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Oral administration of a pharmacologically active agent is the common and most preferred route among patients suffering from different types of illness. In the market, different type of oral dosage form is available among them tablet is the most favorite and demanded formulation. Further, the tablets, which are easy to use and swallow, are the ideal dosage form like orally disintegrating tablets (ODT’s). The main advantage of this type of formulation is that they can give easily to old aged and under-aged patients. In this research work, ODT’s formulation was manufactured, which get easily disintegrates and gives no bitter taste in the buccal cavity during administration. To achieve this task, moxifloxacin was complexed with suitable ion exchange resins (IER) like Kyron T314. In this course of action, multiple trials were performed using variable percentages or ratio of moxifloxacin and Kyron T 314. The resulting complex powder was characterized by different parameters like IR spectroscopy and differential scanning calorimetry (DSC). Along with the other excipients, drug resin complex (DRC) was used to manufacture the tablets. In this process, two super disintegrants viz. cross povidone and Ac di sol were used, and tablets were prepared by direct compression methodology. The finished product parameters of the tablet were estimated using the different available analytical methodologies. In this research work, it was concluded that the minimum time (19 seconds) for the wetting of tablets was observed when the quantity of crospovidone used was around 10% (MIT05). Additionally, this formulation gives maximum drug release (84.48%) after 120 minutes. Therefore, by using a suitable IER, taste-masked ODT’s of moxifloxacin can be prepared. This method is more efficient and effective in the development of such type of formulations.

Gokshura tablet is an ayurvedic formulation with gokhru (Tribulus terrestris) as best fixing recommended for building vitality levels. It enhances life, sexual want and drive. Pushyanug churna is an ayurvedic polyherbal formulation, hence this seems essential to explain the material institutionalization, various bioactive markers, blends exhibit in the polyherbal ayurveda compositions such as pushyanug churna. Point of the exhibit effort has been to create what’s more, approve a high-performance thin layer chromatography (HPTLC) strategy for assurance of diosgenin present in gokshura tablet. Mangiferin and chlorogenic acid are present in pushyanug churna. Diosgenin, a biomarker chemical found in gokshura tablets, and mangiferin, a biomarker compound found in pushyanug churna, were standardized using recently developed easy and accurate HPTLC procedures. Pre-coated silica gel 60-F254 was employed at the stationary phase and a mixture of toluene, ethyl acetate, and formic acid (in the proportions 5:4:1) was employed for the mobile phase in the development methodology for diosgenin. In the mobile phase, mangiferin, ethyl acetate and methanol were added in a ratio of 40:60 v/v were utilized. In the chlorogenic acid mobile phase, ethyl acetate:formic acid:acetic acid:water (10:1.1:1.1:2.6 v/v). It was determined that the Rf value of the marker chemical was 0.77 (diosgenin) in gokhsura tablet and 0.23 mangiferin, 0.75 chlorogenic acid in pushyanug churna. For bioactive marker chemicals found in in-house and commercially available formulations, the developed HPTLC approach has shown to be straightforward, sensitive, specific, and dependable.

There are two important parameters for a control release formulation. Primarily, it should be available in the form of a single-dose formulation. It should be given to the patient per day or few days a week during the treatment of patients suffering from diseases like arthritis, angina and diabetes. The second important characteristic of such formulation is that they release the active molecule at the site of action. This will reduce the chances and the level of the side effects of the drug. Among the available such type of dosage form, sustained-release formulations (SR) give the most promising and desirable results. In the SR dosage form, the drug release profile is controlled by the pharmaceutical engineering in the core matrix of tablet. In this study, SR oral tablet of divalproex sodium was manufactured by varying the quantity of drug release-controlling polymers like metolose 65 SH and metolose 90 SH. In the formulations, these polymers were used in different proportions and evaluated their impact on the physical and chemical characteristics of the finished drug product. The results of all formulations were as per the requirement of standard pharmacopoeial monograph. However, drug dissolution results of two formulations viz. DF9 and DF16 were observed to be optimum and excellent among all batches.

Peripheral neuropathy though a common neurological illness has complex aetiology and several different presentations. The term peripheral neuropathy includes symmetric polyneuropathy, single and multiple mononeuropathy, and radiculopathy. Further classication depends on a mixture of phenomenological, pathological, and genetic or other aetiological features. It is heterogeneous in aetiology, diverse in pathology, and varied in severity. Managing a case of perpipheral neuropathy brings along numerous challenges include identifying a case of peripheral neurophy and differentiating it from mimicks, working up for etiology and treatment based on aetiology. Patients can present with either positive or negative symptoms (or both) linked to motor and sensory systems or with autonomic disturbances in some neuropathies. A detailed history and physical examination provides information regarding onset, course and progression of the disease and the type of involvement like generalized, distal or proximal, symmetric or asymmetric, also the type of bre involvement like large myelinated or small unmyelinated and may give clues to neuro anatomic localization of the disease. The diagnosis can be conrmed through a appropriate investigation for the neuropathic pattern like blood tests, Cerebrospinal uid (CSF) analysis, MRI Brain, Ultrasound (USg). These test along with Electro diagnostic investigations like Nerve Conduction Studies (NCS), needle electromyography (EMG) can narrow down differentials and possible aetiologies, However in signicant cases etiology remain undiagnosed. Genetic testing is most diagnostic in carefully selected cases. Sometimes nerve biopsy and skin biopsy may be needed to conrm the etiologies.

Coronary heart disease (CHD) is a worldwide health epidemic. It has been defined as “impairment of heart function due to inadequate blood flow to heart compared to its needs caused by obstructive changes in the coronary circulation to the heart”(1). It is the cause of 25-30% of deaths in most of the industrialized countries. In India also it is a major public health problem. It is aptly called by WHO as the 'modern epidemic'. The increasing incidence of coronary heart disease may be a reflection of increased longevity, adoption of high fat diet based on meats decreased exercise, modern lifestyle, made possible by increasing affluence.The present study is to ascertain the factors influencing outcome of thrombolysis in acute MI and concludes that Gender and Pre infarction not influence the success rate of thrombolysis, Better success rate has been seen in those consuming alcohol and smokers had a lesser success rate than non smokers but statistically not significant. Hypertensives did not show any difference with non hypertensives in the success rate. Diabetics did not differ much from non diabetics with respect to the success rate of thrombolysis. Inferior wall myocardial infarction had a better success rate than anterior wall myocardial infarctions. Those who are having short window period had a better success rate after thrombolysis. Shorter the window period higher the success rate.

Congestive heart failure is a type of disease which is mainly observed due to the improper supply of blood to the heart. In this disease patient feels severe pain in the chest and may cause serious illness. Sudden treatment is needed in this disease to prevent any fatality. Nitroglycerin is the choice of drug for this disease. This study prepares a dosage form that can deliver the drug at a fast rate like a sublingual tablet of nitroglycerin. Sublingual dosage form was manufactured by direct compression method. For the formulation, multiple excipients like super disintegrants, sweeteners and lubricants were used. The finished dosage form was evaluated for different quality parameters. Optimum formulation was compared with the marketed product and kept on the accelerated stability study. Results were observed as satisfactory and comparable with the marketed product.

We present a multiproxy record of grain size and stable carbon isotope from the Lilaur lake, Ganga Basin, India to understand the history of lake formation linked to changes in Indian monsoon precipitation during ~13714 to 3073 calibrated year before Present (cal yr BP). A comparison is made between Lilaur lake proxy record with those from other parts of South Asia as well as North Atlantic to understand extent and causes of monsoon variability and its influence on the fauna and flora of the region. Chronology of lake core was constrained using AMS 14C and optically stimulated luminescence (OSL) dates. This study suggests a transition from river to lake during ~5800 to 5189 cal yr BP which is supported by reduced precipitation with weakening of the Indian summer monsoon (ISM). This river to lake transition culminated in a severe arid phase during 4250 to 4050 cal yr BP (4.2 ka event), corresponding to enhanced El Nino activity, southward shift of the Inter-Tropical Convergence Zone, and aridification of India when the ISM was weak.

Background: Resident or junior doctors and nursing staff make up the backbone of any public health care facility more so in cases of centers affiliated to teaching hospitals. Resident physicians have the most prolonged contact with patients as they represent the first communication interface between the attending physician and the patient. Similarly, the nursing staff has a critical role in patient care. Therefore, to minimize the morbidity and mortality due to Covid-19, it is important to be fully informed and compliant with measures to contain Covid-19. Objectives: To assess the perception of the junior doctors and nurses regarding the various aspects of Covid-19 disease. Methods: A preformed structured questionnaire with closed end questions was sent to the study subjects using the electronic media. In this study, questionnaire was sent to the convenient sample of 250 persons (100 junior doctors or residents and 150 nurses) working in the clinical departments of the hospital, from July 20 to 27th, 2020. This questionnaire was prepared after literature reviews based on information collected from CDC Atlanta, and Ministry of Health and Family Welfare (MOHFW), New Delhi and consisted of three sections: the demographic data, the knowledge and practices sections. The data were collected through anonymous, self-rated questionnaire that was distributed to all participants over the internet (WhatsApp and email). Results- The questionnaire was sent to 250 persons (100 junior doctors and 150 nurses) working in the clinical departments of the hospital, out of which,139 responded comprising 58 (41.73%) junior doctors and 81 (58.27%) nurses. Overall, 79.14% (n= 110) had sufficient knowledge regarding the disease and majority (94.96%) was practicing safe measures. In univariate logistic regression analysis of various variables with knowledge, the qualification was only variable which was found to be more significantly associated as far as knowledge and practices were concerned (junior doctors as compared to nursing staff). Conclusion- Adequate knowledge apart from defining day to day behavior of health care workers, also prepares them for coping strategies in cases of crisis in critical situation like the our world is experiencing now.

Background There is a continued need for therapeutics for the treatment of COVID-19, including intramuscular (IM) agents, which will enable broader use across a variety of healthcare delivery settings. Methods COMET-PEAK (NCT04779879) is a 3-part study evaluating the safety, tolerability, pharmacokinetics (Part A), and viral pharmacodynamics (PD) of sotrovimab as treatment in adults ≥ 18 years with early mild/moderate COVID-19. In Parts B and C, the safety, tolerability and viral PD of sotrovimab administered as a 500 mg intravenous (IV) infusion or as a 500 mg or 250 mg IM injection, respectively, was evaluated. The primary objective for Parts B and C was to compare the virologic response of sotrovimab IM to IV, with an endpoint of mean area under the curve (AUC) of SARS-CoV-2 viral load as measured by qRT-PCR from Day 1 to Day 8 (AUCD1-8) in nasopharyngeal swabs and predefined 90% confidence interval (CI) limits of 0.5-2.0 indicating equivalence. Results A total of 167 and 157 participants were enrolled in Part B and C, respectively, from February-July 2021. The median age of participants was 47 and 42 years in Part B and C, respectively, and ∼50% had ≥ 1 risk factor for progression to severe disease. The viral load at baseline and through Day 29 of follow-up for each arm is shown in Table 1 and Figure 1. The primary objective was met for both study parts: the ratio of the least square geometric mean viral load AUC(D1-8) of sotrovimab IM vs IV was 1.04 (90% CI, 0.98, 1.09) and 1.02 (90% CI, 0.94, 1.11), for Part B and C, respectively. Through Day 29 of follow-up, the most common adverse event was injection site reactions (ISRs) in the IM arms. A total of 10 (12%) participants in the 500 mg IM group and 4 (5%) participants in the 250 mg IM group experienced an ISR, all Grade 1. Serious adverse events were uncommon, and related to COVID-19 progression, including one death in the 250 mg IM arm (Table 2). ISRs aside, there were few treatment-related AEs (2/84 IV, 1/82 IM) in Part B, none serious. Conclusion IM administration of sotrovimab 500 mg and 250 mg each demonstrated equivalence to 500 mg sotrovimab IV in viral load assessments. Overall, there were no treatment-related serious AEs and sotrovimab was well tolerated. An 500 mg IM formulation will allow for expanded treatment potential with sotrovimab. Funding Vir/GSK (NCT04779879). Disclosures Anil K. Gupta, MD, Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support|Vir Biotechnology: Speaker Moti Ramgopal, MD, FACP, FIDSA, AbbVie: Grant/Research Support|Gilead Sciences Inc.: Advisor/Consultant|Gilead Sciences Inc.: Grant/Research Support|Gilead Sciences Inc.: Honoraria|Gilead Sciences Inc.: Stocks/Bonds|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: Honoraria|GlaxoSmithKline: Stocks/Bonds|Janssen Research & Development LLC: Advisor/Consultant|Janssen Research & Development LLC: Grant/Research Support|Janssen Research & Development LLC: Honoraria|Janssen Research & Development LLC: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Merck: Stocks/Bonds|Shionogi: Grant/Research Support|ViiV: Advisor/Consultant|ViiV: Grant/Research Support Jennifer Han, MD, GlaxoSmithKline: Employee Jennifer Moore, MD, GlaxoSmithKline: Employee Rudrani Banerjee, PhD, GSK: Employee|GSK: Stocks/Bonds Phillip Yates, PhD, GSK: Employee during conduct of this research|GSK: Stocks/Bonds Jill Walker, PhD, GlaxoSmithKline: Employee Gretja Schnell, PhD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Mary Beth Connolly, PharmD, GSK: Employee|GSK: Stocks/Bonds Andrea L. Cathcart, PhD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Varsha Imber, MSc, GSK: Employee|GSK: Stocks/Bonds Rabia Anselm, n/a, GSK: Employee|GSK: Stocks/Bonds Lindsay Winograd, MSc, GSK: Employee|GSK: Stocks/Bonds Nancy Haeusser, n/a, GSK: Employee|GSK: Stocks/Bonds Scott Segal, MD, GSK: Employee|GSK: Stocks/Bonds Andrew Skingsley, MD, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds Melissa Aldinger, PharmD, Vir Biotechnology: Employee|Vir Biotechnology: Stocks/Bonds Amanda Peppercorn, MD, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds.

Background: High-risk pregnancy (HRP) puts current pregnancy at an increased risk of complications. In the absence of pre-existing HRP implementation model of the country, in collaboration with the Government of Himachal Pradesh, a new digital HRP model called the 'SEWA—A System E-approach for Women at risk' was developed. The current article demonstrates a model for the early identification and line listing of high-risk pregnant women (PW) with appropriate referrals and increased engagement with the healthcare workers using a digital tool in the form of the Android App. Methods: SEWA was implemented as a pilot intervention in two community development blocks of the Chamba district. The key implementation steps included finalizing protocols for the identification of HRPs, defining processes and roles, mapping health facilities, setting up the communication loop, and developing of digital solutions. The digital app, used by the auxiliary nurse midwife (ANM) and program officers, tracked PW for a year from October 19 to October 20 and recorded the ANC visits, referrals, and birth outcomes. A qualitative assessment was conducted among the health workers to find out their level of acceptance. Results: A total of 1,340 high-risk PW were identified. The intervention year saw a rise in the identification of HRP to 27.9% from 3.5% in the previous year. A total of 2,559 conditions were tagged to the identified 1,340 women categorized into current pregnancy (81%), previous pregnancy (16%), and any existing chronic illness (3%). A majority of the women who required urgent referrals were provided referrals. The application recorded 53% of the delivered HRP with a digital birth preparedness plan, prepared and shared with the PW and Accredited Social Health Activists (ASHA), by text message for compliance. Conclusion: The SEWA application is a feasible and sustainable solution to complement the competency of the care providers for early identification of the high-risk conditions and reduce the burden of preventable unprecedented deaths around the time of birth.

Heinrich Stadial 4 during the last glacial period was marked by severe cooling at northern high latitudes along with the attendant changes in Asian Monsoon (Chinese Stadial 4) and South American Monsoon (South American Stadial 4). Here we present improved constraints on timings of Heinrich/Chinese/South American Stadial 4 onset and termination at sub-centennial precision based on speleothem records. We show that their initial onsets were essentially synchronous (40.20 ± 0.08 thousand years ago) and led the Antarctic warming by ~300 years. The Heinrich/Chinese Stadial 4 termination commenced at 38.34 ± 0.07 thousand years ago following a centennial-scale reduction in the Amazon River runoff and a poleward shift of the Southern Westerly wind belt. These two precursor events may have contributed to a reduced Amazon Plume Region and an enhanced Agulhas salt/heat leakage that led to an abrupt resumption of the Atlantic Meridional Ocean Circulation eventually triggering the Heinrich/Chinese Stadial 4 termination. Severe cooling at high northern latitudes, which marked the onset of Heinrich Stadial 4, was synchronous with changes in tropical monsoon systems and preceded Antarctic warming by around 300 years, according to a compilation of speleothem and ice core records.

Hominin evolution and dispersal: Insight from surface and subsurface dynamics of the western equatorial Indian Ocean

Prevention of infection and propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a high priority in the Coronavirus Disease 2019 (COVID-19) pandemic. Here we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin-converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 spike protein, thereby inhibiting viral entry, infectivity and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and, thus, the spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model and, thus, provide a novel avenue to pursue therapy.

Lakes provide continuous records of past regional and global climate. Most studies utilize single trench section dig from the lake shore margins or from single core in the central part/depocenter of the lakes for paleoclimate reconstruction. These reconstructions are based on the assumption of homogenous sedimentation across the lake. However, single core approach for paleoclimate reconstruction is often debated due to inter-site spatial and temporal variations in sedimentation and proxy responses. Therefore, in the present study, we explored the spatial–temporal heterogeneity in a small post-glacial lake of the Lahaul Himalaya and its influence on paleoclimate reconstruction. The depocenter of lake received ~ 2.5 times higher average sedimentation compared to the shore margin. Despite the distinct sedimentation rate in depocenter and shore margin, environmental magnetic and total organic carbon (TOC) records showed similar environmental signals over equivalent time periods. The depocenter core provided high-resolution lacustrine environment, whereas the marginal trench recorded major shifts in paleoclimate over a longer time scale. New multi-proxy data showed strengthened Indian summer monsoon (ISM) during medieval climate anomaly (MCA) and weakened ISM during little ice age (LIA) in the NW Himalaya.

Tropical cyclones as natural disturbances, influence ecosystem structure, function and dynamics at the global scale. This study assesses the inundation due to the super cyclone Amphan in coastal districts of eastern India by leveraging the computational power of Google Earth Engine (GEE) and the availability of high resolution Sentinel-1 Synthetic Aperture Radar (SAR) data. A cloud-based image processing framework was developed and implemented in GEE for classification using Random Forest algorithm. The inundation areas due to storm surge owing to cyclone Amphan, were mapped and further categorised to different land use and land cover classes based on an existing land cover map. Sentinel-1 images were useful in post-cyclone studies for the change detection analysis due to its higher temporal resolution and cloud penetration ability. The study found that the majority of agricultural and agricultural fallow lands were inundated in the coastal districts. The availability of open-source cloud-based data processing platforms provides cost effective way to rapidly gather accurate geospatial information. Such information could be useful for emergency response planning and post-event disaster management including relief, rescue and rehabilitation measures; and crop yield loss assessment. Cyclone and Land Use and Land Cover (LULC) change can have significant impacts on the human population and if both coexist, the consequences for people and the surrounding environment may be severe.

Catharanthus roseus is known for its scarce and expensive anticancer bisindole alkaloids, vincristine and vinblastine, which are derived from the coupling of monomeric terpenoid indole alkaloids, catharanthine and vindoline. Vindoline represents the bottleneck in bisindole semi-synthesis as unlike catharanthine, its biosynthesis is restricted to the plant leaves, which are the only commercially-viable source for it. For reducing the exorbitant cost of bisindoles, identification of C. roseus genotypes accumulating higher-than-usual amount of vindoline is urgently required. Here, one such vindoline-rich genotype (CIMAP866) was identified and characterized. It was comparatively analyzed with elite varieties, Dhawal and Nirmal, for morphology, genetic profile, leaf vindoline content (% dry weight), elemental composition, and expression pattern of alkaloid biosynthetic genes. Its vindoline content (~0.20%) was significantly higher than that of Dhawal (~0.09%) and Nirmal (~0.04%). CIMAP866 possesses dwarf character, spreading/bushy growth, wider canopy, shorter petiole and internodes, more laticifers, higher chlorophyll content, altered content of certain elements and distinct genetic profile, as compared to the other genotypes. Significantly higher dat expression in CIMAP866 was a key determinant for its vindoline-rich nature. Vindoline content was a direct function of dat expression and laticifer number. This study has provided a lead towards developing an industrially-useful C. roseus variety.

Variability in enzymatic and non enzymatic antioxidants could be useful for breeding genotypes tolerant to different abiotic stresses. The objective of present study was to determine the variability in enzymatic and non enzymatic antioxidants in wheat at three different stages of development including leaves of vegetative stage, flag leaf stage after 5 days of anthesis and in mature grains. Forty wheat genotypes including 10 commercial cultivars, 5 rainfed cultivars, 17 advanced breeding lines and 8 Australian cultivars were raised under irrigated conditions. At vegetative stage, high activity of superoxide dismutase (SOD), peroxidase (POX), glutathione reductase (GR) and ascorbate peroxidase (APX) and low hydrogen peroxide (H2O2) content was observed in many of the advanced breeding lines, while high proline and low malondialdehyde (MDA) content was observed in many commercial cultivars. In flag leaf after 5 days of anthesis higher activity of SOD and APX was observed in many of rain-fed cultivars; many commercial cultivars showed high activity of POX and GR while low H2O2 content was observed in many of Australian cultivars. Ruby, Binnu and Datatine have low H2O2 and MDA content so they could be used for studying tolerance towards different types of abiotic stresses. PBW 550 showed high antioxidant activity in leaves during vegetative and flag leaf stage, it could be worthwhile to study the performance of this cultivar under different abiotic stresses. Variability was also observed in mature grains of different wheat genotypes. In mature grains high proline content was observed in many of rain-fed cultivars while less GR, CAT and APX activity was observed in many of Australian genotypes. Mature grains of wheat genotypes PBW 644, PBW542, DBW 16, DBW 17, WH 1021, PBW 676, BWL 73 and PBW 175 have high activity of APX, GR and some have high proline content. In general genotypes with high enzymatic antioxidants and low H2O2 and MDA content may be useful for studying tolerance towards different abiotic stresses. Genotypes with high antioxidants were identified for possible use in wheat breeding programme.

Vicinal diamines are a common motif found in biologically active molecules. The hydroamination of allyl amine derivatives is a powerful approach for the synthesis of substituted 1,2-diamines. Herein, the rhodium-catalyzed hydroamination of primary and secondary allylic amines using diverse amine nucleophiles, including primary, secondary, acyclic, and cyclic aliphatic amines to access a wide range of unsymmetrical vicinal diamines, is presented. The utility of this methodology is further demonstrated through the rapid synthesis of several bioactive molecules and analogs.