Rastreamento da síndrome metabólica em participantesdo programa Universidade Aberta da Terceira Idade / Metabolic syndrome screening in the participantsat the Open University of the Third Age

Hábitos alimentares inadequados, sedentarismo e a maior expectativa de vida da população contribuem significativamente para a prevalência da síndrome metabólica. Essa doença predispõe uma pessoa a desenvolver diabetes mellitus tipo 2 e doenças cardiovasculares, as quais têm um amplo impacto na saúde pública, induzindo sobrecarga no sistema de saúde e reduzindo a qualidade de vida dos indivíduos afetados. A síndrome metabólica é uma doença multifatorial e está relacionada ao processo de envelhecimento, contudo, ainda há uma lacuna significativa, em termos de estudos, sobre a prevalência da condição em populações idosas. Nesse contexto, o presente estudo objetivou rastrear a prevalência da síndrome metabólica em participantes da Universidade Aberta da Terceira Idade (UNATI), localizada em Francisco Beltrão, Paraná. Os critérios diagnósticos de síndrome metabólica abordados nesta pesquisa incluem: circunferência abdominal ≥ 90 cm para homens e ≥ 80 cm para mulheres, triglicerídeos ≥ 150 mg/dL, HDL ≤ 40 mg/dL para homens e ≤ 50 mg/dL para mulheres, pressão arterial sistólica ≥ 130 mmHg e/ou pressão arterial diastólica ≥ 85 mmHg ou estar em farmacoterapia para hipertensão, além de glicemia de jejum ≥ 100 mg/dL ou estar em tratamento farmacológico para diabetes. Um total de 44 idosos foram avaliados, apresentando uma média de idade de 66,9 ± 7,1 anos, com uma predominância de mulheres (88%). Os resultados revelaram uma prevalência alarmante de síndrome metabólica, atingindo 36,4% da amostra estudada. Além disso, observou-se uma alta prevalência de condições associadas, como hipertensão arterial (67,2%), sobrepeso (58,6%) e obesidade visceral (31%). Esses achados ressaltam a importância da implementação de medidas preventivas direcionadas à promoção da qualidade de vida saudável e ao controle dos fatores de risco metabólicos.

Inadequate dietary habits, sedentary lifestyle, and increased life expectancy significantly contribute to the prevalence of metabolic syndrome. This condition predisposes an individual to develop type 2 diabetes mellitus and cardiovascular diseases, which have a broad impact on public health, inducing a burden on the healthcare system and reducing the quality of life of affected individuals. Metabolic syndrome is a multifactorial disease and is related to the aging process; however, there is still a significant gap in terms of studies on the prevalence of the condition in elderly populations. In this context, this study aimed to screen the prevalence of metabolic syndrome in participants of the Open University for the Third Age (UNATI), located in Francisco Beltrão, Paraná. The diagnostic criteria for metabolic syndrome addressed in this research include: abdominal circumference ≥ 90 cm for men and ≥ 80 cm for women, triglycerides ≥ 150 mg/dL, HDL ≤ 40 mg/dL for men and ≤ 50 mg/dL for women, systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 85 mmHg or being on pharmacotherapy for hypertension, in addition to fasting glucose ≥ 100 mg/dL or being on pharmacological treatment for diabetes. A total of 44 elderly individuals were evaluated, with a mean age of 66.9 ± 7.1 years, predominantly women (88%). The results revealed an alarming prevalence of metabolic syndrome, affecting 36.4% of the studied sample. Furthermore, a high prevalence of associated conditions was observed, such as arterial hypertension (67.2%), overweight (58.6%), and visceral obesity (31%). These findings underscore the importance of implementing preventive measures aimed at promoting healthy lifestyles and controlling metabolic risk factors.

La aplicación del saber médico. Hipertensión y daño cognitivo

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Introduction: High blood pressure (HBP) is the leading cause of death from cardiovascular disease. Despite the advances, the percentage of undiagnosed and untreated hypertensive patients is 58.4%. The evaluation of cognitive damage in HBP focuses on preventing stroke, while functional damage is ignored. This inadequate management may be multifactorial. The objective was to analyze the opinions that doctors have about the relationship between high blood pressure and cognitive damage. Methodology: Observational, descriptive, cross-sectional study developed in the period between August 2020 and August 2023. Analysis of data obtained from a self-administered, anonymous and voluntary questionnaire. Revealing information on the professional profile, knowledge of HBP, its link with cognitive impairment (CD), diagnosis and treatment. Results: 222 professionals were included, 215 (96.8%) agree with the existence of a link between HBP and other cardiovascular risk factors in CD, and 218 (98.1%) acknowledge assisting patients at risk of suffering from CD. The CD evaluation is carried out in selected cases by 132 (59.4%) participants and 59 (26.7%) always do it. Of those who perform evaluation, 103 (54%) use the Mini Mental State Examination (MMSE), 10 (5.2%) use the Montreal Cognitive Assessment (MoCA) and 9 (4.7%) use the Clock Drawing Test. Regarding the decrease in blood pressure in elderly patients and the link with risk of CD: 54 (24.3%) do not recognize risk and 65 (29.2%) recognize a moderate-high risk. In reference to the implication of the treatment of cardiovascular disease and CD: 217 (97.7%) recognized a beneficial effect. Discussion: Given the recognition of the link between HBP and CD, it would be expected that CD would be investigated in the vast majority, however only 26.7% always evaluate it. There is no consensus on the method, the MMSE being the most used, with a low application of the MoCA test and/or Clock Drawing Test, the latter being the ones that evaluate executive function, mostly altered in CD linked to HBP. Although the treatment of cardiovascular disease is recognized as beneficial with respect to CD, the control of HBP in older adults is considered risky. A diagnosis is made of a situation where a disparity is evident between what one recognizes as knowing and what one claims to do. Conclusions: The role of vascular disease in functional brain damage is recognized, considering it necessary to know the cognitive status of patients, however there is a low application of screening tests that evaluate executive function. In this context, a gap between medical knowledge and practice is shown.

Introdução: A hipertensão arterial (HA) é a principal causa de morte por doenças cardiovasculares. Apesar dos avanços, o percentual de hipertensos não diagnosticados e não tratados é de 58,4%. A avaliação do dano cognitivo na hipertensão concentra-se na prevenção do acidente vascular cerebral, enquanto o dano funcional é ignorado. Esse manejo inadequado pode ser multifatorial. É objetivo fue analisar a opinião dos médicos sobre a relação entre hipertensão arterial e danos cognitivos. Metodologia: Estudo observacional, descritivo, transversal desenvolvido no período entre agosto de 2020 e agosto de 2023. Análise de dados obtidos a partir de questionário autoaplicável, anônimo e voluntário. Revelar informações sobre o perfil profissional, conhecimento sobre a HA, sua ligação com o comprometimento cognitivo (DC), diagnóstico e tratamento. Resultados: Foram incluídos 222 profissionais, 215 (96,8%) concordam com a existência de ligação entre hipertensão e outros fatores de risco cardiovascular na DC e 218 (98,1%) reconhecem ajudar pacientes com risco de sofrer de D.C. A avaliação da DC é realizada em casos selecionados por 132 (59,4%) participantes e 59 (26,7%) a fazem sempre. Dos que realizam avaliação, 103 (54%) utilizam o Mini Exame do Estado Mental (MEEM), 10 (5,2%) utilizam a Avaliação Cognitiva de Montreal (MoCA) e 9 (4,7%) utilizam o Clock Drawing Test. Em relação à diminuição da pressão arterial em pacientes idosos e a ligação com o risco de DC: 54 (24,3%) não reconhecem risco e 65 (29,2%) reconhecem risco moderado-alto. Em referência à implicação do tratamento de doenças cardiovasculares e DC: 217 (97,7%) reconheceram o efeito benéfico. Discussão: Dado o reconhecimento da ligação entre hipertensão e DC, seria de esperar que a DC fosse investigada na grande maioria, no entanto apenas 26,7% sempre a avaliam. Não há consenso sobre o método, sendo o MEEM o mais utilizado, com baixa aplicação do teste MoCA e/ou Clock Drawing Test, sendo estes últimos os que avaliam a função executiva, majoritariamente alterada nos DC vinculados à HA. Embora o tratamento das doenças cardiovasculares seja reconhecido como benéfico em relação à DC, o controle da HA em idosos é considerado arriscado. É feito um diagnóstico de uma situação em que é evidente uma disparidade entre o que se reconhece como saber e o que se afirma fazer. Conclusões: O papel da doença vascular no dano cerebral funcional é reconhecido, considerando-se necessário conhecer o estado cognitivo dos pacientes, porém há baixa aplicação de testes de triagem que avaliam a função executiva. Nesse contexto, evidencia-se uma lacuna entre o conhecimento e a prática médica.

Prevalencia de hipertirotropinemia neonatal comoindicador de deficiencia de yodo en la provincia de La Pampa: un análisis epidemiológico / Prevalence of high neonatal thyroid stimulating hormone levels as an indicator of iodine deficiency in the province of La Pampa: An epidemiological analysis

Introducción. El yodo desempeña un rol fundamental en el metabolismo, el crecimiento y el desarrollo humano. Durante el embarazo y la infancia, la demanda de este micronutriente aumenta considerablemente. La tirotropinemia neonatal (TSHn) aumentada, definida como TSHn ≥5 mUI/l, es un marcador que señala la deficiencia de yodo en una población cuando su prevalencia supera el 3 %. Objetivo. Determinar la prevalencia de TSHn ≥ 5 en La Pampa durante el período 2021-2022, analizar su correlación con diferentes variables y compararla con datos de una cohorte histórica. Población y métodos. Estudio transversal, de diseño descriptivo-analítico, sobre una población de neonatos nacidos en las cinco zonas sanitarias de la provincia de La Pampa durante los años 2021 y 2022. Resultados. De los 5778 neonatos evaluados, el 9,6 % presentó niveles de TSHn ≥5 mUI/l. El 70,4 % de estas mediciones fueron realizadas después del tercer día de vida. No se observaron diferencias significativas en la frecuencia de niveles elevados de TSHn según el año de nacimiento, peso al nacer o días hasta la extracción. Se registró una mayor prevalencia en el sexo masculino (10,6 % versus 8,5 %; p = 0,007) y entre los neonatos nacidos a término (9,8 % versus 6,6 %; p = 0,02). La prevalencia de hipertirotropinemia fue superior a la observada en una cohorte de 2001-2002. Conclusiones. La prevalencia de hipertirotropinemia neonatal en La Pampa durante los años 2021 y 2022 fue del 9,6 %, lo que indica un estado de deficiencia leve de yodo en la provincia, superior al reportado hace dos décadas.

Introduction. Iodine plays a key role in human metabolism, growth, and development. During pregnancy and childhood, the demand for this micronutrient increases notably. Increased neonatal thyroid stimulating hormone (nTSH) levels, defined as nTSH ≥ 5 mIUL, are a marker of iodine deficiency in a population if its prevalence is higher than 3%.Objective. To establish the prevalence of nTSH ≥ 5 in La Pampa in the 2021­2022 period, analyze its correlation with different variables, and compare it with data from a historical cohort.Population and methods. Cross-sectional, descriptive-analytical study in a population of newborn infants born in the 5 health regions of the province of La Pampa in 2021 and 2022. Results. Of  the  5778  assessed  newborn  infants,  9.6%  had  nTSH  levels  ≥  5  mIU/L. It was reported that 70.4% of these measurements were done after the third day of life. No significant differences were observed in the frequency of high nTSH levels by year of birth, birth weight, or days until samplecollection.A higher prevalence was observed among male infants (10.6% versus 8.5%; p = 0.007) and term infants (9.8% versus 6.6%; p = 0.02). The prevalence of high TSH levels was superior to that observed in the 2001­2002 cohort. Conclusions. The  prevalence of high nTSH levels in La Pampa during 2021 and 2022 was 9.6%, suggesting the presence of mild iodine deficiency in the population of this province, higher that what  had been reported 2 decades ago.

Congenital Hypothyroidism and School Achievement in Adolescence: A Population-Based Sibling Control Study.

OBJECTIVE: To study school achievement in grade 9 of compulsory school in children with congenital hypothyroidism (CH), both those detected by the national screening program and those with a normal screening result and thus diagnosed later. STUDY DESIGN: Nationwide study of children in the Swedish Medical Birth Register (n = 1 547 927) from 1982 through 1997, linked to the neonatal screening CH cohort and the National School Register. Dried blood spot (DBS) samples are collected from all newborn infants, according to the neonatal screening program. Thyroid-stimulating hormone was used for CH screening. CH was defined as either having an abnormal screening result (DBS+) and treatment with levothyroxine (LT4+) or having a normal screening result but a CH diagnosis in the National Patient Register and treatment with LT4 (DBS-/ICD+/LT4+). Regression models were used to study school performance, which as measured as grade point sum and national test results. Sibling analysis also was performed to account for unmeasured familial factors. RESULTS: There were 448 children who were DBS+/LT4+ and 475 children who were DBS-/ICD+/LT4+. Children with CH had lower grade point sum, adjusted ß = - 6.34 (95% CI -11.7 to -1.01) and adjusted ß = -10.3 (95% CI -15.5 to -5.20) for those with abnormal (DBS+/LT4+) and normal screening (DBS-/ICD+/LT4+) results, respectively. CH also was associated with lower result on the national tests, especially in mathematics. These associations remained in the sibling analyses. CONCLUSIONS: Youth with CH had slightly lower school achievements compared with those without CH and compared with their siblings. CH children with a normal screening result, and thus diagnosed later, presented the lowest results on grade point sum and national tests.

Essential oil components interacting with insect odorant-binding proteins: a molecular modelling approach.

Essential oils (EOs) are natural products currently used to control arthropods, and their interaction with insect odorant-binding proteins (OBPs) is fundamental for the discovery of new repellents. This in silico study aimed to predict the potential of EO components to interact with odorant proteins. A total of 684 EO components from PubChem were docked against 23 odorant binding proteins from Protein Data Bank using AutoDock Vina. The ligands and proteins were optimized using Gaussian 09 and Sybyl-X 2.0, respectively. The nature of the protein-ligand interactions was characterized using LigandScout 4.0, and visualization of the binding mode in selected complexes was carried out by Pymol. Additionally, complexes with the best binding energy in molecular docking were subjected to 500 ns molecular dynamics simulations using Gromacs. The best binding affinity values were obtained for the 1DQE-ferutidine (-11 kcal/mol) and 2WCH-kaurene (-11.2 kcal/mol) complexes. Both are natural ligands that dock onto those proteins at the same binding site as DEET, a well-known insect repellent. This study identifies kaurene and ferutidine as possible candidates for natural insect repellents, offering a potential alternative to synthetic chemicals like DEET.

Virtual and in Vitro Screening Employing a Repurposing Approach Reveal 13-cis-Retinoic Acid is a PTP1B Inhibitor.

Current treatments for type 2 diabetes (T2D) mainly rely on exercise, dietary control, and anti-diabetic drugs to enhance insulin secretion and improve insulin sensitivity. However, there is a need for more therapeutic options, as approved drugs targeting different pharmacological objectives are still unavailable. One potential target that has attracted attention is the protein tyrosine phosphatase 1B (PTP1B), which negatively regulates the insulin signaling pathway. In this work, a comprehensive computational screening was carried out using cheminformatics and molecular docking on PTP1B, employing a rigorous repurposing approach. The screening involved approved drugs and compounds under research as anti-diabetics that bind to targets such as peroxisome proliferator-activated receptor gamma (PPAR-γ) and α-glucosidase. Several computational hits were then meticulously tested in vitro against PTP1B, with 13-cis-retinoic acid (3a) showing an IC50 of 0.044 mM and competitive inhibition. Molecular dynamics studies further confirmed that 3a can bind to the catalytic binding site of PTP1B. Finally, 3a is the first time it has been reported as an inhibitor of PTP1B, making it a potentially valuable candidate for further studies in D2T treatment.

Characterization of Psychopathology in Latin American Adolescents Using a Web-Based Screening Tool: Cross-Sectional Study.

BACKGROUND: Mental health problems and suicide ideation are common in adolescents. Early detection of these issues could prevent the escalation of mental health-related symptoms in the long term. Moreover, characterizing different profiles of prevalent symptoms in conjunction with emotional regulation strategies could guide the design of specific interventions. The use of web-based screening (WBS) tools has been regarded as a suitable strategy to timely detect symptomatology while improving the appeal, cost, timeliness, and reach of detection in young populations. However, the evidence regarding the accuracy of these approaches is not fully conclusive. OBJECTIVE: The study aims (1) to examine the capability of a WBS to identify adolescents with psychiatric symptoms and suicidality and (2) to characterize the mental health profiles of a large sample of adolescents using WBS. METHODS: A total of 1599 Latin American Spanish-speaking adolescents (mean age 15.56, SD 1.34 years), consisting of 47.3% (n=753) female, 98.5% Chilean (n=1570), and 1.5% Venezuelan (n=24) participants, responded to a mental health WBS. A randomized subsample of participants also responded to the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). McNemar χ2 and receiver-operating characteristic curves tested the detection accuracy of WBS contrasted with the MINI-KID. Latent profile analyses explored the symptomatic and emotional regulation profiles of participants. RESULTS: Both measures showed an adequate level of agreement (area under the curve per symptom domain ranging from 0.70 to 0.89); however, WBS yielded a higher prevalence than MINI-KID for all psychiatric symptoms, except suicide ideation and depression. Latent profile analyses yielded 4 profiles-one of them presented elevated psychopathological symptoms, constituting 11% of the sample (n=175). Rumination (odds ratio [OR] 130.15, 95% CI 51.75-439.89; P<.001), entrapment (OR 96.35, 95% CI 29.21-317.79; P<.001), and defeat (OR 156.79, 95% CI 50.45-487.23; P<.001) contributed significantly to the prediction of latent profile memberships, while cognitive reappraisal did not contribute to the prediction of any latent profile memberships, and expressive suppression was only associated to profile-2 membership. CONCLUSIONS: WBS is acceptable for the timely detection of adolescents at risk of mental health conditions. Findings from the symptomatic and emotional regulation profiles highlight the need for comprehensive assessments and differential interventions.

Case report: Comprehensive follow-up of a Colombian family carrying a novel MEN1 variant linked to a rare ACTH-producing pancreatic neuroendocrine carcinoma.

Background: Multiple 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 presentation: This 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. Conclusion: Our 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.

Experiences of a group of indigenous women from the Colombian Amazon with cervical cancer prevention screening. Qualitative study in the context of participatory research to reduce inequalities.

OBJECTIVES: Despite cervical cancer (CC) being a preventable disease, its incidence remains high in marginalized communities due to inequalities that restrict access to health services. This article investigates the experiences, perceptions, and attitudes regarding the screening of indigenous women in a region of the Colombian Amazon during a cervical cancer prevention initiative facilitated by community participation. DESIGN: Qualitative study based on interviews conducted with women and indigenous leaders from Paujil reserve. They participated in research focused on cervical cancer prevention, which employed a methodology of collaboration between academia and communities aimed at enhancing women's health and reducing inequalities in access to healthcare services. The analysis utilized a deductive and inductive approach. RESULTS: Five main themes were addressed: 'Barriers within health services'; 'Individual and cultural constraints'; 'Motivations and facilitators'; 'Positive experiences within the research framework'; and 'Suggestions for encouraging women's participation.' Challenges related to appointment scheduling and result delivery were frequently cited as obstacles to access. Misinformation, feelings of shame, fear, and distrust towards health services played significant roles in the reluctance to undergo screening. Factors such as support from family and community networks, respectful treatment, ease of scheduling appointments, the presence of female healthcare professionals, and involvement of leaders fluent in indigenous languages were identified as positive facilitators of screening acceptance. CONCLUSION: Understanding the factors that influence access to screening is crucial for reducing inequalities in service delivery for indigenous women. The involvement of trained leaders who can identify these factors and motivate women can have a positive impact on the acceptance and guidance of cervical cancer prevention programs.

Detecting sexually transmitted infections beyond the syndromic approach: lessons from a rural setting in Chiapas, Mexico.

Sexually Transmitted Infections (STIs) are a critical global health concern, with low- and middle-income countries carrying the highest burden. The development of rapid point-of-care STI tests has enabled screening in settings without laboratory access. Yet, high-need settings face unique challenges that may influence the implementation and uptake of STI screening. This piece discusses lessons learned from the implementation of STI screening in a rural, low-resource setting in Chiapas, Mexico. Despite minimal privacy and a low staff-to-patient ratio, a streamlined approach was developed to destigmatize and maximize STI screening. The clinic team developed strategies through practice, including incorporating screening into triage procedures and offering screening to family members. This protocol led to an average screening rate of 37% within three months and acceptance of screening by family units. It was observed that access to treatment was necessary to alleviate patient hesitation to screening due to fears of a positive result. As STI screening increases globally, healthcare systems must develop robust access to treatment to effectively prevent and treat STIs worldwide.

Challenges associated with follow-up care after implementation of an HPV screen-and-treat program with ablative therapy for cervical cancer prevention.

BACKGROUND: Cervical cancer is a preventable cancer; however, decreasing its prevalence requires early detection and treatment strategies that reduce rates of loss to follow-up. This study explores factors associated with loss to follow-up among HPV-positive women after implementation of a new HPV-based screen-and-treat approach for cervical cancer prevention in Iquitos, Peru. METHODS: We conducted semi-structured interviews with "obstetras" (i.e., midwives) (n = 15) working in cervical cancer prevention and women (n = 24) who were recorded as lost to follow-up after positive HPV results. We used the Health Care Access Barriers Model to guide analyses. We utilized manifest content analysis to describe barriers to follow-up according to the obstetras and thematic analysis to report themes from the women's perspectives. We also report the steps and time taken to contact women. RESULTS: We found an incomplete and fragmented patient monitoring system. This incomplete system, in conjunction with challenges in contacting some of the women, led to structural barriers for the obstetras when attempting to deliver positive results. Women in this study expressed a desire to receive treatment, however, faced cognitive barriers including a lack of understanding about HPV results and treatment procedures, fear or anxiety about HPV or treatment, and confusion about the follow-up process. Women also reported having important work matters as a barrier and reported frequently using natural medicine. Reported financial barriers were minimal. CONCLUSION: This study highlights the barriers to follow-up after implementation of a primary-level HPV-based screen-and-treat approach. While some barriers that have previously been associated with loss to follow-up were not as prominently observed in this study (e.g., financial), we emphasize the need for screen-and-treat programs to focus on strategies that can address incomplete registry systems, structural challenges in results delivery, cognitive barriers in understanding results and treatment, and work-related barriers.

Multitarget Compounds for Neglected Diseases: A Review.

Neglected diseases are a group of infectious diseases, many of them parasitic, that mainly affect the poorest populations with limited access to health services, especially those living in remote rural areas and slums. According to the World Health Organization (WHO), neglected diseases put the lives of more than 200 million people at risk, and treatment is made difficult by the occurrence of resistance to existing medications, as well as the high level of toxicity. In this way, the potential of multitarget compounds is highlighted, defined as compounds designed to modulate multiple targets of relevance to disease, with the overall goal of enhancing efficacy and/or improving safety. Thus, the objective of our study is to evaluate existing multitarget compound approaches for neglected diseases, with an emphasis on Leishmaniasis, Chagas Disease, and Arboviruses. A literature review was performed by searching the database "Web of Sciences". In relation to the diseases covered in this work, Leishmaniasis, individually, was the one that presented the largest number of articles (11) that dealt with the topic, which can be justified by the high prevalence of this disease in the world, the second most common disease was Dengue, followed by Chagas disease, Chikungunya virus, and Zika virus. Furthermore, the multitarget potential of phenolic compounds was observed in all diseases under study, with the mechanisms related to the nucleus and transcription being the most reported mechanisms. From this perspective, it is worth highlighting the effectiveness of approaches related to multitarget drugs in discovering new therapeutic agents for neglected diseases.

Screening of the global health priority BoxⓇ reveals potential new disinfectants against the emerging multidrug-resistant pathogen Candida auris.

BACKGROUND: Candida auris has been identified by the World Health Organization as a critical pathogen due to its invasive nature, resistance to multiple drugs, and high mortality rates in hospital outbreaks. This fungus can persist on surfaces and human skin for extended periods, complicating infection control efforts. The need for effective disinfection strategies is urgent, as current disinfectants are often ineffective against C. auris biofilms. OBJECTIVE: The study aimed to identify potential disinfectants from a collection of 240 compounds in the Global Health Priority Box® that are effective against C. auris, particularly strains resistant to existing options. METHODS: The research employed a screening protocol using a fluconazole-resistant strain of C. auris (149/23). Antifungal activity was assessed using the microdilution method to determine Minimum Inhibitory Concentrations (MICs) and Minimum Fungicidal Concentrations (MFCs). Additional assays were conducted to evaluate biofilm inhibition, biofilm eradication, cell membrane integrity, nucleotide leakage, sorbitol protection assay, efflux pump inhibition, and hemolysis assay. RESULTS: Two compounds, Hydramethylnon (MMV1577471) and Flufenerim (MMV1794206), demonstrated significant inhibitory effects against C. auris. Hydramethylnon exhibited potent antifungal activity, inhibiting up to 93 % of fungal growth with an MFC of 16 µg/mL. Flufenerim inhibited up to 58 % of fungal growth, showing fungistatic action with an MFC greater than 4 µg/mL. Biofilm inhibition tests showed that both compounds significantly inhibited biofilm formation, with increased efficacy at higher concentrations. Both compounds showed eradication rates in both stages. Furthermore, Hydramethylnon and Flufenerim did not affect cell membrane integrity or nucleotide leakage, suggesting a mode of action not reliant on disrupting these cellular components. The sorbitol protection assay revealed that neither compound caused cell wall damage. In the efflux pump inhibition assay, Hydramethylnon did not activate efflux pumps, while Flufenerim activated efflux pumps, reducing its effectiveness. Hemocompatibility assay showed safety. CONCLUSION: The study highlights Hydramethylnon and Flufenerim as promising candidates for further development as disinfectants, offering potential solutions to the urgent need for effective disinfection agents against C. auris. The findings underscore the value of screening compound collections to identify novel antifungal agents and understand their mechanisms of action, thereby contributing to the advancement of new disinfection strategies in healthcare settings.

Natural language processing in at-risk mental states: enhancing the assessment of thought disorders and psychotic traits with semantic dynamics and graph theory.

OBJECTIVE: Verbal communication has key information for mental health evaluation. Researchers have linked psychopathology phenomena to some of their counterparts in natural-language-processing (NLP). We study the characterization of subtle impairments presented in early stages of psychosis, developing new analysis techniques and a comprehensive map associating NLP features with the full range of clinical presentation. METHODS: We used NLP to assess elicited and free-speech of 60 individuals in at-risk-mental-states (ARMS) and 73 controls, screened from 4,500 quota-sampled Portuguese speaking citizens in Sao Paulo, Brazil. Psychotic symptoms were independently assessed with Structured-Interview-for-Psychosis-Risk-Syndromes (SIPS). Speech features (e.g.sentiments, semantic coherence), including novel ones, were correlated with psychotic traits (Spearman's-ρ) and ARMS status (general linear models and machine-learning ensembles). RESULTS: NLP features were informative inputs for classification, which presented 86% balanced accuracy. The NLP features brought forth (e.g. Semantic laminarity as 'perseveration', Semantic recurrence time as 'circumstantiality', average centrality in word repetition graphs) carried most information and also presented direct correlations with psychotic symptoms. Out of the standard measures, grammatical tagging (e.g. use of adjectives) was the most relevant. CONCLUSION: Subtle speech impairments can be grasped by sensitive methods and used for ARMS screening. We sketch a blueprint for speech-based evaluation, pairing features to standard thought disorder psychometric items.

Testing an online screening for autism in the COVID-19 pandemic: a psychometric study of the Q-CHAT-24 in Chilean toddlers.

Background: The aim of this study was to examine some psychometric characteristics of the Chilean-adapted version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-24) (24) in a group of unselected children (community sample). This version was administered remotely through an online version during the pandemic period to caregivers of children, aged 18-24 months, registered in four primary care polyclinics of the Health Service Araucanía Sur, Chile. Methods: An intentional non-probabilistic sampling was used. Three hundred and thirteen toddlers were examined. Participants completed an online version of the Q-CHAT-24 which was disseminated through the REDCap platform. Evidence of reliability through internal consistency and evidence of predictive validity through ROC curve analysis were realized. Results: The mean age of the children evaluated was 21.16 months. The Shapiro-Wilk test revealed that Q-CHAT-24 scores was normally distributed. 71 cases (23.12%) scored 38 points or more on the Q-CHAT-24, qualifying as Autistic Risk. 48 cases (15.63%) were confirmed as autistic through the ADOS-2 Module T. All items were positively correlated with Q-CHAT-24 total score. All items were positively correlated with Q-CHAT-24 total score. Internal consistency was acceptable for the Q-CHAT-24 (Cronbach ´s α=0.78). The internal consistencies were analyzed for the Q-CHAT-24 Factors, and they were good for factor 1 "Communication and Social Interaction" (Cronbach ´s α=0.85) and acceptable for factor 2 "Restrictive and Repetitive Patterns" (Cronbach ´s α=0.74). Receiver operating characteristic (ROC) curve analyses were performed. The AUC values were 0.93 with statistical significance (p<0.01). For the cut-off point of 38, the Sensitivity, Specificity and Youden index values were 0.89, 0.8 and 0.7, respectively. The Positive Predictive Value (PPV) was 86% and the Negative Predictive Value (NPV) was 85%. Conclusions: In accordance with the objectives of this study, evidence of reliability and predictive validity was demonstrated for the Q-CHAT-24 in this Chilean population. More importantly, this study provides Sensitivity and Specificity data for a remote application version of an autism screening tool already validated in Chile. The implications of this have to do with the possibility of establishing a remote assessment system for children at risk of autism on a population scale.

Enhancing Cervical Cancer Screening with 7-Type HPV mRNA E6/E7 Testing on Self-Collected Samples: Multicentric Insights from Mexico.

Cervical cancer remains a significant public health issue, particularly in regions with low screening uptake. This study evaluates the effectiveness of self-sampling and the 7-type HPV mRNA E6/E7 test in improving cervical cancer screening outcomes among a referral population in Mexico. A cohort of 418 Mexican women aged 25 to 65, referred for colposcopy and biopsy due to abnormal cytology results (ASC-US+), participated in this study. Self-samples were analyzed using both the 14-type HPV DNA test and the 7-type HPV mRNA E6/E7 test. The study assessed the sensitivity, specificity, positive predictive value (PPV), and the necessity of colposcopies to detect CIN3+ lesions. Participant acceptability of self-sampling was also evaluated through a questionnaire. The 7-type HPV mRNA E6/E7 test demonstrated equivalent sensitivity but significantly higher specificity (77.0%) and PPV for CIN3+ detection compared to the 14-type HPV DNA test (specificity: 45.8%, p < 0.001). The use of the HPV mRNA test as a triage tool reduced the number of colposcopies needed per CIN3+ case detected from 16.6 to 7.6 (p < 0.001). Self-sampling was highly accepted among participants, with the majority reporting confidence in performing the procedure, minimal discomfort, and willingness to undertake self-sampling at home. Self-sampling combined with the 7-type HPV mRNA E6/E7 testing offers a promising strategy to enhance cervical cancer screening by improving accessibility and ensuring precise diagnostics. Implementing these app roaches could lead to a significant reduction in cervical cancer morbidity and mortality, especially in underserved populations. Future research should focus on the long-term impact of integrating these methods into national screening programs and explore the cost-effectiveness of widespread implementation.

Estimation of the population at high risk of developing lung cancer in Chile using simplified eligibility criteria.

OBJECTIVES: Several countries in different global regions are implementing lung cancer (LC) screening programmes. This study aimed to estimate the proportion of the Chilean population ≥15 years who are at high risk of developing LC. STUDY DESIGN: Cross-sectional study. METHODS: Data from the Chilean National Health Survey were used in this study. Information on age and history of tobacco consumption were retrieved to estimate national and regional proportions of the Chilean population ≥15 years who are at high risk of developing LC, according to the inclusion criteria in the NELSON trial, NLST trial and USPSTF2021 recommendations. Stratified analyses were performed by sex and quartiles of monthly household income. RESULTS: An estimated 292,158 (2.2%; 95% confidence interval [CI] 1.6-2.8), 174,196 (1.3%; 95% CI 0.9-1.7) and 404,751 (3.1%; 95% CI 2.4-3.8) of Chileans are at high risk of LC according to NELSON and NLST trial inclusion criteria and USPSTF2021 recommendations, respectively. Proportions of males who are at high risk were higher in comparison to females. The highest proportion of people who are at high risk was found in the lowest household income quartile. Regionally, the lowest percentage of Chileans who are at high risk was found in La Araucanía and the highest in Magallanes y Antártica. CONCLUSIONS: There is a relevant number of Chileans who are at high risk of developing LC. Policymakers in Chile should enhance tobacco control efforts to reduce the prevalence of tobacco smoking and also explore the implementation of LC screening programmes to reduce the burden of LC.

Baseline surveillance in Li Fraumeni syndrome using whole-body MRI: a systematic review and updated meta-analysis.

OBJECTIVES: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. The use of whole-body magnetic resonance imaging (WBMRI) is recommended for regular cancer screening, however, evidence supporting the benefits in asymptomatic LFS patients is limited. This study aims to assess the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and follow-up. MATERIALS AND METHODS: We systematically searched PubMed, Cochrane, and Embase databases for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence of the included variables along with their corresponding 95% confidence intervals (CIs). Statistical analyses were performed using R software, version 4.3.1. RESULTS: From 1687 results, 11 comprising 703 patients (359 females (51%); with a median age of 32 years (IQR 1-74)) were included. An estimated detection rate of 31% (95% CI: 0.28, 0.34) for any suspicious lesions was found in asymptomatic TP53 carriers who underwent baseline WBMRI. A total of 277 lesions requiring clinical follow-up were identified in 215 patients. Cancer was confirmed in 46 lesions across 39 individuals. The estimated cancer diagnosis rate among suspicious lesions was 18% (95% CI: 0.13, 0.25). WBMRI detected 41 of the 46 cancers at an early-disease stage, with an overall detection rate of 6% (95% CI: 0.05, 0.08). The incidence rate was 2% per patient round of WBMRI (95% CI: 0.01, 0.04), including baseline and follow-up. CONCLUSION: This meta-analysis provides evidence that surveillance with WBMRI is effective in detecting cancers in asymptomatic patients with LFS. CLINICAL RELEVANCE STATEMENT: Our study demonstrates that whole-body MRI is an effective tool for early cancer detection in asymptomatic Li-Fraumeni Syndrome patients, highlighting its importance in surveillance protocols to improve diagnosis and treatment outcomes. KEY POINTS: Current evidence for whole-body MRI screening of asymptomatic Li-Fraumeni Syndrome (LFS) patients remains scarce. Whole-body MRI identified 41 out of 46 cancers at an early stage, achieving an overall detection rate of 6%. Whole-body MRI surveillance is a valuable method for detecting cancers in asymptomatic LFS patients.

May Measurement Month 2021: an analysis of blood pressure screening results from Mexico.

May Measurement Month 2021 (MMM21) in Mexico was an opportunistic survey that aimed to improve blood pressure awareness at the individual and population levels and to analyse the impact of the COVID-19 pandemic on the prevalence, knowledge, and rates of hypertension in the country. This survey followed the methodology of MMM, previously published. The total number of participants screened was 77 547, of which 47 793 (61.6%) were female and 29 178 (37.6%) were male. The mean age (SD) was 46.2 (16.6) years. Of all 77 547 participants, 14 939 (19.3%) had hypertension, of which 48% were aware. The frequency and awareness of hypertension in this survey are similar to those reported before the pandemic (MMM19-Mexico and the 2019 National Health Survey), suggesting that the impact of the COVID-19 pandemic in these parameters of arterial hypertension was not as important as expected. These data are concordant with the official reports in Mexico that showed that the pandemic had a severe impact on cardiovascular mortality but did not modify mortality due to hypertension or stroke.

May Measurement Month 2021: an analysis of blood pressure screening results from Venezuela.

Cardiovascular diseases continue to be the main cause of death in Venezuela, and hypertension is the principal risk factor. The May Measurement Month (MMM) campaign is a global initiative aimed to raising awareness of hypertension, which has been conducted in Venezuela since 2017. May Measurement Month 2021 included 46 732 participants with a mean age of 56.4 years (SD 14.4), 57.9% of whom were female. The percentage with hypertension was 60.3% (57.9% of females and 63.7% of males), 82.3% (84.8% of females and 79.2% of males) were aware, and 80.2% were taking antihypertensive medication. Of those on antihypertensive medication, 44.2% (41.2% of females and 48.2% of males) were not controlled [blood pressure (BP) ≥ 140/≥90 mmHg], with 61.3% receiving one drug, 30.0% two drugs, and 8.7% three or more drugs. 87.5% of those on treatment reported taking it regularly. Conditions associated with higher BP levels include fewer years of education, having a previous diagnosis of hypertension, and women who were hypertensive during a previous pregnancy. Physical activity and pregnancy were conditions associated with lower BP levels. A previous positive COVID-19 test was reported in 11.1%, and one or more COVID-19 vaccinations reported in 22.7% of participants. Of those on antihypertensive medication, 78.8% reported their treatment was not affected by COVID-19. Results are consistent with previous MMM campaigns and indicate that the screening campaign is feasible and useful to identify hypertension even in exceptional conditions such as the COVID-19 pandemic.