Sonoanatomy of the Finger Synovio-Entheseal Complexes.

OBJECTIVES: The objectives of this ultrasound and anatomical study were: (1) To evaluate the reliability of ultrasound identification of the enthesis of the central slip of the extensor digitorum tendon (CSET) using cadaver specimens; (2) To assess the concordance of the measurement of the CSET thickness by ultrasound and gross anatomy; (3) To evaluate the variation in ultrasound identification of the CSET enthesis in a cadaveric experimental model of PIP synovitis. METHODS: Four rheumatologist ultrasonographers blindly and independently measured by ultrasound the CSET enthesis thickness in the second to fifth fingers of 8 hands from fresh-frozen human cadavers in two rounds. These fingers were dissected and the thickness of the CSET measured by the anatomist. In addition, an artificial synovitis was created in the proximal interphalangeal (PIP) joints of a different cadaveric hand. The ultrasonographic CSET enthesis thickness was measured by the four investigators before and after intra-articular ultrasound guided injection of material. RESULTS: Intra- and inter-observer reliability of CSET enthesis thickness measurement were good to excellent (ICC 0.93 for intra-observer agreement and 0.89-0.92 for inter-observer agreement). Ultrasound measurements were consistent and only slightly smaller than the anatomical ones (µ = -0.039 mm). The differences between the measurements of CSET enthesis thickness before and after the synovitis model were not statistically significant. CONCLUSION: Ultrasound demonstrated high multiobserver reliability and agreement with gross anatomy in identifying the CSET enthesis and discriminated it from the capsular tissue of the PIP. Furthermore, an experimental model of PIP synovitis did not interfere with its identification.

Novel Approach to Residents Training in Breast Surgery Using Human Donors.

INTRODUCTION: Given the high incidence rate of breast cancer and shortage of fellowship trained specialists, general surgeons are frequently responsible for these patients. Residents have less operative exposure to breast surgery due to duty hour restrictions and decreased resident autonomy. We created a curriculum using human donors designed to teach junior residents to perform breast lumpectomy and sentinel lymph node biopsies. METHODS: All eighteen junior surgery residents were invited. We chose fresh human donors to represent tissue planes more accurately. We inserted Savi Scout reflectors (Merit Oncology, Inc) in each breast for tumor localization. An olive pit plus 1 mL of methylene blue was inserted in the axilla for SLN identification. In session 1, attendings discussed proper technique and residents performed the procedures and received feedback. In session 2 after 2 mo, residents performed the same operation without any guidance. They were graded on technique during both sessions and filled out a postsession survey to gauge confidence. RESULTS: Seven PGY1 and six PGY2 residents participated. Half of the respondents strongly felt this session improved their understanding of lumpectomies, sentinel lymph node biopsies, and axillary anatomy. Most felt strongly that their skills improved and these skills were transferable to the operating room. In attending evaluations, PGY1 residents significantly improved in all aspects of the procedures; PGY2 residents showed nonstatistical significant improvement. CONCLUSIONS: Residents find these sessions helpful in learning anatomy, improving confidence and efficiency, and facilitating skill acquisition that is transferable to the operating room. We believe this approach should be considered in general surgery training programs.

COVID-19 vaccines are not associated with axonal injury in patients with multiple sclerosis.

Objective: To evaluate the safety of COVID-19 vaccines in patients with multiple sclerosis (MS) by assessing their impact on serum neurofilament light chain (sNfL) levels as a marker of neuroaxonal damage. Methods: Single-center observational longitudinal study including patients with MS who consecutively received their initial vaccination against SARS-CoV-2 at Hospital Universitario Ramón y Cajal, following the first national immunization program in Spain. Serum samples were collected at baseline and after receiving the second dose of the vaccine. sNfL levels were quantified using the single molecule array (SIMOA) technique. Adverse events, including clinical or radiological reactivation of the disease, were recorded. Results: Fifty-two patients were included (median age, 39.7 years [range, 22.5-63.3]; 71.2% female). After SARS-CoV-2 vaccination, no increased inflammatory activity, either determined by the presence of relapses and/or new MRI lesions and/or high sNfL levels, was detected. Accordingly, there was no difference between median sNfL levels before and after vaccination (5.39 vs. 5.76 pg/ml, p=0.6). Despite this, when looking at baseline patient characteristics before vaccination, younger age associated with disease activity after vaccination (OR 0.87, 95% CI: 0.77-0.98, p=0.022). Larger studies are needed to validate these results. Conclusion: COVID-19 vaccines did not cause reactivation of disease at a clinical, radiological or molecular level, thus suggesting that they are safe in MS patients.

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.

Development of the Interosseous Muscles of the Human Hand: Morphological and Functional Aspects of the Terminal Insertion.

INTRODUCTION: To date, there have been no studies conducted on the development of interosseous muscles (IO) in the human hand. This study aimed to investigate the development of these muscles in order to clarify their terminal insertions and their relationship with the metacarpophalangeal joints. METHODS: Serial sections of 25 human specimens (9 embryos and 16 fetuses) between the 7th and 14th weeks of development, sourced from the Collection of the Department of Anatomy and Embryology at UCM Faculty of Medicine, were analyzed bilaterally using a conventional optical microscope. RESULTS: Our findings revealed that, during the 7th week of development, the metacarpophalangeal interzone mesenchyme extended into the extensor apparatus of the fingers. Furthermore, we observed that the joint capsule and the tendon of the IO derive from the articular interzone mesenchyme. By the end of the 7th week, corresponding to Carnegie stage 21, the myotendinous junction appeared, initiating cavitation of the metacarpophalangeal joint. During the fetal period, the terminal insertions of the IO were identified: both the dorsal interosseous (DI) and palmar interosseous (PI) muscles insert into the metacarpophalangeal joint capsule and establish a connection with the volar plate located at the base of the proximal phalanx and the extensor apparatus. Some muscle fibers also attach to the joint capsule at the level of the proximal synovial cul-de-sac. The functional implications of these findings are discussed within this work. CONCLUSION: This study provides the first detailed description of the development of the interosseous muscles in the human hand.

Colchicine in acutely decompensated heart failure: the COLICA trial.

BACKGROUND AND AIMS: Acute heart failure (AHF) promotes inflammatory activation, which is associated with worse outcomes. Colchicine has proven effective in other cardiovascular conditions characterized by inflammatory activation, but has never been evaluated in the setting of AHF. METHODS: This multicenter, randomized, double-blind and placebo-controlled trial included patients with AHF, requiring ≥40 mg of intravenous furosemide, regardless of their left ventricular ejection fraction (LVEF) and inpatient or outpatient setting. Patients were randomized within the first 24 hours of presentation to receive either colchicine or placebo, with loading dose of 2 mg followed by 0.5 mg every 12 hours for 8 weeks. RESULTS: A total of 278 patients (median age 75 years, LVEF 40%, baseline N-terminal pro-B-type natriuretic peptide [NT-proBNP] 4390 pg/mL) were randomized to colchicine (n=141) or placebo (n=137). The primary endpoint, the time-averaged reduction in NT-proBNP levels at 8 weeks, did not differ between the colchicine group (-62.2%, 95% confidence interval [CI] -68.9% to -54.2%) and the placebo group (-62.1%, 95% CI -68.6% to -54.3%) (ratio of change 1.0). The reduction in inflammatory markers was significantly greater with colchicine: ratio of change 0.60 (p<0.001) for C-reactive protein and 0.72 (p=0.019) for interleukin-6. No differences were found in new worsening heart failure episodes (14.9% with colchicine vs. 16.8% with placebo, p=0.698); however, the need for intravenous furosemide during follow-up was lower with colchicine (p=0.043). Diarrhea was slightly more common with colchicine, but it did not result in differences in medication withdrawal (8.5% vs. 8.8%). CONCLUSIONS: Colchicine was safe and effective in reducing inflammation in patients with AHF, however colchicine and placebo exhibited comparable effects on reducing NT-proBNP and preventing new worsening heart failure events.

Combination of Machine Learning Techniques to Predict Overweight/Obesity in Adults.

(1) Background: Artificial intelligence using machine learning techniques may help us to predict and prevent obesity. The aim was to design an interpretable prediction algorithm for overweight/obesity risk based on a combination of different machine learning techniques. (2) Methods: 38 variables related to sociodemographic, lifestyle, and health aspects from 1179 residents in Madrid were collected and used to train predictive models. Accuracy, precision, and recall metrics were tested and compared between nine classical machine learning techniques and the predictive model based on a combination of those classical machine learning techniques. Statistical validation was performed. The shapely additive explanation technique was used to identify the variables with the greatest impact on weight gain. (3) Results: Cascade classifier model combining gradient boosting, random forest, and logistic regression models showed the best predictive results for overweight/obesity compared to all machine learning techniques tested, reaching an accuracy of 79%, precision of 84%, and recall of 89% for predictions for weight gain. Age, sex, academic level, profession, smoking habits, wine consumption, and Mediterranean diet adherence had the highest impact on predicting obesity. (4) Conclusions: A combination of machine learning techniques showed a significant improvement in accuracy to predict risk of overweight/obesity than machine learning techniques separately.

Benefits of Incorporating Lignin into Starch-Based Films: A Brief Review.

Polysaccharides are an excellent renewable source for developing food-packing materials. It is expected that these packages can be an efficient barrier against oxygen; can reduce lipid peroxidation, and can retain the natural aroma of a food commodity. Starch has tremendous potential to be explored in the preparation of food packaging; however, due to their high hydrophilic nature, packaging films produced from starch possess poor protective moisture barriers and low mechanical properties. This scenario limits their applications, especially in humid conditions. In contrast, lignin's highly complex aromatic hetero-polymer network of phenylpropane units is known to play a filler role in polysaccharide films. Moreover, lignin can limit the biodegradability of polysaccharides films by a physical barrier, mainly, and by non-productive bindings. The main interactions affecting lignin non-productive bindings are hydrophobic interactions, electrostatic interactions, and hydrogen-bonding interactions, which are dependent on the total phenolic -OH and -COOH content in its chemical structure. In this review, the use of lignin as a reinforcement to improve the biodegradability of starch-based films in wet environments is presented. Moreover, the characteristics of the used lignins, the mechanisms of molecular interaction among these materials, and the sensitive physicochemical parameters for biodegradability detection are related.

Serum biomarkers at disease onset for personalized therapy in multiple sclerosis.

The potential of combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict disability worsening in multiple sclerosis (MS) remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across thirteen European hospitals, spanned from July 15, 1994, to August 18, 2022, with follow-up until September 26, 2023. We enrolled MS patients who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, median age was 34.2 years (IQR, 27.6-42.4), and 509 patients (70.2%) were female. Median follow-up duration was 6.43 years (IQR, 4.65-9.81). Higher sNfL values associated with an elevated risk of RAW (HR of 1.45; 95% CI 1.19-1.76; P < 0.001), PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003), and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We further examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values (NLGL) exhibited a low risk of all outcomes and served as reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA, and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values (NLGH) showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in MS may identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response.

The axiological foundations of innovation in STEM education - A systematic review and ethical meta-analysis.

Introduction: Values are crucial in decision-making, including processes related to science and technology, despite scientists often being unaware of them. Because a goal of science, technology, engineering, and mathematics (STEM) is to foster innovation, values have become fundamental in directing science and technology policies and shaping organizational cultures to leverage innovation. However, most research on STEM education has focused on improving performance or access to STEM education while overlooking its axiological configuration. This study analyzes the different value systems emerging in the current literature on STEM higher education and identifies the relevant stakeholders. Method: In this systematic review and ethical meta-analysis, we aimed to assess the most prominent studies on STEM education and its core values. We followed a Ricoeur-inspired hermeneutical methodology using Atlas ti 8.4.4. Values are identified and classified using a systematic approach to integrate axiological landscapes. Results: The literature does not explicitly discuss the value of STEM education for innovation. However, social values appear to be at the intersection and the cornerstone of basic, economic, aesthetic, and epistemic values, as most social values also manifest these four systems. The most common manifestation of the value system is the capability approach to justice, followed by the beauty of recognition and success and, in third place, racism and social disparities. The analyzed literature emphasizes STEM education's social, political, and economic determinants. However, there is an epistemic gap in the indispensable value of innovating and assessing STEM education. Conclusions: We propose an organizational culture model for STEM education that considers the goals, ends, values, and behaviors of students, teachers, educational institutions, and the government. This model can help fill the axiological gaps in STEM education.

Establishing Normal Serum Values of Neurofilament Light Chains and Glial Fibrillary Acidic Protein Considering the Effects of Age and Other Demographic Factors in Healthy Adults.

Multiple studies have shown the importance of blood-based biomarkers indicating axonal damage (serum neurofilament light chains [sNfL]) or astroglia activation (serum glial fibrillary acidic protein [sGFAP]) for monitoring different neurological diseases. However, normal values of these variables remain to be clearly defined, partly due to the influence of different demographic factors. We investigated demographic differences in a cohort of healthy volunteers. A cross-sectional study was conducted including 116 healthy controls with ages between 18 and 69 years (67.5% females; n = 79). sNfL and sGFAP concentrations were measured using single-molecule arrays. Age and body mass index affected sNfL values, and age was found to be the most important factor. The normal values changed with age, and we established normal values for individuals younger than 45 years as <10 pg/mL and for controls older than 45 years as <15 pg/mL. We established normal values at <10 pg/mL for individuals younger than 45 years and <15 pg/mL for older individuals. Alternatively, a Z-score of 1.5 was relevant for all controls. sGFAP was only affected by age. Differences in normal values were evident by 55 years. The highest normality limit for sGFAP was 140 pg/mL for controls under 55 years and 280 for older controls. We defined normal levels for sNfL and sGFAP and their corresponding age-associated changes. These data may contribute to the application of such variables in clinical practice.

Enhancing Intraoperative Cholangiography Interpretation Skills: A Perceptual Learning Approach for Surgical Residents.

OBJECTIVE: Laparoscopic cholecystectomy is a commonly performed surgery with risk of serious complications. Intraoperative cholangiography (IOC) can mitigate these risks by clarifying the anatomy of the biliary tree and detecting common bile duct injuries. However, mastering IOC interpretation is largely through experience, and studies have shown that even expert surgeons often struggle with this skill. Since no formal curriculum exists for surgical residents to learn IOC interpretation, we developed a perceptual learning (PL)-based training module aimed at improving surgical residents' IOC interpretation skills. DESIGN: Surgical residents were assessed on their ability to identify IOC characteristics and provide clinical recommendations using an online training module based on PL principles. This research had 2 phases. The first phase involved pre/post assessments of residents trained via the online IOC interpretation module, measuring their IOC image recognition and clinical management accuracy (percentage of correct responses), response time and confidence. During the second phase, we explored the impact of combining simulator-based IOC training with the online interpretation module on same measures as used in the first phase (accuracy, response time, and confidence). SETTING: The study was conducted at Rush University Medical College in Chicago. The participants consisted of surgical residents from each postgraduate year (PGY). Residents participated in this study during their scheduled monthly rotation through Rush's surgical simulation center. RESULTS: Total 23 surgical residents participated in the first phase. A majority (95.7%) found the module helpful. Residents significantly increased confidence levels in various aspects of IOC interpretation, such as identifying complete IOCs and detecting abnormal findings. Their accuracy in making clinical management decisions significantly improved from pretraining (mean accuracy 68.1 +/- 17.3%) to post-training (mean accuracy 82.3 +/- 10.4%, p < 0.001). Furthermore, their response time per question decreased significantly from 25 +/- 12 seconds to 17 +/- 12 seconds (p < 0.001). In the second phase, we combined procedural simulator training with the online interpretation module. The 20, first year residents participated and 88% found the training helpful. The training group exhibited significant confidence improvements compared to the control group in various aspects of IOC interpretation with observed nonsignificant accuracy improvements related to clinical management questions. Both groups demonstrated reduced response times, with the training group showing a more substantial, though nonsignificant, reduction. CONCLUSION: This study demonstrated the effectiveness of a PL-based training module for improving aspects of surgical residents' IOC interpretation skills. The module, found helpful by a majority of participants, led to significant enhancements in clinical management accuracy, confidence levels, and decreased response time. Incorporating simulator-based training further reinforced these improvements, highlighting the potential of our approach to address the lack of formal curriculum for IOC interpretation in surgical education.

Anconeus and pronation: a palpatory and ultrasonographic study.

PURPOSE: Depending on its axis, pronation varies from the radius rotation around the steady ulna to the reciprocal adduction of the radius and abduction of the ulna. While there is no question that pronator teres is a central pronation agonist, anconeus's role is not settled. The current investigation comparing palpation and ultrasonography in these two muscles during pronation along the axis capitulum-second digit evolved from a serendipitous finding in a clinical anatomy seminar. METHODS: Single-hand palpation and two-transducer ultrasonography over anconeus and pronator teres were used on ten normal subjects to investigate their contraction during pronation around the capitulum-second digit axis. These studies were done independently and blind to the results of the other. The statistical analysis between palpation and ultrasonography was performed with Cohen's kappa coefficient and the χ2 test. RESULTS: On palpation, on resisted full pronation, anconeus contracted in 8/10 subjects and pronator teres in 10/10 subjects. Without resistance, the corresponding ratios were 5/10 and 9/10. On two-transducer ultrasonography, the comparable ratios were 7/10 and 10/10, and 3/10 and 10/10. A fair concordance (Cohen's kappa = 0.21) between palpation and ultrasonography in detecting the simultaneous status of anconeus and pronator teres during resisted full pronation. Anatomic dissection illustrated the elements involved. CONCLUSIONS: Plain palpation confirmed by ultrasonography showed the simultaneous contraction of anconeus and pronator teres during resisted pronation in most of the studied subjects. The study suggests that palpation can be helpful in directly studying muscle activity during movement.

Diagnostic performance of sixteen biomarkers for MASLD: A study in a Mexican cohort.

BACKGROUND AND AIMS: Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) poses a heightened cardiovascular risk. Identifying efficient biomarkers for early MASLD detection in resource-limited Latin American regions is crucial. We aimed to evaluate the diagnostic efficacy of sixteen biomarkers for MASLD in Mexican individuals. METHODS: In this cross-sectional and analytical study, steatosis was assessed using vibration-controlled transient elastography. MASLD was defined according to international standards. Assessed biomarkers included: Visceral Fat (VF), Waist Circumference (WC), Waist-Height Ratio (WHtr), Waist-Hip Ratio (WHr), Visceral Adiposity Index (VAI), Hepatic Steatosis Index (HSI), Body Mass Index (BMI), Homeostatic Model Assessment (HOMA), Weight-Adjusted-Waist Index (WWI), Lipid Accumulation Product (LAP), Uric Acid-Creatinine Ratio (UACR), Triglyceride-Glucose Index (TyG) and its variants TyG-WC, TyG-HDL, TyG-BMI, TyG-WHtr. RESULTS: 161 participants were included, of which 122 met MASLD criteria (56 % women, age 53.9 years [47.5-64]) and 39 were healthy controls (76 % women, age 52 [45-64]). The AUROCs of the biomarkers for MASLD were: TyG-WC (0.84), LAP (0.84), TyG-BMI (0.82), TyG-WHtr (0.80), WC (0.78), TyG (0.77), WHtr (0.75), BMI (0.76), VF (0.75), HSI (0.75), TyG-HDL (0.75), WHr (0.72), VAI (0.73), UA/CR (0.70), HOMA (0.71), and WWI (0.69). Sex-based differences were observed. After adjusting for sociodemographic variables, the TyG-WC index was the best predictor of MASLD. CONCLUSIONS: In conclusion, our results underscore the potential of several noninvasive biomarkers for MASLD assessment in a Mexican population, highlighting variations in diagnostic efficacy and cut-off values between sexes. After adjusting, TyG-WC was the best MASLD predictor.

Explainable hypoglycemia prediction models through dynamic structured grammatical evolution.

Effective blood glucose management is crucial for people with diabetes to avoid acute complications. Predicting extreme values accurately and in a timely manner is of vital importance to them. People with diabetes are particularly concerned about suffering a hypoglycemia (low value) event and, moreover, that the event will be prolonged in time. It is crucial to predict hyperglycemia (high value) and hypoglycemia events that may cause health damages in the short term and potential permanent damages in the long term. This paper describes our research on predicting hypoglycemia events at 30, 60, 90, and 120 minutes using machine learning methods. We propose using structured Grammatical Evolution and dynamic structured Grammatical Evolution to produce interpretable mathematical expressions that predict a hypoglycemia event. Our proposal generates white-box models induced by a grammar based on if-then-else conditions using blood glucose, heart rate, number of steps, and burned calories as the inputs for the machine learning technique. We apply these techniques to create three types of models: individualized, cluster, and population-based. They all are then compared with the predictions of eleven machine learning techniques. We apply these techniques to a dataset of 24 real patients of the Hospital Universitario Principe de Asturias, Madrid, Spain. The resulting models, presented as if-then-else statements that incorporate numeric, relational, and logical operations between variables and constants, are inherently interpretable. The True Positive Rate and True Negative Rate metrics are above 0.90 for 30-minute predictions, 0.80 for 60 min, and 0.70 for 90 min and 120 min for the three types of models. Individualized models exhibit the best metrics, while cluster and population-based models perform similarly. Structured and dynamic structured grammatical evolution techniques perform similarly for all forecasting horizons. Regarding the comparison of different machine learning techniques, on the shorter forecasting horizons, our proposals have a high probability of winning, a probability that diminishes on the longer time horizons. Structured grammatical evolution provides advanced forecasting models that facilitate model explanation, modification, and retesting, offering flexibility for refining solutions post-creation and a deeper understanding of blood glucose behavior. These models have been integrated into the glUCModel application, designed to serve people with diabetes.

A two-years real-word study with fingolimod: early predictors of efficacy and an association between EBNA-1 IgG titers and multiple sclerosis progression.

Background: Although fingolimod, a sphingosine 1-phosphate receptor agonist, has shown to be an effective treatment reducing relapse rate and also slowing down the disability progression in relapsing-remitting multiple sclerosis (RRMS) patients, it is important to quickly identify those suboptimal responders. Objective: The main objective was to assess different clinical, radiological, genetic and environmental factors as possible early predictors of response in MS patients treated with fingolimod for 24 months. The secondary objective was to analyze the possible contribution of the environmental factors analyzed to the progression and activity of the disease along the 2-years of follow-up. Methods: A retrospective study with 151 patients diagnosed with MS, under fingolimod treatment for 24 months, with serum samples at initiation and six months later, and with clinical and radiological data at initiation and 24 months later, were included in the study. Clinical and radiological variables were collected to establish NEDA-3 (no evidence of disease activity: patients without relapses, disability progression and new T2 lesions or Gd+ lesions) and EDA (evidence of disease activity: patients with relapses and/or progression and/or new T2 lesions or gadolinium-positive [Gd+] lesions) conditions. Human leukocyte antigen II (HLA-II), EBNA-1 IgG and VCA IgG from Epstein-Barr virus (EBV) and antibody titers against Human herpesvirus 6A/B (HHV-6A/B) were also analyzed. Results: A total of 151 MS patients fulfilled the inclusion criteria: 27.8% was NEDA-3 (37.5% among those previously treated with high efficacy therapies >24 months). The following early predictors were statistically significantly associated with NEDA-3 condition: sex (male; p=0.002), age at baseline (older; p=0.009), relapses 2-years before fingolimod initiation ≤1 (p=0.010), and absence of Gd+ lesions at baseline (p=0.006). Regarding the possible contribution of the environmental factors included in the study to the activity or the progression of the disease, we only found that EBNA-1 IgG titers decreased in 20.0% of PIRA (progression independent from relapse activity) patients vs. 73.3% of RAW (relapse-associated worsening) patients (p=0.006; O.R. = 11.0). Conclusion: MS patients that are male, older, and with a low clinical and radiological activity at fingolimod initiation have a greater probability to reach NEDA-3 condition after two years with this therapy. An intriguing association of EBV with the progression of the disease has also been described, but it should be further study in a larger cohort to confirm these results.

Effect of Adding Red Propolis to Edible Biodegradable Protein Films for Coating Grapes: Shelf Life and Sensory Analysis.

Red propolis is an active ingredient of great nutritional interest which offers numerous benefits as an antioxidant and antimicrobial agent. Thus, the objective of this research was to evaluate the application of an edible and antimicrobial gelatine coating containing red propolis to increase the shelf life of grapes. Gelatine films with an addition of 5, 10, 15, 20 and 25% of red propolis extract were produced to evaluate their antimicrobial activity using the disk diffusion test in solid media. The films with 25% red propolis extract showed antimicrobial activity against the bacteria Staphylococcus aureus and Pseudomonas aeruginosa. The grapes were coated with pure gelatine, without a plasticizer and with gelatine with 25% red propolis and then stored for 1, 4, 10, 19 and 25 days at temperatures of 25 °C and 5 °C. The results showed that the gelatine coating with propolis reduced the mass loss of grapes stored at 25 °C for 19 days by 7.82% and by 21.20% for those kept at 5 °C for 25 days. The pH, total titratable acidity, soluble solids and color of the grapes increased due to the ripening process. Furthermore, the sensory acceptability indexes of the refrigerated grapes with coatings were superior (>78%) to those of the control samples (38%), proving the effectiveness of the coatings in maintaining the quality of grapes during storage.