BIA-assessed cellular hydration and strength in healthy older adults.

OBJECTIVES: The objective of this research was to evaluate the differential relationships between various BIA-estimated compartments of body water and strength, among healthy older adults, by age range and sex. DESIGN: Descriptive and correlational study. SETTING AND PARTICIPANTS: A total of 234 healthy older adults (72.59±7.60 years) participated in the study. Participants were recruited from community centers around Portugal and Spain. Data were recorded during May 2023. This is a physically active sample: all the participants are physically active for a minimum of three days a week. METHODS: For the study of body composition the variables extracted from the Tanita were: fat mass (FM), fat free mass (FFM), visceral fat rating (VFR), total body water (TBW), extracellular water (ECW) and intracellular water (ICW). Handgrip Strength was used to evaluate upper body strength and the Chair Stand Test for lower body strength. RESULTS: Differences across the various data sets were recorded in the gender variable. When looking into the gender variable, significant correlations were recorded for the body composition variables analyzed for all age groups in the upper body strength test, except for BMI(r=0.125-0.878) and Fat mass (0.056 - -0.634). For the lower body strength test, no significant correlations were recorded for the Fat-Free mass variables (r= 0.164 - 0.380), as well as for the Visceral Fat Rating(r= 0.082 - 0.213) and the body water variables (TBW, ECW, ICW). CONCLUSIONS: The hydration parameters analyzed can be related to muscle performance for Handgrip in an independent older adult population with ages ranging from 60 to 90 years.

Antibiotics stimulates the development of persistent cells in biofilms of Candida albicans bloodstream isolates.

Candida albicans invasive candidiasis is considered a global health problem. In such cases, biofilm formation on implanted devices represents a therapeutic challenge and the presence of metabolically inactive persistent cells (PCs) in these communities increases their tolerance to fungicidal drugs. This study investigated the influence of amoxicillin, AMX; cefepime, CEF; gentamicin, GEN; amikacin, AMK; vancomycin, VAN; and ciprofloxacin, CIP; on the production of PCs in biofilms of C. albicans bloodstream isolates. 48 h-mature biofilms (n = 6) grown in RPMI-1640 supplemented with antibiotics were treated with 100 µg ml-1 amphotericin B and then evaluated for PCs. Biofilms grown in the presence of antibiotics produced more PCs, up to 10×, when exposed to AMX and CIP; 5 × to CEF; and 6 × to GEN and VAN. The results indicate that antibiotics can modulate PC production in C. albicans biofilms. This scenario may have clinical repercussions in immunocompromised patients under broad-spectrum antibiotic therapy.

Biofilms are microbial communities tolerant to antifungals. Our research showed that antibiotics stimulate the formation of persistent cells within Candida albicans biofilms. These are dormant, metabolically silent cells that resist to therapy and can be related to metastatic and recalcitrant infections.

Descending motor drive does not interact with muscle metaboreflex for ventilation regulation during rhythmic exercise in healthy humans.

The muscle metaboreflex effect on pulmonary ventilation (V̇E) regulation is more apparent during rhythmic exercise than rest, possibly because this reflex interacts with other mechanisms regulating V̇E during voluntary contractions, such as central command. Therefore, we tested whether one part of central command, the descending component of motor execution (i.e., descending motor drive), and the muscle metaboreflex interact synergistically to regulate V̇E. Thirteen healthy adults (9 men) completed four experiments in random order under isocapnia. The muscle metaboreflex was activated by rhythmic handgrip exercise at 60% maximal voluntary contraction (MVC) force with the dominant hand. Then, the muscle metaboreflex remained active during a 4-minute recovery period via post-exercise circulatory occlusion (PECO), or it was inactivated, maintaining free blood flow to the dominant upper limb. During the last 2-minutes of the handgrip exercise recovery, participants either performed rhythmic voluntary plantar flexion with the dominant leg at 30% MVC torque to generate descending motor drive or the dominant leg's calf muscles were involuntarily activated by electrical stimulation at a similar torque level (i.e., without descending motor drive). V̇E increased to a similar level during handgrip exercise in all conditions (≈22 L/min, P = 0.364). PECO maintained V̇E elevated above recovery with free blood flow (≈17 L/min vs. ≈13 L/min, P = 0.009). However, voluntary and involuntary plantar flexion with or without PECO evoked similar V̇E responses (∆ ≈ 4 L/min, P = 0.311). Therefore, an interaction between descending motor drive and muscle metaboreflex is not ubiquitous for V̇E regulation during rhythmic exercise.

Percutaneous Valvular and Structural Heart Disease Interventions.2024 Core Curriculum of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardiovascular Surgery Working Group (WG CVS) of the European Society of Cardiology.

The percutaneous treatment of structural, valvular, and non-valvular heart disease (SHD) is rapidly evolving. The Core Curriculum (CC) proposed by the EAPCI describes the knowledge, skills, and attitudes that define competency levels required by newly trained SHD interventional cardiologists (IC) and provides guidance for training centres. SHD ICs are cardiologists who have received complete interventional cardiology training. They are multidisciplinary team specialists who manage adult SHD patients from diagnosis to follow-up and perform percutaneous procedures in this area. They are competent in interpreting advanced imaging techniques and master planning software. The SHD ICs are expected to be proficient in the aortic, mitral, and tricuspid areas. They may have selective skills in either the aortic area or mitral/tricuspid areas. In this case, they must still have common transversal competencies in the aortic, mitral, and tricuspid areas. Additional SHD domain competencies are optional. Completing dedicated SHD training, aiming for full aortic, mitral, and tricuspid competencies, requires at least 18 months. For full training in the aortic area, with basic competencies in mitral/tricuspid areas, the training can be reduced to 1 year. The same is true for training in the mitral/tricuspid area, with competencies in the aortic area. The SHD IC CC promotes excellence and homogeneous training across Europe and is the cornerstone of future certifications and patient protection. It may be a reference for future CC for national associations and other SHD specialities, including imaging and cardiac surgery.

Breathing variability during running in athletes: The role of sex, exercise intensity and breathing reserve.

Highly trained aerobic athletes progressively use most of their breathing reserve with increased exercise intensity during whole-body exercise. Additionally, females typically present proportionally smaller lungs than males. Therefore, sex, exercise intensity, and breathing reserve use likely influence the volume and time in which respiratory parameters vary between consecutive breaths during whole-body exercise. However, breath-by-breath variability has been scarcely investigated during exercise. Accordingly, we sought to investigate breath-by-breath pulmonary ventilation (V̇E), tidal volume (VT), and respiratory frequency (fR) variability during a maximal treadmill incremental exercise test in 17 females and 18 males highly trained professional endurance runners. The breath-by-breath variability was analyzed by root mean square of successive differences (RMSSD) within 1-minute windows. Females had lower absolute and percent predicted forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) than males, as well as lower height-adjusted absolute FVC than males. V̇E and VT reserve use were similar between the sexes at peak exercise. While RMSSDV̇E and RMSSDfR did not change over exercise (P > 0.05), RMSSDVT progressively decreased (P < 0.001). RMSSDVT was negatively correlated with VT reserve use only in males. Females showed lower RMSSDV̇E than males during the entire exercise test (P < 0.001). At iso-V̇E reserve use, between-sex differences in RMSSDV̇E persisted (P = 0.003). Our findings indicate that exercise intensity decreases VT variability in professional runners, which is linked to VT reserve use in males but not females. Additionally, the female sex lowers V̇E variability regardless of exercise intensity and V̇E reserve use.

Lessons from the COVID-19 pandemic: the unequal burden of COVID-19 on vulnerable populations in the Brazilian Central-West.

This study aimed to estimate the prevalence and identify social factors and preventive strategies associated with the coronavirus disease 2019 (COVID-19) in socio and economically vulnerable people (recyclable waste pikers, immigrants/refugees, and homeless people) in Goiânia, Goiás State, Central-Western Brazil. A cross-sectional study was conducted from July 2020 to October 2020. COVID-19 positivity was defined as a positive total anti-SARS-COV-2 antibody test and/or RNA test for SARS-COV-2. Univariable and multiple regression analyses were performed to identify the variables associated with COVID-19. Of the 594 participants, 47.3% were recyclable waste pickers, 29.6% were immigrants/refugees, and 23.1% were homeless people. The positivity for SARS-CoV-2 RNA was 14.1%, whereas for anti-SARS-CoV-2 a total of 30.8% were positive, and 39.4% were positive for at least one COVID-19 marker. Among the 541 individuals, being immigrants/refugees, not wearing a surgical mask, and having three or more people sleeping in the same room were associated with SARS-CoV-2 infection, while using TV news as the main source of information about the pandemic was a protective predictor of COVID-19. This study revealed ethnic and socioeconomic inequalities in the prevalence of COVID-19 among impoverished people in Brazil. Additionally, a high prevalence of COVID-19 was detected in all three groups. Developing new strategies to combat and prevent communicable diseases affecting this population is essential for mitigating future and ongoing pandemics.

Percutaneous Valvular and Structural Heart Disease Interventions. 2024 Core Curriculum of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

The percutaneous treatment of structural, valvular, and non-valvular heart disease (SHD) is rapidly evolving. The Core Curriculum (CC) proposed by the EAPCI describes the knowledge, skills, and attitudes that define competency levels required by newly trained SHD interventional cardiologists (IC) and provides guidance for training centres. SHD ICs are cardiologists who have received complete interventional cardiology training. They are multidisciplinary team specialists who manage adult SHD patients from diagnosis to follow-up and perform percutaneous procedures in this area. They are competent in interpreting advanced imaging techniques and master planning software. The SHD ICs are expected to be proficient in the aortic, mitral, and tricuspid areas. They may have selective skills in either the aortic area or mitral/tricuspid areas. In this case, they must still have common transversal competencies in the aortic, mitral, and tricuspid areas. Additional SHD domain competencies are optional. Completing dedicated SHD training, aiming for full aortic, mitral, and tricuspid competencies, requires at least 18 months. For full training in the aortic area, with basic competencies in mitral/tricuspid areas, the training can be reduced to 1 year. The same is true for training in the mitral/tricuspid area, with competencies in the aortic area. The SHD IC CC promotes excellence and homogeneous training across Europe and is the cornerstone of future certifications and patient protection. It may be a reference for future CC for national associations and other SHD specialities, including imaging and cardiac surgery.

The Influence of Thoracic Ultrasound on the Clinical Practice of Pulmonologists in Portugal.

BACKGROUND: Thoracic ultrasound (TUS) has garnered increased recognition, both in aiding pleural procedures and as a complement to physical examination. Operator ability is essential to obtain reliable findings. This study aimed to inquire pulmonology specialists and residents about their confidence with the technique and to determine future needs. METHODS: A self-administered online survey, including a total of 24 questions, was sent to pulmonology specialists and residents registered as members of the Portuguese Pulmonology Society. Participation was pseudoanonymized and voluntary. RESULTS: One hundred fourteen valid answers were obtained. Most responders had prior TUS training. The primary method for knowledge consolidation was unsupervised practice. The majority had an ultrasound machine available in their daily practice; only 17% performed TUS more than 3 times per week. Overall confidence in TUS usage for diagnostic purposes (median: 7/10), disease monitoring (median: 7/10), and invasive procedures (median: 8/10) were high. There was a significant relation between higher levels of confidence and regularly attending TUS courses and performing TUS more than 3 times per week. The main reasons cited as preventing regular use of TUS were the availability/cost of courses and the availability/cost of equipment. CONCLUSION: Regular TUS training and utilization are essential to boost user's confidence degree. Its use is already a regular feature in the daily practice of pulmonologists in Portugal, but further and better structured training is required to meet the needs of clinicians. The inclusion of mandatory TUS training in residency programs should be considered in the future.

Plasma EV-miRNAs as Potential Biomarkers of COVID-19 Vaccine Immune Response in Cancer Patients.

Cancer patients, prone to severe COVID-19, face immune challenges due to their disease and treatments. Identifying biomarkers, particularly extracellular vesicle (EV)-derived microRNAs (miRNAs), is vital for comprehending their response to COVID-19 vaccination. Therefore, this study aimed to investigate specific EV-miRNAs in the plasma of cancer patients under active treatment who received the COVID-19 booster vaccine. The selected miRNAs (EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, EV-hsa-miR-145- 5p, and EV-hsa-miR-223-3p) are involved in regulating SARS-CoV-2 spike protein and cytokine release, making them potential biomarkers for vaccination response. The study involved 54 cancer patients. Plasma and serum samples were collected at pre-boost vaccination, and at 3 and 6 months post-boost vaccination. Anti-spike antibody levels were measured. Additionally, RNA was extracted from EVs isolated from plasma and the expression levels of miRNAs were assessed. The results showed a significantly positive antibody response after COVID-19 boost vaccination. The expression levels of EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p increased significantly after 6 months of COVID-19 booster vaccination. Interestingly, an increased expression of certain EV-hsa-miRNAs was positively correlated. Bioinformatic analysis revealed that these correlated miRNAs play a critical role in regulating the targets present in antiviral responses and cytokine production. These findings suggest that EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p may be crucial in immune response induced by mRNA vaccines.

Emotion Detection from EEG Signals Using Machine Deep Learning Models.

Detecting emotions is a growing field aiming to comprehend and interpret human emotions from various data sources, including text, voice, and physiological signals. Electroencephalogram (EEG) is a unique and promising approach among these sources. EEG is a non-invasive monitoring technique that records the brain's electrical activity through electrodes placed on the scalp's surface. It is used in clinical and research contexts to explore how the human brain responds to emotions and cognitive stimuli. Recently, its use has gained interest in real-time emotion detection, offering a direct approach independent of facial expressions or voice. This is particularly useful in resource-limited scenarios, such as brain-computer interfaces supporting mental health. The objective of this work is to evaluate the classification of emotions (positive, negative, and neutral) in EEG signals using machine learning and deep learning, focusing on Graph Convolutional Neural Networks (GCNN), based on the analysis of critical attributes of the EEG signal (Differential Entropy (DE), Power Spectral Density (PSD), Differential Asymmetry (DASM), Rational Asymmetry (RASM), Asymmetry (ASM), Differential Causality (DCAU)). The electroencephalography dataset used in the research was the public SEED dataset (SJTU Emotion EEG Dataset), obtained through auditory and visual stimuli in segments from Chinese emotional movies. The experiment employed to evaluate the model results was "subject-dependent". In this method, the Deep Neural Network (DNN) achieved an accuracy of 86.08%, surpassing SVM, albeit with significant processing time due to the optimization characteristics inherent to the algorithm. The GCNN algorithm achieved an average accuracy of 89.97% in the subject-dependent experiment. This work contributes to emotion detection in EEG, emphasizing the effectiveness of different models and underscoring the importance of selecting appropriate features and the ethical use of these technologies in practical applications. The GCNN emerges as the most promising methodology for future research.

Comparison between Measured and Predicted Resting Metabolic Rate Equations in Cross-Training Practitioners.

This study aimed to investigate the resting metabolic rate (RMR) in cross-training practitioners (advanced and novice) using indirect calorimetry (IC) and compare it with predictive equations proposed in the scientific literature. METHODS: A cross-sectional and comparative study analyzed 65 volunteers, both sexes, practicing cross-training (CT). Anthropometry and body composition were assessed, and RMR was measured by IC (FitMate PRO®), bioimpedance (BIA-InBody 570®), and six predictive equations. Data normality was tested by the Kolgomorov-Smirnov test and expressed as mean ± standard deviation with 95% confidence intervals (CI), chi-square test was performed to verify ergogenic resources, and a Bland-Altman plot (B&A) was made to quantify the agreement between two quantitative measurements. One-way ANOVA was applied to body composition parameters, two-way ANOVA with Bonferroni post hoc was used to compare the RMR between groups, and two-way ANCOVA was used to analyze the adjusted RMR for body and skeletal muscle mass. The effect size was determined using Cohen's d considering the values adjusted by ANCOVA. If a statistical difference was found, post hoc Bonferroni was applied. The significance level was p < 0.05 for all tests. RESULTS: The main results indicated that men showed a higher RMR than women, and the most discrepant equations were Cunningham, Tinsley (b), and Johnstone compared to IC. Tinsley's (a) equation indicated greater precision in measuring the RMR in CM overestimated it by only 1.9%, and BIA and the Harris-Benedict in CW overestimated RMR by only 0.1% and 3.4%, respectively. CONCLUSIONS: The BIA and Harris-Benedict equation could be used reliably to measure the RMR of females, while Tinsley (a) is the most reliable method to measure the RMR of males when measuring with IC is unavailable. By knowing which RMR equations are closest to the gold standard, these professionals can prescribe a more assertive diet, training, or ergogenic resources. An assertive prescription increases performance and can reduce possible deleterious effects, maximizing physical sports performance.

Trustworthy Environmental Monitoring Using Hardware-Assisted Security Mechanisms.

Environmental monitoring is essential for safeguarding the health of our planet and protecting human health and well-being. Without trust, the effectiveness of environmental monitoring and the ability to address environmental challenges are significantly compromised. In this paper, we present a sensor platform capable of performing authenticated and trustworthy measurements, together with a lightweight security protocol for sending the data from the sensor to a central server anonymously. Besides presenting a new and very efficient symmetric-key-based protocol, we also demonstrate on real hardware how existing embedded security modules can be utilized for this purpose. We provide an in-depth evaluation of the performance and a detailed security analysis.

Sporocysts of Sarcocystis bertrami (syn. Sarcocystis fayeri) shed by dogs: Molecular analysis, morphometry and pattern of excretion.

Sarcocystis bertrami (synonym: Sarcocystis fayeri) is a coccidian parasite that infects horses and donkeys in several countries. Dogs are known as definitive hosts of the parasite, however, the patent period is not well defined, and S. bertrami shed by dogs has never been confirmed by molecular methods. Here we investigated the shedding of S. bertrami by experimentally infected dogs and examined the excreted parasites by morphological and molecular tools. Three dogs of small breeds (one Yorkshire terrier and two miniature Pinschers) were acquired with ages of 30 and 60 days and were exclusively fed commercial dog food. Two dogs consumed equine muscle tissues containing cysts of S. bertrami. The third dog served as negative control and was simultaneously fed commercial dog food. The two animals that received equine tissues shed sporocysts and/or oocysts in their feces after prepatent periods of 13 and 23 days. The patent periods were 47 and 14 days. Sporocysts showed average dimensions of 14.19 µm (± 0.53) x 10.06 µm (± 0.44). The control dog did not shed sporocysts or oocysts of the parasite. Interestingly, patent periods had never been reported, and for one dog, the patent period (47 days) was longer than that reported for other Sarcocystidae parasites. PCRs to the gene 18S and to the internal transcribed spacer 1 (ITS1) of the rDNA were successfully performed with DNA extracted from sporocysts. ITS1 sequences were also obtained from the equine tissue cysts used to infect the dogs. Nucleotide sequences of cloned fragments of 18S from sporocysts, and ITS1 from both stages (tissue cysts and sporocysts) matched with S. bertrami (18S: 97.50-99.88 %; ITS1: 88.76-95.21 %), although high molecular diversity was observed with data from these loci. PCR to cox1 using sporocysts' DNA failed to amplify any product. The possibility of the existence of an additional and undescribed Sarcocystis species in the excreted sporocysts, besides S. bertrami, cannot be excluded from this experiment. To our knowledge, this is the first molecular confirmation of S. bertrami in canine feces. Sporocyst dimensions and prepatent periods observed in this study were similar to those previously described for S. bertrami and S. fayeri. In conclusion, the molecular, morphological and biological data generated here fit in previous descriptions for both S. bertrami and S. fayeri.

Emerging Cases of Cat-Transmitted Sporotrichosis Driven by Sporothrix brasiliensis in Northeast Brazil.

Cat-transmitted sporotrichosis is caused by the emerging fungal pathogen Sporothrix brasiliensis and constitutes a significant public health issue that affects people living in resource-poor urban centers in Brazil. The lack of knowledge about transmission dynamics makes it difficult to propose public health policies to contain the advance of sporotrichosis. We describe the recent emergence of 1,176 cases of sporotrichosis in cats (2016 to 2021) in the metropolitan region of Recife, Brazil, leading to significant zoonotic transmission and an overwhelming occurrence of S. brasiliensis as the etiological agent. Most cases were from cats in the cities of Olinda (408/1,176; 34.70%), Jaboatão dos Guararapes (332/1,176; 28.23%), and Recife (237/1,176; 20.15%). Molecular typing using amplified fragment length polymorphism (EcoRI-GA/MseI-AG) revealed low polymorphic information content (PIC = 0.2499) and heterozygosity (H = 0.2928), typical of an outbreak scenario. Dendrogram and multivariate cluster analysis revealed that isolates from Pernambuco are closely related to Rio de Janeiro isolates. We report a substantial occurrence of MAT1-2 idiomorphs in the metropolitan region of Recife (0:60 ratio; χ2 = 60.000, P < 0.0001). The limited population differentiation and genetic diversity of the isolates from Pernambuco suggest a recent introduction, possibly via a founder effect, from the parental population in Rio de Janeiro. Our findings emphasize the critical importance of molecular surveillance of S. brasiliensis for outbreak response. A comprehensive one-health strategy is mandatory to control the spread of cat-transmitted sporotrichosis driven by S. brasiliensis, encompassing sanitary barriers, quick diagnosis, and treatment.

Combination of Neovestitol and Vestitol Modifies the Profile of Periodontitis-Related Subgingival Multispecies Biofilm.

The aim of this study was to evaluate the effect of the combination of neovestitol-vestitol (CNV) compounds obtained from Brazilian red propolis on the microbiological profile of a mature multispecies subgingival biofilm. The biofilm with 32 bacterial species associated with periodontitis was formed for seven days using a Calgary device. Treatment with CNV (1600, 800, 400, and 200 µg/mL), amoxicillin (54 µg/mL), and vehicle control was performed for 24 h on the last day of biofilm formation. Biofilm metabolic activity and DNA-DNA hybridization (checkerboard) assays were performed. The groups treated with CNV 1600 and amoxicillin reduced 25 and 13 species, respectively, compared to the control vehicle treatment (p ≤ 0.05); both reduced P. gingivalis, while only CNV reduced T. forsythia. When the data from the two treatments (CNV and AMOXI) were compared, a statistically significant difference was observed in 13 species, particularly members of Socransky's orange complex. Our results showed that CNV at 1600 µg/mL showed the best results regarding the metabolic activity of mature biofilms and obtained a reduction in species associated with the disease, such as T. forsythia, showing a better reduction than amoxicillin. Therefore, CNV seems to be a promising alternative to eradicate biofilms and reduce their pathogenicity.

Nanocomposite Films of Babassu Coconut Mesocarp and Green ZnO Nanoparticles for Application in Antimicrobial Food Packaging.

In this work, novel nanocomposite films based on babassu coconut mesocarp and zinc oxide nanoparticles (ZnO NPs), synthesized by a green route, were produced for application as food packaging films. The films were prepared using the casting method containing different contents of ZnO NPs (0 wt%, 0.1 wt%, 0.5 wt%, and 1.0 wt%). The films were characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), instrumental color analysis, and optical properties. The water vapor permeability (WVP) and tensile strength of films were also determined. The antimicrobial activity of the films against cooked turkey ham samples contaminated with Staphylococcus aureus was investigated. The results showed that incorporating ZnO NPs into babassu mesocarp matrices influenced the structure of the biopolymer chains and the color of the films. The BM/ZnO-0.5 film (0.5 wt% ZnO NPs) showed better thermal, mechanical, and WVP properties. Furthermore, the synergistic effect of babassu mesocarp and ZnO NPs in the BM/ZnO-0.5 film improved the antimicrobial properties of the material, reducing the microbial count of S. aureus in cooked turkey ham samples stored under refrigeration for 7 days. Thus, the films produced in this study showed promising antimicrobial packaging materials for processed foods.

Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer.

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B+ natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B+ NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.

Early detection of pancreatic cancer by liquid biopsy "PANLIPSY": a french nation-wide study project.

BACKGROUND: Pancreatic cancer, predominantly characterized by ductal adenocarcinoma (PDAC) accounts for 90% of cases and is the fourth leading cause of cancer-related deaths globally. Its incidence is notably increasing. This poor prognosis is primarily due to late-stage diagnosis (approximately 70% to 80% of patients are diagnosed at an advanced stage), aggressive tumor biology, and low sensitivity to chemotherapy. Consequently, it is crucial to identify and develop a simple, feasible and reproducible blood-based signature (i.e., combination of biomarkers) for early detection of PDAC. METHODS: The PANLIPSY study is a multi-center, non-interventional prospective clinical trial designed to achieve early detection of PDAC with high specificity and sensitivity, using a combinatorial approach in blood samples. These samples are collected from patients with resectable, borderline or locally advanced, and metastatic stage PDAC within the framework of the French Biological and Clinical Database for PDAC cohort (BACAP 2). All partners of the BACAP consortium are eligible to participate. The study will include 215 PDAC patients, plus 25 patients with benign pancreatic conditions from the PAncreatic Disease Cohort of TOuLouse (PACTOL) cohort, and 115 healthy controls, totaling 355 individuals. Circulating biomarkers will be collected in a total volume of 50 mL of blood, divided into one CellSave tube (10 mL), two CELL-FREE DNA BCT® preservative tubes (18 mL), and five EDTA tubes (22 mL in total). Samples preparation will adhere to the guidelines of the European Liquid Biopsy Society (ELBS). A unique feature of the study is the AI-based comparison of these complementary liquid biopsy biomarkers. Main end-points: i) to define a liquid biopsy signature that includes the most relevant circulating biomarkers, ii) to validate the multi-marker panel in an independent cohort of healthy controls and patients, with resectable PDAC, and iii) to establish a unique liquid biopsy biobank for PDAC study. DISCUSSION: The PANLIPSY study is a unique prospective non-interventional clinical trial that brings together liquid biopsy experts. The aim is to develop a biological signature for the early detection of PDAC based on AI-assisted detection of circulating biomarkers in blood samples (CTCs, ctDNA, EVs, circulating immune system, circulating cell-free nucleosomes, proteins, and microbiota). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06128343 / NCT05824403. Registration dates: June 8,2023 and April 21, 2023.

Cocaine/crack and cannabis use among transgender women in Goiás, Central Brazil.

INTRODUCTION: Illicit drug use is a significant public health problem. Studies have shown a high prevalence of cocaine and cannabis use in transgender women (TGW). OBJECTIVE: To describe the consumption patterns of cannabis and cocaine/crack use and variables associated with their use in TGW in Central Brazil. METHODS: A cross-sectional study was conducted on TGW in Goiás, Brazil. Participants were recruited using a respondent-driven sampling method and were interviewed face-to-face about cannabis and crack-cocaine and the variables associated with them. The Alcohol Smoking and Substance Involvement Screening Test was used to assess substance use. Unweighted logistic regression was used to identify variables associated with cannabis and crack cocaine use. P-values < 0.05 were considered statistically significant. RESULTS: A total of 440 transgender women participated in the study. Their median age was 25 years (interquartile range: 20.5-29.5 years). Most participants were single (85.5%) and had engaged in sex work in their lifetime (58.6%). Cannabis was reported by 68.9% and 53.4% of participants in their lifetime and in the past three months, respectively, and cocaine/crack use was reported by 59.8% and 44.1% of participants in their lifetime and the past three months, respectively. Of the participants, 10.2% reported high-risk cannabis use, and 9.1% reported high-risk cocaine/crack use. Furthermore, 35% of participants reported using both drugs. Previous physical violence (Adjusted Odds Ratio (AOR): 2.37), inconsistent condom uses during anal sex (AOR: 2.17), and moderate-/high-risk cocaine/crack use (AOR: 3.14) were associated with high-risk cannabis use. Previous sexual violence (AOR: 2.84), previous STI (AOR: 2.90), moderate-/high-risk cannabis (AOR: 3.82), and binge drinking (AOR; 3.28) were associated with high-risk cocaine/crack use. CONCLUSION: Our study found a high frequency, significant overlap in the use of cannabis and cocaine/crack use and violence associated with these drugs consumption among TGW, highlighting the urgent need for health policies for drug disorders among this socially marginalized group.