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1.
BMC Nephrol ; 25(1): 310, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294591

RESUMO

BACKGROUND: Behcet's disease (BD) is an inflammatory disorder of unknown cause that is characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Local vasculitis can cause damage to the visceral system, but it is rare in kidney patients, especially those with IgA nephropathy (IgAN). In China, a small number of related cases have been reported. Here we present a case of co-occurrence of BD and IgAN. CASE PRESENTATION: An 18-year-old female who presented with a history of recurrent oral ulcers was found ten years ago. Four years later, the patient presented with reddish nodules on the skin of both lower limbs and then presented with vulvar ulcers. This patient was clinically diagnosed with Behcet's disease after left calf skin biopsy and presented severe proteinuria and hematuria during this period. IgAN was diagnosed after percutaneous renal biopsy. The patient was treated with hormonal, anti-inflammatory, immunomodulatory, kidney protective, and protein-lowering urine agents. After 3 years of follow-up, the patient reappears oral ulcers, reddish nodules on the skin of both lower limbs and renal dysfunction. CONCLUSIONS: BD is less common in China and is clinically prone to missed diagnosis and misdiagnosis. BD with IgAN is rarer. We should regularly pay attention to the routine urine and renal function of BD patients for early detection and treatment and to prevent further progression of the disease.


Assuntos
Síndrome de Behçet , Glomerulonefrite por IGA , Humanos , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/diagnóstico , Feminino , Adolescente , China
2.
J Dent Sci ; 19(4): 2045-2056, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39347094

RESUMO

Background/purpose: The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) is increasing worldwide. HPV vaccines have shown efficacy in preventing diseases in both males and females. Therefore, there is a need to develop cost-effective strategies for HPV vaccines to prevent HPV-related OPC. This meta-analysis aimed to evaluate cost-effectiveness using the global mean of incremental cost-effectiveness ratios compared to the willingness-to-pay threshold and incremental net benefits (INBs) of HPV vaccination strategies between boys' extension vaccine and girls only. These recommendations will be useful for countries that have not implemented universal HPV vaccines in national programs, such as Taiwan. Materials and methods: Studies evaluating the cost-effectiveness of HPV vaccination strategies in the prevention of OPC that included both sexes versus girls only were identified through the Cochrane Library, EMBASE, PubMed, ScienceDirect, and Web of Science databases on February 05, 2024, and a meta-analysis of pooled INBs was performed using a random-effects model. The outcome was an effective measurement of the OPC burden. The results are represented in USD (2024). Results: Fifteen model analyses were included. All the studies were conducted in high-income countries. The global mean of incremental cost-effectiveness ratio was $39,553 (95% CI, $27,008-66,641) per quality-adjusted life years gained, which was below the global mean of the willingness-to-pay threshold of $65,473 (95% CI, $52,138-83,755). Pooled INBs of $9370 (95% CI, $5046-13,695; P < 0.001) favored the extended HPV in boys. Conclusion: HPV vaccination strategies that include boys are cost-effective compared to those with girls only in preventing OPC burden. By implementing a universal HPV vaccination program, countries can receive $9370 in additional monetary benefits per patient. Given its relevance to high-income countries, this study offers key insights that can aid policymakers in Taiwan.

3.
Cells ; 13(16)2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39195225

RESUMO

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, and cancer-associated fibroblasts (CAFs) play a major role in the tumor microenvironment (TME), which facilitates the progression of CRC. It is critical to understand how CAFs promote the progression of CRC for the development of novel therapeutic approaches. The purpose of this study was to understand how CAF-derived stromal-derived factor-1 (SDF-1) and its interactions with the corresponding C-X-C motif chemokine receptor 4 (CXCR4) promote CRC progression. Our study focused on their roles in promoting tumor cell migration and invasion and their effects on the characteristics of cancer stem cells (CSCs), which ultimately impact patient outcomes. Here, using in vivo approaches and clinical histological samples, we analyzed the influence of secreted SDF-1 on CRC progression, especially in terms of tumor cell behavior and stemness. We demonstrated that CAF-secreted SDF-1 significantly enhanced CRC cell migration and invasion through paracrine signaling. In addition, the overexpression of SDF-1 in CRC cell lines HT29 and HCT-116 triggered these cells to generate autocrine SDF-1 signaling, which further enhanced their CSC characteristics, including those of migration, invasion, and spheroid formation. An immunohistochemical study showed a close relationship between SDF-1 and CXCR4 expression in CRC tissue, and this significantly affected patient outcomes. The administration of AMD3100, an inhibitor of CXCR4, reversed the entire phenomenon. Our results strongly suggest that targeting this signaling axis in CRC is a feasible approach to attenuating tumor progression, and it may, therefore, serve as an alternative treatment method to improve the prognosis of patients with CRC, especially those with advanced, recurrent, or metastatic CRC following standard therapy.


Assuntos
Comunicação Autócrina , Fibroblastos Associados a Câncer , Movimento Celular , Quimiocina CXCL12 , Neoplasias Colorretais , Células-Tronco Neoplásicas , Comunicação Parácrina , Receptores CXCR4 , Transdução de Sinais , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Quimiocina CXCL12/metabolismo , Receptores CXCR4/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Animais , Invasividade Neoplásica , Camundongos , Microambiente Tumoral , Linhagem Celular Tumoral , Células HCT116 , Masculino , Feminino , Células HT29
4.
Int J Biol Macromol ; 278(Pt 3): 134819, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39154672

RESUMO

Treatment of multiple bacterial infected wounds by eliminating bacteria and promoting tissue regeneration remains a clinical challenge. Herein, dual-network hydrogels (CS-GA/A-ß-CD) with snap-structure were designed to achieve curcumin immobilization, using gallic acid-grafted chitosan (CS-GA) and aldehyde-ß-cyclodextrin (A-ß-CD) crosslinked. A-ß-CD were able to achieve rapid dissolution (≥222.35 mg/mL H2O), and helped CS-GA/A-ß-CD achieve rapid gelation (≤66.23 s). By adjusting the ratio of aldehyde groups of A-ß-CD, mechanical properties and drug release can be controlled. CS-GA/A-ß-CD/Cur exhibited excellent antimicrobial properties against S. aureus, E. coli, and P. aeruginosa. In vivo experiments demonstrated that CS-GA/A-ß-CD/Cur achieved acute bacterial infection wound healing after 20th days, proving its great potential for wound dressing.


Assuntos
Antibacterianos , Quitosana , Hidrogéis , Cicatrização , Infecção dos Ferimentos , beta-Ciclodextrinas , Quitosana/química , Hidrogéis/química , Hidrogéis/farmacologia , beta-Ciclodextrinas/química , Animais , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Polifenóis/química , Polifenóis/farmacologia , Liberação Controlada de Fármacos , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Aldeídos/química , Escherichia coli/efeitos dos fármacos , Curcumina/química , Curcumina/farmacologia , Bandagens
5.
Toxics ; 12(7)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39058166

RESUMO

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. METHODS: The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire. RESULTS: These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (ß ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively. CONCLUSION: Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.

6.
Updates Surg ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037684

RESUMO

With the increasing incidence of hepatocellular carcinoma (HCC) in both the United States and globally, the role of liver transplantation in management continues to be an area of active conversation as it is often considered the gold standard in the treatment of HCC. The use of living donor liver transplantation (LDLT) and the indications in the setting of malignancy, both generally and in HCC specifically, are frequently debated. In terms of both overall survival and recurrence-free survival, LDLT is at least equivalent to DDLT, especially when performed for disease within Milan criteria. Emerging and compelling evidence suggests that LDLT is superior to DDLT in treating HCC as there is a significant decrease in waitlist mortality. As the oncologic indications for liver transplantation continue to expand and the gap between organ demand and organ availability continues to worsen, high volumes centers should consider using LDLT to shrink the ever-expanding waitlist.

7.
Bioresour Technol ; 406: 131074, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38971393

RESUMO

The development of biodegradable antimicrobial bioplastics for food packaging holds great promise for solving the pollution and safety problems caused by petrochemical plastics and spoiled food. Herein, a natural active-bioplastic synthesized from citrus peel biomass is presented for perishable fruit preservation. These plastics are characterized by the nanoscale entanglement and recombinant hydrogen bonding between the endogenous pectin, polyphenols and cellulose micro/nanofibrils. They have attractive flexibility, tensile strength, gas barrier properties and antimicrobial activities, and can effectively extend the shelf life of perishable fruits such as banana and mango when used as food packaging. Cytotoxicity, degradability tests and life-cycle assessment show that these plastics had excellent nontoxicity and can be safely degraded or easily recycled. This work demonstrates a sustainable strategy for converting peel waste into eco-friendly bioplastics, providing a unique and novel insight into radically reducing the pollution and life-health threats posed by petrochemical plastics and spoiled food.


Assuntos
Anti-Infecciosos , Frutas , Frutas/química , Anti-Infecciosos/farmacologia , Plásticos Biodegradáveis/farmacologia , Plásticos Biodegradáveis/química , Embalagem de Alimentos/métodos , Conservação de Alimentos/métodos , Citrus/química , Reciclagem , Plásticos/química , Plásticos/farmacologia , Resistência à Tração , Polifenóis/farmacologia , Polifenóis/química , Biodegradação Ambiental
8.
Cells ; 13(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38891100

RESUMO

Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor progression warrants further investigation. Primary cultured cells from samples of patients with MPE from PADC, along with a commonly utilized lung cancer cell line, were employed to examine the role of IL-8 and its receptor, CXCR1, through comparative analysis. Our study primarily assessed migration and invasion capabilities, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties. Additionally, IL-8 levels in MPE fluid versus serum, along with immunohistochemical expression of IL-8/CXCR1 signaling in tumor tissue and cell blocks were analyzed. IL-8/CXCR1 overexpression enhanced EMT and CSC properties. Furthermore, the immunocytochemical examination of 17 cell blocks from patients with PADC and MPE corroborated the significant correlation between upregulated IL-8 and CXCR1 expression and the co-expression of IL-8 and CXCR1 in MPE with distant metastasis. In summary, the IL-8/ CXCR1 axis in FME is pivotal to tumor promotion via paracrine and autocrine signaling. Our study provides a therapeutic avenue for improving the prognosis of PADC patients with MPE.


Assuntos
Adenocarcinoma de Pulmão , Transição Epitelial-Mesenquimal , Interleucina-8 , Neoplasias Pulmonares , Derrame Pleural Maligno , Receptores de Interleucina-8A , Transdução de Sinais , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/complicações , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Interleucina-8/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Derrame Pleural Maligno/patologia , Derrame Pleural Maligno/metabolismo , Receptores de Interleucina-8A/metabolismo , Receptores de Interleucina-8A/genética , Microambiente Tumoral
9.
Front Psychol ; 15: 1384053, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863669

RESUMO

Background: Depression is one of the primary global public health issues, and there has been a dramatic increase in depression levels among young people over the past decade. The neuroplasticity theory of depression postulates that a malfunction in neural plasticity, which is responsible for learning, memory, and adaptive behavior, is the primary source of the disorder's clinical manifestations. Nevertheless, the impact of depression symptoms on associative learning remains underexplored. Methods: We used the differential fear conditioning paradigm to investigate the effects of depressive symptoms on fear acquisition and extinction learning. Skin conductance response (SCR) is an objective evaluation indicator, and ratings of nervousness, likeability, and unconditioned stimuli (US) expectancy are subjective evaluation indicators. In addition, we used associability generated by a computational reinforcement learning model to characterize the skin conductance response. Results: The findings indicate that individuals with depressive symptoms exhibited significant impairment in fear acquisition learning compared to those without depressive symptoms based on the results of the skin conductance response. Moreover, in the discrimination fear learning task, the skin conductance response was positively correlated with associability, as estimated by the hybrid model in the group without depressive symptoms. Additionally, the likeability rating scores improved post-extinction learning in the group without depressive symptoms, and no such increase was observed in the group with depressive symptoms. Conclusion: The study highlights that individuals with pronounced depressive symptoms exhibit impaired fear acquisition and extinction learning, suggesting a possible deficit in associative learning. Employing the hybrid model to analyze the learning process offers a deeper insight into the associative learning processes of humans, thus allowing for improved comprehension and treatment of these mental health problems.

10.
ACS Pharmacol Transl Sci ; 7(5): 1426-1437, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38751623

RESUMO

Protein tyrosine phosphatase 1B (PTP1B) and TC-PTP can function in a coordinated manner to regulate diverse biological processes including insulin and leptin signaling, T-cell activation, and tumor antigen presentation, which makes them potential targets for several therapeutic applications. We have previously demonstrated that the lipidated BimBH3 peptide analogues were a new class of promising PTP1B inhibitors with once-weekly antidiabetic potency. Herein, we chemically synthesized two series of BimBH3 analogues via site-specific modification and studied their structure-activity relationship. The screened analogues S2, S6, A2-14, A2-17, A2-20, and A2-21 exhibited an improved PTP1B/TC-PTP dual inhibitory activity and achieved good stability in the plasma of mice and dogs, which indicated long-acting potential. In mouse models of type 2 diabetes mellitus (T2DM), the selected analogues S6, S7, A2-20, and A2-21 with an excellent target activity and plasma stability generated once-weekly therapeutic potency for T2DM at lower dosage (0.5 µmol/kg). In addition, evidence was provided to confirm the cell permeability and targeted enrichment of the BimBH3 analogues. In summary, we report here that site-specific modification and long fatty acid conjugation afforded cell-permeable peptidomimetic analogues of BimBH3 with enhanced stability, in vivo activity, and long-acting pharmacokinetic profile. Our findings could guide the further optimization of BimBH3 analogues and provide a proof-of-concept for PTP1B/TC-PTP targeting as a new therapeutic approach for T2DM, which may facilitate the discovery and development of alternative once-weekly anti-T2DM drug candidates.

11.
J Pharm Biomed Anal ; 247: 116244, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38810330

RESUMO

Depression currently ranks as the fourth leading cause of disability globally, affecting approximately 20% of the world's population. we established a chronic restraint stress (CRS) induced depression model in mice and employed fluoxetine as a reference drug. We assessed the therapeutic potential of saffron essential oil (SEO) and elucidated its underlying mechanisms through behavioral indices and NMR-based metabolomic analysis. The findings indicate that SEO ameliorates behavioral symptoms of depression, such as the number of entries into the central area, fecal count, latency to immobility, and duration of immobility in both the Tail Suspension Test (TST) and the Forced Swim Test (FST), along with correcting the dysregulation of 5-serotonin. Metabolomic investigations identified sixteen potential biomarkers across the liver, spleen, and kidneys. SEO notably modulated nine of these biomarkers: dimethylglycine, glycerol, adenosine, ß-glucose, α-glucose, uridine, mannose, sarcosine, and aspartate, with glycerol emerging as a common biomarker in both the liver and spleen. Pathway analysis suggests that these biomarkers participate in glycolysis, glycine serine threonine metabolism, and energy metabolism, potentially implicating a role in neural regulation. In summary, SEO effectively mitigates depressive-like behaviors in CRS mice, predominantly via modulation of glycolysis, amino acid metabolism, and energy metabolism, and potentially exerts antidepressant effects through neural regulation. Our study offers insights into small molecule metabolite alterations in CRS mice through a metabolomics lens, providing evidence for the antidepressant potential of plant essential oils and contributing to our understanding of the mechanisms of traditional Chinese medicine in treating depression.


Assuntos
Antidepressivos , Biomarcadores , Crocus , Depressão , Espectroscopia de Ressonância Magnética , Metabolômica , Óleos Voláteis , Animais , Óleos Voláteis/farmacologia , Metabolômica/métodos , Depressão/tratamento farmacológico , Depressão/metabolismo , Camundongos , Crocus/química , Masculino , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Espectroscopia de Ressonância Magnética/métodos , Biomarcadores/metabolismo , Modelos Animais de Doenças , Comportamento Animal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Baço/efeitos dos fármacos , Baço/metabolismo
12.
Int J Biol Macromol ; 270(Pt 1): 132120, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38740153

RESUMO

A novel composite hydrogel was synthesized via Schiff base reaction between chitosan and di-functional poly(ethylene glycol) (DF-PEG), incorporating glucose oxidase (GOx) and cobalt metal-organic frameworks (Co-MOF). The resulting CS/PEG/GOx@Co-MOF composite hydrogel was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and energy-dispersive X-ray spectroscopy (EDS). The results confirmed successful integration and uniform distribution of Co-MOF within the hydrogel matrix. Functionally, the hydrogel exploits the catalytic decomposition of glucose by GOx to generate gluconic acid and hydrogen peroxide (H2O2), while Co-MOF gradually releases metal ions and protects GOx. This synergy enhanced the antibacterial activity of the composite hydrogel against both Gram-positive (S. aureus) and Gram-negative bacteria (E. coli), outperforming conventional chitosan-based hydrogels. The potential of the composite hydrogel in treating wound infections was evaluated through antibacterial and wound healing experiments. Overall, CS/PEG/GOx@Co-MOF hydrogel holds great promise for the treatment of wound infections, paving the way for further research and potential clinical applications.


Assuntos
Antibacterianos , Quitosana , Escherichia coli , Hidrogéis , Estruturas Metalorgânicas , Staphylococcus aureus , Cicatrização , Quitosana/química , Quitosana/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Glucose Oxidase/química , Animais , Cobalto/química , Polietilenoglicóis/química , Testes de Sensibilidade Microbiana
13.
Lancet HIV ; 11(6): e357-e368, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38734016

RESUMO

BACKGROUND: Doravirine and islatravir is an investigational, once-daily regimen with high antiviral potency, favourable safety and tolerability, and a low propensity for resistance. We investigated a switch from bictegravir, emtricitabine, and tenofovir alafenamide to doravirine (100 mg) and islatravir (0·75 mg) in virologically suppressed adults with HIV-1. METHODS: We conducted a phase 3, multicentre, randomised, active-controlled, double-blind, double-dummy, non-inferiority trial at 89 research, community, and hospital-based clinics in 11 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL for at least 3 months on bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation allocation schedule, with block randomisation based on a block size of four, to switch to doravirine (100 mg) and islatravir (0·75 mg) or continue bictegravir, emtricitabine, and tenofovir alafenamide orally once daily, with matching placebos taken by all participants. Participants, investigators, study staff, and sponsor personnel involved in study drug administration or clinical evaluation of participants were masked to treatment assignment until week 48. Participants were instructed at each visit to take one tablet from each of the two bottles received, one of study drug and one of placebo, once daily, and participants were assessed at baseline and weeks 4, 12, 24, 36, and 48. The primary endpoint was the proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug; US Food and Drug Administration snapshot; prespecified non-inferiority margin 4%). The study is ongoing, with all remaining participants in post-treatment follow-up, and is registered with ClinicalTrials.gov, NCT04223791. FINDINGS: We screened 726 individuals for eligibility between Feb 18 and Sept 3, 2020, of whom 643 (88·6%) participants were randomly assigned to a treatment group (183 [28·5%] women and 460 [71·5%] men). 322 participants were switched to doravirine (100 mg) and islatravir (0·75 mg) and 321 continued bictegravir, emtricitabine, and tenofovir alafenamide (two participants [one with a protocol deviation and one who withdrew] assigned to bictegravir, emtricitabine, and tenofovir alafenamide did not receive treatment). The last follow-up visit for the week 48 analysis occurred on Aug 26, 2021. At week 48, two (0·6%) of 322 participants in the doravirine and islatravir group compared with one (0·3%) of 319 participants in the bictegravir, emtricitabine, and tenofovir alafenamide group had greater than or equal to 50 HIV-1 RNA copies per mL (difference 0·3%, 95% CI -1·2 to 2·0). The per-protocol analysis showed consistent results. 25 (7·8%) participants in the doravirine and islatravir group had headache compared with 23 [7·2%] participants in the bictegravir, emtricitabine, and tenofovir alafenamide group; 101 (31·4%) compared with 98 (30·7%) had infections; and eight (2·5%) participants in each group discontinued therapy due to adverse events. 32 (9·9%) participants had treatment-related adverse events in the islatravir and doravirine group comapred with 38 (11·9%) in the bictegravir, emtricitabine, and tenofovir alafenamide group. In the islatravir and doravirine group, CD4 cell counts (mean change -19·7 cells per µL) and total lymphocyte counts (mean change -0·20 × 109/L) were decreased at 48 weeks. INTERPRETATION: Switching to daily doravirine (100 mg) and islatravir (0·75 mg) was non-inferior to bictegravir, emtricitabine, and tenofovir alafenamide at week 48. However, decreases in CD4 cell and total lymphocyte counts do not support the further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.


Assuntos
Adenina , Alanina , Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , HIV-1 , Compostos Heterocíclicos de 4 ou mais Anéis , Piridonas , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Feminino , Masculino , Tenofovir/administração & dosagem , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Adulto , Emtricitabina/administração & dosagem , Emtricitabina/uso terapêutico , HIV-1/efeitos dos fármacos , HIV-1/genética , Método Duplo-Cego , Piridonas/administração & dosagem , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Pessoa de Meia-Idade , Alanina/administração & dosagem , Adenina/análogos & derivados , Adenina/administração & dosagem , Adenina/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Piperazinas/administração & dosagem , Amidas/administração & dosagem , Carga Viral/efeitos dos fármacos , Resultado do Tratamento , Esquema de Medicação , Desoxiadenosinas , Triazóis
15.
BMC Infect Dis ; 24(1): 529, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802771

RESUMO

BACKGROUND: Taiwan, deeply impacted by the 2003 SARS outbreak, promptly implemented rigorous infection control and prevention (ICP) measures in January 2020 to combat the global COVID-19 pandemic. This cross-sectional serologic study was conducted among healthcare workers (HCWs) in a tertiary care hospital in Taiwan from August 1, 2022, to February 28, 2023. The study aimed to assess HCWs' antibody responses to COVID-19 vaccination against Omicron subvariants BA.1, BA.4, and BA.5, considering variations in prior infection. Additionally, it evaluated the effectiveness of ICP and vaccination policies within the hospital setting in Taiwan. METHODS: A cross-sectional serology study was conducted in Taiwan to investigate the seroprevalence rates of Omicron subvariants BA.1, BA.4, and BA.5 among HCWs. A total of 777 HCWs participated in this study. A structured questionnaire was collected to obtain the epidemiological characteristics and risk factors for potential exposure. Enzyme-linked immunosorbent assay was used to detect antibody responses. Serum samples were selected for protection against Omicron subvariants BA.1, BA.4, and BA.5 by using a pseudotyped-based neutralization assay. RESULTS: More than 99% of the participants had received SARS-CoV-2 vaccination. Overall, 57.7% had been infected with SARS-CoV-2, with some being asymptomatic. The SARS-CoV-2 Anti-Spike S1 protein IgG (Anti-S) distribution was 40,000 AU/mL for 20.2% (157/777) of participants, with a mean ± standard deviation of 23,442 ± 22,086. The decay curve for Anti-S was less than 20,000 AU/ml after 120 days. The probability curve of 50% neutralization showed an Anti-S of 55,000 AU/ml. The optimum Anti-S was 41,328 AU/mL (equal to 5,869 WHO's standard BAU/mL), with 86.1% sensitivity and 63.5% specificity. CONCLUSIONS: In this significant study, 20.2% of HCWs achieved seroprotection against Omicron subvariants BA.1, BA.4, and BA.5. Their immunity against Omicron subvariants was further reinforced through recommended vaccinations and the development of natural immunity from SARS-CoV-2 exposure, collectively enhancing their protection against Omicron.


Assuntos
Anticorpos Antivirais , COVID-19 , Pessoal de Saúde , SARS-CoV-2 , Centros de Atenção Terciária , Humanos , Estudos Transversais , Taiwan/epidemiologia , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/epidemiologia , SARS-CoV-2/imunologia , Pessoal de Saúde/estatística & dados numéricos , Anticorpos Antivirais/sangue , Masculino , Feminino , Adulto , Estudos Soroepidemiológicos , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem
16.
Chem Sci ; 15(15): 5604-5611, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38638221

RESUMO

Highly organized π-aggregate architectures can strongly affect electronic couplings, leading to important photophysical behaviors. With the escalating interest in two-dimensional (2D) materials attributed to their exceptional electronic and optical characteristics, there is growing anticipation that 2D radial-π-stacks built upon radial π-conjugation nanorings, incorporating intra- and inter-ring electronic couplings within the confines of a 2D plane, will exhibit superior topological attributes and distinct properties. Despite their immense potential, the design and synthesis of 2D π-stacks have proven to be a formidable challenge due to the insufficient π-π interactions necessary for stable stacking. In this study, we present the successful preparation of single-layer 2D radial-π-stacks in a solution. Pillar-shaped radially π-conjugated [4]cyclo-naphthodithiophene diimide ([4]C-NDTIs) molecules were tetragonally arranged via in-plane intermolecular π-π interactions. These 2D π-stacks have a unique topology that differs from that of conventional 1D π-stacks and exhibit notable properties, such as acting as a 2D template capable of absorbing C60 guest molecules and facilitating the formation of 2D radial-π-stacks comprising [4]C-NDTI-C60 complexes, rapid exciton delocalization across the 2D plane, and efficient excitation energy funneling towards a trap.

17.
Nat Sci Sleep ; 16: 389-400, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646462

RESUMO

Purpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery. Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD. Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04-1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09-9.52], P=0.034) were independent risk factors for the development of POD. Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.

18.
PLoS One ; 19(4): e0299879, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38598447

RESUMO

BACKGROUND: A growing body of research supports dispositional mindfulness as important in influencing physical and mental health as well as physical activities in patients with chronic illnesses. Knee osteoarthritis (OA), which often causes health problems, is one of the most common chronic illnesses, but less is known about dispositional mindfulness in relation to this condition. OBJECTIVE: To explore possible associations between dispositional mindfulness and physical and mental health as well as physical activity in knee OA patients. METHODS: For this cross-sectional study, we recruited a purposive sample of orthopedic clinic patients in hospitals in Southern Taiwan. Instruments included the Mindful Attention Awareness Scale (MAAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Health-related characteristics were also measured. Demographic statistics, bivariate correlations, and multiple linear regression informed our exploration of potentially related factors for dispositional mindfulness. RESULTS: Participants with knee OA (N = 250) were mostly elderly (88%), female (70.5%), and married (84%). Marital status, perceived health status, depression, and physical activity were associated with dispositional mindfulness. Better perceived health, lower depression, and greater physical activity were significantly associated with greater dispositional mindfulness. However, the severity of symptoms, fear of falling, and exercise self-efficacy did not reach statistical significance in relation to dispositional mindfulness. CONCLUSION: Greater emphasis should be placed on the cultivation of mindfulness to enhance individuals' perceived health, decrease their depressive mood, and promote their engagement in physical activity, which could indirectly alleviate their experience of pain and improve their physical function, yielding better quality of life and well-being. Future research should focus on interventions to apply dispositional mindfulness in order to determine whether dispositional mindfulness can effectively improve physical and mental health as well as physical activity in those with knee OA.


Assuntos
Atenção Plena , Osteoartrite do Joelho , Humanos , Feminino , Idoso , Estudos Transversais , Qualidade de Vida/psicologia , Acidentes por Quedas , Medo , Doença Crônica
20.
J Neurosci Res ; 102(3): e25315, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38439584

RESUMO

Post-traumatic stress disorder (PTSD), a psychological condition triggered by exposure to extreme or chronic stressful events, exhibits a sex bias in incidence and clinical manifestations. Emerging research implicates the gut microbiome in the pathogenesis of PTSD and its roles in stress susceptibility. However, it is unclear whether differential gut microbiota contribute to PTSD susceptibility in male and female rats. Here, we utilized the single prolonged stress animal model and employed unsupervised machine learning to classify stressed animals into stress-susceptible subgroups and stress-resilient subgroups. Subsequently, using 16S V3-V4 rDNA sequencing, we investigated the differential gut microbiota alterations between susceptible and resilient individuals in male and female rats. Our findings revealed distinct changes in gut microbiota composition between the sexes at different taxonomic levels. Furthermore, the abundance of Parabacteroides was lower in rats that underwent SPS modeling compared to the control group. In addition, the abundance of Tenericutes in the stress-susceptible subgroup was higher than that in the control group and stress-resilient subgroup, suggesting that Tenericutes may be able to characterize stress susceptibility. What is particularly interesting here is that Cyanobacteria may be particularly associated with anti-anxiety effects in male rats. This study underscores sex-specific variations in gut microbiota composition in response to stress and sex differences should be taken into account when using macrobiotics for neuropsychiatric treatment, highlighting potential targets for PTSD therapeutic interventions.


Assuntos
Microbioma Gastrointestinal , Resiliência Psicológica , Feminino , Masculino , Animais , Ratos , Caracteres Sexuais , Bacteroidetes , Modelos Animais
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