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1.
Eur J Cancer Prev ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38595139

RESUMO

BACKGROUND: This study assessed prostate cancer burden and trends in major BRICS countries (Brazil, Russia, India, China, and South Africa) from 1990 to 2019. METHODS: Utilizing Global Burden of Disease Study 2019 data, we calculated age-standardized rates for prostate cancer incidence, prevalence, mortality, and disability-adjusted life years (DALYs) with 95% uncertainty intervals (UIs). Joinpoint regression analysis determined the average annual percentage change (AAPC) for trend characterization. RESULTS: Prostate cancer ranked highest in China for incidence, prevalence, mortality, and DALYs. In 2019, Brazil had the highest age-standardized incidence rate (ASIR) [55.029 (95% UI: 47.744-81.831)] and age-standardized prevalence rate (ASPR) [372.511 (95% UI: 327.549-549.128)], while South Africa recorded the highest age-standardized mortality rate (ASMR) [42.241 (95% UI: 32.146-47.933)], and age-standardized DALY rate (ASDR) [666.085 (95% UI: 522.626-764.612)]. ASIR and ASPR increased significantly over three decades (AAPC > 0), with varying ASMR and ASDR trends. CONCLUSION: Prostate cancer poses a significant public health challenge. While incidence and prevalence rise, mortality declines in China, India, and Brazil. Tailored health policies are crucial to address diverse disease burden characteristics.

2.
J Glob Health ; 14: 04091, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587297

RESUMO

Background: Stroke has become a significant public health issue in China. Although studies have shown that women's age at first live birth (AFLB) might be associated with incident stroke, there is limited evidence on this relationship among Chinese parous women. Likewise, the nature of this association across urban-rural socioeconomic status (SES) has yet to be explored. In this prospective study, we sought to investigate the associations of women's AFLB with the risk of incident stroke and its subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) and to explore the differences of these associations as well as the population-level impacts across SES classes. Methods: We used data on 290 932 Chinese parous women from the China Kadoorie Biobank who were recruited in the baseline survey between 2004 and 2008 and followed up until 2015. We used latent class analysis to identify urban-rural SES classes and Cox proportional hazard regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for AFLB's association with incident stroke. We then calculated population attributable fraction (PAF) to demonstrate the population-level impact of later AFLB on stroke. Results: Around 8.9% of parous women developed stroke after AFLB. Compared with women with AFLB <22 years, those with older AFLB had a higher risk of total stroke, with fully adjusted HRs (95% CI) of 1.71 (95% CI = 1.65-1.77) for 22-24 years and 3.37 (95% CI = 3.24-3.51) for ≥25 years. The associations of AFLB with ischaemic stroke were stronger among rural-low-SES participants. We found the highest PAFs of ischaemic stroke (60.1%; 95% CI = 46.2-70.3) associated with later AFLB for urban-high-SES individuals. Conclusions: Older AFLB was associated with higher risks of incident stroke and its subtypes among Chinese parous women, with stronger associations between AFLB and ischaemic stroke among rural-low-SES participants. Targeted medical advice for pregnant women of different ages could have long-term benefits for stroke prevention.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Gravidez , Acidente Vascular Cerebral/epidemiologia , Estudos Prospectivos , Disparidades Socioeconômicas em Saúde , Nascido Vivo , China/epidemiologia
3.
Psychon Bull Rev ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653956

RESUMO

Whether information in working memory (WM) is stored in a domain-independent or domain-specific system is still the subject of intense debate. This study used the delayed match-to-sample paradigm, the dual-task paradigm, and the selective interference paradigm to investigate the mechanism of cross-modal storage in visual and vibrotactile WM. We postulated that WM may store cross-modal data from haptics and vision independently, and we proposed domain-specific WM storage. According to the findings, the WM can store cross-modal information from vision and haptics independently, and the storage of visual and tactile WM may be domain-specific. This study provides early support for the hypothesis that haptic and visuospatial sketchpads are dissociated. In addition, the current study provides evidence to elucidate the mechanisms by which WM stores and processes data from different modalities and content. The results also indicate that a cross-modal approach can broaden the cognitive processing bandwidth of WM.

4.
Molecules ; 29(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38542849

RESUMO

Compared to the currently widely used propane dehydrogenation process for propylene production, propane oxidative dehydrogenation (ODHP) offers the advantage of no thermodynamic limitations and lower energy consumption. However, a major challenge in ODHP is the occurrence of undesired over-oxidation reactions of propylene, which reduce selectivity and hinder industrialization. MOFs possess a large number of metal sites that can serve as catalytic centers, which facilitates the easier access of reactants to the catalytic centers for reaction. Additionally, their flexible framework structure allows for easier adjustment of their pores compared to metal oxides and molecular sieves, which is advantageous for the diffusion of products within the framework. This property reduces the likelihood of prolonged contact between the generated propylene and the catalytic centers, thus minimizing the possibility of over-oxidation. The research on MOF catalyzed oxidative dehydrogenation of propane (ODHP) mainly focuses on the catalytic properties of MOFs with cobalt oxygen sites and boron oxygen sites. The advantages of cobalt oxygen site MOFs include significantly reduced energy consumption, enabling catalytic reactions at temperatures of 230 °C and below, while boron oxygen site MOFs exhibit high conversion rates and selectivity, albeit requiring higher temperatures. The explicit structure of MOFs facilitates the mechanistic study of these sites, enabling further optimization of catalysts. This paper provides an overview of the recent progress in utilizing MOFs as catalysts for ODHP and explores how they promote progress in ODHP catalysis. Finally, the challenges and future prospects of MOFs in the field of ODHP reactions are discussed.

5.
J Ethnopharmacol ; 328: 118000, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38527574

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoer Niuhuang Qingxin Powder (XNQP) is a classic traditional Chinese medicine formula with significant clinical efficacy for treating febrile convulsions and influenza. AIM OF THE STUDY: This study aims to explore the potential mechanisms of XNQP in combating combating the influenza A virus, providing a theoretical basis for its clinical application. MATERIALS AND METHODS: The present investigation employed network pharmacology and bioinformatics analysis to determine the TLR4/MyD88/NF-κB signaling pathway as a viable target for XNQP intervention in IAV infection.Subsequently, a mouse model of influenza A virus infection was established, and different doses of XNQP were used for intervention. The protein expression levels of TLR4/MyD88/NF-κB were detected using HE staining, Elisa, immunohistochemistry, immunofluorescence, and western blot. RESULTS: The results showed that treatment with XNQP after IAV infection reduced the mortality and prolonged the survival time of infected mice. It reduced the release of TNF-α and IFN-γ in the serum and alleviated pathological damage in the lung tissue following infection. Additionally, the levels of TLR4, MyD88, NF-κB, and p-NF-κB P65 proteins were significantly reduced in lung tissue by XNQP. The inhibitory effect of XNQP on the expression of MyD88 and NF-κB was antagonized when TLR4 signaling was overexpressed. Consequently, the expression levels of MyD88, NF-κB, and p-NF-κB P65 were increased in lung tissue. Conversely, the expression levels of the proteins MyD88, NF-κB, and p-NF-κB P65 were downregulated when TLR4 signaling was inhibited. CONCLUSIONS: XNQP alleviated lung pathological changes, reduced serum levels of inflammatory factors, reduced mortality, and prolonged survival time in mice by inhibiting the overexpression of the TLR4/MyD88/NF-κB signaling pathway in lung tissues after IAV infection.


Assuntos
Medicamentos de Ervas Chinesas , Vírus da Influenza A , Influenza Humana , Camundongos , Animais , Humanos , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Pós , Transdução de Sinais
6.
Front Endocrinol (Lausanne) ; 15: 1286736, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455651

RESUMO

Objective: This study aimed to investigate and compare the efficacy and safety of retinal laser photocoagulation (PRP) alone, PRP with aflibercept 3+PRN, and PRP with aflibercept 5+PRN in patients with both high-risk proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). Methods: Overall, 170 patients with high-risk PDR and DME (170 eyes from 170 patients) who visited our ophthalmology clinic from December 2018 to December 2020 were divided into the PRP (n=58), aflibercept 5+PRN with PRP (n=53), and aflibercept 3+PRN with PRP (n= 59) groups. General information, such as age, sex, and eye category, was obtained. Moreover, best-corrected visual acuity (BCVA), baseline central macular foveal thickness (CFT), microaneurysm (MA), area of neovascularization (NV), area of hard exudate (HE), and cytokine levels in atrial fluid before and after treatment, were assessed. The χ2 test was used for comparison between groups for statistical data. Analysis of variance was used for the statistical description of measurement data, independent samples were analyzed using Student's t-test, and Student-Newman-Keuls test was used for group comparisons. Differences were considered statistically significant at P < 0.05. Results: After treatment, no significant improvement in the BCVA (logMAR) of patients in the PRP group was observed. The BCVA (log MAR) decreased from 0.72 ± 0.17 and 0.74 ± 0.17 to 0.50 ± 0.13 and 0.53 ± 0.17 in PRP with aflibercept 5+PRN and PRP with aflibercept 3+PRN groups, respectively, with a statistically significant difference compared to those in the PRP group (P<0.05 in all cases). However, no statistically significant difference was observed between the combined treatment groups (P>0.05). The CFT in the PRP-only group decreased slightly from 361.80 ± 36.70 µm to 353.86 ± 40.88 µm, with no statistically significant difference (P>0.05), whereas the CFT in the aflibercept 5+PRN with PRP and aflibercept 3+PRN with PRP groups decreased from 356.57 ± 37.57 µm and 358.17 ± 44.66 µm to 284.87 ± 31.52 µm and 303.19 ± 37.00 µm, respectively, with statistically significant differences before and after treatment (P<0.05 for both groups). Statistically significant differences were observed in CFT between the three groups after treatment (P<0.05 in all cases). The number of MA (pcs) in the PRP, aflibercept 5+PRN with PRP, and aflibercept 3+PRN with PRP groups decreased from 118.34 ± 27.96, 118.60 ± 33.34, and 116.59 ± 28.95 to 92.95 ± 29.04, 44.60 ± 20.73, and 54.26 ± 25.43, respectively. The two-way comparison of the three groups revealed statistically significant differences in MA (P<0.05 in all cases). In the three groups, NV decreased from 1.00 ± 0.21 mm², 1.01 ± 0.18 mm², and 0.98 ± 0.20 mm² before treatment to 0.49 ± 0.17 mm², 0.31 ± 0.16 mm², and 0.38 ± 0.14 mm², respectively, with statistically significant differences (P<0.05 in all cases). After 12 months of treatment, 13, 18, and 18 patients had reduced HE area in the PRP-only, aflibercept 5+PRN with PRP, and aflibercept 3+PRN with PRP groups, respectively, with statistically significant differences (P<0.05 in all cases). After 12 months of treatment, vascular endothelial growth factor, monocyte chemoattractant protein-1, and glial fibrilliary acidic protein levels (pg/mL) in the aqueous humor decreased in both combined treatment groups compared with that at baseline, with statistically significant differences; however, no significant difference was observed between the two combined treatment groups (P>0.05). Conclusion: Aflibercept 5+PRN combined with PRP was safe and effective in treating patients with high-risk PDR and DME, and was more effective than PRP-only and aflibercept 3+PRN with PRP in improving CFT and MA.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Humanos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/cirurgia , Edema Macular/tratamento farmacológico , Edema Macular/cirurgia , Inibidores da Angiogênese/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Retina , Fotocoagulação a Laser , Neovascularização Patológica/tratamento farmacológico , Lasers , Diabetes Mellitus/tratamento farmacológico
7.
J Proteome Res ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546438

RESUMO

Previous metabolomics studies have highlighted the predictive value of metabolites on upper gastrointestinal (UGI) cancer, while most of them ignored the potential effects of lifestyle and genetic risk on plasma metabolites. This study aimed to evaluate the role of lifestyle and genetic risk in the metabolic mechanism of UGI cancer. Differential metabolites of UGI cancer were identified using partial least-squares discriminant analysis and the Wilcoxon test. Then, we calculated the healthy lifestyle index (HLI) score and polygenic risk score (PRS) and divided them into three groups, respectively. A total of 15 metabolites were identified as UGI-cancer-related differential metabolites. The metabolite model (AUC = 0.699) exhibited superior discrimination ability compared to those of the HLI model (AUC = 0.615) and the PRS model (AUC = 0.593). Moreover, subgroup analysis revealed that the metabolite model showed higher discrimination ability for individuals with unhealthy lifestyles compared to that with healthy individuals (AUC = 0.783 vs 0.684). Furthermore, in the genetic risk subgroup analysis, individuals with a genetic predisposition to UGI cancer exhibited the best discriminative performance in the metabolite model (AUC = 0.770). These findings demonstrated the clinical significance of metabolic biomarkers in UGI cancer discrimination, especially in individuals with unhealthy lifestyles and a high genetic risk.

8.
J Autism Dev Disord ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446266

RESUMO

Research is equivocal on whether attention orienting is atypical in autism. This study investigated two types of attention orienting in autistic people and accounted for the potential confounders of alerting level, co-occurring symptoms of attention-deficit/hyperactivity disorder (ADHD) and anxiety, age, and sex. Twenty-seven autistic participants (14 males; 9-43 years) and 22 age- and sex-matched non-autistic participants (13 males; 9-42 years) completed the exogenous and endogenous Posner tasks. Response time and pupillometric data were recorded. Autistic participants were faster at orienting attention to valid cues in the exogenous task and slower at disengaging from invalid cues in the endogenous task compared to non-autistic participants. With increasing age, autistic participants showed faster exogenous and endogenous orienting, whereas non-autistic participants showed faster exogenous orienting but stable speed of endogenous orienting. Higher ADHD symptoms were associated with slower exogenous orienting in both groups, whereas higher anxiety symptoms were associated with faster exogenous orienting only in autistic participants. No group differences were noted for alerting levels, sex, or pupillary responses. This study provides new evidence of superior exogenous orienting and inefficient endogenous orienting in autistic people and suggests that age and co-occurring symptoms are important to consider when assessing attention orienting in autism.

9.
Child Care Health Dev ; 50(2): e13234, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38380766

RESUMO

OBJECTIVE: To investigate the effectiveness of a Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) intervention in schools for improving independent task performance in children with autism spectrum disorders (ASD). METHODS: We screened relevant studies published up to December 2022 from Web of science, ERIC, PsycINFO and other databases using predefined inclusion/exclusion criteria to identify suitable intervention studies for meta-analysis. Tau-U effect sizes were calculated for each A-B comparison extracted from the included experiments. Moderated analyses were conducted to examine the type of intervention (independent variable), intervention target behaviours (dependent variable), participant characteristics, setting characteristics and intervener characteristics. RESULTS: A total of 14 studies (38 participants) met the criteria and were included in the meta-analysis. The analysis results showed that TEACCH had a significant intervention effect, and the overall intervention effect size was Tau-U = 0.85[0.77, 0.91]. There were significant differences in the intervention target behaviour variables (p < 0.01), limited variation in the intervention type variables, but no differences in participant characteristics, setting characteristics and intervenor characteristics. CONCLUSION: The use of TEACCH is effective in improving independent task completion in children with ASD and provides evidence-based recommendations for its extended use in schools.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Transtornos Globais do Desenvolvimento Infantil , Crianças com Deficiência , Criança , Humanos , Transtorno Autístico/terapia , Instituições Acadêmicas , Comunicação , Transtorno do Espectro Autista/terapia
10.
Angew Chem Int Ed Engl ; 63(16): e202317695, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38380831

RESUMO

3D electron diffraction (3D ED) has shown great potential in crystal structure determination in materials, small organic molecules, and macromolecules. In this work, an automated, low-dose and low-bias 3D ED protocol has been implemented to identify six phases from a multiple-phase melt-crystallisation product of an active pharmaceutical ingredient, griseofulvin (GSF). Batch data collection under low-dose conditions using a widely available commercial software was combined with automated data analysis to collect and process over 230 datasets in three days. Accurate unit cell parameters obtained from 3D ED data allowed direct phase identification of GSF Forms III, I and the known GSF inclusion complex (IC) with polyethylene glycol (PEG) (GSF-PEG IC-I), as well as three minor phases, namely GSF Forms II, V and an elusive new phase, GSF-PEG IC-II. Their structures were then directly determined by 3D ED. Furthermore, we reveal how the stabilities of the two GSF-PEG IC polymorphs are closely related to their crystal structures. These results demonstrate the power of automated 3D ED for accurate phase identification and direct structure determination of complex, beam-sensitive crystallisation products, which is significant for drug development where solid form screening is crucial for the overall efficacy of the drug product.


Assuntos
Elétrons , Polímeros , Polímeros/química , Griseofulvina/química , Polietilenoglicóis/química , Cristalização/métodos
11.
Free Radic Biol Med ; 214: 54-68, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311259

RESUMO

Peritoneal mesothelial cell senescence promotes the development of peritoneal dialysis (PD)-related peritoneal fibrosis. We previously revealed that Brahma-related gene 1 (BRG1) is increased in peritoneal fibrosis yet its role in modulating peritoneal mesothelial cell senescence is still unknown. This study evaluated the mechanism of BRG1 in peritoneal mesothelial cell senescence and peritoneal fibrosis using BRG1 knockdown mice, primary peritoneal mesothelial cells and human peritoneal samples from PD patients. The augmentation of BRG1 expression accelerated peritoneal mesothelial cell senescence, which attributed to mitochondrial dysfunction and mitophagy inhibition. Mitophagy activator salidroside rescued fibrotic responses and cellular senescence induced by BRG1. Mechanistically, BRG1 was recruited to oxidation resistance 1 (OXR1) promoter, where it suppressed transcription of OXR1 through interacting with forkhead box protein p2. Inhibition of OXR1 abrogated the improvement of BRG1 deficiency in mitophagy, fibrotic responses and cellular senescence. In a mouse PD model, BRG1 knockdown restored mitophagy, alleviated senescence and ameliorated peritoneal fibrosis. More importantly, the elevation level of BRG1 in human PD was associated with PD duration and D/P creatinine values. In conclusion, BRG1 accelerates mesothelial cell senescence and peritoneal fibrosis by inhibiting mitophagy through repression of OXR1. This indicates that modulating BRG1-OXR1-mitophagy signaling may represent an effective treatment for PD-related peritoneal fibrosis.


Assuntos
Diálise Peritoneal , Fibrose Peritoneal , Animais , Humanos , Camundongos , Senescência Celular/genética , Proteínas Mitocondriais/metabolismo , Mitofagia/genética , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/genética , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/patologia , Peritônio/metabolismo , Peritônio/patologia
12.
Nutr Metab Cardiovasc Dis ; 34(4): 988-997, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38176957

RESUMO

BACKGROUND AND AIMS: No consensus has been reached on the association between serum uric acid (SUA) and hypertension. This study aimed to investigate the associations between SUA and hypertension, including its status, stages, phenotypes and progressions, among middle-aged and older Chinese. METHODS AND RESULTS: Data were obtained from the China Health and Retirement Longitudinal Study 2011-2015. Binary logistic regression was used to evaluate the association between SUA and hypertension status. Multinomial logistic regression was used to explore the associations of SUA with hypertension stages, phenotypes and hypertension status progressions. Models were adjusted for potential confounders and stratified by sex. A total of 7931 individuals aged ≥45 years were included, with 39.16 % of hypertension. Significant associations were found of SUA with stage2 and above hypertension (quartile 4 [Q4] vs quartile 1 [Q1]: odds ratio 1.78, 95 % confidence interval 1.31-2.42, P < 0.001), and systolic diastolic hypertension (SDH) (Q4 vs Q1: 1.53, 1.14-2.06, P = 0.005). In sex stratification, significant associations were found between SUA and stage2 and above hypertension and SDH only for men. Moreover, higher quartiles of baseline SUA showed increased risks of maintained hypertension from 2011 to 2015 (Q3 vs Q1: 1.23, 1.03-1.48, P = 0.024; Q4 vs Q1: 1.73, 1.43-2.10, P < 0.001). CONCLUSION: Higher SUA was associated with hypertension and maintained hypertension among Chinese middle-aged and elderly. Sex-specific associations of SUA with hypertension stages and phenotypes were observed. Regular measurement of SUA in clinical practice may indicate hypertension and its progression, particularly among men.


Assuntos
Hipertensão , Ácido Úrico , Idoso , Pessoa de Meia-Idade , Masculino , Feminino , Humanos , Fatores de Risco , Estudos Longitudinais , Hipertensão/diagnóstico , Hipertensão/epidemiologia , China/epidemiologia , Fenótipo
13.
Int J Biol Macromol ; 260(Pt 1): 129348, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219943

RESUMO

Chronic diabetic wounds remain a globally recognized clinical challenge, which occurs mainly due to the disturbances of wound microenvironmental induced by high concentrations of reactive oxygen species (ROS). Impairments in angiogenesis and inflammation in the wound microenvironment ultimately impede the normal healing process. Therefore, targeting macrophage and vascular endothelial cell dysfunction is a promising therapeutic strategy. In our study, we fabricated artificial composite scaffolds composed of naringin/carboxymethyl chitosan/sodium hyaluronate/silk fibroin (NG/CMCS/HA/SF) to promote wound healing. The NG/CMCS/HA/SF scaffold demonstrated favorable anti-inflammatory, anti-oxidative, and pro-angiogenic properties in both in vitro and in vivo experiments, effectively promoting the healing of diabetic wounds. The positive therapeutic effects observed indicate that the composite scaffolds have great potential in clinical wound healing applications.


Assuntos
Quitosana , Diabetes Mellitus , Fibroínas , Flavanonas , Humanos , Fibroínas/farmacologia , Quitosana/farmacologia , Ácido Hialurônico/farmacologia , Tecidos Suporte , Espécies Reativas de Oxigênio/farmacologia , Cicatrização , Glicosaminoglicanos/farmacologia , Macrófagos
14.
Int J Pharm ; 652: 123761, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38184024

RESUMO

Drug-polymer inclusion complex (IC) has been viewed as a novel solid form of drugs for property modification. Nonetheless, our understanding of the formation mechanism remains limited. This work aims to provide insight into the molecular processes governing the structural construction of carbamazepine (CBZ) and griseofulvin (GSF) channel-type ICs in the presence of guest polymers. Leveraging microdroplet melt crystallization, we successfully unveiled the single-crystal structures of these ICs, enabling structural analysis, density functional theory calculations, and molecular dynamics simulations. The results collectively elucidate the disparity between CBZ and GSF channels in terms of their autonomy in the absence of guest polymers. CBZ molecules can spontaneously assemble into stable channel structures independently, capitalizing on their unique mortise-tenon architecture and robust π…π interactions. Conversely, GSF channels lack sufficient support from weak Cl…O and C-H…π intermolecular interactions and necessitate the insertion of guest molecules to stabilize their structures. We further calculated the eleven structurally determined drug-polymer ICs and found that their channel sizes consistently fall within a narrow range of 3.81-5.18 Å although they adopt diverse approaches to construct channel structures. We anticipate that these findings will inspire continued exploration of this novel solid form, facilitating theoretical predictions and practical applications in pharmaceutical development.


Assuntos
Carbamazepina , Polímeros , Polímeros/química , Cristalização , Carbamazepina/química , Simulação de Dinâmica Molecular
15.
Psychopharmacology (Berl) ; 241(3): 555-567, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38170320

RESUMO

RATIONALE: Atypical attention orienting has been associated with some autistic symptoms, but the neural mechanisms remain unclear. The human Posner task, a classic attention orienting paradigm, was recently adapted for use with mice, supporting the investigation of the neurobiological underpinnings of atypical attention orienting in preclinical mouse models. OBJECTIVE: The current study tested mice expressing the autism-associated R451C gene mutation in neuroligin-3 (NL3) on the mouse-Posner (mPosner) task. METHODS: NL3R451C and wild-type (WT) mice were trained to respond to a validly or invalidly cued target on a touchscreen. The cue was a peripheral non-predictive flash in the exogenous task and a central spatially predictive image in the endogenous task. The effects of dopaminergic- and noradrenergic-modulating drugs, methylphenidate and atomoxetine, on task performance were assessed. RESULTS: In both tasks, mice were quicker and more accurate in the validly versus invalidly cued trials, consistent with results in the human Posner task. NL3R451C and WT mice showed similar response times and accuracy but responded differently when treated with methylphenidate and atomoxetine. Methylphenidate impaired exogenous attention disengagement in NL3R451C mice but did not significantly affect WT mice. Atomoxetine impaired endogenous orienting in WT mice but did not significantly affect NL3R451C mice. CONCLUSIONS: NL3R451C mice demonstrated intact attention orienting but altered responses to the pharmacological manipulation of the dopaminergic and noradrenergic networks. These findings expand our understanding of the NL3R451C mutation by suggesting that this mutation may lead to selective alterations in attentional processes.


Assuntos
Transtorno Autístico , Camundongos , Humanos , Animais , Cloridrato de Atomoxetina/farmacologia , 60519 , Mutação/genética , Atenção
16.
Environ Pollut ; 345: 123454, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38286259

RESUMO

As typical antibiotics, tetracycline (TC) and sulfadiazine (SDZ) enter the human body through the food chain. Therefore, it is necessary to understand their individual and combined toxicity. In this study, the effects of TC, SDZ, and their mixture on cell viability, cell membrane damage, liver cell damage, and oxidative damage were evaluated in in vitro assays with human liver cells Huh-7. The results showed cytotoxicity of TC, SDZ, and their mixture, which induced oxidative stress and caused membrane and cell damage. The effect of antibiotics on Huh-7 cells increased with increasing concentration, except for lactate dehydrogenase (LDH) activity that commonly showed a threshold concentration response and cell viability, which commonly showed a biphasic trend, suggesting the possibility of hormetic responses where proper doses are included. The toxicity of TC was commonly higher than that of SDZ when applied at the same concentration. These findings shed light on the individual and joint effects of these major antibiotics on liver cells, providing a scientific basis for the evaluation of antibiotic toxicity and associated risks.


Assuntos
Antibacterianos , Sulfadiazina , Humanos , Sulfadiazina/toxicidade , Antibacterianos/toxicidade , Tetraciclina/toxicidade , Fígado , Hepatócitos
17.
Exp Dermatol ; 33(1): e14979, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37975615

RESUMO

Although a large number of existing studies have confirmed that people with vitiligo are prone to mental disorders, these observational studies may be subject to confounding factors and reverse causality, so the true causal relationship is inconclusive. We conducted a bidirectional Mendelian randomization (MR) analysis to assess the causality between vitiligo and mental disorders, namely depression, anxiety, insomnia, schizophrenia, bipolar disorder, obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD). Summary statistics from large available genome-wide association study (GWAS) datasets for generalized vitiligo (n = 44 266), depression (n = 173 005), anxiety (n = 17 310), insomnia (n = 386 988), schizophrenia (n = 130 644), bipolar disorder (n = 413 466), OCD (n = 9725) and ADHD (n = 225 534) were utilized. Inverse-variance weighted (IVW), MR-Egger and weighted median were employed to estimate causal effects. Sensitivity analysis and MR Pleiotropy Residual Sum and Outliers (MR PRESSO) were conducted to assess heterogeneity and pleiotropy, ensuring the robustness of the results. Additionally, we corrected for estimating bias that might be brought on by sample overlap using MRlap. In our findings, none of the rigorous bidirectional MR analyses uncovered a significant causal association. Even after applying the MRlap correction, the effect sizes remained statistically nonsignificant, thereby reinforcing the conclusions drawn via IVW. In summary, our genetic-level investigation did not reveal a causal link between generalized vitiligo and mental disorders.


Assuntos
Transtornos Mentais , Distúrbios do Início e da Manutenção do Sono , Vitiligo , Humanos , Vitiligo/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Transtornos Mentais/genética
18.
J Psychosom Res ; 176: 111544, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37977093

RESUMO

OBJECTIVES: To examine the association between meeting the Canadian 24-Hour Movement Guidelines and physical-mental comorbidity among children and adolescents in a cross-sectional study. METHODS: A total of 21,061 students aged 11-17 years from Zhejiang Province, China was recruited in the study. We examined the coexistence of five specific physical illnesses - hypertension, high myopia, dental caries, scoliosis, and obesity - with mental illness, specifically depressive symptoms. Generalized linear mixed models were performed to assess the association between overall and specific combinations of movement guidelines and physical-mental comorbidity, presented by odds ratio (OR) and 95% confidence interval (CI). Population attributable fraction (PAF) was calculated to estimate the preventable proportion of comorbid cases via meeting all three movement recommendations. RESULTS: Of the included participants, 19.3% had physical-mental comorbidity. There were 3.8% and 17.0% meeting all three and none of the recommendations, respectively. Meeting at least one recommendation, except for moderate-to-vigorous physical activity recommendation only, was associated with a lower risk of physical-mental comorbidity, with ORs (95% CIs) ranging from 0.72 (0.66-0.79) to 0.40 (0.31-0.51). Meeting more recommendations was associated with decreased comorbid risks, and the association was stronger in 4th-6th graders. The association between specific combinations of recommendations and comorbid risks showed differences by gender and grade. Of the comorbid cases, 42.1% were attributed to not adhering to all three recommendations, and the PAFs varied from 27.4% to 55.7% across different genders and grades. CONCLUSION: Adherence to the 24-h movement guidelines was associated with lower risks of physical-mental comorbidity among children and adolescents.


Assuntos
Cárie Dentária , Criança , Humanos , Masculino , Feminino , Adolescente , Canadá/epidemiologia , Estudos Transversais , Prevalência , Cárie Dentária/epidemiologia , Exercício Físico , Sono , Fidelidade a Diretrizes , Comportamento Sedentário , Comorbidade , China/epidemiologia
19.
Br J Psychiatry ; 224(2): 36-46, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38073279

RESUMO

BACKGROUND: Data on trends in the epidemiological burden of bipolar disorder are scarce. AIMS: To provide an overview of trends in bipolar disorder burden from 1990 to 2019. METHOD: Revisiting the Global Burden of Disease Study 2019, we analysed the number of cases, calculated the age-standardised rate (per 100 000 population) and estimated annual percentage change (EAPC) of incidence, prevalence and years lived with disability (YLDs) for bipolar disorder from 1990 to 2019. The independent effects of age, period and cohort were estimated by the age-period-cohort modelling. RESULTS: Globally, the bipolar disorder-related prevalent cases, incident cases and number of YLDs all increased from 1990 to 2019. Regionally, the World Health Organization Region of the Americas accounted for the highest estimated YLD number and rate, with the highest age-standardised prevalence rate in 1990 and 2019 and highest EAPC of prevalence. By sociodemographic index (SDI) quintiles, all five SDI regions saw an increase in estimated incident cases. Nationally, New Zealand reported the highest age-standardised rate of incidence, prevalence and YLDs in 1990 and 2019. The most prominent age effect on incidence rate was in those aged 15-19 years. Decreased effects of period on incidence, prevalence and YLD rates was observed overall and in females, not in males. The incidence, prevalence and YLD rates showed an unfavourable trend in the younger cohorts born after 1990, with males reporting a higher cohort risk than females. CONCLUSIONS: From 1990 to 2019, the overall trend of bipolar disorder burden presents regional and national variations and differs by age, sex, period and cohort.


Assuntos
Transtorno Bipolar , Pessoas com Deficiência , Masculino , Feminino , Humanos , Carga Global da Doença , Prevalência , Incidência , Saúde Global , Anos de Vida Ajustados por Qualidade de Vida
20.
Curr Eye Res ; 49(4): 410-416, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38116796

RESUMO

PURPOSE: To evaluate the prevalence and types of artifacts in ultrawide-field swept-source optical coherence tomography angiography (SS-OCTA) scans of diabetic retinopathy (DR) patients. METHODS: This study was a prospective, observational study conducted from May 2022 to October 2022. Participants comprised individuals with proliferative diabetic retinopathy (PDR), nonproliferative diabetic retinopathy (NPDR), no diabetic retinopathy, and healthy controls. SS-OCTA imaging was performed, and a 5-scan composite with a larger field of view (23.5 mm × 17.5 mm) was captured using built-in software. Two experienced ophthalmologists analyzed the images independently, and the image quality and artifact prevalence were recorded and analyzed. RESULTS: The study included 70 eyes (16 with PDR, 24 with NPDR, 12 eyes of diabetic patients without DR, and 18 healthy eyes) in 70 subjects. Imaging artifacts were observed in a high percentage of eyes, with 98.57% of eyes presenting at least one type of artifact. A significant proportion of eyes (58.57%) exhibited a severe degree of artifacts. The most prevalent artifacts were loss of signal in 63 eyes (90%) and displacement artifact and masking artifact in 43 eyes (61.4%). Patients with more severe stages of DR had higher artifact scores (p < 0.05). Multivariate regression analysis indicated that DR severity was the most important factor influencing artifact scores (p < 0.05). CONCLUSIONS: In OCTA photos, various artifacts arise at different frequencies. It is crucial to qualitatively evaluate the images to ensure their quality. The results demonstrate that DR severity has a significant correlation with artifact scores.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Artefatos , Tomografia de Coerência Óptica/métodos , Estudos Prospectivos , Retina , Angiofluoresceinografia/métodos , Vasos Retinianos
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