Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques.

The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates.

Endoxifen: A new, protein kinase C inhibitor to treat acute and mixed mania associated with bipolar I disorder.

OBJECTIVES: Endoxifen is a protein kinase C inhibitor. The objective of the present phase III study was to demonstrate the safety and efficacy of endoxifen in treating bipolar I disorder (BPD I) patients. METHODS: A multicenter, double-blind, active-controlled study was conducted using a daily dose of 8 mg endoxifen compared to 1000 mg divalproex, the current standard treatment, in patients with BPD I acute manic episodes with/without mixed features. The primary endpoint of our study was the mean change in total Young Mania Rating Scale (YMRS) score at day 21. RESULTS: Endoxifen (n = 116) significantly (p < 0.0001) reduced total YMRS score (from 33.1 to 17.8. A significant (p < 0.001) improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score was observed for endoxifen (4.8 to 2.5). Early time to remission of the disease was observed with endoxifen compared to divalproex. None of the patients required rescue medication and there was no drug-associated withdrawals. Changes in Clinical Global Impressions-Bipolar Disorder and Clinical Global Impression-Severity of Illness scores showed that treatment with endoxifen was well-tolerated. CONCLUSIONS: Endoxifen at a low daily dose of 8 mg was as efficacious and safe in patients with BPD I acute manic episodes with/without mixed features.

Synthesis of green marine algal-based biochar for remediation of arsenic(V) from contaminated waters in batch and column mode of operation.

The sorption behavior of biochar derived from green seaweed (Ulva reticulata) toward arsenic(V) ions was explored in both batch and continuous modes. The pH edge experiments indicated optimum arsenic(V) sorption observed at pH 4, with maximum sorptional capacity of 7.67 mg/g through isotherm experiments. The kinetic experimental trials indicated that arsenic(V) sorption onto biochar was a fast electrostatic attraction process, with maximum removal occurred within 30 min. The sorption isotherms were modeled using the Toth, Redlich-Peterson, Langmuir and Freundlich isotherm models while the adsorption kinetics was modeled using the pseudo-first- and pseudo-second-order kinetic equations. The three-parameter models (Redlich-Peterson and Toth) better described the isotherm data, whereas pseudo-first-order model represented kinetic data well with low error and high correlation coefficient values. Among the different alkaline and acidic elutants investigated, the solution of 0.01 M NaOH effectively desorbed arsenic(V) from spent biochar. The feasibility of the biochar in continuous remediation of arsenic(V) from contaminated waters was explored in an up-flow fixed column. The biochar exhibited arsenic(V) removal efficiency and sorptional uptake of 59.5% and 8.12 mg/g, respectively. The biochar-loaded column was effectively desorbed using NaOH (0.01 M), with desorption efficiency of 99.5%.

Profile of Acute Kidney Injury in Hospitalized Children with Idiopathic Nephrotic Syndrome.

OBJECTIVE: To determine the incidence, risk factors and outcome of acute kidney injury (AKI) in hospitalized children with nephrotic syndrome. METHODS: All consecutive hospitalized children (aged 1-14 years) with diagnosis of nephrotic syndrome between February 2016 and February 2017 were enrolled for the study. Children (aged 1-14 years) with features of nephritis, underlying secondary causes of nephrotic syndrome as well as children admitted for diagnostic renal biopsy and intravenous cyclophosphamide or rituximab infusion were excluded. RESULTS: A total of 73 children (81 admissions) were enrolled; incidence of AKI was 16% (95% CI, 9-23). On multivariate logistic regression analysis, furosemide infusion was observed as an independent risk factor for acute kidney injury (OR 23; 95% CI, 3-141; P<0.001). Out of 13 children with AKI, three died. CONCLUSIONS: Acute kidney injury in hospitalized children with nephrotic syndrome has high risk of mortality. Children receiving furosemide infusion should be closely monitored for occurrence of acute kidney injury.

Research orientation in Ayurveda educational institutions: Challenges and the way forward.

This paper examines the scenario of research orientation in Ayurveda educational institutions of India. We demonstrate through the data obtained by searching the SCOPUS that the actual research output by these institutions is not very significant in terms of number of publications. While a lack of research expertise and infrastructure is one contributing factor to this status, a lack of questioning attitude is more crucial one. Mushrooming of new colleges, laxity in regulations, corruption, lack of atmosphere for ethical and quality research make the problem more complex. We show, with the help of SCOPUS Data, that the recent trend of establishing stand-alone institutions of Ayurveda may not help in invigorating research activities since the research contributions from such institutions have always been very poor. Instead, we suggest that existing stand-alone institutions of Ayurveda be merged with other established Central/State universities or other Medical colleges. The data demonstrates that the research output has been always significant when an institution has many experts working in different streams of science within, than when the institutions have only Ayurveda experts. We also take up the question of designing the clinical trials that are suitable for Ayurveda and propose an algorithm that may be considered for research in educational institutions, at least at doctoral level. We further enlist a set of recommendations that could potentially change the scenario. Evidence-informed policy making, inducting clinicians into the education system, making the curricula more attractive by including recent advances, introducing efficient faculty training programs, and rigorous implementation of the existing regulations - are some of the key recommendations we have made.

Green alga-mediated treatment process for removal of zinc from synthetic solution and industrial effluent.

The present work explored biosorption of Zn(II) ions from aqueous and zinc-bearing factory effluent using marine seaweed Ulva lactuca. The batch pH edge experiments using aqueous zinc solution indicated that Zn(II) uptake by U. lactuca was found to be maximum at pH 4.5 and the batch isotherm trials performed at pH 4.5 resulted in maximum uptake capacity of 128.0 mg Zn(II)/g. With 0.1 M CaCl2 (pH 3.5, HCl) as elutant, the elution of Zn(II) ions from Zn(II)-laden U. lactuca biosorbent was effective with possible regeneration and reuse for three cycles. The zinc industrial effluent was found to comprise of 87.8 mg/L of zinc ions along with excess co-ions and high total dissolved solids (838.1 mg/L). Owing to this, Zn(II) uptake from electroplating effluent by U. lactuca was suppressed due to competition from other ions. Continuous-flow sorption trials were conducted at flow rate of 5 mL/min in an up-flow fixed column. The existence of surplus competing ions in zinc wastewater influenced the Zn(II) biosorption by U. lactuca. U. lactuca-loaded packed column exhibited uptakes of 78.3 and 70.8 mg Zn(II)/g for aqueous solution and effluent, respectively. The results of three continuous sorption-desorption cycles demonstrated that reuse of U. lactuca biosorbent in remediation of zinc-containing wastewaters was practical and economical.

Evaluation of effect of poultice (Upanaha Sweda) in low back pain (Katigraha): A randomized comparative clinical trial.

BACKGROUND: Katigraha (low back pain) is a condition where low back is afflicted either with Vata or Sama Vata (Vata involved with the toxins released due to altered digestion and metabolism) and present with symptoms such as pain with stiffness. About 60%-80% population in India suffer from this condition. Upanaha Sweda (poultice) is one of the Swedana (sudation) treatment modalities mentioned for Katigraha. As Sama (affected with toxins released from impaired digestion) and Nirama (without toxins) are two stages of Katigraha, hence, the specific type of Upanaha is required for such condition. AIMS AND OBJECTIVE: The study was conducted to evaluate the effect of Upanaha Sweda in Katigraha (low back pain) as per the presentation of stages of Ama. MATERIALS AND METHODS: Selected patients were categorized into two groups. In group A, patients having Samaja Katigraha, were given Panchakoladi Upanaha once a day till it became Niramaja, then shifted to Godhumadi Upanaha for 7 days and patients who had Niramaja Katigraha, Godhumadi Upanaha was used once a day for 7 days. In group B Godhumadi Upanaha was used once a day for 7 days irrespective of stages. Subjective parameters assessed were pain in the low back, stiffness, and Oswestry Disability Index (ODI) was also used. The Mann-Whitney U test and Wilcoxon signed­rank test were used to assess results. RESULTS: Patients who were treated considering the Sama and Nirama phases had 78.88% better results in relieving pain, stiffness, and in ODI change than the patients treated without considering the phases. CONCLUSION: The present study showed significant results in both the groups, but patients treated as per stage wise treatment showed better effect in treating Katigraha than the patients treated with out considering the stage.

Attitude of interns towards research as a career option.

Although today's Ayurvedic graduates have many career options to select from, they are not given any exposure to these options during their study. This results in apathy towards selection of any career apart from clinical practice. The present study carried out amongst interns of one Ayurvedic college highlights this fact and underlines the importance of introducing 'research' as a subject in the curriculum.

Further evidence for the genetic basis of qualitative traits and their linkage relationships in Dolichos bean (Lablab purpureus L.).

An investigation on inheritance of qualitative traits in dolichos bean revealed biallelic monogenic control of photoperiodinduced sensitivity to flowering time and flower colour in F2 and F2 generations. While, growth habit and pod curvature are each controlled by two genes that exhibit classical complementary epistasis, raceme emergence was controlled by two genes that displayed classical inhibitory epistasis. The dominant alleles, at two different unlinked pairs of genes are necessary for plants to exhibit indeterminate growth habit and bear straight pods. Any other combination of alleles at the two pairs of genes result in plants displaying determinate growth habit and bearing curved pods.While, the genes controlling growth habit, PSFT and raceme emergence are linked. Those controlling flower colour and pod curvature are segregated independent of each other. These results are discussed in relation to strategies for breeding dolichos bean.

Psychiatric morbidity in perimenopausal women.

BACKGROUND: Women in the perimenopausal period are reported to be vulnerable to psychiatric disorders. AIM: To assess the psychiatric morbidity in perimenopausal women aged 45-55 years. MATERIALS AND METHODS: This cross-sectional, observational, hospital-based study was conducted at the Department of Psychiatry in a tertiary care hospital attached to a medical college. The study sample consisted of consecutive women in perimenopause as diagnosed by a gynecologist and written informed consent for inclusion in the study. Women with a previous history of psychiatric illnesses, with a major medical illness, or who had undergone surgical menopause were excluded from the study. All women were evaluated with a brief questionnaire for collecting demographic and clinical information and the Mini International Neuropsychiatric Interview for assessing psychiatric disorders. RESULTS: Of the 108 women in perimenopause included in the study, 31% had depressive disorder, 7% had anxiety, while 5% had depressive disorder with anxiety features. Psychiatric morbidity was significantly more in women having lesser education, from rural background, with a history of psychiatric illness in the family, a later age of menarche, and in the late stage of perimenopause. CONCLUSIONS: Women in the perimenopause affected by psychiatric morbidity were most commonly diagnosed with depression. As perimenopause is a time of vulnerability in women, attention to signs and symptoms of depression may be required so that they may lead a more productive life.

Diet-Delivered dsRNAs for Juvenile Hormone-Binding Protein and Vacuolar ATPase-H Implied Their Potential in the Management of the Melon Aphid (Hemiptera: Aphididae).

RNA interference is a sequence-specific gene silencing mechanism mediated by double-stranded RNA (dsRNA), which has been harnessed as a useful tool in devising novel insect pest management strategies for various pests such as melon aphid, Aphis gossypii (Glover). In the current study, we cloned and sequenced juvenile hormone-binding protein (JHBP) and vacuolar ATPase subunit H (V-ATPase-H) from A. gossypii. We also showed the effectiveness of diet-mediated delivery of dsRNA for JHBP and V-ATPase-H, which silenced the above genes and resulted in mortality. The extent of silencing and mortality were similar for both genes up until 96 h. Bioassay results revealed that the target genes were silenced variably, 1.0 µg/µl concentration having a more profound effect than 0.5 and 0.25 µg/µl concentration in reducing the cognate mRNA transcript level. Results indicated a 9.56­73.21% down regulation (across time and concentrations for both the genes) that resulted in the mortality of A. gossypii. Mortality was in the range of 10­63% for both these genes. Thus, the current study demonstrated the potentiality of both JHBP and V-ATPase-H as excellent targets for the management of A. gossypii.

Pharmacovigilance study of Ayurvedic medicine in Ayurvedic Teaching Hospital: A prospective survey study.

INTRODUCTION: Though Ayurveda is practiced in the Indian subcontinent since centuries, there is a paucity of systematic documentation related to the occurrence of adverse drug reactions (ADR) and other issues regarding the safety of Ayurveda medicines. AIM: To monitor and analyze the pattern and frequency of ADR to Ayurvedic medicines in an Ayurvedic hospital setup. MATERIALS AND METHODS: In this prospective study, ADR monitoring was done in KLE Ayurveda Secondary Care Hospital, Belgaum, Karnataka, India by spontaneous and intensive monitoring technique for a span of 1-year (June 2010 to May 2011). Data pertaining to patient demography, drug and reaction characteristics, organ system involved and reaction outcomes were collected and evaluated. The reaction severity and predisposing factors were also assessed. RESULTS: In a span of one year, 84 adverse drug events were reported out of which 52 confirmed as ADR. The overall incidence of ADR in the patient population was 1.14%, out of which 23 (44.23%) were related to Panchakarma (detoxification process), 13 (25.00%) related to the herbal formulations and 06 (11.53%) were of Rasa Aushadhi (mineral or herbo-mineral formulations). The commonly affected organ systems were gastrointestinal system 24 (46.15%) and skin 15 (28.84%). The majority of the reactions were moderate 30 (57.69%) to mild 20 (38.46%) in severity. Most patients recovered from the incidence. CONCLUSION: The present work has documented the incidence and characteristic of ADR to Ayurvedic medicine in a typical Ayurveda hospital setup. This will help in developing various strategies for boosting pharmacovigilance in Ayurveda, thereby ensuring safer use of Ayurveda medicines.

Analysis of Virechana karma with Danti avaleha: A retrospective study.

Virechana (therapeutic purgation) is a common procedure that is widely practiced among the panchakarma treatments (pentad treatments). Various Virechaka dravyas (purgative drugs) have been described for Virechana. Even after critical analysis of Virechaka dravyas in the literature, still there is difficulty in the fixation of dose. Hence, the retrospective analysis of varied outcomes of Virechana with Danti (Baliospermum montanum) avaleha (linctus) is discussed in this paper. The study included twenty-seven case reports of patients who were administered Virechana with Danti avaleha. These case reports are of patients suffering from various ailments such as irregular menstrual cycles, polycystic ovarian syndrome, primary and secondary infertility, and psoriasis. Danti avaleha was administered at dose of 10 g and 5 g in the Krura (~strong) and Madhyama (~moderate/normal) Koshta (~GI tract) patients, respectively. Among seven Krura koshta patients, three of them resulted with Pravara (excellent) Shuddhi and other four resulted with Madhyama (medium) Shuddhi. In twenty Madhyama koshta patients, sixteen of them resulted with avara (minimum) Shuddhi and remaining four patients resulted with Madhyama shuddhi. Complications like Udara shoola (spasmodic pain of abdomen) and Vamana (emesis) were observed during Virechana. Majority of the patients suffered with Udara shoola were of Madhyama koshta. Vamana was seen in both Krura and Madhyama koshta patients. Irrespective of the type of Shuddhi and complications, all the patients resulted with Samyak Kaphaantiki Virikta lakshana (signs of perfect purgation with end expulsion of Kapha). The study concluded that the Krura koshta patients were tolerable for dose of 10 g and are expected to attain Pravara Shuddhi. Whereas Madhyama koshta patients were intolerable even to mild dose of 5 g, producing Avara shuddhi.

A combined administration of Aragvadadi kasayam and Syrup Talekt induced skin rashes.

It is a common notion among people in India that herbal or Ayurvedic products are safe and do not produce any adverse effect. This is not true since Ayurveda has evaded many adverse effects which occur by combination of herbs. This axiom is potentiated by our report that occurs in the form of skin rashes. A 20-year-old South Indian female of Pittakapha prakrti (constitution) after beginning therapy with Aragvadadi kasayam (ARK) (poly-herbal formulation) and Syrup Talekt (poly-herbal patent formulation) for the treatment of recurrent incidence of abscess. Rash disappeared after stopping the suspected drug and treatment with Vibhitaki kasayam (decoction of Terminilia bellarica) and Satadhauta ghrtam. Possible and probable (score 6) were the causality according to WHO-Uppsala Monitoring Centre and Naranjo's Adverse Drug Reaction Probability Scale and grouped under type-B reaction. To the best of our knowledge, this is the first case of skin rashes which seen after administration of ARK and Syrup Talekt. This report highlights the need of implementation of pharmacovigilance center in the hospital level and additional research in the field of skin toxicity of ARK and Syrup Talekt.

Iniencephaly: Radiological and pathological features of a series of three cases.

Iniencephaly is a rare form of neural tube defect with an incidence of 0.1-10 in 10,000 pregnancies. It is characterized by the presence of occipital bone defects at foramen magnum, fixed retroflexion of head, spinal dysmorphism, and lordosis of cervicothoracic vertebrae. It is usually associated with central nervous system, gastrointestinal, and cardiovascular anomalies. We present radiological and autopsy findings in a series of 3 cases of iniencephaly (gestational ages 29.3, 23, and 24 weeks) first fetus in addition showed omphalocele, pulmonary hypoplasia, two lobes in right lung, accessory spleen, atrial septal defect, bilateral clubfoot, ambiguous genitalia, and single umbilical artery. Second fetus was a classical case of iniencephaly apertus with spina bifida. Third fetus had colpocephaly and bifid spine.

Preduodenal portal vein in adult with polysplenia syndrome revisited with a case report.

Preduodenal portal vein (PDPV) is a rare developmental anomaly. In infants, this is often associated with duodenal obstruction or biliary atresia. It is generally asymptomatic in adults (Ooshima et al., Hepato-Biliary-Pancreat Surg 5(4):455-458, 1998). Here, we report a singular case of adult PDPV that was discovered accidentally during emergency laparotomy for peritonitis due to gastric perforation in a 38-year-old lady. A plethora of congenital anomalies was uncovered, which is consistent with the reported cases of classical polysplenia syndrome, viz., multiple spleens of equal volume, visceral heterotaxia, right (Rt.)-sided stomach, a left (Lt.)-sided or a large midline liver, malrotation of intestine, a short pancreas, PDPV and IVC abnormalities (Gayer et al., Abdom Imaging 24:178-184, 1999). In addition, abnormalities like anamolous origin of Lt. gastric and splenic arteries from the abdominal aorta with absent celiac trunk, hepatic artery arising from the superior mesenteric artery, hepatic veins draining directly to Rt. atrium, etc. along with hypertrophic and lipomatous interatrial septum have also been detected during further investigations. As of now, we have come across 29 cases of adult PDPV reported in world literature and we are reporting our unique case with a review of literature on anomalies of visceral organs associated with PDPV.