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1.
Vet Res Commun ; 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352648

RESUMO

Ovine anaplasmosis is causing relevant economic losses in Spain due to icteric carcass condemnation in lambs. Anaplasma ovis infection occurs through grazing sheep that transfer ticks to their offspring. This study compared the efficacy of deltamethrin and cypermethrin pour-on treatments for tick control. A total of 250 PCR A. ovis-positive ewes and their offspring were divided into 5 groups. Group A (50 ewes/50 lambs) was kept as an untreated control group. In groups B (50/50) and C (45/93), the lambs were treated with deltamethrin pour-on and cypermethrin pour-on, respectively, one week after birth. In groups D (50/75) and E (51/68), the ewes were treated with cypermethrin pour-on and deltamethrin pour-on one week before the estimated parturition. External parasite assessment and A. ovis PCR were conducted before treatment and at 21 and 42 days post-treatment. Ewes were checked weekly for tick-detection until weaning. Lamb carcasses were examined at the slaughterhouse. Riphicephalus sanguineus sensu lato ticks were found in ewes throughout the study, with only one tick found in a control group lamb. Three lambs tested positive for A. ovis during the trial, with one condemnation at the abattoir due to jaundice. However, no significant differences were observed between treatment groups. Overall, a significant decrease in infected animals and condemned carcasses was observed compared to previous years, suggesting that deltamethrin and cypermethrin prevent A. ovis transmission from dams to lambs. Further studies are needed to confirm synthetic pyrethroids' effectiveness in controlling tick infestation and averting A. ovis transmission to lambs.

2.
Front Immunol ; 15: 1454474, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39224593

RESUMO

Introduction: Alemtuzumab is a highly effective pulsed immune reconstitution therapy for multiple sclerosis (MS). Aim: To evaluate serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) in patients with relapsing-remitting MS who have been treated with Alemtuzumab over the course of 2 years. Methods: This prospective study involved MS patients treated with Alemtuzumab at a referral MS center. Both sNfL and sGFAP were analyzed at baseline and then again at 6, 12, and 24 months post-treatment using the single molecule array (SiMoA) technique. We also recruited matched healthy controls (HCs) for comparison. Results: The study included 46 patients (with a median age of 34.2 [Interquartile range (IQR), 28.7-42.3] years, 27 of which were women [58%]) and 76 HCs. No differences in demographic characteristics were observed between patients and HC. The median disease duration was 6.22 (IQR, 1.56-10.13) years. The median annualized relapse rate before treatment was 2 (IQR, 1-3). At baseline, sNfL and sGFAP levels were higher in MS patients (median of 18.8 [IQR, 10.7-52.7] pg/ml and 158.9 [IQR, 126.9-255.5] pg/ml, respectively) when compared to HC (6.11 [IQR, 2.03-8.54] pg/ml and 91.0 [72.6-109] pg/ml, respectively) (p<0.001 for both comparisons). The data indicates that 80% of patients had high (≥10 pg/ml) sNfL values at baseline. We observed a significant decrease in sNfL levels at 6 (65%, p = 0.02), 12 (70.8%, p<0.001), and 24 (78.1%, p<0.001) months. sNfL reached similar levels to HC only after 24 months of Alemtuzumab treatment. During the follow-up period, no changes were identified in the sGFAP values. Conclusion: Alemtuzumab leads to the normalization of sNfL values in MS patients after 2 years of treatment, with no apparent effect on sGFAP values.


Assuntos
Alemtuzumab , Proteína Glial Fibrilar Ácida , Esclerose Múltipla Recidivante-Remitente , Proteínas de Neurofilamentos , Humanos , Alemtuzumab/uso terapêutico , Feminino , Masculino , Adulto , Proteínas de Neurofilamentos/sangue , Estudos Prospectivos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/imunologia , Proteína Glial Fibrilar Ácida/sangue , Biomarcadores/sangue , Resultado do Tratamento , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/sangue
3.
Brain Struct Funct ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39313671

RESUMO

The neurodevelopmental epoch from fetal stages to early life embodies a critical window of peak growth and plasticity in which differences believed to be associated with many neurodevelopmental and psychiatric disorders first emerge. Obtaining a detailed understanding of the developmental trajectories of the cortical gray matter microstructure is necessary to characterize differential patterns of neurodevelopment that may subserve future intellectual, behavioral, and psychiatric challenges. The neurite orientation dispersion density imaging (NODDI) Gray-Matter Based Spatial Statistics (GBSS) framework leverages information from the NODDI model to enable sensitive characterization of the gray matter microstructure while limiting partial volume contamination and misregistration errors between images collected in different spaces. However, limited contrast of the underdeveloped brain poses challenges for implementing this framework with infant diffusion MRI (dMRI) data. In this work, we aim to examine the development of cortical microstructure in infants. We utilize the NODDI GBSS framework and propose refinements to the original framework that aim to improve the delineation and characterization of gray matter in the infant brain. Taking this approach, we cross-sectionally investigate age relationships in the developing gray matter microstructural organization in infants within the first month of life and reveal widespread relationships with the gray matter architecture.

4.
Nat Prod Res ; : 1-8, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39285759

RESUMO

Syzygium aromaticum L. (clove) is a species native to subtropical countries. Its dried flower buds are rich in essential oils, which have shown insecticidal, anti-inflammatory and anaesthetic effects. This work was aimed to study the differences in antioxidant and anticancer activities between clove essential oil (CEO) and its major component, eugenol. The chemical composition of the CEO was determined by GC-MS. The physicochemical properties and antioxidant activity were determined in CEO and eugenol. Finally, anticancer activities were assayed against seven cell lines. Chemical analysis revealed that 80% of the CEO was eugenol. The density and IR were similar, and the colour was ΔE*>3. CEO had a lower phenolic content, but similar antioxidant activity to eugenol. The anticancer activity of the CEO was greater than that of eugenol in all the cell lines except for HeLa cells. These results suggest that secondary compounds in CEO enhance its antioxidant and -anticancer activities.

5.
J Hazard Mater ; 480: 135825, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39326148

RESUMO

Bioaerosols originating from animal feeding operations (AFOs) may carry pathogens, allergens, and other hazardous biocomponents, such as endotoxins, posing a potential risk to community health and the environment when dispersed downwind. This review summarizes and synthesizes existing literature data on bioaerosols downwind from three major types of AFOs (swine, poultry, and cattle), covering their composition, concentration, dispersion patterns, measurement methodologies, potential health effects, and mitigation strategies. While many of these bioaerosols are typically detected only near AFOs, evidence indicates that certain bioaerosols, particularly viruses, can travel up to tens of kilometers downwind and remain infectious. Despite the critical importance of these bioaerosols, a refined modeling framework to simulate their transport and fate in downwind air has not yet been developed, nor have source attribution methods been established to track their origins in complex agricultural environments where multiple bioaerosols could co-exist. Therefore, it is imperative to further research downwind bioaerosols from AFOs, including their assessment, modeling, source attribution, and mitigation, to address the public health and environmental challenges associated with animal agriculture.

6.
J Clin Med ; 13(18)2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39337069

RESUMO

Systemic inflammation and immunodeficiency are important components of cirrhosis-associated immune dysfunction (CAID), the severity of which is dynamic, progressive, and associated with the greater deterioration of liver function. Two inflammation phenotypes have been described: low-grade and high-grade systemic inflammation. Both of these phenotypes are related to liver cirrhosis function; thus, high-grade inflammation is correlated with the severity of hepatic insufficiency, bacterial translocation, and organic insufficiency, with which the risk of infections increases and the prognosis worsens. Bacterial translocation (BT) plays a relevant role in persistent systemic inflammation in patients with cirrhosis, and the prophylactic employment of antibiotics is useful for reducing events of infection and mortality.

7.
Arch Med Res ; 55(7): 103060, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39332151

RESUMO

BACKGROUND: Healthcare systems must adapt iteratively in response to external and local challenges while keeping patients and staff safe. Clinical debriefing is a cost-effective contributor to safety culture, facilitating learning and team adaptations that lead to improved processes, patient outcomes, and staff resilience. In the aftermath of the COVID-19 pandemic, an interest has emerged in adopting TALK© to guide clinical debriefing to promote safety, mutual support, and cultural change within healthcare teams in Latin American contexts. AIMS: To evaluate the quality and applicability of TALK© debriefing training in Latin American settings and the willingness to debrief after an educational intervention. METHODS: Retrospective and descriptive study, examining anonymous data collected over 18 months after completing a "TALK© Debriefing Course for Healthcare Professionals" face-to-face or online. Data collected included participant characteristics, course details, quality and applicability of the intervention, and willingness to debrief. RESULTS: Five hundred and forty-five participants were enrolled, most from Argentina and Mexico. The overall quality of the intervention scored 19.62/20 points, obtaining 4.86/5 points for applicability. There were no significant differences between virtual and face-to-face sessions. After the intervention, ≥93.76% of participants felt able to engage in clinical debriefing, and 97.06% reported willingness to debrief. CONCLUSIONS: Dissemination of multi-professional clinical debriefing training in Latin America is feasible and easily scalable. The quality of the educational intervention was rated excellent in both virtual and face-to-face settings, supporting the value of remote educational diffusion. Most participants in this study intervention felt prepared and willing to debrief following the intervention.

8.
Biomimetics (Basel) ; 9(9)2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39329540

RESUMO

The aim of this systematic review was to determine whether autogenous tooth grafting material (ATGM) is as safe and effective as other bone substitutes used for maxillary sinus augmentation procedures, evaluating histomorphometric and/or histological data, implant primary stability, associated complications and radiographic bone height measurements. An automated electronic search was conducted using four databases (Medline/PubMed, Scopus, Web of Science and Cochrane Library), supplemented by a manual search, to identify clinical human studies using particulate ATGM for the aforementioned procedure. The included studies had a sample size of at least four patients and were published before 31st July 2024. The Newcastle-Ottawa scale (NOS) and Joanna Briggs Institute (JBI) Critical Appraisal Checklist were used to assess the risk of bias in cohort studies and case series, respectively. Seven studies were included in the descriptive analysis, obtaining 128 participants (46.8% only treated with ATGM) and 192 placed implants. Due to the heterogeneity of the studies, meta-analysis could not be performed. The authors concluded that ATGM appears to be a feasible and safe alternative for maxillary sinus augmentation procedures. These results should be interpreted with caution due to the limited amount of scientific evidence on this topic and the heterogeneity between the included studies.

9.
Rev Esp Enferm Dig ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324612

RESUMO

Before starting a drug that suppresses immunity, it is of paramount importance to screen for hidden infections in patients with inflammatory diseases. Latent tuberculosis infection (LTBI) is a condition characterized by an immune response to M. tuberculosis antigens without clinical manifestations. The highest risk of progression to active disease occurs in individuals who are immunosuppressed or in children. Patients who are candidates for treatment with TNF-alpha inhibitors should be evaluated with interferon gamma release assays and a chest radiograph. We present a case of a 42 year old woman with a history of Crohn disease treated with infliximab and fever with adenopatys.

10.
Updates Surg ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300041

RESUMO

Primary ventral hernia repair is a common global surgical procedure, entailing economic burdens and recurrence challenges. Rectus diastasis (RD) is considered a risk factor for midline defects and treatment is symptom-based. When primary ventral hernia and RD coexist, management still remains unclear. This study aims to analyze recurrence rates in patients after umbilical/epigastric hernia repair with untreated diastasis. Observational and retrospective cohort study of 74 patients assessing the recurrence rate of umbilical or epigastric hernias in patients operated with or without RD. Data were obtained from a tertiary hospital's patients between 2015 and 2017. Medium-term recurrences were analyzed after at least 3 year follow up. We compared demographic data, presence of RD (defined as rectus muscles separation exceeding 2 cm), type of repair and surgical complications. Data on 74 patients were collected. The mean age was 57.08 years, and the mean BMI was 31.27 kg/m2. Thirty-one included patients were females (42.9%). RD was documented in 67.1% of the sample. Mean follow-up was 4.23 (± 2.53) years. Postoperative complications were predominantly grade 1 according to the Clavien-Dindo classification, with a 17.14% surgical site infection rate. Female gender (p = 0.039), diabetes (0.016), and RD (0.049) showed statistically significant differences in predicting the risk of medium-term recurrence. Patients with untreated RD face a higher risk of medium-term recurrence following primary ventral hernia repair. Additionally, female gender and diabetes were found to be independent risk factors. Prospective studies are recommended to further assist surgeons in choosing the optimal surgical strategy for patients with umbilical hernia and associated RD.

12.
Front Aging Neurosci ; 16: 1437567, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246594

RESUMO

Introduction: Patients with coronary artery disease (CAD) have a higher risk of developing cognitive impairment and mental health disorders compared to the general population. Physical exercise might improve their brain health. The overall goal of the HEART-BRAIN randomized controlled trial (RCT) is to investigate the effects of different types of exercise on brain health outcomes in patients with CAD, and the underlying mechanisms. Methods: This three-arm, single-blinded RCT will include 90 patients with CAD (50-75 years). Participants will be randomized into: (1) control group-usual care (n = 30), (2) aerobic high-intensity interval training (HIIT) (n = 30), or (3) HIIT combined with resistance exercise training (n = 30). The 12-week intervention includes 3 supervised sessions (45-min each) per week for the exercise groups. Outcomes will be assessed at baseline and post-intervention. The primary outcome is to determine changes in cerebral blood flow assessed by magnetic resonance imaging. Secondary outcomes include changes in brain vascularization, cognitive measures (i.e., general cognition, executive function and episodic memory), and cardiorespiratory fitness. Additional health-related outcomes, and several potential mediators and moderators will be investigated (i.e., brain structure and function, cardiovascular and brain-based biomarkers, hemodynamics, physical function, body composition, mental health, and lifestyle behavior). Conclusion: The HEART-BRAIN RCT will provide novel insights on how exercise can impact brain health in patients with CAD and the potential mechanisms explaining the heart-brain connection, such as changes in cerebral blood flow. The results may have important clinical implications by increasing the evidence on the effectiveness of exercise-based strategies to delay cognitive decline in this high-risk population. Clinical trial registration: ClinicalTrials.gov, identifier [NCT06214624].

13.
Front Artif Intell ; 7: 1408029, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233890

RESUMO

Introduction: Hemorrhage remains a leading cause of death in civilian and military trauma. Hemorrhages also extend to military working dogs, who can experience injuries similar to those of the humans they work alongside. Unfortunately, current physiological monitoring is often inadequate for early detection of hemorrhage. Here, we evaluate if features extracted from the arterial waveform can allow for early hemorrhage prediction and improved intervention in canines. Methods: In this effort, we extracted more than 1,900 features from an arterial waveform in canine hemorrhage datasets prior to hemorrhage, during hemorrhage, and during a shock hold period. Different features were used as input to decision tree machine learning (ML) model architectures to track three model predictors-total blood loss volume, estimated percent blood loss, and area under the time versus hemorrhaged blood volume curve. Results: ML models were successfully developed for total and estimated percent blood loss, with the total blood loss having a higher correlation coefficient. The area predictors were unsuccessful at being directly predicted by decision tree ML models but could be calculated indirectly from the ML prediction models for blood loss. Overall, the area under the hemorrhage curve had the highest sensitivity for detecting hemorrhage at approximately 4 min after hemorrhage onset, compared to more than 45 min before detection based on mean arterial pressure. Conclusion: ML methods successfully tracked hemorrhage and provided earlier prediction in canines, potentially improving hemorrhage detection and objectifying triage for veterinary medicine. Further, its use can potentially be extended to human use with proper training datasets.

14.
Rev Sci Instrum ; 95(9)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39248619

RESUMO

We present the details of a novel ultra-short pulsed laser machining workstation that has been employed for high-throughput laser machining of small-scale mechanical property specimens. This system employs a six degrees of freedom hexapod positioning stage capable of macroscopic movements at high positional accuracy. We developed a methodology that uses quantitative image analysis to measure key parameters required to minimize the hexapod positioning and rotational error. Application of this system to laser machining of small-scale 316L stainless steel tensile specimens and ultra-high molecular weight polyethylene compressive specimens using eucentric tilt and rotation about the specimen axis will be shown, where serial laser milling at a specimen tilt angle of 10° was used to effectively eliminate any taper in the sample cross section that is typically found in laser machining.

15.
Clin Exp Allergy ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39348862

RESUMO

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a food allergy primarily affecting infants, often leading to vomiting and shock. Due to its poorly understood pathophysiology and lack of specific biomarkers, diagnosis is frequently delayed. Understanding FPIES genetics can shed light on disease susceptibility and pathophysiology-key to developing diagnostic, prognostic, preventive and therapeutic strategies. Using a well-characterised cohort of patients we explored the potential genome-wide susceptibility factors underlying FPIES. METHODS: Blood samples from 41 patients with oral food challenge-proven FPIES were collected for a comprehensive whole exome sequencing association study. RESULTS: Notable genetic variants, including rs872786 (RBM8A), rs2241880 (ATG16L1) and rs2289477 (ATG16L1), were identified as significant findings in FPIES. A weighted SKAT model identified six other associated genes including DGKZ and SIRPA. DGKZ induces TGF-ß signalling, crucial for epithelial barrier integrity and IgA production; RBM8A is associated with thrombocytopenia absent radius syndrome, frequently associated with cow's milk allergy; SIRPA is associated with increased neutrophils/monocytes in inflamed tissues as often observed in FPIES; ATG16L1 is associated with inflammatory bowel disease. Coexpression correlation analysis revealed a functional correlation between RBM8A and filaggrin gene (FLG) in stomach and intestine tissue, with filaggrin being a known key pathogenic and risk factor for IgE-mediated food allergy. A transcriptome-wide association study suggested genetic variability in patients impacted gene expression of RBM8A (stomach and pancreas) and ATG16L1 (transverse colon). CONCLUSIONS: This study represents the first case-control exome association study of FPIES patients and marks a crucial step towards unravelling genetic susceptibility factors underpinning the syndrome. Our findings highlight potential factors and pathways contributing to FPIES, including epithelial barrier dysfunction and immune dysregulation. While these results are novel, they are preliminary and need further validation in a second cohort of patients.

16.
Mult Scler Relat Disord ; 90: 105787, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39142050

RESUMO

BACKGROUND: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. METHODS: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. RESULTS: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. CONCLUSIONS: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.


Assuntos
Esclerose Múltipla Crônica Progressiva , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Crônica Progressiva/economia , Esclerose Múltipla Crônica Progressiva/psicologia , Adulto , Estudos Retrospectivos , Espanha
17.
Parkinsonism Relat Disord ; 126: 107072, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39094212

RESUMO

INTRODUCTION: Dysgraphia, a recognized PD motor symptom, lacks effective clinical assessment. Current evaluation relies on motor assessment scales. Computational methods introduced over the past decade offer an objective dysgraphia assessment, considering size, duration, speed, and handwriting fluency. Objective evaluation of dysgraphia may be of help for early diagnosis of PD. OBJECTIVE: Computerized assessment of dysgraphia in de novo PD patients and its correlation with clinical scales. METHODS: We evaluated 38 recently diagnosed, premedication PD patients and age-matched controls without neurological disorders. Participants wrote "La casa de Pamplona es bonita" three times on paper and once on a Wacom tablet under the paper, totaling four phrases. Writing segments of 5-10 s were analyzed. The Wacom tablet captured kinematic data, including mean velocity, mean acceleration, and pen pressure. Data were saved in.svc format and analyzed using specialized software developed by Tecnocampus Mataró. Standard clinical practice data, Hoehn & Yahr staging, and UPDRS scales were used for evaluation. RESULTS: Significant kinematic differences existed; patients had lower mean speed (27 ± 12 vs. 48 ± 18, p < 0.0001) and mean acceleration (7.2 ± 3.9 vs. 15.01 ± 7, p < 0.0001) than controls. Mean speed and mean acceleration correlated significantly with UPDRS III scores (speed: r = -0.52, p < 0.0007; acceleration: r = 0.60, p < 0.0001), indicating kinematic parameters' potential in PD evaluation. CONCLUSIONS: Dysgraphia is identifiable in PD patients, even de novo, indicating an early symptom and correlates with clinical scales, offering potential for objective PD patient evaluation.


Assuntos
Agrafia , Escrita Manual , Doença de Parkinson , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Agrafia/etiologia , Agrafia/fisiopatologia , Agrafia/diagnóstico , Fenômenos Biomecânicos/fisiologia , Diagnóstico por Computador/métodos
18.
STAR Protoc ; 5(3): 103255, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39146190

RESUMO

Many types of neurons exhibit a daily rhythm of intrinsic excitability. Here, we present a protocol for assessing circadian regulation of dentate granule cell excitability using a mouse model for conditional knockout of the molecular clock protein BMAL1. We describe steps for obtaining healthy oblique horizontal slices that contain the hippocampus and measuring intrinsic excitability and synaptic potentials by combining whole-cell patch-clamp recordings and perforant-path electric stimulation. We then detail procedures for validating single-cell genetic deletion of Bmal1 by immunohistochemistry. For complete details on the use and execution of this protocol, please refer to Gonzalez et al.1.


Assuntos
Ritmo Circadiano , Giro Denteado , Animais , Camundongos , Giro Denteado/citologia , Giro Denteado/metabolismo , Giro Denteado/fisiologia , Ritmo Circadiano/fisiologia , Técnicas de Patch-Clamp/métodos , Neurônios/metabolismo , Neurônios/fisiologia , Neurônios/citologia , Fatores de Transcrição ARNTL/metabolismo , Fatores de Transcrição ARNTL/genética , Camundongos Knockout , Masculino
19.
Neuropediatrics ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39102865

RESUMO

BACKGROUND: Due to the limited data from clinical trials and real-world settings in the realm of nusinersen, there is a need for further evidence. This study seeks to assess the impact of nusinersen, when combined with standard care, on bulbar function, respiratory function, and the necessity for respiratory support among pediatric patients with spinal muscular atrophy (SMA). METHODS: Prospective observational study, involving pediatric SMA patients (Types 1-3) undergoing nusinersen treatment at the Hospital Universitario Virgen del Rocío in Spain over at least 24 months. The cohort included 11 SMA type 1 patients, comprising 6 type 1b and 5 type 1c, 12 SMA type 2 patients, and 5 SMA type 3 patients. RESULTS: Twenty-eight pediatric patients were enrolled with the majority being male (n = 20). Patients with type 1 were diagnosed and received treatment significantly earlier than those with types 2 and 3 (p < 0.001). Additionally, there was a longer period between diagnosis and the start of treatment in types 2 and 3 (p = 0.002). Follow-up revealed statistically improved functional and respiratory outcomes associated with earlier initiation of nusinersen treatment at 6, 12, and 24 months in all phenotypes. The ability to swallow and feed correctly remained unchanged throughout the study, with SMA type 1c patients maintaining oral feeding in contrast to patients with SMA type 1b. Notably, no deaths were recorded. CONCLUSIONS: This study provides important insights into the real-world clinical progress of pediatric SMA patients and their response to nusinersen treatment, highlighting the significance of early intervention for better functional and respiratory outcomes.

20.
Ophthalmol Ther ; 13(10): 2715-2730, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39150603

RESUMO

INTRODUCTION: To evaluate the long-term effects of intense pulsed light (IPL) therapy on patients with dry eye disease (DED) associated with meibomian gland dysfunction (MGD). METHODS: A retrospective case series was performed with 110 participants undergoing IPL therapy. Assessments included the eye fitness test (EFT) to gauge subjective symptoms, along with objective measures using the Tearcheck® device (ESW Vision, Houdan, France) noninvasive first breakup time (NIFBUT), noninvasive average breakup time (NIABUT), central tear meniscus height (CTMH), thinnest tear meniscus height (TTMH), and ocular surface inflammatory risk evaluation (OSIE) assessed using the SCHWIND SIRIUS device (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany). RESULTS: This study documented significant improvements in subjective and objective symptoms associated with DED and MGD. Subjective symptoms measured by the EFT showed an average increase of 9.74 points (range -10 to 28, standard deviation [SD] ± 7.54), indicating reduced symptoms. Objective measures of tear film stability, represented by NIABUT, increased by an average of 4.04 s (range -15.00 to 14.40, SD ± 4.91). Tear film stability evaluation (TFSE) scores decreased by 229.12 points on average (range -1775 to 528, SD ± 384.94), suggesting enhanced tear film stability. OSIE type 1 showed a reduction in inflammation, with a percentage decrease of 4.98% (range -45 to 5, SD ± 7.33). Additionally, OSIE capture time decreased by 3.25 s on average (range -27 to 22, SD ± 10.35), further indicating an improvement in ocular surface health. CONCLUSION: IPL therapy was shown to be a promising, noninvasive approach for improving quality of life in patients with DED by effectively managing symptoms and stabilizing tear film. The findings support the use of IPL as a sustainable treatment modality for DED associated with MGD.

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