Sex-specific mechanisms of cerebral microvascular BK dysfunction in a mouse model of Alzheimer's disease.

Introduction: Cerebrovascular dysfunction occurs in Alzheimer's disease (AD), impairing hemodynamic regulation. Large conductance Ca-activated K channels (BK) regulate cerebrovascular reactivity and are impaired in AD. BK activity depends on intracellular Ca (Ca sparks) and nitro-oxidative post-translational modifications.

A Framework for the Use and Likelihood of Regulatory Acceptance of Single-Arm Trials.

Background: Single-arm clinical trials (SAT) are common in drug and biologic submissions for rare or life-threatening conditions, especially when no therapeutic options exist. External control arms (ECAs) improve interpretation of SATs but pose methodological and regulatory challenges.

Objective: Through narrative reviews and expert input, we developed a framework for considerations that might influence regulatory use and likelihood of regulatory acceptance of an SAT, identifying non-oncology first indication approvals as an area of interest.

Effects of multi-walled carbon nanotubes on message and Micro-RNA in human lung BEAS-2B cells.

Multi-walled Carbon nanotubes (MWCNTs) lack sufficient quality cytotoxicity, toxicity, genotoxicity and genomic data on which to make environmental and regulatory decisions. Therefore, we did a multidisciplinary study of 3 MWCNTs in human lung cells (BEAS-2B) with the following endpoints: cytotoxicity, DNA damage, reactive oxygen and nitrogen species, lipid peroxidation and mRNA and microRNA expression analyses. The MWCNTs were either unfunctionalized or functionalized with either -OH or -COOH.

Effects of multi-walled carbon nanotubes on gene and microRNA expression in human hepatocarcinoma HepG2 cells.

The usage of multi-walled carbon nanotubes (MWCNT) has increased exponentially in the past years, but, potential toxicity mechanisms are not clear. We studied the transcriptomic alterations induced by one multi-walled carbon nanotube (MWCNT) and its -OH and -COOH functionalized derivatives in human HepG2 cells. We showed that all three MWCNT treatments induced alterations in stress-related signaling pathways, inflammation-related signaling pathways, cholesterol synthesis pathways, proliferation-related pathways, senescence-related pathways and cancer-related pathways.

Skeletal muscle density performance for screening frailty in older adults with cancer and the impact of diabetes: The CARE Registry.

Introduction: Skeletal muscle density (SMD) measurements from imaging scans identify myosteatosis and could screen patients for geriatric assessment. We assessed SMD performance as a screening tool to identify older adults with cancer likely to be frail and who could benefit from in-depth assessment; we compared performance by sex and diabetes status.

Materials And Methods: We analyzed patients in the Cancer & Aging Resilience Evaluation (CARE) Registry.

An integrated microfluidic and fluorescence platform for probing in vivo neuropharmacology.

Neurotechnologies and genetic tools for dissecting neural circuit functions have advanced rapidly over the past decade, although the development of complementary pharmacological method-ologies has comparatively lagged. Understanding the precise pharmacological mechanisms of neuroactive compounds is critical for advancing basic neurobiology and neuropharmacology, as well as for developing more effective treatments for neurological and neuropsychiatric disorders. However, integrating modern tools for assessing neural activity in large-scale neural networks with spatially localized drug delivery remains a major challenge.

Optimization of Multiplex-PCR Technique To Determine Azf Deletions in infertility Male Patients.

Background: To optimize the multiplex polymerase chain reaction (M-PCR) technique to diagnose microdeletions of azoospermia factors (AZF) on the Y chromosome and initially apply the technique to diagnose male patients with sperm density less than 5×10 million sperm/mL was assigned to do a test to check for AZF microdeletions on the Y chromosome.

Methods: Based on the positive control samples which belong to male subjects who have had 2 healthy children without any assisted reproductive technologies, the M-PCR method was developed to detect simultaneously and accurately AZF microdeletions on 32 male patients with sperm densities below 5×10 million sperm/mL of semen at the Department of Biology and Medical Genetics - Vietnam Military Medical University.

Results: Successful optimization of the M-PCR technique including 7 reactions arranged according to each AZFabc region using 24 STS/gene on the Y chromosome.

On Creating Deeper Relationship Bonds: Felt Understanding Enhances Relationship Identification.

Relational experiences play a critical role in shaping how individuals see themselves. In four studies (=945) using person-perception, longitudinal, and experimental designs, we demonstrate that feeling understood changes individuals' self-concept by increasing the centrality of a specific relationship (relationship identification). Study 1 showed that participants perceived an individual to be more identified with their relationship when their partner was high (vs.

Tendon Transfer to Treat Radial Nerve Palsy Following COVID-19 Infection.

Multiple manifestations have been associated with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Among them are mononeuritis multiplex (MNM) and other neurological complications, whose connection to coronavirus disease 2019 (COVID-19) is still unclear. One of the most common sites of nerve injury is the radial nerve, which can be treated with both nerve or tendon transfer.

Holographic stimulation of opposing amygdala ensembles bidirectionally modulates valence-specific behavior via mutual inhibition.

The basolateral amygdala (BLA) is an evolutionarily conserved brain region, well known for valence processing. Despite this central role, the relationship between activity of BLA neuronal ensembles in response to appetitive and aversive stimuli and the subsequent expression of valence-specific behavior has remained elusive. Here, we leverage two-photon calcium imaging combined with single-cell holographic photostimulation through an endoscopic lens to demonstrate a direct causal role for opposing ensembles of BLA neurons in the control of oppositely valenced behavior in mice.

Geriatric Assessment Impairment Profiles and Mortality in Older Adults With Gastrointestinal Cancers: Latent Class Analysis of the CARE Registry.

Background: Many older adults with cancer have ≥2 impairments on geriatric assessment, which affects present and future frailty status, treatment tolerability, and outcomes. Our objective was to identify and describe distinct geriatric assessment impairment classes using latent class analysis (LCA) in older patients with gastrointestinal malignancies and assess 1-year mortality.

Methods: We used the Cancer & Aging Resilience Evaluation (CARE) Study, a registry of older adults (≥60 years) at University of Alabama at Birmingham.

Differential genomic effects of four nano-sized and one micro-sized CeO particles on HepG2 cells.

The objective of this research was to perform a genomics study of five cerium oxide particles, 4 nano and one micrometer-sized particles which have been studied previously by our group with respect to cytotoxicity, biochemistry and metabolomics. Human liver carcinoma HepG2 cells were exposed to between 0.3 to 300 ug/ml of CeO particles for 72 hours and then total RNA was harvested.

Love under lockdown: How changes in time with partner impacted stress and relationship outcomes during the COVID-19 pandemic.

With the onset of COVID-19, governments around much of the world implemented strict social distancing and stay-at-home orders that profoundly affected the amount of time many couples were spending together. In the present research, we examined whether perceptions of a change in time spent with a partner were associated with stress, and whether stress levels in turn predicted relationship commitment and satisfaction, both in the short term (Time 1) and longer term (Time 2; i.e.

Installing Quaternary Germanium Centers in Sila-Diamondoid Cores via Skeletal Isomerization.

This manuscript describes skeletal isomerization strategies to install one to four quaternary germanium atoms in the sila-adamantane core, in a cluster analogy to precision germanium doping in silicon-germanium alloys. The first strategy embodies an inorganic variant of single-atom skeletal editing, where we use a sila-Wagner-Meerwein bond shift cascade to exchange a peripheral Ge atom with a core Si atom. We can install up to four Ge atoms at the quaternary diamondoid centers based on controlling the SiGe stoichiometry of our precursor.

Epidemiology and clinical characteristics of interstitial lung disease in patients with rheumatoid arthritis from the JointMan database.

Interstitial lung disease (ILD) is a progressive fibrotic disease associated with rheumatoid arthritis (RA); real-world data for evaluating RA-associated ILD (RA-ILD) are limited. We evaluated prevalence, time to onset, clinical characteristics and prognostic factors in patients diagnosed with RA (n = 8963) in the Discus Analytics JointMan database (2009-2019) with and without ILD. ILD prevalence was 4.

Sex-specific mechanisms of cerebral microvascular BK dysfunction in a mouse model of Alzheimer's disease.

Background: Cerebral microvascular dysfunction and nitro-oxidative stress are present in patients with Alzheimer's disease (AD) and may contribute to disease progression and severity. Large conductance Ca -activated K channels (BK ) play an essential role in vasodilatory responses and maintenance of myogenic tone in resistance arteries. BK impairment can lead to microvascular dysfunction and hemodynamic deficits in the brain.

Suboptimal Clinical and Quality of Life Outcomes in Patients with Psoriasis Undertreated with Oral Therapies: International Physician and Patient Survey.

Introduction: Psoriasis is a chronic, inflammatory, immune-mediated disease. This study assessed the time at which patients switched from a conventional oral systemic treatment to a biologic therapy; patient clinical and quality of life (QoL) outcomes associated with oral systemic treatments; and the proportion of patients who persisted on oral therapy (nonswitchers), despite reported suboptimal clinical and QoL outcomes.

Methods: This data analysis used the Adelphi Real World Psoriasis Disease Specific Programme, a non-interventional, retrospective, cross-sectional survey conducted in the USA, France, Germany, and United Kingdom (August 2018-April 2019).

Effect of Early Amiodarone Use on Warfarin Sensitivity, Blood Product Use, and Bleeding in Patients With a Left Ventricular Assist Device.

Data are scarce on the effect of amiodarone on warfarin sensitivity and related outcomes after placement of a left ventricular assist device (VAD). This retrospective study compared 30-day outcomes between patients on amiodarone vs no amiodarone after VAD implant. After exclusions, 220 patients received amiodarone and 136 patients did not.

Real-world treatment patterns and healthcare costs in patients with psoriasis taking systemic oral or biologic therapies.

Background: Psoriasis is a chronic, immune-mediated, systemic inflammatory disorder associated with high costs. This study evaluated real-world treatment patterns and associated costs in patients in the United States with psoriasis initiating systemic oral or biologic treatments.

Methods: This retrospective cohort study used IBM (now Merative™) MarketScan Commercial and Medicare claims (1 January 2006-31 December 2019) to evaluate patterns of switching, discontinuation, and nonswitching in two cohorts of patients initiating oral or biologic systemic therapy.

The political is personal: The costs of daily politics.

Politics and its controversies have permeated everyday life, but the daily impact of politics on the general public is largely unknown. Here, we apply an affective science framework to understand how the public experiences daily politics in a two-part examination. We first used longitudinal, daily diary methods to track two samples of U.

Navigating race in a racially diverse environment: An experience sampling study on the daily use of race in conversations within Hawaii.

As the United States grows more racially diverse, it is imperative to understand whether being in a racially diverse environment impacts conversations about race. This study examines whether exposure to, and interactions with racially diverse others relate to whether people talk about race, the frequency with which people talk about race, and their comfort with doing so within the racially diverse context of Hawaii. We employed experience sampling to measure whether people had conversations about race, how frequently conversations about race occurred and their comfort in those conversations, and whether their exposure to and interactions with racially diverse others predicted these behaviors.

Immunogenicity of the BA.5 Bivalent mRNA Vaccine Boosters.

Waning immunity following mRNA vaccination and the emergence of SARS-CoV-2 variants has led to reduced mRNA vaccine efficacy against both symptomatic infection and severe disease. Bivalent mRNA boosters expressing the Omicron BA.5 and ancestral WA1/2020 Spike proteins have been developed and approved, because BA.

Dynamic changes in perfectionism dimensions and psychological distress among adolescents assessed before and during the COVID-19 pandemic.

This prospective longitudinal study evaluated changes in psychological distress among adolescents, pre-pandemic to intra-pandemic, the extent to which within-person and between-person differences in trait multidimensional perfectionism were associated with such changes, and the role of stress in explaining associations between perfectionism and psychological distress. Adolescents (N = 187; 80% female; 78% White, 7% Asian Canadian, 2% Indigenous Peoples in Canada, 2% Black or African Canadian, 2% Latin Canadian, or 9% Other; M  = 17.96 years) completed online surveys assessing perfectionism (i.

Social-Judgment Comparisons in Daily Life.

Comparison processes are critical to social judgments, yet little is known about how individuals compare people other than themselves in daily life (social-judgment comparisons). The present research employed a 7-day experience-sampling design ( = 93; = 3,960) with end-of-week and 6-month follow-ups, to examine how individuals make social-judgment comparisons in daily life as well as the cumulative impact of these comparisons over time. Participants compared close (vs.