KATP channels in cerebral hemodynamics: a systematic review of preclinical and clinical studies.

Cumulative evidence suggests that ATP-sensitive potassium (KATP) channels act as a key regulator of cerebral blood flow (CBF). This implication seems to be complicated, since KATP channels are expressed in several vascular-related structures such as smooth muscle cells, endothelial cells and pericytes. In this systematic review, we searched PubMed and EMBASE for preclinical and clinical studies addressing the involvement of KATP channels in CBF regulation. A total of 216 studies were screened by title and abstract. Of these, 45 preclinical and 6 clinical studies were included. Preclinical data showed that KATP channel openers (KCOs) caused dilation of several cerebral arteries including pial arteries, the middle cerebral artery and basilar artery, and KATP channel inhibitor (KCI) glibenclamide, reversed the dilation. Glibenclamide affected neither the baseline CBF nor the baseline vascular tone. Endothelium removal from cerebral arterioles resulted in an impaired response to KCO/KCI. Clinical studies showed that KCOs dilated cerebral arteries and increased CBF, however, glibenclamide failed to attenuate these vascular changes. Endothelial KATP channels played a major role in CBF regulation. More studies investigating the role of KATP channels in CBF-related structures are needed to further elucidate their actual role in cerebral hemodynamics in humans. Systematic review registration: Prospero: CRD42023339278 (preclinical data) and CRD42022339152 (clinical data).

The impact of socio-economic factors on parental non-adherence to the Ponseti protocol for clubfoot treatment in low- and middle-income countries: A scoping review.

Background: The Ponseti treatment is considered the gold standard for clubfoot globally, but requires strong engagement from parents. The aim of this review is to assess the impact of socio-economic factors on the presence of drop-out, relapse or non-compliance during Ponseti treatment in low and middle-income countries (LMICs). Methods: This scoping review includes all articles available from inception until 4.4.2022. All articles describing an association between one or more socio-economic factors and one or more adverse outcomes during the Ponseti treatment in an LMICs were considered for inclusion. Studies were identified by searching Medline/PubMed, Embase, Global Health and Global Index Medicus. Data extraction was done using Covidence extraction 2.0 by two independent reviewers. Findings: A total of 281 unique references were retrieved from the database searches, 59 abstracts were retained for full-text review, of which 19 studies were included in the final review. We grouped the identified socio-economic factors into 4 larger themes: poverty and physical accessibility of clubfoot clinics, presence of support systems, educational level of the parents, and household-level factors and cultural norms. Reduced access to care for girls was considered an important risk factor in South Asia and the Caribbean. Lack of family and community support was an issue raised more often in studies from Eastern Africa. The extreme heterogeneity among collected variables within a small sample of papers made it not possible to perform a meta-analysis. Interpretation: The identified factors are very similar to the socio-economic factors identified in studies looking at the barriers parents and children face when seeking care initially. Poverty was identified as a cross-cutting risk factor in all 4 domains and the most important socio-economic risk factor based on this review, reconfirming poverty eradication as the challenge for the 21st century. Funding: None.

Undergraduate Surgical Education: a Global Perspective.

Undergraduate surgical education is failing to prepare medical students to care for patients with surgical conditions, and has been significantly compromised by the COVID-19 pandemic. We performed a literature review and undertook semi-structured reflections on the current state of undergraduate surgical education across five countries: Egypt, Morocco, Somaliland, Kenya, and the UK. The main barriers to surgical education at medical school identified were (1) the lack of standardised surgical curricula with mandatory learning objectives and (2) the inadequacy of human resources for surgical education. COVID-19 has exacerbated these challenges by depleting the pool of surgical educators and reducing access to learning opportunities in clinical environments. To address the global need for a larger surgical workforce, specific attention must be paid to improving undergraduate surgical education. Solutions proposed include the development of a standard surgical curriculum with learning outcomes appropriate for local needs, the incentivisation of surgical educators, the incorporation of targeted online and simulation teaching, and the use of technology.