Epigallocatechin gallate accelerates healing of indomethacin-induced stomach ulcers in mice

Management of the gastric toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) remains a crucial problem because the commercially available drugs have side effects and are often expensive. Therefore, we examined the potential of the green tea-derived polyphenol epigallocatechin gallate (EGCG) to treat indomethacin-induced stomach ulcers in mice. Administration of indomethacin (18 mg/kg, po) to mice induced ulceration in the glandular portion of the gastric mucosa, accompanied by increased lipid peroxidation (LPO) and protein oxidation and reductions in thiol defense, mucin, cyclooxygenase (COX) expression and prostaglandin (PG) synthesis in the gastric tissues. Daily oral administration of EGCG (2 mg/kg) or omeprazole (3 mg/kg) for 3 days produced similar (≈ 72-75%, p < 0.001) beneficial effects on the acute gastric ulceration. Treatment with the test samples partially reversed all the adverse oxidative effects of indomethacin. In addition, EGCG, but not omeprazole, enhanced expression of the COX isoforms and PG synthesis. The results suggest that the non-toxic and inexpensive tea polyphenol EGCG may be an excellent candidate for further evaluation as a potent anti-ulcer drug.     

Percutaneous retrogasserian radiofrequency thermal rhizotomy for trigeminal neuralgia.

Forty patients suffering from intractable unilateral trigeminal neuralgia involving more than one division of the trigeminal nerve were treated by percutaneous radiofrequency thermocoagulation of the trigeminal sensory root. The aim of the operation was to relieve the pain without producing dense sensory deficit in the face. This goal was achieved by making selective lesions in the sensory root with gradually increasing temperature 60 degrees C to 90 degrees C. Three to four consecutive lesions each for 60 seconds have been found to produce excellent pain relief in 77.7% with good and fair results in the rest. The recurrence rate has been found to be 15% during 2 years of follow-up. Considerable dysaesthesia was observed in 5% of cases. Corneal anaesthesia was found in 5% cases while one patient developed neuroparalytic keratitis. Transient trigeminal motor weakness was observed in 10% of patients.     

Are falls more common than road traffic accidents in pediatric trauma? Experience from a Level 1 trauma centre in New Delhi, India

Purpose: The epidemiology of pediatric trauma is different in different parts of the world. Some researchers suggest falls as the most common mechanism, whereas others report road traffic accidents (RTAs) as the most common cause. The aim of this study is to find out the leading cause of pediatric admissions in Trauma Surgery in New Delhi, India. Methods: Inpatient data from January 2012 to September 2014 was searched retrospectively in Jai Prakash Narayan Apex Trauma Centre Trauma Registry. All patients aged 18 years or less on index presentation admitted to surgical ward/ICU or later taken transfer by the Department of Trauma Surgery were included. Data were retrieved in predesigned proformas. Information thus compiled was coded in unique alphanumeric codes for each variable and subjected to statistical analysis using SPSS version 21. Results: We had 300 patients over a 33 month period. Among them, 236 (78.6%) were males and 64 (21.3%) females. Overall the predominant cause was RTAs in 132 (43%) patients. On subgroup analysis of up to 12 years age group (n=147), the most common cause was found to be RTAs again. However, falls showed an incremental upward trend (36.05% in up to 12 age group versus 27% overall), catching up with RTAs (44.89%). Pediatric Trauma Score (PTS) ranged from 0 to 12 with a mean of 8.12 ± 2.022. 223 (74.33%) patients experienced trauma limited to one anatomic region only, whereas 77 (25.66%) patients suffered polytrauma. 288 patients were discharged to home care. Overall, 12 patients expired in the cohort. Median hospital stay was 6 days (range 1e182). Conclusion: Pediatric trauma is becoming a cause of increasing concern, especially in the developing countries. The leading cause of admissions in Trauma Surgery is RTAs (43%) as compared to falls from height (27%); however, falls from height are showing an increasing trend as we move to younger age groups. Enhancing road safety alone may not be a lasting solution for prevention of pediatric trauma and local injury patterns must be taken into account when formulating policies to address this unique challenge.     

A crystalline compound (BM-ANF1) from the Indian toad (Bufo melanostictus, Schneider) skin extract, induced antiproliferation and apoptosis in leukemic and hepatoma cell line involving cell cycle proteins.

In our earlier communication, it was reported that Indian toad (Bufo melanostictus) skin extract (TSE) possesses antiproliferative and apoptogenic activity in U937 and K562 cells [Giri et al., 2006. Antiproliferative, cytotoxic and apoptogenic activity of Indian toad (Bufo melanostictus, Schneider) skin extract in U937 and K562 cells. Toxicon 48 (4), 388-400]. In the present study, a compound (BM-ANF1) has been isolated from the TSE by alumina gel column chromatography, crystallized and evaluated for its antiproliferative and apoptogenic activity in U937, K562 and HepG2 cells. BM-ANF1 produced dose-dependent inhibition of U937, K562 and HepG2 cell growth. The antiproliferative activity was reflected by the MTT assay and demonstrated by the reduced expression of proliferative cell nuclear antigen (PCNA). Flow-cytometric analysis showed that BM-ANF1 arrested the cell cycle at G1 phase and enhanced annexin-V binding in U937 and K562 cells. Scanning electron microscopic and fluorescent microscopic analysis of U937 and K562 cells revealed the apoptogenic nature of the compound. Alkaline comet assay showed that BM-ANF1 produced DNA fragmentation. The dose-dependent expression of caspase 3 indicated that the apoptogenic properties of BM-ANF1 were mediated through the activation of downstream effector nucleases in the cancer cells. The increased expression of p53 and moderate expression of p21(Cip1)/p27(Kip1) due to BM-ANF1 treatment in HepG2 cells supported that the apoptogenic activity of BM-ANF1 was mediated through p53 tumor-suppressor gene expression followed by the expression of p21(Cip1) and p27(Kip1) and it was likely to be linked with cell cycle arrest at G1 phase in cancer cells. From the present study, it may be suggested that the crystalline compound, BM-ANF1, was antiproliferative and apoptogenic in human leukemic and hepatoma cells.     

Problems in using statistical analysis of replacement and silent mutations in antibody genes for determining antigen-driven affinity selection

The analysis of molecular signatures of antigen-driven affinity selection of B cells is of immense use in studies on normal and abnormal B cell development. Most of the published literature compares the expected and observed frequencies of replacement (R) and silent (S) mutations in the complementarity-determining regions (CDRs) and the framework regions (FRs) of antibody genes to identify the signature of antigenic selection. The basic assumption of this statistical method is that antigenic selection creates a bias for R mutations in the CDRs and for S mutations in the FRs. However, it has been argued that the differences in intrinsic mutability among different regions of an antibody gene can generate a statistically significant bias even in the absence of any antigenic selection. We have modified the existing statistical method to include the effects of intrinsic mutability of different regions of an antibody gene. We used this method to analyse sequences of several B cell-derived monoclonals against T-dependent antigens, T-independent antigens, clones derived from lymphoma and amyloidogenic clones. Our sequence analysis indicates that even after correcting for the intrinsic mutability of antibody genes, statistical parameters fail to reflect the role of antigen-driven affinity selection in maturation of many clones. We suggest that, contrary to the basic assumption of such statistical methods, selection can act both for and against R mutations in the CDR as well as in the FR regions. In addition we have identified different methodological difficulties in the current uses of such statistical analysis of antibody genes.     

Classifying spatial patterns of brain activity with machine learning methods: application to lie detection

Patterns of brain activity during deception have recently been characterized with fMRI on the multi-subject average group level. The clinical value of fMRI in lie detection will be determined by the ability to detect deception in individual subjects, rather than group averages. High-dimensional non-linear pattern classification methods applied to functional magnetic resonance (fMRI) images were used to discriminate between the spatial patterns of brain activity associated with lie and truth. In 22 participants performing a forced-choice deception task, 99% of the true and false responses were discriminated correctly. Predictive accuracy, assessed by cross-validation in participants not included in training, was 88%. The results demonstrate the potential of non-linear machine learning techniques in lie detection and other possible clinical applications of fMRI in individual subjects, and indicate that accurate clinical tests could be based on measurements of brain function with fMRI.     

Critical appraisal of laparoscopic vs open rectal cancer surgery

AIM: To evaluate the long-term clinical and oncological outcomes of laparoscopic rectal resection (LRR) and the impact of conversion in patients with rectal cancer.METHODS: An analysis was performed on a prospective database of 633 consecutive patients with rectal cancer who underwent surgical resection. Patients were compared in three groups: Open surgery (OP), laparoscopic surgery, and converted laparoscopic surgery. Short-term outcomes, long-term outcomes, and survival analysis were compared.RESULTS: Among 633 patients studied, 200 patients had successful laparoscopic resections with a conversion rate of 11.1% (25 out of 225). Factors predictive of survival on univariate analysis include the laparoscopic approach (P = 0.016), together with factors such as age, ASA status, stage of disease, tumor grade, presence of perineural invasion and vascular emboli, circumferential resection margin < 2 mm, and postoperative adjuvant chemotherapy. The survival benefit of laparoscopic surgery was no longer significant on multivariate analysis (P = 0.148). Neither 5-year overall survival (70.5% vs 61.8%, P = 0.217) nor 5-year cancer free survival (64.3% vs 66.6%, P = 0.854) were significantly different between the laparoscopic group and the converted group.CONCLUSION: LRR has equivalent long-term oncologic outcomes when compared to OP. Laparoscopic conversion does not confer a worse prognosis.     

Tobacco control and household tobacco consumption: A tale of two educational groups

Since the ratification of the World Health Organization Framework Convention on Tobacco Control in 2004, Pakistan has made modest but continued progress in implementing various tobacco control measures. By 2014, substantial progress was achieved in areas of monitoring, mass media antitobacco campaigns, and advertising bans. However, the findings from the 2014 Global Adult Tobacco Survey of Pakistan show significant differences in antitobacco campaign exposure among individuals of different educational attainment. Given this large variation in noticing antitobacco information, this paper analyzes how heterogeneity in treatment exposure may differentially impact tobacco‐use prevalence across household groups. Household‐level tobacco‐use prevalence in 2014 was, respectively, 56% and 48% for the low‐ and high‐education households. The gap in tobacco‐use prevalence between the two educational groups further widens post 2014. We find that, on average, individuals with higher than primary education are 14 percentage points and 6 percentage points more likely to notice anticigarette and antismokeless tobacco information in 2014, respectively. Subsequently, in 2016, high‐education households experienced a 3.6 percentage point higher reduction in tobacco‐use prevalence compared to the low‐education households. These findings motivate policies to enhance the outreach of tobacco control measures across different educational groups.