Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin. CONCLUSIONS: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).

Curcumin - Bioavailability Enhancement by Prodrug Approach and Novel Formulations.

Curcumin is a diverse natural pharmacological agent involved in various signal transduction mechanisms. Therapeutically, this potent molecule faces different challenges and issues related to low bioavailability due to its poor aqueous solubility, less permeability, faster elimination and clearance. Experts in synthetic chemistry and pharmaceuticals are continuously sparing their efforts to overcome these pharmacokinetic challenges by using different structural modification strategies and developing novel drug delivery systems. In this mini-review article, we are focusing on development of curcumin derivatives by different possible routes like conjugation with biomolecules, natural polymers, synthetic polymers, natural products, metal conjugates and co- administration with natural metabolic inhibitors. In addition to that, it was also focused on the preparation of modified formulations such as micelles, microemulsions, liposomes, complexes with phospholipids, micro and nanoemulsions, solid lipid nanoparticles, nano lipid carriers, biopolymer nanoparticles and microgels to improve the pharmacokinetic properties of the curcumin without altering its pharmacodynamics activity. This review helps to understand the problems associated with curcumin and different strategies to improve its pharmacokinetic profile.

LC-MS/MS assay for the determination of lurasidone and its active metabolite, ID-14283 in human plasma and its application to a clinical pharmacokinetic study.

The authors proposed a sensitive, selective and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay procedure for the quantification of lurasidone and its active metabolite, i.e. ID-14283 in human plasma simultaneously using corresponding isotope labeled compounds as internal standards as per regulatory guidelines. After liquid-liquid extraction with tert-butyl methyl ether, the analytes were chromatographed on a C18 column using an optimized mobile phase composed of 5 mm ammonium acetate (pH 5.0) and acetonitrile (15:85, v/v) and delivered at a flow rate of 1.00 mL/min. The assay exhibits excellent linearity in the concentration ranges of 0.25-100 and 0.10-14.1 ng/mL for lurasidone and ID-14283, respectively. The precision and accuracy results over five concentration levels in four different batches were well within the acceptance limits. Lurasidone and ID-14283 were found to be stable in battery of stability studies. The method was rapid with the chromatographic run time 2.5 min, which made it possible to analyze 300 samples in a single day. Additionally, this method was successfully used to estimate the in vivo plasma concentrations of lurasidone and ID-14283 obtained from a pharmacokinetic study in south Indian male subjects and the results were authenticated by conducting incurred samples reanalysis. Copyright © 2015 John Wiley & Sons, Ltd.

In vitro combination effects of plant-derived quercetin with synthetic bicalutamide on prostate cancer and normal cell lines: in silico comparison.

Prostate cancer is the second most frequent and the fifth greatest cause of death in men. Although diet has been connected to the prevalence of cancer in addition to other factors, the relation between cancer and prevention is weak. Treatment options are at risk due to cell resistance. To identify new combinations, we tried plant-derived quercetin with bicalutamide on cell lines. To determine the cytotoxicity and apoptotic potential of plant-derived quercetin and its combination, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide] and dual stain assays were performed. In silico protein-ligand interaction was performed to support the in vitro findings. A thin layer, column, and high-performance chromatography were used to purify quercetin along with an authentic sample. In the cytotoxic study, quercetin was minimized by 80% similar to bicalutamide and a combination of quercetin and bicalutamide by 50% when compared to controls by 2%. Quercetin and bicalutamide showed a similar binding affinity for androgen receptors (9.7 and 9.8), hub genes (10.8 and 10.0), and a few other PCa-related genes (9.4 and 9.1). We propose to conclude that the combination of quercetin plus bicalutamide can be used for chemotherapy if additional in vivo studies are conducted. The intake of foods high in polyphenolic compounds can help to prevent prostate cancer. Examination of quercetin on several cell lines will provide a definite conclusion to combat cancers.

Novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one derivatives as potential inhibitors of chorismate mutase.

A series of novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one (DHPM) derivatives were designed, synthesized and evaluated in vitro as potential inhibitors of chorismate mutase (CM). All these compounds were prepared via a multi-component reaction (MCR) involving sequential I2-mediated Biginelli reaction followed by Cu-free Sonogashira coupling. Some of them showed promising inhibitory activities when tested at 30µM. One compound showed dose dependent inhibition of CM with IC50 value of 14.76±0.54µM indicating o-alkynylphenyl substituted DHPM as a new scaffold for the discovery of promising inhibitors of CM.

Liquid chromatography-tandem mass spectrometric assay for aliskiren, a novel renin inhibitor in micro-volumes of human plasma: a pharmacokinetic application in healthy South Indian male subjects.

This paper describes a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry assay for the determination of aliskiren in human plasma using nevirapine as an internal standard. Analyte and the internal standard were extracted from 100 µL of human plasma via liquid-liquid extraction using tert-butyl methyl ether. The chromatographic separation was achieved on a C18 column using a mixture of acetonitrile and 0.1% formic acid (90:10, v/v) as the mobile phase at a flow rate of 0.9 mL/min. The calibration curve obtained was linear (r(2) ≥ 0.99) over the concentration range of 0.10-1013 ng/mL. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. A run time of 2.2 min for each sample made it possible to analyze a greater number of samples in a short time, thus increasing the productivity. The proposed method was found to be applicable to clinical studies.

HMPLMD: Handwritten Malayalam palm leaf manuscript dataset.

The realization of high recognition rates of degraded documents such as palm leaf manuscripts primarily relies on document enhancement. Advancement of deep learning models in the process of document enhancement plays a major role among non-deep learning models or thresholding methods. Preparation of readily available ground truth data for creation of deep learning models is of paramount importance as it is highly time consuming task. The ground truth dataset preparation involves greater complexities as ancient documents are affected with degradations such as fungi, humidity, uneven illumination, discoloration, holes, cracks, and other damages. We propose a Handwritten Malayalam Palm Leaf Manuscript Dataset (HMPLMD) and its ground truth data aspiring for advancements in the field of palm leaf image analysis. We employ the palm leaf manuscripts of Kambaramayanam and Jathakas for the sake of experimentations. The proposed ground truth samples of degraded palm leaves plays a crucial role in creation of specialized deep/transfer learning models to handle challenges related to binarization.

Patient perspective on observation methods used in seclusion room in an Irish forensic mental health setting: A qualitative study.

WHAT IS KNOWN ON THE SUBJECT?: Nurses' observation of patients in seclusion is essential to ensure patient safety. Patient observation in seclusion assists nurses in adhering to the requirements of mental health legislation and hospital policy. Direct observation and video monitoring are widely used in observing patients in seclusion. Coercive practices may cause distress to patient-staff relations. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: We add detailed information on specific observation methods in seclusion and compare them from the perspective of patients. Nurses communicating with patients ensures relational contact and that quality care is provided to patients even in the most distressed phase of their illness. Providing prior information to patients on observation methods in seclusion and the need for engaging patients in meaningful activities, while in seclusion are emphasized. Observation via camera and nurses' presence near the seclusion room made patients feel safe and gave a sense of being cared for in seclusion. Pixellating the video camera would give a sense of privacy and dignity. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The overarching goal is to prevent seclusion. However, when seclusion is used as a last resort to manage risk to others, it should be done in ways that recognize the human rights of the patient, in ways that are least harmful, and in ways that recognize and cater to patients' unique needs. A consistent approach to relational contact and communication is essential. A care plan must include patient's preferred approach for interacting while in seclusion to support individualized care provision. Viewing panels (small window on the seclusion door) are important in establishing two-way communication with the patient. Educating nurses to utilize them correctly helps stimulate relational contact and communication during seclusion to benefit patients. Engaging patients in meaningful activities when in seclusion is essential to keep them connected to the outside world. Depending on the patient's presentation in the seclusion room and their preferences for interactions, reading newspapers, poems, stories, or a book chapter aloud to patients, via the viewing panel could help ensure such connectedness. More focus should be placed on providing communication training to nurses to strengthen their communication skills in caring for individuals in challenging care situations. Patient education is paramount. Providing prior information to patients using a co-produced information leaflet might reduce their anxiety and make them feel safe in the room. When using cameras in the seclusion room, these should be pixelated to maintain patients' privacy. ABSTRACT: Introduction A lack of research investigating the specific role that various observational techniques may have in shaping the therapeutic relations in mental health care during seclusion warranted this study. Aim The aim of the study was to explore patients' experience of different methods of observation used while the patient was in seclusion. Method A retrospective phenomenological approach, using semi-structured interviews, ten patients' experiences of being observed in the seclusion room was investigated. Colaizzi's descriptive phenomenological method was followed to analyse the data. Results Communicating and engaging patients in meaningful activities can be achieved via the viewing panel. The camera was considered essential in monitoring behaviour and promoting a sense of safety. Pixelating the camera may transform patient view on privacy in seclusion. Discussion The mental health services must strive to prevent seclusion and every effort should be made to recognise the human rights of the patient. The study reveals numerous advantages when nurses actively engage in patient communication during the process of observation. Implications for Practice Different observation methods yield different benefits; therefore, staff education in using these methods is paramount. Empowering the patient with prior information on seclusion, engaging them in meaningful activities and proper documentation on patient engagement, supports the provision of individualised care in seclusion.

QTL analysis for grain quality traits in 2 BC2F2 populations derived from crosses between Oryza sativa cv Swarna and 2 accessions of O. nivara.

The appearance and cooking quality of rice determine its acceptability and price to a large extent. Quantitative trait loci (QTLs) for 12 grain quality traits were mapped in 2 mapping populations derived from Oryza sativa cv Swarna × O. nivara. The BC(2)F(2) population of the cross Swarna × O. nivara IRGC81848 (population 1) was evaluated during 2005 and that from Swarna × O. nivara IRGC81832 (population 2) was evaluated during 2006. Linkage maps were constructed using 100 simple sequence repeat (SSR) markers in population 1 and 75 SSR markers in population 2. In all, 21 QTLs were identified in population 1 (43% from O. nivara) and 37 in population 2 (38% QTLs from O. nivara). The location of O. nivara-derived QTLs mp1.2 for milling percent, kw6.1 for kernel width, and klac12.1 for kernel length after cooking coincided in the 2 populations and appear to be useful for Marker Assisted Selection (MAS). Four QTLs for milling percent, 1 QTL each for amylose content, water uptake, elongation ratio, 2 QTLs for kernel width, and 3 QTLs for gel consistency, each explained more than 20% phenotypic variance. Three QTL clusters for grain quality traits were close to the genes/QTLs for shattering and seed dormancy. QTLs for 4 quality traits were associated with 5 of the 7 major yield QTLs reported in the same 2 mapping populations. Useful introgression lines have been developed for several agronomic traits. It emerges that 40% O. nivara alleles were trait enhancing in both populations, and QTLs for grain quality overlapped with yield meta-QTLs and QTLs for dormancy and seed shattering.

Assessment of workplace integration of migrant nurses and midwives within international health care settings: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to map the available evidence on the assessment of workplace integration of migrant nurses and midwives in international health care settings. INTRODUCTION: Internationally, migrant nurses and midwives are an increasingly important resource in government strategy for addressing the current and predicted workforce shortages in health care. Much has been documented about the orientation stages of their transition to foreign workplaces but few sources have considered the workplace integration of this population. INCLUSION CRITERIA: The review will include all studies involving migrant nurses and midwives who are working outside their country of initial nurse or midwife registration for at least one year. The context will be all hospital, community, and residential care home settings, including the mental health, intellectual disability, and maternity care sectors. METHODS: The JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews will be used to conduct this review. The databases to be searched will include CINAHL, MEDLINE, Embase, CENTRAL, and Google Scholar. Gray literature will also be searched and a hand search will be conducted of sources that fall outside these database searches. Two reviewers will independently screen titles, abstracts, and full-text articles. The extracted data will be presented in a tabulated chart accompanied by a narrative summary that aligns with the objectives and scope of this review.

Synthesis, characterization and biological evaluation of mononuclear Co(II), Ni(II), Cu(II) and Pd(II) complexes with new N2O2 Schiff base ligands.

New tetradentate N(2)O(2) donor Schiff bases and their mononuclear Co(II), Ni(II), Cu(II), and Pd(II) complexes were synthesized and characterized extensively by IR, (1)H-, (13)C-NMR, mass, ESR, conductivity measurements, elemental and thermal analysis. Specifically the magnetic and electronic spectral measurements demonstrate the octahedral structures of cobalt(II), nickel(II) complexes and square planar geometries of copper(II), palladium(II) complexes. All the ligands and complexes were screened for their in vitro antibacterial activity against two gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus) and two gram-negative bacteria (Escherichia coli, Klebsiella pneumonia). In this study, Pd(II) complexes exhibited potent antibacterial activity against B. subtilis, S. aureus whereas other metal complexes also exerted good activity towards all tested strains even than standard drugs streptomycin and ampicillin.

Response to Commentary: Fungal Infections of Oral Cavity: Diagnosis, Management, and Association with COVID-19.

This letter is a response to commentary by Ambadasu et al. on a review article by Santosh et al. on "Fungal Infections of Oral Cavity: Diagnosis, Management, and Association with COVID-19." In their commentary, Ambadasu et al. mentioned that in the list of COVID-19 associated fungal infections, mucormycosis should be added. In this response, we provide our thoughts on including mucormycosis in COVID-19 associated fungal infections of the oral cavity. We conclude that mucormycosis surge was more prevalent during the second wave of COVID-19 infection. Majority of published reports on oral fungal infections during the years 2019 and 2020 was focused on Oral Candidiasis, whereas mucormycosis appears to be re-emerging opportunistic entry of fungal infection among COVID-19 infection due to associated risk factors. Thus, Physicians and Dentists must be cautioned that other listed opportunistic fungal infections of oral cavity may also be seen among severe COVID-19 patients.be seen among severe COVID-19 patients.

Fungal Infections of Oral Cavity: Diagnosis, Management, and Association with COVID-19.

The frequency of fungal infections is increasing due to immunodeficiency viruses and immunosuppressive drugs. The most common fungal infection of the oral cavity is candidiasis. The existence of Candida can be a part of normal commensal; hence, the isolation of Candida in the absence of clinical symptoms should exclude candidiasis. The pathogenicity of Candida is witnessed as opportunistic when immune status is compromised. Oral fungal infections are uncommon, but when identified, these infections are associated with greater discomfort and are sometimes destruction of tissues. Cytology and tissue biopsy are helpful in confirming the clinical diagnosis. The management of oral fungal infections must strategically focus on signs, symptoms, and culture reports. This article reviews information on diagnosis and therapeutic management of aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, mucormycosis, and geotrichosis.

Design, One Pot Synthesis and Molecular Docking Studies of Substituted-1H-Pyrido[2,1-b] Quinazolines as Apoptosis-Inducing Anticancer Agents.

OBJECTIVE: The present study focused to build pyridine and quinazoline rings in a single molecule and designed a new fused Pyrido[2,1-b] quinazoline to have a better pharmacological activity. MATERIAL AND METHODS: A three component, one-pot synthesis of substituted-1H-Pyrido[2,1-b] quinazoline derivatives has been described by conventional and microwave synthesis using triflic acid as catalyst. These compounds were screened for in vitro cytotoxic activity against the panel of cancer cell lines A549, NCI-H460, HT-29, HCT-15, DU-145, and HFL. RESULTS: Among the tested compounds, 11-(1-benzyl-1H-indol-3-y1)-2, 3, 4, 11-tetrahydro-1H-pyrido[2,1-b] quinazoline (4i) showed most potent cytotoxicity against A549 and NCI-H460 lung cancer cell lines with IC50 values 4.57±0.25 and 5.53±0.49 µM, respectively. Moreover, compound 4i was found to be most potent considerable cell growth inhibition with GI50 values of 2.70±0.18 and 3.24±0.40 µM against A549 and NCI-H460 cell lines, respectively. In addition, induction of apoptosis for compound 4i on A549 was investigated by morphological changes, Acridine orange/ethidium bromide (AO/EB) and DAPI staining. Furthermore, a strong anti-clonogenic effect of compound 4i on lung cancer cells was observed. The flow cytometric analysis investigation reveals that compound 4i arrests the A549 cancer cell lines at the G0/G1 phase of the cell cycle. Molecular docking were also performed on 4i, 4j, and erlotinib to predict the binding mode towards the EGFR kinase (PDB code: 1M17) and the compounds have displayed similar interactions and compared with erlotinib. CONCLUSION: Overall, these findings could suggest that the compound 4i would be an ideal lead as an anticancer agent.

Microprocessor in controlled transdermal drug delivery of anti-cancer drugs.

Microprocessor controlled transdermal delivery of anticancer drugs 5-Fluorouracil (5-FU) and 6-Mercaptopurine (6-MP) was developed and in vitro evaluation was done. Drugs were loaded based on the pharmacokinetics parameters. In vitro diffusion studies were carried at different current density (0.0, 0.1, 0.22, 0.50 mA/cm2). The patches were evaluated for the drug content, thickness, weight, folding endurance, flatness, thumb tack test and adhesive properties all were well with in the specification of transdermal patches with elegant and transparent in appearance. In vitro permeation studies through human cadaver skin showed, passive delivery (0.0 mA/cm2) of 6-MP was low. As the current density was progressively increased, the flux also increased. the flux also increased with 0.1 mA/cm2 for 15-20 min, but it was less than desired flux, 0.2 mA/cm2 for 30 min showed better flux than 0.1 mA/cm2 current, but lag time was more than 4 h, 0.5 mA/cm2 current for more than 1 h, flux was >159 microg/cm2 h which was desired flux for 6-MP. 5-FU flux reached the minimum effective concentration (MEC) of 54 microg/cm2 h with 0.5 mA/cm2 current for 30-45 min, drug concentration were within the therapeutic window in post-current phase. We concluded from Ohm's Law that as the resistance decreases, current increases. Skin resistance decrease with increase in time and current, increase in the drug permeation. Interestingly, for all investigated current densities, as soon as the current was switched off, 5-FU and 6-MP flux decreased fairly, but the controlled drug delivery can be achieved by switching the current for required period of time.

Voltammetric determination of catechol and hydroquinone at poly(murexide) modified glassy carbon electrode.

The electrochemical study of Catechol (CC) was studied in presence of Hydroquinone (HQ) using poly(murexide) modified glassy carbon electrode (MGCE) by cyclic voltammetric study. The modified electrode exhibited good affirmative response towards the electro chemical oxidation of CC in presence of HQ in 0.2 M phosphate buffer solution at the physiological of pH 7.4. The influence of scan rate, concentration and pH parameters were examined with the cyclic voltammetric method. The modified electrode showed good selectivity and sensitivity with an advantage of interference study and free determination of selected analytes in this experiment. Finally a simple, sensitive and selective method was developed for the determination of dihydroxybenzene isomeric compounds.

Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis.

CONTEXT: Venous thromboembolism is one of the leading causes of morbidity and mortality in patients with cancer. Concerns have arisen regarding the risk of venous thromboembolism with the novel antiangiogenic agent bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in venous thromboembolism is controversial. OBJECTIVE: To assess the overall risk of venous thromboembolism associated with the use of bevacizumab, a systematic review and meta-analysis of published randomized controlled trials was performed. DATA SOURCES: The databases of PubMed and Web of Science were searched for articles published in the English language from January 1966 until January 2008 and abstracts presented at American Society of Clinical Oncology conferences held between January 2000 and January 2008 were searched to identify relevant clinical trials. STUDY SELECTION AND DATA EXTRACTION: Eligible studies included prospective randomized controlled trials in which standard antineoplastic therapy was used with and without bevacizumab and data on venous thromboembolism were available. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. DATA SYNTHESIS: A total of 7956 patients with a variety of advanced solid tumors from 15 randomized controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidences of all-grade and high-grade venous thromboembolism were 11.9% (95% CI, 6.8%-19.9%) and 6.3% (95% CI, 4.8%-8.3%), respectively. Patients treated with bevacizumab had a significantly increased risk of venous thromboembolism with an RR of 1.33 (95% CI, 1.13-1.56; P < .001) compared with controls. The risk was significantly increased for both all-grade and high-grade venous thromboembolism. In addition, the risk was similarly increased for bevacizumab at 2.5 mg/kg per week (low dose; RR, 1.31 [95% CI, 1.08-1.60]; P = .007) and 5 mg/kg per week (high dose; RR, 1.31 [95% CI, 1.02-1.68]; P = .04). CONCLUSION: The use of bevacizumab was significantly associated with an increased risk of developing venous thromboembolism in cancer patients receiving this drug.