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1.
J Pharm Bioallied Sci ; 16(Suppl 1): S329-S334, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595513

ABSTRACT

Objective: To evaluate the influence of variations in the upper sulcus depth, nasal tip protrusion, and nasolabial angle on the esthetic perception of profiles. Design: A web-based survey study and was conducted in the Department of Orthodontics and Dentofacial Orthopaedics. This survey was conducted for a period of 10 months and included orthodontists practicing in India. Methods: This study included lateral cephalograms of the most esthetic profiles from a set of 30 profiles that were within Holdaways norms; the most esthetic profile was determined by a panel of two orthodontists and two general dentists. The most esthetic profile photograph will be transferred to a computer in Corel software. The outline of the profile will remain the same, with the inner aspect converted into a dark area (black); now, the profile is completely converted into facial silhouettes. This black facial silhouette is presented to avoid any distractions and bias. There will be a total of 27 silhouettes by various combinations of increased, decreased, and normal values for nasolabial angle, upper sulcus depth, and nasal tip protrusions. Results: Both the orthodontist and layman chose the most favored profile as a normal profile having a normal nasal tip, normal nasolabial angle, and normal upper sulcus depth, whereas among dentists, 50% chose the most favored profile in which the nasolabial angle was normal but the nasal tip and upper labial sulcus were decreased. When it comes to the least favored profiles, opinions varied between orthodontists, dentists, and laymen. Conclusion: The perception of facial esthetics has always been and still is varied between the layman, the dentist, and the orthodontists. Profiles with normal to sharp noses with normal and increased nasolabial angles were considered more attractive than the others. Profiles with fuller upper labial sulci were considered least attractive with other parameters changing.

2.
Front Plant Sci ; 14: 1220973, 2023.
Article in English | MEDLINE | ID: mdl-37636090

ABSTRACT

Reserve starch from seeds and tubers is a crucial plant product for human survival. Much research has been devoted to quantitative and qualitative aspects of starch synthesis and its relation to abiotic factors of importance in agriculture. Certain aspects of genetic factors and enzymes influencing carbon assimilation into starch granules remain elusive after many decades of research. Starch phosphorylase (Pho) can operate, depending on metabolic conditions, in a synthetic and degradative pathway. The plastidial form of the enzyme is one of the most highly expressed genes in potato tubers, and the encoded product is imported into starch-synthesizing amyloplasts. We identified that the genomic locus of a Pho1a-type starch phosphorylase is duplicated in potato. Our study further shows that the enzyme is of importance for a normal starch granule phenotype in tubers. Null mutants created by genome editing display rounded starch granules in an increased number that contained a reduced ratio of apparent amylose in the starch.

3.
Indian J Otolaryngol Head Neck Surg ; 75(2): 523-528, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36540727

ABSTRACT

The aim of this study was to find out the association of sinonasal candidiasis and Covid-19 infection. A prospective observational study was conducted at a tertiary care centre from April to September 2021, involving all patients with invasive candidiasis of the paranasal sinuses having a history of Covid-19 infection. A total of 18 patients of covid associated sinonasal candidiasis among the 475 cases of fungal rhinosinusitis were studied. All patients had involvement of nose and sinuses and 2 patients had orbital involvement with no loss of vision, while 3 had intracranial extensions and 1 had pulmonary involvement. Mandible was involved in 1 patient alone, while the maxilla and palate were involved in 5 patients. 15 patients were hypertensive, 12 diabetics and 1 had aplastic anaemia. Cultures showed that 8 patients had C. parapsilosis, 5 had C. albicans, 3 had C. tropicalis and 2 had mixed fungal infections. All patients underwent surgical debridement and antifungal administration. They were followed up for a minimum of 3 months. There was only one mortality (with aplastic anaemia), rest 17 were disease free at the time of writing this article. This is perhaps the first case series of post covid sinonasal candidiasis in the world. Invasive sinonasal candidiasis is a newer sequela of COVID-19 infection. Uncontrolled diabetes and over-zealous use of steroids at the time of Covid-19 are few of the known risk factors. Early surgical intervention and anti-fungal treatment should be sought for management.

4.
Nucleic Acids Res ; 50(19): 11331-11343, 2022 10 28.
Article in English | MEDLINE | ID: mdl-36243981

ABSTRACT

Transcription of E-cadherin, a tumor suppressor that plays critical roles in cell adhesion and the epithelial-mesenchymal transition, is regulated by a promoter-associated non-coding RNA (paRNA). The sense-oriented paRNA (S-paRNA) includes a functional C/A single nucleotide polymorphism (SNP rs16260). The A-allele leads to decreased transcriptional activity and increased prostate cancer risk. The polymorphic site is known to affect binding of a microRNA-guided Argonaute 1 (AGO1) complex and recruitment of chromatin-modifying enzymes to silence the promoter. Yet the SNP is distant from the microRNA-AGO1 binding domain in both primary sequence and secondary structure, raising the question of how regulation occurs. Here we report the 3D NMR structure of the 104-nucleotide domain of the S-paRNA that encompasses the SNP and the microRNA-binding site. We show that the A to C change alters the locally dynamic and metastable structure of the S-paRNA, revealing how the single nucleotide mutation regulates the E-cadherin promoter through its effect on the non-coding RNA structure.


Subject(s)
MicroRNAs , Polymorphism, Single Nucleotide , Male , Humans , Cadherins/genetics , Cadherins/metabolism , RNA, Untranslated/genetics , MicroRNAs/genetics , Nucleotides , Gene Expression Regulation, Neoplastic , Cell Line, Tumor
5.
Plant J ; 112(2): 518-534, 2022 10.
Article in English | MEDLINE | ID: mdl-36050843

ABSTRACT

There are numerous examples of plant organs or developmental stages that are desiccation-tolerant and can withstand extended periods of severe water loss. One prime example are seeds and pollen of many spermatophytes. However, in some plants, also vegetative organs can be desiccation-tolerant. One example are the tubers of yellow nutsedge (Cyperus esculentus), which also store large amounts of lipids similar to seeds. Interestingly, the closest known relative, purple nutsedge (Cyperus rotundus), generates tubers that do not accumulate oil and are not desiccation-tolerant. We generated nanoLC-MS/MS-based proteomes of yellow nutsedge in five replicates of four stages of tuber development and compared them to the proteomes of roots and leaves, yielding 2257 distinct protein groups. Our data reveal a striking upregulation of hallmark proteins of seeds in the tubers. A deeper comparison to the tuber proteome of the close relative purple nutsedge (C. rotundus) and a previously published proteome of Arabidopsis seeds and seedlings indicates that indeed a seed-like proteome was found in yellow but not purple nutsedge. This was further supported by an analysis of the proteome of a lipid droplet-enriched fraction of yellow nutsedge, which also displayed seed-like characteristics. One reason for the differences between the two nutsedge species might be the expression of certain transcription factors homologous to ABSCISIC ACID INSENSITIVE3, WRINKLED1, and LEAFY COTYLEDON1 that drive gene expression in Arabidopsis seed embryos.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Cyperus , Proteome/metabolism , Arabidopsis/genetics , Abscisic Acid/metabolism , Tandem Mass Spectrometry , Seeds/genetics , Cyperus/genetics , Cyperus/metabolism , Transcription Factors/metabolism , Water/metabolism , Lipids , Arabidopsis Proteins/metabolism
6.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35443322

ABSTRACT

The metabolic syndrome is a cluster of risk factors that are associated with increased risk of cardiovascular diseases and Type 2 diabetes mellitus. The aim was to study the association of plasma procalcitonin with various components of metabolic syndrome (abdominal obsesity, dyslipidemia, hypertension and hyperglycemia) and insulin resistance and compare with healthy controls. In addition, we tried to gauge the association of plasma procalcitonin with complications of metabolic syndrome at presentation. MATERIAL: This was a hospital based observational comparative study on 30 cases of metabolic syndrome in hospital wards and OPD of SMS Medical College, Jaipur and 30 accompanying healthy controls. INCLUSION CRITERIA: Age more than 18 years, and newly diagnosed or old cases of metabolic syndrome using the definition given by International Diabetes Federation (2006). EXCLUSION CRITERIA: Individuals with active infection, trauma, surgery, neoplasms, cirrhosis, pancreatitis and autoimmune diseases or taking medications which can alter the biochemical profile. Detailed history was taken, subjects clinically examined and anthropometric measurements were taken. Required investigations were obtained and statistical analysis done. OBSERVATION: Plasma procalcitonin was significantly higher in cases (mean 0.11 ng/ml) compared to controls (mean 0.002 ng/ml). Waist and neck circumference (102.87±5.19 and 42.03±3.08) values were higher in case group compared to control group (79.67 ±7.98 and 37.10±1.35). Plasma procalcitonin significantly (p<0.05) correlated with level of insulin resistance (HOMA IR), waist circumference, neck circumference, S. Triglycerides, S. VLDL, fasting blood glucose and fasting insulin level in the case group when analyzed by linear regression analysis. We also found that out of 30 subjects in cases, 16.7% had history of MI, whereas in control group no subject was reported with MI. In case of history of CVA, 16.7% had CVA in case group, whereas in control group, no patient was reported with CVA., Conclusion: Our findings based on community-based data showed that higher plasma procalcitonin levels in the normal range are associated with increased measures of obesity, components of the metabolic syndrome, and greater risk of having metabolic syndrome and insulin resistance. Because associations only partly depend on BMI, plasma procalcitonin may serve as a new marker for adipocyte dysfunction, chronic low-grade inflammation, or both.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Metabolic Syndrome , Adolescent , Blood Glucose , Body Mass Index , Diabetes Mellitus, Type 2/diagnosis , Humans , Insulin , Procalcitonin , Risk Factors , Waist Circumference
7.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35443330

ABSTRACT

Adrenal insufficiency (AI) is well entrenched in medical constraints like septic shock, critically ill and multi-morbid hemodynamically unstable patients but its exact prevalence or differences in the cases of chronic liver disease (CLD) at variable grades of severity has recently gained momentum. The eventuality of AI propounding in stable compensated and decompensated cirrhosis without sepsis or in early and late stages of liver desecration are the existing lacunae in popular literature that this study aims to address. MATERIAL: A prospective, analytical study was conducted from March 2021 to December 2021 encompassing 100 hemodynamically stable patients with cirrhosis without infection, admitted at SMS Medical College, Jaipur, who were assessed clinically, biochemically and for adrenal functions. Adrenal insufficiency was defined on multivariable approach including basal 8am cortisol levels, followed by giving 250mcg synthetic adrenocorticotrophic hormone IM injection and retaking serum cortisol levels post-hourly interval to delineate peak and delta cortisol variables. All samples were processed by chemoluminiscence based method on fully automatic immunoassay analyser. OBSERVATION: The study comprised 81 males and 19 females with the mean age being 45.4±12.92 years, with CLD etiology concentrating substantially around alcohol consumption (71%). Viral comorbidities viz. HBV, HCV, both viral and alcohol related and miscellaneous causes were documented in 23, 10, 14 and 12 patients respectively. AI surfaced in 38% patients with CLD being statistically significant with p< 0.001. Inclusively, 10.5% patients with Child-Turcotte-Pugh (CTP) class A, 57.89% with CTP class B and 31.57% cases with CTP class C developed adrenal insufficiency. No statistical differences were found in age, sex; mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption and manifestations of portal hypertension between patients with or without AI. For prudence, serum albumin levels were lower (p<0.5) with INR raised (p<0.33) in patients with AI than their counterparts. However, multivariate analysis revealed no direct independent adrenal insufficiency predictor. ROC curve showed that the CTP score may be a good predictor for AI in liver cirrhosis patients as supplemented by significant negative correlations found between CTP score and peak cortisol levels (p=0.001). CONCLUSION: Adrenal insufficiency found frequent even in stable cirrhotic patients form an integral division of the CLD spectra and worsening glucocorticoid levels should be periodically assessed in such patients for preventing parallel comorbidities.


Subject(s)
Adrenal Insufficiency , Hydrocortisone , Adult , Female , Humans , Male , Middle Aged , Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/epidemiology , Adrenal Insufficiency/etiology , Liver Cirrhosis/complications , Liver Cirrhosis/epidemiology , Prospective Studies
8.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35443339

ABSTRACT

Diabetes mellitus is a major global health problem, increasingly affecting the population across the world. Diabetic patients have an increased risk of developing micro and macro vascular diseases, and platelets may be involved as a causative agent with respect to altered platelet morphology and function. There are studies evaluating the association between Mean Platelet Volume (MPV) and HbA1c and its role in predicting glycaemic control with conflicting results. Thus the present study was conducted to assess the relationship between HbA1c levels and platelet activity (MPV), determine the association among MPV, glycemic control, and diabetic vascular complications and to evaluate the influence of improved glycemic control on MPV in type 2 diabetic patients. MATERIAL: This was a hospital based observational comparative study on 100 cases of diabetes mellitus divided in 2 groups i.e Group A (HbA1c <7) and Group B (HbA1c >7) and 50 healthy controls in Group C in hospital wards and OPD of SMS Medical College, Jaipur. INCLUSION CRITERIA: Age more than 18 years, and newly diagnosed or old cases of diabetes mellitus using the definition given by American Diabetes Association. EXCLUSION CRITERIA: Abnormal platelet count (<100 and >450×103/µL), Acute febrile illness, Use of drugs affecting platelet function, Male patients with Hb<12.5mg/dl and females with Hb<11.5 mg/dl and Pregnant females. OBSERVATION: It was observed that mean MPV(fl) was maximum in Group B (13.35±1.27), followed by Group A (10.77±.77) and Group C (9.09±.85) and a significant (p-value<0.05) relation was found statistically. We also observed that mean HbA1c (%) was maximum in Group B (8.82±1.41), followed by Group A (6.66±.004) and Group C (5.67±.45) and a significant (p-value<0.05) relation was found statistically in these 3 groups. In group B, at baseline MPV(fl) levels were more (13.35±1.26) than at follow up after glycemic control of 3mths (12.13±1.20) and this was found to be statistically significant. CONCLUSION: We found that Mean platelet volume in diabetic mellitus type 2 patients was significantly higher than non-diabetic group. We also found that the mean platelet volume in uncontrolled diabetic group (HbA1c more than 7 percent) was significantly higher than controlled diabetic group (HbA1c less than 7 percent). Our study showed that in diabetes mellitus, platelets become more reactive and aggregable and their mean volume (MPV) is increased. We also found that increase in HbA1c concentration was directly proportional to increased MPV.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Angiopathies , Adolescent , Blood Platelets , Diabetes Mellitus, Type 2/complications , Female , Glycated Hemoglobin/analysis , Humans , Male , Mean Platelet Volume
9.
Plants (Basel) ; 11(7)2022 Mar 26.
Article in English | MEDLINE | ID: mdl-35406869

ABSTRACT

Wheat (Triticum aestivum L.) is one of the major staple crops in the world and is used to prepare a range of foods. The development of new varieties with wider variation in grain composition could broaden their use. We characterized grains and flours from oil-accumulating transgenic wheat expressing the oat (Avena sativa L.) endosperm WRINKLED1 (AsWRI1) grown under field conditions. Lipid and starch accumulation was determined in developing caryopses of AsWRI1-wheat and X-ray microtomography was used to study grain morphology. The developing caryopses of AsWRI1-wheat grains had increased triacylglycerol content and decreased starch content compared to the control. Mature AsWRI1-wheat grains also had reduced weight, were wrinkled and had a shrunken endosperm and X-ray tomography revealed that the proportion of endosperm was decreased while that of the aleurone was increased. Grains were milled to produce two white flours and one bran fraction. Mineral and lipid analyses showed that the flour fractions from the AsWRI1-wheat were contaminated with bran, due to the effects of the changed morphology on milling. This study gives a detailed analysis of grains from field grown transgenic wheat that expresses a gene that plays a central regulatory role in carbon allocation and significantly affects grain composition.

10.
Indian Pediatr ; 59(5): 388-392, 2022 05 15.
Article in English | MEDLINE | ID: mdl-35348124

ABSTRACT

OBJECTIVE: To evaluate the persistence of antibodies three years after primary vaccination with typhoid conjugate vaccine (TCV) of either Cadila Healthcare Ltd. (Cadila-TCV) or Bharat Biotech International Ltd. (Bharat-TCV) administered in a previous phase II/III study, and to study the booster dose response to Cadila-TCV. METHODS: This was an open-label, phase IV extension study conducted in tertiary care and multispecialty hospitals in India. 112 subjects (Cadila-TCV-57, Bharat-TCV-55) who had participated in previous study were enrolled. Of these, eligible subjects received a single-dose of Cadila-TCV and were followed-up for 28 days post-booster. Primary outcome was persistence of antibodies 3 years after primary vaccination and seroconversion (≥4-fold rise in antibody titre from baseline) 28 days post-booster. Safety was based on reported adverse events (AEs) post-booster. RESULTS: The baseline GMT reported in the current study was significantly higher than pre-vaccination GMT reported in the previous study. 89/112 (79.5%) subjects had antibody titer ≥10 IU/mL at baseline; eligible subjects (n=17) who had baseline antibody titre <10 IU/mL were administered booster dose. All the vaccinated subjects showed seroconversion post-booster. The GMTs reported at 10 days and 28 days post-booster were significantly higher as compared to GMTs reported after primary vaccination in previous study. 4 (23.5%) vaccinated subjects reported 9 AEs; all were solicited and of mild/moderate intensity. CONCLUSIONS: There was a significant persistence of immunogenicity after primary vaccination with both the TCVs, and robust immune response after booster vaccination with Cadila-TCV.


Subject(s)
Typhoid Fever , Typhoid-Paratyphoid Vaccines , Humans , Immunization, Secondary , Seroconversion , Typhoid Fever/prevention & control , Typhoid-Paratyphoid Vaccines/adverse effects , Vaccination , Vaccines, Conjugate/adverse effects
11.
Article in English | MEDLINE | ID: mdl-34939555

ABSTRACT

BACKGROUND: Stress hyperglycemia is a common phenomenon in patients presenting with acute myocardial infarction (MI). We aim to evaluate the association of stress hyperglycemia at the time of hospital presentation and adverse cardiac events in myocardial infarction during the course of hospital stay. METHODS: Subjects with age ≥18 years with acute MI were recruited on hospital admission and categorized based on admission blood glucose (<180 and ≥180 mg/dl, 50 patients in each group). Both groups were compared for clinical outcomes, adverse cardiac events and mortality. We also compared the adverse cardiac outcomes based on HbA1c levels (<6% and ≥6%). RESULTS: Patients with high blood glucose on admission (stress hyperglycemia) had significant increased incidences of severe heart failure (Killip class 3 and 4), arrythmias, cardiogenic shock and mortality (p value = 0.001, 0.004, 0.044, and 0.008 respectively). There was no significant association between adverse cardiac events and HbA1c levels (heart failure 18.8% vs. 25%, p value = 0.609 and mortality 16.7% vs. 17.3%, p value = 0.856). CONCLUSIONS: Stress hyperglycemia is significantly associated with adverse clinical outcomes in patients with MI irrespective of previous diabetic history or glycemic control. Clinicians should be vigilant for admission blood glucose while treating MI patients.


Subject(s)
Hyperglycemia , Myocardial Infarction , Adolescent , Blood Glucose , Cohort Studies , Humans , Hyperglycemia/complications , Myocardial Infarction/complications , Myocardial Infarction/epidemiology , Prognosis , Risk Factors , Shock, Cardiogenic
12.
Plant Mol Biol ; 106(3): 259-270, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33837502

ABSTRACT

Black carrots are potent sources of anthocyanin for the natural food color industry as their anthocyanins contain very high percentages of acylated anthocyanins which are much more stable than non-acylated anthocyanins. Anthocyanins are synthesized by a specific branch of the phenylpropanoid pathway activated by a triad of R2R3-MYB, bHLH and WD40 transcription factors (TFs). Recent studies in black carrots have elucidated major anthocyanin related structural genes and also regulatory TFs. However, the active TFs responsible for anthocyanin production in black carrots differ between cultivars. We have previously shown by RNAseq that DcMYB113 (LOC108213488), a R2R3-MYB TF, was up-regulated in colored as compared to non-colored tissues of the black carrots 'Superblack' and 'CH05544' and that this upregulation was positively correlated with anthocyanin content. However, this gene showed no upregulation in the black carrot 'Nightbird' also included in that study. In the present study, we present a novel R2R3-MYB DcMYB113_NB (LOC108212072) and a complementary bHLH DcEGL1_NB (LOC108210744) isolated from the RNA of 'Nightbird'. Their functionality as anthocyanin regulators was confirmed by their simultaneous expression under the control of a constitutive promoter in the background of the orange carrot 'Danvers 126'. Transformants showed activation of the structural anthocyanin genes and accumulation of anthocyanins across leaves, stems and taproots. Interestingly, the anthocyanin profile of the transformants showed increases of 20 to 30% in acylated anthocyanins as compared to 'Nightbird' resulting in transformants with almost 100% acylated anthocyanins.


Subject(s)
Anthocyanins/metabolism , Daucus carota/metabolism , Plant Proteins/metabolism , Transcription Factors/metabolism , Transcriptional Activation/genetics , Transgenes/genetics , Anthocyanins/analysis , Anthocyanins/biosynthesis , Anthocyanins/genetics , Bony Callus/metabolism , Daucus carota/genetics , Gene Expression Regulation, Plant/genetics , Genetic Vectors , Plant Proteins/genetics , Plants, Genetically Modified/genetics , Transcription Factors/genetics , Up-Regulation
13.
Clin Infect Dis ; 73(9): e2722-e2728, 2021 11 02.
Article in English | MEDLINE | ID: mdl-32556113

ABSTRACT

BACKGROUND: Limited supply, cost and potential for severe adverse effects observed with the blood derived rabies immunoglobulin products has led to search for alternative therapies. This issue has been addressed by developing an anti-rabies monoclonal antibody cocktail. METHODS: This is a phase 3, randomized, open-label, noninferiority trial conducted in patients with World Health Organization (WHO) category III exposure with suspected rabid animal. Eligible patients were assigned to either the test arm, TwinrabTM (docaravimab and miromavimab) or the reference arm, human rabies immunoglobulin (HRIG; Imogam® Rabies-HT), in a ratio of 1:1. The primary endpoint was the comparison of responder rates between the 2 arms assessed as percentage of those with rabies virus neutralizing antibodies titers ≥0.5 IU/mL on day 14. RESULTS: A total of 308 patients were equally randomized into the 2 arms. In the per-protocol (PP) population, there were 90.21% responders in the TwinrabTM arm and 94.37% in the HRIG arm. The geometric mean of rapid fluorescent foci inhibition test titers in the PP on day 14 were 4.38 and 4.85 IU/mL, for the TwinrabTM and HRIG arms, respectively. There were no deaths or serious adverse events reported. CONCLUSIONS: This study confirmed that TwinrabTM is noninferior to HRIG in terms of providing an unbroken window of protection up to day 84. This trial in healthy adults with WHO category III exposure from suspected rabid animal also establishes the safety of TwinrabTM in patients with 1 WHO approved vaccine regimen (Essen). CLINICAL TRIALS REGISTRATION: CTRI/2017/07/009038.


Subject(s)
Rabies Vaccines , Rabies virus , Rabies , Animals , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Humans , Post-Exposure Prophylaxis , Rabies/prevention & control
15.
J Phys Chem B ; 124(49): 11041-11054, 2020 12 10.
Article in English | MEDLINE | ID: mdl-33297682

ABSTRACT

Lens crystallins are subject to various types of damage during their lifetime which triggers protein misfolding and aggregation, ultimately causing cataracts. There are several models for crystallin aggregation, but a comprehensive picture of the mechanism of cataract is still underway. The complex biomolecular interactions underlying crystallin aggregation have motivated major efforts to resolve the structural details and mechanism of aggregation using multiple biophysical techniques at different resolutions. Together, experimental and computational approaches identify and characterize both amyloidogenic and amorphous aggregates leading to an improved understanding of crystallin aggregation. A rigorous characterization of the aggregation-prone intermediates is crucial in cataract-mediated drug discovery. This Perspective summarizes recent biophysical studies on lens crystallin aggregation. We evaluate the outstanding challenges, future outlook, and rewards in this fertile field of research. With lessons learned from protein folding and multiple pathways of aggregation, we highlight the differences in the overall mechanisms of age-related and congenital cataracts. We expect that a correlation between the existing and developing biophysical techniques would provide a platform to study amyloid architecture in the eye lens and reduce the existing gaps in our understanding of crystallin biophysics.


Subject(s)
Cataract , Crystallins , Biophysics , Humans , Protein Aggregates , Protein Folding
16.
Ann Acad Med Singap ; 49(7): 449-455, 2020 Jul.
Article in English | MEDLINE | ID: mdl-33000107

ABSTRACT

INTRODUCTION: As the coronavirus disease 2019 (COVID-19) pandemic continues to spread on an unprecedented scale from around the world, we described our experience in treating early COVID-19 cases in India. MATERIALS AND METHODS: An observational study of COVID-19 patients admitted to a tertiary care centre in North India between 2 March-4 April 2020 was performed. The clinical, epidemiological, laboratory, treatment and outcome data of patients were evaluated. RESULTS: A total of 75 patients were treated and 56 (74.66%) were men. The clinical spectrum of COVID-19 ranged from asymptomatic to acute respiratory distress syndrome (ARDS). Fever (85.36%) was the most common symptom followed by cough (56.09%) and dyspnoea (19.51%). Findings from hemogram analysis showed that 32%, 21.33% and 18.67% of patients had lymphopaenia, eosinopenia and thrombocytopaenia, respectively. Inflammatory markers such as C-reactive protein, D-dimer, ferritin, fibrin degradation product and interleukin-6 were significantly elevated (P <0.05) in patients who required oxygen therapy than those who did not require it, suggesting the potential role such markers could play in predicting prognosis in patients. Mean hospital stay was 9.2 days and 72 (96%) patients made a complete recovery, but 3 (4%) patients demised after progressing to ARDS. CONCLUSION: The clinical and epidemiological spectrum of COVID-19 has jeopardised the health system in India. Without a proven therapy to combat this pandemic and with no sight of vaccines in the near future, a preventive strategy should be adopted to contain the spread of this infectious disease.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Tertiary Care Centers , Adolescent , Adult , COVID-19 , Child , Child, Preschool , Coronavirus Infections/epidemiology , Female , Hospitalization , Humans , India , Infant , Male , Middle Aged , Outcome and Process Assessment, Health Care , Oxygen Inhalation Therapy , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Symptom Assessment , Young Adult
17.
Ann Thorac Med ; 15(3): 146-150, 2020.
Article in English | MEDLINE | ID: mdl-32831936

ABSTRACT

CONTEXT: The outbreak and spread of severe acute respiratory syndrome coronavirus 2 has led to a global exigency of colossal and monstrous proportions in terms of public health and economic crisis. Till date, no pharmaceutical agent is known to manage in terms of prevention and treatment of coronavirus disease 2019 (COVID-19), the disease caused by a novel virus. AIMS: The aim of the present work was to understand the underlying disease profile and dynamics that could provide relevant inputs and insight into pathophysiology and prevent further spread and evolve management strategies of COVID-19 patients from data-driven techniques. SETTINGS AND DESIGN: A retrospective observational descriptive study was conducted on 29 COVID-19 patients admitted at a premier medical institution of North India in the months of February and March 2020. METHODS: The patients were diagnosed with reverse transcription-polymerase chain reaction test. Demographic, clinical, and laboratory data were collected. RESULTS: The mean age of population was 38.8 years with male preponderance, of which two patients were residents of Italy, and others hailed from semi-arid and Western sandy arid regions of Rajasthan (urban population). The major presenting symptom complex of said COVID-19 sample population included fever (48%), cough (31%), and shortness of breath (17%). Most of the patients (83%) had no comorbidity. No clinical correlation (r) could be appreciated between the duration of test positivity and age of afflicted COVID-19 patients (r = -0.0976). CONCLUSIONS: The present evaluation of various facets of the ongoing global pandemic of COVID-19 is an attempt to portray early clinical and epidemiological parameters of the menace of COVID-19 patients admitted at SMS Medical College and Attached Hospitals, Jaipur.

18.
Biochem Biophys Res Commun ; 531(4): 522-527, 2020 10 22.
Article in English | MEDLINE | ID: mdl-32807496

ABSTRACT

Flaviviruses are major emerging human pathogenic viruses that pose a persistent and growing menace to global health. They are enveloped single-stranded RNA viruses with positive polarity transmitted by arthropod vectors like mosquitoes or ticks, responsible for a significant and growing number of human deaths and illnesses. The 5'- and 3'-untranslated regions (UTRs) are highly structured and contain conserved cis-acting RNA elements that participate in viral translation, replication and host adaptation. Despite their role in fiaviviruses replication, few high-resolution structural studies have investigated the RNA elements required for viral replication. Here we report the NMR structures of stem-loop B from WNV and DENV4 viruses. Because this element is required for cyclization of the genome and the activity of the replicative viral enzymes, viral replication rates are sensitive to even small changes in these RNAs. Therefore, this work provides structural insight into a new drug target to reduce flavivirus replication rates.


Subject(s)
Dengue Virus/chemistry , RNA, Viral/chemistry , West Nile virus/chemistry , 5' Untranslated Regions , Dengue Virus/physiology , Magnetic Resonance Spectroscopy , Models, Molecular , Mutation , Nucleic Acid Conformation , Temperature , Virus Replication
19.
J Assoc Physicians India ; 68(7): 34-42, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32602679

ABSTRACT

PURPOSE: The present study was undertaken to investigate and quantify the severity of COVID-19 infection on high-resolution chest computed tomography (CT) and to determine its relationship with clinical parameters. This study also aimed to see CT changes with clinical recovery or progression of disease. MATERIALS AND METHODS: In an attempt to provide extensive information pertaining to clinical and radiological characteristics of COVID-19, the present study was undertaken in 80 hospitalized patients. The patients were COVID-19 confirmed positive by genomic analysis through RT-PCR at tertiary care center in Jaipur. Initially all patients were evaluated for their clinical parameters and then correlated with HRCT chest after hospitalization. CT findings correlated with duration of disease to assess progress or recovery. RESULTS: A total of 80 patients of laboratory confirmed COVID-19 test by RT-PCR at SMS Hospitals, Jaipur were assessed. Among the confirmed cases, most of patients were young adults in the fifth and sixth decade of age group with mean age of 50.40 years. There was a male preponderance (59% male and 41% female). Out of total analyzed patients, 39 patients (48.75%) were symptomatic, among them fever (79.47%), cough (74.35%), shortness of breath (36%) and sore throat (17.94%) were the most common presenting clinical manifestations. A few patients (12.82%) also had other symptoms like headache, chest pain, pain abdomen, altered sensorium etc. 54% patients had some underlying co morbid disease in sample population. The most prevalent comorbidities were Diabetes mellitus (56%), Hypertension (48.83%), COPD/K-chest (12%), CAD (9.32%) and others (11.62%) like hypothyroidism, anemia, CVA etc. The lung pathological changes were evaluated by HRCT imaging and by assigning CT severity score. We found Typical COVID findings in 50% patients, Indeterminate in 11%, Atypical in 11% and 28% patients had Negative CT chest for COVID. The clinical status of patients correlated with the CT severity score, with mild cases showing score <15/25 in 45.83% patients and severe cases showing CT severity score >15/25 in 87.50% patients. The CT features varied with duration and course of disease. Proportional GGO was higher (59.37%) in early phase and it was lower (12.5%) in later stage of disease. CONCLUSION: The varied spectra of COVID-19 presentation included fever, cough, shortness of breath, sore throat etc. Diabetes mellitus, hypertension, COPD/K-Chest and CAD were found as major comorbid conditions. Symptomatic presentation of COVID-19 was observed to be higher in patients with co morbid disease, especially if multiple. HRCT chest in COVID-19 patients had a major diagnostic and prognostic importance as positive CT findings were more prominent in symptomatic patients and co-morbid patients. Clinical symptoms of patients directly correlated with CT severity index. CT imaging was found to be useful in predicting clinical recovery of patients or progression of disease.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , COVID-19 , Coronavirus Infections/diagnostic imaging , Female , Humans , Male , Middle Aged , Pneumonia, Viral/diagnostic imaging , SARS-CoV-2 , Tomography, X-Ray Computed , Young Adult
20.
Indian Pediatr ; 57(7): 625-630, 2020 07 15.
Article in English | MEDLINE | ID: mdl-32727938

ABSTRACT

OBJECTIVE: To compare the immunogenicity and safety of an investigational typhoid Vi conjugate vaccine (Test TCV) with a marketed typhoid Vi conjugate vaccine (Comparator TCV). DESIGN: Randomized, controlled trial. SETTING: Tertiary care and multispecialty hospitals. PARTICIPANTS: 240 healthy subjects of 6 months to 45 years. Pediatric (<18 years) subjects were enrolled after day 21 safety assessment of adult subjects. INTERVENTION: Participants received a single-dose of test TCV or comparator TCV at baseline and were followed up for 6 weeks post-vaccination. MAIN OUTCOME MEASURE: Primary variable was to demonstrate non-inferiority of the test TCV with the comparator TCV for seroconversion post-vaccination (³4-fold rise in antibody titre). Secondary variables were seroconversion in the adult and pediatric cohorts, and geometric mean titre of antibodies while the safety was based on reported adverse events. RESULTS: A total of 117 subjects (Adult-58, Pediatric-59) and 119 subjects (Adult-60, Pediatric-59) in test and comparator group, respectively completed the study. The seroconversion rate with test TCV (overall-94.8%, adult-96.6% and pediatric-93.1%) was non-inferior to comparator TCV (overall-91.6%, adult-91.7% and pediatric-91.5%). The geometric mean titres of antibodies (EU/mL) at baseline (test TCV: overall-7.6, adult-10.0, and pediatric-5.7; and comparator TCV: overall-8.0, adult-12.0, and pediatric-5.3) and at end of study (test TCV: overall-1121.0, adult-1411.0 and pediatric-891.1; and comparator TCV: overall-1104.0, adult-1199.0 and pediatric-1014.0) were also comparable between the groups (P>0.05 for all). The most common adverse event was injection-site pain followed by fever in both the groups. CONCLUSIONS: The immunogenicity and safety of test TCV is comparable to already marketed comparator TCV.


Subject(s)
Typhoid Fever/prevention & control , Typhoid-Paratyphoid Vaccines/adverse effects , Typhoid-Paratyphoid Vaccines/immunology , Vaccines, Conjugate/adverse effects , Vaccines, Conjugate/immunology , Adult , Antibodies, Bacterial , Child , Healthy Volunteers , Humans , Middle Aged , Typhoid-Paratyphoid Vaccines/genetics
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