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1.
Eur Heart J Case Rep ; 8(8): ytae404, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39219804

RESUMO

Background: Hydroxychloroquine (HCQ) is a disease-modifying antirheumatic used in rheumatological diseases such as systemic lupus erythematosus. Long-term exposure to HCQ results in drug accumulation and predisposes to adverse effects. Case summary: We present the case of a 45-year-old woman with long-term treatment with HCQ who presented to the Emergency Department with acute heart failure. Transthoracic echocardiogram, previously normal, showed severe biventricular hypertrophy and biventricular systolic dysfunction. Cardiac magnetic resonance (CMR) confirmed the previous findings and showed elevated native T1 and T2 values, elevated extracellular volume, and extensive mid-wall late gadolinium enhancement (LGE). Infiltrative cardiomyopathy was suspected, and endomyocardial biopsy performed. Light microscopy showed myocyte hypertrophy and vacuolar change and absence of lymphocytic inflammatory infiltrates. The diagnosis of HCQ-induced cardiomyopathy was established, and the drug was withdrawn. A CMR performed 1 year later showed normal systolic function of both ventricles and normalization of T2 values, reflecting resolution of myocardial oedema. However, severe hypertrophy, elevated native T1 values, and LGE persisted. Discussion: Our case shows that although discontinuation of the drug stops the progression of the disease, established myocardial structural damage persists. Early diagnosis of this entity is therefore essential to improve prognosis.

2.
Mycoses ; 67(9): e13799, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39289823

RESUMO

BACKGROUND: Several clinical signs in dermatoscopy are very characteristic of onychomycosis and can be a quick complement for the diagnosis of onychomycosis. OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of dermatoscopy compared to microbiological culture and polymerase chain reaction (PCR), as well as the clinical signs associated with onychomycosis. METHODS: The clinical signs of 125 patients were assessed cross-sectionally using dermatoscopy, and a positive or negative result was assigned. A sample was then taken for PCR and microbiological culture. RESULTS: Of the 125 patients, 69.6% (87/125) had positive results when both laboratory tests were combined. When they were not combined, the prevalence was lower at 48% (60/125) with PCR and at 43.2% (54/125) with culture. Furthermore, 76.8% (96/125) were classified as positive with dermatoscopy with a sensitivity of 1, a specificity of 0.76, positive predictive value of 0.91 and negative predictive value of 1 (with 95% confidence intervals). Of the 96 dermatoscopy-positive samples, 36 were negative with PCR (p < 0.001), 42 were negative with culture (p < 0.001) and nine were negative when both tests were combined (p < 0.001). Clinical signs that were significantly associated with the presence of onychomycosis were subungual hyperkeratosis (dermatoscopy: p = 0.004, odds ratio (OR) = 2.438; PCR + microbiological culture: p = 0.004, OR = 3.221), subungual detritus (p = 0.033, OR = 3.01, only with dermatoscopy) and dermatophytoma (dermatoscopy: p = 0.049, OR = 3.02; PCR + microbiological culture: p = 0.022, OR = 2.40). CONCLUSIONS: The results suggest that dermatoscopy is a good tool for the diagnosis of onychomycosis but should be used as a complementary test or for screening patients to be sampled for laboratory testing. The combination of the three tests can lead to a reduction of false-positive and false-negative clinical and laboratory results. This allows for early diagnosis and specific treatment based on test results.


Assuntos
Dermoscopia , Onicomicose , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Humanos , Onicomicose/diagnóstico , Onicomicose/microbiologia , Estudos Transversais , Reação em Cadeia da Polimerase/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Dermoscopia/métodos , Adulto Jovem , Idoso de 80 Anos ou mais , Adolescente , Técnicas Microbiológicas/métodos , Fungos/isolamento & purificação , Fungos/genética , Valor Preditivo dos Testes
3.
Front Public Health ; 12: 1351754, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267653

RESUMO

Objective: To describe the perspectives of a group of COPD patients during the first outbreak of the COVID-19 pandemic and narrate the emotions and polarity (acceptance-rejection) regarding living with COPD during the pandemic. Design/methods: We used a novel application of lemmatization and thematic analysis of participants' narratives. A study was carried out with eight patients with moderate-severe-very severe COPD during the first outbreak of COVID-19 using purposive sampling. In-depth interviews and field notes from the researchers were used to collect data. A statistical content analysis (lemmatization) of the patients' narratives was performed. Additionally, inductive thematic analysis was used to identify emerging themes. This study was conducted following the guidelines of Consolidated Criteria/Standards for Reporting Qualitative Research. The study was conducted in accordance with the principles articulated in the WMA Declaration of Helsinki. Participants provided verbal informed consent prior to their inclusion as previously described. Results: The average age of our sample was 65 years, and 75% of the patients suffered from moderate COPD, 12.5% from severe COPD, and 12.5% from very severe COPD according to GOLD criteria. The lemmatized and sentiment analysis showed a predominance of positive emotions, and the polarity of the interviews indicated a very slight positive trend towards acceptance of the experience lived during the pandemic. Additionally, three main themes were identified: (1) Confinement and restriction measures, (2) COVID-19 and protective measures, and (3) Clinical care during the first outbreak of the pandemic. Conclusion: Patients experienced confinement with a feeling of security and protection. They strictly respect social distancing. They used masks, but these caused them to feel short of breath and fatigue, especially FFP2 masks. Half of the patients rejected the possibility of being vaccinated. Finally, they were very satisfied with the clinical care they received in the COPD unit of their hospital. Our results show that COPD patients have not experienced a negative impact of the COVID-19 pandemic.


Assuntos
COVID-19 , Doença Pulmonar Obstrutiva Crônica , Pesquisa Qualitativa , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/psicologia , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , SARS-CoV-2 , Pandemias , Entrevistas como Assunto , Emoções
4.
Diagn Microbiol Infect Dis ; 110(4): 116539, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39298932

RESUMO

Severe infections caused by multidrug-resistant bacteria have underscored the urgent need for innovative treatment approaches. Novel antimicrobials like cefiderocol have emerged as effective options, but their use in children remains largely unexplored. In this brief report, we describe a severe case of sepsis in a child with an oncohematological disease, caused by a highly drug-resistant strain of Klebsiella pneumoniae. The addition of cefiderocol to other therapies resulted in a successful outcome. Additionally, we provide a literature review of previously published cases involving children treated with this new antibiotic. In our patient, cefiderocol was both safe and effective in combating the multidrug-resistant pathogen. However, further research is needed to better define the indications and safety profile of this novel antibiotic.

5.
Noncoding RNA ; 10(5)2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39311384

RESUMO

Prostate cancer (PCa) is a prevalent malignancy in men globally. Current diagnostic methods like PSA testing have limitations, leading to overdiagnosis and unnecessary treatment. Castration-resistant prostate cancer (CRPC) emerges in some patients receiving androgen deprivation therapy (ADT). This study explores the potential of circulating microRNA-107 (miR-107) in liquid biopsies as a prognosis tool to differentiate CRPC from non-castration-resistant PCa (NCRPC). We designed a case-control study to evaluate circulating miR-107 in serum as a potential prognosis biomarker. We analyzed miR-107 expression in liquid biopsies and found significantly higher levels (p < 0.005) in CRPC patients, compared to NCRPC. Notably, miR-107 expression was statistically higher in the advanced stage (clinical stage IV), compared to stages I-III. Furthermore, CRPC patients exhibited significantly higher miR-107 levels (p < 0.05), compared to NCRPC. These findings suggest that miR-107 holds promise as a non-invasive diagnostic biomarker for identifying potential CRPC patients.

6.
J Med Virol ; 96(9): e29925, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39295250

RESUMO

A plantar wart is a benign hyperplasia that appears on the feet due to the human papillomavirus (HPV). One method used for the treatment of recalcitrant plantar warts, those lasting over 2 years or persisting after at least two treatment attempts, is the cantharidin (1%), podophyllin (5%), and salicylic acid (30%) formulation, also known as the CPS formulation. Although this method is in use, there are few studies on it. This study's objective was to ascertain its cure rate. For this retrospective observational study, we reviewed the medical records of patients treated with the CPS formulation at a podiatric clinic specializing in plantar wart treatment. Our sample size was 48 subjects. The CPS formulation had a cure rate of 62.5%. Out of the cured patients, 86.67% (26/30) required one or two applications. There was no observable correlation (p > 0.05) between wart resolution and virus biotype, evolution time, patient's morphological and clinical attributes, location, number of warts, or preceding treatments. The CPS formulation presents a relatively high efficacy rate for treating recalcitrant HPV plantar warts. Still, additional studies are necessary to evaluate its safety and efficiency.


Assuntos
Cantaridina , Podofilina , Ácido Salicílico , Verrugas , Humanos , Cantaridina/uso terapêutico , Cantaridina/administração & dosagem , Verrugas/tratamento farmacológico , Verrugas/virologia , Estudos Retrospectivos , Masculino , Ácido Salicílico/uso terapêutico , Ácido Salicílico/administração & dosagem , Feminino , Adulto , Resultado do Tratamento , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Podofilina/uso terapêutico , Podofilina/administração & dosagem , Criança
7.
J Cardiovasc Dev Dis ; 11(9)2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39330317

RESUMO

Numerous cases of myocarditis related to mRNA vaccines for COVID-19 have recently been described, usually in young men. Long-term evolutive cardiac magnetic resonance imaging (CMR) data are lacking. We describe four consecutive cases of COVID-19 vaccine-induced myocarditis. The pathological findings of cardiac magnetic resonance confirmed the diagnosis in the acute phase, showing edema, as well as pericardial enhancement, with light pericardial effusion and late gadolinium enhancement (LGE), predominantly in the inferolateral wall. These cases highlight the unique value of cardiac magnetic resonance in patients with suspected myocarditis induced by COVID-19 RNAm vaccines as a tool to confirm the diagnosis, avoiding other invasive techniques, as well as for the long-term follow-up of patients. Our iterative CMR imaging demonstrated frequent long-term LGE persistence.

8.
Sci Data ; 11(1): 1009, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289384

RESUMO

Although Essential Climate Variables (ECVs) have been widely adopted as important metrics for guiding scientific and policy decisions, the Earth Observation (EO) and Land Surface and Hydrologic Model (LSM/HM) communities have yet to treat terrestrial ECVs in an integrated manner. To develop consistent terrestrial ECVs at regional and continental scales, greater collaboration between EO and LSM/HM communities is needed. An essential first step is assessing the LSM/HM simulation uncertainty. To that end, we introduce a new hydrological reference dataset that comprises a range of 19 existing LSM/HM simulations that represent the current state-of-the-art of our LSM/HMs. Simulations are provided on a daily time step, covering Europe, notably the Rhine and Po river basins, alongside the Tugela river basin in Africa, and are uniformly formatted to allow comparisons across simulations. Furthermore, simulations are comprehensively validated with discharge, evapotranspiration, soil moisture and total water storage anomaly observations. Our dataset provides valuable information to support policy development and serves as a benchmark for generating consistent terrestrial ECVs through the integration of EO products.

9.
Inorg Chem ; 63(34): 15762-15771, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39133057

RESUMO

The study of the structural stability of carbonates under different pressure and temperature conditions is important for modeling the carbon budget in the Earth's interior and the stability of carbonation products of carbon capture and storage (CCS) solutions. In this work, we confirm the existence of the two dense polymorphs of the hydrated magnesium carbonate MgCO3·3H2O nesquehonite mineral previously reported, and we characterize their structures using synchrotron single-crystal X-ray diffraction at 3.1 and 11.6 GPa. Phase transitions entail the distortion and atomic rearrangement of the Mg-centered polyhedra and the tilting of the [CO3] carbonate units. In particular, the Mg coordination number increases from 6 in nesquehonite to 7 in the second high-pressure phase, while maintaining a topology based on complex MgCO3(H2O)2 chains. We also studied their vibrational behavior upon compression using Raman spectroscopy and complemented the experimental results with density-functional theory (DFT) calculations. The role played by hydrogen bonds in the compressibility and the polymorphism of this hydrated carbonate is also discussed.

10.
J Am Heart Assoc ; 13(17): e036236, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39206739

RESUMO

BACKGROUND: Unknown cardioembolic sources are frequent causes of cryptogenic stroke. We analyzed the risk of atrial fibrillation (AF) or high burden of ectopic atrial activity (HBEA) in patients with cryptogenic stroke, assessing atrial function and 1-year outcomes. METHODS AND RESULTS: The ARIES (Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke) study is an observational study including patients with cryptogenic stroke. We analyzed the frequency of AF and HBEA (>3000 atrial ectopic beats/day or >2 bursts or atrial tachycardia between 3 beats and ≤30 seconds) in two 30-day Holter-ECGs, comparing advanced echocardiography signs of left atrial (LA) dysfunction according to rhythm: AF, HBEA, and normal sinus rhythm. We also evaluated 1-year stroke recurrence and mortality. The study included 109 patients; 35 (32.1%) patients had AF, 27 (24.8%) HBEA, and 47 (43.1%) normal sinus rhythm. Compared with those with normal sinus rhythm, patients with AF presented higher 2-dimensional and 3-dimensional LA indexed volumes (38.8±11.2 versus 27.3±11.8 mL/m2, and 50.6±17.2 versus 34.0±15.4 mL/m2, respectively, P<0.001), lower 3-dimensional LA ejection fraction (50±14.6 versus 62.7±11.8, P=0.001), LA reservoir strain (22.0±8.6 versus 30.4±10.5, P<0.001), and LA contraction strain (10.5±8.18 versus 17.1±7.5, P<0.001), remaining significant in multivariate analysis. Patients with HBEA showed higher LA indexed volumes and lower LA reservoir strain than patients with normal sinus rhythm only in univariate analysis. There were no differences in ischemic recurrence or mortality among the groups. CONCLUSIONS: Patients with cryptogenic stroke showed a high incidence of AF and HBEA. AF is strongly related to LA volume, LA function, and LA reservoir and contraction strain, whereas HBEA showed milder structural changes. Advanced LA echocardiography could help patient selection for long-term ECG monitoring in suspected cardiac sources.


Assuntos
Fibrilação Atrial , Função do Átrio Esquerdo , Eletrocardiografia Ambulatorial , AVC Embólico , Recidiva , Humanos , Masculino , Feminino , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/diagnóstico , Idoso , Pessoa de Meia-Idade , AVC Embólico/etiologia , AVC Embólico/fisiopatologia , Função do Átrio Esquerdo/fisiologia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Frequência Cardíaca/fisiologia , Fatores de Risco , Complexos Atriais Prematuros/fisiopatologia , Complexos Atriais Prematuros/diagnóstico , Complexos Atriais Prematuros/complicações , Complexos Atriais Prematuros/epidemiologia , Ecocardiografia/métodos , Fatores de Tempo , Medição de Risco/métodos
11.
J Pediatr Gastroenterol Nutr ; 79(4): 841-849, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39175183

RESUMO

OBJECTIVES: Food protein-induced enterocolitis syndrome (FPIES) is a severe type of non-IgE (immunoglobulin E)-mediated (NIM) food allergy, with cow's milk (CM) being the most common offending food. The relationship between the gut microbiota and its metabolites with the inflammatory process in infants with CM FPIES is unknown, although evidence suggests a microbial dysbiosis in NIM patients. This study was performed to contribute to the knowledge of the interaction between the gut microbiota and its derived metabolites with the local immune system in feces of infants with CM FPIES at diagnosis. METHODS: Twelve infants with CM FPIES and a matched healthy control group were recruited and the gut microbiota was investigated by 16S amplicon and shotgun sequencing. Fatty acids (FAs) were measured by gas chromatography, while immune factors were determined by enzyme-linked immunosorbent assay and Luminex technology. RESULTS: A specific pattern of microbiota in the gut of CM FPIES patients was found, characterized by a high abundance of enterobacteria. Also, an intense excretion of FAs in the feces of these infants was observed. Furthermore, correlations were found between fecal bifidobacteria and immune factors. CONCLUSION: These fecal determinations may be useful to gain insight into the pathophysiology of this syndrome and should be taken in consideration for future studies of FPIES patients.


Assuntos
Enterobacteriaceae , Enterocolite , Fezes , Microbioma Gastrointestinal , Hipersensibilidade a Leite , Humanos , Lactente , Masculino , Feminino , Hipersensibilidade a Leite/microbiologia , Hipersensibilidade a Leite/imunologia , Fezes/microbiologia , Enterobacteriaceae/isolamento & purificação , Enterocolite/microbiologia , Animais , Estudos de Casos e Controles , Ácidos Graxos/metabolismo , Leite/microbiologia , Disbiose/microbiologia
12.
Cancers (Basel) ; 16(15)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39123355

RESUMO

BACKGROUND: The purpose of this study is to analyze the long-term evolution of patients with small choroidal melanocytic tumors (SCMTs) undergoing observation, and to assess their rate of transformation into melanomas and survival. METHODS: A retrospective single-cohort study of patients with SCMTs (1-3 mm in height and 5-10 mm in base) diagnosed from January 1992 to February 2023 was carried out, with observation as the initial treatment. The main criterion for a transformation into melanoma is considered to be an increase in size of more than 1 mm in height and/or more than 1 mm in base measured on an ultrasound/retinography, recorded in two consecutive visits separated by one to three months. RESULTS: 243 patients were included with a mean age of 65.3 years and a mean follow-up of 7.9 years (6 months-27.9 years); 27 patients showed tumor growth. The probabilities of growth at 5, 10, and 15 years are 10%, 14%, and 17%, respectively. Regarding survival, 22 patients died and only 3 deaths were due to melanoma metastasis. Survival rates at 5 and 10 years are 99% and 97%. CONCLUSIONS: Observation is a viable therapeutic option for SCMTs, avoiding the side effects of treatment, considering the majority of these tumors do not progress to melanoma. With close monitoring, patients can be treated promptly upon detecting a transformation. Additionally, the findings confirm that small melanocytic tumors can lead to metastatic disease, albeit at a low rate.

13.
Healthcare (Basel) ; 12(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39120180

RESUMO

AIM: To describe the latest scientific evidence regarding community-based interventions performed on patients in need of palliative care worldwide. INTRODUCTION AND BACKGROUND: Given the rise of chronic diseases, their complexities and the fragility of patients, we are facing around 56.8 million people in need of palliative care. Community-based healthcare, particularly palliative care, can address social inequalities and improve the biopsychosocial health of disadvantaged populations. Therefore, primary care, as the main health referent in the community, has a central role in the care of these patients. METHODS: This is an integrative review from January 2017 to June 2022 that follows the PRISMA statement and has been registered in PROSPERO. PubMed, Cuiden, the Web of Science (WoS), Cochrane and LILACS were the five databases searched. The scientific quality assessment of the articles was carried out following the CASPe methodology. Study selection was carried out by two researchers, A.V.L. and J.M.C.T., using the inclusion and exclusion criteria mentioned below. In cases of doubt or discrepancy, a third author (J.R.S.) was consulted. RESULTS: The interventions mentioned in the 16 articles analysed were classified under the following categories: music therapy, laughter therapy, spiritual and cognitive interventions, aromatherapy, interdisciplinary and community-based teams, advance care planning and community, volunteering, telemedicine and care mapping. EXAMPLE: Educating people to talk about different ethical issues could improve their quality of life and help develop more compassionate cities. CONCLUSIONS: We have identified interventions that are easily accessible (laughter therapy, telemedicine or music therapy), simple enough to be carried out at the community level and do not incur high costs. This is why they are recommended for people with palliative care needs in order to improve their quality of life.

14.
bioRxiv ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39149362

RESUMO

Notch signaling regulates cell fate decisions and has context-dependent tumorigenic or tumor suppressor functions. Although several Notch inhibitors are under development as cancer therapies, the mechanical force requirement for Notch receptor activation has hindered attempts to generate soluble agonists. To address this problem, we engineered synthetic Notch agonist (SNAG) proteins that mimic the tension-generating mechanism of endogenous ligands. SNAGs were designed by fusing a high-affinity variant of the Notch ligand Delta-like 4 (DLL4) to antibody fragments that induce target internalization. This bispecific format enables the SNAG-bound biomarkers to "pull" on Notch receptors, triggering Notch activation in mixed populations of biomarker-expressing and non-expressing cells. SNAGs targeting the immune checkpoint PDL1 potently activated Notch in co-cultures of Notch1- and PDL1-expressing cells, but not in monocultures of Notch1-expressing cells alone. Additional SNAGs targeting the tumor antigens CD19 and HER2 also activated Notch in mixed cell populations, indicating that the SNAG design concept is adaptable to multiple biomarkers. SNAG-mediated Notch activation was blocked by a dynamin inhibitor, and efficacy increased dramatically when SNAGs were dimerized via fusion to antibody Fc domains, suggesting that endocytosis and multimerization are important for optimal SNAG function. These insights will greatly expand our ability to modulate Notch signaling for applications in immunotherapy and regenerative medicine.

15.
Artigo em Inglês | MEDLINE | ID: mdl-39033019

RESUMO

BACKGROUND: Brain imaging studies investigating grey matter in functional neurological disorder (FND) have used univariate approaches to report group-level differences compared with healthy controls (HCs). However, these findings have limited translatability because they do not differentiate patients from controls at the individual-level. METHODS: 183 participants were prospectively recruited across three groups: 61 patients with mixed FND (FND-mixed), 61 age-matched and sex-matched HCs and 61 age, sex, depression and anxiety-matched psychiatric controls (PCs). Radial basis function support vector machine classifiers with cross-validation were used to distinguish individuals with FND from HCs and PCs using 134 FreeSurfer-derived grey matter MRI features. RESULTS: Patients with FND-mixed were differentiated from HCs with an accuracy of 0.66 (p=0.005; area under the receiving operating characteristic (AUROC)=0.74); this sample was also distinguished from PCs with an accuracy of 0.60 (p=0.038; AUROC=0.56). When focusing on the functional motor disorder subtype (FND-motor, n=46), a classifier robustly differentiated these patients from HCs (accuracy=0.72; p=0.002; AUROC=0.80). FND-motor could not be distinguished from PCs, and the functional seizures subtype (n=23) could not be classified against either control group. Important regions contributing to statistically significant multivariate classifications included the cingulate gyrus, hippocampal subfields and amygdalar nuclei. Correctly versus incorrectly classified participants did not differ across a range of tested psychometric variables. CONCLUSIONS: These findings underscore the interconnection of brain structure and function in the pathophysiology of FND and demonstrate the feasibility of using structural MRI to classify the disorder. Out-of-sample replication and larger-scale classifier efforts incorporating psychiatric and neurological controls are needed.

16.
Viruses ; 16(7)2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39066263

RESUMO

Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013-2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic.


Assuntos
Amidas , Antivirais , Modelos Animais de Doenças , Ebolavirus , Doença pelo Vírus Ebola , Camundongos Endogâmicos BALB C , Pirazinas , Animais , Amidas/uso terapêutico , Amidas/administração & dosagem , Amidas/farmacologia , Cobaias , Pirazinas/administração & dosagem , Pirazinas/uso terapêutico , Doença pelo Vírus Ebola/tratamento farmacológico , Camundongos , Ebolavirus/efeitos dos fármacos , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Feminino , Vias de Administração de Medicamentos , Esquema de Medicação
17.
Enferm Clin (Engl Ed) ; 34(4): 259-270, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39019328

RESUMO

OBJECTIVE: To establish the construct validity of the Spanish version of the BARRIERS scale. METHOD: Methodological study of validation of a measurement instrument based on data from previously published studies. The study population consisted of nurses from the Basque Health Service and the Canary Health Service. The following variables were extracted and unified: Years of professional experience, possession of a specialist nursing degree, possession of a doctorate, type of activity performed by the professional and field of work. For construct validation, a confirmatory factor analysis (CFA) was performed based on the initial model proposed for the scale and RASCH analysis. A polychoric correlation matrix, factor extraction by unweighted least squares and PROMIN oblique rotation were used. For the RASCH analysis, the Joint Maximun Likelihood estimation (JMLE) method was used; the fit of the items and persons were estimated by means of outfit - Unweighted Mean Square fit statistic (UMS) and infit -Weighted Mean Square Fit Statistic (WMS), as well as the reliability and separation of items and persons. RESULTS: A total of 1200 nurses and midwives made up the final validation sample (n = 1200), with a mean professional experience of 21.22 ± 9.26 years. The CFA presented a good fit to the data (KMO = 0.935 [95% CI: 0.921-0.945]), changing the factorial assignment in 6 items, while 5 items received factorial scores in more than one factor. The fit values for the 4-factor solution were RMSEA = 0.026 [95% CI: 0.026-0.027] and GFI = 0.991 [95% CI: 0.986-0.991]. In the RASCH analysis most items presented infit-WMS and outfit-UMS values with a good fit. CONCLUSIONS: The Spanish version of the BARRIERS scale has adequate construct validity although there are changes in the assignment of items to the dimensions compared to the original model. The RASCH analysis indicates adequate fit for both persons and items.


Assuntos
Autorrelato , Humanos , Reprodutibilidade dos Testes , Espanha , Adulto , Feminino , Masculino , Pessoa de Meia-Idade
18.
Front Med (Lausanne) ; 11: 1407812, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983363

RESUMO

Objective: In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA. Methods: Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application. Results: The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies. Conclusion: The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies.

19.
ACS Appl Bio Mater ; 7(8): 5728-5739, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39037897

RESUMO

Implants made from titanium are used as prostheses because of their biocompatibility and their mechanical properties close to those of human bone. However, the risk of bacterial infection is always a major concern during surgery, and the development of biofilm can make these infections difficult to treat. A promising strategy to mitigate against bacterial infections is the use of antifouling and antimicrobial coatings, where bioresorbable polymers can play an important role due to their controlled degradability and sustained drug release, as well as excellent biocompatibility. In the present study, poly(d,l-lactide) (PDLLA) and poly[d,l-lactide-co-methyl ether poly(ethylene glycol)] (PDLLA-PEG) were studied, varying the PEG content (20-40% w/w) to analyze the effectiveness of PEG as an antifouling molecule. In addition, silver sulfadiazine (AgSD) was used as an additional antimicrobial agent with a concentration ≤5% w/w and incorporated into the PEGylated polymers to create a polymer with both antifouling and antimicrobial properties. Polymers synthesized were applied using spin coating to obtain homogeneous coatings to protect samples made from titanium/aluminum/vanadium (Ti6Al4V). The polymer coatings had a smoothing effect in comparison to that of the uncoated material, decreasing the contact area available for bacterial colonization. It was also noted that PEG addition into the polymeric chain developed amphiphilic materials with a decrease in contact angle from the most hydrophobic (Ti6Al4V) to the most hydrophilic PDLLA-PEG (60/40), highlighting the increase in water uptake contributing to the hydration layer formation, which confers the antifouling effect on the coating. This study demonstrated that the addition of PEG above 20% w/w and AgSD above 1% w/v into the formulation was able to decrease bacterial adherence against clinically relevant biofilm former strains Staphylococcus aureus and Pseudomonas aeruginosa.


Assuntos
Ligas , Antibacterianos , Biofilmes , Materiais Revestidos Biocompatíveis , Teste de Materiais , Poliésteres , Staphylococcus aureus , Titânio , Biofilmes/efeitos dos fármacos , Titânio/química , Titânio/farmacologia , Ligas/química , Ligas/farmacologia , Poliésteres/química , Poliésteres/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Humanos , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Propriedades de Superfície , Próteses e Implantes
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