Anti-bacterial, anti-biofilm and synergistic effects of phenazine-based ruthenium(II) complexes.

Antimicrobial resistance has become a global threat to human health, which is coupled with the lack of novel drugs. Metallocompounds have emerged as promising diverse scaffolds for the development of new antibiotics. Herein, we prepared some metal compounds mainly focusing on cis-[Ru(bpy)(dppz)(SO3)(NO)](PF6) (PR02, bpy = 2,2'-bipyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine), in which phenazinic and nitric oxide ligands along with sulfite conferred some key properties. This compound exhibited a redox potential for bound NO+/0 of -0.252 V (vs. Ag|AgCl) and a high pH for nitrosyl-nitro conversion of 9.16, making the nitrosyl ligand the major species. These compounds were still able to bind to DNA structures. Interestingly, reduced glutathione (GSH) was unable to promote significant NO/HNO release, an uncommon feature of many similar systems. However, this reducing agent was essential to generate superoxide radicals. Antimicrobial studies were carried out using six bacterial strains, where none or very low activity was observed for Gram-negative bacteria. However, PR02 and PR (cis-[Ru(bpy)(dppz)Cl2]) showed high antibacterial activity in some Gram-positive strains (MBC for S. aureus up to 4.9 µmol L-1), where the activity of PR02 was similar to or at least 4-fold better than that of PR. Besides, PR02 showed capacity to inhibit bacterial biofilm formation, a major health issue leading to bacterial tolerance to antibiotics. Interestingly, we also showed that PR02 can function in synergism with the known antibiotic ampicillin, improving their action up to 4-fold even against resistant strains. Altogether, these results showed that PR02 is a promising antimicrobial nitrosyl ruthenium compound combining features beyond its killing action, which deserves further biological studies.

Diagnostic capability of artificial intelligence tools for detecting and classifying odontogenic cysts and tumors: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic capability of artificial intelligence (AI) for detecting and classifying odontogenic cysts and tumors, with special emphasis on odontogenic keratocyst (OKC) and ameloblastoma. STUDY DESIGN: Nine electronic databases and the gray literature were examined. Human-based studies using AI algorithms to detect or classify odontogenic cysts and tumors by using panoramic radiographs or CBCT were included. Diagnostic tests were evaluated, and a meta-analysis was performed for classifying OKCs and ameloblastomas. Heterogeneity, risk of bias, and certainty of evidence were evaluated. RESULTS: Twelve studies concluded that AI is a promising tool for the detection and/or classification of lesions, producing high diagnostic test values. Three articles assessed the sensitivity of convolutional neural networks in classifying similar lesions using panoramic radiographs, specifically OKC and ameloblastoma. The accuracy was 0.893 (95% CI 0.832-0.954). AI applied to cone beam computed tomography produced superior accuracy based on only 4 studies. The results revealed heterogeneity in the models used, variations in imaging examinations, and discrepancies in the presentation of metrics. CONCLUSION: AI tools exhibited a relatively high level of accuracy in detecting and classifying OKC and ameloblastoma. Panoramic radiography appears to be an accurate method for AI-based classification of these lesions, albeit with a low level of certainty. The accuracy of CBCT model data appears to be high and promising, although with limited available data.

Health care accessibility and mobility in breast cancer: a Latin American perspective.

BACKGROUND: Latin America (LATAM) encompasses a vast region with diverse populations. Despite publicly funded health care systems providing universal coverage, significant socioeconomic and ethno-racial disparities persist in health care access across the region. Breast cancer (BC) incidence and mortality rates in Brazil are comparable to those in other LATAM countries, supporting the relevance of Brazilian data, with Brazil's health care policies and expenditures often serving as models for neighboring countries. We evaluated the impact of mobility on oncological outcomes in LATAM by analyzing studies of patients with BC reporting commuting routes or travel distances to receive treatment or diagnosis. METHODS: We searched MEDLINE (PubMed), Embase, Cochrane CENTRAL, LILACS, and Google Scholar databases. Studies eligible for inclusion were randomized controlled trials and observational studies of patients with BC published in English, Portuguese, or Spanish and conducted in LATAM. The primary outcome was the impact of mobility or travel distance on oncological outcomes. Secondary outcomes included factors related to mobility barriers and access to health services. For studies meeting eligibility, relevant data were extracted using standardized forms. Risk of bias was assessed using the Newcastle-Ottawa Scale. Quantitative and qualitative evidence synthesis focused on estimating travel distances based on available data. Heterogeneity across distance traveled or travel time was addressed by converting reported travel time to kilometers traveled and estimating distances for unspecified locations. RESULTS: Of 1142 records identified, 14 were included (12 from Brazil, 1 from Mexico, and 1 from Argentina). Meta-analysis revealed an average travel distance of 77.8 km (95% CI, 49.1-106.48) to access BC-related diagnostic or therapeutic resources. Nonetheless, this average fails to precisely encapsulate the distinct characteristics of each region, where notable variations persist in travel distance, ranging from 88 km in the South to 448 km in the North. CONCLUSION: The influence of mobility and travel distance on access to BC care is multifaceted and should consider the complex interplay of geographic barriers, sociodemographic factors, health system issues, and policy-related challenges. Further research is needed to comprehensively understand the variables impacting access to health services, particularly in LATAM countries, where the challenges women face during treatment remain understudied. TRIAL REGISTRATION: CRD42023446936.

Cardiac dysfunction in sucrose-fed rats is associated with alterations of phospholamban phosphorylation and TNF-α levels.

INTRODUCTION: High sucrose intake is linked to cardiovascular disease, a major global cause of mortality worldwide. Calcium mishandling and inflammation play crucial roles in cardiac disease pathophysiology. OBJECTIVE: Evaluate if sucrose-induced obesity is related to deterioration of myocardial function due to alterations in the calcium-handling proteins in association with proinflammatory cytokines. METHODS: Wistar rats were divided into control and sucrose groups. Over eight weeks, Sucrose group received 30% sucrose water. Cardiac function was determined in vivo using echocardiography and in vitro using papillary muscle assay. Western blotting was used to detect calcium handling protein; ELISA assay was used to assess TNF-α and IL-6 levels. RESULTS: Sucrose led to cardiac dysfunction. RYR2, SERCA2, NCX, pPBL Ser16 and L-type calcium channels were unchanged. However, pPBL-Thr17, and TNF-α levels were elevated in the S group. CONCLUSION: Sucrose induced cardiac dysfunction and decreased myocardial contractility in association with altered pPBL-Thr17 and elevated cardiac pro-inflammatory TNF-α.

Effects of bioconversion by Battus polydamas on the chemical composition of Aristolochia spp. and evaluation of antimicrobial activity and biocompatibility.

Aristolochia plants are emblematic from an ethnopharmacological viewpoint and are know to possess numerous biological properties, including antiseptic. However, the medicinal potential of these species is debatable because of their representative chemical constituents, aristolochic acids (AAs) and aristolactams (ALs), which are associated, for instance, with nephropathy and cancer. These contrasting issues have stimulated the development of approaches intended to detoxification of aristoloquiaceous biomasses, among which is included the bioconversion method using larvae of the specialist phytophagous insect Battus polydamas, previously shown to be viable for chemical diversification and to reduce toxicity. Thus, eleven Aristolochia spp. were bioconverted, and the antimicrobial activities of the plant methanolic extracts and its respective bioconversion products were evaluated. The best results were found for Aristolochia esperanzae, Aristolochia gibertii, and Aristolochia ringens against Bacillus cereus, with MIC ranging from 7.8 to 31.25 µg/mL. These three species were selected for chemical, antioxidant, cytotoxic, hemolytic, and mutagenic analyses. Chemical analysis revealed 65 compounds, 21 of them possible bioconversion products. The extracts showed potential to inhibit the formation and degradation of B. cereus biofilms. Extracts of A. gibertii and its bioconverted biomass showed antioxidant activity comparable to dibutylhydroxytoluene (BHT) standard. Bioconversion decreased the hemolytic activity of A. esperanzae and the cytotoxicities of A. esperanzae and A. gibertii. None of the extracts was found to be mutagenic. The bioactivities of the fecal extracts were maintained, and biocompatibility was improved. Therefore, the results obtained in this study reveal positive expectations about the natural detoxification process of the Aristolochia species.

Carvacrol-Loaded Nanoemulsion Promotes Tocolytic and Anti-Dysmenorrhea Effects in Rodents.

INTRODUCTION: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities. METHOD: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV). RESULTS: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes. CONCLUSIONS: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.

The use of artificial intelligence tools in cancer detection compared to the traditional diagnostic imaging methods: An overview of the systematic reviews.

BACKGROUND AND PURPOSE: In comparison to conventional medical imaging diagnostic modalities, the aim of this overview article is to analyze the accuracy of the application of Artificial Intelligence (AI) techniques in the identification and diagnosis of malignant tumors in adult patients. DATA SOURCES: The acronym PIRDs was used and a comprehensive literature search was conducted on PubMed, Cochrane, Scopus, Web of Science, LILACS, Embase, Scielo, EBSCOhost, and grey literature through Proquest, Google Scholar, and JSTOR for systematic reviews of AI as a diagnostic model and/or detection tool for any cancer type in adult patients, compared to the traditional diagnostic radiographic imaging model. There were no limits on publishing status, publication time, or language. For study selection and risk of bias evaluation, pairs of reviewers worked separately. RESULTS: In total, 382 records were retrieved in the databases, 364 after removing duplicates, 32 satisfied the full-text reading criterion, and 09 papers were considered for qualitative synthesis. Although there was heterogeneity in terms of methodological aspects, patient differences, and techniques used, the studies found that several AI approaches are promising in terms of specificity, sensitivity, and diagnostic accuracy in the detection and diagnosis of malignant tumors. When compared to other machine learning algorithms, the Super Vector Machine method performed better in cancer detection and diagnosis. Computer-assisted detection (CAD) has shown promising in terms of aiding cancer detection, when compared to the traditional method of diagnosis. CONCLUSIONS: The detection and diagnosis of malignant tumors with the help of AI seems to be feasible and accurate with the use of different technologies, such as CAD systems, deep and machine learning algorithms and radiomic analysis when compared with the traditional model, although these technologies are not capable of to replace the professional radiologist in the analysis of medical images. Although there are limitations regarding the generalization for all types of cancer, these AI tools might aid professionals, serving as an auxiliary and teaching tool, especially for less trained professionals. Therefore, further longitudinal studies with a longer follow-up duration are required for a better understanding of the clinical application of these artificial intelligence systems. TRIAL REGISTRATION: Systematic review registration. Prospero registration number: CRD42022307403.

A review of recent developments on drought characterization, propagation, and influential factors.

Droughts have impacted human society throughout its history. However, the occurrence of severe drought events in the last century and the concerns on the potential effects of climate change have prompted remarkable advances in drought conceptualization and modeling in recent years. This review intends to present the state-of-the-art on drought characterization and propagation, as well as providing insights on how climate dynamics and anthropogenic activities might affect this phenomenon. For this purpose, we first address the distinct concepts of droughts and their relationships. Next, we present two frequently utilized methods based on the run theory for drought characterization and explain the development and recovery stages of droughts. Then, we discuss potential drivers for drought occurrence and propagation, with focus on meteorological factors, catchments' physical characteristics and human activities. Later, we describe how droughts can affect several parameters of water quality. This review also addressed flash droughts, encompassing their definitions, commonly used indices, and potential drivers. Finally, we briefly address the roles of climate change and long-term persistence on future drought scenarios. This review may be useful for researchers and stakeholders for attaining a broader understanding on drought dynamics and impacts.

Effect of foraminal enlargement on microcrack formation and apical transportation: a nano-CT assessment.

The aim of this study was to evaluate the foraminal enlargement and its influence on microcrack formation and apical transportation in root canals with apical curvature. Eighteen maxillary lateral incisors with apical curvature were selected by using micro-CT images. Root canals were randomly divided in two groups (n = 9) according to root canal preparation using two working lengths: 1 mm short of the apical foramen (control group) and 1 mm beyond the apical foramen (foraminal enlargement). For both groups Reciproc Blue R40 was used for root canal instrumentation. Specimens were scanned by nano-CT (UniTOM HR) before and after root canal preparation. Percentage, length, and width of microcracks, and apical transportation were assessed. Kappa, chi-square and McNemar tests were used for qualitative analyses while paired and unpaired t-test were used for quantitative analyses (α = 0.05). For both groups, rather similar and low percentages of microcracks were observed before root canal preparation (P > 0.05). The foraminal enlargement promoted new microcracks, not observed in the control group. An increase in microcrack length was observed when the foraminal enlargement was performed (P < 0.05). Higher apical transportation was observed when foraminal enlargement was performed (P < 0.05). Foraminal enlargement using a heat-treated reciprocating file size 40 promoted microcracks and higher apical transportation than root canal preparation up to 1 mm short of apical foramen.

Image quality for visualization of cracks and fine endodontic structures using 10 CBCT devices with various scanning protocols and artefact conditions.

The aim of this study was to evaluate CBCT exposure protocols and CBCT devices in terms of image quality for the detection of cracks and fine endodontic structures using 3 conditions of metallic artifacts. An anthropomorphic phantom containing teeth with cracks, isthmus, narrow canal, and apical delta was scanned using ten CBCT devices. A reference industrial CT image was used to detect and measure all structures. Three conditions were created: (1) metal-free, (2) 'endo' and (3) 'implant' with metallic objects placed next to the teeth of interest. For each condition, three protocols were selected: medium field of view (FOV) standard resolution, small FOV standard and high resolution. The results showed that only small FOV high-resolution metal-free images from two devices (A and H) were appropriate to visualize cracks. For fine structure identification, the best result was observed for small FOV high resolution. However, the visualization significantly worsened in the presence of metallic artefacts. The ability of CBCT images for visualizing cracks is restricted to certain CBCT devices. Once metallic artefacts are present, crack detection becomes unlikely. Overall, small FOV high-resolution protocols may allow detection of fine endodontic structures as long as there are no high-dense objects in the region of interest.

Quality of life in children and adolescents with hemophilia A: A systematic review and meta-analysis.

Background: Various instruments have been used to assess health-related quality of life (HRQoL) in children and adolescents with hemophilia A. Objective: We systematically reviewed the literature to summarize HRQoL measurement instruments and outcomes in this population. Methods: MEDLINE, Embase, Cochrane CENTRAL, and LILACS databases were searched. Studies published from 2010 to 2021, reporting HRQoL assessed by generic or hemophilia-specific instruments in individuals aged 0 to 18 years were included. Two independent reviewers performed screening, selection, and data abstraction. Data were meta-analyzed using the generic inverse variance method with the random-effects model for single-arm studies reporting instrument-specific mean total HRQoL scores. Prespecified subgroup meta-analyses were performed. Heterogeneity among studies was assessed using the I 2 statistic. Results: Six instruments were identified in 29 studies meeting the following inclusion criteria: 4 generic instruments (PedsQL [5 studies], EQ-5D-3L [3 studies], KIDSCREEN-52 [1 study], and KINDL [1 study]) and 2 hemophilia-specific instruments (Haemo-QoL [17 studies] and CHO-KLAT [3 studies]). The overall risk of bias was moderate to low. There was a substantial variability in the primary outcome (mean total HRQoL score) among studies using the same instrument (Haemo-QoL), with scores ranging from 24.10 to 89.58 on a scale from 0 to 100 (higher scores indicating higher HRQoL). Meta-regression with 14 studies using the Haemo-QoL questionnaire demonstrated that 79.34% (R 2 ) of the observed 94.67% total heterogeneity (I 2 ) was explained by the proportion of patients receiving effective prophylactic treatment. Conclusion: HRQoL assessment in young people with hemophilia A is heterogeneous and context specific. The proportion of patients on effective prophylactic treatment is positively correlated with HRQoL. The review protocol was registered prospectively with PROSPERO (CRD42021235453).

Radiographic perception of anatomical structures and bony changes in oncologic patients under antiresorptive therapy.

PURPOSE: To assess radiographic presentation of anatomical structures, bony changes and soft tissue calcifications on panoramic radiographs of oncologic patients under high dose antiresorptive drug therapy (ART) before exposure to dental extraction. METHODS: Panoramic radiographs of 57 patients under ART, taken previously to tooth extraction, and 57 control patients were evaluated by two oral radiologists regarding bone pattern, anatomical structures visibility, estimation of cortical width, mandibular cortical index (MCI), and presence of soft tissue calcifications. Parameters were compared between ART and age- and gender-matched healthy control groups. Bone patterns were further assessed by regions with or without tooth extractions and according to uneventful healing or MRONJ development. All comparisons were made using chi-square test with significance level set at 5%. RESULTS: Mandible and posterior maxilla presented more sclerotic bone patterns in patients under ART, regardless of tooth extraction and MRONJ development status (p < 0.05). Heterogeneous bone pattern was identified in two regions that both were subsequently affected by MRONJ. Anatomical structure visibility and presence of soft tissue calcifications was not different among groups (p > 0.05). ART patients showed significantly more C0 (thickening) and C1 MCI (p < 0.05). CONCLUSION: Sclerotic bone pattern and thicker mandibular cortices may represent a consequence of ART rather than MRONJ specific findings. Prospective studies on larger patient samples radiographically followed-up during the ART treatment are advised, with specific attention to heterogenous trabecular bone pattern as a possible MRONJ predictor.

Radiomics in bone pathology of the jaws.

OBJECTIVE: To define which are and how the radiomics features of jawbone pathologies are extracted for diagnosis, predicting prognosis and therapeutic response. METHODS: A comprehensive literature search was conducted using eight databases and gray literature. Two independent observers rated these articles according to exclusion and inclusion criteria. 23 papers were included to assess the radiomics features related to jawbone pathologies. Included studies were evaluated by using JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies. RESULTS: Agnostic features were mined from periapical, dental panoramic radiographs, cone beam CT, CT and MRI images of six different jawbone alterations. The most frequent features mined were texture-, shape- and intensity-based features. Only 13 studies described the machine learning step, and the best results were obtained with Support Vector Machine and random forest classifier. For osteoporosis diagnosis and classification, filtering, shape-based and Tamura texture features showed the best performance. For temporomandibular joint pathology, gray-level co-occurrence matrix (GLCM), gray level run length matrix (GLRLM), Gray Level Size Zone Matrix (GLSZM), first-order statistics analysis and shape-based analysis showed the best results. Considering odontogenic and non-odontogenic cysts and tumors, contourlet and SPHARM features, first-order statistical features, GLRLM, GLCM had better indexes. For odontogenic cysts and granulomas, first-order statistical analysis showed better classification results. CONCLUSIONS: GLCM was the most frequent feature, followed by first-order statistics, and GLRLM features. No study reported predicting response, prognosis or therapeutic response, but instead diseases diagnosis or classification. Although the lack of standardization in the radiomics workflow of the included studies, texture analysis showed potential to contribute to radiologists' reports, decreasing the subjectivity and leading to personalized healthcare.

There is no correlation between stages of nafld assessed by liver biopsy and the diagnostic criteria for sarcopenia in active populations: a cross-sectional study / Não há correlação entre os estágios da dhgna avaliados por biópsia hepática e os critérios diagnósticos para sarcopenia em populações ativas: um estudo transversal / No existe correlación entre las etapas de ehgna evaluadas mediante biopsia hepática y los criterios diagnósticos de sarcopenia en poblaciones activas: un estudio transversal

Objective: To demonstrate the correlations of the diagnostic criteria for sarcopenia and the levels of Non-alcoholic Fat Liver Disease (NAFLD) assessed by liver biopsy in a physically active population. Methods: Cross-sectional study. Individuals aged >18 years, with NAFLD confirmed by liver biopsy, physically active. Sarcopenia assessment followed EWGSOP2: muscle strength by handgrip, Skeletal Muscle Mass by Bioimpedance, and physical performance by usual gait speed. Statistical Analysis: To test differences between groups in continuous variables, Student's T or Mann-Whitney U Test for independent samples. Pearson and Spearman tests were used for correlations. A 5% significance was considered (p<0.05). Results: 52 patients with NAFLD included, consisting of 35 women and 15 men. There was no difference in age or anthropometric variables. Were found difference statically significant in platelets (higher in women), basal insulin, HOMA-IR and Quick (higher in men). In sarcopenia, the handgrip strength showed difference in favors of men. There was no statistically significant correlation between the sarcopenia and NAFLD levels. Discussion: sarcopenia has been reported as an independent risk factor for NAFLD and its progressions. The physical exercise is one of the most recommended and more effective treatment for both conditions, so is expected that a non-sedentary individual can reduce both indicators. However, there is no consensus about the best method. Also, the both conditions share heterogeneity in diagnosis, prognosis, reason for develop and risk factors across the literature. Conclusion: For populations where most individuals are physically active, it is not possible to find correlation between sarcopenia diagnostic criteria and the stages of NAFLD.

Objetivo: Demonstrar as correlações dos critérios diagnósticos de sarcopenia e dos níveis de doença hepática gordurosa não alcoólica (DHGNA) avaliados por biópsia hepática em uma população fisicamente ativa. Métodos: Estudo transversal. Indivíduos com idade >18 anos, com DHGNA confirmada por biópsia hepática, fisicamente ativos. A avaliação da sarcopenia seguiu o EWGSOP2: força muscular por preensão manual, massa muscular esquelética por bioimpedância e performance física por velocidade usual de marcha. Análise Estatística: Para testar diferenças entre grupos nas variáveis contínuas, teste T de Student ou Teste U de Mann-Whitney para amostras independentes. Os testes de Pearson e Spearman foram utilizados para correlações. Foi considerada significância de 5% (p<0,05). Resultados: Foram incluídos 52 pacientes com DHGNA, sendo 35 mulheres e 15 homens. Não houve diferença na idade ou nas variáveis antropométricas. Foram encontradas diferenças estatisticamente significativas em plaquetas (maior em mulheres), insulina basal, HOMA-IR e Quick (maior em homens). Na sarcopenia, a força de preensão manual apresentou diferença em favor dos homens. Não houve correlação estatisticamente significativa entre os níveis de sarcopenia e DHGNA. Discussão: a sarcopenia tem sido relatada como fator de risco independente para DHGNA e suas progressões. O exercício físico é um dos tratamentos mais recomendados e mais eficazes para ambas as condições, pelo que se espera que um indivíduo não sedentário consiga reduzir ambos os indicadores. No entanto, não há consenso sobre o melhor método. Além disso, ambas as condições compartilham heterogeneidade no diagnóstico, prognóstico, razão de desenvolvimento e fatores de risco em toda a literatura. Conclusão: Para populações onde a maioria dos indivíduos é fisicamente ativo, não é possível encontrar correlação entre os critérios diagnósticos de sarcopenia e os estágios da DHGNA.

Objetivo: demostrar las correlaciones de los criterios diagnósticos de sarcopenia y los niveles de enfermedad del hígado graso no alcohólico (EHGNA) evaluados mediante biopsia hepática en una población físicamente activa. Métodos: Estudio transversal. Individuos mayores de 18 años, con EHGNA confirmada mediante biopsia hepática, físicamente activos. La evaluación de la sarcopenia siguió el EWGSOP2: fuerza muscular mediante agarre manual, masa muscular esquelética mediante bioimpedancia y rendimiento físico mediante velocidad de marcha habitual. Análisis estadístico: Para probar diferencias entre grupos en variables continuas, prueba T de Student o U de Mann-Whitney para muestras independientes. Para las correlaciones se utilizaron las pruebas de Pearson y Spearman. Se consideró una significancia del 5% (p<0,05). Resultados: Se incluyeron 52 pacientes con EHGNA, 35 mujeres y 15 hombres. No hubo diferencia en la edad ni en variables antropométricas. Se encontraron diferencias estadísticamente significativas en plaquetas (mayor en mujeres), insulina basal, HOMA- IR y Quick (mayor en hombres). En la sarcopenia, la fuerza de prensión manual mostró diferencia a favor de los hombres. No hubo correlación estadísticamente significativa entre la sarcopenia y los niveles de NAFLD. Discusión: la sarcopenia ha sido reportada como un factor de riesgo independiente para NAFLD y sus progresiones. El ejercicio físico es uno de los tratamientos más recomendados y efectivos para ambas afecciones, por lo que se espera que una persona no sedentaria pueda reducir ambos indicadores. Sin embargo, no hay consenso sobre cuál es el mejor método. Además, ambas afecciones comparten heterogeneidad en el diagnóstico, pronóstico, motivo de desarrollo y factores de riesgo en la literatura. Conclusión: Para poblaciones donde la mayoría de las personas son físicamente activas, no es posible encontrar correlación entre los criterios de diagnóstico de sarcopenia y las etapas de NAFLD.

Nanomaterials in Drug Delivery Applications.

The "magic bullet" concept paved the way for nanomaterials' development and innovation [...].

EXERCISE IN THE PHYSICAL REHABILITATION OF CIRROTICS: A RANDOMIZED PILOT STUDY.

BACKGROUND: Physical exercise delays the sarcopenic process and can reverse the loss of muscle strength, improve quality of life and prognosis in cirrhotic patients. OBJECTIVE: The aim was to verify the effects of face-to-face versus home aerobic exercise on the variables fatigue, respiratory and peripheral muscle strength, functional capacity and quality of life in patients with compensated cirrhosis. METHODS: Patients were selected by convenience, stratified and randomized into supervised face-to-face exercise (n=13) and home exercise without daily supervision (n=12). Patients were submitted to a program of aerobic physical exercises, with progressive duration of 30 to 50 minutes, twice a week for twelve weeks. Before starting the program and every four weeks, all patients in both groups were assessed for fatigue (fatigue severity scale), respiratory (Pimáx and Pemáx) and peripheral (concentric quadriceps peak torque) muscle strength, functional capacity (6-minute walking distance) and quality of life (Short Form-36 Health Survey questionnaire). RESULTS: The face-to-face group showed reduced fatigue (P<0.001), increased inspiratory (P<0.001), expiratory (P<0.001) and peripheral (P<0.001) muscle strength of the 6MWD (P<0.001) and improved quality of life. The home group showed no significant improvement in these variables. CONCLUSION: A face-to-face program of moderate aerobic exercise in patients with compensated cirrhosis reduces fatigue, improves functional capacity and quality of life and increases respiratory and peripheral muscle strength. Home physical exercises do not cause the same adaptive effects in this population.

Novel Ru(II)-bipyridine/phenanthroline-lapachol complexes as potential anti-cancer agents.

For the first time, we herein report on the syntheses of two new Ru(II)/bipyridine/phenanthroline complexes containing lapachol as ligand: complex (1), [Ru (bipy)2(Lap)]PF6 and complex (2), [Ru(Lap)(phen)2]PF6, where bipy = 2,2'-bipyridine and ph en = 1,10-phenanthroline; Lap = lapachol (2-hydroxy-3-(3-methylbut-2-en-1- yl)naphthalene-1,4-dione). The complexes were synthesized and characterized by elemental analyses, molar conductivity, mass spectrometry, ultraviolet-visible and infrared spectroscopies, nuclear magnetic resonance (1H, 13C), and single crystal X-ray diffraction, for complex (2). In addition, in vitro cytotoxicity was tested against six cancer cells: A549 (lung carcinoma); DU-145 (human prostate carcinoma); HepG2 (human hepatocellular carcinoma), PC-3 (human prostate adenocarcinoma); MDA-MB-231 (human breast adenocarcinoma); Caco-2 (human colorectal adenocarcinoma), and against two non-cancer cells, FGH (human gingival normal fibroblasts) and PNT-2 (prostate epithelial cells). Complex (1) was slightly more toxic and selective than complex (2) for all cell lines, except against the A549 cells, where (2) was more potent than complex (1). The complexes induced an increase in the reactive oxygen species, and the co-treatment with N-acetyl-L-cysteine remarkably suppressed the ROS generation and prevented the reduction of cell viability, suggesting that the cytotoxicity of the complexes is related to the ROS-mediated pathway. Further studies indicated that the complexes may bind to DNA via minor groove interaction. Our studies also revealed that free Lap induces gene mutations in Salmonella Typhimurium, nevertheless, the complexes demonstrated the absence of genotoxicity by the Ames test. The present study provides a relevant contribution to understanding the anti-cancer potential and genetic toxicological events of new ruthenium complexes containing the lapachol molecule as a ligand.

Exercício na reabilitação física de cirróticos: um estudo piloto randomizado / Exercise in the physical rehabilitation of cirrotics: a randomized pilot study

ABSTRACT Background: Physical exercise delays the sarcopenic process and can reverse the loss of muscle strength, improve quality of life and prognosis in cirrhotic patients. Objective: The aim was to verify the effects of face-to-face versus home aerobic exercise on the variables fatigue, respiratory and peripheral muscle strength, functional capacity and quality of life in patients with compensated cirrhosis. Methods: Patients were selected by convenience, stratified and randomized into supervised face-to-face exercise (n=13) and home exercise without daily supervision (n=12). Patients were submitted to a program of aerobic physical exercises, with progressive duration of 30 to 50 minutes, twice a week for twelve weeks. Before starting the program and every four weeks, all patients in both groups were assessed for fatigue (fatigue severity scale), respiratory (Pimáx and Pemáx) and peripheral (concentric quadriceps peak torque) muscle strength, functional capacity (6-minute walking distance) and quality of life (Short Form-36 Health Survey questionnaire). Results: The face-to-face group showed reduced fatigue (P<0.001), increased inspiratory (P<0.001), expiratory (P<0.001) and peripheral (P<0.001) muscle strength of the 6MWD (P<0.001) and improved quality of life. The home group showed no significant improvement in these variables. Conclusion: A face-to-face program of moderate aerobic exercise in patients with compensated cirrhosis reduces fatigue, improves functional capacity and quality of life and increases respiratory and peripheral muscle strength. Home physical exercises do not cause the same adaptive effects in this population.

RESUMO Contexto: O exercício físico retarda o processo sarcopênico e pode reverter a perda de força muscular, melhorar a qualidade de vida e prognóstico em cirróticos. Objetivo: O objetivo foi verificar os efeitos do exercício aeróbico presencial versus domiciliar sobre variáveis fadiga, força muscular respiratória e periférica, capacidade funcional e qualidade de vida em pacientes com cirrose compensada. Métodos: Os pacientes foram selecionados por conveniência, estratificados e randomizados em exercício presencial supervisionado (n=13) e exercício domiciliar sem supervisão diária (n=12). Os pacientes foram submetidos a um programa de exercícios físicos aeróbicos, com duração progressiva de 30 minutos a 1 hora, duas vezes por semana durante 12 semanas. Antes de iniciar o programa e a cada 4 semanas, todos os pacientes de ambos os grupos foram avaliados quanto à fadiga (escala de gravidade da fadiga), força muscular respiratória (Pimáx e Pemáx) e periférica (pico de torque do quadríceps concêntrico), capacidade funcional (distância caminhada de 6 minutos) e qualidade de vida (questionário Short Form-36 Health Survey). Resultados: O grupo presencial apresentou redução da fadiga (P<0,001), aumento da força muscular inspiratória (P<0,001), expiratória (P<0,001), e periférica (P<0,001), da DTC6 (P<0,001) e melhora da qualidade de vida. O grupo domiciliar não apresentou melhora significativa nessas variáveis. Conclusão: Um programa presencial de exercícios aeróbicos moderados em pacientes com cirrose compensada reduz a fadiga, melhora a capacidade funcional e qualidade de vida, aumenta força muscular respiratória e periférica. Os exercícios físicos domiciliares não provocam os mesmos efeitos adaptativos nesta população.

Automated detection and labelling of teeth and small edentulous regions on cone-beam computed tomography using convolutional neural networks.

OBJECTIVE: To assess the accuracy of a novel Artificial Intelligence (AI)-driven tool for automated detection of teeth and small edentulous regions on Cone-Beam Computed Tomography (CBCT) images. MATERIALS AND METHODS: After AI training and testing with 175 CBCT scans (130 for training and 40 for testing), validation was performed on a total of 46 CBCT scans selected for this purpose. Scans were split into fully dentate and partially dentate patients (small edentulous regions). The AI Driven tool (Virtual Patient Creator, Relu BV, Leuven, Belgium) automatically detected, segmented and labelled teeth and edentulous regions. Human performance served as clinical reference. Accuracy and speed of the AI-driven tool to detect and label teeth and edentulous regions in partially edentulous jaws were assessed. Automatic tooth segmentation was compared to manually refined segmentation and accuracy by means of Intersetion over Union (IoU) and 95% Hausdorff Distance served as a secondary outcome. RESULTS: The AI-driven tool achieved a general accuracy of 99.7% and 99% for detection and labelling of teeth and missing teeth for both fully dentate and partially dentate patients, respectively. Automated detections took a median time of 1.5s, while the human operator median time was 98s (P<0.0001). Segmentation accuracy measured by Intersection over Union was 0.96 and 0.97 for fully dentate and partially edentulous jaws respectively. CONCLUSIONS: The AI-driven tool was accurate and fast for CBCT-based detection, segmentation and labelling of teeth and missing teeth in partial edentulism. CLINICAL SIGNIFICANCE: The use of AI may represent a promising time-saving tool serving radiological reporting, with a major step forward towards automated dental charting, as well as surgical and treatment planning.

Fractal dimension analysis on CBCT scans for detecting low bone mineral density in postmenopausal women.

Purpose: The aim of this study was to compare the fractal dimension (FD) measured at 2 bone sites (second cervical vertebra and mandible) on cone-beam computed tomography (CBCT). The research question was whether FD could serve as an accessory tool to refer postmenopausal women for densitometric analysis. Therefore, the reliability and accuracy of FD were evaluated. Materials and Methods: In total, 103 postmenopausal women were evaluated, of whom 52 had normal bone mineral density and 51 had osteoporosis, according to dual X-ray absorptiometry of the lumbar spine and hip. On the CBCT scans, 2 regions of interest were selected for FD analysis: 1 at the second cervical vertebra and 1 located at the mandible. The correlations between both measurements, intra- and inter-observer agreement, and the accuracy of the measurements were calculated. A P value less than 0.05 was considered to indicate statistical significance for all tests. Results: The mean FD values were significantly lower at the mandibular region of interest in osteoporotic patients than in individuals with normal bone mineral density. The areas under the curve were 0.644 (P=0.008) and 0.531 (P=0.720) for the mandibular and vertebral sites, respectively. Conclusion: FD at the vertebral site could not be used as an adjuvant tool to refer women for osteoporosis investigation. Although FD differed between women with normal BMD and osteoporosis at the mandibular site, it demonstrated low accuracy and reliability.