Implementation and Evaluation of a Virtual Skills-Based Dementia Caregiver Group Intervention within a VA Setting: A Pilot Study.

Objectives: This study sought to design, implement, and evaluate a 6-week skills-based telehealth group for dementia caregivers within a VA setting.

Methods: The protocol was designed based on a CBT skill-building approach and was evaluated using the four levels of evaluation developed by Kirkpatrick (1998). Eight spousal caregivers of individuals with MCI or dementia participated in the pilot group within a VA geriatric clinic.

US National Estimates of Contemporary Mortality Rates in Patients With Ulcerative Colitis Undergoing Colectomy.

Introduction: Despite a growing armamentarium of medical therapies for ulcerative colitis, colectomy remains an important therapeutic option. To better inform shared decision-making about surgery, we estimated the contemporary risk of mortality after colectomy.

Methods: Mortality rates were estimated using the National Inpatient Sample (2016-2020).

Use of tRNA gene barriers improves stability of transgene expression in CHO cells.

Instability of transgene expression is a major challenge for the biopharmaceutical industry, which can impact yields and regulatory approval. Some tRNA genes (tDNAs) can resist epigenetic silencing, the principal mechanism of expression instability, and protect adjacent genes against the spread of repressive heterochromatin. We have taken two naturally occurring clusters of human tDNAs and tested their ability to reduce epigenetic silencing of transgenes integrated into the genome of Chinese hamster ovary (CHO) cells.

Graded Multidimensional Clinical and Radiologic Variation in Patients With Alzheimer Disease and Posterior Cortical Atrophy.

Background And Objectives: Alzheimer disease (AD) spans heterogeneous typical and atypical phenotypes. Posterior cortical atrophy (PCA) is a striking example, characterized by prominent impairment in visual and other posterior functions in contrast to typical, amnestic AD. The primary study objective was to establish how the similarities and differences of cognition and brain volumes within AD and PCA (and by extension other AD variants) can be conceptualized as systematic variations across a transdiagnostic, graded multidimensional space.

Strategies for Accelerated Drug Development: An Industry Perspective Based on an IQ Consortium Survey of CMC Considerations.

Over the past decade, there has been an increase in accelerated drug development with successful regulatory approval that has provided rapid access of novel medicines to patients world-wide. This has created the opportunity for the pharmaceutical industry to continuously improve the process of quickly bringing new medicines to patients with unmet medical needs. This can be accomplished through sharing the learnings and advancements in drug development, enhancing regulatory interactions, and collaborating with academics on developing the underlying science to reduce drug development timelines.

Incremental induction of NMDAR-STP and NMDAR-LTP in the CA1 area of ventral hippocampal slices relies on graded activation of discrete NMDA receptors.

-methyl-d-aspartate receptor (NMDAR)-dependent short- and long-term types of potentiation (STP and LTP, respectively) are frequently studied in the CA1 area of dorsal hippocampal slices (DHS). Far less is known about the NMDAR dependence of STP and LTP in ventral hippocampal slices (VHS), where both types of potentiation are smaller in magnitude than in the DHS. Here, we first briefly review our knowledge about the NMDAR dependence of STP and LTP and some other forms of synaptic plasticity.

Promiscuous involvement of metabotropic glutamate receptors in the storage of -methyl-d-aspartate receptor-dependent short-term potentiation.

Short- and long-term forms of -methyl-d-aspartate receptor (NMDAR)-dependent potentiation (most commonly termed short-term potentiation (STP) and long-term potentiation (LTP)) are co-induced in hippocampal slices by theta-burst stimulation, which mimics naturally occurring patterns of neuronal activity. While NMDAR-dependent LTP (NMDAR-LTP) is said to be the cellular correlate of long-term memory storage, NMDAR-dependent STP (NMDAR-STP) is thought to underlie the encoding of shorter-lasting memories. The mechanisms of NMDAR-LTP have been researched much more extensively than those of NMDAR-STP, which is characterized by its extreme stimulation dependence.

Human mesenchymal stromal cells inhibit replication in clinically relevant models of lung infection.

Introduction: Novel therapeutic strategies are urgently needed for complex pulmonary disease (MAC-PD). Human mesenchymal stromal cells (MSCs) can directly inhibit MAC growth, but their effect on intracellular bacilli is unknown. We investigated the ability of human MSCs to reduce bacterial replication and inflammation in MAC-infected macrophages and in a murine model of MAC-PD.

Ageing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination.

Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however, its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood.

The neural substrates of transdiagnostic cognitive-linguistic heterogeneity in primary progressive aphasia.

Background: Clinical variants of primary progressive aphasia (PPA) are diagnosed based on characteristic patterns of language deficits, supported by corresponding neural changes on brain imaging. However, there is (i) considerable phenotypic variability within and between each diagnostic category with partially overlapping profiles of language performance between variants and (ii) accompanying non-linguistic cognitive impairments that may be independent of aphasia magnitude and disease severity. The neurobiological basis of this cognitive-linguistic heterogeneity remains unclear.

Association Between Insurer Connectivity in Appalachian Population Health Networks and Preventable Hospitalizations: Evidence from Kentucky.

Introduction: Addressing complex health and social needs requires cross-sector collaboration to deliver medical, social, and population health services at the community level. Capacity in community health and social services networks may be constrained in regions like Appalachia due to the combined effects of rurality and persistently poor health and social outcomes. One way that cross-sector networks serving low-resource communities can expand their capacity is by engaging partners, like health insurers, who can leverage resources from outside the local area.

Patient Engagement in Patient Portals in Appalachia v. Surrounding U.S. Census Regions: An Analysis of HINTS (Health Information National Trends Survey) Data, 2017-2020.

Introduction: Those living in the Appalachian Region face a greater number of significant health disparities than residents of other areas of the U.S. Patient portals can decrease disparities, increase health literacy, and improve health outcomes.

Validation of a new optical diagnosis training module to improve dysplasia characterization in inflammatory bowel disease: a multicenter international study.

Background And Aims: Inflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aimed to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPtical diagnosis Training to Improve dysplasia Characterization in Inflammatory Bowel Disease (OPTIC-IBD).

Bedside Intestinal Ultrasound Performed in an Inflammatory Bowel Disease Urgent Assessment Clinic Improves Clinical Decision-Making and Resource Utilization.

Background: Patients with inflammatory bowel disease (IBD) require accessible, timely, and noninvasive strategies to monitor disease. The aim was to assess the integration of intestinal ultrasound (IUS) on decision-making and endoscopy utilization in a standardized care pathway.

Methods: This prospective, multicenter, international, observational cohort study included patients seen within a centralized model for IBD care was conducted during the COVID pandemic.

Optoα1AR activation in astrocytes modulates basal hippocampal synaptic excitation and inhibition in a stimulation-specific manner.

Astrocytes play active roles at synapses and can monitor, respond, and adapt to local synaptic activity. While there is abundant evidence that astrocytes modulate excitatory transmission in the hippocampus, evidence for astrocytic modulation of hippocampal synaptic inhibition remains more limited. Furthermore, to better investigate roles for astrocytes in modulating synaptic transmission, more tools that can selectively activate native G protein signaling pathways in astrocytes with both spatial and temporal precision are needed.

Biologically Relevant Murine Models of Chronic Respiratory Infection.

is an opportunistic pathogen and the leading cause of infection in patients with cystic fibrosis (CF). The ability of to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by , with the bead agar model being the most widely used.

The Achromobacter type 3 secretion system drives pyroptosis and immunopathology via independent activation of NLRC4 and NLRP3 inflammasomes.

How the opportunistic Gram-negative pathogens of the genus Achromobacter interact with the innate immune system is poorly understood. Using three Achromobacter clinical isolates from two species, we show that the type 3 secretion system (T3SS) is required to induce cell death in human macrophages by inflammasome-dependent pyroptosis. Macrophages deficient in the inflammasome sensors NLRC4 or NLRP3 undergo pyroptosis upon bacterial internalization, but those deficient in both NLRC4 and NLRP3 do not, suggesting either sensor mediates pyroptosis in a T3SS-dependent manner.

Implementation of a risk-stratified, guideline-based clinical pathway of care to improve health outcomes following whiplash injury (Whiplash ImPaCT): a multicentre, randomized, controlled trial.

Current pathways of care for whiplash follow a "stepped care model," result in modest treatment outcomes and fail to offer efficient management solutions. This study aimed to evaluate the effectiveness of a risk-stratified clinical pathway of care (CPC) compared with usual care (UC) in people with acute whiplash. We conducted a multicentre, 2-arm, parallel, randomised, controlled trial in primary care in Australia.

Adverse Events and Serological Responses After SARS-CoV-2 Vaccination in Individuals With Inflammatory Bowel Disease.

Introduction: We determined adverse events after 4 doses of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine in those with inflammatory bowel disease (IBD), associations between antibodies and injection site reactions (ISR), and risk of IBD flare.

Methods: Individuals with IBD were interviewed for adverse events to SARS-CoV-2 vaccine. Multivariable linear regression assessed the association between antibody titers and ISR.

The association of negative mood with automatic and effortful facial expression mimicry.

The natural process of mimicking the facial expressions of others is well established, as are the deficits in this reflexive behavior for individuals with clinical disorders such as depression. This study examines the extent of this deficit in non-clinical individuals with high transient negative mood, and whether it extends to both automatic and effortful emotion expression behavior. One hundred and thirty-six participants were shown happy, sad, and neutral faces, while electromyography (EMG) recorded facial muscle responses.

Weighted Gene Co-Expression Network Analysis Identifies a Functional Guild and Metabolite Cluster Mediating the Relationship between Mucosal Inflammation and Adherence to the Mediterranean Diet in Ulcerative Colitis.

Diet influences the pathogenesis and clinical course of inflammatory bowel disease (IBD). The Mediterranean diet (MD) is linked to reductions in inflammatory biomarkers and alterations in microbial taxa and metabolites associated with health. We aimed to identify features of the gut microbiome that mediate the relationship between the MD and fecal calprotectin (FCP) in ulcerative colitis (UC).

Nutritional interventions in adult fibrostenotic Crohn's disease: A systematic review.

Background: Management of Crohn's disease (CD) using dietary interventions has become an area of increased research interest. There is a lack of specific research exploring if diet and nutrition interventions are beneficial in patients with strictures, as current dietary recommendations in fibrostenotic CD are often based on clinical judgment. The aim of this systematic review was to assess the impact of dietary interventions in fibrostenotic CD on medical and surgical outcomes.

Development of the Drug Product Formulation of the Bevacizumab Biosimilar PF-06439535 (Bevacizumab-bvzr).

Background: PF-06439535 (bevacizumab-bvzr; Zirabev) is a biosimilar of bevacizumab reference product (RP; Avastin). This study describes the formulation development for PF-06439535.

Methods: PF-06439535 was formulated in several buffers and stored for 12 weeks at 40 °C to determine the optimal buffer and pH under stressed conditions.

A clinical review of mpox for the Aotearoa New Zealand clinician.

The World Health Organization declared mpox (formerly monkeypox) a Public Health Emergency of International Concern in July 2022. Aotearoa New Zealand has reported cases of mpox since July, with reports of locally acquired cases since October 2022. The 2022 global mpox outbreak highlights many features of the illness not previously described, including at-risk populations, mode of transmission, atypical clinical features, and complications.

Innovative Care for Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Use of Bedside Intestinal Ultrasound to Optimize Management.

Background: The COVID-19 pandemic caused by SARS-CoV-2 has reduced access to endoscopy and imaging. Safe alternatives, available at the bedside, are needed for accurate, non-invasive strategies to evaluate disease activity. The aim of this study is to establish the impact of clinic-based bedside intestinal ultrasound (IUS) on decision making, reduction in reliance on endoscopy and short-term healthcare utilization.