Obesity as a risk factor for severe influenza-like illness

Background: Obesity was recognized as in independent risk factor for influenza during the 2009 H1N1 influenza pandemic. Objectives: We evaluated the association between body mass index (BMI) and influenza-like illness (ILI) during two non-pandemic influenza seasons (2003–2004 and 2004–2005) and during the spring and fall waves of the 2009 H1N1 pandemic. Methods: Adults with severe (inpatient) and mild (outpatient) ILI were compared to those without ILI using a case-cohort design. The study was nested among those insured by a single health insurance company, receiving care from a large multispecialty practice. Data were collected from insurance claims and the electronic health record. The primary exposure was obesity (BMI ≥ 30·0 kg/m2). Results: Across three seasons, the crude and adjusted ORs for obesity and severe ILI were 1·65 (95% CI 1·31, 2·08) and 1·23 (95% CI 0·97, 1·57), respectively. An association was observed for those aged 20–59 years (adjusted OR 1·92, 95% CI 1·26, 2·90), but not for those 60 and older (adjusted OR 1·08, 95% CI 0·80, 1·46). The adjusted ORs for obesity and severe ILI in 2003–2004, 2004–2005, and during H1N1 were 1·14 (95% CI 0·80, 1·64), 1·24 (95% CI 0·86, 1·79), and 1·76 (95% CI 0·91, 3·42), respectively. Among those with a Charlson Comorbidity Index score of zero, the adjusted ORs for 2003–2004, 2004–2005, and H1N1 were 1·60 (95% CI 0·93, 2·76), 1·43 (95% CI 0·80, 2·56), and 1·90 (95% CI 0·68, 5·27), respectively. Conclusions: Our results suggest a small to moderate association between obesity and hospitalized ILI among adults

Fostering Emotional, Social, Physical And Educational Wellbeing In Rural India: The Methods Of A Multi-Arm Randomized Controlled Trial Of Girls First

Background: There are 600 million girls in low and middle income countries (LMICs), many of whom are at great risk for poor health and education. There is thus great need for programs that can effectively improve wellbeing for these girls. Although many interventions have been developed to address these issues, most focus on health and education without integrating attention to social and emotional factors. This omission is unfortunate, as nascent evidence indicates that these factors are closely related to health and education. This paper describes the methods of a 4-arm randomized controlled trial among 3,560 adolescent girls in rural Bihar, India that tested whether adding an intervention targeting social-emotional issues (based on a “resilience framework”) to an adolescent health intervention would improve emotional, social, physical, and educational wellbeing to a greater extent than its components and a control group. Study arms were: (1) Girls First, a combination of the Girls First Resilience Curriculum (RC) and the Girls First Health Curriculum (HC); (2) Girls First Resilience Curriculum (RC) alone; (3) Girls First Health Curriculum (HC) alone; and (4) a school-as-usual control group (SC). Methods: Seventy-six schools were randomized (19 per condition) and 74 local women with a tenth grade education were trained and monitored to facilitate the program. Quantitative data were collected from 3,560 girls over 4 assessment points with very low rates of participant attrition. Qualitative assessments were conducted with a subset of 99 girls and 27 facilitators. Results and conclusions: In this article, we discuss guiding principles that facilitated trial implementation, including integrating diverse local and non-local sources of knowledge, focusing on flexibility of planning and implementation, prioritizing systematic measurement selection, and striking a balance between scientific rigor and real-world feasibility

Building Psychosocial Assets And Wellbeing Among Adolescent Girls: A Randomized Controlled Trial

We conducted a randomized controlled trial of a 5-month resilience-based program (Girls First Resilience Curriculum or RC) among 2308 rural adolescent girls at 57 government schools in Bihar, India. Local women with at least a 10th grade education served as group facilitators. Girls receiving RC improved more (vs. controls) on emotional resilience, self-efficacy, social-emotional assets, psychological wellbeing, and social wellbeing. Effects were not detected on depression. There was a small, statistically significant negative effect on anxiety (though not likely clinically significant). Results suggest psychosocial assets and wellbeing can be improved for girls in high-poverty, rural schools through a brief school-day program. To our knowledge, this is one of the largest developing country trials of a resilience-based school-day curriculum for adolescents. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of The Foundation for Professionals in Services for Adolescents. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Pharmacological eEF2K activation promotes cell death and inhibits cancer progression.

Activation of the elongation factor 2 kinase (eEF2K) leads to the phosphorylation and inhibition of the elongation factor eEF2, reducing mRNA translation rates. Emerging evidence indicates that the regulation of factors involved in protein synthesis may be critical for controlling diverse biological processes including cancer progression. Here we show that inhibitors of the HIV aspartyl protease (HIV-PIs), nelfinavir in particular, trigger a robust activation of eEF2K leading to the phosphorylation of eEF2. Beyond its anti-viral effects, nelfinavir has antitumoral activity and promotes cell death. We show that nelfinavir-resistant cells specifically evade eEF2 inhibition. Decreased cell viability induced by nelfinavir is impaired in cells lacking eEF2K. Moreover, nelfinavir-mediated anti-tumoral activity is severely compromised in eEF2K-deficient engrafted tumors in vivo Our findings imply that exacerbated activation of eEF2K is detrimental for tumor survival and describe a mechanism explaining the anti-tumoral properties of HIV-PIs

Comparison of two- and three-dimensional echocardiography with cineventriculography for measurement of left ventricular volume in patients

AbstractObjectives. We compared two- and three-dimensional echocardiopaphy with cineventriculography for measurement of left ventricular volume in patients.Background. Three-dimensional echocardiography has been shown to be highly accurate and superior to two-dimensional echocardiography in measuring left ventricular volume in vitro. However, there has been little comparison of the two methods in patients.Methods. Two- and three-dimensional echocardiography were performed in 35 patients (mean age 48 years) 1 to 3 h before left ventricular cineventriculography. Three-dimensional echocardiography used an acoustic spatial locator to register image position. Volume was computed using a polyhedral surface reconstruction algorithm based on multiple nonparallel, unevenly spaced short-axis cross sections. Two-dimensional echocardiography used the apical biplane summation of disks method. Single-plane cineventriculographic volumes were calculated using the summation of disks algorithm. The methods were compared by linear regression and a limits of agreement analysis. For the latter, systematic error was assessed by the mean of the deferences (cineventriculography minus echocardiography), and the limits of agreement were defined as ±2 SD from the mean difference.Results. Three-dimensional echocardiographic volumes demonstrated excellent correlation (end-diastole r = 0.97; end-systole r = 0.98) with cineventriculography. Standard errors of the estimate were approximately half those of two-dimensional echocardiography (end-diastole ±11.0 ml vs. ±21.5 ml; end-systole ±10.2 ml vs. ±17.0 ml). By limits of agreement analysis the end-diastolic mean diferences for two- and three-dimensional echocardiography were 21.1 and 12.9 ml, respectively. The limits of agreement (±2 SD) were ±54.0 and ±24.8 ml, respectively. For end-systole, comparable improvement was obtained by three-dimensional echocardiography. Results for ejection fraction by the two methods were similar.Conclusions. Three-dimensional echocardiography correlates highly with cineventriculography for estimation of ventricular volumes in patients and has approximately half the variability of two-dimensional echocardiography for these measurements. On the basis of this study, three-dimensional echocardiography is the preferred echocardiographic technique for measurement of ventricular volume. Three-dimensional echocardiography is equivalent to two-dimensional echocardiography for measuring ejection fraction

Prenatal influenza exposure and cardiovascular events in adulthood

Objectives: This study examined the association between prenatal exposure to pandemic influenza and cardiovascular events in adulthood. Design: Using Danish surveillance data to identify months when influenza activity was highest during three previous pandemics (1918, 1957, and 1968), persons were defined as exposed/unexposed based on whether they were in utero during peak months of one of the pandemics. Episodes of acute myocardial infarction (MI) and stroke were identified in the Danish National Registry of Patients covering all Danish hospitals since 1977. Setting/Sample Information from Danish national registries on all persons with a Civil Personal Registry number and birthdates in 1915 through 1922, 1954 through 1960, and 1966 through 1972 was collected. Main outcome measures Crude incidence rate ratios (IRRs) were calculated per pandemic. Generalized linear models were fit to estimate IRRs adjusted for sex. Results: For acute MI, sex-adjusted IRRs for persons in utero during peaks of the 1918, 1957, and 1968 pandemics, compared with those born afterward, were 1·02 (95% confidence interval (CI): 0·99, 1·05), 0·96 (95% CI: 0·87, 1·05), and 1·18 (95% CI: 0·96, 1·45), respectively. For stroke, the corresponding IRRs were 0·99 (95% CI: 0·97, 1·02), 0·99 (95% CI: 0·92, 1·05), and 0·85 (95% CI: 0·77, 0·94), respectively. Conclusions: There was generally no evidence of an association between prenatal influenza exposure and acute MI or stroke in adulthood. However, survivor bias and left truncation of outcomes for the 1918 pandemic are possible, and the current young ages of persons included in the analyses for the 1957 and 1968 pandemics may warrant later re-evaluation

Intensification of the North American Monsoon Rainfall as Observed From a Long‐Term High‐Density Gauge Network

As the atmosphere gets warmer, rainfall intensification is expected across the planet with anticipated impacts on ecological and human systems. In the southwestern United States and northwestern Mexico, the highly variable and localized nature of rainfall during the North American Monsoon makes it difficult to detect temporal changes in rainfall intensities in response to climatic change. This study addresses this challenge by using the dense, subdaily, and daily observations from 59 rain gauges located in southeastern Arizona. We find an intensification of monsoon subdaily rainfall intensities starting in the mid-1970s that has not been observed in previous studies or simulated with high-resolution climate models. Our results highlight the need for long-term, high spatiotemporal observations to detect environmental responses to a changing climate in highly variable environments and show that analyses based on limited observations or gridded data sets fail to capture temporal changes potentially leading to erroneous conclusions.Public domain articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Interleukin 23-Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris.

Treatment of pityriasis rubra pilaris (PRP) is solely based on its resemblance to psoriasis rather than any knowledge of its pathomechanism. Insight into pathogenic mediators of inflammation is essential for targeted and valid treatment options that could replace previous serendipitous therapeutic approaches in refractory PRP. To determine whether blockade of the interleukin 23-helper T cell 17 (IL-23-TH17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP. In this case report, a patient with PRP received outpatient treatment at a university hospital department of dermatology with ustekinumab according to the dosing regimen approved for psoriasis. Lesional skin biopsy samples were taken from this patient and 2 others with refractory PRP. Messenger RNA (mRNA) expression of proinflammatory innate and T-cell-derived cytokines were measured and compared with skin samples from patients with psoriasis and healthy donors. From 1 patient, lesional skin samples were taken before ustekinumab treatment and 4 and 28 weeks after treatment initiation. Follow-up was completed after 6 months. Subcutaneous ustekinumab, 45 mg, at weeks 0 and 4 and quarterly thereafter. The primary outcome was to determine the changes in expression of proinflammatory innate and T-cell-derived cytokines during ustekinumab therapy. The secondary objective was to evaluate the clinical and histopathologic phenotype in relation to the mRNA expression profile of proinflammatory cytokines. In lesional PRP skin samples from a single patient, upregulated expression levels were found for most proinflammatory innate cytokines, including tumor necrosis factor (TNF), IL-6, IL-12, IL-23, and IL-1β. Among adaptive T-cell cytokines, an increase of TH1 cytokines and, in particular, TH17 cytokines IL-17A, IL-17F, and IL-22 was seen in PRP. The patient with PRP who received ustekinumab showed regression of skin lesions after 2 weeks and almost complete resolution after 1 month. Clinical and histopathologic improvement paralleled the expression levels of TH17 cytokines but not of interferon-γ and TNF, which lagged behind the amelioration. In this case report, a role of the IL-23-TH17-axis in PRP was identified, suggesting a shared pathogenic inflammatory pathway with psoriasis, despite evident clinical and histopathologic differences. In addition, this report provides a rationale for targeting the IL-23-TH17-pathway as a treatment option for refractory PRP

Association between Patient Characteristics and HPV Vaccination Recommendation for Postpartum Patients: A National Survey of Obstetrician/Gynecologists

Human papillomavirus (HPV) vaccination rates in the U.S. are relatively low. Provider recommendation rates for HPV vaccination often vary by patient age and relationship status. Obstetrician/gynecologists (OB/GYNs) represent a key provider group that can recommend the HPV vaccine. This study examined differences in OB/ GYN recommendation of HPV vaccination for inpatient postpartum patients by age, parity, and marital status. Data were collected from OB/GYNs nationally via a cross-sectional survey. Participants were randomized to two vignette groups (23-year-old patient or 33-year-old patient). Within each group, participants received 4 vignettes that were identical except for patient marital status (married/not in a committed relationship) and number of children (first/third child), and were asked to indicate HPV vaccination recommendation likelihood on a scale of 0 (definitely would not) to 100 (definitely would). A 2 × 2 × 2 general linear model with repeated measures was used to examine main and interaction effects of patient age, relationship status, and parity. 207 OB/GYNs were included in the final analyses. Recommendation was high for 23-year-old patients (range: 64.5–84.6 out of 100). When marital status and parity were held constant, recommendation likelihood was higher for the younger vs. older patient and was also higher for patients not in a committed relationship, compared to married patients (all p-values \u3c 0.001). Differences in recommendation exist when considering age and relationship status, which provides insight into OB/GYN clinical decision-making. Findings highlight the need to address barriers to HPV vaccination recommendation, including awareness of risk factors to consider when recommending the vaccine

Impairment of both IRE1 expression and XBP1 activation is a hallmark of GCB DLBCL and contributes to tumor growth.

The endoplasmic reticulum kinase inositol-requiring enzyme 1 (IRE1) and its downstream target X-box-binding protein 1 (XBP1) drive B-cell differentiation toward plasma cells and have been shown to contribute to multiple myeloma development; yet, little is known of the role of this pathway in diffuse large B-cell lymphoma (DLBCL). Here, we show that in the germinal center B-cell-like (GCB) DLBCL subtype, IRE1 expression is reduced to a level that prevents XBP1 activation. Gene expression profiles indicated that, in GCB DLBCL cancer samples, expression of IRE1 messenger RNA was inversely correlated with the levels and activity of the epigenetic repressor, histone methyltransferase enhancer of zeste homolog 2 (EZH2). Correspondingly, in GCB-derived cell lines, the IRE1 promoter carried increased levels of the repressive epigenetic mark histone 3 lysine 27 trimethylation. Pharmacological inhibition of EZH2 erased those marks and restored IRE1 expression and function in vitro and in vivo. Moreover, reconstitution of the IRE1-signaling pathway, by expression of the XBP1-active form, compromised GCB DLBCL tumor growth in a mouse xenograft cancer model. These findings indicate that IRE1-XBP1 downregulation distinguishes GCB DLBCL from other DLBCL subtypes and contributes to tumor growth