Treatment of cattle with ivermectin and its effect on dung degradation and larval abundance in a tropical savanna setting.

When ingested as part of a blood meal, the antiparasitic drug ivermectin kills mosquitoes, making it a candidate for mass drug administration (MDA) in humans and livestock to reduce malaria transmission. When administered to livestock, most ivermectin is excreted unmetabolized in the dung within 5 days post administration. Presence of ivermectin, has been shown to adversely affect dung colonizers and dung degradation in temperate settings; however, those findings may not apply to, tropical environment, where ivermectin MDA against malaria would occur.

Ovarian cancer-derived IL-4 promotes immunotherapy resistance.

Ovarian cancer is resistant to immunotherapy, and this is influenced by the immunosuppressed tumor microenvironment (TME) dominated by macrophages. Resistance is also affected by intratumoral heterogeneity, whose development is poorly understood. To identify regulators of ovarian cancer immunity, we employed a spatial functional genomics screen (Perturb-map), focused on receptor/ligands hypothesized to be involved in tumor-macrophage communication.

Effects of nicotine patches on early and late attentional bias to smoking cues: We may know less than we think.

In contrast to overnight deprivation versus satiety studies, a small number of placebo-controlled studies have failed to find that nicotine administration reduces attentional bias (AB) to smoking cues. To assess the reliability of this failure and to address the duration and salience of AB in smokers versus never-smokers, we used a longer-than-typical (i.e.

BOHEMIA: Broad One Health Endectocide-based Malaria Intervention in Africa-a phase III cluster-randomized, open-label, clinical trial to study the safety and efficacy of ivermectin mass drug administration to reduce malaria transmission in two African settings.

Background: Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period.

Facilitated extinction of conditioned fear responses by delta 9-tetrahyrdrocannabidol in humans: a pilot study.

Objective: We sought to determine whether acute delta 9-tetrahyrdrocannabidol (THC) administration would facilitate fear extinction in young occasional cannabis users, given that animal models indicate THC facilitates extinction learning, and recent studies indicate THC administration may also enhance threat memory extinction in humans.

Methods: On each of the 2 days, 24+ hour THC-deprived participants were conditioned to fear visual stimuli in a delay conditioning and extinction paradigm. Both CS+ and CS- were faces of negative emotional valence, with the CS+ paired with mild electric shock.

The Impact of Comprehensive Genomic Profiling (CGP) on the Decision-Making Process in the Treatment of ALK-Rearranged Advanced Non-Small Cell Lung Cancer (aNSCLC) After Failure of 2/3-Generation ALK Tyrosine Kinase Inhibitors (TKIs).

Background: The use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable.

Methods: We prospectively assessed the impact of CGP on the decision-making process in ALK-rearranged aNSCLC patients following progression on 2/3-generation ALK TKIs. Physician's choice of the most recommended next-line systemic treatment (NLST) was captured before and after receival of CGP results; the percentage of cases in which the NLST recommendation has changed was assessed along with the CGP turnaround time (TAT).

Effects of Cannabis-Delivered THC on mood and negative attentional bias in the context of positive vs. neutral Alternatives-a pilot study.

Objective: To assess: (1) the acute effects of smoked marijuana (MJ) on negative attentional bias (NAB), (2) moderation of these effects by positive versus neutral alternatives, and (3) the associations of tetrahydrocannabinol (THC)-induced changes in NAB with changes in affect.

Methods: Fourteen MJ users (1-4 uses/wk) smoked a THC cigarette on 1 day and a placebo cigarette on the other counterbalanced day. After smoking, participants freely gazed back and forth at a series of two side-by-side pictures pairs presented for 3000 ms (one negative, while the other was either positive or neutral) while eye gaze was tracked.

Time-series analysis of recent antihyperglycemic medication prescribing trends for a diverse sample of Medicare enrollees with type 2 diabetes mellitus in an integrated health system.

Purpose: Despite high type 2 diabetes mellitus (T2DM) prevalence in Medicare enrollees, newer therapeutic options, and revised treatment guidelines, little is known about US antihyperglycemic prescribing trends after 2015. This research describes recent monthly antihyperglycemic prescribing trends in a large, diverse population of Medicare enrollees from the US Mid-Atlantic region.

Methods: Encounter data (July 2018-July 2020) for Medicare enrollees 65 years of age or older with T2DM were extracted from electronic health records of a large integrated health system.

Some lessons for malaria from the Global Polio Eradication Initiative.

The Global Polio Eradication Initiative (GPEI) was launched in 1988 with the aim of completely clearing wild polio viruses by 2000. More than three decades later, the goal has not been achieved, although spectacular advances have been made, with wild polio virus reported in only 2 countries in 2019. In spite of such progress, novel challenges have been added to the equation, most importantly outbreaks of vaccine-derived polio cases resulting from reversion to neurovirulence of attenuated vaccine virus, and insufficient coverage of vaccination.

Genetic and Depressive Traits Moderate the Reward-Enhancing Effects of Acute Nicotine in Young Light Smokers.

Introduction: Rates of light smoking have increased in recent years and are associated with adverse health outcomes. Reducing light smoking is a challenge because it is unclear why some but not others, progress to heavier smoking. Nicotine has profound effects on brain reward systems and individual differences in nicotine's reward-enhancing effects may drive variability in smoking trajectories.

Community acceptability to antimalarial mass drug administrations in Magude district, Southern Mozambique: A mixed methods study.

Background: This study aimed to capture the acceptability prior to, during and after the implementation of the first year of MDA rounds conducted under the Magude project, a malaria elimination project in southern Mozambique.

Methods: This was a mixed-methods study, consisting of focus group discussions (FGDs) prior to the implementation of MDA rounds (September 2015), non-participant observations (NPOs) conducted during the MDA rounds (November 2015 -beginning of February 2016), and semi-structured interviews (SSIs) after the second round (end of February 2016). Community leaders, women in reproductive age, general members of the community, traditional healers and health professionals were recruited to capture the opinions of all representing key members of the community.

APOE genotype influences P3b amplitude and response to smoking abstinence in young adults.

Rationale: There is strong evidence that nicotine can enhance cognitive functions and growing evidence that this effect may be larger in young healthy APOE ε4 carriers. However, the moderating effects of the APOE ε4 allele on cognitive impairments caused by nicotine deprivation in chronic smokers have not yet been studied with brain indices.

Objective: We sought to determine whether young female carriers of the APOE ε4 allele, relative to noncarriers, would exhibit larger abstinence-induced decreases in P3b amplitude during a two-stimulus auditory oddball task.

Building momentum for malaria vaccine research and development: key considerations.

To maintain momentum towards improved malaria control and elimination, a vaccine would be a key addition to the intervention toolkit. Two approaches are recommended: (1) promote the development and short to medium term deployment of first generation vaccine candidates and (2) support innovation and discovery to identify and develop highly effective, long-lasting and affordable next generation malaria vaccines.

Effect of mass dihydroartemisinin-piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance.

Background: Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance.

Methods: We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisinin-piperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique.

Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial.

Rationale: Given that tetrahydrocannabinol (THC) and nicotine have similar effects on negative affect (NA), we hypothesized that a 7-mg nicotine patch (NP) would reduce NA-related cannabis (CAN) withdrawal symptoms in cannabis-dependent (CD) individuals who were not nicotine dependent.

Objective: We sought to determine whether NP reduces NA across 15 days of CAN abstinence in two groups: non-tobacco smokers (NTS) and light tobacco smokers (LTS).

Methods: CD participants (N = 127; aged 18-35) who used CAN at least 5 times/week for the past 12 + months were randomized to (1) NP or (2) a placebo patch (PP) and received $300 for sustained biochemically verified CAN abstinence.

Safety of oral ivermectin during pregnancy: a systematic review and meta-analysis.

Background: About 3·7 billion doses of ivermectin have been distributed in mass drug administration (MDA) campaigns globally over the past 30 years. At 10-100 times higher than current human doses, ivermectin is a known teratogen in mammals. During these campaigns with recommended doses, pregnant women might be inadvertently exposed.

Efficacy and Safety of BRAF Inhibitors With or Without MEK Inhibitors in BRAF-Mutant Advanced Non-Small-Cell Lung Cancer: Findings From a Real-Life Cohort.

Background: Real-life comparative data on BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitors (MEKi) combination in BRAF-mutant (BRAFm) non-small-cell lung cancer (NSCLC) is lacking.

Patients And Methods: Consecutive BRAFm advanced NSCLC patients (n = 58) treated in 9 Israeli centers in 2009-2018 were identified. These were divided according to mutation subtype and treatment into groups A1 (V600E, BRAFi; n = 5), A2 (V600E, BRAFi + MEKi; n = 15), A3 (V600E, no BRAFi; n = 7), B1 (non-V600E, BRAFi ± MEKi; n = 7), and B2 (non-V600E, no BRAFi; n = 23); one patient received both BRAFi and BRAFi + MEKi.

Smoking abstinence symptoms across 67 days compared with randomized controls-Moderation by nicotine replacement therapy, bupropion, and negative-affect traits.

Accurate knowledge of negative affect (NA)-related smoking abstinence symptoms (SAS) severity and duration and their moderation by pharmacotherapy and NA-related personality traits is critical for efficacious treatments given that elevated state and trait NA are predictors of relapse. However, SAS severity, duration, and moderation are not well characterized. To date, the longest randomized controlled trial (RCT) of NA-related SAS using randomized delayed-quit smoking controls only examined symptoms across 45 days, despite clinical evidence that SAS may last longer.