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BACKGROUND: Sjögren's disease is a chronic autoimmune disease with an unmet need for targeted therapies. The aim of the TWINSS study is to evaluate the safety and efficacy of iscalimab, a monoclonal antibody against CD40, in patients with active Sjögren's disease. METHODS: This randomised, double-blind, placebo-controlled, phase 2b study, conducted at 71 sites in 23 countries, enrolled patients aged 18 years or older fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) 2016 criteria. In the dose-ranging cohort 1, patients with a EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score of 5 or higher and a EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score of 5 or higher were randomly assigned (1:1:1:1) to subcutaneous iscalimab 150 mg, 300 mg, 600 mg, or placebo. In the proof-of-concept cohort 2, patients with an ESSDAI score of less than 5, ESSPRI (dryness or fatigue) score of 5 or higher, and Impact of Dry Eye on Everyday Life score of 30 or higher were randomly assigned (1:1) to iscalimab 600 mg or placebo. The sponsor, investigator, site personnel, and patients were masked to the treatment assignment. The primary objectives were to demonstrate a dose-response relationship of iscalimab based on the change in ESSDAI from baseline to week 24 in cohort 1 by Multiple Comparison Procedure-Modelling (MCP-Mod), and to assess the effect of iscalimab 600 mg on ESSPRI at week 24 in cohort 2. All the efficacy analyses included all patients who were randomly assigned, and safety analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03905525), and is complete. FINDINGS: Between Oct 1, 2019, and Feb 28, 2022, 460 patients were screened; 173 patients were assigned to cohort 1 (44 to iscalimab 150 mg, 43 to 300 mg, 43 to 600 mg, and 43 to placebo) and 100 to cohort 2 (50 to each group). In cohort 1, the MCP step showed a significant dose-response relationship for placebo-adjusted ESSDAI change from baseline in one of four models (Linlog model, one-sided p=0·0041). ESSDAI decreased from baseline to week 24 with all three doses of iscalimab; 150 mg and 600 mg doses showed statistically significant improvement (placebo-adjusted least squares [LS] mean difference -3·0 [95% CI -4·9 to -1·1]; p=0·0025 for 150 mg and -2·9 [-4·9 to -1·0]; p=0·0037 for 600 mg). In cohort 2, ESSPRI showed a trend towards improvement with iscalimab 600 mg (placebo-adjusted LS mean change from baseline -0·57 points [95% CI -1·30 to 0·15]; p=0·12). Serious adverse events were reported in nine patients in cohort 1 (one [2%] of 43 in the placebo group, one [2%] of 44 in the iscalimab 150 mg group, three [7%] of 42 in the 300 mg group, four [9%] of 44 in the 600 mg group) and four patients in cohort 2 (two [4%] of 50 in each group). No deaths occurred over the 24-week period. INTERPRETATION: The study met the primary objective of demonstrating a significant dose-response relationship with iscalimab in terms of disease activity at week 24. Iscalimab was well tolerated and showed initial clinical benefit over placebo in two distinct populations of patients with Sjögren's disease, to be confirmed in larger trials. FUNDING: Novartis Pharma.
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Relação Dose-Resposta a Droga , Síndrome de Sjogren , Humanos , Método Duplo-Cego , Feminino , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/tratamento farmacológico , Injeções Subcutâneas , Adulto , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Idoso , Índice de Gravidade de Doença , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêuticoRESUMO
Mitochondria play dominant roles in various cellular processes such as energy production, apoptosis, calcium homeostasis, and oxidation-reduction balance. Maintaining mitochondrial quality through mitophagy is essential, especially as its impairment leads to the accumulation of dysfunctional mitochondria in aging oocytes. Our previous research revealed that PKD expression decreases in aging oocytes, and its inhibition negatively impacts oocyte quality. Given PKD's role in autophagy mechanisms, this study investigates whether PKD regulates mitophagy to maintain mitochondrial function and support oocyte maturation. When fully grown oocytes were treated with CID755673, a potent PKD inhibitor, we observed meiosis arrest at the metaphase I stage, along with decreased spindle stability. Our results demonstrate an association with mitochondrial dysfunction, including reduced ATP production and fluctuations in Ca2+ homeostasis, which ultimately lead to increased ROS accumulation, stimulating oxidative stress-induced apoptosis and DNA damage. Further research has revealed that these phenomena result from PKD inhibition, which affects the phosphorylation of ULK, thereby reducing autophagy levels. Additionally, PKD inhibition leads to decreased Parkin expression, which directly and negatively affects mitophagy. These defects result in the accumulation of damaged mitochondria in oocytes, which is the primary cause of mitochondrial dysfunction. Taken together, these findings suggest that PKD regulates mitophagy to support mitochondrial function and mouse oocyte maturation, offering insights into potential targets for improving oocyte quality and addressing mitochondrial-related diseases in aging females.
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OBJECTIVE: To investigate the expression pattern of the D930020B18Rik gene in the testis of the mouse in different stages of development and its possible role in spermatogenesis. METHODS: Using gene expression profile microarray, we identified highly expressed D930020B18Rik in the mouse testis and analyzed the expression pattern of the gene by qPCR, immunohistochemistry, Western blot and immunofluorescence staining, and verified its function and molecular mechanism using bioinformatics analysis, dual-luciferase reporter assay and cell cycle synchronization. RESULTS: The expression of the D930020B18Rik gene remained low in the testis of the mouse and mainly localized in the cytoplasm of spermatogonia during the first 2 postnatal weeks (PNW), increased from the 3rd PNW to sexual maturity, localized in the cytoplasm of spermatogonia and the nuclei of round and elongated spermatids, but was absent in the nuclei of mature sperm. Phylogenetic analysis showed that the D930020B18Rik protein sequence was highly conserved in mammals. Gene set enrichment analysis indicated that D930020B18Rik and its homologous protein might be involved in regulating spermatogenesis of mammals by participating in nucleoplasmic condensation (normalized enrichment score ï¼»NESï¼½ = 1.652, P < 0.01, false discovery rate ï¼»FDRï¼½ = 0.153), meiosis (NES = 1.960, P < 0.01, FDR = 0.001) and formation of microtubule cytoskeleton during mitosis (NES = 1.903, P < 0.01, FDR = 0.009). Dual-luciferase reporter assay revealed that the transcription factors klf5 and foxo1 could identify and bind D930020B18Rik promoters and perform the function of positive or negative transcriptional regulation. CONCLUSION: The D930020B18Rik gene is expressed in the mouse testis in a time- and location-specific manner, highly associated with spermiogenesis, mainly localized in the nuclei of germ cells, and may be involved in the meiosis of spermatocytes and spermiogenesis.
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Espermatogênese , Testículo , Animais , Masculino , Espermatogênese/genética , Camundongos , Testículo/metabolismo , Espermatogônias/metabolismo , Espermatogônias/citologia , Filogenia , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Perfilação da Expressão GênicaRESUMO
Based on first-principles calculations in the density functional theory, we systematically investigated the possible interface structure, magnetism, and electronic properties of the all-Heusler alloy Co2MnGe/CoTiMnGe(100) heterojunction. The calculation indicated that the Co2MnGe Heusler alloy is a half-metal with a magnetic moment of 4.97 µB. CoTiMnGe is a narrow-band gap semiconductor and may act as an ultra-sensitive photocatalyst. We cannot find an "ideal" spin-polarization of 100% in CoCo termination and MnGe termination. Due to the interface interaction, the direct magnetic hybridization or indirect RKKY exchange will be weakened, leading to an increase in the atomic magnetic moment of the interfacial layer. For eight possible heterojunction structures, the half-metallic gaps in the Co2MnGe bulk have been destroyed by the inevitable interface states. The spin-polarization value of 94.31% in the CoCo-TiGe-B heterojunction revealed that it is the most stable structure. It is feasible to search for high-performance magnetic tunnel junction by artificially constructing suitable all-Heusler alloy heterojunctions.
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Within the global architecture, engineering, and construction industry, the use of Building Information Modeling (BIM) technology has significantly expanded. However, given the unique characteristics of road infrastructure, the application of BIM technology is still being explored. This article focuses on the Yuanchen Expressway, exploring innovative applications of BIM technology in comprehensive construction management. The project employs advanced technologies, including BIM, Geographic Information Systems (GIS), and the Internet of Things (IoT), to precisely identify critical nodes and breakthroughs. Supported by a detailed BIM model and a multi-level, diversified digital management platform, the project effectively addresses construction challenges in multiple tunnels, bridges, and complex interchanges, achieving intelligent construction innovation throughout the Yuanchen Expressway with BIM technology. By guiding construction through BIM models, utilizing a BIM+GIS-based management cloud platform system, and employing VR safety briefings, the project effectively reduces the difficulty of communication and coordination in project management, shortens the project measurement cycle, improves on-site work efficiency, and ensures comprehensive control and safety management. This article provides an exemplary case for the application of full-line construction management using BIM technology in the highway sector both in China and globally, offering new perspectives and strategies for highway construction management.
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Objectives: Endotracheal tube (ETT) intubation is a life-saving procedure in patients with respiratory failure. However, the presence of an ETT can cause significant discomfort. A tracheostomy tube is used to administer a mechanical ventilator, resulting in a more stable airway and fewer serious injuries. Noninvasive ventilators (NIPPVs) administer ventilation through masks and must be tightly fixed to the face. ETT, tracheostomy, and NIPPV are the most common methods of ventilator maintenance. However, these interventions often cause discomfort to patients. This study aimed to compare discomfort associated with ETT, tracheostomy, and NIPPV. Materials and Methods: Forty-nine conscious patients with postextubation NIPPV and eight conscious patients who underwent postextubation tracheotomy were evaluated for discomfort. A questionnaire survey on discomfort was performed before and after NIPPV or tracheostomy. These patients reported their level of discomfort on a visual analog scale. Results: The levels of sore throat, nasal pain, body pain, activity limitation, respiratory discomfort, oral discomfort, difficulty coughing sputum, worry about respiratory tube disconnection, back pain, anxiety, worry about long-term admission, sleep disturbance, and general discomfort during ETT intubation were higher than during tracheostomy or NIPPV (all P < 0.05). The mean level of discomfort was approximately 5-6 points (moderate) in patients with ETT and 2-3 points (mild) in patients with NIPPV or tracheostomy. Conclusion: The level of discomfort was higher in patients who underwent ETT intubation than in those who underwent NIPPV or tracheostomy. However, the level of discomfort was similar between the patients with NIPPV and those who underwent tracheostomy.
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BACKGROUND: Obesity is a global concern, driving the search for alternative treatments beyond lifestyle changes and medications. Laser acupuncture (LA) shows promise in obesity management, yet few studies compare it with FDA-approved medications. This study aimed to assess and compare LA's impact with liraglutide on weight reduction in obese individuals. METHODS: Data from the Chang Gung Research Database (CGRD) (2013-2018) were analyzed. Primary outcomes included changes in body weight and BMI within 180 days, with secondary outcomes measuring the proportion achieving 5%, 10%, and 15% weight loss. Adverse events were also assessed. RESULTS: Of 745 subjects (173 LA users, 572 liraglutide users), LA users lost more weight by day 180 (5.82 ± 4.39 vs. 2.38 ± 5.75 kg; p < 0.001) and had a greater BMI reduction (-2.27 ± 1.73 vs. -0.93 ± 2.25 kg/m2; p < 0.001). More LA users achieved 5% and 10% weight loss compared to liraglutide users (64.2% vs. 22.7%, 26.6% vs. 4.2%; all p < 0.001). After balancing baseline differences, LA's benefits remained significant. No adverse events were reported with LA. CONCLUSIONS: LA may offer superior weight reduction compared to liraglutide. Future studies should explore LA alone or in combination with liraglutide for obesity management.
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OBJECTIVE: We present mosaic distal 9p deletion at prenatal diagnosis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 34-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, del(9)(p23)[8]/46,XY[17]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed 43% mosaicism for the 9p24.3p23 deletion. Prenatal ultrasound suspected hypospadias and echogenic bowel. At 23 weeks of gestation, she was referred for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XY,del(9)(p23)[10]/46,XY[10]. The parental karyotypes were normal. Molecular genetic analysis on uncultured amniocytes revealed no uniparental disomy (UPD) 9 by quantitative fluorescence polymerase chain reaction (QF-PCR) and arr 9p24.3p23 × 1.55 (40%-50% mosaicism) by aCGH. At 27 weeks of gestation, she underwent the third amniocentesis which revealed a karyotype of 46,XY,del(9)(p23)[6]/46,XY[14]. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 9p24.3p23 (35% mosaicism). Prenatal ultrasound was normal. She was advised to continue the pregnancy, and a 3020-g phenotypically normal male baby was delivered at 41 weeks of gestation. At birth, the karyotypes of cord blood, umbilical cord and placenta were 46,XY,del(9)(p23)[7]/46,XY[37], 46,XY,del(9)(p23)[17]/46,XY[23] and 46,XY in 40/40 cells, respectively. When follow-up at age three months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY,del(9)(p23)[3]/46,XY[37], and interphase fluorescence in situ hybridization (FISH) analysis on buccal mucosal cells showed 13% (13/102 cells) mosaicism for the distal 9p deletion. CONCLUSION: Mosaic distal 9p deletion with a normal cell line at prenatal diagnosis can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line.
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Amniocentese , Deleção Cromossômica , Cromossomos Humanos Par 9 , Mosaicismo , Humanos , Gravidez , Feminino , Adulto , Mosaicismo/embriologia , Cromossomos Humanos Par 9/genética , Hibridização Genômica Comparativa , Recém-Nascido , Masculino , Aneuploidia , Cariotipagem , Resultado da Gravidez/genéticaRESUMO
Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.
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Radioisótopos de Césio , Mineração , Poluentes Radioativos do Solo , Medição de Risco , China , Poluentes Radioativos do Solo/análise , Radioisótopos de Césio/análise , Humanos , Radioisótopos de Estrôncio/análise , Césio/análise , Cidades , Solo/química , Método de Monte Carlo , Monitoramento de RadiaçãoRESUMO
BACKGROUND: This study adopts a descriptive phenomenological approach to investigate the facilitators and barriers of community nurses' abilities in managing critical and emergency conditions. With the transition of healthcare systems to the community, the evolution of nursing practices, and the attention from policies and practices, community nurses play a crucial role in the management of critical and emergency conditions. However, there is still a lack of comprehensive understanding regarding the factors that promote or hinder their capabilities in this area. AIM: To understand the facilitators and barriers of community nurses in managing critical and emergency conditions, exploring the fundamental reasons and driving forces influencing their treatment capabilities. METHODS: This study utilized the destination sampling method between May 2023 and July 2023. It employed a descriptive phenomenological approach within qualitative research methodologies. Through objective sampling, 17 community nurses from 7 communities in Changning District, Shanghai, were selected as the study subjects. Semi-structured interviews were conducted to gather data, which were subsequently organized and analyzed using Colaizzi's seven-step analysis method, leading to the extraction of final themes. RESULTS: The barrier factors identified from the interviews encompassed three topics: resource allocation, professional factors, and personal literacy. The facilitators comprised three themes: professionalism, management attention, and training and continuing education. We identified that the root causes of the barriers included the lack of practical treatment experience among community nurses, insufficient awareness of self-directed learning, and limited knowledge and technical proficiency. The professional quality of community nurses and management attention serve as motivation for them to enhance their treatment abilities. CONCLUSION: To enhance the capability of community nurses in treating acute and critical patients, it is recommended to bolster training specifically tailored to acute and critical care, raise awareness of first aid practices, and elevate knowledge and skill levels.
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This study aims to investigate the significant relationship between serum heavy metals (lead [Pb], cadmium [Cd], mercury [Hg]) and the risk of herpes simplex virus type 1 (HSV-1) infection. Data were derived from the National Health and Nutrition Examination Survey (NHANES) conducted in the United States from 2007 to 2016. This nationally representative survey, conducted by the National Center for Health Statistics, assessed the health status of participants through interviews, physical examinations, and laboratory tests. After excluding participants lacking serum Pb, Cd, and Hg data, as well as those missing HSV-1 testing data and pregnant women, the analysis included 13 772 participants, among whom 3363 were adolescents. A survey-weighted multivariate logistic regression model was used to evaluate the association between heavy metal exposure and the risk of HSV-1 infection, and to explore the dose-response relationship between them. In adults and adolescents, serum concentrations of Pb and Cd were higher in those infected with HSV-1 than in those not infected. However, an increase in serum Hg concentration was observed only in infected adolescents. After adjusting for potential confounders, elevated serum Pb and Cd concentrations in adults were associated with an increased risk of HSV-1 infection. Higher serum Pb and Cd concentrations were associated with an increased risk of HSV-2 infection, irrespective of HSV-1 infection status. In adults, serum concentrations of Pb and Hg showed an approximately linear relationship with HSV-1 infection risk (p for nonlinearity > 0.05), whereas the dose-response relationship between serum Cd concentration and HSV-1 infection was nonlinear (p for nonlinearity = 0.004). In adolescents, serum concentrations of heavy metals (Pb, Cd, Hg) showed an approximately linear relationship with HSV-1 infection (p for nonlinearity > 0.05). Furthermore, the study examined the relationship between serum heavy metal levels and the risk of HSV-1 infection across different genders, races, income levels, weight statuses, and immune statuses. In conclusion, there is a significant association between serum heavy metal concentrations and HSV-1 infection, which warrants further investigation into the causal relationship between them.
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Herpes Simples , Herpesvirus Humano 1 , Metais Pesados , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Estudos Transversais , Adolescente , Metais Pesados/sangue , Metais Pesados/efeitos adversos , Herpes Simples/epidemiologia , Herpes Simples/sangue , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Cádmio/sangue , Cádmio/efeitos adversos , Chumbo/sangue , Mercúrio/sangue , Criança , Fatores de Risco , Exposição Ambiental/efeitos adversos , IdosoRESUMO
BACKGROUND: Emotional urgency, defined as a trait concept of emotion-based impulsivity, is at least moderately associated with general psychopathology. However, its clinical significance and associations with clinically relevant features of bipolar disorder remain unclear. This scoping review aims address this gap by determining the extent of evidence in this niche scope of study. METHODS: Evidence of between-group differences of positive and negative urgency, its associations with mood severity, and all peripheral associations related to illness and psychosocial outcomes were synthesized based on PRISMA checklists and guidelines for scoping reviews (PRISMA-ScR). DESIGN: Electronic databases were searched for articles published between January 2001 and January 2024. A total of 1013 entries were gathered, and a total of 10 articles were included in the final selection after the removal of duplicates and ineligible articles. RESULTS: Differences in urgency scores between bipolar disorder and healthy controls were large (Cohen's d ranged from 1.77 to 2.20). Negative urgency was at least moderately associated with overall trauma, emotional abuse, neglect, suicide ideation, neuroticism, and irritable/cyclothymic temperament, whereas positive urgency was at least moderately associated with various aspects of aggression and quality of life. Positive but not negative urgency was associated with quality of life in bipolar disorder. CONCLUSION: Large between-group differences found for emotional urgency in bipolar disorder imply large clinical significance. Emotional urgency was associated with worse clinical features and outcomes. Given the high clinical heterogeneity of the disorder, emotional urgency may be an important phenotype indicative of greater disorder severity.
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Transtorno Bipolar , Emoções , Comportamento Impulsivo , Humanos , Transtorno Bipolar/psicologia , Qualidade de Vida/psicologia , Relevância ClínicaRESUMO
INTRODUCTION: The lack of suitable animal models for sarcopenic obesity (SO) limits in-depth research into the disease. Emerging studies have demonstrated that gut dysbiosis is involved in the development of SO. As the importance of microbial metabolites is starting to unveil, it is necessary to comprehend the specific metabolites associated with gut microbiota and SO. OBJECTIVES: We aimed to investigate whether high-fat diet (HFD) causes SO in natural aging animal models and specific microbial metabolites that are involved in linking HFD and SO. METHODS: Young rats received HFD or control diet for 80 weeks, and obesity-related metabolic disorders and sarcopenia were measured. 16S rRNA sequencing and non-targeted and targeted metabolomics methods were used to detect fecal gut microbiota and serum metabolites. Gut barrier function was evaluated by intestinal barrier integrity and intestinal permeability. Trimethylamine N-oxide (TMAO) treatment was further conducted for verification. RESULTS: HFD resulted in body weight gain, dyslipidemia, impaired glucose tolerance, insulin resistance, and systemic inflammation in natural aging rats. HFD also caused decreases in muscle mass, strength, function, and fiber cross-sectional area and increase in muscle fatty infiltration in natural aging rats. 16S rRNA sequencing and nontargeted and targeted metabolomics analysis indicated that HFD contributed to gut dysbiosis, mainly characterized by increases in deleterious bacteria and TMAO. HFD destroyed intestinal barrier integrity and increased intestinal permeability, as evaluated by reducing levels of colonic mucin-2, tight junction proteins, goblet cells and elevating serum level of fluorescein isothiocyanate-dextran 4. Correlation analysis showed a positive association between TMAO and SO. In addition, TMAO treatment aggravated the development of SO in HFD-fed aged rats through regulating the ROS-AKT/mTOR signaling pathway. CONCLUSION: HFD leads to SO in natural aging rats, partially through the gut-microbiota-TMAO-muscle axis.
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BACKGROUND: Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood. METHODS: This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period. RESULTS: We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001). CONCLUSIONS: This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops.
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Neoplasias , Humanos , Feminino , Masculino , Neoplasias/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Estudos Longitudinais , Incidência , Diabetes Mellitus/epidemiologia , Taiwan/epidemiologia , Fatores de Risco , Adulto Jovem , Complicações do Diabetes/epidemiologia , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: We present mosaic distal 10q deletion at prenatal diagnosis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 40-year-old, gravida 2, para 0, woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, del(10) (q26.13)[6]/46,XY[17]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed 35% mosaicism for the 10q26.13q26.3 deletion. At 22 weeks of gestation, she underwent cordocentesis which revealed a karyotype of 46,XY,del(10) (q26.13)[16]/46,XY[24]. Prenatal ultrasound findings were normal. At 24 weeks of gestation, she was referred for genetic counseling, and repeat amniocentesis revealed a karyotype of 46,XY,del(10) (q26.13)[4]/46,XY[22]. The parental karyotypes were normal. Molecular genetic analysis on uncultured amniocytes revealed no uniparental disomy (UPD) 10 by quantitative fluorescence polymerase chain reaction (QF-PCR), arr 10q26.13q26.3 × 1.6 (40% mosaicism) by aCGH, and 29.8% (31/104 cells) mosaicism for the distal 10q deletion by interphase fluorescence in situ hybridization (FISH). The woman was advised to continue the pregnancy, and a phenotypically normal 2,900-g male baby was delivered at 39 weeks of gestation. The cord blood had a karyotype of 46,XY,del(10) (q26.13)[6]/46,XY[34], and both the umbilical cord and the placenta had the karyotype of 46,XY. When follow-up at age four months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XY,del(10) (q26.13)[5]/46,XY[35], and interphase FISH analysis on buccal mucosal cells showed 8% (8/102 cells) mosaicism for distal 10q deletion. CONCLUSION: Mosaic distal 10q deletion with a normal cell line at prenatal diagnosis can be associated with a favorable fetal outcome and perinatal progressive decrease of the aneuploid cell line.
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Amniocentese , Hibridização Genômica Comparativa , Cordocentese , Mosaicismo , Humanos , Gravidez , Feminino , Mosaicismo/embriologia , Adulto , Cromossomos Humanos Par 10/genética , Deleção Cromossômica , Recém-Nascido , Aneuploidia , CariotipagemRESUMO
BACKGROUND: Social support is a robust predictor of post-traumatic stress disorder (PTSD). Although the inverse relationship between perceived social support and PTSD (social causation model) is supported, less is understood about the antecedents of the social causation model. Further, there is limited research in non-Western psychiatric populations that experience elevated rates of trauma and PTSD (e.g., mood disorders). The present study evaluated whether cumulative traumatic life events influenced current PTSD symptoms through maladaptive personality traits and perceptions of social support among Asian patients with mood disorders. METHODS: A total of 200 Asian patients (77.5 % Chinese) with mood disorders were assessed for maladaptive personality traits, perceptions of social support, cumulative traumatic life events, PTSD, and depressive symptoms. Structural equation modelling was conducted to evaluate the extended social causation model. RESULTS: The extended social causation model demonstrated acceptable fit to the data (Comparative Fit Index [CFI] = 0.90; absolute Root Mean Square Error of Approximation [RMSEA] = 0.08). There were significant indirect effects of cumulative traumatic life events on current PTSD symptoms (ß = 0.29, p < .001; 85 % variance explained) and depressive symptoms (ß = 0.28, p < .001; 69 % variance explained). LIMITATIONS: Results may not be generalizable beyond the Singapore population due to the socio-cultural and environmental context. CONCLUSIONS: The present findings provide conceptual support for a maladaptive personality-informed model of social support and PTSD, which could better inform trauma-focused interventions in preventing and treating the debilitating effects of PTSD in psychiatric populations.
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Apoio Social , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Depressão/psicologia , Modelos Psicológicos , Personalidade , Transtornos do Humor/psicologia , Transtornos da Personalidade/psicologia , Acontecimentos que Mudam a Vida , Povo Asiático/psicologiaRESUMO
The objective of this clinical retrospective study was to analyze the prevalence and distribution of different avian and exotic animals presented to 2 exotics-only veterinary hospital in Hong Kong and Taiwan over a 1 year period. Exotic companion mammals, predominated by rabbits (Oryctolagus cuniculus) that were often diagnosed with fractures, were the most commonly presented group of patients in the hospital in Hong Kong while second most of that in Taiwan, with dental disease being commonly presented in the species. This study provided a general overview of avian and exotic patients presented to exotics-only practices in the East Asia region.
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Animais Exóticos , Hospitais Veterinários , Animais , Estudos Retrospectivos , Hong Kong/epidemiologia , Taiwan/epidemiologia , Doenças das Aves/epidemiologia , AvesRESUMO
Diosmetin, a natural occurring flavonoid, is primarily found in citrus fruits, beans, and other plants. Diosmetin demonstrates a variety of pharmacological activities, including anticancer, antioxidant, anti-inflammatory, antibacterial, metabolic regulation, cardiovascular function improvement, estrogenic effects, and others. The process of literature search was done using PubMed, Web of Science and ClinicalTrials databases with search terms containing Diosmetin, content, anticancer, anti-inflammatory, antioxidant, pharmacological activity, pharmacokinetics, in vivo, and in vitro. The aim of this review is to summarize the in vivo, in vitro and clinical studies of Diosmetin over the last decade, focusing on studies related to its anticancer, anti-inflammatory, and antioxidant activities. It is found that DIO has significant therapeutic effects on skin and cardiovascular system diseases, and its research in pharmacokinetics and toxicology is summarized. It provides the latest information for researchers and points out the limitations of current research and areas that should be strengthened in future research, so as to facilitate the relevant scientific research and clinical application of DIO.