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Cenchrus americanus (L.) Morrone (Poaceae), is an important millet crop cultivated mainly in arid and semiarid regions and is a staple food grain for millions of people. During 2021 July surveys in the pearl millet fields in Mysore (12°30'55" N; 76°56'54" E), Karnataka, India, plants showed spathe blight and leaf spot disease with an overall incidence ranging from 5 - 8% in the 15 hectares surveyed. Infected leaves appeared brown, and lesions extended to the sheath. Some spathes were also found infected with similar symptoms. Diseased leaves and spathes were collected (n = 5 each) for pathogen identification. Samples were cut into small pieces (0.5 cm2), sterilized with sodium hypochlorite (2%, v/v), and blotted dried. The associated fungal pathogen was isolated on potato dextrose agar (PDA) medium amended with Streptomycin (40 mg/L) and incubated at 28 ºC for 1 week. Colonies were grey, fluffy, cottony with an irregular margin, undulate and dark brown in the back of the plate. Conidiophores were pale brown, erect, slightly curved, septate, unbranched, verruculose and measured 27.1 - 94 µm in length × 2.3 - 4.5 µm in width (n = 20). Conidiogenous cells were brown, subcylindrical, irregularly shaped, and conidia were straight, mainly elliptical, dark brown smooth, with two to three septa, with measurements of 11.1 - 26.4 µm by 5.7 - 14.3 µm (n = 50). Based on morphological characters, the pathogen was identified as Curvularia sp. Two representative isolates (UOMPM1 & UOMPM2) were molecularly identified. The total genomic DNA was extracted with a CTAB method, and ITS, GAPDH and tef-1α loci were amplified using primers ITS1/ITS4 (White et al., 1990), GPD1/GPD2 (Berbee et al., 1999) and EF1983F/EF-2218R (Schoch et al., 2009) respectively. ITS sequence had 100% similarity (706/706bp) with reference sequence C. spicifera (MH863648; HF934915 & HF934916); tef-1α sequence had 100% (933/933bp) identity with C. spicifera (KM062878, KJ939505), and the GAPDH sequence was 99.8% identical to that of Curvularia sp. (MG979055), and C. spicifera (MH809681). Combined dataset of concatenated sequence (ITS-GAPDH-tef-1α) was used in a phylogenetic analysis and revealed that the isolates were in a common clade with the isolate of Curvularia spicifera (CBS 274.52) thus, confirming the identity of the isolated pathogen as C. spicifera. The sequences obtained in the present study were deposited in the GenBank (ITS: OQ253406, OQ253407; LSU: OQ253429, OQ253430; GAPDH: OQ263372, OQ263373 & TEF: OQ263374, OQ263375). Pathogenicity test was carried out by inoculating (foliar /whole plant spray) 60 healthy pearl millet plants (45-days old), grown in field plot with spore suspension (105 conidia/ml). Control plants (n=20) were treated with sterile water. The experiments were conducted in triplicates and repeated twice. Development of disease symptoms was recorded on 41 plants, and all control plants remained healthy. The identity was confirmed after re-isolation as C. spicifera based on cultural and molecular sequence analysis. To our knowledge, this is the first report of C. spicifera causing a leaf spot and spathe blight disease of pearl millet in India. This disease seriously affects grain production, and effective disease management strategies need to be investigated.
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ABSTRACT: Stroke remained the second leading cause of death globally in 2019. The antiplatelet drug clopidogrel is used to keep blood clots from forming in people who have experienced a stroke. Although most people find clopidogrel to be safe and beneficial, there is inevitably a range in how each patient responds.The review covers about Clopidogrel resistance in stroke patients, their risk factors and the methods to identify it. Clopidogrel resistance is characterized as the drug's inability to prevent the target enzyme from acting. The prognosis of patients with ischemic stroke and the responsiveness to clopidogrel are significantly impacted by the various genetic polymorphism CYP2C19 genotypes. The two primary mutant alleles, CYP2C19 *2 and CYP2C19 *3, have been found to be the most prevalent genotypes. Better mRS scores six months after treatment showed a higher response rate in patients without these CYP2C19 variant alleles. Other factors are drug-drug interaction (proton pump inhibitors), demographics (age, sex, social history), comorbid conditions, etc. Blood samples for testing platelet reactivity were drawn one month after discharge from a peripheral blood sample. Several methods are used to identify the clopidogrel resistance. Some of them are ADP-Induced platelet aggregation, Platelet Reactivity Index VASP, Verify Now Assay, TEG Analyzer, Plasma microRNA-223. Drugs that are not prodrugs and whose metabolism is not dependent upon CYP2C19 can be selected as a superior alternative in case of CR. Ticagrelor is one such effective substitute. Proton pump inhibitors and clopidogrel should only be used concurrently in patients with reliable clinical indications.
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Applications of multidimensional forced choice (MFC) testing have increased considerably over the last 20 years. Yet there has been little, if any, research on methods for linking the parameter estimates from different samples. This research addressed that important need by extending four widely used methods for unidimensional linking and comparing the efficacy of new estimation algorithms for MFC linking coefficients based on the Multi-Unidimensional Pairwise Preference model (MUPP). More specifically, we compared the efficacy of multidimensional test characteristic curve (TCC), item characteristic curve (ICC; Haebara, 1980), mean/mean (M/M), and mean/sigma (M/S) methods in a Monte Carlo study that also manipulated test length, test dimensionality, sample size, percentage of anchor items, and linking scenarios. Results indicated that the ICC method outperformed the M/M method, which was better than the M/S method, with the TCC method being the least effective. However, as the number of items "per dimension" and the percentage of anchor items increased, the differences between the ICC, M/M, and M/S methods decreased. Study implications and practical recommendations for MUPP linking, as well as limitations, are discussed.
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For treating chronic diseases like rheumatoid arthritis, herbal medicines are preferred due to their evident therapeutic effects and lesser side effects as compared to the long-term used conventional drugs. In this study, the anti-rheumatoid arthritis effect of an unexplored marine grass Halodule pinifolia (HP), and a combination of it with Glycyrrhiza glabra (liquorice; LQ), prepared as a conventional suspension (C1) and a lipid nano-emulsion (C1-N) was evaluated in Freund's complete adjuvant (FCA)- and collagen-induced arthritis (CIA) models. Formulations C1 and C1-N contained standardized extract HP (100 mg/kg) as major active ingredient and liquorice LQ (50 mg/kg) as both active ingredient (anti-inflammatory and anti-ulcer) and sweetening agent. Oral administration of HP and C1 to FCA-induced Sprague-Dawley rats significantly reduced the paw oedema, spleen index, controlled the haematological parameters, cytokine levels (IL-1ß, IL-6, TNF-α estimated by ELISA), mRNA expression of cytokines and osteoclast markers (RANK, TRAP and cathepsin K measured by RTPCR). Histopathology and radiological scanning demonstrated lesser joint deterioration in sample-treated rats, as evident phenotypically. The downregulation of CD51 and MMP-3 (western blot) corroborated the anti-arthritic effect of HP and C1. HP showed better results among all. Further, under the CIA model, both C1 and C1-N were found to be potentially active as evidenced by their effect on rat paw oedema, spleen index, haematological parameters, rheumatoid factor, cytokines, osteoclast markers, histology and X-rays. The results proved the anti-arthritic effect of HP and the formulations, particularly the lipid nano-emulsion that showed improved stability as well as activity.
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Artrite Experimental , Artrite Reumatoide , Ratos , Animais , Ratos Sprague-Dawley , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Experimental/metabolismo , Citocinas/metabolismo , Edema/tratamento farmacológico , LipídeosRESUMO
Interleukin-1-beta (IL-1ß) one of the biomarkers for oral squamous cell carcinoma (OSCC), is upregulated in tumor-microenvironment (TME) and associated with poor patient survival. Thus, a novel modulator of IL-1ß would be of great therapeutic value for OSCC treatment. Here we report regulation of IL-1ß and TME by histone deacetylase-6 (HDAC6)-inhibitor in OSCC. We observed significant upregulation of HDAC6 in 4-nitroquniline (4-NQO)-induced OSCC in mice and 4-NQO & Lipopolysaccharide (LPS) stimulated OSCC and fibroblast cells. Tubastatin A (TSA)-attenuated the OSCC progression in mice as observed improvement in the histology over tongue and esophagus, with reduced tumor burden. TSA treatment to 4-NQO mice attenuated protein expression of HDAC6, pro-and-mature-IL-1ß and pro-and-cleaved-caspase-1 and ameliorated acetylated-tubulin. In support of our experimental work, human TCGA analysis revealed HDAC6 and IL-1ß were upregulated in the primary tumor, with different tumor stages and grades. We found TSA modulate TME, indicated by downregulation of CD11b+Gr1+-Myeloid-derived suppressor cells, CD11b+F4/80+CD206+ M2-macrophages and increase in CD11b+F4/80+MHCII+ M1-macrophages. TSA significantly reduced the gene expression of HDAC6, IL-1ß, Arginase-1 and iNOS in isolated splenic-MDSCs. FaDu-HTB-43 and NIH3T3 cells stimulated with LPS and 4-NQO exhibit higher IL-1ß levels in the supernatant. Interestingly, immunoblot analysis of the cell lysate, we observed that TSA does not alter the expression as well as activation of IL-1ß and caspase-1 but the acetylated-tubulin was found to be increased. Nocodazole pre-treatment proved that TSA inhibited the lysosomal exocytosis of IL-1ß through tubulin acetylation. In conclusion, HDAC6 inhibitors attenuated TME and cancer progression through the regulation of IL-1ß in OSCC.
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Desacetilase 6 de Histona , Inibidores de Histona Desacetilases , Ácidos Hidroxâmicos , Indóis , Interleucina-1beta , Neoplasias Bucais , Microambiente Tumoral , Animais , Desacetilase 6 de Histona/antagonistas & inibidores , Desacetilase 6 de Histona/metabolismo , Interleucina-1beta/metabolismo , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/imunologia , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Camundongos , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/imunologia , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral , Progressão da Doença , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/imunologia , Masculino , Tubulina (Proteína)/metabolismo , LipopolissacarídeosRESUMO
3D facial CT has evolved and revolutionized diagnosis leading to better management. The limitations of conventional 2D methods limit the therapeutic options related to leading to an erroneous treatment. Although 3D facial CT is expensive, its advantages outweigh the cons. They are used in surgery, prosthetic replacement, orthodontics and forensics.
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Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Imageamento Tridimensional/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
This study investigated the expression patterns of certain ATP synthesis associated genes (GAPDHS, PGK2, ENO4 and MDH2) in fresh and frozen-thawed bubaline spermatozoa vis-à-vis capacitation. Eight adult Murrah buffalo bulls, aged 5-7 years, were randomly selected from a bull farm and fresh semen was collected once a week for four weeks (n = 32) from the selected bulls. Simultaneously, frozen straws of the same bulls were collected (n = 32, four straws were pooled per sample). The samples were divided into four groups i.e., fresh non capacitated (control/group 1), fresh capacitated (group 2), frozen non capacitated (group 3) and frozen capacitated (group 4). In all groups mRNA extraction was done. The mRNA expression of GAPDHS was significantly higher in group 3 compared to the other groups, whereas the expression of ENO4 was significantly up-regulated in group 2 and 3 compared to the group 4. Similarly, the mRNA expression of PGK2 was significantly up-regulated in group 3 whereas in case of MDH2, it was significantly higher in group 2, 3 and 4 compared group 1. It can be concluded from our study that freezing and capacitation has a significant effect on the expression dynamics of the ATP synthesis-associated genes warranting necessary interventions in handling procedures to minimise the adverse effect of freezing on ATP synthesis process to ensure persistence of fertilizing ability of sperm.
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Background and Aims: It is challenging to give the patient position for subarachnoid block (SAB) as intertrochanteric (IT) fracture of the femur produces intolerable pain. In this study, we have analyzed the usefulness of combined ultrasonography (USG)-guided femoral nerve block (FNB) and lateral femoral cutaneous nerve block (LFCNB) to reduce the fracture pain before performing SAB. Material and Methods: A prospective, randomized, comparative study was conducted on 60 American society of anesthesiologists (ASA) grade I and II patients (18-80 years) scheduled for elective IT fracture surgery. Group A (n = 30) patients received USG-guided FNB and LFCNB using 0.75% ropivacaine before SAB. Group B patients (n = 30) received SAB only. All the patients received SAB (3 mL of 0.5% bupivacaine) by an anesthesiologist blinded to the patient groups. The patients were observed for quality of patient positioning for SAB, perioperative visual analog scale (VAS) scores, time to administration of SAB, and duration of analgesia and motor blockade. Statistical analysis was done by Student's t-test and Chi-square test. Results: Baseline VAS score (T1) was similar in both the groups. Mean T2 (VAS score just before SAB) in group-A (3.2 ± 0.98) was lower compared to group-B (8.23 ± 0.7) with P < 0.0001. The quality of patient positioning in group-A was good to optimal but in group-B, it was satisfactory to not satisfactory. Group-A had longer mean duration of analgesia 804 ± 114.28 minutes with P value < 0.0001 than group-B in which it was 200 ± 28.77 min. Backache was significant in group-B with P value of 0.038 compared to group-A. Conclusion: USG-guided FNB and LFCNB can be used as an effective supplementation to SAB in patients undergoing surgery for IT fracture of the femur as it reduces fracture site pain, provides good patient positioning during SAB, and prolongs postoperative analgesia.
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There is global digitalization. With the increased use of computers in the workplace, refraction and dry eye related health concerns are developing. This study is conducted to evaluate the effects of long-term computer use on tear production and evaporation. Thisis a cross-sectional study among 97 computer operators in a Tertiary care centre. Dry eye disease was assessed subjectively with the Ocular Surface Disease Index (OSDI) questionnaire and objectively by performing Schirmer's test and Tear Break-up Time (TBUT). Majority of participants (59.2%) were male's age group between 36- 40 years. The prevalence of dry eye among the computer Operators was found to be 51%. Mean TBUT and mean Schirmer's Test value for those with dry eye was 12.65s and 10.3mm respectively. This study showed that a positive relation between dry eye and computer usage. Computer users are predisposed to developing dry eye diseases. It is therefore necessary for them to go for regular ophthalmic examination to prevent dry eye symptoms and disease.
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Torsion of epididymal cyst (EC) is an exceedingly rare cause of acute scrotum in both children and adults. We add our case as the ninth case to literature which was an 8-year-old child presented with features of acute scrotum with history of EC on conservative management. Doppler sonography showed perfused normal bilateral testes and a 4.1 × 1.7 cm septate cystic lesion of right epididymis. On scrotal exploration, we found a haemorrhagic cystic lesion attached to the upper pole of right testis and twisted for 540 degrees with normal testis and appendage. Cyst was excised, and histopathology revealed a haemorrhagic EC. Our case was peculiar due to, presenting as acute scrotum in a child of 1-10 years age group who was conservatively managed for right-sided EC and presence of 540 degrees torsion.
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INTRODUCTION: Omental tuberculosis is a rare disease which can mimic Gastrointestinal malignancies. It should be considered as one of the differential diagnosis when the patient presents with abdominal mass with vague symptoms. Histological diagnosis is the final conclusion in these patients. PRESENTATION OF CASE: An elderly male patient who presented with epigastric pain with epigastric mass and diagnosed with omental tuberculosis as a result of USS guided tissue biopsy revealed granuloma with central caseous necrosis. The size of the mass completely resolved after completion of anti TB treatment in this patient. DISCUSSION: Presence of caseous necrosis with granulomas in histology and positive culture of tuberculosis from tissue are the definitive diagnosis for omental tuberculosis. And the response to treatment with anti TB drug supports the diagnosis. CONCLUSION: Omental TB is a rare entity which can be misdiagnosed as GI malignancies. Medical management is the treatment of choice for omental TB. Surgery is needed when complications occur in extrapulmonary TB.
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Polymer fibers with specific chemical and mechanical properties are key components of many biomaterials used for regenerative medicine and drug delivery. Here, we develop a bioinspired, low-energy process to produce mechanically tunable biopolymer fibers drawn from aqueous solutions. Hyaluronic acid (HA) forms dynamic cross-links with branched polyethylene glycol polymers end-functionalized with boronic acids of varied structure to produce extensible polymer networks. This dynamic fiber precursor (DFP) is directly drawn by pultrusion into HA fibers that display high aspect ratios, ranging from 4 to 20 µm in diameter and up to â¼10 m in length. Dynamic rheology measurements of the DFP and tensile testing of the resulting fibers reveal design considerations to tune the propensity for fiber formation and fiber mechanical properties, including the effect of polymer structure and concentration on elastic modulus, tensile strength, and ultimate strain. The materials' humidity-responsive contractile behavior, a unique property of spider silks rarely observed in synthetic materials, highlights possibilities for further biomimetic and stimulus-responsive fiber applications. This work demonstrates that chemical modification of dynamic interactions can be used to tune the mechanical properties of pultrusion-based fibers and their precursors.
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Ácido Hialurônico/química , Polietilenoglicóis/química , Materiais Biomiméticos/química , Módulo de Elasticidade , Umidade , Reologia , Resistência à TraçãoRESUMO
Schwartz Jampel syndrome is a very rare genetically heterogenous disorder characterized by myotonia, typical facies, growth retardation and osteoarticular changes. Prevelance of this syndrome is <1 in 100000. 150 cases have been reported in medical literature so far. We hereby report this rare syndrome in neurology.
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Osteocondrodisplasias , Humanos , SíndromeRESUMO
In this paper, we introduce an integrated, portable, affordable and simple to use heart rate variability (HRV) analysis tool STREME. The system consists of an ECG acquisition device and software for HRV analysis. We assessed the reliability and validity of using STREME against the reference standards RMS VarioWin and Kubios HRV for the short term HRV analysis. The validation study was carried out with the participation of 46 healthy subjects that included 15 men and 31 women with an average age of 27.67 ± 7.75yrs. The results showed that there is a significantly strong correlation (r > 0.95, p < 0.001) between STREME and reference systems in HRV indices. The Bland-Altman analysis of all features computed from STREME and reference system represent a close agreement for all the parameters. Hence STREME HRV analysis tool can be recommended to researchers and other professionals for the evaluation of autonomic function using short term HRV.
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Eletrocardiografia , Software , Adulto , Feminino , Voluntários Saudáveis , Frequência Cardíaca , Humanos , Masculino , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Lipopolysaccharide (LPS) elicitors isolated from Pseudomonas fluorescens UOM SAR 14 effectively induced systemic and durable resistance against pearl millet downy mildew disease caused by the oomycete Sclerospora graminicola. Rapid and increased callose deposition and H2O2 accumulation were evidenced in downy mildew susceptible seeds pre-treated with LPS (SLPS) in comparison with the control seedlings, which also correlated with expression of various other defense responses. Biochemical analysis of enzymes and quantitative real-time polymerase chain reaction data suggested that LPS protects pearl millet against downy mildew through the activation of plant defense mechanisms such as generation of nitric oxide (NO), increased expression, and activities of defense enzymes and proteins. Elevation of NO concentrations was shown to be essential for LPS-mediated defense manifestation in pearl millet and had an impact on the other downstream defense responses like enhanced activation of enzymes and pathogen-related (PR) proteins. Temporal expression analysis of defense enzymes and PR-proteins in SLPS seedlings challenged with the downy mildew pathogen revealed that the activity and expression of peroxidase, phenylalanine ammonia lyase, and the PR-proteins (PR-1 and PR-5) were significantly enhanced compared to untreated control. Higher gene expression and protein activities of hydroxyproline-rich glycoproteins (HRGPs) were observed in SLPS seedlings which were similar to that of the resistant check. Collectively, our results suggest that, in pearl millet-downy mildew interaction, LPS pre-treatment affects defense signaling through the central regulator NO which triggers the activities of PAL, POX, PR-1, PR-5, and HRGPs.
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Mycobacteriophage Superphikiman is a cluster J bacteriophage which was isolated from soil collected in Philadelphia, PA. Superphikiman has a 109,799-bp genome with 239 predicted genes, including 2 tRNA genes.
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The World Health Organization's Expanded Programme on Immunization has led to a dramatic rise in worldwide vaccination rates over the past 40years, yet 19.4 million infants remain underimmunized each year. Many of these infants have received at least one vaccine dose but may remain unprotected because they did not receive subsequent booster doses due to logistical challenges. This study aimed to develop injectable controlled release microparticles with kinetics that mimic common vaccine dosing regimens consisting of large antigen doses administered periodically over the course of months in order to eliminate the need for boosters. Sixteen poly(lactic-co-glycolic acid) (PLGA) microsphere formulations containing bovine serum albumin (BSA) as a model vaccine antigen were screened in vitro to determine their respective release kinetics. Three formulations that exhibited desirable pulsatile release profiles were then selected for studying immunogenicity in mice. Two low-dose microsphere formulations induced peak anti-BSA IgG antibody titers of 13.9±1.3 and 13.7±2.2 log2 compared to 15.5±1.5 log2 for a series of three bolus injections delivered at 0, 4, and 8weeks with an equivalent cumulative dose. Similarly, high-dose formulations induced peak antibody titers that were 16.1±2.1 log2 compared to 17.7±2.2 log2 for controls. All three microparticle formulations studied in vivo induced peak antibody titers that were statistically similar to bolus controls. These results suggest that pulsatile antigen release from polymeric microparticles is a promising approach for single-injection vaccination, which could potentially reduce the logistical burden associated with immunization in the developing world.
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Imunogenicidade da Vacina , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Soroalbumina Bovina/administração & dosagem , Vacinação/métodos , Animais , Anticorpos/sangue , Feminino , Injeções , Cinética , Camundongos , Camundongos Endogâmicos BALB CRESUMO
CONTEXT: Common intronic variants of the fat mass and obesity-associated (FTO) gene have been associated with obesity-related traits in humans. AIMS: (1) The aim of this study is to study the distribution of FTO gene variants across different body mass index (BMI) categories and (2) to explore the association between FTO gene variants and lifestyle factors in obese and normal weight Indian children. SUBJECTS AND METHODS: Fifty-six children (26 boys, mean age 10.3 ± 2.2 years) were studied. Height, weight, and waist and hip circumference were measured. Physical activity (questionnaire) and food intake (food frequency questionnaire) were assessed. Body fat percentage (%BF) was measured by dual-energy X-ray absorptiometry. FTO allelic variants at rs9939609 site were detected by SYBR Green Amplification Refractory Mutation System real-time polymerase chain reaction using allele-specific primers. Generalized linear model was used to investigate the simultaneous influence of genetic and lifestyle factors on %BF. RESULTS: Mean height, weight, and BMI of normal and obese children were 130.6 ± 7.1 versus 143.2 ± 15.6, 24.0 ± 5.2 versus 53.1 ± 15.8, and 13.9 ± 2.1 versus 25.3 ± 3.2, respectively. The frequency of AA allele was 57% among obese children and 35% in normal weight children. Children with the AA allele who were obese had least physical activity, whereas children with AT allele and obesity had the highest intake of calories when compared to children who had AT allele and were normal. %BF was positively associated with AA alleles and junk food intake and negatively with healthy food intake and moderate physical activity. CONCLUSIONS: Healthy lifestyle with high physical activity and diet low in calories and fat may help in modifying the risk imposed by FTO variants in children.
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The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality. Specifically, a series of cucurbit[7]uril (CB[7])-PEG conjugates are shown to substantially increase the stability of three distinct protein drugs in formulation. Leveraging the known and high-affinity interaction between CB[7] and an N-terminal aromatic residue on one specific protein drug, insulin, further results in altering of its pharmacological properties in vivo by extending activity in a manner dependent on molecular weight of the attached PEG chain. Supramolecular modification of therapeutic proteins affords a noncovalent route to modify its properties, improving protein stability and activity as a formulation excipient. Furthermore, this offers a modular approach to append functionality to biopharmaceuticals by noncovalent modification with other molecules or polymers, for applications in formulation or therapy.
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Composição de Medicamentos/métodos , Desenho de Fármacos , Polietilenoglicóis/química , Animais , Biofarmácia/métodos , Hidrocarbonetos Aromáticos com Pontes/química , Linhagem Celular , Química Click , Sistemas de Liberação de Medicamentos , Humanos , Imidazóis/química , Insulina/química , Insulina/farmacocinética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Engenharia de Proteínas , Estabilidade Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacocinéticaRESUMO
OBJECTIVES: Medication communication skills are vital aspects of patient care that may influence treatment outcomes. However, traditional pharmacology curriculum deals with imparting factual information, with little emphasis on patient communication. The current study aims to explore students' perceptions of role-play as an educational tool in acquiring communication skills and to ascertain the need of role-play for their future clinical practice. MATERIALS AND METHODS: This questionnaire-based study was done in 2nd professional MBBS students. A consolidated concept of six training cases, focusing on major communication issues related to medication prescription in pharmacology, were developed for peer-role-play sessions for 2nd professional MBBS (n = 122) students. Structured scripts with specific emphasis on prescription medication communication and checklists for feedback were developed. Prevalidated questionnaires measured the quantitative aspects of role-plays in relation to their relevance as teaching-learning tool, perceived benefits of sessions, and their importance for future use. STATISTICAL ANALYSIS: Data analysis was performed using descriptive statistics. RESULTS: The role-play concept was well appreciated and considered an effective means for acquiring medication communication skills. The structured feedback by peers and faculty was well received by many. Over 90% of the students reported immense confidence in communicating therapy details, namely, drug name, purpose, mechanism, dosing details, and precautions. Majority reported a better retention of pharmacology concepts and preferred more such sessions. CONCLUSIONS: Most students consider peer-role-play as an indispensable tool to acquire effective communication skills regarding drug therapy. By virtue of providing experiential learning opportunities and its feasibility of implementation, role-play sessions justify inclusion in undergraduate medical curricula.