Ultrasonographic findings in patients with abdominal symptoms or trauma presenting to an emergency room in rural Tanzania

BACKGROUND: Frequencies of ultrasonographic findings and diagnoses in emergency departments in sub-Saharan Africa are unknown. This study aimed to describe the frequencies of different sonographic findings and diagnoses found in patients with abdominal symptoms or trauma presenting to a rural referral hospital in Tanzania. METHODS: In this prospective observational study, we consecutively enrolled patients with abdominal symptoms or trauma triaged to the emergency room of the Saint Francis Referral Hospital, Ifakara. Patients with abdominal symptoms received an abdominal ultrasound. Patients with an abdominal or thoracic trauma received an Extended Focused Assessment with Ultrasound in Trauma (eFAST). RESULTS: From July 1st 2020 to June 30th 2021, a total of 88838 patients attended the emergency department, of which 7590 patients were triaged as 'very urgent' and were seen at the emergency room. A total of 1130 patients with abdominal symptoms received an ultrasound. The most frequent findings were abnormalities of the uterus or adnexa in 409/754 females (54.2%) and abdominal free fluid in 368 (32.6%) patients; no abnormality was found in 150 (13.5%) patients. A tumour in the abdomen or pelvis was found in 183 (16.2%) patients, an intrauterine pregnancy in 129/754 (17.1%) females, complete or incomplete abortion in 96 (12.7%), and a ruptured ectopic pregnancy in 32 (4.2%) females. In males, most common diagnosis was intestinal obstruction in 54/376 (14.4%), and splenomegaly in 42 (11.2%). Of 1556 trauma patients, 283 (18.1%) received an eFAST, and 53 (18.7%) had positive findings. A total of 27 (9.4%) trauma patients and 51 (4.5%) non-trauma patients were sent directly to the operating theatre. CONCLUSION: In this study, ultrasound examination revealed abnormal findings for the majority of patients with non-traumatic abdominal symptoms. Building up capacity to provide diagnostic ultrasound is a promising strategy to improve emergency services, especially in a setting where diagnostic modalities are limited

Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data.

In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p < 0.05). One of the genes is RBFOX1, an evolutionarily conserved RNA-binding protein that regulates tissue-specific alternative splicing that we previously reported to be associated with BP using exome array data in CFS. After follow-up analysis of the 25 genes in ten independent TOPMed studies with individuals of European, African, and East Asian ancestry, and Hispanics (N = 29,988), we identified variants in SLX4 (p = 2.19 × 10-4) to be significantly associated with BP traits when accounting for multiple testing. We also replicated the associations previously reported for RBFOX1 (p = 0.007). Follow-up analysis with GTEx eQTL data shows SLX4 variants are associated with gene expression in coronary artery, multiple brain tissues, and right atrial appendage of the heart. Our study demonstrates that linkage analysis of family data can provide an efficient approach for detecting rare variants associated with complex traits in WGS data

Rare coding variants in RCN3 are associated with blood pressure

Abstract Background While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries. Results Associations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10− 7). Conclusions Low frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.http://deepblue.lib.umich.edu/bitstream/2027.42/173468/1/12864_2022_Article_8356.pd

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Abstract Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids