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Alcohol use has been shown to increase stress, and there is some evidence that stress predicts subsequent alcohol use during treatment for alcohol use disorder (AUD), particularly among females who are more likely to report coping-motivated drinking. Gaining a better understanding of the processes by which stress and alcohol use are linked during treatment could potentially inform AUD treatment planning. The current study aimed to characterize the association between stress and drinking during the course of AUD treatment and whether there were sex differences in these associations. Secondary data analyses of the COMBINE study (N = 1375; 69% male, 76.3% non-Hispanic and white, average age of 44.4 years) were conducted to examine self-reported perceived stress and alcohol consumption across 16 weeks of treatment for AUD using a Bayesian random-intercept cross-lagged panel model. There was stronger evidence for any alcohol use predicting greater than typical stress in subsequent weeks and less strong evidence for stress increasing the subsequent probability of alcohol use, particularly among males. For females, greater stress predicted subsequent drinking earlier in the treatment period, and a lower probability of subsequent drinking in the last week of treatment. Interventions might specifically focus on targeting reductions in stress following drinking occasions.

This study investigated the ADL performances of people with VFL after an acute stroke using an observation-based evaluation of ADL skills, the Assessment of Motor and Process Skills. The AMPS was administered on initial assessment and at ≥11 weeks follow-up on 58 adults with a mild stroke, with ( n  = 16) and without VFL ( n  = 42), over a 13-month period. The AMPS guidelines on clinically relevant difference of 0.30 logits were used to determine the differences of the groups' ADL performance on initial assessment and follow-up. The study found that the ADL motor and process scores did not differ significantly on initial assessment. The study observed no clinically relevant difference between the ADL motor and process scores of between the VFL and non-VFL on initial assessment and follow-up but demonstrated clinically relevant improvements in ADL motor and process scores of both groups from initial assessment to follow-up. VFL does not have an additional negative impact on ADL performance of those with a mild stroke and does not impede improvement of ADL performance over time.

Background: We aim to estimate the magnitude of the reduction in pneumococcal pneumonia and meningitis mortality after the mass introduction of pneumococcal conjugate vaccine (PCV)7 and PCV13 in children in the United States., Methods: We assessed the trends in mortality rates from pneumococcal pneumonia and meningitis, in the United States between 1994 and 2017. We fitted an interrupted time-series negative binomial regression model (adjusted by trend, seasonality, PCV7/PCV13 coverage, and H. influenzae type b vaccine coverage) to estimate the counterfactual rates without vaccination. We reported a percent reduction in mortality estimates relative to the projected no-vaccination scenario, using the formula 1 minus the incidence risk ratio, with 95% confidence intervals (CIs)., Results: Between 1994 and 1999 (the prevaccination period), the all-cause pneumonia mortality rate for 0-1-month-old children was 2.55 per 100,00 pop., whereas for 2-11 months-old children, this rate was 0.82 deaths per 100,000 pop. During the PCV7-period in 0-59-month-old children in the United States, the adjusted reduction of all-cause pneumonia was 13% (95% CI: 4-21) and 19% (95% CI: 0-33) of all-cause meningitis For PCV13, the reductions in this age group were 21% (95% CI: 4-35) for all-cause pneumonia mortality and 22% (95% CI: -19 to 48) for all-cause meningitis mortality. PCV13 had greater reductions of all-cause pneumonia than PCV13 in 6-11-month-old infants., Conclusions: The universal introduction of PCV7, and later PCV13, for children 0-59 months old in the United States was associated with decreases in mortality due to all-cause pneumonia., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Influenza seasonality is caused by complex interactions between environmental factors, viral mutations, population crowding, and human travel. To date, no studies have estimated the seasonality and latitudinal patterns of seasonal influenza in Chile. We obtained influenza-like illness (ILI) surveillance data from 29 Chilean public health networks to evaluate seasonality using wavelet analysis. We assessed the relationship between the start, peak, and latitude of the ILI epidemics using linear and piecewise regression. To estimate the presence of incoming and outgoing traveling waves (timing vs distance) between networks and to assess the association with population size, we used linear and logistic regression. We found a north to south gradient of influenza and traveling waves that were present in the central, densely populated region of Chile. Our findings suggest that larger populations in central Chile drive seasonal influenza epidemics., (© 2022. The Author(s).)

Introduction: Autoimmune anti-NMDAr encephalitis is an antibody-mediated disorder characterized by psychiatric symptoms followed by decreased consciousness, dysautonomia and seizures. The pathophysiology of the disease is related to the internalization of NR1 subtype NMDA receptors and the dysfunction of structures where they are abundant (frontotemporal and insular regions). Some reports suggest the existence of cerebral atrophy in the follow-up of these patients, with conflicting evidence regarding its presence and usefulness as a marker of prognosis., Methods: In a longitudinal, observational study, all patients with the diagnosis of definite anti-NMDAr autoimmune encephalitis with initial and control MRI studies were included. Conventional MR Brain acquisition was performed using a 3-Tesla Skyra MRI System. Automated brain segmental analysis was performed using the Volbrain volumetry system. The differences between baseline MRI volumetric characteristics and volumetric measures at follow-up was assessed., Results: 25 patients were included (mean age 26.6, SD 9.6). 44% were females. The mean time between the studies was 24 (SD 21.4, 3-24) months. Significant volume loss was identified in the total brain volume (- 0.02%, p = 0.029), cerebellar volume (- 0.27%, p = 0.048) and brainstem volume (- 0.16%, p = 0.021)., Conclusions: This study supports previous observations regarding volume loss in several brain regions of patients with antiNMDAr encephalitis. Further analyses are required to understand the role of treatment and severe clinical forms, as well as the relationship between volume loss and functional outcome., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Impairments in mitochondrial energy metabolism have been implicated in human genetic diseases associated with mitochondrial and nuclear DNA mutations, neurodegenerative and cardiovascular disorders, diabetes, and aging. Alteration in mitochondrial complex I structure and activity has been shown to play a key role in Parkinson's disease and ischemia/reperfusion tissue injury, but significant difficulty remains in assessing the content of this enzyme complex in a given sample. The present study introduces a new method utilizing native polyacrylamide gel electrophoresis in combination with flavin fluorescence scanning to measure the absolute content of complex I, as well as α-ketoglutarate dehydrogenase complex, in any preparation. We show that complex I content is 19 ± 1 pmol/mg of protein in the brain mitochondria, whereas varies up to 10-fold in different mouse tissues. Together with the measurements of NADH-dependent specific activity, our method also allows accurate determination of complex I catalytic turnover, which was calculated as 10 4 min -1 for NADH:ubiquinone reductase in mouse brain mitochondrial preparations. α-ketoglutarate dehydrogenase complex content was determined to be 65 ± 5 and 123 ± 9 pmol/mg protein for mouse brain and bovine heart mitochondria, respectively. Our approach can also be extended to cultured cells, and we demonstrated that about 90 × 10 3 complex I molecules are present in a single human embryonic kidney 293 cell. The ability to determine complex I content should provide a valuable tool to investigate the enzyme status in samples after in vivo treatment in mutant organisms, cells in culture, or human biopsies., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Cyclophosphamide (CYC) is an alkylating agent with immunosuppressive effect by inhibiting DNA synthesis and producing apoptosis used in many autoimmune diseases, including multiple sclerosis (MS). Here, we analyze the efficacy of CYC treatment in relapsing-remitting (RRMS) and active secondary progressive MS (SPMS) in our center with a monthly scheme., Methods: Patients with MS treated with CYC and a follow up of at least 36 months were eligible for inclusion. All participants had received a standard CYC regimen. The EDSS score mean annualized relapse rate (ARR) and progression index (PI) were measured as efficacy outcomes at 12, 24, and 36 months. Outcomes were also analyzed comparing disease course and activity., Results: A total of 16 patients were included (50% male, 18.75% RRMS and 81.25% SPMS). EDSS remained stable along the follow-up period, with 62.5% improving or maintaining the same EDSS score at 12 months. PI decreased 14% and 21% at 12 and 24-36 months of follow-up, respectively. ARR decreased 20% after 12 months, 19% after 24 months, and 30.23% after 36 months. Median differences in ARR were higher in patients with high relapse activity (0.60 vs 0.07, p = 0.001) and malignant course (0.60 vs 0.17, p = 0.027). PI also differed with higher mean differences in patients with high relapse activity (0.70 vs 0.03, p = 0.016) and malignant course (1.17 vs 0.03, p = 0.003)., Conclusions: CYC continues to be a valid therapeutic option, especially in regions with limited access to high-efficiency therapies particularly in patients with high relapsing activity and malignant course., (© 2021. Fondazione Società Italiana di Neurologia.)

Distinct sub-assemblies (modules) of mitochondrial complex I (CI) are assembled with the assistance of CI Assembly Factors (CIAFs) through mechanisms that are incompletely defined. Here, using genetic analyses in Drosophila , we report that when either of the CIAFs - NDUFAF3 or NDUFAF4 - is disrupted, biogenesis of the Q-, N-, and P P-b -modules of CI is impaired. This is due, at least in part, to the compromised integration of NDUFS3 and NDUFS5 into the Q-, and P P-b -modules, respectively, coupled with a destabilization of another CIAF, TIMMDC1, in assembly intermediates. Notably, forced expression of NDUFAF4 rescues the biogenesis defects in the Q-module and some aspects of the defects in the P P-b -module of CI when NDUFAF3 is disrupted. Altogether, our studies furnish new fundamental insights into the mechanism by which NDUFAF3 and NDUFAF4 regulate CI assembly and raises the possibility that certain point mutations in NDUFAF3 may be rescued by overexpression of NDUFAF4., Competing Interests: The authors declare no competing financial interests.

Background: We aim in our analysis to estimate the reduction of diarrhea-related mortality rates after introduction of a rotavirus vaccine in subregions of 4 Latin American countries., Methods: We selected diarrhea-related deaths from individual-level data from death certificates in Brazil, Colombia, Ecuador, and Mexico. Counts were aggregated by region, year and month, and age group for each country. We ran an interrupted time-series analysis using Poisson regression to obtain seasonal and trend-adjusted estimates of impact. Results are reported as percentages (1 - mortality rate ratio)., Results: We found a reduction in diarrhea-related mortality in children <5 years old of 18% (95% confidence interval [CI], 15 to 20) for Mexico, 39% (95% CI, 35 to 44) for Colombia, 19 (95% CI, 17 to 22) for Brazil, and -26% (95% CI, -40 to -14) for Ecuador. Using wavelet analyses, we found a reduction of 6- and 12-month seasonality in Brazil, Colombia, and Mexico. We also found that the increased reduction of diarrhea-related deaths was larger with greater prevaccine burden of diarrhea in infants., Conclusions: Our findings and available evidence support the recommendation from the World Health Organization for the monovalent and/or pentavalent rotavirus vaccine in countries worldwide. We found an increased benefit in those settings with a higher burden of infant diarrhea-related deaths., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: EGFR/c-Met activation/amplification and co-expression, mTOR upregulation/activation, and Akt/Wnt signaling upregulation have been individually associated with more aggressive disease and characterized as potential prognostic markers for lung cancer patients., Methods: Tumors obtained from 109 participants with stage I-IV non-small cell lung cancer (NSCLC) were studied for EGFR/c-Met co-localization as well as for total and active forms of EGFR, c-Met, mTOR, S6K, beta-catenin, and Axin2. Slides were graded by two independent blinded pathologists using a validated scoring system. Protein expression profile correlations were assessed using Pearson correlation and Spearman's rho. Prognosis was assessed using Kaplan-Meier analysis., Results: Protein expression profile analysis revealed significant correlations between EGFR/p-EGFR ( p  = 0.0412) and p-mTOR/S6K ( p  = 0.0044). Co-localization of p-EGFR/p-c-Met was associated with increased p-mTOR ( p  = 0.0006), S6K ( p  = 0.0018), and p-S6K ( p  < 0.0001) expression. In contrast, active beta-catenin was not positively correlated with EGFR/c-Met nor any activated proteins. Axin2, a negative regulator of the Wnt pathway, was correlated with EGFR, p-EGFR, p-mTOR, p-S6K, EGFR/c-Met co-localization, and p-EGFR/p-c-Met co-localization (all p -values <0.03). Kaplan-Meier analysis revealed shorter median survival in participants with high expression of Axin2, total beta-catenin, total/p-S6K, total/p-mTOR, EGFR, and EGFR/c-Met co-localization compared with low expression. After controlling for stage of disease at diagnosis, subjects with late-stage disease demonstrated shorter median survival when exhibiting high co-expression of EGFR/c-Met (8.1 month versus 22.3 month, p  = 0.050), mTOR (6.7 month versus 22.3 month, p  = 0.002), and p-mTOR (8.1 month versus 25.4 month, p  = 0.004) compared with low levels., Conclusions: These findings suggest that increased EGFR/c-Met signaling is correlated with upregulated mTOR/S6K signaling, which may in turn be associated with shorter median survival in late-stage NSCLC., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Hematopoietic stem/progenitor cells (HSPCs) are responsible for the generation of blood cells throughout life. It is believed that, in addition to soluble cytokines and niche cells, biophysical cues like elasticity and oxygen tension are responsible for the orchestration of stem cell fate. Although several studies have examined the effects of bone marrow (BM) niche elasticity on HSPC behavior, no study has yet investigated the effects of the elasticity of other niche sites like the fetal liver (FL), where HSPCs expand more extensively. In this study, we evaluated the effect of matrix stiffness values similar to those of the FL on BM-derived HSPC expansion. We first characterized the elastic modulus of murine FL tissue at embryonic day E14.5. Fibrin hydrogels with similar stiffness values as the FL (soft hydrogels) were compared with stiffer fibrin hydrogels (hard hydrogels) and with suspension culture. We evaluated the expansion of total nucleated cells (TNCs), Lin - /cKit + cells, HSPCs (Lin - /Sca + /cKit + (LSK) cells), and hematopoietic stem cells (HSCs: LSK- Signaling Lymphocyte Activated Molecule (LSK-SLAM) cells) when cultured in 5% O 2 (hypoxia) or in normoxia. After 10 days, there was a significant expansion of TNCs and LSK cells in all culture conditions at both levels of oxygen tension. LSK cells expanded more in suspension culture than in both fibrin hydrogels, whereas TNCs expanded more in suspension culture and in soft hydrogels than in hard hydrogels, particularly in normoxia. The number of LSK-SLAM cells was maintained in suspension culture and in the soft hydrogels but not in the hard hydrogels. Our results indicate that both suspension culture and fibrin hydrogels allow for the expansion of HSPCs and more differentiated progeny whereas stiff environments may compromise LSK-SLAM cell expansion. This suggests that further research using softer hydrogels with stiffness values closer to the FL niche is warranted.

Objectives: The aim of the present study is to explore the efficacy of rituximab in patients with Neuromyelitis Optica spectrum disorders (NMOsd) with positive AQP4-IgG serostatus., Patients and Methods: In this single center retrospective study, we recruited seropositive anti-AQP4 NMOsd patients who received treatment with Rituximab (RTX) for at least 2 years. Demographics were described and annualized relapse rate (AAR) and survival analysis were performed for time to relapse with Rituximab. All p values ≤0.05 we considered statistically significant., Results: A total of 15 patients (100 % female) were identified. Mean age of disease onset was 34 ± 11 years, mean time of disease was 8.11 ± 4.04 years and the median number of relapses was 5 (2-16). Ten patients received an immunosuppressive agent before RTX. Mean age of RTX initiation was 37 ± 12 with a mean treatment duration of 52 ± 28 months. The median ARR before and after treatment with RTX was 2.08 vs 0.00, respectively, with a difference of -2.08 (p < 0.001) CONCLUSIONS: This study shows a statistically significant reduction in the ARR and an increase in the relapse-free rate in AQP4-IgG NMOsd patients treated with RTX. These findings support the use of rituximab in our population, and indirectly suggests that its prompt use could modify the course of the disease., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This research work is the first to report thermal stability, heat deformation resistance, and crystallization behavior of a Polyethylene (PE)-based biphasic polyolefin system reinforced with Reduced Graphene Oxide (RGO), which was obtained through Graphene Oxide (GO) chemical reduction. Polypropylene (PP) represented the polymeric dispersed phase. A strategic PE/PP/RGO manufacturing procedure was employed to thermodynamically localize RGO at the PE/PP interface, as confirmed by Transmission Electron Microscopy (TEM), bringing a uniform micro phase dispersion into the macro phase. In addition, studies of PE non-isothermal crystallization kinetics indicated that the morphology tunable micro phase and the nanolayered RGO promoted a nucleation-controlled PE crystallization, which was supported by Polarized Light Optical Microscopy (PLOM). This, together with fine morphology, justified the remarkable enhancement registered for the ternary system's thermal stability and heat deformation resistance. Different filler loads were employed, with weight fractions of 2% and 4%. It was observed that the former, being better exfoliated and more homogeneously distributed at the PE/PP interface than the latter, led to a more improved PE crystallization, alongside a greater ternary system's thermal properties. Moreover, the thermal stability of PE/PP reinforced with 2% of RGO was even higher than that of virgin PP, while their heat deformation resistance values were found to be similar. Therefore, this unique outcome provides industries, such as the energy and automotive sectors, with the opportunity to substitute PP-rich products with those mostly comprised of a cheaper, more abundant, yet performant PE.

Introduction: Behçet's disease (BD) is an inflammatory disease of unknown etiology with periods of relapses and remissions. Neuro-Behçet syndrome (NBS) is one of the main causes of long-term morbidity and mortality, making its prompt recognition and early treatment fundamental to achieving a better outcome. Currently there are no treatment guidelines either for BS or NB, making the management of these patients particularly difficult., Case Presentation: We present the case report of a patient with pseudo-tumoral lesion and myelitis refractory to steroids and cyclophosphamide who successfully showed remission after treatment with an anti-CD20 therapy., Conclusion: This is the first report of concomitant pseudo-tumoral lesion and myelitis secondary to BS. We found rituximab treatment to be a safe and effective therapeutic option for NB supported by the radiological and clinical improvement achieved in our patient., Competing Interests: Declaration of Competing Interest All authors declare no competing interests or external funding., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Diabetes is characterized by pancreatic β-cell dedifferentiation. Dedifferentiating β cells inappropriately metabolize lipids over carbohydrates and exhibit impaired mitochondrial oxidative phosphorylation. However, the mechanism linking the β-cell's response to an adverse metabolic environment with impaired mitochondrial function remains unclear., Methods: Here we report that the oxidoreductase cytochrome b5 reductase 3 (Cyb5r3) links FoxO1 signaling to β-cell stimulus/secretion coupling by regulating mitochondrial function, reactive oxygen species generation, and nicotinamide actin dysfunction (NAD)/reduced nicotinamide actin dysfunction (NADH) ratios., Results: The expression of Cyb5r3 is decreased in FoxO1-deficient β cells. Mice with β-cell-specific deletion of Cyb5r3 have impaired insulin secretion, resulting in glucose intolerance and diet-induced hyperglycemia. Cyb5r3-deficient β cells have a blunted respiratory response to glucose and display extensive mitochondrial and secretory granule abnormalities, consistent with altered differentiation. Moreover, FoxO1 is unable to maintain expression of key differentiation markers in Cyb5r3-deficient β cells, suggesting that Cyb5r3 is required for FoxO1-dependent lineage stability., Conclusions: The findings highlight a pathway linking FoxO1 to mitochondrial dysfunction that can mediate β-cell failure., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Advanced power plant alloys must endure high temperatures and pressures for durations at which creep data are often not available, necessitating the extrapolation of creep life. A recently developed creep life extrapolation method is the Wilshire equations, with which multiple approaches can be used to increase the goodness of fit of available experimental data and improve the confidence level of calculating long-term creep strength at times well beyond the available experimental data. In this article, the Wilshire equation is used to extrapolate the creep life of Inconel 617 and Nimonic 105 to 100,000 h. The use of (a) different methods to determine creep activation energy, (b) region splitting, (c) heat- and processing-specific tensile strength data, and (d) short-duration test data were investigated to determine their effects on correlation and extrapolation. For Inconel 617, using the activation energy of lattice self-diffusion as Q C * resulted in a poor fit with the experimental data. Additionally, the error of calculated rupture times worsened when splitting regions. For Nimonic 105, the error was reduced when heat- and processing-specific tensile strengths were used. Extrapolating Inconel 617 creep strength to 100,000 h life gave conservative results when compared to values calculated by the European Creep Collaborative Committee.

Advanced power plant alloys must endure high temperatures and pressures for durations at which creep data are often not available, necessitating the extrapolation of creep life. Many methods have been proposed to extrapolate creep life, and one of recent significance is a set of equations known as the Wilshire equations. With this method, multiple approaches can be used to determine creep activation energy, increase the goodness of fit of available experimental data, and improve the confidence level of calculating long-term creep strength at times well beyond the available experimental data. In this article, the Wilshire equation is used to extrapolate the creep life of HR6W and Sanicro 25, and different methods to determine creep activation energy, region splitting, the use of short-duration test data, and the omission of very-short-term data are investigated to determine their effect on correlation and calculations. It was found that using a known value of the activation energy of lattice self-diffusion, rather than calculating Q C * from each data set, is both the simplest and most viable method to determine Q C * . Region-splitting improved rupture time calculations for both alloys. Extrapolating creep life from short-term data for these alloys was found to be reasonable.

In the United States, lung cancer is the second most common cancer in men and women. In 2017, 222,500 new cases and 155,870 deaths from lung cancer are estimated to have occurred. A tyrosine kinase receptor, epidermal growth factor receptor (EGFR), is over expressed or mutated in non-small cell lung cancer (NSCLC) resulting in increased cell proliferation and survival. Tyrosine kinase inhibitors (TKIs) are currently being used as therapy for NSCLC patients, however, they have limited efficacy in NSCLC patients due to acquisition of resistance. This study investigates the role of epithelial-mesenchymal transition (EMT) in the development of resistance against TKIs in NSCLC. Currently, the role of p120-catenin, Kaiso factor and PRMT-1 in reversal of EMT in T790M mutated and TKI-resistant NSCLC cells is a new line of study. In this investigation we found upregulation of cytoplasmic p120-catenin, which was co-localized with Kaiso factor. In the nucleus, binding of p120-catenin to Kaiso factor initiates transcription by activating EMT-transcription factors such as Snail, Slug, Twist, and ZEB1. PRMT-1 was also found to be upregulated, which induces methylation of Twist and repression of E-cadherin activity, thus promoting EMT. We confirmed that TKI-resistant cells have mesenchymal cell type characteristics based on their cell morphology and gene or protein expression of EMT related proteins. EMT proteins, Vimentin and N-cadherin, displayed increased expression, whereas E-cadherin expression was downregulated. Finally, we found that the knockdown of p120-catenin and PRMT-1 by siRNA or use of a PRMT-1 inhibitor Furamidine increased Erlotinib sensitivity and could reverse EMT to overcome TKI resistance., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Human cytomegalovirus (HCMV) infection in children and young adults has been associated with changes in the innate immune system. We herein analyzed the possible effect of very long term HCMV infection on the expression of several NK cell receptors. Ninety HCMV-seropositive individuals were included and classified as young adults (n=30), elderly (n=30) and very elderly subjects (n=30). A peripheral blood sample was obtained and the expression of NK cell receptors (NKG2A, NKG2C, ILT2, CD161, KIR2DL1, KIR3DL1, and KIR3DL2) by NK and other lymphocyte subsets was assessed by flow cytometry. In addition, the frequency of the sixteen KIR genes was analyzed by polymerase chain reaction. We found a significant increase in the number of NKG2C+ NK and T cells in elderly individuals compared to young adults accompanied by an opposite trend in the number of NKG2A+ lymphocytes, and ILT2+ cells were also increased in elderly individuals. A significant increase in the levels of CD3-CD56+NKG2C+CD57+ cells was also detected in the elderly groups. Finally, KIR gene analysis revealed that the KIR genotype 2 was significantly less frequent in the elderly individuals. Our results support that long-term infection by HCMV exerts a significant progressive effect on the innate immune system., (Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Kisspeptin regulates reproduction via signaling through the receptor, Kiss1r, in GnRH neurons. However, both kisspeptin and Kiss1r are produced in several peripheral tissues, and recent studies have highlighted a role for kisspeptin signaling in metabolism and glucose homeostasis. We recently reported that Kiss1r knockout (KO) mice display a sexually dimorphic metabolic phenotype, with KO females displaying obesity, impaired metabolism, and glucose intolerance at 4-5 months of age. However, it remains unclear when this metabolic phenotype first emerges in development, or which aspects of the pleiotropic phenotype underlie the metabolic defects and which are secondary to the obesity. Here, we studied Kiss1r KO females at different ages, including several weeks before the emergence of body weight (BW) differences and later when obesity is present. We determined that at young adult ages (6 wk old), KO females already exhibit altered adiposity, leptin levels, metabolism, and energy expenditure, despite having normal BWs at this time. In contrast, food intake, water intake, and glucose tolerance are normal at young ages and only show impairments at older adult ages, suggesting that these impairments may be secondary to earlier alterations in metabolism and adiposity. We also demonstrate that, in addition to BW, all other facets of the adult metabolic phenotype persist even when gonadal sex steroids are similar between genotypes. Collectively, these data highlight the developmental emergence of a metabolic phenotype induced by disrupted kisspeptin signaling and reveal that multiple, but not all, aspects of this phenotype are already disrupted before detectable changes in BW.

The neuropeptide kisspeptin regulates reproduction by stimulating gonadotropin-releasing hormone (GnRH) neurons via the kisspeptin receptor KISS1R. In addition to GnRH neurons, KISS1R is expressed in other brain areas and peripheral tissues, which suggests that kisspeptin has additional functions beyond reproduction. Here, we studied the energetic and metabolic phenotype in mice lacking kisspeptin signaling (Kiss1r KO mice). Compared with WT littermates, adult Kiss1r KO females displayed dramatically higher BW, leptin levels, and adiposity, along with strikingly impaired glucose tolerance. Conversely, male Kiss1r KO mice had normal BW and glucose regulation. Surprisingly, despite their obesity, Kiss1r KO females ate less than WT females; however, Kiss1r KO females displayed markedly reduced locomotor activity, respiratory rate, and energy expenditure, which were not due to impaired thyroid hormone secretion. The BW and metabolic phenotype in Kiss1r KO females was not solely reflective of absent gonadal estrogen, as chronically ovariectomized Kiss1r KO females developed obesity, hyperleptinemia, reduced metabolism, and glucose intolerance compared with ovariectomized WT females. Our findings demonstrate that in addition to reproduction, kisspeptin signaling influences BW, energy expenditure, and glucose homeostasis in a sexually dimorphic and partially sex steroid-independent manner; therefore, alterations in kisspeptin signaling might contribute, directly or indirectly, to some facets of human obesity, diabetes, or metabolic dysfunction.

Background: We endeavored to characterize the anesthesia experience with endovascular aneurysm repair (EVAR) at a large academic medical center in the United States., Methods: A retrospective review of electronic medical records was conducted for all patients undergoing elective EVAR from 2002 to 2007 in a large academic medical center., Results: A total of 522 cases met inclusion criteria, with 4% of cases using general anesthesia (GA), 92% regional anesthesia (RA), and 4% local anesthesia (LA). There was no statistically significant difference between the groups for duration of surgery or in-hospital mortality. In-hospital length of stay was longer for GA than LA or RA. Four cases were converted to open repair. Two mortalities occurred during the perioperative period (0.4% of cases)., Conclusions: The vast majority of EVAR were successfully performed under RA, involved mild blood loss, involved infrequent need for conversion to GA, and resulted in brief in-hospital length of stay and low mortality rate.

We describe the clinical characteristics and outcomes of adults hospitalized with pneumonia during the pandemic (H1N1) 2009 outbreak. Patients admitted to a general hospital in San Luis Potosí, Mexico, from April 10 through May 11, 2009, suspected to have influenza virus-associated pneumonia were evaluated. We identified 50 patients with suspected influenza pneumonia; the presence of influenza virus was confirmed in 18: 11 with pandemic (H1N1) 2009 virus, 5 with unsubtypeable influenza A virus, 1 with seasonal influenza A virus (H3N2), and 1 in whom assay results for seasonal and pandemic (H1N1) 2009 viruses were positive. Eighteen patients were treated in the intensive care unit, and 10 died. During the pandemic (H1N1) 2009 outbreak, severe pneumonia developed in young adults who had no identifiable risk factors; early diagnosis and treatment of influenza virus infections may have a determinant role in outcome.

Invasive disease following methicillin-resistant Staphylococcus aureus (MRSA) detection is common, regardless of whether initial detection involves colonization or infection. We assessed the genetic relatedness of isolates obtained > or =2 weeks apart representing either repeated infections or colonization-infection sets to determine if infections are likely to be caused by previously harbored strains. We found that MRSA infection following initial colonization or infection is caused by the same strain in most cases, suggesting that a single successful attempt at decolonization may prevent the majority of later infection.

The proximal region of the high-molecular-weight glutenin promoter of the Dx5 gene (PrHMWG-Dx5) carries an atypical bifactorial endosperm box containing two cis-acting elements, namely a G-box like motif followed by a prolamin-box motif (Pb1). Transient expression assays in maize endosperm indicate that a promoter fragment containing at least the G-box like element is necessary and sufficient for maximal expression of the HMWG-Dx5 promoter. In transformed maize, we have shown that a 89 bp sequence bearing the bifactorial endosperm box behaves like a functional cis-acting unit. Its repetition in tandem confers a strong specific additive effect specifically in endosperm tissue. In contrast, the fusion of the activation sequences 1 (as-1) and 2 (as-2) of the cauliflower mosaic virus (CaMV) 35S promoter with HMWG-Dx5 derived promoter sequences deregulates its activity in transformed maize. By gel mobility shift assays we have demonstrated that the G-box like motif may alternatively bind two protein groups which have the same DNA-binding affinities as the transcription factors of either the Opaque2 (O2) family and/or the ASF-1 family.