Priorities, opportunities, and challenges for integrating microorganisms into Earth system models for climate change prediction.

Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a "top 10" list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy.

GIS modeling to investigate environmental change and degradation in Kohima district, North East Hill (NEH) region of India.

As a part of the Himalayan mountains, the North East Hill (NEH) region of India is geophysically dynamic and seismotectonically active since its formation about 55 million years ago with a head-on collision of the Indian plate and the Eurasian plate. The region still has been underthrusting at a rate of 4.5-5 cm/year causing the reshaping and changing of its geophysical characteristics (geology, geomorphology, relief, slope gradient, drainage system, etc.), whereas anthropogenic activities, particularly shifting cultivation and technological intervention, have caused changes or degradation of the ecological environment (air, land, water, vegetation, crop pattern, climate, wildlife, etc.). Addressing this burning geoecological problem, a geospatial technology-based case study from the Kohima district of Nagaland in the North East Hill region of India is presented here. Through the development and integration of multiple GIS modules, this reconnaissance study suggests that continuous seismic activities (about 27 seismic events/year) along tectonic faults, thrusts, and lithological shear zones have been reshaping and changing the geophysical environment, whereas the ecological environment has been changing or degrading due to decreasing natural landscape and habitats (forest area, water bodies, and shrubs) at an annual rate of 5.91 km2 (0.60%), increasing built-up area, agricultural land, and wasteland at an annual rate of 2.73 km2 (0.28%), 2.69 km2 (0.27%), and 0.49 km2 (0.05%) respectively. Results also suggest that environmental degradation results in accelerated trends of climate change (rising temperature at the rate of 0.13 °C/year, decreasing annual rainy days at the rate of 2 days/year, decreasing annual rainfall at the rate of 9.55 cm/year, mounting climatic zones at the rate of 175 m/year) and its adverse impacts (increasing extreme rainfall events at the rate of 3 events/year and causing cloud burst, erosion, landslides, and floods) in the region.

Findings of second multicentric follow-up serosurvey among Health Care Workers in government hospitals.

Background: The change in serological status of community may be used as input for guiding the public health policy. Hence, the present study was conducted to determine change in seroprevalence of COVID-19 among healthcare workers (HCWs). Methods: From the baseline multicentric study sample, a subsample was followed up, and a seroepidemiological study was conducted among them between 6 and 22 weeks after the second dose of the vaccination. Multistage population proportion to size sampling was performed for the selection of subsample of HCWs. The serosurvey was conducted using the enzyme-linked immunosorbent assay-based IgG antibody test (COVID KAVACH). Results: Follow-up serological testing was done in subsample of 1122 participants of original 3253 participants. The mean age of the participants was 34.6 (8.13) years. A total of 300 (26.7%) participants were females. The seroprevalence was 78.52, (95%CI:76-80.1). Among those who were seronegative at initial test, 708 (77.04%) were seroconverted. Those who were not seroconverted (241 (21.5%)) have longer duration from the second dose of the vaccination (93 (31.4) vs. 56 (38.4); p value < 0.001). The COVID-19 infection was significantly associated with seropositive status and being a medical staff was associated with remaining seronegative on follow-up. The higher age (≥50 years) was found to be significantly associated with seroreversion. Conclusion: Four in five HCWs had detectable antibodies. Seroepidemiological studies carry vital information to control the public health response in the course of the pandemic. The study can also further help as a platform to study the seroconversion and effect of vaccination among HCWs for newer variants of SARS-CoV-2.

Seropositivity of severe acute respiratory syndrome coronavirus 2 infection among healthcare workers of the Armed Forces medical services, India: A multicentric study.

BACKGROUND: Serosurveys provide the prevalence of infection and over time will reveal the trends. The present study was conducted to estimate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCWs) and to analyse various characteristics (risk factors) associated with SARS CoV-2 infection. METHODS: Eight government designated Corona virus disease -19 (COVID-19) hospitals were selected based on the hospital admission of patients with COVID-19 and the local epidemiological situation in the region. Multistage population proportion to size sampling was performed for the selection of HCWs. Serosurvey was conducted using the enzyme-linked immunosorbent assay-based IgG antibody test (COVID KAVACH). Bivariate and multiple logistic regression was performed to find out the factor/factors associated with the positive antibody test. RESULTS: Out of 3255 HCWs that participated in the study, data of 3253 were analysed. The seroprevalence was 19.7% (95% confidence interval: 18.5-21.3%). Factors associated were location, category of HCWs, male sex, previously tested positive by the molecular test, training on infection prevention and control, personal protective measures, handwashing technique, close contact with a patient confirmed with COVID-19, use of personal protective equipment and symptoms in the last 30 days. However, in multiple logistic regression, only location, category, previously tested positive by the molecular test and symptoms in the last 30 days were statistically significant. CONCLUSION: HCWs are vulnerable to SARS-CoV-2 infection. One in five HCWs had detectable antibodies. The presence of antibodies among HCWs may help in their placement and triage. HCWs may be advised to report early in case of any symptoms of COVID-19. Preventive measures may be targeted based on the location, with particular emphasis on ancillary workers and nurses.

Natural drugs, not so natural effects: Neonatal abstinence syndrome secondary to 'kratom'.

BACKGROUND: Mitragyna speciosa, also known as kratom, is obtained from the coffee plant family 'Rubiaceae.' Kratom is available in the form of capsules, whole, processed and powdered leaves, and as liquids. Secondary to its 'natural herb' status and opioid effects, it is misconceived to be a safe alternative for the treatment of chronic pain. The use of kratom has increased by tenfold in the United States since 2010. METHODS AND RESULTS: We report a term neonate who was born to a chronic kratom user and required treatment with opiates for neonatal drug withdrawal. CONCLUSION: Physicians should be aware of these herbal supplements and its potential withdrawal effects in newborn which cannot be picked up by the standard toxicology screen.

Immunization with Salmonella Abortusequi phage lysate protects guinea pig against the virulent challenge of SAE-742.

Salmonella Abortusequi causes important clinical diseases in horses possibly leading to abortion. In the present investigation, the protective efficacy of both plain and aluminum hydroxide gel adjuvanted phage lysate was evaluated in guinea pig model. Broad host range bacteriophage PIZ-SAE-2, was characterized and used for generation of lysates. Three different lysate batches, produced through separate cycles and characterized, were pooled together for immunization study. Plain and adjuvanted phage lysate preparations elicited both humoral and cellmediated immunity. The adjuvanted lysate at a dose of 50 µl elicited the highest protective efficacy against direct challenge at 28th DPI. Thus, the present study describes a new method of bacterial inactivation for producing a new class of better & safe immunprophylactic agents. This is the first report of producing an inactivated vaccine candidate using a new approach against equine salmonellosis.

Apnea, bradycardia and desaturation spells in premature infants: impact of a protocol for the duration of 'spell-free' observation on interprovider variability and readmission rates.

OBJECTIVE: To study the impact of implementing a protocol to standardize the duration of observation in preterm infants with apnea/bradycardia/desaturation spells before hospital discharge on length of stay (LOS) and readmission rates. STUDY DESIGN: A protocol to standardize the duration of in-hospital observation for preterm infants with apnea, bradycardia and desaturation spells who were otherwise ready for discharge was implemented in December 2013. We evaluated the impact of this protocol on the LOS and readmission rates of very low birth weight infants (VLBW). Data on readmission for apnea and an apparent life-threatening event (ALTE) within 30 days of discharge were collected. The pre-implementation epoch (2011 to 2013) was compared to the post-implementation period (2014 to 2016). RESULTS: There were 426 and 368 VLBW discharges before and after initiation of the protocol during 2011 to 2013 and 2014 to 2016, respectively. The LOS did not change with protocol implementation (66±42 vs 64±42 days before and after implementation of the protocol, respectively). Interprovider variability on the duration of observation for apneic spells (F-8.8, P=0.04) and bradycardia spells (F-17.4, P<0.001) decreased after implementation of the protocol. The readmission rate for apnea/ALTE after the protocol decreased from 12.1 to 3.4% (P=0.01). CONCLUSION: Implementing an institutional protocol for VLBW infants to determine the duration of apnea/bradycardia/ desaturation spell-free observation period as recommended by the American Academy of Pediatrics clinical report did not prolong the LOS but effectively reduced interprovider variability and readmission rates.

Spectral investigation of the effect of anion on the stability of non covalent assemblies of 2,3,5,6,8,9,11,12-octahydro-1,4,7,10,13-benzopentaoxacyclopentadecine (benzo-15-crown-5) with sodium halides.

A series of complexes of 2,3,5,6,8,9,11,12-octahydro-1,4,7,10,13-benzopentaoxacyclopentadecine (benzo-15-crown-5) with sodium halides was synthesized in acetonitrile. The effect of anion on the stability and spectral properties of complexes of benzo-15-crown-5 with sodium halides was investigated. The synthesis of complexes of sodium fluoride and sodium chloride are reported for the first time. Chloroform was used as solvent to study the assembly in solution state by 1H and 13C NMR techniques. Single crystal diffraction studies on the easily crystallizable bromide complex confirmed 1:1 stoichiometry of the complex. IR and Raman studies provided valuable evidence for a water molecule shared between the crown encapsulated cation and the counter ion to give a solvent shared ion pair (SSIP). The fluorescence spectra of the complexes were obtained in chloroform by excitation at 270nm to study the effect of complexation on the fluorescent properties of benzo-15-crown-5.

Synthesis of 4-piperidone Based Curcuminoids with Anti-inflammatory and Anti-Proliferation Potential in Human Cancer Cell Lines.

A series of 4-piperidone based curcuminoids were synthesized and anticancer potential of these compounds was evaluated against human myeloid leukemia (KBM5) and colon cancer (HCT116) cell lines. Their anti-inflammatory potential was determined through the down-regulation of tumor necrosis factor (TNF)-α-induced nuclear factor (NF)-κB. All compounds, except one, were found to exhibit better cytotoxicity than curcumin at 5 µM. Furthermore, many compounds have shown good potential to inhibit the TNF-α-induced NF-κB activation. Docking study of the compounds with NF-κB revealed that the binding affinity of the compounds ranged from ‒9.0 to ‒6.5 kcal/mol with 0-8 H-bonds. It was also observed that amido-ether based mono-carbonyl compounds bound around the same region of NF-κB where polynucleotides are known to bind to exhibit their activity.

Synthesis, characterization and in vitro anticancer activity of C-5 curcumin analogues with potential to inhibit TNF-α-induced NF-κB activation.

In a search of new compounds active against cancer, synthesis of a series of C-5 curcumin analogues was carried out. The new compounds demonstrated good cytotoxicity against chronic myeloid leukemia (KBM5) and colon cancer (HCT116) cell lines. Further, these compounds were found to have better potential to inhibit TNF-α-induced NF-κB activation in comparison to curcumin, which show their potential to act as anti-inflammatory agents. Some compounds were found to show higher cytotoxicity against cancer cell lines in comparison to curcumin used as standard.

Novel metronidazole-chalcone conjugates with potential to counter drug resistance in Trichomonas vaginalis.

Trichomoniasis is the most prevalent, curable sexually transmitted disease (STD), which increases risk of viral STDs and HIV. However, drug resistance has been developed by some strains of Trichomonas vaginalis against Metronidazole (MTZ), the FDA approved drug against trichomoniasis. In the present study twenty two chalcone hybrids of metronidazole have been synthesized in a quest to get new molecules with higher potential against metronidazole-resistant T. vaginalis. All new hybrid molecules were found active against T. vaginalis with varying levels of activity against MTZ-susceptible and resistant strains. Eight compounds (4a, 4c, 4d, 4e, 4f, 4h, 4q and 4s) were found as active as the standard drug with an MIC of 1.56 µg/ml against MTZ-susceptible strain. However, compounds 4e, 4h and 4m were 4-times more active than MTZ against drug-resistant T. vaginalis, amongst which 4e and 4h were most promising against both susceptible and resistant strains.

Solvatochromic and single crystal studies of 3-(4-bromophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde.

The structure of 3-(4-bromophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde was determined by using X-ray diffraction analysis. Photophysical studies of the title compound were investigated in the solvents with different polarities. The emission spectrum of the compound was recorded in polar solvent DMSO (356 nm). In different solvents the extinction coefficients and quantum yield of the compound vary from 1.88×10(4) to 3.53×10(4) and 0.01 to 0.25, respectively. The ratio of the dipole moment of excited state to the dipole moment of ground state was calculated by using solvatochromic shift methods.

Quantization of Dextromethorphan and Levocetirizine in Combined Dosage form Using a Novel Validated RP-HPLC Method.

The present study reveals a simple isocratic RP-HPLC method for the simultaneous determination of dextromethorphan hydrobromide and levocetirizine dihydrochloride in a cough syrup. The separation of these compounds was achieved within 10 min on a Phenomenex (USA) C(18) analytical column, 250×4.0 mm i.d., using an isocratic mobile phase consisting of potassium dihydrogen phosphate buffer (pH 2.5) - acetonitrile- tetrahydrofuran (70:25:5, v/v/v). The analysis was performed at a flow rate of 1.2 ml/min and at a detection wavelength of 232 nm. Percentage recovery and RSD were 100.36% and 0.05% for levocetirizine dihydrochloride, 100.35% and 0.27% for dextromethorphan hydrobromide respectively. Quantification of the components in syrup formulation was calculated against the peak areas of freshly prepared standard solutions. The method was validated as per ICH guidelines.

Rutin-phospholipid complex: an innovative technique in novel drug delivery system- NDDS.

Biopharmaceutical properties together with potency contribute critically towards clinical efficacy of the drugs by influencing the dissolution and bioavailability. The aim of this study was to develop an amphiphilic phyto-phospholipid complex in order to enhance the delivery of poorly soluble rutin. The rutin-phospholipid complex (Ru-PLc) was prepared and investigated for various physico-chemical parameters like drug loading, infrared absorption (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM), aqueous/ n-octanol solubility and dissolution study. The in vitro anti-oxidant activity was also studied. In the SEM, Ru-PLc was found fluffy and porous with rough surface morphology. FTIR, DSC and XRPD data confirmed the formation of phospholipid complex. The water/ noctanol solubility of rutin was improved from 2.88 to 45.71 µg/ ml and 68.17 to 245.18 µg/ ml, respectively in the complex. The improved dissolution was shown by the phospholipid complex at different pH buffers. The antioxidant activity indicated that, the bioactivity of rutin was maintained even after being complexed with the phospholipid. Based on the results, it can be concluded that the phospholipid complex may be considered as a promising drug delivery system for improving the overall absorption and bioavailability of the rutin molecule.

Studies on synthetic and structural characterization of new fluorine substituted phthalides of pharmaceutical interest.

An efficient and economical synthesis of some new fluorine substituted phthalides was accomplished from two γ-keto acids, 2-(4-fluorobenzoyl)benzoic acid and 2-(3,5-dinitro-4-flurobenzoyl)benzoic acid. Each acid was reacted with various phenolic compounds in presence of catalytic quantity of concentrated sulphuric acid to get the phthalides. The structures of the synthesized compounds were established on the basis of their elemental analysis, spectral data and chemical reactions. Some of the synthesized phthalides exhibited antibacterial and antifungal activity on antimicrobial screening against human pathogenic bacteria and fungi.

Determination of trace elements in Rheum moorcroftianum by AAS.

Micro and macro elements such as Zn, Cu, Mn, Fe, Co, Na, K, Ca and Li were detected from Rheum moorcroftianum Royle, a plant used in folk medicines. Altitudinal and seasonal variation of these trace elements in cultivated and wild roots and leaves of R. moorcroftianum were quantified by atomic absorption spectroscopy. The highest concentrations of Zn, Cu, Mn, Fe, Co, Na, K, Ca and Li were found to be 376.0 ± 0.9, 83.0 ± 4.6, 322.0 ± 6.0, 920.0 ± 1.9, 72.0 ± 1.5, 402.0 ± 7.8, 10,235.0 ± 7.0, 12,336.0 ± 2.6 and 59.9 ± 0.3 mg kg(-1), respectively, in all the samples analysed.

Synthesis, characterization and fluorescence studies of 3,5-diaryl substituted 2-pyrazolines.

A series of 2-pyrazolines have been synthesized from α, ß unsaturated ketones and hydrazine hydrate with acetic/formic acid in ethanol/DMSO. The structures of 2-pyrazolines have been established by spectroscopic techniques i.e. UV, IR, (1)H NMR, (13)C NMR and micro element analysis. Fluorescence spectra were recorded in the solution at fixed concentration and same excitation wavelength at 290 nm. The absorption band positions of all the compounds broadly lie between 280 and 336 nm and fluorescence band positions in the range between 300 and 370 nm, the near ultraviolet region.

High-performance liquid chromatography analysis of plant saponins: An update 2005-2010.

Saponins are widely distributed in plant kingdom. In view of their wide range of biological activities and occurrence as complex mixtures, saponins have been purified and separated by high-performance liquid chromatography using reverse-phase columns at lower wavelength. Mostly, saponins are not detected by ultraviolet detector due to lack of chromophores. Electrospray ionization mass spectrometry, diode array detector , evaporative light scattering detection, and charged aerosols have been used for overcoming the detection problem of saponins.

Development of repaglinide loaded solid lipid nanocarrier: selection of fabrication method.

Repaglinide solid lipid nanoparticles (RG-SLN) were fabricated using stearic acid as lipid. Pluronic F68 (PLF68) and soya lecithin were used as a stabilizer. SLNs were prepared by modified solvent injection and ultrasonication methods. SLNs prepared with modified solvent injection method have larger particle size (360+/-2.5nm) than prepared with ultrasonication method (281+/-5.3nm). The zeta potential of the prepared formulations by these two methods varied from - 23.10 +/-1.23 to -26.01 +/-0.89 mV. The maximum entrapment efficiency (62.14 +/-1.29%) was obtained in modified solvent injection method. The total drug content was nearly same (98%) in both the methods. In vitro release studies were performed in phosphate buffer (pH 6.8) with 0.5% sodium lauryl sulphate (SLS) using dialysis bag diffusion technique. The cumulative drug release was 30% and 50% within 2 hrs in modified solvent injection and ultrasonication method, respectively. This indicates that RG-SLN prepared from modified injection method released the drug more slowly than SLNs prepared with ultrasonication method. Differential scanning calorimetry indicates that repaglinide (RG) entrapped in the solid lipid nanoparticles (SLN) exist in an amorphous or molecular state. Repaglinide loaded solid lipid nanoparticles prepared with both methods were of spherical shape as observed by transmission electron microscopy (TEM). These results suggest that modified solvent injection method is more suitable for preparation of repaglinide SLNs using stearic acid.