Commodity risk assessment of Tilia cordata and Tilia platyphyllos plants from the UK.

The European Commission requested the EFSA Panel on Plant Health to prepare and deliver risk assessments for commodities listed in Commission Implementing Regulation (EU) 2018/2019 as 'High risk plants, plant products and other objects'. This Scientific Opinion covers plant health risks posed by plants of Tilia cordata and T. platyphyllos imported from the United Kingdom (UK) as: (a) bundles of budwood/graftwood; (b) 1- to 2-year-old whips, seedlings or transplants; (c) bundles of 1- to 2-year-old cell grown plants; (d) 1- to 7-year-old bare root single plants; and (e) up to 25-year-old single plants in pots, taking into account the available scientific information provided by the UK. A list of pests potentially associated with the commodities was compiled. The relevance of any pest was assessed based on evidence following defined criteria. None of the pests on the list fulfilled all relevant criteria and therefore none were selected for further evaluation. As a result, risk mitigation measures proposed in the technical dossier from the UK were listed, but not further evaluated.

Balloon venoplasty for right heart catheterization from the arm in patients with subclavian vein stenosis.

OBJECTIVES: In the trans-radial era, arm venous access for right heart catheterization (RHC) is rising. Procedural success is affected by many factors, including subclavian/innominate vein stenosis (SVS) and pre-existing wires or catheters. In a study published previously by the same authors, 2% of cases had unsuccessful RHC through the arm, predominantly due to SVS. Since that study, techniques to improve RHC success rates have been developed, including crossing the stenosis with a coronary guidewire, followed by balloon dilatation. We aimed to determine whether subclavian/innominate venoplasty allows successful RHC in patients with SVS. METHODS: Our retrospective study included patients who had RHC from the arm between November 1, 2019, and December 31, 2022 that was unsuccessful due to the inability to pass a catheter through the SVS, and then underwent balloon venoplasty. The success rate of completed RHC was then assessed. RESULTS: Out of 2506 RHCs via arm access, 2488 were successful with a catheter alone or over a guidewire. In 18 patients, venoplasty was needed for catheter passage over a guidewire. Post-dilatation, all 18 cases (100%) had successful RHC with a mean procedural time of 35.2 (SD = 15.5) minutes. The most common stenosis site was the subclavian vein in 13 patients (72.2%), and 12 patients (66.7%) had pacemaker/ implantable cardioverter defibrillator wires present. CONCLUSIONS: Balloon dilatation of SVS is an efficacious method to improve the success rate of RHC from the arm. It is a safe technique that may prevent cross-over to a different access site, thereby improving patient satisfaction and reducing the possibility of alternate site complications.

Enhancement of rAAV titers via inhibition of the interferon signaling cascade in transfected HEK293 suspension cultures.

The production of recombinant adeno-associated virus (rAAV) for gene therapy applications relies on the use of various host cell lines, with suspension-grown HEK293 cells being the preferred expression system due to their satisfactory rAAV yields in transient transfections. As the field of gene therapy continues to expand, there is a growing demand for efficient rAAV production, which has prompted efforts to optimize HEK293 cell line productivity through engineering. In contrast to other cell lines like CHO cells, the transcriptome of HEK293 cells during rAAV production has remained largely unexplored in terms of identifying molecular components that can enhance yields. In our previous research, we analyzed global regulatory pathways and mRNA expression patterns associated with increased rAAV production in HEK293 cells. Our data revealed substantial variations in the expression patterns between cell lines with low (LP) and high-production (HP) rates. Moving to a deeper layer for a more detailed analysis of inflammation-related transcriptome data, we detected an increased expression of interferon-related genes in low-producing cell lines. Following upon these results, we investigated the use of Ruxolitinib, an interferon pathway inhibitor, during the transient production of rAAV in HEK293 cells as potential media additive to boost rAAV titers. Indeed, we find a two-fold increase in rAAV titers compared to the control when the interferon pathways were inhibited. In essence, this work offers a rational design approach for optimization of HEK293 cell line productivity and potential engineering targets, ultimately paving the way for more cost-efficient and readily available gene therapies for patients.

Stasis imaging predicts the risk of cardioembolic events related to acute myocardial infarction.

INTRODUCTION AND OBJECTIVES: In the setting of ST-segment elevation myocardial infarction (STEMI), imaging-based biomarkers could be useful for guiding oral anticoagulation to prevent cardioembolism. Our objective was to test the efficacy of intraventricular blood stasis imaging in predicting a composite primary endpoint of cardioembolic risk during the first 6 months after STEMI. METHODS: We designed a prospective clinical study, Imaging Silent Brain Infarct in Acute Myocardial Infarction (ISBITAMI, NCT02917213), including patients with a first STEMI, an ejection fraction ≤ 45% and without atrial fibrillation to assess the performance of stasis metrics to predict cardioembolism. Patients underwent ultrasound-based stasis imaging at enrollment followed by heart and brain magnetic resonance at 1-week and 6-month visits. From the stasis maps, we calculated the average residence time, RT, of blood inside the left ventricle and assessed its ability to predict the primary endpoint. The longitudinal strain of the 4 apical segments was quantified by speckle tracking. RESULTS: A total of 66 patients were assigned to the primary endpoint. Of them, 17 patients had 1 or more events: 3 strokes, 5 silent brain infarctions, and 13 mural thromboses. No systemic embolisms were observed. RT (OR, 3.73; 95%CI, 1.75-7.9; P < .001) and apical strain (OR, 1.47; 95%CI, 1.13-1.92; P = .004) showed complementary prognostic value. The bivariate model showed a c-index = 0.86 (95%CI, 0.73-0.95), a negative predictive value of 1.00 (95%CI, 0.94-1.00), and positive predictive value of 0.45 (95%CI, 0.37-0.77). The results were confirmed in a multiple imputation sensitivity analysis. Conventional ultrasound-based metrics were of limited predictive value. CONCLUSIONS: In patients with STEMI and left ventricular systolic dysfunction in sinus rhythm, the risk of cardioembolism may be assessed by echocardiography by combining stasis and strain imaging.

Porphyromonas gingivalis, a bridge between oral health and immune evasion in gastric cancer.

Porphyromonas gingivalis (P. gingivalis) is a gram-negative oral pathogen associated with chronic periodontitis. Previous studies have linked poor oral health and periodontitis with oral cancer. Severe cases of periodontal disease can result in advanced periodontitis, leading to tissue degradation, tooth loss, and may also correlate with higher gastric cancer (GC) risk. In fact, tooth loss is associated with an elevated risk of cancer. However, the clinical evidence for this association remains inconclusive. Periodontitis is also characterized by chronic inflammation and upregulation of members of the Programmed Death 1/PD1 Ligand 1 (PD1/PDL1) axis that leads to an immunosuppressive state. Given that chronic inflammation and immunosuppression are conditions that facilitate cancer progression and carcinogenesis, we hypothesize that oral P. gingivalis and/or its virulence factors serve as a mechanistic link between oral health and gastric carcinogenesis/GC progression. We also discuss the potential impact of P. gingivalis' virulence factors (gingipains, lipopolysaccharide (LPS), and fimbriae) on inflammation and the response to immune checkpoint inhibitors in GC which are part of the current standard of care for advanced stage patients.

Delayed Sternal Closure vs Emergency Sternal Reopening in Adults with Congenital Heart Disease.

BACKGROUND: Limited data exist regarding outcomes of delayed sternal closure (DSC) in adults with congenital heart disease (ACHD). METHODS: We reviewed 159 ACHD patients undergoing cardiac surgery 1993-2023, who required DSC (open sternum at the end of operation, n=112) or ESR (sternum emergently reopened, n=47). Regression models were performed to determine factors associated with outcomes. RESULTS: Of 112 patients undergoing DSC, 87 patients (77.6%) underwent DSC ≤4 days, and 25 patients (22.3%) >4 days. The most common operations were valve (n=35, 31.2%), aortic (n=33, 29.4%), and right ventricular outflow tract procedures (n=23, 20.5%). Median time to chest closure was 2 days (interquartile range 1, 5). Apart from gender, baseline characteristics were similar between DSC groups. A stepwise increase in early mortality was observed from DSC≤4 days to DSC>4 days (6.8% vs 32%), as well as incidence of early complications, except sternal infection. Risk factors associated with early mortality were age (p=0.02), DSC >4 days (p<0.001), hemodynamic indication (p=0.03), and single ventricle (p=0.02). On multivariable analysis, lower ejection fraction (p=0.04), hemodynamic indication (p=0.02), single ventricle (p=0.004), and diabetes mellitus (p=0.03) were predictors of prolonged time to chest closure. Amongst hospital survivors, there was no difference in late survival between patients undergoing DSC ≤4 days vs >4 days (p=0.48). CONCLUSIONS: Brief duration of DSC in ACHD patients is associated with low morbidity and mortality. Higher early mortality and complications were observed among patients who did not achieve chest closure within 4 days.

Long-term Stroke and Mortality Risk in Nonagenarians Following Transcatheter Aortic Valve Insertion.

BACKGROUND: Limited data exist on the long-term outcomes of transcatheter aortic valve insertion (TAVI) in nonagenarian patients. The purpose of this study is to investigate the relationship between patient baseline comorbidity and frailty on the long-term outcome of the nonagenarian population. METHODS: Retrospective analysis of 187 consecutive nonagenarian patients who underwent TAVI from 2009 to 2020. Multivariable models were utilized to analyze the association between basleline patient and frailty variables and mortality, stroke, and repeat hospitalization. Long-term survival was compared to an age- and sex-matched US population. RESULTS: The median STS-predicted risk of mortality (STS-PROM) was 10% (IQR, 7-17%). Frailty was met in 72% of patients based on the five-meter walk test, 13% based on KCCQ-12 score, 12% based on KATZ activities of daily living, and 8% based on serum albumin levels. Procedure-related mortality occured in 3 (2%) patients and stroke in 8 (4%). The median duration of follow-up was 3.4 years. Outcomes included death in 150 (80%) patients, stroke in 15, and repeat hospitalization in 114. Multivariable analysis identified no association between any of the baseline patient variables with mortality, stroke, repeat hospitalization, or the combined outcomes (all P>0.05). One- and five-year survival rates in TAVI-treated nonagenarians were similar to age- and sex-matched controls (P=0.27). CONCLUSIONS: Long-term death or stroke is independent of STS-PROM and frailty risk variables in this nonagenarian patient population who received TAVI. Furthermore, survival is similar to age- and sex-matched controls.

Effect of three training programs on surgical performance in single-port laparoscopic surgery.

OBJECTIVE: The aim of this study was to evaluate the effect of three training methodologies on the acquisition of psychomotor skills for laparoendoscopic single-site surgery (LESS), using straight and articulating instruments. METHODS: A prospective study was conducted with subjects randomly divided into three groups, who performed a specific training for 12 days using three laparoscopic tasks in a laparoscopic simulator. Group-A trained in conventional laparoscopy setting using straight instruments and in LESS setting using both straight and articulating instruments. Group-B trained in LESS setting using straight and articulating instruments, whereas Group-C trained in LESS setting using articulating instruments. Participants' performance was recorded with a video-tracking system and evaluated with 12 motion analysis parameters (MAPs). RESULTS: All groups obtained significant differences in their performance in most of the MAPs. Group-C showed an improvement in nine MAPs, with a high level of technical competence. Group-A presented a marked improvement in bimanual dexterity skills. CONCLUSIONS: Training in LESS surgery using articulating laparoscopic instruments improves the quality of skills and allows smoother learning curves.

OBJETIVO: Evaluar el efecto de tres métodos de entrenamiento en la adquisición de habilidades psicomotrices para la cirugía laparoendoscópica por puerto único (LESS, laparoendoscopic single-site surgery) utilizando instrumental recto y articulado. MÉTODO: Se realizó un estudio prospectivo con sujetos divididos aleatoriamente en tres grupos, quienes realizaron un entrenamiento específico durante 12 días utilizando tres tareas laparoscópicas en un simulador laparoscópico. El grupo A entrenó en el entorno laparoscópico convencional con instrumentos rectos, y en el entorno LESS con instrumentos rectos y articulados. El grupo B entrenó en el entorno LESS con instrumentos rectos y articulados. El Grupo C entrenó en el entorno LESS con instrumentos articulados. El desempeño de los participantes se registró con un sistema de seguimiento en video y fue evaluado con 12 parámetros de análisis de movimiento (MAP, motion analysis parameters). RESULTADOS: Todos los grupos obtuvieron diferencias significativas en su desempeño para la mayoría de los MAP. El grupo C mostró una mejora en nueve MAP, con un alto nivel de competencia técnica. El grupo A mostró una marcada mejora en la habilidad de destreza bimanual. CONCLUSIONES: El entrenamiento en cirugía LESS con instrumentos articulados mejora la calidad de las habilidades adquiridas y permite curvas de aprendizaje más suaves.

Study of late toxicity biomarkers of locally advanced head and neck cancer patients treated with radiotherapy plus cisplatin or cetuximab points to the relevance of skin macrophages (TOX-TTCC-2015-01).

PURPOSE: Radiotherapy (RT) with concomitant cisplatin (CRT) or cetuximab (ERT) are accepted treatment options for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Long-term adverse events (AEs) have a vast impact on patients' quality of life. This study explored tissue biomarkers which could help predict late toxicity. METHODS/PATIENTS: Single-institution prospective study including patients aged ≥ 18 with histologically confirmed newly diagnosed LA-SCCHN treated with RT and either concomitant cisplatin q3w or weekly cetuximab, according to institutional protocols. All patients underwent pre- and post-treatment skin biopsies of neck regions included in the clinical target volume. Angiogenesis, macrophages, and extracellular matrix (ECM) markers were evaluated by immunohistochemistry (IHC). RESULTS: From April 15, 2016, to December 11, 2017; 31 patients were evaluated [CRT = 12 (38.7%) and ERT = 19 (61.3%)]. 27 patients (87%) had received induction chemotherapy. All patients finished RT as planned. IHC expression of vasculature (CD34) and collagen (Masson's Trichrome) did not differ significantly between and within CRT and ERT arms. Conversely, an increased CD68 and CD163 macrophage infiltration expression was observed after treatment, without significant impact of treatment modality. Patients with higher late toxicity showed lower expression of macrophage markers in pre-treatment samples compared with those with lower late toxicity, with statistically significant differences for CD68. CONCLUSIONS: Angiogenesis and ECM biomarkers did not differ significantly between CRT and ERT. Macrophage markers increased after both treatments and deserve further investigation as predictors of late toxicity in LA-SCCHN patients. [Protocol code: TOX-TTCC-2015-01/Spanish registry of clinical studies (REec): 2015-003012-21/Date of registration: 27/01/2016].

Acute Responses to Traditional and Cluster-Set Squat Training With and Without Blood Flow Restriction.

ABSTRACT: Cornejo-Daza, PJ, Sánchez-Valdepeñas, J, Páez-Maldonado, J, Rodiles-Guerrero, L, Boullosa, D, León-Prados, JA, Wernbom, M, and Pareja-Blanco, F. Acute responses to traditional and cluster-set squat training with and without blood flow restriction. J Strength Cond Res XX(X): 000-000, 2024-To compare the acute responses to different set configurations (cluster [CLU] vs. traditional [TRA]) under distinct blood flow conditions (free vs. restricted) in full-squat (SQ). Twenty resistance-trained males performed 4 protocols that differed in the set configuration (TRA: continuous repetitions; vs. CLU: 30 seconds of rest every 2 repetitions) and in the blood flow condition (FF: free-flow; vs. blood flow restriction [BFR]: 50% of arterial occlusion pressure). The relative intensity (60% 1RM), volume (3 sets of 8 repetitions), and resting time (2 minutes) were equated. Mean propulsive force (MPF), velocity (MPV) and power (MPP), and electromyography (EMG) parameters were recorded during each repetition. Tensiomyography (TMG), blood lactate, countermovement jump (CMJ) height, maximal voluntary isometric contraction, in SQ, and movement velocity against the load that elicited a 1 m·s-1 velocity at baseline (V1-load) in SQ were assessed at pre- and post-exercise. The CLU protocols allowed a better maintenance of MPF, MPV, MPP, and EMG median frequency during the exercise compared to TRA (clu-time interaction, p < 0.05). The TRA protocols experienced greater impairments post-exercise in TMG- and EMG-derived variables (clu-time interaction, p < 0.05) and SQ and CMJ performance (clu-time interaction, p = 0.08 and p < 0.05, respectively), as well as higher blood lactate concentrations (clu-time interaction, p < 0.001) than CLU. Moreover, BFR displayed decreases in TMG variables (bfr-time interaction, p < 0.01), but BFR-CLU resulted in the greatest reduction in twitch contraction time (p < 0.001). Cluster sets reduced fatigue during and after the training session and BFR exacerbated impairments in muscle mechanical properties; however, the combination of both could improve contraction speed after exercise.

Integrating population and single-cell variations in vaccine responses identifies a naturally adjuvanted human immune setpoint.

Multimodal single-cell profiling methods can capture immune cell variations unfolding over time at the molecular, cellular, and population levels. Transforming these data into biological insights remains challenging. Here, we introduce a framework to integrate variations at the human population and single-cell levels in vaccination responses. Comparing responses following AS03-adjuvanted versus unadjuvanted influenza vaccines with CITE-seq revealed AS03-specific early (day 1) response phenotypes, including a B cell signature of elevated germinal center competition. A correlated network of cell-type-specific transcriptional states defined the baseline immune status associated with high antibody responders to the unadjuvanted vaccine. Certain innate subsets in the network appeared "naturally adjuvanted," with transcriptional states resembling those induced uniquely by AS03-adjuvanted vaccination. Consistently, CD14+ monocytes from high responders at baseline had elevated phospho-signaling responses to lipopolysaccharide stimulation. Our findings link baseline immune setpoints to early vaccine responses, with positive implications for adjuvant development and immune response engineering.

Electrophoresis-Based Approach for Characterizing Dendrimer-Protein Interactions: A Proof-of-Concept Study.

Improving the clinical translation of nanomedicine requires better knowledge about how nanoparticles interact with biological environments. As researchers are recognizing the importance of understanding the protein corona and characterizing how nanocarriers respond in biological systems, new tools and techniques are needed to analyze nanocarrier-protein interactions, especially for smaller size (<10 nm) nanoparticles like polyamidoamine (PAMAM) dendrimers. Here, we developed a streamlined, semiquantitative approach to assess dendrimer-protein interactions using a nondenaturing electrophoresis technique combined with mass spectrometry. With this protocol, we detect fluorescently tagged dendrimers and proteins simultaneously, enabling us to analyze when dendrimers migrate with proteins. We found that PAMAM dendrimers mostly interact with complement proteins, particularly C3 and C4a, which aligns with previously published data, verifying that our approach can be used to isolate and identify dendrimer-protein interactions.

Association Between Changes in Sleep, Nap Duration and Bone Mineral Density in Mexican Adults.

Studies have found associations between sleep, nap duration, and bone mineral density (BMD). However, the longitudinal relationship between sleep, nap duration, and BMD has not been explored. We evaluated the association between the change in sleep and nap duration and BMD in Mexican adults. Data come from 1,337 adult participants of the Health Workers Cohort Study (341 were men and 996 were women, including 450 women < 45 years old and 546 ≥ 45 years old), with two study waves. At each wave, sleep and nap duration was assessed using self-administered questionnaires and BMD in g/cm2 was determined by dual X-ray absorptiometry. We used fixed-effect regression models stratified by sex and adjusted for BMI, diet, physical activity, vitamin supplements, and hormone replacement therapy. Women who changed from < 7 to ≥ 7 h/day of sleep from baseline to follow-up were associated with increases in the total hip (ß = 0.012 g/cm2; 95% CI: 0.002, 0.022) and lumbar spine BMD (ß = 0.024 g/cm2; 95% CI: 0.009, 0.039). Furthermore, most of these associations were observed in women ≥ 45 years. For women, a changing from 0 to > 60 min/day of napping was associated with a significant increase in total hip BMD of 0.012 g/cm2 (95% CI: 0.004, 0.024) and lumbar spine BMD of 0.027 g/cm2 (95% CI: 0.009, 0.045). No significant associations were observed for men. Our results suggest that increased sleep and nap duration are associated with gains in BMD in Mexican women, emphasizing sleep's role in promoting bone health and supporting established recommendations.

Effects of Type 2 Diabetes on the Neuropsychological Profile in Mild Cognitive Impairment.

Background: Diabetes is one of the main risk factors for developing mild cognitive impairment (MCI) and Alzheimer's disease. Most studies have demonstrated a worse performance in executive function, verbal fluency, and information processing speed in patients with diabetes. Objective: To assess the cognitive functioning of persons with type 2 diabetes and amnesic mild cognitive impairment (aMCI-T2DM) compared to persons with aMCI without diabetes and persons without diabetes or aMCI as controls, to understand the role of diabetes in the neuropsychological profile. Methods: Cross-sectional study involving a sample of 83 patients, ranging in age from 61 to 85 years and divided into three groups: aMCI-T2DM (27 patients), aMCI (29 patients), Controls (27 individuals). All the participants undertook an exhaustive neuropsychological assessment (auditory-verbal and visual memory, attention, information processing speed, language, executive function, and depression). Results: Both groups of aMCI patients performed significantly worse than the controls in all the neuropsychological tests. A significant linear tendency (p trend <  0.05) was found between groups, with the aMCI-T2DM group presenting worse results in global cognition assessed by the Mini-Mental State Examination and Montreal Cognitive Assessment; Rey-Osterrieth Complex Figure Test; Auditory Verbal Learning Test; Trail Making Test A and B, Verbal Fluency Test, and Hamilton Depression Rating Scale. Conclusions: aMCI patients with or without diabetes showed worse cognitive function compared to persons without diabetes or aMCI. Additionally, aMCI patients without T2DM presented a different cognitive profile than aMCI patients with T2DM, which tended towards presenting worse cognitive functions such as global cognition, memory, attention, executive function, and language.

Effect of GP visits in the compliance of preventive services: a cross-sectional study in Europe.

BACKGROUND: Performing cardiovascular and cancer screenings in target populations can reduce mortality. Visiting a General Practitioner (GP) once a year is related to an increased likelihood of preventive care. The aim of this study was to analyse the influence of visiting a GP in the last year on the delivery of preventive services based on sex and household income. METHODS: Cross-sectional study using data collected from the European Health Interview Survey 2013-2015 of individuals aged 40-74 years from 29 European countries. The variables included: sociodemographic factors (age, sex, and household income (HHI) quintiles [HHI 1: lowest income, HHI 5: more affluent]), lifestyle factors, comorbidities, and preventive care services (cardiometabolic, influenza vaccination, and cancer screening). Descriptive statistics, bivariate analyses and multilevel models (level 1: citizen, level 2: country) were performed. RESULTS: 242,212 subjects were included, 53.7% were female. The proportion of subjects who received any cardiometabolic screening (92.4%) was greater than cancer screening (colorectal cancer: 44.1%, gynaecologic cancer: 40.0%) and influenza vaccination. Individuals who visited a GP in the last year were more prone to receive preventive care services (cardiometabolic screening: adjusted OR (aOR): 7.78, 95% CI: 7.43-8.15; colorectal screening aOR: 1.87, 95% CI: 1.80-1.95; mammography aOR: 1.76, 95% CI: 1.69-1.83 and Pap smear test: aOR: 1.89, 95% CI:1.85-1.94). Among those who visited a GP in the last year, the highest ratios of cardiometabolic screening and cancer screening benefited those who were more affluent. Women underwent more blood pressure measurements than men regardless of the HHI. Men were more likely to undergo influenza vaccination than women regardless of the HHI. The highest differences between countries were observed for influenza vaccination, with a median odds ratio (MOR) of 6.36 (under 65 years with comorbidities) and 4.30 (over 65 years with comorbidities), followed by colorectal cancer screening with an MOR of 2.26. CONCLUSIONS: Greater adherence to preventive services was linked to individuals who had visited a GP at least once in the past year. Disparities were evident among those with lower household incomes who visited a GP. The most significant variability among countries was observed in influenza vaccination and colorectal cancer screening.

Pyroclastic Dust from Arequipa-Peru Decorated with Iron Oxide Nanoparticles and Their Ecotoxicological Properties in Water Flea D. magna.

A novel magnetic composite made of Peruvian pyroclastic dust material decorated with maghemite nanoparticles was synthesized and characterized using a variety of analytic techniques. The 13 nm maghemite nanoparticles were grown on the pyroclastic dust using the conventional coprecipitation chemical route. A short-term acute assay was developed to study the ecotoxicological behavior of the water flea, Daphnia magna. A 24 h-lethal concentration (LC50) value equal to 123.6 mg L-1 was determined only for the magnetic composite. While the pyroclastic dust material did not exhibit a lethal concentration, it caused morphologically significant changes (p < 0.05) for heart and tail parameters at high concentrations. Morphologies exposed to the magnetic composite above the 24 h-LC50 revealed less tolerance and significant changes in the body, heart, antenna, and eye. Hence, it affects biomarker growth and swimming. The reproduction rate was not affected by the raw pyroclastic dust material. However, the number of individuals showed a decrease with increasing composite concentrations. The present study indicates the LC50 value, which can be used as a reference concentration for in-situ water cleaning with this material without damaging or changing the Daphnia magna ecosystem.

Predicted impact of banning nonessential, energy-dense food and beverages in schools in Mexico: A microsimulation study.

BACKGROUND: Childhood obesity is a growing concern worldwide. School-based interventions have been proposed as effective means to improve nutritional knowledge and prevent obesity. In 2023, Mexico approved a reform to the General Education Law to strengthen the ban of sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools and surroundings. We aimed to predict the expected one-year change in total caloric intake and obesity prevalence by introducing the ban of NEDFBs sales in schools, among school-aged children and adolescents (6 to 17 years old) in Mexico. METHODS AND FINDINGS: We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and then estimated total energy intake (TEI) per day. The TEI after the intervention was estimated under 4 scenarios: (1) using national data to inform the intervention effect; (2) varying law compliance; (3) using meta-analytic data to inform the intervention effect size on calories; and (4) using national data to inform the intervention effect by sex and socioeconomic status (SES). We used Hall's microsimulation model to estimate the potential impact on body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools. We found that children could reduce their daily energy intake by 33 kcal/day/person (uncertainty interval, UI, [25, 42] kcal/day/person), reducing on average 0.8 kg/person (UI [0.6, 1.0] kg/person) and 1.5 percentage points (pp) in obesity (UI [1.1, 1.9] pp) 1 year after implementing the law. We showed that compliance will be key to the success of this intervention: considering a 50% compliance the intervention effect could reduce 0.4 kg/person (UI [0.3, 0.5] kg/person). Our sensitivity analysis showed that the ban could reduce body weight by 1.3 kg/person (UI [0.8, 1.8] kg/person) and up to 5.4 kg/person (UI [3.4, 7.5] kg/person) in the best-case scenario. Study limitations include assuming that obesity and the contribution of NEDFBs consumed at school remain constant over time, assuming full compliance, and not considering the potential effect of banning NEDFBs in stores near schools. CONCLUSIONS: Even in the most conservative scenario, banning sales of NEDFBs in schools is expected to significantly reduce obesity, but achieving high compliance will be key to its success. WHY WAS THIS STUDY DONE?: - School-based interventions have been recognized as effective means to improve nutritional knowledge and prevent obesity-related diseases.- In December 2023, the Chamber of Representatives of Mexico approved an amendment that strengthens and updates the General Education Law (Article 75) and nutritional guidelines to ban the sales and advertising of nonessential energy-dense food and beverages (NEDFBs) in schools. WHAT DID THE RESEARCHERS DO AND FIND?: - We used age-specific equations to predict baseline fat-free mass (FFM) and fat mass (FM) and total energy intake (TEI) per day.- We used microsimulation modeling to predict body weight and obesity prevalence of children and adolescents 1 year after implementing the intervention in Mexican schools.- Our modeling study suggests that an important impact on obesity prevalence can be expected if the law is implemented and enforced as intended. WHAT DO THESE FINDINGS MEAN?: - If successful, this law could serve as an example beyond Mexico on how to achieve changes in body weight through school food regulation.- An important limitation of our main scenario is that we assumed full compliance of schools with the law, yet lower compliance will reduce its impact. We also did not consider historical trends on obesity or NEDFBs consumed in schools during our 1 year simulation, and we considered only the ban impact inside schools, excluding effects near and outside schools.

Non-HLA angiotensin-type-1 receptor autoantibodies mediate the long-term loss of grafted neurons in Parkinson's disease models.

BACKGROUND: Clinical trials have provided evidence that transplants of dopaminergic precursors, which may be replaced by new in vitro stem cell sources, can integrate into the host tissue, and alleviate motor symptoms in Parkinson´s disease (PD). In some patients, deterioration of graft function occurred several months after observing a graft-derived functional improvement. Rejection of peripheral organs was initially related to HLA-specific antibodies. However, the role of non-HLA antibodies is now considered also relevant for rejection. Angiotensin-II type-1 receptor autoantibodies (AT1-AA) act as agonists of the AT1 receptors. AT1-AA are the non-HLA antibodies most widely associated with graft dysfunction or rejection after transplantation of different solid organs and hematopoietic stem cells. However, it is not known about the presence and possible functional effects of AT1-AA in dopaminergic grafts, and the effects of treatment with AT1 receptor blockers (ARBs) such as candesartan on graft survival. METHODS: In a 6-hydroxydopamine PD rat model, we studied the short-term (10 days)- and long-term (3 months) effects of chronic treatment with the ARB candesartan on survival of grafted dopaminergic neurons and microglial graft infiltration, as well as the effects of dopaminergic denervation and grafting on serum and CSF AT1-AA levels. The expression of AT1 receptors in grafted neurons was determined by laser capture microdissection. RESULTS: At the early period post-grafting, the number of grafted dopaminergic neurons that survived was not significantly different between treated and untreated hosts (i.e., control rats and rats treated with candesartan), probably because, just after grafting, other deleterious factors are predominant for dopaminergic cell death, such as mechanical trauma, lack of growth factors/nutrients and ischemia. However, several months post-grafting, we observed a significantly higher number of surviving dopaminergic neurons and a higher density of striatal dopaminergic terminals in the candesartan-treated group. For several months, grafted rats showed blood and cerebrospinal fluid levels of AT1-AA higher than normal controls, and also higher AT1-AA levels than non-grafted parkinsonian rats. CONCLUSIONS: The results suggest the use of ARBs such as candesartan in PD patients, particularly before and after dopaminergic grafts, and the need to monitor AT1-AA levels in PD patients, particularly in those candidates for dopaminergic grafting.