Mutant huntingtin protein decreases with CAG repeat expansion: implications for therapeutics and bioassays.

Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in the huntingtin (HTT) protein. The mutant CAG repeat is unstable and expands in specific brain cells and peripheral tissues throughout life. Genes involved in the DNA mismatch repair pathways, known to act on expansion, have been identified as genetic modifiers; therefore, it is the rate of somatic CAG repeat expansion that drives the age of onset and rate of disease progression.

Concurrent Zoster Sine Herpete and Hepatosplenic Fungal Infection in a Cancer Patient: A Case Report.

In patients undergoing treatment for hematological cancers, like hairy cell leukemia (HCL), appropriate management of infections is of utmost importance. This paper describes the successful treatment of an HCL patient who had both visceral zoster sine herpete (ZSH) and hepatosplenic fungal infection, possibly caused by . To our knowledge, this is the first such case to appear in the literature, as these are rare conditions associated with states of immunosuppression, similar to those observed in hematological malignancy.

Impact of an Inpatient Family Medicine Exposure: Changing Student Perception.

Introduction: Currently there is a primary care physician shortage in the United States, and this shortage is expected to worsen into the foreseeable future. In 2023, only 7.5 % of US allopathic graduates entered family medicine (FM) residencies.

The opioid industry's use of scientific evidence to advance claims about prescription opioid safety and effectiveness.

It is widely recognized that pharmaceutical marketing contributed to the ongoing US opioid epidemic, but less is understood about how the opioid industry used scientific evidence to generate product demand, shape opioid regulation, and change clinician behavior. In this qualitative study, we characterize select scientific articles used by industry to support safety and effectiveness claims and use a novel database, the Opioid Industry Documents Archive, to determine notable elements of industry and non-industry documents citing the scientific articles to advance each claim. We found that 15 scientific articles were collectively mentioned in 3666 documents supporting 5 common, inaccurate claims: opioids are effective for treatment of chronic, non-cancer pain; opioids are "rarely" addictive; "pseudo-addiction" is due to inadequate pain management; no opioid dose is too high; and screening tools can identify those at risk of developing addiction.

Blurring Boundaries: A Proposed Research Agenda for Ethical, Legal, Social, and Historical Studies at the Intersection of Infectious and Genetic Disease.

Contemporary understanding of the mechanisms of disease increasingly points to examples of "genetic diseases" with an infectious component and of "infectious diseases" with a genetic component. Such blurred boundaries generate ethical, legal, and social issues and highlight historical contexts that must be examined when incorporating host genomic information into the prevention, outbreak control, and treatment of infectious diseases.

Strengthening community capacity to address trauma through a Community Ambassador Network.

Introduction: Community ambassadors (CAs) are advocates that build trust with communities on behalf of service systems and facilitate access to resources. Whether and how CAs can support community engagement within a large initiative to build capacity to address the impact of trauma is unclear. This study explores how a Community Ambassador Network supported community engagement with "Innovations 2 Initiative" (INN 2), a 5-year initiative that addressed trauma across nine communities in Los Angeles County.

Health Care Workers' Trust in Leadership: Why It Matters and How Leaders Can Build It.

Background: Rebuilding patient trust in the US health care system has received considerable attention recently, but there has been little focus on health care workers' (HCWs) trust in the leaders of health care delivery organizations. This study explores (1) the professional impact on HCWs of trusting the leaders of the organizations where they work and (2) the leadership actions that build HCWs' trust.

Methods: The authors examined these questions using a survey that was crowdsourced to 353 HCWs through social media posts and e-mails from national health organizations.

growth arrest during type-III secretion system expression is associated with altered ribosomal protein expression and decreased gentamicin susceptibility.

It has been long appreciated that expression of the type-III secretion system (T3SS) in culture is associated with growth arrest. Here we sought to understand whether this impacts expression of ribosomal protein genes, which were among the most highly abundant transcripts in exponential phase based on RNA-seq analysis. To visualize changes in ribosomal protein expression, we generated a fluorescent transcriptional reporter with the promoter upstream of /S10 fused to a destabilized variant.

Protozoan Infections in Cancer Patients: A Case Series.

Intestinal parasitic infections can cause significant morbidity and mortality in individuals with cancer. Despite this, they are often self-limiting in healthy individuals. is an anaerobic parasite that causes amebiasis in infected individuals.

Emphysematous Pyelonephritis in Cancer Patients: A Case Report With a Literature Review.

Emphysematous pyelonephritis (EPN) is a severe necrotising infection of the renal parenchyma which is rarely reported in cancer patients. We present a case of a 92-year-old man with urothelial carcinoma of the bladder who developed EPN after resection of the tumour. Septic shock developed and blood cultures grew extended-spectrum beta-lactamase (ESBL)  Because of renal function decline with hematuria a non-contrast CT scan of the abdomen showed gas in the kidney and surrounding area consistent with EPN.

Diagnosis and Treatment Challenges of in Immunocompromised Patients: A Case Study in a Neutropenic AML Patient.

Although fungal infections causing intestinal perforation and necrosis are rare, they can be particularly dangerous in immunosuppressed patients, often leading to increased mortality rates and poor prognoses. Candida species are typically surface fungi, but in patients with compromised immune systems, they can invade the small intestine and cause angioinvasive infections. A case study involving a 30-year-old female with acute myeloid leukemia (AML) illustrates this phenomenon.

HiLo microscopy with caustic illumination.

HiLo microscopy is an optical sectioning structured illumination microscopy technique based on computationally combining two images: one with uniform illumination and the other with structured illumination. The most widely used structured illumination in HiLo microscopy is random speckle patterns, due to their simplicity and resilience to tissue scattering. Here, we present a novel HiLo microscopy strategy based on random patterns.

Invasive phaeohyphomycosis co-infection with Alternaria spp. and Curvularia spp. in a neutropenic host.

Phaeohyphomycoses are infections caused by dark-walled dematiaceous fungi. Alternaria and Curvularia are two genera of dematiaceous molds known to cause invasive fungal rhinosinusitis, particularly in immunocompromised patients. Co-infection with two dematiaceous fungi is rarely reported in the literature.

Continued decline in sublethal effects of Bt toxins on Helicoverpa zea (Lepidoptera: Noctuidae) in field corn.

The majority of field corn, Zea mays L., in the southeastern United States has been genetically engineered to express insecticidal toxins produced by the soil bacterium, Bacillus thuringiensis (Bt). Field corn is the most important mid-season host for corn earworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae), which has developed resistance to all Cry toxins in Bt corn.

Breakthrough Pneumocystis jirovecii Pneumonia in an Allogeneic Hematopoietic Stem Cell Transplant Recipient.

pneumonia (PCP), which is currently referred to as  pneumonia, is an opportunistic fungal infection that commonly affects immunocompromised patients, and it is potentially fatal. Individuals at risk include those whose host immunity has been altered by underlying disease states, such as HIV and cancer patients, as well as transplant recipients and those taking immunosuppressive medications. Here, we present a case of a breakthrough PCP infection of an adult allogeneic hematopoietic stem cell transplant patient who was infected despite prophylaxis with inhaled pentamidine.

National Greenhouse Gas Emission Reduction Potential from Adopting Anaerobic Digestion on Large-Scale Dairy Farms in the United States.

Waste-to-energy systems can provide a functional demonstration of the economic and environmental benefits of circularity, innovation, and reimagining existing systems. This study offers a robust quantification of the greenhouse gas (GHG) emission reduction potential of the adoption of anaerobic digestion (AD) technology on applicable large-scale dairy farms in the contiguous United States. GHG reduction estimates were developed through a robust life cycle modeling framework paired with sensitivity and uncertainty analyses.

EventLFM: event camera integrated Fourier light field microscopy for ultrafast 3D imaging.

Ultrafast 3D imaging is indispensable for visualizing complex and dynamic biological processes. Conventional scanning-based techniques necessitate an inherent trade-off between acquisition speed and space-bandwidth product (SBP). Emerging single-shot 3D wide-field techniques offer a promising alternative but are bottlenecked by the synchronous readout constraints of conventional CMOS systems, thus restricting data throughput to maintain high SBP at limited frame rates.

What Are They Thinking? Exploring College Students' Mental Processing and Decision-Making About COVID-19 (Mis)Information on Social Media.

More and more, people are abandoning the active pursuit of news, assuming instead that important information will be pushed to them via their social media networks. This approach to news makes people susceptible to the vast amounts of misinformation online, yet research on the effects of this kind of engagement is mixed. More research is needed on technology incidental learning effects, defined as changes in knowledge, attitudes, beliefs, and behaviors as a result of being exposed to information while pursuing goals other than learning (e.

Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer's Disease and Multiple Sclerosis.

Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist antibodies in multiple mixed-sex mouse models of Alzheimer's disease (AD) pathology and remyelination. Receptor activation and downstream signaling are explored in vitro, and active dose ranges are determined in vivo based on pharmacodynamic responses from microglia.

Allosteric coupling asymmetry mediates paradoxical activation of BRAF by type II inhibitors.

The type II class of RAF inhibitors currently in clinical trials paradoxically activate BRAF at subsaturating concentrations. Activation is mediated by induction of BRAF dimers, but why activation rather than inhibition occurs remains unclear. Using biophysical methods tracking BRAF dimerization and conformation, we built an allosteric model of inhibitor-induced dimerization that resolves the allosteric contributions of inhibitor binding to the two active sites of the dimer, revealing key differences between type I and type II RAF inhibitors.

Temporal Development of Depression and Anxiety in a Large Facial Palsy Cohort.

Introduction: Diagnosis with facial palsy (FP) has been linked to increased psychosocial distress and communication disorders, but limited data exist on the temporal development of depression and anxiety after diagnosis. In a large cohort of FP patients, we characterize the rates of depression and anxiety at several timepoints post-FP diagnosis.

Methods: A de-identified database of all FP patients who presented to a single healthcare system over 22 years was created using Epic SlicerDicer.