Faecal prevalence and histopathological evaluation of coccidiosis in bovine calves.

Bovine coccidiois, caused by Eimeria spp. is widely prevalent around the globe and responsible for huge economic losses by causing morbidity and mortality among young calves. The present study was designed to evaluate the prevalence as well as to evaluate histopathological alterations associated with it. The faecal samples were collected from 700 bovine calves upto two month of age from August 2019 to July 2021 and screened for Eimeria oocycts. The intestinal tissue samples of 37 calves were also collected which died during the study period after showing symptoms of diarrhea and examined for histological lesions. The faecal prevalence of Eimeria observed in our study was 2.29% (16/700) while in tissue samples only two out of 37 were found positive for Eimeria infection. Tissue sections revealed various stages of Eimeria gametogony, variable congestion, haemorrhage, and necrosis along with cryptic dilatation and mononuclear cell infiltration. Coccidia was not found to be associated with season, age and sex of calf. Bovine coccidiosis was found to be endemic with low prevalence but severe onset characterized by moderate to severe congestion and inflammatory reaction mainly in the ileum and caecum.

Evidence supporting safe diagnosis of coeliac disease in children with antitissue transglutaminase titre ≥5 times upper limit of normal.

OBJECTIVE: European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines on coeliac disease (CD) recommend that children who have IgA-based antitissue transglutaminase (TGA-IgA) titre ≥10× upper limit of normal (ULN) and positive antiendomysial antibody, can be reliably diagnosed with CD via the no-biopsy pathway. The aim of this study was to examine the relationship between TGA-IgA ≥5×ULN and histologically confirmed diagnosis of CD. METHODS: Data including TGA-IgA levels at upper gastrointestinal endoscopy and histological findings from children diagnosed with CD following endoscopy from 2006 to 2021 were analysed. CD was confirmed by Marsh-Oberhuber histological grading 2 to 3 c. Statistical analysis was performed using χ² analysis (p<0.05= significant). RESULTS: 722 of 758 children had histological confirmation of CD. 457 children had TGA-IgA ≥5×ULN and 455 (99.5%) of these had histological confirmation for CD; the two that did not had eventual diagnosis of CD based on clinicopathological features. 114 of 457 had between TGA-IgA ≥5×ULN and <10×ULN, all had confirmed CD. The likelihood of a positive biopsy with TGA-IgA ≥5×ULN (455/457) compared with TGA-IgA <5×ULN (267/301) has strong statistical significance (p<0.00001). The optimal TGA-IgA cut-off from receiver operating characteristic curve analysis was determined to be below 5×ULN for the two assays used. CONCLUSION: 99.5% of children with TGA-IgA ≥5×ULN had histological confirmation of CD, suggesting that CD diagnosis can be made securely in children with TGA-IgA ≥5×ULN. If other studies confirm this finding, there is a case to be made to modify the ESPGHAN guidelines to a lower threshold of TGA-IgA for serological diagnosis of CD.

Structural and Thermal Characterization of Halogenated Azidopyridines: Under-Reported Synthons for Medicinal Chemistry.

Owing to their participation in Click reactions, bifunctional azides are valuable intermediates in the preparation of medicines and biochemical tool compounds. Despite the privileged nature of pyridines among pharmaceutical scaffolds, reports of the synthesis and characterization of azidopyridines bearing a halogen substituent for further elaboration are almost completely unknown in the literature. As azidopyridines carry nearly equal numbers of nitrogen and carbon atoms, we hypothesized that safety concerns limited the application of these useful bifunctional building blocks in medicinal and biological chemistry. To address this concern, we prepared and characterized nine azidopyridines bearing a single fluorine, chlorine, or bromine atom. All were examined by differential scanning calorimetry (DSC), in which they demonstrated exotherms of 228-326 kJ/mol and onset temperatures between 119 and 135 °C. Selected azidopyridines were advanced to mechanical stress testing, in which impact sensitivity was noted for one regioisomer of C5H3FN4. The utility of these versatile intermediates was demonstrated through their use in a variety of Click reactions and the diversification of the halogen handles.

Kinetic and Thermodynamic Considerations in the Rh-Catalyzed Enantioselective Hydrogenation of 2-Pyridyl-Substituted Alkenes.

The mechanism of asymmetric hydrogenation of 2-pyridyl alkenes catalyzed by chiral Rh-phosphine complexes at ambient temperature is examined using kinetic, spectroscopic, and computational tools. The reaction proceeds with reversible substrate binding followed by rate-determining addition of hydrogen. Substrate binding occurs only through the pyridine nitrogen in contrast to other substrate classes exhibiting stronger substrate direction. The lack of influence of hydrogen pressure on the product enantiomeric excess suggests that a pre-equilibrium in substrate binding is maintained across the pressure range investigated. An off-cycle Rh-hydride species is implicated in the mild catalyst deactivation observed. In contrast to Ru-phosphine-catalyzed reactions of the same substrate class, the stereochemical outcome in this system correlates generally with the relative stability of the E and Z rotamers of the substrate.

Change in Incidence and Epidemiology of Inflammatory Bowel Disease in 2- to 9-Year-olds in Southwest England.

OBJECTIVES: The aim of the study was to characterize epidemiology, phenotype, and clinical outcome of Inflammatory Bowel Disease (IBD) diagnosed ages 2 to 9 years, and compare age groups 2 to 5 and 6 to 9 years. METHODS: A population-based retrospective cohort study of all <10-year-olds diagnosed with IBD between 2004 and 2017 in Southwest England was performed. Patients were divided into age groups at diagnosis. Demographics, investigations, and phenotype at diagnosis were collected. Treatments and outcomes were analysed at 1, 2, 5, and 10 years follow-up. Poisson regression was used for IBD incidence rate ratios; Wald test for variation by age group; parametric/nonparametric tests for phenotype. RESULTS: There were 666 new paediatric IBD (pIBD) patients ages ≤16 years, from which 136 were 2 to 9 (2-5 years: 32; 6-9 years: 104). Incidence of pIBD increased from 4 to 6 cases per 100,000 whereas in A1a group was stable around 2 cases per 100,000. Crohn Disease (CD) children were majority boys, 2- to 5-year-olds were more likely to have ileal sparing than 6 to 9-year group but had similar rates of surgery and anti-TNF therapy. Two- to 5-year-olds with ulcerative colitis were more likely to have surgery but rates for anti-TNF therapy were similar. Sixteen percent of 2- to 5-year-olds and 10% of 6- to 9-year-olds had IBD-unclassified. No significant differences in symptoms or time to diagnosis were found. CONCLUSIONS: Twenty percent of pIBD in Southwest England are 2 to 9 years old. pIBD incidence has increased but is stable in that group. In terms of phenotypic differences, ileal sparing in CD and pancolitis and surgery in UC, are more likely in 2- to 5-year-olds.

Diagnosis of celiac disease is being missed in over 80% of children particularly in those from socioeconomically deprived backgrounds.

Population-based screening studies have documented prevalence of celiac disease (CD) at 1% at age 7 years, but 90% of children remain undiagnosed. This prospective cohort study aims to examine whether observed differences in diagnosis rates of CD exist between children from different socioeconomic groups and how this has changed over a 12-year period. All children aged ≤15 years with a postcode within South West of England (SWE) diagnosed with CD during a 12-year period (1999-2010) when all diagnoses were based on endoscopic histology were included in the study. The incidence rates in socioeconomic groups were determined using the Index of Multiple Deprivation Score and Office of National Statistics population data. Four hundred fifteen children were diagnosed with CD; 65 within the City of Bristol (CoB). Diagnosis rate rose 4.2 times in SWE and 3.1 times in CoB between the first and last 4 years of the study. The rate was 1.6 times higher in the least socioeconomically deprived compared to most deprived (2.2 times in CoB), and the gap widened over the 12 years. Missed cases estimates for CoB and SWE are at least 83% and 91%, respectively.Conclusion: These findings suggest that while incidence of diagnosed CD in children has increased over a 12-year period, 83-91% remained undiagnosed. Socioeconomically deprived children are more likely to be underdiagnosed, and the gap between the least and most deprived has widened. To fully address massive underdiagnosis, further strategies including pilot studies using finger prick serological mass screening for CD in children entering primary schools are needed. What is Known: • Epidemiological studies record a 1% prevalence of celiac disease (CD), but up to 90% of children may remain undiagnosed. • Previous studies have documented an increased incidence of CD in higher socioeconomic groups, but proposed reasons remain conflicting. What is New: • Incidence of diagnosed CDhas gone up across all social classes but more so in higher socioeconomic groups and there is an increasing health/wealth gap. • This study estimates that 83-91% of children with CD are still being missed despite improved and easily available serological testing and suggest that population screening should be reconsidered.

Discovery of Annulating Reagents Enabling the One-Step and Highly Stereoselective Synthesis of Cyclopentyl and Cyclohexyl Cores.

The use of the unprecedented annulating reagents methyl N-(tert-butylsulfinyl)-4-chlorobutanimidate and methyl N-(tert-butylsulfinyl)-5-bromopentanimidate enables the diastereoselective preparation of 5- and 6-membered carbocycles bearing three contiguous stereocenters. These synthons undergo cycloaddition with a variety of Michael acceptors to form cyclopentane/cyclohexane rings with excellent stereochemical control, generating only one of the eight possible diastereomers. This novel methodology has enabled the highly enantioselective and high yielding synthesis of novel chemotypes of pharmacological relevance.

Photocatalytic Dearomative Intermolecular [2 + 2] Cycloaddition of Heterocycles for Building Molecular Complexity.

Indole and indoline rings are important pharmacophoric scaffolds found in marketed drugs, agrochemicals, and biologically active molecules. The [2 + 2] cycloaddition reaction is a versatile strategy for constructing architecturally interesting, sp3-rich cyclobutane-fused scaffolds with potential applications in drug discovery programs. A general platform for visible-light mediated intermolecular [2 + 2] cycloaddition of indoles with alkenes has been realized. A substrate-based screening approach led to the discovery of tert-butyloxycarbonyl (Boc)-protected indole-2-carboxyesters as suitable motifs for the intermolecular [2 + 2] cycloaddition reaction. Significantly, the reaction proceeds in good yield with a wide variety of both activated and unactivated alkenes, including those containing free amines and alcohols, and the transformation exhibits excellent regio- and diastereoselectivity. Moreover, the scope of the indole substrate is very broad, extending to previously unexplored azaindole heterocycles that collectively afford fused cyclobutane containing scaffolds that offer unique properties with functional handles and vectors suitable for further derivatization. DFT computational studies provide insights into the mechanism of this [2 + 2] cycloaddition, which is initiated by a triplet-triplet energy transfer process. The photocatalytic reaction was successfully performed on a 100 g scale to provide the dihydroindole analog.

Acute Gastroenteritis in Children of the World: What Needs to Be Done?

The incidence of gastroenteritis has greatly reduced due to improved hygiene conditions in developing countries and the use of rotavirus vaccine. Still thousands of children, however, die from gastroenteritis, most of them in poor countries. Yet gastroenteritis management is simple, inexpensive, and effective and is largely the same all over the world. Universal guidelines for gastroenteritis guide the management and include simple interventions put forward early in the course of the disease. Treatment includes rehydration, continuing oral feeding, and anti-infective drugs in selected clinical conditions related to the symptoms or to host-related risk, and possible additional drug treatment to reduce the duration and severity of symptoms. There may be minor geographical differences in the treatment applied due to health care organizations that do not substantially change the standard universal recommendations. Prevention is recommended with sanitation interventions and rotavirus universal immunization. Implementation of those interventions through educational initiatives and local programs in target areas are needed. A series of recommendations for interventions, education, and research priorities are included here with the aim of reducing the burden of gastroenteritis, to be pursued by scientists, physicians, policy makers, and stakeholders involved. They include the need of recommendations for the management of gastroenteritis in malnourished children, in those with chronic conditions, in neonates, and in emergency settings. A reference system to score dehydration, the definition of optimal composition of rehydration solution and the indications for anti-infective therapy are also included. Rotavirus immunization should be actively promoted, and evidence-based guidelines should be universally implemented. Research priorities are also indicated.

One-Step Diastereoselective Pyrrolidine Synthesis Using a Sulfinamide Annulating Reagent.

This communication highlights the use of chiral sulfinamides as nitrogen nucleophiles in intermolecular aza-Michael reactions. When chiral sulfinamides are coupled to a chloroethyl group, the corresponding novel annulating reagents can be used to streamline the stereoselective synthesis of complex pyrrolidine-containing molecules. As a result, it has enabled a medicinal chemistry campaign for the synthesis of biologically active RORγt inverse agonists.

Estimation of the incidence of animal rabies in Punjab, India.

BACKGROUND: Rabies is a devastating zoonotic disease of mammals that causes encephalitis and death. It is endemic in India, with an estimated annual 20,000 human deaths (one-third of the global rabies burden). The magnitude of animal rabies incidence is unknown. METHODS: In four sub-districts of Punjab, India, we monitored canine and livestock populations from August 15, 2016 to August 14, 2017. Demographic, clinical and rabies diagnostic laboratory (RDL) data were collected from suspected cases of rabies. The annual incidence rate / 10,000 animal years at risk (95% CI) in each sub-district was estimated for each species. RESULTS: During 2016-2017, a total of 41 suspected rabies cases were detected in the four selected sub-districts in Punjab. Laboratory confirmed rabies (LCR) incidence was 2.03/10,000 dog years (0.69, 5.96) and 2.71/10,000 dog years (1.14, 6.43) in stray and pet dogs, respectively. The LCR incidence in farmed buffalo and cattle was 0.19/10,000 buffalo years (0.07, 0.57) and 0.23/10,000 cattle years (0.06, 0.88), respectively. The LCR incidence amongst equine was 4.28/10,000 equine years (0.48, 38.10). Stray cattle rabies incidence in the selected sub-districts was 9.49/10,000 cattle years (3.51, 25.67). If similar enhanced surveillance for rabies was conducted state-wide, we estimate that 98 (34-294) buffalo, 18 (2-156) equine, 56 (15-214) farmed cattle, 96 (35-259) stray cattle, 128 (54-303) pet dogs and 62 (21-182) stray dogs would be expected to be confirmed with rabies in Punjab annually. CONCLUSION: These results indicate that rabies incidence in animals, particularly in dogs and stray cattle, is much higher than previously suspected. We recommend that statewide enhanced disease surveillance should be conducted to obtain more accurate estimates of rabies incidence in Punjab to facilitate better control of this important disease.

Challenges to human rabies elimination highlighted following a rabies outbreak in bovines and a human in Punjab, India.

In August 2015, a rabies outbreak occurred in bovines in a Punjab village, India; subsequently, a farmer in the same village died of rabies in October 2015. We surveyed farmers to describe the outbreak, the demographics and rabies prophylaxis administered to householders on case farms, and farmers' knowledge of rabies prevention and treatment. We used multiple correspondence analysis to guide investigation of associations between demographics, farm status and rabies knowledge, attitudes and practices. The number of affected bovines was unusually high; 15 cattle and buffalo died on 13 smallholder farms (attack rate 4%). Post-exposure vaccinations were administered to 24 people (median 2 doses). Affected farms had significantly larger households and were more likely to keep their livestock outside (therefore, accessible by stray dogs), suggesting that the impact of the outbreak was disproportionally borne by households of lower socio-economic status. Primary sources of rabies information were friends and neighbours, not health authorities or media. Women who had not received formal education were less likely to have heard of rabies. Although case farm participants were more likely to have heard about rabies from a veterinarian, their knowledge and practices to prevent rabies did not reflect the level expected considering their contact with a health professional; they were more likely to believe that traditional remedies prevent rabies and less likely to tell their children to avoid playing with stray dogs than participants from other farms. This study highlights knowledge dissemination disparities that, if typical of rural locations, could obstruct attempts to eliminate canine-mediated human rabies in India. Therefore, understanding the pervasiveness and influence of traditional medical beliefs on treatment-seeking behaviour, communication structures within villages and the impact of local practices such as carcass disposal on dog populations will be essential to ensure that rabies control strategies are effective in rural India.

Universal Recommendations for the Management of Acute Diarrhea in Nonmalnourished Children.

OBJECTIVE: Despite a substantial consistency in recommendations for the management of children with acute gastroenteritis (AGE), a high variability in clinical practice and a high rate of inappropriate medical interventions persist in both developing and developed countries.The aim of this study was to develop a set of clinical recommendations for the management of nonseverely malnourished children with AGE to be applied worldwide. METHODS: The Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) Working Group (WG) selected care protocols on the management of acute diarrhea in infants and children aged between 1 month and 18 years. The WG used a 3-step approach consisting of: systematic review and comparison of published guidelines, agreement on draft recommendations using Delphi methodology, and external peer-review and validation of recommendations. RESULTS: A core of recommendations including definition, diagnosis, nutritional management, and active treatment of AGE was developed with an overall agreement of 91% (range 80%-96%). A total of 28 world experts in pediatric gastroenterology and emergency medicine successively validated the set of 23 recommendations with an agreement of 87% (range 83%-95%). Recommendations on the use of antidiarrheal drugs and antiemetics received the lowest level of agreement and need to be tailored at local level. Oral rehydration and probiotics were the only treatments recommended. CONCLUSIONS: Universal recommendations to assist health care practitioners in managing children with AGE may improve practitioners' compliance with guidelines, reduce inappropriate interventions, and significantly impact clinical outcome and health care-associated costs.

Modulating the physical properties of solid forms of urea using co-crystallization technology.

The solid-form landscape of urea was explored using full interaction maps (FIMs) and data from the CSD to develop optimum protocols for synthesizing co-crystals of urea. As a result, 49 of the 60 attempted reactions produced new co-crystals, and the crystal structures of four of these are presented. Moreover, the goal of reducing the solubility and lowering the hygroscopicity of the parent compound was achieved, which in turn offers new opportunities for application as a slow-release fertilizer with limited hygroscopicity, thereby reducing many current problems of transport, handling, and storage of urea.

Evidence Supporting Serology-based Pathway for Diagnosing Celiac Disease in Asymptomatic Children From High-risk Groups.

OBJECTIVE: The European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines for diagnosing celiac disease (CD) in children were modified in 2012. They recommend that in symptomatic children with anti-tissue transglutaminase antibody (anti-tTG) titer of >10 times upper limit of normal (>10× ULN) and who have positive anti-endomysial antibody and HLA-DQ2/DQ8 haplotype, the diagnosis of CD can be based on serology. The aim of this study is to establish whether serology-based pathway of the ESPGHAN guidelines could also be reliably applied to asymptomatic children from high-risk groups. METHODS: From March 2007 to February 2017, prospective data on anti-tTG titer, age, sex, and reason for screening were collected at diagnostic endoscopy on all asymptomatic children being diagnosed as having CD. The relationship between modified Marsh-Oberhuber classification histological grading and contemporaneous anti-tTG titers was analyzed. RESULTS: A total of 157 asymptomatic children were diagnosed as having CD. Eighty-four of 157 (53.5%) had antitTG >10× ULN (normal <10 IU/mL) and 75 of 84 were from high-risk groups. All 75 had definitive histological evidence (Marsh-Oberhuber 3a-3c) of small bowel enteropathy. Fifty-three of 84 children had anti-tTG >200 IU/mL and total villous atrophy was present in 29 of 53 (55%). Main reasons for serological screening were: type-1 diabetes mellitus (n = 36) and first-degree relatives with CD (n = 24). Mean age at diagnosis was 8.8 years. Serology-based diagnosis is cost-beneficial by around £1275 per child in the United Kingdom. CONCLUSIONS: All 75 asymptomatic children from high-risk groups with anti-tTG >10× ULN had histology-proven CD. This study provides further evidence that the guidelines for diagnosing CD by the serology-based pathway should be extended to these children.

Probiotics for gastrointestinal disorders: Proposed recommendations for children of the Asia-Pacific region.

Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745 (Sb) and Lactobacillus rhamnosus GG (LGG) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of (with the indicated strains): antibiotic-associated diarrhea (LGG or Sb); Clostridium difficile-induced diarrhea (Sb); nosocomial diarrhea (LGG); infantile colic (L reuteri) and as adjunct treatment of Helicobacter pylori (Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials.

Long-term Outcome of Inflammatory Bowel Disease-Unclassified in Children.

OBJECTIVE: To document the frequency at diagnosis and evolution over time of inflammatory bowel disease-unclassified in children. METHODS: Analysis of case records (2004-2011) of patients diagnosed with inflammatory bowel disease-unclassified following upper-gastrointestinal endoscopy, ileocolonoscopy and small bowel imaging. Any subsequent diagnostic reclassification by 2016 was recorded. RESULTS: 344 children diagnosed as inflammatory bowel disease: 58% Crohn's disease, 34.5% ulcerative colitis, and 7.5% (n=26) inflammatory bowel disease-unclassified. 25/26 inflammatory bowel disease-unclassified patients were followed for 4.5-11.5 years. 17 of these patients needed endoscopic re-evaluation leading to changed diagnosis in ten (Crohn's disease 7, ulcerative colitis 3). CONCLUSION: 7.5% (25/344) of inflammatory bowel disease children had inflammatory bowel disease-unclassified at diagnosis; 10 (40%) evolved into Crohn's disease or ulcerative colitis.

Rotavirus immunization: Global coverage and local barriers for implementation.

BACKGROUND: Rotavirus (RV) is a major agent of gastroenteritis and an important cause of child death worldwide. Immunization (RVI) has been available since 2006, and the Federation of International Societies of Gastroenterology Hepatology and Nutrition (FISPGHAN) identified RVI as a top priority for the control of diarrheal illness. A FISPGHAN working group on acute diarrhea aimed at estimating the current RVI coverage worldwide and identifying barriers to implementation at local level. METHODS: A survey was distributed to national experts in infectious diseases and health-care authorities (March 2015-April 2016), collecting information on local recommendations, costs and perception of barriers for implementation. RESULTS: Forty-nine of the 79 contacted countries (62% response rate) provided a complete analyzable data. RVI was recommended in 27/49 countries (55%). Although five countries have recommended RVI since 2006, a large number (16, 33%) included RVI in a National Immunization Schedule between 2012 and 2014. The costs of vaccination are covered by the government (39%), by the GAVI Alliance (10%) or public and private insurance (8%) in some countries. However, in most cases, immunization is paid by families (43%). Elevated cost of vaccine (49%) is the main barrier for implementation of RVI. High costs of vaccination (rs=-0.39, p=0.02) and coverage of expenses by families (rs=0.5, p=0.002) significantly correlate with a lower immunization rate. Limited perception of RV illness severity by the families (47%), public-health authorities (37%) or physicians (24%) and the timing of administration (16%) are further major barriers to large- scale RVI programs. CONCLUSIONS: After 10years since its introduction, the implementation of RVI is still unacceptably low and should remain a major target for global public health. Barriers to implementation vary according to setting. Nevertheless, public health authorities should promote education for caregivers and health-care providers and interact with local health authorities in order to implement RVI.

Limited role of HLA DQ2/8 genotyping in diagnosing coeliac disease.

The European guidelines for diagnosing coeliac disease in children were revised in 2012. These recommend that in symptomatic children, a diagnosis of coeliac disease can be made without small-bowel biopsies provided their anti-tissue transglutaminase (anti-tTG) titre is >10 times of upper-limit-of-normal (>10×ULN) and anti-endomysial antibody is positive. In order to firm up the diagnosis in these children with very high anti-tTG titre, HLA-DQ2/DQ8 should be checked and be positive. Approximately 25-40% of white Caucasian population has HLA-DQ2/DQ8 haplotype. However, only 0.1-1% of the population will develop coeliac disease. Therefore, HLA-DQ2/DQ8 testing must not be done to 'screen' or 'diagnose' children with coeliac disease. Its use by paediatricians should be limited to children with anti-tTG>10×ULN, where the diagnosis of coeliac disease is being made on serology alone. A review of case referrals made to a tertiary paediatric gastroenterology centre in Southwest England demonstrated that HLA-DQ2/DQ8 testing is being requested inappropriately both in primary and secondary care suggesting a poor understanding of its role in diagnosis of coeliac disease. This article aims to clarify the role of HLA-DQ2/DQ8 testing for clinicians working in non-specialist settings.

Investigation of the combined effect of MgO and PEG on the release profile of mefenamic acid prepared via hot-melt extrusion techniques.

This study aimed to investigate the combined effect of magnesium oxide (MgO) as an alkalizer and polyethylene glycol (PEG) as a plasticizer and wetting agent in the presence of Kollidon® 12 PF and 17 PF polymer carriers on the release profile of mefenamic acid (MA), which was prepared via hot-melt extrusion technique. Various drug loads of MA and various ratios of the polymers, PEG 3350 and MgO were blended using a V-shell blender and extruded using a twin-screw extruder (16-mm Prism EuroLab, ThermoFisher Scientific, Carlsbad, CA) at different screw speeds and temperatures to prepare a solid dispersion system. Differential scanning calorimetry and X-ray diffraction data of the extruded material confirmed that the drug existed in the amorphous form, as evidenced by the absence of corresponding peaks. MgO and PEG altered the micro-environmental pH to be more alkaline (pH 9) and increased the hydrophilicity and dispersibility of the extrudates to enhance MA solubility and release, respectively. The in vitro release study demonstrated an immediate release for 2 h with more than 80% drug release within 45 min in matrices containing MgO and PEG in combination with polyvinylpyrrolidone when compared to the binary mixture, physical mixture and pure drug.