Multimodal decoding of human liver regeneration.

The liver has a unique ability to regenerate; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2 migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration.

Van Gogh-like 2 is essential for the architectural patterning of the mammalian biliary tree.

Background & Aims: In the developing liver, bipotent epithelial progenitor cells undergo lineage segregation to form hepatocytes, which constitute the bulk of the liver parenchyma, and biliary epithelial cells (cholangiocytes), which comprise the bile duct (a complex tubular network that is critical for normal liver function). Notch and TGFβ signalling promote the formation of a sheet of biliary epithelial cells, the ductal plate, that organises into discontinuous tubular structures. How these structures elongate and connect to form a continuous duct remains undefined.

The Genomic and Epigenomic Landscape of Double-Negative Metastatic Prostate Cancer.

Unlabelled: Systemic targeted therapy in prostate cancer is primarily focused on ablating androgen signaling. Androgen deprivation therapy and second-generation androgen receptor (AR)-targeted therapy selectively favor the development of treatment-resistant subtypes of metastatic castration-resistant prostate cancer (mCRPC), defined by AR and neuroendocrine (NE) markers. Molecular drivers of double-negative (AR-/NE-) mCRPC are poorly defined.

RNA splicing is a key mediator of tumour cell plasticity and a therapeutic vulnerability in colorectal cancer.

Tumour cell plasticity is a major barrier to the efficacy of targeted cancer therapies but the mechanisms that mediate it are poorly understood. Here, we identify dysregulated RNA splicing as a key driver of tumour cell dedifferentiation in colorectal cancer (CRC). We find that Apc-deficient CRC cells have dysregulated RNA splicing machinery and exhibit global rewiring of RNA splicing.

In Vivo Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma.

Unlabelled: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy of the bile ducts within the liver characterized by high levels of genetic heterogeneity. In the context of such genetic variability, determining which oncogenic mutations drive ICC growth has been difficult, and developing modes of patient stratification and targeted therapies remains challenging. Here we model the interactions between rare mutations with more common driver genes and combine in silico analysis of patient data with highly multiplexed in vivo CRISPR-spCas9 screens to perform a functional in vivo study into the role genetic heterogeneity plays in driving ICC.

Ideal cardiovascular health in urban Jamaica: prevalence estimates and relationship to community property value, household assets and educational attainment: a cross-sectional study.

Objective: Ideal cardiovascular health (ICH) is associated with greater longevity and reduced morbidity, but no research on ICH has been conducted in Jamaica. We aimed to estimate the prevalence of ICH in urban Jamaica and to evaluate associations between ICH and community, household, and individual socioeconomic status (SES).

Design: Cross-sectional study.

Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors.

The number of patients diagnosed with chronic bile duct disease is increasing and in most cases these diseases result in chronic ductular scarring, necessitating liver transplantation. The formation of ductular scaring affects liver function; however, scar-generating portal fibroblasts also provide important instructive signals to promote the proliferation and differentiation of biliary epithelial cells. Therefore, understanding whether we can reduce scar formation while maintaining a pro-regenerative microenvironment will be essential in developing treatments for biliary disease.

Skin Bleaching Among African and Afro-Caribbean Women in New York City: Primary Findings from a P30 Pilot Study.

Introduction: The application of skin bleaching products to inhibit melanogenesis is a common practice within the African diaspora. Despite the adverse health effects of skin bleaching, rigorous studies investigating skin bleaching behavior among these populations in the United States are limited. In our P30 pilot study, we explored predictors of skin bleaching practice intensity among African and Afro-Caribbean women.

Reliance on medicinal plant therapy among cancer patients in Jamaica.

Purpose: Patients' perspective of their treatment regime plays a vital role in its success. Recognizing the high prevalence of medicinal plant usage among Jamaicans at large, we investigated the engagement of such remedies by cancer patients, with the aim of uncovering self-medicating habits, perceptions and details of utilized plants.

Methods: A structured, interviewer-based questionnaire was administered to 100 patients attending the oncology and urology clinics at the University Hospital of the West Indies in Kingston, Jamaica.

Docking and Linking of Fragments To Discover Jumonji Histone Demethylase Inhibitors.

Development of tool molecules that inhibit Jumonji demethylases allows for the investigation of cancer-associated transcription. While scaffolds such as 2,4-pyridinedicarboxylic acid (2,4-PDCA) are potent inhibitors, they exhibit limited selectivity. To discover new inhibitors for the KDM4 demethylases, enzymes overexpressed in several cancers, we docked a library of 600,000 fragments into the high-resolution structure of KDM4A.

TRAMIL ethnomedicinal survey in Jamaica.

Ethnopharmacological Relevance: A survey was undertaken in Jamaica to document medicinal plants frequently used in the treatment or prophylaxis of illness and trends in their use, following the methodology established by the TRAMIL network. TRAMIL, a Caribbean-wide applied research programme, scientifically evaluates and documents the efficacy and safety of medicinal plant remedies used for primary health care. Initial results from this survey, on an aspect of safety, focusing on the concomitant use and prevalence of medicinal plant use in combination with pharmaceutical drugs in Jamaica, were published in an earlier paper in 2011.

Associations between neighborhood effects and physical activity, obesity, and diabetes: The Jamaica Health and Lifestyle Survey 2008.

Objective: To examine the impact of neighborhood disorder, perceived neighborhood safety, and availability of recreational facilities on prevalence of physical activity (PA), obesity, and diabetes mellitus (DM).

Study Design And Setting: Multilevel analyses were conducted among 2,848 respondents from the 2007-08 Jamaica Health and Lifestyle Survey. Neighborhood effects were based on aggregated interviewer responses to systematic social observation questions.

Liposomal bupivacaine infiltration into the transversus abdominis plane for postsurgical analgesia in open abdominal umbilical hernia repair: results from a cohort of 13 patients.

Background: Achieving adequate control of postsurgical pain remains a challenge in patients undergoing abdominal surgery. Transversus abdominis plane (TAP) infiltration has been shown to provide postsurgical analgesia following lower abdominal surgery. We assessed the safety and efficacy of a prolonged-release liposomal formulation of the local anesthetic bupivacaine administered via infiltration into the TAP in a cohort of patients undergoing open abdominal umbilical hernia repair.

OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin.

Organic cation transporter 1, OCT1 (SLC22A1), is the major hepatic uptake transporter for metformin, the most prescribed antidiabetic drug. However, its endogenous role is poorly understood. Here we show that similar to metformin treatment, loss of Oct1 caused an increase in the ratio of AMP to ATP, activated the energy sensor AMP-activated kinase (AMPK), and substantially reduced triglyceride (TG) levels in livers from healthy and leptin-deficient mice.

Diabetic foot complications among patients attending a specialist diabetes clinic in Jamaica: prevalence and associated factors.

Objectives: To estimate the prevalence of diabetic foot complications among patients at a specialist diabetes clinic in Jamaica and identify factors associated with foot complications.

Methods: A stratified random sample of 188 patients were interviewed and examined between 2009 and 2010. Trained nurses obtained demographic and clinical data, measured anthropometrics and performedfoot examinations including inspection for amputations, ulcers or infection and assessment of pain, vibration and pressure perception.

Prevalence of overweight and obesity among children six to ten years of age in the north-east health region of Jamaica.

Objective: To estimate the prevalence and correlates of overweight and obesity among children six to ten years old in the North-East Health Region (NEHR) ofJamaica.

Methods: Weights and heights were measured in a representative sample of 5710 children between the ages of six and ten years in 34 schools between October 2008 and March 2009. Overweight and obesity were defined as body mass index (BMI) Z-score > 1SD and >2SD, respectively based on the World Health Organization (WHO)-endorsed age and gender-specific growth standards for children.

Risky behaviours of Jamaican adolescents with sickle cell disease.

Objectives: To describe the risky behaviours of Jamaican teens with sickle cell disease (SCD) and compare them to a national sample of Jamaican youth.

Methods: One hundred twenty two SCD adolescents, 15-19 years old, completed the standardized questionnaire used in the Jamaican Youth Risk and Resiliency Behaviour Survey (JYRRBS), which was a nationally representative survey of 1317 Jamaican youths. Information was obtained on socio-demographics, smoking, alcohol use, and sexual activity.

Prevalence of high-risk sexual behaviour in Jamaican adults and its relationship to sociodemographic and religious factors: findings from the Jamaica Health and Lifestyle Survey 2007-2008.

Objective: To estimate the prevalence of high-risk sexual behaviours among Jamaican adults and evaluate associations with sociodemographic and religious factors.

Methods: We performed a cross-sectional study, using a nationally representative sample of Jamaicans, 15-74 years old. Participants completed an interviewer-administered questionnaire including questions on sexual activity, sociodemographic factors and religious practice.

What is the best predictor of mortality in a very low birth weight infant population with a high mortality rate in a medical setting with limited resources?

Objective: To determine the best predictor of mortality risk in very low birth weight (VLBW) infants in resource limited settings.

Methods: The Clinical Risk Index for Babies (CRIB) II score and the simplified age-weight-sex (SAWS) score for all VLBW infants born during the period January 2005 to June 2006 at the University Hospital of the West Indies were retrospectively calculated. The respective ability of each score, birth weight, and calculated or assessed gestational age to predict mortality was quantified using the area under receiver operating curves.

Excess Cardiovascular Risk Burden in Jamaican Women Does Not Influence Predicted 10-Year CVD Risk Profiles of Jamaica Adults: An Analysis of the 2007/08 Jamaica Health and Lifestyle Survey.

Background: Black Caribbean women have a higher burden of cardiovascular disease (CVD) risk factors than their male counterparts. Whether this results in a difference in incident cardiovascular events is unknown. The aim of this study was to estimate the 10 year World Health Organization/International Society for Hypertension (WHO/ISH) CVD risk score for Jamaica and explore the effect of sex as well as obesity, physical activity and socioeconomic status on these estimates.

Foot care and footwear practices among patients attending a specialist diabetes clinic in Jamaica.

This study aimed to estimate the proportion of patients at the University Hospital of the West Indies (UHWI) Diabetes Clinic who engage in recommended foot care and footwear practices. Seventy-two participants from the UHWI Diabetes Clinic completed an interviewer-administered questionnaire on foot care practices and types of footwear worn. Participants were a subset of a sex-stratified random sample of clinic attendees and were interviewed in 2010.

Asthma and allergies in Jamaican children aged 2-17 years: a cross-sectional prevalence survey.

Objective: To determine the prevalence and severity of asthma and allergies as well as risk factors for asthma among Jamaican children aged 2-17 years.

Design: A cross-sectional, community-based prevalence survey using the International Study of Asthma and Allergies in Childhood questionnaire. The authors selected a representative sample of 2017 children using stratified, multistage cluster sampling design using enumeration districts as primary sampling units.