Prime-boost vaccination regimens with INO-4800 and INO-4802 augment and broaden immune responses against SARS-CoV-2 in nonhuman primates.

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates.

Optogenetic activators of apoptosis, necroptosis, and pyroptosis.

Targeted and specific induction of cell death in an individual or groups of cells hold the potential for new insights into the response of tissues or organisms to different forms of death. Here, we report the development of optogenetically controlled cell death effectors (optoCDEs), a novel class of optogenetic tools that enables light-mediated induction of three types of programmed cell death (PCD)-apoptosis, pyroptosis, and necroptosis-using Arabidopsis thaliana photosensitive protein Cryptochrome-2. OptoCDEs enable a rapid and highly specific induction of PCD in human, mouse, and zebrafish cells and are suitable for a wide range of applications, such as sub-lethal cell death induction or precise elimination of single cells or cell populations in vitro and in vivo.

Sequence and tissue targeting specificity of ZFP36L2 reveals Elavl2 as a novel target with co-regulation potential.

Zinc finger protein 36 like 2 (ZFP36L2) is an RNA-binding protein that destabilizes transcripts containing adenine-uridine rich elements (AREs). The overlap between ZFP36L2 targets in different tissues is minimal, suggesting that ZFP36L2-targeting is highly tissue specific. We developed a novel Zfp36l2-lacking mouse model (L2-fKO) to identify factors governing this tissue specificity.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Therapeutic Treatment Plan Optimization during the COVID-19 Pandemic: A Comprehensive Physicochemical Compatibility Study of Intensive Care Units Selected Drugs.

Background: The SARS-CoV-2 pandemic has resulted in a dramatic rise of the demand for medical devices and drugs. In this context, an important shortage of programmable syringe pumps, used to administrate different drugs in intensive care units, was seen. The opportunity of administrating combinations of five intensive care units selected drugs (Sufentanil, Clonidine, Loxapine, Midazolam, and Ketamine) was considered.

The Influence of Family Bonding, Support, Engagement in Healthcare, on PrEP Stigma among Young Black and Latino Men Who Have Sex with Men: A Path Analysis.

This study employs the ecodevelopmental theory to examine the influence of mother and father bonding, family engagement in healthcare, and family support on PrEP stigma among BLMSM. We used a cross-sectional sample from wave five of the Healthy Young Men (HYM) study, with a survey sample of 399 participants aged 16−24 years. We conducted two-path analyses to test multiple hypotheses: (1) mother/father bonding is associated with an increase in family engagement in healthcare; (2) family engagement in healthcare is associated with family social support; and (3) family social support is associated with PrEP stigma.

Heat Stress: Effects on Rumen Microbes and Host Physiology, and Strategies to Alleviate the Negative Impacts on Lactating Dairy Cows.

Heat stress (HS) in dairy cows causes considerable losses in the dairy industry worldwide due to reduced animal performance, increased cases of metabolic disorders, altered rumen microbiome, and other health problems. Cows subjected to HS showed decreased ruminal pH and acetate concentration and an increased concentration of ruminal lactate. Heat-stressed cows have an increased abundance of lactate-producing bacteria such as and unclassified Enterobacteriaceae, and soluble carbohydrate utilizers such as , , and unclassified Bacteroidaceae.

Biochar mitigates bioavailability and environmental risks of arsenic in gold mining tailings from the eastern Amazon.

Artisanal gold mining has generated tailings highly contaminated by arsenic (As) in Cachoeira do Piriá, eastern Amazon, leading to severe risks to the environment. Such risks should be mitigated considering the bioavailable concentration of the element, since it implies immediate damage to the ecosystem. The objective of this study was to evaluate the potential of biochars in mitigating the environmental risks of bioavailable As concentrations in gold mining tailings from underground and cyanidation exploration.

Levels and environmental risks of rare earth elements in a gold mining area in the Amazon.

Artisanal gold (Au) mining may have increased the concentrations of rare earth elements (REEs) in the Serra Pelada mine (southeastern Amazon, Brazil), which has not been evaluated so far. The objectives of this study were to determine the concentrations of cerium (Ce), lanthanum (La), scandium (Sc), and yttrium (Y) in the surroundings of the Serra Pelada mine, as well as the environmental risks associated with these elements. Therefore, 27 samples were collected in agricultural, forest, mining, and urban areas, and submitted to chemical and particle size characterization.

Soil-sediment linkage and trace element contamination in forested/deforested areas of the Itacaiúnas River Watershed, Brazil: To what extent land-use change plays a role?

Trace elements (TE) contamination in forested areas of the Itacaiúnas River Watershed (IRW), Brazilian Amazon, arouses growing interest owing to the rapid deforestation and mining activities. In this study, soils (surface, SS; bottom, BS) and stream sediments (SD) from forested/deforested areas of IRW were analyzed with the aim of (1) evaluating the major sources of TE (mainly As, Ba, Cd, Cu, Co, Cr, Hg, Mo, Mn, Ni, Pb, V, and Zn), and (2) examining the soil-sediment TE link related to land-use change and/or geologic factors. Compositional data analysis (CoDA) was used to eliminate data closure issues and the centred log-ratio (clr) transformation yielded better results in Principal Component Analysis (PCA).

Proteomic Profiling and Rhizosphere-Associated Microbial Communities Reveal Adaptive Mechanisms of Kunth in Eastern Amazon's Rehabilitating Minelands.

Kunth is native to ferruginous rocky outcrops (known as ) in the eastern Amazon. Native are considered hotspots of biological diversity and have one of the largest iron ore deposits in the world. There, can grow in post-mining areas where molecular mechanisms and rhizospheric interactions with soil microorganisms are expected to contribute to their establishment in rehabilitating minelands (RM).

Changes in soil properties during iron mining and in rehabilitating minelands in the Eastern Amazon.

Open-cast iron mining causes drastic disturbances in soil properties. Recovery of soil chemical and physical properties is essential for successful revegetation and landscape rehabilitation. To identify changes in soil properties during the mining and revegetation process, soil samples were collected from undisturbed sites represented by forest and ferriferous savannas stocking above iron outcrops, called "cangas," in open-pit benches, and in rehabilitation chronosequences of iron waste piles in the Carajás Mineral Province (CMP), Eastern Amazon, Brazil.

Supplementation with a Cocoa-Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats.

Diabetic cardiomyopathy (DCM) is one of the main causes of mortality among diabetic patients, with oxidative stress and inflammation major contributors to its development. Dietary flavonoids show strong antioxidant and anti-inflammatory activities, although their potential additive outcomes in combination with antidiabetic drugs have been scarcely explored. The present study investigates the cardioprotective effects of a cocoa-carob blend (CCB) diet, rich in flavonoids, alone or in combination with metformin, in the development of DCM.

Low-Resolution Electrogastrogram at Baseline and Response to Temporary Gastric Electrical Stimulation-A Comparison of Cutaneous With Mucosal Recordings.

Introduction: Gastric electrical stimulation (GES) is a widely accepted therapy for gastroparesis symptoms, but how a brief cutaneous electrogastrogram (EGG) can be used in conjunction with GES has not been well defined. We evaluated the clinical importance of EGG, its correlation with mucosal electrograms (mEGs), gastric emptying tests (GETs), and gastrointestinal symptoms before and after temporary GES (tGES).

Materials And Methods: We studied 1345 patients; 991 had complete data.

Determination of Psychosocial Factors of Drinking Chlorinated Water to Design Behavior Change Interventions in Rohingya Camps in Bangladesh.

The purpose of this study was to identify the psychosocial factors of chlorinated water uptake and to design effective behavior change techniques applying the risk, attitude, norm, ability, and self-regulation (RANAS) behavior change model. This cross-sectional study was conducted in two Rohingya refugee camps in Cox's Bazar, Bangladesh. In total, 596 respondents were recruited through systematic random sampling.

Theories of Change and Mediators of Psychotherapy Effectiveness in Adolescents With Externalising Behaviours: A Systematic Review.

Background: Externalising behaviours are becoming a remarkably prevalent problem during adolescence, often precipitating both externalising and internalising disorders in later adulthood. Psychological treatments aim to increase the social functioning of adolescents in order for them to live a more balanced life and prevent these negative trajectories. However, little is known of the intervening variables and mediators involved in these treatments' change mechanisms.

Caesarean birth in public maternities in Argentina: a formative research study on the views of obstetricians, midwives and trainees.

Objectives: To explore obstetricians', midwives' and trainees' perceptions of caesarean section (CS) determinants in the context of public obstetric care services provision in Argentina. Our hypothesis is that known determinants of CS use may differ in settings with limited access to essential obstetric services.

Setting: We conducted a formative research study in 19 public maternity hospitals in Argentina.

Assessing Different Types of HIV Communication and Sociocultural Factors on Perceived HIV Stigma and Testing among a National Sample of Youth and Young Adults.

In the United States, racial/ethnic and sexual youth and young adults (YYA) of color are disproportionately affected by HIV. Subsequently, YYA experience HIV stigma and engage in increased risk behaviors and reduced HIV testing. HIV communication has been identified as a potential buffer to HIV stigma, resulting in health-seeking behaviors, such as HIV testing.

The Role Of Comorbidities On Outcome Prediction In Acute Burn Patients.

Burn trauma is a leading cause of mortality and morbidity. None of the currently available formulas for mortality prediction take into account the impact of comorbidities on burn patients' outcome. In this study, we evaluate the impact of comorbidities on in-hospital mortality and prolonged length of hospital stay (≥30 days).

Implementation of Client-Centered Care Coordination for HIV Prevention with Black Men Who Have Sex with Men: Activities, Personnel Costs, and Outcomes-HPTN 073.

Background: Black men who have sex with men (MSM) experience disproportionate rates of HIV infection in the USA, despite being no more likely to engage in sexual risk behaviors than other MSM racial/ethnic groups. HIV pre-exposure prophylaxis (PrEP) has been shown to reduce risk of HIV acquisition; however, rates of PrEP use among Black MSM remain low. Clinical, psychosocial, and structural factors have been shown to impact PrEP use and adherence among Black MSM.