Let-7a-regulated translational readthrough of mammalian AGO1 generates a microRNA pathway inhibitor.

Translational readthrough generates proteins with extended C-termini, which often possess distinct properties. Here, we have used various reporter assays to demonstrate translational readthrough of AGO1 mRNA. Analysis of ribosome profiling data and mass spectrometry data provided additional evidence for translational readthrough of AGO1. The endogenous readthrough product, Ago1x, could be detected by a specific antibody both in vitro and in vivo. This readthrough process is directed by a cis sequence downstream of the canonical AGO1 stop codon, which is sufficient to drive readthrough even in a heterologous context. This cis sequence has a let-7a miRNA-binding site, and readthrough is promoted by let-7a miRNA. Interestingly, Ago1x can load miRNAs on target mRNAs without causing post-transcriptional gene silencing, due to its inability to interact with GW182. Because of these properties, Ago1x can serve as a competitive inhibitor of miRNA pathway. In support of this, we observed increased global translation in cells overexpressing Ago1x. Overall, our results reveal a negative feedback loop in the miRNA pathway mediated by the translational readthrough product of AGO1.

Naturally occurring fluorescence protects the eutardigrade Paramacrobiotus sp. from ultraviolet radiation.

Naturally occurring fluorescence has been observed in multiple species ranging from bacteria to birds. In macroscopic animals such as birds, fluorescence provides a visual communication signal. However, the functional significance of this phenomenon is unknown in most cases. Though photoprotection is attributed to fluorescence under ultraviolet (UV) light in some organisms, it lacks direct experimental evidence. Here, we demonstrate naturally occurring fluorescence under UV light in a eutardigrade belonging to the genus Paramacrobiotus. Using a natural variant that lacks fluorescence, we show that the fluorescence confers tolerance to lethal UV radiation. Remarkably, the fluorescent extract from Paramacrobiotus sp. could protect the UV-sensitive tardigrade Hypsibius exemplaris and nematode Caenorhabditis elegans from germicidal UV radiation. We propose that Paramacrobiotus sp. possess a protective fluorescent shield that absorbs harmful UV radiation and emits harmless blue light.

Infant and young child feeding practices, sociodemographic factors and their association with nutritional status of children aged <3 years in India: findings of the National Nutrition Monitoring Bureau survey, 2011-2012.

OBJECTIVE: To study infant and young child feeding (IYCF) practices and their association with nutritional status among young children. DESIGN: A community-based, cross-sectional study was carried out in ten states of India, using a multistage random sampling method. Anthropometric measurements such as length/height and weight were conducted and nutritional assessment was done using the WHO child growth standards. SETTING: National Nutrition Monitoring Bureau survey, 2011-2012.ParticipantsChildren aged <3 years and their mothers. RESULTS: Only 36 % of infants received breast-feeding within an hour of birth and 50 % were exclusively breast-fed up to 6 months. Prevalence of underweight, stunting and wasting was 38, 41 and 22 %, respectively. The chance of undernutrition among <3-year-old children was significantly higher among those from scheduled caste/scheduled tribe communities, the lowest-income group, with illiterate mothers and lack of sanitary latrine. Among infants, the chance of undernutrition was significantly higher among low-birth-weight babies, and among children whose mother had not consumed iron-folic acid tablets during pregnancy. Immunization practices and minimum dietary diversity were observed to be associated with undernutrition among 12-23-month-old children. CONCLUSIONS: Undernutrition is still an important public health problem in India and observed to be associated with low socio-economic status, illiteracy of mother, low birth weight and dietary diversity. Improving socio-economic and literacy status of mothers can help in improving maternal nutrition during pregnancy and thus low birth weight. Also, improving knowledge of mothers about IYCF practices will help in improving children's nutritional status.

Micronutrient deficiency disorders among the rural children of West Bengal, India.

BACKGROUND: Multiple micronutrient deficiencies continue to be a major nutritional problem of public health significance in India. AIM: To assess the prevalence of micronutrient deficiencies among rural children of West Bengal, India. SUBJECTS AND METHODS: A community-based cross-sectional study was carried out on 9228 and 437 pre-school children, respectively, for assessment of vitamin A deficiency (VAD) and anaemia. Iodine deficiency disorders (IDD) were assessed in 3490 children of 6-12 years. RESULTS: The prevalence of Bitot's spots, an objective sign of clinical VAD, was 0.6% and was significantly (p < 0.01) higher among children of 3-5 years. Prevalence of blood vitamin A deficiency ( < 20 µg/dL) was 61% and ∼81% of children were anaemic. About 25% children had both sub-clinical VAD and anaemia. The children of Scheduled Caste and Scheduled Tribe (OR = 2.3: 95% CI = 1.3-3.9) were at higher risk of anaemia, whereas children of Scheduled Tribe (OR = 4.5; 95% CI = 2.1-10.5) and 3-5 years (OR = 1.4; 95% CI = 1.0-2.0) were at risk for VAD. The prevalence of goitre was 9%. CONCLUSIONS: Micronutrient deficiencies were found to be of public health significance among rural children of West Bengal. Therefore, there is a need to initiate sustainable long-term interventions for prevention and control of micronutrient deficiencies in children.

Acute Pancreatitis Complicating Liver Transplantation in a Case of Fulminant Hepatic Failure Due to Yellow Phosphorus Poisoning.

INTRODUCTION: Yellow phosphorus (YP) is a general protoplasmic poison causing hepatic, cardiac, renal, and multiorgan failure. We report an unusual case of fulminant liver failure due to ratol (YP) poisoning complicated by acute pancreatitis postoperatively after liver transplantation. CASE REPORT: A 25-yr-old man presented with alleged consumption of approximately 7 gm of Ratol paste. Serum amylase and lipase levels were 880 and 2423, respectively, and CT imaging of pancreas was normal. He developed fulminant liver failure, fulfilling King's college criteria and an living donor liver transplantation was performed. Intraoperatively fat saponification was seen at the root of mesentery. On postoperative day (POD) 13, he developed incisional wound dehiscence and he underwent laparotomy with extensive slough removal from the lateral aspect of wound. On POD 21, wound showed evidence of burst abdomen. CT abdomen revealed inflamed tail of pancreas with peripancreatic fat stranding and an exploratory laparotomy was performed again. Intraoperatively, walled-off necrotic collection was seen in the tail of the pancreas and necrosectomy was carried out. All the aforementioned re-explorations were carried out under steroid immunosuppression. He was restarted on tacrolimus on POD27. Graft function and cholestatic biochemistry improved progressively, and he was discharged and is on regular follow-up. DISCUSSION: YP is very toxic with rapid absorption and gets accumulated in liver causing acute liver failure. Acute pancreatitis in a patient after liver transplantation for fulminant liver failure owing to Ratol poisoning has not been reported in published English literature. Although clinically relevant pancreatitis is rare in ratol poisoning, despite elevated pancreatic enzymes, it is prudent to meticulously image pancreas before embarking on liver transplantation. In those with pretransplant elevation of pancreatic enzymes, it is desirable to follow up the enzyme values postoperatively.

Correlation between insulin resistance and liver histology in patients with nonalcoholic steatohepatitis with and without obesity.

INTRODUCTION: Insulin resistance (IR) plays a central role in pathogenesis of nonalcoholic steatohepatitis (NASH). The aim of this study was to correlate histopathological grading and IR in overweight/obese patients with NASH as compared with lean NASH. METHODS: Patients with NASH who underwent liver biopsy between January 2012 and December 2012 were included. Anthropometric, clinical, and biochemical features, necro-inflammatory grades, and fibrosis stage on liver biopsies were scored according to Brunt and non-alcoholic fatty liver disease (NAFLD) activity score (NAS). RESULTS: Of 42 patients, 33 (78.6%) had body mass index (BMI) ≥ 23 kg/m2 (overweight/obese) while 9 had BMI < 23 kg/m2 (lean). Mean fasting blood sugar (FBS) and HbA1c levels in overweight/obese patients with NASH were higher than in lean NASH (p < 0.05). The median homeostatic model assessment-estimated insulin resistance (HOMA-IR) among NASH patients with BMI ≥ 23 kg/m2 was higher than among those with BMI < 23 kg/m2 (3.02 [0.34-17.22] vs. 2 [0.52-5.26]; p = 0.045). However, fasting insulin levels were comparable among lean and overweight/obese patients with NASH. Metabolic syndrome could be predicted with 75% sensitivity and 85.3% specificity at a HOMA-IR cutoff value of 3.9. No significant difference was observed with regard to HOMA-IR levels with Brunt grades, Brunt staging, Brunt grades 1 and 2, Brunt scores < 2 and > 2, and NAS scores, and NAS scores < 4 and > 4. CONCLUSIONS: Although IR was significantly higher in overweight/obese patients with NASH as compared with that in lean patients with NASH, there was no difference in the correlation of HOMA-IR with histology between these groups.

Adrenal insufficiency in decompensated cirrhotic patients without infection: prevalence, predictors and impact on mortality.

BACKGROUND: Relative adrenal insufficiency (RAI) is common in compensated and decompensated chronic liver disease in the presence of sepsis. This study was performed to find out the prevalence of RAI in decompensated cirrhotic patients presenting with hepatic encephalopathy and variceal bleeding without any evidence of infection. METHODS: The study prospectively included 75 cirrhotic patients with signs of decompensation. The short Synacthen test (SST) was performed on all patients after ruling out infection. Patients with positive blood, urine, sputum, ascitic and pleural fluid cultures or evidence of infection on chest X-ray and those with elevated procalcitonin levels (>0.05 ng/ml) were excluded. RAI in critical illness was defined by a delta cortisol level (difference between basal and post-stimulation cortisol) of ≤9 µg/dl after SST. RESULTS: The mean age of the study population was 54 ± 11 years. Upper gastrointestinal bleed and hepatic encephalopathy were seen in 56.6% and 41.5%, respectively, and both were seen in 1.9%. Of the 75 patients, 55 (73%) were in Child-Turcotte-Pugh (CTP) class C and the mean model for end-stage liver disease (MELD) score was 21 ± 7. Forty-five patients (60%) met our criteria for RAI. Those with RAI had lower serum albumin (2.4 ± 0.5 g/dl vs 2.7 ± 0.5 g/dl, p = 0.03) and higher MELD scores (22 ± 7 vs 19 ± 6, p = 0.03). Prevalence of RAI in CTP class C was 65% (36 out of 55 patients) compared to 45% (9 out of 20 patients) in Child-Pugh stage A and B. Similarly, 82% (23 out of 28 patients) with MELD scores >25 had RAI compared to 54% with MELD scores <20. None of biochemical parameters were predictive of RAI on logistic regression analysis. Three-month mortality rate was not significantly different in patients with or without adrenal insufficiency (44% vs 28%, p = 0.11). CONCLUSION: The present study showed RAI to be common in noninfected decompensated cirrhotic patients, but did not predict 3-month mortality. There were no other predictive factors in those with RAI. Hence, in patients with cirrhosis without infection, the clinical utility of routine adrenal function testing needs further elucidation.

Clinical and sub-clinical vitamin A deficiency among rural pre-school children of Maharashtra, India.

BACKGROUND: Although a national vitamin A prophylaxis programme has been in operation for more than three decades, vitamin A deficiency (VAD) continues to be a major nutritional problem of public health significance in India. AIM: The present study was carried out with the aim of assessing the prevalence of clinical and sub-clinical VAD among rural pre-school children. SUBJECTS AND METHODS: A community-based cross-sectional study was carried out in rural areas of Maharashtra State during 2002-2003. A total of 8646 pre-school children were examined for the presence of signs and symptoms of VAD. A sub-sample (494) of them was used to estimate blood vitamin A levels. RESULTS: The prevalence of Bitot's spots (1.3%) and night blindness (1.1%) was higher than the WHO cut-off levels used to define a public health problem, and it increased significantly (p<0.001) with increase in age. The prevalence of Bitot's spots was 13 times higher among children belonging to the Scheduled Caste (OR=12.8), and 20 times higher among the children of labourers (OR=19.8). The prevalence of sub-clinical VAD (55%) was significantly (p<0.001) high among the children with night blindness (100%) and Bitot's spots (89%). CONCLUSIONS: Increased vitamin A supplementation, health and nutrition education and consumption of vitamin A rich foods are essential to prevent VAD.

Dissolution of pharmacobezoar using carbonated beverage.

Bezoars are concretion of undigested material found in the upper alimentary tract, particularly the stomach. Physiologic disturbances such as gastrointestinal dysmotility or anatomical derangements have been described as contributory in most cases of pharmacobezoars. Gastric phamacobezoars can be treated with endoscopic fragmentation or surgery. Gastric lavage with carbonated beverage has been successfully used to treat gastric phytobezoars. We report a 67-year-old man with pharmacobezoar successfully treated by infusion and intrabezoar injection of carbonated beverage. Subsequent endoscopy revealed an underlying adenocarcinoma in the stomach.

Small cell carcinoma occurring in a case of ulcerative colitis.

A 61-year-old man, with an 8-year history of ulcerative colitis, presented with bleeding per rectum for 4 weeks' duration. Colonoscopy revealed polypoidal neoplasm at the rectosigmoid junction. Histopathology depicted small cell carcinoma. On immunohistochemical staining, chromogranin A and synaptophysin were positive. The tumour was diagnosed as undifferentiated small cell carcinoma, which is unusual since generally it is the adenocarcinoma that occurs on a background of ulcerative colitis and there are only three previous reports of small cell carcinoma occurring in UC.

Stimulation of angiogenesis using single-pulse low-pressure shock wave treatment.

Endothelial cells respond to mechanical stimuli such as stretch. This property can be exploited with caution to induce angiogenesis which will have immense potential to treat pathological conditions associated with insufficient angiogenesis. The primary aim of this study is to test if low-pressure shock waves can be used to induce angiogenesis. Using a simple diaphragm-based shock tube, we demonstrate that a single pulse of low pressure (0.4 bar) shock wave is enough to induce proliferation in bovine aortic endothelial cells and human pulmonary microvascular endothelial cells. We show that this is associated with enhanced Ca++ influx and phosphorylation of phosphatidylinositol-3-kinase (PI3K) which is normally observed when endothelial cells are exposed to stretch. We also demonstrate the pro-angiogenic effect of shock waves of single pulse (per dose) using murine back punch wound model. Shock wave treated mice showed enhanced wound-induced angiogenesis as reflected by increased vascular area and vessel length. They also showed accelerated wound closure compared to control mice. Overall, our study shows that just a single pulse/shot (per dose) of shock waves can be used to induce angiogenesis. Importantly, we demonstrate this effect using a pulse of low-pressure shock waves (0.4 bar, in vitro and 0.15 bar, in vivo). KEY MESSAGES: Low-pressure single-pulse shock waves can induce endothelial cell migration and proliferation. This effect is endothelial cell specific. These shock waves enhance wound-induced angiogenesis in vivo. These shock waves can also accelerate wound healing in vivo.

Rapunzel syndrome: a case report and review of literature.

Bezoars consist of ingested foreign material or organic matter which forms a mass in the gastrointestinal tract, usually in stomach. Trichobezoars formed by swallowed hair present with malnutrition, weight loss, abdominal pain with signs of gastrointestinal obstruction. Gastric trichobezoar with a tail reaching the small intestine is called Rapunzel syndrome. Although endoscopic methods are available to remove bezoars, majority of trichobezoars with Rapunzel syndrome undergo surgical removal.

Gall bladder carcinoid: a case report and review of literature.

Gall bladder carcinoid tumours are rare and usually lack specific symptoms. In most instances, they are incidentally detected after a cholecystectomy and rarely do they manifest with carcinoid syndrome. We report a case of gall bladder carcinoid in a patient who had undergone surgery for rectal carcinoid 10 years back. Occurrence of rectal carcinoid and gall bladder carcinoid in the same patient has not been reported before.

Endoscopic abnormalities in the oesophagus after variceal sclerotherapy--a long-term follow up study.

Endoscopic sclerotherapy is a well-established treatment modality for oesophageal varices. Various local, regional and systemic complications occur after sclerotherapy. Altered endoscopic appearances of the oesophagus have been observed on follow-up of patients after sclerotherapy. 171 consecutive patients with extra-hepatic portal venous obstruction on follow up after achieving variceal eradication by sclerotherapy during the period from January 2004 to June 2005 were enrolled in this study. The oesophagus was closely observed for mucosal abnormalities and the endoscopic findings were recorded. Out of 171 patients, 95 (55.5%) patients had no specific endoscopic changes in the oesophagus. The most common finding was mucosal neovascularization which was seen in 56 (32.7%) patients. Oval or oblong depressed areas were seen in 41 (23.9%) patients. Mucosal tags and polypoidal lesions were seen in 37 (21.6%) patients. 25 (15.6%) patients had stenosis of the lower oesophagus and 3 (1.7%) patients had mucosal bridges. On multivariate analysis, these abnormal endoscopic findings in the oesophagus correlated with the total volume of sclerosant injected when compared with those patients without similar findings on endoscopy (p value < 0.001). Endoscopic sclerotherapy leads to various abnormalities at the injection sites like neovascularization, oval or oblong depressed areas, mucosal tags, polypoidal lesions, stenosis and mucosal bridges. Endoscopic abnormalities correlated with the total volume of sclerosant used. The long-term significance of these changes is not known at present and further follow-up studies will be required.

Listening to music decreases need for sedative medication during colonoscopy: a randomized, controlled trial.

BACKGROUND: Music played during endoscopic procedures may alleviate anxiety and improve patient acceptance of the procedure. A prospective randomized, controlled trial was undertaken to determine whether music decreases the requirement for midazolam during colonoscopy and makes the procedure more comfortable and acceptable. METHODS: Patients undergoing elective colonoscopy between October 2003 and February 2004 were randomized to either not listen to music (Group 1; n=40) or listen to music of their choice (Group 2; n=38) during the procedure. All patients received intravenous midazolam on demand in aliquots of 2 mg each. The dose of midazolam, duration of procedure, recovery time, pain and discomfort scores and willingness to undergo a repeat procedure using the same sedation protocol were compared. RESULTS: Patients in Group 2 received significantly less midazolam than those in Group 1 (p=0.007). The pain score was similar in the two groups, whereas discomfort score was lower in Group 2 (p=0.001). Patients in the two groups were equally likely to be willing for a repeat procedure. CONCLUSION: Listening to music during colonoscopy helps reduce the dose of sedative medications and decreases discomfort experienced during the procedure.

Abrikosoff's tumor of the esophagus: case report and review of literature.

Abrikosoff's tumor or granular cell tumor is a neoplasm of neural origin, usually located in the head and neck region. A majority of these neoplasms are benign. Only 4-6% of granular cell tumors are located in the gastrointestinal tract. It is extremely unusual for these tumors to be located in the esophagus. This case is being reported in view of the rarity of this lesion. A brief review of literature with stress on diagnostic evaluation and management issues is also included.

Prevalence of Hepatitis B and C in the normal population and high risk groups in north Kerala.

BACKGROUND: Our aim is to assess the prevalence of Hepatitis B and Hepatitis C infections among normal healthy persons and high risk groups in the northern part of Kerala state in South India as there is insufficient published literature related to this subject. METHODS: HBsAg and AntiHCV screening were done in normal persons and in high risk groups. Normal persons screened included voluntary blood donors, those attending mandatory medical check up for jobs in middle east Asia and pregnant women. High risk groups were health care workers, intravenous drug abusers, commercial sex workers and male homosexuals. RESULTS: HBsAg and anti HCV antibody test results in the various groups were as follows. Voluntary blood donors--HBsAg was positive in 0.71 % and anti HCV was positive in 0.33%; job seekers to middle east Asia had 0.89% and 0.12% prevalence of HBV and HCV respectively. Among the pregnant women, 0.21% were HBsAg positive. Among the high risk groups, none of the health care workers were HbsAg positive and 0.79% were antiHCV positive. Among the IV drug abusers 2.7% were HBsAg positive and 51.89% were positive for antiHCV. In commercial sex workers, 3.47 % were HBsAg positive and 2.6 % were antiHCV positive. In male homosexuals, 4.49% were HBsAg positive and 3.37% were antiHCV positive. CONCLUSIONS: The prevalence of Hepatitis B and C in the normal population of Calicut in the northern part of Kerela is 0.52% and 0.24%. Compared to other areas of India, the seroprevalence of Hepatitis B and C are low in the normal population of Calicut. Among the high-risk groups, IV drug users have a high prevalence of AntiHCV.

Sub-site specific time trends of carcinoma stomach in North Kerala--a retrospective analysis.

The time trends in the incidence of carcinoma stomach in the various sub-sites in stomach have been documented in the western population. The incidence of carcinoma of gastric cardia is found to be increasing, while that of the antrum is seen to be decreasing. Data from tropics is lacking on this aspect. This retrospective study was performed to look into the site-specific time trends of carcinoma stomach. Endoscopy registers maintained in the Department of Gastroenterology, Medical College, Kozhikode, Kerala in South India were screened over the period of 20 years from 1982 to 2001. Histopathologically confirmed cases of adenocarcinoma were included in the study. The cases were categorized according to different areas of stomach--cardia, fundus, body and antrum as per International classification of diseases 0-9 (zero-nine) codes. Time trend for each sub site was calculated using one-way ANOVA and Chi-square for trend. Of the 26,886 upper GI endoscopies done over 20 years, 1771 were found to be gastric adenocarcinomas. Gastric antrum was the most common site of cancer over the years (47.8%). There was a significant rising trend for gastric cancer of the cardia without a similar trend for the cancer of the body and antrum during the study period. The sub site-specific time trends of carcinoma stomach are not similar to the pattern seen in western countries. There is a rising trend for the cancer of the cardia with a stable trend for distal cancers over 20 years.

Umbilical hemorrhage as first manifestation in a case of cirrhosis.

Portal hypertension is often associated with an extensive collateral circulation. The paraumbilical vein is a relatively common collateral pathway recognized in these patients but cutaneous bleeding from the umbilicus is rare; the same as first manifestation of cirrhosis is exceptional. We report a case of umbilical venous bleed causing hemodynamic compromise, which turned out to be a case of alcoholic cirrhosis with portal hypertension. The patient was managed with suture ligation of the vessels.

Prospective evaluation of abnormal liver function tests in pregnancy.

Abnormalities in liver function tests (LFT) during pregnancy are a commonly encountered problem often associated with serious consequences especially when it occurs in the third trimester. The spectrum of abnormal liver functions in pregnancy can be fairly wide and diagnostic work up often challenging. There is insufficient prospective data on the spectrum and outcome of liver disease in pregnant population from south India. This study was performed to assess the causes of deranged liver function in the pregnant population and also to prospectively determine the outcome of liver dysfunction in pregnancy. All abnormal LFT results observed in serum samples from pregnant patients attending the obstetric unit of our hospital from January 2003 to January 2005 were evaluated and prospectively followed throughout pregnancy. Laboratory investigations included coagulation profile, renal function tests, serology for viral markers (HBsAg, anti-HCV, IgM anti-HEV and IgM anti-HAV) and other relevant biochemical tests. In those with liver dysfunction in the third trimester the maternal and perinatal outcome was evaluated. A total of 125 patients were identified with abnormalities in LFT results during this period. The majority of causes were related to pregnancy specific conditions (57.6%). Most episodes of abnormal LFT occurred in the third trimester (59.2%). Hyperemesis gravidarum (55.8%) and viral hepatitis (47%) were the most common causes of abnormal LFT in the first and second trimesters respectively. HELLP (28.3%) and AFLP (14.8%) were the most common causes of abnormal LFT in the third trimester. There were no mAternal deaths due to liver dysfunction in the first or second trimester. Liver dysfunction in the third trimester (74 patients) was associated with serious consequences. DIC was the most common complication (20.2%). The overall and perinatal mortality was 20.2% and 24.6% respectively. AFLP and HELLP syndromes were associated with poor maternal and fetal outcome. We conclude that liver dysfunctions were directly related to pregnancy in the majority of patients especially in the third namely trimester. Incidence of the most serious conditions AFLP and HELLP syndromes is much greater than what has been reported and is often associated with a high maternal mortality and poor perinatal outcome.