The role of preclinical models in creatine transporter deficiency: Neurobiological mechanisms, biomarkers and therapeutic development

Creatine (Cr) Transporter Deficiency (CTD) is an X-linked metabolic disorder, mostly caused by missense mutations in the SLC6A8 gene and presenting with intellectual disability, autistic behavior, and epilepsy. There is no effective treatment for CTD and patients need lifelong assistance. Thus, the research of novel intervention strategies is a major scientific challenge. Animal models are an excellent tool to dissect the disease pathogenetic mechanisms and drive the preclinical development of therapeutics. This review illustrates the current knowledge about Cr metabolism and CTD clinical aspects, with a focus on mainstay diagnostic and therapeutic options. Then, we discuss the rodent models of CTD characterized in the last decade, comparing the phenotypes expressed within clinically relevant domains and the timeline of symptom development. This analysis highlights that animals with the ubiquitous deletion/mutation of SLC6A8 genes well recapitulate the early onset and the complex pathological phenotype of the human condition. Thus, they should represent the preferred model for preclinical efficacy studies. On the other hand, brain-and cell-specific conditional mutants are ideal for understanding the basis of CTD at a cellular and molecular level. Finally, we explain how CTD models might provide novel insight about the pathogenesis of other disorders, including cancer

A tale of two community networks program centers: Operationalizing and assessing CBPR principles and evaluating partnership outcomes

BACKGROUND: Community Networks Program (CNP) centers are required to use a community-based participatory research (CBPR) approach within their specific priority communities. Not all communities are the same and unique contextual factors and collaborators’ priorities shape each CBPR partnership. There are also established CBPR and community engagement (CE) principles shown to lead to quality CBPR in any community. However, operationalizing and assessing CBPR principles and partnership outcomes to understand the conditions and processes in CBPR that lead to achieving program and project level goals is relatively new in the science of CBPR. OBJECTIVES: We sought to describe the development of surveys on adherence to and implementation of CBPR/CE principles at two CNP centers and examine commonalities and differences in program- versus project-level CBPR evaluation. METHODS: A case study about the development and application of CBPR/CE principles for the Missouri CNP, Program for the Elimination of Cancer Disparities, and Minnesota CNP, Padres Informados/Jovenes Preparados, surveys was conducted to compare project versus program operationalization of principles. Survey participant demographics were provided by CNP. Specific domains found in CBPR/CE principles were identified and organized under an existing framework to establish a common ground. Operational definitions and the number of survey items were provided for each domain by CNP. CONCLUSION: There are distinct differences in operational definitions of CBPR/CE principles at the program and project levels of evaluation. However, commonalities support further research to develop standards for CBPR evaluation across partnerships and at the program and project levels

His bundle pacing: Clinical consequences of unnecessary right ventricle backup pacing

As a backup lead in right ventricle (RV) is often used in His-bundle pacing (HBP) implants, in sinus rhythm patients the His lead is connected to the left ventricular (LV) port of a CRT device. In current devices, the backup pacing will be delivered 100% of time due to cross-channel ventricular refractory periods. Beyond an impact on battery, unnecessary RV pacing could find excitable tissue and capture a portion of the myocardium tissue potentially reducing the benefits of physiological HBP as shown in this case report where the switch from biventricular to LV-only pacing improved acute and 2-month echocardiography parameters

Prise en charge pluridisciplinaire des syndromes de dumping après chirurgie bariatrique [Multidisciplinary management of dumping syndromes after bariatric surgery]

Dumping syndromes are a frequent complication of gastric or bariatric surgery and include early and late dumping. Early dumping is a consequence of rapid delivery of hyperosmolar nutrients into the bowel. Late dumping is the result of a reactive hypoglycemia induced by a hyperinsulinemic response. These syndromes are becoming increasingly prevalent with the rising incidence of bariatric surgery. Effective management of these complications requires multidisciplinary collaboration. First line management of early and late dumping syndrome involves specific dietary and behavioral modifications which generally improve the quality of life of patients

NUTRITION AND IMMUNITY IN OLDER PEOPLE.

IF 2.86