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Burn injury remains a serious cause of morbidity and mortality worldwide. Severity of burns is determined by the percentage of burned area compared to the body surface area, age of patient, and by the depth of skin and soft tissue involvement; these factors determine management as well as prospective outcomes. The pathophysiology of partial- to full-thickness burn conversion remains poorly understood and is associated with a worse overall prognosis. Recent studies have demonstrated that an altered inflammatory response may play a significant role in this conversion and therefore a reduction in early inflammation is crucial to ultimately decreasing burn severity and morbidity. We hypothesize that the application of a microcapillary gelatin-alginate hydrogel loaded with anti-TNF-α (infliximab) monoclonal antibodies to a partial-thickness burn will reduce inflammation within partially burned skin and prevent further progression to a full-thickness burn.Assembly of the microfluidic hydrogels is achieved by embedding microfibers within a hydrogel scaffold composed of a gelatin-alginate blend, which is then soaked in a solution containing anti-TNF-α antibodies for drug loading. 12 young (2-4 months) and 12 old (16 months) mice were given partial thickness burns. The treatment cohort received the anti-TNF-α infused hydrogel with an occlusive dressing and the control cohort only received an occlusive dressing. Mice were euthanized at post-burn day 3 and skin samples were taken. Burn depth was evaluated using Vimentin immunostaining.All mice in the treatment cohort demonstrated decreased conversion of burn from partial to full thickness injury (old = p0.01, young = p0.001) as compared to the control group. Old mice had greater depth of burn than young mice (p0.001). There were greater eosinophils in the treatment cohort for both young and old mice, but it did not reach statistical significance.The application of a novel microcapillary gelatin-alginate hydrogel infused with anti-TNF-α antibody to partial thickness burns in mice showed reduction in partial to full thickness burn secondary progression as compared to controls using this murine model; this promising finding might help decrease the high morbidity and mortality associated with burn injuries.

Extracorporeal membrane oxygenation (ECMO) is used to support patients with refractory cardiopulmonary failure. Given ECMO's increased use in adults and the fact that many ECMO patients are cared for by anesthesiologists, the Society of Cardiovascular Anesthesiologists ECMO working group created an expert consensus statement that is intended to help anesthesiologists manage adult ECMO patients who are cared for in the operating room. In the first part of this 2-part series, technical aspects of ECMO are discussed, and related expert consensus statements are provided.

In the second part of the Society of Cardiovascular Anesthesiologists Extracorporeal Membrane Oxygenation (ECMO) working group expert consensus statement, venoarterial (VA) and venovenous (VV) ECMO management and troubleshooting in the operating room are discussed. Expert consensus statements are provided about intraoperative monitoring, anesthetic drug dosing, and management of intraoperative problems in VA and VV ECMO patients.

Regulation of endothelial nitric oxide synthase (eNOS) in hepatocytes may be an important target in nonalcoholic fatty liver disease (NAFLD) development and progression to nonalcoholic steatohepatitis (NASH). In this study, we show genetic deletion and viral knockdown of hepatocyte-specific eNOS exacerbated hepatic steatosis and inflammation, decreased hepatic mitochondrial fatty acid oxidation and respiration, increased mitochondrial H2O2 emission, and impaired the hepatic mitophagic (BNIP3 and LC3II) response. Conversely, overexpressing eNOS in hepatocytes in vitro and in vivo increased hepatocyte mitochondrial respiration and attenuated Western diet–induced NASH. Moreover, patients with elevated NAFLD activity score (histology score of worsening steatosis, hepatocyte ballooning, and inflammation) exhibited reduced hepatic eNOS expression, which correlated with reduced hepatic mitochondrial fatty acid oxidation and lower hepatic protein expression of mitophagy protein BNIP3. The current study reveals an important molecular role for hepatocyte-specific eNOS as a key regulator of NAFLD/NASH susceptibility and mitochondrial quality control with direct clinical correlation to patients with NASH.

Background Despite existing anthropometric data in the literature regarding the variation of female external genital anatomy, the ideal aesthetic characteristics have yet to be defined. Objectives The authors utilized crowdsourcing to better evaluate preferred anatomic characteristics of external female genitalia. Methods Fifty-six total images were digitally created by altering the proportions of the labia minora, labia majora, and clitoral hood. Images with differing ratios were presented in pairs to Amazon Mechanical Turk (Seattle, WA, USA) raters. Three different experiments were performed with each varying 2 of the 3 image characteristics to permit 2-factor modeling. The Bradley-Terry-Luce model was applied to the pairwise comparisons ratings to create a rank order for each image. Preferences for each anatomic variable were compared with chi-squared tests. Results A total of 5000 raters participated. Experiment 1 compared differing widths of the labia majora and labia minora and determined a significant preference for larger labia majora width and mid-range labia minora width (P = 0.007). Experiment 2 compared labia minora width vs clitoral hood length and showed a statistically significant preference for wider majoras (P Conclusions Raters preferred a labia majora to labia minora width ratio of 3:1 with minimal preference in clitoral hood length.

Background: Tanzania has a double burden of malnutrition, including a high prevalence of undernutrition and an increasing prevalence of overweight and obesity among adolescents. Schools present a valuable opportunity to reach a large section of the country’s adolescent population with nutrition-oriented interventions. Objective: The objective of this study was to assess the current state of adolescent school nutrition interventions in Dodoma, Tanzania, with emphasis on 3 potential school-based nutrition interventions, school vegetable gardens, school meals, and education (on nutrition, agriculture, and water, sanitation, and hygiene). Methods: Focus group discussions were conducted with several regional and district-level governmental stakeholders, including health, education, and agricultural officers. Ten public secondary schools were visited, and interviews with school administrators, teachers, students, and parents were conducted. Results: All stakeholders interviewed supported interventions to improve school-based nutrition, including school gardens, school feeding, and nutrition education. All 10 schools visited had some experience providing school meals, but parents’ contributions were essential for the program’s sustainability. Most schools visited had land available for a school garden program, but water availability could be challenging during certain times of the year. The teachers interviewed expressed that the curriculum on nutrition education was highly theoretical and did not allow students to practice the knowledge and skills they learned in the classroom. Conclusions: The current school-based approach to tackling the double burden of adolescent malnutrition in Dodoma is localized and ad hoc. To leverage the potential of schools as a platform for nutrition interventions, integrated and policy-mandated interventions are needed.

Background: Treatment-dose enoxaparin is not well studied in obese patients. Guidelines suggest that obese patients receiving enoxaparin therapy for acute venous thromboembolism (VTE) should receive a standard initial dose, 1 mg/kg, based on actual body weight. It is possible that this dosing strategy in obese patients may be overestimated, leading to a higher bleeding risk compared to non-obese patients. Objective: To gather data regarding enoxaparin treatment dosing and anti-Xa level monitoring in patients who are obese to guide dose adjustments. Methods: A single-center, retrospective chart review that included patients who were ordered treatment-dose enoxaparin and had a BMI ≥ 40 kg/m2, which resulted in an automatic pharmacy consult.The primary endpoint of this study was incidence of bleeding. Results: The analysis included 102 patients. Most patients (92.1%) had a BMI of ≥ 40-60 kg/m2 while 7.8% of patients had a BMI of > 60 kg/m2. The average initial and final doses were 1.0 ± 0.1 mg/kg and 0.9 ± 0.2 mg/kg, respectively. The incidence of bleeding was 4.9%. The average dose for those that bled was 0.7 ± 0.1 mg/kg. On average, patients who bled had higher BMIs than patients who did not bleed (51.6 kg/m2 vs. 48.0 kg/m2). Of the 71 patients with an initial anti-Xa level, 42 of the levels were considered supratherapeutic (59.2%). Conclusion: A 1 mg/kg starting dose of enoxaparin may be too high for patients who are obese as many patients required an adjustment to their dose after initial anti-Xa levels.

Objective To review the use of Von Willebrand Factor (VWF) concentrate for treatment of acquired Von Willebrand syndrome (VWS) related bleeding in adult extracorporeal membrane oxygenation (ECMO) patients and determine whether it was associated with improved VWF laboratory parameters. Design Retrospective observational cohort study. Setting Tertiary care academic medical center. Participants Adult ECMO patients who received VWF concentrate for treatment of acquired VWS related bleeding. Interventions None, observational study. Measurements and Main Results Ten adult ECMO patients received VWF concentrate for treatment of bleeding with evidence of acquired VWS over a 15-month period. Six patients were on veno-arterial ECMO and 4 were on veno-venous ECMO. The most common site of bleeding was airway or tracheal bleeding. The mean dose of VWF concentrate was 41 IU/kg. Mean VWF antigen was 263 ± 93 IU/dL before treatment and 394 ± 54 after treatment. Mean ristocetin cofactor activity was 127 ± 47 IU/dL before treatment and 240 ± 33 after treatment. The mean VWF ristocetin cofactor activity antigen ratio increased from 0.52 ± 0.14 before treatment to 0.62 ± 0.04 after treatment. Four of 10 patients had complete resolution of their bleeding within 24 hours while 6 of 10 had complete resolution of their bleeding within 2 to 4 days. There were 3 patients who had thrombotic events potentially related to VWF concentrate administration. No patient had an arterial thrombosis, stroke, or myocardial infarction. Conclusions VWF concentrate administration increases VWF function in adult ECMO patients, but may also be associated with increased thrombotic risk. Larger studies are needed to determine VWF concentrate's safety, efficacy, and optimal dosing in adult ECMO patients.

Mucus is an integral part of the respiratory physiology. It protects the respiratory tract by acting as a physical barrier against inhaled particles and microbes. Excessive inflammation in conditions such as COVID-19 can result in over-production of mucus which obstructs the airway. Build-up of mucus can also contribute to recurrent airway infection, causing further obstruction. This article summarizes the current understanding and knowledge of respiratory mucus production and proposes the role of cytokine storm in inducing sudden mucus hypersecretion in COVID-19. Based on these cascades, the active constituents that inhibit or activate several potential targets are outlined for further research. These may be explored for the discovery and design of drugs to combat cytokine storm and its ensuing complications.

This article examines a series of Service Employees’ International Union (SEIU) campaigns for protection from needlestick injuries, led by women health-care workers, from the dawn of the HIV/AIDS epidemic in the 1980s through battles over the 1992 OSHA standard on blood-borne pathogens and the Needlestick Safety and Prevention Act of 2000. We argue that these campaigns developed in response to the growing physical precarity of women health-care workers in the era of “managed care,” caused by the intensification and flexibilization of health-care labor and the deregulation and underfunding of OSHA and the CDC. We show how women workers challenged employers, OSHA, and elected federal officials to address workplace health hazards, through unions like SEIU and women’s, gay rights, and public health organizations. More broadly, we argue that the occupational hazards of health-care workers are a crucial but underexplored facet of workplace studies and the history of women workers in the late twentieth and early twenty-first centuries.

Aging adults are impacted by pain. Technology can assist older adults with pain self-management while allowing for independence. The current usability study explored the use of voice assistant reminders for two pain self-management tasks in aging adults. Fifteen community-dwelling older adults with chronic pain and an average age of 65 years used the voice assistant for 4 weeks. Participants had moderate scores for pain severity (mean = 4.6 [ SD = 2.3]) and pain interference (mean = 4 [ SD = 2.6]). Voice assistant usability was above average (78 of 100). Median time to set up the Google Home Assistant profile was 5 minutes ( SD = 7.5), with a median of asking for help two times. Pain self-management task reminders from the voice assistant were perceived as consistent, easy to set up, and helpful for accountability. Voice assistant reminders may be an option to help encourage a variety of pain self-management tasks in aging adults. [ Journal of Gerontological Nursing, 46 (10), 27–33.]

Nonalcoholic fatty liver disease (NAFLD) is a major health problem and its prevalence has increased in recent years, concurrent with rising rates of obesity and other metabolic diseases. Currently, there are no FDA-approved pharmacological therapies for NAFLD, and lifestyle interventions, including weight loss and exercise, remain the cornerstones for treatment. Manipulating diet composition and eating patterns may be a sustainable approach to NAFLD treatment. Dietary strategies including Paleolithic, ketogenic, Mediterranean, high-protein, plant-based, low-carbohydrate, and intermittent fasting diets have become increasingly popular due to their purported benefits on metabolic disease. In this review, we will highlight what is currently known about these popular dietary approaches in the management of NAFLD in clinical populations with mechanistic insight from animal studies. We will also identify key knowledge gaps to better inform future preclinical and clinical studies aimed at the treatment of NAFLD.

Combined elevated sputum eosinophils+neutrophils in asthma associated with lowest lung function, greater healthcare utilization, and longitudinally, further spirometric loss, implicating cell-cell interactions or overlapping inflammatory pathways while increased eosinophils or neutrophils alone show less effect.

The public’s understanding of climate change has been plagued by poor communication, misinformation, and disinformation. Fortunately, there is a growing body of research on effective climate change...

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) reportedly promotes, or conversely, resolves inflammation in asthma. In this study of TRAIL and cell receptors in sputum, bronchoalveolar lavage and biopsy from subjects in the Severe Asthma Research Program at Wake Forest, the high TRAIL group had significant increases in all leucocytes, and was associated with increased type 1, type 2 and type 17 cytokines, but not type 9 interleukin 9. Two variants at loci in the TRAIL gene were associated with higher sputum levels of TRAIL. Increased TRAIL decoy receptor R3/DcR1 was observed on sputum leucocytes compared with death receptor R1/DR4, suggesting reduced apoptosis and prolonged cellular inflammation.

Patients supported with venovenous extracorporeal membrane oxygenation are at risk for intra-abdominal hypertension and abdominal compartment syndrome. Flow through the return cannula may be compromised in these patients, resulting in inadequate support and end-organ malperfusion. Early decompressive laparotomy can mitigate these complications and potentially improve outcomes. Here we review a series of nine patients undergoing early decompressive laparotomy for abdominal compartment syndrome at a single institution and propose an algorithmic approach to the management of these patients.

Hepatic steatosis, the excess storage of intrahepatic lipids, is a rampant clinical problem associated with the obesity epidemic. Hepatic steatosis is linked to increased risk for insulin resistance, type 2 diabetes, and cardiovascular and advanced liver disease. Accumulating evidence shows that physical activity, exercise, and aerobic capacity have profound effects on regulating intrahepatic lipids and mediating susceptibility for hepatic steatosis. Moreover, exercise can effectively reduce hepatic steatosis independent of changes in body mass. In this perspective, we highlight 1) the relationship between obesity and metabolic pathways putatively driving hepatic steatosis compared with changes induced by exercise; 2) the impact of physical activity, exercise, and aerobic capacity compared with caloric restriction on regulating intrahepatic lipids and steatosis risk; 3) the effects of exercise training (modalities, volume, intensity) for treatment of hepatic steatosis, and 4) evidence for a sustained protection against steatosis induced by exercise. Overall, evidence clearly indicates that exercise powerfully regulates intrahepatic storage of fat and risk for steatosis.

A study was undertaken to identify patterns of consumer use of outdoor wood boilers or outdoor wood furnaces (technically referred to as outdoor wood-fired hydronic heaters (OWHHs)) and indoor wood stoves (IWSs) to inform the development of performance testing protocols that reflect real-life operating conditions. These devices are manually fed, and their usage protocols are a function of a number of variables, including user habits, household characteristics, and environmental factors. In this study, researchers logged the stack wall temperatures of 4 OWHH and 20 IWS units in the states of New York and Washington over two heating seasons. Stack wall temperature is an indicator of changes in combustion modes. Two algorithms were developed to identify usage modes and cold and warm start refueling events from the stack wall temperature time series. A linear correlation analysis was conducted to evaluate the effect of heat demand on usage patterns. The results and methods presented here will inform the cataloging of typical operational patterns of OWHHs and IWSs as a step in the development of performance testing procedures that represent actual in-home usage patterns. Implications: Current US regulatory programs for residential wood heating use a certification program to assess emissions and efficiency performance. Testing under this program uses a test that burns 100% of a single, standardized wood fuel charge to assess performance at different steady-state load conditions. This study assessed in-field operational patterns to determine if the current certification approach accurately characterized typical homeowner use patterns. The data from this study can be used to inform revisions to testing methods to increase certification test comparability between lab and field performance.

Backgrounds Cervical cancer (CC) is one of the leading cause of death in women worldwide, HPV infection is the major risk factor in the disease development, 0and however other risk factor such as chemical carcinogens, genetic susceptibility and altered immune system are also a cause of the disease progression. In the light of the above statement we studied the base excision repair pathway (BER). Methods We identified and studied the association of Single Nucleotide polymorphisms in the DNA repair genes of XRCC1 (Arg194Trp, Arg399G,) and APE-1Asp/148Glu to the susceptibility of cervical cancer (CC) in North Indian population. In our study of cases (n=102). Controls (n=109) were recruited from among women without cervical abnormalities. Genotypes were determined by PCR-CTPP method, Taking DNA from peripheral blood in a case control study. Results A positive association was observed between the polymorphisms of XRCC1 genes, that is, in codons 194 (P=0.03, odds ratio (OR) =2.39, 95% confidence interval (CI)=5.2-1.1), 280 (P=0.01, OR=4.1, 95% CI=11.5-1.3) and 399 (P=0.01, OR=3.4, 95% CI=8.6-1.3) while APE-1 genotype GG (p=0.03,odds ratio(OR)=0.2,95% confidence interval (CI)=0.97-0.004) we observed a statistically significant protective role in developing cervical cancer. Conclusion Our results suggested that, XRCC1 gene is an important candidate gene for susceptibility to cervical cancer. Although the sample size was small, the present study indicate a statistical association between cervical cancer and XRCC1 SNPs. Future studies are needed that may provide a better understanding of the association between gene polymorphism and cervical carcinoma risk. .

In the second part of the Society of Cardiovascular Anesthesiologists Extracorporeal Membrane Oxygenation (ECMO) working group expert consensus statement, venoarterial (VA) and venovenous (VV) ECMO management and troubleshooting in the operating room are discussed. Expert consensus statements are provided about intraoperative monitoring, anesthetic drug dosing, and management of intraoperative problems in VA and VV ECMO patients.

Inpatient management of sickle cell disease (SCD) vaso-occlusive crisis (VOC) often involves use of high-dose opioids, which may result in opioid-induced pruritus (OIP). This OIP is typically treated with antihistamines like diphenhydramine either orally or intravenously. The oversedation adverse effects of diphenhydramine may be magnified when given in combination with high-dose opioid therapy. Current recommendations made by the National Heart, Lung, and Blood Institute endorse using oral rather than intravenous (IV) antihistamines to avoid the cumulative effect on sedation. Despite this guideline, IV diphenhydramine use is still prevalent in many hospitals that treat persons with SCD. We performed a retrospective, single-center, cohort study comparing rates of oversedation among patients who received IV and oral diphenhydramine for management of opioid-induced pruritus in a large SCD inpatient population. Patients with SCD VOC admitted to an urban hospital between June 1, 2016 to July 30, 2017 were included if they were ≥ 18 years old and received either IV or oral diphenhydramine for OIP. Exclusion criteria: Pregnancy, received Disclosures Osunkwo: Terumo BCT: Speakers Bureau; Prolog Pharmaceuticals LLC: Consultancy; Novartis Pharmaceuticals LLC: Consultancy, Speakers Bureau. Symanowski:Immatics: Other: Data Safety Monitoring Board; Eli Lily & Co: Other: Data Safety Monitoring Board; Boston Biomedical: Other: Data Safety Monitoring Board ; Five Prime Therapeutics: Other: Data Safety Monitoring Board .

Physical activity is an important part of quality life, however people with visual impairments (PVIs) are less likely to participate in physical activity than their sighted peers. One barrier is that exercise instructors may not give accessible verbal instructions. There is a potential for text analysis to determine these phrases, and in response provide more accessible instructions. First, a taxonomy of accessible phrases needs to be developed. To address this problem, we conducted user studies with 10 PVIs exercising along with audio and video aerobic workouts. We analyzed video footage of their exercise along with interviews to determine a preliminary set of phrases that are helpful or confusing. We then conducted an iterative qualitative analysis of six other exercise videos and sought expert feedback to derive our taxonomy. We hope these findings inform systems that analyze instructional phrases for accessibility to PVIs.

Non-alcoholic fatty liver disease (NAFLD) is a multimorbidity disorder ranging from excess accumulation of fat in the liver (steatosis) to steatohepatitis (NASH) and end-stage cirrhosis, and the development of hepatocellular carcinoma (HCC) in a subset of patients. The defining features of NASH are inflammation and progressive fibrosis. Currently, no pharmaceutical therapies are available for NAFLD, NASH and HCC; therefore, developing novel treatment strategies is desperately needed. Reversion Inducing Cysteine Rich Protein with Kazal motifs (RECK) is a well-known modifier of the extracellular matrix in hepatic remodeling and transition to HCC. More recently, its role in regulating inflammatory and fibrogenic processes has emerged. Here, we summarize the most relevant findings that extend our current understanding of RECK as a regulator of inflammation and fibrosis, and its induction as a potential strategy to blunt the development and progression of NASH and HCC.

Assisted living is a fast-growing living option for seniors who require residence-based activities for maintaining mental and physical health. Guided equine interactions may benefit seniors, so an on-site equine program was started at Hacienda at the River senior living community. For research purposes, twenty-four residents and associates, aged fifty-five or over, consented to physiological measurements before, during and after four guided sessions of stroking one of three horses for 10 min over 4–6 weeks. Heart rate variability (HRV) was measured simultaneously in humans and horses during interactions. We hypothesized that human heart rate (HR) and HRV would increase during stroking and HRV power would shift toward the very low frequency (VLF) range common in horses, indicative of healthy function. During stroking, human HR increased (p &lt, 0.05) but HRV (SDRR) and %VLF of HRV power did not change. Diastolic blood pressure (DBP), an exploratory measure, significantly increased after stroking, consistent with arousal. Two horses showed no significant changes in HR or HRV, but one relaxed. Sixteen horse–human pairs demonstrated synchronized HRV peak frequencies during sessions, suggestive of social connection. Participants used more positive than negative words describing their experience during exit interviews (p &lt, 0.05). These data show that horses animate seniors without causing emotional stress and provide opportunities for social bonding.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become an important support modality for patients with acute respiratory failure refractory to optimal medical therapy, such as low tidal volume mechanical ventilator support, early paralytic infusion, and early prone positioning. The objective of this cohort study was to investigate the causes and timing of in-hospital mortality in patients on VV ECMO. All patients, excluding trauma and bridge to lung transplant, admitted 8/2014–6/2019 to a specialty ICU for VV ECMO were reviewed. Two hundred twenty-five patients were included. In-hospital mortality was 24.4% ( n = 55). Most non-survivors (46/55, 84%) died prior to lung recovery and decannulation from VV ECMO. Most common cause of death (COD) for patients who died on VV ECMO was removal of life sustaining therapy (LST) in setting of multisystem organ failure (MSOF) ( n = 24). Nine patients died a median of 9 days [6, 11] after decannulation. Most common COD in these patients was palliative withdrawal of LST due to poor prognosis ( n = 3). Non-survivors were older and had worse predictive mortality scores than survivors. We found that death in patients supported with VV ECMO in our study most often occurs prior to decannulation and lung recovery. This study demonstrated that the most common cause of death in patients supported with VV ECMO was removal of LST due MSOF. Acute hemorrhage (systemic or intracranial) was not found to be a common cause of death in our patient population.

We assessed the relationship between serum alkaline phosphatase (ALP) and liver fibrosis by histology, in addition to other noninvasive parameters, in obese patients undergoing metabolic surgery. Patients scheduled for elective bariatric surgery were prospectively recruited from a bariatric clinic. An intraoperative liver biopsy was performed, and liver histology was evaluated by a pathologist blinded to the patients’ data. The endpoint was significant fibrosis defined as fibrosis stage ≥ 2. Independent predictors of fibrosis were identified by logistic regression. Two hundred ten patients were recruited. Liver histology revealed steatosis in 87.1%, steatohepatitis in 21.9%, and significant fibrosis in 10%. Independent predictors of significant fibrosis were ALP (Odds Ratio (OR) 1.03, 95% Confidence interval (CI), 1.01–1.05), alanine aminotransferase (OR 1.02, 95% CI, 1.01–1.03), HbA1c (OR 1.58, 95% CI, 1.20–2.09), and body mass index (OR 1.06, 95% CI, 1.00–1.13). A tree-based model was developed to predict significant fibrosis, with a receiver operating characteristic (ROC) area of 0.845, sensitivity of 0.857, specificity of 0.836, and accuracy of 0.931. The applicability of serum ALP as an independent biomarker of liver fibrosis should be considered in obesity surgery patients, and in the broader context of obese patients with nonalcoholic fatty liver disease.

The Rio Grande Valley (RGV) in South Texas has one of the highest prevalence of obesity and type 2 diabetes (T2D) in the United States (US). We report for the first time the T2D prevalence in persons with HIV (PWH) in the RGV and the interrelationship between T2D, cardiometabolic risk factors, HIV-related indices, and antiretroviral therapies (ART). The PWH in this study received medical care at Valley AIDS Council (VAC) clinic sites located in Harlingen and McAllen, Texas. Henceforth, this cohort will be referred to as Valley AIDS Council Cohort (VACC). Cross-sectional analyses were conducted using retrospective data obtained from 1,827 registries. It included demographic and anthropometric variables, cardiometabolic traits, and HIV-related virological and immunological indices. For descriptive statistics, we used mean values of the quantitative variables from unbalanced visits across 20 months. Robust regression methods were used to determine the associations. For comparisons, we used cardiometabolic trait data obtained from HIV-uninfected San Antonio Mexican American Family Studies (SAMAFS; N = 2,498), and the Mexican American population in the National Health and Nutrition Examination Survey (HHANES; N = 5,989). The prevalence of T2D in VACC was 51% compared to 27% in SAMAFS and 19% in HHANES, respectively. The PWH with T2D in VACC were younger (4.7 years) and had lower BMI (BMI 2.43 units less) when compared to SAMAFS individuals. In contrast, VACC individuals had increased blood pressure and dyslipidemia. The increased T2D prevalence in VACC was independent of BMI. Within the VACC, ART was associated with viral load and CD4+ T cell counts but not with metabolic dysfunction. Notably, we found that individuals with any INSTI combination had higher T2D risk: OR 2.08 (95%CI 1.67, 2.6; p < 0.001). In summary, our results suggest that VACC individuals may develop T2D at younger ages independent of obesity. The high burden of T2D in these individuals necessitates rigorously designed longitudinal studies to draw potential causal inferences and develop better treatment regimens.

The ICDD's Powder Diffraction File™ (PDF®) is a database of inorganic and organic diffraction data used for phase identification and materials characterization by powder diffraction. The PDF has been available for over 75 years and finds application in X-ray, synchrotron, electron, and neutron diffraction analyses. With entries based on powder and single crystal data, the PDF is the only crystallographic database where every entry is editorially reviewed and marked with a quality mark that alerts the user to the reliability/quality of the submitted data. The editorial processes of ICDD's quality management system are unique in that they are ISO 9001:2015 certified. Initially offered as text on paper cards and books, the PDF evolved to a computer-readable database in the 1960s and today is both computer and web accessible. With data mining and phase identification software available in PDF products, and the databases’ compatibility with vendor (third party) software, the 1 000 000+ published PDF entries serve a wide range of disciplines covering academic, industrial, and government laboratories. Details describing the content of database entries are presented to enhance the use of the PDF.

The ability of current renal replacement therapy modalities to achieve rapid solute removal is limited by membrane surface area and blood flow rate. Extracorporeal membrane oxygenation offers high blood flow and hemodynamic support that may be harnessed to overcome limitations in traditional renal replacement therapy. Using an extracorporeal membrane oxygenation circuit, we describe a high blood flow, high-efficiency hemofiltration technique using in-line hemofilters (hemoconcentrators) and standard replacement fluid to enhance solute clearance. Using this approach and a total of 5 L of replacement volume per treatment, creatinine (Cr) clearances of 8.3 L/hour and 11.2 L/hour using one and two hemoconcentrators, respectively, were achieved. With use of a high blood flow rate of up to 5 L/min, this hemofiltration technique can potentially offer clearance of 30 times that of continuous renal replacement therapy and of 6 times that of hemodialysis which may expand the ability to remove substances traditionally not considered removable via existing extracorporeal therapies.

Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) support can be associated with significant deconditioning due to the requirement for strict bedrest as a result of femoral arterial cannulation. To address this issue, we evaluated our experience with ambulation in patients with peripheral femoral cannulation for VA-ECMO. Methods All patients that were peripherally cannulated for VA-ECMO over a 2-year period were retrospectively reviewed. Patients that ambulated at least once while supported with VA-ECMO were included in the analysis. The primary outcomes were safety and feasibility of ambulation, defined as the absence of major bleeding, vascular, or decannulation events. Results Of 104 patients placed on VA-ECMO, 15 ambulated with a femoral arterial cannula. Forty-six percent of patients were placed on VA-ECMO for decompensated heart failure, and 54% for massive pulmonary embolism. Twenty-seven percent of patients were cannulated during active cardiopulmonary resuscitation. The median length of time from cannulation to out of bed was 3 (range, 0 to 26) days. The median length of time from cannulation to initial ambulation was 4 (range, 1 to 42) days. The median distance of the first postcannulation walk was 300 feet. Neither flow nor speed decreased during or after ambulation. There were no major bleeding events, vascular complications, or decannulation events associated with ambulation. The median intensive care unit length of stay and hospital length of stay were 12 and 21 days, respectively. One-year survival was 100% for ambulating patients. Conclusions Ambulating patients supported with VA-ECMO, despite femoral arterial cannulation, appears feasible and safe in carefully selected patients.

Obesity can lead to impairments in hepatic glucose and insulin homeostasis, and although exercise is an effective treatment, the molecular targets remain incompletely understood. As IL-6 is an exercise-inducible cytokine, we aimed to identify whether IL-6 itself influences hepatic glucose and insulin homeostasis and whether this response differs during obesity. In vivo, male mice were fed a low-fat diet (LFD; 10% kcal) or a high-fat diet (HFD; 60% kcal) for 7 wk, which induced obesity and hepatic lipid accumulation. LFD- and HFD-fed mice were injected with IL-6 (400 ng, 75 min) or PBS and then with insulin (1 U/kg; ~15 min) or saline, at which point livers were collected. In both LFD- and HFD-fed mice, IL-6 decreased blood glucose and mRNA expression of gluconeogenic genes alongside increased phosphorylation of AKT in comparison to PBS controls, and this occurred without changes in circulating insulin. To determine whether this effect of IL-6 was directly on the liver, we completed in vitro isolated primary hepatocyte experiments from chow-fed mice and cultured with or without exposure to free fatty acid (250 μm palmitate and 250 μm oleate, 24 h) to induce lipid accumulation. In both control and free fatty acid-treated hepatocytes, IL-6 (20 ng/ml, 75 min) slightly attenuated insulin-stimulated (10 nM; ~15 min) AKT phosphorylation. Together, these data suggest that IL-6 may lead to improvements in indices of hepatic glucose and insulin homeostasis in vivo; however, this is likely due to an indirect effect on the hepatocyte. NEW & NOTEWORTHY In this study, we used lean and obese mice and found that a single injection of IL-6 improved glucose tolerance, decreased hepatic gluconeogenic gene expression, and increased hepatic phosphorylation of AKT. In primary hepatocytes cultured under control and lipid-laden conditions, IL-6 had a mild, but deleterious, effect on phosphorylation of AKT. Our results show that the beneficial effects of IL-6 on glucose and insulin homeostasis, in vivo, are maintained in obesity.

BACKGROUND Geriatricians are often confronted with unexpected health outcomes in older adults with complex multimorbidity. Aging researchers have recently called for a focus on physical resilience as a new approach to explaining such outcomes. Physical resilience, defined as the ability to resist functional decline or recover health following a stressor, is an emerging construct. METHODS Based on an outline of the state-of-the-art in research on the measurement of physical resilience, this article describes what tests to predict resilience can already be used in clinical practice and which innovations are to be expected soon. RESULTS An older adult's recovery potential is currently predicted by static tests of physiological reserves. Although geriatric medicine typically adopts a multidisciplinary view of the patient and implicitly performs resilience management to a certain extent, clinical management of older adults can benefit from explicitly applying the dynamical concept of resilience. Two crucial leads for advancing our capacity to measure and manage the resilience of individual patients are advocated: first, performing multiple repeated measurements around a stressor can provide insight about the patient's dynamic responses to stressors; and, second, linking psychological and physiological subsystems, as proposed by network studies on resilience, can provide insight into dynamic interactions involved in a resilient response. CONCLUSION A big challenge still lies ahead in translating the dynamical concept of resilience into clinical tools and guidelines. As a first step in bridging this gap, this article outlines what opportunities clinicians and researchers can already exploit to improve prediction, understanding, and management of resilience of older adults. J Am Geriatr Soc 67:2650-2657, 2019.

Contains fulltext : 202766.pdf (Publisher’s version ) (Closed access) Background: Despite the benefits of physical activity, a large majority of adults fail to get the recommended amount of regular exercise, and interventions to increase physical activity typically achieve only temporary improvements. The potential contribution of positive psychological functioning to the maintenance of physical activity has not been widely examined. Purpose: To test the hypothesis that psychological well-being would increase the likelihood of sustained physical activity in adults using a person-centered approach with longitudinal data. Methods: Participants (N = 2,214) were from the longitudinal Survey of Midlife Development in the United States (MIDUS). Continuous latent variables representing physical activity at three waves of MIDUS were used to partition respondents into distinct (categorical) classes based on longitudinal activity profiles. Results: Latent class analyses identified three distinct physical activity profiles: sustained, consistently low, and declining activity (the normative class). Multinomial logistic regression analyses showed that the odds of membership in the sustained activity class were significantly higher for those with higher eudaimonic well-being (OR = 1.08 [1.03-1.13], p = .001), after adjustment for diverse covariates. Supplemental analyses revealed similar associations for specific subdomains of eudaimonic well-being. Conclusion: This study provides evidence that greater well-being may help sustain physical activity in the long term. These results suggest that improving well-being may be a useful addition to interventions aimed at increasing long-term physical activity participation.

BackgroundIn clinical trials, several SARS-CoV-2 vaccines were shown to reduce risk of severe COVID-19 illness. Local, population-level, real-world evidence of vaccine effectiveness is accumulating. We assessed vaccine effectiveness for community-dwelling New York City (NYC) residents using a quasi-experimental, regression discontinuity design, leveraging a period (January 12–March 9, 2021) when ≥65-year-olds were vaccine-eligible but younger persons, excluding essential workers, were not.MethodsWe constructed segmented, negative binomial regression models of age-specific COVID-19 hospitalization rates among 45–84-year-old NYC residents during a post-vaccination program implementation period (February 21–April 17, 2021), with a discontinuity at age 65 years. The relationship between age and hospitalization rates in an unvaccinated population was incorporated using a pre-implementation period (December 20, 2020–February 13, 2021). We calculated the rate ratio (RR) and 95% confidence interval (CI) for the interaction between implementation period (pre or post) and age-based eligibility (45–64 or 65–84 years). Analyses were stratified by race/ethnicity and borough of residence. Similar analyses were conducted for COVID-19 deaths.ResultsHospitalization rates among 65–84-year-olds decreased from pre- to post-implementation periods (RR 0.85, 95% CI: 0.74–0.97), controlling for trends among 45–64-year-olds. Accordingly, an estimated 721 (95% CI: 126–1,241) hospitalizations were averted. Residents just above the eligibility threshold (65–66-year-olds) had lower hospitalization rates than those below (63–64-year-olds). Racial/ethnic groups and boroughs with higher vaccine coverage generally experienced greater reductions in RR point estimates. Uncertainty was greater for the decrease in COVID-19 death rates (RR 0.85, 95% CI: 0.66–1.10).ConclusionThe vaccination program in NYC reduced COVID-19 hospitalizations among the initially age-eligible ≥65-year-old population by approximately 15%. The real-world evidence of vaccine effectiveness makes it more imperative to improve vaccine access and uptake to reduce inequities in COVID-19 outcomes.

Insulin resistance is a key characteristic in the development of nonalcoholic fatty liver disease (NAFLD) and NASH. The present study tested the effects of lifestyle intervention (9 months, energy restriction, high intensity interval training) on glucose utilization and liver disease in patients with NASH. Before and after treatment, subjects underwent histologically-graded liver biopsies and two-step, labeled (13C6 glucose), hyperinsulinemic-euglycemic clamps. Glucose appearance (Ra) and glucose disposal (Rd) were measured in eight subjects (mean±SD, age 38.9±8.3y, BMI 38.8±5.4 kg/m2) with a NAFLD activity score (ranging from NAS 1-8) of 5.3±1.2. Following the intervention, BMI (5%, P=0.045), liver fat (35%, P=0.017), plasma glucose (15%, P=0.043), and NAS (28%, P=0.035) were significantly reduced. VO2 max increased 25% (P=0.046) and the change correlated positively with Rd (r=0.925, P=0.001). Absolute changes in Ra and Rd were associated with the individual changes in NAS (Figure 1A-B). Further, absolute change in hepatocyte lobular inflammation and Ra (Figure 1C) and change in hepatocellular ballooning and Rd were correlated (Figure 1D). These data demonstrate improvements in liver health may be driven by enhancing hepatic and peripheral insulin sensitivity through weight loss and exercise. The rerouting of substrates away from the liver may reduce nutrient toxicity and contribute to improvement in NASH. Disclosure J. M. Mucinski: None. N. S. Nallapeta: None. M. P. Moore: None. J. A. Ibdah: None. R. Rector: None. E. J. Parks: Advisory Panel; Self; Atkins Nutritionals, Inc., Consultant; Self; Genentech, Inc. Funding National Institutes of Health (R01DK113701)

Individuals with heart failure (HF) frequently present with comorbidities, including obesity, insulin resistance, hypertension, and dyslipidemia. Many patients with HF experience cardiogenic dementia, yet the pathophysiology of this disease remains poorly understood. Using a swine model of cardiometabolic HF (Western diet+aortic banding; WD-AB), we tested the hypothesis that WD-AB would promote a multidementia phenotype involving cerebrovascular dysfunction alongside evidence of Alzheimer's disease (AD) pathology. The results provide evidence of cerebrovascular insufficiency coupled with neuroinflammation and amyloidosis in swine with experimental cardiometabolic HF. Although cardiac ejection fraction was normal, indices of arterial compliance and cerebral blood flow were reduced, and cerebrovascular regulation was impaired in the WD-AB group. Cerebrovascular dysfunction occurred concomitantly with increased MAPK signaling and amyloidogenic processing (i.e., increased APP, BACE1, CTF, and Aβ40 in the prefrontal cortex and hippocampus) in the WD-AB group. Transcriptomic profiles of the stellate ganglia revealed the WD-AB group displayed an enrichment of gene networks associated with MAPK/ERK signaling, AD, frontotemporal dementia, and a number of behavioral phenotypes implicated in cognitive impairment. These provide potentially novel evidence from a swine model that cerebrovascular and neuronal pathologies likely both contribute to the dementia profile in a setting of cardiometabolic HF.

Vehicle manufacturers and government agencies are considering using vehicle-to-pedestrian (V2P) communication to improve pedestrian safety. However, there are unanswered questions about whether people will heed alerts and warnings presented through a smartphone. We conducted between-subject studies with younger and older adults where they physically crossed a virtual street. They received either permissive alerts (safe to cross), prohibitive warnings (not safe to cross), or no alerts or warnings (control). We found that both older and younger adults were highly likely to heed permissive alerts, even when this meant taking gaps between two vehicles that were smaller than they would typically take on their own. We also found that we could shift participants’ road-crossing behavior toward greater caution when they were only alerted to cross very large gaps between two vehicles. Participants stated that alerts and warnings were useful, but that prohibitive warnings were annoying. These findings give insights into V2P design and pedestrian behavior when smartphone assistance is provided.

Extracorporeal cardiopulmonary resuscitation (ECPR)-veno-arterial extracorporeal membrane oxygenation (ECMO) for refractory cardiac arrest-has grown rapidly, but its widespread adoption has been limited by frequent neurologic complications. With individual centers developing best practices, utilization may be increasing with an uncertain effect on outcomes. This study describes the recent ECPR experience at the University of Maryland Medical Center from 2016 through 2018, with attention to neurologic outcomes and predictors thereof. The primary outcome was dichotomized Cerebral Performance Category (≤2) at hospital discharge; secondary outcomes included rates of specific neurologic complications. From 429 ECMO runs over 3 years, 57 ECPR patients were identified, representing an increase in ECPR utilization compared with 41 cases over the previous 6 years. Fifty-two (91%) suffered in-hospital cardiac arrest, and 36 (63%) had an initial nonshockable rhythm. Median low-flow time was 31 minutes. Overall, 26 (46%) survived hospitalization and 23 (88% of survivors, 40% overall) had a favorable discharge outcome. Factors independently associated with good neurologic outcome included lower peak lactate, initial shockable rhythm, and higher initial ECMO mean arterial pressure. Neurologic complications occurred in 18 patients (32%), including brain death in 6 (11%), hypoxic-ischemic brain injury in 11 (19%), ischemic stroke in 6 (11%), intracerebral hemorrhage in 1 (2%), and seizure in 4 (7%). We conclude that good neurologic outcomes are possible for well-selected ECPR patients in a high-volume program with increasing utilization and evolving practices. Markers of adequate peri-resuscitation tissue perfusion were associated with better outcomes, suggesting their importance in neuroprognostication.