Welfare Status in Dairy Cows during Confined and Grazing Periods in the North American Pacific Northwest using Blood Parameters and Visual Assessments.

Grazing is usually associated with higher well-being in dairy cows. However, current research on the welfare of grazing cows lacks validation via blood profiling. We monitored four dairy farms that seasonally graze in the temperate North American Pacific Northwest, USA, to address this gap.

Readiness of primary healthcare and community markets for joint delivery of cardiovascular disease prevention services in Kenya: an observational feasibility study of Health Kiosks in Markets (HEKIMA).

Objectives: The increasing burden of cardiovascular diseases (CVDs) in Kenya threatens its healthcare system. There is a need for innovative models that improve equitable access to CVD prevention services. Community markets are social establishments with untapped potential to promote public health.

Microfluidic Platform for Generating and Releasing Patient-Derived Cancer Organoids with Diverse Shapes: Insight into Shape-Dependent Tumor Growth.

Multicellular spheroids and patient-derived organoids find many applications in fundamental research, drug discovery, and regenerative medicine. Advances in the understanding and recapitulation of organ functionality and disease development require the generation of complex organoid models, including organoids with diverse morphologies. Microfluidics-based cell culture platforms enable time-efficient confined organoid generation.

Readiness of primary care centres for a community-based intervention to prevent and control noncommunicable diseases in the Caribbean: A participatory, mixed-methods study.

Introduction: Epidemiological transition to NCDs is a challenge for fragile health systems in the Caribbean. The Congregations Taking Action against NCDs (CONTACT) Study intervention proposes that trained health advocates (HAs) from places of worship (PoWs), supervised by nurses at nearby primary healthcare centres (PHCs), could facilitate access to primary care among vulnerable communities. Drawing on participatory and systems thinking, we explored the capacity of local PHCs in three Caribbean countries to support this intervention.

Current obstetric outcomes in Jamaican women with sickle hemoglobinopathy - a balance of risks for aspirin?

Objectives: Sickle cell disease (SCD) occurs in 2.8 % of our Jamaican antenatal population with homozygous HbSS being most associated with adverse maternal and perinatal outcomes.

Methods: A retrospective comparative analysis of HbSS, HbSC and HbSβThal pregnancy outcomes at the University Hospital of the West Indies (UHWI) between January 2012 and December 2022 was conducted.

Topoisomerase 1 Inhibition in MYC-Driven Cancer Promotes Aberrant R-Loop Accumulation to Induce Synthetic Lethality.

Unlabelled: MYC is a central regulator of gene transcription and is frequently dysregulated in human cancers. As targeting MYC directly is challenging, an alternative strategy is to identify specific proteins or processes required for MYC to function as a potent cancer driver that can be targeted to result in synthetic lethality. To identify potential targets in MYC-driven cancers, we performed a genome-wide CRISPR knockout screen using an isogenic pair of breast cancer cell lines in which MYC dysregulation is the switch from benign to transformed tumor growth.

Feeding spent hemp biomass to lactating dairy cows: Effects on performance, milk components and quality, blood parameters, and nitrogen metabolism.

The legalization of industrial hemp by the 2018 Farm Bill in the United States has driven a sharp increase in its cultivation, including for cannabinoid extraction. Spent hemp biomass (SHB), produced from the extraction of cannabinoids, can potentially be used as feed for dairy cows; however, it is still illegal to do so in the United States, according to the US Food and Drug Administration Center for Veterinary Medicine, due to the presence of cannabinoids and the lack of data on the effect on animals. To assess the safety of this byproduct as feed for dairy cows, late-lactation Jersey cows (245 ± 37 d in milk; 483 ± 38 kg body weight; 10 multiparous and 8 primiparous) received a basal total mixed ration (TMR) diet plus 13% alfalfa pellet (CON) or 13% pelleted SHB for 4 wk (intervention period [IP]) followed by 4 wk of withdrawal period (WP), where all cows received only the basal TMR during WP.

Contextually appropriate communication strategies for COVID-19 prevention in Kenya border regions: evidence from a mixed methods observational study in Busia and Mandera counties.

Objectives: Kenya has long and porous borders with its neighbouring countries. These regions, predominantly inhabited by highly mobile rural communities with strong cross-border cultural ties, present major challenges in managing movement of people and COVID-19 preventive measures. Our study sought to assess knowledge of COVID-19 prevention behaviours, how these varied by socioeconomic (SEC) factors and the challenges of engagement and implementation, in two border counties of Kenya.

Associations between air pollutants and blood pressure in an ethnically diverse cohort of adolescents in London, England.

Longitudinal evidence on the association between air pollution and blood pressure (BP) in adolescence is scarce. We explored this association in an ethnically diverse cohort of schoolchildren. Sex-stratified, linear random-effects modelling was used to examine how modelled residential exposure to annual average nitrogen dioxide (NO2), particulate matter (PM2.

Computational pharmacogenomic screen identifies drugs that potentiate the anti-breast cancer activity of statins.

Statins, a family of FDA-approved cholesterol-lowering drugs that inhibit the rate-limiting enzyme of the mevalonate metabolic pathway, have demonstrated anticancer activity. Evidence shows that dipyridamole potentiates statin-induced cancer cell death by blocking a restorative feedback loop triggered by statin treatment. Leveraging this knowledge, we develop an integrative pharmacogenomics pipeline to identify compounds similar to dipyridamole at the level of drug structure, cell sensitivity and molecular perturbation.

Association of Ambient Air Pollution with Blood Pressure in Adolescence: A Systematic-review and Meta-analysis.

We systematically reviewed the association of ambient air pollution with blood pressure (BP) as a primary outcome in adolescents (10-19 years). Five databases (Ovid Medline, Ovid Embase, Web of Science, The Cochrane Library, and LILACS) were searched for relevant articles published up to August 2022. Meta-analyses were conducted using STATA v17 (Protocol - OSF Registries https://doi.

The effects of Aronia berry (poly)phenol supplementation on arterial function and the gut microbiome in middle aged men and women: Results from a randomized controlled trial.

Background And Aims: Berry (poly)phenol consumption has been associated with cardioprotective benefits, however little is known on the role the gut microbiome may play on such health benefits. Our objective was to investigate the effects of aronia berry (poly)phenol consumption on cardiometabolic health and gut microbiome richness and composition in prehypertensive middle-aged men and women.

Methods: A total of 102 prehypertensive participants were included in a parallel 12-week randomized double-blind placebo-controlled trial.

The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor-resistant ER breast cancer with mitotic aberrations.

Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are standard first-line treatments for metastatic ER breast cancer. However, acquired resistance to CDK4/6i invariably develops, and the molecular phenotypes and exploitable vulnerabilities associated with resistance are not yet fully characterized. We developed a panel of CDK4/6i-resistant breast cancer cell lines and patient-derived organoids and demonstrate that a subset of resistant models accumulates mitotic segregation errors and micronuclei, displaying increased sensitivity to inhibitors of mitotic checkpoint regulators TTK and Aurora kinase A/B.

Glycoproteomics Identifies Plexin-B3 as a Targetable Cell Surface Protein Required for the Growth and Invasion of Triple-Negative Breast Cancer Cells.

Driven by the lack of targeted therapies, triple-negative breast cancers (TNBCs) have the worst overall survival of all breast cancer subtypes. Considering that cell surface proteins are favorable drug targets and are predominantly glycosylated, glycoproteome profiling has significant potential to facilitate the identification of much-needed drug targets for TNBCs. Here, we performed -glycoproteomics on six TNBCs and five normal control (NC) cell lines using hydrazide-based enrichment.

Are you as old as your arteries? Comparing arterial aging in Japanese and European patient groups using cardio-ankle vascular index.

Background: Most comparisons of arterial stiffness between ethnic groups focus on pulse wave velocity. This study used the cardio-ankle vascular index (CAVI) in European compared to Japanese individuals to investigate how cardiovascular risk factors affect arterial aging across geographic regions.

Methods: Four hundred and ninety-four European and 1044 Japanese individuals underwent measurements of CAVI, blood pressure and information on cardiovascular risk factors.

Maternal Factors in Pregnancy and Ethnicity Influence Childhood Adiposity, Cardiac Structure, and Function.

Importance: The links between maternal and offspring adiposity and metabolic status are well established. There is much less evidence for the impact of these relationships combined with ethnic background on cardiac structure and function in childhood.

Objective: To test the hypothesis that ethnicity, maternal adiposity and glycemic status, and child adiposity affect cardiac structure and function.

Effect of moderate to high intensity aerobic exercise on blood pressure in young adults: The TEPHRA open, two-arm, parallel superiority randomized clinical trial.

Background: Exercise is advised for young adults with elevated blood pressure, but no trials have investigated efficacy at this age. We aimed to determine whether aerobic exercise, self-monitoring and motivational coaching lowers blood pressure in this group.

Methods: The study was a single-centre, open, two-arm, parallel superiority randomized clinical trial with open community-based recruitment of physically-inactive 18-35 year old adults with awake 24 h blood pressure 115/75mmHg-159/99 mmHg and BMI<35 kg/m.

PRMT inhibition induces a viral mimicry response in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here we identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), which has antitumor growth activity in TNBC. Pathway analysis of TNBC cell lines indicates that the activation of interferon responses before and after MS023 treatment is a functional biomarker and determinant of response, and these observations extend to a panel of human-derived organoids.

Biomimetic hydrogel supports initiation and growth of patient-derived breast tumor organoids.

Patient-derived tumor organoids (PDOs) are a highly promising preclinical model that recapitulates the histology, gene expression, and drug response of the donor patient tumor. Currently, PDO culture relies on basement-membrane extract (BME), which suffers from batch-to-batch variability, the presence of xenogeneic compounds and residual growth factors, and poor control of mechanical properties. Additionally, for the development of new organoid lines from patient-derived xenografts, contamination of murine host cells poses a problem.