The Use of a Theory of Change Model to Guide the Implementation of a Comprehensive Surgical Specialty Training Program in Equatorial Guinea.

Background: Equatorial Guinea (EG) is located on the African west coast, with only 0.4 trained physicians per 1,000 resident population. The country has one medical school and there is no specialist training program. From 2000 to 2022, 524 doctors have received their medical degree. However, the number of national surgical specialists in the entire country is currently 42. Objective: Formación Especializada Sanitaria en Guinea Ecuatorial (FES Guinea) is a program specifically aimed at designing and implementing a long-term national surgical specialist training program. Methods: Más Que Salud (+QS), which means "More than Health" in Spanish, is a nonprofit organization leading the FES Guinea program. We used the theory of change (ToC) framework to evaluate the work accomplished and implement subsequent phases. The initial phase (A) included a needs assessment and mapping of available resources. An intermediate phase (B) started with a memorandum of understanding to implement a Train the Trainer program. The consolidation phase (C) consists of educational interventions and future advanced training projects. Findings: The ToC model allowed us an analyses of initial and intermediate phases. The needs assessments and resources mapping were executed while several scientific meetings and workshops were given. Scholarships to support specialist training abroad benefited six physicians in a diverse set of surgical disciplines. A regulatory commission to implement the FES Guinea program and the National Medical Council of EG were created. Working directly with the EG Ministry of Health, +QS codesigned a National Health Development Plan that began implementation in 2021 to continue until 2025. Conclusions: The ToC model allowed us to predict the current and future potential effects of FES Guinea on surgical workforce development in EG. This is a unique surgical training program, which combined effective initiatives spearheaded initially by an NGO that successfully incorporated both local health and academic authorities, ensuring sustainability.

Integrative genetic analysis illuminates ALS heritability and identifies risk genes.

Amyotrophic lateral sclerosis (ALS) has substantial heritability, in part shared with fronto-temporal dementia (FTD). We show that ALS heritability is enriched in splicing variants and in binding sites of 6 RNA-binding proteins including TDP-43 and FUS. A transcriptome wide association study (TWAS) identified 6 loci associated with ALS, including in NUP50 encoding for the nucleopore basket protein NUP50. Independently, rare variants in NUP50 were associated with ALS risk (P = 3.71.10-03; odds ratio = 3.29; 95%CI, 1.37 to 7.87) in a cohort of 9,390 ALS/FTD patients and 4,594 controls. Cells from one patient carrying a NUP50 frameshift mutation displayed a decreased level of NUP50. Loss of NUP50 leads to death of cultured neurons, and motor defects in Drosophila and zebrafish. Thus, our study identifies alterations in splicing in neurons as critical in ALS and provides genetic evidence linking nuclear pore defects to ALS.

Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells.

Around 30-40% of patients with colorectal cancer (CRC) undergoing curative resection of the primary tumour will develop metastases in the subsequent years1. Therapies to prevent disease relapse remain an unmet medical need. Here we uncover the identity and features of the residual tumour cells responsible for CRC relapse. An analysis of single-cell transcriptomes of samples from patients with CRC revealed that the majority of genes associated with a poor prognosis are expressed by a unique tumour cell population that we named high-relapse cells (HRCs). We established a human-like mouse model of microsatellite-stable CRC that undergoes metastatic relapse after surgical resection of the primary tumour. Residual HRCs occult in mouse livers after primary CRC surgery gave rise to multiple cell types over time, including LGR5+ stem-like tumour cells2-4, and caused overt metastatic disease. Using Emp1 (encoding epithelial membrane protein 1) as a marker gene for HRCs, we tracked and selectively eliminated this cell population. Genetic ablation of EMP1high cells prevented metastatic recurrence and mice remained disease-free after surgery. We also found that HRC-rich micrometastases were infiltrated with T cells, yet became progressively immune-excluded during outgrowth. Treatment with neoadjuvant immunotherapy eliminated residual metastatic cells and prevented mice from relapsing after surgery. Together, our findings reveal the cell-state dynamics of residual disease in CRC and anticipate that therapies targeting HRCs may help to avoid metastatic relapse.

Prevalencia y distribución corporal de agentes causantes de pitiriasis versicolor en una comunidad marginal de Caracas / Prevalence and corporal distribution of agents causing pityriasis versicolor in a marginal community of Caracas

Se realizó un estudio sobre la prevalencia de microorganismos causantes de pitiriasis versicolor en pacientes con lesiones cutáneas sugestivas, en una consulta ambulatoria en una zona urbano-marginal de Caracas, los resultados de esta investigación señalan que de 250 pacientes, 75 presentaron lesiones en la piel, sospechosas de pitiriasis versicolor, de los cuales en 23 se identificó Malassezia. 22 M. furfur y en solo 1 caso M. ovalis no hubo diferencias significativas en la prevalencia entre los diferentes grupos etarios y por sexo. Se observó un claro predominio de las lesiones localizadas en la cara (82,2//), de manera aislada (43,48//), o asociadas a lesiones en tronco (26,09//) o miembros superiores (13,04//), sobre otras regiones anatómicas

Epidemiología de la toxocariasis canina en una zona urbano-marginal de Caracas / Epidemiology of canine toxocariasis in an urbane-marginal zone of Caracas

Se realizó un estudio sobre la prevalencia de toxocariasis en una población canina de una zona urbano-marginal de Caracas, de acuerdo a los hábitos callejeros o domésticos del animal, encontrándose un predominio de infección intestinal en perros callejeros sobre domésticos (52