Cost-effectiveness of intraoperative radiation therapy versus intensity-modulated radiation therapy for the treatment of early breast cancer: a disinvestment analysis.

BACKGROUND: Adjuvant radiotherapy represents a key component in curative-intent treatment for early-stage breast cancer patients. In recent years, two accelerated partial breast irradiation (APBI) techniques are preferred for this population in our organization: electron-based Intraoperative radiation therapy (IORT) and Linac-based External Beam Radiotherapy, particularly Intensity-modulated radiation therapy (IMRT). Recently published long-term follow-up data evaluating these technologies have motivated a health technology reassessment of IORT compared to IMRT. METHODS: We developed a Markov model to simulate health-state transitions from a cohort of women with early-stage breast cancer, after lumpectomy and adjuvant APBI using either IORT or IMRT techniques. The cost-effectiveness from a private health provider perspective was assessed from a disinvestment point of view, using life-years (LYs) and recurrence-free life-years (RFLYs) as measure of benefits, along with their respective quality adjustments. Expected costs and benefits, and the incremental cost-effectiveness ratio (ICER) were reported. Finally, a sensitivity and scenario analyses were performed to evaluate the cost-effectiveness using lower IORT local recurrence and metastasis rates in IORT patients, and if equipment maintenance costs are removed. RESULTS: IORT technology was dominated by IMRT in all cases (i.e., fewer benefits with greater costs). Despite small differences were found regarding benefits, especially for LYs, costs were considerably higher for IORT. For sensitivity analyses with lower recurrence and metastasis rates for IORT, and scenario analyses without equipment maintenance costs, IORT was still dominated by IMRT. CONCLUSIONS: For this cohort of patients, IMRT was, at least, non-inferior to IORT in terms of expected benefits, with considerably lower costs. As a result, IORT disinvestment should be considered, favoring the use of IMRT in these patients.

Evaluation of different isotope dilution mass spectrometry strategies for the characterization of naturally abundant and isotopically labelled peptide standards.

Natural abundance and isotopically labelled tryptic peptides are routinely employed as standards in quantitative proteomics. The certification of the peptide content is usually carried out by amino acid analysis using isotope dilution mass spectrometry (IDMS) after the acid hydrolysis of the peptide. For the validation and traceability of the amino acid analysis procedure, expensive certified peptides must be employed. In this work we evaluate different IDMS alternatives which will reduce the amount of certified peptide required for validation of the amino acid analysis procedure. In this context, the characterization of both natural and isotopically labelled synthetic angiotensin I peptides was carried out. First, we applied a fast procedure for peptide hydrolysis based on microwave-assisted digestion and employed two certified peptide reference materials SRM 998 angiotensin I and CRM 6901-b C-peptide for validation of the hydrolysis procedure. The amino acids proline, leucine, isoleucine, valine, tyrosine, arginine and phenylalanine were evaluated for their suitability for peptide certification by IDMS by both liquid chromatography with tandem mass spectrometry (LC-MS/MS) and gas chromatography with mass spectrometry (GC)-MS/MS. Then, natural angiotensin I and 13C1-labelled angiotensin I were synthesized in-house and purified by preparative liquid chromatography. The concentration of the 13C1-labelled angiotensin I peptide was established by reverse IDMS in its native form using SRM 998 angiotensin I as reference. The concentration of the natural synthesized peptide was determined by IDMS both using the 13C1-labelled peptide in its native form and by amino acid analysis showing comparable results. Finally, the synthetic naturally abundant angiotensin I peptide was employed as "in-house" standard for the validation of subsequent peptide characterization procedures. Therefore, the novelty of this work relies on, first, the development of a faster hydrolysis procedure assisted by focused microwaves, providing complete hydrolysis in 150 min, and secondly, a validation strategy combining GC-MS and LC-MS/MS that allowed us to certify the purity of an in-house-synthesized peptide standard that can be employed as quality control in further experiments.

Chilean consensus by expert panel using the Delphi technique for primary and secondary prevention of gastric cancer. / Estrategias para la prevención primaria y secundaria del cáncer gástrico: consenso chileno de panel de expertos con técnica Delfi.

INTRODUCTION: Gastric cancer (GC) is the first cause of cancer-related death in Chile and 6th in Latin America and the Caribbean (LAC). Helicobacter pylori (H. pylori) is the main gastric carcinogen, and its treatment reduces GC incidence and mortality. Esophageal-gastro-duodenoscopy (EGD) allows for the detection of premalignant conditions and early-stage GC. Mass screening programs for H. pylori infection and screening for premalignant conditions and early-stage GC are not currently implemented in LAC. The aim of this study is to establish recommendations for primary and secondary prevention of GC in asymptomatic standard-risk populations in Chile. METHODS: Two on-line synchronous workshops and a seminar were conducted with Chilean experts. A Delphi panel consensus was conducted over 2 rounds to achieve>80% agreement on proposed primary and secondary prevention strategies for the population stratified by age groups. RESULTS: 10, 12, and 12 experts participated in two workshops and a seminar, respectively. In the Delphi panel, 25 out of 37 experts (77.14%) and 28 out of 52 experts (53.85%) responded. For the population aged 16-34, there was no consensus on non-invasive testing and treatment for H. pylori, and the use of EGD was excluded. For the 35-44 age group, non-invasive testing and treatment for H. pylori is recommended, followed by subsequent test-of-cure using non-invasive tests (stool antigen test or urea breath test). In the ≥45 age group, a combined strategy is recommended, involving H. pylori testing and treatment plus non-invasive biomarkers (H. pylori IgG serology and serum pepsinogens I and II); subsequently, a selected group of subjects will undergo EGD with gastric biopsies (Sydney Protocol), which will be used to stratify surveillance according to the classification Operative Link for Gastritis Assessment (OLGA); every 3 years for OLGA III-IV and every 5 years for OLGA I-II. CONCLUSION: A "test-and-treat" strategy for H. pylori infection based on non-invasive studies (primary prevention) is proposed in the 35-44 age group, and a combined strategy (serology and EGD) is recommended for the ≥45 age group (primary and secondary prevention). These strategies are potentially applicable to other countries in LAC.

Immunomodulation with AM3 and antioxidants creates an adequate framework for skin repair and decreases the monocyte proinflammatory stage in smoker women.

Smoking has been considering a crucial factor in promoting skin and systemic aging that is associated with the development of a low-level, systemic, chronic inflammation known as "inflammaging" in which monocytes play a pivotal role. Our aim was to investigate the effects of AM3 plus antioxidants vs placebo in the activation status, function of monocytes and cutaneous aging parameters in healthy smoker middle-aged women. A total of 32 women were 1:1 randomly assigned to AM3 plus antioxidants or placebo for three months. Peripheral mononuclear blood cells and cutaneous biopsy were obtained and flow cytometry and immunohistological studies, respectively, were performed before and after the treatment. AM3 plus antioxidants treatment compared with placebo significantly reduced the monocyte production of the proinflammatory interleukin 1 (IL-1), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) cytokines as well as increased the regulatory IL-10 in middle-aged smoker women. Furthermore, AM3 and antioxidants did not modify ROS production by monocytes and granulocytes but increased their phagocytic activity. The active combination also stimulated a significative increase in reticular dermis depth as well as an increase in the expression of CD117 and CD31. Thus, AM3 and antioxidants treatment reduces the systemic proinflammatory monocyte disturbance of heathy smoker middle-aged women and encourage skin repair mechanisms.

From cultivation to cancer: formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications.

Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.

Natural Killer T Cell Diversity and Immunotherapy.

Invariant natural killer T cells (iNKTs), a type of unconventional T cells, share features with NK cells and have an invariant T cell receptor (TCR), which recognizes lipid antigens loaded on CD1d molecules, a major histocompatibility complex class I (MHC-I)-like protein. This interaction produces the secretion of a wide array of cytokines by these cells, including interferon gamma (IFN-γ) and interleukin 4 (IL-4), allowing iNKTs to link innate with adaptive responses. Interestingly, molecules that bind CD1d have been identified that enable the modulation of these cells, highlighting their potential pro-inflammatory and immunosuppressive capacities, as required in different clinical settings. In this review, we summarize key features of iNKTs and current understandings of modulatory α-galactosylceramide (α-GalCer) variants, a model iNKT cell activator that can shift the outcome of adaptive immune responses. Furthermore, we discuss advances in the development of strategies that modulate these cells to target pathologies that are considerable healthcare burdens. Finally, we recapitulate findings supporting a role for iNKTs in infectious diseases and tumor immunotherapy.

Estimation of Obesity Levels through the Proposed Predictive Approach Based on Physical Activity and Nutritional Habits.

Obesity is the excessive accumulation of adipose tissue in the body that leads to health risks. The study aimed to classify obesity levels using a tree-based machine-learning approach considering physical activity and nutritional habits. Methods: The current study employed an observational design, collecting data from a public dataset via a web-based survey to assess eating habits and physical activity levels. The data included gender, age, height, weight, family history of being overweight, dietary patterns, physical activity frequency, and more. Data preprocessing involved addressing class imbalance using Synthetic Minority Over-sampling TEchnique-Nominal Continuous (SMOTE-NC) and feature selection using Recursive Feature Elimination (RFE). Three classification algorithms (logistic regression (LR), random forest (RF), and Extreme Gradient Boosting (XGBoost)) were used for obesity level prediction, and Bayesian optimization was employed for hyperparameter tuning. The performance of different models was evaluated using metrics such as accuracy, recall, precision, F1-score, area under the curve (AUC), and precision-recall curve. The LR model showed the best performance across most metrics, followed by RF and XGBoost. Feature selection improved the performance of LR and RF models, while XGBoost's performance was mixed. The study contributes to the understanding of obesity classification using machine-learning techniques based on physical activity and nutritional habits. The LR model demonstrated the most robust performance, and feature selection was shown to enhance model efficiency. The findings underscore the importance of considering both physical activity and nutritional habits in addressing the obesity epidemic.

Quantification of modified nucleotides and nucleosides by isotope dilution mass spectrometry.

Epigenetic modifications are closely related to certain disorders of the organism, including the development of tumors. One of the main epigenetic modifications is the methylation of DNA cytosines, 5-methyl-2'-deoxycycytidine. Furthermore, 5-mdC can be oxidized to form three new modifications, 5-(hydroxymethyl)-2'-deoxycytidine, 5-formyl-2'-deoxycytidine, and 5-carboxy-2'-deoxycytidine. The coupling of liquid chromatography with tandem mass spectrometry has been widely used for the total determination of methylated DNA cytosines in samples of biological and clinical interest. These methods are based on the measurement of the free compounds (e.g., urine) or after complete hydrolysis of the DNA (e.g., tissues) followed by a preconcentration, derivatization, and/or clean-up step. This review highlights the main advances in the quantification of modified nucleotides and nucleosides by isotope dilution using isotopically labeled analogs combined with liquid or gas chromatography coupled to mass spectrometry reported in the last 20 years. The different possible sources of labeled compounds are indicated. Special emphasis has been placed on the different types of chromatography commonly used (reverse phase and hydrophilic interaction liquid chromatography) and the derivatization methods developed to enhance chromatographic resolution and ionization efficiency. We have also revised the application of bidimensional chromatography and indicated significant biological and clinical applications of these determinations.

Dolor tóraco-abdominal: "Si miras el corazón, encontrarás la razón". Serie de casos

La isquemia miocárdica es un fenómeno secundario a la perfusión insuficiente del músculo cardíaco que en algunos casos puede ocurrir de forma aguda llevando a la necrosis celular y constituyendo el infarto agudo al miocardio (IAM). A pesar de que el diagnóstico de IAM es principalmente clínico, en ciertos casos en que no se sospeche de forma activa por presentar síntomas no típicos de isquemia miocárdica, el diagnóstico puede sugerirse por la Tomografía Computarizada (TC), que puede mostrar hallazgos sugerentes de IAM. A continuación, se comunica una serie de 4 casos clínicos con diagnóstico imagenológico incidental de IAM.

Myocardial ischemia is secondary to myocardial under perfusion. It can develop acutely leading to cell necrosis and myocardial infarction (AMI), or have a chronic course. Though the diagnosis of AMI is mainly clinical, in certain cases the symptoms may be atypical and the diagnosis can be suggested by images such as Computed Tomography (CT). Herein we report a series of 4 clinical cases with diagnosis of AMI following incidental CT imaging. There was an abdominal pain in 3 patients and a cervical pain in the remaining one. CT scan showed a hypodense myocardial image. The final diagnosis was confirmed by the appropriate laboratory and angiographic methods.

The G protein-coupled receptor GPRC5A-a phorbol ester and retinoic acid-induced orphan receptor with roles in cancer, inflammation, and immunity.

GPRC5A is the first member of a new class of orphan receptors coupled to G proteins, which also includes GPRC5B, GPRC5C, and GPRC5D. Since its cloning and identification in the 1990s, substantial progress has been made in understanding the possible functions of this receptor. GPRC5A has been implicated in a variety of cellular events, such as cytoskeleton reorganization, cell proliferation, cell cycle regulation, migration, and survival. It appears to be a central player in different pathological processes, including tumorigenesis, inflammation, immune response, and tissue damage. The levels of GPRC5A expression differ depending on the type of cancer, with increased expression in colon, pancreas, and prostate cancers; decreased expression in lung cancer; and varied results in breast cancer. In this review, we discuss the early discovery of GPRC5A as a phorbol ester-induced gene and later as a retinoic acid-induced gene, its regulation, and its participation in important canonical pathways related to numerous types of tumors and inflammatory processes. GPRC5A represents a potential new target for cancer, inflammation, and immunity therapies.

La importancia de la evaluación de tecnologías sanitarias: estado del arte / The importance of health technology assessment: state of the art / A importância da avaliação da tecnologia em saúde: o estado da arte

En un contexto de atención médica en constante evolución, la evaluación de tecnologías sanitarias se ha vuelto esencial. Este proceso evalúa la efectividad, seguridad y costo-efectividad de las tecnologías médicas, desde medicamentos hasta dispositivos. La evaluación respalda decisiones clínicas informadas, reduciendo la variabilidad en la práctica y mejorando la atención al paciente. Además, desempeña un papel crucial en las políticas de salud al guiar la asignación eficiente de recursos y promover el acceso equitativo a las tecnologías sanitarias. Como conclusión se puede decir que la evaluación de tecnologías sanitarias es esencial para garantizar sistemas de salud sostenibles y una atención de calidad.

In an ever-evolving healthcare environment, health technology assessment has become essential. This process evaluates the effectiveness, safety and cost-effectiveness of medical technologies, from drugs to devices. The assessment supports informed clinical decisions, reducing practice variability and improving patient care. It also plays a crucial role in health policy by guiding the efficient allocation of resources and promoting equitable access to health technologies. In conclusion, health technology assessment is essential to ensure sustainable health systems and quality care.

Em um contexto de saúde em constante evolução, a avaliação da tecnologia da saúde tornou-se essencial. Esse processo avalia a eficácia, a segurança e a relação custo-benefício das tecnologias médicas, de medicamentos a dispositivos. A avaliação apóia decisões clínicas fundamentadas, reduzindo a variabilidade na prática e melhorando o atendimento ao paciente. Ela também desempenha um papel fundamental na política de saúde, orientando a alocação eficiente de recursos e promovendo o acesso equitativo às tecnologias de saúde. Em conclusão, a avaliação da tecnologia em saúde é essencial para garantir sistemas de saúde sustentáveis e atendimento de qualidade.

Ferroptosis is the key cellular process mediating Bisphenol A responses in Chlamydomonas and a promising target for enhancing microalgae-based bioremediation.

Microplastics are one of the major pollutants in aquatic environments. Among their components, Bisphenol A (BPA) is one of the most abundant and dangerous, leading to endocrine disorders deriving even in different types of cancer in mammals. However, despite this evidence, the xenobiotic effects of BPA over plantae and microalgae still need to be better understood at the molecular level. To fill this gap, we characterized the physiological and proteomic response of Chlamydomonas reinhardtii during long-term BPA exposure by analyzing physiological and biochemical parameters combined with proteomics. BPA imbalanced iron and redox homeostasis, disrupting cell function and triggering ferroptosis. Intriguingly, this microalgae defense against this pollutant is recovering at both molecular and physiological levels while starch accumulation at 72 h of BPA exposure. In this work, we addressed the molecular mechanisms involved in BPA exposure, demonstrating for the first time the induction of ferroptosis in a eukaryotic alga and how ROS detoxification mechanisms and other specific proteomic rearrangements reverted this situation. These results are of great significance not only for understanding the BPA toxicology or exploring the molecular mechanisms of ferroptosis in microalgae but also for defining novel target genes for microplastic bioremediation efficient strain development.

Macular vessel density in the superficial plexus is not associated to cerebrospinal fluid core biomarkers for Alzheimer's disease in individuals with mild cognitive impairment: The NORFACE cohort.

Background: Optical coherence tomography angiography (OCT-A) is a novel method in the dementia field that allows the detection of retinal vascular changes. The comparison of OCT-A measures with established Alzheimer's disease (AD)-related biomarkers is essential to validate the former as a marker of cerebrovascular impairment in the AD continuum. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus quantified by OCT-A with the AT(N) classification based on cerebrospinal fluid (CSF) Aß1-42, p181-tau and t-tau measurements in individuals with mild cognitive impairment (MCI). Materials and methods: Clinical, demographic, ophthalmological, OCT-A and CSF core biomarkers for AD data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences in macular VD in four quadrants (superior, nasal, inferior, and temporal) among three AT(N) groups [Normal, Alzheimer and Suspected non-Alzheimer pathology (SNAP)] were assessed in a multivariate regression model, adjusted for age, APOE ε4 status, hypertension, diabetes mellitus, dyslipidemia, heart disease, chronic obstructive pulmonary disease and smoking habit, using the Normal AT(N) group as the reference category. Results: The study cohort comprised 144 MCI participants: 66 Normal AT(N), 45 Alzheimer AT(N) and 33 SNAP AT(N). Regression analysis showed no significant association of the AT(N) groups with any of the regional macular VD measures (all, p > 0.16). The interaction between sex and AT(N) groups had no effect on differentiating VD. Lastly, CSF Aß1-42, p181-tau and t-tau measures were not correlated to VD (all r < 0.13; p > 0.13). Discussion: Our study showed that macular VD measures were not associated with the AT(N) classification based on CSF biomarkers in patients with MCI, and did not differ between AD and other underlying causes of cognitive decline in our cohort.

Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment.

In the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aß and p-tau-mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neuronal damage is already established and irreversible. Therefore, a differential diagnosis of MCI causes in these prodromal stages is one of the greatest challenges for clinicians. Blood biomarkers are emerging as desirable tools for pre-screening purposes, but the current results are still being analyzed and much more data is needed to be implemented in clinical practice. Because of that, plasma extracellular vesicles (pEVs) are gaining popularity as a new source of biomarkers for the early stages of AD development. To identify an exosome proteomics signature linked to prodromal AD, we performed a cross-sectional study in a cohort of early-onset MCI (EOMCI) patients in which 184 biomarkers were measured in pEVs, cerebrospinal fluid (CSF), and plasma samples using multiplex PEA technology of Olink© proteomics. The obtained results showed that proteins measured in pEVs from EOMCI patients with established amyloidosis correlated with CSF p-tau181 levels, brain ventricle volume changes, brain hyperintensities, and MMSE scores. In addition, the correlations of pEVs proteins with different parameters distinguished between EOMCI Aß( +) and Aß(-) patients, whereas the CSF or plasma proteome did not. In conclusion, our findings suggest that pEVs may be able to provide information regarding the initial amyloidotic changes of AD. Circulating exosomes may acquire a pathological protein signature of AD before raw plasma, becoming potential biomarkers for identifying subjects at the earliest stages of AD development.

Procoagulant phenotype induced by oxidized high-density lipoprotein associates with acute kidney injury and death.

BACKGROUND: Oxidative stress derived from severe systemic inflammation promotes conversion from high-density lipoprotein HDL to oxidized HDL (oxHDL), which interacts with vascular endothelial cells (ECs). OxHDL acquires procoagulant features playing a role in modulating coagulation, which has been linked with organ failure in ICU patients. However, whether oxHDL elicits a ECs-mediated procoagulant phenotype generating organ failure and death, and the underlying molecular mechanism is not known. Therefore, we studied whether oxHDL-treated rats and high-oxHDL ICU patients exhibit a procoagulant phenotype and its association with kidney injury and mortality and the endothelial underlying molecular mechanism. METHODS: Human ECs, oxHDL-treated rats and ICU patients were subjected to several cellular and molecular studies, coagulation analyses, kidney injury assessment and mortality determination. RESULTS: OxHDL-treated ECs showed a procoagulant protein expression reprograming characterized by increased E-/P-selectin and vWF mRNA expression through specific signaling pathways. OxHDL-treated rats exhibited a procoagulant phenotype and modified E-/P-selectin, vWF, TF and t-PA mRNA expression correlating with plasma TF, t-PA and D-dimer. Also, showed increased death events and the relative risk of death, and increased creatinine, urea, BUN/creatinine ratio, KIM-1, NGAL, ß2M, and decreased eGFR, all concordant with kidney injury, correlated with plasma TF, t-PA and D-dimer. ICU patients showed correlation between plasma oxHDL and increased creatinine, cystatin, BUN, BUN/creatinine ratio, KIM-1, NGAL, ß2M, and decreased GFR. Notably, ICU high-oxHDL patients showed decreased survival. Interestingly, altered coagulation factors TF, t-PA and D-dimer correlated with both increased oxHDL levels and kidney injury markers, indicating a connection between these factors. CONCLUSION: Increased circulating oxHDL generates an endothelial-dependent procoagulant phenotype that associates with acute kidney injury and increased risk of death.

The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment.

Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of these two risk factors. AT(N) profiles were created using AD-core biomarkers quantified in cerebrospinal fluid (CSF) (normal, brain amyloidosis, suspected non-Alzheimer pathology (SNAP) and prodromal AD). NPSs were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). A total of 500 individuals with MCI were followed-up yearly in a memory unit. Cox regression analysis was used to determine risk of conversion, considering additive and multiplicative interactions between AT(N) profile and NPSs on the conversion to dementia. A total of 224 participants (44.8%) converted to dementia during the 2-year follow-up study. Pathologic AT(N) groups (brain amyloidosis, prodromal AD and SNAP) and the presence of depression and apathy were associated with a higher risk of conversion to dementia. The additive combination of the AT(N) profile with depression exacerbates the risk of conversion to dementia. A synergic effect of prodromal AD profile with depressive symptoms is evidenced, identifying the most exposed individuals to conversion among MCI patients.

Effectiveness of interventions using apps to improve physical activity, sedentary behavior and diet: An umbrella review.

Technology has been recently found to be an effective tool to deliver public health interventions [1]. More specifically, the effects of interventions using apps to improve health have been targeted lately [2]. The goal of the present study was to conduct a systematic review of systematic reviews to summarize the scientific evidence. Three research questions were formulated to guide the research: RQ1. Are interventions using apps effective to improve PA? RQ2. Are interventions using apps effective to improve sedentary behavior? RQ3. Are interventions using apps effective to improve diet? This review of reviews was registered with PROSPERO (CRD42022345909). Systematic reviews were included following the PICOTS framework (population, intervention, comparator, outcomes, time and setting). In addition, reviews with several research objectives were included only when they comprised more than two-thirds of the studies analyzing one or more of the objectives of this review. As a result, 12 systematic reviews were selected for data extraction. Findings uncovered that apps could be effective to improve individuals' PA, sedentary behavior and diet. However, elements like the intervention components, the context/environment/setting, the length of the intervention or the population targeted should be carefully considered in future studies.

Duplicidad intestinal y diagnóstico diferencial prenatal de lesiones quísticas intraabdominales / Intestinal duplication and prenatal differential diagnosis of intra-abdominal cysts

Resumen ANTECEDENTES: Las duplicaciones del aparato digestivo son una variante poco frecuente de malformación congénita. Si bien la mejora de los equipos de ecografía ha aumentado la tasa diagnóstica, solo el 30% se diagnostican antes del nacimiento. El diagnóstico diferencial de lesiones quísticas intraabdominales es amplio e incluye, por ejemplo, a los quistes de ovario, colédoco, mesenterio o pseudoquistes de meconio. El tratamiento es quirúrgico mediante la resección y restauración de la continuidad intestinal. CASO CLÍNICO: Paciente de 32 años, con un embarazo previo y en el segundo trimestre del actual, con sospecha de un quiste de duplicación intestinal. El estudio genético no evidenció anomalía alguna. La lesión, de morfología quística tubular, fue aumentando progresivamente de tamaño conforme avanzaban las semanas de embarazo. En la semana 39 se indicó, por diabetes gestacional insulinodependiente, la inducción del parto. Nació un varón, asintomático, mediante parto eutócico, sin complicaciones. La ecografía abdominal, resonancia magnética nuclear y estudio del tránsito intestinal del periodo neonatal temprano confirmó el diagnóstico prenatal de sospecha. Mediante una laparoscopia exploradora, a las dos semanas de vida se practicó la resección del defecto que se reportó como: duplicación intestinal ileal, sin comunicación con la luz intestinal. El curso posoperatorio fue favorable. CONCLUSIONES: El diagnóstico prenatal de quistes de duplicación en el aparato digestivo está en aumento debido a la mejoría en las técnicas de diagnóstico prenatal. La valoración multidisciplinaria es decisiva para procurar una adecuada vigilancia médica del embarazo y del recién nacido.

Abstract BACKGROUND: Duplications of the digestive tract are a rare variant of congenital malformation that can occur anywhere in the digestive tract. Although improved ultrasound equipment has increased the diagnostic rate, only 30% are diagnosed before birth. The differential diagnosis of intra-abdominal cystic lesions is broad and includes, for example, cysts of the ovary, common bile duct, mesentery or meconium pseudocysts. Treatment is surgical by resection and restoration of intestinal continuity. CLINICAL CASE: 32-year-old patient, with a previous pregnancy and in the second trimester of the current pregnancy, with suspicion of an intestinal duplication cyst. The genetic study did not reveal any abnormality. The lesion, of tubular cystic morphology, progressively increased in size as the weeks of pregnancy progressed. Induction of labour was indicated in week 39 due to insulin-dependent gestational diabetes. An asymptomatic male was born by euthecological delivery, without complications. Abdominal ultrasound, nuclear magnetic resonance imaging and intestinal transit study of the early neonatal period confirmed the suspected prenatal diagnosis. By means of exploratory laparoscopy, at two weeks of life, resection of the defect was performed, which was reported as: ileal intestinal duplication, without communication with the intestinal lumen. The postoperative course was favourable. CONCLUSIONS: Prenatal diagnosis of duplication cysts in the digestive tract is increasing due to improved prenatal diagnostic techniques. Multidisciplinary assessment is crucial to ensure adequate medical surveillance of the pregnancy and the newborn.

Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring.

Introduction: Gestational hypothyroxinemia (HTX) is a condition that occurs frequently at the beginning of pregnancy, and it correlates with cognitive impairment, autism, and attentional deficit in the offspring. Evidence in animal models suggests that gestational HTX can increase the susceptibility of the offspring to develop strong inflammation in immune-mediated inflammatory diseases. Ulcerative colitis (UC) is a frequent inflammatory bowel disease with unknown causes. Therefore, the intensity of ulcerative colitis-like disorder (UCLD) and the cellular and molecular factors involved in proinflammatory or anti-inflammatory responses were analyzed in the offspring gestated in HTX (HTX-offspring) and compared with the offspring gestated in euthyroidism (Control-offspring). Methods: Gestational HTX was induced by the administration of 2-mercapto-1-methylimidazole in drinking water to pregnant mice during E10-E14. The HTX-offspring were induced with UCLD by the acute administration of dextran sodium sulfate (DSS). The score of UCLD symptomatology was registered every day, and colon histopathology, immune cells, and molecular factors involved in the inflammatory or anti-inflammatory response were analyzed on day 6 of DSS treatment. Results: The HTX-offspring displayed earlier UCLD pathological symptoms compared with the Control-offspring. After 6 days of DSS treatment, the HTX-offspring almost doubled the score of the Control-offspring. The histopathological analyses of the colon samples showed signs of inflammation at the distal and medial colon for both the HTX-offspring and Control-offspring. However, significantly more inflammatory features were detected in the proximal colon of the HTX-offspring induced with UCLD compared with the Control-offspring induced with UCLD. Significantly reduced mRNA contents encoding for protective molecules like glutamate-cysteine ligase catalytic subunit (GCLC) and mucin-2 (MUC-2) were found in the colon of the HTX-offspring as compared with the Control-offspring. Higher percentages of Th17 lymphocytes were detected in the colon tissues of the HTX-offspring induced or not with UCLD as compared with the Control-offspring. Discussion: Gestational HTX accelerates the onset and increases the intensity of UCLD in the offspring. The low expression of MUC-2 and GCLC together with high levels of Th17 Lymphocytes in the colon tissue suggests that the HTX-offspring has molecular and cellular features that favor inflammation and tissue damage. These results are important evidence to be aware of the impact of gestational HTX as a risk factor for UCLD development in offspring.

Motoric performance variation from morning to evening: 80% intensity post-activation potentiation protocol impacts performance and its diurnal amplitude in basketball players.

Introduction: Post-activation potentiation (PAP) can be defined as the acute enhancement in muscle performance after preload stimulation that occurs during strength exercises or warm-up protocols, and the contractile history of any muscle group can directly influence the presented performance. The purpose of this study was to compare the results of motoric performance tests carried out at two different times of the day using three different PAP protocols. Methods: Thirty-two male basketball players with at least 2 years of training experience and who competed at the national level were recruited for this study [age: 21.80 ± 1.91 years; body height: 178.40 ± 6.85 cm; body mass: 72.50 ± 7.16 kg; body mass index (BMI): 22.81 ± 2.28]. After control and experimental-specific warm-up (SWU) sessions, participants completed a countermovement jump (CMJ) and seated medicine ball throw (SMBT). The SWU protocol was developed based on the athlete's typical warm-up routine. The experimental warm-ups included the same exercises as the SWU, with one set of bench presses for five repetitions at 80% (80% PAP) and one repetition at 100% of 1 RM (100% PAP). Each of the protocols consists of 15 min. The SWU and experimental warm-up sessions were completed in a random, counterbalanced order, completed in a period of 3-weeks. Results: According to the research findings, carrying out the protocols in the evening led to a larger improvement in SMBT than in the morning (F = 35.94, p < 0.001, η 2 p = 0.537). Additionally, the SMBT results were statistically more significant in the group that received 80% PAP compared to the SWU (p = 0.034), and the SMBT results were also higher in the group that received 100% PAP compared to the SWU (p = 0.002). Furthermore, the interaction effect (time × PAP) was statistically significant in SMBT (F = 6.39, p = 0.003, η 2 p = 0.17). Discussion: These results may provide more particular recommendations than previously thought to basketball coaches for the planning of basketball-specific PAP exercises prior to the start of training programs.