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In recent years organic food is gaining popularity as it is believed to promote better human health and improve soil sustainability, but there are apprehensions about pathogens in organic produces. This study was designed to understand the effect of different composts and soils on the status of the microbiome present in organically grown leafy vegetables. 16S rRNA metagenomic profiling of the leaves was done, and data were analyzed. It was found that by adding composts, the OTU of the microbiome in the organic produce was higher than in the conventional produce. The beneficial genera identified across the samples included plant growth promoters (Achromobacter, Paenibacillus, Pseudomonas, Sphingobacterium) and probiotics (Lactobacillus), which were higher in the organic produce. Some pathogenic genera, viz., plant pathogenic bacteria (Cellvibrio, Georgenia) and human pathogenic bacteria (Corynebacterium, Acinetobacter, Streptococcus, Streptomyces) were also found but with relatively low counts in the organic produce. Thus, the present study highlights that organic produce has lesser pathogen contamination than the conventional produce. KEY POINTS: ⢠16S rRNA metagenomics profiling done for organic red amaranth cultivar ⢠Microbial richness varied with respect to the soil and compost type used ⢠The ratio of beneficial to pathogenic genera improves with the addition of compost.
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Compostagem , Humanos , RNA Ribossômico 16S/genética , Solo , Bactérias/genética , MetagenomaRESUMO
BACKGROUND: Increasing strength through weightlifting has become a core component of competitive sports training, recreational exercise programs, and school physical education classes. Although many health benefits exist, there is concern for injury, especially with improper supervision and accelerated progression of training loads. Though organizations have advocated safe training practices, trends in the national health burden of injuries, specifically fractures, associated with weightlifting in the adolescent population have not been investigated. METHODS: The National Electronic Injury Surveillance System database was queried between 2002 and 2021 for patients aged 11 to 21 years presenting to US Emergency Departments with weight lifting-related injuries. The narrative component of each case identified was analyzed to include only patients noted to be using weightlifting equipment or free weights at the time of injury. Estimates and analyses were performed with 95% CIs. RESULTS: Although there has been some variability in weight lifting-related injuries, the incidence remained roughly constant over the 20 years ( R2 =0.0364). 14,497 cases were identified, reflecting a national estimate of 540,986 total injuries and an annual estimate of 27,049 injuries. Most injuries occurred among 15-to-18-year olds (44.1%±1.6%) and 19-to-21-year olds (38.3%±2.0%). The most common injuries were sprain/strain (36.7%±1.3%), contusion/abrasion (15.7%±0.7%), and fracture (9.9%±0.3%). There were 53,813 estimated fractures, giving an annual incidence of 2,691 fractures. As a portion of all injuries, the number of fractures decreased significantly as patients got older, accounting for 26.8%±3.3% at age 11 and only 8.3%±0.9% at age 21 ( R2 =0.6626). Fingers (37.1%±1.8%) and toes (27.9%±1.4%) were the most fractured body parts. Overall, fractures mainly occurred either at school (25.3%±2.0%) or places of recreation (24.7%±2.2%). CONCLUSIONS: Despite the guidelines to improve safety, the national health burden of weight lifting-related injuries among adolescents has remained constant over the past 20 years. Given that most of the fractures occur in the distal extremities, such as toes and fingers, at school and places of recreation, there may be an opportunity to promote safer weightlifting practices and the development of weightlifting equipment with in-built safety mechanisms, especially at gyms and schools. LEVEL OF EVIDENCE: Level III-prognostic.
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Fraturas Ósseas , Levantamento de Peso , Humanos , Adolescente , Levantamento de Peso/lesões , Levantamento de Peso/estatística & dados numéricos , Feminino , Masculino , Criança , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Estados Unidos/epidemiologia , Adulto Jovem , Incidência , Traumatismos em Atletas/epidemiologia , Bases de Dados FactuaisRESUMO
BACKGROUND: Biking is a popular childhood activity with an intrinsic risk of injury. While advocacy groups have promoted protective equipment to help mitigate these risks, trends in the national health burden of fractures associated with biking in the pediatric population have not been explored in depth. METHODS: The National Electronic Injury Surveillance System database was queried between 2001 and 2020 to identify patients aged 18 years or below with fractures presenting to US emergency departments associated with riding bicycles. The patient narratives were analyzed to exclude patients not actively riding bicycles and to note helmet use and collisions with motor vehicles (MVs). RESULTS: A total of 33,955 fractures were identified in the database, representing an estimated 1,007,714 fractures from 2001 to 2020, or 50,331 fractures annually. Linear regression noted a significant decrease in fractures over the period ( R2 =0.899; P <0.001). Most fractures occurred in patients who were male (71.8%, 95% CI: 70.4% to 73.2%), White (53.1%, 46.0% to 60.0%), and aged 10 to 12 (30.6%, 29.6% to 31.7%) or 13 to 15 years (24.8%, 23.4% to 26.2%). Fractures occurred most frequently in the forearm (25.2%, 22.8% to 27.8%), wrist (21.2%, 19.5% to 22.9%), and shoulder (10.5%, 9.7% to 11.3%). Patients who sustained fractures after being struck by a MV were >6 times more likely to be admitted to the hospital (36.0%, 28.6% to 44.2%) compared with patients not struck by a MV (5.4%, 4.3% to 6.8%). When helmet use was recorded in patients with skull fractures, most patients were not wearing helmets at the time of injury (85.7%, 74.6% to 92.5%). CONCLUSIONS: Although the national burden of fractures associated with riding bicycles in pediatric populations has steadily decreased, it remains a significant cause of injury for children. Fractures involving MV more often require hospitalization, and an alarming number of skull fractures are noted in children not wearing helmets. These data support continued efforts to promote consistent helmet use and safer riding environments around MV in all children, but especially among 10- to 15-year-old males. LEVEL OF EVIDENCE: Level III-prognostic.
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Ciclismo , Fraturas Cranianas , Criança , Humanos , Masculino , Adolescente , Feminino , Ciclismo/lesões , Fraturas Cranianas/epidemiologia , Fraturas Cranianas/etiologia , Dispositivos de Proteção da Cabeça , Hospitalização , Serviço Hospitalar de EmergênciaRESUMO
AIM: Amnion and chorion membranes possess unique inherited biological properties that enhance wound healing and may accelerate periodontal regeneration. The present study aims to evaluate and compare the efficacy of amnion and chorion membranes in the treatment of furcation defects. MATERIALS AND METHODS: A total of 20 patients were selected and were randomly allocated to group I and group II with 10 subjects in each group. Amnion and chorion membranes are placental-derived membranes that accelerate regeneration by having natural growth factors with their antimicrobial and inflammation reduction properties. Group I was treated using bone grafting with decalcified freeze-dried bone allograft (DFDBA) and placement of amnion as a membrane for guided tissue regeneration (GTR) whereas group II was treated using bone grafting with DFDBA and placement of chorion as a membrane for GTR. The patients were followed for clinical and radiographic parameters and were evaluated between 3 and 6 months after surgery. RESULT: In intragroup comparison, a significant difference was evident in both the groups for all the clinical and radiographic parameters within the groups. (p = 0.01) This means both amnion and chorion membranes showed statistically significant regenerative efficacy. In intergroup comparison, the results show that all the clinical parameters and radiographic parameters show no significant difference between the groups. CONCLUSION: The amnion and chorion membranes had similar regenerative efficacy in combination with DFDBA in patients with buccal degree II furcation defects in mandibular molars. CLINICAL SIGNIFICANCE: The amnion and chorion membranes have shown significant improvement in clinical and radiographic parameters when used for the treatment of buccal degree II furcation defects in mandibular molars. How to cite this article: Mallapragda S, Gupta R, Gupta S, et al. Evaluation of Regenerative Efficacy of Amnion and Chorion Membrane in Treatment of Mandibular Molar Furcation Defects: A Clinico-radiographic Study. J Contemp Dent Pract 2024;25(2):160-167.
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Defeitos da Furca , Gravidez , Humanos , Feminino , Defeitos da Furca/cirurgia , Âmnio/transplante , Regeneração Tecidual Guiada Periodontal/métodos , Placenta/cirurgia , Dente Molar/cirurgia , Transplante Ósseo/métodos , Córion/cirurgia , Membranas ArtificiaisRESUMO
A young male patient of 22 years inducted at 11,000 feet altitude presented with a sudden onset bilateral diminution of vision associated with easy fatiguability and generalised weakness. Fundus examination revealed preretinal haemorrhages and Roth spots both eyes, owing to which differential diagnosis of high altitude retinopathy (HAR) and haematological disorders was considered. On systemic examination, he had pallor with massive splenomegaly. Haematological investigation revealed high total leucocyte count (TLC) 2.96 lac (normal 4000-11,000/uL) with peripheral blood smear showing increase in basophils, neutrophil precursors, myelocyte bulge, anaemia with no blasts suggestive of chronic myeloid leukaemia-chronic phase. Hence, a diagnosis of chronic myeloid leukaemia (chronic phase) with no features of tumour lysis syndrome was made. Patient was started on Tab hydroxyurea 50 mg twice a daily and managed by haemato-oncologist and required no further active ophthalmological intervention.
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BACKGROUND: Health technology assessment (HTA) is the systematic evaluation of various properties and effects of a health technology. HTA can serve as a bridge between the world of knowledge and that of decision making, offering decision makers the best summary of scientific evidence. Scoping HTA reports in the context of dentistry can help researchers identify grey areas; help practitioners make evidence-based decisions and further initiate better policy making. AIM: To provide an overview on HTAs pertaining to oral health and dentistry in the past decade, map the extension and scope of the methodological practices, key findings, and limitations. METHODOLOGY: A scoping review was conducted using the Joanna Briggs Institute framework. A comprehensive search for HTA reports was done through the International Network of Agencies for Health Technology Assessment Database from January 2010 to December 2020. Consecutively, electronic databases (PubMed and Google Scholar) were searched. Finally, thirty-six reports were included in this review and analyzed. RESULTS: A total of 709 articles were initially identified, of which thirty-six met the inclusion criteria. Reviewed HTAs focused on various specialties of dentistry worldwide. Maximum number of reports (N = 5) were related to "prosthodontics and dental implants" and technologies related to preventive dentistry were most commonly assessed (N = 4). CONCLUSION: Functional, appropriate, and evidence-based information provided through HTA pertaining to oral health on a regular basis will enable decision makers to have enough data to make decisions on the future use of new technology, modify existing policies, accelerate its translation into practice, and ensure provision of robust dental healthcare services.
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Saúde Bucal , Avaliação da Tecnologia Biomédica , Formulação de Políticas , Tecnologia BiomédicaRESUMO
INTRODUCTION: Increasing affordability, accessibility and penetration of internet services worldwide, have substantially changed the ways of gathering health-related information. This has led to the origin of concept infodemiology that allows the information to be collected and analysed in near real time. Globally, oral diseases affect nearly 3.5 billion people; thus, volume and profile of oral health searches would help in understanding specific community dental needs and formulation of pertinent oral health strategies. AIM: To review the published literature on infodemiological aspects of oral health and disease. METHODOLOGY: This scoping review was conducted in accordance with PRISMA-ScR guidelines. Electronic search engines (Google Scholar) and databases (PubMed, Web of science, Scopus) were searched from 2002 onwards. RESULTS: Thirty-eight articles were included in this review. The infodemiological studies for oral health and disease were mainly used in two domains. Out of 38 articles, 24 accessed the quality of available online information and 15 studied online oral health-related information seeking behaviour. CONCLUSION: The most commonly searched oral diseases were toothache, oral cancer, dental caries, periodontal disease, oral maxillofacial surgical procedures and paediatric oral diseases. Most of the studies belonged to developed countries and Google was the most researched search engine.
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Cárie Dentária , Saúde Bucal , Criança , Cárie Dentária/prevenção & controle , Humanos , Infodemiologia , Comportamento de Busca de Informação , Internet , Ferramenta de BuscaRESUMO
The human pathogen Mycobacterium tuberculosis (Mtb) harbors a well-orchestrated Clp (caseinolytic protease) proteolytic machinery consisting of two oligomeric segments, a barrel-shaped heterotetradecameric protease core comprising the ClpP1 and ClpP2 subunits, and hexameric ring-like ATP-dependent unfoldases composed of ClpX or ClpC1. The roles of the ClpP1P2 protease subunits are well-established in Mtb, but the potential roles of the associated unfoldases, such as ClpC1, remain elusive. Using a CRISPR interference-mediated gene silencing approach, here we demonstrate that clpC1 is indispensable for the extracellular growth of Mtb and for its survival in macrophages. The results from isobaric tags for relative and absolute quantitation-based quantitative proteomic experiments with clpC1- and clpP2-depleted Mtb cells suggested that the ClpC1P1P2 complex critically maintains the homeostasis of various growth-essential proteins in Mtb, several of which contain intrinsically disordered regions at their termini. We show that the Clp machinery regulates dosage-sensitive proteins such as the small heat shock protein Hsp20, which exists in a dodecameric conformation. Further, we observed that Hsp20 is poorly expressed in WT Mtb and that its expression is greatly induced upon depletion of clpC1 or clpP2 Remarkably, high Hsp20 protein levels were detected in the clpC1(-) or clpP2(-) knockdown strains but not in the parental bacteria, despite significant induction of hsp20 transcripts. In summary, the cellular levels of oligomeric proteins such as Hsp20 are maintained post-translationally through their recognition, disassembly, and degradation by ClpC1, which requires disordered ends in its protein substrates.
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Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteínas de Choque Térmico/metabolismo , Proteínas Intrinsicamente Desordenadas/biossíntese , Mycobacterium tuberculosis/metabolismo , Proteínas de Bactérias/genética , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico/genética , Humanos , Proteínas Intrinsicamente Desordenadas/genética , Mycobacterium tuberculosis/genética , Domínios Proteicos , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Células THP-1RESUMO
BACKGROUND: There is an urgent need for mental health promotion in nonclinical settings. Mindfulness-based programmes (MBPs) are being widely implemented to reduce stress, but a comprehensive evidence synthesis is lacking. We reviewed trials to assess whether MBPs promote mental health relative to no intervention or comparator interventions. METHODS AND FINDINGS: Following a detailed preregistered protocol (PROSPERO CRD42018105213) developed with public and professional stakeholders, 13 databases were searched to August 2020 for randomised controlled trials (RCTs) examining in-person, expert-defined MBPs in nonclinical settings. Two researchers independently selected, extracted, and appraised trials using the Cochrane Risk-of-Bias Tool 2.0. Primary outcomes were psychometrically validated anxiety, depression, psychological distress, and mental well-being questionnaires at 1 to 6 months after programme completion. Multiple testing was performed using p < 0.0125 (Bonferroni) for statistical significance. Secondary outcomes, meta-regression and sensitivity analyses were prespecified. Pairwise random-effects multivariate meta-analyses and prediction intervals (PIs) were calculated. A total of 11,605 participants in 136 trials were included (29 countries, 77% women, age range 18 to 73 years). Compared with no intervention, in most but not all scenarios MBPs improved average anxiety (8 trials; standardised mean difference (SMD) = -0.56; 95% confidence interval (CI) -0.80 to -0.33; p-value < 0.001; 95% PI -1.19 to 0.06), depression (14 trials; SMD = -0.53; 95% CI -0.72 to -0.34; p-value < 0.001; 95% PI -1.14 to 0.07), distress (27 trials; SMD = -0.45; 95% CI -0.58 to -0.31; p-value < 0.001; 95% PI -1.04 to 0.14), and well-being (9 trials; SMD = 0.33; 95% CI 0.11 to 0.54; p-value = 0.003; 95% PI -0.29 to 0.94). Compared with nonspecific active control conditions, in most but not all scenarios MBPs improved average depression (6 trials; SMD = -0.46; 95% CI -0.81 to -0.10; p-value = 0.012, 95% PI -1.57 to 0.66), with no statistically significant evidence for improving anxiety or distress and no reliable data on well-being. Compared with specific active control conditions, there is no statistically significant evidence of MBPs' superiority. Only effects on distress remained when higher-risk trials were excluded. USA-based trials reported smaller effects. MBPs targeted at higher-risk populations had larger effects than universal MBPs. The main limitation of this review is that confidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach is moderate to very low, mainly due to inconsistency and high risk of bias in many trials. CONCLUSIONS: Compared with taking no action, MBPs of the included studies promote mental health in nonclinical settings, but given the heterogeneity between studies, the findings do not support generalisation of MBP effects across every setting. MBPs may have specific effects on some common mental health symptoms. Other preventative interventions may be equally effective. Implementation of MBPs in nonclinical settings should be partnered with thorough research to confirm findings and learn which settings are most likely to benefit.
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Promoção da Saúde , Transtornos Mentais/prevenção & controle , Atenção Plena , Adulto , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Quantum chemical calculations and NBO, ETS-NOCV, QTAIM and ELF interpretative approaches have been carried out on C-donor ligand-stabilized dihydrido borenium cations. Numerous descriptors of the C-B π-bond strength obtained from orbital localization, energy partitioning or topological methods as well as from structural and chemical parameters have been calculated for 39 C-donor ligands including N-heterocyclic carbenes and carbones. Comparison of the results allows the identification of relative and absolute descriptors of the π interaction. For both families of descriptors excellent correlations are obtained. This enables the establishment of a π-donation capability scale and shows that the interpretative methods, despite their conceptual differences, describe the same chemical properties. These results also reveal noticeable shortcomings in these popular methods, and some precautions that need to be taken to interpret their results adequately.
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AIM: This study aimed to compare the effects of subgingival delivery of 2% curcumin gel and 0.2% chlorhexidine gel as an adjunct to scaling and root planing (SRP) on clinical and microbiological parameters in the management of patients with chronic periodontitis. MATERIALS AND METHODS: In total, 25 systemically healthy individuals with age group ≥30 years diagnosed with chronic periodontitis were included in the study. The study was a double-blind split-mouth randomized control clinical trial. Two sites were selected in each patient and were randomly allocated to experimental and control sites. At baseline, measurements of site-specific periodontal parameters and collection of subgingival plaque sample were done. After full-mouth SRP, subgingival delivery of 2% curcumin gel in experimental sites and 0.2% chlorhexidine gel in control sites was done. At 1 and 3 months, subgingival plaque samples were collected again and site-specific periodontal parameters were measured. RESULTS: The experimental group (2% curcumin gel) showed statistically significant improvements in periodontal [i.e., sulcus bleeding index (SBI), probing pocket depth (PPD), and relative attachment level (RAL)] and microbiologic parameters in the form of colony-forming units (CFUs) in comparison with control group (0.2% chlorhexidine gel). CONCLUSION: Subgingival delivery of curcumin has shown effective anti-inflammatory and antibacterial properties. Since it is biologically accepted by the patients and its delivery in periodontal pockets can be recommended as an adjunct to SRP therapy for the treatment of patients with localized, moderate chronic periodontitis and in patients under the periodontal maintenance phase. CLINICAL SIGNIFICANCE: Curcumin being a herbal agent may be excellent alternative to chlorhexidine. It is biologically accepted by the patients and can be recommended as an adjunct to SRP in the treatment of localized moderate chronic periodontitis and periodontal maintenance patients.
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Anti-Infecciosos Locais , Periodontite Crônica , Curcumina , Clorexidina , Raspagem Dentária , Humanos , Aplainamento RadicularRESUMO
AIM: Periodontitis, a chronic infectious disease, affects most of the population at one time or the other and its expression is a combination of hosts, microbial agents, and environmental factors. Extensive literature exists for the relationship between periodontal disease and diabetes mellitus, cardiovascular diseases, and adverse pregnancy outcomes. Only a few studies performed in a limited number of patients have reported peri-odontal health status in chronic renal failure patients. Hence, the aim of the present study is to assess and compare the periodontal status of patients with chronic renal failure undergoing dialysis, predialysis with systemically healthy individuals. MATERIALS AND METHODS: A total of 90 patients were divided into three groups. Group I: 30 renal dialysis patients. Group II: 30 predialysis patients. Control group comprised 30 systemically healthy patients who formed group III. Periodontal examination was carried out using oral hygiene index-simplified (OHI-S), plaque index (PI), gingival index (GI), probing depth, and clinical attachment loss. RESULTS: The results of the study showed that the periodontal status of patients with chronic renal failure undergoing dialysis (dialysis group) and patients with chronic renal failure not undergoing renal dialysis (predialysis) when compared with systemically healthy subjects showed significantly higher mean scores of OHI-S, PI, and clinical attachment loss. CONCLUSION: Thus, patients with chronic renal failure showed poor oral hygiene and higher prevalence of periodontal disease. CLINICAL SIGNIFICANCE: The dental community's awareness of implications of poor health within chronic renal failure patients should be elevated.
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Falência Renal Crônica/complicações , Periodontite/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Índice de Placa Dentária , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Higiene Oral , Perda da Inserção Periodontal/etiologia , Índice Periodontal , Bolsa Periodontal/etiologia , Diálise Renal , Adulto JovemRESUMO
Policy Points: Randomized trials-the gold standard of evaluating effectiveness-constitute a small minority of existing evidence on agents given accelerated approval. One-third of randomized trials are in therapeutic areas outside of FDA approval and less than half evaluate the therapeutic benefits of these agents but use them instead as common backbone treatments. Agents receiving accelerated approval are often tested concurrently in several therapeutic areas. For most agents, no substantial time lag is apparent between the average start dates of randomized trials evaluating their effectiveness and those using them as part of background therapies. There appears to be a tendency for therapeutic agents receiving accelerated approval to quickly become an integral component of standard treatment, despite potential shortcomings in their evidence base. CONTEXT: Therapeutic agents treating serious conditions are eligible for Food and Drug Administration (FDA) accelerated approval. The clinical evidence accrued on agents receiving accelerated approval has not been systematically evaluated. Our objective was to assess the timing and characteristics of available studies. METHODS: We first identified clinical studies of novel therapeutic agents receiving accelerated approval. We then (1) categorized those studies as randomized or nonrandomized, (2) explored whether they evaluated the FDA-approved indications, and (3) documented the available treatment comparisons. We also meta-analyzed the difference in start times between randomized studies that (1) did or did not evaluate approved indications and (2) were or were not designed to evaluate the agent's effectiveness. FINDINGS: In total, 37 novel therapeutic agents received accelerated approval between 2000 and 2013. Our search of ClinicalTrials.gov identified 7,757 studies, which included 1,258,315 participants. Only one-third of identified studies were randomized controlled trials. Of 1,631 randomized trials with advanced recruitment status, 906 were conducted in therapeutic areas for which agents received initial accelerated approval, 202 were in supplemental indications, and 523 were outside approved indications. Only 411 out of 906 (45.4%) trials were designed to test the effectiveness of agents that received accelerated approval ("evaluation" trials); others used these agents as common background treatment in both arms ("background" trials). There was no detectable lag between average start times of trials conducted within and outside initially approved indications. Evaluation trials started on average 1.52 years (95% CI: 0.87 to 2.17) earlier than background trials. CONCLUSIONS: Cumulative evidence on agents with accelerated approvals has major limitations. Most clinical studies including these agents are small and nonrandomized, and about a third are conducted in unapproved areas, typically concurrently with those conducted in approved areas. Most randomized trials including these therapeutic agents are not designed to directly evaluate their clinical benefits but to incorporate them as standard treatment.
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Aprovação de Drogas/organização & administração , Medicina Baseada em Evidências , United States Food and Drug Administration , Controle de Medicamentos e Entorpecentes , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Estados UnidosRESUMO
With 8.9 million new cases and 1.7 million deaths per year, tuberculosis is a leading global killer that has not been effectively controlled. The causative agent, Mycobacterium tuberculosis, proliferates within host macrophages where it modifies both its intracellular and local tissue environment, resulting in caseous granulomas with incomplete bacterial sterilization. Although infection by various mycobacterial species produces a cyclic AMP burst within macrophages that influences cell signalling, the underlying mechanism for the cAMP burst remains unclear. Here we show that among the 17 adenylate cyclase genes present in M. tuberculosis, at least one (Rv0386) is required for virulence. Furthermore, we demonstrate that the Rv0386 adenylate cyclase facilitates delivery of bacterial-derived cAMP into the macrophage cytoplasm. Loss of Rv0386 and the intramacrophage cAMP it delivers results in reductions in TNF-alpha production via the protein kinase A and cAMP response-element-binding protein pathway, decreased immunopathology in animal tissues, and diminished bacterial survival. Direct intoxication of host cells by bacterial-derived cAMP may enable M. tuberculosis to modify both its intracellular and tissue environments to facilitate its long-term survival.
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Adenilil Ciclases/metabolismo , AMP Cíclico/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/patogenicidade , Tuberculose/patologia , Adenilil Ciclases/genética , Animais , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Citosol/metabolismo , Citosol/microbiologia , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/crescimento & desenvolvimento , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Fosforilação , Tuberculose/imunologia , Tuberculose/microbiologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/metabolismo , Virulência/genéticaRESUMO
The host-pathogen interactions in Mycobacterium tuberculosis infection are significantly influenced by redox stimuli and alterations in the levels of secreted antigens. The extracytoplasmic function (ECF) σ factor σ(K) governs the transcription of the serodominant antigens MPT70 and MPT83. The cellular levels of σ(K) are regulated by the membrane-associated anti-σ(K) (RskA) that localizes σ(K) in an inactive complex. The crystal structure of M. tuberculosis σ(K) in complex with the cytosolic domain of RskA (RskAcyto) revealed a disulfide bridge in the -35 promoter-interaction region of σ(K). Biochemical experiments reveal that the redox potential of the disulfide-forming cysteines in σ(K) is consistent with its role as a sensor. The disulfide bond in σ(K) influences the stability of the σ(K)-RskAcyto complex but does not interfere with σ(K)-promoter DNA interactions. It is noted that these disulfide-forming cysteines are conserved across homologues, suggesting that this could be a general mechanism for redox-sensitive transcription regulation.
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Mycobacterium tuberculosis/química , Proteínas Repressoras/química , Fatores de Transcrição/química , Sequência de Aminoácidos , Modelos Moleculares , Dados de Sequência Molecular , Mycobacterium tuberculosis/metabolismo , Oxirredução , Ligação Proteica , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Proteínas Repressoras/metabolismo , Análise de Sequência de Proteína , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: An increasing reliance on patient-reported outcomes has led to greater emphasis on minimal clinically important difference (MCID), substantial clinical benefit (SCB), and Patient Acceptable Symptom State (PASS) thresholds in assessing rotator cuff repairs. PURPOSE: To review the MCID, SCB, and PASS thresholds reported for patient-reported outcome measures (PROMs) after rotator cuff repair. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: The PubMed, Embase, Ovid, Cochrane, and Google Scholar databases were queried for full-text journal articles in English published between January 1, 2000, and May 31, 2022. Studies with MCID, SCB, and PASS thresholds reported for patients with rotator cuff repair and a minimum of 12 months of follow-up were included. Reported MCID, SCB, and PASS thresholds and associated calculation methods were extracted. RESULTS: There were 41 unique studies (6331 shoulders) that met the inclusion criteria. Of these, 37 (90%) reported MCID; 16 (39%), PASS; and 11 (27%), SCB values. The most common PROMs were the American Shoulder and Elbow Surgeons score and the Constant-Murley score. In total, 71% (29/41) of these studies referenced values in the literature, usually studies of patients undergoing rotator cuff repair (21/29). Twelve studies calculated MCID, SCB, or PASS thresholds using anchor-based approaches, whereas 6 studies also calculated thresholds using distribution-based methods. The use of MCID, SCB, and PASS in the rotator cuff repair literature is increasing, with half of the included studies published within the final 17 months of the studied period. CONCLUSION: Significant variability was seen in the reporting of MCID, SCB, and PASS threshold values after rotator cuff repair. Researchers should prioritize studies that report clinical outcome thresholds calculated using anchor-based methods and should critically review both the anchor question and its response choices. Standardization of MCID, SCB, and PASS values and calculation methods will allow for a more reliable assessment of PROMs in rotator cuff repair moving forward.