Systematic review and meta-analysis of the management of acute uncomplicated diverticulitis: time to change traditional practice.

BACKGROUND: To evaluate comparative outcomes of outpatient (OP) versus inpatient (IP) treatment and antibiotics (ABX) versus no antibiotics (NABX) approach in the treatment of uncomplicated (Hinchey grade 1a) acute diverticulitis. METHODS: A systematic online search was conducted using electronic databases. Comparative studies of OP versus IP treatment and ABX versus NABX approach in the treatment of Hinchey grade 1a acute diverticulitis were included. Primary outcome was recurrence of diverticulitis. Emergency and elective surgical resections, development of complicated diverticulitis, mortality rate, and length of hospital stay were the other evaluated secondary outcome parameters. RESULTS: The literature search identified twelve studies (n = 3,875) comparing NABX (n = 2,008) versus ABX (n = 1,867). The NABX group showed a lower disease recurrence rate and shorter length of hospital stay compared with the ABX group (P = 0.01) and (P = 0.004). No significant difference was observed in emergency resections (P = 0.33), elective resections (P = 0.73), development of complicated diverticulitis (P = 0.65), hospital re-admissions (P = 0.65) and 30-day mortality rate (P = 0.91). Twelve studies (n = 2,286) compared OP (n = 1,021) versus IP (n = 1,265) management of uncomplicated acute diverticulitis. The two groups were comparable for the following outcomes: treatment failure (P = 0.10), emergency surgical resection (P = 0.40), elective resection (P = 0.30), disease recurrence (P = 0.22), and mortality rate (P = 0.61). CONCLUSION: Observation-only treatment is feasible and safe in selected clinically stable patients with uncomplicated acute diverticulitis (Hinchey 1a classification). It may provide better outcomes including decreased length of hospital stay. Moreover, the OP approach in treating patients with Hinchey 1a acute diverticulitis is comparable to IP management. Future high-quality randomised controlled studies are needed to understand the outcomes of the NABX approach used in an OP setting in managing patients with uncomplicated acute diverticulitis.

Preparation of novel clay/chitosan/ZnO bio-composite as an efficient adsorbent for tannery wastewater treatment.

This study focuses on the preparation of an activated clay/chitosan/ZnO bio-composite using solvent casting method. Clay was activated through microwave radiation using 1 M H2SO4 at a minimum liquid to solid ratio (L/S). Chitosan was extracted from waste prawn shell and ZnO nanoparticles (ZnO-NPs) were synthesized from zinc acetate di-hydrate (Zn (CH3CO2)2·2H2O) using the sol-gel method. The produced bio-composite were characterized using FT-IR, TGA, XRD and SEM. Response surface methodology (RSM) was used for experimental design to find out the optimum conditions, e.g., pH of the solution, dosage of adsorbent and contact time for the removal of methylene blue (MB) and Cr (VI) using MINITAB 18.1 software. The optimum conditions obtained for the highest removal of MB were pH 9.57, dosage 55.44 mg and contact time 114.09 min. Similarly, for the highest removal of Cr (VI) the optimum conditions were pH 3.75, dosage 67.42 mg and contact time 111.27 min. Applying these optimum conditions, the highest removal efficiency for MB and Cr (VI) was obtained at 84.21 % and 82.67 % with 9.57 mg g-1 and 10.45 mg g-1 of adsorption capacity respectively. The adsorption data were studied for both Langmuir and Freundlich isotherm. The value of maximum Langmuir sorption was (qm) 17.346 mg g-1 and 17.621 mg g-1 for MB and Cr (VI) respectively.

Structural exploration of selected C6 and C7-substituted coumarin isomers as selective MAO-B inhibitors.

Monoamine Oxidase B is considered a successful target for developing antiparkinsonian drugs. Due to the side effects of current MAO-B inhibitors, there's an urgent need for novel potent and highly selective MAO-B inhibitors. A recent study has shown that coumarins tend to be more selective towards MAO-B than MAO-A when connected to a hex-5-ynyloxy chain at position 6 in contrast to their C7-isomers. The present study describes the mode of interaction of the C6 and C7-substituted coumarin isomers characterized by their difference in selectivity towards MAO-B through molecular docking and molecular dynamics simulations in an effort to elucidate the structural components and molecular interactions that may be responsible for MAO-B selectivity. Three isomeric coumarin pairs connected to ether chain at position 6 or 7 were taken from the literature and modelled according to their IUPAC nomenclature. Molecular docking study revealed one π- π stacking interaction with Tyr-326 in common between the selective coumarin C6-isomers. Resulting complexes of one isomeric coumarin pair that displayed the highest selectivity shift towards MAO-B were subject to 100 ns molecular dynamics simulations study to analyze the stability of the docked complexes. Molecular dynamics revealed that the C7-isomer is relatively stable in both MAO isoforms through the simulation duration, whereas the C6-isomer deemed unstable for MAO-A which may be due to the bulky Phe-208 residue in MAO-A. Our results might be applied for further development and optimization of coumarin derivatives into a successful drug against Parkinson's disease.Communicated by Ramaswamy H. Sarma.

In-silico design and ADMET predictions of some new imidazo[1,2-a]pyridine-3-carboxamides (IPAs) as anti-tubercular agents.

Tuberculosis (TB) is one of the leading infectious diseases worldwide even with the ravaging COVID-19 pandemic in recent times. This mandated further search and exploration of more possible anti-TB drug candidates against M. tuberculosis strains. As an extension of our previous work on the homology modeled cytochrome b subunit of the bc1 complex (QcrB) of Mycobacterium tuberculosis, an in-silico design was carried out in order to further explore more newly potential anti-TB compounds. Ligand 26 was selected as the lead template (scaffold A) based on our previous docking results and its less bulky structure. Successively, eight (8) new ligands (A1-A8) were designed with better binding affinities in comparison to the scaffold template (-6.8 kcal/mol) and isoniazid standard drug (-6.00 kcal/mol) respectively. In addition, three (3) designed ligands namely, A6, A2, and A7 with higher binding affinities were validated via ADME and toxicity prediction analysis, and the results showed zero violations of Lipinski rules with similar bioavailability, and high rate in gastrointestinal absorption, while toxicity parameters such as carcinogenicity and cytotoxicity were all predicted as non-toxic (inactiveness). The designed IPA compounds in the present study could serve as a promising gateway that could help the medicinal and synthetic chemist in the exploration of a new set of derivatives as anti-TB agents. Therefore, this research strongly recommends further experimental consideration of the newly designed IPA compounds through synthesis, in-vitro and in-vivo studies to validate the theoretical findings.

Microbiome signature and diversity regulates the level of energy production under anaerobic condition.

The microbiome of the anaerobic digester (AD) regulates the level of energy production. To assess the microbiome diversity and composition in different stages of anaerobic digestion, we collected 16 samples from the AD of cow dung (CD) origin. The samples were categorized into four groups (Group-I, Group-II, Group-III and Group-IV) based on the level of energy production (CH4%), and sequenced through whole metagenome sequencing (WMS). Group-I (n = 2) belonged to initial time of energy production whereas Group-II (n = 5), Group-III (n = 5), and Group-IV (n = 4) had 21-34%, 47-58% and 71-74% of CH4, respectively. The physicochemical analysis revealed that level of energy production (CH4%) had significant positive correlation with digester pH (r = 0.92, p < 0.001), O2 level (%) (r = 0.54, p < 0.05), and environmental temperature (°C) (r = 0.57, p < 0.05). The WMS data mapped to 2800 distinct bacterial, archaeal and viral genomes through PathoScope (PS) and MG-RAST (MR) analyses. We detected 768, 1421, 1819 and 1774 bacterial strains in Group-I, Group-II, Group-III and Group-IV, respectively through PS analysis which were represented by Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Spirochaetes and Fibrobacteres phyla (> 93.0% of the total abundances). Simultaneously, 343 archaeal strains were detected, of which 95.90% strains shared across four metagenomes. We identified 43 dominant species including 31 bacterial and 12 archaeal species in AD microbiomes, of which only archaea showed positive correlation with digester pH, CH4 concentration, pressure and temperature (Spearman correlation; r > 0.6, p < 0.01). The indicator species analysis showed that the species Methanosarcina vacuolate, Dehalococcoides mccartyi, Methanosarcina sp. Kolksee and Methanosarcina barkeri were highly specific for energy production. The correlation network analysis showed that different strains of Euryarcheota and Firmicutes phyla exhibited significant correlation (p = 0.021, Kruskal-Wallis test; with a cutoff of 1.0) with the highest level (74.1%) of energy production (Group-IV). In addition, top CH4 producing microbiomes showed increased genomic functional activities related to one carbon and biotin metabolism, oxidative stress, proteolytic pathways, membrane-type-1-matrix-metalloproteinase (MT1-MMP) pericellular network, acetyl-CoA production, motility and chemotaxis. Importantly, the physicochemical properties of the AD including pH, CH4 concentration (%), pressure, temperature and environmental temperature were found to be positively correlated with these genomic functional potentials and distribution of ARGs and metal resistance pathways (Spearman correlation; r > 0.5, p < 0.01). This study reveals distinct changes in composition and diversity of the AD microbiomes including different indicator species, and their genomic features that are highly specific for energy production.

Gestational Age Assessment with Anthropometric Parameters in Newborns.

OBJECTIVES: We sought to evaluate the relationship between gestational age (GA) and neonatal anthropometric parameters, namely head circumference (HC) and crown-heel length (CHL). METHODS: We conducted a cross-sectional study in a tertiary care hospital with 530 consecutively live-born newborns of 28-41 weeks gestation. Anthropometric parameters were measured after three days of life. We summarized the variables using descriptive statistics, including percentile values, and the strength of association was determined through correlation analysis. The correlation was strong for HC and CHL, and linear regression analysis was done to develop predictive equations. RESULTS: HC and CHL correlated well with GA with r-values of 0.863 and 0.859, respectively. The regression equations derived were GA (week) = 9.2671 + [0.8616 × HC (cm)] and GA (weeks) = 7.2489 + [0.621 × CHL (cm)]. Multiple regression gave the relationship as GA (weeks) = 4.0244 + [0.4058 × HC (cm)] + [0.4249 × CHL (cm)]. Application of this multiple regression equation to a test cohort of 30 babies for prediction of GA gave a mean margin of error of 2.9%, indicating that it is a satisfactory tool for prediction. CONCLUSIONS: HC and CHL can be used as simple tools for predicting GA in babies when this is in doubt. This can help in identification of high-risk newborns at primary care level without recourse to imaging modalities.

Early Onset Neonatal Septicaemia Caused by Pantoea agglomerans.

Pantoea agglomerans is an opportunistic pathogen causing infection in the immunocompromised patients. It is a plant pathogen and a rare human pathogen causing neonatal sepsis, joint infection, urinary tract infection and bloodstream infections. Neonatal Gram negative septicaemia may have an unusual presentation of subtle generalised neonatal seizures without any other cardinal features of sepsis. An appropriate diagnosis is therefore the key to proper management. P. agglomerans being an unusual cause of neonatal sepsis should be diagnosed early with proper antibiogram for clinical cure. Here, we report a case of neonatal sepsis caused by P. agglomerans in a tertiary care hospital in Eastern India.

What to do with a non-rolling stone? Surgical on-table dilemma in large bowel obstruction due to an impacted gallstone.

We present a rare case of large bowel obstruction secondary to colonic gallstones in a frail nonagenarian. Uniquely, the stone was impacted in the descending colon-sigmoid junction, in the absence of underlying bowel pathology distal to the stone. In light of worsening pain and distension after failed endoscopic treatment, the patient was treated with an emergency laparotomy. After an on-table dilemma, a proximal defunctioning loop colostomy was fashioned and the stone left in situ, with the eventual fate of the stone currently undecided. We also discuss alternative treatment options and explain the thought processes that lead to our decision.

Spirometric evaluation in juvenile idiopathic arthritis: data from eastern India.

OBJECTIVE: To evaluate lung function in juvenile idiopathic arthritis (JIA) patients. METHODS: This was a case control study carried out at Institute of Post-Graduate Medical Education & Research, Kolkata, involving JIA patients between 5 and 12 y. They were diagnosed and classified on the basis of International League of Associations for Rheumatology (ILAR) criteria and compared with same number of age, sex, height and weight matched controls. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, forced expiratory flow between 25 and 75% of vital capacity (FEF25-75%) and peak expiratory flow rate (PEFR) of cases were compared to those of matched controls. RESULTS: Among 36 JIA patients initially recruited, 9 were excluded. Of the remaining 27 patients, male: female ratio was 17:10. Mean age, height and weight of JIA patients were 9.15 y, 124.67 cm and 23.78 kg respectively. Six patients had oligoarthritis, 3 had rheumatoid factor positive (RF+) polyarthritis, 10 had rheumatoid factor negative (RF-) polyarthritis and 8 had systemic JIA. Eleven patients had active disease and 15 patients required methotrexate. None had respiratory symptoms. Mean duration of the disease was 2.96 y. Mean FVC and FEV1 were significantly less in JIA patients compared to controls (p value=0.0003 and 0.0007, respectively). FEV1/FVC in both the groups was similar (p value=0.96). Mean Z scores for FVC and FEV1 were significantly higher in JIA patients (p value=0.0064 and 0.0030, respectively). CONCLUSION: Spirometry in JIA patients demonstrated statistically significant restrictive pattern of alteration in pulmonary function.

Growth of children with juvenile idiopathic arthritis.

OBJECTIVE: To evaluate the growth pattern in children with juvenile idiopathic arthritis and its subtypes in comparison with age, sex and temporally matched controls. STUDY DESIGN: Prospective study. SETTING: Pediatric rheumatology clinic of a tertiary care hospital in Eastern part of India. PARTICIPANTS: Seventy-five children (2-12 years) diagnosed as juvenile idiopathic erthritis by International League of Associations for Rheumatology criteria and 75 age- and sex- matched controls. INTERVENTION: Weight, height and body mass index were recorded at six monthly interval in both groups over a period of 3 years. MAIN OUTCOME MEASURES: weight, height and body mass index. RESULTS: Subtype distribution of juvenile idiopathic arthritis was: oligoarthritis (49%, n=37), rheumatoid factor negative polyarthritis (27%, n=20), rheumatoid factor positive polyarthritis (8%, n=6), systemic onset (15%, n=11) and enthesitis related arthritis (1.3%, n=1). Anthropometric parameters in children with juvenile idiopathic arthritis were not significant different from controls. Comparison between the subtypes showed significant differences in height (P=0.011), weight (P=0.005), and growth velocity (P=0.005), but not in body mass index. Systemic onset disease led to significant restriction in height (P=0.018; 95% CI 2.13-33.77) and weight (P=0.008; 95% CI 1.47-14.43) compared to controls. Growth velocity was significantly affected in rheumatoid factor positive polyarthritis (P=0.003; 95% CIO. 46-3.14). CONCLUSIONS: Children with juvenile idiopathic arthritis do not have significantly lower values of anthropometric parameters compared to controls. Significant restriction in height and weight is seen in systemic onset disease, and growth velocity is significantly reduced in rheumatoid factor positive subjects.

Tryptophan dynamics in the exploration of micro-conformational changes of refolded ß-lactoglobulin after thermal exposure: a steady state and time-resolved fluorescence approach.

Refolding intermediates of proteins, including molten globules, are likely to undergo dynamic conformational transitions. In this work, thermal unfolding and refolding of bovine ß-lactoglobulin (ß-lg) have been revisited to encounter such intermediate states. Lower thermal range (< 80°C) was selected to avoid irreversible aggregate formation. The gross kinetic refolding as monitored with the fluorophore, Trp19, was likely to be reversible but alteration in time resolved fluorescence parameters ruled out the possibility of micro-structural reversibility for the refolded partner. Time resolved fluorescence showed that the refolded protein still lacks some intact native conformation. Far-UV CD signals lack the signature of any secondary structural distortion in global structural context whereas near-UV CD signals were strongly indicative of perturbation in micro-structure surrounding the aromatic moieties which hardly revives after cooling. Steady state anisotropy results showed successfully the break-down of dimer to monomer form of ß-lg within 50°C temperature range and augmentation in anisotropy up on further thermal stress reflected the reorganization of tryptophan residues into more restricted and rigid micro-environment as well as irreversible disulfide-linked dimer formation. Reliability of conformational reversibility in the thermal unfolding-refolding is still enigmatic on micro and global structural perspectives. Intermediate state prior to the completion of refolding of thermally exposed ß-lg was identified through fluorescence studies.

Unilateral pulmonary hypoplasia with abdominal situs inversus.

A case of unilateral pulmonary hypoplasia in association with abdominal situs inversus (Situs Inversus Partialis) is described here in a 2-mo-old baby. The normally related heart (levocardia) is dextroposed due to the hypoplastic right lung and compensatory hyper-inflation of the opposite lung which clinically mimicked a mirror-image situs inversus totalis. Such a combination, to the best of authors' knowledge, has never been reported in the world literature.

Unfolding diminishes fluorescence resonance energy transfer (FRET) of lysine modified ß-lactoglobulin: Relevance towards anti-HIV binding.

In accordance with the recent reports by Ng et al. (2001) [12] and Pellengrini et al. (2001) [13], that acetylated and succinylated ß-lg has a potent HIV-I and HIV-II type enzyme inhibitory activity, a spectro-fluoremetric approach has been made to understand the mode of interactions playing the key role in inhibition process. In this article, interactions between lysine modified bovine ß-lactoglobulin (ß-lg) and a hydrophobic fluorescence probe, 1-anilinonapthalene-8-sulfonate (ANS), have been studied with the help of fluorescence resonance energy transfer (FRET) process. Lysine residues of ß-lg were modified by acetylation and succinylation. Tryptophan-19 of intact ß-lg efficiently transfers energy to ANS, whereas in derivatives, it unexpectedly failed to promote energy transfer in spite of being more solvent exposed with an appreciable overlap integral. Efficient fluorescence resonance energy transfer (FRET) is a consequence of good overlap between emission and absorption spectra of donor and acceptor respectively. Therefore, linearity of this relationship becomes questionable in case of modified bio-molecules. Furthermore, time resolved studies showed that in the derivatives, hydrophobic cavities of ß-lg were collapsed so that ANS failed to recognize the deep interior pockets leading to the loss of longer lifetime component. Modifications also prohibited the ionic association through surface leading to the loss of shorter lifetime component. Hence, chemical modification destabilizes ß-lg conformations that affect FRET and interactions are strictly electrostatic.