Inhibition of GPR68 induces ferroptosis and radiosensitivity in diverse cancer cell types.

Radioresistance is thought to be a major consequence of tumor milieu acidification resulting from the Warburg effect. Previously, using ogremorphin (OGM), a small molecule inhibitor of GPR68, an extracellular proton sensing receptor, we demonstrated that GPR68 is a key pro-survival pathway in glioblastoma cells. Here, we demonstrate that GPR68 inhibition also induces ferroptosis in lung cell carcinoma (A549) and pancreatic ductal adenocarcinoma (Panc02) cells.

Multistate outbreak of Oranienburg infections linked to bulb onions imported from Mexico - United States, 2021.

In 2021, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state and local health and regulatory partners investigated an outbreak of serovar Oranienburg infections linked to bulb onions from Mexico, resulting in 1040 illnesses and 260 hospitalizations across 39 states, the District of Columbia, and Puerto Rico.

Peripheral blood transcriptomic profiling of molecular mechanisms commonly regulated by binge drinking and placebo effects.

Molecular responses to alcohol consumption are dynamic, context-dependent, and arise from a complex interplay of biological and external factors. While many have studied genetic risk associated with drinking patterns, comprehensive studies identifying dynamic responses to pharmacologic and psychological/placebo effects underlying binge drinking are lacking. We investigated transcriptome-wide response to binge, medium, and placebo alcohol consumption by 17 healthy heavy social drinkers enrolled in a controlled, in-house, longitudinal study of up to 12 days.

Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma.

Background: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.

Methods: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent.

South African healthcare reforms towards universal healthcare - where to next?

The National Assembly approval of the National Health Insurance (NHI) Bill represents an important milestone, but there are many uncertainties concerning its implementation and timeline. The challenges faced by the South African healthcare system are huge, and we cannot afford to wait for NHI to address them all. It is critical that the process of strengthening the health system to advance universal healthcare (UHC) begins now, and there are several viable initiatives that can be implemented without delay.

GPR68-ATF4 signaling is a novel prosurvival pathway in glioblastoma activated by acidic extracellular microenvironment.

Background: Glioblastoma multiforme (GBM) stands as a formidable challenge in oncology because of its aggressive nature and severely limited treatment options. Despite decades of research, the survival rates for GBM remain effectively stagnant. A defining hallmark of GBM is a highly acidic tumor microenvironment, which is thought to activate pro-tumorigenic pathways.

CCR5 regulates Aβ-induced learning and memory deficits in mice.

C-C chemokine receptor 5 (CCR5) is a chemokine receptor involved in immune responses and a co-receptor for HIV infection. Recently, CCR5 has also been reported to play a role in synaptic plasticity, learning and memory, and cognitive deficits associated with normal aging, traumatic brain injury (TBI), and HIV-associated neurocognitive disorder (HAND). In contrast, the role of CCR5 in cognitive deficits associated with other disorders, including Alzheimer's disease (AD), is much less understood.

Yeast Chaperone Hsp70-Ssb Modulates a Variety of Protein-Based Heritable Elements.

Prions are transmissible self-perpetuating protein isoforms associated with diseases and heritable traits. Yeast prions and non-transmissible protein aggregates (mnemons) are frequently based on cross-β ordered fibrous aggregates (amyloids). The formation and propagation of yeast prions are controlled by chaperone machinery.

An Outbreak Investigation of Infections in the United States Linked to Crabmeat Imported from Venezuela: 2018.

is the leading cause of seafood-related foodborne illness globally. In 2018, the U.S.

Peripheral blood transcriptomic profiling indicates molecular mechanisms commonly regulated by binge-drinking and placebo-effects.

Molecular changes associated with alcohol consumption arise from complex interactions between pharmacological effects of alcohol, psychological/placebo context surrounding drinking, and other environmental and biological factors. The goal of this study was to tease apart molecular mechanisms regulated by pharmacological effects of alcohol - particularly at binge-drinking, from underlying placebo effects. Transcriptome-wide RNA-seq analyses were performed on peripheral blood samples collected from healthy heavy social drinkers (N=16) enrolled in a 12-day randomized, double-blind, cross-over human laboratory trial testing three alcohol doses: Placebo, moderate (0.

A Pilot Analysis of Circulating cfRNA Transcripts for the Detection of Lung Cancer.

Lung cancers are the leading cause of cancer-related deaths worldwide. Studies have shown that non-small cell lung cancer (NSCLC), which constitutes the majority of lung cancers, is significantly more responsive to early-stage interventions. However, the early stages are often asymptomatic, and current diagnostic methods are limited in their precision and safety.

Thematic analysis of the challenges and options for the Portfolio Committee on Health in reviewing the National Health Insurance Bill.

The Portfolio Committee on Health (PCH) obtained public input on the National Health Insurance Bill from a wide array of individuals and organisations between May and September 2021. The record of these submissions collated by the Parliamentary Monitoring Group provided the source material for this article. The concerns, suggestions and other issues raised by respondents were analysed to determine what challenges and options the PCH needs to take seriously as they prepare the Bill for Parliament.

The Nurse Empowerment Program for Nurses in Direct Care Positions.

Objective: An educational program including online generic and nursing-specific content was evaluated for self-assessed leadership skill outcomes.

Background: Leadership development for nurses in direct care positions has not received the same support as for nurses in formal leadership positions. Pandemic and workforce changes make it critical that leadership skills be built at all levels of nursing.

Integration of virtual platforms for enhanced conference experience: Data-based evidence from the Society of Interdisciplinary Placebo Studies 2021 conference.

Background: The Society of Interdisciplinary Placebo Studies (SIPS) was one of many organizations that hosted a virtual scientific conference in response to the COVID-19 pandemic restrictions. Retaining essential benefits of an in-person conference experience was a primary objective for the SIPS conference planning committee and guided the selection of a virtual platform on which to host the 2021 meeting. This article reports on the methods used to design and analyze an engaging, virtual scientific conference, along with the findings and implications for future meetings.

Validation of serotonin transporter mRNA as a quantitative biomarker of heavy drinking and its comparison to ethyl glucuronide/ethyl sulfate: A randomized, double-blind, crossover trial.

Background: The serotonin transporter (SERT) mRNA was previously reported to be a quantitative and pathophysiology-based biomarker of heavy drinking in 5HTTLPR:LL genotype-carriers treated with ondansetron. Here, we validated the potential use of SERT mRNA for quantitative prediction of recent alcohol consumption (in the absence of treatment) and compared it with the known biomarkers ethyl glucuronide (EtG) and ethyl sulfate (EtS).

Methods: Binge drinking men and women of European ancestry aged 21 to 65 years were enrolled in a 12-day, in-patient, randomized, double-blind, crossover study, where they were administered three beverage doses (placebo, 0.

The role of CCR5 in HIV-associated neurocognitive disorders.

While combination antiretroviral therapy (cART) has successfully increased the lifespan of individuals infected with HIV, a significant portion of this population remains affected by HIV-associated neurocognitive disorder (HAND). C-C chemokine receptor 5 (CCR5) has been well studied in immune response and as a co-receptor for HIV infection. HIV-infected (HIV) patients experienced mild to significant amelioration of cognitive function when treated with different CCR5 antagonists, including maraviroc and cenicriviroc.

The role of the Minister of Health in the National Health Insurance Bill: Challenges and options for the Portfolio Committee on Health.

The Portfolio Committee on Health (PCH) is responsible for obtaining public input on the National Health Insurance Bill, reviewing the Bill based on these inputs, and presenting the final Bill to the National Assembly. More than 130 individuals, organisations and institutions requested to make oral presentations, which commenced on 18 May 2021. Drawing on Parliamentary Monitoring Group meeting summaries and the presentations and submissions made by 82 respondents between 18 May and 10 September 2021, we examine governance concerns, especially in relation to the role and powers of the Minister of Health, and respondents' proposals for addressing them, and outline the challenges and options for the PCH in responding to the proposals.

Simple and statistically sound recommendations for analysing physical theories.

Physical theories that depend on many parameters or are tested against data from many different experiments pose unique challenges to statistical inference. Many models in particle physics, astrophysics and cosmology fall into one or both of these categories. These issues are often sidestepped with statistically unsound ad hoc methods, involving intersection of parameter intervals estimated by multiple experiments, and random or grid sampling of model parameters.

Examining the Dynamics of Belonging and Alienation in Higher Education Through Photovoice.

The higher education system globally is inherently inequitable. Discriminatory practices and oppressive power dynamics are particularly prevalent in the South African higher education landscape, which is characterized by a legacy of colonialism and apartheid. As a result, although students from a wide range of backgrounds are increasingly participating in higher education, many students who do not fit the dominant status quo question their belonging within these spaces.

Genomes of Novel Reveal Severely Curtailed Machineries for Predation and Cellular Differentiation.

Cultured are predominantly aerobic soil inhabitants, characterized by their highly coordinated predation and cellular differentiation capacities. Little is currently known regarding yet-uncultured from anaerobic, nonsoil habitats. We analyzed genomes representing one novel order (o__JAFGXQ01) and one novel family (f__JAFGIB01) in the from an anoxic freshwater spring (Zodletone Spring) in Oklahoma, USA.

Microglia regulation of synaptic plasticity and learning and memory.

Microglia are the resident macrophages of the central nervous system. Microglia possess varied morphologies and functions. Under normal physiological conditions, microglia mainly exist in a resting state and constantly monitor their microenvironment and survey neuronal and synaptic activity.