Screening for rare variants in the coding region of ALS-associated genes at 9p21.2 and 19p13.3

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that causes progressive muscle weakness, eventually resulting in death because of respiratory failure. Genetic variants are thought to predispose to the disease. A recent, large, genome-wide association study identified 2 loci that increase susceptibility to ALS. These 2 loci on chromosomes 9 and 19 consist of 4 genes: UNC13a, IFNK, MOBKL2b, and C9ORF72. A hexanucleotide repeat expansion in the noncoding region of C9ORF72 was recently identified as the cause of chromosome 9-linked ALS-FTD (frontotemporal dementia). In this study, our aim was to determine whether the coding regions of these genes harbor rare, nonsynonymous variants that play a role in ALS pathogenesis. In DNA from 1019 sporadic ALS patients and 1103 control subjects of Dutch descent, we performed a mutation screening analysis in the coding region of these 4 genes by resequencing the exons. A total of 16 amino acid-changing rare variations were identified, 11 in UNC13a and 5 on chromosome 9. Some of these were unique to ALS, but were detected in a single patient. None of the genes showed significant enrichment of rare variants in the coding sequence. Rare variants in the coding region of UNC13a, IFNK, MOBKL2b, and C9ORF72 are unlikely to be a genetic cause of ALS.     

Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).     

Household Survey in Sierra Leone Reveals High Prevalence of Surgical Conditions in Children

Background

Although great efforts are being undertaken to reduce child morbidity and mortality globally, there is limited knowledge about the need for pediatric surgical care. Some data on surgical need is available from hospital registries, but it is difficult to interpret for countries with limited surgical capacity.

Methods

A cross-sectional two-stage cluster-based sample survey was undertaken in Sierra Leone, using the Surgeons OverSeas Assessment of Surgical Need tool. Data were collected and analyzed on numbers of children needing surgical care and pediatric deaths that may have been averted if surgical care had been available.

Results

A total of 1,583 children out of 3,645 individuals (43.3 %) were interviewed. Most (64.0 %, n = 1,013) participants lived in rural areas. At the time of interview, 279 (17.6; 95 % confidence interval (95 % CI): 15.7–19.5 %) had a possible surgical condition in need of a consultation. Children in the northern and eastern provinces of Sierra Leone were much more likely to report a surgical problem than those in the urban-west.

Conclusions

There is a high need for surgical care in the pediatric population of Sierra Leone. While additional resources should be allocated to address that need, more research is needed. Ideally, questions on surgically treatable conditions should be added to the frequently performed health care surveys on the pediatric population.     

Ratio of Cesarean Deliveries to Total Operations and Surgeon Nationality Are Potential Proxies for Surgical Capacity in Central Haiti

Background

The World Health Organization has a standardized tool to assess surgical capacity in low- and middle-income countries (LMICs), but it is often resource- and time-intensive. There currently exists no simple, evidence-based measure of surgical capacity in these settings. The proportion of cesarean deliveries in regard to the total operations (C/O ratio) has been suggested as a way to assess quickly the capacity for emergency and essential surgery in LMICs. This ratio has been estimated to be between 23.3 and 41.5 % in LMICs, but the tool’s utility has not been replicated.

Methods

We reviewed operative logbooks for the Partners In Health/Zanmi Lasante hospital in Cange, Haiti. We recorded data on all consecutive surgical patients from July 2008 to 2010 and calculated the C/O ratio by dividing the number of cesarean deliveries by the total number of operations performed. We also analyzed surgical data by surgeon nationality to provide additional information about local surgical capacity.

Results

A total of 3,641 operations were performed between 2008 and 2010. The C/O ratio decreased significantly between 2008–2009 and 2009–2010 (13.4 vs. 10.7 %, p = 0.001) as the surgical volume and resources increased. Nationality analysis demonstrated that Haitian surgeons were able to provide a spectrum of general and specialist surgical care.

Conclusions

In its inherent relation to essential surgical procedures and to the overall rate of cesarean deliveries in the region, the C/O ratio can provide an accessible assessment of regional surgical resources. In Haiti, the change in the C/O ratio demonstrated a relative increase in surgical capacity from 2008 to 2010. An additional analysis of surgeon nationality ensured that C/O ratio estimates more accurately reflect local practitioner activity, but deficiencies in the regional capacity to address the local burden of surgical disease may still exist.