Development of an HPLC-PDA Method for the Simultaneous Estimation of Three Antibiotics in Pharmaceutical Formulations and Bovine Milk and Health Risk Assessment.

A simple new, rapid, sensitive, and cost-effective HPLC-PDA method was developed and validated for the determination of tetracycline (TC), oxytetracycline (OTC), and ciprofloxacin (CIP) simultaneously. Chromatographic separations were carried out using a reversed-phase Shim-pack GIS C18 column (4.60 × 250.00 mm; 5.00 µm) at 30°C. Oxalic acid (0.05 M), acetonitrile, and methanol were used as mobile phase under gradient elution conditions at the flow rate of 1.50 mL min-1. Detection wavelength was set at 330 nm. An aliquot of 20.00 µL solution was injected, and three drugs were eluted within 7.39 ± 0.05 min. As per ICH guidelines linearity, recovery, accuracy, precision, selectivity, specificity, sensitivity, stability, column efficiency, system suitability, and robustness were determined for the validation of the proposed method. Calibration curves were linear over a studied concentration range of 8.00 µg mL-1 with a correlation coefficient (r) of 0.999 for all drugs. Relative standard deviation (RSD) for intra- and interday precision was found less than 2.87% and 3.22%, respectively, indicating the method to be reproducible. The proposed method has been suitably applied for the estimation of TC, OTC, and CIP in pharmaceutical formulation and milk samples collected from local market in Bangladesh. Among 15 milk samples analyzed, most of the cases (more than 50%) TC, OTC, and CIP were detected above maximum residue levels (MRLs) though no significant toxicological effect on the health of consumers in the study area was identified.

UV-VUV absorption spectra of azido-based energetic plasticizer bis(1,3-diazido prop-2-yl)malonate in gas phase.

Ultraviolet and vacuum ultraviolet photo-absorption spectra of azido (-N3)-based energetic plasticizer, bis(1,3-diazido-prop-2-yl)-malonate (abbreviated as BDAzPM), in the gas phase is recorded at room temperature and in the photon energy range of 5.5-9.9 eV using a synchrotron radiation source. Complementary computational results obtained using the time-dependent density functional theory document the vertical transition energies and oscillator strengths. Comparison of the simulated spectra with the experimental absorption spectrum of BDAzPM reveals that the early part of the absorption spectrum of BDAzPM is of pure valence excitation character, whereas the later intense part of the absorption spectrum is dominated by mixed Rydberg and valence electronic excitations.

Mucosal Microbiome Disruption in Acute Laryngeal Injury Following Intubation.

The objective of this study was to characterize mucosal microbial shifts in patients with acute laryngeal injury (ALgI) after intubation. This cross-sectional study included 20 patients with ALgI who underwent early endoscopic intervention with tissue culture, 20 patients with idiopathic subglottic stenosis (iSGS) who underwent tissue culture during the routine endoscopic intervention, and 3 control patients who underwent mucosal swab culture. 70% of the ALgI patients had a positive culture compared to 5% of the iSGS patients and none of the controls. The most identified microbes isolated from ALgI patients included Staphylococcus species in 30% and Streptococcus species in 25%. The high rate of pathologic bacterial infiltration into postintubation laryngeal wounds supports efforts to reduce bacterial colonization of endotracheal tubes and highlights the role of culture-directed antibiotic therapy as a part of early intervention to improve outcomes for patients with ALgI.

Merging Photocatalytic Doubly-Decarboxylative Csp 2 -Csp 2 Cross-Coupling for Stereo-Selective (E)-α,ß-Unsaturated Ketones Synthesis.

A photocatalytic domain of doubly decarboxylative Csp 2 -Csp 2 cross coupling reaction is disclosed. Merging iridium and palladium photocatalysis manifested carbon-carbon bonds in a tandem dual-radical pathway. Present catalytic platform efficiently cross-coupled α, ß-unsaturated acids and α-keto acids to afford a variety of α, ß-unsaturated ketones with excellent (E)-selectivity and functional group tolerance. Mechanistically, photocatalyst implicated through reductive quenching cycle whereas cross coupling proceeded over one electron oxidative pallado-cycle.

Elements in cultured fishes in Chittagong, Bangladesh and risk assessment.

The concentrations of manganese, iron, copper, lead, nickel, cadmium, arsenic, copper and mercury were determined in 10 cultured fish species, which were collected from local markets of Chittagong, Bangladesh, in June 2021. Measurements were performed by atomic absorption spectrophotometry, after acid digestion of the samples. In some cases, the concentration of the investigated elements was more than the maximum limit set by the WHO. Although the concentration of toxic elements in fishes was relatively high in some species, no health risk has been identified in comparison to the estimated daily intake and the maximum limit. Calculated hazard indices were below 1, which indicates the investigated fish would not cause human health risks. Carcinogenic risk indices for Cr, As, and Cu in all species were considered to be significant.

Proton Pump Inhibitors Modulate Gene Expression Profile in Esophageal Mucosa and Microbiome.

OBJECTIVE: Proton pump inhibitors (PPIs) are commonly used to manage children with upper gastrointestinal symptoms and without a formal diagnosis. We investigated the effect of PPIs on esophageal mucosal transcriptome and active microbiota in children with normal esophagi. Furthermore, we examined whether the differences in host esophageal mucosal gene expression were driven by an underlying esophageal epithelial cell type composition. METHODS: Using metatranscriptomics, the host transcriptional and active microbial profiles were captured from 17 esophageal biopsy samples (PPI naïve [PPI-], n = 7; PPI exposed [PPI+], n = 10) collected from children without any endoscopic and histologic abnormalities in their esophagus (normal esophagus). Deconvolution computational analysis was performed with xCell to assess if the observed epithelial gene expression changes were related to the cell type composition in the esophageal samples. RESULTS: The median (IQR) age of our cohort was 14 years (12-16) with female (63%) preponderance. Both groups were similar in terms of their demographics and clinical features. Compared with PPI-, the PPI+ had upregulation of 27 genes including the MUC genes. The cell type composition was similar between the PPI- and PPI+ groups. Prevotella sp and Streptococcus sp were abundant in PPI+ group. CONCLUSIONS: In children with normal esophagus, PPI exposure can be associated with upregulation of esophageal mucosal homeostasis and epithelial cell function genes in a cell-type independent manner, and an altered esophageal microbiome. Additional studies are warranted to validate our findings and to investigate the causal effect of PPIs on the normal esophageal epithelium and microbial communities.

Cadmium, lead, and zinc immobilization in the soil using a phosphate compound with citric acid present.

Low molecular weight organic acids (LMWOAs) are common in rhizospheric soil and may impede the interaction between phosphate and metals. Thus, studying how phosphate compounds impact metal immobilization in rhizospheric soil using LMWOAs is crucial. An incubation experiment examined the effects of NaH2PO4 (a P compound) (3%), various concentrations of citric acid (CA), and combinations of P and CA, on soil cadmium (Cd), lead (Pb), and zinc (Zn) immobilization using the European Community Bureau of Reference (BCR) sequential extraction method, CaCl2 extraction method, zeta potential, fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The P, low CA (2 mmol kg-1 soil) (CA2), and P-CA2 treatments reduced acid-soluble and CaCl2-extractable Cd, Pb, and Zn, indicating metal immobilization, with the P-CA2 treatment being the most effective. High CA (>5-20 mmol kg-1 soil) or a P with high CA reversed prior patterns, suggesting metal mobilization. The zeta potential study indicated that when pH increased, treatments became more negative, notably P-CA2 followed by P, suggesting that electrostatic adsorption was the predominant metal immobilization mechanism, especially in P-CA2. XRD tests, however, showed that the P treatment alone produced Cd phosphate, pyromorphite, and hopeite, indicating that sorption and precipitation were the main metal immobilization processes in the P treatment alone. In conclusion, P-CA2 was found to be the most efficient metal immobilization and redistribution treatment for contaminated soils. Rhizospheric CA may alter Cd, Pb, and Zn mineral stability. Therefore, when treating Cd, Pb, and Zn-contaminated soils with a P compound, CA should be addressed.

The relationship between the intestinal microbiome and body mass index in children with cystic fibrosis.

BACKGROUND: The nutritional status of children with cystic fibrosis (CF), as assessed by their body mass index percentile (BMIp), is a critical determinant of long-term health outcomes. While the intestinal microbiome plays an important role in nutrition, little is known regarding the relationship of the microbiome and BMIp in children with CF. METHODS: Pediatric patients (< 18 years old) with CF and healthy comparison patients (HCs) were enrolled in the study and stool samples obtained. BMIp was categorized as Green Zone (BMIp > 50th), Yellow Zone (BMIp 25th-49th) and Red Zone (BMIp < 25th). Intestinal microbiome assessment was performed via 16S rRNA gene sequencing; microbial richness, diversity, and differential species abundance were assessed. RESULTS: Stool samples were collected from 107 children with CF and 50 age-matched HCs. Compared to HCs, children with CF were found to have lower bacterial richness, alpha-diversity, and a different microbial composition. When evaluating them by their BMIp color zone, richness and alpha-diversity were lowest in those in the Red Zone. In addition, an unclassified amplicon sequence variant (ASV) of Blautia, a known butyrate-producing anaerobe, was of lowest abundance in children in the Red Zone. CONCLUSION: Children with CF have a dysbiotic intestinal microbiome with specific changes that accompany changes in BMIp. Longitudinal assessments of the microbiome and its metabolic activities over time are needed to better understand how improvements in the microbiome may improve nutrition and enhance long-term survival in children with CF.

The Spectrum of Intracranial Hypertrophic Pachymeningitis at an Eastern Indian Tertiary Care Center.

Introduction: Hypertrophic pachymeningitis (HP) is a treatable, rare inflammatory disease, either primary or secondary to systemic causes. Aims: To characterize the etiology, clinical manifestations, and treatment outcomes of HP patients and determine the factors influencing the radiological resolution of the pachymeningeal enhancement and recurrence of symptoms within the follow-up period. Materials and Methods: We collected data for this prospective observational study between March 1, 2021 and May 31, 2022, at the Bangur Institute of Neurosciences, Kolkata, and the patients were followed for a 6-month period. Demographic, clinical, laboratory, and treatment-related data were collected. A univariate logistic regression model was used for comparison between patients with and without radiological resolution of pachymeningitis and between patients with and without symptom recurrence. Results: Among 44 patients, the male: female ratio was 1.2:1. The median age at disease onset was 35.5 (28.5-49.5) years. The etiologies were idiopathic (56.8%), tuberculosis (22.8%), immunoglobulin G subtype 4 (IgG4) disease (9.2%), other infections (6.8%), and neoplastic (4.4%). Headache was the most common presentation (95.4%), followed by cranial neuropathies (68.2%). Optic and oculomotor neuropathies were the most common. In terms of radiological features, 27.27, 29.54, and 43.18% of patients had diffuse, focal regular, and focal irregular enhancement, respectively. Temporal (50%), followed by cavernous sinus (38.63%) enhancement, was the most common. Recurrence occurred in 36 and 50% of idiopathic and IgG4-related HP cases, respectively. Mycophenolate mofetil was added to their steroid regimen with no further recurrences. Conclusion: The cohort had a marked absence of (antineutrophil cytoplasmic antibodies) ANCA-associated HP. The severity of clinical manifestations or distribution of pachymeningitis did not differ significantly among the etiological groups. The presence of idiopathic etiology and focal regular enhancement had a significantly higher chance of radiological resolution. The response to therapy was satisfactory. Recurrence was significantly related to shorter steroid courses (

Base-Promoted Tandem Pathway for Keto-Amides: Visible Light-Mediated Room-Temperature Amidation Using Molecular Oxygen as an Oxidant.

Herein, we report metal- and photocatalyst-free room-temperature amidation for α-ketoamide synthesis from feedstock phenacyl bromides and amines using molecular oxygen as an oxidant as well as a source of oxygen in the amide segment. Visible light-mediated base-promoted one-pot sequential C-N/C═N/C═O bond formation takes place in a tandem manner to afford the desired product. Functional group tolerance (benzylic alcohol, keto, cyano, nitro, halo, etc.), a broad substrate scope, and gram-scale synthesis make this synthetic methodology more attractive. We have observed that electron-rich aromatic amines, aliphatic amines, and phenacyl bromide derivatives proceeded the present transformation with marginally superior reactivity in comparison to electron-deficient aromatic amines and phenacyl bromide derivatives. Moreover, several control experiments, in situ isolation of secondary amine and imine as key intermediates, and 18O-labeling experiments provide complete insight into the mechanism of the tandem pathway.

Cu/Pd-catalyzed arylboration of a 1-silyl-1,3-cyclohexadiene for stereocontrolled and diverse cyclohexane/ene synthesis.

The synthesis and Cu/Pd-catalyzed arylboration of 1-silyl-1,3-cyclohexadiene is described. This diene is significant as it allows for synthesis of polyfunctional cyclohexane/enes. To achieve high levels of diastereoselectivity, the use of a pyridylidene Cu-complex was employed. In addition, through the use of a chiral catalyst, an enantioselective reaction was possible. Due to the presence of the silyl and boron substituents, the products can be easily diversified into a range of valuable cyclohexane/ene products.

Tubular lysosome induction couples animal starvation to healthy aging.

Dietary restriction promotes longevity in several species via autophagy activation. However, changes to lysosomes underlying this effect remain unclear. Here using the nematode Caenorhabditis elegans, we show that the induction of autophagic tubular lysosomes (TLs), which occurs upon dietary restriction or mechanistic target of rapamycin inhibition, is a critical event linking reduced food intake to lifespan extension. We find that starvation induces TLs not only in affected individuals but also in well-fed descendants, and the presence of gut TLs in well-fed progeny is predictive of enhanced lifespan. Furthermore, we demonstrate that expression of Drosophila small VCP-interacting protein, a TL activator in flies, artificially induces TLs in well-fed worms and improves C. elegans health in old age. These findings identify TLs as a new class of lysosomes that couples starvation to healthy aging.

Dangling Water Molecules Bridge for ESIPT in Aggregated TMP: A Theoretical Study.

We present a theoretical study on the occurrence of excited-state proton transfer in an aggregated structure of 2-(benzo[d]thiazol-2-yl)-6-methoxyphenol (TMP) exclusively in water among polar solvents, as reported in a recent experiment (Bhattacharyya, A. New J. Chem. 2019, 43, 15087). Our extensive investigation of the TMP monomer and dimer implementing density functional theory (DFT) and time-dependent density functional theory (TDDFT) methods, in three different solvents, namely, water, methanol, and dimethyl sulfoxide (DMSO), with explicit inclusion of solvent molecules demonstrated the existence of both enol and keto forms of the TMP dimer in the excited state, but only in water; this confirmed the experimental emission spectra completely and simultaneously validated the aggregation-induced emission phenomenon. Further analysis of various parameters such as potential energy scan (PES) of the hydroxyl (O-H) bond involved in hydrogen bonding, frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), and infrared (IR) stretching frequencies of both the monomer and dimer forms of TMP in different solvents clearly indicated the geometry of the dimer, with the arrangement of the solvent molecules to be the sole reason for the excited-state charge transfer. The bridging alignment of water molecules in between the stacked units of the TMP dimer results in intermolecular interactions, ultimately leading to intermolecular proton transfer in the excited state.

New insights into self-structure induction in poly (rA) by Quinacrine through non-classical intercalation: Spectroscopic and theoretical perspectives.

Self-structure induction in a single stranded polyriboadenylic acid [poly (rA)] is an auspicious physiological phenomenon which switches off protein production in tumor cells. In the present study, the self-structure induction process in poly (rA) moiety was thoroughly investigated using various steady state and time resolved techniques. Optical melting pattern directly evidenced the formation of self-structured assembly in single stranded poly (rA) upon complexation with quinacrine. Further, UV-absorption spectroscopic studies revealed that quinacrine binds to poly (rA) in co-operative fashion and the indication of intercalative mode of binding first came out with the involvement of around two base pairs of poly (rA) in the complexation. Experimental observations established the unconventional or non-classical intercalation of quinacrine molecule inside self-structured duplex poly (rA) moiety. This complexation was accompanied with negative enthalpy change and positive entropy change; suggesting strong van der Waals and the H-bonding interactions as the major governing forces in the complexation. Moreover, ionic strength dependent binding study established that the non-polyelectrolytic forces were the dominating forces. Further, the photo physical behavior of QN was authenticated using time dependent density functional theory (TDDFT) where both the ground and excited states were exploited.

Pd-Catalyzed Tandem Pathway for Stereoselective Synthesis of (E)-1,3-Enyne from ß-Nitroalkenes by Using a Sacrificial Directing Group.

The involvement of nitroalkenes instead of minimal one alkyne motif for (E)-1,3-enynes synthesis through a palladium catalyzed stereoselective bond forming pathway at room temperature is presented. Implication of nitro group as a sacrificial directing group, formation of magical alkyne on a newly developed Csp 3 -Csp 3 bond with initial palladium-MBH adduct make this methodology distinctive. This protocol features an unprecedented sequential acetate addition, carbon-carbon bond formation, isomerization of double bond and nitromethane degradation in a tandem catalytic walk via dancing hybridization. Mechanistic understanding through identification of intermediates and computational calculations furnishes complete insight into the tandem catalytic pathway. Broad substrates scope and functional groups tolerance make this synthetic methodology magnificent and dynamic. This represents the first example of stereoselective 1,3-enyne synthesis exclusively from alkene substrates by introducing the concept of sacrificial directing group.

Surgical outcome of extrahepatic portal venous obstruction: Audit from a tertiary referral centre in Eastern India.

Backgrounds/Aims: Extra hepatic portal venous obstruction (EHPVO) is the most common cause of portal hypertension in Indian children. While endoscopy is the primary modality of management, a subset of patients require surgery. This study aims to report the short- and long-term outcomes of EHPVO patients managed surgically. Methods: All the patients with EHPVO who underwent surgery between August 2007 and December 2021 were retrospectively reviewed. Postoperative complications were classified after Clavien-Dindo. Binary logistic regression in Wald methodology was used to determine the predictive factors responsible for unfavourable outcome. Results: Total of 202 patients with EHPVO were operated. Mean age of patients was 20.30 ± 9.96 years, and duration of illness, 90.05 ± 75.13 months. Most common indication for surgery was portal biliopathy (n = 59, 29.2%), followed by bleeding (n = 50, 24.8%). Total of 166 patients (82.2%) had shunt procedure. Splenectomy with esophagogastric devascularization was the second most common surgery (n = 20, 9.9%). Nine major postoperative complications (Clavien-Dindo > 3) were observed in 8 patients (4.0%), including 1 (0.5%) operative death. After a median follow-up of 56 months (15-156 months), 166 patients (82.2%) had favourable outcome. In multivariate analysis, associated splenic artery aneurysm (p = 0.007), isolated gastric varices (p = 0.004), preoperative endoscopic retrograde cholangiography and stenting (p = 0.015), and shunt occlusion (p < 0.001) were independent predictors of unfavourable long-term outcome. Conclusions: Surgery in EHPVO is safe, affords excellent short- and long-term outcome in patients with symptomatic EHPVO, and may be considered for secondary prophylaxis.

Idiopathic subglottic stenosis arises at the epithelial interface of host and pathogen.

Background: Idiopathic subglottic stenosis (iSGS) is a rare fibrotic disease of the proximal airway affecting adult Caucasian women nearly exclusively. Life-threatening ventilatory obstruction occurs secondary to pernicious subglottic mucosal scar. Disease rarity and wide geographic patient distribution has previously limited substantive mechanistic investigation into iSGS pathogenesis. Result: By harnessing pathogenic mucosa from an international iSGS patient cohort and single-cell RNA sequencing, we unbiasedly characterize the cell subsets in the proximal airway scar and detail their molecular phenotypes. Results show that the airway epithelium in iSGS patients is depleted of basal progenitor cells, and the residual epithelial cells acquire a mesenchymal phenotype. Observed displacement of bacteria beneath the lamina propria provides functional support for the molecular evidence of epithelial dysfunction. Matched tissue microbiomes support displacement of the native microbiome into the lamina propria of iSGS patients rather than disrupted bacterial community structure. However, animal models confirm that bacteria are necessary for pathologic proximal airway fibrosis and suggest an equally essential role for host adaptive immunity. Human samples from iSGS airway scar demonstrate adaptive immune activation in response to the proximal airway microbiome of both matched iSGS patients and healthy controls. Clinical outcome data from iSGS patients suggests surgical extirpation of airway scar and reconstitution with unaffected tracheal mucosa halts the progressive fibrosis. Conclusion: Our data support an iSGS disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. These results refine our understanding of iSGS and implicate shared pathogenic mechanisms with distal airway fibrotic diseases.

The Spectrum of Pediatric Infection-Associated Intracranial Arteriopathies and Acute Ischemic Stroke at 2 Eastern Indian Tertiary Care Centres.

INTRODUCTION: Major and minor pediatric infections may cause intracranial arteriopathies, the long-term outcome of which we investigated and identified the factors influencing the progression/resolution of arteriopathies. METHODS: We collected the clinical and radiological data of children aged 1 month-15 years who had ischemic stroke with definite arteriopathy following a recent febrile infection. Repeated neuroimaging was done over the next year to ascertain recurrent strokes and the progression and resolution of arteriopathies. RESULTS: The anterior circulation was more frequently affected (83.33%), predominantly involving the middle cerebral artery (41.67%), resolving in 20.84% of cases and progressing in 33.33% of cases. Lesions were commonly unilateral (54.17%) and stenotic (75%), resulting predominantly in cortical infarcts (45.83%), with hemiparesis being the most common neurodeficiency. Apart from tubercular meningitis patients, others had a good functional outcome. CONCLUSION: Lower age, minor infections, and unilateral arteriopathies had a significantly higher chance of resolution. Postviral arteriopathies had a significantly lower chance of progression compared with those following bacterial infections. Progressive and bilateral arteriopathies were significantly associated with worse outcomes and recurrent strokes.