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Domestic travel creates a serious risk of spreading COVID-19, including novel strains of the virus. Motivating potential travelers to take precautions is critical, especially for those at higher risk for severe illness. To provide an evidence base for communication efforts, we examined the experiences and views of travelers during the summer of 2020 through a telephone survey of 1,968 US adults, conducted in English and Spanish, July 2 through July 16, 2020. The survey found that more than one-quarter (28%) of adults had traveled domestically in the prior 30 days, most commonly for "vacation" (43%), and less than half wore masks (46%) or practiced social distancing (47%) "all of the time." Although high-risk adults were significantly less likely to travel than non-high-risk adults (23% vs 31%; P < .001), they were no more likely to take precautions. Many travelers did not wear a mask or practice social distancing because they felt such actions were unnecessary (eg, they were outside or with friends and family). Although a substantial share of travelers (43% to 53%) trusted public health agencies "a great deal" for information about reducing risks while traveling, more travelers (73%) trusted their own healthcare providers. Findings suggest that outreach may be improved by partnering with providers to emphasize the benefits of layering precautions and provide targeted education to high-risk individuals. Messages that are empathetic to the need to reduce stress and convey how precautions can protect loved ones may be particularly resonant after more than a year of pandemic-related restrictions.

Background The first documented human leptospirosis cases in the U.S. Virgin Islands (USVI) occurred following 2017 Hurricanes Irma and Maria. We conducted a representative serosurvey in USVI to estimate the seroprevalence and distribution of human leptospirosis and evaluate local risk factors associated with seropositivity. Methodology/Principal findings A stratified, two-stage cluster sampling design was used and consisted of three island strata and random selection of census blocks and then households. All eligible members of selected households were invited to participate (≥5 years old, resided in USVI ≥6 months and ≥6 months/year). Household and individual-level questionnaires were completed, and serum collected from each enrolled individual. Microscopic agglutination test serology was conducted, and bivariate and logistic regression analyses completed to identify risk factors for seropositivity. In March 2019, 1,161 individuals were enrolled from 918 households in St. Croix, St. Thomas, and St. John. The territory-wide weighted seroprevalence was 4.0% (95% CI:2.3–5.7). Characteristics/exposures independently associated with seropositivity using logistic regression included contact with cows (OR: 39.5; 95% CI: 9.0–172.7), seeing rodents/rodent evidence or contact with rodents (OR: 2.6; 95% CI: 1.1–5.9), and increasing age (OR: 1.02; 95% CI: 1.002–1.04); full or partial Caucasian/White race was negatively correlated with seropositivity (OR: 0.02, 95% CI: 0.04–0.7). Bivariate analysis showed self-reported jaundice since the 2017 hurricanes (pRR: 5.7; 95% CI: 1.0–33.4) was associated with seropositivity and using a cover/lid on cisterns/rainwater collection containers (pRR: 0.3; 95% CI: 0.08–0.8) was protective against seropositivity. Conclusions/Significance Leptospirosis seropositivity of 4% across USVI demonstrates an important human disease that was previously unrecognized and emphasizes the importance of continued leptospirosis surveillance and investigation. Local risk factors identified may help guide future human and animal leptospirosis studies in USVI, strengthen leptospirosis public health surveillance and treatment timeliness, and inform targeted education, prevention, and control efforts.

Background Breast/Chestfeeding remains a public health issue for African Americans, and increased rates would mitigate many health disparities, thus promoting health equity. Research Aims To explore the interplay of generational familial roles and meaning (or value) ascribed to communicating infant feeding information across three generations. Method This prospective, cross-sectional qualitative study used an asset-driven approach and was guided by Black Feminist Thought and Symbolic Interactionism. African American women ( N = 35; 15 family triads/dyads), residing in the southeastern United States were interviewed. Data were analyzed using thematic analysis. Results The older two generations described their role using assertive yet nurturing terms, while the younger generation carefully discussed the flexibility between their familial roles. Emergent themes described the meaning each generation attributed to communicating infant feeding information: “My Responsibility,” “Comforting,” “Bonding Experience,” “She Cared,” and “Gained Wisdom.” Conclusions Our findings have potential to contribute to achieving health equity in African American families. Future breast/chestfeeding promotion efforts may benefit from reframing the current approach to including protection language and not solely support language. Lactation professionals should further recognize and support strengths and resource-richness of intergenerational infant feeding communication within African American families using strength-based, empowerment-oriented, and ethnically sensitive approaches.

Background: Nearly 74% of U.S. mothers work full-time and employment is a cited reason for stopping breastfeeding. In the effort to increase breastfeeding duration, childcare providers could facilitate continuation of human milk feeding when mothers return to work. Yet, mothers report receiving little support when transitioning infants into childcare. Objective: Explore the themes of comfort with human milk and formula feeding among childcare administrators near Tampa, Florida. Material and Methods: Twenty-eight childcare administrators participated in semistructured interviews regarding policies and perceptions about infant feeding practices at their center. Using Applied Thematic Analysis, interview themes were identified. Results: Most administrators agreed "breastfeeding is best." However, they expressed discomfort with mothers breastfeeding at the center and perceived risk with handling and feeding human milk. These perceptions are illustrated through the theme "Formula feeding is normative" and four emergent subthemes: "Human milk is potentially harmful," "People are uncomfortable with breastfeeding in public," "I'm not the expert," and "'Breastfeeding is best', in theory." Conclusion: While breastfeeding may be best for health, from the childcare administrators' perspectives, it may not be best for the childcare environment. A cultural shift may be needed to change norms and perceptions in the childcare environment to support mothers in their effort to provide human milk. Perhaps it is time for a new message, such as "We can help you."

Background: Ten years ago, the U.S. Surgeon General’s Call to Action to Support Breastfeeding made recommendations for childcare settings, including: (1) accommodating and supporting breastfeeding families; and (2) adopting national guidelines on breastfeeding support in childcare settings. Research Aims: To (1) describe the existing breastfeeding friendly childcare designation programs in the United States; and (2) describe how states are accommodating breastfeeding families in childcare settings. Method: The study design was cross-sectional, prospective thematic description of existing publicly available documents. A search of state breastfeeding coalitions was conducted to assess the number of states with breastfeeding friendly childcare designation programs. A definitive yes-or-no answer regarding whether each state had a program was obtained from all 50 states. For states with programs, designation materials were analyzed using thematic analysis and the framework method to compare designation components. Results: Fifteen states had evidence of breastfeeding friendly childcare designation programs and similarities exist across designation program components. Four standards were common to all 15 programs: written policy on breastfeeding, suitable space within the center where mothers can breastfeed or express their milk, educational materials, and resources on breastfeeding available to parents. Most states required self-assessment to achieve designation status. Conclusion: Research is needed to enable evidence-based programs and decision-making regarding components and processes. Federal funding should support these programs’ mission, including funding research to assess how and in what circumstances these programs are improving breastfeeding-related outcomes and supporting breastfeeding families.

Switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing antiretroviral therapy may negatively influence weight, cholesterol, and atherosclerotic cardiovascular disease risk. The extent of these changes and their association with TAF remain unclear.This retrospective cohort evaluated metabolic changes in virologically suppressed patients with HIV infection who switched from TDF to TAF without switching other antiretroviral therapy medications. Adult patients on TDF and with no HIV viral load values200 copies/mL for ≥2 years prior to and following a TAF switch were included. Weight and other variables were collected for 2 years before and after the switch. Longitudinal linear mixed-effects models evaluated changes at 1 and 2 years after the switch.In the unadjusted analysis, there were increases in weight, BMI, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, fasting glucose, and atherosclerotic cardiovascular disease risk scores 2 years after switching to TAF (each p ≤ 0.03). However, only increases in total and low-density lipoprotein cholesterol were associated with TAF and were significantly different from expected changes predicted in the adjusted longitudinal models.Despite observing significant unadjusted metabolic changes after switching to TAF, only changes in cholesterol were associated with TAF and were different from changes expected in time-trend adjusted models.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with few effective treatment options. We found a highly significant correlation between pregnancy-associated plasma protein (PAPP)-A expression in IPF lung tissue and disease severity as measured by various pulmonary and physical function tests. PAPP-A is a metalloproteinase that enhances local insulin-like growth factor (IGF) activity. We used primary cultures of normal adult human lung fibroblasts (NHLF) to test the hypothesis that PAPP-A plays an important role in the development of pulmonary fibrosis. Treatment of NHLF with pro-fibrotic transforming growth factor (TGF)-β stimulated marked increases in IGF-I mRNA expression (>20-fold) and measurable IGF-I levels in 72-h conditioned medium (CM). TGF-β treatment also increased PAPP-A levels in CM fourfold (p = 0.004) and proteolytic activity ~2-fold. There was an indirect effect of TGF-β to stimulate signaling through the PI3K/Akt pathway, which was significantly inhibited by both IGF-I-inactivating and PAPP-A inhibitory antibodies. Induction of senescence in NHLF increased PAPP-A levels in CM 10-fold (p = 0.006) with attendant increased proteolytic activity. Thus, PAPP-A is a novel component of the senescent lung fibroblast secretome. In addition, NHLF secreted extracellular vehicles (EVs) with surface-bound active PAPP-A that were increased fivefold with senescence. Regulation of PAPP-A and IGF signaling by TGF-β and cell senescence suggests an interactive cellular mechanism underlying the resistance to apoptosis and the progression of fibrosis in IPF. Furthermore, PAPP-A-associated EVs may be a means of pro-fibrotic, pro-senescent communication with other cells in the lung and, thus, a potential therapeutic target for IPF.

Leptospirosis is a global zoonotic disease caused by pathogenic bacteria of the genus Leptospira. We sought to determine if rodents in U.S. Virgin Islands (USVI) are carriers of Leptospira. In total, 140 rodents were sampled, including 112 Mus musculus and 28 Rattus rattus. A positive carrier status was identified for 64/140 (45.7%); 49 (35.0%) were positive by dark-field microscopy, 60 (42.9%) by culture, 63 (45.0%) by fluorescent antibody testing, and 61 (43.6%) by real-time polymerase chain reaction (rtPCR). Molecular typing indicated that 48 isolates were L. borgpetersenii and 3 were L. kirschneri; the remaining nine comprised mixed species. In the single culture-negative sample that was rtPCR positive, genotyping directly from the kidney identified L. interrogans. Serotyping of L. borgpetersenii isolates identified serogroup Ballum and L. kirschneri isolates as serogroup Icterohaemorrhagiae. These results demonstrate that rodents are significant Leptospira carriers and adds to understanding the ecoepidemiology of leptospirosis in USVI.

During 2019–2020, the Virgin Islands Department of Health investigated potential animal reservoirs of Leptospira spp., the bacteria that cause leptospirosis. In this cross-sectional study, we investigated Leptospira spp. exposure and carriage in the small Indian mongoose (Urva auropunctata, syn: Herpestes auropunctatus), an invasive animal species. This study was conducted across the three main islands of the U.S. Virgin Islands (USVI), which are St. Croix, St. Thomas, and St. John. We used the microscopic agglutination test (MAT), fluorescent antibody test (FAT), real-time polymerase chain reaction (lipl32 rt-PCR), and bacterial culture to evaluate serum and kidney specimens and compared the sensitivity, specificity, positive predictive value, and negative predictive value of these laboratory methods. Mongooses (n = 274) were live-trapped at 31 field sites in ten regions across USVI and humanely euthanized for Leptospira spp. testing. Bacterial isolates were sequenced and evaluated for species and phylogenetic analysis using the ppk gene. Anti-Leptospira spp. antibodies were detected in 34% (87/256) of mongooses. Reactions were observed with the following serogroups: Sejroe, Icterohaemorrhagiae, Pyrogenes, Mini, Cynopteri, Australis, Hebdomadis, Autumnalis, Mankarso, Pomona, and Ballum. Of the kidney specimens examined, 5.8% (16/270) were FAT-positive, 10% (27/274) were culture-positive, and 12.4% (34/274) were positive by rt-PCR. Of the Leptospira spp. isolated from mongooses, 25 were L. borgpetersenii, one was L. interrogans, and one was L. kirschneri. Positive predictive values of FAT and rt-PCR testing for predicting successful isolation of Leptospira by culture were 88% and 65%, respectively. The isolation and identification of Leptospira spp. in mongooses highlights the potential role of mongooses as a wildlife reservoir of leptospirosis; mongooses could be a source of Leptospira spp. infections for other wildlife, domestic animals, and humans., Author summary Leptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira. To better understand local reservoirs and risk factors to humans and animals, during 2019–2020, the Virgin Islands Department of Health (VIDOH) investigated Leptospira spp. in association with the small Indian mongoose (Urva auropunctata, syn: Herpestes auropunctatus) across the three main islands of the United States Virgin Islands (USVI) (St. Croix, St. Thomas, and St. John). Mongoose blood and kidney samples were evaluated by laboratory testing: microscopic agglutination test, fluorescent antibody test (FAT), real-time polymerase chain reaction (lipl32 rt-PCR), and culture. Of 256 mongooses, 34% were exposed to Leptospira spp. To assess active infection in mongooses, kidney samples were examined resulting 5.8% (16/270) FAT-positive, 10% (27/274) culture-positive, and 12.4% (34/274) rt-PCR-positive. Validity was compared between test types showing higher positive predictive value for FAT and rt-PCR testing for predicting successful culture, the reference standard for diagnosis. Through the detection and isolation of Leptospira spp. in mongooses across the USVI, we identified mongooses as potential disease vectors to the local population and added to the limited data for the Caribbean region. Furthermore, a validity assessment of reference testing provides data to potentially inform future leptospirosis diagnostics.

Background: Current guidelines advocate for antiretroviral therapy (ART) simplification in patients on complicated regimens. Simplifying ART improves patient adherence and quality of life, but changes in drug interactions (DIs) are uncertain. Objective: This study assessed changes in DIs following ART simplification in patients with HIV. Methods: This was an observational, retrospective cohort study of patients attending an urban HIV clinic. Patients were included if they had ART simplification (a decreased number of daily tablets) and ≥1 concomitant medication (CM). Total DI scores were generated for each patient pre–ART simplification and post–ART simplification using an online DI database. Each ART-CM pair labeled as “do not co-administer” was given a score of 2, “potential interaction” a score of 1, or “no interaction” a score of 0. Differences in total DI scores following simplification were analyzed with a Wilcoxon Signed-Rank test. Predictors of DI score reductions were examined with linear regression. Results: A total of 99 patients were included. Their median age was 54 years, and 79% were male. The median durations of HIV infection and ART were 16 and 10 years, respectively. Patients were receiving an average of 4.5 CMs. Median interaction scores presimplification and postsimplification were 3 (interquartile range [IQR], 1-6) and 1 (IQR, 0-2) respectively ( P < 0.001). Predictors of score reductions were the patient’s number of CMs, discontinuing a protease inhibitor, and switching to a dolutegravir-based regimen. Conclusion and Relevance: ART simplification decreased the incidence of DIs in this analysis of patients with advanced age who had ART experience and polypharmacy.

Cellular senescence has emerged as a significant and potentially tractable mechanism of aging and multiple aging‐related conditions. Biomarkers of senescent cell burden, including molecular signals in circulating immune cells and the abundance of circulating senescence‐related proteins, have been associated with chronological age and clinical parameters of biological age in humans. The extent to which senescence biomarkers are affected by interventions that enhance health and function has not yet been examined. Here, we report that a 12‐week structured exercise program drives significant improvements in several performance‐based and self‐reported measures of physical function in older adults. Impressively, the expression of key markers of the senescence program, including p16, p21, cGAS, and TNFα, were significantly lowered in CD3+ T cells in response to the intervention, as were the circulating concentrations of multiple senescence‐related proteins. Moreover, partial least squares discriminant analysis showed levels of senescence‐related proteins at baseline were predictive of changes in physical function in response to the exercise intervention. Our study provides first‐in‐human evidence that biomarkers of senescent cell burden are significantly lowered by a structured exercise program and predictive of the adaptive response to exercise., Our study provides first‐in‐human evidence that biomarkers of senescent cell burden are significantly lowered by a structured exercise program and predictive of the adaptive response to exercise.

Background: Recent studies suggest that statins are underprescribed in patients living with HIV (PLWH) at risk for atherosclerotic cardiovascular disease (ASCVD), but none have assessed if eligible patients receive the correct statin and intensity compared to uninfected controls. Objectives: The primary objective was to determine whether statin-eligible PLWH are less likely to receive appropriate statin therapy compared to patients without HIV. Methods: This retrospective study evaluated statin eligibility and prescribing among patients in both an HIV and internal medicine clinic at an urban, academic medical center from June-September 2018 using the American College of Cardiology/American Heart Association guideline on treating blood cholesterol to reduce ASCVD risk. Patients were assessed for eligibility and actual treatment with appropriate statin therapy. Characteristics of patients appropriately and not appropriately treated were compared with chi-square testing and predictors for receiving appropriate statin therapy were determined with logistic regression. Results: A total of 221/300 study subjects were statin-eligible. Fewer statin-eligible PLWH were receiving the correct statin intensity for their risk benefit group versus the uninfected control group (30.2% vs 67.0%, p < 0.001). In the multivariable logistic regression analysis, PLWH were significantly less likely to receive appropriate statin therapy, while those with polypharmacy were more likely to receive appropriate statin therapy. Conclusion: Our study reveals that PLWH may be at a disadvantage in receiving appropriate statin therapy for ASCVD risk reduction. This is important given the heightened risk for ASCVD in this population, and strategies that address this gap in care should be explored.

BACKGROUND: Seasonal influenza vaccination rates among pregnant women remain well below the Healthy People 2020 target of 80%. Obstetrician–gynecologist (OB/GYN) recommendations are a critical means of encouraging pregnant women to get vaccinated, but there are limited data about their views. MATERIALS AND METHODS: A nationally representative survey of 506 practicing OB/GYNs was completed between October 26, 2015, and May 8, 2016. Analyses included univariate distributions and comparisons based on age, size of practice, and academic affiliation using all-pairs, dependent t-tests. RESULTS: A majority of OB/GYNs report they ‘‘strongly recommend’’ seasonal influenza vaccination for their pregnant patients in the first (79%) or second and third trimesters (81%). Among those who do not strongly recommend the flu vaccine in the first trimester, many say this is because of their own concerns (28%) or their patients’ concerns (44%) about safety. Older OB/GYNs, those in smaller practices, and those without academic affiliation were less likely to recommend the vaccine and more likely to have safety concerns. For example, 72% of those age 60+ strongly recommended the vaccine in the second and third trimester, compared with 86% of those ages 30–44 and 83% of those ages 45–59 ( p < 0.05 for all comparisons). CONCLUSIONS: OB/GYNs across the country largely support seasonal flu vaccination among pregnant women. Nonetheless, safety is a concern for them and their patients. Outreach to support clinician decisions and conversations with pregnant patients may be most needed among older physicians, those in smaller practices, and those without academic affiliation.

Background Estrogen may inhibit cell senescence that contributes to age‐related disorders. This study determined the effects of menopausal hormone treatments on circulating levels of markers of cell senescence. Methods Growth differentiation factor 15 (GDF15), tumor necrosis factor receptor 1 (TNFR1), FAS, and macrophage inflammatory protein 1α (MIP1α) were measured in serum using multiplexed bead‐based assays and compared among menopausal women participating in the Kronos Early Estrogen Prevention Study randomized to either placebo (n = 38), oral conjugated equine estrogen (oCEE, n = 37), or transdermal 17β‐estradiol (tE2, n = 34). Serum levels of the senescent markers for each treatment were compared to placebo 36 months after randomization using the Wilcoxon rank sum test. Results Serum levels of GDF15, TNFR1, and FAS, but not MIP1α, were lower in both the oCEE and tE2 groups compared to placebo. The difference in levels between treatment and placebo for GDF15, TNFR1, and FAS were greater for oCEE [−108 pg/mL (p = .008), −234 pg/mL (p = .0006), and −1374 pg/mL (p, Hormonal treatments reduced the levels of selected markers of aging in the blood of recently menopausal women.

OBJECTIVE. To investigate the extent to which antibiotic exposure in the first two years of life is associated with the risk of immunological, metabolic, and neurobehavioral health conditions with childhood onset. PATIENTS AND METHODS. In this population-based cohort study we identified all children born in Olmsted County, Minnesota, between January 1, 2003 and December 31, 2011 through the Rochester Epidemiology Project (REP) medical records-linkage system. Demographic characteristics, antibiotic prescriptions, and diagnostic codes through June 30, 2017 were retrieved using the REP infrastructure. Time-to-event analysis was conducted to assess the impact of antibiotic exposure on the risk of several adverse health conditions. RESULTS. This study included 14,572 children (7,026 girls and 7,546 boys), of whom 70% received at least one antibiotic prescription during the first two years of life. Early antibiotic exposure was associated with an increased risk of childhood onset asthma, allergic rhinitis, atopic dermatitis, celiac disease, overweight, obesity, and attention deficit hyperactivity disorder (hazard ratios ranging from 1.20 to 2.89, all P

Produced by senescent cells, the senescence-associated secretory phenotype (SASP) is a potential driver of age-related dysfunction. We tested whether circulating concentrations of SASP proteins reflect age and medical risk in humans. We first screened senescent endothelial cells, fibroblasts, preadipocytes, epithelial cells, and myoblasts to identify candidates for human profiling. We then tested associations between circulating SASP proteins and clinical data from individuals throughout the life span and older adults undergoing surgery for prevalent but distinct age-related diseases. A community-based sample of people aged 20–90 years (retrospective cross-sectional) was studied to test associations between circulating SASP factors and chronological age. A subset of this cohort aged 60–90 years and separate cohorts of older adults undergoing surgery for severe aortic stenosis (prospective longitudinal) or ovarian cancer (prospective case-control) were studied to assess relationships between circulating concentrations of SASP proteins and biological age (determined by the accumulation of age-related health deficits) and/or postsurgical outcomes. We showed that SASP proteins were positively associated with age, frailty, and adverse postsurgery outcomes. A panel of 7 SASP factors composed of growth differentiation factor 15 (GDF15), TNF receptor superfamily member 6 (FAS), osteopontin (OPN), TNF receptor 1 (TNFR1), ACTIVIN A, chemokine (C-C motif) ligand 3 (CCL3), and IL-15 predicted adverse events markedly better than a single SASP protein or age. Our findings suggest that the circulating SASP may serve as a clinically useful candidate biomarker of age-related health and a powerful tool for interventional human studies.

The interest in dry EEG electrodes has increased in recent years and especially as everyday suitability earplugs for measuring drowsiness or focus of auditory attention. However, the challenge is still the need for a good electrode material, which is reliable and can be easily processed for highly personalized applications. Laser processing as used here is a fast and very precise method to produce personalized electrode configurations that meet the high requirements of in-ear EEG electrodes, for example. The arrangement of the electrodes on the very flexible and compressible mats allows an exact alignment of the electrodes to the ear mold and contributes to a high wearing comfort, as no edges or metal protrusions are present. For better transmission properties, an adapted coating process for surface enlargement of platinum electrodes is used, which allows easy control of the thickness and growth form of the porous layer. The porous platinum-copper alloy is chemically very stable, shows no exposed copper residues and enlarges the effective surface area by 40. In a proof-of-principle experiment, these porous platinum electrodes could be used to measure the Berger effect in a dry state using just one ear of a test person. Their signal-to-noise ration and frequency transfer function is comparable to gel-based silver/silver chloride electrodes.

Background Uganda has experienced seven Ebola Virus Disease (EVD) outbreaks and four Marburg Virus Disease (MVD) outbreaks between 2000 and 2019. We investigated the seroprevalence and risk factors for Marburg virus and ebolaviruses in gold mining communities around Kitaka gold mine in Western Uganda and compared them to non-mining communities in Central Uganda. Methods A questionnaire was administered and human blood samples were collected from three exposure groups in Western Uganda (gold miners, household members of miners, non-miners living within 50 km of Kitaka mine). The unexposed controls group sampled was community members in Central Uganda far away from any gold mining activity which we considered as low-risk for filovirus infection. ELISA serology was used to analyse samples, detecting IgG antibodies against Marburg virus and ebolaviruses (filoviruses). Data were analysed in STATA software using risk ratios and odds ratios. Results Miners in western Uganda were 5.4 times more likely to be filovirus seropositive compared to the control group in central Uganda (RR = 5.4; 95% CI 1.5–19.7) whereas people living in high-risk areas in Ibanda and Kamwenge districts were 3.6 more likely to be seropositive compared to control group in Luweeero district (RR = 3.6; 95% CI 1.1–12.2). Among all participants, filovirus seropositivity was 2.6% (19/724) of which 2.3% (17/724) were reactive to Sudan virus only and 0.1% (1/724) to Marburg virus. One individual seropositive for Sudan virus also had IgG antibodies reactive to Bundibugyo virus. The risk factors for filovirus seropositivity identified included mining (AOR = 3.4; 95% CI 1.3–8.5), male sex (AOR = 3.1; 95% CI 1.01–9.5), going inside mines (AOR = 3.1; 95% CI 1.2–8.2), cleaning corpses (AOR = 3.1; 95% CI 1.04–9.1) and contact with suspect filovirus cases (AOR = 3.9, 95% CI 1.04–14.5). Conclusions These findings indicate that filovirus outbreaks may go undetected in Uganda and people involved in artisan gold mining are more likely to be exposed to infection with either Marburg virus or ebolaviruses, likely due to increased risk of exposure to bats. This calls for active surveillance in known high-risk areas for early detection and response to prevent filovirus epidemics.

α-Klotho is a geroprotective protein that can attenuate or alleviate deleterious changes with ageing and disease. Declines in α-Klotho play a role in the pathophysiology of multiple diseases and age-related phenotypes. Pre-clinical evidence suggests that boosting α-Klotho holds therapeutic potential. However, readily clinically-translatable, practical strategies for increasing α-Klotho are not at hand. Here, we report that orally-active, clinically-translatable senolytics can increase α-Klotho in mice and humans.We examined α-Klotho expression in three different human primary cell types co-cultured with conditioned medium (CM) from senescent or non-senescent cells with or without neutralizing antibodies. We assessed α-Klotho expression in aged, obese, and senescent cell-transplanted mice treated with vehicle or senolytics. We assayed urinary α-Klotho in patients with idiopathic pulmonary fibrosis (IPF) who were treated with the senolytic drug combination, Dasatinib plus Quercetin (D+Q).We found exposure to the senescent cell secretome reduces α-Klotho in multiple nonsenescent human cell types. This was partially prevented by neutralizing antibodies against the senescence-associated secretory phenotype (SASP) factors, activin A and Interleukin 1α (IL-1α). Consistent with senescent cells' being a cause of decreased α-Klotho, transplanting senescent cells into younger mice reduced brain and urine α-Klotho. Selectively removing senescent cells genetically or pharmacologically increased α-Klotho in urine, kidney, and brain of mice with increased senescent cell burden, including naturally-aged, diet-induced obese (DIO), or senescent cell-transplanted mice. D+Q increased α-Klotho in urine of patients with IPF, a disease linked to cellular senescence.Senescent cells cause reduced α-Klotho, partially due to their production of activin A and IL-1α. Targeting senescent cells boosts α-Klotho in mice and humans. Thus, clearing senescent cells restores α-Klotho, potentially opening a novel, translationally-feasible avenue for developing orally-active small molecule, α-Klotho-enhancing clinical interventions. Furthermore, urinary α-Klotho may prove to be a useful test for following treatments in senolytic clinical trials.This work was supported by National Institute of Health grants AG013925 (J.L.K.), AG062413 (J.L.K., S.K.), AG044271 (N.M.), AG013319 (N.M.), and the Translational Geroscience Network (AG061456: J.L.K., T.T., N.M., S.B.K., S.K.), Robert and Arlene Kogod (J.L.K.), the Connor Group (J.L.K.), Robert J. and Theresa W. Ryan (J.L.K.), and the Noaber Foundation (J.L.K.). The previous IPF clinical trial was supported by the Claude D. Pepper Older Americans Independence Centers at WFSM (AG021332: J.N.J., S.B.K.), UTHSCA (AG044271: A.M.N.), and the Translational Geroscience Network.

Bilateral oophorectomy in premenopausal women is a unique condition causing the abrupt and premature loss of ovarian hormones, primarily estrogen. Bilateral oophorectomy causes an alteration of several fundamental aging processes at the cellular, tissue, organ, and system levels, leading to multimorbidity, frailty, and reduced survival. However, many questions remain unanswered.

ObjectiveBreast-feeding initiation rates have increased in the USA; however, maintenance of breast-feeding for recommended durations is low. The objective of the present study was to identify factors that may facilitate breast-feeding for longer durations among first-time mothers, including physiological and social experiences and changes in maternal perceptions.DesignSurvival analysis and linear regression methods were used to explore the relationship between experiences and breast-feeding duration, and the possible mediating effect of changes in maternal perceptions.SettingSecondary data from the Infant Feeding Practices Study II, conducted in the USA between 2005 and 2007.SubjectsData from 762 first-time mothers who ever breast-fed were analysed.ResultsExperiencing trouble with baby’s latch, problems with milk flow/supply and painful breast-feeding were significantly associated with breast-feeding duration (64, 26 and 36 % shorter duration, respectively). Meanwhile, positive changes in perception with respect to breast-feeding self-efficacy, opinion about infant feeding and belief about breast milk were associated with 16–27 % longer duration. Furthermore, changes in perception were observed to partially mediate the impact of physiological experiences on breast-feeding duration.ConclusionsPerceptions of breast-feeding self-efficacy, beliefs and opinions can change over time and are influenced by breast-feeding experiences. The combined effect of experience and perception plays a key role in influencing breast-feeding duration. Future research should explore interventions to maintain or improve these perceptions while accounting for physiological experiences to support breast-feeding for recommended durations among first-time mothers.

BACKGROUND: Disrupted gait has been associated with an increased risk of frailty, disability, and death, but the causal molecular pathways are not well understood. Sphingolipids, including ceramides, are associated with multiple age-related diseases. Ceramides promote atrophy, necrosis, and proteolysis in cellular and animal models, and ceramide C16:0 levels are negatively correlated with muscle mass in men. However, there is a paucity of evidence examining sphingolipids and physical function. METHODS: We examined the cross-sectional association between plasma ceramides, sphingosine-1-phosphate (S1P), and ceramide/S1P ratios and gait, a robust measure of physical function, in 340 clinically normal participants aged 70 years and older enrolled in the Mayo Clinic Study of Aging. GAITRite® instrumentation was used to measure gait speed, cadence, step width, double support time, and intra-individual stride time variability. Based on previous studies, we hypothesized that higher plasma levels of ceramide C16:0 would be associated with worse gait. RESULTS: Multivariable adjusted linear regression models revealed that higher levels of ceramide C16:0 were associated with slower gait speed, decreased cadence, and increased double support time. CONCLUSIONS: These results suggest an association between plasma ceramide C16:0 and physical function. Longitudinal studies are needed to determine whether elevated ceramide C16:0 can be utilized as a prognostic marker for functional decline.

Certain English intonational contours facilitate a conversational implicature that a relevant alternative to the stated proposition does not hold true. We evaluated how frequently and how quickly naïve participants achieved such pragmatically enriched meanings when their attention had not already been drawn to a set of alternatives. Sentences with L+H* L-H% intonational contours, along with broad focus affirmative and negative counterparts, were tested in a pair of experiments. Experiment 1 revealed that most interpretations of the L+H* L-H% sentences evidenced the expected implicature, but a substantial number did not. Experiment 2 mapped the activation levels across time for the asserted state and a contradictory/implicated alternative for the same three sentence types, using a picture-naming paradigm. The results revealed that lexical negation produced a contrast in activation levels between the two alternatives at an earlier time point than the L+H* L-H% contour, and that the relative activation of the two states shifted over time for L+H* L-H% sentences, such that an intonationally implicated alternative was highly activated at a time point when the activation for the asserted meaning had declined. These results further our understanding of the pragmatic processes involved in the interpretation of negation and intonation.

Background Frailty confers risk for surgical morbidity and mortality. Whether patient-reported measures of health, well-being, or quality of life respond differently to surgery in non-frail and frail individuals is unknown. Methods Older adults with severe aortic stenosis presenting for surgery were assessed for frailty using Cardiovascular Health Study Criteria. Patient-reported measures of functional capacity (Duke Activity Status Index [DASI]), physical and mental health (Medical Outcomes Study Short Form-Physical and Mental Component Scales [SF-12 PCS and SF-12 MCS, respectively]), well-being (linear analogue self-assessment [LASA]), and quality of life (LASA) were administered before and 3 months after surgery. Results Of 103 participants (mean age of 80.6 years), 54 were frail. Frail participants had lower baseline DASI, SF-12 PCS, SF-12 MCS, physical well-being, and quality of life scores than non-frail participants. At follow-up, frail participants showed significant improvement in physical function, with DASI and SF-12 PCS scores improving by 50% and 14%, respectively. Non-frail subjects did not significantly improve in these measures. SF-12 MCS scores also improved to a greater extent in frail compared to non-frail participants (3.6 vs < 1 point). Furthermore, the frail participants improved to a greater extent than non-frail participants in physical well-being (21.6 vs 7.1 points) and quality of life measures (25.1 vs 8.7 points). Conclusions Frailty is prevalent in older adults with severe aortic stenosis and is associated with poor physical and mental function, physical well-being, and quality of life. In response to surgery, frail participants exhibited greater improvement in these patient-centered outcomes than non-frail peers.

The flexibility to learn diverse tasks is a hallmark of human cognition. To improve our understanding of individual differences and dynamics of learning across tasks, we analyse the latent structure of learning trajectories from 36,297 individuals as they learned 51 different tasks on the Lumosity online cognitive training platform. Through a data-driven modelling approach using probabilistic dimensionality reduction, we investigate covariation across learning trajectories with few assumptions about learning curve form or relationships between tasks. Modelling results show substantial covariation across tasks, such that an entirely unobserved learning trajectory can be predicted by observing trajectories on other tasks. The latent learning factors from the model include a general ability factor that is expressed mostly at later stages of practice and additional task-specific factors that carry information capable of accounting for manually defined task features and task domains such as attention, spatial processing, language and math.

This study examines how individual pragmatic skills, and more specifically, empathy, influences language processing when a temporary lexical ambiguity can be resolved via intonation. We designed a visual-world eye-tracking experiment in which participants could anticipate a referent before disambiguating lexical information became available, by inferring either a contrast meaning or a confirmatory meaning from the intonation contour alone. Our results show that individual empathy skills determine how listeners deal with the meaning alternatives of an ambiguous referent, and the way they use intonational meaning to disambiguate the referent. Listeners with better pragmatic skills (higher empathy) were sensitive to intonation cues when forming sound-meaning associations during the unfolding of an ambiguous referent, and showed higher sensitivity to all the alternative interpretations of that ambiguous referent. Less pragmatically skilled listeners showed weaker processing of intonational meaning because they needed subsequent disambiguating material to select a referent and showed less sensitivity to the set of alternative interpretations. Overall, our results call for taking into account individual pragmatic differences in the study of intonational meaning processing and sentence comprehension in general.

The HIV genome is rich in A but not G or U and deficient in C. This nucleotide bias controls HIV phenotype by determining the highly unusual composition of all major HIV proteins. The bias is also responsible for the high frequency of narrow DNA minor groove sites in the double-stranded HIV genome as compared to cellular protein coding sequences and the bulk of the human genome. Since drugs that bind in the DNA minor groove disrupt nucleosomes on sequences that contain closely spaced oligo-A tracts which are prevalent in HIV DNA because of its bias, it was of interest to determine if these drugs exert this selective inhibitory effect on HIV chromatin. To test this possibility, nucleosomes were reconstituted onto five double-stranded DNA fragments from the HIV-1 pol gene in the presence and in the absence of several minor groove binding drugs (MGBDs). The results demonstrated that the MGBDs inhibited the assembly of nucleosomes onto all of the HIV-1 segments in a manner that was proportional to the A-bias, but had no detectable effect on the formation of nucleosomes on control cloned fragments or genomic DNA from chicken and human. Nucleosomes preassembled onto HIV DNA were also preferentially destabilized by the drugs as evidenced by enhanced nuclease accessibility in physiological ionic strength and by the preferential loss of the histone octamer in hyper-physiological salt solutions. The drugs also selectively disrupted HIV-containing nucleosomes in yeast as revealed by enhanced nuclease accessibility of the in vivo assembled HIV chromatin and reductions in superhelical densities of plasmid chromatin containing HIV sequences. A comparison of these results to the density of A-tracts in the HIV genome indicates that a large fraction of the nucleosomes that make up HIV chromatin should be preferred in vitro targets for the MGBDs. These results show that the MGBDs preferentially disrupt HIV-1 chromatin in vitro and in vivo and raise the possibility that non-toxic derivatives of certain MGBDs might serve as a novel class of anti-HIV agents.

Genome instability is a hallmark of aging and contributes to age-related disorders such as cancer and Alzheimer’s disease. The accumulation of DNA damage during aging has been linked to altered cell cycle dynamics and the failure of cell cycle checkpoints. Here, we use single cell imaging to study the consequences of increased genomic instability during aging in budding yeast and identify striking age-associated genome missegregation events. This breakdown in mitotic fidelity results from the age-related activation of the DNA damage checkpoint and the resulting degradation of histone proteins. Disrupting the ability of cells to degrade histones in response to DNA damage increases replicative lifespan and reduces genomic missegregations. We present several lines of evidence supporting a model of antagonistic pleiotropy in the DNA damage response where histone degradation, and limited histone transcription are beneficial to respond rapidly to damage but reduce lifespan and genomic stability in the long term.

African American women have much lower breastfeeding rates than other racial and ethnic groups in the USA. While researchers are beginning to explore contemporary factors contributing to this inequality, much less research has been devoted to the historical conditions that have contributed to these disparities. The aim of this paper was to describe the social, economic, and political factors that have influenced African American breastfeeding behavior in the USA from the colonial era through the mid-twentieth century. A thematic analysis was conducted across multiple databases and sources. A social history framework, which focuses on the experiences of ordinary people and events, was used to identify and integrate themes found within the reviewed literature. Three themes emerged: (1) Labor forces and other socio-cultural factors affected feeding practices and communal caregiving; (2) history of supplementation; and (3) influence of medicalization of birth and mobility on infant feeding in the twentieth century. These themes illustrate how African American women’s ability to breastfeed has been significantly constrained throughout the U.S. history. Supplementation with non-human milk substitutes and communal caregiving helped African American women navigate infant rearing under adverse socioeconomic circumstances. Social, political, and economic factors have contributed significantly to African American women’s ability to breastfeed throughout the U.S. history. Understanding the influences of historical antecedents on breastfeeding decisions over time may be key to finding effective interventions that might increase breastfeeding rates within this population.

Travelers to areas with Zika virus transmission are at risk of infection and of transmitting the virus after returning home. While protective behaviors during and after travel can reduce these risks, information about traveler practices or underlying views is limited. We examined these issues using data from the first representative poll of travelers from US states to Zika-affected areas, including US territories and Miami, Florida, conducted December 1 to 23, 2016. We analyzed results among all travelers (

Adipose tissue inflammation and dysfunction are associated with obesity‐related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug‐inducible “suicide” genes driven by the p16Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra‐abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity‐related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity‐related metabolic dysfunction and its complications.

ObjectiveHeavy alcohol consumption can alter vitamin D status; however, the relationships between alcohol consumption and vitamin D concentrations in pregnant women have not been well studied. The aim of this study was to investigate the vitamin D status in a population of alcohol-exposed (N = 180) and low/unexposed control (N = 179) Ukrainian pregnant women.MethodsWomen who attended prenatal care facilities in 2 regions of Ukraine (Rivne and Khmelnytsky) for a routine prenatal visit were screened for the study. At the time of enrollment (20.4 ± 7.0 weeks of gestation), blood samples and alcohol consumption data (during a typical week around conception and the most recent 2 weeks) were collected. Vitamin D status was assessed by 25-hydroxyvitamin D [25(OH)D] concentrations.ResultsA high prevalence of suboptimal vitamin D status in pregnant Ukrainian women was observed. Overall, 50.1% and 33.4% of the women were classified as vitamin D deficient [25(OH)D < 20ng/mL] or insufficient [25(OH)D ≥ 20ng/mL and ≤30ng/mL], respectively, based on 2011 Endocrine Society guidelines. Alcohol-exposed women had significantly lower 25(OH)D concentrations than low/unexposed women in Spring (p = 0.006) and Winter (p = 0.022). When vitamin D concentrations were grouped into sunny season (Summer + Fall) compared to not sunny season (Winter + Spring), there was a significant ethanol by season interaction (p = 0.0028), with alcohol-drinking women having lower circulating vitamin D compared to low/unexposed women in seasons of low sun availability.ConclusionsThese data suggest that when vitamin D concentrations are generally low (e.g., during seasons of low sun availability), alcohol consumption during pregnancy has a negative impact on vitamin D status.

Dr. Mark Mattson has had a highly productive and impactful tenure as a neuroscientist at the Intramural Research Program of the National Institute on Aging. He has made notable contributions to understanding the mechanisms by which energetic stress, imparted by behaviors such as physical activity and periods of fasting, promotes rejuvenation and resilience within brain regions critical for learning and memory. In honor of Dr. Mattson’s work, this manuscript will highlight the fascinating mechanisms by which endurance exercise training conveys beneficial effects upon the structure and function of the nervous system; that is, by mediating the synthesis and secretion of factors that directly support brain homeostasis, including brain-derived neurotrophic factor, FNDC5/irisin, ketone bodies, growth factors, cathepsin B, serotonin, and 4-hydroxynonenal. The molecular and cellular effects of these factors are discussed herein. In the face of population aging and an overwhelming surge in the prevalence of Alzheimer’s disease and related disorders, Dr. Mattson’s work as a champion and role model for physically active lifestyles is more important than ever.

ObjectiveMothers’ return to work and childcare providers’ support for feeding expressed human milk are associated with breast-feeding duration rates in the USA, where most infants are regularly under non-parental care. The objective of the present study was to explore Florida-based childcare centre administrators’ awareness and perceptions of the Florida Breastfeeding Friendly Childcare Initiative.DesignSemi-structured interviews were based on the Consolidated Framework for Implementation Research and analysed using applied thematic analysis.SettingChildcare centre administrators in Tampa Bay, FL, USA, interviewed in 2015.ParticipantsTwenty-eight childcare centre administrators: female (100 %) and Non-Hispanic White (61 %) with mean age of 50 years and 13 years of experience.ResultsMost administrators perceived potential implementation of the Florida Breastfeeding Friendly Childcare Initiative as simple and beneficial. Tension for change and a related construct (perceived consumer need for the initiative) were low, seemingly due to formula-feeding being normative. Perceived financial costs and relative priority varied. Some centres had facilitating structural characteristics, but none had formal breast-feeding policies.ConclusionsA cultural shift, facilitated by state and national breast-feeding-friendly childcare policies and regulations, may be important for increasing tension for change and thereby increasing access to breast-feeding-friendly childcare. Similar to efforts surrounding the rapid growth of the Baby Friendly Hospital Initiative, national comprehensive evidence-based policies, regulations, metrics and technical assistance are needed to strengthen state-level breast-feeding-friendly childcare initiatives.

Objectives To assess the association of the Pharmacists' Pneumonia Prevention Program (PPPP) with changes in beliefs related to pneumonia vaccination (PV) in a predominately older African American population. Methods PPPP was an educational intervention delivered using a senior center model of care consisting of a formal pharmacist presentation, live skit, small group action planning, and optional PV. A 15-item instrument assessed participants' beliefs at baseline, post-test, and three months across four domains: pharmacists and pharmacies, vaccination, pneumococcal disease, and physicians. Friedman tests and pairwise Wilcoxon signed rank tests were used to determine the statistical significance of the mean change in belief responses across timepoints. Results 190 older adults participated; the sample was majority female (76.3%) and African American (80.5%), and had a mean age of 74.3 years. Statistically significant improvements in beliefs at post-test were observed in the following domains: pharmacists and pharmacies, vaccination, and the pneumococcal disease; however, some of these gains were incompletely sustained at three months. Conclusion PPPP positively impacted beliefs post-program regarding the pneumococcal disease, pharmacists and pharmacies, and vaccination; however, sustained efforts may be needed to reinforce these gains. Policy implications Support for pharmacist educational services in senior centers should be considered.

Leptospirosis is a bacterial zoonosis that affects many mammals, including humans and dogs; dogs can transmit the bacteria to humans, but the frequency of transmission and highest risk exposures are poorly understood. During 2016-2017, the Maricopa County Department of Public Health, Arizona Department of Health Services and Centers for Disease Control and Prevention investigated the zoonotic potential of a canine leptospirosis outbreak in the Phoenix metro area. We identified symptomatic persons exposed to canine leptospirosis cases by conducting active and passive surveillance. We tested dog owners (n = 9) and animal care providers (n = 109) for serological evidence of Leptospira spp. infection (via the microscopic agglutination test [MAT]) and interviewed these persons about their specific exposures to canine cases and general exposures to canine blood and urine. Through surveillance, seven symptomatic persons were identified; six were tested and all were negative by MAT, and of these six, four persons were negative by PCR (two did not have PCR testing). All serosurvey participants (n = 118) were also seronegative. Among animal care providers, bare skin contact with urine/blood from a canine case was reported by 23.2%; two persons reported dog urine splashing in their face. Veterinary technicians were more likely to have bare skin contact with blood from a canine case compared to veterinarians and boarding facility staff (p < 0.001). Infection control practices were inconsistent; when working with specimens from a canine leptospirosis case, 44.6% of participants reported always wearing gloves when working with urine (i.e., collecting specimens), and 54.5% always wore gloves when working with blood. Veterinary technicians were also most likely to engage in all activities involving potential urine/blood contact, such as conducting laboratory tests (p < 0.01). We therefore recommend that veterinary technicians specifically receive targeted education about infection control practices. Our results suggest that dog-to-human transmission of leptospirosis is uncommon.

While most mothers initiate breastfeeding, many do not continue for recommended durations. This study aimed to understand the gap between breastfeeding initiation and duration through an in-depth exploration of first-time mothers' breastfeeding experiences. Contextual factors that may facilitate or deter breastfeeding maintenance were explored by identifying common turning points (significant events or periods promoting a change in thoughts/behaviors or facilitating maintenance) described by mothers with varied breastfeeding durations. In semistructured interviews conducted from March to June 2015, twenty-eight first-time mothers in Iowa were asked to describe their breastfeeding experiences from initiation through cessation. Using thematic analysis, seven turning points, consistent across varied durations and experiences were identified: breastfeeding problems, the unknowns, recurring stressors, living new life with baby, reentering social roles, special occasions, and letting go. Turning points were usually associated with stressful situations, and mothers described intrapersonal (e.g., determination) and interpersonal (e.g., social support) coping resources as facilitators of breastfeeding maintenance. These findings highlight contextual factors that may trigger turning points, representing critical intervention periods, and the importance of enhancing support networks. Interventions to facilitate longer breastfeeding durations should consider key turning points and availability of coping resources to determine strategies that best fit the mother at each point.

Hurricane Maria made landfall in Puerto Rico on September 20, 2017, causing major damage to infrastructure and severely limiting access to potable water, electric power, transportation, and communications. Public services that were affected included operations of the Puerto Rico Department of Health (PRDOH), which provides critical laboratory testing and surveillance for diseases and other health hazards. PRDOH requested assistance from CDC for the restoration of laboratory infrastructure, surveillance capacity, and diagnostic testing for selected priority diseases, including influenza, rabies, leptospirosis, salmonellosis, and tuberculosis. PRDOH, CDC, and the Association of Public Health Laboratories (APHL) collaborated to conduct rapid needs assessments and, with assistance from the CDC Foundation, implement a temporary transport system for shipping samples from Puerto Rico to the continental United States for surveillance and diagnostic and confirmatory testing. This report describes the initial laboratory emergency response and engagement efforts among federal, state, and nongovernmental partners to reestablish public health laboratory services severely affected by Hurricane Maria. The implementation of a sample transport system allowed Puerto Rico to reinitiate priority infectious disease surveillance and laboratory testing for patient and public health interventions, while awaiting the rebuilding and reinstatement of PRDOH laboratory services.

In 2005, joint guidelines issued by the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) provided the first definition of healthcare-associated pneumonia (HCAP).[1][1] This new classification was added to the existing classes of community-acquired pneumonia (CAP

ObjectiveTo identify the social contextual factors, specifically the presence of information that supports v. undermines clinical recommendations, associated with infant feeding behaviours among mothers in low-income areas.DesignCross-sectional survey evaluating social support networks and social relationships involved in providing care to the infant along with feeding beliefs and practices.SettingOut-patient paediatric and government-funded (Women, Infants, and Children) clinics in an urban, low-income area of the south-eastern USA.SubjectsEighty-one low-income mothers of infants between 0 and 12 months old.ResultsMost mothers reported receiving both supportive and undermining advice. The presence of breast-feeding advice that supports clinical recommendations was associated with two infant feeding practices that are considered beneficial to infant health: ever breast-feeding (OR=6·7; 95 % CI 1·2, 38·1) and not adding cereal in the infant’s bottle (OR=15·9; 95 % CI 1·1, 227·4). Advice that undermines clinical recommendations to breast-feed and advice about solid foods were not associated with these behaviours.ConclusionsEfforts to facilitate optimal infant feeding practices may focus on increasing information supportive of clinical recommendations while concentrating less on reducing the presence of undermining information within mothers’ networks. Cultural norms around breast-feeding may be stronger than the cultural norms around the introduction of solid foods in mothers’ social environments; thus, additional efforts to increase information regarding introduction of solid foods earlier in mothers’ infant care career may be beneficial.

In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription–polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. Average RT-PCR cycle threshold values for fatal cases during the acute phase of illness were significantly lower than those for nonfatal cases. Following the institution of contact tracing, active case surveillance, care of patients with isolation precautions, community mobilization, and rapid diagnostic testing, the outbreak was successfully contained 14 days after its initial detection.

As the disease spread, the scale of the epidemic required a multi-faceted public health response., Over the span of a few weeks during July and August 2014, events in West Africa changed perceptions of Ebola virus disease (EVD) from an exotic tropical disease to a priority for global health security. We describe observations during that time of a field team from the Centers for Disease Control and Prevention and personnel of the Liberian Ministry of Health and Social Welfare. We outline the early epidemiology of EVD within Liberia, including the practical limitations on surveillance and the effect on the country’s health care system, such as infections among health care workers. During this time, priorities included strengthening EVD surveillance; establishing safe settings for EVD patient care (and considering alternative isolation and care models when Ebola Treatment Units were overwhelmed); improving infection control practices; establishing an incident management system; and working with Liberian airport authorities to implement EVD screening of departing passengers.

People speak metaphorically about abstract concepts—for instance, a person can be “full of love” or “have a lot of love to give.” Over the past decade, research has begun to focus on how metaphors are processed during language comprehension. Much of this work suggests that understanding a metaphorical expression involves activating brain and body systems involved in perception and motor control. However, no research to date has asked whether the same is true while speakers produce language. We address this gap using a sentence production task. Its results demonstrate that visually activating a concrete source domain can trigger the use of metaphorical language drawn from that same concrete domain, even in sentences that are thematically unrelated to the primes, a metaphorical priming effect. This effect suggests that conceptual metaphors play a part in language production. It also shows that activation in the perceptual system that is not part of an intended message can nevertheless influence sentence formulation.

Senescent cells have the capacity to both effect and limit fibrosis. Senotherapeutics target senescent cells to improve aging conditions. Here, we review the contexts in which senescent cells mediate wound healing and fibrotic pathology and the potential utility of senotherapeutic drugs for treatment of fibrotic disease. Multi-action and temporal considerations influence deleterious versus beneficial actions of senescent cells. Acutely generated senescent cells can limit proliferation, and the senescence-associated secretory phenotype (SASP) contains factors that can facilitate tissue repair. Long-lived senescent cells that evade clearance or are generated outside of programmed remodeling can deplete the progenitor pool to exhaust regenerative capacity and through the SASP, stimulate continual activation, leading to disorganized tissue architecture, fibrotic damage, sterile inflammation, and induction of bystander senescence. Senescent cells contribute to fibrotic pathogenesis in multiple tissues, including the liver, kidney, and lung. Senotherapeutics may be a viable strategy for treatment of a range of fibrotic conditions.

Summary A serum biomarker of biological versus chronological age would have significant impact on clinical care. It could be used to identify individuals at risk of early‐onset frailty or the multimorbidities associated with old age. It may also serve as a surrogate endpoint in clinical trials targeting mechanisms of aging. Here, we identified MCP‐1/CCL2, a chemokine responsible for recruiting monocytes, as a potential biomarker of biological age. Circulating monocyte chemoattractant protein‐1 (MCP‐1) levels increased in an age‐dependent manner in wild‐type (WT) mice. That age‐dependent increase was accelerated in Ercc1 −/Δ and Bubr1 H/H mouse models of progeria. Genetic and pharmacologic interventions that slow aging of Ercc1 −/Δ and WT mice lowered serum MCP‐1 levels significantly. Finally, in elderly humans with aortic stenosis, MCP‐1 levels were significantly higher in frail individuals compared to nonfrail. These data support the conclusion that MCP‐1 can be used as a measure of mammalian biological age that is responsive to interventions that extend healthy aging.

Background: Vaccination is the best way to prevent pneumococcal disease (PD), but 40% of older adults remain unvaccinated nationwide, with even greater nonvaccination rates among African Americans (AAs). Prior studies suggest that insufficient knowledge contributes to low vaccination rates. The Pharmacists’ Pneumonia Prevention Program (PPPP) was designed to improve older adults’ knowledge about PD and pneumococcal vaccination (PV). Objective: To measure PPPP’s effect on knowledge and activation in a predominantly AA population and determine program costs. Methods: PPPP uses a senior center model with a pharmacist presentation, actors’ skit, and small-group action planning. Knowledge about PD risk, transmission, symptoms, and PV side effects was assessed at baseline (BL), postintervention (PT), and 3 months (M3) and analyzed using an intention-to-treat (ITT) approach. Actions taken (got vaccinated, spoke to doctor or pharmacist, discussed with family/friends) were assessed at M3. PPPP costs ($US 2013) included staff time, PV, actor, and site fees. Results: Of 276 attending PPPP, 190 consented and were included in the ITT sample, which was largely black (80.5%) and female (76.3%) and had a mean age of 74.4 years. Knowledge improved by 46.8% (BL vs PT), with significant gains in all domains. At M3, knowledge improved by 54.2% vs BL, indicating sustained gains; 37.2% of previously unvaccinated participants reported receiving PV by M3. Program cost was $119 per attendee. Conclusion: PPPP significantly improved PD and PV knowledge. It could be delivered more efficiently by holding larger events on fewer dates, staffing with volunteers where appropriate, and utilizing a local pharmacy to manage the vaccine supply.

Breastfeeding is critical to maternal and infant health. Psychosocial factors are associated with lactation outcomes, and perinatal mood disorders (PMDs) are often linked with breastfeeding difficulties and early, unexpected weaning. Parents may utilize human milk sharing to ensure their infant receives human milk when breastfeeding requires supplementation or is not possible, but this practice carries health risks and is often stigmatized. Milk sharing recipient mothers may be particularly vulnerable to PMDs associated with breastfeeding difficulties. The study objective was to explore factors associated with emotional responses to a parent's decision to feed their infant with shared human milk. An online cross-sectional survey of 205 milk sharing recipients was analysed with linear regression. Controlling for participants' education and breastfeeding difficulties, higher perceived social stigma was associated with more negative emotional responses (p < .01). Receiving strong spousal/partner support for milk sharing (p < .001) and screening donors regarding the health of their nursling(s) (p < .05) were associated with more positive emotional responses. Social stigmatization of milk sharing may negatively influence emotional responses among recipient mothers. Based on these results, it can be recommended that health professionals screen breastfeeding mothers with lactation difficulties for emotional distress that may lead to PMDs and provide evidence-based information about milk sharing in a nonstigmatizing way. Health professionals may support informed decision-making for infant feeding practices, including human milk sharing, by providing information on milk sharing risks and risk mitigation, developing evidence-based practices and guidelines that facilitate safe milk sharing, and directing families to available resources for psychosocial support.

The first two integrase strand transfer inhibitors (INSTIs) approved for treatment of patients infected with human immunodeficiency virus (HIV) were raltegravir and elvitegravir. Both raltegravir and elvitegravir are now guideline-preferred agents as part of an antiretroviral regimen for treatment-naive patients. However, raltegravir is dosed twice/day. Elvitegravir is available in a single-tablet regimen and dosed once/day because it is administered with the pharmacokinetic booster cobicistat, a potent CYP3A4 inhibitor that can lead to clinically significant drug-drug interactions. In addition, raltegravir and elvitegravir have a low genetic barrier to resistance and are associated with cross-resistance. Dolutegravir is a new-generation INSTI administered once/day without a pharmacokinetic booster and can be coformulated in a single-tablet regimen. Phase III studies have demonstrated the efficacy and safety of dolutegravir for treatment-naive and treatment-experienced patients. Compared with other INSTIs, dolutegravir has a higher genetic barrier to resistance. Dolutegravir was approved by the U.S. Food and Drug Administration in August 2013 and joins raltegravir and elvitegravir as guideline-preferred agents for the management for HIV-infected treatment-naive patients.

Low bone mineral density is common among persons with human immunodeficiency virus (HIV) infection, and studies reporting increased fracture rates in this patient population are emerging. The causes of low bone mineral density, osteoporosis, and fractures in persons with HIV are likely multifactorial, involving traditional risk factors, HIV infection, and exposure to antiretroviral treatment. Specific antiretrovirals such as tenofovir may cause a greater loss of bone mineral density compared with other agents and have recently been linked to an increased risk for fracture. As a result, recent treatment guidelines suggest that clinicians consider avoiding tenofovir as initial therapy in postmenopausal women. Evaluating bone mineral density and vitamin D status in persons with HIV may be important steps in identifying those requiring pharmacotherapy; however, the appropriate timing for bone mineral density and vitamin D screening is uncertain, as is the appropriate method of replacing vitamin D in HIV-positive patients who are deficient. Further study is necessary to definitively determine the approach to evaluating bone health and managing low bone mineral density and vitamin D deficiency in patients with HIV infection.