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1.
JAMA Cardiol ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581643

RESUMO

Importance: The association between antibiotic prophylaxis and infective endocarditis after invasive dental procedures is still unclear. Indications for antibiotic prophylaxis were restricted by guidelines beginning in 2007. Objective: To systematically review and analyze existing evidence on the association between antibiotic prophylaxis and infective endocarditis following invasive dental procedures. Data Sources: PubMed, Cochrane-CENTRAL, Scopus, Web of Science, Proquest, Embase, Dentistry and Oral Sciences Source, and ClinicalTrials.gov were systematically searched from inception to May 2023. Study Selection: Studies on the association between antibiotic prophylaxis and infective endocarditis following invasive dental procedures or time-trend analyses of infective endocarditis incidence before and after current antibiotic prophylaxis guidelines were included. Data Extraction and Synthesis: Study quality was evaluated using structured tools. Data were extracted by independent observers. A pooled relative risk (RR) of developing infective endocarditis following invasive dental procedures in individuals who were receiving antibiotic prophylaxis vs those who were not was computed by random-effects meta-analysis. Main Outcomes and Measures: The outcome of interest was the incidence of infective endocarditis following invasive dental procedures in relation to antibiotic prophylaxis. Results: Of 11 217 records identified, 30 were included (1 152 345 infective endocarditis cases). Of them, 8 (including 12 substudies) were either case-control/crossover or cohort studies or self-controlled case series, while 22 were time-trend studies; all were of good quality. Eight of the 12 substudies with case-control/crossover, cohort, or self-controlled case series designs performed a formal statistical analysis; 5 supported a protective role of antibiotic prophylaxis, especially among individuals at high risk, while 3 did not. By meta-analysis, antibiotic prophylaxis was associated with a significantly lower risk of infective endocarditis after invasive dental procedures in individuals at high risk (pooled RR, 0.41; 95% CI, 0.29-0.57; P for heterogeneity = .51; I2, 0%). Nineteen of the 22 time-trend studies performed a formal pre-post statistical analysis; 9 found no significant changes in infective endocarditis incidence, 7 demonstrated a significant increase for the overall population or subpopulations (individuals at high and moderate risk, streptococcus-infective endocarditis, and viridans group streptococci-infective endocarditis), whereas 3 found a significant decrease for the overall population and among oral streptococcus-infective endocarditis. Conclusions and Relevance: While results from time-trend studies were inconsistent, data from case-control/crossover, cohort, and self-controlled case series studies showed that use of antibiotic prophylaxis is associated with reduced risk of infective endocarditis following invasive dental procedures in individuals at high risk, while no association was proven for those at low/unknown risk, thereby supporting current American Heart Association and European Society of Cardiology recommendations. Currently, there is insufficient data to support any benefit of antibiotic prophylaxis in individuals at moderate risk.

2.
ACS Appl Mater Interfaces ; 16(15): 18386-18399, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38591243

RESUMO

Cryogels exhibit unique shape memory with full recovery and structural stability features after multiple injections. These constructs also possess enhanced cell permeability and nutrient diffusion when compared to typical bulk hydrogels. Volumetric processing of cryogels functionalized with nanosized units has potential to widen their biomedical applications, however this has remained challenging and relatively underexplored. In this study, we report a novel methodology that combines suspension 3D printing with directional freezing for the fabrication of nanocomposite cryogels with configurable anisotropy. When compared to conventional bulk or freeze-dried hydrogels, nanocomposite cryogel formulations exhibit excellent shape recovery (>95%) and higher pore connectivity. Suspension printing, assisted with a prechilled metal grid, was optimized to induce anisotropy. The addition of calcium- and phosphate-doped mesoporous silica nanoparticles into the cryogel matrix enhanced bioactivity toward orthopedic applications without hindering the printing process. Notably, the nanocomposite 3D printed cryogels exhibit injectable shape memory while also featuring a lamellar topography. The fabrication of these constructs was highly reproducible and exhibited potential for a cell-delivery injectable cryogel with no cytotoxicity to human-derived adipose stem cells. Hence, in this work, it was possible to combine a gravity defying 3D printed methodology with injectable and controlled anisotropic macroporous structures containing bioactive nanoparticles. This methodology ameliorates highly tunable injectable 3D printed anisotropic nanocomposite cryogels with a user-programmable degree of structural complexity.


Assuntos
Criogéis , Impressão Tridimensional , Humanos , Criogéis/química , Anisotropia , Adipócitos , Engenharia Tecidual/métodos , Tecidos Suporte/química
3.
PLoS One ; 19(3): e0298181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38530823

RESUMO

INTRODUCTION: Worldwide, demographic ageing is a major social, economic and health challenge. Despite the increase in life expectancy, elderly often live with multiple chronic conditions, exposing them to multiple medications. Concerns have been raised about the growing issue of inappropriate long-term usage of proton-pump inhibitors (PPI), which have been associated with adverse outcomes and increased healthcare costs. Deprescribing is a recommended intervention to reduce or withdraw medicines that might be causing harm or might no longer be of benefit. This protocol details a trial to assess the effectiveness and cost-effectiveness of a collaborative deprescribing intervention of PPI among community-dwelling elderly, involving community pharmacists and general practitioners. METHODS AND ANALYSIS: A pragmatic, multicentre, two-arm, non-randomised controlled trial of a structured PPI collaborative deprescribing intervention in the primary care setting with a 6-month follow-up will be conducted. Patients must be 65 years old or older, live in the community and have been using PPI for more than 8 weeks. We hypothesize that the intervention will reduce the PPI usage in the intervention group compared to the control group. The primary outcome is the successful discontinuation or dose decrease of any PPI, defined as a statistically significant absolute 20% reduction in medication use between the intervention and control groups at 3- and 6-month follow-ups. An economic evaluation will be conducted alongside the trial. This study was approved by the Ethics Research Committee of Nova Medical School, NOVA University of Lisbon and by the Ethics Committee from the Local Health Unit Alto Minho, Portugal. DISCUSSION: This pragmatic trial will provide evidence on the effectiveness and cost-effectiveness of a patient-centred collaborative deprescribing intervention in the community setting in Portugal. It will also inform improvements for the development of future multi-faceted interventions that aim to optimise medication for the community-dwelling elderly. CLINICAL TRIAL REGISTRATION: ISRCTN 49637686.


Assuntos
Desprescrições , Inibidores da Bomba de Prótons , Idoso , Humanos , Análise Custo-Benefício , Vida Independente , Inibidores da Bomba de Prótons/uso terapêutico , Prótons , Ensaios Clínicos Pragmáticos como Assunto , Ensaios Clínicos Controlados não Aleatórios como Assunto
4.
Nat Commun ; 15(1): 1816, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418829

RESUMO

The design of human model systems is highly relevant to unveil the underlying mechanisms of aging and to provide insights on potential interventions to extend human health and life span. In this perspective, we explore the potential of 2D or 3D culture models comprising human induced pluripotent stem cells and transdifferentiated cells obtained from aged or age-related disorder-affected donors to enhance our understanding of human aging and to catalyze the discovery of anti-aging interventions.


Assuntos
Células-Tronco Pluripotentes Induzidas , Humanos , Idoso , Envelhecimento , Reprogramação Celular/genética , Longevidade
5.
BMC Infect Dis ; 24(1): 130, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267905

RESUMO

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, predominantly affecting the peripheral nerves, resulting in sensory and motor deficits in the feet. Foot ulcers and imbalances are frequent manifestations in leprosy, often correlating with diminished sensitivity. While clinical scales and monofilament esthesiometers are conventionally utilized to evaluate foot sensitivity and balance in these patients, their discriminatory power is limited and their effectiveness is greatly dependent on the examiner's proficiency. In contrast, baropodometry and posturography offer a more comprehensive evaluation, aiming to preempt potential damage events. This study aimed was to assess the correlation between baropodometry and force plate measurements in leprosy patients and control participants, to improve the prevention and treatment of foot ulcers and complications associated with leprosy. METHODOLOGY: This cross-sectional study was conducted during 2022 and enrolled 39 participants (22 patients with multibacillary leprosy and 17 non-leprosy controls). Demographic data were collected, and a monofilament esthesiometer was used to assess sensory deficits. In addition, physical examinations and balance and plantar pressure tests were conducted. The Student's t-test was used to compare mean and maximum plantar pressures between groups. For most COP variables, a Mann-Whitney Wilcoxon test was used, except for AP amplitude which was analyzed with the Student's t-test due to its normal distribution. The relationship between foot pressure and balance control was assessed using Spearman's correlation, focusing on areas with significant pressure differences between groups. PRINCIPAL FINDINGS: Leprosy patients showed increased pressure in forefoot areas (T1, M1, T2-T5, and M2) and decreased pressure in hindfoot regions (MH and LH) compared to controls. These patients also displayed higher AP and ML amplitudes, suggesting poorer COP control. Correlation analyses between the two groups revealed that foot plantar pressures significantly impact balance control. Specifically, increased T1 region pressures correlated with greater sway in balance tasks, while decreased MH region pressures were linked to reduced COP control. CONCLUSIONS/SIGNIFICANCE: The findings suggest a joint disturbance of plantar pressure distribution and static balance control in leprosy patients. These alterations may increase the risk of tissue injuries, including calluses and deformities, as well as falls.


Assuntos
Pé Diabético , Hanseníase Multibacilar , Humanos , Estudos Transversais , , Extremidade Inferior
6.
J Clin Exp Dent ; 15(11): e912-e919, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38074165

RESUMO

Background: Prisoners constitute one of the disadvantaged groups and it is observed that these individuals suffer from poor oral hygiene and the prevalence of oral diseases is higher compared to the general population. Material and Methods: The aim of this study is to assess the state of the oral health in a prison population in Northern Portugal. A cross-sectional observational study was conducted involving 103 male prisoners with age between 25 and 75 years old. A questionnaire was presented to all the prisoners and an intraoral clinical examination was performed in each of them. Results: The sample mean age was 41.58 ± 8.94 years. Most participants consume sugary foods, with 32% consuming then on a daily basis. It was noticed that 13.6% of the participants do not brush their teeth. Most of the prisoners smoke (78.6%) and 70 smoke more than 10 cigarettes per day. The mean DMFT was 17.17 ± 8.23 and the component with the highest weight was the number of missing teeth, with a mean value of 13.14 ± 8.32. It was observed that 7 individuals are edentulous and 64 (62.1%) have caries lesions. It has been noted that of the 64 individuals presenting caries lesions, 47 (73.4%) eat sugary foods, however this relationship is not statistically significant. It was found that the prevalence of periodontal health was 26%, gingivitis was 32.3% and periodontitis was 41.7%. Plaque Index was evaluated according to the periodontal condition, it was observed a significantly lower level of plaque index in the periodontally healthy subjects compared to the subjects with gingivitis and the subjects with periodontitis. Conclusions: The prevalence of oral diseases in this prison population is high, as is the loss of teeth. Dental caries is the most observed oral disease, and periodontitis the most common of the periodontal diseases. Key words:Prisoners, Oral health, Caries, DMFT, Periodontitis, Oral diseases.

7.
Healthcare (Basel) ; 11(21)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37958045

RESUMO

This study examines the effect of gender, age, and a 4-year training course for police officers (CFOP) on the physical fitness attributes of Portuguese police academy cadets. This longitudinal cohort study considered 686 police cadets (female, n = 131; male, n = 555 male), corresponding to 2578 fitness assessments (female, n = 509; male, n = 2069). The database of police cadets' physical fitness evaluations (from 2004/2005 to 2019/2020) comprises body size, speed, agility, strength, flexibility, and aerobic capacity first assessment (T0) and evaluations at the end of the first four years of the CFOP (T1, T2, T3, T4). Results showed that (i) female cadets are younger (p < 0.05), shorter, lighter, less fast, less agile, less strong, and perform worse in aerobic capacity assessments than male cadets (all, p < 0.001) but perform better in the flexibility assessment (p < 0.001); (ii) female cadets > 29 years are significantly heavier, slower, jump less, perform fewer sit-ups, and perform less on the Cooper test (but they have more handgrip strength), and male cadets > 29 years are significantly heavier, slower, jump less, perform fewer sit-ups, and have less flexibility and aerobic capacity (still, they have superior back and lumbar strength and handgrip strength); and (iii) from T0 to T4 (Δ), female cadets are significantly faster (60 m, -0.32 s; slalom, -0.78 s), jump further (+4 cm), have more abdominal strength endurance (+2.6 repetitions) and more back and lumbar strength (+89.8 kg), and male cadets are significantly heavier (+3.27 kg), faster (60 m, -0.23 s; 30 m, -0.15 s; slalom, -0.91 s), jump further (+8 cm), complete more repetitions in the sit-ups (+4.9 repetitions) and in pull-ups (+2.5 repetitions) and have more back and lumbar strength (+92.1 kg) and handgrip strength (+8.6 kg) but a lower aerobic capacity (Cooper test, -74.8 m; VO2max, -1.3 mL/kg/min) when compared to T0. The study's findings lead to widely accepted conclusions within the discipline. Nevertheless, this work provides valuable insights into the impact of various factors on the physical fitness of Portuguese police academy cadets, i.e.: (i) it is an essential study with practical implications for recruitment, training, and the ongoing development of Portuguese police academy cadets and police officers; and (ii) these results can also assist in tailoring training programs to different age groups and genders, which is crucial in police training.

8.
Biomater Adv ; 155: 213670, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37952461

RESUMO

Conventional surgical closure techniques, such as sutures, clips, or skin closure strips, may not always provide optimal wound closure and may require invasive procedures, which can result in potential post-surgical complications. As result, there is a growing demand for innovative solutions to achieve superior wound closure and improve patient outcomes. To overcome the abovementioned issues, in situ generated hemostatic adhesives/sealants have emerged as a promising alternative, offering a targeted, controllable, and minimally invasive procedure for a wide variety of medical applications. The aim of this review is to provide a comprehensive overview of the mechanisms of action and recent advances of in situ generated hemostatic adhesives, particularly protein-based, thermoresponsive, bioinspired, and photocrosslinkable formulations, as well as the design challenges that must be addressed. Overall, this review aims to enhance a comprehensive understanding of the latest advancements of in situ generated hemostatic adhesives and their mechanisms of action, with the objective of promoting further research in this field.


Assuntos
Hemostáticos , Adesivos Teciduais , Humanos , Adesivos/uso terapêutico , Adesivos Teciduais/uso terapêutico , Hemostáticos/uso terapêutico , Cicatrização , Técnicas de Fechamento de Ferimentos
9.
PLOS Digit Health ; 2(8): e0000304, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37585430

RESUMO

The Finger Tapping Test (FTT) is a classical neuropsychological test that assesses motor functioning, and recently it has been employed using smartphones. For classical protocols, it has been observed that sex and handedness influence the performance during the test. By assessing the influence of sex and handedness on the test, it is possible to adjust the performance measurements to ensure the validity of test results and avoid sex- and handedness-related bias. The present study aimed to evaluate the influence of sex and handedness on smartphone-based FTT performance. We developed an Android application for the FTT and recruited 40 males and 40 females to carry out three spatial designs on it (protocols I, II, and III). Participants' performance was measured using the global, temporal, and spatial parameters of the FTT. We observed that for the performance in protocol I, handedness had a significant influence on global and temporal variables, while the interaction between handedness and sex had a greater influence on spatial variables. For protocols II and III, we observed that handedness had a significant influence on global, temporal, and spatial variables compared to the other factors. We concluded that the smartphone-based test is partly influenced by handedness and sex, and in clinical implications, these factors should be considered during the evaluation of the smartphone-based FTT.

10.
Healthcare (Basel) ; 11(13)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37444783

RESUMO

We aim to examine the changes in health-related physical fitness components, before and after COVID-19 social restrictions, in Police Academy cadets by age, sex, and physical activity (PA) level. A longitudinal analysis of 156 cadets (29.5% women) aged 25.4 ± 5.3 years old was conducted. All variables were collected before and after the lockdown period (13 weeks). PA levels were assessed with a self-reported questionnaire. Health-related physical fitness components were assessed based on the standardized protocols of morphological evaluation, speed, agility, strength, flexibility, and aerobic capacity tests. Despite the high correlations between pre- and post-pandemic social restrictions, we found significantly higher values for anthropometric indicators and lower physical fitness levels in post-pandemic restrictions, except for lower-body strength. When stratifying the sample by sex, age, and PA categories, the results indicate that the COVID-19 lockdown tends to differently impact anthropometric indicators and the physical fitness of the cadets, according to their sex, age, and PA categories. Our findings show that our sample reduces several health-related physical fitness components due to the social lockdown, with emphasis on cardiorespiratory fitness in men and upper-limb strength in women, highlighting the need to create effective strategies to keep police officers active during situations of less physical work.

11.
Front Neurosci ; 17: 1130867, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37404467

RESUMO

The scientific need for standardized, high-quality facial stimuli has driven the creation of several face image databases in recent years. These stimuli are particularly important in facial asymmetry research. However, previous studies have reported facial anthropometric differences across a variety of ethnicities. This highlights the need to investigate whether these differences can also impact the use of face image databases, particularly in facial asymmetry research. In this study, we investigated facial asymmetry-based morphometric differences between the multi-ethnic Chicago Face Database (CFD) and the LACOP Face Database, which is composed of Brazilian subjects. We found reliable differences in facial asymmetry between the two databases, which were related to ethnic groups. Specifically, differences in eye and mouth asymmetry seem to drive these differences. The asymmetry-based morphometric differences among databases and ethnicities found in this study reinforce the necessity of creating multi-ethnic face databases.

12.
Pharmaceutics ; 15(6)2023 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-37376101

RESUMO

Oral cancer is a highly aggressive tumor with invasive properties that can lead to metastasis and high mortality rates. Conventional treatment strategies, such as surgery, chemotherapy, and radiation therapy, alone or in combination, are associated with significant side effects. Currently, combination therapy has become the standard practice for the treatment of locally advanced oral cancer, emerging as an effective approach in improving outcomes. In this review, we present an in-depth analysis of the current advancements in combination therapies for oral cancer. The review explores the current therapeutic options and highlights the limitations of monotherapy approaches. It then focuses on combinatorial approaches that target microtubules, as well as various signaling pathway components implicated in oral cancer progression, namely, DNA repair players, the epidermal growth factor receptor, cyclin-dependent kinases, epigenetic readers, and immune checkpoint proteins. The review discusses the rationale behind combining different agents and examines the preclinical and clinical evidence supporting the effectiveness of these combinations, emphasizing their ability to enhance treatment response and overcome drug resistance. Challenges and limitations associated with combination therapy are discussed, including potential toxicity and the need for personalized treatment approaches. A future perspective is also provided to highlight the existing challenges and possible resolutions toward the clinical translation of current oral cancer therapies.

13.
J Mater Chem B ; 11(28): 6671-6684, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37377032

RESUMO

The layer-by-layer (LbL) assembly technology has been widely used to functionalise surfaces and precisely engineer robust multilayered bioarchitectures with tunable structures, compositions, properties, and functions at the nanoscale by resorting to a myriad of building blocks exhibiting complementary interactions. Among them, marine-origin polysaccharides are a sustainable renewable resource for the fabrication of nanostructured biomaterials for biomedical applications owing to their wide bioavailability, biocompatibility, biodegradability, non-cytotoxicity, and non-immunogenic properties. Chitosan (CHT) and alginate (ALG) have been widely employed as LbL ingredients to shape a wide repertoire of size- and shape-tunable electrostatic-driven multilayered assemblies by exploring their opposite charge nature. However, the insolubility of CHT in physiological conditions intrinsically limits the range of bioapplications of the as-developed CHT-based LbL structures. Herein, we report the preparation of free-standing (FS) multilayered membranes made of water-soluble quaternised CHT and ALG biopolymers for controlled release of model drug molecules. The influence of the film structure in the drug release rate is studied by assembling two distinct set-ups of FS membranes, having the model hydrophilic drug fluorescein isothiocyanate-labelled bovine serum albumin (FITC-BSA) either as an intrinsic building block or added as an outer layer after the LbL assembly process. Both FS membranes are characterised for their thickness, morphology, in vitro cytocompatibility, and release profile, with those having FITC-BSA as an intrinsic LbL ingredient denoting a more sustained release rate. This work opens up new avenues for the design and development of a wide array of CHT-based devices for biomedical applications, overcoming the limitations associated with the insolubility of native CHT under physiological conditions.


Assuntos
Quitosana , Polissacarídeos , Materiais Biocompatíveis/química , Quitosana/química , Sistemas de Liberação de Medicamentos , Alginatos/química
14.
BMJ Open ; 13(5): e068725, 2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-37147092

RESUMO

OBJECTIVES: Anxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms. METHODS: This is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built. RESULTS: According to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression. CONCLUSION: At least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.


Assuntos
Asma , Qualidade de Vida , Adulto , Adolescente , Criança , Humanos , Feminino , Masculino , Depressão/diagnóstico , Estudos Transversais , Ansiedade/diagnóstico , Asma/complicações , Asma/epidemiologia , Inquéritos e Questionários
15.
Healthcare (Basel) ; 11(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37174794

RESUMO

Physical fitness tests are a standard means of evaluating the competence of police officers. This qualitative review aims (i) to document, compare, and examine the reference values available in the current literature regarding fitness tests for Law Enforcement Officers (LEOs), and (ii) to define reference values for the most used fitness tests to assess and predict police officer performance. A total of 1879 records were collected for review from two major literature databases, PubMed and ScienceDirect. After applying our exclusion criteria, a total of 19 studies were considered. All studies demonstrated acceptable methodological quality in fitness assessment, and the most used components were muscle strength, muscular endurance, muscle power, aerobic and anaerobic capacity, flexibility, and agility. This review provides (i) a methodological definition for the physical fitness assessment that helps select the most used fitness tests, (ii) a standardised methodology for establishing reference data for fitness tests appropriate for LEOs; and (iii) aggregate reference values for selected fitness tests. This may improve selection and retention procedures, considering that this group performs its duties in an environment and under conditions that differ from those of other occupational groups. Complementarily, this qualitative review also provides a foundation for developing effective interventions to improve each aspect of fitness testing for police officers.

16.
J Biomol Struct Dyn ; : 1-12, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37158092

RESUMO

The search for Golgi α-mannosidase II (GMII) potent and specific inhibitors has been a focus of many studies for the past three decades since this enzyme is a key target for cancer treatment. α-Mannosidases, such as those from Drosophila melanogaster or Jack bean, have been used as functional models of the human Golgi α-mannosidase II (hGMII) because mammalian mannosidases are difficult to purify and characterize experimentally. Meanwhile, computational studies have been seen as privileged tools able to explore assertive solutions to specific enzymes, providing molecular details of these macromolecules, their protonation states and their interactions. Thus, modelling techniques can successfully predict hGMII 3D structure with high confidence, speeding up the development of new hits. In this study, Drosophila melanogaster Golgi mannosidase II (dGMII) and a novel human model, developed in silico and equilibrated via molecular dynamics simulations, were both opposed for docking. Our findings highlight that the design of novel inhibitors should be carried out considering the human model's characteristics and the enzyme operating pH. A reliable model is evidenced, showing a good correlation between Ki/IC50 experimental data and theoretical ΔGbinding estimations in GMII, opening the possibility of optimizing the rational drug design of new derivatives.Communicated by Ramaswamy H. Sarma.

17.
PLoS One ; 18(4): e0284464, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37079629

RESUMO

BACKGROUND: Older patients are more likely to have medication-related problems, which are associated with changes in pharmacokinetics and pharmacodynamics, multimorbidity, and polypharmacy. Polypharmacy and inappropriate prescribing are well-known risk factors which commonly cause adverse clinical outcomes in older people. Prescribers struggle to identify potentially inappropriate medications and to choose an adequate tapering approach. METHODS/DESIGN: The goal of the study is to translate and culturally adapt MedStopper®, an original English language web-based decision aid system in deprescribing medication, to the Portuguese population. A translation-back translation method, with validation of the obtained Portuguese version of MedStopper® will be used, followed by a comprehension test. DISCUSSION: This is the first research in the Portuguese primary care setting that aims to provide a useful online tool for the appropriate prescription of older patients. The translated version in Portuguese version of the MedStopper® tool will represent an advance that seeks to continue improving the management of medications in the elderly. The adaptation into Portuguese of the educational tool provides clinicians with a screening tool to detect potentially inappropriate prescribing in patients older than 65 that reliable and easier to use. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Desprescrições , Humanos , Idoso , Prescrição Inadequada/prevenção & controle , Lista de Medicamentos Potencialmente Inapropriados , Polimedicação , Técnicas de Apoio para a Decisão , Internet
18.
Artigo em Inglês | MEDLINE | ID: mdl-37105883

RESUMO

OBJECTIVE: To determine dentists' awareness and/or adherence to antibiotic prophylaxis (AP) guidelines for preventing infective endocarditis (IE) in patients with high-risk heart conditions. STUDY DESIGN: A systematic literature review was performed on MEDLINE/PubMed, Scopus, Web of Science, Cochrane Library, Proquest, Embase, Dentistry, and Oral Sciences Source databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Nationwide studies based on questionnaires, surveys, and interviews completed by dentists and published since 2007 were included. RESULTS: From 2907 articles screened, 28 studies were selected (across 20 countries). The quality of included studies was poor due to a lack of standard evaluation tools, low response rates, and lack of questionnaire validity and/or reliability. Approximately 75% of surveyed dentists reported being knowledgeable about AP guidelines, but only ∼25% complied. Reported compliance with American Heart Association (AHA) guidelines was 4 times higher than with the National Institute for Health and Care Excellence (NICE) recommendations. Some of the highest adherence rates were reported for other national AP guidelines. Significant geographic differences were observed in the estimated adherence to AHA guidelines and the percentage of dentists who reported seeking advice from physicians and/or cardiologists. CONCLUSION: Rates of compliance and/or adherence were substantially different from rates of knowledge and/or awareness, including relevant geographic dissimilarities. Compliance/adherence was higher for AHA than NICE.


Assuntos
Endocardite Bacteriana , Endocardite , Estados Unidos , Humanos , Antibioticoprofilaxia , Reprodutibilidade dos Testes , Fidelidade a Diretrizes , Endocardite/prevenção & controle , Endocardite Bacteriana/prevenção & controle , Odontólogos
19.
Healthcare (Basel) ; 11(7)2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37046959

RESUMO

Cardiovascular events are the leading cause of on-duty deaths among firefighters. Screening firefighters for risk of sudden cardiac event is a critical element of a comprehensive medical program. Although intense physical exertion has been shown to trigger sudden cardiac events in the general population, it is unclear how hemodynamic responses following clinical exercise testing compare to that of performing firefighting tasks in personal protective equipment. Therefore, the purpose of this study was to compare hemodynamic responses following rescue simulation (RS) and maximal exercise in firefighters. This was a cross-over repeated measures study. Thirty-eight professional firefighters (31.8 ± 5.2 yr; VO2peak: 57.9 mL/kg/min) completed a maximal aerobic exercise test (MAET) and an RS. Pulse wave velocity (PWV), pulse pressure (PP), and brachial and central mean arterial pressure (MAP) were measured before and 5 and 15 min post-exercise. The findings indicated that femoral PWV decreased after MAET and RS at both time points (p < 0.005). No significant differences were found in aortic and carotid PWV over time or between conditions (p ≥ 0.05). Significant increases in brachial and central PP and MAP were noted 5 min post-MAET and RS (p = 0.004). In conclusion, the present study demonstrated that peripheral arterial stiffness (AS) decreased in firefighters following both conditions, with no differences in central AS. Our findings provide valuable information on hemodynamic responses similar between RS and MAET, and are important for controlling CVD risk and the AS response.

20.
Clin Transl Allergy ; 13(2): e12210, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36825517

RESUMO

BACKGROUND: Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment. METHODS: This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0-100). RESULTS: A total of 193 patients (72% female; median [P25-P75] age 28 [19-41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0-71]%; 1 month: 18 [0-48]%) than patient self-report (80 [60-95]) and physician assessment (82 [51-94]) (p < 0.001). A negligible non-significant correlation was found between the app and subjective measurements (ρ 0.118-0.156, p > 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001). CONCLUSIONS: Adherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.

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