Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the foremost cause of global dementia, also characterized by retinal changes involving Aβ, hyperphosphorylated-tau (p-tau), neuronal degeneration, and tissue atrophy. Mitochondrial-driven reactive oxygen species (ROS) production, linked to synaptic dysfunction, is common to various neurodegenerative conditions, including AD. Despite synaptic dysfunction being an early predictor of cognitive decline in AD, its occurrence in the AD retina is unexplored.

Basic Science and Pathogenesis.

Background: This study identifies and quantifies diverse pathological tau forms in the retina at both early and advanced stages of Alzheimer's disease (AD) and assesses their correlation with disease status. In the pathogenesis of AD, the tau protein undergoes post-translational modifications, including hyperphosphorylation (p-tau). As the disease progresses, pathological tau can propagate as oligomers, aggregate into fibrils, and paired helical filaments (PHF), and ultimately form intraneuronal neurofibrillary tangles (NFTs).

Intractable conflicts over end-of-life decisions: A descriptive and ethical analysis of French case-law.

Context: In European and Anglo-Saxon countries, life-sustaining treatment (LST) limitation decisions precede more than 80% of ICU deaths. However, there is now increasing evidence of disagreement and conflict between clinical teams and family members over LST limitation decisions. In some cases, these conflicts are brought to the courts.

Physician vs. AI-generated messages in urology: evaluation of accuracy, completeness, and preference by patients and physicians.

Purpose: To evaluate the accuracy, comprehensiveness, empathetic tone, and patient preference for AI and urologist responses to patient messages concerning common BPH questions across phases of care.

Methods: Cross-sectional study evaluating responses to 20 BPH-related questions generated by 2 AI chatbots and 4 urologists in a simulated clinical messaging environment without direct patient interaction. Accuracy, completeness, and empathetic tone of responses assessed by experts using Likert scales, and preferences and perceptions of authorship (chatbot vs.

Triangulating evidence from the GALENOS living systematic review on trace amine-associated receptor 1 (TAAR1) agonists in psychosis.

Background: Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.

Aims: To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.

Method: This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis).

Analysis of the progression of cervical cancer in a low-and-middle-income country: From pre-malignancy to invasive disease.

To better understand cervical cancer progression, we analyzed RNA from 262 biopsies from women referred for colposcopy. We determined the HPV type and analyzed the expression of 51 genes. HPV31 was significantly more prevalent in precancer than stage 1 cancer and invasive cancer (p < 0.

Evaluating the association between the introduction of mandatory calorie labelling and energy consumed using observational data from the out-of-home food sector in England.

In April 2022, mandatory kilocalorie (kcal) labelling in the out-of-home food sector was introduced as a policy to reduce obesity in England. Here we examined whether the implementation of this policy was associated with a consumer behaviour change. Large out-of-home food sector outlets subject to kcal labelling legislation were visited pre- and post-implementation, and customer exit surveys were conducted with 6,578 customers from 330 outlets.

LNC-ing Genetics in Mitochondrial Disease.

Primary mitochondrial disease (MD) is a group of rare genetic diseases reported to have a prevalence of 1:5000 and is currently without a cure. This group of diseases includes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), Leber's hereditary optic neuropathy (LHON), Leigh syndrome (LS), Kearns-Sayre syndrome (KSS), and myoclonic epilepsy and ragged-red fiber disease (MERRF). Additionally, secondary mitochondrial dysfunction has been implicated in the most common current causes of mortality and morbidity, including cardiovascular disease (CVD) and cancer.

Financial Toxicity in High-Grade Glioma Resection: A Retrospective Analysis.

Background: Despite its association with lower survival rates among patients in various disease states, financial toxicity is often overlooked in health care. The aims of our study are to elucidate the effect of financial toxicity on the care of glioma patients.

Methods: We retrospectively evaluated clinical information of 130 patients with newly diagnosed glioblastoma from a single institution between 2014 and 2021.

The Road Beyond Academic Pharmacy Leadership.

Individuals in positions of leadership, of which there are a myriad of these positions in pharmacy education, will experience a transition from this position in most situations. This transition from a leadership position, be it voluntary or involuntary, can be challenging time. It can leave an individual wondering how to either channel their passion to new areas or recognize a new passion for future opportunities.

Molecular signatures of cortical expansion in the human foetal brain.

The third trimester of human gestation is characterised by rapid increases in brain volume and cortical surface area. Recent studies have revealed a remarkable molecular diversity across the prenatal cortex but little is known about how this diversity translates into the differential rates of cortical expansion observed during gestation. We present a digital resource, μBrain, to facilitate knowledge translation between molecular and anatomical descriptions of the prenatal brain.

Using heart rate data from wrist worn activity trackers to define thresholds for moderate to vigorous physical activity in children and young people with cystic fibrosis.

Background: Children and young people with cystic fibrosis (CYPwCF) are encouraged to do an average of 60 min of moderate-to-vigorous physical activity (MVPA) daily. However, there are no agreed heart rate (HR) thresholds for defining MVPA, so it is difficult to ascertain whether these targets are actually achieved. Wearable activity trackers enable continuous monitoring of fitness-related measures such as HR and could be used to measure duration and intensity of habitual MVPA.

An End-of-Life Ethics Consult in the ICU: Who Has the Final Say-The Patient or the Family?

A 72-year-old man with metastatic pancreatic cancer was admitted to the ICU with increased oxygen demand and confusion, likely related to pulmonary metastases. In the presence of his son, the health care agent, and the team, the patient requested to be do-not-attempt-resuscitation (DNR) and do-not-intubate (DNI) before losing decision-making capacity. When the patient's brother and another son heard of the code status change, they insisted on a return to Full Code.

Identifying cognitive, affective, and developmental mechanisms linking threat and deprivation with adolescent psychopathology.

Background: The mechanisms linking early-life adversity with psychopathology over the life-course are complex. In this prospective study, we collectively examined cognitive, affective, and developmental mediators previously found to individually link childhood threat and deprivation experiences to adolescent psychopathology to identify the most potent mechanisms.

Methods: Data came from a community sample of 227 children (mean child age 11.

Preclinical models for evaluating psychedelics in the treatment of major depressive disorder.

Psychedelic drugs have seen a resurgence in interest as a next generation of psychiatric medicines with potential as rapid-acting antidepressants (RAADs). Despite promising early clinical trials, the mechanisms which underlie the effects of psychedelics are poorly understood. For example, key questions such as whether antidepressant and psychedelic effects involve related or independent mechanisms are unresolved.

Development and Implementation of a Multicenter Registry for Resuscitation-Focused Transesophageal Echocardiography.

Study Objective: To evaluate the clinical effect, safety, and clinical outcomes of focused transesophageal echocardiography (TEE) in the evaluation of critically ill patients in the emergency department (ED) and ICUs.

Methods: We established a prospective, multicenter, observational registry involving adult critically ill patients in whom focused TEE was performed for evaluation of out-of-hospital cardiac arrest (OHCA), inhospital cardiac arrest, evaluation of undifferentiated shock, hemodynamic monitoring, and/or procedural guidance in the ED, ICU, or operating room setting. The primary objective of the current investigation was to evaluate the clinical influence and safety of focused, point-of-care TEE in critically ill patients.

Spatial patterns of rural opioid-related hospital emergency department visits: A machine learning analysis.

As opioid-related overdose emergency department visits continue to rise in the United States, there is a need to understand the location and magnitude of the crisis, especially in at-risk rural areas. We analyzed sets of ZIP code level electronic health records for emergency department visits from 6 hospitals for two rural regions of Maryland with higher opioid-related overdose rates. Analysis of the demographics of visits found Black or African American emergency department visits in both rural regions were higher than the proportion of their population per region.

Ultraprocessed food (UPF), health, and mechanistic uncertainty: What should we be advising the public to do about UPFs?

In this perspective, we discuss why current mechanistic uncertainty on ultraprocessed foods (UPFs) and health acts as a major challenge to providing informed dietary guidelines and public advice on UPFs. Based on the balance of current evidence, we do not believe it is appropriate to be advising consumers to avoid all UPFs and we await further evidence to inform consumer guidance on the need to limit consumption of specifics foods based on their degree or type of processing.