Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 553
Filtrar
1.
BMJ Open ; 14(10): e088301, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39414298

RESUMO

BACKGROUND: Less than 50% of stroke survivors regain their pre-stroke level of upper limb function, compounded with a lack of long-term rehabilitation options available. The Graded Repetitive Arm Supplementary Programme (GRASP) is an evidence-based upper limb programme delivered as a standalone programme to stroke survivors. To improve access to such a programme, there is the potential to combine it with a high-utility community-based exercise programme, such as the post-rehabilitation enablement programme (PREP). We aimed to establish if this was feasible to deliver alongside the experience of stroke survivors and therapists, identify any refinements the intervention and the acceptability of the intervention and trial procedures. METHODS: A cluster feasibility-controlled trial was conducted using both quantitative and qualitative outcome measures with stroke survivors who were discharged from NHS care. Participants completed PREP for 6 weeks (control), with the intervention group also completing GRASP. The GRASP intervention was refined in between five iterative testing cycles. Focus groups with participants explored the acceptability and feasibility. Individual interviews with intervention therapists explored how feasible it was to embed the intervention into practice, and determine the feasibility of a future larger, mixed methods, randomised controlled trial. Clinical endpoints for upper limb and overall function were explored through the Rating of Everyday Arm use in the Community and Home, 10-metre walk test (10MWT) and quality of life via the Shortened Edinburgh Warwick questionnaire. No further suggestions for intervention design were noted after cycle 4. RESULTS: Recruitment (n=72) and retention levels (84.7%) were high with 61 participants (mean age of 66 years and 49 weeks post-stroke) completing the study. Participants and therapists reported positive acceptability of the intervention with goal setting and family support noted as beneficial. The home exercise programme was noted as challenging. Participants within both groups demonstrated improvements in clinical measures, with the intervention group demonstrating a greater improvement within the Rating of Everyday Arm-use in the Community and Home and the 10MWT. CONCLUSION: This study successfully recruited and retained stroke survivors into an upper limb community-based programme. It poses a feasible delivery mechanism to combine evidence-based upper limb approaches with established physical activity programmes in a future large scale and fully powered study. TRIAL REGISTRATION NUMBER: NCT05090163.


Assuntos
Terapia por Exercício , Estudos de Viabilidade , Vida Independente , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral , Extremidade Superior , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Feminino , Extremidade Superior/fisiopatologia , Masculino , Idoso , Pessoa de Meia-Idade , Terapia por Exercício/métodos , Sobreviventes , Grupos Focais , Qualidade de Vida , Acidente Vascular Cerebral
2.
Acta Psychol (Amst) ; 250: 104526, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39405742

RESUMO

The use of E-wallets in the Philippines experienced remarkable growth in recent years. This study investigated the key factors influencing the intention to use E-wallets among Generation Z and Millennials in the country, employing an extended Technology Acceptance Model (TAM) framework. A total of 500 respondents from these demographic groups participated in an online survey featuring 24 indicators, selected through a stratified sampling method. Using Partial Least Square - Structural Equation Modeling (PLS-SEM), the analysis revealed that perceived ease of use, perceived usefulness, social influence, attractiveness of alternatives, perceived trust, perceived security, and perceived value significantly influenced users' intention to adopt E-wallets. Notably, perceived trust emerged as a stronger predictor than perceived value. This research provided valuable insights into the factors shaping user intentions and consumer satisfaction, enhancing the understanding of E-wallet adoption in the industry. Furthermore, the incorporation of the extended TAM strengthened the theoretical framework for studying E-wallet adoption in developing countries like the Philippines.

3.
Acta Psychol (Amst) ; 250: 104521, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39405740

RESUMO

In recent years, a variety of alternative keyboard designs have emerged with the primary goal of enhancing user comfort and productivity compared to conventional keyboards. The objective of this study was to determine the variables affecting the acceptance and perceptions of people towards chording-enabled keyboards. A holistic analysis was done with the use of an extended framework of unified theory of acceptance and use of technology (UTAUT2), analyzed through partial least square structural equation modeling. Gathering a total of 430 valid respondent through purposive sampling, perceived usability, behavioral intention, usage behavior, habit, performance expectancy, social influence, and hedonic motivation were seen to be important factors in adopting chord-enabled keyboards. From the output, it was posited that the attributes of the keyboards' functionality, ease of use, adaptability, and people's willingness to use it, significantly affected their intention of using the keyboard. The findings and suggestions included in this study will benefit not only users but also the developers by providing insights into user preferences. Efficiently improving and marketing chording enabled keyboards could be considered as suggested in the implications. Moreover, the study's model construct could also be utilized in other studies related to user acceptance of technology in different countries.

4.
Antimicrob Agents Chemother ; 68(10): e0061524, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39287403

RESUMO

Despite known treatments, tuberculosis (TB) remains the world's top infectious killer, highlighting the pressing need for new drug regimens. To prioritize the most efficacious drugs for clinical testing, we previously developed a PK-PD translational platform with bacterial dynamics that reliably predicted short-term monotherapy outcomes in Phase IIa trials from preclinical mouse studies. In this study, we extended our platform to include PK-PD models that account for drug-drug interactions in combination regimens and bacterial regrowth in our bacterial dynamics model to predict cure at the end of treatment and relapse 6 months post-treatment. The Phase III STAND trial testing a new regimen comprised of pretomanid (Pa), moxifloxacin (M), and pyrazinamide (Z) (PaMZ) was suspended after a separate ongoing trial (NC-005) suggested that adding bedaquiline (B) to the PaMZ regimen would improve efficacy. To forecast if the addition of B would, indeed, benefit the PaMZ regimen, we applied an extended translational platform to both regimens. We predicted currently available short- and long-term clinical data well for drug combinations related to BPaMZ. We predicted the addition of B to PaMZ to shorten treatment duration by 2 months and to have similar bacteriological success to standard HRZE treatment (considering only treatment success but not withdrawal from side effects and other adverse events), both at the end of treatment for treatment efficacy and 6 months after treatment has ended in relapse prevention. Using BPaMZ as a case study, we have demonstrated our translational platform can predict Phase II and III outcomes prior to actual trials, allowing us to better prioritize the regimens most likely to succeed.


Assuntos
Antituberculosos , Diarilquinolinas , Moxifloxacina , Mycobacterium tuberculosis , Pirazinamida , Antituberculosos/uso terapêutico , Antituberculosos/farmacologia , Pirazinamida/uso terapêutico , Pirazinamida/farmacologia , Animais , Camundongos , Diarilquinolinas/farmacologia , Diarilquinolinas/uso terapêutico , Moxifloxacina/uso terapêutico , Moxifloxacina/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Humanos , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Quimioterapia Combinada , Nitroimidazóis/uso terapêutico , Nitroimidazóis/farmacologia , Resultado do Tratamento , Interações Medicamentosas
5.
Am J Ophthalmol ; 268: 329-339, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293569

RESUMO

PURPOSE: To evaluate the clinical characteristics and management of patients with an anteriorly and nasally inserted superior oblique tendon. DESIGN: Retrospective interventional case series. METHODS: Institutional clinical records between 2020 and 2024 were retrospectively reviewed for 9 consecutive patients in whom the superior oblique (SO) tendon was inserted anterior to the equator and nasal to the superior rectus muscle. Information collected included age, sex, ocular and surgical history, preoperative and postoperative data (ophthalmologic examinations, strabismus measurements, ductions and versions), intraoperative findings, need for additional surgery, and follow-up time. RESULTS: All nine patients were found to have an anomalous insertion of the SO tendon. Three were of congenital origin and six were acquired following ocular surgery. Among the acquired cases, all but one resulted from incarceration of the tendon from postsurgical scar tissue formation. The remaining acquired case was due to a prior deliberate anterior and nasal transposition of the superior oblique. This case series demonstrated varying degrees of vertical deviation, lateral incomitance, and limited depression. Repositioning the SO to its normal insertion site yielded equivocal improvement in ocular alignment. CONCLUSION: Anterior nasal superior oblique tendon syndrome is a rare clinical entity characterized by an antidepressor effect. Vertical deviations, hypertropia worse in downgaze, limited depression worse in adduction for congenital cases and in abduction for acquired cases, and lateral incomitance may be indicative of this anomaly. In acquired cases following surgery, additional findings may include limited depression worse in abduction, esotropia in abduction, V-pattern esotropia, and enophthalmos in downgaze. Surgical repositioning of the SO along its normal anatomical trajectory is recommended for treatment. However, outcomes may be variable and achieving a complete resolution of this syndrome can be challenging.

6.
Genes (Basel) ; 15(9)2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39336751

RESUMO

In the era of precision oncology, identifying abnormal genetic and epigenetic alterations has transformed the way cancer is diagnosed, managed, and treated. 5-hydroxymethylcytosine (5hmC) is an emerging epigenetic modification formed through the oxidation of 5-methylcytosine (5mC) by ten-eleven translocase (TET) enzymes. DNA hydroxymethylation exhibits tissue- and cancer-specific patterns and is essential in DNA demethylation and gene regulation. Recent advancements in 5hmC detection methods and the discovery of 5hmC in cell-free DNA (cfDNA) have highlighted the potential for cell-free 5hmC as a cancer biomarker. This review explores the current and emerging techniques and applications of DNA hydroxymethylation in cancer, particularly in the context of cfDNA.


Assuntos
5-Metilcitosina , Biomarcadores Tumorais , Ácidos Nucleicos Livres , Metilação de DNA , Neoplasias , Humanos , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Neoplasias/genética , Neoplasias/diagnóstico , Ácidos Nucleicos Livres/genética , Biomarcadores Tumorais/genética , Epigênese Genética
7.
PLoS One ; 19(8): e0308098, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39208259

RESUMO

The massage industry has been in the market for more than thousands of years. Consumers purchase massage services to treat illnesses, alleviate pain, or improve well-being. Despite the popularity of this industry and the benefits it entails, consumers' preferences vary and massage parlors' stakeholders have inconsistent market segmentation. Therefore, the purpose of this study was to investigate consumer preferences toward massage services offered by massage parlors in Indonesia through conjoint analysis. Conjoint analysis' orthogonal design concentrated on stimuli preferences and it was further supported by generating 1.000 consistency and reliability based on Kendall Tau's holdout. A total of 212 respondents answered the online questionnaire voluntarily. The results showed that the Google rating was the most important attribute (68.5%), followed by the gender of the massage therapist (12.4%), the type of massage (9.6%), the type of room (4.5%), the duration (3.6%) and the price (1.4%). Moreover, this research assessed 27 stimuli and found that the best combination was employing female massage therapists, IDR 100k-150k price every session, 90 minutes massage duration, couple room with two beds, acupuncture and cupping massage type, and massage parlors with greater than 4.6 Google review rating. This present research was one of the first studies that explored unique and holistic massage services through conjoint analysis. Unlike the previous studies that only focused on one massage service attribute or did not provide specific levels for evaluated attributes, the conjoint's orthogonal design delivered a new perception of prioritizing both consumers and the business side as some would only focus on one or the other. Also, the findings could be useful for massage parlors' stakeholders in developing marketing strategies, enhancing operational strategies, and promoting customer satisfaction. Marketing tactics such as promotional discounts would inspire customers to provide an optimistic Google review. Business owners were encouraged to focus on giving the best experience starting with a well-trained massage therapist, clean and hygienic rooms, and quality materials. These theoretical and practical implications aid in building the massage parlor's credibility that could be perceived positively by consumers.


Assuntos
Comportamento do Consumidor , Massagem , Massagem/métodos , Humanos , Feminino , Masculino , Adulto , Indonésia , Inquéritos e Questionários , Pessoa de Meia-Idade , Adulto Jovem
8.
Acta Psychol (Amst) ; 249: 104473, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39182357

RESUMO

In modern marketing, the emergence of mass customization has reoriented the focus from traditional marketing practices toward a customer-centric approach. The individualization feel among consumers and the innovative approach taken by businesses are currently evident in the market but has yet been holistically analyzed. This study applied a modified Theory of Planned Behavior by incorporating the need for individualization, hedonic and utilitarian motivations, with a 4Ps marketing mix - with the main objective to identify factors contributing to the intention to make purchase of customized products. The survey involved 311 participants who completed an online questionnaire utilizing purposive sampling approach, focusing on those who had previously bought customized products. Structural Equation Modeling was employed as a statistical method to analyze the data with SPSS AMOS v25. Findings revealed that the need for individualization proved to have the highest effect on the intention to purchase customized products, explaining that consumers who are strongly inclined toward individualization not only perceive greater value in customized products but also express a higher intention to purchase them. This was followed by its direct significant effect on attitude, with an even higher effect on perceived behavioral control, along with the marketing mix latent variable and customer perceived value on purchasing intention. This study offers valuable insights for retail brand management and provides potential strategies for business improvement. Moreover, a valuable contribution to the limited literature on the promotion of customized product purchases was identified. Lastly, the developed framework and implications may be applied and extended by future research in the consumer behavior field.


Assuntos
Comportamento do Consumidor , Intenção , Marketing , Humanos , Masculino , Feminino , Adulto , Inquéritos e Questionários , Motivação , Adulto Jovem , Pessoa de Meia-Idade , Individualidade
9.
J Am Med Dir Assoc ; 25(10): 105195, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39122234

RESUMO

OBJECTIVES: This study aimed to assess indoor air quality (IAQ) in long-term care facilities (LTCFs) in California during the COVID-19 pandemic and evaluate their implementation of IAQ best practices described by public health authorities to control respiratory pathogen transmission via inhalation. DESIGN: This observational study conducted IAQ assessments in a convenience sample of LTCFs to gather qualitative data on the implementation of IAQ best practices. The design included 5 pilot visits to develop a standardized method of data collection and then systematic data collection at 10 facilities. SETTING AND PARTICIPANTS: The study focused on 10 LTCFs across California, chosen from facilities that responded to flyers advertising free IAQ assessments. Some of the facilities had previously experienced COVID-19 outbreaks affecting residents and staff. METHODS: State health department industrial hygienists performed site visits to collect data on each facility's heating, ventilation, and air-conditioning (HVAC) system operation, outdoor air introduction, recirculated air filtration, use of portable air cleaners, and directional airflow in isolation areas to evaluate implementation of IAQ best practices in each of these areas. Qualitative data were obtained through visual inspections and interviews with maintenance personnel. RESULTS: Findings indicated suboptimal implementation of IAQ best practices across the assessed facilities: no facility operated HVAC systems continuously, 40% had all outdoor air dampers open, 20% used MERV-13 or higher rated filters, 20% used portable air cleaners, and 20% performed directional airflow assessment and management for isolating COVID-19 cases. CONCLUSIONS AND IMPLICATIONS: Most LTCFs assessed were not adhering to IAQ best practices, highlighting a significant opportunity for improvement. IAQ best practices described in this study are achievable with existing systems and are critical for reducing virus transmission through the air in LTCFs. The findings underscore the need for more systematic assessments and improvements in IAQ within LTCFs to protect staff and residents.


Assuntos
Poluição do Ar em Ambientes Fechados , COVID-19 , Assistência de Longa Duração , COVID-19/prevenção & controle , COVID-19/epidemiologia , Poluição do Ar em Ambientes Fechados/prevenção & controle , Humanos , California , Assistência de Longa Duração/normas , SARS-CoV-2 , Ventilação/normas , Pandemias/prevenção & controle , Casas de Saúde/normas
10.
Stroke ; 55(9): 2202-2211, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39113181

RESUMO

BACKGROUND: Limited evidence supports the effects of short-interval high-intensity interval training (HIIT) for improving cardiorespiratory fitness (V̇O2peak) after stroke. We aimed to compare the effects of 12 weeks of short-interval HIIT versus moderate-intensity continuous training (MICT) on V̇O2peak, cardiovascular risk factors, and mobility outcomes among individuals ≥6 months poststroke. METHODS: This study was a multi-site, 12-week randomized controlled trial (NCT03614585) with an 8-week follow-up. Participants were randomized into 3 d/wk of HIIT (10×1 minute 80%-100% heart rate reserve interspersed with 1 minute 30% heart rate reserve [19 minutes]) or MICT (20-30 minutes 40%-60% heart rate reserve). Secondary outcomes of the trial, including V̇O2peak, cardiovascular risk factors (carotid-femoral pulse wave velocity, blood pressure, and waist-hip ratio), and mobility (6-minute walk test, 10 m gait speed), were reported. Linear mixed model analyses with a group×study time point interaction evaluated between-group differences. RESULTS: Of the 305 potential participants, 82 consented (mean [SD] age 64.9 [9.3] years, 32 females [39%], 1.8 [1.2] years poststroke) and were randomized to HIIT (n=42, mean [SD] baseline V̇O2peak 17.3 [5.9] mL/kg·min) or MICT (n=40, mean [SD] baseline V̇O2peak 17.2 [6.0] mL/kg·min). Participants attended 82% of visits (n=2417/2952). No adverse events occurred during the study period. A significant group×study time point interaction was found (χ2=8.46; P=0.015) for V̇O2peak at 12 weeks (mean difference, 1.81 [95% CI, 0.58-3.04]; P=0.004) whereby the HIIT group had greater gains in V̇O2peak (∆3.52 mL/kg·min [95% CI, 2.47-4.57]; P<0.001) compared with the MICT group (∆1.71 mL/kg·min [95% CI, 0.55-2.86]; P=0.001). There was no between-group difference in V̇O2peak (mean difference, 1.08 [95% CI, -0.26 to 2.42]; P=0.11) at 8-week follow-up. No group×study time point interactions were found for cardiovascular risk factors or mobility outcomes. CONCLUSIONS: Short-interval HIIT may be an effective alternative to MICT for improving V̇O2peak at 12 weeks postintervention. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03614585.


Assuntos
Aptidão Cardiorrespiratória , Treinamento Intervalado de Alta Intensidade , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Treinamento Intervalado de Alta Intensidade/métodos , Aptidão Cardiorrespiratória/fisiologia , Idoso , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Consumo de Oxigênio/fisiologia , Frequência Cardíaca/fisiologia , Terapia por Exercício/métodos
11.
PLoS One ; 19(8): e0306701, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39088508

RESUMO

PURPOSE: StaySafe PH is the Philippines' official contact tracing software for controlling the propagation of COVID-19 and promoting a uniform contact tracing strategy. The StaySafe PH has various features such as a social distancing system, LGU heat map and response system, real-time monitoring, graphs, infographics, and the primary purpose, which is a contact tracing system. This application is mandatory in establishments such as fast-food restaurants, banks, and malls. OBJECTIVE AND METHODOLOGY: The purpose of this research was to determine the country's willingness to utilize StaySafe PH. Specifically, this study utilized 12 latent variables from the integrated Protection Motivation Theory (PMT), Unified Theory of Acceptance and Use of Technology (UTAUT2), and System Usability Scale (SUS). Data from 646 respondents in the Philippines were employed through Structural Equation Modelling (SEM), Deep Learning Neural Network (DLNN), and SUS. RESULTS: Utilizing the SEM, it is found that understanding the COVID-19 vaccine, understanding the COVID-19 Delta variant, perceived vulnerability, perceived severity, performance expectancy, social influence, hedonic motivation, behavioral intention, actual use, and the system usability scale are major determinants of intent to utilize the application. Understanding of the COVID-19 Delta Variant was found to be the most important factor by DLNN, which is congruent with the results of SEM. The SUS score of the application is "D", which implies that the application has poor usability. IMPLICATIONS: It could be implicated that large concerns stem from the trust issues on privacy, data security, and overall consent in the information needed. This is one area that should be promoted. That is, how the data is stored and kept, utilized, and covered by the system, how the assurance could be provided among consumers, and how the government would manage the information obtained. Building the trust is crucial on the development and deployment of these types of technology. The results in this study can also suggest that individuals in the Philippines expected and were certain that vaccination would help them not contract the virus and thus not be vulnerable, leading to a positive actual use of the application. NOVELTY: The current study considered encompassing health-related behaviors using the PMT, integrating with the technology acceptance model, UTAUT2; as well as usability perspective using the SUS. This study was the first one to evaluate and assess a contact tracing application in the Philippines, as well as integrate the frameworks to provide a holistic measurement.


Assuntos
COVID-19 , Busca de Comunicante , Motivação , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Busca de Comunicante/métodos , Filipinas , Masculino , Feminino , Adulto , Intenção , SARS-CoV-2 , Pessoa de Meia-Idade , Adulto Jovem
12.
Cureus ; 16(6): e63395, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39070389

RESUMO

BACKGROUND AND PURPOSE: Hyperbaric oxygen therapy (HBOT) has been reported to improve neurological function in the chronic phase of stroke in a single trial having significant limitations, including a lack of a sham control. METHODS: We conducted a single-center, parallel-group, randomized trial to determine the effectiveness of HBOT compared with a sham control in adults who were 6 to 36 months post-ischemic stroke. The treatment group received 40 sessions of HBOT at the Vancouver General Hospital Hyperbaric Unit. The control group received 40 sessions of sham treatment designed to replicate an HBOT experience. Due to recruitment challenges and timeline/feasibility tracking by the research team, the control arm was altered after 20 months to a waitlist in the hope of increasing participation. In the second phase, participants were randomized to receive HBOT immediately or following an eight-week observation period. The primary outcome was the post-treatment Stroke Impact Scale-16 (SIS-16). Secondary outcomes included the National Institute of Health Stroke Scale, Berg Balance Test, Digit Symbol Substitution Test, 5-Metre Walk Test, 6-Minute Walk Test, Grip Strength, Montreal Cognitive Assessment, Box/Block Test, and Center for Epidemiological Studies - Depression and Short Form-36. Based on detecting a clinically important between-group difference of 10 on the SIS-16 score, our target sample size was 68 participants per arm.  Results: From January 5, 2016 to October 9, 2018, 34 participants were enrolled in the trial, 27 during the first phase and seven in the second phase. The study was stopped after 36 months, and prior to meeting the sample size target, due to low recruitment. At the end of treatment, the difference in the SIS-16 between groups was 5.5 (95% CI: 1.3 to 9.7, p = 0.01) in favor of the sham group. CONCLUSIONS: Our results exclude a clinically important benefit of HBOT on the primary outcome of the SIS-16. These findings do not support the use of HBOT in chronic stroke survivors.

13.
bioRxiv ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38948778

RESUMO

SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. We identified the host E3-ubiquitin ligase TRIM7 as an inhibitor of apoptosis and SARS-CoV-2 replication via ubiquitination of the viral membrane (M) protein. Trim7 -/- mice exhibited increased pathology and virus titers associated with epithelial apoptosis and dysregulated immune responses. Mechanistically, TRIM7 ubiquitinates M on K14, which protects cells from cell death. Longitudinal SARS-CoV-2 sequence analysis from infected patients revealed that mutations on M-K14 appeared in circulating variants during the pandemic. The relevance of these mutations was tested in a mouse model. A recombinant M-K14/K15R virus showed reduced viral replication, consistent with the role of K15 in virus assembly, and increased levels of apoptosis associated with the loss of ubiquitination on K14. TRIM7 antiviral activity requires caspase-6 inhibition, linking apoptosis with viral replication and pathology.

14.
iScience ; 27(6): 110122, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38947502

RESUMO

Drug efflux transporters are a major determinant of drug efficacy and toxicity. A canonical example is P-glycoprotein (P-gp), an efflux transporter that controls the intestinal absorption of diverse compounds. Despite a rich literature on the dietary and pharmaceutical compounds that impact P-gp activity, its sensitivity to gut microbial metabolites remains an open question. Surprisingly, we found that the cardiac drug-metabolizing gut Actinobacterium Eggerthella lenta increases drug absorption in mice. Experiments in cell culture revealed that E. lenta produces a soluble factor that post-translationally inhibits P-gp ATPase efflux activity. P-gp inhibition is conserved in the Eggerthellaceae family but absent in other Actinobacteria. Comparative genomics identified genes associated with P-gp inhibition. Finally, activity-guided biochemical fractionation coupled to metabolomics implicated a group of small polar metabolites with P-gp inhibitory activity. These results highlight the importance of considering the broader relevance of the gut microbiome for drug disposition beyond first-pass metabolism.

15.
J Cell Sci ; 137(12)2024 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-38832513

RESUMO

Division plane positioning is crucial for proper growth and development in many organisms. In plants, the division plane is established before mitosis, by accumulation of a cytoskeletal structure called the preprophase band (PPB). The PPB is thought to be essential for recruitment of division site-localized proteins, which remain at the division site after the PPB disassembles. Here, we show that the division site-localized protein TANGLED1 (TAN1) is recruited independently of the PPB to the cell cortex by the plant cytokinetic machinery, the phragmoplast, from experiments using both the PPB-defective mutant discordia1 (dcd1) and chemical treatments that disrupt the phragmoplast in maize. TAN1 recruitment to de novo sites on the cortex is partially dependent on intact actin filaments and the myosin XI motor protein OPAQUE1 (O1). These data imply a yet unknown role for TAN1 and possibly other division site-localized proteins during the last stages of cell division when the phragmoplast touches the cell cortex to complete cytokinesis.


Assuntos
Citocinese , Proteínas de Plantas , Zea mays , Zea mays/metabolismo , Zea mays/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Citoesqueleto de Actina/metabolismo
16.
Trop Med Infect Dis ; 9(6)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38922041

RESUMO

L-arginine metabolism is strongly linked with immunity to mycobacteria, primarily through the antimicrobial activity of nitric oxide (NO). The potential to modulate tuberculosis (TB) outcomes through interventions that target L-arginine pathways are limited by an incomplete understanding of mechanisms and inadequate in vivo modeling. These gaps in knowledge are compounded for HIV and Mtb co-infections, where activation of arginase-1 due to HIV infection may promote survival and replication of both Mtb and HIV. We utilized in vitro and in vivo systems to determine how arginase inhibition using Nω-hydroxy-nor-L-arginine (nor-NOHA) alters L-arginine pathway metabolism relative to immune responses and disease outcomes following Mtb infection. Treatment with nor-NOHA polarized murine macrophages (RAW 264.7) towards M1 phenotype, increased NO, and reduced Mtb in RAW macrophages. In Balb/c mice, nor-NOHA reduced pulmonary arginase and increased the antimicrobial metabolite spermine in association with a trend towards reduced Mtb CFU in lung. In humanized immune system (HIS) mice, HIV infection increased plasma arginase and heightened the pulmonary arginase response to Mtb. Treatment with nor-NOHA increased cytokine responses to Mtb and Mtb/HIV in lung tissue but did not significantly alter bacterial burden or viral load. Our results suggest that L-arginine pathway modulators may have potential as host-directed therapies to augment antibiotics in TB chemotherapy.

17.
Aust Occup Ther J ; 71(5): 868-893, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38757659

RESUMO

INTRODUCTION: Individuals with acquired brain injury (ABI) experience high rates of poor functional outcomes such as inability to complete activities of daily living (ADL). Occupational therapy needs to be customised to the individual's function, goals, and environment to facilitate improvement in ADLs after ABI. Virtual reality (VR) is a novel treatment approach that aims to improve skills within an individualised environment. This study aimed to review the current literature for the use of VR platforms that incorporate ADLs to improve functional outcomes after ABI. METHODS: This review followed the six-stage framework by Arksey & O'Malley (2005). Electronic databases were searched for peer-reviewed journal articles based on inclusion and exclusion criteria. RESULTS: One thousand and six hundred eighty articles were screened, including 413 full text articles and 13 articles were included for review. Among the 13 articles, six were RCTs and the rest were pre-post intervention studies. Studies largely used non-immersive VR platforms, which incorporated ADLs such as grocery shopping, aiming to improve functional outcomes. CONSUMER AND COMMUNITY CONSULTATION: Consumer and community were not involved in executing this study. CONCLUSION: This review suggests mixed results if VR is effective at treating upper limb, cognition, and ADL function after ABI. Using their clinical reasoning, occupational therapists can determine the suitability of VR for ADL rehabilitation for specific patient populations and settings. Plain Language Summary Individuals who sustain an acquired brain injury can have difficulty performing their daily activities such as, making a meal or getting dressed, because of limited function (e.g., physical and cognitive problems). To help improve their ability to complete daily activities, occupational therapy needs to be customised to the individual's function, goals, and environment. Virtual reality is a new rehabilitation approach that allows individuals to improve their function in an individualised environment. In this study, we reviewed the current studies that have used virtual reality platforms that incorporate daily activities to improve function after acquired brain injury. We searched databases and screened the titles and abstracts of 1,680 studies. Then, 413 full-text studies were screened, and 13 studies were included. Studies mostly used non-immersive platforms to practise daily activities such as, grocery shopping, aiming to improve function after acquired brain injury. This review suggests mixed results if virtual reality can effectively treat function after acquired brain injury.


Assuntos
Atividades Cotidianas , Lesões Encefálicas , Terapia Ocupacional , Realidade Virtual , Humanos , Terapia Ocupacional/métodos , Lesões Encefálicas/reabilitação
18.
Obesity (Silver Spring) ; 32(7): 1329-1338, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38764181

RESUMO

OBJECTIVE: Obesity is associated with alterations in eating behavior and neurocognitive function. In this study, we investigate the effect of obesity on brain energy utilization, including brain glucose transport and metabolism. METHODS: A total of 11 lean participants and 7 young healthy participants with obesity (mean age, 27 years) underwent magnetic resonance spectroscopy scanning coupled with a hyperglycemic clamp (target, ~180 mg/dL) using [1-13C] glucose to measure brain glucose uptake and metabolism, as well as peripheral markers of insulin resistance. RESULTS: Individuals with obesity demonstrated an ~20% lower ratio of brain glucose uptake to cerebral glucose metabolic rate (Tmax/CMRglucose) than lean participants (2.12 ± 0.51 vs. 2.67 ± 0.51; p = 0.04). The cerebral tricarboxylic acid cycle flux (VTCA) was similar between the two groups (p = 0.64). There was a negative correlation between total nonesterified fatty acids and Tmax/CMRglucose (r = -0.477; p = 0.045). CONCLUSIONS: We conclude that CMRglucose is unlikely to differ between groups due to similar VTCA, and, therefore, the glucose transport Tmax is lower in individuals with obesity. These human findings suggest that obesity is associated with reduced cerebral glucose transport capacity even at a young age and in the absence of other cardiometabolic comorbidities, which may have implications for long-term brain function and health.


Assuntos
Encéfalo , Glucose , Resistência à Insulina , Obesidade , Humanos , Adulto , Obesidade/metabolismo , Masculino , Feminino , Glucose/metabolismo , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Adulto Jovem , Glicemia/metabolismo , Espectroscopia de Ressonância Magnética , Ciclo do Ácido Cítrico , Transporte Biológico , Técnica Clamp de Glucose , Metabolismo Energético , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos não Esterificados/metabolismo , Imageamento por Ressonância Magnética
19.
J Bacteriol ; 206(6): e0005224, 2024 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-38819154

RESUMO

Microbes encounter a myriad of stresses during their life cycle. Dysregulation of metal ion homeostasis is increasingly recognized as a key factor in host-microbe interactions. Bacterial metal ion homeostasis is tightly regulated by dedicated metalloregulators that control uptake, sequestration, trafficking, and efflux. Here, we demonstrate that deletion of the Bacillus subtilis yqgC-sodA (YS) complex operon, but not deletion of the individual genes, causes hypersensitivity to manganese (Mn). YqgC is an integral membrane protein of unknown function, and SodA is a Mn-dependent superoxide dismutase (MnSOD). The YS strain has reduced expression of two Mn efflux proteins, MneP and MneS, consistent with the observed Mn sensitivity. The YS strain accumulated high levels of Mn, had increased reactive radical species (RRS), and had broad metabolic alterations that can be partially explained by the inhibition of Mg-dependent enzymes. Although the YS operon deletion strain and an efflux-deficient mneP mneS double mutant both accumulate Mn and have similar metabolic perturbations, they also display phenotypic differences. Several mutations that suppressed Mn intoxication of the mneP mneS efflux mutant did not benefit the YS mutant. Further, Mn intoxication in the YS mutant, but not the mneP mneS strain, was alleviated by expression of Mg-dependent, chorismate-utilizing enzymes of the menaquinone, siderophore, and tryptophan (MST) family. Therefore, despite their phenotypic similarities, the Mn sensitivity in the mneP mneS and the YS deletion mutants results from distinct enzymatic vulnerabilities.IMPORTANCEBacteria require multiple trace metal ions for survival. Metal homeostasis relies on the tightly regulated expression of metal uptake, storage, and efflux proteins. Metal intoxication occurs when metal homeostasis is perturbed and often results from enzyme mis-metalation. In Bacillus subtilis, Mn-dependent superoxide dismutase (MnSOD) is the most abundant Mn-containing protein and is important for oxidative stress resistance. Here, we report novel roles for MnSOD and a co-regulated membrane protein, YqgC, in Mn homeostasis. Loss of both MnSOD and YqgC (but not the individual proteins) prevents the efficient expression of Mn efflux proteins and leads to a large-scale perturbation of the metabolome due to inhibition of Mg-dependent enzymes, including key chorismate-utilizing MST (menaquinone, siderophore, and tryptophan) family enzymes.


Assuntos
Bacillus subtilis , Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Magnésio , Manganês , Óperon , Superóxido Dismutase , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Bacillus subtilis/enzimologia , Manganês/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Magnésio/metabolismo
20.
Foods ; 13(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38731795

RESUMO

With the rising popularity of fitness supplements, understanding the factors driving their consumption behaviors is crucial. This study investigated the actual consumption of fitness supplements utilizing the Theory of Planned Behavior (TPB), Health Belief Model (HBM), and the Theory of Effort Minimization in Physical Activity (TEMPA) frameworks. The TPB provided insights into how attitudes, subjective norms, and perceived behavioral control influence individuals' intentions to consume fitness supplements. Additionally, the HBM sheds light on perceived effectiveness, benefits, barriers, and health motivation related to supplement consumption. Integrating the TEMPA framework further investigated the role of effort minimization in physical activity contexts. Through an online questionnaire, data were collected from a sample of 250 fitness supplement-consuming respondents. SEM analysis revealed significant associations between behavioral intentions and attitudes, perceived behavioral control, health motivation, and controlled precursors. However, it was seen that subjective norms, perceived effectiveness, perceived benefits, and automatic precursors were deemed insignificant. The findings contribute to a comprehensive understanding of the factors shaping actual consumption behaviors, offering valuable implications for marketers, health professionals, and policymakers seeking to promote informed and responsible supplement use among health and fitness enthusiasts.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA