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The objective of this study was to determine and compare the moment-to-force (Mc/F) ratio and the type of tooth movement generated in the anterior and posterior segments in orthodontic space closure with stainless steel and titanium-molybdenum alloy loop archwires. Three-dimensional model of the maxilla from which the first premolar was extracted, 18 × 25-mil slot stainless steel brackets, and 16 × 22-mil stainless steel and β titanium-molybdenum alloy (TMA) closing loop archwires with anterior gable bend of 15° and posterior gable bend of 25° were constructed. The archwires were engaged in the brackets, and 1-mm activations were carried out, which were repeated 5 times. The anterior and posterior segment Mc/F ratio and the type of tooth movement generated by the 2 wires were compared. It was found that the Mc/F ratio for the anterior segment was approximately 5 mm, and for posterior teeth was approximately 10 mm for both stainless steel and TMA closing loop archwire. The anterior teeth exhibited controlled tipping, whereas the posterior teeth showed bodily tooth movement, which was in accordance with the Mc/F ratio that was obtained. The Mc/F ratio and the type of tooth movement exhibited by stainless steel and TMA closing loop archwires were similar in both anterior and posterior segments. • The moment to force ratio exhibited by stainless steel and TMA closing loop archwires was similar in both anterior and posterior segments. • The type of tooth movement exhibited by stainless steel and TMA archwires was also similar with controlled tipping of the anterior segment and translation in the posterior segment. • Therefore, TMA is more useful when used with more amounts of gable bends and more complex loop designs when compared to stainless steel archwires when used as closing loop archwires. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the effect of platelet-rich plasma (PRP) on the rate of orthodontic tooth movement (OTM) during en-masse anterior retraction.Methods: Twenty adult patients with Angles Class I bimaxillary protrusion or crowding requiring first premolar extraction for routine orthodontic treatment were divided into control and experimental groups. The control group did not receive PRP, whereas the experimental group received PRP in the alveolar mucosa of the maxillary 6 anterior teeth just before starting en-masse retraction. Measurements were recorded on digital models made from scanned plaster casts at the beginning of space closure and the end of 3 months. The overall rate of OTM between both groups was compared. The amount of anchorage loss and type of anterior retraction on lateral cephalogram was also compared between the groups.Results: The overall rate of OTM was minimally increased but not statistically significant in the experimental vs control group (P = 0.838). Anterior retraction parameters in both groups showed incisors moving primarily by controlled tipping and partly by translation. An intergroup comparison of all cephalometric parameters for anchorage loss and anterior retraction showed statistically insignificant differences between both groups.Conclusions: PRP is ineffective in accelerating the rate of OTM during en-masse anterior retraction. [ABSTRACT FROM AUTHOR]

US food and drug administration has recently approved deflazacort for Duchenne muscular dystrophy (DMD) and recommended the dosage of 0.9 mg/kg/d for patients aged ≥5years. However, data assessing the minimal efficacious dose and need of dose-titration based on age or disease severity is limited. To determine whether deflazacort 0.45 mg/kg/d (proposed lower dosage) is non-inferior to 0.9 mg/kg/d among newly diagnosed patients with DMD. A double-blinded, non-inferiority, randomized trial, conducted between December 2018 and July 2020. Newly diagnosed patient aged 5–15 years with genetic or muscle biopsy confirmed DMD and baseline 6-min walk distance (6MWD) > 150 m were screened. Patients were randomly assigned (1:1), stratified to prespecified subgroups by age (≤7years and >7years), and baseline 6MWD (≤350 m and >350 m), to receive either 0.45 mg/kg/d or 0.9 mg/kg/d regimens. The primary endpoint was the change in 6MWD, from baseline to week-24 of intervention. The trial was powered with a predefined, non-inferiority margin of 30 m. The analyses were by modified intention-to-treat (mITT). A total of 97 patients were enrolled, 40 receiving 0.45 mg/kg/d and 45 receiving 0.9 mg/kg/d deflazacort comprised of mITT population. For primary endpoint analysis the mean (SD) change in 6MWD from baseline to week-24 was 9.7 m (41.5) in deflazacort 0.45 mg/kg/d, and 34.7 m (43.5) for 0.9 mg/kg/d. The mean difference in change in 6MWD across the group was 24.8 m (95% CI 6.7 to 43, p value 0.008). The mean difference in change in 6MWD in the subgroups of boys ≤7 years of age was 21.8 m (95% CI -0.82, 44.5, p = 0.059), with baseline 6MWD of >350 m was 19.9 m (95% CI -2.4, 42.4; p = 0.08). The incidence of combined moderate to severe treatment-related adverse events was significant in the 0.9 mg/kg/d group by week 24 (odds ratio 0.36 [95% CI, 0.14 to 0.89], p = 0.03). The efficacy of proposed low dose deflazacort in comparison to the standard dose did not meet the prespecified criteria for non-inferiority. The low dose deflazacort was non-inferior in subgroup of patients with age ≤7 years and baseline 6MWD of >350 m. Clinical Trial Registry-India Identifier: CTRI/2019/02/017388. • US food and drug administration has recently approved deflazacort for Duchenne muscular dystrophy (DMD). • Data assessing dose response and minimal efficacious dose is limited. • Efficacy of low dose deflazacort (0.45 mg/kg/day) is inferior to standard recommended (0.9 mg/kg/day) dose measured by change in 6-min walk distance (6MWD) from baseline to week 24. • The proposed low dose deflazacort was non-inferior to standard dose in a subgroup of boys with age <7 years and baseline 6MWD >350 m. • Combined moderate to severe side-effects were significantly less with low dose deflazacort. [ABSTRACT FROM AUTHOR]

Objective: To assess the characteristics of an unpaid Facebook page for drug information (DI) and its reachability to users.Methods: In this retrospective observational study over a 6-month duration, a Facebook page for the DI Center was created. One drug-related clinical question recently asked in the DI Center by a hospital clinician and its evidence-based answer along with the appropriate references were framed in a scenario and posted on the Facebook page on working days. The Facebook page likes, consumption, reach, engagement, impressions, and total number of followers were obtained from Facebook insights. The monthly averages of these parameters were assessed using the augmented Dickey-Fuller (ADF) test.Results: The cointegration (ADF) test revealed a statistically significant time-dependent correlation trend between the mean engaged users and mean monthly reach (ADF, -4.904; P = 0.01). Similarly, a statistically significant time-dependent correlation trend was observed with mean engaged users and mean monthly impressions (ADF, -5.456; P = 0.01).Conclusion: The knowledge gap between quality DI and evidence-based medicine practice in a developing country can be bridged with a novel DI Center Facebook page initiative. [ABSTRACT FROM AUTHOR]

Highlights • Coupled SMAR model with EnKF to update root zone soil moisture for improving streamflow. • Study involves both synthetic and real data experiments. • SMOS and ASCAT soil moisture retrievals are used for assimilation. • Proposed approach enhances the assimilation efficiency for streamflow simulations. • Streamflow simulations are improved but only to a moderate level. Abstract The present study investigates the potential of coupled Soil Moisture Analytical Relationship (SMAR) and Ensemble Kalman Filter (EnKF) based surface soil moisture data assimilation for improving the streamflow simulations. For this purpose, synthetic and real data assimilation experiments were carried out using Soil and Water Assessment Tool (SWAT) hydrological model in two different sub-catchments lying in the Krishna River basin, India. Here, the satellite-based surface soil moisture estimates from Soil Moisture and Ocean Salinity (SMOS) and Advanced Scatterometer (ASCAT) are used for assimilation. Results of the synthetic experiment show that the use of physically based SMAR scheme coupled with EnkF for updating profile soil moisture has better ability to improve the surface flow, groundwater flow and consequently streamflow over the covariance-based updates using EnKF only. Likewise, the real data assimilation experiment also shows SMAR-EnKF assimilation strategy performs better than the EnKF only updates for simulating streamflow. However, in both the synthetic as well as real data experiment, the improvements are only moderate. This restricted success in improving streamflow simulations indicate that updating only the soil moisture through any updating scheme adopted here is not sufficient to reduce the effect of the errors in model forcing on subsequent simulation days. [ABSTRACT FROM AUTHOR]

Abstract: The decay of 124Sb (60d half-life) to levels of 124Te has been studied using two HPGe detectors in singles and coincidence mode. We identify 75 transitions in this decay, including 14 gamma rays, the emission of which are being reported here for the first time. In confirming the existence of 26 well-established levels below 2900keV excitation, we also introduce 5 other levels at 2490.5, 2618.4, 2747.05, 2834.99, and 2859.4keV. The data on energies of gamma transitions and the levels are reported at high precision. [Copyright &y& Elsevier]

Bone marrow stromal cell antigen 2 (BST2) is an interferon induced host restriction factor for HIV-1 that blocks the release of nascent virions from infected T cells. We aimed to characterize BST2 gene variants in HIV-1 positive individuals in Indian cohort and study the association of these variants with disease progression in long term non progressors (LTNPs) and progressors. Archived samples of 32 LTNPs, 17 progressors, and 78 controls were screened for BST2 gene polymorphisms using Sanger's sequencing method. Frequency distribution, survival analysis and bioinformatics tools were used to study the association of BST2 variants with disease progression. Eighteen variants of BST2 gene were observed in Indian cohort. Intronic SNP rs919267T/C (OR = 4.489 [0.8494–27.03], p =.04157) and exonic SNP rs13485C/G (OR = 3.887 [0.8262–25.56], p =.0488) were found to be significantly associated with disease progression. Also, rs13485C/C genotype in combination with rs919267C/T (OR = 9.406 [1.384–111], p =.0085) and rs145303329 Δ19bp (OR = 3.887 [0.826–25.5], p =.048) were found to be significantly associated with disease progression. 19 bp indel rs145303329 and its allele c.1-443_1–442insCGCCCCCAGAC[C/T]CAGGCCC from BST2 promoter also showed association with disease progression (OR = 12.97 [0.9731–850.5], p =.026). Docking of AP2 repressor with above allele showed the total binding energy of LTNPs and progressors to be −2581.42 kcal/mol and −3563.27/−3562.84 kcal/mol respectively. We have identified the novel association of three BST2 gene SNPs; rs919267, rs13485 and indel rs145303329 from Indian cohort to be associated with the risk of HIV-1 disease progression for the first time. [ABSTRACT FROM AUTHOR]

• At Kumbh Mela 2019, disease surveillance was established for 22 acute diseases and syndromes. • Among the reported illnesses, 95% were communicable diseases such as acute respiratory illness (35%), acute fever (28%), and skin infections (18%). • The incident command centre generated 12 early warning signals from indicator-based and event-based surveillance: acute diarrheal diseases (n = 8, 66%), vector-borne diseases (n = 2, 16%), vaccine-preventable disease (n = 1, 8%), and thermal event (n = 1, 8%). • There were two outbreaks (acute gastroenteritis and chickenpox) that were investigated and controlled. • Implementation of disease surveillance facilitated early outbreak detection and response. Mass gathering (MG) events are associated with public health risks. During the period January 14 to March 4, 2019, Kumbh Mela in Prayagraj, India was attended by an estimated 120 million visitors. An onsite disease surveillance was established to identify and respond to disease outbreaks. A health coordination committee was established for planning. Disease surveillance was prioritized and risk assessment was done to identify diseases/conditions based on epidemic potential, severity of illness, and reporting requirement under the International Health Regulations (IHR) of 2005. A daily indicator and event-based disease surveillance was planned. The indicator-based surveillance (IBS) manually and electronically recorded data from patient hospital visits and collected MG area water testing data to assess trends. The event-based surveillance (EBS) helped identify outbreak signals based on pre-identified event triggers from the media, private health facilities, and the food safety department. Epidemic intelligence was used to analyse the data and events to detect signals, verify alerts, and initiate the response. At Kumbh Mela, disease surveillance was established for 22 acute diseases/syndromes. Sixty-five health facilities reported 156 154 illnesses (21% of a total 738 526 hospital encounters). Among the reported illnesses, 95% (n = 148 834) were communicable diseases such as acute respiratory illness (n = 52 504, 5%), acute fever (n = 41 957, 28%), and skin infections (n = 27 094, 18%). The remaining 5% (n = 7300) were non-communicable diseases (injuries n = 6601, 90%; hypothermia n = 224, 3%; burns n = 210, 3%). Water samples tested inadequate for residual chlorine in 20% of samples (102/521). The incident command centre generated 12 early warning signals from IBS and EBS: acute diarrheal disease (n = 8, 66%), vector-borne disease (n = 2, 16%), vaccine-preventable disease (n = 1, 8%), and thermal event (n = 1, 8%). There were two outbreaks (acute gastroenteritis and chickenpox) that were investigated and controlled. This onsite disease surveillance imparted a public health legacy by successfully implementing an epidemic intelligence enabled system for early disease detection and response to monitor public health risks. Acute respiratory illnesses emerged as a leading cause of morbidity among visitors. Future MG events should include disease surveillance as part of planning and augment capacity for acute respiratory illness diagnosis and management. [ABSTRACT FROM AUTHOR]

Tacrolimus is a narrow therapeutic index drug. As a result, regulatory agencies worldwide recommend stringent bioequivalence evaluation criteria for approval of generics. Despite this, the professional transplantation societies have raised concerns over the safety and efficacy of generic substitutions. We conducted this pragmatic real-life bioequivalence study to assess the effect of generic substitutions of tacrolimus. This was an observational study including recipients of renal transplantation who were considered for generic medication substitution. Transplanted organs were from living-related donors and were performed at least 1 month before the study. Time of administration of the drug, time of dosing with respect to meals, and time of blood sample collection were controlled; however, the lot number of the generic drugs was not controlled. The participants were allowed to use their usual supplies irrespective of the lot number. Concentration (C 0) was quantified by liquid chromatography with tandem mass spectrometry after the generic substitution from ABC brand to XYZ brand. The average C 0 ± SD with generic ABC was 11.09 ± 4.26 ng/mL and generic ABC was 9.7 ± 4.12 ng/mL. Though there was no statistically significant difference observed between the concentrations, when the individual patient data was examined, 2 patients were found to have a very high concentration of tacrolimus and at least 7 patients fell below the therapeutic range. These derangements called for retitration with the new generic tacrolimus (40%). The results of our study suggest that generic-to-generic substitutions should be carried out very carefully in a closely observed setting in patients with renal transplants. The strength of our study is that it matched the real clinical practice setting as much as possible unlike a bioequivalence study. Therefore, we recommend repeating C 0 at least 3 times over a period of 7 to 10 days with a generic substitution to prevent untoward consequences. • Use of generic tacrolimus is commonplace after its patent expiration in 2008. • Concerns over the use of generic tacrolimus are due to considerable differences in the settings for bioequivalence studies for regulatory approval and the real-life use in the setting of organ transplantation. • During generic substitution of any drug, a cautious approach must be exercised by physicians. • Patient education is also imperative to ensure correct drug usage and to prevent adverse consequences. [ABSTRACT FROM AUTHOR]

Epithelial–mesenchymal transition (EMT) is critical for embryonic development, and this process is recapitulated in adults during wound healing, tissue regeneration, fibrosis and cancer progression. Cell migration is believed to play a key role in both normal wound repair and in abnormal tissue remodeling. Prostaglandin E 2 (PGE 2 ) inhibits fibroblast chemotaxis, but stimulates chemotaxis in airway epithelial cells. The current study was designed to explore the role of PGE 2 and its four receptors on airway epithelial cell migration following EMT using both the Boyden blindwell chamber chemotaxis assay and the wound closure assay. EMT in human bronchial epithelial cells (HBECs) was induced by TGF-β 1 and a mixture of cytokines (IL-1β, TNF-α, and IFN-γ). PGE 2 and selective agonists for all four EP receptors stimulated chemotaxis and wound closure in HBECs. Following EMT, the EP1 and EP3 agonists were without effect, while the EP2 and EP4 agonists inhibited chemotaxis as did PGE 2 . The effects of the EP2 and EP4 receptors on HBEC and EMT cell migration were further confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE 2 switches from a stimulator to an inhibitor of cell migration following EMT of airway epithelial cells and that this inhibition is mediated by an altered effect of EP2 and EP4 signaling and an apparent loss of the stimulatory effects of EP1 and EP3. Change in the PGE 2 modulation of chemotaxis may play a role in repair following injury. [ABSTRACT FROM AUTHOR]

[Display omitted] Remdesivir, the first drug approved by the FDA to treat COVID-19, is in high demand for patients infected with the SARS-CoV-2 virus. Herein, we report a facile approach minimizing the protecting group manipulations to afford remdesivir in good overall yield. [ABSTRACT FROM AUTHOR]