3, CD8, CD20, HLA-DR, phosphatase and tensin homolog (PTEN), PD-1, and PD-L1 and pyrosequencing for assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status in 135 glioblastoma specimens (117 initial resection, 18 first local recurrence). PD-L1 gene expression was analyzed in 446 cases from The Cancer Genome Atlas. Diffuse/fibrillary PD-L1 expression of variable extent, with or without interspersed epithelioid tumor cells with membranous PD-L1 expression, was observed in 103 of 117 (88.0%) newly diagnosed and 13 of 18 (72.2%) recurrent glioblastoma specimens. Sparse-to-moderate density of tumor-infiltrating lymphocytes (TILs) was found in 85 of 117 (72.6%) specimens (CD3+ 78/117, 66.7%; CD8+ 52/117, 44.4%; CD20+ 27/117, 23.1%; PD1+ 34/117, 29.1%). PD1+ TIL density correlated positively with CD3+ (P < .001), CD8+ (P < .001), CD20+ TIL density (P < .001), and PTEN expression (P = .035). Enrichment of specimens with low PD-L1 gene expression levels was observed in the proneural and G-CIMP glioblastoma subtypes and in specimens with high PD-L1 gene expression in the mesenchymal subtype (P = 5.966e-10). No significant differences in PD-L1 expression or TIL density between initial and recurrent glioblastoma specimens or correlation of PD-L1 expression or TIL density with patient age or outcome were evident. TILs and PD-L1 expression are detectable in the majority of glioblastoma samples but are not related to outcome. Because the target is present, a clinical study with specific immune checkpoint inhibitors seems to be warranted in glioblastoma.


Spatiotopic updating across saccades revealed by spatially-specific fMRI adaptation.
Brain representations of visual space are predominantly eye-centred (retinotopic) yet our experience of the world is largely world-centred (spatiotopic). A long-standing question is how the brain creates continuity between these reference frames across successive eye movements (saccades). Here we use functional magnetic resonance imaging (fMRI) to address whether spatially specific repetition suppression (RS) is evident during trans-saccadic perception. We presented two successive Gabor patches (S1 and S2) in either the upper or lower visual field, left or right of fixation. Spatial congruency was manipulated by having S1 and S2 occur in the same or different upper/lower visual field. On half the trials, a saccade was cued between S1 and S2, placing spatiotopic and retinotopic reference frames in opposition. Equivalent RS was observed in the posterior parietal cortex and frontal eye fields when S1-S2 were spatiotopically congruent, irrespective of whether retinotopic and spatiotopic coordinates were in accord or were placed in opposition by a saccade. Additionally the post-saccadic response to S2 demonstrated spatially-specific RS in retinotopic visual regions, with stronger RS in extrastriate than striate cortex. Collectively, these results are consistent with a robust trans-saccadic spatial updating mechanism for object position that directly influences even the earliest levels of visual processing.


Plasma cytokine profiles in elderly humans.
It is known that as we age, immune dysregulation often occurs, leading to failing health, and increased susceptibility to a number of different diseases. In this study we have investigated plasma cytokine profiles in order to identify immune markers of ageing. Plasma samples were obtained from 138 participants of the Swedish longitudinal NONA study (aged 86, 90 and 94 years) and 18 healthy Swedish volunteers (aged between 32 and 59 years). Our results show significantly increased levels of the pro-inflammatory cytokine interleukin-6 (P<0.0001) and soluble intercellular adhesion molecule-1 (P<0.0001) in the elderly group. The anti-inflammatory cytokine interleukin-10 did not alter with age whereas active (naturally processed) transforming growth factor-beta levels were significantly (P<0.0001) increased in the elderly group. No difference was observed between males and females. These data suggest that there are measurable changes in cytokine profiles with ageing with increased levels of potentially harmful molecules, which may contribute to immune alterations and declining health in the elderly population.


Ecologic regression analysis and the study of the influence of air quality on mortality.
This presentation focuses entirely on the use and evaluation of regression analysis applied to ecologic data as a method to study the effects of ambient air pollution on mortality rates. Using extensive national data on mortality, air quality and socio-economic status regression analyses are used to study the influence of air quality on mortality. The analytic methods and data are selected in such a way that direct comparisons can be made with other ecologic regression studies of mortality and air quality. Analyses are performed by use of two types of geographic areas, age-specific mortality of both males and females and three pollutants (total suspended particulates, sulfur dioxide and nitrogen dioxide). The overall results indicate no persuasive evidence exists of a link between air quality and general mortality levels. Additionally, a lack of consistency between the present results and previous published work is noted. Overall, it is concluded that linear regression analysis applied to nationally collected ecologic data cannot be used to usefully infer a causal relationship between air quality and mortality which is in direct contradiction to other major published studies.


For me the taste of soy is not a barrier to its consumption. And how about you?
This research investigates the cultural influence on beliefs about and attitudes towards soy foods (French from France vs. Vietnamese from Vietnam) and possible change of beliefs and attitudes and soy consumption habits with a change in cultural environment (French from France vs. French from Vietnam, Vietnamese from Vietnam vs. Vietnamese from France) of French and Vietnamese participants, two countries with very different soy food consumption. Expressed beliefs and attitudes of soy foods resulting from discussions in focus groups, conducted in both countries, were collected and used to derive a questionnaire. French participants differ mainly from Vietnamese participants in questions associated to taste and price of soy foods. Both groups reported positive attitudes towards health benefits of soy foods. With a change in cultural environment, French participants showed a notable change in attitudes related to taste and price of soy foods and in soy consumption habit whereas almost no change was observed in Vietnamese participants. The asymmetry in magnitude of change and cultural differences in components of beliefs and attitudes are discussed.


Antiapoptotic mechanism of cannabinoid receptor 2 agonist on cisplatin-induced apoptosis in the HEI-OC1 auditory cell line.
Cisplatin is a highly effective chemotherapeutic agent but with significant ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell loss following exposure to an ototoxic level of cisplatin. The present study investigated the effects of the cannabinoid receptor 2 (CB2) ligand JWH-015 on cisplatin-induced apoptosis. CB2 mRNA was constitutively expressed in the auditory cell line HEI-OC1. By using MTT assay, DNA fragmentation, and FACS analysis, we demonstrated that apoptosis induced by cisplatin was inhibited by treatment with JWH-015 in a dose-dependent manner. Activation of caspase-3, caspase-8, and caspase-9 was detected after treatment with cisplatin, and the cleavage of poly-(ADP)-ribose polymerase (PARP) was observed within cisplatin-treated HEI-OC1 cells. JWH-015 inhibited the activation of caspase-3, caspase-8, and caspase-9; cleavage of PARP; and release of cytochrome c. JWH-015 also inhibited the apoptosis through activation of the extracellular signal-regulated kinase pathway. Finally, JWH-015 inhibited cisplatin-induced reactive oxygen species and tumor necrosis factor-alpha production. Collectively, these findings show that blocking a critical step in apoptosis by using JWH-015 may be a useful strategy to prevent harmful side effects of cisplatin ototoxicity in patients having to undergo chemotherapy.


Long-term remodeling of vascularized and nonvascularized onlay bone grafts: a macroscopic and microscopic analysis.
The present study was performed to compare vascularized and nonvascularized onlay bone grafts to investigate the potential effect of graft-to-recipient bed orientation on long-term bone remodeling and changes in thickness and microarchitectural patterns of remodeling within the bone grafts. In two groups of 10 rabbits each, bone grafts were raised bilaterally from the supraorbital processes and placed subperiosteally on the zygomatic arch. The bone grafts were oriented parallel to the zygomatic arch on one side and perpendicular to the arch on the contralateral side. In the first group, vascularized bone grafts were transferred based on the auricularis anterior muscle, and in the second group nonvascularized bone grafts were transferred. Fluorochrome markers were injected during the last 3 months of animal survival, and animals were killed either 6 or 12 months postoperatively. The nonvascularized augmented zygoma showed no significant change in thickness 6 months after bone graft placement and a significant decrease in thickness 1 year after graft placement (p < 0.01). The vascularized augmented zygoma showed a slight but statistically significant decrease in thickness 6 months after graft placement (p < 0.003), with no significant difference relative to its initial thickness 1 year after graft placement. In animals killed 6 months after bone graft placement, both the rate of remodeling and the bone deposition rate measured during the last 3 months of survival were significantly higher in the vascularized bone grafts compared with their nonvascularized counterparts (p < 0.02). By 1 year postoperatively, there were no significant differences in thickness, mineral apposition rate, or osteon density between bone grafts oriented perpendicular and parallel to the zygomatic arch. These findings indicate that the vascularity of a bone graft has a significant effect on long-term thickness and histomorphometric parameters of bone remodeling, whereas the direction of placement of a subperiosteal graft relative to the recipient bed has minimal effect on these parameters. In vascularized bone grafts, both bone remodeling and deposition are accelerated during the initial period following graft placement. Continued bone deposition renders vascularized grafts better suited for the long-term maintenance of thickness and contour relative to nonvascularized grafts.


Lymphoproliferative disorders after immunosuppressive therapy for aplastic anemia: a case report and literature review.
A 61-year-old Japanese man was referred to our hospital in 2002 due to severe pancytopenia. Bone marrow and peripheral blood findings indicated he had severe aplastic anemia (AA). A whole-body CT scan and Ga scintigraphy revealed no abnormal findings. Antithymocyte globulin and cyclosporine A (CyA) were administered and he got transfusion independently. In September 2004, he complained of abdominal fullness and a skin eruption in the lower abdomen. An abdominal CT revealed a spleen mass and lymphoadenopathy of the pancreas head. Splenectomy was done, and he was diagnosed with a diffuse large B cell lymphoma (DLBCL) of the spleen and skin. His karyotype was associated with t(14; 18). CyA was stopped, all lesions disappeared, and then his AA relapsed. In January 2007, antithymocyte globulin/CyA was readministered. In May 2007, he complained of acute swelling in his right thigh. A biopsy from the tumor revealed DLBCL. CyA was stopped again, yet the lymphoma did not regress. He was given R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisolone), followed by 5 cycles of R-VP (rituximab, vincristine, prednisolone) and radiation therapy, resulting in a partial remission. We report DLBCL after immunosuppressive therapy for AA. Although this is a rare complication, it should be considered before beginning immunosuppressive therapy.


GENDER AND THE MBA: Differences in Career Trajectories, Institutional Support, and Outcomes.
This study asks how men's and women's careers diverge following MBA graduation from an elite university, using qualitative interview data from 74 respondents. We discover men and women follow three career pathways post-graduation: lockstep (stable employment), transitory (3 or more employers), and exit (left workforce). While similar proportions of men and women followed the lockstep pathways and launched accelerated careers, sizable gender differences emerged on the transitory pathway; men's careers soared as women's faltered on this path-the modal category for both. On the transitory path, men fared much better than women when moving to new organizations, suggesting that gender may become more salient when people have a shorter work history with a company. Our findings suggest that clear building blocks to promotions reduce gender bias and ambiguity in the promotion process, but multiple external moves hamper women, putting them at a clear disadvantage to men whose forward progress is less likely to be stalled by such moves.


[Intestinal duplication. A diagnostic and therapeutic challenge].
Duplications of the alimentary tract are rare congenital anomalies. The symptoms often mimic other surgical diseases and the diagnostic workup presents low accuracy. The charts of twelve children with intestinal duplications were reviewed. Their ages ranged from 13 days to 12 years (median: 12 months). The majority of the cases were located at ileum (n = 9). These children presented: rectal bleeding (n = 4), intussusception (n = 3), intestinal obstruction (n = 1) and hemoperitoneum (n = 1). All that were symptomatic before 1 year of age presented with intussusception (n = 3/3). All, except one colonic case was cystic. 99mTc abdominal scan was positive in 3 cases presenting rectal bleeding. One child with gastric duplication was diagnosed prenatally. Treatment consisted of enterectomy in all but one case, with no complications. Experience in the diagnostic workup and management is important to achieve a low morbidity rate in this congenital anomaly, which may present delayed manifestations.


Chronically critically ill patients: health-related quality of life and resource use after a disease management intervention.
Chronically critically ill patients often have high costs of care and poor outcomes and thus might benefit from a disease management program. To evaluate how adding a disease management program to the usual care system affects outcomes after discharge from the hospital (mortality, health-related quality of life, resource use) in chronically critically ill patients. In a prospective experimental design, 335 intensive care patients who received more than 3 days of mechanical ventilation at a university medical center were recruited. For 8 weeks after discharge, advanced practice nurses provided an intervention that focused on case management and interdisciplinary communication to patients in the experimental group. A total of 74.0% of the patients survived and completed the study. Significant predictors of death were age (P = .001), duration of mechanical ventilation (P = .001), and history of diabetes (P = .04). The disease management program did not have a significant impact on health-related quality of life; however, a greater percentage of patients in the experimental group than in the control group had "improved" physical health-related quality of life at the end of the intervention period (P = .02). The only significant effect of the intervention was a reduction in the number of days of hospital readmission and thus a reduction in charges associated with readmission. The intervention was not associated with significant changes in any outcomes other than duration of readmission, but the supportive care coordination program could be provided without increasing overall charges.


Circadian and ultradian rhythms of peripheral prolactin concentrations in lactating dairy cows.
To investigate possible circadian and ultradian periodicities for peripheral prolactin in lactating dairy cows, integrated 15-min blood samples taken sequentially over 48 h from six cows were analyzed by radioimmunoassay. Cows were housed in an environmental chamber at 19 degrees C with lights on 0700 to 2300, fed daily at 0900, and milked at 0800 and 2000. Peripheral concentrations exhibited sinusoidal circadian rhythms. For two cows, a nadir of 15 ng/ml occurred around 1900 and a zenith of 29 ng/ml around 0730. For four cows, circadian rhythms were 180 degrees out of phase, with a nadir of 28 ng/ml around 0840 and a zenith of 40 mg/ml around 1920. Ultradian peaks, which varied in amplitude within and among animals, showed no consistent relationship with either milking or feeding. Spectral analyses indicated rhythms around 100 min for the first two animals and 150 min for the four animals. In conclusion, there were no simple relations between prolactin rhythms and lights on or lights off. Further, results suggest that changes in the phase of circadian rhythms may be associated with changes in the periods of ultradian rhythms.


Vitamin D supplementation for prevention of mortality in adults.
The available evidence on vitamin D and mortality is inconclusive. To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults. We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). Six authors extracted data independently. Random-effects and fixed-effect model meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta-analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors. Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive. Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.


Definitive reconstruction of full-thickness abdominal wall defects initially treated with skin grafting of exposed intestines.
The reconstruction of wide, full-thickness abdominal wall defects of the midline presents a continuing challenge, and consensus concerning the appropriate surgical treatment is lacking. In this retrospective review, we describe a simple method of reconstruction in full-thickness defects initially treated with skin grafting directly on to the surface of the intestines. Instead of removing the split-thickness grafts from the surface of the intestines, the abdominal wall was reconstructed by inverting the grafted area and advancing the rectus muscles towards the midline. Four patients with full-thickness transverse defects larger than 10 cm at the level of the waist and extending from the xiphoid to the suprapubic region were operated with this method. All healed uneventfully. In one case, microscopic examination of the inverted skin showed transformation to normal connective tissue. Reconstruction of abdominal wall defects previously treated with skin grafting directly on to the intestines can be safely done by reposition of the skin-grafted intestines into the abdominal cavity and realignment of the rectus muscles in the midline.


Characterization of advanced wastewater treatment with ozone and activated carbon using LC-HRMS based non-target screening with automated trend assignment.
Advanced treatment is increasingly being applied to improve abatement of micropollutants in wastewater effluent and reduce their load to surface waters. In this study, non-target screening of high-resolution mass spectrometry (HRMS) data, collected at three Swiss wastewater treatment plants (WWTPs), was used to evaluate different advanced wastewater treatment setups, including (1) granular activated carbon (GAC) filtration alone, (2) pre-ozonation followed by GAC filtration, and (3) pre-ozonation followed by powdered activated carbon (PAC) dosed onto a sand filter. Samples were collected at each treatment step of the WWTP and analyzed with reverse-phase liquid chromatography coupled to HRMS. Each WWTP received a portion of industrial wastewater and a prioritization method was applied to select non-target features potentially resulting from industrial activities. Approximately 37,000 non-target features were found in the influents of the WWTPs. A number of non-target features (1207) were prioritized as likely of industrial origin and 54 were identified through database spectral matching. The fates of all detected non-target features were assessed through a novel automated trend assignment method. A trend was assigned to each non-target feature based on the normalized intensity profile for each sampling date. Results showed that 73±4% of influent non-target features and the majority of industrial features (89%) were well-removed (i.e., >80% intensity reduction) during biological treatment in all three WWTPs. Advanced treatment removed, on average, an additional 11% of influent non-target features, with no significant differences observed among the different advanced treatment settings. In contrast, when considering a subset of 66 known micropollutants, advanced treatment was necessary to adequately abate these compounds and higher abatement was observed in fresh GAC (7,000-8,000 bed volumes (BVs)) compared to older GAC (18,000-48,000 BVs) (80% vs 56% of micropollutants were well-removed, respectively). Approximately half of the features detected in the WWTP effluents were features newly formed during the various treatment steps. In ozonation, between 1108-3579 features were classified as potential non-target ozonation transformation products (OTPs). No difference could be observed for their removal in GAC filters at the BVs investigated (70% of OTPs were well-removed on average). Similar amounts (67%) was observed with PAC (7.7-13.6 mg/L) dosed onto a sand filter, demonstrating that a post-treatment with activated carbon is efficient for the removal of OTPs.


Self-management support in "real-world" settings: an empowerment-based intervention.
This study examined the impact of a 6-month, empowerment-based diabetes self-management support (DSMS) intervention on clinical outcomes, self-care behaviors, and quality of life (QOL) compared to a 6-month control period. This control-intervention cohort study recruited 77 African-American adults with type 2 diabetes. Baseline, 6-month, and 12-month assessments measured A1C, weight, body mass index (BMI), blood pressure, lipids, self-care behaviors, and QOL. During the control period, participants received weekly educational newsletters. During the intervention period, participants attended weekly DSMS groups as frequently as they needed. Sessions were guided by participants' self-management questions and concerns, and also emphasized experiential learning, coping, problem-solving, and goal-setting. The control period found significant improvements for diastolic BP (p<0.05), serum cholesterol (p<0.001), following a healthy diet (p<0.01), and monitoring blood glucose (p<0.01). The intervention period found significant additional improvements for A1C (p<0.001), weight (p<0.05), BMI (p<0.05), and LDL (p<0.001). Compared to the control period, participation in the intervention led to a significant reduction in A1C (p<0.01). Findings suggest that an empowerment-based, DSMS intervention is promising for improving and/or maintaining diabetes-related health, particularly A1C. Incorporating empowerment principles in DSMS interventions may be useful for supporting patients' self-management efforts in "real-world" settings.


Factors associated with falling in early, treated Parkinson's disease: The NET-PD LS1 cohort.
Recognizing the factors associated with falling in Parkinson's disease (PD) would improve identification of at-risk individuals. To examine frequency of falling and baseline characteristics associated with falling in PD using the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1) dataset. The LS-1 database included 1741 early treated PD subjects (median 4year follow-up). Baseline characteristics were tested for a univariate association with post-baseline falling during the trial. Significant variables were included in a multivariable logistic regression model. A separate analysis using a negative binomial model investigated baseline factors on fall rate. 728 subjects (42%) fell during the trial, including at baseline. A baseline history of falls was the factor most associated with post-baseline falling. Men had lower odds of post-baseline falling compared to women, but for men, the probability of a post-baseline fall increased with age such that after age 70, men and women had similar odds of falling. Other baseline factors associated with a post-baseline fall and increased fall rate included the Unified PD Rating Scale (UPDRS) Activities of Daily Living (ADL) score, total functional capacity (TFC), baseline ambulatory capacity score and dopamine agonist monotherapy. Falls are common in early treated PD. The biggest risk factor for falls in PD remains a history of falling. Measures of functional ability (UPDRS ADL, TFC) and ambulatory capacity are novel clinical risk factors needing further study. A significant age by sex interaction may help to explain why age has been an inconsistent risk factor for falls in PD.


Localization of inhibition by adenosine diphosphate of phosphoglycerate-dependent oxygen evolution in a reconstituted chloroplast system.
ADP was shown to inhibit phosphoglycerate-dependent O2 evolution in a simplified reconstituted chloroplast system containing 3-phosphoglycerate kinase and triose phosphate dehydrogenase. Rates of O2 evolution in the simplified system are comparable with those obtained by using stromal protein rather than purified enzymes. ADP does not inhibit O2 evolution with glycerate 1,3-biphosphate as substrate nor does it inhibit triose phosphate dehydrogenase. The inhibitory effect of ADP is attributed to an increase in the rate of conversion of glycerate biphosphate into phosphoglycerate. The results are discussed in terms of control by ADP of phosphoglycerate-dependent oxygen evolution.


Immediate aesthetic provisionalization for the dental implant patient.
Providing an acceptable provisional restoration for the patient undergoing tooth extraction in conjunction with bone grafting and dental implant treatment can present a challenge for the restorative dentist. The unnatural appearance and function of the typical temporary is often unacceptable to the patient whose treatment requires long-term temporization. This article describes a technique for using heat-cured acrylics to provide immediate aesthetics in a provisional bridge for such patients.


The Prognostic Impact of Primary Tumor Site Differs According to the KRAS Mutational Status: A Study By the International Genetic Consortium for Colorectal Liver Metastasis.
To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status. Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivocal outcomes of patients with CLM with RS versus left-sided (LS) primary tumors. Importantly, recent evidence from unresectable metastatic CRC suggests that tumor laterality impacts prognosis only in those with wild-type tumors. Patients with rectal or transverse colon tumors and those with unknown KRAS mutational status were excluded from analysis. The prognostic impact of RS versus LS primary CRC was determined after stratifying by KRAS mutational status. 277 patients had a RS (38.6%) and 441 (61.4%) had a LS tumor. Approximately one-third of tumors (28.1%) harbored KRAS mutations. In the entire cohort, RS was associated with worse 5-year overall survival (OS) compared with LS (39.4% vs 50.8%, P = 0.03) and remained significantly associated with worse OS in the multivariable analysis (hazard ratio 1.45, P = 0.04). In wild-type patients, a worse 5-year OS associated with a RS tumor was evident in univariable analysis (43.7% vs 55.5%, P = 0.02) and persisted in multivariable analysis (hazard ratio 1.49, P = 0.01). In contrast, among patients with KRAS mutated tumors, tumor laterality had no impact on 5-year OS, even in the univariable analysis (32.8% vs 34.0%, P = 0.38). This study demonstrated, for the first time, that the prognostic impact of primary tumor side differs according to KRAS mutational status. RS tumors were associated with worse survival only in patients with wild-type tumors.


Knock-down of plasminogen-activator inhibitor-1 enhances expression of E-cadherin and promotes epithelial differentiation of human pancreatic adenocarcinoma cells.
High levels of plasminogen activator inhibitor-1 (PAI-1), which is produced by stromal, endothelial, and cancer cells and has multiple complex effects on cancers, correlate with poor cancer prognosis. To more definitively study the role of endogenously produced PAI-1 in human pancreatic adenocarcinoma (PAC) PANC-1 cell line biology, we used anti-PAI-1 shRNA to create stable PAI-1 deficient cells (PD-PANC-1s). PD-PANC-1s exhibited a heterogeneous morphology. While the majority of cells exhibited a cuboidal shape similar to the parental PANC-1 or the vector-infected control cells, numerous large cells with long filopodia and a neuronal-like appearance were observed. Although both Vector-control cells and PD-PANC-1s expressed mRNAs that are characteristic of mesenchymal, neural, and epithelial phenotypes, epithelial marker RNAs were up-regulated (e.g., E-cadherin, 32-fold) whereas mesenchymal marker RNAs were down-regulated (e.g., Thy1, ninefold) in PD-PANC-1s, suggesting mesenchymal-to-epithelial transition. Neural markers exhibited both up- and down-regulation. Immunocytochemistry indicated that epithelial-like PD-PANC-1s expressed E-cadherin and β-catenin in significantly more cells, while neural-like cells exhibited robust expression of organized β-3-tubulin. PAI-1 and E-cadherin were rarely co-expressed in the same cells. Indeed, examination of PAI-1 and E-cadherin mRNAs expression in additional cell lines yielded clear inverse correlation. Indeed, infection of Colo357 PAC cells (that exhibit high expression of E-cadherin) with PAI-1-expressing adenovirus led to a marked decrease in E-cadherin expression and to enhanced migration of cells from clusters. Our results suggest that endogenous PAI-1 suppresses expression of E-cadherin and differentiation in PAC cells in vitro, supporting its negative impact on tumor prognosis.


Lymphocyte responses to Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA) peptides in individuals with naturally acquired Plasmodium falciparum malaria.
Antibody titers and lymphocyte responses to synthetic peptides corresponding to repeated amino acid sequences of the 3' and 5' regions of Pf155/ring-infected erythrocyte surface antigen (RESA) were studied in two groups of Thai subjects, soldiers (Rangers), and villagers who differed in their history of malaria exposure. The frequency of Pf155/RESA seropositivity was similar in the two groups while the frequency of high titer antibody was significantly greater in villagers than in Rangers. Lymphocyte responsiveness in vitro to all Pf155/RESA peptides was infrequent for both groups although half of the subjects studied responded to crude Plasmodium falciparum asexual blood stage malaria antigen (MA). Among responders, Pf155/RESA peptides elicited lymphocyte responses in which proliferation and interferon-gamma (IFN-gamma) production were not associated, whereas with MA, the two responses were associated. The MA-stimulated lymphocyte proliferation and IFN-gamma production for both groups of volunteers appeared to be independent of antibody titer. In this study, antibody, but not lymphocyte, responses to Pf155/RESA peptides were shown to reflect differences in prior exposure and levels of acquired immunity to falciparum malaria.


[Ambulatory surgery in plastic surgery].
The spectrum of plastic surgery is wide. It covers constructive, reconstructive and anaplastic surgery. A considerable portion of the operations can be carried out ambulatorily. Several examples show the practicability and limits. They are different according to the orientation of the surgeon and the equipment in his practice. Unfortunately also economic problems must be pointed out.


Delivering RapidArc®: A comprehensive study on accuracy and long term stability.
To establish the reliability and accuracy of a UNIQUE Linac in delivering RapidArc treatments and assess its long term stability. UNIQUE performance was monitored and analyzed for a period of nearly two years. 2280 Dynalog files, related to 179 clinical RapidArc treatments were collected. Different tumor sites and dose scheduling were included, covering the full range of our treatment plans. Statistical distributions of MLC motion error, gantry rotation error and MU delivery error were evaluated. The stochastic and systematic nature of each error was investigated together with their variation in time. All the delivery errors are found to be small and more stringent tolerances than those proposed by TG142 are suggested. Unlike MLC positional errors, where a linear relationship with leaf speed holds, other Volumetric Modulated Arc Therapy (VMAT) parameters reveal a random nature and, consequently, a reduced clinical relevance. MLC errors are linearly related only to leaf speed no matter the shape of the MLC apertures. Gantry rotation and MU delivery are as accurate as major competing Linacs. UNIQUE was found to be reliable and accurate throughout the investigation period, regardless of the specific tumor sites and fractionation schemes. The accuracy of RapidArc treatments delivered with UNIQUE has been established. The stochastic nature of delivery errors is proven. Long term statistics of the delivery parameter errors do not show significant variations, confirming the reliability of the VMAT delivery system.


Value of PCR detection of TCR gamma gene rearrangement in the diagnosis of cutaneous lymphocytic infiltrates.
In this study, we analyzed the reliability and usefulness of the polymerase chain reaction (PCR) for the detection of T-cell receptor (TCR)gamma gene monoclonal rearrangement. We first tested for the specificity and sensitivity of this strategy, against the classical criteria of Southern blot analysis (SBA). Of the 27 samples tested, results agreed in all but two. Broader analysis of these cases demonstrated the high specificity (absence of false positives) of the PCR strategy, together with its limited sensitivity (10% of false negatives). The usefulness of this PCR approach was then tested on a panel of 28 biopsy specimens of cutaneous lymphocytic infiltrates. Monoclonal TCR gamma rearrangement was detected in seven of eight cases of early stage mycosis fungoides (MF), one of two Sezary syndrome (SS) cases, two of two non-MF T-cell lymphoma, and two of three lymphomatoid papulosis. Monoclonality was not detected in any of the 11 benign cases (parapsoriasis and inflammatory dermatosis). Results obtained with this new molecular strategy provide additional support for the hypothesis of a monoclonal origin for most early stage T-cell MF. They also suggest the heterogeneous nature of some lymphomatoid papulosis lesions. Therefore, due to the difficulty in detecting T-cell monoclonality by immunohistochemical techniques, PCR can be a useful alternative strategy to SBA. It could also be used as a complementary technique in the routine diagnosis of T-cell cutaneous infiltrates.


What Do Social Media Influencers Say about Health? A Theory-Driven Content Analysis of Top Ten Health Influencers' Posts on Sina Weibo.
Social media health influencers play an increasingly important role in disseminating health-related information to the public. To explore how health influencers in China communicate with their followers, we conducted a content analysis of the top ten health influencers' posts (n = 1000) on Sina Weibo guided by the Extended Parallel Processing Model (EPPM) and the transportation theory. These posts were coded in terms of demographic information, topics, message properties (informative, persuasive, and interactive), EPPM variables, and types of evidence (statistical and narrative) used. Results showed that these influencers had a clear emphasis on women's health (OB/GYN diseases and risks related to pregnancy and childcare) and beauty and skincare (in terms of risks and benefits). Overall, they used low fear appeal and high efficacy messages. However, messages containing efficacy information were less likely to be liked. These influencers relied heavily on narrative evidence; however, there was no significant relationship between the use of either narrative or statistical evidence and the number of likes. Differences in the communication strategies in posts about different diseases did exist but were not prevalent.


The development of lasting impairments: a mild pediatric brain injury alters gene expression, dendritic morphology, and synaptic connectivity in the prefrontal cortex of rats.
Apart from therapeutic discovery, the study of mild traumatic brain injury (mTBI) has been focused on two challenges: why do a majority of individuals recover with little concern, while a considerable proportion suffer with persistent and often debilitating symptomology; and, how do mild injuries significantly increase risk for an early-onset neurodegeneration? Owing to a lack of observable damage following mTBI, this study was designed to determine if there were changes in neuronal morphology, synaptic connectivity, and epigenetic patterning that could contribute to the manifestation of persistent neurological dysfunction. Prefrontal cortex tissue from male and female rats was used for Golgi-Cox analysis along with the profiling of changes in gene expression (BDNF, DNMT1, FGF2, IGF1, Nogo-A, OXYR, and TERT) and telomere length (TL), following a single mTBI or sham injury in the juvenile period. Golgi-Cox analysis of dendritic branch order, dendritic length, and spine density demonstrate that an early mTBI increases complexity of pyramidal neurons in the mPFC. Furthermore, there are also substantial changes in the expression levels of the seven genes of interest and TL following a single mild injury in this brain region. The results from the neuroanatomical measures and changes in gene expression indicate that the mTBI disrupts normal pruning processes that are typically underway at this point in development. In addition, there are significant interactions between the social environment and epigenetic processes that work in concert to perpetuate neurological dysfunction.


Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms.
Epidemiological, clinical and laboratory studies have implicated solar ultraviolet (UV) radiation in various skin diseases including, premature aging of the skin and melanoma and non-melanoma skin cancers. Chronic UV radiation exposure-induced skin diseases or skin disorders are caused by the excessive induction of inflammation, oxidative stress and DNA damage, etc. The use of chemopreventive agents, such as plant polyphenols, to inhibit these events in UV-exposed skin is gaining attention. Chemoprevention refers to the use of agents that can inhibit, reverse or retard the process of these harmful events in the UV-exposed skin. A wide variety of polyphenols or phytochemicals, most of which are dietary supplements, have been reported to possess substantial skin photoprotective effects. This review article summarizes the photoprotective effects of some selected polyphenols, such as green tea polyphenols, grape seed proanthocyanidins, resveratrol, silymarin and genistein, on UV-induced skin inflammation, oxidative stress and DNA damage, etc., with a focus on mechanisms underlying the photoprotective effects of these polyphenols. The laboratory studies conducted in animal models suggest that these polyphenols have the ability to protect the skin from the adverse effects of UV radiation, including the risk of skin cancers. It is suggested that polyphenols may favorably supplement sunscreens protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and DNA damage.


Consequences of partial axotomy for production of neurotransmitter vesicles and routing of rapidly transported membrane glycoproteins in the axonal tree.
It was found previously that transection of one branch of the bifurcate axon of a giant serotonergic neuron of Aplysia causes a proportionate decrease in the export of transmitter storage vesicles from the cell body, despite the ability of the remaining branch to transport all of the vesicles normally exported (Aletta and Goldberg, 1982). We report here evidence that this down-regulation is achieved by a decrease in the production of vesicles, rather than a slowing of the processing of vesicles for export from the cell body. Counts of serotonergic vesicles in the cell body show that the size of the somal pool of vesicles is not increased at a time when their rate of export has been halved. Also, transection of one or both branches of the axon decreases the amount of 3H-fucose incorporated during a short period into a putative vesicle membrane glycoprotein but not into other glycoproteins. The results indicate that axotomy should be a useful technique for studying the mechanism of regulation of the synthesis of a secretory organelle. It was also previously shown that transection of one branch of the axon far from the cell body does not impair the ability of the injured branch to transport serotonergic vesicles, yet the majority of vesicles that would normally enter that branch are nevertheless rerouted into the uninjured branch. We have studied quantitatively the partitioning between the 2 branches, after one has been transected distally, of 6 fucosyl glycoproteins, including the putative vesicle glycoprotein and a glycoprotein whose transport moderately increases after transection.(ABSTRACT TRUNCATED AT 250 WORDS)


Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial.
BRAF mutations act as an oncogenic driver via the mitogen-activated protein kinase (MAPK) pathway in non-small cell lung cancer (NSCLC). BRAF inhibition has shown antitumour activity in patients with BRAF(V600E)-mutant NSCLC. Dual MAPK pathway inhibition with BRAF and MEK inhibitors in BRAF(V600E)-mutant NSCLC might improve efficacy over BRAF inhibitor monotherapy based on observations in BRAF(V600)-mutant melanoma. We aimed to assess the antitumour activity and safety of dabrafenib plus trametinib in patients with BRAF(V600E)-mutant NSCLC. In this phase 2, multicentre, non-randomised, open-label study, we enrolled adult patients (aged ≥18 years) with pretreated metastatic stage IV BRAF(V600E)-mutant NSCLC who had documented tumour progression after at least one previous platinum-based chemotherapy and had had no more than three previous systemic anticancer therapies. Patients with previous BRAF or MEK inhibitor treatment were ineligible. Patients with brain metastases were allowed to enrol only if the lesions were asymptomatic, untreated (or stable more than 3 weeks after local therapy if treated), and measured less than 1 cm. Enrolled patients received oral dabrafenib (150 mg twice daily) plus oral trametinib (2 mg once daily) in continuous 21-day cycles until disease progression, unacceptable adverse events, withdrawal of consent, or death. The primary endpoint was investigator-assessed overall response, which was assessed by intention to treat in the protocol-defined population (patients who received second-line or later treatment); safety was also assessed in this population and was assessed at least once every 3 weeks, with adverse events, laboratory values, and vital signs graded according to the Common Terminology Criteria for Adverse Events version 4.0. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT01336634. Between Dec 20, 2013, and Jan 14, 2015, 59 patients from 30 centres in nine countries across North America, Europe, and Asia met eligibility criteria. Two patients who had previously been untreated due to protocol deviation were excluded; thus, 57 eligible patients were enrolled. 36 patients (63·2% [95% CI 49·3-75·6]) achieved an investigator-assessed overall response. Serious adverse events were reported in 32 (56%) of 57 patients and included pyrexia in nine (16%), anaemia in three (5%), confusional state in two (4%), decreased appetite in two (4%), haemoptysis in two (4%), hypercalcaemia in two (4%), nausea in two (4%), and cutaneous squamous cell carcinoma in two (4%). The most common grade 3-4 adverse events were neutropenia in five patients (9%), hyponatraemia in four (7%), and anaemia in three (5%). Four patients died during the study from fatal adverse events judged to be unrelated to treatment (one retroperitoneal haemorrhage, one subarachnoid haemorrhage, one respiratory distress, and one from disease progression that was more severe than typical progression, as assessed by the investigator). Dabrafenib plus trametinib could represent a new targeted therapy with robust antitumour activity and a manageable safety profile in patients with BRAF(V600E)-mutant NSCLC. GlaxoSmithKline.


Task-dependent estimability index to assess the quality of cardiac computed tomography angiography for quantifying coronary stenosis.
Purpose: Quantifying stenosis in cardiac computed tomography angiography (CTA) images remains a difficult task, as image noise and cardiac motion can degrade image quality and distort underlying anatomic information. The purpose of this study was to develop a computational framework to objectively assess the precision of quantifying coronary stenosis in cardiac CTA. Approach: The framework used models of coronary vessels and plaques, asymmetric motion point spread functions, CT image blur (task-based modulation transfer functions) and noise (noise-power spectrums), and an automated maximum-likelihood estimator implemented as a matched template squared-difference operator. These factors were integrated into an estimability index ( e ' ) as a task-based measure of image quality in cardiac CTA. The e ' index was applied to assess how well it can to predict the quality of 132 clinical cases selected from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain trial. The cases were divided into two cohorts, high quality and low quality, based on clinical scores and the concordance of clinical evaluations of cases by experienced cardiac imagers. The framework was also used to ascertain protocol factors for CTA Biomarker initiative of the Quantitative Imaging Biomarker Alliance (QIBA). Results: The e ' index categorized the patient datasets with an area under the curve of 0.985, an accuracy of 0.977, and an optimal e ' threshold of 25.58 corresponding to a stenosis estimation precision (standard deviation) of 3.91%. Data resampling and training-test validation methods demonstrated stable classifier thresholds and receiver operating curve performance. The framework was successfully applicable to the QIBA objective. Conclusions: A computational framework to objectively quantify stenosis estimation task performance was successfully implemented and was reflective of clinical results in the context of a prominent clinical trial with diverse sites, readers, scanners, acquisition protocols, and patients. It also demonstrated the potential for prospective optimization of imaging protocols toward targeted precision and measurement consistency in cardiac CT images.


Barriers to participation in and adherence to cardiac rehabilitation programs: a critical literature review.
Despite the documented evidence of the benefits of cardiac rehabilitation (CR) in enhancing recovery and reducing mortality following a myocardial infarction, only about one third of patients participate in such programs. Adherence to these programs is an even bigger problem, with only about one third maintaining attendance in these programs after 6 months. This review summarizes research that has investigated barriers to participation and adherence to CR programs. Some consistent factors found to be associated with participation in CR programs include lack of referral by physicians, associated illness, specific cardiac diagnoses, reimbursement, self-efficacy, perceived benefits of CR, distance and transportation, self-concept, self-motivation, family composition, social support, self-esteem, and occupation. Factors associated with non-adherence include being older, female gender, having fewer years of formal education, perceiving the benefits of CR, having angina, and being less physically active during leisure time. However, many of the studies have methodologic flaws, with very few controlled, randomized studies, making the findings tentative. Problems in objectively measuring adherence to unstructured, non-hospital-based programs, which are an increasingly popular alternative to traditional programs, are discussed. Suggestions for reducing barriers to participation and adherence to CR programs, as well as for future research aimed at clearly identifying these barriers, are discussed.


A hemispherical, high-solid-angle optical micro-cavity for cavity-QED studies.
We report a novel hemispherical micro-cavity that is comprised of a planar integrated semiconductor distributed Bragg reflector (DBR) mirror, and an external, concave micro-mirror having a radius of curvature 50 microm. The integrated DBR mirror containing quantum dots (QD), is designed to locate the QDs at an antinode of the field in order to maximize the interaction between the QD and cavity. The concave micro-mirror, with high-reflectivity over a large solid-angle, creates a diffraction-limited (sub-micron) mode-waist at the planar mirror, leading to a large coupling constant between the cavity mode and QD. The half-monolithic design gives more spatial and spectral tuning abilities, relatively to fully monolithic structures. This unique micro-cavity design will potentially enable us to both reach the cavity quantum electrodynamics (QED) strong coupling regime and realize the deterministic generation of single photons on demand.


The role of the σ-holes in stability of non-bonded chalcogenidebenzene interactions: the ground and excited states.
The stability of the T-shaped and stacked complexes of benzene with methanethial (CH2S) and methaneselone (CH2Se) and their difluoro-, dichloro-, dibromo-derivatives is investigated in their ground and first electronic excited states by means of the SCS-ADC2 method. The origin of the stabilization in the ground state is discussed based on the results of calculations performed using the DFT-SAPT method. Calculations show that the stability of the T-shaped conformers increases upon electronic excitation, while it decreases for most of the stacked conformers. Both effects are explained by the changes in the electrostatic potential (ESP) of isolated monomers upon the electronic excitation.


Longitudinal Assessment of Mobility and Self-care Among Critically Ill Older Adults. An Age-Friendly Health Systems Initiative Quality Improvement Study.
Early mobility in the intensive care unit (ICU) is vital to maintaining an older adult patient's performance of activities of daily living, functional mobility, and overall quality of life. Prior studies have shown reduced length of inpatient stay and onset of delirium in patients with early mobilization. Despite these benefits, many ICU patients are often labeled as too sick to participate in therapy and frequently do not receive physical (PT) or occupational therapy (OT) consults until they are considered floor status. This delay in therapy can negatively affect a patient's capacity to participate in his/her self-care, add to the burden on caregivers, and limit disposition options. Our goals were to perform a longitudinal assessment of mobility and self-care among older patients through their medical ICU (MICU) stays and to quantify visits by therapy services to identify areas for improvement in achieving early intervention in this at-risk population. This was a retrospective quality improvement analysis of a cohort of admissions to the MICU at a large tertiary academic medical center between November 2018 and May 2019. Admission information, PT and OT consult information, Perme Intensive Care Unit Mobility Score, and Modified Barthel Index scores were entered into a quality improvement registry. Inclusion criteria consisted of age older than 65 years and at least 2 distinct visits by PT and/or OT for evaluation. Patients without consults and patients with weekend-only MICU stays were not assessed. There were 302 MICU patients 65 years or older admitted during the study period. Forty-four percent (132) of these patients received PT/OT consults, and among these, 32% (42) had at least 2 visits to allow comparison of objective scores. Seventy-five percent of patients had improved Perme scores (median, 9.4%; interquartile range, 2.3%-15.6%), and 58% of patients had improved Modified Barthel Index scores (median, 3%; interquartile range, -2% to 13.5%). However, 17% of potential therapy days were missed because of inadequate staffing/time, and 14% were missed because of being sedated or unable to participate. In our cohort of patients older than 65 years, receipt of therapy in the MICU led to modest improvements in score-assessed mobility and self-care before transfer to floor. Staffing, time constraints, and patient sedation or encephalopathy appeared to interfere most with further potential benefits. In the next phase, we plan to implement strategies to increase PT/OT availability in the MICU and implement a protocol to increase identification and referral of candidates for whom early therapy can prevent loss of mobility and ability to perform self-care.


Resection of giant invasive pituitary tumors through a transfacial approach: technical case report.
Giant invasive pituitary adenomas are rare tumors that have been reported to extensively involve the cranial base, as well as other intra- and extra-cranial structures, making surgical resection by traditional approaches impossible. We report two cases, each of a giant invasive adenoma involving the entire length of the clivus and adjacent structures that was resected via a transfacial approach with excellent results. Both tumors were in middle-aged men; one was nonsecreting, and the other secreted follicle-stimulating hormone alpha-subunit. Most previously reported giant invasive adenomas have been prolactinomas. Both tumors were resected via a transfacial approach that incorporated an osteoplastic maxillotomy with palatal division and a posterior pharyngeal incision that provided exposure from the suprasellar region to C2. Both of the patients received postoperative radiation and have done very well. Their cosmetic results were excellent. The complications included postoperative meningitis in one patient and a nasal voice in the other. The transfacial approach provides excellent access for this type of extensive midline tumor requiring resection from the suprasellar region down to the foramen magnum.


Effect of Foeniculum vulgare (fennel) on symptoms of depression and anxiety in postmenopausal women: a double-blind randomised controlled trial.
The aim of this study was to evaluate the effect of Foeniculum vulgare (fennel) on anxiety and depression symptoms in postmenopausal women. This study was a double-blind, randomised, placebo-controlled trial, in which 60 eligible postmenopausal women were selected and then randomly assigned to fennel and placebo groups. Then, symptoms of anxiety and depression were measured using Hospital Anxiety and Depression Scale (HADS) and Zung's Self Rating Depression Scale (SDS). Following the intervention, the score of HADS (depression and anxiety subgroups) and SDS did not show any significant decrease in the sample under study. However, the analysis of patients with depression or anxiety disorder showed a borderline or significant improvement. Further studies with a larger sample size are required to confirm the findings. Impact statement Current knowledge on the subject: Based on the results of in vivo and in vitro animal studies, fennel may have anti-depressant and anti-anxiety properties. The contribution made by this study: It appears that fennel is effective in menopausal women with depression and anxiety disorders. The implications of findings for clinical practice and future research: Further studies with a larger sample size are required to confirm the actual effect of fennel in clinical setting.


A simple method using the light microscope to visualize spermatozoon tail swelling in the hypo-osmotic test.
The functional integrity of the sperm (SPTZ) membrane is believed to be an important factor in fertilization. This function was assessed by Jeyendran et al. (Journal of Reproduction and Fertility, 70: 219-228, 1984), who concluded that when SPTZ from normal fertile men are exposed to a hypo-osmotic solution with an ionic strength of 0.15 mol/l, 60% or more will exhibit tail swelling Essentially no changes have occurred in the test procedure since it was first published, except that SPTZ could be fixed after exposure to the hypo-osmotic solution and observed at a later time using a phase-contrast microscope. We describe here a simple test which does not require phase-contrast microscopy to read a stained preparation after the hypo-osmotic test. A drop of semen preincubated in the hypo-osmotic medium of Jeyendran et al. and fixed with 18.5% formalin is placed on an albumin-coated slide. A second (spreader) slide is placed on the first as a coverslip and pulled forward at moderate speed until all the sperm has been spread into a moderately thin film. The preparation is then air dried and submitted to Papanicolaou staining. The slide can be read at any time after staining with a light microscope and provides permanent documentation.


Expressing grief through metaphors: family caregivers' experience of care and grief during the Covid-19 pandemic.
The COVID-19 pandemic has disrupted thousands of individuals' experience of caregiving and grief. This qualitative study aimed to gain in-dept understanding of family caregivers' lived experiences of caregiving and bereavement in the context of the COVID-19 pandemic in Quebec, Canada. The study also aimed at providing new insight about caregiving and bereavement by analysing the metaphors family caregivers use to report their experiences. The design of this study was guided by an interpretative phenomenological approach. In-depth interviews were conducted with twenty bereaved family caregivers who had lost a loved one during the first waves of the pandemic. Results indicate that bereaved family caregivers lived and understood their experience in terms of metaphoric cut-offs, obstructions and shockwaves. These three metaphors represented the grief process and the bereaved's quest for social connection, narrative coherence and recognition. By identifying the meaning of the bereaved's metaphors and the quest they reveal, our study underlines the singularity of pandemic grief and points to the value and meaning of caregiving with regard to the grieving process.


Advanced neuroimaging applied to veterans and service personnel with traumatic brain injury: state of the art and potential benefits.
Traumatic brain injury (TBI) remains one of the most prevalent forms of morbidity among Veterans and Service Members, particularly for those engaged in the conflicts in Iraq and Afghanistan. Neuroimaging has been considered a potentially useful diagnostic and prognostic tool across the spectrum of TBI generally, but may have particular importance in military populations where the diagnosis of mild TBI is particularly challenging, given the frequent lack of documentation on the nature of the injuries and mixed etiologies, and highly comorbid with other disorders such as post-traumatic stress disorder, depression, and substance misuse. Imaging has also been employed in attempts to understand better the potential late effects of trauma and to evaluate the effects of promising therapeutic interventions. This review surveys the use of structural and functional neuroimaging techniques utilized in military studies published to date, including the utilization of quantitative fluid attenuated inversion recovery (FLAIR), susceptibility weighted imaging (SWI), volumetric analysis, diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), positron emission tomography (PET), magnetoencephalography (MEG), task-based and resting state functional MRI (fMRI), arterial spin labeling (ASL), and magnetic resonance spectroscopy (MRS). The importance of quality assurance testing in current and future research is also highlighted. Current challenges and limitations of each technique are outlined, and future directions are discussed.


Cerebral white matter abnormalities and lifetime cognitive change: a 67-year follow-up of the Scottish Mental Survey of 1932.
Cerebral white matter abnormalities relate to cognitive functioning in elders. We examine whether this association is (a) independent of mental ability in youth and (b) related to general and/or specific mental abilities. We retested 83 participants of the Scottish Mental Survey of 1932 on a battery of mental tests. Their brains were scanned by magnetic resonance imaging. Three independent ratings (Fazekas) were made of periventricular, and subcortical and deep white matter abnormalities. Structural equation models showed that, irrespective of brain location, white matter abnormalities contributed about 14% of cognitive function variance in old age. Some of this effect might be due to hypertension. This contribution is independent of mental function in early life and is associated with general cognitive ability.


HER2 and responsiveness of breast cancer to adjuvant chemotherapy.
Amplification of the human epidermal growth factor receptor type 2 (HER2, also called HER2/neu) gene and overexpression of its product in breast-cancer cells may be associated with responsiveness to anthracycline-containing chemotherapy regimens. In the randomized, controlled Mammary.5 trial, we studied 639 formalin-fixed paraffin-embedded specimens obtained from 710 premenopausal women with node-positive breast cancer who had received either cyclophosphamide, epirubicin, and fluorouracil (CEF) or cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant chemotherapy. HER2 amplification or overexpression was evaluated with the use of fluorescence in situ hybridization, immunohistochemical analysis, and polymerase-chain-reaction analysis. Amplification of HER2 was associated with a poor prognosis regardless of the type of treatment. In patients whose tumors showed amplification of HER2, CEF was superior to CMF when assessed on the basis of relapse-free survival (hazard ratio, 0.52; 95 percent confidence interval, 0.34 to 0.80; P=0.003) and overall survival (hazard ratio, 0.65; 95 percent confidence interval, 0.42 to 1.02; P=0.06). For women whose tumors lacked amplification of HER2, CEF did not improve relapse-free survival (hazard ratio for relapse, 0.91; 95 percent confidence interval, 0.71 to 1.18; P=0.49) or overall survival (hazard ratio for death, 1.06; 95 percent confidence interval, 0.83 to 1.44; P=0.68). The adjusted hazard ratio for the interaction between treatment and HER2 amplification was 1.96 for relapse-free survival (95 percent confidence interval, 1.15 to 3.36; P=0.01) and 2.04 for overall survival (95 percent confidence interval, 1.14 to 3.65; P=0.02). Amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracycline-containing chemotherapy. (cancer.gov number, NCI-V90-0027.).


Why do Sequence Signatures Predict Enzyme Mechanism? Homology versus Chemistry.
First, we identify InterPro sequence signatures representing evolutionary relatedness and, second, signatures identifying specific chemical machinery. Thus, we predict the chemical mechanisms of enzyme-catalyzed reactions from catalytic and non-catalytic subsets of InterPro signatures. We first scanned our 249 sequences using InterProScan and then used the MACiE database to identify those amino acid residues that are important for catalysis. The sequences were mutated in silico to replace these catalytic residues with glycine and then again scanned using InterProScan. Those signature matches from the original scan that disappeared on mutation were called catalytic. Mechanism was predicted using all signatures, only the 78 "catalytic" signatures, or only the 519 "non-catalytic" signatures. The non-catalytic signatures gave indistinguishable results from those for the whole feature set, with precision of 0.991 and sensitivity of 0.970. The catalytic signatures alone gave less impressive predictivity, with precision and sensitivity of 0.791 and 0.735, respectively. These results show that our successful prediction of enzyme mechanism is mostly by homology rather than by identifying catalytic machinery.


Automated MRI Volumetric Analysis in Patients with Rasmussen Syndrome.
Rasmussen syndrome, also known as Rasmussen encephalitis, is typically associated with volume loss of the affected hemisphere of the brain. Our aim was to apply automated quantitative volumetric MR imaging analyses to patients diagnosed with Rasmussen encephalitis, to determine the predictive value of lobar volumetric measures and to assess regional atrophy differences as well as monitor disease progression by using these measures. Nineteen patients (42 scans) with diagnosed Rasmussen encephalitis were studied. We used 2 control groups: one with 42 age- and sex-matched healthy subjects and the other with 42 epileptic patients without Rasmussen encephalitis with the same disease duration as patients with Rasmussen encephalitis. Volumetric analysis was performed on T1-weighted images by using BrainSuite. Ratios of volumes from the affected hemisphere divided by those from the unaffected hemisphere were used as input to a logistic regression classifier, which was trained to discriminate patients from controls. Using the classifier, we compared the predictive accuracy of all the volumetric measures. These ratios were used to further assess regional atrophy differences and correlate with epilepsy duration. Interhemispheric and frontal lobe ratios had the best prediction accuracy for separating patients with Rasmussen encephalitis from healthy controls and patient controls without Rasmussen encephalitis. The insula showed significantly more atrophy compared with all the other cortical regions. Patients with longitudinal scans showed progressive volume loss in the affected hemisphere. Atrophy of the frontal lobe and insula correlated significantly with epilepsy duration. Automated quantitative volumetric analysis provides accurate separation of patients with Rasmussen encephalitis from healthy controls and epileptic patients without Rasmussen encephalitis, and thus may assist the diagnosis of Rasmussen encephalitis. Volumetric analysis could also be included as part of follow-up for patients with Rasmussen encephalitis to assess disease progression.


Rational design of the gram-scale synthesis of nearly monodisperse semiconductor nanocrystals.
We address two aspects of general interest for the chemical synthesis of colloidal semiconductor nanocrystals: (1) the rational design of the synthesis protocol aiming at the optimization of the reaction parameters in a minimum number of experiments; (2) the transfer of the procedure to the gram scale, while maintaining a low size distribution and maximizing the reaction yield. Concerning the first point, the design-of-experiment (DOE) method has been applied to the synthesis of colloidal CdSe nanocrystals. We demonstrate that 16 experiments, analyzed by means of a Taguchi L16 table, are sufficient to optimize the reaction parameters for controlling the mean size of the nanocrystals in a large range while keeping the size distribution narrow (5-10%). The DOE method strongly reduces the number of experiments necessary for the optimization as compared to trial-and-error approaches. Furthermore, the Taguchi table analysis reveals the degree of influence of each reaction parameter investigated (e.g., the nature and concentration of reagents, the solvent, the reaction temperature) and indicates the interactions between them. On the basis of these results, the synthesis has been scaled up by a factor of 20. Using a 2-L batch reactor combined with a high-throughput peristaltic pump, different-sized samples of CdSe nanocrystals with yields of 2-3 g per synthesis have been produced without sacrificing the narrow size distribution. In a similar setup, the gram-scale synthesis of CdSe/CdS/ZnS core/shell/shell nanocrystals exhibiting a fluorescence quantum yield of 81% and excellent resistance of the photoluminescence in presence of a fluorescent quencher (aromatic thiol) has been achieved.PACS: 81.20.Ka, 81.07.Bc, 78.67.Bf.


Specific Intratumor Bacteria Genera and TRG Recombinations Associated with Greater Survival Probability in Alimentary Tract Cancers.
There remains a lack of knowledge regarding the effects of the intratumor microbiome on the tumor immune milieu. We aimed to investigate whether intratumoral bacterial RNA sequence abundance in gastric and esophageal cancers is associated with T-cell infiltrate features. We assessed cases representing the stomach adenocarcinoma (STAD) and esophageal cancer (ESCA) databases of The Cancer Genome Atlas. RNA-seq data estimating intratumoral bacterial abundance was obtained from publicly available sources. TCR recombination reads were mined from exome files. Survival models were generated using the lifelines python package. Increasing levels of the Klebsiella genus were associated with a better OS probability (hazard ratio, 0.5), via a Cox proportional hazards model. The higher Klebsiella abundance was associated with a significantly increased overall (p = 0.0001) and disease-specific survival (p = 0.0289) probability for the STAD dataset. Cases representing the upper 50th percentile of Klebsiella abundance also represented a significantly increased recovery of TRG and TRD recombination reads (p = 0.00192). Analogous results were found for the Aquincola genus in ESCA. This is the first report of associations between low biomass bacterial samples from primary tumor samples with patient survival and with an increased gamma-delta T cell infiltrate. Results indicate that the gamma-delta T cells potentially play a role in the dynamics of the bacterial infiltration of primary tumors of the alimentary tract.


Monoclonal antibody specific for carbodiimide-fixed glutamate: immunocytochemical localization in the rat CNS.
Glutamate is widely distributed in the central nervous system (CNS) and is present in greater amounts than any other putative neurotransmitter. To study its distribution in the CNS, a monoclonal antibody was raised against gamma-L-glutamyl-L-glutamic acid (gamma-Glu-Glu) conjugated to keyhole limpet hemocyanin (KLH) using glutaraldehydeborohydride. By use of this antibody, indirect immunoperoxidase staining was observed in CNS tissue fixed with carbodiimide to form gamma-Glu-Glu from glutamate and post-fixed with glutaraldehyde or paraformaldehyde. In contrast, immunoreactivity was quite low in tissues fixed only with glutaraldehyde. Absorption controls indicated that the staining of carbodiimide-fixed tissue could be inhibited by micromolar concentrations of gamma-Glu-Glu but not by other small molecules. Using ELISA, the antibody reacted strongly with the gamma-Glu-Glu/KLH conjugate used to immunize the mouse, but not with other small molecules conjugated to KLH. The reactivity of the antibody with the gamma-Glu-Glu/KLH conjugate on ELISA was inhibited by free gamma-Glu-Glu in micromolar concentrations, but not by similar dipeptides or amino acids. Dense immunocytochemical staining was observed in cortical pyramidal cells, cerebellar granule cells, and the cochlear nuclei. Staining with this monoclonal antibody correlated well with other methods of localizing glutamate in the CNS.


Dysfunction of the belch reflex. A cause of incapacitating chest pain.
We report a 25-yr-old woman who suffered incapacitating chest pain caused by upper esophageal sphincter (UES) dysfunction. She presented with a long history of severe episodic chest pain associated with gurgling noises in her chest and was unable to belch despite feeling a need to do so during pain episodes. Fluoroscopic and manometric studies confirmed that the patient's chest pain and gurgling noise were associated with dysfunction of the belch reflex. Although reflux of gas from the stomach into the esophageal body occurred normally, the extreme esophageal distention resulting from the gas reflux failed to trigger UES relaxation. Consequently, there was no venting of gas across the UES. The gurgling noise was caused by the gastroesophageal reflux of gas and the pain was associated with profound esophageal distention. A manometric study of the UES revealed absent or incomplete UES relaxation in response to abrupt esophageal distention by gastroesophageal gas reflux, so that the nadir of UES pressure always exceeded esophageal body pressure. The distended esophagus was repeatedly cleared by secondary peristalsis. To our knowledge this is the first description of chest pain caused by dysfunction of the belch reflex. We speculate that the mechanism described in this patient may account for a subgroup of patients with "chest pain of esophageal origin."


The Case of Successful Surgical Treatment of a Patient With Thoracic Endograft Infection in 5 Years After Thoracic Endovascular Aortic Repair.
We present here a case of successful staged treatment of a patient with para-aortic abscess that arose 5 years after thoracic endovascular aortic repair because of thoracic aortic aneurysm. After stabilization of the patient's condition by intensive antibiotic therapy we performed left-subclavian extra-thoracic debranching as the first stage of the surgical treatment. In 2 weeks via median sternotomy and on-pump we removed the infected endograft and performed extraanatomical ascending-to-descending aortic bypass with good postoperative result.


Hypothalamic response to starvation: implications for the study of wasting disorders.
Weight loss is a potent stimulus to food intake in normal individuals. The persistence of anorexia in wasting disorders, therefore, implies a failure of this adaptive feeding response. We describe a model for the normal hypothalamic response to starvation composed of the stimulation of neuronal pathways that promote energy intake and storage coupled with the inhibition of pathways that exert opposing effects. This model provides a framework for investigating disturbances of the normal hypothalamic response to weight loss and suggests a specific mechanism by which cytokines contribute to wasting in acquired immune deficiency syndrome and other cachexic disorders.


LIN28A inhibits lysosome‑associated membrane glycoprotein 1 protein expression in embryonic stem and bladder cancer cells.
Tumor cells and embryonic stem cells (ESCs) have similar transcription mechanisms. LIN28A is an important factor in tumor cells and ESCs, it is an inhibitor of intracellular endoplasmic reticulum (ER)‑related protein translation in ESCs. The present study aimed to examine the effects of LIN28A on an ER‑related protein, lysosome‑associated membrane glycoprotein 1 (LAMP1), in human bladder cancer cells and mouse (m)ESCs, using reverse transcription‑quantitative polymerase chain reaction and western blotting to detect the expression of LAMP1 mRNA and protein, respectively, following LIN28A knockdown. LIN28A was revealed to promote the proliferation, migration and invasion in human bladder cancer cells. These data suggested similarities between ESC cells and cancer cells and may provide novel ideas for the use of induced embryonic stem cell differentiation to treat tumors.


Laminaria japonica Extract Enhances Intestinal Barrier Function by Altering Inflammatory Response and Tight Junction-Related Protein in Lipopolysaccharide-Stimulated Caco-2 Cells.
In the normal physiological state, intestinal epithelial cells act as a defensive frontline of host mucosal immunity to tolerate constant exposure to external stimuli. In this study, we investigated the potential anti-inflammatory and gut permeability protective effects of Laminaria japonica (LJ) water extract (LJE) and three types of fermented Laminaria japonica water extracts (LJE-F1, LJE-F2, and LJE-F3) in lipopolysaccharide (LPS)-stimulated Caco-2, human intestinal epithelial cells. All four extracts significantly decreased the production of nitric oxide and interleukin-6 induced by LPS stimulus. In addition, LJE and the three types of LJE-Fs also inhibited LPS-induced loss of monolayer permeability, as assessed by changes in transepithelial electrical resistance. All four LJ extracts significantly prevented the inhibition of the protein levels of occludin, whereas LJE, LJE-F1, and LJE-F3 significantly attenuated the reduction in phosphorylation of adenosine monophosphate-activated protein kinase compared with the LPS-treated group in Caco-2 cells. In conclusion, LJE and its fermented water extracts appear to have potential gut health-promoting effects by reducing inflammation and partially regulating the tight junction-related proteins in human intestinal epithelial cells. Thus, additional studies are warranted to evaluate Laminaria japonica as a therapeutic agent for inflammatory bowel diseases.


Incorporation of quantum dots on virus in polycationic solution.
Developing methods to label viruses with fluorescent moieties has its merits in elucidating viral infection mechanisms and exploring novel antiviral therapeutics. Fluorescent quantum dots (QDs), an emerging probe for biological imaging and medical diagnostics, were employed in this study to tag retrovirus encoding enhanced green fluorescent protein (EGFP) genes. Electrostatic repulsion forces generated from both negatively charged retrovirus and QDs were neutralized by cationic Polybrene, forming colloidal complexes of QDs-virus. By examining the level of EGFP expression in 3T3 fibroblast cells treated with QDs-tagged retroviruses for 24 hours, the infectivity of retrovirus incorporated with QDs was shown to be only slightly decreased. Moreover, the imaging of QDs can be detected in the cellular milieu. In summary, the mild method developed here makes QDs-tagged virus a potential imaging probe for direct tracking the infection process and monitoring distribution of viral particles in infected cells.


Screening for Depression in Adolescents with Developmental Disabilities: Brief Report.
Objectives: (1) To examine adherence of universal screening for adolescent depression at initial visits by using an established screening instrument (Patient Health Questionnaire 9 [PHQ-9]) in a university-affiliated urban developmental center that serves children with developmental disabilities (DDs); (2) to study the frequency of positive screening for depression in adolescents with DD. Methods: Review of all adolescents referred for multidisciplinary evaluation in a developmental center in 2019. Data included demographics, DD diagnoses, and use of and scores on the PHQ-9 at initial visit. Statistics included chi-square and non-parametrics. Results: Of all the children evaluated in 2019 (n = 240), 52 were adolescents, 35 boys (63%)/17 girls (37%), age 14 ± 2 years old, and 27 (54%) belonging to a bilingual English-Spanish household. DD: Developmental Language Disorder (88%), Learning Disabilities (54%), attention-deficit/hyperactivity disorder (44%), Autism Spectrum Disorder (25%), Intellectual Disabilities (12%), and Phonological Disorder (8%). The PHQ-9 was administered to 30 (58%) individuals. Scores varied from minimal depression for 17 (57%), mild for 10 (33%), and moderate and severe for 3 (10%); 3 patients endorsed suicidality. Females were more likely to obtain higher scores on the PHQ-9 than males. Adolescents diagnosed with Autism Spectrum Disorder, Intellectual Disabilities, and Phonological Disorder were less likely to be screened. Conclusion: More than half of the sample of urban adolescents with DD were screened for depression at initial visit, and 10% screened positive for moderate to severe depression. Efforts to follow the U.S. Preventive Services Task Force recommendation of universal screening of adolescent depression should continue. However, given challenges with reading and verbal abilities, screening modifications (reading to them) should be considered.


The allocation of energy to echolocation pulses produced by soprano pipistrelles (Pipistrellus pygmaeus) during the wingbeat cycle.
Soprano pipistrelles exhibit considerable plasticity in both the structure and rate of echolocation call production. In search phase in the laboratory, calls are produced either as a single pulse per wingbeat cycle, or as double pulses. The amplitude of double pulses is reduced compared to the preceding single pulse. The energy flux density of either pulse of a double pulse per wingbeat was lower than a single pulse per wingbeat, and is achieved by a combination of reduction in both duration and amplitude. The combined energy of the double pulses is not significantly greater than the single pulse which precedes it. The decision to produce a double pulse may be an indication of the bat requiring additional information from the target. The production of double pulses per wingbeat may serve to achieve a higher rate of information flow for no significant increase in energetic expenditure when a possible target is detected. The proposal that echolocation during flight comes for free as a by-product of the intimate coupling among wingbeat, respiration, and echolocation is discussed.


Jaynes-Cummings photonic superlattices.
A classical realization of the Jaynes-Cummings (JC) model, describing the interaction of a two-level atom with a quantized cavity mode, is proposed based on light transport in engineered waveguide superlattices. The optical setting enables us to visualize in Fock space dynamical regimes not yet accessible in quantum systems, providing new physical insights into the deep strong coupling regime of the JC model. In particular, bouncing of photon number wave packets in Hilbert space and revivals of populations are explained as generalized Bloch oscillations in an inhomogeneous tight-binding lattice.


Investigating partner abuse among HIV-positive men who have sex with men.
High rates of partner abuse (PA) of all types-physical, sexual, and psychological-have been identified in studies of HIV-positive individuals. We examined both the prevalence and correlates of same-sex PA in HIV-positive men who have sex with men (MSM). Participants recruited from public outpatient HIV clinics (N = 168) completed CASI surveys about PA and current physical and mental health. Electronic medical record data were obtained for HIV biomarkers. Results indicate high rates of past year PA (physical, 19%; sexual, 17%; psychological, 51%; any, 54%), with rates comparable to, or higher than, those reported in recent studies of HIV-positive women and older studies of HIV-positive MSM. Overall, participants endorsing past year PA reported poorer mental but not physical health. Participants who endorsed past year physical PA, specifically, reported the largest number of mental health problems. HIV care providers should routinely assess PA, especially physical PA, in all MSM patients.


Inhibition of signal termination-related kinases by membrane-permeant bitter and sweet tastants: potential role in taste signal termination.
Sweet and bitter taste sensations are believed to be initiated by the tastant-stimulated T1R and T2R G protein-coupled receptor (GPCR) subfamilies, respectively, which occur in taste cells. Although such tastants, with their significantly diverse chemical structures (e.g., sugar and nonsugar sweeteners), may share the same or similar T1Rs, some nonsugar sweeteners and many bitter tastants are amphipathic and produce a significant delay in taste termination (lingering aftertaste). We report that such tastants may permeate rat taste bud cells rapidly in vivo and inhibit known signal termination-related kinases in vitro, such as GPCR kinase (GRK)2, GRK5, and PKA. GRK5 and perhaps GRK2 and GRK6 are present in taste cells. A new hypothesis is proposed in which membrane-permeant tastants not only interact with taste GPCRs but also interact intracellularly with the receptors' downstream shutoff components to inhibit signal termination.


E Pluribus Unum: 50 Years of Research, Millions of Viruses, and One Goal--Tailored Acceleration of AAV Evolution.
Fifty years ago, a Science paper by Atchison et al. reported a newly discovered virus that would soon become known as adeno-associated virus (AAV) and that would subsequently emerge as one of the most versatile and most auspicious vectors for human gene therapy. A large part of its attraction stems from the ease with which the viral capsid can be engineered for particle retargeting to cell types of choice, evasion from neutralizing antibodies or other desirable properties. Particularly powerful and in the focus of the current review are high-throughput methods aimed at expanding the repertoire of AAV vectors by means of directed molecular evolution, such as random mutagenesis, DNA family shuffling, in silico reconstruction of ancestral capsids, or peptide display. Here, unlike the wealth of prior reviews on this topic, we especially emphasize and critically discuss the practical aspects of the different procedures that affect the ultimate outcome, including diversification protocols, combinatorial library complexity, and selection strategies. Our overall aim is to provide general guidance that should help users at any level, from novice to expert, to safely navigate through the rugged space of directed AAV evolution while avoiding the pitfalls that are associated with these challenging but promising technologies.


Genetic variation in PEAR1 is associated with platelet aggregation and cardiovascular outcomes.
BACKGROUND- Aspirin or dual antiplatelet therapy with aspirin and clopidogrel is a standard therapy for patients who are at increased risk for cardiovascular events. However, the genetic determinants of variable response to aspirin (alone and in combination with clopidogrel) are not known. METHODS AND RESULTS- We measured ex vivo platelet aggregation before and after dual antiplatelet therapy in individuals (n=565) from the Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study and conducted a genome-wide association study of drug response. Significant findings were extended by examining genotype and cardiovascular outcomes in 2 independent aspirin-treated cohorts: 227 percutaneous coronary intervention patients and 1000 patients of the International Verapamil SR/Trandolapril Study (INVEST) Genetic Substudy (INVEST-GENES). Results from the genome-wide association study revealed a strong association between single-nucleotide polymorphisms on chromosome 1q23 and post-dual antiplatelet therapyplatelet aggregation. Further genotyping revealed rs12041331 in the platelet endothelial aggregation receptor-1 (PEAR1) gene to be most strongly associated with dual antiplatelet therapy response (P=7.66×10(-9)). In white and black patients undergoing percutaneous coronary intervention, A-allele carriers of rs12041331 were more likely to experience a cardiovascular event or death compared with GG homozygotes (hazard ratio, 2.62; 95% confidence interval, 0.96-7.10; P=0.059; and hazard ratio, 3.97; 95% confidence interval, 1.10-14.31; P=0.035, respectively). In aspirin-treated INVEST-GENES patients, rs12041331 A-allele carriers had significantly increased risk of myocardial infarction compared with GG homozygotes (odds ratio, 2.03; 95% confidence interval, 1.01-4.09; P=0.048). CONCLUSION- Common genetic variation in PEAR1 may be a determinant of platelet response and cardiovascular events in patients on aspirin alone or in combination with clopidogrel. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00799396 and NCT00370045.


[Regulation of snail heart contractions by neurons of the visceral ganglion].
The system of neurons regulating the frequency and strength of heart beats was studied in the snail subesophageal ganglia. Three out of four neurons exerted a short-term phasic effect on the heart. Stimulation of the V6 neuron led to a prolonged increase in the frequency and strength of the heart beats. Activity of two inhibitory cells (about 1-3/sec) was observed whereas excitatory neurons were silent. All the efferent neurons were involved in parallel and did not affect each other.