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Background: Anti-CD20 monoclonal antibodies are a class of immunosuppressive drugs widely used in the treatment of central nervous system (CNS) inflammatory diseases, with well-established efficacy and safety. Although rare, these therapies can be associated with serious adverse events including hematological and infectious complications. This study aims to evaluate their safety and tolerability profile in real-world clinical practice., Methods: We conducted a retrospective cohort study comprising patients diagnosed with multiple sclerosis (MS) treated with anti-CD20 drugs since 2016 followed in the Demyelinating Diseases clinic of a tertiary center. Clinical and paraclinical parameters were evaluated, including complete blood count and immunoglobulins measurements., Results: A total of 160 with multiple sclerosis (pwMS) were included in our study, of whom 110 (68.8%) were female and 147 are currently receiving anti-CD20 therapies. Half of the patients were diagnosed with relapsing-remitting MS, while the remaining had progressive forms, including 23 with primary-progressive MS and 57 with secondary-progressive MS. Eighty-three patients were on ocrelizumab, 48 on rituximab, and 29 on ofatumumab. The mean follow-up duration from the start of anti-CD20 therapy was 30.5 ± 21.3 months. During this period, serious adverse events were observed in 9 patients, including SARS-CoV-2 infection (resulting in one death), urinary tract infection, febrile neutropenia, severe diarrhea, and acute hepatitis. The rate of serious infections in the ocrelizumab subgroup was consistent with the literature, although a higher rate was observed in the rituximab subgroup. A positive correlation was found between serious infectious complications and lower IgG levels. Additionally, longer exposure to anti-CD20 therapy in our cohort was associated with an increased risk of IgG deficiency and a higher incidence of serious infections. Lymphopenia was detected in 25 patients, though it was not directly linked to the occurrence of serious infections., Conclusion: Our work confirms the tolerability and safety of anti-CD20 drugs in a real-world clinical practice MS cohort, despite their frequent association with analytical changes such as lymphopenia and hypogammaglobulinemia. To better understand the clinical significance of hypogammaglobulinemia secondary to anti-CD20 treatment and to develop strategies for mitigating the associated potential infection risk, future studies with larger populations are essential., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Fernandes, Neves, Ferro, Seabra, Mendonça, dos Reis, Sá, Guimarães and Abreu.)

Background : Animal-Assisted Therapy (AAT) is a clinical approach aimed at building valuable human-animal relationships with both preventive and therapeutic goals. It is provided by a healthcare professional and involves animals (meeting certain criteria) as an integral part of the treatment process. This type of therapy has been shown to have multiple benefits in several areas, such as reducing anxiety in a variety of different groups of people. However, few studies have specifically investigated the benefits of AAT in reducing anxiety in children and adolescents. This systematic review aimed to comprehensively assess the evidence regarding the effectiveness of AAT in reducing anxiety among children and adolescents while also identifying research gaps in this field. Methods : Studies focusing on the relationship of these two variables were obtained from multiple databases (EBSCO, PubMed, and Web of Science). Results : AAT has grown and the literature demonstrates several benefits of this approach. However, few studies have demonstrated the benefits of AAT for reducing anxiety in children and adolescents. Conclusions : Most of these few studies show that this type of intervention can help reduce anxiety levels.

Enzalutamide (ENZ) has emerged as a major treatment advance in castration-resistant prostate cancer (CRPC) patients; however the development of resistance remains a key challenge. The extracellular vesicles (VEs)-derived miRNAs play crucial roles tumor microenvironment cell communication, thereby influencing resistance mechanisms. Considering the urgent need for molecular biomarkers to monitor ENZ response and predict resistance, we intend to identify an EV-derived miRNA profile associated with ENZ resistance using an innovative 3D-spheroid in vitro model. Through the generation of this model, we provide a comprehensive platform for elucidating the molecular alterations involved in the process. An in vitro model of ENZ resistance was established through continuous exposure of LNCaP to increasing ENZ concentrations. A screening of 799 miRNAs from resistant and normal LNCaP cells were quantified. A bioinformatic analysis was performed using miRTarbase and Cytoscape and top 5 overexpressed miRNAs were selected, that will be analyzed in extracellular vesicles derived from ENZ resistance 3D spheroid models. We identified 12 up- and 13 downregulated miRNAs in LNCaP 30 μM ENZ cells compare to LNCaP·In silico analysis led to the construction of a 76 proteins cluster and functional enrichment revealed terms like PI3K/AKT, TFG-β and FOXO. hsa-miR-22-3p was significantly decreased at 5 and 20 μM ENZ concentration intracellularly, but significantly increased at 20 μM ENZ in EVs. hsa-miR-221-3p and miR-222-3p were upregulated in all concentrations both intracellularly and in EVs. The developed 3D-spheroid model effectively replicated the ENZ resistance to ENZ in an AR-independent manner, underscoring the importance of EVs-derived miRNAs in this adaptive process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To evaluate the effectiveness of a positive mental health program for adults (PMHP) in the community., Background: Positive mental health (PMH) can be seen as a construct represented by six factors (personal satisfaction, prosocial attitude, self-control, autonomy, problem resolution, and self-actualization, and interpersonal relationship skills) according to the Multifactorial Model for PMH. Although there are several interventions in promoting mental health, research on effective promotion of PMH for adults in the community with structured and validated programs of PMH is scarce., Methods: This study protocol describes a randomized controlled trial (RCT) following a wait-list control design, aimed at evaluating the effectiveness of a PMHP in the community. This study was approved in June 2019 by the Ethics Committee. Participants will be recruited from the school community of teachers. Participants aged ≥ 18 years. The participants will be randomized 1:1 to either (a) an intervention group, which will integrate the PMHP, or (b) the standby control group. Three assessment moments for both groups will take place initial, after the intervention, and a follow-up of 3-6 months. The evaluation instruments will include a sociodemographic questionnaire, a PMH questionnaire, and a psychological vulnerability scale., Conclusion: The current study provides an innovative approach to PMH. Further, the study may demonstrate new interventions in PMH in the community, based on a program with systematized guidelines and sessions structured according to individual needs. It is expected that at the end of the program, the experimental group will increase the level of PMH., Relevance to Clinical Practice: To allow future official implementation of the PMH program and the replication of the study in other professional groups as a promotion tool., No Patient or Public Contribution: There was no funding to remunerate a participant for this study., Trial Registration: ClinicalTrials.gov identifier: NCT04600401. Registered on May 15, 2020., (© 2024 Wiley Periodicals LLC.)

Epigenetics is the study of changes in organisms that result from modifications in gene expression rather than alterations in the genetic code itself [...].

Background: Molecular profiling of estrogen receptor (ER), progesterone receptor (PR), and ERBB2 (also known as Her2) is essential for breast cancer diagnosis and treatment planning. Nevertheless, current methods rely on the qualitative interpretation of immunohistochemistry and fluorescence in situ hybridization (FISH), which can be costly, time-consuming, and inconsistent. Here we explore the clinical utility of predicting receptor status from digitized hematoxylin and eosin-stained (H&E) slides using machine learning trained and evaluated on a multi-institutional dataset., Methods: We developed a deep learning system to predict ER, PR, and ERBB2 statuses from digitized H&E slides and evaluated its utility in three clinical applications: identifying hormone receptor-positive patients, serving as a second-read tool for quality assurance, and addressing intratumor heterogeneity. For development and validation, we collected 19,845 slides from 7,950 patients across six independent cohorts representative of diverse clinical settings., Results: Here we show that the system identifies 30.5% of patients as hormone receptor-positive, achieving a specificity of 0.9982 and a positive predictive value of 0.9992, demonstrating its ability to determine eligibility for hormone therapy without immunohistochemistry. By restaining and reassessing samples flagged as potential false negatives, we discover 31 cases of misdiagnosed ER, PR, and ERBB2 statuses., Conclusions: These findings demonstrate the utility of the system in diverse clinical settings and its potential to improve breast cancer diagnosis. Given the substantial focus of current guidelines on reducing false negative diagnoses, this study supports the integration of H&E-based machine learning tools into workflows for quality assurance., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ovarian cancer (OC) presents daunting lethality rates worldwide, with frequent late-stage diagnosis and chemoresistance, highlighting the need for improved prognostic approaches. Venous thromboembolism (VTE), a major cancer mortality factor, is partially driven by endothelial dysfunction (ED). ED's pro-inflammatory state fosters tumour progression, suggesting a VTE-independent link between ED and cancer. Given this triad's interplay, ED markers may influence OC behaviour and patients' prognosis. Thus, the impact of ED-related genes and single-nucleotide polymorphisms (SNPs) on OC-related VTE and patient thrombogenesis-independent prognosis was investigated. NOS3 upregulation was linked to lower VTE incidence (χ 2 , p = 0.013), while SELP upregulation was associated with shorter overall survival (log-rank test, p = 0.048). Dismissing patients with VTE before OC diagnosis, SELP rs6136 T allele carriers presented lower progression-free survival (log-rank test, p = 0.038). Nevertheless, due to the SNP minor allele underrepresentation, further investigation is required. Taken together, ED markers seem to exhibit roles that depend on the clinical context, such as tumour-related thrombogenesis or cancer prognosis. Validation with larger cohorts and more in-depth functional studies are needed for data clarification and potential therapeutic strategies exploitation to tackle cancer progression and thrombosis in OC patients.

Canine mammary tumors (CMTs) represent a significant health concern in dogs, with a high incidence among intact female dogs. CMTs are a promising comparative model for human breast cancer, due to sharing several pathophysiological features. Additionally, CMTs have a strong genetic correlation with their human counterpart, including the expression of microRNAs (miRNAs). MiRNAs are a class of non-coding RNAs that play important roles in post-translational regulation of gene expression, being implicated in carcinogenesis, tumor progression, and metastasis. Moreover, miRNAs hold promise as diagnostic, prognostic, and metastatic biomarkers. Understanding the molecular mechanisms underlying CMTs is crucial for improving diagnosis, prognosis, and monitoring of treatments. Herein, we provide a comprehensive overview of the current knowledge on miRNAs in CMTs, highlighting their roles in carcinogenesis and their potential as biomarkers. Additionally, we highlight the current limitations and critically discuss the overarching challenges in this field, emphasizing the need for future research to translate miRNA findings into veterinary clinical practice., (© 2024. The Author(s).)

Objectives . This study aimed to investigate 12-month and 7-day prevalence of musculoskeletal symptoms among workers of the pulp and paper industry, and assess the contribution of age, gender, body mass index (BMI) and physical activity (PA). Methods . The sample comprised 904 workers. Musculoskeletal symptoms were assessed using the Nordic musculoskeletal questionnaire. χ 2 tests assessed the association between musculoskeletal symptoms and age/gender/BMI/PA, and multivariate logistic regression models predicted the 12-month occurrence of symptoms in the five most prevalent regions. Results . The five most affected body regions were the lower back, shoulders, neck, knees and wrists/hands. Older workers presented more symptoms in all body regions, except dorsal; female gender was associated with neck symptoms ( p  = 0.001); overweight was associated with a higher prevalence of lower back ( p  = 0.01), knee ( p  = 0.017) and ankle/foot ( p  = 0.037) symptoms; and a moderate PA level was associated with thigh/hip symptoms ( p  = 0.006). Age was a significant predictor in all five most affected regions; gender was a significant predictor for shoulders, neck and wrists/hands; and BMI was a significant predictor for lower back symptoms. Conclusion. The 12-month and 7-day prevalence of musculoskeletal symptoms among workers of the pulp and paper industry is higher in the lower back, shoulders, neck, knees and wrists/hands.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously nonalcoholic fatty liver disease (NAFLD), is the number one chronic liver disorder worldwide. Progression to advanced fibrosis marks the emergence of a significant risk of liver-related negative outcomes. However, only a minority of patients will present at this stage. Since widespread liver biopsy in unfeasible at such high disease prevalence, there was a need to develop noninvasive tests (NITs) that could easily and reliably be applied to patients with MASLD, regardless of clinical setting. The NITs include simple scores, like the fibrosis-4 (FIB-4) Index, patented serum tests, like the Enhanced Liver Fibrosis test (ELF™), and imaging-based modalities, like the vibration-controlled transient elastography (VCTE). Guidelines suggests a stepwise approach that utilizes more than one NIT, with FIB-4 <1.30 being used as a first step to rule out patients that do not need further testing. Subsequent choice of NIT will be influenced by setting, cost, and local availability. While these NITs are accurate, they are not perfect. As such, research is ongoing. A promising avenue is that of omics, a group of technologies that provide concomitant results on a large number of molecules (and other variables). With the advance of artificial intelligence, new NITs may arise from large demographic, biochemical, and radiological data sets.

Background/Objectives: Tendon structure is predominantly composed of the extracellular matrix (ECM), and genetic variants in non-collagenous ECM components may influence susceptibility to tendinopathy. We investigated the potential influence of single nucleotide polymorphisms (SNPs) in fibrillin-2 ( FBN2 ), tenascin-C ( TNC ), and matrix metalloproteinase-3 ( MMP3 ) on the tendon regeneration failure phenotype and impact on the susceptibility to tendinopathy in Brazilian high-performance athletes. Methods: This case-control study was conducted with 397 high-performance athletes from different sports modalities (197 tendinopathy cases and 200 controls), and they were analyzed by validated TaqMan TM SNP genotyping assays of the SNPs FBN2 (rs331079), TNC (rs2104772), and MMP3 (rs591058). Results: Out of the 197 tendinopathy cases, 63% suffered from chronic tendon pain and 22% experienced more than three episodes of disease manifestation. The TNC -rs2104772- A allele was significantly associated with tendinopathy (OR: 1.4; 95% CI: 1.1-1.8), while athletes carrying the MMP3 -rs591058- T allele were linked to an increased risk of more episodes of disease manifestation (OR: 1.7; 95% CI: 1.1-2.8). The TNC-MMP3 tendon regeneration failure phenotype ( TNC-A/MMP3-T ) was associated with an increased risk of tendinopathy (OR: 1.4; 95% CI: 1.1-2.0) and episodes of disease manifestation (OR: 2.0; 95% CI: 1.2-3.5). Athletes with tendinopathy who had the TNC-A/MMP3-T interaction were more prone to experiencing more than three disease exacerbations (OR: 4.3; 95% CI: 1.8-10.5) compared to TNC-A/TNC-C . Conclusions: This study suggests that rs2104772 and rs591058 SNPs could be involved in the tendon regeneration failure phenotype and may influence the molecular mechanism related to the regulation of the tendon ECM during training workload.

Background and Aim: Papillomaviruses (PVs) infections have been documented in numerous animal species across different regions worldwide. They often exert significant impacts on animal health and livestock production. Scientists have studied natural products for over half a century due to their diverse chemical composition, acknowledging their value in fighting cancer. Acorns ( Quercus ilex ) are believed to have several unexplored pharmacological properties. This study aimed to evaluate the in vivo safety and cancer chemopreventive activity of an infusion extract of Q. ilex in a transgenic mouse model of human PV (HPV)-16, which developed squamous cell carcinomas through a multistep process driven by HPV16 oncogenes., Materials and Methods: Q. ilex extract was prepared by heating in water at 90°C and then characterized by mass spectrometry. Phenolic compounds from this extract were administered in drinking water to female mice in three different concentrations (0.03, 0.06, and 0.09 g/mL) over a period of 28 consecutive days. Six groups (n = 6) were formed for this study: group 1 (G1, wildtype [WT], water), group 2 (G2, HPV, water), group 3 (G3, WT, 0.09 g/mL), group 4 (G4, HPV, 0.03 g/mL), group 5 (G5, HPV, 0.06 g/mL), and group 6 (G6, HPV, 0.09 g/mL). Throughout the experiment, humane endpoints, body weight, food intake, and water consumption were recorded weekly. Following the experimental period, all mice were sacrificed, and blood, internal organs, and skin samples were collected. Blood was used to measure glucose and microhematocrit and later biochemical parameters, such as creatinine, urea, albumin, alanine aminotransferase, and total proteins. Histological analysis was performed on skin and organ samples., Results: The administration of Q. ilex extract resulted in a statistically significant increase in relative organ weight among HPV transgenic animals, indicating adaptive biological response to the tested concentrations. Moreover, a reduction in characteristic skin lesions was observed in animals treated with the 0.06 and 0.09 g/mL extract., Conclusion: These results provide a favorable chemopreventive profile for Q. ilex extract at concentrations of 0.06 and 0.09 g/mL. This study highlights the potential of Q. ilex extract as a safe and effective therapeutic strategy against HPV16-associated lesions in transgenic mouse models. The limitation of our study was the durability of transgenic animals. As a more sensitive species, we must always be careful with the durability of the test. We intend to study concentrations of 0.06 and 0.09 g/mL for longer to further investigate their possible effects., Competing Interests: The authors declare that they have no competing interests. The funders had no role in study design, data collection and analysis, decision to publish, or manuscript preparation., (Copyright: © Medeiros-Fonseca, et al.)

Nanomedicine, an area that uses nanomaterials for theragnostic purposes, is advancing rapidly, particularly in the detection and treatment of neurodegenerative diseases. The design of nanocarriers can be optimized to enhance drug bioavailability and targeting to specific organs, improving therapeutic outcomes. However, clinical translation hinges on biocompatibility and safety. Nanocarriers can cross the blood-brain barrier (BBB), potentially causing neurotoxic effects through mechanisms such as oxidative stress, DNA damage, and neuroinflammation. Concerns about their accumulation and persistence in the brain make it imperative to carry out a nanotoxicological risk assessment. Generally, this involves identifying exposure sources and routes, characterizing physicochemical properties, and conducting cytotoxicity assays both in vitro and in vivo. The lack of a specialized regulatory framework creates substantial gaps, making it challenging to translate findings across development stages. Additionally, there is a pressing need for innovative testing methods due to constraints on animal use and the demand for high-throughput screening. This review examines the mechanisms of nanocarrier-induced neurotoxicity and the challenges in risk assessment, highlighting the impact of physicochemical properties and the advantages and limitations of current neurotoxicity evaluation models. Future perspectives are also discussed. Additional guidance is crucial to improve the safety of nanomaterials and reduce associated uncertainty. STATEMENT OF SIGNIFICANCE: Nanocarriers show tremendous potential for theragnostic purposes in neurological diseases, enhancing drug targeting to the brain, and improving biodistribution and pharmacokinetics. However, their neurotoxicity is still a major field to be explored, with only 5% of nanotechnology-related publications addressing this matter. This review focuses on the issue of neurotoxicity and safety assessment of nanocarriers for brain delivery. Neurotoxicity-relevant exposure sources, routes, and molecular mechanisms, along with the impact of the physicochemical properties of nanomaterials, are comprehensively described. Moreover, the different experimental models used for neurotoxicity evaluation are explored at length, including their main advantages and limitations. To conclude, we discuss current challenges and future perspectives for a better understanding of risk assessment of nanocarriers for neurobiomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Lung cancer is the most common cause of cancer death in Portugal. The Dutch-Belgian lung cancer screening (LCS) study (NELSON), the biggest European LCS study, showed a lung cancer mortality reduction in a high-risk population when being screened. In this study, the cost-effectiveness of LCS, based on the NELSON study protocol and outcomes, was evaluated compared with no screening in Portugal. Methods: The present study modified an established decision tree by incorporating a state-transition Markov model to evaluate the health-related advantages and economic implications of low-dose computed tomography (LDCT) LCS from the healthcare standpoint in Portugal. The analysis compared screening versus no screening for a high-risk population aged 50-75 with a smoking history. Various metrics, including clinical outcomes, costs, quality-adjusted life years (QALYs), life-years (LYs) and the incremental cost-effectiveness ratio (ICER), were calculated to measure the impact of LDCT LCS. Furthermore, scenario and sensitivity analyses were executed to assess the robustness of the obtained results. Results: Annual LCS with volume-based LDCT resulted in €558 million additional costs and 86,678 additional QALYs resulting in an ICER of €6440 per QALY for one screening group and a lifetime horizon. In total, 13,217 premature lung cancer deaths could be averted, leading to 1.41 additional QALYs gained per individual diagnosed with lung cancer. Results are robust based on the sensitivity analyses. Conclusion: This study showed that annual LDCT LCS for a high-risk population could be cost-effective in Portugal based on a willingness to pay a threshold of one-time the GDP (€19,290 per QALY gained).

Background: Cancer patients face a greater risk of complications and death after contracting the SARS-CoV-2 virus. Booster doses of the COVID-19 vaccine were suggested to provide additional protection. This study aimed to assess how cancer patients' immune systems respond to the booster shots and categorize their responses., Methods: We analyzed 735 samples from 422 individuals, including patients followed at the Portuguese Oncology Institute of Porto (IPO-Porto). Three cohorts were recruited, and blood samples were collected 3- and 6-months post-booster dose: cohort 1 cancer patients (also collected before the booster); cohort 2 cancer patients; and cohort 3 (healthy individuals). Humoral immune response was evaluated by analyzing IgG levels against the SARS-CoV-2 Spike (S) protein. IgG levels against the SARS-CoV-2 Nucleocapsid(N) protein was also analyzed in order to address previous contact with the virus., Results: Among Cohort 1 patients with solid tumors, when compared to pre-boost, IgG S levels increased 3 months after the boost and remained high after 6 months. Patients with hematologic tumors demonstrated lower IgG S levels at both timepoints. Comparing the IgG S levels among hematological tumors, solid tumors, and healthy individuals in both timepoints we observed that the healthy individuals had the strongest IgG S response, followed by the solid, and, lastly, the hematologic tumors. Solid tumor patients undergoing chemotherapy had reduced IgG S levels, especially those on high febrile neutropenia risk regimens., Conclusions: In conclusion, cancer patients have a weaker immune response to the SARS-CoV-2 vaccine, especially those with hematological cancers. Chemotherapy and febrile neutropenia risk further reduce booster effectiveness. Further research is needed to optimize vaccine timing for cancer patients undergoing chemotherapy., Competing Interests: The authors declare no conflicts of interest.

MicroRNAs are a conserved class of small, tissue-specific, non-coding RNAs that regulate gene expression to preserve cellular homeostasis. Proper miRNA expression is crucial for physiological balance because it affects numerous genetic pathways, including cell cycle control, proliferation, and apoptosis, through gene expression targeting. Deregulated miRNA expression has been implicated in several cancer types, including prostate cancer (PC), acting as tumor suppressors or oncogenes. Despite the availability of promising therapies to control tumor growth and progression, effective diagnostic and therapeutic strategies for different types of cancer are still lacking. PC continues to be a significant health challenge, particularly its castration-resistant (CRPC) form, which presents major therapeutic obstacles because of its resistance to conventional androgen deprivation treatments. This review explores miRNAs' critical roles in gene regulation and cancer biology, as well as various miRNA delivery systems, highlighting their potential and the challenges in effectively targeting cancer cells. It aims to provide a comprehensive overview of the status of miRNA research in the fight against CRPC, summarizing miRNA-based therapies' successes and limitations. It also highlights the promise of miRNAs as therapeutic agents for CRPC, underlining the need for further research to overcome existing challenges and move these therapies toward clinical applications.

Objectives: This study aimed to compare the anthropometry and body composition of vegetarian and omnivorous adults living in Portugal, while exploring nutritional and health parameters underlying observed differences., Methods: 425 omnivorous (OMNI), lacto-ovo-vegetarian (LOV), or vegan (VEG) healthy adults were recruited. Anthropometry was measured, and bioelectrical impedance analysis was performed. Participants answered food frequency, sociodemographic, and lifestyle questionnaires. Serum iron, ferritin, and CRP were quantified by spectrophotometry, and serum B12 vitamin and homocysteine were quantified by chemiluminescent microparticle immunoassay., Results: Total protein intake significantly decreased with increasing strictness of vegetarian habits (median (P25; P75) in g/day: 98.6 (79.5; 123.1), 90.4 (65.9; 121.0), and 87.6 (59.8; 118.5) for OMNI, LOV and VEG, respectively; p = 0.020), and carbohydrate intake was the highest in LOV (median (P25; P75) in g/day: 231.5 (178.4; 287.9), 283.9 (227.3; 342.6), and 263.0 (222.0; 348.3) for OMNI, LOV and VEG, respectively; p = 0.001). VEG were the main users of B12 vitamin (93% in VEG vs. 17% in OMNI and 59% in LOV, p = 0.001), and LOV were the main users of iron supplements (29% in LOV vs. 14% in OMNI and 13% in VEG, p = 0.042), respectively. Blood levels of B12 vitamin correlated negatively with blood homocysteine ( r s = -0.386, p < 0.001) and positively with % muscle mass ( r s = 0.136, p = 0.005). Participants using iron supplements presented higher C-reactive protein (CRP) ( p = 0.014) and they had lower % MM ( p = 0.003). Finally, when compared to being OMNI, being LOV independently associated with: (a) having +4.8% ( p = 0.002) of fat mass, which could be due to higher carbohydrate intake, and (b) having -2.2% ( p = 0.043) of muscle mass. Our data suggest that the association between diet and muscle mass could be attenuated in VEG due to B12 supplementation and/or aggravated in LOV due to iron supplementation-associated inflammation.

Introduction: Due to the large amount of scientific evidence on the subject and the limitations and incongruities in previous reviews, the primary aim of this umbrella review is to gather all the information regarding the importance of vitamin D levels in the osseointegration of dental implants., Methods: The literature search was performed in PubMed, Web of Science, CINAHL Plus, Cochrane Library, and Academic Search Complete throughout the search expression ["vitamin D" AND ("dental implant" OR "dental implants")]., Results: The initial search yielded 351 results, but at the end of the process, only five systematic reviews were selected., Conclusions: Vitamin D seems to have a positive effect on the osseointegration of dental implants and on the reduction of dental implant failures; however, it is recommended that future studies take into account the limitations mentioned in this study in order to increase the validity and quality of scientific evidence on the subject.

Prostate cancer (PC) is one of the most commonly diagnosed tumours among men. Second-generation androgen receptor axis-targeted (ARAT) agents, namely abiraterone acetate (AbA) and enzalutamide (ENZ), are currently used in the management of metastatic castration-resistant PC (mCRPC). However, the treatment is challenging due to the lack of prognostic biomarkers. Meanwhile, single-nucleotide polymorphisms (SNPs) have emerged as potential prognostic indicators of mCRPC. Thus, this study evaluated the impact of relevant SNPs on the treatment outcomes of 123 mCRPC patients enrolled in a hospital-based cohort study. The CYP17A1 rs2486758 C allele was associated with a 50% reduction in the risk of developing castration resistance (hazard ratio (HR) = 0.55; p = 0.003). Among patients without metastasis at tumour diagnosis and under AbA, a marginal association between YBX1 rs10493112 and progression-free survival was detected (log-rank test, p = 0.056). In the same subgroup, significant associations of HSD3B1 rs1047303 (CC/CA vs. AA; HR = 3.41; p = 0.025), YBX1 rs12030724 (AT vs. AA; HR = 3.54; p = 0.039) and YBX1 rs10493112 (log-rank test, p = 0.041; CC vs. AA/AC; HR = 3.22; p = 0.053) with overall survival were also observed, which were confirmed by multivariate Cox analyses. Although validation with larger cohorts is required, these findings suggest that SNPs could enhance the prognosis assessment of mCRPC patients, leading to a more personalised treatment.

Background: Atherosclerotic Cardiovascular Disease (ASCVD) is a global public health concern. This study aimed to estimate the healthcare resource utilization (HRU) and costs stratified by cardiovascular disease (CVD) risk categories using real-world evidence, in a regional population in Portugal., Methods: This is a retrospective observational study, using data from Electronic Health Records between 2017 and 2021. Patients aged ≥ 40 years, and with at least one general practitioner (GP) appointment in the 3 years before 31st of December 2019, were included. CVD risk categories were determined based on 2021 ESC prevention guidelines. HRU encompassed hospital data (hospitalizations, outpatient and emergency room visits) and GP appointments. Total direct costs per patient were calculated based on the reference cost of the Portuguese legislation for payment methodology on Diagnosis-Related Groups (DRGs)., Results: Analysis of 3 122 695 episodes, revealed consistent HRU and costs across the five years. Very high-risk patients, showed higher HRU, particularly in hospital admissions. Costs tended to rise with higher CVD risk level. Very high-risk patients with ASCVD had higher costs for hospital admissions, while low-to-moderate risk patients had higher costs for GP visits. Despite a smaller proportion, very high-risk patients with prior ASCVD represent the highest costs per patient across healthcare settings (from 115€ in emergency visits to 2 673€ in hospitalizations), followed by very high-risk patients without prior ASCVD (ASCVD-risk equivalents)., Conclusion: This study revealed a substantial HRU and costs by patients with very high CVD risk, particularly those with prior ASCVD. Moreover, ASCVD-risk equivalents emerge as notable consumers, emphasizing the importance of risk assessment and preventive measures in cost-effective management of these patients., (© 2024. The Author(s).)

Purpose: Castration Resistant Prostate Cancer (CRPC) is characterized by poor prognosis and limited therapeutic options. AgNPs functionalized with glucose (G-AgNPs) were observed cytotoxic to CRPC cell lines (PC-3 and Du-145) and not LNCaP. This study aims to evaluate AgNPs and G-AgNPs' uptake mechanisms in these cells and understand their role in the selective effect against CRPC cells., Methods: Uptake of AgNPs and G-AgNPs was assessed through transmission electron microscopy (TEM). A microRNA (miRNAs) analysis approach was used to uncover the main molecular differences responsible for the endocytic mechanisms' regulation. Caveolin (Cav) 1 and 2 mRNA and protein levels were assessed in the three cell lines. Caveolae-dependent endocytosis was inhibited with genistein or siCav1 - and siCav2 - in PC-3 and Du-145 and resazurin assay was used to evaluate viability after AgNPs and G-AgNPs administration. Caveolae-dependent endocytosis was induced with Cav1 + and Cav2 + plasmids in LNCaP, resazurin assay was used to evaluate viability after AgNPs and G-AgNPs administration and TEM to assess their location., Results: AgNPs and G-AgNPs were not uptaked by LNCaP. miRNA analysis revealed 37 upregulated and 90 downregulated miRNAs. Functional enrichment analysis of miRNAs' targets resulted in enrichment of terms related to endocytosis and caveolae. We observed that Cav1 and Cav2 are not expressed in LNCaP. Inhibiting caveolae-dependent endocytosis in Du-145 and PC-3 led to a significative reduction of cytotoxic capacity of AgNPs and G-AgNPs and induction of caveolae-dependent endocytosis in LNCaP lead to a significative increase as well as their uptake by cells., Conclusion: This study shows the potential of these AgNPs as a new therapeutic approach directed to CRPC patients, uncovers caveolae-dependent endocytosis as the uptake mechanism of these AgNPs and highlights deregulation of Cav1 and Cav2 expression as a key difference in hormone sensitive and resistant PCa cells which may be responsible for drug resistance., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Morais et al.)

Cancer is a complex pathological condition associated with substantial rates of mortality and morbidity in both humans and animals. Mammary gland tumors in intact female dogs are the most prevalent neoplasms. Surgical intervention remains the primary treatment choice. Alternative therapeutic options have emerged, with histopathological examination being fundamental to confirm the diagnosis and to decide the best therapy. This research focused on the clinicopathological, immunohistochemical, and cytogenetic aspects of canine mammary tumors (CMTs). Most of the animals were mixed-breed, with the majority being older than seven years, and only 16.7% had been spayed before surgery. Caudal abdominal and inguinal mammary glands were the most affected, with regional mastectomy being the predominant treatment (75.0%). Of all the tumors, 29.1% were benign, while 70.9% were malignant. Complex adenoma was the most common benign tumor, whereas tubulopapillary carcinoma was the most common malignant type. Grade III tumors (17.6%) were the least encountered, while grades I and II exhibited a similar prevalence (41.2%). All the carcinomas were classified as luminal, and cytogenetics analysis demonstrated a high chromosomal instability with significant aneuploidy observed in all cases and polyploidy detected in 62.5%. This study holds significance as canine and human breast cancers share similar characteristics, suggesting that dogs could be a valuable model for human breast cancer research. Further studies with larger sample sizes are needed to enhance our understanding of CMTs.

Introduction: Dysgraphia, a recognized PD motor symptom, lacks effective clinical assessment. Current evaluation relies on motor assessment scales. Computational methods introduced over the past decade offer an objective dysgraphia assessment, considering size, duration, speed, and handwriting fluency. Objective evaluation of dysgraphia may be of help for early diagnosis of PD., Objective: Computerized assessment of dysgraphia in de novo PD patients and its correlation with clinical scales., Methods: We evaluated 38 recently diagnosed, premedication PD patients and age-matched controls without neurological disorders. Participants wrote "La casa de Pamplona es bonita" three times on paper and once on a Wacom tablet under the paper, totaling four phrases. Writing segments of 5-10 s were analyzed. The Wacom tablet captured kinematic data, including mean velocity, mean acceleration, and pen pressure. Data were saved in.svc format and analyzed using specialized software developed by Tecnocampus Mataró. Standard clinical practice data, Hoehn & Yahr staging, and UPDRS scales were used for evaluation., Results: Significant kinematic differences existed; patients had lower mean speed (27 ± 12 vs. 48 ± 18, p < 0.0001) and mean acceleration (7.2 ± 3.9 vs. 15.01 ± 7, p < 0.0001) than controls. Mean speed and mean acceleration correlated significantly with UPDRS III scores (speed: r = -0.52, p < 0.0007; acceleration: r = 0.60, p < 0.0001), indicating kinematic parameters' potential in PD evaluation., Conclusions: Dysgraphia is identifiable in PD patients, even de novo, indicating an early symptom and correlates with clinical scales, offering potential for objective PD patient evaluation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Renal cell carcinoma is the most common adult renal solid tumor and the deadliest urological cancer, with clear cell renal cell carcinoma (ccRCC) being the predominant subtype. The PI3K/AKT signaling pathway assumes a central role in ccRCC tumorigenesis, wherein its abnormal activation confers a highly aggressive phenotype, leading to swift resistance against current therapies and distant metastasis. Thus, treatment resistance and disease progression remain a persistent clinical challenge in managing ccRCC effectively. PTEN, an antagonist of the PI3K/AKT signaling axis, emerges as a crucial factor in tumor progression, often experiencing loss or inactivation in ccRCC, thereby contributing to elevated mortality rates in patients. Therefore, understanding the molecular mechanisms underlying PTEN suppression in ccRCC tumors holds promise for the discovery of biomarkers and therapeutic targets, ultimately enhancing patient monitoring and treatment outcomes. The present review aims to summarize these mechanisms, emphasizing their potential prognostic, predictive, and therapeutic value in managing ccRCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objectives . Associations between shift-work, musculoskeletal symptoms and absenteeism are poorly investigated in the manufacturing industry. This study aimed to investigate associations between working schedule, musculoskeletal symptoms and days of absenteeism among pulp and paper industry workers. Methods . Musculoskeletal symptoms of 904 workers were assessed through the Nordic Musculoskeletal Questionnaire. χ 2 tests assessed associations between being a day-worker or shift-worker, the prevalence of musculoskeletal symptoms and days of absenteeism. Results . A significant association was found between working schedule and symptoms in the lower back in the last 12 months, with shift-workers presenting higher prevalence than day-workers ( p  = 0.022). Significant associations were also found between days of absenteeism and symptoms in the shoulders ( p  = 0.002), which mostly led to absenteeism of 100-365 days; elbows ( p  < 0.001), wrists/hands ( p  = 0.045) and ankles/feet ( p  = 0.042), which produced absenteeism mostly of 25-99 days; and dorsal region ( p  = 0.001), which mainly led to absenteeism of 10-24 days. No associations were found between working schedule and days of absenteeism ( p  = 0.265). Conclusion . Shift-work is associated with increased prevalence of lower back symptoms, but seems not to influence days of absenteeism. Shoulders seem to be the region leading to higher days of absenteeism, followed by elbows, wrists/hands, ankles/feet and the dorsal region.

The aims of this study were to assess the impact of exclusive breastfeeding up to 6 months of age on reducing the incidence of overweight and obesity in children up to 10 years of age and to estimate the annual incidence of obesity and overweight in the study population. Our retrospective cohort analysis using electronic health records included children from zero to ten years old, born between 1 January 2006 and 31 December 2022, followed up at the Unidade Local de Saúde de Matosinhos (ULSM). Information on their comorbidity history was collected, and positive or negative control results were defined. In the first year of life, around 29% of the children on exclusive breastfeeding were obese and 20% were overweight. This trend was reversed by the age of 9. Asthma and allergic rhinitis were used as positive control outcomes and allergic dermatitis as a negative control outcome. There seems to be no relationship between exclusive and non-exclusive breastfeeding and the development of overweight or obesity at the age of 10. The results showed that breastfeeding is associated with a lower risk of asthma in the future.

The goal of this comprehensive review was to verify if the prevalence of Helicobacter pylori ( Hp ) bacteria in patients with dyspepsia is higher in the oral cavity of periodontal or non-periodontal patients. The bibliographic search was conducted on scientific studies published in PubMed, Cochrane Library, SciELO, and BVS. The focus question was: "In patients with dyspepsia and periodontitis, is the prevalence of Hp bacteria in the oral cavity higher than in patients with only dyspepsia or without any disease?" The inclusion criteria were human studies in English, Portuguese, or Spanish languages, published between 2000 and 2022, that included patients over the age of 18 and aimed to evaluate the presence of Hp bacteria in the oral cavity and in the protective mucosal layer of the gastric lining of patients with the diseases (periodontitis and dyspepsia) or without disease; clinical trials, randomized controlled clinical trials, comparative studies, case-control studies, cross-sectional studies, and cohort studies. The methodological quality evaluation of the included articles was performed using the Joanna Briggs Institute tools. The final scores could be of "Low" quality (at least two "no" [red] or ≥ five "unclear" found), "Moderate" quality (one "no" [red] was found or up to four "unclear" criteria were met), or "High" quality (all green [yes] or at maximum two "unclear"). Of 155 potentially eligible articles, 10 were included in this comprehensive review after the application of the eligibility criteria. The selected studies were scrutinized regarding the relationship between Hp colonization in the oral cavity and stomach, its impact on severity and complications of gastric infection, as well as the effect of the presence of oral and gastric Hp on dental and systemic parameters. Hp can colonize periodontal pockets regardless of its presence in the stomach. There was a higher prevalence of oral biofilm in dyspeptic patients with periodontal disease, and worse control of bleeding and low oral hygiene was observed in periodontal compared to non-periodontal patients. For que quality assessment, the scientific studies included presented low to moderate methodological quality. Conclusions: It is possible to conclude that Hp is a bacterium that can colonize dental plaque independently of the stomach and vice versa; however, when both diseases are found, its presence may be more significant. Supra and subgingival dental plaque may be a reservoir of Hp , suggesting that patients with gastric infections are more likely to have Hp in the oral cavity. The results must be carefully analyzed due to the limitations present in this review.

Ovarian cancer (OC) is a leading cause of death among gynaecological malignancies. The haemostatic system, which controls blood flow and prevents clotting disorders, paradoxically drives OC progression while increasing the risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) have emerged as crucial in understanding VTE pathogenesis. Exploring the connection between cancer and thrombosis through these RNAs could lead to novel biomarkers of cancer-associated thrombosis (CAT) and OC, as well as potential therapeutic targets for tumour management. Thus, this study examined the impact of eight plasma miRNAs targeting the tissue factor (TF) coagulation pathway-miR-18a-5p, -19a-3p, -20a-5p, -23a-3p, -27a-3p, -103a-3p, -126-5p and -616-3p-in 55 OC patients. Briefly, VTE occurrence post-OC diagnosis was linked to shorter disease progression time (log-rank test, p = 0.024) and poorer overall survival (OS) (log-rank test, p < 0.001). High pre-chemotherapy levels of miR-20a-5p (targeting coagulation factor 3 ( F3 ) and tissue factor pathway inhibitor 2 ( TFPI2 )) and miR-616-3p (targeting TFPI2 ) predicted VTE after OC diagnosis (χ 2 , p < 0.05). Regarding patients' prognosis regardless of VTE, miR-20a-5p independently predicted OC progression (adjusted hazard ratio (aHR) = 6.13, p = 0.005), while miR-616-3p significantly impacted patients' survival (aHR = 3.72, p = 0.020). Further investigation is warranted for their translation into clinical practice.

This study aims to assess the self-perception of the QoL (WHOQOL-bref) in the Canal of Anil zone and its neighbor zone of the center of the District of Anil in Rio de Janeiro and to identify which factors are associated with the population self-perception of the need to "improve" their quality of life (QoL). A cross-sectional observational analytical study was carried out after approval by the competent ethics committee (CEP/CONEP) approval. A non-probabilistic sampling of residents of the Canal of Anil (n = 494) and the central district of Anil (n = 250) was used. A questionnaire was administered in person to collect data on self-reported sociodemographic characteristics, general health, sanitation, lifestyle in the residential area, and the WHOQOL-Bref. Although with a worse self-perceived water/sanitation participants in the Anil Canal community report fewer allergies, less medication, fewer skin diseases, less Zika virus, and less Chikungunya, among others. The self-perception of the need to improve the QoL in the Anil Canal community and the zone at the central District of Anil has proved to be influenced by several social and economic factors as well as residential practices and conditions. The multivariate analysis allowed us to identify both modifiable and non-modifiable risk factors for the need to improve physical QoL: taking medication, respiratory problems, skin disease diagnosed by a doctor, having a water tank at home or having filtered water at home, unpleasant odor of the water of the Anil Canal and the level of education, and age. Regarding the need to improve the environmental QoL, both areas are largely modifiable (e.g., having had ascariasis/roundworm; having a water tank in the house; not drinking bottled water; not having pavements in the street). Sociodemographic and environmental factors, in addition to health conditions, play a pivotal role in influencing individuals' perceptions of the necessity for enhanced physical and environmental well-being.

Background: Cardiovascular (CV) risk scores identify individuals at higher long-term risk of CV events that may benefit from more aggressive preventive interventions., Objective: To assess the association of CV-risk categories and criteria with long-term CV events., Methods: Observational cohort study between 2000-2019 on patients aged 40-80 years, followed by 14 primary care centers assisted by 1 hospital in Portugal. Follow-up began when electronic health records data allowed for CV-risk classification and dynamic reassessment per 2019 ESC/EAS Guidelines. Inclusion criteria required at least one appointment with a primary care physician within three years before follow-up initiation. We assessed the 10-year adjusted hazard-ratio of combined CV death and non-fatal atherosclerotic cardiovascular disease (ASCVD) hospitalization, across SCORE risk categories and criteria, using Cox proportional hazards models adjusted for sex, age, competing comorbidities, and medication., Results: The study included 161 681 observations from 87 035 unique patients. During the observation period, 71 787 patients were classified as low/moderate, 51 476 as high and 38 418 as very-high CV-risk categories. In the very-high group, prevalent comorbidities were hypertension (69%), hypercholesterolemia (69%) and type 2 diabetes (61%), and 13% were hospitalized for ASCVD. The adjusted 10-year hazard ratio of the composite of CV death or ASCVD hospitalization was 2.10 (95% CI: 1.91-2.32) for high-risk and 3.56 (95% CI: 3.21-3.96) for very-high-risk patients (low-risk as reference)., Conclusion: Our study reinforces the prognostic relevance of CV-risk stratification for long-term prediction of CV death and ASCVD hospitalization in an unselected cohort, independently of sex, age, competing comorbidities and medication., Competing Interests: Declaration of competing interest C.G. declares speaker and consulting fees from AstraZeneca, Bayer, BIAL, Boehringer-Ingelheim, Daiichi-Sankyo, Lilly, MSD, Novartis and Novo Nordisk. D.S. declares speaker fees from Daiichi-Sankyo. F.A. declares speaker and consulting fees from AstraZeneca, Bayer, BIAL, Daiichi-Sankyo, Ferrer, MSD, Novartis, Novo Nordisk and Servier. M.A.-S. is an employee of Novartis Farma, Produtos Farmacêuticos SA. T.T.-G. declares speaker and consulting fees from AstraZeneca, BIAL, Daiichi-Sankyo, MSD and Medinfar. T.T.-G. holds shares in MTG. M.A.-S. is an employee of Novartis. D.A. and M.C.-P. declare no interest conflicts. The results presented in this article have not been published previously in whole or part., (Copyright © 2024. Published by Elsevier Inc.)

Ovarian cancer (OC) is the deadliest gynaecological malignancy. Identifying new prognostic biomarkers is an important research field. Haemostatic components together with leukocytes can drive cancer progression while increasing the susceptibility to venous thromboembolism (VTE) through immunothrombosis. Unravelling the underlying complex interactions offers the prospect of uncovering relevant OC prognostic biomarkers, predictors of cancer-associated thrombosis (CAT), and even potential targets for cancer therapy. Thus, this study evaluated the expression of F3 , F5 , F8 , F13A1 , TFPI1 , and THBD in peripheral blood cells (PBCs) of 52 OC patients. Those with VTE after tumour diagnosis had a worse overall survival (OS) compared to their counterparts (mean OS of 13.8 ± 4.1 months and 47.9 ± 5.7 months, respectively; log-rank test, p = 0.001). Low pre-chemotherapy F3 and F8 expression levels were associated with a higher susceptibility for OC-related VTE after tumour diagnosis (χ 2 , p < 0.05). Regardless of thrombogenesis, patients with low baseline F8 expression had a shorter progression-free survival (PFS) than their counterparts (adjusted hazard ratio (aHR) = 2.54; p = 0.021). Among those who were not under platelet anti-aggregation therapy, low F8 levels were also associated with a shorter OS (aHR = 6.16; p = 0.006). Moving forward, efforts should focus on external validation in larger cohorts.

Background: Despite recent improvements in cancer detection and survival rates, managing cancer-related pain remains a significant challenge. Compared to neuropathic and inflammatory pain conditions, cancer pain mechanisms are poorly understood, despite pain being one of the most feared symptoms by cancer patients and significantly impairing their quality of life, daily activities, and social interactions. The objective of this work was to select a panel of biomarkers of central pain processing and modulation and assess their ability to predict chronic pain in patients with cancer using predictive artificial intelligence (AI) algorithms., Methods: We will perform a prospective longitudinal cohort, multicentric study involving 450 patients with a recent cancer diagnosis. These patients will undergo an in-person assessment at three different time points: pretreatment, 6 months, and 12 months after the first visit. All patients will be assessed through demographic and clinical questionnaires and self-report measures, quantitative sensory testing (QST), and electroencephalography (EEG) evaluations. We will select the variables that best predict the future occurrence of pain using a comprehensive approach that includes clinical, psychosocial, and neurophysiological variables., Discussion: This study aimed to provide evidence regarding the links between poor pain modulation mechanisms at precancer treatment in patients who will later develop chronic pain and to clarify the role of treatment modality (modulated by age, sex and type of cancer) on pain. As a final output, we expect to develop a predictive tool based on AI that can contribute to the anticipation of the future occurrence of pain and help in therapeutic decision making., (© 2024. The Author(s).)

Background: This systematic review was conducted to assess the effects of whole-body vibration (WBV) exercises on muscles responses and on risk of falls in elderly individuals., Methods: Searches were conducted in MEDLINE/PubMed, Physiotherapy Evidence Database (PEDro), Web of Science, CINAHL and Scopus databases in Feb 2023 to identify studies with the potential to be included according to the eligibility criteria. Relevant data from included studies were extracted. The methodological quality was evaluated for each study included by PEDro scale, risk of bias (Cochrane Collaboration's tool), and the level of evidence by National Health and Medical Research Council (NHMRC)., Results: Six randomized clinical trial (RCT) were included. In respect of the level of evidence, all studies were classified as Level II (NHMRC) and regarding to the methodological quality (PEDro scale), four studies were considered 'high' and two were 'fair'. Two publications presented low risk of bias, three with high risk of bias and one unclear. All the selected studies reported positive effects and improvements on risk of falls and muscle response after WBV exercise., Conclusion: WBV exercise may contribute to reduce the risk of falls and improve muscle responses in the elderly individuals., (Copyright© 2024 Meirelles et al. Published by Tehran University of Medical Sciences.)

Introduction: Cancer-associated thrombosis (CAT) is a significant concern among patients with malignant diseases, leading to increased mortality. While current guidelines recommend primary thromboprophylaxis for venous thromboembolism (VTE) in medium-to-high-risk outpatients, this practice remains controversial. A better understanding of primary thromboprophylaxis is crucial, yet there is a lack of Real-World Evidence (RWE) in Portugal., Aims: This RWE study aimed to elucidate primary thromboprophylaxis practices among cancer outpatients in Portugal., Methods: A five-year observational multicentric study in eight Portuguese health institutions enrolled 124 adult cancer outpatients under primary thromboprophylaxis for VTE. The endpoints were CAT, bleeding, cancer progression and death., Results: High thrombotic risk tumours were prevalent, with 57% (71) of the patients presenting with pancreatic and gastric cancers. Regarding primary thromboprophylaxis, 55% (68) received Low-Molecular-Weight Heparin (LMWH). VTE was presented in 11% (14) of the patients and major bleeding in 2% (2). Vascular compression, elevated D-dimer and previous VTE were significantly associated with VTE occurrence under primary thromboprophylaxis. The Onkotev model was shown to be the best risk assessment model (RAM) in this population (p = 0.007). CAT patients exhibited a lower progression-free survival than non-CAT patients (p = 0.021), while thrombosis did not influence overall survival (p = 0.542)., Conclusion: Primary thromboprophylaxis in medium-to-high-risk cancer outpatients is a safe and effective practice in real-world settings. This study is the first Portuguese RWE on primary thromboprophylaxis, highlighting evidence for improving prophylactic strategies in this population., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Venous thromboembolism (VTE) is a challenging clinical obstacle in oncological settings, marked by elevated incidence rates and resulting morbidity and mortality. In the context of cancer-associated thrombosis (CAT), endothelial dysfunction (ED) plays a crucial role in promoting a pro-thrombotic environment as endothelial cells lose their ability to regulate blood flow and coagulation. Moreover, emerging research suggests that this disorder may not only contribute to CAT but also impact tumorigenesis itself. Indeed, a dysfunctional endothelium may promote resistance to therapy and favour tumour progression and dissemination. While extensive research has elucidated the multifaceted mechanisms of ED pathogenesis, the genetic component remains a focal point of investigation. This comprehensive narrative review thus delves into the genetic landscape of ED and its potential ramifications on cancer progression. A thorough examination of genetic variants, specifically polymorphisms, within key genes involved in ED pathogenesis, namely eNOS , EDN1 , ACE , AGT , F2 , SELP , SELE , VWF , ICAM1 , and VCAM1 , was conducted. Overall, these polymorphisms seem to play a context-dependent role, exerting both oncogenic and tumour suppressor effects depending on the tumour and other environmental factors. In-depth studies are needed to uncover the mechanisms connecting these DNA variations to the pathogenesis of malignant diseases.

Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ferreira, et al.)

Cancer-associated cachexia (CAC) is a complex multiple organ syndrome that significantly contributes to reduced quality of life and increased mortality among many cancer patients. Its multifactorial nature makes its early diagnosis and effective therapeutic interventions challenging. Adipose tissue is particularly impacted by cachexia, typically through increased lipolysis, browning and thermogenesis, mainly at the onset of the disease. These processes lead to depletion of fat mass and contribute to the dysfunction of other organs. The β-adrenergic signalling pathways are classical players in the regulation of adipose tissue metabolism. They are activated upon sympathetic stimulation inducing lipolysis, browning and thermogenesis, therefore contributing to energy expenditure. Despite accumulating evidence suggesting that β3-adrenergic receptor stimulation may be crucial to the adipose tissue remodelling during cachexia, the literature remains controversial. Moreover, there is limited knowledge regarding sexual dimorphism of adipose tissue in the context of cachexia. This review paper aims to present the current knowledge regarding adipose tissue wasting during CAC, with a specific focus on the role of the β3-adrenergic receptor, placing it as a potential therapeutic target against cachexia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Colorectal cancer (CRC) is a significant global health concern, ranking as the third most common cancer and the second leading cause of cancer-related deaths. However, in Africa, CRC is the fifth most common invasive malignancy. Limited data hinder our understanding of the evolving burden of CRC in sub-Saharan Africa. This study explores CRC trends in Mozambique, utilising data from population-based oncological registries., Methods: CRC data were gathered from Beira and Maputo population-based cancer registries, along with supplementary information from pathology-based and hospital-based registries. Comparative analyses were performed across different time periods, focusing on trends and epidemiological characteristics., Results: Incidence rates of CRC in Maputo and Beira were relatively low historically. However, data from recent years showed an increase, especially in age groups above 50. Analyses from pathology-based and hospital-based registries affirmed the rising trend. The age-standardised incidence rate in Maputo (2015-2017) was 3.17 for males and 2.55 for females. Beira exhibited increasing rates between 2009 and 2020, particularly in individuals aged 50 and above., Conclusion: The study reveals an emerging burden of CRC in Mozambique, challenging the perception of low incidence. The rising trend underscores the necessity for tailored interventions, emphasizing early diagnosis, preventive strategies, and investments in healthcare infrastructure to address the increasing CRC burden in the region., Competing Interests: The authors declared that they have no competing interests., (© the authors; licensee ecancermedicalscience.)