Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease

Peripheral arterial disease (PAD) results in a failure to adequately supply blood and oxygen (O(2)) to working tissues and presents as claudication pain during walking. Nitric oxide (NO) bioavailability is essential for vascular health and function. Plasma nitrite (NO(2)(-)) is a marker of vascular NO production but may also be a protected circulating "source" that can be converted to NO during hypoxic conditions, possibly aiding perfusion. We hypothesized that dietary supplementation of inorganic nitrate in the form of beetroot (BR) juice would increase plasma NO(2)(-) concentration, increase exercise tolerance, and decrease gastrocnemius fractional O(2) extraction, compared with placebo (PL). This was a randomized, open-label, crossover study. At each visit, subjects (n = 8) underwent resting blood draws, followed by consumption of 500 ml BR or PL and subsequent blood draws prior to, during, and following a maximal cardiopulmonary exercise (CPX) test. Gastrocnemius oxygenation during the CPX was measured by near-infrared spectroscopy. There were no changes from rest for [NO(2)(-)] (152 ± 72 nM) following PL. BR increased plasma [NO(2)(-)] after 3 h (943 ± 826 nM; P ≤ 0.01). Subjects walked 18% longer before the onset of claudication pain (183 ± 84 s vs. 215 ± 99 s; P ≤ 0.01) and had a 17% longer peak walking time (467 ± 223 s vs. 533 ± 233 s; P ≤ 0.05) following BR vs. PL. Gastrocnemius tissue fractional O(2) extraction was lower during exercise following BR (7.3 ± 6.2 vs. 10.4 ± 6.1 arbitrary units; P ≤ 0.01). Diastolic blood pressure was lower in the BR group at rest and during CPX testing (P ≤ 0.05). These findings support the hypothesis that NO(2)(-)-related NO signaling increases peripheral tissue oxygenation in areas of hypoxia and increases exercise tolerance in PAD.     

HIV-mediated phosphatidylinositol 3-kinase/serine-threonine kinase activation in APCs leads to programmed death-1 ligand upregulation and suppression of HIV-specific CD8 T cells

Recent evidence demonstrates that HIV-1 infection leads to the attenuation of cellular immune responses, which has been correlated with the increased expression of programmed death (PD)-1 on virus-specific CD8(+) T cells. PD-1 is induced upon T cell activation, and its prolonged expression facilitates CD8(+) T cell inhibitory signals when bound to its B7 family ligands, PD-ligand (L)1/2, which are expressed on APCs. Importantly, early reports demonstrated that blockade of the PD-1/PD-L interaction by Abs may help to counter the development of immune exhaustion driven by HIV viral persistence. To better understand the regulation of the PD-1 pathway during HIV infection, we examined the ability of the virus to induce PD-L expression on macrophages and dendritic cells. We found a direct relationship between the infection of APCs and the expression of PD-L1 in which virus-mediated upregulation induced a state of nonresponsiveness in uninfected HIV-specific T cells. Furthermore, this exhaustion phenotype was revitalized by the blockade of PD-L1, after which T cells regained their capacity for proliferation and the secretion of proinflammatory cytokines IFN-γ, IL-2, and IL-12 upon restimulation. In addition, we identify a critical role for the PI3K/serine-threonine kinase signaling pathway in PD-L1 upregulation of APCs by HIV, because inhibition of these intracellular signal transducer enzymes significantly reduced PD-L1 induction by infection. These data identify a novel mechanism by which HIV exploits the immunosuppressive PD-1 pathway and suggest a new role for virus-infected cells in the local corruption of immune responses required for viral suppression.     

GLIMMPSE Lite: Calculating Power and Sample Size on Smartphone Devices

Researchers seeking to develop complex statistical applications for mobile devices face a common set of difficult implementation issues. In this work, we discuss general solutions to the design challenges. We demonstrate the utility of the solutions for a free mobile application designed to provide power and sample size calculations for univariate, one-way analysis of variance (ANOVA), GLIMMPSE Lite. Our design decisions provide a guide for other scientists seeking to produce statistical software for mobile platforms.     

Evaluation of a community-based mobile video breastfeeding intervention in Khayelitsha,South Africa: The Philani MOVIE cluster-randomized controlled trial

BackgroundIn South Africa, breastfeeding promotion is a national health priority. Regular perinatal home visits by community health workers (CHWs) have helped promote exclusive breastfeeding (EBF) in underresourced settings. Innovative, digital approaches including mobile video content have also shown promise, especially as access to mobile technology increases among CHWs. We measured the effects of an animated, mobile video series, the Philani MObile Video Intervention for Exclusive breastfeeding (MOVIE), delivered by a cadre of CHWs (“mentor mothers”).Methods and findingsWe conducted a stratified, cluster-randomized controlled trial from November 2018 to March 2020 in Khayelitsha, South Africa. The trial was conducted in collaboration with the Philani Maternal Child Health and Nutrition Trust, a nongovernmental community health organization. We quantified the effect of the MOVIE intervention on EBF at 1 and 5 months (primary outcomes), and on other infant feeding practices and maternal knowledge (secondary outcomes). We randomized 1,502 pregnant women in 84 clusters 1:1 to 2 study arms. Participants’ median age was 26 years, 36.9% had completed secondary school, and 18.3% were employed. Mentor mothers in the video intervention arm provided standard-of-care counseling plus the MOVIE intervention; mentor mothers in the control arm provided standard of care only. Within the causal impact evaluation, we nested a mixed-methods performance evaluation measuring mentor mothers’ time use and eliciting their subjective experiences through in-depth interviews.At both points of follow-up, we observed no statistically significant differences between the video intervention and the control arm with regard to EBF rates and other infant feeding practices [EBF in the last 24 hours at 1 month: RR 0.93 (95% CI 0.86 to 1.01, P = 0.091); EBF in the last 24 hours at 5 months: RR 0.90 (95% CI 0.77 to 1.04, P = 0.152)]. We observed a small, but significant improvement in maternal knowledge at the 1-month follow-up, but not at the 5-month follow-up. The interpretation of the results from this causal impact evaluation changes when we consider the results of the nested mixed-methods performance evaluation. The mean time spent per home visit was similar across study arms, but the intervention group spent approximately 40% of their visit time viewing videos. The absence of difference in effects on primary and secondary endpoints implies that, for the same time investment, the video intervention was as effective as face-to-face counseling with a mentor mother. The videos were also highly valued by mentor mothers and participants. Study limitations include a high loss to follow-up at 5 months after premature termination of the trial due to the COVID-19 pandemic and changes in mentor mother service demarcations.ConclusionsThis trial measured the effect of a video-based, mobile health (mHealth) intervention, delivered by CHWs during home visits in an underresourced setting. The videos replaced about two-fifths of CHWs’ direct engagement time with participants in the intervention arm. The similar outcomes in the 2 study arms thus suggest that the videos were as effective as face-to-face counselling, when CHWs used them to replace a portion of that counselling. Where CHWs are scarce, mHealth video interventions could be a feasible and practical solution, supporting the delivery and scaling of community health promotion services.Trial registrationThe study and its outcomes were registered at clinicaltrials.gov (#{"type":"clinical-trial","attrs":{"text":"NCT03688217","term_id":"NCT03688217"}}NCT03688217) on September 27, 2018.

Maya Adam and colleagues study a video intervention, delivered by community health workers, to promote breastfeeding in South Africa.     

Effect of sunflower seed oil emollient therapy on newborn infant survival in Uttar Pradesh,India: A community-based,cluster randomized,open-label controlled trial

BackgroundHospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in newborn infants. We hypothesized that SSO therapy may reduce NMR in such settings.Methods and findingsThis was a population-based, cluster randomized, controlled trial in 276 clusters in rural Uttar Pradesh, India. All newborn infants identified through population-based surveillance in the study clusters within 7 days of delivery were enrolled from November 2014 to October 2016. Exclusive, 3 times daily, gentle applications of 10 ml of SSO to newborn infants by families throughout the neonatal period were recommended in intervention clusters (n = 138 clusters); infants in comparison clusters (n = 138 clusters) received usual care, such as massage practice typically with mustard oil. Primary analysis was by intention-to-treat with NMR and post-24-hour NMR as the primary outcomes. Secondary analysis included per-protocol analysis and subgroup analyses for NMR. Regression analysis was adjusted for caste, first-visit weight, delivery attendant, gravidity, maternal age, maternal education, sex of the infant, and multiple births. We enrolled 13,478 (52.2% male, mean weight: 2,575.0 grams ± standard deviation [SD] 521.0) and 13,109 (52.0% male, mean weight: 2,607.0 grams ± SD 509.0) newborn infants in the intervention and comparison clusters, respectively. We found no overall difference in NMR in the intervention versus the comparison clusters [adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.84 to 1.11, p = 0.61]. Acceptance of SSO in the intervention arm was high at 89.3%, but adherence to exclusive applications of SSO was 30.4%. Per-protocol analysis showed a significant 58% (95% CI 42% to 69%, p < 0.01) reduction in mortality among infants in the intervention group who were treated exclusively with SSO as intended versus infants in the comparison group who received exclusive applications of mustard oil. A significant 52% (95% CI 12% to 74%, p = 0.02) reduction in NMR was observed in the subgroup of infants weighing ≤1,500 g (n = 589); there were no statistically significant differences in other prespecified subgroup comparisons by low birth weight (LBW), birthplace, and wealth. No severe adverse events (SAEs) were attributable to the intervention. The study was limited by inability to mask allocation to study workers or participants and by measurement of emollient use based on caregiver responses and not actual observation.ConclusionsIn this trial, we observed that promotion of SSO therapy universally for all newborn infants was not effective in reducing NMR. However, this result may not necessarily establish equivalence between SSO and mustard oil massage in light of our secondary findings. Mortality reduction in the subgroup of infants ≤1,500 g was consistent with previous hospital-based efficacy studies, potentially extending the applicability of emollient therapy in very low-birth-weight (VLBW) infants along the facility–community continuum. Further research is recommended to develop and evaluate therapeutic regimens and continuum of care delivery strategies for emollient therapy for newborn infants at highest risk of compromised skin barrier function.Trial registrationISRCTN Registry ISRCTN38965585 and Clinical Trials Registry—India (CTRI/2014/12/005282) with WHO UTN # U1111-1158-4665.

In a cluster randomized trial, Aarti Kumar and colleagues study the effectiveness of a topical sunflower seed oil therapy in reducing neonatal mortality in Uttar Pradesh, India.     

Airborne Penicillium in the grain shops of Nagpur (India)

The airborne Penicillium spp. and total airborne fungal spore concentration was investigated in the grain shops of Nagpur city, India, using a volumetric Hi‐Air sampler system Mark II (Hi Media Laboratories Ltd., India). The mycotoxins were analysed from the Penicillium isolates obtained from the seeds by thin layer chromatography.

The mean concentration of the total fungi isolated from different grain shops ranged from 7.8×10² to 1.1×10³ CFU/m³. The mean concentration of Penicillium isolated from the air of grain shops ranged from 8.6×10¹ CFU/m³ (10.8%) to 1.7×10² CFU/m³ (19.9%). Among the 13 species of Penicillium which were isolated, P. citrinum Thom was the most prevalent species (24.2%), followed by P. oxalicum Currie & Thom (16.5), P. digitatum Saccardo (8.9%), P. janthinellum Biourge (8.7%), P. funiculosum Thom (8.3%), P. chrysogenum Thom (6.4%), P. purpurogenum Stoll (6.2%), P. brevicompactum Dierckx (4.8%), P. frequentans Westling (4.2%), P. italicum Wehmer (3.8%), P. rubrum Stoll (3.4%), P. expansum Link (2.9%) and P. cyclopium Westling (1.6%).

Penicillium species were also isolated from seeds such as wheat, maize, soybean, and groundnut. The mycotoxins roquefortin C, citrinin, rubratoxin B, cyclopiazonic acid, verrucosidin, mitorubrinic acid and two unknown metabolites were isolated from Penicillium isolates.     

Efficient Solar Cells Based on Light‐Harvesting Antimony Sulfoiodide

Although antimony sulfoiodide (SbSI) exhibits very interesting properties including high photoconductivity, ferroelectricity, and piezoelectricity, it is not applied to solar cells. Meanwhile, SbSI is predominantly prepared as a powder using a high‐temperature, high‐pressure system. Herein, the fabrication of solar cells utilizing SbSI as light harvesters is reported for the first time to the best of knowledge. SbSI is prepared by solution processing, followed by annealing under mild temperature conditions by a reaction between antimony trisulfide, which is deposited by chemical bath deposition on a mesoporous TiO₂ electrode and antimony triiodide, under air at a low temperature (90 °C) without any external pressure. The solar cells fabricated using SbSI exhibit a power conversion efficiency of 3.05% under standard illumination conditions of 100 mW cm^?2.     

Antibody Profiling in Na?ve and Semi-immune Individuals Experimentally Challenged with Plasmodium vivax Sporozoites

BackgroundAcquisition of malaria immunity in low transmission areas usually occurs after relatively few exposures to the parasite. A recent Plasmodium vivax experimental challenge trial in malaria naïve and semi-immune volunteers from Colombia showed that all naïve individuals developed malaria symptoms, whereas semi-immune subjects were asymptomatic or displayed attenuated symptoms. Sera from these individuals were analyzed by protein microarray to identify antibodies associated with clinical protection.ConclusionClinical protection against experimental challenge in volunteers with previous P. vivax exposure was associated with elevated pre-existing antibodies, an attenuated serological response to the challenge and reactivity to new antigens.