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BACKGROUND AND PURPOSE: The co-occurrence of amyloid-ß pathology in Parkinson's disease (PD) is common; however, the role of amyloid-ß deposition in motor prognosis remains elusive. This study aimed to investigate the association between striatal amyloid deposition, motor complications and motor prognosis in patients with PD. METHODS: Ninety-six patients with PD who underwent 18F florbetaben (FBB) positron emission tomography were retrospectively assessed. The ratio of the striatum to global (STG) FBB uptake was obtained for each individual, and patients were allotted into low and high STG groups according to the median value. The effect of STG group on regional amyloid deposition, the occurrence of motor complications and longitudinal change in levodopa equivalent dose (LED) requirement were investigated after controlling for age, sex, LED and disease duration at FBB scan. RESULTS: The high STG group was associated with lower cortical FBB uptake in the parietal, occipital and posterior cingulate cortices and higher striatal FBB uptake compared to the low STG group. Patients in the high STG group had a higher risk of developing wearing off and levodopa-induced dyskinesia than those in the low STG group, whereas the risk for freezing of gait was comparable between the two groups. The high STG group showed a more rapid increase in LED requirements over time than the low STG group. CONCLUSIONS: These findings suggest that relatively high striatal amyloid deposition is associated with poor motor outcomes in patients with PD.
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α,ω-Dicarboxylic acids, ω-aminoalkanoic acids, and α,ω-diaminoalkanes are valuable building blocks for the production of biopolyesters and biopolyamides. One of the key steps in producing these chemicals is the oxidation of ω-hydroxycarboxylic acids using alcohol dehydrogenases (e.g., ChnD of Acinetobacter sp. NCIMB 9871). However, the reaction and structural features of these enzymes remain mostly undiscovered. Thereby, we have investigated characteristics of ChnD based on enzyme kinetics, substrate-docking simulations, and mutation studies. Kinetic analysis revealed a distinct preference of ChnD for medium chain ω-hydroxycarboxylic acids, with the highest catalytic efficiency of 18.0â¯mM-1s-1 for 12-hydroxydodecanoic acid among C6 to C12 ω-hydroxycarboxylic acids. The high catalytic efficiency was attributed to the positive interactions between the carboxyl group of the substrates and the guanidino group of two arginine residues (i.e., Arg62 and Arg266) in the substrate binding site. The ChnD_R62L variant showed the increased efficiency and affinity, particularly for fatty alcohols (i.e., C6-C10) and branched-chain fatty alcohols, such as 3-methyl-2-buten-1-ol. Overall, this study contributes to the deeper understanding of medium-chain primary aliphatic alcohol dehydrogenases and their applications for the production of industrially relevant chemicals such as α,ω-dicarboxylic acids, ω-aminoalkanoic acids, and α,ω-diaminoalkanes from renewable biomass.
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Acinetobacter , Acinetobacter/enzimologia , Acinetobacter/genética , Especificidade por Substrato , Cinética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Simulação de Acoplamento Molecular , Oxirredutases do Álcool/metabolismo , Oxirredutases do Álcool/química , Oxirredutases do Álcool/genética , Modelos MolecularesRESUMO
PURPOSE: This study aimed to examine the adequacy of current nurse staffing levels by identifying nursing activities and workload. METHODS: The study used a mixed-method design. A nursing activity survey was conducted using the work sampling method over 2 working days with 119 general ward nurses. A focus group interview was conducted with 12 nurses. Quantitative and qualitative data were analyzed using SPSS 20.0 and content analysis, respectively. RESULTS: The most amount of time was spent on medication (in direct nursing) and electronic medical record documentation (in indirect nursing). The appropriate nurse-to-patient ratio is 1:7.7 for the day shift, 1:9.0 for the evening shift, and 1:11.9 for the night shift. However, the current nurse-to-patient ratio is 1:9.4, 1:11.0, and 1:13.8 for the day, evening, and night shifts, respectively. Therefore, the current nurse staffing level is insufficient for the workload. In the focus group interview, the main reasons cited for being unable to complete tasks within working hours were communication and coordination, and the nursing electronic medical record. The essential nursing activities of basic nursing and emotional support were overlooked owing to a heavy workload. Therefore, an adequate nurse staffing level should be higher than the measured quantitative workload. CONCLUSION: These results suggest the general wards of tertiary hospitals should evaluate the adequacy of their current nurse staffing and allocate sufficient nurses to improve patient safety and nursing care quality.
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Grupos Focais , Entrevistas como Assunto , Recursos Humanos de Enfermagem Hospitalar , Admissão e Escalonamento de Pessoal , Centros de Atenção Terciária , Carga de Trabalho , Humanos , Recursos Humanos de Enfermagem Hospitalar/psicologia , Adulto , Inquéritos e Questionários , Feminino , Masculino , Registros Eletrônicos de SaúdeRESUMO
Type 2 diabetes mellitus (T2DM) and periodontitis (PD) have intricated connections as chronic inflammatory diseases. While the immune response is a key factor that accounts for their association, the underlying mechanisms remain unclear. To gain a deeper understanding of the connection, we conducted research using a multiomics approach. We generated whole genome and methylation profiling array data from the periodontium of PD patients with DM (PDDM) and without DM to confirm genetic and epigenetic changes. Independent bulk and single-cell RNA sequencing data were employed to verify the expression levels of hypo-methylated genes. We observed a gradual rise in C>T base substitutions and hypomethylation in PD and PDDM patients compared with healthy participants. Furthermore, specific genetic and epigenetic alterations were prominently associated with the Fc-gamma receptor-mediated phagocytosis pathway. The upregulation of these genes was confirmed in both the periodontal tissues of PD patients and the pancreatic tissues of T2DM patients. Through single-cell RNA analysis of peripheral blood mononuclear cells, substantial upregulation of Fc-gamma receptors and related genes was particularly identified in monocytes. Our findings suggest that targeting the Fc-gamma signaling pathway in monocytes holds promise as a potential treatment strategy for managing systemic complications associated with diabetes.
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The topology of the basement membrane (BM) affects cell physiology and pathology, and BM thickening is associated with various chronic lung diseases. In addition, the topology of commercially available poly (ethylene terephthalate) (PET) membranes, which are used in preclinical in vitro models, differs from that of the human BM, which has a fibrous and elastic structure. In this study, we verified the effect of BM thickness on the differentiation of normal human bronchial epithelial (NHBE) cells. To evaluate whether the thickness of poly-ε-carprolactone (PCL) mesh affects the differentiation of NHBE cells, cells were grown on thin- (6-layer) and thick-layer (80-layer) meshes consisting of electrospun PCL nanofibers using an air-liquid interface (ALI) cell culture system. It was found that the NHBE cells formed a normal pseudostratified epithelium composed of ciliated, goblet, and basal cells on the thin-layer PCL mesh; however, goblet cell hyperplasia was observed on the thick-layer PCL mesh. Differentiated NHBE cells cultured on the thick-layer PCL mesh also demonstrated increased epithelial-mesenchymal transition (EMT) compared to those cultured on the thin-layer PCL mesh. In addition, expression of Sox9, nuclear factor (NF)-κB, and oxidative stress-related markers, which are also associated with goblet cell hyperplasia, was increased in the differentiated NHBE cells cultured on the thick-layer PCL mesh. Thus, the use of thick electrospun PCL mesh led to NHBE cells differentiating into hyperplastic goblet cells via EMT and the oxidative stress-related signaling pathway. Therefore, the topology of the BM, for example, thickness, may affect the differentiation direction of human bronchial epithelial cells.
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Membrana Basal , Diferenciação Celular , Células Epiteliais , Poliésteres , Humanos , Poliésteres/química , Membrana Basal/metabolismo , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Nanofibras/química , Células Cultivadas , Brônquios/citologia , Brônquios/metabolismoRESUMO
In this study, changes in bioactive compound contents and the in vitro biological activity of mixed grains, including oats, sorghum, finger millet, adzuki bean, and proso millet, with eight different blending ratios were investigated. The total phenolic compounds and flavonoid contents ranged from 14.43-16.53 mg gallic acid equivalent/g extract and 1.22-5.37 mg catechin equivalent/g extract, respectively, depending on the blending ratio. The DI-8 blend (30% oats, 30% sorghum, 15% finger millet, 15% adzuki bean, and 10% proso millet) exhibited relatively higher antioxidant and anti-diabetic effects than other blending samples. The levels of twelve amino acids and eight organic acids in the grain mixes were measured. Among the twenty metabolites, malonic acid, asparagine, oxalic acid, tartaric acid, and proline were identified as key metabolites across the blending samples. Moreover, the levels of lactic acid, oxalic acid, and malonic acid, which are positively correlated with α-glucosidase inhibition activity, were considerably higher in the DI-blending samples. The results of this study suggest that the DI-8 blend could be used as a functional ingredient as it has several bioactive compounds and biological activities, including anti-diabetic activity.
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Antioxidantes , Grão Comestível , Antioxidantes/farmacologia , Antioxidantes/química , Grão Comestível/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Flavonoides/análise , Flavonoides/química , Flavonoides/farmacologia , Fenóis/análise , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Aminoácidos/metabolismo , Aminoácidos/análiseRESUMO
Hypertension remains a significant global health concern, contributing significantly to cardiovascular diseases and mortality rates. The inhibition of angiotensin-converting enzyme (ACE) plays a crucial role in alleviating high blood pressure. We investigated the potential of finger millets (Eleusine coracana) as a natural remedy for hypertension by isolating and characterizing its ACE-inhibitory compound. First, we evaluated the ACE-inhibitory activity of the finger millet ethanol extract and subsequently proceeded with solvent fractionation. Among the solvent fractions, the ethyl acetate fraction exhibited the highest ACE inhibitory activity and was further fractionated. Using preparative high-performance liquid chromatography, the ethyl acetate fraction was separated into four subfractions, with fraction 2 (F2) exhibiting the highest ACE inhibitory activity. Subsequent 1 H-nuclear magnetic resonance (NMR) and 13 C-NMR analyses confirmed that the isolated compound from F2 was catechin. Furthermore, molecular docking studies indicated that catechin has the potential to act as an ACE inhibitor. These findings suggest that finger millets, particularly as a source of catechin, have the potential to be used as a natural antihypertensive.
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Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Eleusine , Simulação de Acoplamento Molecular , Extratos Vegetais , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/química , Eleusine/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/química , Cromatografia Líquida de Alta Pressão , Peptidil Dipeptidase A/metabolismo , Hipertensão/tratamento farmacológico , Espectroscopia de Ressonância MagnéticaRESUMO
PURPOSE: This study comprehensively examines the disability acceptance experience of individuals who become disabled following accidents in the military after enlistment. METHODS: In-depth interviews and participative observation of two soldiers with disabilities are conducted. Data sources encompass the transcripts from these interviews, relevant news videos, and articles on the participants. A qualitative case study approach is applied to conduct both "within-case" and "cross-case" analyses. RESULTS: Although the two participants survived a crippling accidents, their military units did not actively attempt to resolve the accident. They grappled with despair and found it challenging to accept their new status as individuals with disability. Over time, they noticed changes in their personal relationships and started considering themselves burdens on their caregivers. However, despite encountering psychological challenges, which were marked by repeated setbacks and disappointments, the soldiers consistently made determined efforts to realize their objectives. Moreover, they strove to lead purposeful lives despite suffering the adversities caused by their disabilities. CONCLUSIONS: This study is the first in-depth examination of the disability acceptance experiences of soldiers with disability. The insights gleaned from our in-depth interviews will help formulate psychological and physical support systems for such individuals.
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Pessoas com Deficiência , Militares , Pesquisa Qualitativa , Humanos , Pessoas com Deficiência/psicologia , Militares/psicologia , Masculino , Adulto , Adaptação Psicológica , Adulto Jovem , Entrevistas como Assunto , Cuidadores/psicologiaRESUMO
The anti-diabetic properties of whole groats and dietary fibers from various grains and legumes are well known. Nevertheless, studies on the anti-diabetic effects of their extracts are limited, and it is difficult to compare their efficacy. This study investigated the anti-diabetic potential of ethanol extracts from oats (OE), sorghum (SE), foxtail millet (FE), proso millet (PE), adzuki bean (AE), and black soybean (BE) in a high-fat diet and streptozotocin-nicotinamide-induced diabetic rat models. The extracts, obtained using 99.9 % ethanol, were orally administered to diabetic rats for four weeks. Various parameters were evaluated, including fasting blood glucose levels, glucose tolerance, insulin sensitivity, serum insulin levels, and pancreas histological analysis. OE and SE effectively reduced fasting blood glucose levels and the area under the curve (AUC) in the oral glucose tolerance test. Only OE significantly decreased the AUC in the insulin tolerance test and increased insulin concentration and homeostatic model assessment of the ß-cell function index, indicating improved insulin sensitivity and ß-cell function. Histological and immunohistochemical analysis of the pancreas supported these findings, demonstrating that OE protected against pancreatic cell damage. In contrast, FE, PE, AE, and BE did not have a significant effect on diabetes-related parameters. These findings identify OE as the most promising natural intervention for diabetes management.
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BACKGROUND: Postoperative respiratory failure is a serious complication that could benefit from early accurate identification of high-risk patients. We developed and validated a machine learning model to predict postoperative respiratory failure, defined as prolonged (>48 h) mechanical ventilation or reintubation after surgery. METHODS: Easily extractable electronic health record (EHR) variables that do not require subjective assessment by clinicians were used. From EHR data of 307,333 noncardiac surgical cases, the model, trained with a gradient boosting algorithm, utilised a derivation cohort of 99,025 cases from Seoul National University Hospital (2013-9). External validation was performed using three separate cohorts A-C from different hospitals comprising 208,308 cases. Model performance was assessed by area under the receiver operating characteristic (AUROC) curve and area under the precision-recall curve (AUPRC), a measure of sensitivity and precision at different thresholds. RESULTS: The model included eight variables: serum albumin, age, duration of anaesthesia, serum glucose, prothrombin time, serum creatinine, white blood cell count, and body mass index. Internally, the model achieved an AUROC of 0.912 (95% confidence interval [CI], 0.908-0.915) and AUPRC of 0.113. In external validation cohorts A, B, and C, the model achieved AUROCs of 0.879 (95% CI, 0.876-0.882), 0.872 (95% CI, 0.870-0.874), and 0.931 (95% CI, 0.925-0.936), and AUPRCs of 0.029, 0.083, and 0.124, respectively. CONCLUSIONS: Utilising just eight easily extractable variables, this machine learning model demonstrated excellent discrimination in both internal and external validation for predicting postoperative respiratory failure. The model enables personalised risk stratification and facilitates data-driven clinical decision-making.
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Aprendizado de Máquina , Complicações Pós-Operatórias , Insuficiência Respiratória , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/diagnóstico , Adulto , Estudos de Coortes , Medição de Risco/métodos , Respiração Artificial , Reprodutibilidade dos Testes , Registros Eletrônicos de Saúde , Valor Preditivo dos Testes , Procedimentos Cirúrgicos Operatórios/efeitos adversosRESUMO
BACKGROUND: Evidence on the association between obesity parameters, including body mass index (BMI) and waist circumference (WC), and osteoarthritis is limited. This study aimed to investigate these associations in Korean adults. METHODS: This nationwide cross-sectional study used data from 24,101 adults aged ≥19 years who participated in the Korea National Health and Nutrition Examination Survey 2016-2020. Odds ratios (ORs) and 95% confidence intervals (CIs) for osteoarthritis according to BMI and WC were analyzed using multivariable logistic regression analyses. RESULTS: The prevalence of osteoarthritis was higher in individuals with general (10.0%) and abdominal obesity (12.8%) compared with those without. Greater BMI and WC were associated with a higher prevalence (P<0.001) and risk of osteoarthritis (Model 3, P for trend <0.001). Individuals with general and abdominal obesity were associated with a 1.50-fold (OR, 1.50; 95% CI, 1.35-1.67) and 1.64-fold (OR, 1.64; 95% CI, 1.47-1.84) increased risk of osteoarthritis, compared with those without. Similar associations were observed in subgroups according to age, sex, smoking status, and presence of diabetes mellitus. The odds of osteoarthritis 1.73-fold increased (OR, 1.73; 95% CI, 1.53-1.95) in individuals with both general and abdominal obesity compared with those without any of them. CONCLUSION: Greater BMI, WC, and general and abdominal obesity were associated with an increased risk of osteoarthritis in Korean adults. Appropriate management of abdominal and general obesity may be important to reduce the risk of osteoarthritis.
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This study investigated the antihypertensive effects of the combined extract of sorghum, adzuki bean, and finger millet (SAFE) on spontaneously hypertensive rats. The rats were divided into four groups (n = 8): WKY, SHR, SAFE (500 mg/kg SAFE), and CAP (50 mg/kg captopril). SAFE significantly decreased the lean-to-fat mass ratio with no notable changes in body weight, food intake, or food efficiency ratio, and it effectively lowered both systolic and diastolic blood pressures, comparable to CAP. Moreover, it significantly reduced the cardiac mass index and alleviated cardiac fibrosis. SAFE did not induce hepatotoxicity, as indicated by the maintenance of aspartate aminotransferase and alanine aminotransferase levels in the normal range, confirming its safety. Taken together, these findings suggested that SAFE can be used as a dietary supplement for blood pressure regulation and cardiovascular disease prevention.
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Eleusine , Sorghum , Vigna , Ratos , Animais , Ratos Endogâmicos WKY , Ratos Endogâmicos SHR , Anti-Hipertensivos/farmacologia , Suplementos Nutricionais , Extratos Vegetais/farmacologiaRESUMO
AIM: Periodontitis is caused by dysbiosis of oral microbes and is associated with increased cognitive decline in Alzheimer's disease (AD), and recently, a potential functional link was proposed between oral microbes and AD. We compared the oral microbiomes of patients with or without AD to evaluate the association between oral microbes and AD in periodontitis. MATERIALS AND METHODS: Periodontitis patients with AD (n = 15) and cognitively unimpaired periodontitis patients (CU) (n = 14) were recruited for this study. Each patient underwent an oral examination and neuropsychological evaluation. Buccal, supragingival and subgingival plaque samples were collected, and microbiomes were analysed by next-generation sequencing. Alpha diversity, beta diversity, linear discriminant analysis effect size, analysis of variance-like differential expression analysis and network analysis were used to compare group oral microbiomes. RESULTS: All 29 participants had moderate to severe periodontitis. Group buccal and supragingival samples were indistinguishable, but subgingival samples demonstrated significant alpha and beta diversity differences. Differential analysis showed subgingival samples of the AD group had higher prevalence of Atopobium rimae, Dialister pneumosintes, Olsenella sp. HMT 807, Saccharibacteria (TM7) sp. HMT 348 and several species of Prevotella than the CU group. Furthermore, subgingival microbiome network analysis revealed a distinct, closely connected network in the AD group comprised of various Prevotella spp. and several anaerobic bacteria. CONCLUSIONS: A unique microbial composition was discovered in the subgingival region in the AD group. Specifically, potential periodontal pathogens were found to be more prevalent in the subgingival plaque samples of the AD group. These bacteria may possess a potential to worsen periodontitis and other systemic diseases. We recommend that AD patients receive regular, careful dental check-ups to ensure proper oral hygiene management.
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Doença de Alzheimer , Placa Dentária , Microbiota , Periodontite , Humanos , Periodontite/microbiologia , Bactérias/genética , Placa Dentária/microbiologia , RNA Ribossômico 16SRESUMO
BACKGROUND: Type 2 diabetes mellitus (DM) is a complex metabolic disorder that causes various complications, including periodontitis (PD). Although a bidirectional relationship has been reported between DM and PD, their immunological relationship remains poorly understood. Therefore, this study aimed to compare the immune response in patients with PD alone and in those with both PD and DM (PDDM) to expand our knowledge of the complicated connection between PD and DM. METHODS: Peripheral blood mononuclear cells were collected from 11 healthy controls, 10 patients with PD without DM, and six patients with PDDM, followed by analysis using single-cell RNA sequencing. The differences among groups were then compared based on intracellular and intercellular perspectives. RESULTS: Compared to the healthy state, classical monocytes exhibited the highest degree of transcriptional change, with elevated levels of pro-inflammatory cytokines in both PD and PDDM. DM diminished the effector function of CD8+ T and natural killer (NK) cells as well as completely modified the differentiation direction of these cells. Interestingly, a prominent pathway, RESISTIN, which is known to increase insulin resistance and susceptibility to diabetes, was found to be activated under both PD and PDDM conditions. In particular, CAP1+ classical monocytes from patients with PD and PDDM showed elevated nuclear factor kappa B-inducing kinase activity. CONCLUSIONS: Overall, this study elucidates how the presence of DM contributes to the deterioration of T/NK cell immunity and the immunological basis connecting PD to DM.
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Diabetes Mellitus Tipo 2 , Periodontite , Humanos , Diabetes Mellitus Tipo 2/complicações , Leucócitos Mononucleares , Periodontite/genética , Periodontite/complicações , Periodontite/metabolismo , Citocinas/metabolismo , Células Matadoras NaturaisRESUMO
Peanut shells, rich in antioxidants, remain underutilized due to limited research. The present study investigated the changes in the functional compound content and skin aging-related enzyme inhibitory activities of peanut shells by electron-beam treatment with different sample states and irradiation doses. In addition, phenolic compounds in the peanut shells were identified and quantified using ultra-performance liquid chromatography with ion mobility mass spectrometry-quadrupole time-of-flight and high-performance liquid chromatography with a photodiode array detector, respectively. Total phenolic compound content in solid treatment gradually increased from 110.31 to 189.03 mg gallic acid equivalent/g as the irradiation dose increased. Additionally, electron-beam irradiation significantly increased 5,7-dihydroxychrome, eriodictyol, and luteolin content in the solid treatment compared to the control. However, liquid treatment was less effective in terms of functional compound content compared to the solid treatment. The enhanced functional compound content in the solid treatment clearly augmented the antioxidant activity of the peanut shells irradiated with an electron-beam. Similarly, electron-beam irradiation substantially increased collagenase and elastase inhibitory activities in the solid treatment. Mutagenicity assay confirmed the stability of toxicity associated with the electron-beam irradiation. In conclusion, electron-beam-irradiated peanut shells could serve as an important by-product with potential applications in functional cosmetic materials.
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Arachis , Elétrons , Arachis/química , Fenóis/análise , Antioxidantes/química , Cromatografia Líquida de Alta PressãoRESUMO
INTRODUCTION: Timely diagnosis of interstitial lung disease (ILD) is limited by obstacles in the current patient pathway. Misdiagnosis and delays are common and may lead to a significant burden of diagnostic procedures and worse outcomes. This Delphi survey aimed to identify consensus on the key steps that facilitate the patient journey to an accurate ILD diagnosis and appropriate management in the US. METHODS: A modified Delphi analysis was conducted, comprising three online surveys based on a comprehensive literature search. The surveys spanned five domains (guidelines, community screening, diagnosis, management and specialist referral) and were completed by a panel of US physicians, including primary care physicians and pulmonologists practising in community or academic settings. A priori definitions of consensus agreement were median scores of 2-3 (agree strongly/agree), with an IQR of 0-1 for questions on a 7-point Likert scale from -3 to 3, or ≥80% agreement for binary questions. RESULTS: Forty-nine panellists completed the surveys and 62 statements reached consensus agreement. There was consensus agreement on what should be included in the primary care evaluation of patients with suspected ILD and the next steps following workup. Regarding diagnosis in community pulmonology care, consensus agreement was reached on the requisition and reporting of high-resolution CT scans and the appropriate circumstances for holding multidisciplinary discussions. Additionally, there was consensus agreement on which symptoms and comorbidities should be monitored, the frequency of consultations and the assessment of disease progression. Regarding specialist referral, consensus agreement was reached on which patients should receive priority access to ILD centres and the contents of the referral package. CONCLUSIONS: These findings clarify the most common issues that should merit further evaluation for ILD and help define the steps for timely, accurate diagnosis and appropriate collaborative specialty management of patients with ILD.
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Doenças Pulmonares Intersticiais , Médicos , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/terapia , Comorbidade , Inquéritos e Questionários , Erros de DiagnósticoRESUMO
BACKGROUND: Peri-implantitis is similar to periodontitis, but there are some differences. For the effective control of peri-implantitis, it is necessary to clarify its similarities and differences with periodontitis in terms of gene expression. METHODS: This cross-sectional study included 20 participants (10 healthy subjects and 10 patients with periodontitis and peri-implantitis). Gingival tissue samples (10 healthy, 10 periodontitis, and 10 peri-implantitis tissues) were collected, RNAs were extracted, and RNA sequencing and analysis were performed. RESULTS: Differentially expressed gene (DEG) analysis identified 757 upregulated and 159 downregulated genes common between periodontitis and peri-implantitis. Periodontitis tissues uniquely showed 186 overexpressed and 22 suppressed genes compared with peri-implantitis and healthy tissues, while peri-implantitis had 1974 and 642, respectively. Each common and unique differential gene set showed distinct enriched biological features between periodontitis and peri-implantitis after the pathway enrichment analysis. The expression pattern of selected DEGs focused on the representability of the disease was validated by RT-qPCR. CONCLUSIONS: Although periodontitis and peri-implantitis showed common gene expression that was clearly differentiated from healthy conditions, there were also unique gene patterns that were differentially expressed only in peri-implantitis. These findings will help elucidate the mechanisms involved in the progression of peri-implantitis.
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For patients with severe burns that consist of contractures induced by fibrous scar tissue formation, a graft must adhere completely to the wound bed to enable wound healing and neovascularization. However, currently available grafts are insufficient for scar suppression owing to their nonuniform pressure distribution in the wound area. Therefore, considering the characteristics of human skin, which is omnidirectionally stretched via uniaxial stretching, we proposed an auxetic skin scaffold with a negative Poisson's ratio (NPR) for tight adherence to the skin scaffold on the wound bed site. Briefly, a skin scaffold with the NPR effect was fabricated by creating a fine pattern through 3D printing. Electrospun layers were also added to improve adhesion to the wound bed. Fabricated skin scaffolds displayed NPR characteristics (-0.5 to -0.1) based on pulling simulation and experiment. Finger bending motion tests verified the decreased marginal forces (<50%) and deformation (<60%) of the NPR scaffold. In addition, the filling of human dermal fibroblasts in most areas (>95%) of the scaffold comprising rarely dead cells and their spindle-shaped morphologies revealed the high cytocompatibility of the developed scaffold. Overall, the developed skin scaffold may help reduce wound strictures in the joints of patients with burns as it exerts less pressure on the wound margin.
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Meat tenderness is considered the most important trait contributing to beef quality, level of consumer satisfaction, willingness to pay premium prices and industry profit. Genomic selection method would be helpful for genetic improvement of traits with low heritability and that are difficult to measure. The identification of core genes can aid genomic selection for complex traits with low heritability that are difficult to measure. We performed statistical analysis of associations between longissimus dorsi muscle tenderness and gene expression in 20 Hanwoo cattle, using Warner-Bratzler shear force and RNAseq data, respectively. We found a total of 166 core genes, from which six (ASAP1, CAPN5, ELN, SUMF2, TTC8 and MGAT4A) were regulated by 16 cis-expression quantitative trait loci (eQTL) SNPs. Notably, we found that a cis-eQTL SNP of the ELN gene contained an MFZ-1 binding site in its putative promoter region. These findings provide useful information for genomic prediction of beef tenderness in Hanwoo cattle.
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Carne , Locos de Características Quantitativas , Bovinos/genética , Animais , Carne/análise , Fenótipo , Biomarcadores , República da Coreia , Músculo Esquelético/fisiologiaRESUMO
Background: Genetic variations in Idiopathic Pulmonary Fibrosis (IPF) affect survival and outcomes. Current antifibrotic agents are managed based on the patient's reported side effects, although certain single nucleotide polymorphisms (SNPs) might alter treatment response and survival depending on the antifibrotic administered. This study investigated variations in response and outcomes to pirfenidone based on patients-specific genetic profiles. Methods: Retrospective clinical data were collected from 56 IPF patients and had blood drawn for DNA extraction between 7/2013 and 3/2016, with the last patient followed until 10/2018. Nine SNPs were selected for pharmacogenetic investigation based on prior associations with IPF treatment outcomes or implications for pirfenidone metabolism. Genetic variants were examined in relation to clinical data and treatment outcomes. Results: Of the 56 patients, 38 were males (67.85%). The average age of IPF at diagnosis was 66.88 years. At the initiation of pirfenidone, the average percent predicted FVC was 70.7%, and the average DLCO percent predicted was 50.02% (IQR 40-61%). Among the genetic variants tested, the TOLLIP rs5743890 risk allele was significantly associated with improved survival, with increasing pirfenidone duration. This finding was observed with CC or CT genotype carriers but not for those with the TT genotype (p = 0.0457). Similarly, the TGF-B1 rs1800470 risk allele was also significantly associated with improved survival with longer pirfenidone therapy (p = 0.0395), even though it was associated with disease progression. Conclusion: This pilot study suggests that in IPF patients, the TOLLIP rs5743890 genotypes CC and CT, as well as TGF-B1 rs 1800470 may be associated with increased survival when treated with pirfenidone.