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1.
Genome ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39047299

RESUMO

Cricula trifenestrata Helfer (commonly known as Amphutukoni muga/Cricula silkworm), a wild sericigenous insect produces golden yellow silk similar to Antheraea assamensis (muga silkworm), with significant potential as a natural fiber and biomaterial. Cricula is considered as a pest as it competes for food with muga, which produces the prized golden silk. This study focuses on decoding the mitochondrial genome of C. trifenestrata using next-generation sequencing technology and includes comparative analysis with Bombycoids and other lepidopteran insects. We found that the Cricula mitogenome spans 15,425 bp and exhibits typical gene content and arrangement consistent with other Saturniids and lepidopterans. All protein-coding genes were found to undergo purifying selection, with the highest and lowest conservation observed in the cox1 and atp8 gene respectively, indicating their potential role in future evolutionary events. We identified two types of mismatches: 23 "G-U" and 6 "U-U" pairs, similar to those found in Actias selene among the Saturniids. Additionally, our study uncovered the presence of two 33 bp repeat units and a 'TTAGA' motif in the control region, in contrast to the typical 'ATAGA' motif, suggesting functional similarity with evolving sequences. Furthermore, phylogenetic analysis supports the close relationship of Cricula with other species within the Saturniidae family.

2.
Proc Biol Sci ; 291(2027): 20241190, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39043245

RESUMO

Many environmental features are cyclic, with predictable changes across the day, seasons and latitudes. Additionally, anthropogenic, artificial-light-induced changes in photoperiod or shiftwork-driven novel light/dark cycles also occur. Endogenous timekeepers or circadian clocks help organisms cope with such changes. The remarkable plasticity of clocks is evident in the waveforms of behavioural and molecular rhythms they govern. Despite detailed mechanistic insights into the functioning of the circadian clock, practical means to manipulate activity waveform are lacking. Previous studies using a nocturnal rodent model showed that novel light regimes caused locomotor activity to bifurcate such that mice showed two bouts of activity restricted to the dimly lit phases. Here, we explore the generalizability of these findings and leverage the genetic toolkit of Drosophila melanogaster to obtain mechanistic insights into this unique phenomenon. We find that dim scotopic illumination of specific durations induces circadian photoreceptor CRYPTOCHROME-dependent activity bifurcation in male flies. We show circadian reorganization of the pacemaker circuit, wherein the 'evening' neurons regulate the timing of both bouts of activity under novel light regimes. Our findings indicate that such environmental regimes can be exploited to design light cycles, which can ease the circadian waveform into synchronizing with challenging conditions.


Assuntos
Ritmo Circadiano , Drosophila melanogaster , Animais , Drosophila melanogaster/fisiologia , Masculino , Fotoperíodo , Luz , Relógios Circadianos/fisiologia , Criptocromos/metabolismo , Criptocromos/genética
3.
Transfusion ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979963

RESUMO

INTRODUCTION: Phosphatidylethanol (PEth) is a long-term marker of alcohol consumption used frequently in clinical scenarios such as liver transplant evaluation. Recent cases have demonstrated that packed red blood cell (pRBC) transfusion creates the potential for artificial elevation or decrease of observed PEth concentrations in recipients. Very little is known about the prevalence or stability of PEth in pRBCs. METHODS: Apheresis and whole-blood (WB) donations were tested for PEth using liquid chromatography - tandem mass spectrometry with limit of quantitation 10 ng/mL. Units were stored under routine blood bank conditions to evaluate the stability of PEth and the impact of irradiation. RESULTS: Over 40% of apheresis and WB donors had PEth ≥10 ng/mL (maximum observed 587 ng/mL). As WB units were processed into component pRBCs, PEth concentrations increased and were higher than donor WB levels (EDTA sample) prior to collection (maximum observed 711 ng/mL). Storage for up to 5 weeks post donation resulted in mean 17.3% decrease in PEth-positive units; in contrast to a prior report, we observed no PEth formation in units with negative (<10 ng/mL) baseline concentrations. Irradiation of pRBCs did not substantially affect PEth concentrations in either PEth-positive or PEth-negative units. DISCUSSION: PEth concentrations in healthy blood donors may potentially confound alcohol use or abstinence assessment in pRBC recipients. Transfusion medicine services and clinical practices such as transplantation and behavioral medicine should recognize this phenomenon and collaborate on testing protocols to appropriately interpret PEth in pRBC recipients.

4.
Chem Commun (Camb) ; 60(56): 7200-7203, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38904468

RESUMO

Fused pyranochromenone derivatives have extensive applications in medicinal chemistry. Herein, we report the first HFIP/TsOH catalyzed, one-pot domino reaction by cleavage of the C(sp2)-OMe bond. Control experiments reveal that 1,3,5-trimethoxybenzene is rapidly protonated in the presence of HFIP to yield a dearomatized cationic diene intermediate. The gram-scale reaction and late-stage functionalization of natural products justified the practicality of this protocol.

5.
Eur J Med Chem ; 275: 116598, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38925013

RESUMO

Lactate dehydrogenase-A (LDHA) is the major isoform of lactate dehydrogenases (LDH) that is overexpressed and linked to poor survival in pancreatic ductal adenocarcinoma (PDAC). Despite some progress, current LDH inhibitors have poor structural and physicochemical properties or exhibit unfavorable pharmacokinetics that have hampered their development. The present study reports the synthesis and biological evaluation of a novel class of LDHA inhibitors comprising a succinic acid monoamide motif. Compounds 6 and 21 are structurally related analogs that demonstrated potent inhibition of LDHA with IC50s of 46 nM and 72 nM, respectively. We solved cocrystal structures of compound 21-bound to LDHA that showed that the compound binds to a distinct allosteric site between the two subunits of the LDHA tetramer. Inhibition of LDHA correlated with reduced lactate production and reduction of glycolysis in MIA PaCa-2 pancreatic cancer cells. The lead compounds inhibit the proliferation of human pancreatic cancer cell lines and patient-derived 3D organoids and exhibit a synergistic cytotoxic effect with the OXPHOS inhibitor phenformin. Unlike current LDHA inhibitors, 6 and 21 have appropriate pharmacokinetics and ligand efficiency metrics, exhibit up to 73% oral bioavailability, and a cumulative half-life greater than 4 h in mice.


Assuntos
Antineoplásicos , Proliferação de Células , Inibidores Enzimáticos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Animais , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Proliferação de Células/efeitos dos fármacos , Administração Oral , Camundongos , Relação Estrutura-Atividade , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Disponibilidade Biológica , Relação Dose-Resposta a Droga , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/metabolismo , Linhagem Celular Tumoral , Modelos Moleculares
6.
Small ; 20(30): e2309428, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38529777

RESUMO

Bismuth sulfide (Bi2S3) exhibits a direct energy bandgap and an exceptional optical absorption capability over a broadband radiation, thus presents a novel class of 2D photodetector material. The field effect transistor (FET) photodetector device is fabricated from 2D Bi2S3. An anomalous variation in the transport characteristics of 2D Bi2S3 is observed with the variation in temperature. The electrical resistance reduces by 99.26% at 10 K compared to the response at 300 K. Defects due to the bismuth and sulfur vacancies play a critical role in the dramatic behavior, which is confirmed using photoluminescence, time-resolved photoluminescence, Hall measurements, and energy dispersive X-ray spectroscopy. The density functional theory calculations provide a significant insight into the thermodynamic properties of intrinsic defects in Bi2S3. Moreover, the effect of gate bias on responsivity additionally confirms its invariance at low temperature. The Bi2S3 based FET photodetector achieves ultrahigh responsivity in the order of ≈106 A W-1 and detectivity of ≈1014 Jones. Moreover, the external quantum efficiency of ≈107% is measured in a wide spectrum of optical illumination (532 to 1064 nm) with a noise-equivalent power of 3.5 × 10-18 W/√Hz at a bias of 0.2 V. The extraordinary performance of Bi2S3 photodetector outstands 2D photodetectors.

7.
J Eat Disord ; 11(1): 225, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102717

RESUMO

BACKGROUND: Eating disorders are strongly associated with body image concerns. Eating disorders tend to significantly impact the current and future health and quality of life of affected persons, their caregivers, and society. As body image is based on a social construct of ideal body image, it is essential to evaluate it in its cultural context. METHODS: The current study explored the relationship among body image perception, perceived stress, eating disorder behaviour and quality of life among female medical students (n = 777). Measurements included Body Shape Questionnaire, Body Image Quality of Life Inventory, Eating Attitudes Test-26 and Rosenberg Self-Esteem Scale. Multivariate analysis was conducted. RESULTS: There was a significant correlation between eating disorder behaviour and perceived body shape, body image, quality of life and self-esteem among our study participants. We also found eating disorder status was significantly associated with BMI, perceived body shape, quality of life and self-esteem. CONCLUSIONS: This is of clinical implication to female medical students and healthcare professionals to engage early in primary and secondary prevention of eating pathologies. Increasing awareness of these facts among female students can help identify at-risk students and help them seek timely medical help.


Eating disorders significantly impact the current and future health and quality of life of affected persons, their caregivers, and society. Young people are persistently flooded with social media conceptualizations of what beauty should look like. The current study explored the relationship between how we perceive our body, perceived stress, maladaptive eating behaviours and quality of life among female medical students (n=777). Measurements included those measuring perceived body shape and body image, quality of life, eating attitudes, and self-esteem. We found that a preoccupation with weight and food, crash diets, fasting, binge eating, and purging behaviours was related to how we perceived our body shape, our quality of life and self-esteem among the study participants. This is important for female medical students and healthcare professionals because it enables them to identify students at risk of eating disorders and assist them in obtaining timely medical help, thus promoting early prevention.

8.
J Org Chem ; 88(23): 16104-16115, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37983472

RESUMO

The facile and efficient synthesis of a unique class of 4-aryl-hydrocoumarins having enormous applications in medicinal chemistry and natural products is presented. We have for the first time developed a Brønsted acid-catalyzed, multicomponent, one-pot approach for producing various 4-aryl-coumarin derivatives. The feedstock availability of these precursors allowed access to a wide range of 2-chromanone derivatives in good to excellent yields under mild conditions. The practicality of this protocol was justified by the synthesis of bioactive compounds, late-stage functionalization of natural products, and gram-scale synthesis.

9.
Cureus ; 15(8): e44305, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37779778

RESUMO

Background Leptospirosis is a worldwide prevalent zoonotic infection and re-emerging disease caused by the bacterium of genus Leptospira transmitted by infected animals in the environment. Andaman and Nicobar Islands has one of the highest incidence rates of leptospirosis in India with a seroprevalence of 52.7%. This study examined the knowledge, attitudes, and practices (KAP) regarding leptospirosis among the urban and rural populations of the Union Territory (UT) of India. Aim and objective This study aims to assess the knowledge, attitude, and practices regarding leptospirosis in a rural and an urban community of Andaman and Nicobar Islands. Materials and methods This community-based cross-sectional study was conducted at rural and urban field practice areas under the aegis of the Department of Community Medicine, Andaman and Nicobar Islands Institute of Medical Sciences (ANIIMS), Port Blair, for a period of three months. A semi-structured interview schedule was administered to 450 participants in community settings selected from a list of households obtained from the municipal council using a systematic random sampling method. All interviews were conducted face-to-face by the investigators to collect data on the sociodemographic variables of the study participants and their knowledge, attitudes, and practices regarding the disease. The data was analyzed using Statistical Package for the Social Sciences (SPSS) version 27.0 (IBM SPSS Statistics, Armonk, NY, USA). Results The knowledge and attitude regarding leptospirosis and henceforth the likelihood of individuals using preventive practices were evaluated. The majority of respondents (97%) had previously heard about leptospirosis; however, specific knowledge regarding its risk factors, causative agent, and complications was limited among the participants. Although more than 90% of them had a favorable attitude toward seeking treatment for the disease and adopting specific preventive measures and general hygiene, they did not practice these hygiene habits nor used self-protective equipment in their day-to-day lives. Less than 50% of participants wore protective clothing, boots, and gloves while cleaning cattle sheds, and only 40% of them used rodenticides despite the presence of rodents in their houses. Most of the owners (60%) had not vaccinated their pets. We also found a significant association between the male gender and urban residence with a good knowledge score (p=0.05). Conclusion Despite having knowledge of and a positive attitude toward the disease, the participants did not practice preventive measures. We recommend that health interventions in endemic communities should focus on the implementation of protective measures by raising awareness in the susceptible population on multiple dimensions of leptospirosis in order to attain and ensure better compliance.

10.
J Trace Elem Med Biol ; 80: 127308, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37801785

RESUMO

Spatial and temporal variations have been found in the levels of arsenic (As) throughout the groundwater of the Ghaghara basin. Fifteen out of twenty-five districts in this basin are reported to be affected by As, where the levels of As in groundwater and soil exceed the permissible limits set by the WHO (10 µgl-1) and FAO (20 mgkg-1) respectively. These districts include a total of four municipalities in Nepal and eighty-six blocks in India, all of which have varying degrees of As contamination. Approximately 17 million people are at risk of As poisoning, with more than two orders of magnitude higher potential lifetime incremental cancer risk, constituting over 153 thousand potential additional cases of cancer due to As-contaminated drinking water. Out of the 90 As-contaminated blocks in the Ghaghara basin, 4 blocks have about 7-fold higher potential risk of developing cancer, 49 blocks have 8-37-fold higher risk, and 37 blocks have up to 375-fold higher risk compared to the upper limit of the USEPA acceptable range, which is 1 × 10-6-1 × 10-4. High accumulation of As has been reported in the nails, hair, and urine of local inhabitants, with higher levels observed in females than males. The toxicity of As is manifested in terms of a higher occurrence of various diseases. Reproductive endpoints, such as increased incidences of preterm birth, spontaneous abortion, stillbirth, low-birth weight, and neonatal death, have also been reported in the basin. The level of As in tube wells has been found to be negatively correlated with the depth (r = -0.906), and tube wells with high levels of As (>150 µgl-1) are generally located within close proximity (<10 km) to abandoned or present meander channels in the floodplain areas of the Ghaghara river. In addition to As contamination, the water quality index (WQI) in the Ghaghara basin is poor according to the BIS standards for drinking water. Groundwater in six out of fifteen districts is unsuitable for drinking purposes, with a WQI exceeding 100. The levels of As in agricultural soil in many villages of Ballia, Bahraich, and Lakhimpur Kheri districts have exceeded the FAO limit. Water from deep tube wells has been found to be relatively safe in terms of As content, and thus can be recommended for drinking purposes. However, the use of surface water needs to be encouraged for irrigation purposes in order to preserve soil health and reduce As contamination in the food chain, thereby minimizing the risk of cancer.


Assuntos
Arsênio , Água Potável , Água Subterrânea , Neoplasias , Nascimento Prematuro , Poluentes Químicos da Água , Recém-Nascido , Masculino , Gravidez , Feminino , Humanos , Arsênio/análise , Poluentes Químicos da Água/análise , Neoplasias/epidemiologia , Solo , Índia/epidemiologia , Monitoramento Ambiental
11.
Ann Maxillofac Surg ; 13(1): 116-119, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711523

RESUMO

Rationale: Vanishing bone disease (VBD) is a rare bone disorder in which progressive osteolysis may lead to complete disappearance of involved bones. The diagnosis of this disease requires a high degree of clinical suspicion. We present a case of progressive osteolysis of mandible in a patient. Patient Concerns: The patient had been without definitive diagnosis and treatment for over a year. Diagnosis: Diagnosis was made by exclusion of genetic, traumatic, inflammatory, infective, endocrine and neoplastic aetiologies and by carefully correlating clinical, imaging and histopathological findings of the patient. Treatment: Segmental resection of the advancing edge of the lesion was carried out. Outcome: The patient is disease free, with no evidence of further osteolysis, after six months of follow-up. Take-Away Lessons: This article describes the exclusion-based approach adopted to diagnose a case of VBD, aiming to standardise a workup for the diagnosis.

12.
J Pharm Bioallied Sci ; 15(Suppl 2): S968-S970, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37694093

RESUMO

Introduction: Chronic periodontitis is an infectious disease which is multifactorial in etiology. The red complex bacteria have an enzyme capable of hydrolyzing the synthetic trypsin substrate, N-benzoyl-DL-arginine-2-napthylamide (BANA). Tetracycline as a bacteriostatic agent is used in the treatment of periodontitis. Objective: The aim of this study was to evaluate clinically and microbiologically the efficacy of tetracycline fibers in conjunction with scaling and root planning in chronic periodontitis patients. Methodology: A Split mouth clinical and microbiological randomized control study was done to compare the clinical effects of subgingivally delivered antimicrobial bioabsorbable controlled release 2 mg tetracycline fibers as an adjunct to scaling and root planning on one side and comparing the other side treated only with scaling and root planning only. Result: Showed both scaling and root planning and the use of tetracycline an adjunct with scaling and root planning are equally effective. Conclusion: It can be concluded that Scaling and root planing (SRP) with or without use of adjunct local drug delivery agent like tetracycline is effective in treating chronic periodontitis.

13.
Protein Sci ; 32(10): e4779, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37695939

RESUMO

Malate (2-hydroxysuccinic acid) and tartrate (2,3-dihydroxysuccinic acid) are chiral substrates; the former existing in two enantiomeric forms (R and S) while the latter exists as three stereoisomers (R,R; S,S; and R,S). Dehydration by stereospecific hydrogen abstraction and antielimination of the hydroxyl group yield the achiral products fumarate and oxaloacetate, respectively. Class-I fumarate hydratase (FH) and L-tartrate dehydratase (L-TTD) are two highly conserved enzymes belonging to the iron-sulfur cluster hydrolyase family of enzymes that catalyze reactions on specific stereoisomers of malate and tartrate. FH from Methanocaldococcus jannaschii accepts only (S)-malate and (S,S)-tartrate as substrates while the structurally similar L-TTD from Escherichia coli accepts only (R)-malate and (R,R)-tartrate as substrates. Phylogenetic analysis reveals a common evolutionary origin of L-TTDs and two-subunit archaeal FHs suggesting a divergence during evolution that may have led to the switch in substrate stereospecificity preference. Due to the high conservation of their sequences, a molecular basis for switch in stereospecificity is not evident from analysis of crystal structures of FH and predicted structure of L-TTD. The switch in enantiomer preference may be rationalized by invoking conformational plasticity of the amino acids interacting with the substrate, together with substrate reorientation and conformer selection about the C2C3 bond of the dicarboxylic acid substrates. Although classical models of enzyme-substrate binding are insufficient to explain such a phenomenon, the enantiomer superposition model suggests that a minor reorientation in the active site residues could lead to the switch in substrate stereospecificity.


Assuntos
Malatos , Tartaratos , Humanos , Tartaratos/metabolismo , Malatos/metabolismo , Filogenia , Desidratação , Hidroliases/genética , Hidroliases/metabolismo , Fumarato Hidratase/química , Fumarato Hidratase/genética , Fumarato Hidratase/metabolismo , Escherichia coli/metabolismo , Domínio Catalítico , Especificidade por Substrato , Cinética
14.
Artigo em Inglês | MEDLINE | ID: mdl-37714050

RESUMO

Phosphatidylethanol (PEth) is a group of phospholipids formed exclusively in the presence of ethanol on the erythrocyte membrane, making it a direct biomarker for long-term ethanol consumption for which a clinical reference interval has been established. Here, we describe an assay for quantitation for two most abundant PEth homologues, PEth 16:0/18:1 and PEth 16:0/18:2, from human whole blood, and present challenges overcome throughout the development process. Since PEth is localized within erythrocyte membranes, a reliable sample preparation technique is an important aspect of PEth analysis. Therefore, various erythrocyte lysing agents for recovery of exogenously spiked standards and controls were evaluated to identify one that performed comparably to the recovery of endogenous analytes found in authentic samples. A supported liquid extraction (SLE) technique was employed for sample cleanup and enrichment which together with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis enabled automated sample preparation, appropriate chromatographic resolution, and minimal system carryover. This resulted in a laboratory developed test with an analytical measurement range (AMR) of 10-1000 ng/mL (slope = 0.9902-1.0138, R2 = 0.9958-0.9972), that was precise (intra-day precision: 3.4-4.1%; inter-day precision: 4.4-8.2% over the AMR), accurate when compared with an available external laboratory test (slope = 0.9943-1.0206, R2 = 0.9635-0.9678, no lower decision point interpretation changes), with effective analyte recovery (77.2-83.5%), and established stability characteristics, while chromatographically separating the analytes to ensure no additive effects due to the isotopic distribution of the opposing analyte.


Assuntos
Glicerofosfolipídeos , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Etanol , Biomarcadores
15.
Org Lett ; 25(32): 6029-6034, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37539966

RESUMO

Herein, we develop a metal-free, nondirected, site-selective, one-pot approach to meta-arylation of arylamines. This Brønsted acid-catalyzed, direct C-C bond formation offers a broad substrate scope and scalability and creates the ideal conditions for overriding the conventional site-selectivity to furnish meta-substituted anilines. Additionally, the protocol applies to the meta-allylation of anilines and has been extended to afford late-stage functionalization and synthesis of medicinally privileged arylated diamines and densely functionalized anilines. The control experiments and density functional theory studies provide evidence for the proposed mechanism and selectivity.

16.
Cureus ; 15(5): e39135, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37332442

RESUMO

Background Adolescence represents the period of transition from puberty to adulthood, encompassing development in the physical, cognitive, and psychosocial domains. Thus, this is a period of rapid growth, which is only second to that of infancy. Since the dietary patterns in this age group are influenced by many factors, adolescents have a higher tendency to remain malnourished. Aim and objective To find out the prevalence of and the socio-demographic factors associated with malnutrition among adolescents in a rural and an urban community of Delhi. Materials and methods This community-based cross-sectional study was conducted in rural and urban field practice areas under the aegis of the Department of Community Medicine, Maulana Azad Medical College, for the duration of one year. All eligible adolescents (10-19 years) residing in both study areas were included as the sampling frame. A total of 420 participants were enrolled in the study using the simple random sampling technique. All interviews were conducted face-to-face by the investigator to collect data on the nutritional status and socio-demographic variables of the study participants. The data were analyzed using SPSS version 26.0 (IBM Corp., Armonk, NY). Results The mean age of the participants in our study was found to be 15.65 ± 2.10 years. About 63% of males and 37% of females participated in the study. Participants from urban areas had a better socio-economic status, as 67.1% of participants were either in Class II or Class III of the modified BG Prasad Scale, vis-à-vis 36.6% of participants from rural areas. The overall prevalence of malnutrition was found to be 46% with overnutrition being more rampant than undernutrition. Conclusion The overall prevalence of malnutrition was 46% in the present study, out of which 18% were undernourished while 28% were over-nourished. The prevalence of undernutrition was approximately three times more in rural areas as compared to urban areas while the prevalence of obesity/overweight was more rampant in urban areas in comparison to rural areas.

17.
Indian J Med Res ; 157(6): 509-518, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37322634

RESUMO

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (≤ or ≥60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants - ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post-omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months.


Assuntos
COVID-19 , Humanos , Lactente , COVID-19/prevenção & controle , Imunidade Humoral , SARS-CoV-2 , ChAdOx1 nCoV-19 , Vacinação , Anticorpos Neutralizantes , Imunoglobulina G , Anticorpos Antivirais
18.
Appl Microbiol Biotechnol ; 107(12): 4009-4024, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37154908

RESUMO

Smokeless tobacco (SLT) is certainly one of the major risk factors associated with oral cancer. Disruption of oral microbiota-host homeostasis contributes to the progression of oral cancer. Here, we profiled SLT users' oral bacterial composition and inferred their functions by sequencing 16S rDNA V3-V4 region and PICRUSt2, respectively. Oral bacteriome of SLT users (with or without oral premalignant lesions), SLT with alcohol co-users, and non-SLT consumers were compared. Oral bacteriome is shaped primarily by SLT use and the incidence of oral premalignant lesions (OPL). A significantly increased bacterial α-diversity was monitored in SLT users with OPL compared to in SLT users without OPL and non-users, whereas ß-diversity was significantly explained by OPL status. Overrepresented genera were Prevotella, Fusobacterium, Veillonella, Haemophilus, Capnocytophaga, and Leptotrichia in SLT users having OPL. LEfSe analysis identified 16 genera as a biomarker that were differentially abundant in SLT users having OPL. The functional prediction of genes significantly increased for several metabolic pathways, more importantly, were nitrogen metabolism, nucleotide metabolism, energy metabolism, and biosynthesis/biodegradation of secondary metabolites in SLT users having OPL. Furthermore, HPV-16 and EBV, but not HPV-18, were considerably connected with the SLT users having OPL. Overall, this study provides evidence that SLT utilization and OPL development are associated with oral bacteriome dysbiosis indicating the enrichment of bacterial species known for their contribution to oral carcinogenesis. Therefore, delineating the cancer-inducing bacterial population in SLT users will facilitate the future development of microbiome-targeted therapies. KEY POINTS: • SLT consumption significantly elevates oral bacterial diversity. • Prevalent significant genera are Prevotella, Veillonella, and Haemophilus in SLT users with OPL. • SLT promotes the occurrence of the cancer-inducing bacterial population.


Assuntos
Neoplasias Bucais , Tabaco sem Fumaça , Humanos , Tabaco sem Fumaça/efeitos adversos , Neoplasias Bucais/etiologia , Uso de Tabaco/efeitos adversos , Uso de Tabaco/epidemiologia , Consumo de Bebidas Alcoólicas , Incidência
19.
Artigo em Inglês | MEDLINE | ID: mdl-37027790

RESUMO

Objective: To assess children in the community for autism spectrum disorder (ASD) and associated risk factors.Methods: In this 2-stage, cross-sectional study, children between 1.5 and 10 years of age were screened using the Chandigarh Autism Screening Instrument. Those with a score above the cutoff of 10 were assessed in detail using the Childhood Autism Rating Scale and the Autism Diagnostic Interview-Revised, and a detailed pediatric assessment was conducted. Risk factors were evaluated, and karyotype and fragile X genetic testing was done for those diagnosed with ASD. The study was conducted from July 2014 to December 2017.Results: Compared to the control group, mothers of ASD children had more pregnancy-induced hypertension (PIH) and bleeding per vaginum (BPV) during the antenatal period. In the multivariate analysis, there was 6.3 times higher odds of having history of PIH (P = .02) and 7.7 times higher odds of BPV (P = .011) among children with ASD. There were much higher odds of having birth asphyxia (OR = 12.6), cardiorespiratory problems (OR = 10), metabolic abnormalities (hypoglycemia/ hypocalcemia) (OR = 12), and neonatal sepsis (OR = 16) in the ASD group compared to controls.Conclusions: ASD patients experienced more antenatal and neonatal problems compared to controls.Trial Registration: Clinical Trials Registry-India (CTRI/2017/02/007935).


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Criança , Feminino , Humanos , Recém-Nascido , Gravidez , Transtorno do Espectro Autista/diagnóstico , Estudos Transversais , Mães , Fatores de Risco
20.
Indian J Psychol Med ; 45(2): 168-172, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36925495

RESUMO

Background: Family accommodation (FA) is defined as a family members' involvement by doing certain behavior in response to the daily rituals of patients with obsessive-compulsive disorder (OCD). FA is associated with more severe symptoms of OCD. Similarly, poor insight is associated with high severity of OCD symptoms. FA and insight are also related to each other, as more accommodative behavior of family members is associated with poor insight. Methods: This cross-sectional observational study assessed 103 adult OCD patients with an illness duration of at least one year. Participants were assessed using Yale-Brown Obsessive Compulsive Scale (Y-BOCS) symptom checklist, Y-BOCS to assess severity, and Family Accommodation Scale-SR (Hindi) to evaluate FA. Insight was assessed with the 11th item of Y-BOCS. Results: FA was common in the families of our participants. The mean±SD Y-BOCS score was 28.72±5.09, and the mean FAS-SR score was 44.1±12.03. A significant positive correlation existed between the FA and YBOCS scores, that is, with the increase in FA, YBOCS scores also significantly increased. A considerable number reported poor insight, and had high scores on YBOCS and their caregiver had high FA scores. Conclusion: FA is indicative of high symptom severity of OCD and higher FA is associated with poor insight, so FA needs further research for its interplay with OCD symptomatology and role in the maintenance of symptoms.

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