The educational impact of bench model fidelity on the acquisition of technical skill: the use of clinically relevant outcome measures

OBJECTIVE: To evaluate the impact of bench model fidelity on the acquisition of technical skill using clinically relevant outcome measures. METHODS: Fifty junior surgery residents participated in a 1-day microsurgical training course. Participants were randomized to 1 of 3 groups: 1) high-fidelity model training (live rat vas deferens; n = 21); 2) low-fidelity model training (silicone tubing; n = 19); or 3) didactic training alone (n = 10). Following training, all participants were assessed on the high- and low-fidelity bench models. Immediate outcome measures included procedure times, blinded, expert assessment of videotaped performance using checklists and global rating scales, anastomotic patency, suture placement precision, and final product ratings. Delayed outcome measures (obtained from the live rat vas deferens 30 days following training) included anastomotic patency, presence of a sperm granuloma, and the presence of sperm on microscopy. RESULTS: Following training, checklist (P < 0.001) and global rating scores (P < 0.001) on the bench model simulators were higher among subjects who received hands-on training, irrespective of model fidelity. Immediate anastomotic patency rates of the rat vas deferens were higher with increasing model fidelity training (P = 0.048). Delayed anastomotic patency rates were higher among subjects who received bench model training, irrespective of model fidelity (P = 0.02). Rates of sperm presence on microscopy were higher among subjects who received high-fidelity model training compared with subjects who received didactic training (P = 0.039) but did not differ among subjects in the high- and low-fidelity groups. CONCLUSIONS: Surgical skills training on low-fidelity bench models appears to be as effective as high-fidelity model training for the acquisition of technical skill among novice surgeons.     

An association study of thrombospondin 1 and 2 SNPs with coronary artery disease and myocardial infarction among South Indians

Introduction

Thrombospondin 1 and 2 are multidomain calcium-binding extracellular glycoproteins and they play a role in platelet aggregation, inflammatory response and assembly of connective tissue extracellular matrix. The association of thrombospondins (TSP) in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) is well established. The association of the TSP-1 (Asn700Ser, 2210A → G, rs2228262) and TSP-2 un-translated region (UTR) (3949 T → G, rs8089) gene variations among South Indian CAD and MI patients has been examined in the present study.

Materials and Methods

We analyzed the thrombospondin polymorphisms in unrelated CAD patients (n = 511) and a subgroup with an event of MI (n = 173) compared with controls (n = 522). The polymorphisms were assessed using polymerase chain reaction, restriction fragment length analysis and the circulating TSP concentration were measured using enzyme linked immune-sorbent assay.

Results

The prevalence of TSP-1 and TSP-2 alleles did not show any significant difference statistically, when compared controls against CAD/MI patients. The rare GG genotype of the N700S polymorphism was not observed among the studied population. Further, multiple regression analysis revealed that there was no significant risk for CAD (OR = 1.68; 95% CI 0.927 - 3.055; p = 0.087) or MI (OR = 1.84; 95% CI 0.846 - 4.007; p = 0.124) for the GA genotype. The GA genotype showed no impact on clinical characteristics of the CAD patients and their circulating TSP-1 levels. A similar non-association was observed for the TSP-2 in 3949 T → G polymorphism (GG genotype) for CAD (OR = 0.64; 95% CI 0.278 - 1.455; p = 0.636) and MI (OR = 0.53; 95% CI 0.166 - 1.675; p = 0.278).

Conclusions

Our data suggests that the presence of thrombospondin-1 (rs2228262) and thrombospondin-2 (rs8089) variants need not be considered a risk for coronary artery disease or myocardial infarction among South Indians.     

Drug-induced leukoencephalopathy presenting as catatonia

We discuss the case of a 35-year-old woman who presented with thought impoverishment, disorganized behavior, and echolalia. The patient's condition progressed to treatment-refractory catatonia. She was started on oral Coenzyme Q10 after magnetic resonance imaging of the brain showed findings consistent with drug-induced leukoencephalopathy (DIL). Following improvement, she acknowledged cocaine use that suggested a diagnosis of cocaine-induced leukoencephalopathy (CIL). This case report seeks to elucidate radiological and clinical features of DIL.     

Inhibition of aldose reductase by Aegle marmelos and its protective role in diabetic cataract

Ethnopharmacological relevance

Aegle marmelos (L.) Corr. Serr. (Aegle marmelos) leaves were extensively used in the Ayurvedic, Unani and Siddha systems of Indian medicine as an anti-diabetic agent, which serves as hypoglycemic agent. However, the significance of this plant on secondary complications of diabetes such as cataract remained unknown. The aim of the study was to investigate the possible anti-cataractous activity of Aegle marmelos against streptozotocin (STZ) induced diabetic cataract in rats.

Materials and methods

Aegle marmelos leaf extract was prepared using three different solvents (petroleum ether, ethyl acetate and methanol) and tested for inhibition against rat lens aldose reductase (AR), a key enzyme of polyol pathway. Furthermore, the pharmacological potential of Aegle marmelos extract was investigated against osmotic stress induced opacification of lens in ex vivo organ culture and streptozotocin (STZ) induced diabetic cataract in rats.

Results

Ethyl acetate extract of Aegle marmelos inhibited rat lens AR in vitro with an IC₅₀ value of ∼15 µg/ml. This extract also prevented the hyperglycemia induced increase in AR activity, sorbitol accumulation and opacification of rat lens in ex vivo lens organ culture. Supplementation of ethyl acetate extract of Aegle marmelos to STZ-induced diabetic rats decreased the blood glucose levels due to hyperglycemia and inhibited the AR activity and delayed cataract progression in dose dependent manner. α-crystallin isolated from diabetic rats fed with Aegle marmelos showed improved chaperone activity than that of isolated from rats naïve to Aegle marmelos.

Conclusion

This study indicates that ethyl acetate extract of Aegle marmelos has pharmacologically active components with a potential to inhibit rat lens AR and consequential decrease in osmotic stress. Besides this, the present study also demonstrates that the extract prevented loss of antioxidants contributing to the integrity of α-crystallin's chaperone activity and thereby delaying cataract.     

Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in Northern India

Background

A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Indian women. We investigated the distribution and the nature of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of 204 Indian breast cancer patients and 140 age-matched controls.

Method

Cases were selected with regard to early onset disease (≤40 years) and family history of breast and ovarian cancer. Two hundred four breast cancer cases along with 140 age-matched controls were analyzed for mutations. All coding regions and exon-intron boundaries of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis followed by direct sequencing of detected variants.

Results

In total, 18 genetic alterations were identified. Three deleterious frame-shift mutations (185delAG in exon 2; 4184del4 and 3596del4 in exon 11) were identified in BRCA1, along with one missense mutation (K1667R), one 5'UTR alteration (22C>G), three intronic variants (IVS10-12delG, IVS13+2T>C, IVS7+38T>C) and one silent substitution (5154C>T). Similarly three pathogenic protein-truncating mutations (6376insAA in exon 11, 8576insC in exon19, and 9999delA in exon 27) along with one missense mutation (A2951T), four intronic alterations (IVS2+90T>A, IVS7+75A>T, IVS8+56C>T, IVS25+58insG) and one silent substitution (1593A>G) were identified in BRCA2. Four previously reported polymorphisms (K1183R, S1613G, and M1652I in BRCA1, and 7470A>G in BRCA2) were detected in both controls and breast cancer patients. Rare BRCA1/2 sequence alterations were observed in 15 out of 105 (14.2%) early-onset cases without family history and 11.7% (4/34) breast cancer cases with family history. Of these, six were pathogenic protein truncating mutations. In addition, several variants of uncertain clinical significance were identified. Among these are two missense variants, one alteration of a consensus splice donor sequence, and a variant that potentially disrupts translational initiation.

Conclusion

BRCA1 and BRCA2 mutations appear to account for a lower proportion of breast cancer patients at increased risk of harboring such mutations in Northern India (6/204, 2.9%) than has been reported in other populations. However, given the limited extent of reported family history among these patients, the observed mutation frequency is not dissimilar from that reported in other cohorts of early onset breast cancer patients. Several of the identified mutations are unique and novel to Indian patients.