Time to Attain Full Enteral Feeds Among Preterm Fetal Growth Restricted Neonates With Absent/Reversed End-Diastolic Flow.

OBJECTIVES: To determine the difference in time to attainment of full enteral feeds between fetal growth restricted (FGR) preterm neonates with and without absent/reversed end-diastolic flow (AREDF). Secondary objectives were to compare the short-term outcomes including the incidence of necrotizing enterocolitis (NEC) and feed intolerance between the two groups and to determine the factors affecting the time to attainment of full enteral feeds (FEF) among preterm FGR neonates. METHODS: A prospective cohort study was conducted among consecutive preterm FGR neonates delivered at 28-36 weeks gestation admitted in level III NICU. An umbilical artery doppler ultrasound was performed antenatally for all participants to detect AREDF. FGR neonates with AREDF were taken as the study group and those without AREDF were taken as the comparison group. Time to attain FEF was defined as time taken to establish enteral feeds of 150 ml/kg/day and tolerating it for the next 3 consecutive days. Delayed attainment of FEF was taken as ≥10 days needed to attain FEF. RESULTS: The median (IQR) time to attainment of full feeds was longer among neonates with AREDF compared to those without AREDF [12 (8, 16.5) vs 8 (5, 10) days; P < 0.001]. Neonates with AREDF had more feed intolerance [RR, 95% CI = 1.51 (1.13 - 2.02); P = 0.004], higher mortality [RR, 95% CI = 2.5 (1.02 - 6.2); P = 0.036], prolonged time to regain birth weight [15 (11.5, 19) days, P = 0.035], longer NICU stay [10 (7, 15), P < 0.001] and longer hospital stay [33 (23, 49), P < 0.001]. Also, neonates with AREDF had more hypoglycemia [RR, 95% CI=2.15 (1.2-3.7); P = 0.004], hypoxic ischemic encephalopathy [RR, 95% CI 5.05 (1.13 - 22.4); P = 0.016], hypothyroidism [RR, 95% CI= 8.08 (1.02 - 63.4), P = 0.016], cholestasis (P = 0.007), prolonged parenteral nutrition requirement [10 (7, 15) days, P < 0.001] and oxygen requirement [4.5 (2, 8) days, P < 0.001]. Multivariable logistic regression showed, AREDF [aOR 95% CI 2.91 (1.49 - 5.68), P = 0.002], lower gestational age [aOR 95% CI 0.724 (0.604 - 0.867), P < 0.001] and thrombocytopenia at birth [aOR 95% CI 2.625 (1.342 - 5.136), P = 0.005] are significant predictors of delayed attainment of full feeds among preterm FGR neonates. CONCLUSION: Preterm FGR neonates with AREDF are slower to attain FEF, have more feed intolerance, higher mortality, need longer time to regain birth weight, prolonged NICU stay and hospital stay. AREDF, lower gestation, sepsis and thrombocytopenia at birth are significant predictors of delayed full feed attainment among preterm FGR neonates. It is essential to devise strategies to reduce morbidity and mortality among this group of preterm neonates.

Trends in the Use of Oral Anticoagulants for Adults With Venous Thromboembolism in the US, 2010-2020.

Importance: The introduction of direct oral anticoagulants (DOACs) has transformed the treatment of venous thromboembolism (VTE). Large health care databases offer valuable insight into how oral anticoagulants (OACs) are used in clinical practice and may aid in understanding reasons for changes in therapy. Objectives: To evaluate prescribing patterns of OACs for patients with VTE and identify clinical events that precede treatment changes. Design, Setting, and Participants: This retrospective cohort study used data from a public (Medicare fee-for-service) and a commercial (IBM MarketScan) health insurance database on 298 609 patients initiating OACs within 90 days of index VTE hospitalization from January 1, 2009, to December 31, 2020. Statistical analysis was conducted from April to August 2022. Exposures: Warfarin and the DOACs rivaroxaban, apixaban, dabigatran, and edoxaban. Main Outcomes and Measures: Characteristics of patients initiating different OACs, along with trends over time of patients initiating OACs, were compared. Time receiving continuous anticoagulant therapy, patterns of anticoagulant discontinuation (treatment gap of ≥30 days), and treatment switches were assessed. Clinical events in the 30 days preceding treatment modifications were identified. Results: A total of 203 378 individuals with Medicare (mean [SD] age, 76.9 [7.6] years; 122 554 women [60.3%]) and 95 231 with commercial insurance (mean [SD] age, 57.6 [15.8] years; 47 139 women [49.5%]) were included (N = 298 609). Warfarin was the most frequent OAC prescribed (163 044 [54.6%]), followed by rivaroxaban (66 882 [22.3%]) and apixaban (65 997 [22.1%]). The proportion of patients initiating DOACs increased from 0% in 2010 to 86.8% (22 420 of 25 817) in 2019 for patients with Medicare and 92.1% (4012 of 4357) in 2020 for commercially insured patients. Patients with chronic kidney disease were more likely to initiate warfarin (35 561 [11.9%]) or apixaban (16 294 [5.5%]) than rivaroxaban (10 136 [3.4%]), and those with a history of bleeding were more likely to initiate apixaban (5424 [1.8%]) than rivaroxaban (3007 [1.0%]). Overall, patients received persistent OAC treatment for approximately 6 months (Medicare: median, 175 days [IQR, 76-327 days]; commercial insurance: median, 168 days [IQR, 83-279 days]). A total of 33 011 patients (11.1%) switched anticoagulant therapy within a year. Switching to another anticoagulant was preceded most frequently by codes for a VTE diagnostic procedure (27.2% of all switchers [8983 of 33 011]). Conclusions and Relevance: This cohort study using data from 2 US health insurance databases suggests that most patients with VTE continued oral anticoagulant treatment for approximately 6 months. Clinical reasons for modifying anticoagulant therapy were identified in one-third of patients. Identifying reasons for treatment modification is crucial for generating valid evidence on drug safety and effectiveness.

Impact of smoking status on health-related quality of life (HRQoL) in cancer survivors.

Introduction: The Health-Related Quality of Life (HRQoL) often declines among cancer survivors due to many factors. Some cancer patients who smoke before the cancer diagnosis continue this harmful habit, potentially contributing to a more significant decline in their HRQoL. Therefore, this study investigates the association between smoking status and HRQoL in cancer survivors. Methods: We conducted a cross-sectional study utilizing self-reported cancer history from 39,578 participants of the Behavioral Risk Factor Surveillance System (BRFSS) database, leveraging 2016 and 2020 year questionaries. A multidimensional composite outcome was created to assess HRQoL, integrating four distinct dimensions - general health, mental health, physical health, and activity limitations. After accounting for the complex survey design, logistic regression models were used to analyze the association between smoking status and poor HRQoL, adjusting for demographic, socioeconomic, and health-related confounders. Results: Our study found that, after adjusting for potential confounders, current smokers exhibited a significantly poorer HRQoL than never smokers (OR 1.65, 95%CI 1.40-1.93). Furthermore, former smokers showed a poorer HRQoL than never smokers; however, this association was not as strong as current smokers (OR 1.22, 95%CI 1.09-1.38). Conclusion: Our findings highlight the adverse association of smoking with poor HRQoL in cancer survivors, underscoring the importance of healthcare professionals prioritizing smoking cessation and providing tailored interventions to support this goal.

Impact of radical dose escalation by endoluminal brachytherapy and induction chemotherapy in the definitive treatment of locally advanced esophageal cancer - A retrospective study.

Background: The loco-regional recurrence rate remains the main concern in the treatment of esophageal cancer. However, there are controversial data regarding the benefit of dose escalation in the treatment of esophageal cancer. The study examines the implications of dose escalation with endoluminal brachytherapy after induction chemotherapy and definitive chemoradiation in cases of carcinoma esophagus. Material and Methods: Total 31 biopsy-proven patients with inoperable, locally advanced esophageal cancer of stage IIA-IIIB were enrolled from January 2006 till December 2018. All patients underwent two cycles of three weekly induction chemotherapy followed by definitive external beam radiotherapy of 45-50.4 Gray (Gy) at 1.8 Gy per fraction along with chemotherapy, followed by intraluminal brachytherapy boost of two fractions with 5 Gy each. Overall survival (OS) was censored at death or the last follow-up. Results: Of 31 patients, 26 (83.97%) received concurrent chemotherapy and 30 (96.77%) completed radiation therapy. At the end of 3 months, 10 (32.2%), 13 (41.9%), 5 (16.1%), and 3 (9.6%) had complete response, partial response, stable disease, and progression of the disease, respectively. Distal failure was seen in five (16.1%) cases. The median OS was 28 months. OS at 2 years and 5 years was 20 (64.5%) and 9 (28.3%), respectively. At the end of 3 months, 17 (54.8%) of patients had no dysphagia, four (12.9%) of patients had improvement of more than 2 points in dysphagia score, five (16.1%) of patients had no change in the score and five (16.1%) of the patients had worsening of the dysphagia score by 1 point. Median dysphagia-free survival was 10.7 months, eight (25.8%) developed dysphagia after the dysphagia-free interval and two (6.4%) had worsening of dysphagia after treatment. There were no reported grade III or grade IV acute toxicities. Conclusion: The protocol has shown an acceptable survival and dysphagia-free interval. The study suggests intraluminal brachytherapy with induction chemotherapy and definitive chemoradiation is a feasible option in locally advanced esophageal cancer.

NADH-depletion triggered energy shutting with cyclometalated iridium (III) complex enabled bimodal Luminescence-SERS sensing and photodynamic therapy.

The nicotinamide adenine dinucleotide-reduced (NADH) function as a hydride (H) carrier to maintain cellular homeostasis. Herein, we report a quinoline appended iridium complex (QAIC) as a molecular probe in fluorescence and surface-enhanced Raman spectroscopy (SERS) modalities to evaluate the endogenous NADH status. NADH-triggered activation of QAIC enabled luminescence (turn-ON) and SERS (turn-OFF) switching phenomenon with a detection limit of 25.6 nM and 15 pM for NADH in luminescence and SERS respectively. Transition state modelling using density functional theory calculations proved that a facile migration of H from NADH to QAIC transformed the activated QAIC (N-QAIC) with an energy span of 19.7 kcal/mol. Furthermore, N-QAIC is probed as a photosensitizer to source singlet oxygen by blocking the photo induced electron transfer (PeT) and generate NAD radicals. Therefore, an efficient light triggered cyclometalated iridium-based molecular probe has been divulged to promote bimodal NADH sensing and multiphase photodynamic therapy.

Prevalence and Relevance of Multiple Renal Arteries: A Radioanatomical Perspective.

BACKGROUND: A single renal artery supplies the kidney in 70% of the population but variation exists in the remaining 30%. Multiple renal arteries (MRA) in different permutations and combinations are one of the many forms of variants. Lack of awareness of multiplicity could have detrimental effects on the outcome of renal surgery. The present study aims at identifying the variants of renal artery based on its origin, multiplicity, and portal of entry in a cohort of people belonging to Southern India and its clinical implications thereof. METHODS: Multi-detector CT (MDCT) images of renal vasculature of 100 kidneys from 50 live kidney donors who attended the Department of Nephrology of our institution, from 2016 to 2018 were collected and studied for variations in renal arterial anatomy. RESULTS: Out of the 18% of kidneys observed with multiple renal arteries, 88.8% had double renal arteries (DRA) and 11.1% had triple renal arteries (TRA). Common types of the double renal arteries were - two hilar arteries (31.3%) and one hilar with one inferior polar artery (IPA, 31.3%). Triple renal arteries types - 50% with one hilar, one superior polar, and one inferior polar; 50% with two hilar and one inferior polar artery. No statistically significant association was noted between the incidence of multiple renal arteries and its laterality (p-value=0.193). CONCLUSION: A thorough understanding of the renal artery variants is crucial for safe and efficacious uro-radiological interventional procedures.

Morpho-Physiological Traits and Functional Markers Based Molecular Dissection of Heat-Tolerance in Urdbean.

Urdbean (Vigna mungo L. Hepper) is one of the important pulse crops. Its cultivation is not so popular during summer seasons because this crop is unable to withstand excessive heat stress beside lack of humidity in the atmosphere. Therefore, a panel of 97 urdbean diverse genotypes was assessed for yield under stress and non-stress conditions with an aim to identify heat tolerant genotypes. This study identified 8 highly heat tolerant and 35 highly heat sensitive genotypes based on heat susceptibility index. Further, physiological and biochemical traits-based characterization of a group of six highly heat sensitive and seven highly heat tolerant urdbean genotypes showed genotypic variability for leaf nitrogen balance index (NBI), chlorophyll (SPAD), epidermal flavnols, and anthocyanin contents under 42/25°C max/min temperature. Our results showed higher membrane stability index among heat tolerant genotypes compared to sensitive genotypes. Significant differences among genotypes for ETR at different levels of PAR irradiances and PAR × genotypes interactions indicated high photosynthetic ability of a few genotypes under heat stress. Further, the most highly sensitive genotype PKGU-1 showed a decrease in different fluorescence parameters indicating distortion of PS II. Consequently, reduction in the quantum yield of PS II was observed in a sensitive one as compared to a tolerant genotype. Fluorescence kinetics showed the delayed and fast quenching of Fm in highly heat sensitive (PKGU 1) and tolerant (UPU 85-86) genotypes, respectively. Moreover, tolerant genotype (UPU 85-86) had high antioxidant activities explaining their role for scavenging superoxide radicals (ROS) protecting delicate membranes from oxidative damage. Molecular characterization further pinpointed genetic differences between heat tolerant (UPU 85-86) and heat sensitive genotypes (PKGU 1). These findings will contribute to the breeding toward the development of heat tolerant cultivars in urdbean.

Kabasura Kudineer (KSK), a poly-herbal Siddha medicine, reduced SARS-CoV-2 viral load in asymptomatic COVID-19 individuals as compared to vitamin C and zinc supplementation: findings from a prospective, exploratory, open-labeled, comparative, randomized controlled trial, Tamil Nadu, India.

INTRODUCTION: Despite several ongoing efforts in biomedicine and traditional medicine, there are no drugs or vaccines for coronavirus disease 2019 (COVID-19) as of May 2020; Kabasura Kudineer (KSK), a polyherbal formulation from India's Siddha system of medicine, has been traditionally used for clinical presentations similar to that of COVID-19. We explored the efficacy of KSK in reducing viral load and preventing the disease progression in asymptomatic, COVID-19 cases. METHODS: A prospective, single-center, open-labeled, randomized, controlled trial was conducted in a COVID Care Centre in Chennai, India. We recruited reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 of 18 to 55 years of age, without clinical symptoms and co-morbidities. They were randomized (1:1 ratio) to KSK (60 mL twice daily for 7 days) or standard of care (7 days supplementation of vitamin C 60,000 IU morning daily and zinc 100 mg evening daily) groups. The primary outcomes were reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR], prevention of progression of asymptomatic to symptomatic state, and changes in the immunity markers including interleukins (IL-6, IL-10, IL-2), interferon gamma (IFNγ), and tumor necrosis factor (TNF α). Siddha clinical assessment and the occurrence of adverse effects were documented as secondary outcomes. Paired t-test was used in statistical analysis. RESULTS: Viral load in terms of the CT value (RdRp: 95% CI = 1.89 to 5.74) declined significantly on the seventh day in the KSK group and that of the control group, more pronounced in the study group. None progressed to the symptomatic state. There was no significant difference in the biochemical parameters. We did not observe any changes in the Siddha-based clinical examination and adverse events in both groups. CONCLUSION: KSK significantly reduced SARS-CoV-2 viral load among asymptomatic COVID-19 cases and did not record any adverse effect, indicating the use of KSK in the strategy against COVID-19. Larger, multi-centric trials can strengthen the current findings. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI2020/05/025215 . Registered on 16 May 2020.

Computational investigation, comparative approaches, molecular structural, vibrational spectral, non-covalent interaction (NCI), and electron excitations analysis of benzodiazepine derivatives.

The present work explores the structural parameters and vibrational frequencies as well as molecular interactions of benzodiazepine derivatives, such as clothiapine (CT), clozapine (CZ), and loxapine (LX). Employing fitting experimental data to theoretical results is used to assess the structural parameters of heading composites. The main assignment is passed out according to the overall distribution of energy of the vibrational modes. From the hyper-conjugative interaction, the permanency of the structure had been predicted through natural bond orbital analysis; it is also used to identify the bonding and antibonding regions of the molecules. Moreover, electrostatic potential (ESP), density of states (DOS), and charge transfer occurring of the molecule among HOMO as well as LUMO energy were calculated and presented; utilizing electron localized field (ELF), localized orbital locator (LOL), and reduced density gradient (RDG), the chemical interactive regions are found. Additionally, mean polarizability (αtot), the first-order hyperpolarizability (ßtot), and softness and hardness of the entitled compounds were also performed. The interaction between protein-ligand was also predicted by docking studies.

Burden of congenital rubella syndrome (CRS) in India based on data from cross-sectional serosurveys, 2017 and 2019-20.

BACKGROUND: India has set a goal to eliminate measles and rubella/Congenital Rubella Syndrome (CRS) by 2023. Towards this goal, India conducted nationwide supplementary immunization activity (SIA) with measles-rubella containing vaccine (MRCV) targeting children aged between 9 months to <15 years and established a hospital-based sentinel surveillance for CRS. Reliable data about incidence of CRS is necessary to monitor progress towards the elimination goal. METHODS: We conducted serosurveys in 2019-20 among pregnant women attending antenatal clinics of 6 hospitals, which were also sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella. We systematically sampled 1800 women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We used rubella seroprevalence data from the current survey and the survey conducted in 2017 among antenatal women from another 6 CRS surveillance sites to construct a catalytic models to estimate the incidence and burden of CRS. RESULT: The seroprevalence of rubella antibodies was 82.3% (95% CI: 80.4-84.0). Rubella seropositivity did not differ by age group and educational status. Based on the constant and age-dependent force of infection models, we estimated that the annual incidence of CRS in India was 225.58 per 100,000 live births (95% CI: 217.49-232.41) and 65.47 per 100,000 live births (95% CI: 41.60-104.16) respectively. This translated to an estimated 14,520 (95% CI: 9,225-23,100) and 50,028 (95% CI: 48,234-51,543) infants with CRS every year based on age-dependent and constant force of infection models respectively. CONCLUSIONS: Our findings indicated that about one fifth of women in the reproductive age group in India were susceptible for rubella. The estimates of CRS incidence will serve as a baseline to monitor the impact of MRCV SIAs, as well progress towards the elimination goal of rubella/CRS.

Clinical Profile and Short-Term Outcome of Children With SARS-CoV-2 Related Multisystem Inflammatory Syndrome (MIS-C) Treated With Pulse Methylprednisolone.

OBJECTIVE: To study the clinical profile and outcome of children with MIS-C treated with methylprednisolone pulse therapy and /or intravenous immunoglobulin (IVIG). METHOD: This prospective observational study included children satisfying CDC MIS-C criteria admitted from September to November, 2020. Primary outcome was persistence of fever beyond 36 hours after start of immunomodulation therapy. Secondary outcomes included duration of ICU stay, mortality, need for repeat immunomodulation, time to normalization of CRP and persistence of coronary abnormalities at 2 weeks. RESULTS: Study population included 32 patients with MIS-C with median (IQR) age of 7.5 (5-9.5) years. The proportion of children with gastrointestinal symptoms was 27 (84%), cardiac was 29 (91%) and coronary artery dilatation was 11 (34%). Pulse methylprednisolone and intravenous immunoglobulin were used as first line therapy in 26 (81%), and 6 (19%) patients, respec-tively. Treatment failure was observed in 2/26 patients in methylprednisolone group and 2/6 patients in IVIG group. C-reactive protein levels less than 60mg/L by day 3 was seen in 17(74%) in methylprednisolone group and 2 (25%) in IVIG group (P=0.014). There was no mortality. At 2 weeks follow-up coronary artery dilatation persisted in 4 in methylprednisolone group and 1 in IVIG group. CONCLUSIONS: In patients with SARS-CoV-2 related MIS-C, methylprednisolone pulse therapy was associated with favorable short-term outcomes.

Genome-Wide DArTSeq Genotyping and Phenotypic Based Assessment of Within and Among Accessions Diversity and Effective Sample Size in the Diverse Sorghum, Pearl Millet, and Pigeonpea Landraces.

Germplasm should be conserved in such a way that the genetic integrity of a given accession is maintained. In most genebanks, landraces constitute a major portion of collections, wherein the extent of genetic diversity within and among landraces of crops vary depending on the extent of outcrossing and selection intensity infused by farmers. In this study, we assessed the level of diversity within and among 108 diverse landraces and wild accessions using both phenotypic and genotypic characterization. This included 36 accessions in each of sorghum, pearl millet, and pigeonpea, conserved at ICRISAT genebank. We genotyped about 15 to 25 individuals within each accession, totaling 1,980 individuals using the DArTSeq approach. This resulted in 45,249, 19,052, and 8,211 high-quality single nucleotide polymorphisms (SNPs) in pearl millet, sorghum, and pigeonpea, respectively. Sorghum had the lowest average phenotypic (0.090) and genotypic (0.135) within accession distances, while pearl millet had the highest average phenotypic (0.227) and genotypic (0.245) distances. Pigeonpea had an average of 0.203 phenotypic and 0.168 genotypic within accession distances. Analysis of molecular variance also confirms the lowest variability within accessions of sorghum (26.3%) and the highest of 80.2% in pearl millet, while an intermediate in pigeonpea (57.0%). The effective sample size required to capture maximum variability and to retain rare alleles while regeneration ranged from 47 to 101 for sorghum, 155 to 203 for pearl millet, and 77 to 89 for pigeonpea accessions. This study will support genebank curators, in understanding the dynamics of population within and among accessions, in devising appropriate germplasm conservation strategies, and aid in their utilization for crop improvement.

WHO 2009 Warning Signs as Predictors of Time Taken for Progression to Severe Dengue in Children.

OBJECTIVES: To identify WHO 2009 warning signs that can predict time taken for progression to severe dengue in a pediatric population. DESIGN: Prospective analytical study over 1 year and 2 months. SETTING: Tertiary care center. PARTICIPANTS: 350 children aged 1 mo-12 y with serologically confirmed dengue without co-morbidities/co-infections; conse-cutive sampling. PROCEDURE: At admission, clinical and laboratory details were noted. Disease progression, time of onset of each warning sign, hematocrit, and platelet counts were recorded daily till discharge/ death. If progressing to severe dengue, its time of onset was noted. Time to event analysis with Log Rank test, Kaplan Meier plots and Cox Proportional Hazards Model was done. OUTCOME MEASURES: Primary outcome was time interval from onset of first warning sign to onset of severe dengue (defined as per WHO 2009 guidelines). Predictors were WHO 2009 warning signs: abdominal pain, lethargy, persistent vomiting, mucosal bleed, clinical fluid accumulation, hepatomegaly >2 cm, hematocrit ≥0.40 and platelet count <100x109/L. RESULTS: Among 350 children followed up completely till discharge/death, 90 developed severe dengue (event) while 260 did not (censored). Median age of study population was 7.75 y. Clinical fluid accumulation [(P=0.002, Hazard Ratio (HR) 2.19, 95% CI 1.33-3.60)] and hematocrit ≥0.40 [(P=0.009, HR (95%CI) 1.715, (1.13-2.60)] were significant in univariate analysis. Final multivariate model includes clinical fluid accumulation [(P=0.02, HR (95%CI) 1.89, (1.116-3.202)], hematocrit ≥0.40 (P=0.07), mucosal bleed (P=0.56) and persistent vomiting (P=0.32). CONCLUSION: WHO warning signs that predict time taken for progression to severe dengue in children include clinical fluid accumulation, hematocrit ≥0.40, persistent vomiting and mucosal bleed. Study results have implications in policy making and practice guidelines to triage children attending a health care facility with or without warning signs.

A new distribution record of Albunea groeningi (Crustacea: Anomura: Decapoda: Albuneidae) from the Digha Coast, West Bengal, India.

Members of the genus Albunea Weber, 1795 (family Albuneidae) are commonly known as sand crabs. Albuneidae contains 59 species belonging to 13 genera (Boyko McLaughlin 2010; WoRMS 2019), of which four genera and nine species are known only as fossils. Most species are relatively uncommon and adapted to living in sandy habitats (Boyko Harvey 1999). Among the 24 species of Albunea, four are known only as fossils (WoRMS 2019). The diversity and distributions of most albuneids were reported by Boyko (2002, 2010).

The efficacy of Siddha Medicine, Kabasura Kudineer (KSK) compared to Vitamin C & Zinc (CZ) supplementation in the management of asymptomatic COVID-19 cases: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objectives of this study are to determine efficacy of Siddha medicine, Kabasura kudineer in reduction of SARS-CoV-2 viral load and reducing the onset of symptoms in asymptomatic COVID-19 when compared to Vitamin C and Zinc (CZ) supplementation. In addition, the trial will examine the changes in the immunological markers of the Siddha medicine against control. The secondary objectives of the trial are to evaluate the safety of the Siddha medicine and to document clinical profile of asymptomatic COVID-19 as per principles of Siddha system of Medicine. TRIAL DESIGN: A single centre, open-label, parallel group (1:1 allocation ratio), exploratory randomized controlled trial. PARTICIPANTS: Cases admitted at non-hospital settings designated as COVID Care Centre and managed by the State Government Stanley Medical College, Chennai, Tamil Nadu, India will be recruited. Eligible participants will be those tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain reaction (RT-PCR) aged 18 to 55 years without any symptoms and co-morbidities like diabetes mellitus, hypertension and bronchial asthma. Those pregnant or lactating, with severe respiratory disease, already participating in COVID trials and with severe illness like malignancy will be excluded. INTERVENTION AND COMPARATOR: Adopting traditional methods, decoction of Kabasura kudineer will be prepared by boiling 5g of KSK powder in 240 ml water and reduced to one-fourth (60ml) and filtered. The KSK group will receive a dose of 60ml decoction, orally in the morning and evening after food for 14 days. The control group will receive Vitamin C (60000 IU) and Zinc tablets (100mg) orally in the morning and evening respectively for 14 days. MAIN OUTCOMES: The primary outcomes are the reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR] from the baseline to that of seventh day of the treatment, prevention of progression of asymptomatic to symptomatic state (clinical symptoms like fever, cough and breathlessness) and changes in the immunity markers [Interleukins (IL) 6, IL10, IL2, Interferon gamma (IFNγ) and Tumor Necrosis Factor (TNF) alpha]. Clinical assessment of COVID-19 as per standard Siddha system of medicine principles and the occurrence of adverse effects will be documented as secondary outcomes. RANDOMISATION: The assignment to the study or control group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and informed consent procedures. BLINDING (MASKING): This study is unblinded. The investigators will be blinded to data analysis, which will be carried out by a statistician who is not involved in the trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size could not be calculated, as there is no prior trial on KSK. This trial will be a pilot trial. Hence, we intend to recruit 60 participants in total using a 1:1 allocation ratio, with 30 participants randomised into each arm. TRIAL STATUS: Protocol version 2.0 dated 16th May 2020. Recruitment is completed. The trial started recruitment on the 25th May 2020. We anticipate study including data analysis will finish on November 2020. We also stated that protocol was submitted before the end of data collection TRIAL REGISTRATION: The study protocol was registered with clinical trial registry of India (CTRI) with CTRI/2020/05/025215 on 16 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Guidelines on Diagnosis and Management of Cow's Milk Protein Allergy.

JUSTIFICATION: Cow's milk protein allergy (CMPA) is increasingly being diagnosed in the West, while there is scant data on the subject from India. There is low awareness among pediatricians about its diagnosis and management; leading to improper diagnosis. PROCESS: A group of experts from the pediatric gastroenterology sub-specialty chapter of Indian Academy of Pediatrics (Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition) met at Mumbai on 26 October, 2018 and discussed various issues relating to the subject. A broad consensus was reached and a writing committee was formed. They met again on 11 August, 2019 at Chennai for a detailed discussion. The statement was sent to the entire group by e-mail and their approval obtained. OBJECTIVE: To formulate a consensus statement enable proper diagnosis and management of Cow's milk protein allergy. RECOMMENDATIONS: Cow's milk protein allergy is most common in the first year of life. Gastrointestinal manifestations are usually non-IgE mediated and therefore skin prick test and specific IgE levels are not useful in diagnosis. Clinical response to elimination diet followed by a positive oral food challenge is diagnostic. In patients with only gastrointestinal manifestations, sigmoidoscopy and rectal biopsy may be considered as an alternative. Management involves strict avoidance of all forms of bovine milk protein. For infants who are artificially fed, an extensively hydrolyzed formula is the first choice. Soy formula is an alternative in those above six months of age. Since most infants outgrow the allergy, elimination diet is only for a limited period and re-evaluation should be done periodically.

Substituent Effect Parameters: Extending the Applications to Organometallic Chemistry.

Typically, metal complexes are constituted of an acceptor metal ion and one or more Iigands containing the donor atoms. Accordingly, the properties of a metal complex are equally dependent on the nature of the metal ion and the ligands. Minute structural variations in the ligand will may result in linear changes in the respective energetic parameters and such linear relationships have paramount importance in organometallic chemistry. The variation in ligands is virtually limitless and substantial because of the extent of organic chemistry available for the modelling of desirable ligands, apart from the variation in metal ions. Anyhow, there is still a need for new parameters for the design and quantification of new ligands which in turn leads to the synthesis of metal complexes with possibly predictable chemical properties. Previous studies have demonstrated that quantum chemically derived molecular electrostatic potential (MESP) parameters can be listed as one of the superior quantifiers in this regard, which can act as an effective ligand electronic parameter. The interaction between the ligand part and metal-containing part will be crucial in assessing the reactivity of organometallic complexes. Here we are applying MESP based substituent constants derived from substituted benzenes to forecast the interaction energies in (pyr* )W(CO)5 , (NHC* )Mo(CO)5 and (η6 -arene* )Cr(CO)3 complexes. Ligands and metal ions are varied in each case for better understanding and transparency.

Efficient high capacity technique to embed EPR information and to detect tampering in medical images.

Reversible data hiding (RDH) is one of the well-known and highly recommended method to enhance medical data security or electronic patient record (EPR), privacy and truthfulness. In clinical images, while hiding the data, care must be taken to maintain the confidentiality of the information that is to be hidden within the clinical images because the hidden information should not bring down the original quality of the image. Mostly, the investigations carried out for medical diagnosis are usually constructed on the basis of investigation systems used for diagnosis and are grounded on the images usually used for medical study. Magnetic resonance image (MRI), CR and CT, digital format images which are acquired are related to the patient's data and information regarding their diagnosis study. In this presented approach, we introduce an RDH scheme that can also be combined with encryption and reversible watermarking techniques. Here, we use the data related to the patient diagnosis as the secret information to embed in medical images. Quality of the marked image after embedding the data is usually measured with metrics that are usually used in image processing such as PSNR and SSIM.

Dental caries prevalence among HIV adult population in India: A systematic review.

Dental caries is a universal disease. Untreated dental caries adds to the existing burden of diseases. It is necessary to have national data on the same, especially in HIV cases, to understand the epidemiological aspects and formulate a treatment plan for the population. Hence, a systematic review was carried out to collectively report the dental caries prevalence among this population. A systematic search for articles was done in PubMed and Google Scholar using the keywords: Dental Caries, India, HIV, AIDS and adults from January 1990 to December 2019. All freely available full-text articles were evaluated based on the inclusion criteria. Only four articles fulfilled the criteria based on qualitative analysis. Decayed, Missing and Filled Teeth index was used to record dental caries. Risk factors related to the same were not specified by any of the authors. Studies were not from different regions of India. More epidemiological studies are needed to understand the prevalence rate and correlated to dental caries among HIV-positive population in India.

Predicting the Spread of COVID-19 Using SIR Model Augmented to Incorporate Quarantine and Testing.

India imposed a nationwide lockdown from 25th March 2020 onwards to combat the spread of COVID-19 pandemic. To model the spread of a disease and to predict its future course, epidemiologists make use of compartmental models such as the SIR model. In order to address some of the assumptions of the standard SIR model, a new modified version of SIR model is proposed in this paper that takes into account the percentage of infected individuals who are tested and quarantined. This approach helps overcome the assumption of homogenous mixing of population which is inherent to the conventional SIR model. Using the available data of the number of COVID-19 positive cases reported in the state of Kerala, and in India till 26th April, 2020 and 12th May 2020, respectively, the parameter estimation problem is converted into an optimization problem with the help of a least squared cost function. The optimization problem is then solved using differential evolution optimizer. The impact of lockdown is quantified by comparing the rising trend in infections before and during the lockdown. Using the estimated set of parameters, the model predicts that in the state of Kerala, by using certain interventions the pandemic can be successfully controlled latest by the first week of July, whereas the R0 value for India is still greater than 1, and hence lifting of lockdown from all regions of the country is not advisable.