Mental health disorders and pain modulation in orthopedic shoulder patients.

Background: Various studies have examined the relationship between preoperative mental health diagnoses (MHDs) and postoperative outcomes in orthopedic shoulder patients. However, few investigations delve into the relationship between a preoperative MHD and postoperative opioid pain control regimens in patients who have undergone rotator cuff repair (RCR), total shoulder arthroplasty (TSA), and reverse TSA (rTSA). We hypothesize that orthopedic shoulder patients with a preoperative MHD will be prescribed more opioids (ie, request more refills) postoperatively than those without a MHD. Methods: An institutional review board-approved retrospective chart review was performed on 438 patients, 18 years or older, who underwent RCR, TSA, or rTSA. Patients were divided into two groups: those diagnosed with depression, anxiety, bipolar disorder, and/or schizophrenia (n = 193), and those with no previous MHD (n = 245). Statistical outcomes were analyzed with the independent t-test, Mann-Whitney U test, one-way Analysis of Variance, and Kruskal-Wallis test. Results: Univariate analysis demonstrated significant differences between the MHD group and non-MHD group in average 90-day postoperative opioid scripts (2.10 vs. 1.55, respectively, P < .001) and median 90-day postoperative morphine milligram equivalents (MMEs) prescribed (225 MME vs. 185.25 MME, respectively, P < .001). Among patients who were opioid naive 90 days preoperatively, significant differences were found in MMEs prescribed between the MHD and non-MHD group (225 MME vs. 150 MME, respectively, P < .001). Further analysis of opioid naive patients with specifically depression compared to patients with an alternate or no MHD diagnosis yielded significant differences in scripts (1.78 vs. 1.33, respectively, P = .031) and MMEs prescribed (225 MME vs. 150 MME, respectively, P < .001). Conclusion: This study found that RCR, TSA, or rTSA patients with a preoperative MHD were prescribed significantly more postoperative MMEs and more opioid scripts (ie, requested more refills) than those without MHD. This is despite preoperative education on postoperative pain expectations and limiting opioid use. Our findings support our hypothesis and emphasize the clinical importance of recognizing mental health disease while navigating postoperative pain control expectations. Given the rising prevalence of mental health disorders nationwide, considering the effect of these comorbidities on postoperative pain in RCR, TSA, and rTSA patients will be essential to enhance preoperative and postoperative counseling and management by orthopedic surgeons. We further recommend a multidisciplinary approach to help manage pain in these patients.

Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria.

Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled the NK cell response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56neg population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56dim NK cells, including decreased expression of PLZF and the Fc receptor γ-chain, increased histone methylation, and increased protein expression of LAG-3, KIR, and LILRB1. CD56neg NK cells were highly functional and displayed greater antibody-dependent cellular cytotoxicity than CD56dim NK cells. Higher frequencies of CD56neg NK cells were associated with protection against symptomatic malaria and high parasite densities. After marked reductions in malaria transmission, frequencies of these cells rapidly declined, suggesting that continuous exposure to Plasmodium falciparum is required to maintain this modified, adaptive-like NK cell subset.

New physics searches at kaon and hyperon factories.

Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.

Susceptibility and infectiousness of SARS-CoV-2 in children versus adults, by variant (wild-type, Alpha, Delta): a systematic review and meta-analysis of household contact studies

ImportanceUnderstanding the susceptibility and infectiousness of children and adolescents in comparison to adults is important to appreciate their role in the COVID-19 pandemic. ObjectiveTo determine SARS-CoV-2 susceptibility and infectiousness of children and adolescents with adults as comparator for three variants (wild-type, Alpha, Delta) in the household setting. We aimed to identify the effects independent of vaccination. Data SourcesWe searched EMBASE, PubMed and medRxiv up to January 2022. Additional studies were identified through contacting subject experts. Study SelectionTwo reviewers independently identified studies providing secondary attack rates (SAR) for SARS-CoV-2 infection in children (0-9 years), adolescents (10-19 years) or both compared with adults (20 years and older) derived from household data. Data Extraction and SynthesisTwo reviewers independently performed data extraction. We assessed risk of bias of included studies using a critical appraisal checklist and a random-effects meta-analysis model to pool association estimates. Main Outcomes and MeasuresOdds ratio (OR) for SARS-CoV-2 infection comparing children and adolescents with adults stratified by wild-type, Alpha, and Delta variant, respectively. Susceptibility was defined as the secondary attack rate (SAR) among susceptible household contacts irrespective of the age of the index case. Infectiousness was defined as the SAR irrespective of the age of household contacts when children/adolescents/adults were the index case. ResultsTwenty-eight studies (308,857 contacts) were included in the susceptibility analysis, for Delta only one (large) study was available. Compared to adults children and adolescents were less susceptible to the wild-type and Delta variant, but equally susceptible to the Alpha variant. In the infectiousness analysis, 21 studies (201,199 index cases) were included. Compared to adults, children and adolescents were less infectious when infected with the wild-type and Delta variant. Alpha variant-related infectiousness remained unclear, 0-9 year old children were at least as infectious as adults. SAR among household contacts was highest during circulation of the Alpha variant, lowest during wild-type circulation and intermediate during Delta circulation. Conclusions and RelevanceWhen considering the potential role of children and adolescents, for each variant susceptibility, infectiousness, age group and overall transmissibility need to be assessed to guide public health policy. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat is the evidence on the susceptibility and infectiousness of wild-type, Alpha and Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and adolescents compared with adults in the household setting? FindingsIn this systematic review and meta-analysis of 28 studies that included 308,857 household contacts, children and adolescents were less susceptible to the wild-type and Delta variant and likely equally susceptible to the Alpha variant of SARS-Cov-2. Children aged 0-9 years old infected with the Alpha variant may be more infectious than adults, but for adolescents, Alpha infectiousness is unclear. The overall secondary attack rate (SAR) rose substantially from wild-type to Alpha and dropped somewhat from Alpha to Delta. MeaningThe epidemiological role of children and adolescents towards SARS-CoV-2 may be influenced by susceptibility, infectiousness, variant, age group and overall (relative) contagiousness.

Simple and statistically sound recommendations for analysing physical theories.

Physical theories that depend on many parameters or are tested against data from many different experiments pose unique challenges to statistical inference. Many models in particle physics, astrophysics and cosmology fall into one or both of these categories. These issues are often sidestepped with statistically unsound ad hoc methods, involving intersection of parameter intervals estimated by multiple experiments, and random or grid sampling of model parameters. Whilst these methods are easy to apply, they exhibit pathologies even in low-dimensional parameter spaces, and quickly become problematic to use and interpret in higher dimensions. In this article we give clear guidance for going beyond these procedures, suggesting where possible simple methods for performing statistically sound inference, and recommendations of readily-available software tools and standards that can assist in doing so. Our aim is to provide any physicists lacking comprehensive statistical training with recommendations for reaching correct scientific conclusions, with only a modest increase in analysis burden. Our examples can be reproduced with the code publicly available at Zenodo.

Endoscopic ultrasonography-guided celiac plexus neurolysis in patients with unresectable pancreatic cancer: An update.

Pancreatic cancer produces disabling abdominal pain, and the pain medical management for pancreatic cancer is often challenging because it mainly relies on the use of narcotics (major opioids). However, opioids often provide suboptimal pain relief, and the use of opioids can lead to patient tolerance and several side effects that considerably reduce the quality of life of pancreatic cancer patients. Endosonography-guided celiac plexus neurolysis (EUS-CPN) is an alternative for pain control in patients with nonsurgical pancreatic cancer; EUS-CPN consists of the injection of alcohol and a local anesthetic into the area of the celiac plexus to achieve chemical ablation of the nerve tissue. EUS-CPN via the transgastric approach is a safer and more accessible technique than the percutaneous approach. We have reviewed most of the studies that evaluate the efficacy of EUS-CPN and that have compared the different approaches that have been performed by endosonographers. The efficacy of EUS-CPN varies from 50% to 94% in the different studies, and EUS-CPN has a pain relief duration of 4-8 wk. Several factors are involved in its efficacy, such as the onset of pain, previous use of chemotherapy, presence of metastatic disease, EUS-CPN technique, type of needle or neurolytic agent used, etc. According to this review, injection into the ganglia may be the best technique, and a good visualization of the ganglia is the best predictor for a good EUS-CPN response, although more studies are needed. However, any of the 4 different techniques could be used to perform EUS-CPN effectively with no differences in terms of complications between the techniques, but more studies are needed. The effect of EUS-CPN on pain improvement, patient survival and patient quality of life should be evaluated in well-designed randomized clinical trials. Further research also needs to be performed to clarify the best time frame in performing a EUS-CPN.

Trends in Covid-19 hospital mortality in women and men

IntroductionIt remains unclear if the development of health services, clinical management, and scientific evidence, during the pandemic is associated with better medical outcomes, sustained in the long term, for Covid-19 patients of each gender. This study presents the trends in mortality associated with Covid-19 for women and men during the first year of the pandemic. MethodsThis study was based in 17 Spanish hospitals. Sociodemographic, clinical, and mortality data from all patients with Covid-19, who had been discharged alive, or had died after being admitted, between March 2020 and February 2021, were used. The association between time of admission and mortality was examined with multivariate logistic regression models. Results3390 Covid-19 patients were included in the study, of which 1330 were women, the age was M(SD): 66.55(16.55) Death was reported for 451 patients. There was a significant decreasing trend in mortality by time of admission for the whole year with an OR: 0.86(0.77-0.96) p=0.005. No significant trend in mortality for women was observed OR: 1.00(0.85-1.19) p=0.959, while there was a significant decreasing trend for men OR: 0.78 (0.68-0.90) p=0.001 DiscussionThe health policies put in place, the scientific evidence developed by researchers, and the experienced acquired by clinicians, are likely to explain this improvement in mortality. More epidemiological and clinical studies addressing trends of mortality in patients with different sociodemographic and clinical profile and the improvement of clinical outcomes are required. Future research may address the safety and efficacy of interventions specifically in female patients.

Early immune responses have long-term associations with clinical, virologic, and immunologic outcomes in patients with COVID-19

The great majority of SARS-CoV-2 infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, mild to moderate infections are an important contributor to ongoing transmission. There remains a critical need to identify host immune biomarkers predictive of clinical and virologic outcomes in SARS-CoV-2-infected patients. Leveraging longitudinal samples and data from a clinical trial of Peginterferon Lambda for treatment of SARS-CoV-2 infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients within the first 2 weeks of symptom onset. We define early immune signatures, including plasma levels of RIG-I and the CCR2 ligands (MCP1, MCP2 and MCP3), associated with control of oropharyngeal viral load, the degree of symptom severity, and immune memory (including SARS-CoV-2-specific T cell responses and spike (S) protein-binding IgG levels). We found that individuals receiving BNT162b2 (Pfizer-BioNTech) vaccine had similar early immune trajectories to those observed in this natural infection cohort, including the induction of both inflammatory cytokines (e.g. MCP1) and negative immune regulators (e.g. TWEAK). Finally, we demonstrate that machine learning models using 8-10 plasma protein markers measured early within the course of infection are able to accurately predict symptom severity, T cell memory, and the antibody response post-infection.

Sox9EGFP Defines Biliary Epithelial Heterogeneity Downstream of Yap Activity.

BACKGROUND & AIMS: Defining the genetic heterogeneity of intrahepatic biliary epithelial cells (BECs) is challenging, and tools for identifying BEC subpopulations are limited. Here, we characterize the expression of a Sox9EGFP transgene in the liver and demonstrate that green fluorescent protein (GFP) expression levels are associated with distinct cell types. METHODS: Sox9EGFP BAC transgenic mice were assayed by immunofluorescence, flow cytometry, and gene expression profiling to characterize in vivo characteristics of GFP populations. Single BECs from distinct GFP populations were isolated by fluorescence-activated cell sorting, and functional analysis was conducted in organoid forming assays. Intrahepatic ductal epithelium was grown as organoids and treated with a Yes-associated protein (Yap) inhibitor or bile acids to determine upstream regulation of Sox9 in BECs. Sox9EGFP mice were subjected to bile duct ligation, and GFP expression was assessed by immunofluorescence. RESULTS: BECs express low or high levels of GFP, whereas periportal hepatocytes express sublow GFP. Sox9EGFP+ BECs are differentially distributed by duct size and demonstrate distinct gene expression signatures, with enrichment of Cyr61 and Hes1 in GFPhigh BECs. Single Sox9EGFP+ cells form organoids that exhibit heterogeneous survival, growth, and HNF4A activation dependent on culture conditions, suggesting that exogenous signaling impacts BEC heterogeneity. Yap is required to maintain Sox9 expression in biliary organoids, but bile acids are insufficient to induce BEC Yap activity or Sox9 in vivo and in vitro. Sox9EGFP remains restricted to BECs and periportal hepatocytes after bile duct ligation. CONCLUSIONS: Our data demonstrate that Sox9EGFP levels provide readout of Yap activity and delineate BEC heterogeneity, providing a tool for assaying subpopulation-specific cellular function in the liver.

Survival and clinical behavior of hypertrophic cardiomyopathy in a latin american cohort in contrast to cohorts from the developed world.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common hereditary heart disease with diverse phenotipyc, genetic expession and clinical presentations. The evolution of patients with HCM in Latin America has not been properly described being the frequency, the long-term prognosis as well as the predominant phenotypic expression still unknown. The aim of this study was to determine the survival rate of HCM patients having different phenotypes in a Mexican cohort of patients. METHODS: Clinical and echocardiographic data obtained from 77 Mexican patients with recently diagnosed HCM were analyzed. The follow-up was of 12.5 years. RESULTS: 96.1% of patients were in functional class I/II according to the New York Heart Association, 2.6% in class III and 1.3% in class IV. Only 3.9% of them went to surgery for myectomy. During the follow-up, 17 patients (22%) died: 4/9 (44%) had apical HCM, 5/20 (25%) had obstructive septal asymmetric HCM, 6/35 (17%) had nonobstructive septal asymmetric HCM and 2/3 (15%) had concentric HCM. The survival rate was worse for patients with apical HCM, followed by those with obstructive and nonobstructive septal asymmetric HCM and patients showing concentric HCM had the best survival rates. There is significant difference in survival rates which declined in 65% in a 9 years-period. Log rank test showed significant differences (p < 0.002). CONCLUSION: The survival rate of patients with HCM was worse in those with apical variety. The majority of patients received medical treatment. The indication for myectomy was below that observed in other international centers.

Survival and Clinical Behavior of Hypertrophic Cardiomyopathy in a Latin American Cohort in Contrast to Cohorts from the Developed World

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common hereditary heart disease with diverse phenotipyc, genetic expession and clinical presentations. The evolution of patients with HCM in Latin America has not been properly described being the frequency, the long-term prognosis as well as the predominant phenotypic expression still unknown. The aim of this study was to determine the survival rate of HCM patients having different phenotypes in a Mexican cohort of patients. METHODS: Clinical and echocardiographic data obtained from 77 Mexican patients with recently diagnosed HCM were analyzed. The follow-up was of 12.5 years. RESULTS: 96.1% of patients were in functional class I/II according to the New York Heart Association, 2.6% in class III and 1.3% in class IV. Only 3.9% of them went to surgery for myectomy. During the follow-up, 17 patients (22%) died: 4/9 (44%) had apical HCM, 5/20 (25%) had obstructive septal asymmetric HCM, 6/35 (17%) had nonobstructive septal asymmetric HCM and 2/3 (15%) had concentric HCM. The survival rate was worse for patients with apical HCM, followed by those with obstructive and nonobstructive septal asymmetric HCM and patients showing concentric HCM had the best survival rates. There is significant difference in survival rates which declined in 65% in a 9 years-period. Log rank test showed significant differences (p < 0.002). CONCLUSION: The survival rate of patients with HCM was worse in those with apical variety. The majority of patients received medical treatment. The indication for myectomy was below that observed in other international centers.

Polarographic study on the evolution of the diphenylamine as stabiliser of the solid propellants.

Differential pulse polarography (DPP) and square wave voltammetry (SWV) were investigated, in order to know the stability of solid propellants which contain diphenylamine. The simultaneous determination of N-nitrousdiphenylamine (NnDPA), 2-nitrodiphenylamine (2nDPA), 4-nitrodiphenylamine (4nDPA) and 2,4-dinitrodiphenylamine (2,4dnDPA) by DPP and SWV was proposed due to these nitro-derivatives appear during the stabilisation process from degradation of diphenylamine (DPA) used as stabiliser in propellant compositions. The proposed methods were successfully applied to the simple base solid propellant (with nitrocellulose as the only active component), with its stabiliser DPA. In all cases and with both the techniques, detection limits