Incidence and associated factors of surgical site infection in patients undergoing foot and ankle surgery: a 7-year cohort study.

Surgical site infections (SSI) constitute 31% of all hospital-acquired conditions, with ankle and foot surgical procedures showing an incidence of SSI ranging from 0.5% to 6.5%. This study aimed to assess the incidence of both superficial and deep surgical site infections in foot and ankle surgery, along with associated factors. Conducted as a retrospective cohort study, it included 2180 patients undergoing foot and ankle surgery in a private hospital between 2014 and 2020, encompassing elective and trauma cases. Outcome variables comprised SSI, while predictor variables encompassed sex, age, diabetes mellitus, systemic arterial hypertension, smoking, American Society of Anesthesiologists (ASA) score, and body mass index. Logistic regression models were employed to identify associations between study variables. The incidence of surgical site infections stood at 4% (83/2180), comprising a rate of 2.8% (57/2180) for superficial infections and 1.2% (26/2180) for deep infections. Smoking (OR 2.9, 95%CI 1.4-5.3) and ASA score >2 (OR 3.4, 95%CI 1.2-8.4) emerged as independent factors associated with surgical site infections. The group with deep infections exhibited higher proportions of smokers (p = 0.002), systemic arterial hypertension (p = 0.018), trauma surgery (p = 0.049), and an ASA score >2 (p = 0.011). Overall infection incidence in this cohort reached 4%, with trauma cases, smoking, hypertension, and an ASA score >2 independently linked to deep infections. Surgeons should be cognizant of these risk factors when managing prophylactic antibiotic regimens for patients.

BjussuMP-II, a venom metalloproteinase, induces the release and cleavage of pro-inflammatory cytokines and disrupts human umbilical vein endothelial cells.

Snake venom metalloproteases (SVMPs) are hydrolytic enzymes dependent on metal binding, primarily zinc (Zn2+), at their catalytic site. They are classified into three classes (P-I to P-III). BjussuMP-II, a P-I SVMP isolated from Bothrops jararacussu snake venom, has a molecular mass of 24 kDa. It exhibits inhibitory activity on platelet aggregation and hydrolyzes fibrinogen. TNF-α upregulates the expression of adhesion molecules on endothelial cell surfaces, promoting leukocyte adhesion and migration during inflammation. Literature indicates that SVMPs may cleave the TNF-α precursor, possibly due to significant homology between metalloproteases from mammalian extracellular matrix and SVMPs. This study aimed to investigate BjussuMP-II's effects on human umbilical vein endothelial cells (HUVEC), focusing on viability, detachment, adhesion, release, and cleavage of TNF-α, IL-1ß, IL-6, IL-8, and IL-10. HUVEC were incubated with BjussuMP-II (1.5-50 µg/mL) for 3-24 h. Viability was determined using LDH release, MTT metabolization, and 7AAD for membrane integrity. Adhesion and detachment were assessed by incubating cells with BjussuMP-II and staining with Giemsa. Cytokines were quantified in HUVEC supernatants using EIA. TNF-α cleavage was evaluated using supernatants from PMA-stimulated cells or recombinant TNF-α. Results demonstrated BjussuMP-II's proteolytic activity on casein. It was not toxic to HUVEC at any concentration or duration studied but interfered with adhesion and promoted detachment. PMA induced TNF-α release by HUVEC, but this effect was not observed with BjussuMP-II, which cleaved TNF-α. Additionally, BjussuMP-II cleaved IL-1ß, IL-6, and IL-10. These findings suggest that the zinc metalloprotease BjussuMP-II could be a valuable biotechnological tool for treating inflammatory disorders involving cytokine deregulation.

Evidence of a pan-tissue decline in stemness during human aging.

Despite their biological importance, the role of stem cells in human aging remains to be elucidated. In this work, we applied a machine learning methodology to GTEx transcriptome data and assigned stemness scores to 17,382 healthy samples from 30 human tissues aged between 20 and 79 years. We found that ~60% of the studied tissues exhibit a significant negative correlation between the subject's age and stemness score. The only significant exception was the uterus, where we observed an increased stemness with age. Moreover, we observed that stemness is positively correlated with cell proliferation and negatively correlated with cellular senescence. Finally, we also observed a trend that hematopoietic stem cells derived from older individuals might have higher stemness scores. In conclusion, we assigned stemness scores to human samples and show evidence of a pan-tissue loss of stemness during human aging, which adds weight to the idea that stem cell deterioration may contribute to human aging.

Somatic mutations in human ageing: New insights from DNA sequencing and inherited mutations.

The accumulation of somatic mutations is a driver of cancer and has long been associated with ageing. Due to limitations in quantifying mutation burden with age in non-cancerous tissues, the impact of somatic mutations in other ageing phenotypes is unclear. Recent advances in DNA sequencing technologies have allowed the large-scale quantification of somatic mutations in ageing tissues. These studies have revealed a gradual accumulation of mutations in normal tissues with age as well as a substantial clonal expansion driven mostly by cancer-related mutations. Nevertheless, it is difficult to envision how the burden and stochastic nature of age-related somatic mutations identified so far can explain most ageing phenotypes that develop gradually. Studies across species have also found that longer-lived species have lower somatic mutation rates, though these could be due to selective pressures acting on other phenotypes such as perhaps cancer. Recent studies in patients with higher somatic mutation burden and no signs of accelerated ageing further question the role of somatic mutations in ageing. Overall, with a few exceptions like cancer, recent DNA sequencing studies and inherited mutations do not support the idea that somatic mutations accumulating with age drive ageing phenotypes, and the phenotypic role, if any, of somatic mutations in ageing remains unclear.

Minimally Invasive Peroneal Tenodesis Assisted by Peroneal Tendoscopy: Technique and Preliminary Results.

Introduction: Peroneal disorders are a common cause of ankle pain and lateral instability and have been described in as much as 77% of patients with lateral ankle instability. Clicking, swelling, pain, and tenderness in the peroneal tendons track are frequent symptoms, but they can be confused with other causes of lateral ankle pain. The management of peroneal disorders can be conservative or surgical. When the conservative treatment fails, surgery is indicated, and open or tendoscopic synovectomy, tubularization, tenodesis or tendon transfers can be performed. The authors present a surgical technique of tendoscopy associated to minimally invasive tenodesis for the treatment of peroneal tendon tears, as well as the preliminary results of patients submitted to this procedure. Methods: Four patients with chronic lateral ankle pain who were diagnosed with peroneal brevis pathology were treated between 2020 and 2022 with tendoscopic-assisted minimally invasive synovectomy and tenodesis. Using a 2.7 mm 30° arthroscope and a 3.0 mm shaver blade, the entire length of the peroneus brevis tendon and most parts of the peroneus longus tendon can be assessed within Sammarco's zones 1 and 2. After the inspection and synovectomy, a minimally invasive tenodesis is performed. Results: All patients were evaluated at least six months after surgery. All of them reported improvement in daily activities and in the Foot Function Index (FFI) questionnaire (pre-surgery mean FFI = 23.86%; post-surgery mean FFI = 6.15%), with no soft tissue complications or sural nerve complaints. Conclusion: The tendoscopy of the peroneal tendons allows the surgeon to assess their integrity, confirm the extent of the lesion, perform synovectomy, prepare the tendon for tenodesis, and perform it in a safe and minimally invasive way, reducing the risks inherent to the open procedure.

Diferenças Étnicas na Sobrevida entre Medalhistas Olímpicos Brasileiros da Era Moderna de 1920 a 1992: Um Estudo de Coorte / Ethnic Differences in Survival among Brazilian Modern-era Olympic Medalists from 1920 to 1992: A Cohort Study

Resumo Fundamento: As disparidades nos resultados de saúde entre grupos raciais merecem investigação, mesmo em atletas de elite. Portanto, compreender o impacto da raça na sobrevida pós-medalha em atletas olímpicos brasileiros torna-se essencial. Objetivo: Comparar a sobrevida pós-medalha entre medalhistas olímpicos brasileiros brancos e não brancos de 1920 a 1992. Métodos: Utilizamos dados disponíveis publicamente para um estudo de coorte retrospectivo de todos os medalhistas olímpicos brasileiros de 1920 a 1992 (somente homens). Os atletas foram classificados nos grupos brancos e não brancos usando determinação estruturada de etnia. As análises de Kaplan-Meier calcularam o tempo médio de sobrevida restrito (TMSR) para cada grupo étnico. Uma análise de riscos proporcionais de Cox avaliou as diferenças de sobrevida baseadas na etnia, ajustando para a idade da conquista da medalha e ano de nascimento (p<0,05). Resultados: Entre 123 atletas (73,9% brancos), a idade média da conquista de medalhas foi de 25,03 ± 4,8 anos. Durante o estudo, 18,7% dos atletas brancos e 37,5% dos atletas não brancos morreram (p=0,031). Os atletas brancos tiveram média de idade ao óbito de 75,10 ± 18,01 anos, enquanto os atletas não brancos tiveram idade média de 67,13 ± 14,90 anos (p=0,109). O TMSR para atletas brancos foi de 51,59 (IC 95%, 49,79 - 53,39) anos, e para atletas não brancos foi de 45,026 (IC 95%, 41,31 - 48,74) anos, resultando em um ΔTMSR de 6,56 (IC 95%, 2,43 - 10,70; p=0,0018). A análise multivariada mostrou que atletas não brancos apresentavam maior risco de mortalidade do que atletas brancos (RC 5,58; IC 95%, 2,18 - 14,31). Conclusão: Após a primeira medalha, os atletas olímpicos brasileiros brancos normalmente desfrutam de uma expectativa de vida seis anos mais longa do que seus colegas não brancos, ilustrando uma acentuada diferença de mortalidade e disparidades de saúde entre indivíduos saudáveis no Brasil.

Abstract Background: Disparities in health outcomes among racial groups warrant investigation, even among elite athletes. Therefore, understanding the impact of race upon post-medal survival in Brazilian Olympians becomes essential. Objective: To compare post-medal survival between white and non-white Brazilian Olympic medalists from 1920 to 1992. Methods: This study used publicly available data for a retrospective cohort study on all Brazilian Olympic medalists from 1920 to 1992 (males only). Athletes were classified into white and non-white groups using structured ethnicity determination. Kaplan-Meier analyses computed the restricted mean survival time (RMST) for each ethnic group. A Cox proportional hazards analysis assessed ethnicity-based survival differences, adjusting for medal-winning age and birth year (p<0.05) Results: Among 123 athletes (73.9% white), the mean age of medal achievement was 25.03±4.8 years. During the study, 18.7% of white and 37.5% of non-white athletes died (p=0.031). White athletes had a mean age at death of 75.10±18.01 years, while non-white athletes had an age of 67.13±14.90 years (p=0.109). The RMST for white athletes was 51.59 (95% CI 49.79-53.39) years, while for non-white athletes, it was 45.026 (95% CI 41.31-48.74) years, resulting in a ΔRMST of 6.56 (95% CI 2.43-10.70; p=0.0018). Multivariate analysis showed that non-white athletes had a higher mortality risk than did white athletes (HR 5.58; 95% CI, 2.18-14.31). Conclusion: Following their first medal, white Brazilian Olympians typically enjoy a six-year longer lifespan than their non-white counterparts, illustrating a marked mortality gap and health disparities among healthy individuals in Brazil.

Transcriptomic analysis reveals a tissue-specific loss of identity during ageing and cancer.

INTRODUCTION: Understanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx. RESULTS: We found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age. For most cancer types, we have noted a consistent pattern of downregulation in genes that are specific to the tissue from which the tumor originated. Moreover, we observed in cancer an activation of genes not usually expressed in the tissue of origin as well as an upregulation of genes specific to other tissues. These patterns in cancer were associated with patient survival. The age of the patient, however, did not influence these patterns. CONCLUSION: We identified loss of cellular identity in 40% of the tissues analysed during human ageing, and a clear pattern in cancer, where during tumorigenesis cells express genes specific to other organs while suppressing the expression of genes from their original tissue. The loss of cellular identity observed in cancer is associated with prognosis and is not influenced by age, suggesting that it is a crucial stage in carcinogenesis.

Effects of exercise training on cancer patients undergoing neoadjuvant treatment: A systematic review.

OBJECTIVES: This systematic review aimed to analyze the effects of different exercise protocols on physical fitness (cardiorespiratory fitness, muscle strength, and body composition), quality of life, cancer-related fatigue, and sleep quality in patients with different types of cancer undergoing neoadjuvant treatment. DESIGN: Systematic review. METHOD: A comprehensive search of existing literature was carried out using four electronic databases: PubMed, Scopus, Web of Science, and Cochrane Library (published until October 19, 2022). All databases were searched for randomized controlled trials, quasi-experimental investigations, and pre-post investigations assessing the effects of exercise in cancer patients during neoadjuvant treatment. Excluded articles included multicomponent interventions, such as exercise plus diet or behavioral therapy, and investigations performed during adjuvant treatment or survivorship. The methodological quality of each study was assessed using the Physiotherapy Evidence Database (PEDro) scale. RESULTS: Twenty-seven trials involving 999 cancer patients were included in this review. The interventions were conducted in cancer patients undergoing neoadjuvant treatment for rectal (n = 11), breast (n = 5), pancreatic (n = 4), esophageal (n = 3), gastro-esophageal (n = 2), and prostate (n = 1) cancers, and leukemia (n = 1). Among the investigations included, 14 utilized combined exercise protocols, 11 utilized aerobic exercise, and two utilized both aerobic and resistance training separately. Exercise interventions appeared to improve cardiorespiratory fitness, muscle strength, body composition, and quality of life, although many investigations lacked a between-group analysis. CONCLUSION: Despite limited evidence, exercise interventions applied during neoadjuvant treatment demonstrate promising potential in enhancing cardiorespiratory fitness, muscle strength, body composition, and overall quality of life. However, a scarcity of evidence remains on the effects of exercise on cancer-related fatigue and sleep quality. Further research with high-quality randomized controlled trials is warranted.

Predicting lifespan-extending chemical compounds for C. elegans with machine learning and biologically interpretable features.

Recently, there has been a growing interest in the development of pharmacological interventions targeting ageing, as well as in the use of machine learning for analysing ageing-related data. In this work, we use machine learning methods to analyse data from DrugAge, a database of chemical compounds (including drugs) modulating lifespan in model organisms. To this end, we created four types of datasets for predicting whether or not a compound extends the lifespan of C. elegans (the most frequent model organism in DrugAge), using four different types of predictive biological features, based on: compound-protein interactions, interactions between compounds and proteins encoded by ageing-related genes, and two types of terms annotated for proteins targeted by the compounds, namely Gene Ontology (GO) terms and physiology terms from the WormBase's Phenotype Ontology. To analyse these datasets, we used a combination of feature selection methods in a data pre-processing phase and the well-established random forest algorithm for learning predictive models from the selected features. In addition, we interpreted the most important features in the two best models in light of the biology of ageing. One noteworthy feature was the GO term "Glutathione metabolic process", which plays an important role in cellular redox homeostasis and detoxification. We also predicted the most promising novel compounds for extending lifespan from a list of previously unlabelled compounds. These include nitroprusside, which is used as an antihypertensive medication. Overall, our work opens avenues for future work in employing machine learning to predict novel life-extending compounds.

Effects of home-based exercise programs on physical fitness in cancer patients undergoing active treatment: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This systematic review and meta-analysis aimed to investigate the effects of home-based exercise on physical fitness (cardiorespiratory fitness, muscle strength, and body composition) in cancer patients undergoing active treatment. DESIGN: Systematic review with meta-analysis and Grading Recommendations Assessment, Development, and Evaluation of the evidence. METHODS: A comprehensive search of existing literature was carried out in four electronic databases: PubMed, Web of Science, Scopus, and PEDro. All databases were searched for randomized controlled trials assessing the effects of home-based exercise on physical fitness outcomes in cancer patients during active treatment. Multicomponent interventions (i.e., exercise plus diet/behavioral therapy) were excluded. The methodological quality of each study was assessed using the Revised Cochrane risk-of-bias tool for randomized trials. Meta-analytical procedures were performed when appropriate and standardized mean differences (SMD) were calculated. RESULTS: Twenty-eight randomized controlled trials (n = 2424 cancer patients) were included. Most of the interventions were conducted in breast cancer patients (n = 13) during the adjuvant treatment period (n = 17); 18 studies included a walking component in their home-based protocol. Home-based exercise was effective at improving the distance of the 6-minute walk test (k = 6; SMD = 0.321, p = 0.010). However, the results were no longer significant when performing sensitivity analysis based on exclusively walking (k = 1) and non-exclusively walking interventions (k = 5; SMD = 0.258; p = 0.072). No effects were found for muscle strength and body composition outcomes (p > 0.05). CONCLUSIONS: Regular home-based exercise programs are an effective strategy to improve 6-minutes walk test in cancer patients undergoing active treatment. Conversely, no alterations were found in muscle strength and body composition.

Selective ablation of primary and paracrine senescent cells by targeting iron dyshomeostasis.

Senescent cells can spread the senescent phenotype to other cells by secreting senescence-associated secretory phenotype factors. The resulting paracrine senescent cells make a significant contribution to the burden of senescent cell accumulation with age. Previous efforts made to characterize paracrine senescence are unreliable due to analyses being based on mixed populations of senescent and non-senescent cells. Here, we use dipeptidyl peptidase-4 (DPP4) as a surface maker to isolate senescent cells from mixed populations. Using this technique, we enrich the percentage of paracrine senescence from 40% to 85%. We then use this enriched culture to characterize DPP4+ primary and paracrine senescent cells. We observe ferroptosis dysregulation and ferrous iron accumulation as a common phenomenon in both primary and paracrine senescent cells. Finally, we identify ferroptosis induction and ferrous iron-activatable prodrug as a broad-spectrum senolytic approach to ablate multiple types of primary and paracrine senescent cells.

Intensity matters: impact of physical activity energy expenditure at moderate and vigorous intensity on total and abdominal obesity in children.

BACKGROUND/OBJECTIVES: Physical activity (PA) guidelines advocate that children should accumulate at least 60 min of moderate-to-vigorous PA daily. Still, it is not clear how body fat may differ if the same dose of PA is accumulated at different intensities. We aimed to determine the independent associations of energy expenditure (EE) at moderate (MPA) and vigorous (VPA) PA intensity on total and abdominal fat in children and if these associations were moderated by cardiorespiratory fitness (CRF). SUBJECTS/METHODS: A total of 326 children (girls = 171, boys = 151) aged 10-12 years had PA assessed with accelerometers. Total fat mass index (FMI) and abdominal FMI were assessed with DXA. CRF was assessed by a cycle ergometer test. Linear regression models were used to model the outcomes with the inclusion of an interaction term to test for moderation effects. RESULTS: An inverse association was found between VPA EE and FMI (ß = -0.013, p < 0.001) and abdominal FMI (ß = -0.0014, p < 0.001) independent of MPA EE. In contrast, MPA EE was not related to adiposity independent of VPA EE (p > 0.05). The relationships between the PA intensities and FMI and abdominal FMI were moderated by CRF. MPA EE was positively associated with adiposity in children with high levels of CRF, whereas VPA EE remained inversely associated with adiposity regardless of CRF level, although the strength of the association was lower in those with higher CRF levels. CONCLUSION: PA programs should provide opportunities for children to perform VPA in order to achieve healthier body fat profiles and avoid excess adiposity.

Systematic review of pharmacological management in Creutzfeldt-Jakob disease: no options so far?

BACKGROUND: The Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy that manifests as a rapidly progressive dementia syndrome. Currently, CJD has no cure, and many patients die within the first year, but some drugs are being studied as options for managing this condition. OBJECTIVE: To evaluate the effectiveness of pharmacological treatments offered to patients with CJD as a means to increase survival and reduce cognitive deterioration. METHODS: A systematic review of the literature was performed using 4 independent reviewers and 1 extra reviewer to resolve possible divergences in the search and analysis of papers indexed in MedLINE (PubMed), SciELO and Lilacs databases. The Medical Subject Heading (MeSH) terms used were: prion diseases, Creutzfeldt-Jakob disease, pharmacologic therapy, therapeutics, quinacrine, doxycycline, flupirtine, and pentosan polysulfate, with the Boolean operators AND and OR. This search included controlled clinical trials, uncontrolled clinical trials, and case series published from the year 2000 onwards, in the English language. RESULTS: A total of 85 papers were found using the descriptors used. At the end of the selection analyses, 9 articles remained, which were analyzed fully and individually. CONCLUSIONS: None of the drugs evaluated proved significantly effective in increasing survival in patients with CJD. Flupirtine appears to have a beneficial effect in reducing cognitive deterioration in patients with CJD. However, additional studies are needed to establish better evidence and therapeutic options for the management of patients with CJD.

ANTECEDENTES: A doença de Creutzfeldt-Jakob (DCJ) é uma encefalopatia espongiforme que se manifesta como síndrome demencial rapidamente progressiva. Atualmente, a DCJ não possui cura e muitos pacientes morrem no primeiro ano de doença, mas alguns medicamentos vêm sendo estudados como opções no manejo desta condição. OBJETIVO: Avaliar a eficácia dos tratamentos farmacológicos oferecidos aos pacientes com DCJ no aumento de sobrevida e na redução da deterioração cognitiva. MéTODOS: Foi realizada uma revisão sistemática da literatura utilizando 4 revisores independentes e 1 extra para resolver divergências eventuais na busca e na análise de trabalhos indexados nas bases de dados MedLINE (via PubMed), SciELO e Lilacs. Os termos Medical Subjects Heading (MeSH) utilizados foram: prion diseases, creutzfeldt jakob disease, pharmacologic therapy, therapeutics, quinacrine, doxycycline, flupirtine e pentosan polysulfate, com os operadores booleanos AND e OR. Essa pesquisa incluiu ensaios clínicos controlados, não controlados e séries de casos, publicados a partir do ano 2000 no idioma inglês. RESULTADOS: Ao todo, foram encontrados 85 trabalhos através dos descritores utilizados. Ao final das análises de seleção, restaram 9 artigos, que foram analisados na íntegra individualmente. CONCLUSõES: Nenhuma das drogas avaliadas se mostrou significativamente eficaz no aumento da sobrevida dos pacientes com DCJ. A flupirtina parece ter um efeito benéfico na redução da deterioração cognitiva dos pacientes com DCJ. Entretanto, estudos adicionais são necessários para o estabelecimento de melhores evidências e opções terapêuticas para o manejo dos pacientes com DCJ.

m6A-TSHub: Unveiling the Context-specific m6A Methylation and m6A-affecting Mutations in 23 Human Tissues.

As the most pervasive epigenetic marker present on mRNA and lncRNA, N6-methyladenosine (m6A) RNA methylation has been shown to participate in essential biological processes. Recent studies have revealed the distinct patterns of m6A methylome across human tissues, and a major challenge remains in elucidating the tissue-specific presence and circuitry of m6A methylation. We present here a comprehensive online platform m6A-TSHub for unveiling the context-specific m6A methylation and genetic mutations that potentially regulate m6A epigenetic mark. m6A-TSHub consists of four core components, including: (1) m6A-TSDB, a comprehensive database of 184,554 functionally annotated m6A sites derived from 23 human tissues and 499,369 m6A sites from 25 tumor conditions, respectively; (2) m6A-TSFinder, a web server for high-accuracy prediction of m6A methylation sites within a specific tissue from RNA sequences, which was constructed using multi-instance deep neural networks with gated attention; (3) m6A-TSVar, a web server for assessing the impact of genetic variants on tissue-specific m6A RNA modifications; and (4) m6A-CAVar, a database of 587,983 The Cancer Genome Atlas (TCGA) cancer mutations (derived from 27 cancer types) that were predicted to affect m6A modifications in the primary tissue of cancers. The database should make a useful resource for studying the m6A methylome and the genetic factors of epitranscriptome disturbance in a specific tissue (or cancer type). m6A-TSHub is accessible at www.xjtlu.edu.cn/biologicalsciences/m6ats.

Systematic review of pharmacological management in Creutzfeldt-Jakob disease: no options so far? / Revisão sistemática do manejo farmacológico na doença de Creutzfeldt-Jakob: ainda sem opções?

Abstract Background The Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy that manifests as a rapidly progressive dementia syndrome. Currently, CJD has no cure, and many patients die within the first year, but some drugs are being studied as options for managing this condition. Objective To evaluate the effectiveness of pharmacological treatments offered to patients with CJD as a means to increase survival and reduce cognitive deterioration. Methods A systematic review of the literature was performed using 4 independent reviewers and 1 extra reviewer to resolve possible divergences in the search and analysis of papers indexed in MedLINE (PubMed), SciELO and Lilacs databases. The Medical Subject Heading (MeSH) terms used were: prion diseases, Creutzfeldt-Jakob disease, pharmacologic therapy, therapeutics, quinacrine, doxycycline, flupirtine, and pentosan polysulfate, with the Boolean operators AND and OR. This search included controlled clinical trials, uncontrolled clinical trials, and case series published from the year 2000 onwards, in the English language. Results A total of 85 papers were found using the descriptors used. At the end of the selection analyses, 9 articles remained, which were analyzed fully and individually. Conclusions None of the drugs evaluated proved significantly effective in increasing survival in patients with CJD. Flupirtine appears to have a beneficial effect in reducing cognitive deterioration in patients with CJD. However, additional studies are needed to establish better evidence and therapeutic options for the management of patients with CJD.

Resumo Antecedentes A doença de Creutzfeldt-Jakob (DCJ) é uma encefalopatia espongiforme que se manifesta como síndrome demencial rapidamente progressiva. Atualmente, a DCJ não possui cura e muitos pacientes morrem no primeiro ano de doença, mas alguns medicamentos vêm sendo estudados como opções no manejo desta condição. Objetivo Avaliar a eficácia dos tratamentos farmacológicos oferecidos aos pacientes com DCJ no aumento de sobrevida e na redução da deterioração cognitiva. Métodos Foi realizada uma revisão sistemática da literatura utilizando 4 revisores independentes e 1 extra para resolver divergências eventuais na busca e na análise de trabalhos indexados nas bases de dados MedLINE (via PubMed), SciELO e Lilacs. Os termos Medical Subjects Heading (MeSH) utilizados foram: prion diseases, creutzfeldt jakob disease, pharmacologic therapy, therapeutics, quinacrine, doxycycline, flupirtine e pentosan polysulfate, com os operadores booleanos AND e OR. Essa pesquisa incluiu ensaios clínicos controlados, não controlados e séries de casos, publicados a partir do ano 2000 no idioma inglês. Resultados Ao todo, foram encontrados 85 trabalhos através dos descritores utilizados. Ao final das análises de seleção, restaram 9 artigos, que foram analisados na íntegra individualmente. Conclusões Nenhuma das drogas avaliadas se mostrou significativamente eficaz no aumento da sobrevida dos pacientes com DCJ. A flupirtina parece ter um efeito benéfico na redução da deterioração cognitiva dos pacientes com DCJ. Entretanto, estudos adicionais são necessários para o estabelecimento de melhores evidências e opções terapêuticas para o manejo dos pacientes com DCJ.

Age-associated differences in the cancer molecular landscape.

Cancer is an age-related disease, as incidence and mortality for most types of cancer increase with age. However, how molecular alterations in tumors differ among patients of different ages remains poorly understood. Recent studies have shed light on the age-associated molecular landscapes in cancer. Here, we summarize the main findings of these current studies, highlighting major differences in the genomic, transcriptomic, epigenetic, and immunological landscapes between cancer in younger and older patients. Importantly, some cancer driver genes are mutated more frequently in younger or older patients. We discuss the potential roles of aging-related processes in shaping these age-related differences in cancer. We further emphasize the remaining unsolved questions that could provide important insights that will have implications in personalized medicine.

Skin Aging in Long-Lived Naked Mole-Rats Is Accompanied by Increased Expression of Longevity-Associated and Tumor Suppressor Genes.

Naked mole-rats (NMRs) (Heterocephalus glaber) are long-lived mammals that possess a natural resistance to cancer and other age-related pathologies, maintaining a healthy life span >30 years. In this study, using immunohistochemical and RNA-sequencing analyses, we compare skin morphology, cellular composition, and global transcriptome signatures between young and aged (aged 3‒4 vs. 19‒23 years, respectively) NMRs. We show that similar to aging in human skin, aging in NMRs is accompanied by a decrease in epidermal thickness; keratinocyte proliferation; and a decline in the number of Merkel cells, T cells, antigen-presenting cells, and melanocytes. Similar to that in human skin aging, expression levels of dermal collagens are decreased, whereas matrix metalloproteinase 9 and matrix metalloproteinase 11 levels increased in aged versus in young NMR skin. RNA-sequencing analyses reveal that in contrast to human or mouse skin aging, the transcript levels of several longevity-associated (Igfbp3, Igf2bp3, Ing2) and tumor-suppressor (Btg2, Cdkn1a, Cdkn2c, Dnmt3a, Hic1, Socs3, Sfrp1, Sfrp5, Thbs1, Tsc1, Zfp36) genes are increased in aged NMR skin. Overall, these data suggest that specific features in the NMR skin aging transcriptome might contribute to the resistance of NMRs to spontaneous skin carcinogenesis and provide a platform for further investigations of NMRs as a model organism for studying the biology and disease resistance of human skin.

Neurological manifestations as prognostic factors in COVID-19: a retrospective cohort study.

BACKGROUND: Neurological manifestations are frequent during COVID-19 but have been poorly studied as prognostic markers of COVID-19. OBJECTIVES: The aim of this study was to assess whether neurological manifestations are associated with a poor prognosis of COVID-19, and which patient and COVID-19 characteristics were associated with encephalopathy. METHODS: This was a retrospective cohort study and included patients admitted with COVID-19 in four hospitals from Recife, Brazil. Data were collected by reviewing medical records. RESULTS: 613 were included; 54.6% were male, the median age was 54 (41-68) years, 26.4% required mechanical ventilation, and 24.1% died. The neurological symptoms presented were: myalgia (25.6%), headache (22%), fatigue (22%), drowsiness (16%), anosmia (14%), disorientation (8.8%), ageusia (7.3%), seizures (2.8%), and dizziness (1.5%). Twelve patients (2%) had strokes (ischemic strokes: 9) and 149 (24.3%), encephalopathy. Older age, a prolonged hospitalization, diabetes mellitus, a previous history of stroke and having epileptic seizures during hospitalization were significantly associated with the occurrence of encephalopathy. Older age, smoking and requiring mechanical ventilation were associated with prolonged hospitalization. Older patients, those requiring mechanical ventilation and those with encephalopathy presented a significantly higher risk, while those who had anosmia presented a significantly lower risk of dying. CONCLUSIONS: Neurological symptoms are frequent among patients with COVID-19. Encephalopathy was the most frequent neurological complication and was associated with a higher mortality. Those with anosmia had a lower mortality.