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Objective Penetrating atherosclerotic ulcers (PAUs) in aortic branch vessels are rare. There is a paucity of data regarding their long-term natural history and associated management. This study aimed to determine the prevalence and natural history of aortic branch PAUs. Methods Institutional data on all patients with an aortic branch PAU from 2005 to 2020 were retrospectively reviewed. Branch PAUs were defined as any PAU in the iliac, mesenteric, or arch vessels. End points included symptoms, end-organ events, and interventions. All computed tomography angiographies (CTAs) for each patient were reviewed, and total diameter, ulcer width, and ulcer depth were recorded on each computed tomography scan for the branch PAUs. Rate of change was compared between groups (iliac vs arch and visceral vessels) using a linear mixed-effects model. Results Among 58,800 patients who underwent a CTA, 367 patients had an aortic PAU (prevalence: 0.6%) and 58 patients had a branch PAU (prevalence: 0.1%). Among those 58 patients, there were 66 ulcerated branches. There were 50 iliac (42 common iliac, 7 internal, and 1 external), 11 arch (8 left subclavian, 3 innominate), and 5 visceral ulcers (3 superior mesenteric artery, 1 celiac, and 1 renal). Mean age was 74.0 ± 8.8 years, and 86% of patients were male; 74% had hypertension, 79% had hyperlipidemia, and 59% had a concomitant aortic aneurysm. There were 45 PAU vessels with >1 CTA (total of 167 CTAs) with a median follow-up of 4.0 years (interquartile range: 2.0-6.2 years). Total vessel diameter increased in size by 0.27 mm/y but did not differ between groups (iliac vs visceral/arch vessels). PAU width and depth also did not significantly change over time, nor did it differ between groups. No branch PAUs caused symptoms, end-organ events, or rupture, nor required intervention due to symptoms and/or progression. Four PAUs spontaneously resolved (2 iliac, 2 other), and 1 iliac PAU progressed to a saccular aneurysm. Conclusions This is one of the largest studies evaluating the natural history of branched PAUs objectively via CTA. Branch PAUs are rare—the prevalence was one-sixth that of aortic PAUs. There was minimal growth noted in a median follow-up of 4 years, and no PAUs required intervention for symptoms or progression. Asymptomatic branch PAUs may be safely observed.

HIV service providers are the primary implementers of HIV care services, but rural HIV service providers are under researched. We used an interpretative phenomenological analysis to explore rural HIV service providers' lived experiences of working in HIV care, who work in a rural region of a Midwestern state in the United States. From July to August 2019, 15 HIV service providers participated in a one-hour semi-structured telephone interview that elicited their experiences working in the rural HIV care continuum. Participants were tired of constantly educating and working to reduce HIV stigma; however, they received support from family and friends once they educated them about HIV. Participants felt they lacked control over systems and they developed emotional-based coping to address constant occupational stressors. Findings highlight the importance of resiliency and advocacy research and practice across ecological levels.

We evaluated the effects of a culturally adapted evidence-based HIV prevention intervention (Mpowerment), named “Tayf”, on condom use and HIV testing among young men who have sex with men (YMSM) in Beirut. A 2-year implementation of Tayf was carried out independently and in parallel with a research cohort of 226 YMSM who were surveyed at baseline and months 6, 12, 18 and 24 after Tayf initiation. Primary outcomes were (1) any condomless anal sex with HIV-positive or unknown status partners in the past 3 months, and (2) HIV testing in the past six months. Hierarchical logistic regression models examined the association of Tayf participation with the outcomes averaged across all assessments, and the moderating effect of Tayf participation on change in the outcomes over the follow-up period. A total of 331 YMSM attended at least one event, including 33% of the cohort. Tayf participation was associated with a higher rate of any condomless sex with HIV-positive or unknown status partners averaged across the five assessments, but there was no moderating effect of Tayf participation on change in this outcome over time. Tayf participation was associated with higher HIV testing when averaged across all assessments, but its interaction with time showed that the strength of this association diminished over time. In conclusion, Tayf proved feasible and acceptable in Beirut, but with limited effects. Further work is needed, including innovative publicity and marketing strategies, to bolster effects in high stigma settings where security and legal risks are prominent.

Changed synapse density has been suggested to be involved in the altered brain connectivity underlying schizophrenia (SCZ) pathology. However, postmortem studies addressing this topic are heterogeneous and it is not known whether changes are restricted to specific brain regions. Using meta-analysis, we systematically and quantitatively reviewed literature on the density of postsynaptic elements in postmortem brain tissue of patients with SCZ compared to healthy controls. We included 3 outcome measurements for postsynaptic elements: dendritic spine density (DSD), postsynaptic density (PSD) number, and PSD protein expression levels. Random-effects meta-analysis (31 studies) revealed an overall decrease in density of postsynaptic elements in SCZ (Hedges’s g: −0.33; 95% CI: −0.60 to −0.05; P = .020). Subgroup analyses showed reduction of postsynaptic elements in cortical but not subcortical tissues (Hedges’s g: −0.44; 95% CI: −0.76 to −0.12; P = .008, Hedges’s g: −0.11; 95% CI: −0.54 to 0.35; P = .671) and specifically a decrease for the outcome measure DSD (Hedges’s g: −0.81; 95% CI: −1.37 to −0.26; P = .004). Further exploratory analyses showed a significant decrease of postsynaptic elements in the prefrontal cortex and cortical layer 3. In all analyses, substantial heterogeneity was present. Meta-regression analyses showed no influence of age, sex, postmortem interval, or brain bank on the effect size. This meta-analysis shows a region-specific decrease in the density of postsynaptic elements in SCZ. This phenotype provides an important cellular hallmark for future preclinical and neuropathological research in order to increase our understanding of brain dysconnectivity in SCZ.

This study tested a three-component community prevention intervention with alcohol businesses to reduce alcohol overservice and to reduce drinking and driving crashes using a longitudinal design. The intervention involved a responsible beverage serving practices toolkit, a series of on-site visits from law enforcement, and a supporting media campaign. The effort achieved a reduction in the monthly percentage of drivers arrested for driving under the influence who cited the alcohol-licensed establishments as the place of last drink, and the number of establishments mentioned 2+ times as well as a decline in alcohol-involved crashes in the 12-month postintervention period. Results supported a conclusion that the intensive intervention media can achieve a reduction in the frequency with which drinking drivers utilized bars and restaurants and overall impaired driving-related crashes.

Spinal cord ischemia (SCI) is one of the most devastating complications after descending thoracic aortic (DTA) and thoracoabdominal aortic (TAA) repairs. Patients who develop SCI have a poor prognosis, with mortality rates reaching 75% within the first year after surgery. Many factors have been shown to increase the risk of this complication, including the extent of TAA repair, length of aortic and collateral network coverage, embolization, and reduced spinal cord perfusion pressure. As a result, a variety of treatment strategies have been developed. We aimed to provide an up-to-date review of SCI rates with associated treatment algorithms from open and endovascular DTA and TAA repair.Using PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, a literature review with the MeSH (medical subject headings) terms "spinal cord ischemia," "spinal cord ischemia prevention and mitigation strategies," "spinal cord ischemia rates," and "spinal cord infarction" was performed in the Cochrane and PubMed databases to find all peer-reviewed studies of DTA and TAA repair with SCI complications reported. The search was limited to 2012 to 2021 and English-language reports. MeSH subheadings, including diagnosis, complications, physiopathology, surgery, mortality, and therapy, were used to further restrict the included studies. Studies were excluded if they were not of humans, had not pertained to SCI after DTA or TAA operative repair, and if the study had primarily discussed neuromonitoring techniques. Additionally, studies with 40 patients or limited information regarding SCI protection strategies were excluded. Each study was individually reviewed by two of us (S.L. and A.D.) to assess the type and extent of aortic pathology, operative technique, SCI protection or mitigation strategies, rates of overall and permanent SCI symptoms, associations with SCI on multivariate analysis, and mortality.Of the 450 studies returned by the MeSH search strategy, 41 met the inclusion criteria and were included in the final analysis. For the endovascular DTA repair patients, the overall SCI rates ranged from 0% to 10.6%, with permanent SCI symptoms ranging from 0% to 5.1%. The rate of overall SCI after endovascular and open TAA repair was 0% to 35%. The permanent SCI symptom rate was reported by only one study of open repair at 1.1%. The permanent SCI symptom rate after endovascular TAA repair was 2% to 20.5%.The present review has provided an up-to-date review of the current rates of SCI and the prevention and mitigation strategies used during DTA and TAA repair. We found that a multimodal approach, including a bundled institutional protocol, staging of multiple repairs, preservation of the collateral blood flow network, augmented spinal cord perfusion, selective cerebrospinal fluid drainage, and distal aortic perfusion during open TAA repairs, appears to be important in reducing the risk of SCI.

We conducted a pilot randomized controlled trial of Game Changers, a 6-session group intervention that empowers people with HIV to be HIV prevention advocates in their social networks. Ninety-nine people with HIV (51 intervention, 48 wait-list control) and 58 of their social network members (alters) completed baseline and 5- and 8-month post-baseline assessments. Results indicated high acceptability, demonstrated by participants’ and facilitators’ positive attitudes qualitatively and favorable ratings of intervention sessions quantitatively, and high feasibility (76% attended all intervention sessions). Intention-to-treat analyses indicated significantly increased HIV prevention advocacy among HIV-positive participants and alters [b (SE) = 0.4 (0.2), p = .017; b (SE) = 0.4 (0.2), p = .035]; reduced internalized HIV stigma [b (SE) = − 0.3 (0.1), p = .012], increased HIV-serostatus disclosure [b (SE) = 0.1 (0.1), p = .051], and increased social network density among HIV-positive participants [b (SE) = 0.1 (0.03), p = .004]; and marginally reduced condomless sex among alters [OR (95% CI) = 0.3 (0.1–1.2), p = .08]. Positioning people with HIV as central to prevention has the potential to reduce stigma and improve prevention outcomes throughout social networks.

Alcohol's impact on global health is substantial and of a similar order of magnitude to that from COVID-19. Alcohol now also poses specific concerns, such as increased risk of severe lung infections, domestic violence, child abuse, depression and suicide. Its use is unlikely to aid physical distancing or other preventative behavioural measures. Globally, alcohol contributes to 20% of injury and 11.5% of non-injury emergency room presentations. We provide some broad comparisons between alcohol-attributable and COVID-19-related hospitalisations and deaths in North America using most recent data. For example, for Canada in 2017 it was recently estimated there were 105 065 alcohol-attributable hospitalisations which represent a substantially higher rate over time than the 10 521 COVID-19 hospitalisations reported during the first 5 months of the pandemic. Despite the current importance of protecting health-care services, most governments have deemed alcohol sales to be as essential as food, fuel and pharmaceuticals. In many countries, alcohol is now more readily available and affordable than ever before, a situation global alcohol producers benefit from and have helped engineer. We argue that to protect frontline health-care services and public health more generally, it is essential that modest, evidence-based restrictions on alcohol prices, availability and marketing are introduced. In particular, we recommend increases in excise taxation coupled with minimum unit pricing to both reduce impacts on health-care services and provide much-needed revenues for governments at this critical time.

The current Society for Vascular Surgery practice guidelines recommend carotid revascularization for asymptomatic disease in patients with at least a 3-year life expectancy and stenosis60% when the expected perioperative stroke and death rate is 3%. Based on this recommendation, it was previously determined that asymptomatic patients who require dialysis would not meet the perioperative stroke and death thresholds nor the long-term survival benchmarks to justify carotid surgery. To determine whether carotid surgery for patients requiring dialysis is appropriate, the present study compared the perioperative outcomes after carotid revascularization for dialysis-dependent patients relative to nondialysis patients in a contemporary, national cohort.The targeted vascular module from the American College of Surgeons National Surgical Quality Improvement Program was queried to identify patients who undergone carotid endarterectomy or carotid artery stenting for asymptomatic carotid disease from 2011 to 2018. The cohort was categorized as requiring or not requiring dialysis. The primary 30-day outcomes included mortality and the composite of stroke/death and stroke/death/myocardial infarction (MI). Univariate analyses were performed using the Fisher exact test and Wilcoxon rank sum test. Multivariable analyses were used to assess the independent associations of the estimated glomerular filtration rate and dialysis dependence with the stroke/death rate.A total of 17,579 patients met the inclusion criteria. Of these patients, 226 (1.3%) required dialysis at revascularization. No difference was found in the degree of severe stenosis (80%-99%) demonstrated by 69% of the dialysis cohort and 72% of the nondialysis cohort (P = .9). Of the dialysis and nondialysis cohorts, 5% and 3.6% underwent carotid artery stenting (P = .3). The dialysis-dependent patients were younger (68 vs 71 years; P .001) and were more likely to have insulin-dependent diabetes (47% vs 12%; P .001), congestive heart failure (8.4% vs 1.4%; P .001), and severe chronic obstructive pulmonary disease (15% vs 10%; P = .03). In the dialysis and nondialysis cohort, 2 (0.9%) and 88 (0.5%) patients died (P = .3); 4 (1.8%) and 247 (1.4%) experienced strokes (P = .6); and 3 (1.3%) and 185 (1.1%) patients experienced MI (P = .5), respectively. The composite outcomes of stroke/death and stroke/death/MI was 2.2% (n = 5) and 1.8% (n = 319; P = .6) and 3.5% (n = 8) and 2.8% (n = 479; P = .4) in the dialysis and nondialysis cohorts, respectively. After multivariable analysis, neither the estimated glomerular filtration rate (adjusted odds ratio, 1.0; 95% confidence interval, 1.00-1.01; P = .26) nor dialysis dependence (adjusted odds ratio, 0.21; 95% confidence interval, 0.03-1.57; P = .13) was independently associated with the composite outcome of stroke/death.The 30-day carotid revascularization outcomes for asymptomatic disease in dialysis-dependent patients met the Society for Vascular Surgery guidelines in this national cohort and might be better than previously surmised. Hence, vascular surgeons could consider carotid revascularization for select dialysis-dependent patients with the appropriate expected longevity and perioperative risk.

Background: In Australia’s Northern Territory, 33% of babies are born to Indigenous mothers, who experience high rates of hyperglycemia in pregnancy. We aimed to determine the extent to which pregnancy outcomes for Indigenous Australian women are explained by relative frequencies of diabetes type [type 2 diabetes (T2DM) and gestational diabetes (GDM)]. Methods: This prospective birth cohort study examined participants recruited from a hyperglycemia in pregnancy register. Baseline data collected were antenatal and perinatal clinical information, cord blood and neonatal anthropometry. Of 1135 women (48%Indigenous), 900 had diabetes: 175 T2DM, 86 newly diagnosed diabetes in pregnancy(DIP) and 639 had GDM. A group of 235 women without hyperglycemia in pregnancywas also recruited. Results: Diabetes type differed for Indigenous and non-Indigenous women (T2DM, 36 vs5%; DIP, 15 vs 7%; GDM, 49 vs 88%, p < 0.001). Within each diabetes type, Indigenous women were younger and had higher smoking rates. Among women with GDM/DIP,Indigenous women demonstrated poorer birth outcomes than non-Indigenous women:large for gestational age, 19 vs 11%, p ¼ 0002; neonatal fat 11.3 vs 10.2%, p < 0.001. Inthe full cohort, on multivariate regression, T2DM and DIP were independently associated(and Indigenous ethnicity was not) with pregnancy outcomes Conclusions: Higher rates of T2DM among Indigenous women predominantly contribute to absolute poorer pregnancy outcomes among Indigenous women with hyperglycemia.As with Indigenous and minority populations globally, prevention or delay of type 2 diabetes in younger women is vital to improve pregnancy outcomes and possibly to improve the long-term health of their offspring. Refereed/Peer-reviewed

Heart failure (HF) is a global public health problem that, independent of its etiology [reduced (HFrEF) or preserved ejection fraction (HFpEF)], is characterized by functional impairments of cardiac function, chemoreflex hypersensitivity, baroreflex sensitivity (BRS) impairment, and abnormal autonomic regulation, all of which contribute to increased morbidity and mortality. Exercise training (ExT) has been identified as a nonpharmacological therapy capable of restoring normal autonomic function and improving survival in patients with HFrEF. Improvements in autonomic function after ExT are correlated with restoration of normal peripheral chemoreflex sensitivity and BRS in HFrEF. To date, few studies have addressed the effects of ExT on chemoreflex control, BRS, and cardiac autonomic control in HFpEF; however, there are some studies that have suggested that ExT has a beneficial effect on cardiac autonomic control. The beneficial effects of ExT on cardiac function and autonomic control in HF may have important implications for functional capacity in addition to their obvious importance to survival. Recent studies have suggested that the peripheral chemoreflex may also play an important role in attenuating exercise intolerance in HFrEF patients. The role of the central/peripheral chemoreflex, if any, in mediating exercise intolerance in HFpEF has not been investigated. The present review focuses on recent studies that address primary pathophysiological mechanisms of HF (HFrEF and HFpEF) and the potential avenues by which ExT exerts its beneficial effects.

We tested the generalizability of a science-based community prevention design to reduce DUI crashes. Previous researcher-led studies have confirmed the effects of an intervention design of visible enforcement coupled with heightened public awareness of enforcement to increase driver perception of likely detection for drinking and driving. A community coalition based the project on a prevention intervention model that included two key intermediate variables: levels of visible enforcement and of public awareness of enforcement. We evaluated the project using community-specific monthly time-series measures of DUI crashes and state level trends in DUI crashes, indicators of enforcement, and public attention to enforcement. We devised the evaluation design to determine if an observed trend in DUI crashes declined and to verify if key intermediate variables increased, as stimulated by local efforts. DUI crash analysis documented an upward trend during a pre-trial period from July 2010-December 2011, which matched the upward trend in state DUI crashes. After the local intervention began in January 2012, local DUI crashes began a clear downward trend (average 2013 crashes were 23% lower than in 2012 and a 5-month post-intervention average from 2013 was lower than the equivalent 5-month pre-intervention average). This contrasted with the continued upward state DUI crash trend, with a 2-year increase of 16%. The downward trend in local crashes was associated with an increase in DUI enforcement as well as news stories concerning DUI enforcement that were stimulated by the efforts of the community prevention project. These results confirm the generalizability of two previous community research trials that were conducted with limited or no research resources or leadership. We discuss the importance of controlling for external factors in attributing causation in a local prevention evaluation by confirming both sufficient local prevention efforts and a decline in DUI crashes.

Epidemiological studies have shown deterioration in dental health accompanying the ageing process. Tooth loss increases with age. Chewing ability is closely correlated with number of natural teeth present: there is a threshold of 20-21 teeth, below which chewing ability declines. The government of Israel is currently considering adding dental treatment for elderly to the basket of services of the National Health Insurance Law. Information on the influence of elderly's dental health on nutrition and general health status can contribute to the decision making process.Secondary analysis of data collected on a subsample (N = 1776) of the cross-sectional Mabat Zahav - National Health and Nutrition Survey of the Elderly was done. Intakes of energy, fiber, protein, fruits and vegetables, associations with dental visits, dentures presence and functional ability were analyzed. Linear regression adjusted for confounders was performed.Statistically significant differences in dietary intake of energy, fiber, protein and vegetables were found between elderly who visited a dentist in the last year and those who did not. Elderly who possessed dentures had lower dietary intakes than their dentate counterparts. Elderly with functional problems such as impaired chewing had worse dietary intakes than the others. This was so after controlling for education, degree of interest in the relationship between nutrition and health and reading the nutrition label.The findings in our study suggest that those who visited a dentist in the last year, had natural teeth and no denture/s and reported no chewing problems had better dietary intake. The results emphasize the importance of maintaining adequate dental health, preserving natural teeth and regular dental visits in the elderly to assure adequate nutrient status in this age group.

Four patients were recently seen at our institution presenting with severe hypobicarbonatemia and elevated anion gap on serum specimens processed by an autoanalyzer using enzymatic reactions. Arterial blood gas values in each case revealed no significant acid-base disturbance and a marked discordance between arterial blood gas calculated bicarbonate levels and those reported on the basic metabolic panel. All patients had profound hyperlipidemia (triglycerides > 3,500mg/L), and ultracentrifugation of one patient's serum corrected the discordance. Lipid interference with the photometric measurement of light absorbance after enzymatic reaction in the autoanalyzer is thought to be responsible for the low reported bicarbonate values. Use of an indirect ion-specific electrode method for total carbon dioxide analysis would avoid this pitfall. Caution is advised when enzymatic autoanalyzer–calculated laboratory values are used to diagnose acid-base disturbances in patients with severe hyperlipidemia. Physicians involved in the diagnosis of acid-base disorders in hospitalized patients should always be aware of the method used by their chemistry laboratories to determine total carbon dioxide values.

Background Gum infection, known as gingivitis, is a global issue. Gingivitis does not cause pain; however, if left untreated, it can worsen, leading to bad breath, bleeding gums, and even tooth loss, as the problem spreads to the underlying structures anchoring the teeth in the jaws. The asymptomatic nature of gingivitis leads people to postpone dental appointments until clinical signs are obvious or pain is evident. The COVID-19 pandemic has necessitated social distancing, which has caused many people to postpone dental visits and neglect gingival health. iGAM is a dental mobile health (mHealth) app that remotely monitors gum health, and an observational study demonstrated the ability of iGAM to reduce gingivitis. We found that a weekly dental selfie using the iGAM app reduced the signs of gingivitis and promoted oral health in a home-based setting. Objective The aim of this mixed methods study is to assess perceptions, attitudes, willingness to pay, and willingness to use an mHealth app. Methods The first qualitative phase of the study included eight semistructured interviews, and the second quantitative phase included data collected from responses to 121 questionnaires. Results There was a consensus among all interviewees that apps dealing with health-related issues (mHealth apps) can improve health. Three themes emerged from the interviews: the iGAM app is capable of improving health, the lack of use of medical apps, and a contradiction between the objective state of health and the self-definition of being healthy. Participants were grouped according to how they responded to the question about whether they believed that mHealth apps could improve their health. Participants who believed that mHealth apps can enhance health (mean 1.96, SD 1.01) had a higher willingness to pay for the service (depending on price) than those who did not believe in app efficacy (mean 1.31, SD 0.87; t119=−2417; P=.02). A significant positive correlation was found between the amount a participant was willing to pay and the benefits offered by the app (rs=0.185; P=.04). Conclusions Potential mHealth users will be willing to pay for app use depending on their perception of the app’s ability to help them personally, provided they define themselves as currently unhealthy.

Despite improvements in medical therapy and device-based treatment, heart failure (HF) continues to impose enormous burdens on patients and health care systems worldwide. Alterations in autonomic nervous system (ANS) activity contribute to cardiac disease progression, and the recent development of invasive techniques and electrical stimulation devices has opened new avenues for specific targeting of the sympathetic and parasympathetic branches of the ANS. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop which brought together clinicians, trialists and basic scientists to discuss the ANS as a therapeutic target in HF. The questions addressed were: (i) What are the abnormalities of ANS in HF patients? (ii) What methods are available to measure autonomic dysfunction? (iii) What therapeutic interventions are available to target the ANS in patients with HF, and what are their specific strengths and weaknesses? (iv) What have we learned from previous ANS trials? (v) How should we proceed in the future?

Chronic heart failure is characterized by autonomic imbalance, cardiac dysfunction, and arrhythmogenesis. It has been shown that exercise training (ExT) improves central nervous system oxidative stress, autonomic control, and cardiac function in heart failure with reduced ejection fraction; however, to date no comprehensive studies have addressed the effects of ExT, if any, on oxidative stress in brain stem cardiovascular areas, cardiac autonomic balance, arrhythmogenesis, and cardiac function in heart failure with preserved ejection fraction (HFpEF). We hypothesize that ExT reduces brain stem oxidative stress, improves cardiac autonomic control and cardiac function, and reduces arrhythmogenesis in HFpEF rats. Rats underwent sham treatment or volume overload to induce HFpEF. ExT (60 min/day, 25 m/min, 10% inclination) was performed for 6 wk starting at the second week after HFpEF induction. Rats were randomly allocated into Sham+sedentary (Sed) ( n = 8), Sham+ExT ( n = 6), HFpEF+Sed ( n = 8), and HFpEF+ExT ( n = 8) groups. Compared with the HFpEF+Sed condition, HFpEF+ExT rats displayed reduced NAD(P)H oxidase activity and oxidative stress in the rostral ventrolateral medulla (RVLM), improved cardiac autonomic balance, and reduced arrhythmogenesis. Furthermore, a threefold improvement in cardiac function was observed in HFpEF+ExT rats. These novel findings suggest that moderate-intensity ExT is an effective means to attenuate the progression of HFpEF through improvement in RVLM redox state, cardiac autonomic control, and cardiac function. NEW & NOTEWORTHY In the present study, we found that exercise reduced oxidative stress in key brain stem areas related to autonomic control, improved sympathovagal control of the heart, reduced cardiac arrhythmias, and delayed deterioration of cardiac function in rats with heart failure with preserved ejection fraction (HFpEF). Our results provide strong evidence for the therapeutic efficacy of exercise training in HFpEF.

Enhanced carotid body (CB) chemoreflex function is strongly related to cardiorespiratory disorders and disease progression in heart failure (HF). The mechanisms underlying CB sensitization during HF are not fully understood, however previous work indicates blood flow per se can affect CB function. Then, we hypothesized that the CB-mediated chemoreflex drive will be enhanced only in low output HF but not in high output HF. Myocardial infarcted rats and aorto-caval fistulated rats were used as a low output HF model (MI-CHF) and as a high output HF model (AV-CHF), respectively. Blood flow supply to the CB region was decreased only in MI-CHF rats compared to Sham and AV-CHF rats. MI-CHF rats exhibited a significantly enhanced hypoxic ventilatory response compared to AV-CHF rats. However, apnea/hypopnea incidence was similarly increased in both MI-CHF and AV-CHF rats compared to control. Kruppel-like factor 2 expression, a flow sensitive transcription factor, was reduced in the CBs of MI-CHF rats but not in AV-CHF rats. Our results indicate that in the setting of HF, potentiation of the CB chemoreflex is strongly associated with a reduction in cardiac output and may not be related to other pathophysiological consequences of HF.

While there has been considerable effort devoted to developing alternative payment models (APMs) for primary care physicians and for episodes of care beginning with inpatient admissions, there has been relatively little attention by payers to developing APMs for specialty ambulatory care, and no efforts to develop APMs that explicitly focus on emergency care. In order to ensure that emergency care is appropriately integrated and valued in future payment models, emergency physicians (EPs) must engage with the stakeholders within the broader health care system. In this article, we describe a framework for the development of APMs for emergency medicine and present four examples of APMs that may be applicable in emergency medicine. A better understanding of how APMs can work in emergency medicine will help EPs develop new APMs that improve the cost and quality of care, and leverage the value that emergency care brings to the system.

Our aims were to determine if targeting protein for Xklp2 (TPX2) is correlated with clear cell renal cell carcinoma (ccRCC) histology and oncologic outcomes using The Cancer Genome Atlas (TCGA) and an institutional tissue microarray (TMA).Clinicopathological data obtained from the TCGA consisted of 415 samples diagnosed with ccRCC. A TMA was constructed from tumors of 207 patients who underwent radical nephrectomy for ccRCC. TPX2 expression by immunohistochemistry on TMA was assessed by a genitourinary pathologist. Clinical data were extracted and linked to TMA cores. TPX2 and Aurora-A mRNA coexpression were evaluated in the TCGA cohort. Overall survival (OS), cancer-specific survival, and recurrence-free survival (RFS) were analyzed using the Kaplan-Meier method and log-rank statistics. Univariate and multivariate analyses were conducted using Cox proportional hazard models.Median follow-up time for the TCGA cohort was 3.07 years. Aurora-A and TPX2 mRNA coexpression were significantly correlated (Pearson correlation = 0.918). High TPX2 mRNA expression was associated with advanced stage, metastasis, poor OS, and RFS. Median follow-up time for the TMA cohort was 5.3 years. Elevated TPX2 protein expression, defined as greater than 75th percentile staining intensity, was identified in 47/207 (22.7%) patients. Increased TPX2 immunostaining was associated with poor OS (P = 0.0327, 53% 5-year mortality), cancer-specific survival (P0.01, 47.8% 5-year cancer-specific mortality), RFS (P = 0.0313, 73.6%, 5-year recurrence rate), grade, T stage, and metastasis. Multivariate analysis demonstrated elevated expression served as an independent predictor of RFS (hazard ratio = 3.62 (1.13-11.55), P = 0.029).We show TPX2, a regulator of Aurora-A, is associated with high grade and stage of ccRCC, and is an independent predictor of recurrence. Future studies are warranted testing its role in ccRCC biology, and its potential as a therapeutic target.

Key points Heart failure with preserved ejection fraction (HFpEF) is associated with disordered breathing patterns, and sympatho-vagal imbalance. Although it is well accepted that altered peripheral chemoreflex control plays a role in the progression of heart failure with reduced ejection fraction (HFrEF), the pathophysiological mechanisms underlying deterioration of cardiac function in HFpEF are poorly understood. We found that central chemoreflex is enhanced in HFpEF and neuronal activation is increased in pre-sympathetic regions of the brainstem. Our data showed that activation of the central chemoreflex pathway in HFpEF exacerbates diastolic dysfunction, worsens sympatho-vagal imbalance and markedly increases the incidence of cardiac arrhythmias in rats with HFpEF. Abstract Heart failure (HF) patients with preserved ejection fraction (HFpEF) display irregular breathing, sympatho-vagal imbalance, arrhythmias and diastolic dysfunction. It has been shown that tonic activation of the central and peripheral chemoreflex pathway plays a pivotal role in the pathophysiology of HF with reduced ejection fraction. In contrast, no studies to date have addressed chemoreflex function or its effect on cardiac function in HFpEF. Therefore, we tested whether peripheral and central chemoreflexes are hyperactive in HFpEF and if chemoreflex activation exacerbates cardiac dysfunction and autonomic imbalance. Sprague-Dawley rats (n = 32) were subjected to sham or volume overload to induce HFpEF. Resting breathing variability, chemoreflex gain, cardiac function and sympatho-vagal balance, and arrhythmia incidence were studied. HFpEF rats displayed [mean ± SD; chronic heart failure (CHF) vs. Sham, respectively] a marked increase in the incidence of apnoeas/hypopnoeas (20.2 ± 4.0 vs. 9.7 ± 2.6 events h−1), autonomic imbalance [0.6 ± 0.2 vs. 0.2 ± 0.1 low/high frequency heart rate variability (LF/HFHRV)] and cardiac arrhythmias (196.0 ± 239.9 vs. 19.8 ± 21.7 events h−1). Furthermore, HFpEF rats showed increase central chemoreflex sensitivity but not peripheral chemosensitivity. Accordingly, hypercapnic stimulation in HFpEF rats exacerbated increases in sympathetic outflow to the heart (229.6 ± 43.2% vs. 296.0 ± 43.9% LF/HFHRV, normoxia vs. hypercapnia, respectively), incidence of cardiac arrhythmias (196.0 ± 239.9 vs. 576.7 ± 472.9 events h−1) and diastolic dysfunction (0.008 ± 0.004 vs. 0.027 ± 0.027 mmHg μl−1). Importantly, the cardiovascular consequences of central chemoreflex activation were related to sympathoexcitation since these effects were abolished by propranolol. The present results show that the central chemoreflex is enhanced in HFpEF and that acute activation of central chemoreceptors leads to increases of cardiac sympathetic outflow, cardiac arrhythmogenesis and impairment in cardiac function in rats with HFpEF.

Wilms tumor (WT) is the most common renal neoplasm of childhood and affects 1 in 10 000 children aged less than 15 years. These embryonal tumors are thought to arise from primitive nephrogenic rests that derive from the metanephric mesenchyme during kidney development and are characterized partly by increased Wnt/β-catenin signaling. We previously showed that coordinate activation of Ras and β-catenin accelerates the growth and metastatic progression of a murine WT model. Here, we show that activating KRAS mutations can be found in human WT. In addition, high levels of phosphorylated AKT are present in the majority of WT. We further show in a mouse model and in renal epithelial cells that Ras cooperates with β-catenin to drive metastatic disease progression and promotes in vitro tumor cell growth, migration, and colony formation in soft agar. Cellular transformation and metastatic disease progression of WT cells are in part dependent on PI3K/AKT activation and are inhibited via pharmacological inhibition of this pathway. Our studies suggest both KRAS mutations and AKT activation are present in WT and may represent novel therapeutic targets for this disease.

Objectives: To investigate the prospective association between parental pre-pregnancy BMI and adult male and female offspring BMI and waist circumference (WC). Methods: Sub-sample of 2,229 parent-offspring pairs with parental pre-pregnancy BMI and offspring BMI and WC at 21 years were used from the MUSP (Mater-University of Queensland Study of Pregnancy cohort). Multivariable results were adjusted for maternal factors around pregnancy (e.g. gestational weight and smoking during pregnancy) and offspring factors in early life (e.g. birth weight) and at 14 years (e.g. sports participation and mealtime with family). Results: After adjustments for confounders, each unit increase in paternal and maternal BMI, the BMI of young adult offspring increased by 0.33kg/m2 and 0.35kg/m2, and the WC increased by 0.76 cm and 0.62 cm, respectively. In the combination of parents' weight status, offspring at 21 years were six times the risk being overweight/obese (OW/OB) when both parents were OW/OB, compared to offspring of healthy weight parents. Conclusions: Prenatal parental BMI are independently related to adult offspring BMI and WC. Implications: Both prenatal paternal-maternal weight status are important determinants of offspring weight status in long-term. Further studies are warranted to investigate the underlying mechanisms.

This article discusses rearfoot fusions for foot and ankle surgeons. It establishes normal foot and ankle function primarily in the stance phase of gait. The foot is greatly affected by external and internal forces, which contribute to normal function or the need for compensatory mechanisms. As a result of compensation, many symptoms develop, often leading to debilitating disorders such as degenerative joint disease. The interaction of the ankle, subtalar, and midtarsal joints are outlined. Congenital deformities, trauma and abnormal compensation are reviewed along with corresponding sequelae. Surgery is often indicated to reduce symptoms, improve position, and help stabilize the foot.

Enhanced central chemoreflex (CC) gain is observed in volume overload heart failure (HF) and is correlated with autonomic dysfunction and breathing disorders. The aim of this study was to determine the role of the CC in the development of respiratory and autonomic dysfunction in HF. Volume overload was surgically created to induce HF in male Sprague-Dawley rats. Radiotelemetry transmitters were implanted for continuous monitoring of blood pressure and heart rate. After recovering from surgery, conscious unrestrained rats were exposed to episodic hypercapnic stimulation [EHS; 10 cycles/5 min, inspiratory fraction of carbon dioxide ([Formula: see text]) 7%] in a whole body plethysmograph for recording of cardiorespiratory function. To determine the contribution of CC to cardiorespiratory variables, selective ablation of chemoreceptor neurons within the retrotrapezoid nucleus (RTN) was performed via injection of saporin toxin conjugated to substance P (SSP-SAP). Vehicle-treated rats (HF+Veh and Sham+Veh) were used as controls for SSP-SAP experiments. Sixty minutes post-EHS, minute ventilation was depressed in sham animals relative to HF animals (ΔV̇e: −5.55 ± 2.10 vs. 1.24 ± 1.35 mL/min 100 g, P < 0.05; Sham+Veh vs. HF+Veh). Furthermore, EHS resulted in autonomic imbalance, cardiorespiratory entrainment, and ventilatory disturbances in HF+Veh but not Sham+Veh rats, and these effects were significantly attenuated by SSP-SAP treatment. Also, the apnea-hypopnea index (AHI) was significantly lower in HF+SSP-SAP rats compared with HF+Veh rats (AHI: 5.5 ± 0.8 vs. 14.4 ± 1.3 events/h, HF+SSP-SAP vs. HF+Veh, respectively, P < 0.05). Finally, EHS-induced respiratory-cardiovascular coupling in HF rats depends on RTN chemoreceptor neurons because it was reduced by SSP-SAP treatment. Overall, EHS triggers ventilatory plasticity and elicits cardiorespiratory abnormalities in HF that are largely dependent on RTN chemoreceptor neurons.

We assessed how egocentric (i.e., self-generated descriptions of a person's social contacts) network structure and composition corresponded with reported instances of condomless receptive and insertive anal intercourse with men who were reportedly HIV-infected or of unknown HIV serostatus in a sample of black men who have sex with men (MSM) in six U.S. cities. Ratings showing a higher percentage of network members who provided social participation and medical support were positively associated with reporting condomless sex. There were also significant positive associations between stimulant use and condomless insertive and receptive anal sex. Future research should examine the social processes that underlie these associations and explore ways that social support can affect HIV prevention efforts for black MSM.

Excessive sympathoexcitation characterizes the chronic heart failure (CHF) state. An exaggerated cardiac sympathetic afferent reflex (CSAR) contributes to this sympathoexcitation. Prior studies have demonstrated that the CSAR to capsaicin [transient receptor potential (TRP) vanilloid 1 agonist] is exaggerated in CHF animal models. We recently discovered that capsaicin application to the lung visceral pleura in anesthetized, vagotomized, open-chested rats increases mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). We named this response the pulmonary spinal afferent reflex (PSAR). Due to the similarities between TRP vanilloid 1 and TRP ankyrin 1 (TRPA1) channels as well as the excessive sympathoexcitation of CHF, we hypothesized that stimulation of the CSAR and PSAR with a specific TRPA1 agonist would result in an augmented response in CHF rats (coronary ligation model) compared with sham control rats. In response to a TRPA1 agonist, both CSAR and PSAR in sham rats resulted in biphasic changes in MAP and increases in HR and RSNA 10–12 wk postmyocardial infarction (post-MI). These effects were blunted in CHF rats. Assessment of TRPA1 expression levels in cardiopulmonary spinal afferents by immunofluorescence, quantitative RT-PCR, and Western blot analysis 10–12 wk post-MI all indicates reduced expression in CHF rats but no reduction at earlier time points. TRPA1 protein was reduced in a dorsal root ganglia cell culture model of inflammation and simulated tissue ischemia, raising the possibility that the in vivo reduction of TRPA1 expression was, in part, caused by CHF-related tissue ischemia and inflammation. These data provide evidence that reflex responses to cardiopulmonary spinal afferent TRPA1 stimulation may be attenuated in CHF rather than enhanced.NEW & NOTEWORTHY Excessive sympathoexcitation characterizes chronic heart failure (CHF). The contribution of transient receptor potential ankyrin 1 (TRPA1) channel-mediated reflexes to this sympathoexcitation is unknown. We found that application of TRPA1 agonist to the heart and lung surface resulted in increased heart rate and sympathetic output and a biphasic change in mean arterial pressure in control rats. These effects were attenuated in CHF rats, decreasing the likelihood that TRPA1 channels contribute to cardiopulmonary afferent sensitization in CHF.

KEY POINTS A strong association between disordered breathing patterns, elevated sympathetic activity, and enhanced central chemoreflex drive has been shown in experimental and human heart failure (HF). The aim of this study was to determine the contribution of catecholaminergic rostral ventrolateral medulla catecholaminergic neurones (RVLM-C1) to both haemodynamic and respiratory alterations in HF. Apnoea/hypopnoea incidence (AHI), breathing variability, respiratory-cardiovascular coupling, cardiac autonomic control and cardiac function were analysed in HF rats with or without selective ablation of RVLM-C1 neurones. Partial lesion (∼65%) of RVLM-C1 neurones reduces AHI, respiratory variability, and respiratory-cardiovascular coupling in HF rats. In addition, the deleterious effects of central chemoreflex activation on cardiac autonomic balance and cardiac function in HF rats was abolished by ablation of RVLM-C1 neurones. Our findings suggest that RVLM-C1 neurones play a pivotal role in breathing irregularities in volume overload HF, and mediate the sympathetic responses induced by acute central chemoreflex activation. ABSTRACT Rostral ventrolateral medulla catecholaminergic neurones (RVLM-C1) modulate sympathetic outflow and breathing under normal conditions. Heart failure (HF) is characterized by chronic RVLM-C1 activation, increased sympathetic activity and irregular breathing patterns. Despite studies showing a relationship between RVLM-C1 and sympathetic activity in HF, no studies have addressed a potential contribution of RVLM-C1 neurones to irregular breathing in this context. Thus, the aim of this study was to determine the contribution of RVLM-C1 neurones to irregular breathing patterns in HF. Sprague-Dawley rats underwent surgery to induce volume overload HF. Anti-dopamine β-hydroxylase-saporin toxin (DβH-SAP) was used to selectively lesion RVLM-C1 neurones. At 8 weeks post-HF induction, breathing pattern, blood pressures (BP), respiratory-cardiovascular coupling (RCC), central chemoreflex function, cardiac autonomic control and cardiac function were studied. Reduction (∼65%) of RVLM-C1 neurones resulted in attenuation of irregular breathing, decreased apnoea-hypopnoea incidence (11.1 ± 2.9 vs. 6.5 ± 2.5 events h-1 ; HF+Veh vs. HF+DβH-SAP; P 0.5 between breathing and cardiovascular signals) and was attenuated by DβH-SAP treatment (coherence: 0.74 ± 0.12 vs. 0.54 ± 0.10, HF+Veh vs. HF+DβH-SAP rats; P

Background Government alcohol monopolies were created in North America and Scandinavia to limit health and social problems. The Swedish monopoly, Systembolaget, reports to a health ministry and controls the sale of all alcoholic beverages with > 3.5% alcohol/volume for off-premise consumption, within a public health mandate. Elsewhere, alcohol monopolies are being dismantled with evidence of increased consumption and harms. We describe innovative modelling techniques to estimate health outcomes in scenarios involving Systembolaget being replaced by 1) privately owned liquor stores, or 2) alcohol sales in grocery stores. The methods employed can be applied in other jurisdictions and for other policy changes. Methods Impacts of the privatisation scenarios on pricing, outlet density, trading hours, advertising and marketing were estimated based on Swedish expert opinion and published evidence. Systematic reviews were conducted to estimate impacts on alcohol consumption in each scenario. Two methods were applied to estimate harm impacts: (i) alcohol attributable morbidity and mortality were estimated utilising the International Model of Alcohol Harms and Policies (InterMAHP); (ii) ARIMA methods to estimate the relationship between per capita alcohol consumption and specific types of alcohol-related mortality and crime. Results Replacing government stores with private liquor stores (Scenario 1) led to a 20.0% (95% CI, 15.3–24.7) increase in per capita consumption. Replacement with grocery stores (Scenario 2) led to a 31.2% (25.1–37.3%) increase. With InterMAHP there were 763 or + 47% (35–59%) and 1234 or + 76% (60–92%) more deaths per year, for Scenarios 1 and 2 respectively. With ARIMA, there were 850 (334–1444) more deaths per year in Scenario 1 and 1418 more in Scenario 2 (543–2505). InterMAHP also estimated 10,859 or + 29% (22–34%) and 16,118 or + 42% (35–49%) additional hospital stays per year respectively. Conclusions There would be substantial adverse consequences for public health and safety were Systembolaget to be privatised. We demonstrate a new combined approach for estimating the impact of alcohol policies on consumption and, using two alternative methods, alcohol-attributable harm. This approach could be readily adapted to other policies and settings. We note the limitation that some significant sources of uncertainty in the estimates of harm impacts were not modelled.

A hallmark of chronic heart failure (HF) with low ejection fraction (HFrEF) is exercise intolerance. We hypothesized that reduced expression of nuclear factor E2-related factor 2 (Nrf2) in skeletal muscle contributes to impaired exercise performance. We further hypothesized that curcumin, a Nrf2 activator, would preserve or increase exercise capacity in HF. Experiments were carried out in mice with coronary artery ligation-induced HFrEF. Curcumin was deliveried by a subcutaneous osmotic minipump at a dose of 50 mg·kg−1·day−1 for 8 weeks. In vivo, in situ, and in vitro experiments were employed to evaluate exercise capacity, muscle function, and molecular mechanisms. We found that: 1) the maximal speed, running distance to exhaustion, and limb grip force were significantly lower in HFrEF mice compared with sham. Curcumin-treated HF mice displayed enhanced exercise performance compared with vehicle-treated HF mice; 2) both soleus (Sol) and extensor digitorum longus (EDL) muscles of HFrEF mice exhibited reduced force and rapid fatigue, which were ameliorated by curcumin; and 3) protein expression of Nrf2, hemeoxygenase-1, SOD2, myogenin, and MyoD were significantly lower, but total ubiquitinated proteins, MURF1, and atrogen-1 were higher in Sol and EDL of HFrEF compared with sham mice, whereas these alterations in Nrf2 signaling and antioxidant defenses in HFrEF were attenuated by curcumin, which had no effect on cardiac function per se in mice with severe HFrEF. These data suggest that impaired Nrf2 signaling intrinsic to skeletal muscle contributes to exercise intolerance in HFrEF. Skeletal muscle Nrf2 should be considered as a novel therapeutic target in severe HF. NEW & NOTEWORTHY These studies suggest that impaired nuclear factor E2-related factor 2 (Nrf2) signaling is a critical mechanism underlying the enhanced oxidative stress in skeletal muscle in heart failure with low ejection fraction (HFrEF). Curcumin prevents the decline in running performance in HFrEF mice by upregulating antioxidant defenses in skeletal muscle, likely mediated by activating Nrf2 signaling. These findings suggest a novel therapeutic target for the improvement of exercise capacity and quality of life in HFrEF patients.

Physiological systems often display 24 h rhythms that vary with the light/dark cycle. Disruption of circadian physiological rhythms have been linked to the progression of various cardiovascular diseases, and advances in the understanding of these rhythms have led to novel interventions and improved clinical outcomes. Although respiratory function has been known to vary between the light and dark periods, circadian rhythms in breathing have been understudied in clinical conditions. In the current study, we have begun to assess light/dark variations in respiration in chronic heart failure (CHF), a condition associated with abnormal resting and chemoreflex breathing as well as exercise intolerance. CHF was induced using coronary artery ligation and verified using echocardiography. Sham animals underwent a thoracotomy without coronary artery ligation. Tidal volume, respiratory frequency, and minute ventilation were all determined by whole body plethysmography under resting conditions and in response to chemoreflex challenges during the light and dark periods. Light/dark differences in voluntary exercise were assessed using a running wheel. The sham control group showed light/dark differences in resting and chemoreflex breathing, as well as arterial pressure, and these effects were eliminated in the CHF group. Both groups completed more rotations on the running wheel during the dark period compared to during the light period. The data suggest that CHF disrupts cardiovascular and respiratory circadian rhythms.

In 2012, our research with young men who have sex with men (YMSM) in Beirut showed high rates of recent condomless anal sex and low rates of recent HIV testing. In 2017, we collected data from YMSM to assess for temporal changes and sociodemographic correlates. Propensity score weighting was used to eliminate any sociodemographic differences between the 2012 (n = 164) and 2017 (n = 226) samples of YMSM (age 18–29) recruited with long-chain peer referral sampling. Regression analysis was used to examine sociodemographic correlates of recent condomless anal sex and HIV testing using the 2017 sample, and whether these behaviors differed between the samples. Compared to the 2012 sample, the 2017 sample was about half as likely to report any condomless anal sex in the past 3 months with partners whose HIV status was positive or unknown (14% vs. 23%; OR [95%CI] 0.56 [0.32, 0.98]), and nearly 2.5 times as likely to report HIV testing in the past 6 months (48% vs. 27%; OR [95%CI] 2.44 [1.46, 4.10]). In the 2017 sample, any recent condomless anal sex with partners whose HIV status was positive or unknown was associated with employment and Christian religious affiliation. Low income was the sole correlate of having recently tested for HIV. These findings suggest a temporal trend toward increased HIV protective behaviors among YMSM in Beirut over the past 5 years. Further inroads could be secured if HIV prevention programming targeted economic influences.

The liver of the cobia, Rachycentron canadum, was examined by gross dissection, histological, and ultrastructural procedures. Other visceral organs were examined by histological techniques only. Unique perivenous smooth muscle cords are associated with veins in these systems, but they are particularly prominent in their association with the hepatic portal veins and their numerous intrahepatic branches. The perivenous smooth muscle cords accompany tributaries of the portal veins to the junction of the venules with the hepatic sinusoids. The reciprocal contraction and relaxation of various segments of the smooth muscle cords appear to result in pooling of blood in temporary reservoirs and in its transport to various regions of the organ. This process might apply to other organ systems as well. Possibly this unique relationship of the smooth muscle cords with veins functions in a diving reflex. Triads are occasionally encountered in the cobia liver. © 1992 Wiley-Liss, Inc.

Backgroud The need for dental treatments, especially those related to dental caries, may be associated with and influenced by a wide range of demographic variables. The aim of this study was to describe caries related treatment needs among young Israeli adults and the association with several socio-demographic factors, including socio-economic cluster (SEC), intellectual capabilities, ethnicity and other variables. Methods Data were collected from dental records of army recruits between 2012 and 2013. We cross-examined data regarding dental treatment needs with socio-demographic variables: age, gender, SEC, intellectual capability score (ICS), birth place of participant and parents, education and immigration. Results Data received regarding 13,398 combat recruits during their first four months of military training. Most subjects were males (92.4%), with a mean age of 18.9 years. 10.8% were immigrants, with 12.2 years living in Israel before their recruitment. Only 17.7% had no dental treatment needs. Mean number of teeth needing treatment was: for restorations 1.96 ± 2.59, for root canal therapies 0.07 ± 0.44 and for extractions 0.05 ± 0.28. Low ICS scores and low SEC group were significantly associated with higher treatment needs (P

The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague-Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1-expressing afferent soma at the level of T1-T4 dorsal root ganglia pleura. This treatment abolished all sympatho-excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9-10 weeks post-RTX. These data suggest the presence of an excitatory pulmonary chemosensitive sympathetic afferent reflex. This finding may have important clinical implications in pulmonary conditions inducing sensory nerve activation such as pulmonary inflammation and inhalation of chemical stimuli.

Objective Many national HIV guidelines recommend that health care providers encourage patients to identify a treatment partner from their social network to support antiretroviral therapy adherence. This study examined associations of patient and treatment partner characteristics with patient viral suppression in Botswana. Design One hundred thirty-one patients [67 (51.1%) virally suppressed and 64 (48.9%) not suppressed] and their treatment partners were recruited for cross-sectional interviews from one HIV clinic. Methods Participants completed surveys assessing social network, sociodemographic, and psychosocial characteristics. Open-ended questions explored treatment partner relationship quality. Results Multivariate logistic regressions indicated a higher likelihood of viral suppression among patients who reported greater average emotional closeness to their network members [odds ratio (95% confidence interval) = 3.8 (1.3 to 11.5), P = 0.02] and whose treatment partners were spouses/partners [odds ratio (95% confidence interval) = 2.6 (1.0 to 6.7), P = 0.04]. Qualitative analyses indicated that treatment partners of suppressed patients provided both medical and nonmedical support, whereas treatment partners of unsuppressed patients focused mainly on adherence reminders and appointment accompaniment. Treatment partners, especially of unsuppressed patients, requested ongoing training and counseling skills. Conclusions Additional research is needed to further explore effective characteristics of treatment partners to inform HIV treatment guidelines. Standard training for treatment partners could include medical-related information and counseling education.

In contrast to self-produced media like reversion stories, chapter 4 documents and assesses journalistic representations of Latino Muslims. In a post-9/11 media context, Latino Muslims received increased attention from journalists. It argues that these news stories have, however, reductively focused on “conversion” at the expense of more complex and diverse representations. Although much of this coverage has been reductive, it has generally not been overtly negative. An exception to this pattern is Spanish language news media, which has represented Latino Muslims in negative ways that echo the form but not the function of broader sets of orientalist images. Latino Muslims have responded by calling for boycotts and writing petitions to end the defamation of their identity group. The chapter argues that some of their responses are more reasonable than others and that they will require much broader support if these are to make any positive contributions to public discourse.

We examined how functional social support, HIV-related discrimination, internalized HIV stigma, and social network structure and composition were cross-sectionally associated with network members’ knowledge of respondents’ serostatus among 244 HIV-positive African Americans in Los Angeles. Results of a generalized hierarchical linear model indicated people in respondents’ networks who were highly trusted, well-known to others (high degree centrality), HIV-positive, or sex partners were more likely to know respondents’ HIV serostatus; African American network members were less likely to know respondents’ serostatus, as were drug-using partners. Greater internalized stigma among respondents living with HIV was associated with less knowledge of their seropositivity within their social network whereas greater respondent-level HIV discrimination was associated with more knowledge of seropositivity within the network. Additional research is needed to understand the causal mechanisms and mediating processes associated with serostatus disclosure as well as the long-term consequences of disclosure and network members’ knowledge of respondents’ serostatus.

In the kidney, 20-hydroxyeicosatetraenoic acid (20-HETE) is a primary cytochrome P450 4 (Cyp4)-derived eicosanoid that enhances vasoconstriction of renal vessels and induces hypertension, renal tubular cell hypertrophy, and podocyte apoptosis. Hypertension and podocyte injury contribute to diabetic nephropathy and are strong predictors of disease progression. In this study, we defined the mechanisms whereby 20-HETE affects the progression of diabetic nephropathy. We used Cyp4a14KO male mice that exhibit androgen-sensitive hypertension due to increased Cyp4a12-mediated 20-HETE production. We show that, upon induction of diabetes type 1 via streptozotocin injection, Cyp4a14KO male mice developed worse renal disease than streptozotocin-treated wild-type mice, characterized by increased albuminuria, mesangial expansion, glomerular matrix deposition, and thickness of the glomerular basement membranes. Castration blunted androgen-mediated Cyp4a12 synthesis and 20-HETE production, normalized BP, and ameliorated renal damage in diabetic Cyp4a14KO mice. Notably, treatment with a 20-HETE antagonist or agents that normalized BP without affecting Cyp4a12 expression and 20-HETE biosynthesis also ameliorated diabetes-mediated renal damage and albuminuria in Cyp4a14KO male mice. Taken together, these results suggest that hypertension is the major contributor to 20-HETE-driven diabetes-mediated kidney injury.

Recent advances have drawn interest in the potential for carotid body (CB) ablation or desensitization as an effective strategy for clinical treatment and management of cardio-respiratory diseases including hypertension, heart failure, diabetes mellitus, metabolic syndrome, and renal failure. These disease states have in common sympathetic overactivity, which plays an important role in the development and progression of the disease and is often associated with breathing dysregulation, which in turn likely mediates or aggravates the autonomic imbalance. Evidence from both chronic heart failure (CHF) patients and animal models indicates that the CB chemoreflex is enhanced in CHF and contributes to the tonic elevation in sympathetic activity and the development of periodic breathing associated with the disease. Although this maladaptive change likely derives from altered function at all levels of the reflex arc, a tonic increase in afferent activity from CB glomus cells is likely to be a main driving force. This report will focus on our understanding of mechanisms that alter CB function in CHF and their potential translational impact on treatment of CHF.

Chronic heart failure (CHF) is a leading medical problem worldwide. Common hallmarks of CHF include autonomic imbalance and breathing disorders, both of which are closely related to the progression of the disease and strongly predict mortality in CHF patients. The role played by the carotid body (CB) chemoreceptors on the progression of CHF has received attention since enhanced carotid chemoreflex drive is thought to contribute to autonomic dysfunction, abnormal breathing patterns, and increased mortality in CHF. Therefore, therapeutic tools intended to normalize CB-mediated chemoreflex drive could have the potential to better improve life quality and decrease mortality of CHF patients. In experimental CHF it has been shown an enhancement of the CB chemoreflex drive, elevated sympathetic outflow, increased resting breathing variability and apnoea incidence, and desensitization of the baroreflex. Notably, selective elimination of the CB reduced central presympathetic neuronal activation, normalized sympathetic outflow and baroreflex sensitivity, and stabilized breathing function in CHF. More remarkably, CB ablation has been shown to be a valuable therapeutic tool that significantly reduced aberrant cardiac remodeling and improved left ventricle ejection fraction and reduced cardiac arrhythmogenesis. Most importantly, CHF animals that underwent CB ablation showed a marked improvement in survival rate. Interestingly, a case report from a heart failure patient in which unilateral CB ablation was performed showed promising results with significant improvement in autonomic balance and breathing variability. Together, CHF data from experimental animals as well as humans unveil a major role for the carotid body chemoreceptors in the progression of heart failure and support the notion that CB ablation could represent a novel therapeutic strategy to reduce cardiorespiratory dysfunction and improve survival during heart failure.

Chronic heart failure (CHF) is a global health problem affecting millions of people. Autonomic dysfunction and disordered breathing patterns are commonly observed in patients with CHF, and both are strongly related to poor prognosis and high mortality risk. Tonic activation of carotid body (CB) chemoreceptors contributes to sympathoexcitation and disordered breathing patterns in experimental models of CHF. Recent studies show that ablation of the CB chemoreceptors improves autonomic function and breathing control in CHF and improves survival. These exciting findings indicate that alterations in CB function are critical to the progression of CHF. Therefore, better understanding of the physiology of the CB chemoreflex in CHF could lead to improvements in current treatments and clinical management of patients with CHF characterized by high chemosensitivity. Accordingly, the main focus of this brief review is to summarize current knowledge of CB chemoreflex function in different experimental models of CHF and to comment on their potential translation to treatment of human CHF.

Wilms tumor (WT) is the most common renal malignancy in children and the fourth most common pediatric solid malignancy in the US. Although the mechanisms underlying the WT biology are complex, these tumors most often demonstrate activation of the canonical Wnt/β-catenin pathway. We and others have shown that constitutive activation of β-catenin restricted to the renal epithelium is sufficient to induce primitive renal epithelial tumors, which resemble human WT. Here we demonstrate that pharmacologic inhibition of β-catenin gene transcription with pyrvinium inhibits tumor growth and metastatic progression in a murine model of WT. Cellular invasion is significantly inhibited in both murine WT-like and human WT cells and is accompanied by downregulation of the oncogenes Myc and Birc5 (survivin). Our studies provide proof of the concept that the canonical Wnt/β-catenin pathway may be a novel therapeutic target in the management of WT.

Until recently, genetic testing for hereditary breast cancer has primarily focused on pathogenic variants in the BRCA1 and BRCA2 (BRCA) genes. However, advances in DNA sequencing technologies have made simultaneous testing for multiple genes possible. We examined correlates of interest in multigene panel testing and risk communication preferences in an ethnically diverse sample of women who tested negative for BRCA mutations previously but remain at high risk based on their family history (referred to as “BRCA-uninformative”) and their at-risk female family members. Two-hundred and thirteen women with a previous breast cancer diagnosis and a BRCA-uninformative test result and their first-degree relatives completed a survey on interest in multigene panel testing, communication preferences, and sociodemographic, psychological, and clinical factors. Stepwise logistic regression was used to identify factors associated with testing interest. Chi-square analyses were used to test differences in risk communication preferences. Interest in multigene panel testing was high (84%) and did not considerably differ by cancer status or ethnicity. In multivariable analysis, factors significantly associated with interest in genetic testing were having had a mammogram in the past 2 years (odds ratio (OR) = 4.04, 95% confidence interval (CI) 1.80–9.02) and high cancer worry (OR = 3.77, 95% CI 1.34–10.60). Overall, the most commonly preferred genetic communication modes were genetic counselors, oncologists, and print materials. However, non-Hispanic women were more likely than Hispanic women to prefer web-based risk communication (p

The effects of short‐term (ST; 10 days) and long‐term (LT; 30 days) intermittent hypoxia (IH) on blood pressure (BP), breathing and carotid body (CB) chemosensory reflex were examined in adult rats.ST‐ and LT‐IH treated rats exhibited hypertension, irregular breathing with apnoea and augmented the CB chemosensory reflex, with all these responses becoming normalized during recovery from ST‐ but not from LT‐IH.The persistent cardiorespiratory responses to LT‐IH were associated with elevated reactive oxygen species (ROS) levels in the CB and adrenal medulla, which were a result of DNA methylation‐dependent suppression of genes encoding anti‐oxidant enzymes (AOEs).Treating rats with decitabine either during LT‐IH or during recovery from LT‐IH prevented DNA methylation of AOE genes, normalized the expression of AOE genes and ROS levels, reversed the heightened CB chemosensory reflex and hypertension, and also stabilized breathing.