Search for Baryon Number Violation in Top Quark Production and Decay Using Proton-Proton Collisions at sqrt[s]=13 TeV.

A search is presented for baryon number violating interactions in top quark production and decay. The analysis uses data from proton-proton collisions at a center-of-mass energy of 13 TeV, collected with the CMS detector at the LHC with an integrated luminosity of 138 fb^{-1}. Candidate events are selected by requiring two oppositely charged leptons (electrons or muons) and exactly one jet identified as originating from a bottom quark. Multivariate discriminants are used to separate the signal from the background. No significant deviation from the standard model prediction is observed. Upper limits are placed on the strength of baryon number violating couplings. For the first time the production of single top quarks via baryon number violating interactions is studied. This allows the search to set the most stringent constraints to date on the branching fraction of the top quark decay to a lepton, an up-type quark (u or c), and a down-type quark (d, s, or b). The results improve the previous bounds by 3 to 6 orders of magnitude based on the fermion flavor combination of the baryon number violating interactions.

Total temporomandibular joint reconstruction prosthesis in hemifacial microsomia: A systematic review.

Hypoplastic asymmetry due to hemifacial microsomia (HFM) often represents the most difficult reconstruction in the craniomaxillofacial clinic. Although autogenous grafts are generally used for temporomandibular joint reconstruction (TMJR), the use of TMJR prostheses is not well established. The aim of this review was to identify, collect and analyse the use of extended TMJR (eTMJR) prostheses in patients with HFM, describing clinical features, surgical procedures and postoperative complications. Online searches of all major databases were performed according to PRISMA guidelines. All studies with HFM patients treated with the eTMJR prostheses were included. Descriptive statistics were used for data analysis. A total of 19 studies, including 08 case studies, 06 case series and 05 retrospective cohort studies, met the inclusion criteria, where a total of 42 HFM patients were reported from 18 countries, mostly from the United States (05; 26%). Fifteen of the 42 cases (~36%) were male. The mean ± SD (range) age of patients in all studies was 19.79 ± 5.81 (9-36) years. The mean ± SD (range) of patient follow-up was 41.30 ± 35.50 (6-136) months. A total of 5 (10.6%) patients were implanted with bilateral eTMJR prostheses. The Pruzansky classification was used in 18 (~89.5%) studies, OMENS classification in 01 (~5%) study, whereas no classification was reported in one study. Only 01 (7.1%) study had documented the eTMJR classification for the prosthesis used. In growing patients with or without a history of failed autogenous tissues, TMJR prostheses may provide a viable alternative. Randomized studies with large cohorts are warranted to validate these preliminary results.

Development of PCR based SSR markers for Wilsonomyces carpophilus and a PCR based diagnosis protocol for the early detection of shot hole disease in stone fruit crops.

BACKGROUND: The conidial Ascomycota fungus Wilsonomyces carpophilus causing shot hole in stone fruits is a major constraint in the production of stone fruits worldwide. Shothole disease symptoms appear on leaves, fruits, and twigs. Successful isolation of the pathogen from different hosts on synthetic culture medium is a time consuming and tedious procedure for identification of the pathogen based on morpho-cultural characterization. METHODS AND RESULTS: The present research was carried out to develop a successful PCR based early detection protocol for the shot hole disease of stone fruits, viz., peach, plum, apricot, cherry, and almond using the pathogen specific SSR markers developed from the Wilsonomyces carpophilus genome using Genome-wide Microsatellite Analysing Tool package (GMATA) software. Diseased leaf samples of different stone fruits were collected from the SKUAST-K orchard and the pathogen was isolated on potato dextrose agar (PDA) medium and maintained on Asthana and Hawkers' medium with a total of 50 pathogen isolates comprised of 10 isolates each from peach, plum, apricot, cherry and almond. The DNA was extracted from both healthy and infected leaf samples of different stone fruits. The DNA was also extracted from the isolated pathogen cultures (50 isolates). Out of 2851 SSR markers developed, 30 SSRs were used for the successful amplification of DNA extracted from all the 50 pathogen isolates. These SSRs were used for the amplification DNA from shot hole infected leaf samples of different stone fruits, but the amplification was not observed in the control samples (DNA from healthy leaves), thus confirming the detection of this disease directly from the shot hole infected samples using PCR based SSR markers. To our knowledge, this forms the first report of SSR development for the Wilsonomyces carpophilus and their validation for the detection of shot hole disease directly from infected leaves. CONCLUSION: PCR based SSR makers were successfully developed and used for the detection of Wilsonomyces carpophilus causing shot hole disease in stone fruits including almond in nuts for the first time. These SSR markers could successfully detect the pathogen directly from the infected leaves of stone fruits namely peach, plum, apricot and cherry including almond from the nuts.

Biochemical and proteomic insights revealed selenium priming induced phosphorus stress tolerance in common bean (Phaseolus vulgaris L.).

BACKGROUND: Mineral stress is one of the dominating abiotic stresses, which leads to decrease in crop production. Selenium (Se) seed priming is a recent approach to mitigate the plant's mineral deficiency stress. Although not an essential element, Se has beneficial effects on the plants in terms of growth, quality, yield and plant defense system thus, enhancing plant tolerance to mineral deficiency. METHODS AND RESULTS: The present research was accomplished to find out the effect of Se priming on common bean plant (SFB-1 variety) under phosphorus (P) stress. The seeds were grown invitro on four different MGRL media which are normal MGRL media as control with non-Se primed seeds (Se- P+), non -Se primed seeds grown on P deficient MGRL media (Se- P-), Se primed seeds grown on normal MGRL media (Se+P+) and Se primed seeds grown on P deficient MGRL media (Se+P -). The various morphological and biochemical parameters such as proline content, total sugar content, polyphenols and expression of proteins were analyzed under P stress. The results showed that Se priming has significantly (p ≤ 0.05) affected the morphological as well as biochemical parameters under normal and P stress conditions. The morphological parameters-length, weight, number of nodes and leaves of Se+P+, Se+P- root and shoot tissue showed significant increase as compared to Se-P+, Se-P-. Similarly various biochemical parameters such as total chlorophyll content, proline, total sugar content and polyphenols of Se+P+, Se+P- increased significantly as compared to Se-P+, Se-P-. The differential protein expression in both Se+P+, Se+P- and Se-P+, Se-P- plants were determined using MALDI-MS/MS. The differentially expressed proteins in Se+P+, Se+P- plants were identified as caffeic acid-3-O-methyltransferase (COMT) and SecA protein (a subunit of Protein Translocan transporter), and are found responsible for lignin synthesis in root cell walls and ATP dependent movement of thylakoid proteins across the membranes in shoot respectively. The differential expression of proteins in plant tissues, validated morphological and biochemical responses such as maintaining membrane integrity, enhanced modifications in cellular metabolism, improved polyphenol activities and expression of defensive proteins against mineral deficiency. CONCLUSIONS: The study provided an understanding of Se application as a potential approach increasing tolerance and yield in crop plants against mineral deficiency.

Comparative analysis of biochemical, hormonal, and mineral compositions of preovulatory and cystic ovarian follicles in buffalo during the non-breeding season.

This study is a comparative analysis of the biochemical, hormonal, and mineral compositions of follicular fluid in preovulatory and cystic follicles of water buffalo (Bubalus bubalis). In total, reproductive tracts from 215 buffalo along with intact ovaries were collected randomly from an abattoir. The incidence of cystic conditions found in this study was 3.72% (8/215), involving the right ovary in 62.5% of instances and the left ovary in 37.5% of instances during the non-breeding season. Follicular fluid was aspirated from preovulatory follicles (12-15 mm diameter, oestrogen-active, follicular phase or stage IV corpus luteum on one of the two ovaries, n = 10) and cystic follicles (at least 20 mm diameter, no corpus luteum on any one of the two ovaries, n = 8). The follicular fluid samples were assayed for biochemical components (uric acid, creatinine, blood urea nitrogen, cholesterol, total protein, glucose, ascorbic acid, and alkaline phosphatase), hormones (progesterone, estradiol, and insulin), and minerals (calcium, magnesium, phosphorus, copper, zinc, and cobalt). Cystic follicles had greater (P < 0.05) concentrations of creatinine, blood urea nitrogen, cholesterol, progesterone, copper, zinc, and cobalt, and lesser (P < 0.05) concentrations of uric acid, glucose, ascorbic acid, estradiol, insulin, calcium, magnesium, and phosphorus compared with preovulatory follicles. These results indicated the marked differences in follicular fluid composition between preovulatory and cystic follicles in buffalo. Some of the changes were indicative of oxidative stress and disturbed steroidogenesis, two important mechanisms shown to be associated with cystic ovarian disease in various species. Further studies are warranted to investigate whether these differences are directly or indirectly involved in the formation of cystic follicles or are mere manifestations of the condition.

Use of monofilament sutures and triclosan coating to protect against surgical site infections in spinal surgery: a laboratory-based study.

PURPOSE: We investigated bacterial propagation through multifilament, monofilament sutures and whether sutures coated with triclosan would exhibit a different phenomenon. METHODS: One centimetre (cm) wide trenches were cut in the middle of Columbia blood Agar plates. We tested a 6 cm length of two Triclosan-coated (PDS plus®, Vicryl plus®) and two uncoated (PDS ®, Vicryl ®) sutures. Each suture was inoculated with a bacterial suspension containing methicillin-sensitive Staphylococcus aureus (MSSA), Escherichia coli (E. coli), Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus (MRSA) at one end of each suture. The plates were incubated at 36C for 48 h, followed by room temperature for a further 5 days. We established bacterial propagation by observing for any bacterial growth on the Agar on the opposite side of the trench. RESULTS: Bacterial propagation was observed on the opposite side of the trench with both suture types, monofilament PDS and multifilament Vicryl, when tested with the motile bacterium (E. coli). Propagation was not observed on the other side of the trench with the monofilament PDS suture following incubation with MSSA and S. epidermidis, and in 66% of MRSA. With multifilament suture Vicryl, propagation was observed on the other side of the trench in 90% (MSSA), 80% (S. epidermidis), and 100% (MRSA) of plates tested. No bacterial propagation was observed in any of the triclosan-coated sutures (monofilament or multifilament). CONCLUSIONS: Monofilament sutures are associated in vitro with less bacterial propagation along their course when compared to multifilament sutures. Inhibition in both sutures can be further enhanced with a triclosan coating.

LAPAROSCOPIC APPROACH TO A GIANT RUPTURED SPLENIC CYST: A CHALLENGING CASE REPORT.

Splenic cysts are rare; their absence of an epithelial wall determines whether they're real cysts or pseudocysts. Spontaneous nonparasitic actual tumors are those that develop early in life at the anterior pole of the splenic and are typically epidermoid, dermoid, or endodermal. Surgical therapy is suggested for symptomatic, large (more than 5 cm) cysts or complicated. Inhaling splenic excision is a substitute for surgery, depending on the quantity, location, connection to the hilus, and dimension of the tumors. With an emphasis on less invasive treatments that preserve the spleen, laparoscopic methods have already established themselves as the accepted method for treating numerous disorders, including splenic cysts. They describe the effective decapsulation of a massive epidermoid spleen tumor under a prolonged, partially endoscopic technique. Laparoscopy, an operation commonly referred to as surgery with minimally invasive or keyhole surgery, is a technique that makes many tiny incisions in the belly to carry out different surgical procedures.

Political stringency, infection rates, and higher education students' adherence to government measures in the Nordic countries and the UK during the first wave of the COVID-19 outbreak.

Understanding predictors of adherence to governmental measures to prevent the spread of the COVID-19 is fundamental to guide health communication. This study examined whether political stringency and infection rates during the first wave of the pandemic were associated with higher education students' adherence to COVID-19 government measures in the Nordic countries (Denmark, Finland, Norway, Iceland, and Sweden) and the United Kingdom. Both individual- and country-level data were used in present study. An international cross-sectional subsample (n = 10,345) of higher-education students was conducted in May-June 2020 to collect individual-level information on socio-demographics, study information, living arrangements, health behaviors, stress, and COVID-19-related concerns, including adherence to government measures. Country-level data on political stringency from the Oxford COVID-19 Government Response Tracker and national infection rates were added to individual-level data. Multiple linear regression analyses stratified by country were conducted. Around 66% of students reported adhering to government measures, with the highest adherence in the UK (73%) followed by Iceland (72%), Denmark (69%), Norway (67%), Finland (64%) and Sweden (49%). Main predictors for higher adherence were older age, being female and being worried about getting infected with COVID-19 (individual-level), an increase in number of days since lockdown, political stringency, and information about COVID-19 mortality rates (country-level). However, incidence rate was an inconsistent predictor, which may be explained by imperfect data quality during the onset of the pandemic. We conclude that shorter lockdown periods and political stringency are associated with adherence to government measures among higher education students at the outset of the COVID-19 pandemic.

Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort.

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

A Novel Genetic Variant Resulting in Familial Hypocalciuric Hypercalcaemia.

Presentation A 17-year-old male was referred to the endocrinology service with an incidental finding of hypercalcaemia. Over the course of the previous year his calcium ranged from 2.64-2.77mmol/L (reference range: 2.2-2.6mmol/L) in the setting of a normal/low parathyroid hormone (PTH) of 14-35pg/ml (reference range: 15-65pg/ml). Diagnosis Following biochemical confirmation of hypocalciuric hypercalcaemia he was referred for molecular genetic analysis which showed a heterozygous variant in the CASR gene previously undescribed in the literature: c.491A>G; p.GIn164Arg. Treatment The patient and his parents were reassured with regard to the benign nature of the condition and counselled with regard to its inheritance. Discussion Though there is little data on this genetic variant, it is assumed to have caused familial hypocalciuric hypercalcaemia (FHH) in this gentleman. FHH is an important differential in hypercalcaemia as it can be misdiagnosed as primary hyperparathyroidism, potentially leading to unnecessary surgical intervention.

The novel collagen matrikine, endotrophin, is associated with mortality and cardiovascular events in patients with atherosclerosis.

BACKGROUND: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. OBJECTIVE: In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO-C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker. METHODS: Sections from the stenotic human carotid plaques were stained with the PRO-C6 antibody. PRO-C6 was measured in serum of patients enrolled in the Carotid Plaque Imagining Project (CPIP) (discovery cohort, n = 577) and the innovative medicines initiative surrogate markers for micro- and macrovascular hard end-points for innovative diabetes tools (IMI-SUMMIT, validation cohort, n = 1,378). Median follow-up was 43 months. Kaplan-Meier curves and log-rank tests were performed in the discovery cohort. Cox proportional hazard regression analysis (HR with 95% CI) was used in the discovery cohort and binary logistic regression (OR with 95% CI) in the validation cohort. RESULTS: PRO-C6 was localized in the core and shoulder of the atherosclerotic plaque. In the discovery cohort, PRO-C6 independently predicted future cardiovascular events (HR 1.089 [95% CI 1.019 -1.164], p = 0.01), cardiovascular death (HR 1.118 [95% CI 1.008 -1.241], p = 0.04) and all-cause death (HR 1.087 [95% CI 1.008 -1.172], p = 0.03). In the validation cohort, PRO-C6 predicted future cardiovascular events (OR 1.063 [95% CI 1.011 -1.117], p = 0.017). CONCLUSION: PRO-C6 is present in the atherosclerotic plaque and associated with future cardiovascular events, cardiovascular death and all-cause mortality in two large prospective cohorts.

Molecular approaches to lung cancer prevention.

Lung cancer is generally diagnosed at advanced stages when surgical resection is not possible. Late diagnosis, along with development of chemoresistance, results in high mortality. Preventive approaches, including smoking cessation, chemoprevention and early detection are needed to improve survival. Smoking cessation combined with low-dose computed tomography screening has modestly improved survival. Chemoprevention has also shown some promise. Despite these successes, most lung cancer cases remain undetected until advanced stages. Additional early detection strategies may further improve survival and treatment outcome. Molecular alterations taking place during lung carcinogenesis have the potential to be used in early detection via noninvasive methods and may also serve as biomarkers for success of chemopreventive approaches. This review focuses on the utilization of molecular biomarkers to increase the efficacy of various preventive approaches.

Diagnostic analysis of baseline brain MRI features in infants with congenital cytomegalovirus infection: a simplified scoring system.

AIM: To characterise the magnetic resonance imaging (MRI) features of infants with congenital cytomegalovirus (CMV) and categorise those into a simplified MRI scoring system. MATERIALS AND METHODS: Three neuroradiologists reviewed the examinations of 71 infants retrospectively and scored for the presence of a white matter signal abnormality and structural lesion and each MRI was given a score of 0, 1, 2, or 3 for normal, structural abnormality alone, white matter abnormality alone, white matter abnormality plus structural lesion, respectively. Imaging features were outlines according to symptomatology. Chi-square and Spearman's rho were used to test relationships between MRI features and viral loads and MRI score/symptomatic disease respectively. Cohen's Kappa coefficient was used to assess interobserver agreement. RESULTS: Of the 49 abnormal studies, 40% (n=20) were seen in asymptomatic infants. The commonest finding was white matter signal abnormality, followed by cyst formation and polymicrogyria (86%, n=42; 71%, n=35; and 33%, n=16, respectively). Cysts were significantly positively correlated with white matter abnormalities and polymicrogyria. On the MRI score, 31%, 10%, 15%, and 44% obtained a score of 0, 1, 2, and 3, respectively; the MRI score was positively correlated with log-transformed viral loads. Interobserver agreement for the presence of white matter signal abnormality, cyst formation, malformations of cortical development (MCD), and global MRI score was excellent (k = 0.82, 0.94, 0.96, and 0.86, respectively). CONCLUSION: Baseline MRI provides information valuable for treatment decisions, especially in "asymptomatic" infants. The simplified scoring system is easier to use, incorporating solely the imaging findings that are anticipated to have an effect on clinical outcome.

Impact of mismatches in HbA1c vs glucose values on the diagnostic classification of diabetes and prediabetes.

AIMS: To determine whether HbA1c mismatches (HbA1c levels that are higher or lower than expected for the average glucose levels in different individuals) could lead to errors if diagnostic classification is based only on HbA1c levels. METHODS: In a cross-sectional study, 3106 participants without known diabetes underwent a 75-g oral glucose tolerance test (fasting glucose and 2-h glucose) and a 50-g glucose challenge test (1-h glucose) on separate days. They were classified by oral glucose tolerance test results as having: normal glucose metabolism; prediabetes; or diabetes. Predicted HbA1c was determined from the linear regression modelling the relationship between observed HbA1c and average glucose (mean of fasting glucose and 2-h glucose from the oral glucose tolerance test, and 1-h glucose from the glucose challenge test) within oral glucose tolerance test groups. The haemoglobin glycation index was calculated as [observed - predicted HbA1c ], and divided into low, intermediate and high haemoglobin glycation index mismatch tertiles. RESULTS: Those participants with higher mismatches were more likely to be black, to be men, to be older, and to have higher BMI (all P<0.001). Using oral glucose tolerance test criteria, the distribution of normal glucose metabolism, prediabetes and diabetes was similar across mismatch tertiles; however, using HbA1c criteria, the participants with low mismatches were classified as 97% normal glucose metabolism, 3% prediabetes and 0% diabetes, i.e. mostly normal, while those with high mismatches were classified as 13% normal glucose metabolism, 77% prediabetes and 10% diabetes, i.e. mostly abnormal (P<0.001). CONCLUSIONS: Measuring only HbA1c could lead to under-diagnosis in people with low mismatches and over-diagnosis in those with high mismatches. Additional oral glucose tolerance tests and/or fasting glucose testing to complement HbA1c in diagnostic classification should be performed in most individuals.

Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs.

We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful within-subject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis. MFAP3, which had no prior evidence in the literature for involvement in pain, had the most robust empirical evidence from our discovery and validation steps, and was a strong predictor for pain in the independent cohorts, particularly in females and males with PTSD. Other biomarkers with best overall convergent functional evidence for involvement in pain were GNG7, CNTN1, LY9, CCDC144B, and GBP1. Some of the individual biomarkers identified are targets of existing drugs. Moreover, the biomarker gene expression signatures were used for bioinformatic drug repurposing analyses, yielding leads for possible new drug candidates such as SC-560 (an NSAID), and amoxapine (an antidepressant), as well as natural compounds such as pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), and apigenin (a plant flavonoid). Our work may help mitigate the diagnostic and treatment dilemmas that have contributed to the current opioid epidemic.

Resource implications of the latent tuberculosis cascade of care: a time and motion study in five countries.

BACKGROUND: The End TB Strategy calls for global scale-up of preventive treatment for latent tuberculosis infection (LTBI), but little information is available about the associated human resource requirements. Our study aimed to quantify the healthcare worker (HCW) time needed to perform the tasks associated with each step along the LTBI cascade of care for household contacts of TB patients. METHODS: We conducted a time and motion (TAM) study between January 2018 and March 2019, in which consenting HCWs were observed throughout a typical workday. The precise time spent was recorded in pre-specified categories of work activities for each step along the cascade. A linear mixed model was fit to estimate the time at each step. RESULTS: A total of 173 HCWs in Benin, Canada, Ghana, Indonesia, and Vietnam participated. The greatest amount of time was spent for the medical evaluation (median: 11 min; IQR: 6-16), while the least time was spent on reading a tuberculin skin test (TST) (median: 4 min; IQR: 2-9). The greatest variability was seen in the time spent for each medical evaluation, while TST placement and reading showed the least variability. The total time required to complete all steps along the LTBI cascade, from identification of household contacts (HHC) through to treatment initiation ranged from 1.8 h per index TB patient in Vietnam to 5.2 h in Ghana. CONCLUSIONS: Our findings suggest that the time requirements are very modest to perform each step in the latent TB cascade of care, but to achieve full identification and management of all household contacts will require additional human resources in many settings.

A pilot study on the rational use of medicines in four tertiary care hospitals through validated World Health Organization prescribing drugs indicators.

BACKGROUND: Appropriate utilization of therapeutic agents is a basic component of the quality of health outcomes for the patients and the community. A pilot study was conducted to evaluate the rational use of medicines and antibiotics, based on World Health Organization (who) prescribing indicators. STUDY DESIGN: We performed a retrospective, descriptive, cross-sectional pilot study in the medical outpatient departments in four tertiary care hospitals of Islamabad, Pakistan, in order to verify the correct prescribing of medicines according to the validated indicators prepared by the World Health Organization (who). METHODS: The Registries of all the prescriptions formulated during the period April 02 2017 - April 01 2018 by the outpatient departments of four tertiary care hospitals (two government funded hospitals (GH-A and GH-B) and two private funded hospitals (PH-C and PH-D) were considered. According to the World Health Organization recommendations, during the following month (April 02 2018 to May 1 2018), 600 prescriptions (150 per hospital) were collected by a random sampling method, verified and analyzed through a statistical tool (SPSS version 22.0). RESULTS: Mean number of medicines per prescription were 4.6 (Optimal value ≤ 2), with the highest value observed in GH-B hospital. Out of these, 350 (58.3%) (Optimal value < 30%) prescriptions consisted of antibiotics and 340 (56.6%) (Optimal value < 25%) prescriptions consisted of injectable medicines, with marked differences between hospitals. About 550 (19.6%) medicines were prescribed by generic name in all selected prescriptions with the lowest value observed in PH-D (9.9%) (Optimal value = 100%). Overall, 88% medicines were prescribed from National essential medicine list/formulary (Optimal value = 100%). All the prescribing core indicators showed significant difference between hospitals (P = 0.001). The most commonly prescribed antibiotic was ceftriaxone (37.4%), followed by ciprofloxacin (15.1%). CONCLUSIONS: Poor adherence to WHO prescribing indicators were observed in all medical outpatient departments in selected hospitals. WHO recommended core interventions should be implemented on trial basis to develop strategies to achieve long-lasting benefits.

Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.

Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7 and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.

Difference in the frequency of pouchitis between ulcerative colitis and familial adenomatous polyposis: is the explanation in peripouch fat?

AIM: Patients with ulcerative colitis (UC) have an unexplained higher incidence of pouchitis and a greater amount of peripouch fat compared with patients with familial adenomatous polyposis (FAP). The aims of this study were to compare the peripouch fat areas between patients with UC and patients with FAP, and to explore relationship between peripouch fat and pouchitis or chronic antibiotic-refractory pouchitis (CARP). METHOD: Patients with an abdominal CT image from our prospectively maintained Pouch Database were included. Abdominal fat and peripouch fat were measured on CT images at different levels or planes. Comparisons of peripouch fat and CARP were performed before and after propensity score matching. RESULTS: A total of 277 patients with UC and 40 patients with FAP were included. Compared with patients with FAP, patients with UC were found to have a higher incidence of pouchitis (58.5% vs 15.0%, P < 0.001) and CARP (24.5% vs 2.5%, P = 0.002) and a higher total peripouch fat area (P = 0.030) and mesenteric peripouch fat area (P = 0.022) at Level-3. Univariate and multivariate analyses showed that diagnosis (UC vs FAP) and peripouch fat areas at Level-3 and Level-5 were independent risk factors for CARP. With propensity score matching, 38 pairs of patients with UC and FAP were matched successfully. After matching, patients with UC were found to have higher total peripouch fat area and higher mesenteric peripouch fat area at Level-3, and a higher incidence of pouchitis (57.9% vs 13.2%, P < 0.001) and CARP (23.7% vs 2.6%, P = 0.007). CONCLUSION: Our study demonstrates that patients with UC have more peripouch fat than those with FAP, which may explain the difference in the frequency of pouchitis and CARP between these groups of patients.

Systematic analyses for candidate genes of milk production traits in water buffalo (Bubalus Bubalis).

Water buffalo (Bubalus bubalis) is of great economic importance as a provider of milk and meat in many countries. However, the milk yield of buffalo is much lower than that of Holstein cows. Selection of candidate genes related to milk production traits can be applied to improve buffalo milk performance. A systematic review of studies of these candidate genes will be greatly beneficial for researchers to timely and efficiently understand the research development of molecular markers for buffalo milk production traits. Here, we identified and classified the candidate genes associated with buffalo milk production traits. A total of 517 candidate genes have been identified as being associated with milk performance in different buffalo breeds. Nineteen candidate genes containing 47 mutation sites have been identified using the candidate gene approach. In addition, 499 candidate genes have been identified in six genome-wide association studies (GWASes) including two studies performed with the bovine SNP chip and four studies with the buffalo SNP chip. Genes CTNND2 (catenin delta 2), APOB (apolipoprotein B), FHIT (fragile histidine triad) and ESRRG (estrogen related receptor gamma) were identified in at least two GWASes. These four genes, especially APOB, deserve further study to explore regulatory roles in buffalo milk production. With growth in the number of buffalo genomic studies, more candidate genes associated with buffalo milk production traits will be identified. Therefore, future studies, such as those investigating gene location and functional analyses, are necessary to facilitate the exploitation of genetic potential and the improvement of buffalo milk performance.