On the pathogenesis of obesity: causal models and missing pieces of the puzzle.

Application of the physical laws of energy and mass conservation at the whole-body level is not necessarily informative about causal mechanisms of weight gain and the development of obesity. The energy balance model (EBM) and the carbohydrate-insulin model (CIM) are two plausible theories, among several others, attempting to explain why obesity develops within an overall common physiological framework of regulation of human energy metabolism. These models have been used to explain the pathogenesis of obesity in individuals as well as the dramatic increases in the prevalence of obesity worldwide over the past half century. Here, we summarize outcomes of a recent workshop in Copenhagen that brought together obesity experts from around the world to discuss causal models of obesity pathogenesis. These discussions helped to operationally define commonly used terms; delineate the structure of each model, particularly focussing on areas of overlap and divergence; challenge ideas about the importance of purported causal factors for weight gain; and brainstorm on the key scientific questions that need to be answered. We hope that more experimental research in nutrition and other related fields, and more testing of the models and their predictions will pave the way and provide more answers about the pathogenesis of obesity than those currently available.

Trapped fat: Obesity pathogenesis as an intrinsic disorder in metabolic fuel partitioning.

Our understanding of the pathophysiology of obesity remains at best incomplete despite a century of research. During this time, two alternative perspectives have helped shape thinking about the etiology of the disorder. The currently prevailing view holds that excessive fat accumulation results because energy intake exceeds energy expenditure, with excessive food consumption being the primary cause of the imbalance. The other perspective attributes the initiating cause of obesity to intrinsic metabolic defects that shift fuel partitioning from pathways for mobilization and oxidation to those for synthesis and storage. The resulting reduction in fuel oxidation and trapping of energy in adipose tissue drives a compensatory increase in energy intake and, under some conditions, a decrease in expenditure. This theory of obesity pathogenesis has historically garnered relatively less attention despite its pedigree. Here, we present an updated comprehensive formulation of the fuel partitioning theory, focused on evidence gathered over the last 80 years from major animal models of obesity showing a redirection of fuel fluxes from oxidation to storage and accumulation of excess body fat with energy intake equal to or even less than that of lean animals. The aim is to inform current discussions about the etiology of obesity and by so doing, help lay new foundations for the design of more efficacious approaches to obesity research, treatment and prevention.

Rationale for Hepatitis C Virus Treatment During Hematopoietic Stem Cell Transplant in the Era of Novel Direct-Acting Antivirals.

BACKGROUND AND AIMS: Untreated hepatitis C (HCV) infection in patients undergoing hematopoietic stem cell transplantation (HSCT) can lead to worse outcomes. Traditionally, HSCT patients infected with HCV would wait until after immune reconstitution to receive HCV therapy, as the oncologic urgency of transplant would not allow time for a full preceding treatment course of HCV therapy. However, in the era of newer direct-acting antivirals (DAAs), we propose that concomitant treatment of HCV while undergoing HSCT is safe and feasible, while keeping in mind potential drug-drug interactions. METHODS: A literature review was performed to summarize the available data on the impact of HCV on patients undergoing HSCT. Drug-drug interactions for DAA's and pertinent HSCT drugs were evaluated using Lexicomp online® and http://hep-druginteractions.org . RESULTS: During HSCT, HCV appears to be a conditional risk factor for sinusoidal obstruction syndrome and a potential risk factor for graft versus host disease, both of which are associated with increased mortality. HCV reactivation and exacerbation may impact the use of chemotherapeutics, but available studies haven't shown impact specifically on HSCT. Limited case reports exist but demonstrate safe and effective use DAAs during HSCT. These, along with a drug-drug interaction review demonstrate agents such as sofosbuvir/velpatasvir and glecaprevir/pibrentasvir are promising DAAs for use in HSCT. CONCLUSION: HCV infection may worsen outcomes for patients undergoing HSCT. Concomitant treatment of HCV during HSCT using newer DAAs appears feasible and may improve patient morbidity and mortality, however large-scale studies are needed to further support this practice.

Protocol paper for an implementation science approach to promoting colorectal cancer screening in Federally Qualified Health Center clinics: A stepped-wedge, multilevel intervention trial.

Background: Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Despite the Healthy People 2030 goal of 70.5%, colorectal cancer (CRC) screening rates in Federally Qualified Health Centers (FQHCs) are suboptimal at about 40%. The Colorectal Cancer Awareness, Research, Education and Screening-Rural Expansion, Access, and Capacity for Health (CARES-REACH) study seeks to address this disparity and accelerate the adoption and utilization of effective, evidence-based CRC screening practices. This paper describes the CARES-REACH study design and implementation methods. Methods: Informed by a community-based participatory research (CBPR) framework and enriched by implementation science approaches, CARES-REACH features a stepped wedge design with extension for maintenance to support an implementation strategy focused on multiple levels: organizational, provider, and patient levels that entail processes to boost initial and repeat screening among average risk and age-eligible adults. This multilevel study entails the implementation of a core set of evidence-based interventions (EBIs) that include low literacy patient education (English, Spanish, and Haitian Creole language); provider education, system-wide electronic medical record (EMR) tools including provider prompts and patient reminders, FIT (fecal immunochemical test) kit distribution, plus an organization-wide cancer control champion who motivates providers, coaches and navigates patients, and monitors system-wide CRC screening activities. Trial registration: NCT04464668.

Impact of Patient Blood Management on Red Blood Cell Utilization in an Urban Community Teaching Hospital: A Seven-Year Retrospective Study.

OBJECTIVES: This study aimed to showcase how implementing a patient blood management (PBM) program effectively cuts unnecessary red blood cell (RBC) transfusions in a New York City urban community teaching hospital. METHODS: Analyzing seven years from 2013 to 2019, a retrospective review of RBC transfusions was conducted. RESULTS: Following the introduction of PBM, considerable improvements were observed annually. These included a drop in mean pretransfusion hemoglobin levels from 7.26 g/dL (2013) to 6.58 g/dL (2019), a 34% reduction in yearly RBC unit transfusions, and fewer units given to patients with pre-Hgb levels ≥ 7 g/dL (from 1210 units in 2013 to 310 units in 2019). Furthermore, this study noted a decline in two-unit RBC orders when Hgb levels were ≥ 7 g/dL from 65 orders in 2013 to merely 3 in 2019. The estimated total cost savings attributed to the six-year PBM program duration after full implementation in 2014 amounted to USD 2.1 million. CONCLUSIONS: Overall, PBM implementation significantly decreased RBC transfusions and enhanced transfusion practices. The findings emphasize that successful PBM strategies do not always necessitate extensive resources or increased budgets but instead rely on the application of intuitive methods, as evidenced by this study.

Preliminary factor analysis of the O'Kelly Women Beliefs Scale in a US sample / Análisis factorial preliminar de la O'Kelly Women Beliefs Scale en una muestra estadounidense

Using a Rational Emotive Behavior Therapy framework, the O'Kelly Women Beliefs Scale (O'Kelly, in press) was originally constructed in Australia to measure sex-role beliefs women may develop through sex-role stereotyping. Factor analysis of the 92 original items showed that 64 items loaded into a single component that accounted for 18.2% of the variance in a sample of 974 Australian women. The present exploratory study examined the psychometric properties of the OWBS in a sample of 202 women born and living in the US. A varimax rotation with cutoff eigenvalues of 3, showed that 37 items loaded into 3 components which accounted for 58.48% of the variance. The items were subsequently grouped into two factors: Irrationality, with a total of 27 items was created by merging component 1 and 3 (Pearson's r = 0.8 between them), and Rationality, with the 10 items from component 2. Analyses indicated a Cronbach's alpha of 0.91 for Factor 1, and a Cronbach's alpha 0.74 for Factor 2. Results indicate that this version of the instrument may be used to evaluate both the rational and irrational content of sex-role beliefs of women born in the US.

En el contexto de la Terapia Racional Emotivo-Conductual, se desarrolló la O'Kelly Women Beliefs Scale (OWBS) construída originalmente en Australia, para evaluar las creencias sobre el rol sexual que las mujeres pueden desarrollar como estereotipo. En una muestra de 974 mujeres australianas, el análisis factorial de los 92 reactivos originales mostró que 64 de ellos cargaron en un solo componente que explica el 18.2 % de la varianza total. El objetivo del presente estudio exploratorio es determinar la estructura factorial del OWBS, en 202 mujeres nacidas en E.E. U.U. La rotación Varimax con punto de corte de autovalor en 3, arrojó que 37 ítems cargan en tres componentes que explican el 58.48 % de la varianza total. Los reactivos se agruparon en dos factores: Irracionalidad, con un total de 27 reactivos que se integraron en los componentes 1 y 3 (r = 0.8) y Racionalidad, con 10 reactivos integrados en el componente 2. El alfa de Cronbach fue de 0.91 para el Factor 1 y de 0.74 para el Factor 2. Los resultados indican que esta versión del instrumento puede ser usada para evaluar tanto el contenido racional como el irracional de las creencias sobre el rol sexual de las mujeres nacidas en E.E. U.U.

Aculturación y diferencias en las creencias irracionales sobre el rol femenino tradicional (O’Kelly Women Beliefs Scale) en mujeres colombianas residentesen su país de origen y en Estados Unidos / Acculturation and differences in the irrational beliefs about traditional female roles (O’Kelly Women Beliefs Scale) in Colombian women living in Colombia and U. S. A

La Escala de Creencias de las Mujeres de O’Kelly (O’Kelly Women Beliefs Scale., O’Kelly, en prensa; Ellis, 1985) fue aplicada a colombianas residentes en Cali, Colombia, colombianas residentes en el noreste de los Estados Unidos y sus contrapartes estadounidenses (20 madres y 20 hijas mayores de 17 años en cada grupo). Se encontró que existen diferencias transculturales en los puntajes totales de los tres grupos. Comparaciones posthoc (LSD) indicaron que las diferencias significativas se encuentran en las hijas colombianas residentes en Estados Unidos, comparadas con las madres colombianas residentes en Colombia y las madres e hijas estadounidenses. No existen diferencias entre madres e hijas colombianas residentes en Estados Unidos. Los resultados sugieren que el patrón deaculturación de los colombianos en los Estados Unidos es el de asimilación al país de adopción conservando aspectos de la tradición y la cultura del país de origen.

The O’Kelly Women Beliefs Scale (O’Kelly, in press) was given to 120 females: Colombians living in Colombia, and Colombians, and their non- Hispanic US counterparts living in the USA (20 mother-daughter pairs in each group). An ANOVA indicated significant cross-cultural differences among the groups, where posthoc comparisons (LSD) revealed they were largely due to differences between Colombian daughters in the USA and three subgroups: Colombian mothers inColombia, non- Hispanic US mothers, and non- Hispanic US daughters. Results suggest that the acculturation patternof Colombians to the USA seems to be one of assimilation to the new culture keeping several aspects of the traditions and costumes of the country of origin.