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1.
Proc Natl Acad Sci U S A ; 121(34): e2408551121, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39145934

RESUMO

The first steps of vision take place in the ciliary outer segment compartment of photoreceptor cells. The protein composition of outer segments is uniquely suited to perform this function. The most abundant among these proteins is the visual pigment, rhodopsin, whose outer segment trafficking involves intraflagellar transport (IFT). Here, we report three major findings from the analysis of mice in which ciliary transport was acutely impaired by conditional knockouts of IFT-B subunits. First, we demonstrate the existence of a sorting mechanism whereby mislocalized rhodopsin is recruited to and concentrated in extracellular vesicles prior to their release, presumably to protect the cell from adverse effects of protein mislocalization. Second, reducing rhodopsin expression significantly delays photoreceptor degeneration caused by IFT disruption, suggesting that controlling rhodopsin levels may be an effective therapy for some cases of retinal degenerative disease. Last, the loss of IFT-B subunits does not recapitulate a phenotype observed in mutants of the BBSome (another ciliary transport protein complex relying on IFT) in which non-ciliary proteins accumulate in the outer segment. Whereas it is widely thought that the role of the BBSome is to primarily participate in ciliary transport, our data suggest that the BBSome has another major function independent of IFT and possibly related to maintaining the diffusion barrier of the ciliary transition zone.


Assuntos
Camundongos Knockout , Rodopsina , Animais , Camundongos , Rodopsina/metabolismo , Cílios/metabolismo , Transporte Proteico , Transporte Biológico , Flagelos/metabolismo , Compartimento Celular , Vesículas Extracelulares/metabolismo
2.
Small ; : e2400878, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105375

RESUMO

Amateurs often struggle with detecting and quantifying protein biomarkers in body fluids due to the high expertise required. This study introduces a Lab-in-a-Vial (LV) rapid diagnostic platform, featuring hydrangea-like platinum nanozymes (PtNH), for rapid, accurate detection and quantification of protein biomarkers on-site within 15 min. This method significantly enhances detection sensitivity for various biomarkers in body fluids, surpassing traditional methods such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays (LFA) by ≈250 to 1300 times. The LV platform uses a glass vial coated with specific bioreceptors such as antigens or antibodies, enabling rapid in vitro evaluation of disease risk from small fluid samples, similar to a personal ELISA-like point-of-care test (POCT). It overcomes challenges in on-site biomarker detection, allowing both detection and quantification through a portable wireless spectrometer for healthcare internet of things (H-IoT). The platform's effectiveness and adaptability are confirmed using IgG/IgM antibodies from SARS-CoV-2 infected patients and nuclear matrix protein (NMP22) from urothelial carcinoma (UC) patients as biomarkers. These tests demonstrated its accuracy and flexibility. This approach offers vast potential for diverse disease applications, provided that the relevant protein biomarkers in bodily fluids are identified.

3.
World J Urol ; 42(1): 305, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724829

RESUMO

PURPOSE: Postoperative urinary retention (PUR) is a common complication after prostate enucleation, which leads to an increased length of hospital stay and decreased postoperative satisfaction. This study determined the predictive factors of postoperative urine retention within 1 month after prostate enucleation and investigated whether PUR influences surgical outcomes at the 2-week, 3-month, and 6-month follow-up time points. METHODS: Data were collected from the electronic medical records of 191 patients with benign prostatic obstruction (BPO) during October 2018 to September 2021. Of them, 180 patients who underwent thulium laser or plasma kinetic enucleation of the prostate (ThuLEP, PKEP) were separated into the PUR group (n = 24) and the non-PUR (NPUR) group (n = 156). Uroflowmetry and the International Prostate Symptom Score (IPSS) questionnaire were followed up at 2 weeks, 3 months, and 6 months postoperatively. RESULTS: The PUR group had a significantly higher percentage of patients with type 2 diabetes mellitus (DM) than the NPUR group. Postoperatively, compared with the NPUR group, the PUR group had significantly less improvement in changes in the IPSS Quality of Life scores at 2 weeks, the total IPSS(International Prostate Symptom Score) at all follow-up times, the IPSS-S(IPSS storage subscores) at 2 weeks and 3 months, and the IPSS-V(IPSS voiding subscores) at all follow-up times. Predictive factors for PUR include lower preoperative maximum urinary flow (Qmax), lower preoperative total IPSS, and higher operation time. CONCLUSION: Lower preoperative Qmax, lower IPSS scores, and longer operation time were risk factors for PUR. Furthermore, PUR could be a prognostic factor for prostatic enucleation surgical outcomes.


Assuntos
Complicações Pós-Operatórias , Prostatectomia , Hiperplasia Prostática , Retenção Urinária , Humanos , Masculino , Retenção Urinária/etiologia , Retenção Urinária/epidemiologia , Hiperplasia Prostática/cirurgia , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos , Endoscopia
4.
J Chem Inf Model ; 64(15): 6132-6146, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39078379

RESUMO

Staphylococcus aureus (S. aureus) is a major global health concern, causing various infections and presenting challenges due to antibiotic resistance. In particular, methicillin-resistant S. aureus, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus pose significant obstacles in treating S. aureus infections. Therefore, the critical need for novel drugs to counter these resistant forms is pressing. Two-component systems (TCSs), integral to bacterial regulation, offer promising targets for disruption. In this study, a comprehensive approach, involving pharmacophore-based inhibitor screening, along with biochemical and biophysical analyses were conducted to identify, characterize, and validate potential inhibitors targeting the response regulator VraRC of S. aureus. The constructed pharmacophore model, Phar-VRPR-N3, demonstrated effectiveness in identifying a potent inhibitor, TST1N-224 (IC50 = 60.2 ± 4.0 µM), against the formation of the VraRC-DNA complex. Notably, TST1N-224 exhibited strong binding to VraRC (KD = 23.4 ± 1.2 µM) using a fast-on-fast-off binding mechanism. Additionally, NMR-based molecular modeling revealed that TST1N-224 predominantly interacts with the α9- and α10-helixes of the DNA-binding domain of VraR, where the interactive and functionally essential residues (N165, K180, S184, and R195) act as hotspots for structure-based inhibitor optimization. Furthermore, TST1N-224 evidently enhanced the susceptibility of VISA to both vancomycin and methicillin. Importantly, TST1N-224 distinguished by 1,2,5,6-tetrathiocane with the 3 and 8 positions modified with ethanesulfonates holds significant potential as a lead compound for the development of new antimicrobial agents.


Assuntos
Antibacterianos , Proteínas de Bactérias , Antibacterianos/farmacologia , Antibacterianos/química , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Staphylococcus aureus/efeitos dos fármacos , Descoberta de Drogas , Testes de Sensibilidade Microbiana , Avaliação Pré-Clínica de Medicamentos , Simulação de Acoplamento Molecular , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Modelos Moleculares , Farmacóforo
5.
PLoS Genet ; 17(4): e1009484, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33886537

RESUMO

Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS). Here, we demonstrate that BBS mice have significant impairments in context fear conditioning, a form of associative learning. Moreover, we show that postnatal deletion of BBS gene function, as well as congenital deletion, specifically in the forebrain, impairs context fear conditioning. Analyses indicated that these behavioral impairments are not the result of impaired hippocampal long-term potentiation. However, our results indicate that these behavioral impairments are the result of impaired hippocampal neurogenesis. Two-week treatment with lithium chloride partially restores the proliferation of hippocampal neurons which leads to a rescue of context fear conditioning. Overall, our results identify a novel role of cilia genes in hippocampal neurogenesis and long-term context fear conditioning.


Assuntos
Síndrome de Bardet-Biedl/genética , Medo/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Neurônios/metabolismo , Animais , Síndrome de Bardet-Biedl/tratamento farmacológico , Síndrome de Bardet-Biedl/patologia , Proliferação de Células/efeitos dos fármacos , Cílios/genética , Cílios/metabolismo , Cílios/patologia , Modelos Animais de Doenças , Medo/fisiologia , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Lítio/farmacologia , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/genética , Transtornos da Memória/patologia , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Neurogênese/genética , Neurônios/patologia
6.
Hum Mol Genet ; 30(1): 87-102, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33517424

RESUMO

The BBSome is a protein complex consisting of BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBS18 that associates with intraflagellar transport complexes and specializes in ciliary trafficking. In primary cilia, ciliary entry requires the fully assembled BBSome as well as the small GTPase, ARL6 (BBS3). Retinal photoreceptors possess specialized cilia. In light of key structural and functional differences between primary and specialized cilia, we examined the principles of BBSome recruitment to photoreceptor cilia. We performed sucrose gradient fractionation using retinal lysates of Bbs2-/-, Bbs7-/-, Bbs8-/- and Bbs3-/- mice to determine the status of BBSome assembly, then determined localization of BBSome components using immunohistochemistry. Surprisingly, we found that a subcomplex of the BBSome containing at least BBS1, BBS5, BBS8 and BBS9 is recruited to cilia in the absence of BBS2 or BBS7. In contrast, a BBSome subcomplex consisting of BBS1, BBS2, BBS5, BBS7 and BBS9 is found in Bbs8-/- retinas and is denied ciliary entry in photoreceptor cells. In addition, the BBSome remains fully assembled in Bbs3-/- retinas and can be recruited to photoreceptor cilia in the absence of BBS3. We compared phenotypic severity of their retinal degeneration phenotypes. These findings demonstrate that unlike primary cilia, photoreceptor cilia admit a partially assembled BBSome meeting specific requirements. In addition, the recruitment of the BBSome to photoreceptor cilia does not require BBS3. These findings indicate that the ciliary entry of the BBSome is subjected to cell-specific regulation, particularly in cells with highly adapted forms of cilia such as photoreceptors.


Assuntos
Cílios/genética , Complexos Multiproteicos/genética , Células Fotorreceptoras/metabolismo , Retina/metabolismo , Fatores de Ribosilação do ADP/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteínas de Transporte/genética , Cílios/ultraestrutura , Proteínas do Citoesqueleto/genética , Humanos , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/genética , Complexos Multiproteicos/metabolismo , Neuritos/metabolismo , Proteínas de Ligação a Fosfato/genética , Células Fotorreceptoras/patologia , Células Fotorreceptoras/ultraestrutura , Transporte Proteico , Proteínas/genética , Retina/patologia , Relação Estrutura-Atividade
7.
J Magn Reson Imaging ; 2023 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-37572087

RESUMO

BACKGROUND: Deep learning-based segmentation algorithms usually required large or multi-institute data sets to improve the performance and ability of generalization. However, protecting patient privacy is a key concern in the multi-institutional studies when conventional centralized learning (CL) is used. PURPOSE: To explores the feasibility of a proposed lesion delineation for stereotactic radiosurgery (SRS) scheme for federated learning (FL), which can solve decentralization and privacy protection concerns. STUDY TYPE: Retrospective. SUBJECTS: 506 and 118 vestibular schwannoma patients aged 15-88 and 22-85 from two institutes, respectively; 1069 and 256 meningioma patients aged 12-91 and 23-85, respectively; 574 and 705 brain metastasis patients aged 26-92 and 28-89, respectively. FIELD STRENGTH/SEQUENCE: 1.5T, spin-echo, and gradient-echo [Correction added after first online publication on 21 August 2023. Field Strength has been changed to "1.5T" from "5T" in this sentence.]. ASSESSMENT: The proposed lesion delineation method was integrated into an FL framework, and CL models were established as the baseline. The effect of image standardization strategies was also explored. The dice coefficient was used to evaluate the segmentation between the predicted delineation and the ground truth, which was manual delineated by neurosurgeons and a neuroradiologist. STATISTICAL TESTS: The paired t-test was applied to compare the mean for the evaluated dice scores (p < 0.05). RESULTS: FL performed the comparable mean dice coefficient to CL for the testing set of Taipei Veterans General Hospital regardless of standardization and parameter; for the Taichung Veterans General Hospital data, CL significantly (p < 0.05) outperformed FL while using bi-parameter, but comparable results while using single-parameter. For the non-SRS data, FL achieved the comparable applicability to CL with mean dice 0.78 versus 0.78 (without standardization), and outperformed to the baseline models of two institutes. DATA CONCLUSION: The proposed lesion delineation successfully implemented into an FL framework. The FL models were applicable on SRS data of each participating institute, and the FL exhibited comparable mean dice coefficient to CL on non-SRS dataset. Standardization strategies would be recommended when FL is used. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.

8.
Br J Clin Pharmacol ; 89(1): 187-200, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35821614

RESUMO

AIMS: While certain drug-use indicators are known to be associated with clinical outcomes, the relationship is unclear for some highly prevalent conditions in in patients aged ≥65 years. We examine correlations between 3 drug-use indicators and postdischarge healthcare services use by older patients according to the presence of dementia, advanced age and frailty. METHODS: This retrospective cohort study analysed data collected from hospital electronic health records between April and December 2017. Potentially inappropriate medications (PIMs) and anticholinergic burden were assessed using the 2015 Beers Criteria and anticholinergic cognitive burden scale (ACBS) score. Minor and major polypharmacy were defined as the use of 5-9 and ≥10 drugs, respectively. Outcomes were set as emergency room revisits and readmissions at 1, 3 and 6 months postdischarge. The correlation between drug-use indicators and outcomes was analysed by multivariable logistic regression. RESULTS: The final cohort included 3061 patients for the analysis, and 2930, 2671 and 2560 patients were followed up to 1, 3 and 6 months after discharge. After controlling for confounders, all 3 drug-use indicators were significantly associated with readmission and emergency room revisits except for the relationship between PIMs and readmission within 6 months. These associations were significantly observed among patients without dementia, aged >80 years and with frailty. CONCLUSION: PIMs, polypharmacy and anticholinergic burden are common at discharge and correlate with future use of healthcare services. In older patients, the absence of dementia, advanced age and frailty should be given extra consideration with regard to medication safety.


Assuntos
Demência , Fragilidade , Humanos , Idoso , Lista de Medicamentos Potencialmente Inapropriados , Alta do Paciente , Readmissão do Paciente , Prescrição Inadequada , Estudos Retrospectivos , Assistência ao Convalescente , Fragilidade/tratamento farmacológico , Polimedicação , Antagonistas Colinérgicos/uso terapêutico , Hospitais , Demência/tratamento farmacológico , Serviço Hospitalar de Emergência
9.
Am J Respir Cell Mol Biol ; 67(5): 562-573, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35926106

RESUMO

Pulmonary hypertension (PH) is a multifaceted condition characterized by elevated pulmonary arterial pressure, which can result in right ventricular dysfunction and failure. Disorders of lung development can present with secondary PH, which is a leading cause of mortality in infants with bronchopulmonary dysplasia (BPD). DDR1 (discoidin domain receptor 1) is a collagen-binding receptor that regulates tissue fibrosis and inflammation and controls cellular growth and migration. However, the roles of DDR1 in lung development or the pathogenesis of PH are unknown. Studying mice with a DDR1 deletion (Ddr1-/-), we have noted 35% mortality between 1 and 4 months of age, and we demonstrate that DDR1 deficiency results in reduced right ventricular contractility and muscularization of distal pulmonary arteries, consistent with PH. Pathology analysis revealed enlarged alveolar spaces in Ddr1-/- mice by Postnatal Day 7, consistent with impaired alveolar development. Gene expression analysis showed that Ddr1-/- mice have reduced concentrations of alveologenesis factors and epithelial-to-mesenchymal transition markers. Mechanistic studies in vitro confirmed that DDR1 mediated epithelial-to-mesenchymal transition, migration, and growth of alveolar epithelial cells. Taken together, these data suggest that DDR1 plays important roles mediating alveolarization during lung development. Our studies also describe a new model of spontaneous PH and bronchopulmonary dysplasia in mice.


Assuntos
Displasia Broncopulmonar , Receptor com Domínio Discoidina 1 , Hipertensão Pulmonar , Animais , Humanos , Recém-Nascido , Camundongos , Receptor com Domínio Discoidina 1/genética , Receptor com Domínio Discoidina 1/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Fibrose
10.
Inorg Chem ; 61(30): 11981-11991, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35838662

RESUMO

We report herein a porous supramolecular framework formed by a linear mononuclear Au(I) complex (1) via the tongue-and-groove-like joinery between the pentiptycene U-cavities (grooves) and the rod-shaped π-conjugated backbone and alkyl chains (tongues) with the assistance of C-H···π and aurophilic interactions. The framework contains distorted tetrahedral Au4 units, which undergo stepwise and persistent photoinduced Au(I)-Au(I) bond shortening (excited-state aurophilicity), leading to multicolored luminescence photochromism. The one-dimensional pore channels could accommodate different solvates and guests, and the guest inclusion-induced luminescence enhancement (up to 300%) and/or vapochromism are characterized. A correlation between the aurophilic bonding and the luminescence activity is uncovered by TDDFT calculations. Isostructural derivatives 2 and 3 corroborate both the robustness of the porous supramolecular assembly and the mechanisms of the stimulation-induced luminescence properties of 1. This work demonstrates the cooperation of aurophilicity and structural porosity and adaptability in achieving novel supramolecular photochemical properties.

11.
Phys Chem Chem Phys ; 24(34): 20064-20072, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-35856694

RESUMO

Type II clathrate hydrates (CHs) with tetrahydrofuran (THF), cyclobutanone (CB) or 1,3-dioxolane (DXL) guest molecules collapse to an amorphous state near 1 GPa on pressurization below 140 K. On subsequent heating in the 0.2-0.7 GPa range, thermal conductivity and heat capacity results of the homogeneous amorphous solid show two glass transitions, first a thermally weak glass transition, GT1, near 130 K; thereafter a thermally strong glass transition, GT2, which implies a transformation to an ultraviscous liquid on heating. Here we compare the GTs of normal and deuterated samples and samples with different guest molecules. The results show that GT1 and GT2 are unaffected by deuteration of the THF guest and exchange of THF with CB or DXL, whereas the glass transition temperatures (Tgs) shift to higher temperatures on deuteration of water; Tg of GT2 increases by 2.5 K. These results imply that both GTs are associated with the water network. This is corroborated by the fact that GT2 is detected only in the state which is the amorphized CH's counterpart of expanded high density amorphous ice. The results suggest a rare transition sequence of an orientational glass transition followed by a glass to liquid transition, i.e., kinetic unfreezing of H2O reorientational and translational mobility in two distinct processes.

12.
J Formos Med Assoc ; 121(12): 2644-2648, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35871037

RESUMO

Previous studies had showed that indigenous clones of Salmonella Typhi and S. Paratyphi were originally imported from other countries in Taiwan. We presented the clinical manifestations and laboratory findings of indigenous and imported enteric fever cases in Taiwan in the current decade. We retrospectively reviewed typhoid and paratyphoid fever cases in two medical centers of Chang Gung Memorial Hospitals in 2010-2020. A total of 37 enteric fever cases including 24 typhoid fever and 13 paratyphoid fever were recorded. There were 20 indigenous cases, 16 imported cases, and one indetermined case. Splenomegaly and hepatitis were more frequent in typhoid fever than in paratyphoid fever (P < 0.05). Imported cases had more ciprofloxacin non-susceptibility rate (8/16, 50.0%) than indigenous cases (2/20, 10%). Indigenous ciprofloxacin non-susceptible S. Typhi isolates were found in 2018. One indigenous S. Paratyphi B isolate was multi-drug resistant (MDR) to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole.


Assuntos
Febre Paratifoide , Febre Tifoide , Humanos , Febre Tifoide/diagnóstico , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia , Febre Paratifoide/tratamento farmacológico , Febre Paratifoide/epidemiologia , Febre Paratifoide/microbiologia , Salmonella paratyphi A , Estudos Retrospectivos , Taiwan/epidemiologia , Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico
13.
Sensors (Basel) ; 22(9)2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35591180

RESUMO

The majority of digital sensors rely on von Neumann architecture microprocessors to process sampled data. When the sampled data require complex computation for 24×7, the processing element will a consume significant amount of energy and computation resources. Several new sensing algorithms use deep neural network algorithms and consume even more computation resources. High resource consumption prevents such systems for 24×7 deployment although they can deliver impressive results. This work adopts a Computing-In-Memory (CIM) device, which integrates a storage and analog processing unit to eliminate data movement, to process sampled data. This work designs and evaluates the CIM-based sensing framework for human pose recognition. The framework consists of uncertainty-aware training, activation function design, and CIM error model collection. The evaluation results show that the framework can improve the detection accuracy of three poses classification on CIM devices using binary weights from 33.3% to 91.5% while that on ideal CIM is 92.1%. Although on digital systems the accuracy is 98.7% with binary weight and 99.5% with floating weight, the energy consumption of executing 1 convolution layer on a CIM device is only 30,000 to 50,000 times less than the digital sensing system. Such a design can significantly reduce power consumption and enables battery-powered always-on sensors.


Assuntos
Algoritmos , Redes Neurais de Computação , Humanos
14.
Int J Mol Sci ; 23(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35008983

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease with a multifactorial etiology. A multitarget treatment that modulates multifaceted biological functions might be more effective than a single-target approach. Here, the therapeutic efficacy of combination treatment using anti-Aß antibody NP106 and curcumin analog TML-6 versus monotherapy was investigated in an APP/PS1 mouse model of AD. Our data demonstrate that both combination treatment and monotherapy attenuated brain Aß and improved the nesting behavioral deficit to varying degrees. Importantly, the combination treatment group had the lowest Aß levels, and insoluble forms of Aß were reduced most effectively. The nesting performance of APP/PS1 mice receiving combination treatment was better than that of other APP/PS1 groups. Further findings indicate that enhanced microglial Aß phagocytosis and lower levels of proinflammatory cytokines were concurrent with the aforementioned effects of NP106 in combination with TML-6. Intriguingly, combination treatment also normalized the gut microbiota of APP/PS1 mice to levels resembling the wild-type control. Taken together, combination treatment outperformed NP106 or TML-6 monotherapy in ameliorating Aß pathology and the nesting behavioral deficit in APP/PS1 mice. The superior effect might result from a more potent modulation of microglial function, cerebral inflammation, and the gut microbiota. This innovative treatment paradigm confers a new avenue to develop more efficacious AD treatments.


Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Precursor de Proteína beta-Amiloide/deficiência , Anticorpos Monoclonais/farmacologia , Curcumina/farmacologia , Presenilina-1/deficiência , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Animais , Comportamento Animal/efeitos dos fármacos , Biomarcadores , Curcumina/análogos & derivados , Gerenciamento Clínico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Microbiota/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Terapia de Alvo Molecular , Placa Amiloide/tratamento farmacológico , Placa Amiloide/patologia
15.
J Community Psychol ; 50(6): 2703-2725, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35187691

RESUMO

The pandemic has disproportionately affected African American college students, who have experienced significant work-related, academic, financial, and socio-emotional challenges due to COVID-19. The purpose of the study is to investigate how African American students cope with the severe impact of COVID-19 on their emotional well-being leveraging the benefits of self-care coping measures, COVID-19 knowledge, and communication with others to enhance perceived control and social connectedness. A structural equation modeling and a path analysis of 254 responses from a Historically Black College and University showed that emotional well-being was positively predicted by self-care coping strategies, feelings of being in control in life, and social connectedness. In addition, respondents who adopted mind-body balance coping strategies, those who are knowledgeable about COVID-19, and those in more constant communication with others attained a strong sense of being in control, and in turn the empowerment increased their emotional well-being.


Assuntos
Negro ou Afro-Americano , COVID-19 , Saúde Mental , Estudantes , Adaptação Psicológica , Negro ou Afro-Americano/psicologia , COVID-19/etnologia , COVID-19/psicologia , Comunicação , Emoções , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Humanos , Controle Interno-Externo , Saúde Mental/etnologia , Coesão Social/etnologia , Estudantes/psicologia , Universidades
16.
Cytokine ; 148: 155616, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34134911

RESUMO

BACKGROUND: To find a less invasive method of cytokine detection for premature neonates, we conducted this cohort study to investigate the salivary cytokines and to analyze their correlations with bronchopulmonary dysplasia (BPD). METHODS: Premature neonates younger than 34 weeks of gestational age without maternal or neonatal infection were recruited. Salivary samples were collected on their first (D1) and seventh (D7) days of life. The cytokine levels were detected by MILLPLEX® MAP Human multiplex assay. One-way analysis of variance, the Kruskal-Wallis test, Pearson's chi-square test, and logistic regression were used to analyze the data. RESULTS: Totally 125 neonates were enrolled and separated into four groups: control, mild, moderate, and severe BPD group. The salivary levels of D1 interleukin (IL)-6, IL-8, IL-10, IL-17, interferon (IFN)-γ, and D7 IL-6 (p = 0.001, 0.001, 0.000, 0.043, 0.037 and 0.001, respectively) were significantly higher in the BPD groups than in the control group. After adjusting for the gestational age, acid-base equivalent, and absolute neutrophil count, comparing to the control group, the levels of D7 IL-17 became significantly lower in all three BPD groups (p = 0.032, 0.030, and 0.030, respectively) and that of D7 IFN-α2 became significantly lower in the severe BPD group (p = 0.037). CONCLUSION: Early-life salivary cytokine levels were correlated with the development of BPD in premature neonates. This study provides a novel method to predict BPD early and non-invasively.


Assuntos
Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/metabolismo , Citocinas/metabolismo , Recém-Nascido Prematuro/fisiologia , Saliva/metabolismo , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Análise Multivariada
17.
Sleep Breath ; 25(4): 2141-2152, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33216312

RESUMO

PURPOSE: No study to date has described the overall landscape of sleep disorders management and training in otolaryngology departments of different countries. The aim of our study was to investigate and compare settings, diagnostic and therapeutic approaches and training programmes. METHODS: An international online survey was developed with the collaboration of the YO-IFOS (Young Otolaryngologists-International Federation of Otorhinolaryngological Societies) to assess the current practice of otolaryngologists in the management of sleep disorders. The survey also included a session dedicated to training. RESULTS: A total of 126 otolaryngologists completed the survey. The larger part of responses was collected from Central/South America and Europe. The majority of responders from South/Central America (97%) declared to be certified as sleep specialist while 49% of Europeans stated the opposite. Of responders 83% perform a drug-induced sleep endoscopy (DISE) before planning a possible surgical intervention. Soft palate and base of tongue interventions were the most common procedure, respectively performed in 94% and 79% of the cases. Residents were allowed to perform soft palate surgery in 77% of the cases. Upper airway stimulation (26% vs 10%), trans-oral robotic surgery (36% vs 11%) and radiofrequency of the base of the tongue (58% vs 25%) were preferred more frequently by European responders. The highest caseloads of soft palate surgery and bi-maxillary advancement were registered in the academic institutions. CONCLUSION: Significant concordance and few interesting divergences in diagnosis and treatment of sleep disorders were observed between nationalities and types of institution. Economic resources might have played a significant role in the therapeutic choice. Trainees' lack of exposure to certain interventions and to a sufficient caseload appeared to be the main burden to overcome.


Assuntos
Competência Clínica/estatística & dados numéricos , Otorrinolaringologistas/estatística & dados numéricos , Procedimentos Cirúrgicos Otorrinolaringológicos/estatística & dados numéricos , Transtornos do Sono-Vigília/terapia , América , Europa (Continente) , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Departamentos Hospitalares/estatística & dados numéricos , Humanos , Otolaringologia/estatística & dados numéricos
18.
Am J Emerg Med ; 46: 456-461, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33143958

RESUMO

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis and a highly variable survival rate. Few studies have focused on outcomes in rural and urban groups while also evaluating underlying diseases and prehospital factors for OHCAs. OBJECTIVE: To investigate the relationship between the patient's underlying disease and outcomes of OHCAs in urban areas versus those in rural areas. METHODS: We reviewed the emergency medical service (EMS) database for information on OHCA patients treated between January 2015 and December 2019, and collected data on pre-hospital factors, underlying diseases, and outcomes of OHCAs. Univariate and multivariate logistic regression analyses were used to evaluate the prognostic factors for OHCA. RESULTS: Data from 4225 OHCAs were analysed. EMS response time was shorter and the rate of attendance by EMS paramedics was higher in urban areas (p < 0.001 for both). Urban area was a prognostic factor for >24-h survival (odds ratio [OR] = 1.437, 95% confidence interval [CI]: 1.179-1.761). Age (OR = 0.986, 95% CI: 0.979-0.993). EMS response time (OR = 0.854, 95% CI: 0.811-0.898), cardiac arrest location (OR = 2.187, 95% CI: 1.707-2.795), attendance by paramedics (OR = 1.867, 95% CI: 1.483-2.347), and prehospital defibrillation (OR = 2.771, 95% CI: 2.154-3.556) were independent risk factors for survival to hospital discharge, although the influence of an urban area was not significant (OR = 1.211, 95% CI: 0.918-1.584). CONCLUSIONS: Compared with rural areas, OHCA in urban areas are associated with a higher 24-h survival rate. Shorter EMS response time and a higher probability of being attended by paramedics were noted in urban areas. Although shorter EMS response time, younger age, public location, defibrillation by an automated external defibrillator, and attendance by Emergency Medical Technician-paramedics were associated with a higher rate of survival to hospital discharge, urban area was not an independent prognostic factor for survival to hospital discharge in OHCA patients.


Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Parada Cardíaca Extra-Hospitalar/mortalidade , População Rural/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar , Diabetes Mellitus/epidemiologia , Cardioversão Elétrica/estatística & dados numéricos , Feminino , Humanos , Hepatopatias/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/epidemiologia , Parada Cardíaca Extra-Hospitalar/terapia , Prognóstico , Insuficiência Renal/epidemiologia , Doenças Respiratórias/epidemiologia , Retorno da Circulação Espontânea , Acidente Vascular Cerebral/epidemiologia , Taiwan/epidemiologia
19.
BMC Geriatr ; 21(1): 681, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876057

RESUMO

BACKGROUND: Insomnia is a common sleep disturbance in older adults and is associated with many poor health outcomes. This study aimed to explore factors associated with insomnia in older adult outpatient clinics, and to further analyze the influence of gender on factors associated with insomnia. METHODS: This cross-sectional study was conducted in the outpatient clinics of a tertiary hospital in Southern Taiwan from July to September 2018. A total of 400 consecutive subjects aged 60 years or older were recruited. Insomnia was defined as a score of ≥6 points on the Athens Insomnia Scale (AIS). Socio-demographics, health behaviors and clinical data were collected by face-to-face interview. Multivariable logistic regression was adopted for statistical analysis of the entire sample and stratified by gender. RESULTS: Participants' mean age was 74.74 ± 8.54 years, and the majority (93%) had more than one chronic disease. The prevalence of insomnia accounted for 30% (120/400) of all subjects, with males 22.9% (46/201) and females 37.2% (74/199). Gender, appetite, exercise, depressive symptoms, and sleep-related conditions such as short sleep duration, sleeping pills usage, medium-high risk of obstructive sleep apnea (OSA) and restless leg syndrome (RLS) were factors associated with insomnia in older adults. Exercise, sleeping pills usage, and RLS were independently associated with insomnia only in men, while appetite and medium-high risk of OSA were associated with insomnia in women only. In addition, after further adjusting for covariates, prevalence of the insomnia-related symptoms such as sleep induction, total sleep duration, sleep quality and sleepiness during the day was significantly higher in females than in males. CONCLUSIONS: Insomnia symptoms are highly prevalent among older adults, predominantly females. Significant differences are found between genders in factors associated with insomnia and insomnia-related symptoms. Understanding gender differences may help clinicians to modify associated factors when managing older adults with insomnia.


Assuntos
Apneia Obstrutiva do Sono , Distúrbios do Início e da Manutenção do Sono , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pacientes Ambulatoriais , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Qualidade do Sono
20.
J Health Commun ; 26(8): 523-533, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34424140

RESUMO

The United States is one of the hardest-hit countries by the COVID-19 pandemic and yet there is widespread hesitancy to take the vaccine. In order to address vaccine hesitancy and foster public understanding of the COVID-19 vaccine, it is necessary to strategize public health messages based on evidence. To this end, we use experimental data to examine the effects of four message frames on participants' attitudes toward the COVID-19 vaccine and their vaccine intention. The primary purposes of this paper are to examine the 1) impact of loss vs. gain frames and individual vs. collective frames and 2) role of perceived benefits on participants' attitudes toward the COVID-19 vaccine and their vaccine intention. Our findings show that participants with higher perceived benefits and exposed to the loss frame showed higher positive attitudes toward the COVID-19 vaccine and greater intention to vaccinate. Similar patterns were revealed in case of the individual frame message. Implications are discussed.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Intenção , Vacinação/psicologia , Adulto , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Aceitação pelo Paciente de Cuidados de Saúde , Estados Unidos , Recusa de Vacinação/psicologia
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