Laparoscopy or clinical follow-up to detect occult diaphragm injuries following left-sided thoracoabdominal stab wounds: A pilot randomized controlled trial.

BACKGROUND: The purpose of this study was to determine whether patients with left-sided thoracoabdominal (TA) stab wounds can be safely treated with clinical and chest X-ray follow up. METHOD: A prospective, randomized control study was conducted at Groote Schuur Hospital from September 2009 through to November 2014. Patients with asymptomatic left TA stab wounds included in the trial were randomized into two groups. Group A underwent diagnostic laparoscopy and Group B underwent clinical and radiological follow-up. RESULTS: Twenty-seven patients were randomized to Group A (N=27) and thirty-one to Group B (N=31). All patients were young males with a median age of 26 years (range 18 to 48). The incidence of occult diaphragm injury in Group A was 29%. All diaphragm injuries found at laparoscopy were repaired. The mean hospital stay for the patients in Group A was 5 days (SD 1.3), compared to a mean hospital stay of 2.9 days (SD, 1.5), in Group B (p < 0.001). All patients in Group B had normal chest X-rays at their last visit. The mean follow-up time was 24 months (median: 24; interquartile range: 1-40). There was no morbidity or mortality in Group B. CONCLUSION: Clinical and radiological follow-up are feasible and appear to be safe, in the short term, in patients who harbour occult diaphragm injuries after left TA stab wounds. Until studies showing the natural history of diaphragm injury in humans are available, laparoscopy should remain the gold standard in treatment.

HIV drug resistance levels in adults failing first-line antiretroviral therapy in an urban and a rural setting in South Africa.

OBJECTIVES: Urban and rural HIV treatment programmes face different challenges in the long-term management of patients. There are few studies comparing drug resistance profiles in patients accessing treatment through these programmes. The aim of this study was to perform such a comparison. METHODS: HIV drug resistance data and associated treatment and monitoring information for adult patients failing first-line therapy in an urban and a rural programme were collected. Data were curated and managed in SATuRN RegaDB before statistical analysis using Microsoft Excel 2013 and stata Ver14, in which clinical parameters, resistance profiles and predicted treatment responses were compared. RESULTS: Data for 595 patients were analysed: 492 patients from a rural setting and 103 patients from an urban setting. The urban group had lower CD4 counts at treatment initiation than the rural group (98 vs. 126 cells/µL, respectively; P = 0.05), had more viral load measurements performed per year (median 3 vs. 1.4, respectively; P < 0.01) and were more likely to have no drug resistance mutations detected (35.9% vs. 11.2%, respectively; P < 0.01). Patients in the rural group were more likely to have been on first-line treatment for a longer period, to have failed for longer, and to have thymidine analogue mutations. Notwithstanding these differences, the two groups had comparable predicted responses to the standard second-line regimen, based on the genotypic susceptibility score. Mutations accumulated in a sigmoidal fashion over failure duration. CONCLUSIONS: The frequency and patterns of drug resistance, as well the intensity of virological monitoring, in adults with first-line therapy failure differed between the urban and rural sites. Despite these differences, based on the genotypic susceptibility scores, the majority of patients across the two sites would be expected to respond well to the standard second-line regimen.

Stochastic modeling of gene activation and applications to cell regulation.

Transcription factors (TFs) are key regulators of gene expression. Based on the classical scenario in which the TF search process switches between one-dimensional motion along the DNA molecule and free Brownian motion in the nucleus, we study the arrival time of several TFs to multiple binding sites. In the presence of a TF influx and competitive binding ligands, we derive the probability that a fixed number of target sites are simultaneously bound. We obtain analytic expressions for this probability as a function of the mean number of TFs. When there are multiple binding sites, because this probability is a sigmoidal curve, our analysis shows that a bistable regime is possible, which can be interpreted as a genetic switch, occurring without requiring cooperative binding (change in the binding probability depending on the previous bounds). Finally, we use our model to analyze fly embryo patterning and show that bicoid can induce a sharp hunchback concentration, resulting in the formation of a sharp boundary and stripes. To conclude, we have proposed here a general mechanism that allows cells to read a morphogenetic gradient. Thus activating the transcription of an auto-activated TF can lead to the conversation of a broad gradient of morphogens into a sharp boundary.

Obsessive-compulsive disorder and a novel polymorphism adjacent to the oestrogen response element (ERE 6) upstream from the COMT gene.

Family and twin studies have consistently provided evidence for involvement of genetic mechanisms in obsessive-compulsive disorder (OCD). This has given rise to association studies involving several candidate genes in an endeavour to identify susceptibility factors. One of the more promising candidate genes appears to be the catecol-O-methyltransferase (COMT) gene. Recent association studies in North American and Afrikaner populations have reported a likely association between a functional polymorphism of COMT (linked with COMT enzyme activity levels) and OCD. COMT expression has been demonstrated to be regulated by oestrogen through the oestrogen-response elements (EREs) in the promoter region of the gene. In the light of this association, the authors tested for an association between a novel polymorphism (C --> T transition) adjacent to ERE 6 in the promoter area of COMT and OCD in 48 Afrikaners and 48 ethnically matched controls. The C --> T transition was not significantly associated with OCD (P = 0.93) or gender (P = 0.67). These findings, although limited by a small sample size, suggest that the novel polymorphism adjacent to ERE 6 in the promoter area of COMT does not play a major role in the genetic predisposition to OCD.