Limited Effect Research Articles

Tumor markers in non-small cell lung cancer spine metastasis: an assessment of prognosis and overall survival.

The identification of gene mutations in the modern medical workup of metastatic spine tumors has become more common but has not been highly utilized in surgical planning. Potential utility of these genetic markers as surrogates for cancer behavior in current prognosis scoring systems and overall survival (OS) remains underexplored in existing literature. This study seeks to investigate the association of frequently identified tumor markers, EGFR, ALK, and PD-L1, in metastatic non-small cell lung cancer (NSCLC) to the spine with Tokuhashi prognosis scoring and OS. Patients with NSCLC metastasis to spine were identified through chart review. EGFR, ALK, and PD-L1 wild type vs. mutant type were identified from targeted chemotherapy genetic testing. Multiple linear regression was performed to assess gene profile contributions to Tokuhashi score. Cox Proportional Hazards models were generated for each tumor marker to assess the relationship between each marker and OS. A total of 119 patients with NSCLC spine metastasis were identified. We employed a multiple linear regression analysis to investigate the influence of EGFR, ALK, and PD-L1 genotypes on the Tokuhashi score, revealing statistically significant relationships overall (p = 0.002). Individual genotype contributions include EGFR as a non-significant contributor (p = 0.269) and ALK and PD-L1 as significant contributors (p = 0.037 and p = 0.001 respectively). Overall survival was not significantly associated with tumor marker profiles through Kaplan-Meier analysis (p = 0.46) or by multivariable analysis (p = 0.108). ALK and PD-L1 were significantly associated with Tokuhashi score while EGFR was not. Tumor markers alone were not predictive of OS. These findings indicate that genetic markers found in NSCLC metastases to the spine may demonstrate prognostic value. Therefore, employing standard tumor markers could enhance the identification of appropriate surgical candidates, although they demonstrate limited effectiveness in predicting overall survival.

Adenoid cystic carcinoma: insights from molecular characterization and therapeutic advances.

Adenoid cystic carcinoma (ACC) is a malignant tumor primarily originating from the salivary glands, capable of affecting multiple organs. Although ACC typically exhibits slow growth, it is notorious for its propensity for neural invasion, local recurrence, and distant metastasis, making it a particularly challenging cancer to treat. The complexity of ACC's histological and molecular features poses significant challenges to current treatment modalities, which often show limited effectiveness. Recent advancements in single-cell RNA-sequencing (scRNA-seq) have begun to unravel unprecedented insights into the heterogeneity and subpopulation diversity within ACC, revealing distinct cellular phenotypes and origins. This review delves into the intricate pathological and molecular characteristics of ACC, focusing on recent therapeutic advancements. We particularly emphasize the insights gained from scRNA-seq studies that shed light on the cellular landscape of ACC, underscoring its heterogeneity and pathobiology. Moreover, by integrating analyses from public databases, this review proposes novel perspectives for advancing treatment strategies in ACC. This review contributes to the academic understanding of ACC by proposing novel therapeutic approaches informed by cutting-edge molecular insights, paving the way for more effective, personalized therapeutic approaches for this challenging malignancy.

A Multi-Machine Learning Consensus Model Based on Clinical Features Reveals That Interleukin-10 Derived from Monocytes Leads to a Poor Prognosis in Patients with Coronavirus Disease-2019.

Despite ongoing interventions, SARS-CoV-2 continues to cause significant global morbidity and mortality. Early diagnosis and intervention are crucial for effective clinical management. However, prognostic features based on transcriptional data have shown limited effectiveness, highlighting the need for more precise biomarkers to improve COVID-19 treatment outcomes. We retrospectively analyzed 149 clinical features from 189 COVID-19 patients, identifying prognostic features via univariate Cox regression. The cohort was split into training and validation sets, and 77 prognostic models were developed using seven machine learning algorithms. Among these, the least absolute shrinkage and selection operator (Lasso) method was employed to refine the selection of prognostic variables by ten-fold cross-validation strategy, which were then integrated with random survival forests (RSF) to build a robust COVID-19-related prognostic model (CRM). Model accuracy was evaluated across training, validation, and entire cohorts. The diagnostic relevance of interleukin-10 (IL-10) was confirmed in bulk transcriptional data and validated at the single-cell level, where we also examined changes in cellular communication between mononuclear cells with differing IL-10 expression and other immune cells. Univariate Cox regression identified 43 prognostic features. Among the 77 machine learning models, the combination of Lasso and RSF produced the most robust CRM. This model consistently performed well across training, validation, and entire cohorts. IL-10 emerged as a key prognostic feature within the CRM, validated by single-cell transcriptional data. Transcriptome analysis confirmed the stable diagnostic value of IL-10, with mononuclear cells identified as the primary IL-10 source. Moreover, differential IL-10 expression in these cells was linked to altered cellular communication in the COVID-19 immune microenvironment. The CRM provides accurate prognostic predictions for COVID-19 patients. Additionally, the study underscores the importance of early IL-10 level testing upon hospital admission, which could inform therapeutic strategies.

Evidence-Based Review of Randomized Controlled Trials of Interventions for Mental Health Management Post-Moderate to Severe Traumatic Brain Injury.

To present an evidence-based review of randomized controlled trials (RCTs) evaluating interventions for mental health post-moderate to severe traumatic brain injury (post-MSTBI), as part of an extensive database that has been conceptualized as a living systematic review. Systematic searches were conducted for RCTs published in the English language in MEDLINE, PubMed, Scopus, CINAHL, EMBASE, and PsycINFO, up to and including December 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methodological quality of RCTs was assessed using the Physiotherapy Evidence Database scale, and the level of evidence was assigned using a modified Sackett scale. Eighty-seven RCTs examining mental health interventions and outcome measures post-MSTBI were included. These studies collectively enrolled 6471 participants. A total of 41 RCTs (47.1%) were conducted in the United States and 56 studies (64.4%) were published after 2010. A total of 62 RCTs (71.3%) examined nonpharmacological interventions and 25 RCTs (28.7%) examined pharmacological interventions. Effective pharmacological treatments included desipramine and cerebrolysin; methylphenidate and rivastigmine showed conflicting evidence. Cognitive behavioral therapy (CBT) was found to be effective for hopelessness, stress, and anxiety, compared to usual care; however, it may be as effective as supportive psychotherapy for depression. CBT combined with motivational interviewing may be as effective as CBT combined with nondirective counseling for depression, stress, and anxiety. Acceptance and commitment therapy was effective for anxiety, stress, and depression. Tai Chi, dance, and walking appeared to be effective for depression and stress, while other nonpharmacological treatments such as peer mentoring showed limited effectiveness. This evidence-based review provides a comprehensive overview of the research landscape of RCTs addressing mental health post-MSTBI. The findings from these RCTs may be valuable for health care professionals, researchers, and policymakers involved in the field of mental health and neurorehabilitation.

The efficacy of diazepam administration during embryo transfer: a retrospective multicenter cohort study on reproductive outcomes.

This retrospective multicenter cohort study aimed to investigate the impact of diazepam administration during embryo transfer on reproductive outcomes, focusing primarily on the live birth rate. Secondary outcomes included the positive beta-hCG rate, clinical pregnancy rate, miscarriage rate, ectopic pregnancy rate, and preterm birth rate. Data from 5607 embryo transfers, encompassing 465 cases with diazepam administration, were retrospectively analyzed. The study included single blastocyst transfers from 12 clinics in Portugal and Spain between January 2015 and December 2022. Comparison of reproductive outcomes between patients receiving diazepam and those who did not showed no statistically significant differences. Positive beta-hCG rates (60.8% non-diazepam vs. 60.4% diazepam, p = 0.92, adjusted p = 0.32) and clinical pregnancy rates (45.6% non-diazepam vs. 46.2% diazepam, p = 0.81, adjusted p = 0.11) were comparable. Miscarriage rates (11.0% diazepam vs. 9.3% non-diazepam, p = 0.25, adjusted p = 0.26) and ectopic pregnancy rates (0.9% diazepam vs. 0.1% non-diazepam, p = 0.1, adjusted p = 0.20) were similar. Live birth rates (36.3% non-diazepam vs. 35.3% diazepam, p = 0.69, adjusted p = 0.82) and prematurity rates (0.3% non-diazepam vs. 0% diazepam, p > 0.99, adjusted p = 0.99) also exhibited no statistically significant differences. Based on the results, diazepam administration during embryo transfer did not show a discernible impact on reproductive outcomes, including live birth rates, suggesting its limited effectiveness in enhancing success.

THE EFFECT OF RISK BASED CAPITAL ON THE PROFITABILITY OF INSURANCE COMPANIES REGISTERED WITH THE FINANCIAL SERVICES AUTHORITY

This research aims to determine the development of Risk Based Capital, profitability, and the effect of Solvency Rate Limit (RBC) on profitability in Syariah Unit Insurance registered with the Financial Services Authority. This research is a quantitative research, and the source of data obtained is secondary data. The population is 25 Syariah Unit General Insurance companies registered with Financial Services Authority (OJK). This research sample uses a purposive sampling technique by 9 Syariah Unit General Insurance companies registered with OJK using annual financial statements in accordance with the variables used during the period (2018-2023). The data analysis uses multiple linear regression analysis with a constant of 41.513 which means, if the Risk Based Capital variable is fixed, then the Return On Asset will increase by 41.513 and the regression coefficient value for the Investment variable in the regression equation shows a positive value of 0.023 X, this means that if the Risk Based Capital variable is fixed, then the Return On Asset variable will increase by 0.023. The Coefficient of Determination (R) for Risk Based Capital on Return On Asset is 0.609, then for the Risk Based Capital variable on Return On is 0.515. And the Analysis of the Hypothesis Test is known that Risk Based Capital (X) shows at an alpha coefficient of 5% (t-stat = 3.119 > 1.674) and prob. 0.006 < 0.05. So the hypothesis is accepted, namely Risk Based Capital has a significant effect on Return On Equity in the Alpha 5% Syariah unit insurance company.

Why do preconception and pregnancy lifestyle interventions demonstrate limited success in preventing overweight and obesity in children? A scoping review investigating intervention complexity, process evaluation components, and author interpretations.

Preventing childhood obesity from early life is considered essential. However, evidence from recent systematic reviews has highlighted inconsistent results and limited effectiveness of preconception and pregnancy lifestyle interventions regarding offspring weight outcomes and adiposity. Therefore, to improve our understanding regarding the mixed success of these early life interventions, we conducted a scoping review examining intervention complexity, process evaluation components, and authors' statements. Eligible articles (preconception or pregnancy lifestyle trials with offspring data beyond 1month of age) were identified by searching databases (PubMed, Embase, and CENTRAL), previous reviews, and performing CLUSTER searches. The Intervention Complexity Assessment Tool for Systematic Reviews (iCAT_SR) was used to evaluate intervention complexity. A thematic analysis provided insight into process evaluation components and authors' interpretations. Finally, an expert consultation on the results was conducted. We identified 40 eligible publications corresponding to 27 trials. Only two trials started before conception. Potential reasons for interventions' limited success included the late intervention initiation, short intervention duration, and insufficient sample size. Few studies reported process evaluations and included stakeholder involvement, which are essential according to the expert group. We discuss current limitations and outline suggestions for future interventions in this field of research.

Exit, or Voice? A Quantitative Investigation of Out Migration Intentionality From Venezuela

Executive Summary Why some residents around the world facing chronic and acute stressors seek to exit their home communities while others do not, remains an unanswered question. People living in Venezuela face poverty, inflation, and food shortages and hold strong reasons to seek life elsewhere. Using a new survey of 100 residents in two communities in Venezuela — Santa Rita and Maracaibo — we qualitatively and quantitatively capture the intention to leave a failing state along a variety of potential explanatory characteristics at the individual and environmental levels. Testing the relationship with several sets of factors, including social capital, access to critical infrastructure, and anxiety about the political and economic environment, we find that optimism and access to electricity strongly correlate with intention to depart. Venezuelans who hold positive views of the future and have more regular access to electricity indicate less desire to emigrate, while individual and communal resources like social capital and individual resources like access to US dollars have no measurable impact. These findings bring with them important policy recommendations for NGOs and policymakers alike. Policies that promote optimism and psychological well-being within communities may indirectly contribute to reducing emigration intentions. Moreover, policymakers should be aware of the limits of bonding ties in helping communities experiencing multidimensional shocks. Our findings also point to the limited effectiveness of external resources in fostering a desire to stay and improve local conditions, and instead reinforce the importance of critical conditions at home.

Untargeted Blood Lipidomics Analysis in Critically Ill Pediatric Patients with Ventilator-Associated Pneumonia: A Pilot Study.

This study aims to explore the diagnostic potential of blood lipid profiles in suspected ventilator-associated pneumonia (VAP). Early detection of VAP remains challenging for clinicians due to subjective clinical criteria and the limited effectiveness of current diagnostic tests. Blood samples from 20 patients, with ages between 6 months and 15 years, were collected at days 1, 3, 6, and 12, and an untargeted lipidomics analysis was performed using a Ultra high Pressure Liquid Chromatography hyphenated with High Resolution Mass Spectrometry UPLC-HRMS (TIMS-TOF/MS) platform. Patients were stratified based on modified pediatric clinical pulmonary index score (mCPIS) into high (mCPIS ≥ 6, n = 12) and low (mCPIS < 6, n = 8) VAP suspicion groups. With the untargeted lipid profiling, we were able to identify 144 lipid species from different lipid groups such as glycerophospholipids, glycerolipids, and sphingolipids, in the blood of children with VAP. Multivariate and univariate statistical analyses revealed a distinct distribution of blood lipid profiles between the studied groups, indicating the potential utility of lipid biomarkers in discriminating VAP presence. Additionally, specific lipids were associated with pharyngeal culture results, notably the presence of Klebsiella pneumoniae and Staphylococcus aureus, underscoring the importance of lipid profiling in identifying the microbial etiology of VAP.

Asymmetric effectiveness of price limits: evidence from a quasi-natural experiment

Asymmetric effectiveness of price limits: evidence from a quasi-natural experiment

Corruption and foreign investments: Empirical lessons from treaties and arbitration cases

Abstract As legally binding instruments for the protection of cross-border investments, international investment agreements (IIAs) increasingly include anti-corruption provisions. This article empirically analyzes international investment agreements and the practice of investor–state tribunals related to corruption in foreign investments. It introduces a typology of treaty provisions and discusses their limited practical effectiveness and perverse incentives they create. The article also addresses the broader question of how to deal with corruption-related obligations of investors and states in the context of public international law. It presents and analyzes new empirical data showing that parties to investor–state disputes increasingly allege corruption, and states are responsible for most of such allegations. However, in most cases, tribunals either ignore such allegations or decide that they have not been proven. In the small number of cases where tribunals found allegations proven, they declined jurisdiction or declared the investor’s claim inadmissible. The article makes proposals on how international investment law can become more effective in tackling the supply and demand side of corruption and discusses the relevant obligations of investment tribunals.

Transthyretin amyloid cardiomyopathy: Literature review and red-flag symptom clusters for each cardiology specialty.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is a progressive and infiltrative cardiac disorder that may cause fatal consequences if left untreated. The estimated survival time from diagnosis is approximately 3-6years. Because of the non-specificity of initial symptom manifestation and insufficient awareness among treating physicians, approximately one-third of patients with ATTRwt-CM are initially misdiagnosed with other cardiac diseases. Although heart failure (HF) is the most common initial manifestation of ATTRwt-CM, observed in nearly 70% of affected patients, patients may also present with other cardiologic symptoms, such as atrial fibrillation (AF) and aortic stenosis (AS). This non-specific and diverse nature of the initial ATTRwt-CM presentation indicates that various cardiology subspecialties are involved in patient diagnosis and management. Standard guideline-directed pharmacological treatment for HF is not recommended for patients with ATTRwt-CM because of its limited effectiveness. However, no established algorithms are available regarding HF management in this patient population. This literature review provides an overview of the red flags for ATTRwt-CM and research findings regarding HF management in this patient population. In addition to commonly recognized red flags for ATTRwt-CM (e.g., HF, AF and severe AS), published literature identified potential red flags such as coronary microvascular dysfunction. For HF management in patients with ATTRwt-CM, the use of mineralocorticoid receptor antagonists (MRAs) was reported as a well-tolerated option associated with a low discontinuation rate and reduced mortality. Although there is no concrete evidence for recommendations against sodium-glucose cotransporter 2 inhibitor (SGLT2i) administration, research supporting its use is limited to small-scale studies. Robust evidence is lacking for AF ablation, implantable cardioverter-defibrillators and cardiac resynchronization therapy. Based on the published findings and our clinical experience as Japanese ATTRwt-CM experts, red-flag symptom clusters for each cardiology specialty (HF, arrhythmia and ischaemia/structural heart disease) and a treatment scheme for HF management are presented. As this research area remains at an exploratory stage, our observations would require further discussion among experts worldwide.

Gold Nano Frameworks with Mesopores for Synergistic Immune-Thermal Therapy in Hepatic Carcinoma: A Paradigm Shift in Immune Checkpoint Blockade.

Immune checkpoint blockade (ICB) therapy, while showing promise in various cancers, exhibits limited effectiveness in hepatic carcinoma due to the tumor's immunosuppressive microenvironment (TME) and challenges associated with immune cell infiltration. Efforts to transform the "cold" TME into an "inflamed" state, notably through chemo-immunotherapy, have sparked interest due to their potential to induce immunogenic cell death and augment the infiltration of cytotoxic T lymphocytes (CTLs). Nonetheless, the efficacy of chemo-immunotherapy is often compromised by suboptimal pharmacokinetics, poor tumor accumulation, and off-target toxicity. Herein, in response, we introduce an innovative, milder thermal therapeutic approach leveraging gold nano frameworks with mesopores for the targeted delivery of the immunostimulant imiquimod and NIR-II photothermal therapy. This strategy employs targeted molecule modifications to ensure precise tumor targeting, guided by photoacoustic imaging. Subsequent to mild thermal treatment, there is a release of immunogenic proteins (CRT and HSP90), enhancing tumor immunogenicity. Assisted by imiquimod, substantial CTL infiltration occurs, accompanied by pro-inflammatory factor release (TNF-α, IL-6), transforming M2 macrophages into the M1 phenotype. Ultimately, the proposed strategy combines PD-L1/PD-1 blockade, imiquimod and mild thermal treatment to synergistically enhance tumor immunogenicity, remodel the TME, and restrain hepatic carcinoma, making strides in ICB synergistic immune-thermal therapy.

Intra-articular interventions in osteoarthritis: Navigating the landscape of hyaluronic acid, mesenchymal stem cells, and platelet-rich plasma

Osteoarthritis (OA) poses a substantial burden on patients, leading to pain, functional decline, and reduced quality of life. While conventional treatments focus on symptom management, disease-modifying interventions are yet to be established. This review explores the efficacy of intra-articular interventions, particularly hyaluronic acid (HA), mesenchymal stem cells (MSCs), and platelet-rich plasma (PRP), in the context of OA management. HA injections, with diverse formulations like Hylan G-F20, sodium hyaluronate, and hyaluronan, present varying outcomes, necessitating a nuanced understanding of their effectiveness and timing. MSC therapy, derived from adipose tissue, umbilical cord, or bone marrow, shows promising results in clinical improvement, with adipose-derived MSCs demonstrating efficacy in maintaining benefits over 6 mo. Conversely, bone-marrow-derived MSCs show limited effectiveness, highlighting the need for source-specific considerations. PRP has emerged as a superior option for long-term pain reduction and quality of life improvement, with leukocyte-poor formulations and a critical platelet count of 10 billion demonstrating optimal results. This comprehensive analysis underscores the potential of intra-articular interventions in OA management, emphasizing the need for personalized and evidence-based approaches to enhance treatment efficacy and patient outcomes.

Development and Evaluation of Reconstructed Nanovesicles from Turmeric for Multifaceted Obesity Intervention.

The escalating prevalence of obesity poses significant health challenges due to its direct association with various diseases. Most existing medications, such as appetite suppressants and fat absorption inhibitors, suffer from limited effectiveness and undesirable side effects. Here, inspired by the versatile metabolic effects of turmeric, we developed a naturally derived nanoformulation of "Reconstructed Turmeric-derived Nanovesicles (Rec-tNVs)" for obesity treatment. Employing quantitative nanoflow cytometry, a four-orders-of-magnitude increase in curcumin content (∼108 molecules per particle) was identified in individual Rec-tNVs compared to their ultracentrifugation-isolated counterparts. Rec-tNVs, featuring highly aggregated curcumin arrangements and other coencapsulated bioactive compounds, demonstrated a dose-dependent lipid-lowering effect in mature 3T3-L1 cells by promoting lipolysis, suppressing lipogenesis, inducing adipocyte browning, and triggering apoptosis after internalization via multiple pathways. In vivo experiments revealed that Rec-tNVs alleviated obesity more effectively than free curcumin and achieved weight reductions of 18.68 and 14.56% through intragastric and subcutaneous delivery, respectively, in high-fat-diet mouse models over a four-week treatment period. These effects were attributed to targeted actions on adipose tissues and systemic impacts on metabolism and gut microbiota composition. Overall, this study underscores the multifaceted antiobesity efficacy of Rec-tNVs, and offers a promising paradigm for developing plant-derived nanovesicle-based therapeutics.

Adipose-derived stem cell conditioned medium for hair regeneration therapy in alopecia: a review of literature.

To date, therapeutic choices for alopecia have shown limited effectiveness and safety, making the discovery of new therapeutic choices challenging. Adipose-derived stem cells conditioned-medium (ADSC-CM) contain various growth factors released by ADSCs that may support hair regrowth. This literature review aims to discover the effect and clinical impact of ADSC-CM in the treatment of alopecia. A comprehensive literature search was performed through four databases (Pubmed, ScienceDirect, Cochrane, and Scopus) in September 2021. A combination of search terms including "adipose-derived stem cells" and "alopecia" was used. Studies published in English that included ADSC-CM interventions on alopecia of all types were selected and summarized. A total of five studies were selected for review, all of which were case series. All studies showed a positive outcome for intervention. Outcomes measured in the studies include hair count or hair density, hair thickness, anagen, and telogen hair count. No adverse effects were reported from all studies. Limitations lie in the differences in intervention method, application, and length of treatment. ADSC-CM hair regeneration therapy is an effective and safe treatment for alopecia that may be combined with other types of therapy to improve outcomes.

Cellular and Molecular Genetic Mechanisms of Lung Fibrosis Development and the Role of Vitamin D: A Review.

Idiopathic pulmonary fibrosis remains a relevant problem of the healthcare system with an unfavorable prognosis for patients due to progressive fibrous remodeling of the pulmonary parenchyma. Starting with the damage of the epithelial lining of alveoli, pulmonary fibrosis is implemented through a cascade of complex mechanisms, the crucial of which is the TGF-β/SMAD-mediated pathway, involving various cell populations. Considering that a number of the available drugs (pirfenidone and nintedanib) have only limited effectiveness in slowing the progression of fibrosis, the search and justification of new approaches aimed at regulating the immune response, cellular aging processes, programmed cell death, and transdifferentiation of cell populations remains relevant. This literature review presents the key modern concepts concerning molecular genetics and cellular mechanisms of lung fibrosis development, based mainly on in vitro and in vivo studies in experimental models of bleomycin-induced pulmonary fibrosis, as well as the latest data on metabolic features, potential targets, and effects of vitamin D and its metabolites.

Rebalancing Investment Protection Standards

Abstract Treaty reform has largely focused on refining the various investment protection standards under IIAs to achieve a more appropriate balance between investment protection and preserving the state’s right to regulate. This article takes stock of the treaty language used to recalibrate investment protection standards and evaluates their effectiveness in preserving policy space. The article ultimately concludes that greater precision in the various investment protection standards has been effective in preserving regulatory space in some cases, notably in the case of indirect expropriation. By contrast, reform of the fair and equitable treatment may be of limited effectiveness, whereas the reforms of national treatment clauses and most favoured nation clauses have yet to be tested by arbitral treatment. While in principle the latter reforms appear to directly address the concerns raised by previous arbitral authority, it remains to be seen whether they will prove to be effective.

Jump Squat Vs. Resisted Sprint Training Programs Applied to Elite Youth Soccer Players: Effects on Sprint and Power-Related Performance.

Loturco, I, Pereira, LA, Mercer, VP, Oliveira, LP, Zanetti, V, Lima, L, Bastos, T, Moura, TBMA, and McGuigan, MR. Jump squat vs. resisted sprint training programs applied to elite youth soccer players: effects on sprint and power-related performance. J Strength Cond Res XX(X): 000-000, 2024-This study examined the effectiveness of 2 different and widely used training programs on the sprint and power-related performance of youth soccer players. Two distinct training strategies-vertically oriented jump squats (JSs) or horizontally oriented resisted sprints (RSs)-were executed under the same absolute loading conditions (i.e., 30% of the athletes' body mass [BM]) during a 4-week preseason period. Training schemes, loading intensities (based on %BM), and the number of experimental sessions were designed in conjunction with the soccer club's coaching staff, considering the calendar, available resources, and regular training programs. Twenty-five under-17 soccer players performed a series of speed, power, and jump tests before and after 10 resisted training sessions, consisting solely of loaded JS or RS. Overall, neither group (i.e., JS or RS training groups) exhibited any improvement in linear sprint and change-of-direction (COD) speed. Conversely, vertical jumping ability and peak velocity in the loaded JS increased significantly only in the JS group, which may positively affect players' performance and training prescription during short soccer preseasons. Given the challenges in enhancing sprint speed among soccer players during preseasons (and even over the competitive season), coupled with the limited effectiveness of RS in improving sprinting, COD, and jumping capabilities within congested and short training phases (i.e., ≤4 weeks), the regular use of RS training methods during these phases may be highly questionable. Coaches should carefully consider these critical limitations and potential disadvantages when designing neuromuscular training programs for soccer players during the preparatory phases of the annual training season.

Streptococcus pneumoniae carriage, serotypes, genotypes, and antimicrobial resistance trends among children in Portugal, after introduction of PCV13 in National Immunization Program: A cross-sectional study

Streptococcus pneumoniae carriage studies are crucial to monitor changes induced by use of pneumococcal conjugate vaccines and inform vaccination policies. In this cross-sectional study, we examined changes within the pneumococcal population following introduction of PCV13 in 2015 in the National Immunization Program (NIP), in Portugal. In 2018–2020 (NIP-PCV13), we obtained 1450 nasopharyngeal samples from children ≤6 years attending day-care. We assessed serotypes, antimicrobial resistance, and genotypes (MLST and GPSC) and compared findings with earlier periods: 2009–2010 (pre-PCV13), 2011–2012 (early-PCV13), and 2015–2016 (late-PCV13). Pneumococcal carriage prevalence remained stable at 60.2 %. Carriage of PCV13 serotypes was 10.7 %, markedly reduced compared to pre-PCV13 period (47.6 %). The most prevalent PCV13 serotypes were 19F, 3, and 19A all showing a significant decreasing trend compared to the pre-PCV13 period (from 7.1 % to 4.7 %, 10.1 % to 1.8 %, and 14.1 % to 1.8 %, respectively), a notable observation given the described limited effectiveness of PCV13 against serotype 3. Non-vaccinated children and children aged 4–6 years were more likely to carry PCV13 serotypes (2.5-fold, 95 %CI [1.1–5.6], and 2.9-fold, 95 %CI [1.3–6.8], respectively). The most prevalent non-PCV13 serotypes were 15B/C, 11A, 23B, 23A, and NT, collectively accounting for 51.9 % of all isolates. In total, 30.5 % of all pneumococci were potentially covered by PCV20. Resistance to penicillin (low-level) and macrolides increased significantly, from 9.3 % and 13.4 %, respectively, in the late-PCV13 period, to approximately 20 % each, mostly due to lineages expressing non-PCV13 serotypes, nearing pre-PCV13 levels. An expansion of lineages traditionally associated with PCV13 serotypes, like CC156-GPSC6 (serotype 14) and CC193-GPSC11 (serotype 19F), but now predominantly expressing non-PCV13 serotypes (11A, 15B/C, and 24F for GPSC6; and 15A and 21 for GPSC11) was noted. These findings indicate that the pneumococcal population is adapting to the pressures conferred by PCV13 and antimicrobial use and indicate the need to maintain close surveillance.