AML typical mutations (CEBPA, FLT3, and NPM1) identify a high-risk CMML independent of CPSS-Mol classification.

Mutations commonly associated with acute myeloid leukemia (AML), such as CEBPA, FLT3, IDH1/2 and NPM1 are rarely found in chronic myelomonocytic leukemia (CMML) and their prognostic significance in CMML has not been clearly identified. In 127 CMML patients, we have retrospectively analyzed next-generation sequencing and PCR data from analyses of bone marrow samples performed at diagnosis of CMML. Seven patients harbored CEBPA mutations, eight FLT3 mutations, 12 IDH1 mutations, 26 IDH2 mutations and 11 NPM1 mutations. CMML patients harboring CEBPA, FLT3, and/or NPM1 mutations (mutCFN)were more frequently associated with the myeloproliferative subtype (MP-CMML) , a high prevalence of severe cytopenia, and elevated blast counts. Regardless of their CPSS-Mol classification, mutCFN CMML patients had a poor prognosis, and the multivariate analysis identified mutCFN as an independent marker of overall survival. The genetic profile of these mutCFN CMML patients closely resembled that of AML, with higher-risk clinical characteristics. Our findings lead us to suggest including the assessment of these mutations in CMML prognostic models and treating these patients with AML-type therapies, including intensive chemotherapy and allogeneic stem cell transplantation, whenever feasible, and consider certain targeted therapies approved for use in AML.

Tick control prevents carcass condemnations in lambs caused by Anaplasma ovis.

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.

Effectiveness of conservative treatment of dentigerous cyst in the pediatric patient: a systematic review.

The dentigerous cyst is defined as a pathological cavity whose origin is produced by developmental alterations. Most usual treatment is the enucleation of the cyst with the extraction of the tooth. The current approach tends to preserve the tooth. The aim of this study was to determine the total and partial success of the conservative treatment of the dentigerous cyst in terms of eruption of the associated permanent tooth. Pub-Med, Scopus and the Cochrane Central Register of Controlled Trials were searched from January 2012 to December 2023, including patients aged 18 years old or less with a dentigerous cyst associated with a repositionable permanent tooth in the arch. 118 articles were found and 24 were included in full text. 40 cases were reported in the mandible (83%) and 8 in the maxilla (17%). 29 cases of marsupialization were included (60%), 17 of enucleation (36%) and 2 of decompression (4%). The percentage of teeth that erupted spontaneously, either completely or partially, after marsupialization, enucleation and decompression was 83%, 59% and 100% respectively. No recurrences have been described in any case. This study highlights that the conservative treatment was a predictable procedure with a total success of 83% by marsupialization and 100% after decompression.

Influence of coffee roasting degree on antioxidant and metabolic parameters: Comprehensive in vitro and in vivo analysis.

This study aimed to assess the impact of roasting degree on antioxidant and metabolic parameters in vitro and in vivo. In vitro, we evaluated radical scavenging, lipid peroxidation, and the activity of digestive enzymes (α-glucosidase, α-amylase, and lipase). In vivo, we first examined coffee's effect on carbohydrate and lipid absorption in healthy rats, followed by a chronic evaluation of metabolic disorders and antioxidant markers using a diet-induced obesity model. In vitro results revealed that increased roasting degree reduced the antioxidant capacity of coffee brews. All brews showed lower inhibition of α-glucosidase and α-amylase, and lipase inhibition compared to the positive control (acarbose or orlistat). In vivo, all roasting degrees consistently reduced postprandial glucose levels by 20%. Notably, coffee with a high roasting degree (HRD) decreased serum triglycerides (TG) by ∼44% after a lipid load, while other roasts did not. Chronic administration of unroasted (UN) or HRD coffee significantly reduced weight gain compared to the obese control (∼15% and ∼10%, respectively). Notably, all coffee samples improved lipid metabolism parameters. UN and HRD coffee significantly decreased adipocyte volume by 58% and 48%, respectively, compared to the obese control. Additionally, all groups exhibited less than 30% hepatic lipid droplets independent of roasting degree. HRD treatment notably increased liver catalase (CAT) activity and reduced lipid peroxidation in serum (∼90%), liver (∼59%), and adipose tissue (∼37%) compared to the obese control group. These findings suggest that HRD in coffee may confer certain biological advantages.

Current Overview of Spinocerebellar Ataxia Type 7 in Mexican Population: Challenges in Specialized Care for a Rare Disease.

Spinocerebellar ataxia type 7 (SCA7) is a rare genetic disease characterized by progressive cerebellar syndrome and macular degeneration. In a previous study, we clinically and genetically characterized a group of Mexican patients, which represented one of the largest cohorts of SCA7 patients worldwide and demonstrated that all patients had a unique genetic origin. Our laboratory developed a program for the diagnosis, medical care, and long-term follow-up of these patients living in Veracruz State, and in this report, we present an update to this research, covering 2013 to 2024. So far, we identified 172 SCA7 carriers, with a few cases outside Veracruz, and our data support that the length of the CAG repeat tract mainly determines disease severity and life expectancy, and accordingly, we define three different phenotypes, early-onset (EO), classical-onset (CO), and late-onset (LO), with EO patients showing the lowest life expectancy. Furthermore, we found that parental transmission of mutant alleles leads to increased CAG repeat instability, compared to maternal ones. Interestingly, a haplotype analysis revealed that patients outside Veracruz may have different genetic origins. In conclusion, longitudinal observations of SCA7 patients provide insight into the natural history of SCA7 and help to design strategies for diagnosis, genetic counseling, physical rehabilitation, and therapeutic alternatives.

Enhancing Lessons on the Internet of Things in Science, Technology, Engineering, and Medical Education with a Remote Lab.

Integrating remote Internet of Things (IoT) laboratories into project-based learning (PBL) in higher education institutions (HEIs) while exploiting the approach of technology-enhanced learning (TEL) is a challenging yet pivotal endeavor. Our proposed approach enables students to interact with an IoT-equipped lab locally and remotely, thereby bridging theoretical knowledge with practical application, creating a more immersive, adaptable, and effective learning experience. This study underscores the significance of combining hardware, software, and coding skills in PBL, emphasizing how IoTRemoteLab (the remote lab we developed) supports a customized educational experience that promotes innovation and safety. Moreover, we explore the potential of IoTRemoteLab as a TEL, facilitating and supporting the understanding and definition of the requirements of remote learning. Furthermore, we demonstrate how we incorporate generative artificial intelligence into IoTRemoteLab's settings, enabling personalized recommendations for students leveraging the lab locally or remotely. Our approach serves as a model for educators and researchers aiming to equip students with essential skills for the digital age while addressing broader issues related to access, engagement, and sustainability in HEIs. The practical findings following an in-class experiment reinforce the value of IoTRemoteLab and its features in preparing students for future technological demands and fostering a more inclusive, safe, and effective educational environment.

Randomized Controlled Trial to Assess the Feasibility of a Novel Clinical Decision Support System Based on the Automatic Generation of Alerts through Remote Patient Monitoring.

Background/Objectives: Early identification of complications in chronic and infectious diseases can reduce clinical deterioration, lead to early therapeutic interventions and lower morbidity and mortality rates. Here, we aimed to assess the feasibility of a novel clinical decision support system (CDSS) based on the automatic generation of alerts through remote patient monitoring and to identify the patient profile associated with the likelihood of severe medical alerts. Methods: A prospective, multicenter, open-label, randomized controlled trial was conducted. Patients with COVID-19 in home isolation were randomly assigned in a 1:1 ratio to receive either conventional primary care telephone follow-up plus access to a mobile app for self-reporting of symptoms (control group) or conventional primary care telephone follow-up plus access to the mobile app for self-reporting of symptoms and wearable devices for real-time telemonitoring of vital signs (case group). Results: A total of 342 patients were randomized, of whom 247 were included in the per-protocol analysis (103 cases and 144 controls). The case group received a more exhaustive follow-up, with a higher number of alerts (61,827 vs. 1825; p < 0.05) but without overloading healthcare professionals thanks to automatic alert management through artificial intelligence. Baseline factors independently associated with the likelihood of a severe alert were having asthma (OR: 1.74, 95% CI: 1.22-2.48, p = 0.002) and taking corticosteroids (OR: 2.28, 95% CI: 1.24-4.2, p = 0.008). Conclusions: The CDSS could be successfully implemented and enabled real-time telemonitoring of patients' clinical status, providing valuable information to physicians and public health agencies.

Evaluation of TALK© training for interprofessional clinical debriefing in Latin America.

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.

Whole Exome Sequencing Identifies Epithelial and Immune Dysfunction-Related Biomarkers in Food Protein-Induced Enterocolitis Syndrome.

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.

Maxillary Sinus Augmentation with Autogenous Tooth Grafting Material: A Systematic Review.

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.

Liver Cirrhosis: The Immunocompromised State.

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.

Clove essential oil and its major component, eugenol: a comparative study of their in vitro antioxidant and anticancer properties.

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.

Gray matter based spatial statistics framework in the 1-month brain: insights into gray matter microstructure in infancy.

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.

Is it necessary to repeat the interferon gamma? Disseminated tuberculosis in a patient receiving anti-TNF alpha treatment.

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.

Effect of alemtuzumab over sNfL and sGFAP levels in multiple sclerosis.

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.

Exercise and brain health in patients with coronary artery disease: study protocol for the HEART-BRAIN randomized controlled trial.

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].

Long-term outcomes of primary ventral hernia repair associated with rectus diastasis.

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.

Bioaerosols downwind from animal feeding operations: A comprehensive review.

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.