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An extremely rare, long-lost, monotypic endemic, Indian liverwort, Sewardiella tuberifera Kash. has recently been recollected after a gap of over three-and-a-half decades from an altogether new location, the Mukteshwar region (2,171 m) of Nainital district in the Kumaun Himalaya, Uttarakhand. The remarkable rediscovery of this monotypic, endemic Himalayan liverwort is a significant finding for the world’s bryological treasure. Along with other rare Himalayan monotypic endemics such as Aitchisoniella himalayensis Kash. and Stephensoniella brevipedunculata Kash., the currently located sporiferous population of Sewardiella was discovered persisting in small, dispersed, sparse patches with 5–30 individuals. The currently spotted collection site is being considered a ‘bryological hotspot’. As the area develops as a popular ecotourism destination, the original habitat of these hepatics in a lime stone-dominated, south-west facing, unstable sloppy site at Mukteshwar is under constant pressure from several developmental activities. Hence, serious conservation steps are needed to protect this hotspot supporting Himalayan bryophyte jewels. To ensure long term perpetuation and conservation of red-listed hepatic taxa, an attempt is being made to translocate part of the population to ecologically and climatically identical safer site, including a developing ‘moss garden’ at Lingadhar (Nainital). more...

Background: Fixed-dose combinations (FDCs) are renowned formulations that contain two or more drugs pooled in a single dosage form. Their recognition is justified due to several advantages, such as impending therapeutic efficacy, reducing the episodes of adverse drug effects, having pharmacokinetic advantages, reducing pill burden, reducing the dose of individual drugs, and decreasing drug resistance development. Objective: Recently, an FDC tablet of remogliflozin etabonate (100 mg), vildagliptin (50 mg), and metformin HCl (500/1000 mg) has been approved for the treatment of type 2 diabetes mellitus. No analytical method has been reported thus far for this newly approved combination. Methods: Thus, this review collected and simplified information on reported analytical techniques and physicochemical and biological properties for the above-cited FDCs. The authors have explored various authenticated scientific journals, and simplified information was presented to meet the objectives. Results: The reported methods are spectroscopy (40%, 20% & 33%), HPTLC (10%, 14% & 20%), HPLC (50%, 49% & 41%), hyphenated techniques (Nil, 14% & 5%) and electrophoresis methods (Nil, 2% & 1%) for remogliflozin etabonate, vildagliptin and metformin HCl, respectively. Conclusion: Such extensive data would be useful to analysts in developing an analytical method for the analysis of the recently approved FDCs more...

Arsenic (As)-bearing water treatment residuals (WTRs) from household sand filters are usually disposed on top of floodplain soils and may act as a secondary As contamination source. We hypothesized that open disposal of these filter-sands to soils will facilitate As release under reducing conditions. To quantify the mobilization risk of As, we incubated the filter-sand, the soil, and a mixture of the filter-sand and soil in anoxic artificial rainwater and followed the dynamics of reactive Fe and As in aqueous, solid, and colloidal phases. Microbially mediated Fe(III)/As(V) reduction led to the mobilization of 0.1-4% of the total As into solution with the highest As released from the mixture microcosms equaling 210 μg/L. Due to the filter-sand and soil interaction, Mössbauer and X-ray absorption spectroscopies indicated that up to 10% Fe(III) and 32% As(V) were reduced in the mixture microcosm. Additionally, the mass concentrations of colloidal Fe and As analyzed by single-particle ICP-MS decreased by 77-100% compared to the onset of reducing conditions with the highest decrease observed in the mixture setups (95%). Overall, our study suggests that (i) soil provides bioavailable components (e.g., organic matter) that promote As mobilization via microbial reduction of As-bearing Fe(III) (oxyhydr)oxides and (ii) As mobilization as colloids is important especially right after the onset of reducing conditions but its importance decreases over time. more...

The present study reports the levels of maternal serum calcium and magnesium from early pregnancy until delivery, along with cord levels, in women who developed preeclampsia (PE) and compares them with those without PE. A total of 324 pregnant women (216 non-PE and 108 PE women) were included in this retrospective case-control study of prospectively collected data nested in an observational cohort study. Maternal blood was collected at 4 time points during pregnancy (V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery) and umbilical cord blood at delivery. Independent t tests were used to compare calcium, magnesium, and their ratio between two groups, and their associations with PE were studied using regression models. Calcium levels were similar between groups at all time points. Magnesium levels were lower (p = 0.021) at V2 in PE group as compared with non-PE group. Maternal calcium and magnesium levels were negatively associated, with blood pressure in early pregnancy. In fully adjusted logistic regression analysis, lower magnesium levels were associated with an increased risk of PE at V2 (OR 0.25 [95% CI 0.07, 0.94] p = 0.04). Lower magnesium in mid-pregnancy was associated with higher risk of PE. These changes were observed before the diagnosis of PE, thereby suggesting that they may have a role in the etiology of PE. more...

Objectives The objective is to present the patterns of dual primary malignancies diagnosed at the Pathology Laboratory of Cancer Hospital with the support from hospital-based cancer registry (HBCR), Sangrur, Punjab, India for the years 2018 and 2019. Methods HBCR abstracts data from electronic medical records. Trained cancer registry staff abstracts cases in standard pro forma. Dual primary was coded as per the International Agency for Research on Cancer rule and was rechecked by the pathologist. Statistical Analysis Data about multiple primary was entered and documented in an Excel sheet. Time interval was calculated by subtracting the date of diagnosis for second primary and first primary. Results A total of 6,933 cases were registered, 45 cases are dual primary (26 females, 19 males) of which 64.4% are synchronous and 35.6% metachronous cases. Seventy-nine percent received cancer-directed treatment for synchronous and 87% for metachronous. The most common sites of the primary tumor were breast (33%), head and neck (22.2%), gynecological sites (11%), prostate (9%), esophagus (4%), and remaining other tumors (20.8%). Most common sites for second malignancies were gastrointestinal (GI) tract (31%), gynecological sites (18%), head and neck (16%), hematological malignancies (7%), soft tissue sarcoma (4%), breast (2%), and other sites (22%). Conclusion More than 70% of cases of primary tumors were in breast, head and neck, gynecological, and prostate. Of these, more than 60% of the second malignancy was found in the GI tract, gynecological, and head and neck sites. Around two-thirds of dual tumors are synchronous. Breast cancer cases have higher incidence of second malignancy. Regular follow-up is necessary to assess the survival of the second primary. more...

Banded Iron Formations (BIFs) are marine chemical sediments consisting of alternating iron (Fe)-rich and silica (Si)-rich bands which were deposited throughout much of the Precambrian era. BIFs represent important proxies for the geochemical composition of Precambrian seawater and provide evidence for early microbial life. Iron present in BIFs was likely precipitated in the form of Fe3+ (Fe(III)) minerals, such as ferrihydrite (Fe(OH)3), either through the metabolic activity of anoxygenic photoautotrophic Fe2+ (Fe(II))-oxidizing bacteria (photoferrotrophs), by microaerophilic bacteria, or by the oxidation of dissolved Fe(II) by O2 produced by early cyanobacteria. However, in addition to oxidized Fe-bearing minerals such as hematite (FeIII2O3), (partially) reduced minerals such as magnetite (FeIIFeIII2O4) and siderite (FeIICO3) are found in BIFs as well. The presence of reduced Fe in BIFs has been suggested to reflect the reduction of primary Fe(III) minerals by dissimilatory Fe(III)-reducing bacteria, or by metamorphic (high pressure and temperature) reactions occurring in presence of buried organic matter. Here, we present the current understanding of the role of Fe-metabolizing bacteria in the deposition of BIFs, as well as competing hypotheses that favor an abiotic model for BIF deposition. We also discuss the potential abiotic and microbial reduction of Fe(III) in BIFs after deposition. Further, we review the availability of essential nutrients (e.g. P and Ni) and their implications on early Earth biogeochemistry. Overall, the combined results of various ancient seawater analogue experiments aimed at assessing microbial iron cycling pathways, coupled with the analysis of the BIF rock record, point towards a strong biotic influence during BIF genesis. more...

The propensity of poorly water-soluble drugs to aggregate at supersaturation impedes their bioavailability. The emergence of supersaturated amorphous drug-salt-polymer systems provides a new approach to this problem. However, the effects of polymers on drug-drug interactions in aqueous phase are largely unexplored and it is unclear how to choose an optimal salt-polymer combination for a particular drug. We describe a comparative experimental and computational characterization of amorphous solid dispersions containing the drug celecoxib, and PVP-VA or HPMCAS polymers with or without Na+/K+salts. Classical models for drug-polymer interactions fail to identify the best drug-salt-polymer combination. In contrast, more stable drug-polymer interaction energies computed from molecular dynamics simulations correlate with prolonged stability of supersaturated amorphous drug-salt-polymer systems, along with better dissolution and pharmacokinetic profiles. The celecoxib-salt-PVP-VA formulations exhibit excellent biopharmaceutical performance, offering the prospect of less frequent administration and lower doses of this widely used anti-inflammatory, thereby increasing cost-effectiveness, and reducing side-effects. more...

As permafrost thaws, vast stocks of organic carbon previously accumulated within these systems are vulnerable to microbial decomposition and may be released as the greenhouse gases CO2 and CH4. The release of carbon from permafrost systems is expected to lead to runaway positive feedbacks. The timescale and magnitude of the permafrost-climate feedback is highly uncertain as knowledge gaps remain regarding the rate of decomposition of permafrost organic carbon. These knowledge gaps stem, in part, from poor understanding of the association between organic carbon (in the form of organic matter) and minerals, especially high surface area iron minerals. In this work, we investigated the coupling of iron and carbon cycles in permafrost peatlands and its effect on greenhouse gas release. We first showed that up to 20% of the organic carbon in intact permafrost sites may be associated with iron(III) (oxyhydr)oxides and thereby protected from microbial decomposition. At the onset of thaw, this association is broken down, likely due to the microbial reduction of iron(III), and previously protected carbon is thus released. Using microbiological and molecular biological tools, we linked this breakdown to an increase in the abundance of methanogenic microorganisms and concentrations of methane. Preliminary work also suggests that part of the released organic carbon may re-associate with dissolved iron in thaw ponds to form flocs. Currently, we are investigating the molecular composition of organic matter as it undergoes these redox processes with the goal of linking bioavailability to composition. We complement this work with enrichment experiments and microbial community analyses to determine the microbial key players controlling iron(III) reduction and the potential for subsequent microbial Fe(II) oxidation. Collectively, the results of this project suggest that upon thawing, organic matter previously associated with minerals is mobilized and is likely susceptible to microbially-mediated release as CO2 and CH4. more...

Abstract: The nasal route, a subgroup of mucosal delivery systems, constitutes a lucrative and encouraging substitute for administering drugs and vaccines. Over the years, a lot of research has been done in this area, and scientists have successfully explored this pathway using novel formulations to combat several infections. This review article aims to address the pathways of mucosal immunization, the dominance of the nasal route over other mucosal routes for immunization, and the mechanism of generation of immunogenic response via nasal route and nanotechnology-based approaches for intranasal vaccination. The immunotherapeutic and vaccinations for intranasal administration available in the market are also discussed, along with a brief overview of the products in the pipeline. It can also be assumed that such an approach can prove to be favorable in designing vaccinations for the current uncertain times. In spite of some dubious views on this. more...

The Pleistocene archaeological record of South Asia is important for addressing questions relating to the origin and evolution of Palaeolithic cultures, continuity or change in lithic technologies, and population dispersals across Asia. Here, the authors report on intensive regional studies to investigate variability within this record, employing field survey, lithic analysis and experimental knapping. They examine Palaeolithic hominin behavioural change in the Wainganga Basin, central India, focusing on variability in spatial distribution, stratigraphy and lithic reduction strategies in Acheulian to Late Palaeolithic sites. This emphasises the diversity of cultural sequences in South Asia and contributes to questions of transition and change based on cultural preferences, raw materials and lithic strategies in different regions. more...

Fe(II) oxidation coupled to nitrate reduction is a widely observed metabolism. However, to what extent the observed Fe(II) oxidation is driven enzymatically or abiotically by metabolically produced nitrite remains puzzling. To distinguish between biotic and abiotic reactions, we cultivated the mixotrophic nitrate-reducing Fe(II)-oxidizing Acidovorax strain BoFeN1 over a wide range of temperatures and compared it to abiotic Fe(II) oxidation by nitrite at temperatures up to 60°C. The collected experimental data were subsequently analyzed through biogeochemical modeling. At 5°C, BoFeN1 cultures consumed acetate and reduced nitrate but did not significantly oxidize Fe(II). Abiotic Fe(II) oxidation by nitrite at different temperatures showed an Arrhenius-type behavior with an activation energy of 80±7 kJ/mol. Above 40°C, the kinetics of Fe(II) oxidation were abiotically driven, whereas at 30°C, where BoFeN1 can actively metabolize, the model-based interpretation strongly suggested that an enzymatic pathway was responsible for a large fraction (ca. 62%) of the oxidation. This result was reproduced even when no additional carbon source was present. Our results show that at below 30°C, i.e. at temperatures representing most natural environments, biological Fe(II) oxidation was largely responsible for overall Fe(II) oxidation, while abiotic Fe(II) oxidation by nitrite played a less important role. more...

Microbial reduction of Fe(III) minerals is a prominent process in redoximorphic soils and is strongly affected by organic matter (OM). We herein determined the rate and extent of microbial reduction of ferrihydrite (Fh) with either adsorbed or coprecipitated OM by Geobacter sulfurreducens. We focused on OM-mediated effects on electron uptake and alterations in Fh crystallinity. The OM was obtained from anoxic soil columns (effluent OM, efOM) and included-unlike water-extractable OM-compounds released by microbial activity under anoxic conditions. We found that organic molecules in efOM had generally no or only very low electron-accepting capacity and were incorporated into the Fh aggregates when coprecipitated with Fh. Compared to OM-free Fh, adsorption of efOM to Fh decelerated the microbial Fe(III) reduction by passivating the Fh surface toward electron uptake. In contrast, coprecipitation of Fh with efOM accelerated the microbial reduction, likely because efOM disrupted the Fh structure, as noted by Mossbauer spectroscopy. Additionally, the adsorbed and coprecipitated efOM resulted in a more sustained Fe(III) reduction, potentially because efOM could have effectively scavenged biogenic Fe(II) and prevented the passivation of the Fh surface by the adsorbed Fe(II). Fe(III)-OM coprecipitates forming at anoxic-oxic interfaces are thus likely readily reducible by Fe(III)-reducing bacteria in redoximorphic soils. more...