RESUMEN
INTRODUCTION AND HYPOTHESIS: Urinary tract infection (UTI) is one of the most common human infections. Evidence suggests that there might be a genetic predisposition to UTI. Previous small candidate gene studies have suggested that common variants in genes involved in the immune response to UTI could increase susceptibility to the development of recurrent UTI (rUTI). The objective was to conduct a gene association study to replicate previous gene association studies identifying single nucleotide polymorphisms (SNPs) putatively associated with rUTI in adult women. METHODS: Women with a history of rUTI and healthy controls were recruited (n = 1,008) from gynaecology outpatient clinics. Participants completed a signed consent form and questionnaire for phenotyping. DNA was extracted from blood or saliva samples for each participant. Putative associated SNPs were identified from a comprehensive systematic review of prior gene association studies. Primers for each selected SNP were designed, and genotyping was conducted using a competitive polymerase chain reaction (PCR) method. The Chi-squared test was used to assess the association between each variant and rUTI. Genotyping quality was assessed by checking for deviation from Hardy-Weinberg equilibrium. RESULTS: We found no association between SNPs tested in the VDR (p = 0.16, p = 0.09, p = 0.36), CXCR1 (p = 0.09), CXCR2 (p = 0.39), PSCA (p = 0.74) genes, and rUTI in adult women. CONCLUSIONS: To our knowledge, this is the largest study to date, finding no significant associations. Previously reported positive associations may have been due to type 1 error, or genotyping errors. Future studies should adjust for confounders and employ adequate sample sizes. A greater understanding of the genetic components associated with rUTI may influence future treatment guidelines and screening for susceptible patients.
Asunto(s)
Infecciones Urinarias , Adulto , Humanos , Femenino , Infecciones Urinarias/prevención & control , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Antígenos de Neoplasias , Proteínas de Neoplasias/genética , Proteínas Ligadas a GPI/genética , Receptores de Calcitriol/genéticaRESUMEN
Gastric neuroendocrine carcinomas (G-NEC) are aggressive malignancies with poorly understood biology and a lack of disease models. Here, we use genome sequencing to characterize the genomic landscapes of human G-NEC and its histologic variants. We identify global and subtype-specific alterations and expose hitherto unappreciated gains of MYC family members in a large part of cases. Genetic engineering and lineage tracing in mice delineate a model of G-NEC evolution, which defines MYC as a critical driver and positions the cancer cell of origin to the neuroendocrine compartment. MYC-driven tumors have pronounced metastatic competence and display defined signaling addictions, as revealed by large-scale genetic and pharmacologic screening of cell lines and organoid resources. We create global maps of G-NEC dependencies, highlight critical vulnerabilities, and validate therapeutic targets, including candidates for clinical drug repurposing. Our study gives comprehensive insights into G-NEC biology.
Asunto(s)
Carcinoma Neuroendocrino , Tumores Neuroendocrinos , Neoplasias Gástricas , Humanos , Animales , Ratones , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Modelos Moleculares , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/genéticaRESUMEN
An adult old cyclist presented to our hospital and was referred to the orthopaedic department with a left shoulder posterolateral acromion avulsion fracture and subacromial impingement demonstrated on X-ray and CT. This highly unusual fracture pattern was treated by open reduction and internal fixation with cannulated screws and a tension band suture technique. This fracture went onto successful union with full range of motion and good patient-reported outcome measures by the Oxford Shoulder Score at 3 months. Informed consent was taken for the following case report.