Understanding how self-management education and support programmes for type 2 diabetes are expected to change behaviour: A document analysis of two programmes.

AIMS: Attendance at diabetes self-management education and support (DSMES) programmes for type 2 diabetes is associated with positive outcomes, but the impact on some outcomes is inconsistent and tends to decline over time. Understanding the active ingredients of effective programmes is essential to optimise their effectiveness. This study aimed to (1) retrospectively identify behaviour change techniques (BCTs), mechanisms of action (MoAs) and intervention functions in two DSMES programmes, the Community-Oriented Diabetes Education and the Diabetes Education and Self-Management for Ongoing and Newly Diagnosed and (2) examine variation in content between programmes. METHODS: A multiple case study approach, including a documentary analysis of the programme materials, was conducted. Materials were coded using the BCT Taxonomy v1, the Mode of Delivery Ontology v1 and the Intervention Source Ontology v1. The Behaviour Change Wheel guidance and the Theory and Techniques tool were used to identify intervention functions and MoAs. Programme stakeholders provided feedback on the findings. RESULTS: Thirty-four BCTs were identified across the programmes, with 22 common to both. The identified BCTs were frequently related to 'goals and planning', 'feedback and monitoring' and 'natural consequences'. BCTs were linked with 15 MoAs, predominantly related to reflective motivation ('beliefs about capabilities' and 'beliefs about consequences') and psychological capability ('knowledge'). BCTs served six intervention functions, most frequently 'education', 'enablement' and 'persuasion'. CONCLUSIONS: Although both programmes included several BCTs, some BCTs were rarely or never used. Additional BCTs could be considered to potentially enhance effectiveness by addressing a wider range of barriers.

Enablers and barriers to accessing self-management support services for those living with and beyond cancer: A qualitative study using the theoretical domains framework.

BACKGROUND: Supporting those living with and beyond cancer to self-manage their health can optimise health-related quality of life and reduce symptom burden. Self-management support (SMS) programmes have been shown to be effective, but uptake is often low. This qualitative study aimed to identify experienced and perceived enablers and barriers to accessing SMS services among those who had completed primary cancer treatment and were living with and beyond cancer. METHODS: Participants were recruited through social media and cancer advocacy groups. Semi-structured telephone and online interviews were conducted. Transcripts were coded inductively based on participants' reported experiences. Statements related to factors that enable or inhibit access to SMS were then mapped to the Theoretical Domains Framework (TDF). RESULTS: Twenty-six people participated. Six themes explain the factors that act as barriers and enablers which mapped to 11 TDF domains. Lack of knowledge of available SMS was a prominent barrier, as well as inaccessible services due to timing and place of delivery. Lack of confidence and emotional factors including fear were barriers to seeking SMS. Social influences shaped knowledge, attitudes and readiness to access SMS. Perceptions of SMS service goals and if in alignment with self-identity, intentions and goals also shaped decisions around accessing support. CONCLUSIONS: While lack of knowledge and provider signposting were common barriers, findings suggest that other psychosocial and emotional factors may be barriers, even if SMS services are accessible. Findings are relevant for oncology healthcare services developing strategies to increase reach of SMS for those living with and beyond cancer.

Systematic documentation of the introduction of COVID-19 vaccines in Latin America and the Caribbean.

Objective: To document the process of introducing COVID-19 vaccines in a selection of Latin American and Caribbean countries, including the lessons learned and the strengths and weaknesses, and similarities and differences among programs. Methods: This descriptive study is based on a systematic evaluation of the process of introducing COVID-19 vaccines in Argentina, Belize, Brazil, Costa Rica, Panama and Peru. Data were collected through a questionnaire distributed to key stakeholders. Six informants from each of the included countries participated in this study. The period of the study was from December 2021 through September 2022. Results: The main strengths reported by countries were health workers' commitment to delivering vaccinations, evidence-based decision-making, the development of plans for vaccine introduction, the participation of national immunization technical advisory groups, the availability of economic resources and positive actions from the respective Ministry of Health. The main challenges were the actions of antivaccination groups, problems with electronic immunization registries, a lack of vaccines, delays in the delivery of vaccines and the scarcity of health personnel at the local level. Conclusions: Commitment, the participation of multiple sectors, the availability of resources and preparedness planning were some of the many strengths shown by countries introducing COVID-19 vaccines. Weaknesses included third parties' interests, the lack of information systems and difficulty in accessing vaccines and vaccine services. There is a window of opportunity for countries to maintain the good practices that allowed for the processes' strengths and to assess the identified weaknesses to invigorate immunization programs and prepare for future health crises.

Metabolomics Reveals Tyrosine Kinase Inhibitor Resistance-Associated Metabolic Events in Human Metastatic Renal Cancer Cells.

The development of resistance to tyrosine kinase inhibitors (TKIs) is a major cause of treatment failure in metastatic renal cell carcinoma (mRCC). A deeper understanding of the metabolic mechanisms associated with TKI resistance is critical for refining therapeutic strategies. In this study, we established resistance to sunitinib and pazopanib by exposing a parental Caki-1 cell line to increasing concentrations of sunitinib and pazopanib. The intracellular and extracellular metabolome of sunitinib- and pazopanib-resistant mRCC cells were investigated using a nuclear magnetic resonance (NMR)-based metabolomics approach. Data analysis included multivariate and univariate methods, as well as pathway and network analyses. Distinct metabolic signatures in sunitinib- and pazopanib-resistant RCC cells were found for the first time in this study. A common metabolic reprogramming pattern was observed in amino acid, glycerophospholipid, and nicotinate and nicotinamide metabolism. Sunitinib-resistant cells exhibited marked alterations in metabolites involved in antioxidant defence mechanisms, while pazopanib-resistant cells showed alterations in metabolites associated with energy pathways. Sunitinib-resistant RCC cells demonstrated an increased ability to proliferate, whereas pazopanib-resistant cells appeared to restructure their energy metabolism and undergo alterations in pathways associated with cell death. These findings provide potential targets for novel therapeutic strategies to overcome TKI resistance in mRCC through metabolic regulation.

Hyperfunctioning papillary thyroid carcinoma - a case report and literature review.

BACKGROUND: Malignant hyperfunctioning thyroid nodules are rare and more likely to occur in follicular cancer types rather than papillary variants. The authors present a case of a papillary thyroid carcinoma associated with a hyperfunctioning nodule. METHODS: A single adult patient submitted to total thyroidectomy with the presence of thyroid carcinoma within hyperfunctioning nodules was selected. Additionally, brief literature was conducted. RESULTS: An asymptomatic 58-year-old male was subjected to routine blood analysis and a TSH level of <0.003 mIU/L was found. Ultrasonography revealed a 21 mm solid, hypoechoic, and heterogenous nodule with microcalcifications in the right lobe. A fine needle aspiration guided by ultrasound resulted in a follicular lesion of undetermined significance. A 99mTc thyroid scintigram was followed and identified a right-sided hyperfunctioning nodule. Another cytology was performed and a papillary thyroid carcinoma was derived as a result. The patient underwent a total thyroidectomy. Postoperative histology confirmed the diagnosis and a tumor-free margin with no vascular or capsular invasions. CONCLUSION: Hyperfunctioning malignant nodules are a rare association, although a careful approach should be led since major clinical implications arise. Selective fine needle aspiration in all suspicious ≥1 cm nodules should be considered.

Chronic Kidney Disease: Underlying Molecular Mechanisms-A Special Issue Overview.

Chronic kidney disease (CKD) is an epidemic health issue that requires global attention [...].

Comprehensive Metabolomics and Lipidomics Profiling of Prostate Cancer Tissue Reveals Metabolic Dysregulations Associated with Disease Development.

Prostate cancer (PCa) is a global health problem that affects millions of men every year. In the past decade, metabolomics and related subareas, such as lipidomics, have demonstrated an enormous potential to identify novel mechanisms underlying PCa development and progression, providing a good basis for the development of new and more effective therapies and diagnostics. In this study, a multiplatform metabolomics and lipidomics approach, combining untargeted mass spectrometry (MS) and nuclear magnetic resonance (NMR)-based techniques, was applied to PCa tissues to investigate dysregulations associated with PCa development, in a cohort of 40 patients submitted to radical prostatectomy for PCa. Results revealed significant alterations in the levels of 26 metabolites and 21 phospholipid species in PCa tissue compared with adjacent nonmalignant tissue, suggesting dysregulation in 13 metabolic pathways associated with PCa development. The most affected metabolic pathways were amino acid metabolism, nicotinate and nicotinamide metabolism, purine metabolism, and glycerophospholipid metabolism. A clear interconnection between metabolites and phospholipid species participating in these pathways was observed through correlation analysis. Overall, these dysregulations may reflect the reprogramming of metabolic responses to produce high levels of cellular building blocks required for rapid PCa cell proliferation.

Sunitinib versus Pazopanib Dilemma in Renal Cell Carcinoma: New Insights into the In Vitro Metabolic Impact, Efficacy, and Safety.

Sunitinib and pazopanib are tyrosine kinase inhibitors (TKIs) used as first-line therapy for metastatic renal cell carcinoma (RCC). Although these TKIs are associated with similar survival outcomes, some differences have been reported in their safety profiles. In this work, traditional toxicological endpoints (cell viability and growth, oxidative stress, and nuclear morphology) and 1H NMR spectroscopy-based metabolomics analysis were used to provide new insights into the cytotoxicity and metabolic mechanisms underlying sunitinib and pazopanib treatments. Tumoral (Caki-1) and non-tumoral (HK-2) human renal cells were exposed to clinically relevant concentrations of sunitinib (2 µM) or pazopanib (50 µM). Sunitinib showed selectivity for cancer cells, inhibiting proliferation, and inducing apoptotic death of Caki-1 cells, whereas pazopanib had a similar cytotoxic effect in both tumoral and non-tumoral cells. 1H-NMR metabolomics unveiled a higher impact of sunitinib on the levels of intracellular metabolites of Caki-1 cells (seven dysregulated metabolites), suggesting dysregulations on amino acid, glutathione and glycerophospholipid metabolisms. In contrast, pazopanib had a higher impact on the levels of extracellular metabolites of Caki-1 cells (seven dysregulated metabolites in culture medium), unveiling alterations on amino acid and energetic metabolisms. In HK-2 cells, sunitinib caused only a minor increase in intracellular isoleucine levels, whereas pazopanib induced several alterations on the intracellular (three dysregulated metabolites) and extracellular (three dysregulated metabolites) compartments suggesting changes on amino acid, glycerophospholipid, and energy metabolisms. Our results demonstrate that these TKIs elicit distinct cellular and metabolic responses, with sunitinib showing better in vitro efficacy against target RCC cells and lesser nephrotoxic potential than pazopanib.

Accuracy of guided dental implant surgery using a fully digital workflow: A case series.

STATEMENT OF PROBLEM: Computer-guided implant surgery facilitated by intraoral scanning may enhance the efficiency of the digital workflow. However, it is necessary to assess technique accuracy to evaluate the accuracy of implant placement. PURPOSE: The purpose of this clinical study was to evaluate the accuracy of a virtual computer-aided design and computer-aided manufacturing (CAD-CAM) static guided surgery technique associated with intraoral scanning in partially edentulous participants by analyzing the overlap among preoperative and postoperative cone beam computed tomography (CBCT) scans, virtual planning, and the guided surgery performed. MATERIAL AND METHODS: Eleven partially edentulous participants underwent CBCT and intraoral scanning (TRIOS3). Data were integrated into a software program (ImplantViewer 3.5) for the virtual planning of implants and 3-dimensional (3D) printing of the prototype CAD-CAM surgical guide. A total of 18 implants were placed using the CAD-CAM static computer-aided implant surgery technique (Strong SW). After 15 days, postoperative CBCT scans were made and 4 variables (angular, coronal, apical, and vertical deviation) were measured to compare the virtually planned implants and the implants placed by analyzing the overlap between preoperative and postoperative of the virtual planning and guided surgery performed using the ImplantViewer 3.5 and Rhino 6 software programs. RESULTS: Deviations were found in all parameters analyzed. The mean angular deviation was 2.68 ±1.62 degrees; mean coronal deviation, 0.82 ±0.44 mm; mean apical deviation, 1.14 ±0.44 mm; and mean vertical deviation, 0.62 ±0.44 mm. CONCLUSIONS: The implants placed using the CAD-CAM static guided surgery technique associated with intraoral scanning in partially edentulous participants exhibited angular and linear deviations when compared with virtual planning implants. However, these deviations were not clinically significant.

Pectinases Secretion by Saccharomyces cerevisiae: Optimization in Solid-State Fermentation and Identification by a Shotgun Proteomics Approach.

A sequential design strategy was applied to optimize the secretion of pectinases by a Saccharomyces cerevisiae strain, from Brazilian sugarcane liquor vat, on passion fruit residue flour (PFRF), through solid-state fermentation (SSF). A factorial design was performed to determine the influence variables and two rotational central composite designs were executed. The validated experimental result was of 7.1 U mL-1 using 50% PFRF (w/w), pH 5, 30 °C for 24 h, under static SSF. Polygalacturonase, pectin methyl esterase, pectin-lyase and pectate-lyase activities were 3.5; 0.08; 3.1 and 0.8 U mL-1, respectively. Shotgun proteomics analysis of the crude extract enabled the identification of two pectin-lyases, one pectate-lyase and a glucosidase. The crude enzymatic extract maintained at least 80% of its original activity at pH values and temperatures ranging from 2 to 8 and 30 to 80 °C, respectively, over 60 min incubation. Results revealed that PFRF might be a cost-effective and eco-friendly substrate to produce pectinases. Statistical optimization led to fermentation conditions wherein pectin active proteins predominated. To the extent of our knowledge, this is the first study reporting the synthesis of pectate lyase by S. cerevisiae.

Urinary Volatilomics Unveils a Candidate Biomarker Panel for Noninvasive Detection of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer usually associated with asymptomatic development and risk of systemic progression. Hence, reliable molecular biomarkers of ccRCC are needed to provide early and minimally invasive detection. In this study, urinary volatilome profiling of patients diagnosed with ccRCC (n = 75), and cancer-free controls (n = 75), was performed to investigate the presence of a volatile signature characteristic of ccRCC. Volatile organic compounds (VOCs) in general, and more specifically volatile carbonyl compounds (VCCs), present in urine were extracted by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). Supervised multivariate models showed a good discriminatory power of ccRCC patients from controls in urine. Overall, 22 volatile metabolites were found significantly altered between the two groups, including aldehydes, ketones, aromatic hydrocarbons, and terpenoids. A candidate six-biomarker panel, comprising octanal, 3-methylbutanal, benzaldehyde, 2-furaldehyde, 4-heptanone, and p-cresol, depicted the best performance for ccRCC detection with 83% sensitivity, 79% specificity, and 81% accuracy. Moreover, the ccRCC urinary volatilome signature suggested dysregulation of energy metabolism and overexpression of enzymes associated with carcinogenesis. These findings provide the molecular basis for the fine-tuning of gas-sensing materials for application in the development of a bioelectronic sensor.

In vivo toxicometabolomics reveals multi-organ and urine metabolic changes in mice upon acute exposure to human-relevant doses of 3,4-methylenedioxypyrovalerone (MDPV).

3,4-Methylenedioxypyrovalerone (MDPV) is consumed worldwide, despite its potential to cause toxicity in several organs and even death. There is a recognized need to clarify the biological pathways through which MDPV elicits general and target-organ toxicity. In this work, a comprehensive untargeted GC-MS-based metabolomics analysis was performed, aiming to detect metabolic changes in putative target organs (brain, heart, kidneys and liver) but also in urine of mice after acute exposure to human-relevant doses of MDPV. Male CD-1 mice received binge intraperitoneal administrations of saline or MDPV (2.5 mg/kg or 5 mg/kg) every 2 h, for a total of three injections. Twenty-four hours after the first administration, target organs, urine and blood samples were collected for metabolomics, biochemical and histological analysis. Hepatic and renal tissues of MDPV-treated mice showed moderate histopathological changes but no significant differences were found in plasma and tissue biochemical markers of organ injury. In contrast, the multivariate analysis significantly discriminated the organs and urine of MDPV-treated mice from the control (except for the lowest dose in the brain), allowing the identification of a panoply of metabolites. Those levels were significantly deviated in relation to physiological conditions and showed an organ specific response towards the drug. Kidneys and liver showed the greatest metabolic changes. Metabolites related with energetic metabolism, antioxidant defenses and inflammatory response were significantly changed in the liver of MDPV-dosed animals, while the kidneys seem to have developed an adaptive response against oxidative stress caused by MDPV. On the other hand, the dysregulation of metabolites that contribute to metabolic acidosis was also observed in this organ. The heart showed an increase of fatty acid biosynthesis, possibly as an adaptation to maintain the cardiac energy homeostasis. In the brain, changes in 3-hydroxybutyric acid levels may reflect the activation of a neurotoxic pathway. However, the increase in metabolites with neuroprotective properties seems to counteract this change. Metabolic profiling of urine from MDPV-treated mice suggested that glutathione-dependent antioxidant pathways may be particularly involved in the compensatory mechanism to counteract oxidative stress induced by MDPV. Overall, this study reports, for the first time, the metabolic profile of liver, kidneys, heart, brain, and urine of MDPV-dosed mice, providing unique insights into the biological pathways of toxicity. Our findings also underline the value of toxicometabolomics as a robust and sensitive tool for detecting adaptive/toxic cellular responses upon exposure to a physiologically relevant dose of a toxic agent, earlier than conventional toxicity tests.

PPAR Gamma: From Definition to Molecular Targets and Therapy of Lung Diseases.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that regulate the expression of genes related to lipid and glucose metabolism and inflammation. There are three members: PPARα, PPARß or PPARγ. PPARγ have several ligands. The natural agonists are omega 9, curcumin, eicosanoids and others. Among the synthetic ligands, we highlight the thiazolidinediones, clinically used as an antidiabetic. Many of these studies involve natural or synthetic products in different pathologies. The mechanisms that regulate PPARγ involve post-translational modifications, such as phosphorylation, sumoylation and ubiquitination, among others. It is known that anti-inflammatory mechanisms involve the inhibition of other transcription factors, such as nuclear factor kB(NFκB), signal transducer and activator of transcription (STAT) or activator protein 1 (AP-1), or intracellular signaling proteins such as mitogen-activated protein (MAP) kinases. PPARγ transrepresses other transcription factors and consequently inhibits gene expression of inflammatory mediators, known as biomarkers for morbidity and mortality, leading to control of the exacerbated inflammation that occurs, for instance, in lung injury/acute respiratory distress. Many studies have shown the therapeutic potentials of PPARγ on pulmonary diseases. Herein, we describe activities of the PPARγ as a modulator of inflammation, focusing on lung injury and including definition and mechanisms of regulation, biological effects and molecular targets, and its role in lung diseases caused by inflammatory stimuli, bacteria and virus, and molecular-based therapy.

3,4-Methylenedioxymethamphetamine Hepatotoxicity under the Heat Stress Condition: Novel Insights from in Vitro Metabolomic Studies.

Hyperthermia has been extensively reported as a life-threatening consequence of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) abuse. In this work, we used a sensitive untargeted metabolomic approach based on gas chromatography-mass spectrometry to evaluate the impact of hyperthermia on the hepatic metabolic changes caused by MDMA. For this purpose, primary mouse hepatocytes were exposed to subtoxic (LC01 and LC10) and toxic (LC30) concentrations of MDMA for 24 h, at 37 or 40.5 °C (simulating body temperature increase after MDMA consumption), and alterations on both intracellular metabolome and extracellular volatilome were evaluated. Multivariate analysis showed that metabolic patterns clearly discriminate MDMA treated cells from control cells, both in normothermic and hyperthermic conditions. The metabolic signature was found to be largely common to MDMA subtoxic and toxic concentrations, although with evident differences in the magnitude of response, with metabolic changes significantly more pronounced at 40.5 °C. Discriminant metabolites associated with MDMA-induced hepatotoxicity are mostly involved in the amino acid metabolism, aminoacyl tRNA biosynthesis, glutathione metabolism, tricarboxylic acid cycle, and pyruvate metabolism. Moreover, our metabolomic findings were corroborated by classical toxicity parameters, demonstrating the high sensitivity of this omic approach to assess molecular-level effects. Overall, this study indicates that MDMA triggers significant metabolic alterations on hepatic cells, even at low concentrations, that are clearly exacerbated at high temperatures. These findings provide new metabolic pieces to solve the puzzle of MDMA's hepatotoxicity mechanism and emphasize the increased risks of MDMA abuse due to the thermogenic action of the drug.

New findings on urinary prostate cancer metabolome through combined GC-MS and 1H NMR analytical platforms.

INTRODUCTION: The inherent sensitivity of metabolomics allows the detection of subtle alterations in biological pathways, making it a powerful tool to study biomarkers and the mechanisms that underlie cancer. OBJECTIVES: The purpose of this work was to characterize the urinary metabolic profile of prostate cancer (PCa) patients and cancer-free controls to obtain a holistic coverage of PCa metabolome. METHODS: Two groups of samples, a training set (n = 41 PCa and n = 42 controls) and an external validation set (n = 18 PCa and n = 18 controls) were analyzed using a dual analytical platform, namely gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance spectroscopy (1H NMR). RESULTS: The multivariate analysis models revealed a good discrimination between cases and controls with an AUC higher than 0.8, a sensitivity ranging from 67 to 89%, a specificity ranging from 74 to 89% and an accuracy from 73 to 86%, considering the training and external validation sets. A total of 28 metabolites (15 from GC-MS and 13 from 1H NMR) accounted for the separation. These discriminant metabolites are involved in 14 biochemical pathways, indicating that PCa is highly linked to dysregulation of metabolic pathways associated with amino acids and energetic metabolism. CONCLUSION: These findings confirmed the complementary information provided by GC-MS and 1H NMR, enabling a more comprehensive picture of the altered metabolites, underlying pathways and deepening the understanding of PCa development and progression.

Proteomic changes in skeletal muscle of aged rats in response to resistance training.

Sarcopenia is a multifactorial process defined by loss of strength and skeletal muscle mass, which leads to a reduction in muscle cross-sectional area (CSA). Although resistance training (RT) has been indicated as a tool to counteract sarcopenia, the protein profile associated with skeletal muscle adaptations remains to be determined. We investigated the effects of 12 weeks of RT on the skeletal muscle proteome profile and CSA of young and older rats. Twenty-four animals were divided into four groups: young sedentary or trained and older sedentary or trained (six animals per group). A 12-week RT protocol was performed, which consisted of climbing a vertical ladder. The proteins from the gastrocnemius were analysed by LC-ESI-MS/MS. One-hundred and thirty-one proteins were identified, of which 28 were assessed between the groups. Ageing induced an increase in proteins associated with the glycolytic pathway, transport and stress response, which represent crucial mechanisms for muscle adaptation. RT upregulated metabolic enzymes, anti-oxidant activity and transport proteins, besides increasing hypertrophy, regardless of age, suggesting a beneficial adaptation to mitigate age-related sarcopenia. RT reduced muscle atrophy through the regulation of stress response and by increasing proteins related to energy production and transport, which in turn might protect tissue damage arising from exercise and ageing. SIGNIFICANCE OF THE STUDY: Protein abundance levels related to the metabolic process and stress response were increased in the aged muscle. RT proved to be an important intervention capable of inducing significant effects on muscle proteome regardless of ageing, due to upregulation of glycolytic enzymes, and anti-oxidant and transport proteins. This effect could lead to a beneficial adaptation in muscle structure, cellular function and overall homeostasis maintenance. This study contributes to better understanding of the basic biology of ageing and clarifies more profoundly the molecular networks behind physiological adaptations promoted by exercise training. Therefore, the results open new perspectives and insights for studies based on transcriptomics, metabolomics and functional assays.

Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine.

BACKGROUND: The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management. METHODS: A metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection. RESULTS: Results showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients' urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%. CONCLUSIONS: It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.

Metabolic signature of methylone in primary mouse hepatocytes, at subtoxic concentrations.

Methylone (3,4-methylenedioxymethcathinone) is one of the most popular new psychoactive drugs worldwide. Although advertised as a safe drug, its use has been associated to several cases of liver damage. In this work, a metabolomics approach based on gas chromatography-mass spectrometry (GC-MS) combined with chemometric analyses was used to characterize the disturbances occurring in the intra- and extracellular metabolome of primary mouse hepatocytes exposed to two subtoxic concentrations (LC01 and LC10) of methylone to better understand the early hepatotoxic events. Results showed a characteristic metabolic fingerprint for methylone, where aspartate, cysteine, 2-methyl-1-pentanol, 4-methylheptane, dodecane, 2,4-dimethyl-1-heptene, 1,3-di-tert-butylbenzene, acetophenone, formaldehyde and glyoxal levels were significantly changed at both concentrations tested. Furthermore, subtoxic concentrations of methylone caused profound changes in several biochemical pathways, suggesting adaptations in energy production processes (TCA cycle, amino acids metabolism and pyruvate metabolism), cellular antioxidant defenses (glutamate, cysteine and glutathione metabolism) and hepatic enzymes (associated to hydrocarbons, alcohols, aldehydes and ketones metabolism). This metabolic response to the initial methylone challenge most probably reflects the activation of protective mechanisms to restore cellular homeostasis. Overall, this study highlights the potential of untargeted metabolomic analysis to reveal the hepatic metabolic signature of methylone at subtoxic concentrations, and also provides clues to clarify the early mechanisms underlying the toxicity triggered by this new psychoactive substance, opening a new perspective for the study of toxicity mechanisms of new xenobiotics.

Environmental and biological monitoring of benzene, toluene, ethylbenzene and xylene (BTEX) exposure in residents living near gas stations.

The volatile organic compounds benzene, toluene, ethylbenzene, and xylene (BTEX) are emitted into the atmosphere at gas stations (GS) leading to chronic exposure of nearby residents, which raises public health concerns. This study aimes at determining the contribution of GS emissions to BTEX exposure in nearby residents. Three Control and Exposed areas to BTEX emissions from GS were defined in a medium-sized European city (Porto, Portugal). BTEX atmospheric levels were determined in Control and Exposed areas using passive samplers deployed outdoors (n = 48) and indoors (n = 36), and human exposure was estimated for 119 non-smoking residents using the first urine of the day. Results showed that median BTEX outdoor and indoor concentrations were significantly higher for Exposed than Control areas, with exception of ethylbenzene and xylene indoor concentrations, where no marked differences were found. Comparison of urinary concentrations between Exposed and Control residents demonstrated no significant differences for benzene and ethylbenzene, whereas levels of toluene and xylene were significantly higher in Exposed residents. No marked correlation was obtained between atmospheric BTEX concentrations and urinary concentrations. Data indicate the potential impact on air quality of BTEX emissions from GS, which confirms the importance of these findings in urban planning in order to minimize the impact on health and well-being of surrounding populations.

Cadmium toxicity and its relationship with disturbances in the cytoskeleton, cell cycle and chromosome stability.

This study aimed to investigate the mode of action of cadmium (Cd) toxicity at cell level, especially at early stages of plant exposure. Tomato seedlings were cultivated in growth media containing from 0.1 to 70 µM CdCl2 for 24 h. Mitotic index, chromosome abnormality, DNA integrity and organization of tubulin-based structures were assessed in root cells. As higher the Cd concentration in the growth media, higher was the DNA damage intensity and the occurrence of chromosomal abnormalities that included chromosome lost, bridges, stickiness, C-metaphase and polyploidy. The profile of chromosomal aberrations also varied with elevated Cd concentration, being observed increases in the frequency of chromosome stickiness. The mitotic index was reduced at the lowest Cd concentration, but such reduction was statistically similar to that detected at the highest concentration, suggesting that mitotic depression is a rapid outcome and, at same time, a Cd-induced effect that is limited at the first 24 h of direct root exposure to this metal. Under exposure to 20 µM CdCl2, heterogenous distribution of the spindle fibers, formation of two spindle complexes in both of the cell poles, absence of centrosome center, polarization of the spindle fibers during cell division, and non-uniform tubulin deposition in microtubule and phragmoplast were noticed. The results indicate that the tubulin-dependent components of cytoskeleton are Cd targets, and the sensitivity of tubulin-based structures to Cd exposure depends on cell cycle phase. Moreover, DNA damage intensity and chromosomal abnormality profile can be employed as markers of Cd toxicity level.