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Molecular self-assembly is the spontaneous association of simple molecules into larger and ordered structures1. It is the basis of several natural processes, such as the formation of colloids, crystals, proteins, viruses and double-helical DNA2. Molecular self-assembly has inspired strategies for the rational design of materials with specific chemical and physical properties3, and is one of the most important concepts in supramolecular chemistry. Although molecular self-assembly has been extensively investigated, understanding the rules governing this phenomenon remains challenging. Here we report on a simple hydrochloride salt of fampridine that crystallizes as four different structures, two of which adopt unusual self-assemblies consisting of polyhedral clusters of chloride and pyridinium ions. These two structures represent Frank-Kasper (FK) phases of a small and rigid organic molecule. Although discovered in metal alloys4,5 more than 60 years ago, FK phases have recently been observed in several classes of supramolecular soft matter6-11 and in gold nanocrystal superlattices12 and remain the object of recent discoveries13. In these systems, atoms or spherical assemblies of molecules are packed to form polyhedra with coordination numbers 12, 14, 15 or 16. The two FK structures reported here crystallize from a dense liquid phase and show a complexity that is generally not observed in small rigid organic molecules. Investigation of the precursor dense liquid phase by cryogenic electron microscopy reveals the presence of spherical aggregates with sizes ranging between 1.5 and 4.6 nanometres. These structures, together with the experimental procedure used for their preparation, invite interesting speculation about their formation and open different perspectives for the design of organic crystalline materials.
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Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid-base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids. The use of Parallel Java and OpenMM combines to offer shared memory, message passing, and graphics processing unit parallelization for high performance simulations. Overall, the FFX platform serves as a computational microscope to study systems ranging from organic crystals to solvated biomolecular systems.
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Software , Simulação de Dinâmica Molecular , Variação Genética , Algoritmos , Termodinâmica , Proteínas/química , Cristalização , Ácidos Nucleicos/químicaRESUMO
This study describes the comparison between the interaction of a series of peptide-functionalized chitosan-based nanocapsules and liposomes with two cell lines, i.e., mouse macrophages RAW 264.7 and human endothelial cells EA.hy926. Both types of nanocarriers are loaded with magnetic nanoparticles and designed for anti-inflammatory therapy. The choice of these magnetic nanostructures is argued based on their advantages in terms of size, morphology, chemical composition, and the multiple possibilities of modifying their surface. Moreover, active targeting might be ensured by using an external magnetic field. To explore the impact of chitosan-based nanocapsules and liposomes on cell cytophysiology, the cell viability, using the MTT assay, and cell morphology were investigated. The results revealed low to moderate cytotoxicity of free nanocapsules and significant cytotoxicity induced by chitosan-coated liposomes loaded with dexamethasone, confirming its release from the delivery system. Thus, after 48 h of treatment with nanocapsules, the viability of RAW 264.7 cells varied between 88.18% (OCNPM-1I, 3.125 µg/mL) and 76.37% (OCNPM-1, 25 µg/mL). In the same conditions, EA.hy926 cell viability was between 99.91% (OCNPM-3, 3.125 µg/mL) and 75.15% (OCNPM-3, 25 µg/mL) at the highest dose (25 µg/mL), the values being comparable for both cell lines. Referring to the cell reactivity after dexamethasone-loaded liposome application, the lowest viability of RAW 264.7 cells was 41.25% (CLDM5CP-1, 25 µg/mL) and 58.20% (CLDMM2CP-1 1.25 µg/mL) in the endothelial cell line, proving a selective character of action of nanocarriers. The cell morphology test, performed to support and confirm the results obtained by the MTT test, revealed a differentiated response for the two types of nano-carriers. As expected, an intense cytotoxic effect in the case of dexamethasone-loaded liposomes and a lack of cytotoxicity for drug-free nanocapsules were noticed. Therefore, our study demonstrated the biocompatible feature of the studied nanocarriers, which highlights them for future research as potential drug delivery systems for pharmacological applications, including anti-inflammatory therapy.
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Anti-Inflamatórios , Sobrevivência Celular , Quitosana , Lipossomos , Nanocápsulas , Lipossomos/química , Quitosana/química , Camundongos , Nanocápsulas/química , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/administração & dosagem , Humanos , Células RAW 264.7 , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/farmacologia , Dexametasona/química , Dexametasona/administração & dosagem , Linhagem Celular , Nanopartículas de Magnetita/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
Computational simulation of biomolecules can provide important insights into protein design, protein-ligand binding interactions, and ab initio biomolecular folding, among other applications. Accurate treatment of the solvent environment is essential in such applications, but the use of explicit solvents can add considerable cost. Implicit treatment of solvent effects using a dielectric continuum model is an attractive alternative to explicit solvation since it is able to describe solvation effects without the inclusion of solvent degrees of freedom. Previously, we described the development and parameterization of implicit solvent models for small molecules. Here, we extend the parameterization of the generalized Kirkwood (GK) implicit solvent model for use with biomolecules described by the AMOEBA force field via the addition of corrections to the calculation of effective radii that account for interstitial spaces that arise within biomolecules. These include element-specific pairwise descreening scale factors, a short-range neck contribution to describe the solvent-excluded space between pairs of nearby atoms, and finally tanh-based rescaling of the overall descreening integral. We then apply the AMOEBA/GK implicit solvent to a set of ten proteins and achieve an average coordinate root mean square deviation for the experimental structures of 2.0 Å across 500 ns simulations. Overall, the continued development of implicit solvent models will help facilitate the simulation of biomolecules on mechanistically relevant timescales.
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Amoeba , Solventes/química , Proteínas/química , Simulação por Computador , Fenômenos Biofísicos , TermodinâmicaRESUMO
OBJECTIVE: To describe a novel orthodontic appliance to prevent pedicle trauma in patients undergoing double-opposing buccal flap surgery for secondary palatal lengthening. DESIGN: Case series. SETTING: Cleft and craniofacial clinic, Johns Hopkins Children's Center. PATIENTS, PARTICIPANTS: Four patients undergoing double-opposing buccal flap surgery for repair of velopharyngeal insufficiency. INTERVENTIONS: Patients were fitted with the device, which consists of a lower lingual holding arch with acrylic bite blocks. MAIN OUTCOME MEASURE: Presence of pedicle trauma postsurgery and tolerability of the device. RESULTS: The appliance was well tolerated in all 4 patients and no biting trauma to the pedicles was observed. CONCLUSIONS: A reliable appliance has been developed to prevent biting trauma to the pedicles in patients undergoing double-opposing buccal flap surgery in the permanent dentition stage.
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Fissura Palatina , Procedimentos de Cirurgia Plástica , Insuficiência Velofaríngea , Criança , Humanos , Fissura Palatina/cirurgia , Retalhos Cirúrgicos , Insuficiência Velofaríngea/cirurgia , Insuficiência Velofaríngea/complicações , Aparelhos Ortodônticos , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Maternal and fetal pregnancy outcomes related to placental function vary based on fetal sex, which may be due to sexually dimorphic epigenetic regulation of RNA expression. We identified sexually dimorphic miRNA expression throughout gestation in human placentae. Next-generation sequencing identified miRNA expression profiles in first and third trimester uncomplicated pregnancies using tissue obtained at chorionic villous sampling (n = 113) and parturition (n = 47). Sequencing analysis identified 986 expressed mature miRNAs from female and male placentae at first and third trimester (baseMean>10). Of these, 11 sexually dimorphic (FDR < 0.05) miRNAs were identified in the first and 4 in the third trimester, all upregulated in females, including miR-361-5p, significant in both trimesters. Sex-specific analyses across gestation identified 677 differentially expressed (DE) miRNAs at FDR < 0.05 and baseMean>10, with 508 DE miRNAs in common between female-specific and male-specific analysis (269 upregulated in first trimester, 239 upregulated in third trimester). Of those, miR-4483 had the highest fold changes across gestation. There were 62.5% more female exclusive differences with fold change>2 across gestation than male exclusive (52 miRNAs vs 32 miRNAs), indicating miRNA expression across human gestation is sexually dimorphic. Pathway enrichment analysis identified significant pathways that were differentially regulated in first and third trimester as well as across gestation. This work provides the normative sex dimorphic miRNA atlas in first and third trimester, as well as the sex-independent and sex-specific placenta miRNA atlas across gestation, which may be used to identify biomarkers of placental function and direct functional studies investigating placental sex differences.
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MicroRNAs , Placenta , Caracteres Sexuais , Epigênese Genética , Feminino , Humanos , Masculino , MicroRNAs/genética , Placenta/metabolismo , Gravidez , Primeiro Trimestre da Gravidez , Terceiro Trimestre da GravidezRESUMO
AIM: To investigate the impact of expression mode: electric breast pump or hand expression, and timing of sample collection: pre- and post-milk ejection on human milk (HM) bacterial DNA profiles. METHODS AND RESULTS: Three HM samples from the same breast were collected from 30 breastfeeding mothers: a pre-milk ejection pump-expressed sample (pre-pump), a post-milk ejection pump-expressed sample (post-pump) and a post-milk ejection hand-expressed sample (post-hand). Full-length 16S rRNA gene sequencing was used to assess milk bacterial DNA profiles. Bacterial profiles did not differ significantly based on mode of expression nor timing of sample collection. No significant differences were detected in the relative abundance of any OTUs based on expression condition (pre-pump/ post-pump and post-pump/post-hand) with univariate linear mixed-effects regression analyses (all P-values > 0·01; α = 0·01). Similarly, no difference in richness was observed between sample types (number of observed OTUs: post-pump/post-hand P = 0·13; pre-pump/post-pump P = 0. 45). CONCLUSION: Bacterial DNA profiles of HM did not differ according to either expression method or timing of sample collection. SIGNIFICANCE AND IMPACT OF THE STUDY: Hand or pump expression can be utilized to collect samples for microbiome studies. This has implications for the design of future HM microbiome studies.
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Extração de Leite , DNA Bacteriano , Leite Humano , Aleitamento Materno , DNA Bacteriano/genética , Feminino , Humanos , Lactação , Ejeção Láctea , RNA Ribossômico 16S/genéticaRESUMO
The identification and SAR development of a series of negative allosteric modulators of the GABAA α5 receptor is described. This novel series of compounds was optimised to provide analogues with high GABAA α5 binding affinity, high α5 negative allosteric modulatory activity, good functional subtype selectivity and low microsomal turnover, culminating in identification of ONO-8590580.
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Transtornos Cognitivos/tratamento farmacológico , Descoberta de Drogas , Imidazóis/farmacologia , Piridinas/farmacologia , Receptores de GABA-A/metabolismo , Regulação Alostérica/efeitos dos fármacos , Transtornos Cognitivos/metabolismo , Relação Dose-Resposta a Droga , Humanos , Imidazóis/síntese química , Imidazóis/química , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Piridinas/síntese química , Piridinas/química , Relação Estrutura-AtividadeRESUMO
Identifying predictors of treatment outcome for nicotine use disorders (NUDs) may help improve efficacy of established treatments, like varenicline. Brain reactivity to drug stimuli predicts relapse risk in nicotine and other substance use disorders in some studies. Activity in the default mode network (DMN) is affected by drug cues and other palatable cues, but its clinical significance is unclear. In this study, 143 individuals with NUD (male n = 91, ages 18-55 years) received a functional magnetic resonance imaging scan during a visual cue task during which they were presented with a series of smoking-related or food-related video clips prior to randomization to treatment with varenicline (n = 80) or placebo. Group independent components analysis was utilized to isolate the DMN, and temporal sorting was used to calculate the difference between the DMN blood-oxygen-level dependent signal during smoke cues and that during food cues for each individual. Food cues were associated with greater deactivation compared with smoke cues in the DMN. In correcting for baseline smoking and other clinical variables, which have been shown to be related to treatment outcome in previous work, a less positive Smoke - Food difference score predicted greater smoking at 6 and 12 weeks when both treatment groups were combined (P = 0.005, ß = -0.766). An exploratory analysis of executive control and salience networks demonstrated that a more positive Smoke - Food difference score for executive control network predicted a more robust response to varenicline relative to placebo. These findings provide further support to theories that brain reactivity to palatable cues, and in particular in DMN, may have a direct clinical relevance in NUD.
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Encéfalo/diagnóstico por imagem , Fumar Cigarros/tratamento farmacológico , Sinais (Psicologia) , Alimentos , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Tabagismo/diagnóstico por imagem , Vareniclina/uso terapêutico , Adolescente , Adulto , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Abandono do Hábito de Fumar , Tabagismo/tratamento farmacológico , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Asthma is recognized as a complex, multifactorial disease with a genetic component that is well recognized. Certain genetic variants are associated with asthma in a number of populations. OBJECTIVE: To determine whether the same variants increase the risk of asthma among American Indian children. METHODS: The electronic medical records of an Indian Health Service facility identified all children between 6 and 17 years of age with case-defining criteria for asthma (n = 108). Control children (n = 216), matched for age, were also identified. Real-time polymerase chain reaction assays were used to genotype 10 single-nucleotide polymorphisms (SNPs) at 6 genetic loci. Genotypic distributions among cases and controls were evaluated by χ2 and logistic regression methods. RESULTS: A variant at 5q22.1 revealed a statistically significant imbalance in the distribution of genotypes between case-control pairs (rs10056340, P < .001). In logistic regression analyses, the same variant at 5q22.1 and a variant at 17q21 were associated with asthma at P < .05 (rs10056340 and rs9303277). Inclusions of age, body mass index, and atopy in multivariate models revealed significant associations between rs10056340 (odds ratio, 2.020; 95% confidence interval, 1.283-3.180; P = .002) and all 5 17q21 SNPs and asthma in this population. In analyses restricted to atopic individuals, the association of rs10056340 was essentially unchanged, whereas among nonatopic individuals the trend was in the same direction but nonsignificant. The reverse was true for the 17q21 SNPs. CONCLUSION: These findings demonstrate that many variants commonly associated with asthma in other populations also accompany this condition among American Indian children. American Indian children also appear to have an increased risk of asthma associated with obesity.
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Asma/epidemiologia , Asma/etiologia , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Indígenas Norte-Americanos/genética , Adolescente , Alelos , Criança , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 5 , Feminino , Frequência do Gene , Loci Gênicos , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , PrevalênciaRESUMO
BACKGROUND: Asthma is recognized as intimately related to immunologic factors and inflammation, although there are likely multiple phenotypes and pathophysiologic pathways. Biomarkers of inflammation may shed light on causal factors and have potential clinical utility. Individual and population genetic factors are correlated with risk for asthma and improved understanding of these contributions could improve treatment and prevention of this serious condition. METHODS: A population-based sample of 108 children with clinically defined asthma and 216 control children were recruited from a small community in the northern plains of the United States. A complete blood count, high sensitivity C-reactive protein, total IgE and specific antibodies to 5 common airborne antigens (CAA), in addition to basic demographic and anthropomorphic data were obtained. Logistic regression was primarily used to determine the association between these humoral factors and risk of asthma. RESULTS: The body mass index (BMI) of those with asthma and their total leukocyte counts, percentage of eosinophils, and levels of total IgE were all greater than corresponding control values in univariate analysis. The presence of detectable, specific IgE antibodies to five common airborne antigens was more likely among cases compared with controls. In multivariate analysis, total IgE was independently associated with asthma; but not after inclusion of a cumulative measure of specific IgE sensitization. CONCLUSION: Many previously reported associations between anthropomorphic and immune factors and increased risk of asthma appear to be also present in this American Indian population. In this community, asthma is strongly associated with sensitization to CAA.
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Alérgenos/imunologia , Asma/etnologia , Proteína C-Reativa/análise , Imunidade Humoral , Imunoglobulina E/sangue , Indígenas Norte-Americanos , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , Contagem de Leucócitos , Modelos Logísticos , Masculino , Análise Multivariada , Estados Unidos/etnologiaRESUMO
BACKGROUND: Accurate measurement of the extent skin has aged is crucial for skin aging research. Image analysis offers a quick and consistent approach for quantifying skin aging features from photographs, but is prone to technical bias and requires proper validation. METHODS: Facial photographs of 75 male and 75 female North-European participants, randomly selected from the Rotterdam Study, were graded by two physicians using photonumeric scales for wrinkles (full face, forehead, crow's feet, nasolabial fold and upper lip), pigmented spots and telangiectasia. Image analysis measurements of the same features were optimized using photonumeric grades from 50 participants, then compared to photonumeric grading in the 100 remaining participants stratified by sex. RESULTS: The inter-rater reliability of the photonumeric grades was good to excellent (intraclass correlation coefficients 0.65-0.93). Correlations between the digital measures and the photonumeric grading were moderate to excellent for all the wrinkle comparisons (Spearman's rho ρ = 0.52-0.89) bar the upper lip wrinkles in the men (fair, ρ = 0.30). Correlations were moderate to good for pigmented spots and telangiectasia (ρ = 0.60-0.75). CONCLUSION: These comparisons demonstrate that all the image analysis measures, bar the upper lip measure in the men, are suitable for use in skin aging research and highlight areas of improvement for future refinements of the techniques.
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Face/anatomia & histologia , Interpretação de Imagem Assistida por Computador/métodos , Reconhecimento Automatizado de Padrão/métodos , Fotografação/métodos , Envelhecimento da Pele/patologia , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Spinal disorders are some of the most prevalent health concerns, especially among students. Based on student demographics, this cross-sectional study evaluated the correlation between functional tests (FTs) and spinal range of motion (ROM). This study included 206 students (age = 19.85 ± 1.80 years) from the Vasile Alecsandri University of Bacau. Participants' assessments were conducted using the following tests: (i) Ott, (ii) Schober, (iii) Stibor, (iv) finger-to-floor distance, (v) lateral flexion of the cervical and lumbar spine, and (vi) flexion of the cervical spine. Correlation analyses were evaluated using the Spearman correlation coefficient analysis. The results indicated a very strong relationship between lateral flexion of the lumbar spine on the left (LFLSL) and right (LFLSR) for all departments (r = 0.85 to 0.97, p < 0.05). There was a stronger relationship between FT results and spinal ROM for physical-education-department students compared to students from other departments (n = 17, r = -0.38 to 0.93, p < 0.05). There was no statistically significant correlation between FTs and spinal ROM based on age (p > 0.05). The study results provide evidence of the primary risk factors that predispose students to postural deviations. Practitioners and physiotherapists can utilize these values as a reference for potential therapeutic interventions.
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Although myofascial release techniques (MRTs) are commonly used to improve athletes' range of motion (ROM), the effectiveness of MRTs may vary depending on the specific method performed. This systematic review and meta-analysis aimed to evaluate the effects of MRTs on the ROM performance of athletes. (2) Methods: The electronic databases of Cochrane Library, PubMed, Scopus, and Web of Science were searched to identify relevant articles published up to June 2023. This study utilized the PRISMA guidelines, and four databases were searched. The methodological quality of the studies was assessed using the PEDro scale, and the certainty of evidence was reported using the GRADE scale. The overall effect size was calculated using the robust variance estimator, and subgroup analyses were conducted using the Hotelling Zhang test. (3) Ten studies met the inclusion criteria. The overall effect size results indicated that the myofascial release intervention had a moderate effect on ROM performance in athletes when compared to the active or passive control groups. (4) Conclusions: Alternative MRTs, such as myofascial trigger point therapy, can further improve the ROM performance of athletes. Gender, duration of intervention, and joint type may have a moderating effect on the effectiveness of MRTs.
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Chronic threatening limb ischemia of the inferior limbs (CLTI) is the final stage of peripheral arterial disease (PAD) and is one of the most feared atherosclerotic manifestations because if left untreated, in time, it can lead to amputation. Although there are currently numerous treatment techniques, both open and endovascular, it is a pathology that has no underlying treatment. Therefore, current studies are very much focused on new therapeutic possibilities that can be applied in the early stages of the atherosclerotic process. In numerous studies in the literature, miRNAs have been identified as important markers of atherosclerosis. The present study aims to identify the expression of three miRNAs-miR-199a, miR-20a, and miR-30c-in patients with chronic limb-threatening ischemia in the pre- and post-revascularization periods. The aim of the study is to identify whether these three markers play a role in critical ischemia and whether they have the potential for future use in new treatments of this pathology.
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Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8+ T cell responses mediate disease. Although these responses originate in the lymph node, we found that expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8+ T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induced cytolytic function. Expression of Blimp-1 (Prdm1), a transcription factor necessary for cytolytic CD8+ T cell differentiation, was driven by hypoxia within the inflamed skin. Hypoxia was further enhanced by the recruitment of neutrophils that consumed oxygen to produce ROS and ultimately increased the hypoxic state and granzyme B expression in CD8+ T cells. Importantly, lesions from patients with cutaneous leishmaniasis exhibited hypoxia transcription signatures that correlated with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8+ T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as for other inflammatory skin diseases in which cytolytic CD8+ T cells contribute to pathogenesis.
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Linfócitos T CD8-Positivos , Leishmaniose Cutânea , Neutrófilos , Fator 1 de Ligação ao Domínio I Regulador Positivo , Animais , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/patologia , Leishmaniose Cutânea/parasitologia , Camundongos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Neutrófilos/imunologia , Neutrófilos/patologia , Neutrófilos/metabolismo , Humanos , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/imunologia , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Granzimas/metabolismo , Granzimas/imunologia , Granzimas/genética , Hipóxia Celular/imunologia , FemininoRESUMO
BACKGROUND: Although COVID-19 infection has been associated with a number of clinical and environmental risk factors, host genetic variation has also been associated with the incidence and morbidity of infection. The CRP gene codes for a critical component of the innate immune system and CRP variants have been reported associated with infectious disease and vaccination outcomes. We investigated possible associations between COVID-19 outcome and a limited number of candidate gene variants including rs1205. METHODOLOGY/PRINCIPAL FINDINGS: The Strong Heart and Strong Heart Family studies have accumulated detailed genetic, cardiovascular risk and event data in geographically dispersed American Indian communities since 1988. Genotypic data and 91 COVID-19 adjudicated deaths or hospitalizations from 2/1/20 through 3/1/23 were identified among 3,780 participants in two subsets. Among 21 candidate variants including genes in the interferon response pathway, APOE, TMPRSS2, TLR3, the HLA complex and the ABO blood group, only rs1205, a 3' untranslated region variant in the CRP gene, showed nominally significant association in T-dominant model analyses (odds ratio 1.859, 95%CI 1.001-3.453, p = 0.049) after adjustment for age, sex, center, body mass index, and a history of cardiovascular disease. Within the younger subset, association with the rs1205 T-Dom genotype was stronger, both in the same adjusted logistic model and in the SOLAR analysis also adjusting for other genetic relatedness. CONCLUSION: A T-dominant genotype of rs1205 in the CRP gene is associated with COVID-19 death or hospitalization, even after adjustment for relevant clinical factors and potential participant relatedness. Additional study of other populations and genetic variants of this gene are warranted.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/genética , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/virologia , Feminino , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , Idoso , Polimorfismo de Nucleotídeo Único , Adulto , Proteína C-Reativa/genética , Predisposição Genética para Doença , Fatores de Risco , Genótipo , Hospitalização , Variação GenéticaRESUMO
High levels of antiretroviral therapy (ART) adherence are required to achieve optimal viral suppression. To better understand mechanisms associated with ART adherence, this study characterized demographic and social-cognitive correlates of ART adherence among HIV-infected individuals from a medium-sized northeastern US city (n=116; 42% female; 43% African-American). Participants completed an audio computer-assisted self-interviewing survey assessing demographics, social-cognitive constructs, and ART adherence, and the participants' most recent viral load was obtained from their medical charts. Suboptimal ART adherence (taking less than 95% of prescribed medications during the past month) was reported by 39% of participants and was associated with being female, being a minority, and having a detectable viral load. In a hierarchical logistic regression analysis, greater than 95% ART adherence was associated with higher levels of adherence self-efficacy (AOR =1.1; p=0.015), higher perceived normative beliefs about the importance of ART adherence (AOR=1.3; p=0.03), and lower concern about missing ART doses (AOR=0.63; p=0.002). Adherence did not differ based on ART outcome expectancies, ART attitudes, or the perceived necessity of ART. In fact, most participants endorsed positive attitudes and expectancies regarding the need for and effectiveness of ART. Taken together, results indicate that suboptimal adherence remains high among HIV-infected minority women, a subpopulation that experiences particularly high rates of chronic stress due to both illness-specific stressors and broader environmental stressors. Consistent with social-cognitive theory, adherence problems in our sample were linked with deficits in self-efficacy as well as perceived norms and behavioral intentions that do not support a goal of 100% adherence. We suggest that interventions to improve adherence informed by social-cognitive theory (1) target patients who are at risk for adherence problems, (2) provide a supportive environment that promotes high rates of adherence, and (3) address inaccurate beliefs regarding optimal adherence levels.
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Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação/psicologia , Cooperação do Paciente/psicologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Cidades , Feminino , Infecções por HIV/etnologia , Infecções por HIV/virologia , Humanos , Masculino , Adesão à Medicação/etnologia , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , New York , Cooperação do Paciente/etnologia , Cooperação do Paciente/estatística & dados numéricos , População UrbanaRESUMO
Although magnetic resonance imaging (MRI) findings are the gold standard for diagnosing herniated discs, there are many limitations to accessing MRI scanning devices in practice. This study aimed to evaluate the relationship between functional tests (the visual analog scale (VAS), the SLUMP test, the Sciatica Bothersomeness Index (SBI), the Oswestry Disability Index (ODI), and the LASEGUE test and MRI findings (LSA, IVDH L4-L5, IVDH L5-S1, DHS L4-L5, and DHS L5-S1) in patients diagnosed with disc herniation. Seventy-eight patients who met the inclusion criteria participated in the study. Radiologists and neurologists evaluated patients with disc herniation. After the disc hernia diagnosis, the patients were referred to a physical therapist for conservative management of the disk hernia. The physical therapists assessed the pain level and performed functional tests on patients. All statistical analyses were performed using R (Core Team) software. The correlation between the measured variables was conducted using the Pearson and Spearman tests. The study results indicated statistically significant correlations between DHS L4-L5 vertebral level and functional tests (VAS: r = 0.49, p = 0.00; SBI: r = 0.44, p = 0.00; ODI: r = 0.49, p = 0.00; LASEGUE: r = -0.48, p = 0.00; SLUMP: r = 0.50, p = 0.00). In conclusion, physiotherapists may prefer functional tests to diagnose the herniated disc, and these functional tests may contribute to performing evidence-based assessments.