Constipation in children

Constipation remains a frequent presentation to paediatricians, with significant health resource implications. We present a practical guide to the management of paediatric constipation and evaluate the current evidence for treatment regimens, to help the clinician in treating a condition that can be distressing and has a significant impact on affected families

Boundary layer flow of nanofluid over an exponentially stretching surface

The steady boundary layer flow of nanofluid over an exponential stretching surface is investigated analytically. The transport equations include the effects of Brownian motion parameter and thermophoresis parameter. The highly nonlinear coupled partial differential equations are simplified with the help of suitable similarity transformations. The reduced equations are then solved analytically with the help of homotopy analysis method (HAM). The convergence of HAM solutions are obtained by plotting h-curve. The expressions for velocity, temperature and nanoparticle volume fraction are computed for some values of the parameters namely, suction injection parameter α, Lewis number Le, the Brownian motion parameter Nb and thermophoresis parameter Nt

Exome analysis of patients with concurrent pediatric inflammatory bowel disease (PIBD) and autoimmune disease

BACKGROUND: Pediatric Inflammatory Bowel Disease (PIBD) is a chronic condition seen in genetically predisposed individuals. Genome-wide association studies have implicated >160 genomic loci in IBD with many genes coding for proteins in key immune pathways. This study looks at autoimmune disease burden in patients diagnosed with PIBD and interrogates exome data of a subset of patients. METHODS: Patients were recruited from the Southampton Genetics of PIBD cohort. Clinical diagnosis of autoimmune disease in these individuals was ascertained from medical records. For a subset of patients with PIBD and concurrent asthma, exome data was interrogated to ascertain the burden of pathogenic variants within genes implicated in asthma. Association testing was conducted between cases and population controls using the SKAT-O test. RESULTS: Forty-nine (28.3%) PIBD children (18.49% CD, 8.6% UC, and 21.15% IBDU patients) had a concurrent clinical diagnosis of at least one other autoimmune disorder; asthma was the most prevalent, affecting 16.2% of the PIBD cohort. Rare and common variant association testing revealed 6 significant genes (P < 0.05) before Bonferroni adjustment. Three of these genes were previously implicated in both asthma and IBD (ZPBP2 IL1R1, and IL18R1) and 3 in asthma only (PYHIN1, IL2RB, and GSTP1). CONCLUSIONS: One-third of our cohort had a concurrent autoimmune condition. We observed higher incidence of asthma compared with the overall pediatric prevalence. Despite a small sample size, SKAT-O evaluated a significant burden of rare and common mutations in 6 genes. Variant burden suggests that a systemic immune dysregulation rather than organ-specific could underpin immune dysfunction for a subset of patients

Exome analysis of rare and common variants within the NOD signaling pathway

Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort (BIRC2 p = 0.004, NFKB1 p =  0.005, NOD2 p = 0.029 and SUGT1 p = 0.047). Statistical significance was replicated for BIRC2 (p = 0.041) and NOD2 (p = 0.045) in an independent validation cohort. A gene based test on the combined discovery and replication cohort confirmed association for BIRC2 (p = 0.030). We successfully applied burden of mutation testing that jointly assesses common and rare variants, identifying two previously implicated genes (NFKB1 and NOD2) and confirmed a possible role in disease risk in a previously unreported gene (BIRC2). The identification of this novel gene provides a wider role for the inhibitor of apoptosis gene family in IBD pathogenesis

16S sequencing and functional analysis of the fecal microbiome during treatment of newly diagnosed pediatric inflammatory bowel disease

JJA is funded by a National Institute of Health Research Academic Clinical Fellowship and has received an Action Medical Research training fellowship. TC is funded by a Crohn’s in Childhood research association fellowship. CMC received a PhD studentship from SULSA Spirit industrial studentship. The NGS analysis was made possible by the award of a grant from the Source Bioscience 110th year anniversary promotion to CMC. The Rowett Institute receives funding from the Scottish Government (RESAS).Peer reviewedPublisher PD

Development of Paracetamol-Caffeine co-crystals to improve compressional, formulation and in-vivo performance

Paracetamol, a frequently used antipyretic and analgesic drug, has poor compression moldability owing to its low plasticity. In this study, new co-crystals of paracetamol (PCM) with caffeine (as a co-former) were prepared and delineated. Co-crystals exhibited improved compaction and mechanical behavior. A screening study was performed by utilizing a number of methods namely dry grinding, liquid assisted grinding (LAG), solvent evaporation (SE) and anti-solvent addition using various weight ratios of starting materials. LAG and SE were found successful in the screening study. Powders at 1:1 and 2:1 weight ratio of PCM/CAF by LAG and SE respectively resulted in the formation of co-crystals. Samples were characterized by PXRD, DSC and ATR-FTIR techniques. Compressional properties of PCM and developed co-crystals were analyzed by in-die heckle model. Mean yield pressure (Py), an inverse measure of plasticity, obtained from the heckle plots decreased significantly (p<0.05) for co-crystals than pure drug. Intrinsic dissolution profile of co-crystals showed up to 2.84 fold faster dissolution than PCM and physical mixtures in phosphate buffer pH 6.8 at 37 oC. In addition co-crystals formulated into tablets by direct compression method showed better mechanical properties like hardness and tensile strength. In vitro dissolution studies on tablets also showed enhanced dissolution profiles (~90- 97%) in comparison to the tablets of PCM prepared by direct compression (~55%) and wet granulation (~85%) methods. In a single dose sheep model study co-crystals showed up to two fold increase in AUC and Cmax. A significant (p < 0.05) decrease in clearance as compared to pure drug was also recorded. In conclusion new co-crystals of PCM were successfully prepared with improved tabletability in-vitro and in-vivo profile. Enhancement in AUC and Cmax of PCM by co-crystallisation might suggest the dose reduction and avoidance of side effects

Chemical Characterisation, Antidiabetic, Antibacterial, and In Silico Studies for Different Extracts of Haloxylon stocksii (Boiss.) Benth: A Promising Halophyte

The objective of the study is to evaluate the chemical characterisation, and biological and in silico potential of Haloxylon stocksii (Boiss.) Benth, an important halophyte commonly used in traditional medicine. The research focuses on the roots and aerial parts of the plant and extracts them using two solvents: methanol and dichloromethane. Chemical characterisation of the extracts was carried out using total phenolic contents quantification, GC-MS analysis, and LC-MS screening. The results exhibited that the aerial parts of the plant have significantly higher total phenolic content than the roots. The GC-MS and LC-MS analysis of the plant extracts revealed the identification of 18 bioactive compounds in each. The biological evaluation was performed using antioxidant, antibacterial, and in vitro antidiabetic assays. The results exhibited that the aerial parts of the plant have higher antioxidant and in vitro antidiabetic activity than the roots. Additionally, the aerial parts of the plant were most effective against Gram-positive bacteria. Molecular docking was done to evaluate the binding affinity (BA) of the bioactive compounds characterised by GC-MS with diabetic enzymes used in the in vitro assay. The results showed that the BA of γ-sitosterol was better than that of acarbose, which is used as a standard in the in vitro assay. Overall, this study suggests that the extract from aerial parts of H. stocksii using methanol as a solvent have better potential as a new medicinal plant and can provide a new aspect to develop more potent medications. The research findings contribute to the scientific data of the medicinal properties of Haloxylon stocksii and provide a basis for further evaluation of its potential as a natural remedy

Recent technologies for nutrient removal and recovery from wastewaters: A review

Water scarcity and its pollution has become a concern in recent times. The disposal of nutrient-rich (nitrogen and phosphorous) wastewater is also one of the main cause of water pollution through eutrophication, reduced dissolved oxygen that poses threat to aquatic ecosystems. As a result, nutrient removal has become a mandate apart from the removal of organics. However, the removal of nutrients from sewage is a challenging task. Conversely, conventional biological treatment processes provide little relief in nutrient removal. The treated effluents from conventional biological processes do not achieve the stringent nutrient removal disposal standard limits and become primary cause of pollution in the receiving water bodies. This has stressed upon the need for eco-friendly, low-energy and cost-efficient nutrient removal treatment technologies. Various biological treatment combinations or variants are in use for the efficient removal of nutrients. The biological processes in itself or in combination with chemical processes are preferred over technologies based solely on physico-chemical processes for its treatment performance at lower cost. This review summarizes the existing treatment processes and their possible up-gradation with the aim to accomplish the marked effluent standards for the nutrients. The concept of conventional systems and advanced systems for nutrients (nitrogen and phosphorous) removal which are already developed or under development are deeply discussed. Further, the challenges of each treatment systems are abridged. Finally, the possible suggestions for the modification/retrofitting of existing treatment systems for achieving stringent disposal standards are pointed out

Effect of Kohl-Chikni Dawa – a compound ophthalmic formulation of Unani medicine on naphthalene-induced cataracts in rats

BACKGROUND: Cataracts are the leading cause of blindness worldwide, accounting for 13-27% of cases. Kohl-Chikni Dawa (KCD) is reputed for its beneficial effects in the treatment of premature cataracts. However, its efficacy is yet to be tested. To investigate the rationality of the therapeutic use of Kohl-Chikni Dawa (KCD) in Unani medicine. METHODS: The effect of Kohl-Chikni Dawa eye drops on naphthalene-induced cataracts in rats was investigated by slit-lamp biomicroscopic analysis. The normal group of experimental animals was administered with mineral oil (orally), while other groups were given naphthalene (orally) along with local application of KCD eye drops (once and twice daily), placebo and distilled water (twice daily). Initial morphological changes of the lenses were observed twice a week for two weeks, and thereafter once a week for four weeks. RESULTS: Local application of KCD (twice daily) caused significant reduction in the lens opacification after 2 to 4 weeks of naphthalene administration. CONCLUSION: KCD eye drops may have the potential to delay progression of naphthalene-induced cataracts in rats