Bedside Index of Severity in Acute Pancreatitis (BISAP) Score on Outcome of Patients Presenting with Acute Pancreatitis in a Tertiary Care Hospital.

Background Acute pancreatitis is a life-threatening condition characterized by inflammation of the pancreas causing intense abdominal pain and potential harm to multiple organs. The mortality rate is 1-5% and thus requires specialized and interdisciplinary care to inhibit it. Objective To describe the bedside index of severity in acute pancreatitis score on the outcome of acute pancreatitis patients in a tertiary care hospital. Method This is a hospital based observational cross-sectional study conducted in the internal medicine inpatient department of Dhulikhel Hospital from April 2018 and March 2019. This study reviewed the medical records of the department. Result The study included 70 participants with 44 (±14) years of average age and stating common cause as gallstone (45.7%). The study showed that those with bedside index of severity in acute pancreatitis score ≥ 3 during hospital admission had significantly higher rate of organ failure (p-value < 0.05), as well as had a prolonged hospital stay (mean: 20 [±7.9] days). The mean hospital stay was 12.9 days. Conclusion Patients with bedside index of severity in acute pancreatitis score greater than three at admission were found to have an increased risk of organ failure, significantly higher chances of requiring mechanical ventilation, and a longer duration of hospital stay.

Rickettsial Infection amongst Febrile Illness Patient in a Tertiary Care Hospital: A Retrospective Cross-sectional Study.

Background Rickettsial infection is an emerging neglected tropical disease in the Southeast Asia. In past few years Nepal is also reporting escalating prevalence of rickettsia. The under evaluation is resulting it as undiagnosed or are simply labeled as pyrexia of unknown origin. Objective To find out the prevalence of rickettsia in a hospital setting, assess the sociodemographic and other relevant clinical features of the rickettsia patients. Method This is a hospital based retrospective cross-sectional study from October 2020 to October 2021. This study reviewed the medical records of the department. Result The study included 105 eligible patients and the prevalence rate was 4.38 per 100 patients. The mean age of the participants was 42 years, and the mean hospital stay was 3 (SD ±2.06) days. More than 55% of the participants had fever for less than or equal to 5 days and 9% had Eschar present. Vomiting, headache, and myalgia were the most common symptoms and hypertension, and diabetes were the common comorbidities. Pneumonia and the acute kidney injury were the two complications of the patients as stated in the study. The severity of the thrombocytopenia deducted from admission time to discharge, and the case fatality was 4%. Conclusion The future studies shall consider on collaborative clinical and entomological research. This would help in better understanding of the etiology of supposedly unknown febrile illness and the under-investigated field of emerging rickettsia in Nepal.

Persistent circulating platelet and endothelial derived microparticle signature may explain on-going pro-thrombogenicity after acute coronary syndrome.

AIMS: Microparticles (MPs) are submicron vesicles, released from activated, and apoptotic cells. MPs are elevated in the circulation of patients with coronary artery disease (CAD) and have pro-thrombotic potential. However, limited data exists on MP signature over time following an acute coronary event. METHODS & RESULTS: Circulating total annexin v + (Anv+) MPs of endothelial (EMP), platelet (PMP), monocyte (MMP), neutrophil (NMP) and smooth muscle cell (SMMP) origin were quantified by flow cytometry. 13 patients with acute coronary syndrome (ACS) were prospectively enrolled and 12 patients with stable angina (SA) were included as a comparator group. A panel of MP was measured at baseline, after percutaneous coronary intervention (PCI) and at days 1, 7, 30 and 6 months. Intra & inter group comparison was made between various time points. MP mediated thrombin generation was measured by recording lag phase, velocity index, peak thrombin and endogenous thrombin potential at these time points and compared with healthy controls. The total AnV+ MP levels were similar in ACS and SA groups at baseline, peaked immediately after PCI and were at their lowest on day 1. PMP & EMP levels remained significantly elevated in ACS patients at 6 months when compared to SA. No such difference was noted with NMP, MMP and SMMP. Patients with coronary artery disease showed abnormal thrombograms when compared to controls. Peak thrombin (nano moles) was significantly higher in CAD when compared to controls (254 IQR [226, 239] in ACS, 255 IQR [219, 328] in SA and 132 IQR [57, 252] in controls; p = 0.006). Differences in thrombin generation between ACS and SA were not significant (p = 1). Furthermore, thrombin parameters remained abnormal in ACS & SA patients at 6 months. CONCLUSIONS: Total MP and individual MP phenotypes were significantly elevated after PCI reflecting endothelial injury. Elevated PMP and EMP levels at 6 months in ACS patients is suggestive of on-going inflammation, endothelial injury and may explain on-going pro-thrombogenicity seen up to 6 months after ACS despite dual antiplatelet therapy.

Associations of young onset age and genetic risk of beta cell dysfunction with glycaemic progression in individuals with type 2 diabetes.

AIM: To study the relationship between genetic risk of beta cell dysfunction, young onset age and glycaemic progression in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: 1385 T2D outpatients were included in cross-sectional sub-study and 730 insulin-naïve outpatients were followed for 3 years in prospective sub-study. Genetic risk score (GRS) was derived from 24 beta cell dysfunction-related single nucleotide polymorphisms, with lower and upper 25 percentiles defined as low and high genetic risk. Glycaemic progression was defined as requirement for sustained insulin therapy. RESULTS: 388 participants in cross-sectional and 128 in prospective sub-study experienced glycaemic progression. Young onset age (T2D diagnosis below 40 year-old) was associated with high risk of glycaemic progression as compared to usual-onset counterparts (adjusted OR 1.64 [95% CI 1.14-2.36], and 2.92 [95% CI 1.76-4.87] in cross-sectional and prospective sub-study, respectively). As compared to those with intermediate risk, a low GRS was associated with lower risk for glycaemic progression (adjusted OR 0.72 [95% CI 0.49-1.06], and 0.51 [95% CI 0.29-0.90]) whereas a high GRS was not significantly associated with glycaemic progression. Notably, the association of young-onset T2D with high risk of glycaemic progression was independent of known clinical risk factors and beta cell dysfunction GRS (P interaction > 0.10). CONCLUSION: Young onset age and low genetic risk of beta cell dysfunction are independently associated with risk of glycaemic progression. Our data do not support that genetic risk modulates the risk of glycaemic progression in individuals with young-onset T2D.

The role of laboratories in animal-related disasters and emergencies.

This paper outlines the role of laboratories in animal-health-related disasters and emergencies, with a particular focus on biological threats - intentional, accidental and natural. Whilst multisectoral coordination is increasingly recognised as necessary for effective preparedness and response to all kinds of disasters, the role of the laboratory is often overlooked. The laboratories' involvement, not just in the response, but across all phases of disaster management - mitigation, planning, response and recovery - is essential, not only for improved animal health but for preservation of livelihoods and for food security, social cohesion and economic stability.

Les auteurs examinent le rôle des laboratoires dans les catastrophes et les urgences affectant les animaux, en se centrant particulièrement sur les menaces biologiques (qu'elles soient intentionnelles, accidentelles ou naturelles). Si la nécessité d'une coordination multisectorielle pour une préparation et une intervention efficaces face aux catastrophes de toute nature est désormais mieux perçue, le rôle des laboratoires est souvent négligé. La participation des laboratoires est essentielle, non seulement dans les interventions mais aussi dans chacune des phases de la gestion des catastrophes, à savoir l'atténuation, la planification, l'intervention et le redressement et ce, non seulement pour améliorer la santé animale, mais aussi pour préserver les moyens de subsistance et la sécurité alimentaire, la cohésion sociale et la stabilité économique.

Los autores exponen a grandes líneas la función que cumplen los laboratorios frente a desastres o emergencias que guardan relación con el mundo animal, prestando especial atención a las amenazas biológicas, ya sean de origen natural, accidental o intencionado. Mientras que por un lado se asienta cada vez más la idea de que la coordinación multisectorial es indispensable para una eficaz labor de preparación y respuesta ante todo tipo de desastres, a menudo se pasa por alto la función que en la materia incumbe a los laboratorios. Es esencial que estos participen no solo en las labores de respuesta, sino en todas las fases del proceso de gestión de desastres (mitigación, planificación, respuesta y recuperación), y ello no solo para mejorar la situación zoosanitaria, sino también para preservar los medios de sustento y proteger la seguridad alimentaria, la cohesión social y la estabilidad económica.

Extensive Surgical Emphysema in a Child after Primary Closure of Tracheocutaneous Fistula.

A 4-year-old child had closure of tracheocutaneous fistula under general anaesthesia. He developed extensive surgical emphysema over the face, chest, and upper abdomen immediately in the recovery room. We gave him oxygen supplementation, removed surgical stitch, and inserted a 4 mm tracheostomy tube to secure airway. Chest X-ray ruled out pneumothorax or pneumomediastinum. After a week, a tight bandage was applied which approximated the tissue and helped in the closure of stoma; no suture was applied. The patient was discharged home on the fourth postoperative day. The patient needs close observation in the postoperative period with likely complication in mind. Recognizing early signs and symptoms of respiratory distress with quick intervention is lifesaving during the complication of tracheocutaneous fistula surgery. In absence of pneumothorax or pneumomediastinum, extensive surgical emphysema occurring during primary closure of tracheocutaneous fistula can be treated without inserting any drainage tube.

Investigating the Efficacy of Triple Drug Therapy and Sequential Drug Therapy in the Eradication of Helicobacter Pylori with Respect to Antigen Stool test: A Pilot Study.

Background Helicobacter pylori is one of the most prevalent infectious disease worldwide. The treatment regimens involve mainly two therapies: Standard Triple drug therapy and Sequential drug therapy. Several studies have shown that the sequential therapy has higher eradication rates of H. pylori than the standard triple drug therapy and since proper study on sequential drug therapy and standard triple drug therapy is still lacking in Nepal, this study is attempted to compare efficacy of Sequential Drug Therapy in the eradication of H. pylori in gastritis with respect to the Standard triple drug therapy. Objective To investigate the efficacy of Triple Drug Therapy and Sequential Drug Therapy in the eradication of Helicobacter pylori with respect to Antigen Stool test. Method This study was the prospective study conducted in 62 patients attending the Department of Gastroenterology, Dhulikhel Hospital, meeting the inclusion criteria who were confirmed as H. pylori positive by histopathology and stool antigen test. Patients were randomized into two groups. One group prescribed with Standard triple drug regimen and another group with Sequential drug regimen. Eradication of H. pylori infection was confirmed by repeating the stool antigen test at least five weeks after the completion of the regimen. Result Among the 62 participants included in this study, 54.5% of them were males. Among the study population, the eradication achieved by standard triple drug therapy was 87.8% and 89.6% with Sequential drug therapy. Higher numbers (82.3%) of patients were compliant to the prescribed medication. Forgetfulness was the main reason for missing the dose (91%) of the non-compliant patients. Conclusion The study revealed an equal efficacy of both Standard Triple drug regimen and Sequential drug regimen in the eradication of H. pylori infection. Further, Stool antigen test can be preferred as a non-invasive test, for diagnosis of H. pylori infection, monitoring the response to treatment and in epidemiological studies.

Endoscopic Management of Foreign Body Impaction in the Upper Gastrointestinal Tract in a Tertiary Care Centre of Nepal.

Background Ingested foreign body impaction on upper gastrointestinal tract is common incidence among children, older age group, mentally challenged individuals, and people the influence of alcohol. In most cases, the foreign bodies pass spontaneously and uneventfully but when this does not occur; endoscopic management to ensure removal under direct visualization is required. Relief upon removal of foreign body and prevention of complications is essential. Objective To assess the endoscopic management and outcome of foreign body impacted in the upper gastrointestinal tract. Method This is a hospital based observational retrospective cross sectional study involving 165 patients at Endoscopy Department of Dhulikhel Hospital in Nepal between November 2015 and October 2019. The data regarding the demographic profile, clinical characteristics and endoscopic findings were retrieved and analyzed to determine endoscopic interventions performed, complications and outcomes. Result One hundred and sixty five patients presenting with history of ingestion of foreign body were included in the study. The mean age of the patients was 46.8 ± 19.1 years with male predominance (60%). The most common site of foreign body impaction was oesophagus (70%). The most common foreign body encountered was bone (62.2%) among which chicken bones (91.1%) were most frequent. For the retrieval of sharp-pointed foreign bodies, rat forceps and graspers (45.7%) were most commonly used. Total 14 cases required rigid oesophagoscopy as the foreign body could not be retrieved by flexible endoscopy. Conclusion Foreign body ingestion and its impaction in the upper gastrointestinal tract has been found to be common in endoscopic practise. Early detection and timely removal of foreign bodies is of utmost importance to avoid discomfort to the patient as well as to ensure successful removal without complications.

Outcomes of Endoscopic Sphincteroplasty Using Large Balloon Dilatation for Difficult Common Bile Duct Stone Removal at Dhulikhel Hospital.

Background Endoscopic sphincteroplasty (ESPT) using a large Controlled Radial Expansion (CRE) Wire guided balloon dilatation has gained acceptance in removing a difficult common bile duct (CBD) stones. Objective To evaluate effectiveness and complications of removing large and difficult bile duct stones with sphincterotomy combined with large balloon dilatation. Method A total of 132 patients, from February 2014 to June 2017, who had biliary ductal calculus which was either greater than 15 mm or difficult to remove with standard technique, underwent Endoscopic Retrograde Cholangiopancreaticography (ERCP) with Endoscopic sphincteroplasty using a large Controlled radial expansion wire guided balloon dilatation. The success rate of complete stone clearance and post Endoscopic Retrograde Cholangiopancreaticography complications were analyzed. Result There were 48 (36.4 %) male and 84 (63.6%) female patients with mean age of 55.48 ± 16.36 years. Stones were removed with sphincteroplasty in first attempt in 90 out of 132 (68.2%) patients, 26 out of 37 (70.27%) patients in second session and in all 7(100%) patients in third attempt. Five (11.90%) patients were lost to follow up and 4 were advised for surgery because of failure to remove stones by sphincteroplasty. Overall success of endoscopic sphincterotomy and large balloon dilatation in our study was 93.18%. Complications were seen in 17 (13.6%) patients; bleeding seen in 9 (6.8%) patients and mild pancreatitis in 8 (6.1%) patients. None of the patients had severe pancreatitis or perforation secondary to the procedure. Conclusion Endoscopic sphincteroplasty after sphincterotomy is an effective and safe technique for a difficult common bile duct stone removal.

Where is the Perforation ? Rare Complication of Endoscopic Retrograde Cholangio Pancreatography.

Perforation is one of the most feared complications of Endoscopic Retrograde Cholangio Pancreatography (ERCP). ERCP has become important method for treating biliary-pancreatic diseases. Perforation related with Endoscopic Retrograde Cholangio Pancreatography is an infrequent, but if happens is a severe complication. Reported incidence of Edoscopic Retrograde Cholangio Pancreatography related perforation is 0.3-6%. Its mortality is as high as 37.5%. In our hospital since 2010 AD, There were 6 Perforations related to Endoscopic Retrograde Cholangio Pancreatography done in 4787 cases. This is a case of Endoscopic Retrograde Cholangio Pancreatography related perforation with no site of perforation recognized during surgical management.

The impact of ocular trauma during the Nepal earthquake in 2015.

BACKGROUND: Nepal was struck by a massive earthquake on the 25th April 2015 and major aftershock on the 12th of May 2015, resulting in widespread devastation with a death toll in the thousands. The burden of ocular trauma resulting from the recent earthquakes in Nepal has not been described thus far. The aim of this study was to determine the types of ocular injuries sustained in the earthquake in Nepal and its management in Tilganga Institute of Ophthalmology (TIO) in Gaushala, Kathmandu. METHODS: This is a hospital-based retrospective study of patients presenting to TIO following repeated earthquake. Variables that were recorded included patients' presenting symptoms and time to presentation, visual acuities at presentation and at follow-up, diagnosis of ocular injury and surgery performed. RESULTS: There were 59 cases of earthquake victims visiting TIO, Gaushala, Kathmandu from April 2015 to July 2015, with 64 affected eyes due to 5 cases of bilateral involvement. The majority of patients were from the district Sindhupalchowk (14 cases, 23.7%), which was the epicenter of the main earthquake. The average duration between the earthquake and presentation was 13 · 9 days (range 1-120 days). Closed globe injury was most frequent (23 cases), followed by open globe injuries (8 cases). While 24 patients (38%) initially presented with a visual acuity <3/60 in their affected eye, 15 patients (23%) had a visual acuity of <3/60 on follow-up. A variety of surgical treatments were required including anterior and posterior segment repair. CONCLUSIONS: Immediate management of ocular trauma is critical in order to prevent blindness. Characterizing the burden of earthquake-related ocular trauma will facilitate planning for service provision in the event of a future earthquake in Nepal, or in countries, which are similarly at risk of having natural disasters.

Clinico-Pathological Correlation of Colorectal Diseases by Colonoscopy and Biopsy.

Background Colonoscopy is a simple, safe and well tolerated procedure, the visualization of the mucosa of the entire colon and terminal ileum to detect intestinal abnormalities and obtain biopsy leads to the early detection of the pathologic process and institution of appropriate therapy. Objective To find out the correlation between clinical and histopathological diagnosis of colorectal diseases. Method A cross-sectional study was conducted at Department of Pathology, Dhulikhel Hospital, Kathmandu University Hospital from Jan. 2015 - Jan. 2016. Altogether, 95 colonoscopic biopsies were examined and recorded clinical data using pre-designed pro forma. The specimens were grossed, processed and embedded using standard procedures, stained with Hematoxylin and Eosin stain and were analyzed using light microscope. Special stains Ziehl Neelsen, and Periodic Acid-Schiff were used whenever necessary. Result Analyses of 95 cases of colonoscopic biopsies were done. The most common clinical diagnosis was polyp in 49 cases (51.57%) and the common histopathological diagnosis was non-neoplastic polyps 31(32.63%). There was no correlation in cases for suspected infectious colitis, microscopic colitis and hemorrhoids. Conclusion Colonoscopy is incomplete without biopsy and histopathology is the gold standard for the diagnosis of colorectal lesions. The clinico-pathological correlation for neoplastic lesions was excellent. However, correlation was poor in non-neoplastic lesion.

The Etiology of Upper Gastrointestinal Bleeding in Patients with Liver Cirrhosis in Dhulikhel Hospital.

Background Acute upper gastrointestinal bleeding is a serious medical problem in cirrhotic patients. Patients with cirrhosis may develop upper gastrointestinal bleeding from a variety of lesions, including those due to portal hypertension, namely gastroesophageal varices and portal hypertensive gastropathy and other lesions as seen in the general population. Objective To investigate the etiology of upper gastrointestinal bleeding in liver cirrhotic patients. Method A retrospective review of 72 patients with liver cirrhosis and upper gastrointestinal bleeding from January 2013 to March 2016 was carried out at Dhulikhel Hospital. Child Pugh score was used to assess severity. Endoscopic diagnosis was documented. Result Out of 72 patients, 56 (77.8 %) were male and 16 (22.2%) were female. The most common age group was 30-42 years age. Fifty four cases of cirrhosis were associated with alcohol consumption. The Child-Pugh score was A in 20 patients (27.8%), B in 15 patients (20.8%) and C in 37 patients (51.4%). A combination of alcohol consumption and HCV infection was significantly associated with a higher Child-Pugh score (p=0.031). Twenty six (36.11%) patients had esophageal varices as cause of bleeding on endoscopic examination while 29(40.28%) had varices and other lesions identified at endoscopy. Of these 29 patients, 18 were found to have bled from esophageal varices, and 11 were found to have bled from coexisting lesion. Conclusion We found that variceal bleeding was the commonest cause of bleeding in cirrhotic patients, with 55 (78.5%) having varices and 44 (61%) actually bleeding from varices.

Medication Adherence Pattern and Factors affecting Adherence in Helicobacter Pylori Eradication Therapy.

Background Helicobacter pylori (H. pylori) infection is the most common chronic bacterial infection worldwide affecting approximately half of the world's population. A number of screening tests as well as complex multi-drug therapies are available for the detection and treatment of H. pylori infection. However, the optimum eradication rates of H. pylori infection can only be achieved if adherence to drug therapy is higher. Therefore, it is of utmost importance to determine the factors leading to poor adherence to obtain successful treatment outcomes. Objective To determine the medication adherence pattern in patients with H. pylori infection and assess the factors associated with non-adherence to the prescribed drug therapy. Method Patients meeting the inclusion criteria who were confirmed as H. pylori positive by rapid urease test (histopathology) and/ or stool antigen test and those under H. pylori eradication therapy were considered. Informed consent was taken from the patients or from the patient party in incapacitated patients. They were then interviewed using structured questionnaire. Statistical analysis was done using SPSS version 20 and a p-value < 0.05 was considered as statistically significant. Result Among the 70 participants included in this study, 57.10% (n=40) of them were males. The mean (±SD) age of the patients was 42.36 years (±17.93). Higher number (85.70% (n=60)) of the patients were adherent to the recommended medication. Forgetfulness was the reason for missing dose in a majority (80% (n=8)) of the nonadherent patients. A highly significant association (p<0.05) was observed between adherence and absence of symptomatic relief. However, there was no statistically significant association (p>0.05) between patients' adherence to gender, age, literacy, and the prescribed treatment regimen. Conclusion Majority of the patients with H. pylori infection were adherent to medication. Forgetfulness was the major reason for missing dose in the non-adherent patients.

Evaluation of Oral Bait Vaccine Efficacy Against Classical Swine Fever in Village Backyard Pig Farms in Bhutan.

Control and eradication of classical swine fever (CSF) in countries with a high proportion of backyard holdings is a challenge. Conventional attenuated Chinese C-strain vaccines, though safe and effective, are difficult to use in backyard farms due to various practical reasons. The aim of this study was to evaluate the efficacy of the CSF oral bait vaccine in village backyard pig farms and to assess the farmers' knowledge on CSF and motivation on using oral vaccines. The pigs were fed the bait by the farmers themselves; one bait was given on day 0, followed by second bait on the next day. Seventy-three per cent (140 of 193 pigs) of vaccinated pigs had either a slight (2-fold-3-fold; 60 pigs) or significant (at least 4-fold; 80 pigs) increase of the antibody titre against CSFV. A significant increase of the antibody titres was mainly observed in pigs with no pre-vaccination titre (OR = 12, 95% CI = 4-40). The number of pigs with protective antibody titres (≥40) rose from 47 (24%) to 115 (60%) following vaccination. Only 30% of the farmers claimed to be familiar with CSF, although clinical signs they mentioned were rather unspecific and could relate to many other pig diseases. Most of the farmers claimed to be motivated to use oral vaccines if made available. The oral vaccine could be a substitute for the conventional attenuated CSF vaccines in areas where it is logistically difficult for veterinarians to visit. It may therefore be a useful tool to combat endemic CSF disease in regions where the disease continues to have a serious impact on the backyard farmers who depend on pig farming for their sustenance and livelihoods.

A Cross-Sectional Study of Medication Adherence Pattern and Factors Affecting the Adherence in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is considered as a major health problem, associated with mortality and morbidities. Various disease management strategies have been established to optimize patient's longevity and functional status where patient adherence to the prescribed treatment plays a key role. Poor adherence to medication is common among COPD patients and is affected by number of factors like number of medicines, delivery devices and patient-related factors. OBJECTIVE: This study aims to investigate the adherence pattern in the management of COPD and factors affecting patient adherence to the prescribed treatment. METHOD: This study is a cross-sectional study which was conducted in a tertiary care hospital. Those patients suffering from COPD of all age were enrolled in this study and prior informed consent was obtained from patients. The structured questionnaire was used to interview those patients. RESULT: Total 100 patients were enrolled in this study, among which most patients (45%) were of age groups 60-70 years. Unintentional non-adherence to medication attributed for 65% of patients and the major reason was forgetfulness (52.3%). Most patients had discontinued the medication due to experience of side effects (63.3%). The result showed significant association between adherence and polypharmacy (p=0.00). However, there was no significant association between adherence and age, sex, mode of administration of drugs, technics to use delivery devices etc. CONCLUSION: Majority of COPD patients were elderly (mean age= 68.4 years). Forgetfulness was associated with medication non-adherence. Most of the patients had discontinued medication because of side effects. Polypharmacy is one of the major factors associated with non-adherence to medication in COPD.

What is the impact of genome-wide supported risk variants for schizophrenia and bipolar disorder on brain structure and function? A systematic review.

The powerful genome-wide association studies (GWAS) revealed common mutations that increase susceptibility for schizophrenia (SZ) and bipolar disorder (BD), but the vast majority were not known to be functional or associated with these illnesses. To help fill this gap, their impact on human brain structure and function has been examined. We systematically discuss this output to facilitate its timely integration in the psychosis research field; and encourage reflection for future research. Irrespective of imaging modality, studies addressing the effect of SZ/BD GWAS risk genes (ANK3, CACNA1C, MHC, TCF4, NRGN, DGKH, PBRM1, NCAN and ZNF804A) were included. Most GWAS risk variations were reported to affect neuroimaging phenotypes implicated in SZ/BD: white-matter integrity (ANK3 and ZNF804A), volume (CACNA1C and ZNF804A) and density (ZNF804A); grey-matter (CACNA1C, NRGN, TCF4 and ZNF804A) and ventricular (TCF4) volume; cortical folding (NCAN) and thickness (ZNF804A); regional activation during executive tasks (ANK3, CACNA1C, DGKH, NRGN and ZNF804A) and functional connectivity during executive tasks (CACNA1C and ZNF804A), facial affect recognition (CACNA1C and ZNF804A) and theory-of-mind (ZNF804A); but inconsistencies and non-replications also exist. Further efforts such as standardizing reporting and exploring complementary designs, are warranted to test the reproducibility of these early findings.

Correlation between Endoscopic and Histopathological Findings in Gastric Lesions.

Background Stomach is a common site for wide variety of lesions. The visualisation of the site with biopsy leads to the early detection of the pathologic process and appropriate therapy. Objectives The objective of this study is to correlate the histopathological pattern of endoscopic biopsies with distribution of gastric lesions according to age and sex. Method The retrospective study was carried out among 50 cases with endoscopic biopsies and histopathological assessment, received at Department of Pathology, Dhulikhel Hospital- Kathmandu University Hospital. Result Out of 50 cases majority of cases were of male gender with male: female ratio was 1.3:1. Our study showed a poor correlation between endoscopic and histopathological evidence of inflammation in the stomach. Two cases were diagnosed as intestinal metaplasia which were diagnosed as ulcer and erosion endoscopically. Out of 32% of cases diagnosed endoscopically as ulcer, only one case was confirmed histopathologically. Our study showed good correlation in the cases of carcinoma. Out of 17 cases diagnosed endoscopically as gastric carcinoma correlated histopathologically as gastric adenocarcinoma. Majority of carcinoma cases showed ulcerating fungating growth followed by ulcero-proliferative growth. Conclusion Endoscopy is incomplete without biopsy and histopathology is the gold standard for the diagnosis of endoscopically detected lesions. Endoscopic examination and histopathological examination of suspected gastric lesions should go parallel and neither should be a substitute of each other.

Development of 316v antibody enzyme-linked immunosorbent assay for detection of paratuberculosis in sheep.

An enzyme-linked immunosorbent assay (ELISA) was developed and optimised using a Mycobacterium avium subspecies paratuberculosis (MAP) antigen prepared from a C strain (316v) passed through a French press. The optimised assay was evaluated with a panel of sera from MAP infected (n = 66) and uninfected (n = 1,092) sheep. Animals in the MAP infected category were positive on either tissue culture or histopathology but were of unknown serum antibody status. The diagnostic performance and cost of the assay were compared with those of a commercial ELISA (IDEXX). At 99.8% diagnostic specificity the assay showed a diagnostic sensitivity of 23% (95% CI: 15.1-35.8) compared with 36.4% (95% CI: 25.8-48.4) for the commercial ELISA (McNemar's test: chi-square 5.82, p < 0.05). The sensitivities were 5.9% (95% CI: 1-26.9), 27.9% (95% CI: 14.7-45.7) and 35% (95% CI: 18.1-56.7), for low grade, paucibacillary and multibacillary lesion grades, respectively. The cost of the commercial assay kit was 2.7 to 5.2 times greater than that of the 316v ELISA for an equivalent number of tests, the multiple depending on the number of plates processed per run. For flock-level surveillance, to account for the lower sensitivity of the 316v ELISA compared with the commercial ELISA, sample sizes would be increased but the test cost would still be lower. The 316v assay will be useful for diagnosis of Johne's disease in sheep flocks, particularly in developing countries where labour costs are low relative to the cost of consumables.

Differential SKIP expression in PTEN-deficient glioblastoma regulates cellular proliferation and migration.

Glioblastoma is the most common and lethal primary malignant brain tumor in adults. The tumor suppressor gene PTEN is deleted, mutated or hypermethylated in more than 60% of glioblastoma cases resulting in hyperactivation of the phosphoinositide 3-kinase pathway, which leads to sustained PI(3,4,5)P3 signaling, and thereby hyperactivation of Akt and other effectors. PI(3,4,5)P3 is also hydrolyzed to PI(3,4)P2 by inositol polyphosphate 5-phosphatases such as SKIP, but the role this pathway has in glioblastoma is unknown. Microarray expression profiling of SKIP in human glioblastoma has revealed both increased and decreased SKIP gene expression. Here we have screened PTEN-deficient glioblastoma for SKIP protein expression by immunohistochemistry and report that SKIP expression is increased in some cases or decreased relative to normal brain. Using the U-87MG PTEN-deficient cell line we show that SKIP knockdown did not further enhance cell proliferation or survival. However, SKIP overexpression in U-87MG cells suppressed anchorage-independent cell growth and growth factor-induced PI(3,4,5)P3/Akt signaling. Although, SKIP knockdown did not affect cell proliferation or survival, cell migration was significantly retarded, associated with significantly increased PI(4,5)P2 signals, and decreased phosphorylation of the actin-regulatory protein cofilin, a PI(4,5)P2-binding protein. Notably, overexpression of SKIP also inhibited migration of U-87MG cells to a similar degree as observed with PTEN reconstitution, however, via distinct mechanisms. PTEN reconstitution promoted sustained lamellipodia generation and focal adhesion formation. In contrast, SKIP overexpression reduced sustained lamellipodia formation, talin incorporation into focal adhesions and recruitment of PI(4,5)P2-binding proteins to the plasma membrane. Notably, analysis of two independent ONCOMINE microarray data sets revealed a significant correlation between increased SKIP mRNA expression in glioblastoma and improved long-term survival. Therefore, SKIP expression in glioblastoma may affect the local invasion of PTEN-deficient tumors.