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Germán Alberto Nolasco-Rosales,1,&ast; Cecilia Yazmin Alonso-García,1,&ast; David Gustavo Hernández-Martínez,1 Mario Villar-Soto,2 José J Martínez-Magaña,3 Alma Delia Genis-Mendoza,4 Thelma Beatriz González-Castro,5 Carlos Alfonso Tovilla-Zarate,6 Crystell Guadalupe Guzmán-Priego,1 Mirian Carolina Martínez-López,1 Humberto Nicolini,7 Isela Esther Juárez-Rojop1 1División Académica de Ciencias de la Salud, Universidad Juarez Autónoma de Tabasco, Villahermosa, Tabasco, México; 2Hospital Regional de Alta Especialidad de Salud Mental, Villahermosa, Tabasco, México; 3Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; 4Hospital Psiquiátrico Infantil “Dr. Juan N. Navarro”, Ciudad de México, México; 5División Académica Multidisciplinaria de Jalpa de Méndez, Universidad Juarez Autónoma de Tabasco, Jalpa de Méndez, Tabasco, México; 6División Académica Multidisciplinaria de Comalcalco, Universidad Juarez Autónoma de Tabasco, Comalcalco, Tabasco, México; 7Departamento de Genética Psiquiátrica, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de México, México&ast;These authors contributed equally to this workCorrespondence: Isela Esther Juárez-Rojop, División Académica de Ciencias de la Salud, Universidad Juarez Autónoma de Tabasco, Av. Gregorio Méndez 2838-A, Col. Tamulté, Villahermosa, 86100, México, Email iselajuarezrojop@hotmail.com Humberto Nicolini, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de México, 86100, México, Email hnicolini@inmegen.gob.mxPurpose: Epigenetic age and inflammatory markers have been proposed as indicators of severity and mortality in patients with COVID-19. Furthermore, they have been associated with the occurrence of neurological symptoms, psychiatric manifestations, and cognitive impairment. Therefore, we aimed to explore the possible associations between epigenetic age, neuropsychiatric manifestations and inflammatory markers (neutrophil-lymphocyte ratio [NLR], platelet-lymphocyte ratio [PLR], monocyte-lymphocyte ratio [MLR], and systemic immune-inflammation index [SII]) in healthcare personnel with post-COVID condition.Patients and Methods: We applied the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) tests to 51 Mexican healthcare workers with post-COVID-19 condition; we also estimated their epigenetic age using the PhenoAge calculator.Results: The participants had a post-COVID condition that lasted a median of 14 months (range: 1– 20). High NLR (> 1.73) had association with mild cognitive impairment by MMSE (p=0.013). Likewise, high MLR (> 0.24) were associated with language domain in MOCA (p=0.046). Low PLR (< 103.9) was also related to delayed recall in MOCA (p=0.040). Regarding comorbidities, hypertension was associated with SII (p=0.007), overweight with PLR (p=0.047) and alcoholism was associated with MLR (p=0.043). Interestingly, we observed associations of low PLR (< 103.9) and low SII (< 1.35) levels with increased duration of post-COVID condition (p=0.027, p=0.031). Likewise, increases in PhenoAge were associated with high levels of SII (OR=1.11, p=0.049), PLR (OR=1.12, p=0.035) and MLR (OR=1.12, p=0.030).Conclusion: We observed neurocognitive changes related to inflammatory markers and increases in epigenetic age in healthcare personnel with post-COVID-19 condition. Future research is required to assess mental and physical health in individuals with post-COVID-19 symptoms.Keywords: post-COVID-19, cognitive manifestation, inflammatory markers, epigenetic age

Background/aimsBipolar disorder (BP) is a severe psychiatric illness, characterised by alternating episodes of depression and mania, which ranks among the top ten causes of morbidity and life-long disability world-wide. We have previously performed a whole-genome linkage scan on 6 pedigrees segregating severe BP from the well-characterised population isolate of Antioquia, Colombia. We recently collected genotypes for the same set of 382 autosomal microsatellite markers in 9 additional Antioquian BP pedigrees. Here, we report the analysis of the combined pedigree set.MethodsLinkage analysis using both parametric and nonparametric approaches was conducted for 3 different diagnostic models: severe BP only (BPI); mood disorders (BPI, BPII and major depression); and psychosis (operationally defined by the occurrence of at least 1 episode of hallucinations and/or delusions).Results and conclusionFor BPI only, the most interesting result was obtained for chromosome 7p21.1-p22.2 under a recessive model of inheritance (heterogeneity LOD score = 2.80), a region that had previously been linked to BP in a study on Portuguese Island families. For both BPI and mood disorders, nonparametric analyses identified a locus on chromosome 12ct-q14 (nonparametric linkage = 2.55 and 2.35, respectively). This locus has not previously been reported as a candidate region for BP. Additional candidate regions were found on chromosomes 1p22-31 (mood disorders) and 21q21-22 (BPI), 2 loci that have repeatedly been implicated in BP susceptibility. Linkage analysis of psychosis as a phenotype identified candidate regions on chromosomes 2q24-31 and 16p12-q12. The finding on chromosome 16p is noteworthy because the same locus has been implicated by genome-wide association analyses of BP.

Objective: To determine the prevalence of subclinical hypothyroidism in the general population of an urban health center and describe the clinical characteristics and cardiovascular risk factors in patients with subclinical hypothyroidism. Methods: An observational study, retrospective, reviewing the medical histories of patients sampled from June 2005 until July 2007. We analyzed the following variables; facts: age and sex. Family history thyroid disease and other diseases. Personal history: cardiovascular pulmonary autoimmune, alterations gynecology obstetric diabetes, hypertension (HT) dislipemia, obesity, psychiatric alterations and haematological. Laboratory data: novel TSH, free T4, antiperoxidase antibodies, total cholesterol and its fractions. Results: The prevalence of the sample of 100 patients collected over 8 months was 3.8% in the general population over 14 years, of which 79 were women and 21 were men. 13% were type 2 diabetics, 23% had HT and 40% had dyslipidemia. Overweight and obesity were present in 26%. The average level of TSH was 6.92 ± 2.29 [mu]U/ml and the average level of free T4 was 1.16 ± 0.16 ng/ml. Conclusions: Prevalence subclinical hypothyroidism was 3.8%. especially in women with a mean age of 46. The incidence of cardiovascular risk factors in the subjects studied is higher in DM (13%), similar to general population in terms of dyslipidemia (40%) and obesity (23%) and lowest in hypertension (23%). In our study we observed a common pattern in the management of subclinical hypothyroidism, requiring the implementation and promotion of practice guidelines in primary care. [ABSTRACT FROM AUTHOR]

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Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of methylxanthines in preventing or treating intermittent hypoxemia or respiratory insufficiency in late preterm infants., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background and Aims: Somatic mutations in the TET2 gene that lead to clonal haematopoiesis (CH) are associated with accelerated atherosclerosis development in mice and a higher risk of atherosclerotic disease in humans. Mechanistically, these observations have been linked to exacerbated vascular inflammation. This study aimed to evaluate whether colchicine, a widely available and inexpensive anti-inflammatory drug, prevents the accelerated atherosclerosis associated with TET2-mutant CH., Methods: In mice, TET2-mutant CH was modelled using bone marrow transplantations in atherosclerosis-prone Ldlr-/- mice. Haematopoietic chimeras carrying initially 10% Tet2-/- haematopoietic cells were fed a high-cholesterol diet and treated with colchicine or placebo. In humans, whole-exome sequencing data and clinical data from 37 181 participants in the Mass General Brigham Biobank and 437 236 participants in the UK Biobank were analysed to examine the potential modifying effect of colchicine prescription on the relationship between CH and myocardial infarction., Results: Colchicine prevented accelerated atherosclerosis development in the mouse model of TET2-mutant CH, in parallel with suppression of interleukin-1β overproduction in conditions of TET2 loss of function. In humans, patients who were prescribed colchicine had attenuated associations between TET2 mutations and myocardial infarction. This interaction was not observed for other mutated genes., Conclusions: These results highlight the potential value of colchicine to mitigate the higher cardiovascular risk of carriers of somatic TET2 mutations in blood cells. These observations set the basis for the development of clinical trials that evaluate the efficacy of precision medicine approaches tailored to the effects of specific mutations linked to CH., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Sucralose stands as the most common non-nutritive sweetener; however, its metabolic effects have sparked significant controversy over the years. We aim to examine the effects of sucralose daily intake on glycemia, subjective appetite, and gut microbiota (GM) changes in subjects with overweight or obesity. In this randomized, crossover, and controlled trial, 23 participants with a body mass index between 25 kg/m 2 and 39.9 kg/m 2 will be assigned to one of two interventions to receive either sucralose (2 mg/kg/day equivalent to 40% of the acceptable daily intake) or glucose (control) for 4 weeks, each phase separated by a 4-week washout period. The glycemic response will be determined during a meal tolerance test, subjective appetite will be evaluated using a visual analog scale, and GM changes will be analyzed by next-generation sequencing of the bacterial rRNA 16S gene from fecal samples. All measures will be performed before and after intervention periods. We hypothesize that sucralose supplementation induces changes in glycemic response, subjective appetite, and gut microbiota in overweight and obese participants. This protocol was approved by the Ethics Committee of the UJAT (No. 0721) and was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12621001531808).

Chagas disease is caused by the parasite Trypanosoma cruzi and affects over 7 million people worldwide. The two actual treatments, Benznidazole (Bzn) and Nifurtimox, cause serious side effects due to their high toxicity leading to treatment abandonment by the patients. In this work, we propose DNA G-quadruplexes (G4) as potential therapeutic targets for this infectious disease. We have found 174 PQS per 100,000 nucleotides in the genome of T. cruzi and confirmed G4 formation of three frequent motifs. We synthesized a family of 14 quadruplex ligands based in the dithienylethene (DTE) scaffold and demonstrated their binding to these identified G4 sequences. Several DTE derivatives exhibited micromolar activity against epimastigotes of four different strains of T. cruzi, in the same concentration range as Bzn. Compounds L3 and L4 presented remarkable activity against trypomastigotes, the active form in blood, of T. cruzi SOL strain (IC 50  = 1.5-3.3 μM, SI = 25-40.9), being around 40 times more active than Bzn and displaying much better selectivity indexes., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The increase in fertilizer prices was 20% after the pandemic, which increased the cost of crop production in Peru. For this reason, research was conducted on the analysis of the chemical and biological characteristics and their relationship with the yield of radish nourished with compost based on plant residues. The objective was to analyze the chemical and biological characteristics and their relationship with the yield of radish nourished with vegetable waste-based compost. It is based on the methodology applied with an experimental approach; therefore, the statistical model of the Completely Randomized Block Design was used, which consisted of 3 blocks and 5 treatments that were T1 with 0, T2 with 4, T3 with 6, T4 with 8 and T5 with 10 t/ha of compost based on vegetable residues, and the doses were applied 14 days after sowing. Physical characteristics (total plant length, plant weight, bulb equatorial diameter and marketable yield), nutrient concentrations (nitrogen, potassium, phosphorus, calcium, magnesium, sulfur, molybdenum, iron, manganese, copper, zinc, boron, chlorides and sodium) in leaves and stomata density were evaluated. The results determined that T5 stood out in total plant length with 28.07 cm, plant weight with 75 g, bulb equatorial diameter with 4.52 cm and commercial yield with 22.53 t/ha. In the total contribution of nitrogen in relation to yield with 300.44 kg/ha. Profitability with 186.8%. Quantification of stomata per treatment with 598 stomata/mm2 and concentration of nutrients in leaves at T3 with nitrogen, potassium, phosphorus and magnesium. It concludes that T5, which has an adequate concentration of nutrients in leaves such as magnesium, manganese, zinc and stomata density of 598 stomata/mm2 influenced optimal biochemical reactions that resulted in the highest yield with 22.53 t/ha, differing by 31.38% in relation to T1.

Surface-enhanced Raman scattering (SERS) is a powerful technique primarily due to its high sensitivity and signal-enhancing properties, which enable the identification of unique vibrational fingerprints. These fingerprints can be used for the diagnosis and monitoring of diseases such as cancer. It is crucial to selectively identify cancer biomarkers for early diagnosis. A correlation has been established between the reduction in the concentration of specific amino acids and the stage of the disease, particularly tryptophan (TPP) and tyrosine (TRS) in individuals diagnosed with prostate cancer. In this work, we present a strategy to analyze TPP and TRS amino acids using molecularly imprinted polymer nanoparticles (nanoMIPs), which selectively detect target molecules in a SERS sensor. NanoMIPs are synthesized using the solid-phase molecular imprinting method with TPP and TRS as templates. These are then immobilized on a SERS substrate with gold nanoparticles to measure samples prepared from tryptophan and tyrosine in phosphate-buffered saline. The detection and quantification limits of the designed sensor are 7.13 μM and 23.75 μM for TPP, and 22.11 μM and 73.72 μM for TRS, respectively. Our study lays the groundwork for future investigations utilizing nanoMIPs in SERS assessments of TPP and TRS as potential biomarkers for prostate cancer detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Here we investigate infectious diseases that potentially contribute to osteological lesions in individuals from the early medieval necropolis of La Olmeda (6th-11th c. CE) in North Iberia., Materials and Methods: We studied a minimum number of 268 individuals (33 adult females; 38 adult males, 77 unknown/indeterminate sex; and 120 non-adults), including articulated and commingled remains. Individuals with differential diagnoses suggesting chronic systemic infectious diseases were sampled and bioinformatically screened for ancient pathogen DNA., Results: Five non-adults (and no adults) presented skeletal evidence of chronic systemic infectious disease (1.87% of the population; 4.67% of non-adults). The preferred diagnoses for these individuals included tuberculosis, brucellosis, and malaria. Ancient DNA fragments assigned to the malaria-causing pathogen, Plasmodium spp., were identified in three of the five individuals. Observed pathology includes lesions generally consistent with malaria; however, additional lesions in two of the individuals may represent hitherto unknown variation in the skeletal manifestation of this disease or co-infection with tuberculosis or brucellosis. Additionally, spondylolysis was observed in one individual with skeletal lesions suggestive of infectious disease., Conclusions: This study sheds light on the pathological landscape in Iberia during a time of great social, demographic, and environmental change. Genetic evidence challenges the hypothesis that malaria was absent from early medieval Iberia and demonstrates the value of combining osteological and archaeogenetic methods. Additionally, all of the preferred infectious diagnoses for the individuals included in this study (malaria, tuberculosis, and brucellosis) could have contributed to the febrile cases described in historical sources from this time., (© 2024 The Author(s). American Journal of Biological Anthropology published by Wiley Periodicals LLC.)

Biomarkers play a pivotal role in the screening, diagnosis, prevention, and post-treatment follow-up of various malignant tumors. In certain instances, identifying these markers necessitates prior treatment due to the complex nature of the tumor microenvironment. Consequently, advancing techniques that exhibit selectivity, specificity, and enable streamlined analysis hold significant importance. Molecularly imprinted polymers (MIPs) are considered synthetic antibodies because they possess the property of molecular recognition with high selectivity and sensitivity. In recent years, there has been a notable surge in the investigation of these materials, primarily driven by their remarkable adaptability in terms of tailoring them for specific target molecules and integrating them into diverse analytical technologies. This review presents a comprehensive analysis of molecular imprinting techniques, highlighting their application in developing sensors and analytical methods for cancer detection, diagnosis, and monitoring. Therefore, MIPs offer great potential in oncology and show promise for improving the accuracy of cancer screening and diagnosis procedures.

Chagas disease, caused by the parasite Trypanosoma cruzi, affects over 6 million people, mainly in Latin America. Two different clinical phases, acute and chronic, are recognised. Currently, 2 anti-parasitic drugs are available to treat the disease (nifurtimox and benznidazole), but diagnostic methods require of a relatively complex infrastructure and trained personnel, limiting its widespread use in endemic areas, and the access of patients to treatment. New diagnostic methods, such as rapid tests (RDTs) to diagnose chronic Chagas disease, or loop-mediated isothermal amplification (LAMP), to detect acute infections, represent valuable alternatives, but the parasite's remarkable genetic diversity might make its implementation difficult. Furthermore, determining the efficacy of Chagas disease treatment is complicated, given the slow reversion of serological anti-T. cruzi antibody reactivity, which may even take decades to occur. New biomarkers to evaluate early therapeutic efficacy, as well as diagnostic tests able to detect the wide variety of circulating genotypes, are therefore, urgently required. To carry out studies that address these needs, high-quality and traceable samples from T. cruzi-infected individuals with different geographical backgrounds, along with associated clinical and epidemiological data, are necessary. This work describes the framework for the creation of such repositories, following standardised and uniform protocols, and considering the ethical, technical, and logistic aspects of the process. The manual can be adapted according to the resources of each laboratory, to guarantee that samples are obtained in a reproducible way, favouring the exchange of data among different work groups, and their generalizable evaluation and analysis. The main objective of this is to accelerate the development of new diagnostic methods and the identification of biomarkers for Chagas disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Martínez-Peinado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease frequently accompanied by malnutrition due to weight loss, increased energy expenditure, and muscle mass loss. This study aimed to evaluate morphofunctional assessment tools as predictors of malnutrition and to investigate their relationship with muscle status and disease severity in ALS patients. A cross-sectional study was conducted with 45 ALS patients at the San Cecilio University Hospital in Granada. Malnutrition was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Morphofunctional assessment was performed using Bioimpedance Vectorial Analysis (BIVA), handgrip strength (HGS), and Short Physical Performance Battery (SPPB). Malnutrition prevalence was 38% according to GLIM criteria. Significant differences were observed between malnourished and non-malnourished groups in age (70 ± 9 vs. 62 ± 10 years, p = 0.01), sex (female prevalence: 58.8% vs. 25.0%, p = 0.02), dysphagia prevalence (83% vs. 29%, p < 0.001), PEG/PRG use (35.3% vs. 3.6%, p = 0.01), and ALSFRS-R scores (30 ± 12 vs. 34 ± 12, p = 0.02). Malnourished patients had lower values in anthropometric measurements, muscle mass obtained by BIVA, and phase angle (PA) (4.05 ± 0.8° vs. 5.09 ± 0.8°, p < 0.001). No significant differences were found in muscle strength or functional status. PA showed significant correlations with muscle strength (r = 0.52, p < 0.001) and muscle mass measures (r = 0.48, p < 0.001). Moreover, PA was associated with poorer disease progression and physical performance. In our sample, BIVA metrics such as PA (<4.3°), SPA (<-0.8), body cell mass (<9.2 kg/m), and extracellular water (>49.75%) were identified as malnutrition risk factors. The study underscores the critical importance of comprehensive morphofunctional assessment and the use of advanced diagnostic criteria, for early identification and intervention in malnutrition among people with ALS. Further research is warranted to validate these findings and develop targeted nutritional strategies into routine clinical practice.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included.  Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Chagas disease, caused by the Trypanosoma cruzi parasite infection, is a potentially life-threatening neglected tropical disease with a worldwide distribution. During the chronic phase of the disease, there exists a fragile balance between the host immune response and parasite replication that keeps patients in a clinically-silent asymptomatic stage for years or even decades. However, in 40% of patients, the disease progresses to clinical manifestations mainly affecting and compromising the cardiac system. Treatment is recommended in the chronic phase, although there are no early markers of its effectiveness. The aim of this study is to identify differential expression changes in genes involved in the immune response in antigen-restimulated PBMC from chronic patients with Chagas disease due to benznidazole treatment., Methods: Thus, high-throughput real-time qPCR analysis has been performed to simultaneously determine global changes in the expression of 106 genes involved in the immune response in asymptomatic (IND) and early cardiac manifestations (CCC I) Chagas disease patients pre- and post-treatment with benznidazole., Results and Discussion: The results revealed that 7 out of the 106 analyzed genes were differentially expressed (4 up- and 3 downregulated) after treatment in IND patients and 15 out of 106 (3 up- and 12 downregulated) after treatment of early cardiac Chagas disease patients. Particularly in CCC I patients, regulation of the expression level of some of these genes towards a level similar to that of healthy subjects suggests a beneficial effect of treatment and supports recommendation of benznidazole administration to early cardiac Chagas disease patients. The data obtained also demonstrated that both in asymptomatic patients and in early cardiac chronic patients, after treatment with benznidazole there is a negative regulation of the proinflammatory and cytotoxic responses triggered as a consequence of T. cruzi infection and the persistence of the parasite. This downregulation of the immune response likely prevents marked tissue damage and healing in early cardiac patients, suggesting its positive effect in controlling the pathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gómez, Egui, Palacios, Carrilero, Benítez, Simón, Segovia, Carmelo, López and Thomas.)

With the increased life expectancy of people with cystic fibrosis (CF), clinical attention has focused on prevention and treatment of non-pulmonary comorbidities. CF-related bone disease (CFBD) is a common complication and leads to increased fracture rates. Dual energy X-ray absorptiometry (DXA) is the recommended and gold standard technique to identify and monitor bone health. However, DXA has limitations because of its two-dimensional nature. Complementary tools to DXA are available, such as trabecular bone score (TBS) and vertebral fracture assessment (VFA). Quantitative computed tomography (QCT), magnetic resonance imaging (MRI) and quantitative ultrasound (QUS) may also be useful., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

This study aimed to evaluate the effect of early time-restricted eating (eTRE) on metabolic markers and body composition in individuals with overweight or obesity. Seventeen subjects completed a randomized, crossover, and controlled clinical trial. Twelve women and five men participated, with a mean age of 25.8 ± 10.0 years and a BMI of 32.0 ± 6.3 kg/m 2 . The eTRE intervention included 16 h of fasting (3:00 pm to 7:00 am) and 8 h of ad libitum eating (7:00 am to 03:00 pm) (16:8). The trial included four weeks of interventions followed by a four-week washout period. Body weight, waist and hip circumferences, and body composition measurements were taken. Additionally, a venous blood sample was collected for biochemical determinations. In a before-after analysis, eTRE induced a reduction in BW and BMI in women but this was not significant when compared to the control group. eTRE did not modify any other anthropometric measurements, fasting biochemical parameters, glycemic and insulinemic responses, blood pressure, or subjective appetite. In conclusion, eTRE did not induce beneficial effects on the glycemic and lipid metabolisms, body composition, subjective appetite, or blood pressure. These findings may be attributed to the special characteristics of the population and the short intervention period.