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Intensifying permafrost thaw alters carbon cycling by mobilizing large amounts of terrestrial substrate into aquatic ecosystems. Yet, few studies have measured aquatic carbon fluxes and constrained drivers of ecosystem carbon balance across heterogeneous Arctic landscapes. Here, we characterized hydrochemical and landscape controls on fluvial carbon cycling, quantified fluvial carbon fluxes, and estimated fluvial contributions to ecosystem carbon balance across 33 watersheds in four ecoregions in the continuous permafrost zone of the western Canadian Arctic: unglaciated uplands, ice-rich moraine, and organic-rich lowlands and till plains. Major ions, stable isotopes, and carbon speciation and fluxes revealed patterns in carbon cycling across ecoregions defined by terrain relief and accumulation of organics. In previously unglaciated mountainous watersheds, bicarbonate dominated carbon export (70% of total) due to chemical weathering of bedrock. In lowland watersheds, where soil organic carbon stores were largest, lateral transport of dissolved organic carbon (50%) and efflux of biotic CO2 (25%) dominated. In watersheds affected by thaw-induced mass wasting, erosion of ice-rich tills enhanced chemical weathering and increased particulate carbon fluxes by two orders of magnitude. From an ecosystem carbon balance perspective, fluvial carbon export in watersheds not affected by thaw-induced wasting was, on average, equivalent to 6%–16% of estimated net ecosystem exchange (NEE). In watersheds affected by thaw-induced wasting, fluvial carbon export approached 60% of NEE. Because future intensification of thermokarst activity will amplify fluvial carbon export, determining the fate of carbon across diverse northern landscapes is a priority for constraining trajectories of permafrost region ecosystem carbon balance.

Recurrent attacks of rheumatic fever can lead to mitral stenosis. In a country like India mitral stenosis can develop in the first decade of life. Our patient presented with recurrent mitral stenosis at twelve years of age. He had undergone balloon mitral valvotomy at the age of seven. However this time he developed anterior mitral valve leaflet tear after balloon mitral valvotomy and had to be taken for mitral valve repair. Due to severe fibrosis of mitral valve the patient underwent mitral valve replacement. He was started on warfarin and dose titrated according to PT / INR. Patient was discharged but has to be on lifelong anticoagulation from the age of twelve.

Background: CIN is an important cause of morbidity and mortality post cardiac procedures. Renal derangement and diabetes being the most important risk factors. Multifactorial causation of the disorder led us to study the risk factors associated with CIN. Methods: All patients who underwent cardiac procedures between March 2019 and March 2020 were screened for CIN and included in the study. Out of the 3192 patients screened 99 patients were diagnosed with CIN. Parameters such as diabetes mellitus, hypertension, CKD, anemia, duration of hospital stay, cardiogenic shock, number of stents, amount and type of contrast, Ejection Fraction, creatinine clearance before and after the procedure, concomitant nephrotoxic drugs were also recorded. Results: Ninety-nine patients developed CIN amounting to 3% of the total procedures, 11% expired, 18% required dialysis, average creatinine clearance before the procedure was 53.15 ml/min/1.73 m2 and post procedure it was 29.16 ml/min/1.73 m2, 51.5% of cases had creatinine clearance prior to procedure

Aim: Single coronary artery is a rare anomaly. Patients may present with syncope, angina or rarely sudden cardiac death. Presentation of Case: Patient presented with dyspnea on exertion for one year. On 2D Echo patient had small restrictive VSD. On coronary angiography single coronary artery from right cusp was seen. On CT angiography anomalous origin was confirmed. There was no malignant course of coronary artery. Discussion: Anomalous origin of coronary arteries are rare cardiac anomalies. It can present as syncope, angina, or sudden cardiac death especially in patients with malignant course of coronary artery passing between aorta and pulmonary artery. Hence CT coronary angiography is useful to rule out the malignant course. In our patient, there was no malignant course hence managed conservatively. Conclusion: Anomalous origin of coronary artery is a rare anomaly and requires tailored treatment according to type and course of artery.

Objective: The present study aimed to improve the rate of dissolution of furosemide by solid dispersion technique. Methods: Solid dispersion of furosemide was prepared by using hydrogel isolated from the seeds of Lepidium sativum as a novel carrier by the solvent evaporation method. Solid dispersion was evaluated to study the improvement in the rate of dissolution. Molecular dispersion of furosemide in the novel carrier was studied by DSC and FTIR studies. Solid dispersion was filled in capsules after stability studies and the formulation was optimized by adopting factorial design. Results: Solid dispersion of furosemide exhibited dissolution improvement from 13.54 % (plain furosemide) to 69.12% (solid dispersion) in the first 60 min. Improvement in dissolution efficiency was found to be retained after stability studies. Capsules were filled with the formulation of solid dispersion using two different grades of lactose-α lactose monohydrate and anhydrous lactose and were found stable after stabilization studies. Conclusion: The dissolution improvement of furosemide was attributed to its molecular dispersion in the novel carrier selected for this study. The recrystallization of furosemide was prevented due to intermolecular interaction between the novel carrier and furosemide. This was confirmed by FTIR. Evaluation of the dissolution data of factorial batches was analyzed by ANOVA. Analysis of the data revealed that selected levels of α lactose monohydrate and anhydrous lactose would be useful to navigate design space.

Displacement of leads due to coiling around the pacemaker in the sagittal axis can result in Reel syndrome. Rotation of pulse generator can be due to self-manipulation, ratchet-like mechanism, or due to enlarged pocket. Our case presented with complete heart block with lead displacement and protrusion of pulse generator. Chest X-ray was suggestive of Reel syndrome. The pacemaker was explanted and implanted on the other side. To prevent recurrence, adequate pocket size was created with proper suturing to the underlying fascia and adequate compression for 5–7 days was applied after implantation.

S100P has been shown to be a marker for carcinogenesis where its expression in solid tumours correlates with metastasis and a poor patient prognosis. This protein’s role in any physiological process is, however, unknown. Here we first show that S100P is expressed both in trophoblasts in vivo as well as in some corresponding cell lines in culture. We demonstrate that S100P is predominantly expressed during the early stage of placental formation with its highest expression levels occurring during the first trimester of gestation, particularly in the invading columns and anchoring villi. Using gain or loss of function studies through overexpression or knockdown of S100P expression respectively, our work shows that S100P stimulates both cell motility and cellular invasion in different trophoblastic and first trimester EVT cell lines. Interestingly, cell invasion was seen to be more dramatically affected than cell migration. Our results suggest that S100P may be acting as an important regulator of trophoblast invasion during placentation. This finding sheds new light on a hitherto uncharacterized molecular mechanism which may, in turn, lead to the identification of novel targets that may explain why significant numbers of confirmed human pregnancies suffer complications through poor placental implantation.

This manuscript demonstrates a Quality by Design approach using Design of Experiments to prove the robustness of a stability indicating HPLC method. The method determines the omeprazole in the presence of eight related substances and ketoprofen with six impurities developed for pellets filled capsule as a combined finished drug product. Based on the results, controllable factors that have influential effect on the resolution between peaks were identified and were examined while blocking the uncontrollable factors. The design employs a full factorial design of experiment for the interaction of controllable factors. A flowchart parades all steps of QbD approach by blocking and varying certain factors. Thus, the primary objective of this manuscript is to demonstrate the method's robustness by clarifying various steps systematically.

A novel gradient reversed-phase high-performance liquid chromatographic method has been developed for quantitative determination of Ropinirole hydrochloride and its six impurities in pharmaceutical dosage forms. Chromatographic separation has been achieved on an Inertsil ODS-3V (250 mm × 4.6 mm) 5 µm with buffered mobile phase consisting of solvent A (mixture of 0.1 molar (M) phosphate (pH 7.1) buffer and acetonitrile in the ratio 90:10 (v/v); respectively) and solvent B (mixture of 0.1 molar (M) phosphate (pH 7.1) buffer and acetonitrile in the ratio 60:40 (v/v); respectively) delivered at flow rate of 1.2 mL min−1 and the detection wavelength of 215 nm. Resolution of Ropinirole hydrochloride and all the six potential impurities has been achieved greater than 2.0 for all closely eluting impurities. This drug product was subjected to the stress conditions and stability studies were one degradant impurity was crossing reporting threshold those degradants were separated by preparative high performance liqui...

This paper describes a systematic design of experiments (DoE) approach by applying the principle of quality by design (QbD) to determine the design space for a stability-indicating HPLC method prior to validation. By employing DoE, a simultaneous multivariate approach was carried out for mobile phase pH, flow rate, percentage of organic content and column temperature. A two-level fractional factorial design (24−1 + 2 center points = 10 experiments) was employed and statistical analysis of the experimental data uncovered the significant influential chromatographic factors. The experimental data for USP tailing and resolution were analyzed statistically to screen the chromatographic factors. This approach determined the most influential chromatographic factors. During this process, inferences were evaluated from various data tables, for example, analysis of variance, summary of fit, lack of fit, and parameter estimates. The study also explained various plots such as actual vs. predicted plot, Pareto plot, and prediction profiler. The acceptable range of the chromatographic factors was displayed as a Contour plot defining the ‘design space’ of the method. The range of operating conditions that guarantee a satisfactory QbD was deduced to finalize the method prior to validation. The method is simple, rapid, and robust for the determination of montelukast in montelukast sodium oral granules dosage form. The method was validated according to ICH guidelines for accuracy, precision, linearity, range, specificity, ruggedness and robustness (one factor varied at a time). The method has been successfully transferred to the quality control department for quality analysis of manufactured batches and stability samples.

A complex, sensitive, and precise high-performance liquid chromatographic method for the profiling of impurities of esomeprazole in low-dose aspirin and esomeprazole capsules has been developed, validated, and used for the determination of impurities in pharmaceutical products. Esomeprazole and its related impurities' development in the presence of aspirin was traditionally difficult due to aspirin's sensitivity to basic conditions and esomeprazole's sensitivity to acidic conditions. When aspirin is under basic, humid, and extreme temperature conditions, it produces salicylic acid and acetic acid moieties. These two byproducts create an acidic environment for the esomeprazole. Due to the volatility and migration phenomenon of the produced acetic acid and salicylic acid from aspirin in the capsule dosage form, esomeprazole's purity, stability, and quantification are affected. The objective of the present research work was to develop a gradient reversed-phase liquid chromatographic method to separate all the degradation products and process-related impurities from the main peak. The impurities were well-separated on a RP8 column (150 mm × 4.6mm, X-terra, RP8, 3.5μm) by the gradient program using a glycine buffer (0.08 M, pH adjusted to 9.0 with 50% NaOH), acetonitrile, and methanol at a flow rate of 1.0 mL min(-1) with detection wavelength at 305 nm and column temperature at 30°C. The developed method was found to be specific, precise, linear, accurate, rugged, and robust. LOQ values for all of the known impurities were below reporting thresholds. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation in the presence of aspirin. The developed RP-HPLC method was validated according to the present ICH guidelines for specificity, linearity, accuracy, precision, limit of detection, limit of quantification, ruggedness, and robustness.