Multi-omic cross-sectional cohort study of pre-malignant Barrett's esophagus reveals early structural variation and retrotransposon activity.

Barrett's esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett's natural history and may inform the potential for cancer beyond the clinically discernible phenotype.

Effectiveness of two tobacco cessation methods among TB patients.

BACKGROUND: Tobacco and TB are the world´s two greatest public health problems. Exposure to tobacco has been shown to be associated with higher risk of acquiring TB and adverse outcomes such as relapse and TB mortality.OBJECTIVE: To assess and compare self-reported tobacco quit status and biochemically verified cotinine levels among TB patients at different time intervals among two study groups.METHODS: A cluster, randomised controlled trial was conducted on TB patients attending DOTS centres in Delhi, India, who reported using tobacco in any form. Participants were assigned into one of two treatment groups. Centres were randomly assigned to two intervention groups: 1) integrated intervention using behavioural counselling with nicotine replacement therapy (NRT) gum, and 2) intervention using behavioural counselling alone (50 each in intervention and control group). The subjects were followed at Week 1, Month 1, Month 3 and Month 6 for tobacco cessation.RESULTS: At the end of 6 months, patients who received the integrated intervention had significantly higher rate of success in quitting tobacco than those who received the conventional TB treatment alone (78.7% vs. 57.8%; P < 0.03).CONCLUSION: DOTS with tobacco use dependence treatment was successful in our study in helping TB patients to quit tobacco dependence and should therefore be offered to every tobacco user.

Radiological evaluation of lacrimal apparatus injury after functional endoscopic sinus surgery.

OBJECTIVE: To determine the incidence of nasolacrimal duct injury after functional endoscopic sinus surgery radiologically, using computed tomography. METHODS: Fifty patients of either sex who underwent functional endoscopic sinus surgery were evaluated for nasolacrimal duct injury by computed tomography. Computed tomography was conducted pre-operatively, and post-operatively at the end of four weeks, and nasolacrimal duct injury was analysed. RESULTS: The prevalence of nasolacrimal duct injury dehiscence was 1.16 per cent, with a similar incidence of 1.16 per cent for nasolacrimal duct injury post-operatively. However, no cases of symptomatic nasolacrimal duct injury were recorded. CONCLUSION: Computed tomography scan is an effective, non-invasive method to evaluate nasolacrimal duct injury following functional endoscopic sinus surgery, in accordance with evidence-based medicine.

Nutritional intervention during maxillomandibular fixation of jaw fractures prevents weight loss and improves quality of life.

Maxillomandibular fixation (MMF) for the management of jaw fractures leads to compromised nutritional intake and consequent weight loss and poor quality of life (QoL). The present study aimed to evaluate the effectiveness of a home-based dietary plan to prevent weight loss, and its effect on the QoL of patients who underwent four weeks of MMF for the treatment of maxillofacial fractures. A total of 50 patients were randomised into nutritional intervention (Group1) and non-intervention groups (Group 2). Patients in Group1 were counselled by a dietitian and given a diet plan. Patients in Group 2 were advised to take a liquid diet of their own choice in the form of shakes, juices, and milk, along with protein supplements. Patients in Group1 lost significantly less weight than those in Group 2 (p=0.001) at week four of follow up. Group1 patients had significantly better oral health-related QoL in the 'physical pain' domain during the two weeks of MMF, and in the 'physical discomfort' and 'psychological disability' domains two weeks after the release of MMF. They had significantly better nutrition-related QoL in all the domains during the two weeks of MMF and, except for the 'physical' domain, also during the two weeks after its release. Individual home-based diet plans effectively helped the patients maintain their weight and improved QoL.

Lactobacillus rhamnosus NCDC17 ameliorates type-2 diabetes by improving gut function, oxidative stress and inflammation in high-fat-diet fed and streptozotocintreated rats.

Restoration of dysbiosed gut microbiota through probiotic may have profound effect on type 2 diabetes. In the present study, rats were fed high fat diet (HFD) for 3 weeks and injected with low dose streptozotocin to induce type 2 diabetes. Diabetic rats were then fed Lactobacillus rhamnosus NCDC 17 and L. rhamnosus GG with HFD for six weeks. L. rhamnosus NCDC 17 improved oral glucose tolerance test, biochemical parameters (fasting blood glucose, plasma insulin, glycosylated haemoglobin, free fatty acids, triglycerides, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol), oxidative stress (thiobarbituric acid reactive substance and activities of catalase, superoxide dismutase and glutathione peroxidase in blood and liver), bifidobacteria and lactobacilli in cecum, expression of glucagon like peptide-1 producing genes in cecum, and adiponection in epididymal fat, while decreased propionate proportions (%) in caecum, and expression of tumour necrosis factor-α and interlukin-6 in epididymal fat of diabetic rats as compared to diabetes control group. These findings offered a base for the use of L. rhamnosus NCDC 17 for the improvement and early treatment of type 2 diabetes.

Effect of cryogenic grinding on volatile and fatty oil constituents of cumin (Cuminum cyminum L.) genotypes.

Effect of cryogenic grinding on recovery of volatile oil, fatty oil percentage and their constituents in two cumin (Cuminum cyminum L.) genotypes have been analyzed. Cryogenic grinding not only retains the volatiles but enhanced the recovery by 33.9 % in GC 4 and 43.5 % in RZ 209. A significant increase (29.9 %) over normal grinding in oil percentage was also observed in genotype RZ 209. This increase was, however, less (15.4 %) in genotype GC 4. Nineteen major compounds were identified in the essential oil of both genotypes. The two grinding techniques had significant effects on dependent variables, viz., volatile oil and monoterpenes. Cuminaldehyde was the main constituent in both genotypes, content of which increased from 48.2 to 56.1 % in GC 4 on cryo grinding. Content of terpines were found to decrease in cryo ground samples of GC 4 and either decrease or no change was found in RZ 209. Organoleptic test showed more pleasant aroma in cryo ground seeds of both the genotypes. Significant increase was also reported in fatty oil yield due to cryogenic grinding. Fatty acid methyl ester (FAME) analysis showed oleic acid as major FAME content of which increased from 88.1 to 94.9 % in RZ 209 and from 88.2 to 90.1 % in GC 4 on cryogenic grinding. Other prominent FAME were palmitic, palmitoleic and stearic acid. Results indicated commercial potential of cryogenic grinding technology for cumin in general and spices in particular for better retention of flavour and quality in spices.

Comparison of success rate of intubation through Air-Q with ILMA using two different endotracheal tubes.

BACKGROUND AND AIMS: Air-Q™ is a newly introduced airway device, which can be used to facilitate endotracheal intubation. The primary aim of this study was to assess whether use of two different endotracheal tubes (ETTs) (standard polyvinyl chloride [PVC] and reinforced PVC) increases the success rate of blind intubation through Air-Q™ (Group Q) when compared with intubating laryngeal mask airway (ILMA- Fastrach™) keeping ILMA as control (Group I). METHODS: One hundred and twenty patients aged between 18 and 60 years with American Society of Anesthesiologists physical status I-II, undergoing elective surgery under general anaesthesia, were enrolled into this prospective, randomised, case-control study to compare the success rate of tracheal intubation between ILMA (Fastrach™) and Air-Q™ intubating laryngeal airway. Those patients with anticipated difficult airway were excluded from the study. All the recruited patients completed the study. Reinforced PVC ETT was used in both airway devices to secure intubation. Since standard PVC tube is recommended for use in Air-Q, when first intubation attempt failed, second or third attempt was made with standard PVC ETT. Total of three attempts were made for each procedure: Whereas in ILMA group, only reinforced tube was used in all three attempts. RESULTS: The overall success rate after three attempts was more with Air-Q (96.6%) in our study compared with ILMA (91.6%) but no significant difference was seen between the groups (P = 0.43). CONCLUSION: The present study shows that when intubation with reinforced tube fails, the success rate with use of conventional PVC tube is more with Air-Q when compared with ILMA.

Clinico-radiological Correlation of Bone Changes in Leprosy Patients Presenting with Disabilities/Deformities.

Leprosy is a medical - social disease, it is associated with stigma in the society due to the resulting deformities in some persons. Although stigma has decreased after the widespread use of MDT, some disabilities do occur which are mostly due to late initiation of treatment and inappropriate care. Besides the nerve and skin involvement bone changes have been reported to be common in leprosy. These bony changes need to be understood in the present MDT era specially in the context of clinical spectrum and duration of disease/ deformities. Fifty clinically diagnosed and histologically classified leprosy patients with deformities/ disabilities of either hands/feet/face who attended the OPD of Department of Dermatology, Venereology and Leprosy, Government Medical College, Amritsar were examined and evaluated in the study. Radiological examination of hands, feet and skull was done in each case and the bone changes in hands and feet; and skull and paranasal sinus changes were correlated with clinical parameters. Bone changes were observed in 90% of cases radiologically. Specific bone changes in hands and feet, non-specific bone changes in hands, feet, skull and paranasal sinuses were seen in 66%, 82% and 32% of cases respectively. Common specific bone changes in hands and feet observed were primary periostitis (14%), honey combing (46%), bone cyst (36%), thinning and irregularity of cortex (28%) and area of bone destruction (20%); Among the non-specific bone changes observed were contracted fingers/claw hands/claw toes (64%) and absorption of terminal phalanges (40%). The maxillary sinus, and paranasal sinus changes were the most common radiological findings observed in skull. The study of the radiological changes may help the clinicians to understand the gravity of the situation and undertake steps for timely prevention of permanent loss of function and the occurrence of deformities and disabilities.

An analysis of time utilization and cancellations of scheduled cases in the main operation theater complex of a tertiary care teaching institute of North India.

CONTEXT: Operation theater (OT) utilization. AIMS: To analyze the time utilization and to assess the stated causes of cancellations of scheduled cases in the OT complex of a tertiary care teaching institute. SETTINGS AND DESIGN: This prospective study was carried out from December 2010 to April 2011. MATERIALS AND METHODS: each of the 16 OT tables was observed for 6 days (total 96 days). The available resource hours were taken as 0800-1600 hrs. (480 min/day; 46,080 min in 96 days). The following parameters were recorded--time spent on supportive services, time spent on actual surgery, room turn over time, time spent for total procedure and time between entry and exit of patient. STATISTICAL ANALYSIS: Data were analyzed using the SPSS software version 15. RESULTS: Of the total 325 scheduled cases, 252 were operated and 73 (22.5%) were cancelled. There were delays on 15 days (15.63%) in starting the OT table at the scheduled time. Of the total resource hours (46,080 min), the mean "Raw utilization" was 37,573 min (81.54%) and the "Adjusted utilization" was 39,668 min (86.09%). The mean time spent on "supportive services" was 5539 min (12.02%) and on "actual surgery"' was 28,277 min (61.37%), and the "room turn over time" was 2095 min (5.39%). Among the stated reasons for cancellations, lack of operating time--57 cases (78.1%)--was the most common. CONCLUSION: Study of time utilization and cancellation are important tools in assessing the optimal utilization of available resource hours in an OT.

Drug utilisation study in a tertiary care center: recommendations for improving hospital drug dispensing policies.

Drug therapy accounts for a major portion of health expenditure. A useful strategy for achieving cost efficient healthcare is drug utilisation research as it forms the basis for making amendments in drug policies and helps in rational drug use. The present observational study was conducted to generate data on drug utilization in inpatients of our tertiary care hospital to identify potential targets for improving drug prescribing patterns. Data was collected retrospectively from randomly selected 231 medical records of patients admitted in various wards of the hospital. WHO Anatomical Therapeutic Chemical/Defined Daily Dose methodology was used to assess drug utilisation data and drug prescriptions were analysed by WHO core drug indicators. Antibiotics were prescribed most frequently and also accounted for majority of drug costs. The prescribed daily dose for most of the antibiotics corresponded to defined daily dose reflecting adherence to international recommendations. Brand name prescribing and polypharmacy was very common.78% of the total drugs prescribed were from the National List of Essential Medicines 2003. Restricting the use of newer and costlier antibiotics, branded drugs and number of drugs per prescription could be considered as targets to cut down the cost of drug therapysignificantly.

Pilot study of cytological testing for oesophageal squamous cell dysplasia in a high-risk area in Northern Iran.

BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) is a fatal disease with 5-year survival rates of <5% in Northern Iran. Oesophageal squamous dysplasia (ESD) is the precursor histologic lesion of ESCC. This pilot study was conducted to assess the feasibility, safety, and acceptability of non-endoscopic cytological examination of the oesophagus and to provide initial data on the accuracy of cytological atypia for identifying patients with ESD in this very-high-risk area. METHODS: Randomly selected asymptomatic participants of the Golestan Cohort Study were recruited. A cytological specimen was taken using a capsule sponge device and evaluated for atypical cells. Sections of the cytological specimen were also stained for p53 protein. Patient acceptability was assessed using a visual analogue scale. The cytological diagnosis was compared with a chromoendoscopic examination using Lugol's solution. RESULTS: Three hundred and forty-four subjects (43% male, mean (s.d.) age 55.6 (7.9) years) were referred to the study clinic. Three hundred and twelve met eligibility criteria and consented, of which 301 subjects (96.5%) completed both cytological and endoscopic examinations. There were no complications. Most of the participants (279; 92.7%) were satisfied with the examination. The sensitivity and specificity of the cytological examination for identifying subjects with high-grade ESD were 100 and 97%, respectively. We found an accuracy of 100% (95% CI=99-100%) for a combination of cytological examination and p53 staining to detect high-grade ESD. CONCLUSIONS: The capsule sponge methodology seems to be a feasible, safe, and acceptable method for diagnosing precancerous lesions of the oesophagus in this population, with promising initial accuracy data for the detection of high-grade ESD.

Synthetic and application perspectives of azapodophyllotoxins: alternative scaffolds of podophyllotoxin.

Podophyllotoxin (1) has been known to possess anti-tumor activity and is still considered an important lead for research and development of antineoplastic agents. Derivatives of podophyllotoxin, namely etoposide (2), etopophos (3) and teniposide (4) have been developed and are currently used in clinic for the treatment of a variety of malignancies. These agents are also used in combination therapies with other drugs. Due to the drug resistance developed by cancer cells as well as side effects associated with the use of these agents in clinic, the search for new effective anticancer analogues of podophyllotoxin remains an intense area of research. The structural complexity of podophyllotoxin, arising from the presence of four stereogenic carbons in ring C has restricted most of the structural activity relationship (SAR) studied by derivatization of the parent natural product rather than by de novo multi-step chemical synthesis. These issues provide strong impetus to a search for analogues of 1 with simplified structures, which can be accessible via short synthetic sequences from simple starting materials. Even if such initial compounds might have diminished cytotoxic potencies compared with the parent cyclolignan, the ease of preparation of carefully designed libraries of analogues would lead to more informative SAR studies and expeditious structure optimization. In this regard, during the last two decades considerable efforts have been made to synthesize aza- analogs of podophyllotoxin, i. e. aza-podophyllotoxins, with hetero atoms at different positions of the podophyllotoxin skeleton, while keeping the basic podophyllotoxin structure. Recently, there have been significant efforts towards the convenient synthesis of aza-analogs of 1. The use of multicomponent reactions (MCRs) and the synergies of ultrasound and microwave irradiations have increased the synthetic speed and variety of azapodophyllotoxins which are and will be available to be tested against a diverse population of carcinomas and other diseases. It has been reported that several aza-podophyllotoxins retain a great fraction of the cytotoxicity associated with the parent lignan. This review focuses on the strategies towards synthesis of various aza-podophyllotoxin analogues and their biological activities.

Adrenocortical oncocytoma: Review of imaging and histopathological implications.

Oncocytomas are rare tumours of the adrenal glands whose malignant potential is difficult to assess with certainty. We report a case of an adrenal oncocytoma and present a review of the literature particularly with regards to the radiological and histopathological features and their impact on the management.Adrenal oncocytomas are usually identified incidentally on imaging and can achieve large sizes. They should be considered in the differential diagnosis of any large upper abdominal lesion including those apparently arising from the liver as in this case report. MRI scan appears to be the ideal imaging modality to characterise such lesions. There seems to be little benefit in biopsying these masses and surgery remains the most optimal management. It remains difficult to predict metastatic behaviour based on histological findings and so long term surveillance is advisable.

Characterization of seed storage proteins in high protein genotypes of cowpea [Vigna unguiculata (L.) Walp].

Twenty one genotypes and two check varieties viz. CS-88 and V-240 of cowpea [Vigna unguiculata (L.) Walp. ] were screened for total proteins. The total protein content ranged from 22.4 (HC-3) to 27.9 % (HC-98-64) in 21 genotypes whereas in check varieties it was 25.6 (V-240) and 26.0 % (CS-88). Seven genotypes viz. HC-6, HC-5, CP-21, LST-II-C-12, CP-16, COVU-702 and HC-98-64 having high protein content (26.7 to 27.9 %) were selected for further characterization of their seed storage proteins. Globulins were the major protein fraction ranging from 55.6 (LST-II-C-12) to 58.8 % (CP-16 and HC-6) of total protein. Glutelins was the second major fraction ranging from 14.4 to 15.6 % followed by albumins (8.2 to 11.9 %) and prolamins (2.3 to 5.0 %). Content of free amino acids also showed variations amongst genotypes with COVU-702 having maximum and LST-II-C-12 having minimum content. Essential amino acid analysis revealed that S-amino acids (cysteine and methionine) were the first limiting amino acids followed by tryptophan. From the results presented here it could be suggested that two genotypes viz. LST-II-C-12 and HC-5 be used in breeding programmes aimed at developing high protein moth bean varieties with good quality.

Identification of novel susceptibility genes in ozone-induced inflammation in mice.

Ozone (O(3)) remains a prevalent air pollutant and public health concern. Inf2 is a significant quantitative trait locus on murine chromosome 17 that contributes to susceptibility to O(3)-induced infiltration of polymorphonuclear leukocytes (PMNs) into the lung, but the mechanisms of susceptibility remain unclear. The study objectives were to confirm and restrict Inf2, and to identify and test novel candidate susceptibility gene(s). Congenic strains of mice that contained overlapping regions of Inf2 and their controls, and mice deficient in either major histocompatibility complex (MHC) class II genes or the Tnf cluster, were exposed to air or O(3). Lung inflammation and gene expression were assessed. Inf2 was restricted from 16.42 Mbp to 0.96 Mbp, and bioinformatic analysis identified MHC class II, the Tnf cluster and other genes in this region that contain potentially informative single nucleotide polymorphisms between the susceptible and resistant mice. Furthermore, O(3)-induced inflammation was significantly reduced in mice deficient in MHC class II genes or the Tnf cluster genes, compared with wild-type controls. Gene expression differences were also observed in MHC class II and Tnf cluster genes. This integrative genetic analysis of Inf2 led to identification of novel O(3) susceptibility genes that may provide important, new therapeutic targets in susceptible individuals.

Relationship between 31P metabolites and oncolytic viral therapy sensitivity in human colorectal cancer xenografts.

BACKGROUND: Studies using phosphorus magnetic resonance spectroscopy (MRS) have pointed to the significance of phospholipid metabolite alterations as biochemical markers for tumour progression or therapy response. METHODS: Spectroscopic imaging was performed in colorectal flank tumours in nude mice. In vivo tumour doubling times for each cell line were measured. In vivo sensitivity of each tumour line to treatment with G207 and NV1020 oncolytic viruses was assessed. Correlations between viral sensitivity and tumour doubling time and phosphorus MRS were estimated. RESULTS: For G207 virus, in vitro cytotoxicity tests showed cell viability at multiplicities of infection (ratio of viral particles per tumour cell) of 0.1 on day 6 as follows: C85, less than 1 per cent; HCT8, 1 per cent; LS174T, 9 per cent; HT29, 18 per cent; and C18, 92 per cent. Respective values for NV1020 were 1, 18, 4, 18 and 86 per cent. The phosphoethanolamine to phosphocholine ratio was significantly lower in virus-sensitive than -insensitive cells, and was dependent on tumour doubling time. CONCLUSION: Alterations in membrane phospholipid metabolites that relate to proliferation of cancer cells affect the efficacy of oncolytic viral therapy. MRS proved a highly sensitive non-invasive tool for predicting the efficacy of viruses.

Efficacy of biologicals in the treatment of rheumatoid arthritis. a meta-analysis.

Rheumatoid arthritis (RA) is a chronic multisystem disease. A characteristic feature of RA is persistent inflammatory synovitis, usually involving the peripheral joints in a symmetric distribution. The prevalence of RA is approximately 0.8% of the population (range: 0.3-2.1%); women are affected approximately 3 times more often than men. The current therapeutic approach is to start a disease-modifying agent early in the illness to prevent eventual joint damage. Older disease-modifying anti-rheumatic drugs include methotrexate, sulphasalazine and hydroxychloroquine. Newer ones such as leflunomide and cyclosporin are also used. A recent advance in the management of rheumatoid arthritis is the use of biological agents, which block certain key molecules involved in the pathogenesis of the illness. They include tumour-necrosis-factor-alpha-blocking agents such as infliximab, etanercept and adalimumab, the anti-CD-20 agent, rituximab, and CTLA-4 Ig abatacept. The present study was planned with the aim of evaluating the efficacy of such newer biological therapies in refractory RA at various time points. Databases including Medline, Embase and the Cochrane Library were searched for all relevant studies up to January 2007. A total of 26 studies were included in present meta-analysis. The method of DerSimonian and Laird [Control Clin Trials 1986;7:177-188] was used to calculated a pooled odds ratio (OR) for the American College of Rheumatology (ACR) criteria 20, 50 and 70, at 24, 54 and 96 weeks. The overall pooled OR were found to be significantly more than the placebo at all 3 time points for all 3 criteria (ACR 20, 50 70). In conclusion, biologicals as a group are highly effective in the treatment of RA. Biologicals were efficacious both in treatment naïve and methotrexate-refractory patients.