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Cervical cancer is a significant public health issue in Mexico and many developing countries. Early detection is crucial for combating this disease. The official screening test for cervical cancer is cytology, but this technique faces several barriers, including methodological, educational, and sociocultural challenges. Liquid-based cytology is an improved version of this test, however it does not address the aforementioned complications. Biomarkers for cervical precursor lesions and cervical cancer can improve timely detection of the disease. A previous study from our group identified four circulating human proteins as potential biomarkers for these conditions. For molecular screening, we selected GAPDH as the biomarker for cervical precursor lesions and HNRNPA1 as the biomarker for cervical cancer -chosen from the three previously identified options based on antibody availability- to be detected in sera. Participants underwent a comprehensive panel of tests, including liquid-based cytology, PCR detection of Human papillomavirus (HPV), colposcopy, and histopathology -when applicable-. The last two tests were used as references for determining sensitivity and specificity, with histopathology being the gold standard for cervical cancer diagnosis. All the participants successfully received colposcopies (n = 99) and only those women with visible or suspected cervical lesions/malignancies were biopsied (n = 62). A subset of randomly selected biopsies underwent p16INK4a immunohistochemistry (n = 36). This study compares the performance of liquid-based cytology with the molecular screening. With colposcopy as reference, liquid-based cytology showed 30% sensitivity and 96% specificity, while the molecular screening showed 90% sensitivity and 43% specificity. With histopathology as reference, liquid-based cytology showed 21% sensitivity and 93% specificity, while the molecular screening showed 85% sensitivity and 61% specificity. The molecular screening outperformed the liquid-based cytology in several areas, including detecting true-positive cases, reducing false-negative cases by 34.62%, application time, simplicity of result´s categories, and acceptance among participants. An ideal screening test requires high sensitivity, maintains moderate specificity, and minimizes false negatives. Our proposed screening test meets these criteria, making it an ideal complement -or alternative- for cervical cancer screening.

BackgroundLiver transplantation (LT) improves survival in end-stage liver disease. Several reports have addressed the impact of LT on patients’ lives, beyond purely medical outcomes. Although the quality of life and mental health have been demonstrated to improve with this procedure, such studies are still missing in Latin America.MethodsPatients who received LT at the Fundación Santa Fe de Bogotá between 2017 and 2019 were assessed for quality of life (QoL), anxiety, and depression and they were followed up for one year after the procedure. Pre-transplant data were gathered at inclusion on the waiting list, while post-transplant data at 3- and 12 months after LT. European Quality of Life-5 Dimensions (EQ-5D) and European Quality of Life-Visual Analog Scale (EQ-VAS) instruments were used to evaluate QoL. The Hospital Anxiety and Depression Scale (HADS) was used for evaluating anxious and depressive symptoms.Results115 recipients met the inclusion criteria. Mean pre-transplant EQ-VAS was 70.78, rising to 87.16 and 92.56 at 3- and 12-months, respectively. Improvements in all EQ-5D dimensions were found in response to LT. According to the HADS questionnaire, anxiety was reduced by 2.35 points and depression by 1.63 points after LT.Conclusionin the short term, LT is a successful strategy for enhancing QoL, anxiety, and depression in patients with liver disease. Long-term benefits must be assessed.

POCOP-Ni(II) pincer compounds have primarily been explored as catalysts, but their potential biological activity has been scarcely studied. To address this gap, we evaluated the anticancer and antioxidant potential of four POCOP-Ni(II) complexes derived from phloroglucinol. A comprehensive supramolecular analysis, based on single-crystal X-ray diffraction (DRX) structures, was conducted using Hirshfeld surfaces and non-covalent interaction analysis. The cytotoxicity of all complexes was systematically assessed against various cancerous cell lines, as well as a non-cancerous cell line (COS-7). The results revealed that complexes 1b and 1c exhibited remarkable antiproliferative activity, with IC50 values ranging from 2.43 to 7.85 μM against cancerous cell lines U251, K562, HCT-15, MCF-7, and SK-LU-1. To further elucidate their mechanism of action, a competitive fluorescence displacement assay with ethidium bromide (EB) suggested that these complexes possess the ability to intercalate with DNA. This multifaceted investigation not only enhances our understanding of the biological potential of POCOP-Ni complexes but also provides valuable insights into their structural features and interactions, paving the way for future exploration in both catalytic and therapeutic domains.

IntroductionImplementing sex education programs during adolescence is crucial for addressing the risks associated with sexuality. However, some of these interventions lack proper incorporation of a gender perspective and maintain a heteronormative and biologically-focused approach, potentially resulting in inequitable outcomes for adolescents. In response, comprehensive sex education is most effective due to its multidimensional view of sexuality. However, integrating a comprehensive perspective on sexuality and a gender lens that contributes to adolescent health equity presents challenges, especially in low and middle-income countries. This study aimed to develop a comprehensive and gender-transformative sex education program for adolescents in a middle-income country of Latin America, utilizing the Intervention Mapping Approach.MethodsThis exploratory sequential mixed-method study comprised two phases. In the first phase, a literature review, nine focus groups with high school students, and 14 interviews with school professionals were conducted to inform program design. Subsequently, the program underwent validation through expert judgment. In the second phase—as part of program development—a preliminary evaluation was conducted by implementing the program in two high schools with 30 students from public high schools, who were administered a pre-post ad hoc survey.ResultsA comprehensive and gender-transformative sex education program was designed based on literature review findings and input from students and school workers. The ad hoc survey revealed a statistically significant increase in protective skills in sexuality (W = 59, p = .01) among all participants.DiscussionDesigning a sex education intervention through Intervention Mapping allowed for the integration of evidence and the needs of the target population. The results of the preliminary evaluation suggest the potential of the developed program to enhance protective skills in sexuality and promote health equity through gender-equitable outcomes in adolescent sex education.

This article presents a method for contextualizing school education and initial teacher training, using the case of Mapuche in schools in central-southern Chile to change the ambivalence of teaching in an indigenous context. The analysis is based on a dispositionalist-contextualist theoretical framework and the results of empirical research projects on Mapuche socio-educational knowledge. It examines the co-construction of intercultural knowledge by researchers and parents. It concludes with a Mapuche educational knowledge base that can contextualize the school curriculum and teacher training plans.

Outer membrane vesicles (OMVs) are spherical structures that contain a small fraction of the periplasm of Gram-negative bacteria, surrounded by its outer membrane. They are naturally produced and detached from the bacterial surface, participate in diverse biological processes, and their diameter size is in the range of 10–300 nm. OMVs have gained interest in different applications, such as the development of biosensors, vaccines, protein chips, and the encapsulation of heterologous proteins and peptides expressed by these microorganisms. However, the use of OMVs in these applications is limited due to the low yields and high purification costs. In this study, we produced green fluorescent protein (GFP) encapsulated into OMVs using Escherichia coli JC8031 transformed with pTRC99A-ssTorA-GFP to establish the production and purification route. Results showed that the motility of the strain prevents its immobilization in alginate, which hampers the purification of OMVs. To address this issue, a zeolite-based column was used to chromatographically separate the OMVs from smaller particles. Further experiments will be focused on standardizing the production and purification of OMVs at a scalable level.

The formation of pathogenic multispecies biofilms in the human oral cavity can lead to implant-associated infections, which may ultimately result in implant failure. These infections are neither easily detected nor readily treated. Due to high complexity of oral biofilms, detailed mechanisms of the bacterial dysbiotic shift are not yet even fully understood. In order to study oral biofilms in more detail and develop prevention strategies to fight implant-associated infections, in vitro biofilm models are sorely needed. In this study, we adapted an in vitro biofilm flow chamber model to include miniaturized transparent 3D-printed flow chambers with integrated optical pH sensors – thereby enabling the microscopic evaluation of biofilm growth as well as the monitoring of acidification in close proximity. Two different 3D printing materials were initially characterized with respect to their biocompatibility and surface topography. The functionality of the optically accessible miniaturized flow chambers was then tested using five-species biofilms (featuring the species Streptococcus oralis, Veillonella dispar, Actinomyces naeslundii, Fusobacterium nucleatum, and Porphyromonas gingivalis) and compared to biofilm growth on titanium specimens in the established flow chamber model. As confirmed by live/dead staining and fluorescence in situ hybridization via confocal laser scanning microscopy, the flow chamber setup proved to be suitable for growing reproducible oral biofilms under flow conditions while continuously monitoring biofilm pH. Therefore, the system is suitable for future research use with respect to biofilm dysbiosis and also has great potential for further parallelization and adaptation to achieve higher throughput as well as include additional optical sensors or sample materials.

IntroductionHemorrhage remains the leading cause of preventable death on the battlefield. The most effective means to increase survivability is early hemorrhage control and fluid resuscitation. Unfortunately, fluid resuscitation requires constant adjustments to ensure casualty is properly managed, which is often not feasible in the pre-hospital setting. In this study, we showed how an adaptive closed-loop controller for hemorrhage resuscitation can be used to automate hemodynamic management using a swine hemorrhagic shock injury model.MethodsThe adaptive resuscitation controller (ARC) was previously developed to track pressure–volume responsiveness in real time and adjust its infusion rate to reach the target mean arterial pressure (MAP). Swine while maintained under a surgical plane of anesthesia and analgesia underwent a splenectomy, followed by two hemorrhage and resuscitation events. For the first resuscitation event, hemorrhage was induced to reduce the MAP to 35 mmHg until arterial lactate reached 4 mmol/L. The ARC system then infused whole blood (WB) to reach the target MAP and maintained the subject using crystalloids for 120 min. For the second resuscitation event, the subjects were hemorrhaged again but resuscitated using only crystalloid infusion to reach the target MAP and 120-min maintenance.ResultsThe ARC was effective at WB resuscitation, reaching the target MAP in 2.0 ± 1.0 min. The median performance error was 1.1% ± 4.6%, and target overshoot was 14.4% ± 7.0% of the target MAP. The ARC maintained all animals throughout the 120 min maintenance period. For the second crystalloid-based resuscitation, ARC required a longer time to reach the target MAP, at an average rise time of 4.3 ± 4.0 min. However, target overshoot was reduced to 8.4% ± 7.3% of the target MAP. Much higher flow rates were required to maintain the target MAP during the second resuscitation event than during the first resuscitation event.DiscussionThe ARC was able to rapidly reach and maintain the target MAP effectively. However, this sometimes required large volumes of fluid as the ARC’s only goal was to reach the target MAP. Further clinical insight is needed regarding the preferred aggression level to achieve the target MAP. In conclusion, the ARC was successful in its programmed objective of reaching and maintaining the target MAP for extended periods of time in vivo, a critical next step toward improving hemorrhage treatment in the pre-hospital environment.

Impaired mitochondrial function has been associated with the onset of neurodegenerative diseases. Specifically, certain mitochondrial toxins, such as 3-nitropropionic acid (3-NP), initiate cellular changes within the striatum that closely resemble the pathology observed in Huntington’s disease (HD). Among the pivotal signaling molecules contributing to neurodegeneration, cyclin-dependent kinase 5 (Cdk5) stands out. In particular, Cdk5 has been implicated not only in cellular pathology but also in the modulation of synaptic plasticity. Given its widespread presence in the striatum, this study seeks to elucidate the potential role of Cdk5 in the induction of corticostriatal synaptic plasticity in murine striatal cells subjected to subchronic doses of 3-NP in vivo, aiming to mimic the early stages of HD. Immunostaining analyses revealed an increase in Cdk5 in tissues from animals treated with 3-NP, without a significant change in protein levels. Regarding striatal plasticity, long-term depression (LTD) was induced in both control and 3-NP cells when recorded in voltage clamp mode. The Cdk5 inhibitor roscovitine-reduced LTD in most cells. A minority subset of cells exhibited long-term potentiation (LTP) generation in the presence of roscovitine. The inhibitor of D1 receptors SCH23390 prevented LTP in three of nine cells, implying that MSN cells lacking D1/PKA activation were capable of LTP induction when Cdk5 was also blocked. Nevertheless, the co-administration of H89, a PKA inhibitor, along with roscovitine, prevented the generation of any type of plasticity in all recorded cells. These findings show the impact of 3-NP treatment on striatal plasticity and suggest that Cdk5 during early neurodegeneration may attenuate signaling pathways that lead neurons to increase their activity.

ObjectivesTo investigate the factors influencing medication errors made by informal caregivers while providing care at home.MethodsA cross-sectional study based on an online survey, which included both structured and open-ended questions, was conducted in Spain. The survey comprised 49 questions to collect self-reported avoidable medication errors made by caregivers at home.ResultsA total of 685 caregivers participated in the survey, with 346 considered qualified (having received >20 h of training). On average, 13.5 (SD 38.2, 95% CI 10.5–16.5) errors per caregiver per year were self-reported. Errors were more prevalent among non-qualified caregivers, males, direct relatives of the care recipient, those with external occupations, or those who used external aids.ConclusionErrors made by informal caregivers occur more frequently than expected, and recognizing these errors remains a challenge. Training is essential for creating safer care environments by increasing awareness of error sources and the risks associated with medication. Recipients’ direct relatives should receive appropriate training, considering differences between male and female caregivers. Associations and companies within the care economy sector should prioritize the creation of safer home care environments as a key objective.

BackgroundMetformin is the first-line antidiabetic therapy for type 2 diabetes in Mexico, despite recent recommendations highlighting alternatives like GLP-1 receptor agonists for individuals with obesity. Metformin elimination is reliant on liver and kidney function, and variants in transport proteins such as Multidrug and Toxin Extrusion Protein 1 (MATE1), MATE2, and Organic Cation Transporter 2 (OCT2) can influence its pharmacokinetics. Understanding these variants’ frequencies in the Mexican population is crucial for tailoring personalized treatment strategies.ObjectiveThis study aimed to determine the genotypic and allelic frequencies of key variants in metformin transporters within a Mexican population, addressing the interindividual variability in drug response.MethodologyGenetic analysis was conducted on 101 healthy, unrelated Mexican subjects who were genotyped for the MATE1, MATE2, and OCT2 variants using allele-specific real-time PCR assays.ResultsThe allele frequencies were 0.07 for OCT2, 0.23 for MATE1, and 0.67 for MATE2. The g.–66T→C variant was found only in wild-type and heterozygous forms. Comparative analysis indicated significant differences in allele frequencies between this Mexican population and other ethnic groups, highlighting potential implications for metformin efficacy and safety.ConclusionThis study provides crucial insights into the genetic variability of metformin transporter genes in a Mexican population, offering a foundation for personalized therapeutic approaches in type 2 diabetes management.

IntroductionCOVID-19-associated acute respiratory distress syndrome (CARDS) poses significant challenges in resource-limited settings. This case series explores the role of bronchoscopy and molecular techniques in identifying superimposed infections in CARDS patients during the second wave of the pandemic in Ecuador.MethodsNine critically ill CARDS patients underwent bronchoscopy and molecular testing to detect co-infections and superinfections. Clinical presentations, diagnostic findings, and outcomes were analyzed.ResultsBronchoscopy and molecular techniques identified a range of secondary infections, including multidrug-resistant pathogens such as Acinetobacter baumannii and Klebsiella pneumoniae. The case series highlights the complexities of managing severe COVID-19 cases in resource-constrained environments.DiscussionEarly identification of microorganisms using PCR methods allows for rapid and accurate diagnosis, facilitating targeted management of critically ill CARDS patients. The study underscores the importance of advanced diagnostic tools and adaptable strategies in pandemic situations, particularly in low-resource settings.

IntroductionThis study aims to estimate the validity and reliability of sound transmission tests using a tuning fork and stethoscope compared with the usual clinical procedures for the diagnosis of developmental dysplasia of the hip in newborns from the state of Guanajuato, Mexico.MethodologyThis is a cross-sectional study of newborns at the Guanajuato General Hospital of the Institute of Public Health from Guanajuato. The population under study comprised newborns born from April to May 2023. All parents of newborns were invited to participate. The Ortolani, Barlow, Peter–Baden, and sound transmission tests were performed with a tuning fork and stethoscope three times by two observers. Ultrasonography using the Graf technique was also applied to both hips. We evaluated the validity and repeatability of clinical procedures and sound transmission tests against ultrasonography as the gold standard. We calculated sensitivity, specificity, and predictive values for validity and Cohen's kappa for repeatability.ResultsThe sample consisted of 100 newborns (56% male and 44% female); 65% born by vaginal delivery. Sound transmission test results for sensitivity, specificity, the positive predictive value, and the negative predictive value were 87.88%, 95.81%, 80%, and 97.53%, respectively. The intra-observer kappa was 0.89 (95% CI = 0.80–0.97) and the inter-observer kappa was 0.85 (95% CI = 0.73–0.97). The validity and repeatability of the Ortolani, Barlow, and Peter–Baden tests were low compared with the sound transmission test.ConclusionThe sound transmission test using a tuning fork and stethoscope is helpful for the diagnosis of developmental dysplasia of the hip.

Croton guatemalensis Lotsy (Euphorbiaceae) is an important traditional medicine that is used by the Cakchiquels of Guatemala to control hyperglycemia in patients with type 2 diabetes. Previous studies have shown that administration of this plant induces an acute hypoglycemic effect during fasting and that the main compound is junceic acid, a diterpenoid with a clerodane skeleton; however, junceic acid has not been reported to have hypoglycemic activity in the literature. As the mechanisms involved in the hypoglycemic effect of C. guatemalensis remain unknown, the objective of the present investigation was to elucidate the hypoglycemic mechanisms of this species, as well as its major compound, junceic acid. The results indicated that, similar to complete extract, junceic acid exhibited a hypoglycemic effect in hyperglycemic rats. Both C. guatemalensis extract and junceic acid inhibited the activity of two rate-limiting enzymes involved in hepatic glucose production; however, compared with chlorogenic acid, junceic acid had a more potent effect on glucose-6-phosphatase levels than chlorogenic acid, which was used as a positive control. Furthermore, both fasting and postprandial insulin levels decreased in healthy and hyperglycemic rats despite reduced blood glucose levels in both metabolic states, suggesting a potential insulin-sensitizing effect. However, neither of these compounds potentiated the effect of insulin in insulin tolerance tests nor inhibited the enzyme activity of protein tyrosine phosphatase 1B, a negative regulator of the insulin pathway. Therefore, the insulin-sensitizing effect is thought to be independent of insulin and mediated by potential activation of the AMP-activated protein kinase pathway. The specific activation of this master regulator in β-cells results in the inhibition of insulin secretion in a healthy state and the restoration of the insulin response under conditions of glucotoxicity; these effects were observed after the administration of the extract and junceic acid in healthy and hyperglycemic rats. Overall, the main findings of this study establish a basis of the mechanisms of action of C. guatemalensis and its main compound, junceic acid, in terms of their hypoglycemic effect.

Bioregenerative food systems that routinely produce fresh, safe-to-eat crops onboard spacecraft can supplement the nutrition and variety of shelf-stable spaceflight food systems for use during future exploration missions (i.e., low earth orbit, Mars transit, lunar, and Martian habitats). However, current space crop production systems are not yet sustainable because they primarily utilize consumable granular media and, to date, operate like single crop cycle, space biology experiments where root modules are sanitized prior to launch and discarded after each grow-out. Moreover, real-time detection of the cleanliness of crops produced in spacecraft is not possible. A significant paradigm shift is needed in the design of future space crop production systems, as they transition from operating as single grow-out space biology experiments to becoming sustainable over multiple cropping cycles. Soilless nutrient delivery systems have been used to demonstrate post-harvest sanitization and inflight microbial monitoring technologies to enable sequential cropping cycles in spacecraft. Post-harvest cleaning and sanitization prevent the buildup of biofilms and ensure a favorable environment for seedling establishment of the next crop. Inflight microbial monitoring of food and watering systems ensures food safety in spaceflight food systems. A sanitization protocol, heat sterilization at 60°C for 1 h, and soaking for 12 h in 1% hydrogen peroxide, developed in this study, was compared against a standard hydroponic sanitization protocol during five consecutive crop cycles. Each cropping cycle included protocols for the cultivation of a crop to maturity, followed by post-harvest cleaning and inflight microbial monitoring. Microbial sampling of nutrient solution reservoirs, root modules, and plants demonstrated that the sanitization protocol could be used to grow safe-to-eat produce during multiple crop cycles. The cleanliness of the reservoir and root module surfaces measured with aerobic plate counts was verified in near real time using a qPCR-based inflight microbial monitoring protocol. Post-harvest sanitization and inflight microbial monitoring are expected to significantly transform the design of sustainable bioregenerative food and life support systems for future exploration missions beyond low earth orbit (LEO).

PurposeImmunoglobulin replacement therapy remains a cornerstone of treatment in antibody deficiencies and other inborn errors of immunity. While patient preferences between subcutaneous and intravenous immunoglobulin have been studied through questionnaires, no study has yet explored patient perspectives in a free environment. Therefore, we aimed to conduct a sentiment analysis as well as a temporal and geographical analysis on public opinions obtained from social media to better understand patient satisfaction and public perception on immunoglobulin therapy.MethodsA dataset of 43,700 tweets spanning from the 1st of January of 2012 to the 31st of December of 2022 was obtained. A Valence Aware Dictionary for Sentiment Reasoning sentiment analysis was performed, followed by statistical, geographical and temporal analyses.ResultsMean polarity of intravenous immunoglobulin related tweets was 0.1295 (positive), while mean polarity for subcutaneous immunoglobulin was 0.2117 (positive). Temporal analysis through a statistical model demonstrated that the volume of tweets increased over time for both subcutaneous and intravenous treatment. Geographical analysis revealed that the majority of texts originated from the United States. The highest mean polarity was observed in Romania with a mean value of 0.2966, while the lowest polarity was documented in Norway with a mean of -0.0211.ConclusionTweets linked to subcutaneous immunoglobulin treatment had a higher average polarity, indicating a more positive public perception. The amount of tweets relating to both therapies showed a tendency to increase as the years progressed, implying an increase in public discussion on immunoglobulin treatment.

IntroductionThe COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high pro-inflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the AKT1 gene associated with severe COVID-19 outcomes.MethodsPeripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the AKT1 variants.ResultsThe rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease.DiscussionOur findings contribute to understanding the influence of the AKT1 gene variants on the immunological damage in individuals infected with SARS-CoV-2.

IntroductionSolid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear.MethodsWe investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination.ResultsWe corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion.DiscussionOur study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients.

BackgroundPatients with chronic kidney disease (CKD) are at increased risk for cardiovascular disease. Up to 80% of patients with CKD may exhibit inadequate vitamin D (VD) levels, which have been linked to the presence of cardiometabolic factors (CFs) in the adult population. However, research on this association in the pediatric population is limited.ObjectiveTo analyze the effects of 25-hydroxyvitamin D3 (25-[OH]D) levels and status on the presence of CFs in children receiving kidney replacement therapy (KRT).Materials and methodsThis cross-sectional study included pediatric patients receiving KRT, aged 8–17 years, who were receiving hemodialysis or peritoneal dialysis from January 2021 to March 2024. We conducted anthropometric measurements, blood pressure assessments, and glucose, 25-(OH)D, and lipid profiling for all participants. The daily dose of cholecalciferol supplementation, as well as other medications affecting bone and lipid metabolism and antihypertensive drugs, were documented. Statistical analyses were performed using Student’s t-tests and chi-square tests to compare the CFs between groups with and without VD deficiency.ResultsThe study involved 156 patients with an average age of 12.9 years and a mean serum VD level of 22.5 ng/dL. Patients with VD deficiency presented higher levels of total cholesterol and diastolic blood pressure (p

Dyadic social interactions evoke complex dynamics between two agents that, while exchanging unequal levels of body autonomy and motor control, may find a fine balance to synergize, take turns, and gradually build social rapport. To study the evolution of such complex interactions, we currently rely exclusively on subjective pencil and paper means. Here, we complement this approach with objective biometrics of socio-motor behaviors conducive to socio-motor agency. Using a common clinical test as the backdrop of our study to probe social interactions between a child and a clinician, we demonstrate new ways to streamline the detection of social readiness potential in both typically developing and autistic children by uncovering a handful of tasks that enable quantification of levels of motor autonomy and levels of motor control. Using these biometrics of autonomy and control, we further highlight differences between males and females and uncover a new data type amenable to generalizing our results to any social setting. The new methods convert continuous dyadic bodily biorhythmic activity into spike trains and demonstrate that in the context of dyadic behavioral analyses, they are well characterized by a continuous Gamma process that can classify individual levels of our thus defined socio-motor agency during a dyadic exchange. Finally, we apply signal detection processing tools in a machine learning approach to show the validity of the streamlined version of the digitized ADOS test. We offer a new framework that combines stochastic analyses, non-linear dynamics, and information theory to streamline and facilitate scaling the screening and tracking of social interactions with applications to autism.

BackgroundColorectal cancer (CRC) continues to be a major health concern in today’s world. Despite conflictive findings, evidence supports systemic inflammation’s impact on CRC patients’ survival rates. Therefore, this study aims to assess the prognostic role of the innate immune system in patients with CRC.MethodA total of 449 patients were included, with a 5-year follow-up period, and absolute neutrophil counts and their related ratios were measured.ResultsThe non-survival group had increased levels of white blood cells, neutrophils (both p

BackgroundFibromyalgia (FM) is characterized by widespread chronic pain. Although pain is the main symptom, approximately 90% of patients have depression. This study aimed to analyze the effects of Resistance Training (RT) with low and high intensity on depression in patients with FM.MethodsThirty-eight women with FM and 31 healthy women were allocated to the low-intensity, high-intensity, preferred-intensity, and control groups. The patients underwent 8 weeks of supervised RT, with two sessions per week of approximately 1 h. The low-intensity resistance training group (LIRT) performed two sets of 12 maximum repetitions. The high-intensity resistance training group (HIRT) performed four sets with six maximum repetitions, and the preferred intensity group (PI) performed three sets, with eight to 12 repetitions, according to the patient’s tolerance. The healthy control group did not perform any type of exercise. Depression was assessed using the Beck depression inventory before the start of the intervention, after 4 and 8 weeks.ResultsFM patients have higher levels of depression than women without the disease. After 4 weeks, there was a difference in depressive symptoms between the HIRT and LIRT (p = 0.048), and the PI and LIRT (p = 0.048).ConclusionPrescribing RT with low or high intensity did not significantly reduce depression in patients with FM after 8 weeks, however, analyses between groups after 4 weeks indicated that low-intensity training is more effective than high-intensity training. The prescription of RT exercise to FM could vary among low, high, and preferred intensity, following the patient’s tolerance for pain.Clinical trial registrationhttps://ensaiosclinicos.gov.br/rg/RBR-74pcmw, RBR-74pcmw.

HIV-1 infection cannot be cured due to long-lived viral reservoirs formed by latently infected CD4+ T cells. “Shock and Kill” strategy has been considered to eliminate the viral reservoir and achieve a functional cure but the stimulation of cytotoxic immunity is necessary. Ponatinib is a tyrosine kinase inhibitor (TKI) clinically used against chronic myeloid leukemia (CML) that has demonstrated to be effective against HIV-1 infection in vitro. Several TKIs may induce a potent cytotoxic response against cancer cells that makes possible to discontinue treatment in people with CML who present long-term deep molecular response. In this longitudinal study, we analyzed the capacity of ponatinib to induce an antiviral response against HIV-1 infection in peripheral blood mononuclear cells (PBMCs) obtained from people with CML previously treated with imatinib for a median of 10 years who changed to ponatinib for 12 months to boost the anticancer response before discontinuing any TKI as part of the clinical trial NCT04043676. Participants were followed-up for an additional 12 months in the absence of treatment. PBMCs were obtained at different time points and then infected in vitro with HIV-1. The rate of infection was determined by quantifying the intracellular levels of p24-gag in CD4+ T cells. The levels of p24-gag+ CD4+ T−cells were lower when these cells were obtained during and after treatment with ponatinib in comparison with those obtained during treatment with imatinib. Cytotoxicity of PBMCs against HIV-infected target cells was significantly higher during treatment with ponatinib than during treatment with imatinib, and it was maintained at least 12 months after discontinuation. There was a significant negative correlation between the lower levels of p24-gag+ CD4+ T−cells and the higher cytotoxicity induced by PBMCs when cells were obtained during and after treatment with ponatinib. This cytotoxic immunity was mostly based on higher levels of Natural Killer and Tγδ cells seemingly boosted by ponatinib. In conclusion, transient treatment with immunomodulators like ponatinib along with ART could be explored to boost the antiviral activity of cytotoxic cells and contribute to the elimination of HIV-1 reservoir.

IntroductionCannabis, commonly known for both therapeutic and intoxicating effects, is gaining accessibility on legal markets and traction as a potential alternative therapy for pain mediation, particularly in those suffering from chronic low back pain. However, the effectiveness in this population of legal market forms of cannabis, particularly commonly used edibles, is unknown.MethodsTherefore, this study utilized a naturalistic prospective design where participants with chronic low back pain with intentions to initiate cannabis use for treatment were recruited and self-selected edible cannabis products containing varying amounts of delta- 9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Products were categorized as CBD-dominant, THC-dominant, or combined THC and CBD (THC + CBD).Results249 participants [140 female (56.62%), mean (SD) age of 46.30 (16.02), 90% White] were tracked over 2 weeks of ad libitum use and assessed during a naturalistic acute cannabis administration session on changes in pain, mood, and subjective drug effects. During acute administration, a significant correlation between THC dose and short-term pain relief was found, suggesting that higher THC doses were associated with greater pain reduction (p < .05). In addition, THC was associated with higher levels of subjective cannabis drug effects (p < .001), regardless of whether CBD was also in the edible product. Acute CBD dose was primarily associated with short-term tension relief (p < .05); however, there were no associations between CBD dose and acute pain. Over the 2-week ad libitum administration period results suggested pain reductions across participants using all forms of cannabis. However, trends suggested that more frequent use of CBD-dominant edible cannabis may be associated with greater reductions in perceived pain over the 2-week observation period (p = .07).DiscussionThese findings support the short-term analgesic effects of THC and anxiolytic effects of CBD and further suggest that orally-administered THC and CBD should continue to be evaluated for the potential to provide both acute and extended relief from chronic low back pain.Clinical Trial Registration:https://clinicaltrials.gov/study/NCT03522324?locStr=Boulder,%20CO&country=United%20States&state=Colorado&city=Boulder&cond=chronic%20low%20back%20pain&intr=Cannabis&rank=1, identifier NCT03522324.

Global estimates of the supply of dissolved and suspended materials to the ocean, in order to be relevant at either political or ecological scales, belie a finer-scale analysis necessary for understanding specific terrestrial-marine interactions. This is especially true for continental runoff to the marine critical zone of inland fjords and channels, where mechanisms, drivers, and predictions need to be elaborated in the context of changing land use and shifting climate forcing. In fjords in south-western Patagonia, runoff from small coastal and large continental basins (~310 x103 km2), sourced from a diverse geography and wide climatic gradient (

IntroductionChronic stress is a condition characterized by prolonged stimulation, leading to mental and physical weakness. It can have detrimental effects on individuals’ mental health and cognitive function, potentially causing various health issues. This article explores the potential of non-invasive neuromodulation techniques, specifically transcranial direct current stimulation (tDCS) and transcutaneous auricular vagus nerve stimulation (taVNS), in managing chronic stress and improving sleep quality.MethodsThe study conducted a randomized, double-blinded, controlled trial with participants experiencing chronic stress. In total, 100 participants were randomly assigned to one of four conditions: the anodal tDCS group (n = 50), the sham tDCS group (n = 50), the taVNS group (n = 50), or the sham taVNS group (n = 50). Within each condition, participants received five sessions of either active treatment or sham treatment, with 20 min of tDCS over the dorsolateral prefrontal cortex (2 mA) for the tDCS groups, or taVNS on the left ear (20 Hz) for the taVNS groups. At baseline, post-intervention, and 4 weeks thereafter, we evaluated stress using the Lipp’s Inventory of Stress Symptoms for Adults (LSSI), perceived stress through the Perceived Stress Scale (PSS-10), and sleep quality via the Pittsburgh Sleep Quality Index (PSQI).ResultsThe tDCS and taVNS interventions resulted in reduced stress levels, improved sleep quality, and enhanced perception of stress.DiscussionThese findings suggest that tDCS and taVNS hold promise as effective treatments for chronic stress, offering a safe and accessible approach to improving individuals’ wellbeing and overall quality of life.Clinical trial registrationhttps://ensaiosclinicos.gov.br/rg/RBR-2ww2ts8, identifier UTN: U1111-1296-1810; Brazilian Registry of Clinical Trials (REBEC) RBR-2ww2ts8.

IntroductionAlpha-cell hyperplasia (ACH) is a rare pancreatic endocrine condition. Three types of ACH have been described: functional or nonglucagonoma hyperglucagonemic glucagonoma syndrome, reactive or secondary to defective glucagon signaling, and non-functional. Few cases of ACH with concomitant pancreatic neuroendocrine tumors (pNETs) have been reported and its etiology remains poorly understood. A case report of non-functional ACH with glucagon-producing NET is herein presented.Case reportA 72-year-old male was referred to our institution for a 2 cm single pNET incidentally found during imaging for acute cholecystitis. The patient’s past medical history included type 2 diabetes (T2D) diagnosed 12 years earlier, for which he was prescribed metformin, dapagliflozin, and semaglutide. The pNET was clinically and biochemically non-functioning, apart from mildly elevated glucagon 217 pg/ml (

Microglia are highly dynamic cells that have been mainly studied under pathological conditions. The present review discusses the possible implication of microglia as modulators of neuronal electrical responses in physiological conditions and hypothesizes how these cells might modulate hypothalamic circuits in health and during obesity. Microglial cells studied under physiological conditions are highly diverse, depending on the developmental stage and brain region. The evidence also suggests that neuronal electrical activity modulates microglial motility to control neuronal excitability. Additionally, we show that the expression of genes associated with neuron-microglia interaction is down-regulated in obese mice compared to control-fed mice, suggesting an alteration in the contact-dependent mechanisms that sustain hypothalamic arcuate-median eminence neuronal function. We also discuss the possible implication of microglial-derived signals for the excitability of hypothalamic neurons during homeostasis and obesity. This review emphasizes the importance of studying the physiological interplay between microglia and neurons to maintain proper neuronal circuit function. It aims to elucidate how disruptions in the normal activities of microglia can adversely affect neuronal health.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children around the world. The post-pandemic era has resulted in a notable increase in reported cases of RSV infections, co-circulation of other respiratory viruses, shifts in epidemiology, altered respiratory season timing, and increased healthcare demand. Low- and middle-income countries are responsible for the highest burden of RSV disease, contributing significantly to health expenses during respiratory seasons and RSV-associated mortality in children. Until recently, supportive measures were the only intervention to treat or prevent RSV-infection, since preventive strategies like palivizumab are limited for high-risk populations. Advances in new available strategies, such as long-acting monoclonal antibodies during the neonatal period and vaccination of pregnant women, are now a reality. As the Regional Expert Group of the Latin American Pediatric Infectious Diseases Society (SLIPE), we sought to evaluate the burden of RSV infection in Latin America and the Caribbean (LAC) region, analyze current strategies to prevent RSV infection in children, and provide recommendations for implementing new strategies for preventing RSV infection in children in LAC region.

BackgroundMultiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder marked by pathogenic variants in the MEN1 tumor suppressor gene, leading to tumors in the parathyroid glands, pancreas, and pituitary. The occurrence of ACTH-producing pancreatic neuroendocrine carcinoma is exceedingly rare in MEN1.Case presentationThis report details a Colombian family harboring a novel MEN1 variant identified through genetic screening initiated by the index case. Affected family members exhibited primary hyperparathyroidism (PHPT) symptoms from their 20s to 50s. Uniquely, the index case developed an ACTH-secreting pancreatic neuroendocrine carcinoma, a rarity in MEN1 syndromes. Proactive screening enabled the early detection of pituitary neuroendocrine tumors (PitNETs) as microadenomas in two carriers, with subsequent surgical or pharmacological intervention based on the clinical presentation.ConclusionOur findings underscore the significance of cascade screening in facilitating the early diagnosis and individualized treatment of MEN1, contributing to better patient outcomes. Additionally, this study brings to light a novel presentation of ACTH-producing pancreatic neuroendocrine carcinoma within the MEN1 spectrum, expanding our understanding of the disease’s manifestations.

Introduction and objectivesCorticosteroids are among the drugs demonstrating a mortality benefit for coronavirus disease 2019 (COVID-19). The RECOVERY trial highlighted that dexamethasone reduced 28-day mortality for hospitalized COVID-19 patients requiring either supplemental oxygen or mechanical ventilation. It is noted that approximately 30% of COVID-19 patients, initially presenting with mild symptoms, will advance to acute respiratory distress syndrome (ARDS), especially those with detectable laboratory markers of inflammation indicative of disease progression. Our research aimed to explore the efficacy of dexamethasone in preventing the progression to ARDS in patients hospitalized with COVID-19 pneumonia who do not yet require additional oxygen but are at high risk of developing ARDS, potentially leading to a reduction in morbimortality.MethodsIn this multicenter, randomized, controlled trial, we evaluated the impact of dexamethasone on adult patients diagnosed with COVID-19 pneumonia who did not need supplementary oxygen at admission but were identified as having risk factors for ARDS. The risk of ARDS was determined based on specific criteria: elevated lactate dehydrogenase levels over 245 U/L, C-reactive protein levels exceeding 100 mg/L, and a lymphocyte count below 0.80 × 109/L. Participants were randomly allocated to either receive dexamethasone or the standard care. The primary endpoints included the incidence of moderate or severe ARDS and all-cause mortality within 30 days post-enrollment.ResultsOne hundred twenty-six patients were randomized. Among them, 41 were female (30.8%), with a mean age of 48.8 ± 14.4 years. Ten patients in the dexamethasone group (17.2%) and ten patients in the control group (14.7%) developed moderate ARDS with no significant differences. Mechanical ventilation was required in six patients (4.7%), with four in the treatment group and two in the control group. There were no deaths during hospitalization or during follow-up. An intermediate analysis for futility showed some differences between the control and treatment groups (Z = 0.0284). However, these findings were within the margins close to the region where the null hypothesis would not be rejected.ConclusionIn patients with COVID-19 pneumonia without oxygen needs but at risk of progressing to severe disease, early dexamethasone administration did not lead to a decrease in ARDS development.Clinical trial registrationClinicalTrials.gov, identifier NCT04836780.

Tick-borne infections are increasing in the United States and around the world. The most common tick-borne disease in the United States is Lyme disease caused by infection with the spirochete Borrelia burgdorferi (Bb), and pathogenesis varies from subclinical to severe. Bb infection is transmitted by Ixodes ticks, which can carry multiple other microbial pathogens, including Ehrlichia species. To address how the simultaneous inoculation of a distinct pathogen impacted the course of Bb-induced disease, we used C57BL/6 (B6) mice which are susceptible to Bb infection but develop only mild joint pathology. While infection of B6 mice with Bb alone resulted in minimal inflammatory responses, mice co-infected with both Bb and the obligate intracellular pathogen Ehrlichia muris (Em) displayed hematologic changes, inflammatory cytokine production, and emergency myelopoiesis similar to what was observed in mice infected only with Em. Moreover, infection of B6 mice with Bb alone resulted in no detectable joint inflammation, whereas mice co-infected with both Em and Bb exhibited significant inflammation of the ankle joint. Our findings support the concept that co-infection with Ehrlichia can exacerbate inflammation, resulting in more severe Bb-induced disease.

IntroductionIn post-COVID survivors, transforming growth factor-beta-1 (TGF-β1) might mediate fibroblast activation, resulting in persistent fibrosis.MethodsIn this study, 82 survivors of COVID-19-associated ARDS were examined at 6- and 24-months post-ICU discharge. At 6-months, quantitative CT analysis of lung attenuation was performed and active TGF-β1 was measured in blood and exhaled breath condensate (EBC).ResultsAt 6-months of ICU-discharge, patients with reduced DmCO/alveolar volume ratio exhibited higher plasma and EBC levels of active TGF-β1. Plasma TGF-β1 levels were elevated in dyspneic survivors and directly related to the high-attenuation lung volume. In vitro, plasma and EBC from survivors induced profibrotic changes in human primary fibroblasts in a TGF-β receptor-dependent manner. Finally, at 6-months, plasma and EBC active TGF-β1 levels discriminated patients who, 24-months post-ICU-discharge, developed gas exchange impairment.DiscussionTGF-β1 pathway plays a pivotal role in the early-phase fibrotic abnormalities in COVID-19-induced ARDS survivors, with significant implications for long-term functional impairment.

Since the SARS-CoV-2 outbreak in 2019, a diversity of viral genomic variants has emerged and spread globally due to increased transmissibility, pathogenicity, and immune evasion. By the first trimester of 2023 in Chile, as in most countries, BQ and XBB were the predominant circulating sub-lineages of Omicron. The molecular and antigenic characteristics of these variants have been mainly determined using non-authentic spike pseudoviruses, which is often described as a limitation. Additionally, few comparative studies using isolates from recent Omicron sub-lineages have been conducted. In this study, we isolated SARS-CoV-2 variants from clinical samples, including the ancestral B.1.1, Delta, Omicron BA.1, and sub-lineages of BA.2 and BA.5. We assessed their infectivity through cell culture infections and their antibody evasion using neutralization assays. We observed variations in viral plaque size, cell morphology, and cytotoxicity upon infection in Vero E6-TMPRSS2 cells for each variant compared to the ancestral B.1.1 virus. BA.2-derived sub-variants, such as XBB.1.5, showed attenuated viral replication, while BA.5-derived variants, such as BQ.1.1, exhibited replication rates similar to the ancestral SARS-CoV-2 virus. Similar trends were observed in intestinal Caco-2 cells, except for Delta. Antibody neutralization experiments using sera from individuals infected during the first COVID-19 wave (FWI) showed a consistent but moderate reduction in neutralization against Omicron sub-lineages. Interestingly, despite being less prevalent, BQ.1.1 showed a 6.1-fold greater escape from neutralization than XBB.1.5. Neutralization patterns were similar when tested against sera from individuals vaccinated with 3xBNT162b2 (PPP) or Coronavac-Coronavac-BNT162b2 (CCP) schedules. However, CCP sera showed 2.3-fold higher neutralization against XBB.1.5 than FWI and PPP sera. This study provides new insights into the differences between BA.2 and BA.5-derived variants, leading to their eventual outcompetition. Our analysis offers important evidence regarding the balance between infectivity and antigenic escape that drives the evolution of second-generation SARS-CoV-2 variants in the population.

IntroductionAfter mild COVID-19 that does not require hospitalization, some individuals develop persistent symptoms that may worsen over time, producing a multisystemic condition termed Post-COVID condition (PCC). Among other disorders, PCC is characterized by persistent changes in the immune system that may not be solved several months after COVID-19 diagnosis.MethodsPeople with PCC were recruited to determine the distribution and functionality of CD4+ T helper (Th) subsets in comparison with individuals with mild, severe, and critical presentations of acute COVID-19 to evaluate their contribution as risk or protective factors for PCC.ResultsPeople with PCC showed low levels of Th1 cells, similar to individuals with severe and critical COVID-19, although these cells presented a higher capacity to express IFNγ in response to stimulation. Th2/Th1 correlation was negative in individuals with acute forms of COVID-19, but there was no significant Th2/Th1 correlation in people with PCC. Th2 cells from people with PCC presented high capacity to express IL-4 and IL-13, which are related to low ventilation and death associated with COVID-19. Levels of proinflammatory Th9 and Th17 subsets were significantly higher in people with PCC in comparison with acute COVID-19, being Th1/Th9 correlation negative in these individuals, which probably contributed to a more pro-inflammatory than antiviral scenario. Th17 cells from approximately 50% of individuals with PCC had no capacity to express IL-17A and IL-22, similar to individuals with critical COVID-19, which would prevent clearing extracellular pathogens. Th2/Th17 correlation was positive in people with PCC, which in the absence of negative Th1/Th2 correlation could also contribute to the proinflammatory state. Finally, Th22 cells from most individuals with PCC had no capacity to express IL-13 or IL-22, which could increase tendency to reinfections due to impaired epithelial regeneration.DiscussionPeople with PCC showed skewed polarization of CD4+ Th subsets with altered functionality that was more similar to individuals with severe and critical presentations of acute COVID-19 than to people who fully recovered from mild disease. New strategies aimed at reprogramming the immune response and redirecting CD4+ Th cell polarization may be necessary to reduce the proinflammatory environment characteristic of PCC.

BackgroundEchinococcosis is a uncommon condition in pediatric patients, and encompasses alveolar and cystic forms, predominantly affecting the lungs and liver. Transmission occurs primarily through zoonotic means, such as the contamination of water and food by infected dog and other canid feces. Diagnosis can be challenging due to nonspecific symptoms that often mimic pneumonia.The caseA 6-year-old female patient from a rural area in Ecuador who initially presented with nonspecific symptoms indicative of pneumonia. However, further investigation into socio-environmental factors led to a diagnosis of pulmonary and hepatic hydatid disease.ConclusionThe timely and accurate diagnosis of this infectious disease enabled the patient to receive appropriate treatment and surgical intervention, leading to her complete recovery.

Enhancing the reliability of literature reviews and evidence synthesis is crucial for advancing the transformation of agriculture and food (agri-food) systems as well as for informed decisions and policy making. In this perspective, we argue that evidence syntheses in the field of agri-food systems research often suffer from a suite of methodological limitations that substantially increase the risk of bias, i.e., publication and selection bias, resulting in unreliable and potentially flawed conclusions and, consequently, poor decisions (e.g., policy direction, investment, research foci). We assessed 926 articles from the Collaboration for Environmental Evidence Database of Evidence Reviews (CEEDER) and recent examples from agri-food systems research to support our reasoning. The analysis of articles from CEEDER (n = 926) specifically indicates poor quality (Red) in measures to minimize subjectivity during critical appraisal (98% of all reviews), application of the eligibility criteria (97%), cross-checking of extracted data by more than one reviewer (97%), critical appraisal of studies (88%), establishment of an a priori method/protocol (86%), and transparent reporting of eligibility decisions (65%). Additionally, deficiencies (Amber) were found in most articles (>50%) regarding the investigation and discussion of variability in study findings (89%), comprehensiveness of the search (78%), definition of eligibility criteria (72%), search approach (64%), reporting of extracted data for each study (59%), consideration and discussion of the limitations of the synthesis (56%), documentation of data extraction (54%) and regarding the statistical approach (52%). To enhance the quality of evidence synthesis in agri-food science, review authors should use tried-and-tested methodologies and publish peer-reviewed a priori protocols. Training in evidence synthesis methods should be scaled, with universities playing a crucial role. It is the shared duty of research authors, training providers, supervisors, reviewers, and editors to ensure that rigorous and robust evidence syntheses are made available to decision-makers. We argue that all these actors should be cognizant of these common mistakes to avoid publishing unreliable syntheses. Only by thinking as a community can we ensure that reliable evidence is provided to support appropriate decision-making in agri-food systems science.

Metropolitan Mexico City (MMC) children and young adults exhibit overlapping Alzheimer and Parkinsons’ diseases (AD, PD) and TAR DNA-binding protein 43 pathology with magnetic ultrafine particulate matter (UFPM) and industrial nanoparticles (NPs). We studied magnetophoresis, electron microscopy and energy-dispersive X-ray spectrometry in 203 brain samples from 14 children, 27 adults, and 27 ALS cases/controls. Saturation isothermal remanent magnetization (SIRM), capturing magnetically unstable FeNPs ̴ 20nm, was higher in caudate, thalamus, hippocampus, putamen, and motor regions with subcortical vs. cortical higher SIRM in MMC ≤ 40y. Motion behavior was associated with magnetic exposures 25–100 mT and children exhibited IRM saturated curves at 50–300 mT associated to change in NPs position and/or orientation in situ. Targeted magnetic profiles moving under AC/AD magnetic fields could distinguish ALS vs. controls. Motor neuron magnetic NPs accumulation potentially interferes with action potentials, ion channels, nuclear pores and enhances the membrane insertion process when coated with lipopolysaccharides. TEM and EDX showed 7–20 nm NP Fe, Ti, Co, Ni, V, Hg, W, Al, Zn, Ag, Si, S, Br, Ce, La, and Pr in abnormal neural and vascular organelles. Brain accumulation of magnetic unstable particles start in childhood and cytotoxic, hyperthermia, free radical formation, and NPs motion associated to 30–50 μT (DC magnetic fields) are critical given ubiquitous electric and magnetic fields exposures could induce motion behavior and neural damage. Magnetic UFPM/NPs are a fatal brain cargo in children’s brains, and a preventable AD, PD, FTLD, ALS environmental threat. Billions of people are at risk. We are clearly poisoning ourselves.

This study focuses on the Ecuadorian Amazon, a crucial region for forest biodiversity and conservation of native species, which faces challenges due to timber extraction. The research objective was to characterize timber harvesting during 2012 to 2021, focusing on the ten most harvested forest species in terms of volume and provincial distribution, as well as their conservation status according to the IUCN. For the methodology, data were extracted and analyzed from Ecuador’s Forest Management System (SAF), focusing on timber extraction in six provinces and assessing 210 species. The results revealed that, from 2,627,659.17 m3 authorized, 2,296,238.08 m3 were harvested, representing 54.17% of the national timber harvest from native forests. Species of the Fabaceae family predominated in number and volume, with yields varying from 0.5 m3/ha in Orellana to 2.8 m3/ha in Zamora Chinchipe. Analysis of the IUCN categories showed that 67.6% (142 species) are Least Concern (LC), while 3.3% (7 species) are Vulnerable (VU), and 1% (2 species) Endangered (EN). Two species were listed as Data Deficient (DD), one as Critically Endangered (CR) and one as Near Threatened (NT). It is crucial to note that, of the 210 species analyzed, 55 species (26.2%) are not included in the IUCN database, highlighting the importance of more detailed assessments for their conservation and distribution.

IntroductionBrown rot is the most important fungal disease affecting stone fruit and it is mainly caused by Monilinia fructicola, M. laxa and M. fructigena. Monilinia spp. are necrotrophic plant pathogens with the ability to induce plant cell death by the secretion of different phytotoxic molecules, including proteins or metabolites that are collectively referred to as necrotrophic effectors (NEs).MethodsWe exploited the genomes of M. fructicola, M. laxa and M. fructigena to identify their common group of secreted effector proteins and tested the ability of a selected set of effectors to induce cell death in Nicotiana benthamiana, Solanum lycopersicum and Prunus spp. leaves.ResultsFourteen candidate effector genes of M. fructicola, which displayed high expression during infection, were transiently expressed in plants by agroinfiltration using a modified Tobacco Rattle Virus (TRV)-based expression system. Some, but not all, effectors triggered leaf discoloration or cell death in N. benthamiana and S. lycopersicum, which are non-hosts for Monilinia and in Prunus spp., which are the natural hosts. The effector MFRU_030g00190 induced cell death in almost all Prunus genotypes tested, but not in the Solanaceous plants, while MFRU_014g02060, which is an ortholog to BcNep1, caused necrosis in all plant species tested.ConclusionThis method provides opportunities for screening Prunus germplasm with Monilinia effector proteins, to serve as a tool for identifying genetic loci that confer susceptibility to brown rot disease.

Virtual culinary medicine education interventions have the potential to improve dietary behaviors, nutrition knowledge, cooking skills, and health outcomes for ethnically diverse individuals with type 2 diabetes. The purpose of this study is to describe the adaptation of the Nourishing the Community through Culinary Medicine (NCCM) program for virtual delivery, and the protocol for pilot testing this intervention. The intervention includes five 90-min virtual NCCM sessions streamed live from a Teaching Kitchen. Feasibility outcomes are recruitment, retention, acceptability, and satisfaction. Short-term effectiveness outcomes are measured through self-administered questionnaires, including perceived health, average daily servings of fruits and vegetables, frequency of healthy food consumption, shopping, cooking, and eating behaviors, cooking self-efficacy, diabetes self-management, perceived barriers to healthy eating, and nutrition knowledge. Demographics and biometric outcomes are sourced from the patient’s electronic medical records including glycosylated hemoglobin (HbA1c), Body Mass Index, and blood pressure. We will conduct a single-arm pilot study to test the feasibility and short-term effectiveness of NCCM program with individuals with type 2 diabetes.

IntroductionNewborn resuscitation algorithms emphasize that resuscitation is time-critical, and all algorithm steps are related to the time of birth. Infrared thermal video has the potential to capture events in the delivery room, such as birth, cord clamping, and resuscitative interventions, while upholding the privacy of patients and healthcare providers.ObjectivesThe objectives of this concept study were to (i) investigate the technical feasibility of using thermal video in the delivery room to detect birth and cord clamping, and (ii) evaluate the accuracy of manual real-time registrations of the time of birth and cord clamping by comparing it with the accuracy of registrations abstracted from thermal videos.MethodsAn observational study with data collected at Stavanger University Hospital, Norway, from September 2022 to August 2023. The time of birth and cord clamping were manually registered on a portable tablet by healthcare providers. Thermal cameras were placed in the delivery rooms and operating theatre to capture births. Videos were retrospectively reviewed to determine the time of birth and cord clamping.ResultsParticipation consent was obtained from 306 mothers, of which 195 births occurred in delivery rooms or an operating theatre with a thermal camera installed. We excluded 12 videos in which no births occurred. Births were detectable in all 183 (100%) thermal videos evaluated. There was a median (quartiles) of 1.8 (0.7, 5.4) s deviation in the manual registrations of the times of births relative to those abstracted from thermal videos. Cord clamping was detectable in 173 of the 183 (95%) thermal videos, with a median of 18.3 (3.3, 108) s deviation in the manual registrations of the times of cord clampings relative to those abstracted from thermal videos.ConclusionRecognizing the time of birth and cord clamping from thermal videos is technically feasible and provides a method for determining when resuscitative events occur.

BackgroundProstate cancer (PCa) is a leading cause of cancer-related deaths in European men, emphasizing the urgent need for effective risk assessment strategies. The TP53 gene, a tumor suppressor gene frequently mutated in cancer, commonly harbors the rs1042522 single nucleotide polymorphism (SNP), known as the P72R SNP, which may influence PCa susceptibility. This study investigated the prevalence of the P72R SNP in European Caucasian PCa samples and its association with PCa risk.MethodsGenotyping was conducted on 12 hormone-naïve aggressive PCa cultures (hnPCs) from untreated patients (Gleason ≥8), 11 radical prostatectomies (RP), and 94 serum samples using DNA Sanger sequencing and melting curve analysis. Comparative analysis utilized data from the GnomAD database’s European Caucasian non-cancer population.ResultsOur results demonstrate a significantly higher frequency of the P72R SNP in PCa samples and serums compared to the general European non-cancer population. A robust and statistically significant association (p < 0.0001) between the SNP and prostate cancer risk was identified, with an odds ratio of 7.937 (95% CI 5.37-11.00). Notably, the G allele (R72) showed a pronounced prevalence in high Gleason score (≥8) patients, although statistical significance was not reached. These results highlight a potential association with undifferentiated and malignant PCa lesions.ConclusionThe compelling association between the P72R SNP and prostate cancer risk underscores the potential utility of this marker for the early identification of patients at risk of aggressive metastatic prostate cancer. This insight could empower further research to intervene at an early stage by offering enhanced opportunities for timely and targeted interventions.

Objectives: To know the frequency and characteristics of neurological manifestations of probable immune origin occurring after exposure to COVID-19 vaccination. In addition, to pre-study the usefulness of the Spanish pharmacovigilance system and lymphocyte transformation test in establishing causality.Methods: Retrospective case study, including patients admitted to the Neurology department from January 2021 to May 2022 with a probable neuroimmune disorder. Demographic, clinical and COVID-19 vaccination antecedent data were collected from medical records.Results: From a total of 108 patients, 30 were excluded due to a different etiological diagnosis after follow-up. Thirty-six patients (46.2%) had received the COVID-19 vaccine in the previous 3 months (21.8% during the previous month). BioNTech-Pfizer vaccine was the most frequent in this group (63.9%). 69/108 were female and mean age 51.2 years (SD 22.59), with no significant difference with not recently-vaccinated (U-Mann Whitney, p = 0.256). The neurological syndromes found were (vaccinated/total): polyradiculoneuropathy (8/16), encephalitis (5/11), multiple sclerosis relapse (5/16), optic neuritis (1/4), myelitis (3/6), cranial neuropathy (6/10), aseptic meningitis (1/3) and others (7/11). Acute immunosuppressive treatment was administered in 61.1% of cases and 47.2% presented complete clinical improvement, without significant differences with non-vaccinated patients (chi-square, p = 0.570). Eleven vaccinated patients were studied in the pharmacovigilance office for possible adverse drug reaction. Causality according to the Spanish pharmacovigilance system (SPVS) algorithm was “Related” to COVID-19 vaccine (score ≥ 4) in 11 cases with positive in vitro study (lymphocyte transformation test) to polyethylene glycol-2000 and polysorbate-80 in 4 cases.Conclusion: Neuroimmune disorders appearing after administration of COVID-19 vaccine do not seem to present important differentiating clinical and/or evolutive features. Delayed hypersensitivity to vaccine excipients could be one of the pathophysiological mechanisms, and lymphocyte transformation test is a useful tool to identify it.

The extremotolerant red yeast Rhodotorula mucilaginosa displays resilience to diverse environmental stressors, including cold, osmolarity, salinity, and oligotrophic conditions. Particularly, this yeast exhibits a remarkable ability to accumulate lipids and carotenoids in response to stress conditions. However, research into lipid biosynthesis has been hampered by limited genetic tools and a scarcity of studies on adaptive responses to nutrient stressors stimulating lipogenesis. This study investigated the impact of nitrogen stress on the adaptive response in Antarctic yeast R. mucilaginosa M94C9. Varied nitrogen availability reveals a nitrogen-dependent modulation of biomass and lipid droplet production, accompanied by significant ultrastructural changes to withstand nitrogen starvation. In silico analysis identifies open reading frames of genes encoding key lipogenesis enzymes, including acetyl-CoA carboxylase (Acc1), fatty acid synthases 1 and 2 (Fas1/Fas2), and acyl-CoA diacylglycerol O-acyltransferase 1 (Dga1). Further investigation into the expression profiles of RmACC1, RmFAS1, RmFAS2, and RmDGA1 genes under nitrogen stress revealed that the prolonged up-regulation of the RmDGA1 gene is a molecular indicator of lipogenesis. Subsequent fatty acid profiling unveiled an accumulation of oleic and palmitic acids under nitrogen limitation during the stationary phase. This investigation enhances our understanding of nitrogen stress adaptation and lipid biosynthesis, offering valuable insights into R. mucilaginosa M94C9 for potential industrial applications in the future.

BackgroundStigmatising attitudes among healthcare professionals can hinder access to healthcare, making it important to address this issue. This study aimed to investigate the prevalence of stigma related to mental illness among Portuguese healthcare professionals and to compare the results among mental health professionals, General Practitioners (GPs) and other health professionals.MethodsAn online cross-sectional observational study was conducted in Portugal using Google Forms® to collect data. The data collection process lasted five months, from September 2023 to January 2024. Participants were recruited from various professional associations and Health Centre Groups, through a purposive sampling. The study used the Portuguese version of the Opening Minds Stigma Scale for Healthcare Providers (OMS-HC) to measure stigma which assesses three dimensions: attitudes towards disclosure and help-seeking, attitudes towards people with mental illness, and attitudes towards social distance.ResultsA total of 292 healthcare professionals participated in the study. In Portugal, healthcare professionals displayed low to moderate levels of stigma towards mental illness (M = 22.17, SD = 5.41). Mental health professionals demonstrated significantly lower levels of stigma (M=20.37, SD=5.37) compared to other healthcare professionals (M=24.15, SD=4.71), including GPs (M=23.97, SD=5.03). Additionally, having a close friend or relative with mental illness seemed to be related with lower levels of stigma for the dimension attitudes towards social distance (M=6.93, SD=2.50), compared to not having one (M=7.60, SD=2.56). On the other hand, a personal history of mental illness indicated higher levels of stigma for the dimension disclosure and help-seeking (M=8.95, SD=3.07), compared to having no history of mental illness (M=8.16, SD=2.67).ConclusionThis study indicates that Portuguese healthcare professionals have stigmatising attitudes towards mental illness, although at low to moderate levels. Training and frequent interaction with people with mental illness seem to be associated with lower levels of stigma. Personal experience of mental illness seems to follow the opposite path regarding disclosure and seeking help. Thus, further research is necessary to evaluate the effectiveness of anti-stigma measures and deepen the study of the concept of self-stigma in healthcare professionals.