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1.
ACS Omega ; 9(13): 14648-14671, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38585101

RESUMO

The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut-lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut-lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.

2.
Geroscience ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38499959

RESUMO

Mice with cardiac-specific overexpression of adenylyl cyclase (AC) type 8 (TGAC8) are under a constant state of severe myocardial stress. They have a remarkable ability to adapt to this stress, but they eventually develop accelerated cardiac aging and experience reduced longevity. We have previously demonstrated through bioinformatics that constitutive adenylyl cyclase activation in TGAC8 mice is associated with the activation of inflammation-related signaling pathways. However, the immune response associated with chronic myocardial stress in the TGAC8 mouse remains unexplored. Here we demonstrate that chronic activation of adenylyl cyclase in cardiomyocytes of TGAC8 mice results in activation of cell-autonomous RelA-mediated NF-κB signaling. This is associated with non-cell-autonomous activation of proinflammatory and age-associated signaling in myocardial endothelial cells and myocardial smooth muscle cells, expansion of myocardial immune cells, increase in serum levels of inflammatory cytokines, and changes in the size or composition of lymphoid organs. All these changes precede the appearance of cardiac fibrosis. We provide evidence indicating that RelA activation in cardiomyocytes with chronic activation of adenylyl cyclase is mediated by calcium-protein Kinase A (PKA) signaling. Using a model of chronic cardiomyocyte stress and accelerated aging, we highlight a novel, calcium/PKA/RelA-dependent connection between cardiomyocyte stress, myocardial inflammation, and systemic inflammation. These findings suggest that RelA-mediated signaling in cardiomyocytes might be an adaptive response to stress that, when chronically activated, ultimately contributes to both cardiac and systemic aging.

4.
Mol Metab ; 82: 101906, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423253

RESUMO

OBJECTIVE: Type 1 diabetes (T1D) occurs because of islet infiltration by autoreactive immune cells leading to destruction of beta cells and it is becoming evident that beta cell dysfunction partakes in this process. We previously reported that genetic deletion and pharmacological antagonism of the cannabinoid 1 receptor (CB1) in mice improves insulin synthesis and secretion, upregulates glucose sensing machinery, favors beta cell survival by reducing apoptosis, and enhances beta cell proliferation. Moreover, beta cell specific deletion of CB1 protected mice fed a high fat high sugar diet against islet inflammation and beta cell dysfunction. Therefore, we hypothesized that it would mitigate the dysfunction of beta cells in the precipitating events leading to T1D. METHODS: We genetically deleted CB1 specifically from beta cells in non-obese diabetic (NOD; NOD RIP Cre+ Cnr1fl/fl) mice. We evaluated female NOD RIP Cre+ Cnr1fl/fl mice and their NOD RIP Cre-Cnr1fl/fl and NOD RIP Cre+ Cnr1Wt/Wt littermates for onset of hyperglycemia over 26 weeks. We also examined islet morphology, islet infiltration by immune cells and beta cell function and proliferation. RESULTS: Beta cell specific deletion of CB1 in NOD mice significantly reduced the incidence of hyperglycemia by preserving beta cell function and mass. Deletion also prevented beta cell apoptosis and aggressive insulitis in NOD RIP Cre+ Cnr1fl/fl mice compared to wild-type littermates. NOD RIP Cre+ Cnr1fl/fl islets maintained normal morphology with no evidence of beta cell dedifferentiation or appearance of extra islet beta cells, indicating that protection from autoimmunity is inherent to genetic deletion of beta cell CB1. Pancreatic lymph node Treg cells were significantly higher in NOD RIP Cre+ Cnr1fl/flvs NOD RIP Cre-Cnr1fl/fl. CONCLUSIONS: Collectively these data demonstrate how protection of beta cells from metabolic stress during the active phase of T1D can ameliorate destructive insulitis and provides evidence for CB1 as a potential pharmacologic target in T1D.


Assuntos
Canabinoides , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Hiperglicemia , Ilhotas Pancreáticas , Camundongos , Feminino , Animais , Camundongos Endogâmicos NOD , Diabetes Mellitus Tipo 1/metabolismo , Ilhotas Pancreáticas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Canabinoides/metabolismo , Hiperglicemia/genética , Hiperglicemia/metabolismo
5.
Biophys J ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38268189

RESUMO

Time-dependent single-molecule experiments contain rich kinetic information about the functional dynamics of biomolecules. A key step in extracting this information is the application of kinetic models, such as hidden Markov models (HMMs), which characterize the molecular mechanism governing the experimental system. Unfortunately, researchers rarely know the physicochemical details of this molecular mechanism a priori, which raises questions about how to select the most appropriate kinetic model for a given single-molecule data set and what consequences arise if the wrong model is chosen. To address these questions, we have developed and used time-series modeling, analysis, and visualization environment (tMAVEN), a comprehensive, open-source, and extensible software platform. tMAVEN can perform each step of the single-molecule analysis pipeline, from preprocessing to kinetic modeling to plotting, and has been designed to enable the analysis of a single-molecule data set with multiple types of kinetic models. Using tMAVEN, we have systematically investigated mismatches between kinetic models and molecular mechanisms by analyzing simulated examples of prototypical single-molecule data sets exhibiting common experimental complications, such as molecular heterogeneity, with a series of different types of HMMs. Our results show that no single kinetic modeling strategy is mathematically appropriate for all experimental contexts. Indeed, HMMs only correctly capture the underlying molecular mechanism in the simplest of cases. As such, researchers must modify HMMs using physicochemical principles to avoid the risk of missing the significant biological and biophysical insights into molecular heterogeneity that their experiments provide. By enabling the facile, side-by-side application of multiple types of kinetic models to individual single-molecule data sets, tMAVEN allows researchers to carefully tailor their modeling approach to match the complexity of the underlying biomolecular dynamics and increase the accuracy of their single-molecule data analyses.

6.
bioRxiv ; 2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-37645812

RESUMO

Time-dependent single-molecule experiments contain rich kinetic information about the functional dynamics of biomolecules. A key step in extracting this information is the application of kinetic models, such as hidden Markov models (HMMs), which characterize the molecular mechanism governing the experimental system. Unfortunately, researchers rarely know the physico-chemical details of this molecular mechanism a priori, which raises questions about how to select the most appropriate kinetic model for a given single-molecule dataset and what consequences arise if the wrong model is chosen. To address these questions, we have developed and used time-series Modeling, Analysis, and Visualization ENvironment (tMAVEN), a comprehensive, open-source, and extensible software platform. tMAVEN can perform each step of the single-molecule analysis pipeline, from pre-processing to kinetic modeling to plotting, and has been designed to enable the analysis of a single-molecule dataset with multiple types of kinetic models. Using tMAVEN, we have systematically investigated mismatches between kinetic models and molecular mechanisms by analyzing simulated examples of prototypical single-molecule datasets exhibiting common experimental complications, such as molecular heterogeneity, with a series of different types of HMMs. Our results show that no single kinetic modeling strategy is mathematically appropriate for all experimental contexts. Indeed, HMMs only correctly capture the underlying molecular mechanism in the simplest of cases. As such, researchers must modify HMMs using physico-chemical principles to avoid the risk of missing the significant biological and biophysical insights into molecular heterogeneity that their experiments provide. By enabling the facile, side-by-side application of multiple types of kinetic models to individual single-molecule datasets, tMAVEN allows researchers to carefully tailor their modeling approach to match the complexity of the underlying biomolecular dynamics and increase the accuracy of their single-molecule data analyses.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38155014

RESUMO

Primary intraosseous carcinoma (PIOC) of the jaw is a rare neoplasm arising from the lining epithelium of odontogenic cysts or de novo from odontogenic epithelial rests that has no communication with the surrounding mucosa of the upper aerodigestive tract. We present a case of PIOC ex-odontogenic keratocyst (PIOC ex-OKC) in a 35-year-old male. Histopathologic examination revealed a cystic lesion with a fibrous capsule lined by corrugated parakeratinized stratified squamous epithelium resting on a basal cell layer composed of columnar cells exhibiting palisaded hyperchromatic nuclei, features consistent with OKC. Surgical treatment consisted of bilateral crestal and crevicular incision, a reflection of the flap, breaking of all OKC locules, creation of a continuous cavity, and fitting of a decompression mold around the mandibular teeth. This case highlights the importance of knowing the features of PIOC and considering PIOC in the differential diagnosis of malignant tumors of odontogenic epithelium for timely surgical treatment.


Assuntos
Carcinoma de Células Escamosas , Cistos Odontogênicos , Tumores Odontogênicos , Masculino , Humanos , Adulto , Carcinoma de Células Escamosas/patologia , Tumores Odontogênicos/cirurgia , Tumores Odontogênicos/patologia , Cistos Odontogênicos/cirurgia , Cistos Odontogênicos/patologia , Diagnóstico Diferencial
8.
Clin Med Insights Endocrinol Diabetes ; 16: 11795514231220780, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38148756

RESUMO

A complex metabolic condition referred to as Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and decreased insulin production. Obesity, dyslipidemia, hypertension, and chronic inflammation are just a few of the cardiometabolic illnesses that people with T2DM are more likely to acquire and results in cardiovascular issues. It is essential to comprehend the mechanistic insights into these risk variables in order to prevent and manage cardiovascular problems in T2DM effectively. Impaired glycemic control leads to upregulation of De novo lipogenesis (DNL), promote hepatic triglyceride (TG) synthesis, worsening dyslipidemia that is accompanied by low levels of high density lipoprotein cholesterol (HDL-C) and high amounts of small, dense low-density lipoprotein cholesterol (LDL-C) further developing atherosclerosis. By causing endothelial dysfunction, oxidative stress, and chronic inflammation, chronic hyperglycemia worsens already existing cardiometabolic risk factors. Vasoconstriction, inflammation, and platelet aggregation are caused by endothelial dysfunction, which is characterized by decreased nitric oxide production, increased release of vasoconstrictors, proinflammatory cytokines, and adhesion molecules. The loop of IR and endothelial dysfunction is sustained by chronic inflammation fueled by inflammatory mediators produced in adipose tissue. Infiltrating inflammatory cells exacerbate inflammation and the development of plaque in the artery wall. In addition, the combination of chronic inflammation, dyslipidemia, and IR contributes to the emergence of hypertension, a prevalent comorbidity in T2DM. The ability to target therapies and management techniques is made possible by improvements in our knowledge of these mechanistic insights. Aim of present review is to enhance our current understanding of the mechanistic insights into the cardiometabolic risk factors related to T2DM provides important details into the interaction of pathophysiological processes resulting in cardiovascular problems. Understanding these pathways will enable us to create efficient plans for the prevention, detection, and treatment of cardiovascular problems in T2DM patients, ultimately leading to better overall health outcomes.


Understanding the factors that increase the risk of type 2 diabetes: Exploring how the body works Type 2 diabetes mellitus (T2DM) is a complex condition where the body struggles to use insulin properly and doesn't produce enough of it. This often leads to other health issues like obesity, high cholesterol, high blood pressure, and chronic inflammation. These problems increase the risk of heart and blood vessel diseases in people with T2DM. To tackle these issues effectively, it's crucial to understand the underlying mechanisms. When blood sugar levels are not controlled, the body starts making more fat and storing it in the liver, leading to high triglycerides and low levels of good cholesterol. This process can block arteries, causing heart problems. High blood sugar also damages blood vessel linings, making them inflamed and less functional. This inflammation, combined with other factors like high cholesterol and insulin resistance, can lead to high blood pressure. Chronic inflammation, where the body's defense system stays active for too long, worsens these problems. In T2DM, inflammation occurs in fat tissues, making the situation even worse. Inflammatory cells infiltrate blood vessel walls, promoting plaque buildup and further worsening heart issues. Understanding these processes helps us develop better strategies to prevent, detect, and treat heart problems in people with T2DM. By targeting these mechanisms, doctors can create more effective plans to improve the overall health of individuals with diabetes and reduce the risk of cardiovascular diseases.

9.
Curr Microbiol ; 81(1): 16, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38006423

RESUMO

Humans are colonized by large number of microorganisms-bacteria, fungi, and viruses. The overall genome of entire viruses that either lives on or inside the human body makes up the human virome and is indeed an essential fraction of the human metagenome. Humans are constantly exposed to viruses as they are ubiquitously present on earth. The human virobiota encompasses eukaryotic viruses, bacteriophages, retroviruses, and even giant viruses. With the advent of Next-generation sequencing (NGS) and ongoing development of numerous bioinformatic softwares, identification and taxonomic characterization of viruses have become easier. The viruses are abundantly present in humans; these can be pathogenic or commensal. The viral communities occupy various niches in the human body. The viruses start colonizing the infant gut soon after birth in a stepwise fashion and the viral composition diversify according to their feeding habits. Various factors such as diet, age, medications, etc. influence and shape the human virome. The viruses interact with the host immune system and these interactions have beneficial or detrimental effects on their host. The virome composition and abundance change during the course of disease and these alterations impact the immune system. Hence, the virome population in healthy and disease conditions influences the human host in numerous ways. This review presents an overview of assembly and composition of the human virome in healthy asymptomatic individuals, changes in the virome profiles, and host-virome interactions in various disease states.


Assuntos
Bacteriófagos , Microbiota , Vírus , Lactente , Humanos , Viroma , Vírus/genética , Bacteriófagos/genética , Metagenoma
10.
bioRxiv ; 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-37790465

RESUMO

Background: Mice with cardiac-specific overexpression of adenylyl cyclase (AC) type 8 (TG AC8 ) are under a constant state of severe myocardial stress. They have a remarkable ability to adapt to this stress, but they eventually develop accelerated cardiac aging and experience reduced longevity. Results: Here we demonstrate that activation of ACVIII in cardiomyocytes results in cell-autonomous RelA-mediated NF-κB signaling. This is associated with non-cell-autonomous activation of proinflammatory and age-associated signaling in myocardial endothelial cells and myocardial smooth muscle cells, expansion of myocardial immune cells, increase in serum levels of inflammatory cytokines, and changes in the size or composition of lymphoid organs. These changes precede the appearance of cardiac fibrosis. We provide evidence indicating that ACVIII-driven RelA activation in cardiomyocytes is mediated by calcium-Protein Kinase A (PKA) signaling. Conclusions: Using a model of chronic cardiomyocyte stress and accelerated aging we highlight a novel, PKA/RelA-dependent connection between cardiomyocyte stress, myocardial para-inflammation and systemic inflammation. These findings point to RelA-mediated signaling in cardiomyocytes and inter-organ communication between the heart and lymphoid organs as novel potential therapeutic targets to reduce age-associated myocardial deterioration.

11.
ACS Omega ; 8(39): 35452-35469, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37810640

RESUMO

Pomegranate peel, derived from the processing of Punica granatum L. (pomegranate), has traditionally been considered agricultural waste. However, recent studies have revealed its potential as a rich source of bioactive compounds with diverse pharmacological effects. Pomegranate peel is a rich reservoir of antioxidants, polyphenols, dietary fiber, and vitamins, which contribute to its remarkable bioactivity. Studies have demonstrated the anti-inflammatory, cardioprotective, wound healing, anticancer, and antimicrobial properties of pomegranate peel owing to the presence of phytochemicals, such as gallic acid, ellagic acid, and punicalagin. The extraction of bioactive compounds from pomegranate peel requires a careful selection of techniques to maximize the yield and quality. Green extraction methods, including pressurized liquid extraction (PLE), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), and enzyme-assisted extraction (EAE), offer efficient and sustainable alternatives to traditional methods. Furthermore, pomegranate peel has been utilized in the food industry, where it can significantly enhance the nutritional value, organoleptic characteristics, and shelf life of food products. Pomegranate peel has the potential to be used to develop innovative functional foods, nutraceuticals, and other value-added products, providing new opportunities for the pharmaceutical, cosmetic, and food industries.

12.
J Oral Maxillofac Surg ; 81(9): 1072-1082, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37315927

RESUMO

PURPOSE: The literature is replete with various approaches for the temporomandibular joint (TMJ), each with its own distinct advantages and disadvantages. None of these approaches, however, have been associated with superior operative outcomes. The purpose of this study was to measure the efficacy of three operative approaches to TMJ, namely superficial, subfascial, and deep subfascial approaches. The aim was to contrast selected intraoperative and postoperative outcomes among these surgical approaches. METHODS: This was a prospective randomized clinical trial of subjects presenting to outpatient department. The primary predictor variables were three dissection planes of TMJ: Group-I (superficial), Group-II (subfascial), and Group-III (deep subfascial). The primary outcome variables were quality of surgical field employing fromme scale, dissection time in minutes, amount of blood loss in milliliters, and facial nerve function (FNF) using House-Brackmann scale. The secondary outcome variables were postoperative pain using visual-analog scale and swelling in millimeters measured on 1st, 3rd, and 7th postoperative days and quality of life using facial clinimetric evaluation questionnaire at 6-month follow-up. Age, gender, side, diagnosis, and type of surgery were the covariates. The data were analyzed using descriptive, comparative, and regression analysis. A P value of less than .05 was considered statistically significant. RESULT: The study included thirty subjects (8 males and 22 females) with various TMJ disorders ranging in age from 8 years to 65 years (mean 27.83 ± 10.52). On evaluation of intraoperative parameters, subfascial approach had statistically significant superior quality of surgical field (Group-I: 1.90 ± 0.57; Group-II: 1.10 ± 0.32; Group-III: 1.40 ± 0.52; P value = .006), statistically significant shortest dissection time (Group-I: 18.30 ± 3.74 min; Group-II: 13.240 ± 1.96 min; Group-III: 16.20 ± 1.99 min; with P value = .03), and statistically significant lower amount of blood loss compared with other groups (Group-I: 92.40 ± 4.74 ml: Group-II: 82.30 ± 3.77 ml; Group-III: 84.60 ± 3.06 ml; P value<.001). On assessment of postoperative parameters, only FNF of temporal branch showed statistically significant difference from 24 hours till 3 months with better outcome in deep subfascial approach. Mean scores of FNF at 24 hours and 1-week (Group-I: 4.20 ± 2.39; Group-II: 2.40 ± 2.27; Group-III: 1.50 ± 1.58 P = .02) and 1-month and 3-month (Group-I: 2.70 ± 1.82; Group-II: 1.20 ± 0.63; Group-III: 1.00 ± 0.00 P = .04). CONCLUSIONS: The subfascial approach significantly improved intraoperative outcomes and deep subfascial approach was comparatively safe with fewer incidence of facial nerve injury.


Assuntos
Transtornos da Articulação Temporomandibular , Anquilose Dental , Masculino , Feminino , Humanos , Criança , Estudos Prospectivos , Qualidade de Vida , Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/cirurgia , Resultado do Tratamento
13.
J Craniomaxillofac Surg ; 51(5): 316-320, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37355374

RESUMO

Dental extraction in hemophiliacs can be complicated by perilous bleeding. Although developments in local hemostatics and factor replacement have made outpatient extraction feasible, there is no standard protocol for preventing hemorrhagic exigency. Low-level laser therapy (LLLT) has firmly established role in hemostasis due to its ability to seal vessels, but this function has not been conclusively established in hemophiliac patients. The objective of our study was to evaluate the effectiveness of LLLT as compared with the standard protocol alone in achieving post-extraction hemostasis. A prospective interventional cohort study was designed and consisted of 60 patients with hemophilia A or B, who reported to the Maulana Azad Institute of Dental Sciences, New Delhi between October 2021 and March 2022. These were divided equally into test and control groups, both following the standard protocol. In the test group, extraction sockets were exposed to LLLT. The study assessed time required, instance of rebleeding, and additional methods employed for hemostasis in each group. The results showed a 22.42% reduction in average time taken to achieve hemostasis in the test group as compared with the control group. The tranexamic acid pack was replaced in two cases in both groups after 60 min of procedure. Three cases in the control group required suturing, and one case required cauterization. Rebleeding occurred in four cases in the test group and in 13 cases among the controls. Postoperative factor was infused in three and 12 cases in the test and control groups, respectively. The authors believe that perioperative use of LLLT should be encouraged because it demonstrated a significantly reduced time for hemostasis among hemophilia patients.


Assuntos
Hemofilia A , Terapia com Luz de Baixa Intensidade , Humanos , Hemofilia A/complicações , Hemofilia A/radioterapia , Estudos Prospectivos , Estudos de Coortes , Extração Dentária , Hemostasia
14.
J Dent Child (Chic) ; 90(1): 57-61, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37106535

RESUMO

Bilateral dentigerous cysts (DC) associated with unerupted mandibular first molars in a non-syndromic pediatric individual are rare. Secondary infections may lead to complications, such as discomfort due to pain, disfigurement caused by enlargement of the cyst with cortical expansion of the jawbone, displacement of teeth and paraesthesia of the adjacent nerve. This case report describes the occurrence of bilateral DC in an eight-year-old patient. Marsupialization was the treatment of choice to preserve the permanent teeth and other adjacent tissues.


Assuntos
Cisto Dentígero , Dente não Erupcionado , Humanos , Criança , Dente não Erupcionado/complicações , Cisto Dentígero/diagnóstico por imagem , Cisto Dentígero/cirurgia , Cisto Dentígero/complicações , Dente Molar/cirurgia , Mandíbula , Cabeça
15.
Sci Data ; 10(1): 32, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650149

RESUMO

Grass pea (Lathyrus sativus) is a cool-season legume crop tolerant to drought, salinity, waterlogging, insects, and other biotic stresses. Despite these beneficial traits, this crop is not cultivated widely due to the accumulation of a neurotoxin - ß-N-oxalyl-L-α, ß-diaminopropionic acid (ß-ODAP) in the seeds and its association with neurolathyrism. In this study, we sequenced and assembled the genome of Lathyrus sativus cultivar Pusa-24, an elite Indian cultivar extensively used in breeding programs. The assembled genome of Lathyrus was 3.80 Gb in length, with a scaffold N50 of 421.39 Mb. BUSCO assessment indicated that 98.3% of highly conserved Viridiplantae genes were present in the assembly. A total of 3.17 Gb (83.31%) of repetitive sequences and 50,106 protein-coding genes were identified in the Lathyrus assembly. The Lathyrus genome assembly reported here thus provides a much-needed and robust foundation for various genetic and genomic studies in this vital legume crop.


Assuntos
Diamino Aminoácidos , Lathyrus , Fabaceae , Lathyrus/genética , Melhoramento Vegetal , Sementes/genética , Genoma de Planta
16.
Lung Cancer ; 172: 142-153, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36099709

RESUMO

Targeted therapy against actionable variants has revolutionised the treatment landscape for non-small cell lung cancer (NSCLC). Approximately half of NSCLC adenocarcinomas have an actionable variant, making molecular testing a critical component of the diagnostic process to personalise therapeutic options, optimise clinical outcomes and minimise toxicity. Recently, genomic testing in England has undergone major changes with the introduction of Genomic Laboratory Hubs, designed to consolidate and enhance existing laboratory provision and deliver genomic testing as outlined in the National Genomic Test Directory. Similar changes are ongoing in Scotland, Wales and Northern Ireland. However, multiple challenges exist with current tissue acquisition procedures and the molecular testing pathway in the UK, including quantity and quality of available tissue, adequacy rates, test availability among genomic laboratories, turnaround times, multidisciplinary team communication, and limited guidance and standardisation. The COVID-19 pandemic has added an extra layer of complexity. Herein, we summarise best practice recommendations, based on expert opinion, to overcome existing challenges in the UK. The least invasive biopsy technique should be undertaken with the aim of acquiring the greatest quality and quantity of tissue. Use of sedation should be considered to improve patient experience. Rapid on-site evaluation may also be useful to help guide adequate sampling, and liquid biopsy may be beneficial in some instances. Sample processing should be appropriate to facilitate biomarker testing, in particular, next-generation sequencing for comprehensive genomic information. Steps to optimise tissue utilisation and turnaround times, such as planning of tissue usage, limiting immunohistochemistry, tumour enrichment, and reflex testing at diagnosis, should be implemented. Guidelines for tissue acquisition and sample processing may help to improve sample adequacy to perform downstream testing. Communication among genomic laboratories will help to standardise test availability across England and local auditing could identify further areas for optimisation, including ways to improve turnaround times and adequacy rates.


Assuntos
COVID-19 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Técnicas de Diagnóstico Molecular , Pandemias , Reino Unido
17.
Front Immunol ; 13: 900594, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757701

RESUMO

Organ allotransplantation has now reached an impassable ceiling inherent to the limited supply of human donor organs. In the United States, there are currently over 100,000 individuals on the national transplant waiting list awaiting a kidney, heart, and/or liver transplant. This is in contrast with only a fraction of them receiving a living or deceased donor allograft. Given the morbidity, mortality, costs, or absence of supportive treatments, xenotransplant has the potential to address the critical shortage in organ grafts. Last decade research efforts focused on creation of donor organs from pigs with various genes edited out using CRISPR technologies and utilizing non-human primates for trial. Three groups in the United States have recently moved forward with trials in human subjects and obtained initial successful results with pig-to-human heart and kidney xenotransplantation. This review serves as a brief discussion of the recent progress in xenotransplantation research, particularly as it concerns utilization of porcine heart, renal, and liver xenografts in clinical practice.


Assuntos
Doadores de Tecidos , Transplantes , Animais , Xenoenxertos , Humanos , Primatas , Suínos , Transplante Heterólogo , Estados Unidos
18.
J Family Med Prim Care ; 11(4): 1395-1400, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35516722

RESUMO

Background: Acute exacerbation of asthma is a common condition leading to emergency visits. Prednisolone is a commonly prescribed drug in the standard management of acute exacerbation of asthma along with other drugs. This study was planned to see the efficacy of oral dexamethasone when compared with oral prednisolone in the management of acute exacerbation of asthma. Methods: A single-center pilot study in the form of randomized control trial was done by recruiting children aged 2-14 years diagnosed with acute asthma exacerbation with mild to moderate severity. A total of 88 patients received oral dexamethasone (0.3 mg/kg) in two doses 24 h apart, which was compared with 87 patients who received oral prednisolone (1 mg/kg) in two divided doses 12 h apart for 5 days. The patients were assessed at the time of admission (zero hour), at 4th hour, and on the 5th day by various parameters such as respiratory rate, use of accessory muscles, Pediatric Respiratory Assessment Measure (PRAM) score, peak expiratory flow rate (PEFR), 6-h admission stay, and rate of hospital admission. Results: Baseline demographic profile, clinical characteristics, comorbidities, indoor pollution, and use of Metered Dose Inhaler (MDI) among the two study groups were comparable. Six-hour emergency stay and rate of admission were significantly lower in the dexamethasone group (P < 0.05). Improvement in PRAM score, PEFR, use of accessory muscles, and respiratory rate was also better in dexamethasone group at the 4th hour and 5th day (P < 0.05). In addition, oral dexamethasone was shown to have less incidence of vomiting/gastritis than prednisolone (P < 0.05). Conclusion: Oral dexamethasone can be considered a reliable and better option as compared with prednisolone due to its faster action and minimal side effects.

19.
J Family Med Prim Care ; 11(2): 603-607, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35360767

RESUMO

Objective: Celiac disease (CD) is a multifactorial immune-mediated enteropathy caused by a response to ingested gluten. The current available treatment for CD is lifelong gluten-free diet (GFD). This study was done to see the effect of GFD on Vitamin D levels and bone mass density in celiac patients. Methods: A prospective interventional study on newly diagnosed celiac patients was conducted in the Pediatrics department of a tertiary care teaching institute in 2 stages viz. on presentation and after 6 months of GFD. Anthropometric measurements, biochemical investigations, Vitamin D levels, and DEXA scan was done at recruitment and after 6 months of GFD and was analyzed. Results: In newly diagnosed 60 pediatric celiac patients, positive effect of GFD on anthropometry, hemoglobin, Vitamin D levels, DEXA scan parameters was observed. Significant difference was found in Vitamin D levels which increased from baseline 14.85 ± 5.39 to 18.22 ± 5.67 ng/ml after 6 months of GFD (P < 0.05). Significant difference was found in BMD (mean Z-score) which increased from -0.941 ± 0.738 to -0.640 ± 0.60 after 6 months of GFD (P < 0.001). Conclusion: Our study concluded that there is significant increase in vitamin D levels as well as Z-score, bone mass density (BMD) and bone Mass Content (BMC) after 6 months of GFD.

20.
J Oral Maxillofac Surg ; 80(7): 1158-1173, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35397232

RESUMO

PURPOSE: A proper anatomical disc-condyle position is a prerequisite to prevent progressive deteriorating changes within the temporomandibular joint. Surgery becomes the primary treatment option for patients who do not recover with nonoperative management. The present study aimed to compare the clinical outcome of 2 different surgical procedures in patients with internal derangement of the temporomandibular joint. METHODS: A prospective clinical cohort study was conducted among patients presenting to outpatient department of Oral and Maxillofacial Surgery at Maulana Azad Institute of Dental Sciences. The study sample was alternatively allocated into 2 treatment groups; Group I: modified condylotomy (MC) and Group II: high-condylar shave with eminectomy (HCSE). The primary outcome variables included pain on function, tenderness on palpation, and maximum mouth opening. The secondary outcome variables included joint sounds, jaw deviation on opening, maximum protrusive jaw movement, maximum ipsilateral jaw movement, and maximum contralateral jaw movement. The covariates were age, sex of the patient, duration of illness, the diagnosis based on Wilkes's staging, and the laterality (whether unilateral or bilateral). Descriptive, comparative, and regression analyses were conducted. RESULTS: Twenty-one patients with Wilkes Stage II, III, and IV were included in the study (MC: 10 patients and HCSE: 11 patients). The mean age of the study sample was 32.67 (±11.66) years. Among 21 patients recruited in our study, 18 were females. It was observed that after 1-year follow-up, patients in Group I had significantly lower pain on function (0.30 ± 0.48) compared with Group II (3.00 ± 1.18). (P < .001). Similarly, tenderness on palpation was significantly decreased in Group I (0.80 ± 0.48) compared with Group II (2.45 ± 0.93; P < .001). Joint sounds were significantly lower in Group I (1.20 ± 0.63) compared with Group II (2.27 ± 0.90) after 1 year (P < .001). Maximum protrusive jaw movement and maximum ipsilateral jaw movement were significantly higher in Group I compared with Group II after 1 year. CONCLUSION: MC is a comparatively better surgical procedure than HCSE in patients with internal derangement of the TMJ.


Assuntos
Luxações Articulares , Transtornos da Articulação Temporomandibular , Adulto , Osso e Ossos , Estudos de Coortes , Feminino , Humanos , Luxações Articulares/cirurgia , Masculino , Côndilo Mandibular/cirurgia , Dor , Estudos Prospectivos , Amplitude de Movimento Articular , Articulação Temporomandibular/cirurgia , Disco da Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/cirurgia , Resultado do Tratamento , Adulto Jovem
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