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The surface of proteins is covered by side chains of polar amino acids that are imperative for modulating protein functionality through the formation of noncovalent intermolecular interactions. However, despite their tremendous importance, the unique structures of protein side chains require tailored approaches for investigation by nuclear magnetic resonance spectroscopy and so have traditionally been understudied compared with the protein backbone. Here, we review substantial recent methodological advancements within nuclear magnetic resonance spectroscopy to address this issue. Specifically, we consider advancements that provide new insight into methyl-bearing side chains, show the potential of using non-natural amino acids and reveal the actions of charged side chains. Combined, the new methods promise unprecedented characterisations of side chains that will further elucidate protein function.

Low-frequency vibrations are one of the many non-surgical modalities aimed at increasing the rate of orthodontic tooth movement.The present trial was conducted to assess the efficacy of low-frequency vibrations in increasing the rate of orthodontic tooth movement in adolescent patients undergoing fixed mechanotherapy with passive self-ligating brackets and conventional brackets.Setting and sample population: department of orthodontics and dentofacial orthopaedics in a nationally accredited dental college. Participants, study design and methods: 65 patients were randomly allocated to three groups. Two experimental groups consisted of passive self-ligating and conventionally ligated appliances received low-frequency vibrations. The control group did not receive any vibrations. Allocation ratio was 1:1:1.32. Eligibility criteria: adolescent patients with sound and healthy dentition, incisor irregularity5mm.rate of orthodontic tooth movement in mm/month. Randomization and blinding: computer-generated random allocation sequencing was done and data assessor was blinded.the Q-Q plot and Shapiro-Wilks test judged the normality of the data. The parametric test included ANCOVA and post-hoc analysis.No statistically significant enhancement of tooth movement was seen in the experimental groups, when comparison was done with the control group P0.05. Comparison between the two experimental groups did not reveal any significant difference either.No statistically significant increase of orthodontic tooth movement was seen with low-frequency vibrations and the mode of ligation did not have any effect in increasing the rate of tooth movement either.

Introduction Risk assessment models are used to stratify cancer patients according to their underlying risk of VTE. The CATS score has been shown to enhance VTE risk stratification as compared to the modified Khorana score by incorporating d-dimer and soluble p-selectin measurements. Our aim was to evaluate the performance of the CATS score with respect to VTE risk stratification. Materials and methods Analysis of a subset of the AVERT trial population for whom biomarker data was available. All patients included in the AVERT trial were at increased risk of VTE based on a modified Khorana score of ≥2. Patients were stratified according to the modified Khorana score and CATS score. Kaplan-Meier analysis was used to calculate the 6-month cumulative probabilities of VTE. Results A total of 466 patients were included in the analysis, 229 and 237 patients in the placebo and apixaban arms, respectively. The 6-month cumulative probability of VTE among patients with a modified Khorana score ≥ 3 was 13% [95% CI 7 to 23], whereas it was 20% [95% CI 11 to 35] for patients with a CATS score ≥ 4. The absolute risk reduction achieved with apixaban VTE prophylaxis among patients with modified Khorana ≥2, modified Khorana ≥3 and CATS ≥4 was −5.9% [−10.9 to −0.8], −5.8% [−16.0 to 4.5] and −10.1% [−22.9 to 2.6], respectively. Apixaban VTE prophylaxis among patients with increasing modified Khorana or CATS scores was not associated with an increased risk of bleeding events. Conclusions The use of a CATS score of ≥4 to identify ambulatory cancer patients at very high risk of VTE could enhance the benefit/risk ratio achieved with apixaban VTE prophylaxis.

Emergency Response Services (ERS) in the developing countries often face the challenge of distributing the resources in a manner to provide optimal service. Moreover, the exclusion of heterogeneous urban fabric and considerable variations of travel time and coverage demand throughout the day often leads to inadequate solutions. Hence, we propose an approach to incorporate dynamic aspects like demand, travel time, and coverage area in developing an asset location model. We illustrate how the travel time distribution produces more reliable coverage results when compared to the model considering fixed travel times over the periods. We also incorporate the influence of urban settlement elements like built-up compactness etc. in the resource allocation. A machine learning based approach is proposed to estimate the varying demand. The prediction model predicts the firefighting vehicles demand with high accuracy. We formulate a mixed-integer program to maximize the empirical demand coverage by firefighting vehicles. The proposed model is applied to the southern region of Mumbai, India. We use percentage coverage and coverage variation difference as the metrics to test the performance of the model. When compared to the static travel time model considering fixed average travel times the dynamic model showed more variability in the coverage. This supports our hypothesis that demand and the travel time variations influence the coverage. For the dynamic case, the maximum coverage variability for the vehicles was found to be in the range of 9%, whereas for the static case it was found to be in the range of 6%.

To report the spectrum of ethambutol induced optic neuropathy in a group of renal patients with tuberculosis and the role of visual evoked response (VER) in evaluating this disorder.Twenty-three renal patients who were started on ethambutol as a part of anti-tubercular treatment for tuberculosis in India, were divided into 4 groups based on glomerular filtration rate (GFR): group 1-chronic kidney disease (CKD) with GFR10 mL/min; group 2-CKD with GFR 10-30 mL/min; group 3-GFR30 ≤ 60 mL/min; and group 4-GFR60 90 mL/min. Detailed clinical and electrophysiological (VER) examinations were carried out in all patients before starting the treatment with ethambutol and at a 3-month interval. Twenty healthy subjects formed the control group.Ethambutol optic neuropathy developed in 6 (26%) patients with higher incidence (40%) in end-stage renal disease (group 1: CKD on dialysis). Vision was recovered in 4 cases on stoppage of ethambutol, whereas 2 patients (group 1: CKD on dialysis) developed bilateral severe irreversible visual loss and also had associated hepatic dysfunction. Three patients of ethambutol optic neuropathy showed increased latency in VER recording prior to visual loss and 1 patient showed demyelinating lesions in both optic nerves and optic radiation.Ethambutol should be avoided in renal disorder patients in view of the high incidence of toxic optic neuropathy. Follow-up VER can detect sub-clinical ethambutol toxicity and would be useful for early diagnosis of optic neuropathy.

Our understanding of crop response to elevated [CO2] concerning its growth and yield has improved significantly. However, little is known about the germination and vigour of seeds harvested from mother plant grown under elevated [CO2], particularly in rice. Since elevated [CO2] influences the physiological functions of crop and seed development process, it is expected that such changes will alter the quality of the seed. To test this hypothesis, rice crop (IR 36) was grown in open top chamber (OTC) with varying [CO2] [410 (ambient), 510, 610 and 720 ppm] and seed quality in terms of germination and vigour [accelerated ageing test (AAT) and electrical conductivity (EC)] was assessed. Elevated [CO2] up to 610 ppm had no effect on seed germination; but, [CO2] at 720 ppm reduced the germination of freshly harvested seeds. Elevated [CO2] at 610 and 720 ppm reduced seed vigour. An increase in abnormal seedlings and dead seeds were symptomatic of the seed physiological deterioration associated with loss of seed vigour. Elevated [CO2] at 720 ppm reduced seed nitrogen content, substrate availability, and its subsequent translocation. Thus, atmospheric [CO2] above 610 ppm reduced seed vigour of rice.

Summary Background: SARS-Cov2 has caused millions of deaths worldwide and effective antivirals are not yet available. We evaluated the efficacy, tolerability and safety of Umifenovir, a drug used originally against influenza in Russia and China, in non-severe COVID19 adult patients from India. Method : A double-blind placebo controlled Phase III trial spread over 3 hospitals in Lucknow, India viz. King George’s Medical University, ERAs Lucknow Medical College and Ram Manohar Lohia Institute of Medical Sciences was carried out. RT-PCR confirmed COVID19 patients in the age group from 18-75 yrs. were recruited and further stratified into Mild-asymptomatic and Moderate cases. Exclusions included, pregnant or lactating women, severe patients, those suffering from Acute respiratory distress syndrome (ARDS), sepsis shock, requiring invasive ventilator support, ECMO or shock requiring vasopressor support, severe liver disease, severe renal impairment, comorbid conditions like asthma, diabetes with second-third line medicines as defined in the WHO guidance document. Patients were randomized 1:1 on placebo with standard care of therapy or Umifenovir (800 mg BID, maximum 14 days) with standard care of therapy respectively. Computerized randomization was carried out for each group separately through sequentially numbered, opaque, sealed envelopes (SNOSE) in block sizes of six and was administered independently through clinical-site coordinators and to have sufficient number of Mild-asymptomatic and moderate patients. The primary endpoint for Asymptotic-mild patients was time to nasopharyngeal swab negativity by two RT-PCR tests for SARS COV2 antigens taken 24 hrs apart from the date of randomization. For Moderate patients, the average change in the ordinal scale from the baseline scores from randomization on the eight-point ordinal scale as defined by WHO was calculated as the primary endpoint. This trial is registered with the Clinical Trial Registry of India (CTRI) Number: CTRI/2020/09/027535. Findings: A total of 132 patients were recruited in the trial after screening between 3rd October 2020 to 28th April 2021. Of these, 9 patients withdrew consent/ stopped medication on their own. The remaining 123 patients were almost equally distributed into Asymptomatic (35%), Mild (32%) and Moderate (33%) symptoms groups respectively. No Serious adverse events were noted in any of the patients. Only few minor events like headache, stomach ache and nausea were reported and this also was observed almost equally between the Umifenovir and Standard-of-care arms respectively. In the Primary endpoint corresponding to the Mild-asymptomatic patient group (n=82), we found that 73% patients in the Umifenovir arm were RT-PCR negative on the 5th day (P=0.004), while only 40% patients in the placebo arm were negative. In the moderate group, the WHO scores for the Umifenovir arm corresponded to faster clinical improvement as compared to the Placebo arm (P=0.125 on day 3). In the Mild-asymptomatic group, the clinical improvement assessed by the WHO score on day 5 was statistically significant (P=0.019) in the Umifenovir arm compared to the placebo arm and agrees well with the primary endpoint results. Interpretation: Umifenovir is efficacious for Mild-asymptomatic patients and meets the primary and secondary endpoint criteria of the trial. The drug is safe and well tolerated at a dosage of 800 mg BID, maximum 14 days, in adult patients. It exhibits faster time to cure with median 5 days (95%CI, 5-14) in Umifenovir group and median 7 days (95%CI, 5-14) for the placebo group. In moderate patients, administration of Umifenovir co-relates with faster clinical recovery, albeit with less statistical significance. In future studies, the drug should be evaluated as a prophylactic in high-risk adults, and for efficacy in children and pregnant/lactating women.

When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments.

Background Twinstar is an ADF/cofilin family protein, which is expressed by the tsr gene in Drosophila melanogaster. Twinstar is one of the main regulators of actin cytoskeleton remodelling and is essential for vital cellular processes like cytokinesis and endocytosis. Methods We have characterized the structure and dynamics of Twinstar by solution NMR spectroscopy, the interaction of Twinstar with rabbit muscle actin by ITC, and biochemical activities of Twinstar through different biochemical assays using fluorescence spectroscopy and ultra-centrifugation. Results The solution structure of Twinstar shows characteristic ADF-H fold with well-formed G/F-site and F-site for interaction with actin. The structure possesses an extended F-loop, which is rigid at the base, but flexible towards its apical region. Twinstar shares similar dynamics for the G/F-site with C. elegans homologs, UNC-60A and UNC-60B. However, the dynamics of its F-loop are different from its C. elegans homologs. Twinstar shows strong affinity for ADP-G-Actin and ATP-G-Actin with Kds of ~7.6 nM and ~0.4 μM, respectively. It shows mild F-actin depolymerizing activity and stable interaction with F-actin with a Kd of ~5.0 μM. It inhibits the rate of the nucleotide exchange in a dose dependent manner. Conclusion On the basis of structure, dynamics, and biochemical activity, Twinstar can be taken to execute its biochemical role by facilitating directional growth and maintenance of length of actin filaments. General significance This study characterizes the structure, backbone dynamics, and biochemical activities of Twinstar of Drosophila, which provides an insight into the regulation of actin dynamics in the member of phylum insecta.

We study the problem of scheduling packet transmissions with the aim of minimizing the energy consumption and data transmission delay of users in a wireless network in which spatial reuse of spectrum is employed. We approach this problem using the theory of Whittle index for cost minimizing restless bandits, which has been used to effectively solve problems in a variety of applications. We design two Whittle index based policies the first by treating the graph representing the network as a clique and the second based on interference constraints derived from the original graph. We evaluate the performance of these two policies via extensive simulations, in terms of average cost and packets dropped, and show that they outperform the well-known Slotted ALOHA and maximum weight scheduling algorithms., Comment: Revision