Search Results (1,431)

Background/Objectives: In the last decade, several studies revealed individual response variability to different antiplatelet agents, and patients who have no response to these drugs are considered poor responders. Some studies explored platelet function during antiplatelet treatment to identify those patients with “high on-treatment platelet reactivity” (HPR), which exposes them to increased risk of major adverse cardiovascular events (MACE). Methods: We conducted a study with patients with ST-elevation myocardial infarction (STEMI) treated with dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, including long-term follow-up after 5 years. We used thromboelastography, the total thrombus formation analysis system, and vasodilator-stimulated phosphoprotein phosphorylation assay (VASP) to analyze HPR with different methods; selected laboratory parameters were measured during hospitalization to check significant correlations. Results: We identified STEMI patients treated with DAPT with HPR as a risk group for MACE in a 5-year follow-up. Additionally, we have shown that HPR is associated with atherosclerosis by analyzing lipid profile parameters. Conclusions: High on-treatment platelet reactivity (HPR) increases the risk of major adverse cardiovascular events in the long term, especially with elevated C-reactive protein or an atherogenic lipid profile. Standardizing HPR assessment is crucial for optimizing individualized antiplatelet therapy and improving patient outcomes post-STEMI. Full article

Background/Objectives: Recent data shows increasing diabetes prevalence among African Americans. Youth with a family history of diabetes are at high risk for diabetes. This study explores the multilevel risk factors associated with a family history of diabetes among African American youth in public housing. Methods: This study used a cross-sectional, quantitative, and community-based participatory research (CBPR) approach. The research team, comprising community stakeholders and academic researchers, employed respondent-driven sampling (RDS) for data collection (survey) and used univariate and bivariate analyses to examine variable relationships. A sequential logistic regression highlighted factors influencing the likelihood of having a family history of diabetes. Results: The final sample (n = 190, mean age 18.5 years, 58% female) included 35% of youth with a family history of diabetes. Forty-six percent reported medium to severe household hardships. Results suggest that reporting a family history of diabetes is correlated with maternal substance use (tau-b = 0.27 **) and alcohol problems (tau-b = 0.16 ***), paternal substance use (tau-b = 0.17 *), and eating fewer fruits (tau-b = 0.17 *). With an odds ratio (OR) of 1.70 [0.68, 4.13] and attributable fraction among the exposed at 41.3%, the final model (3) was not significant [χ² = 11.19(8)]. Thus, we fail to reject the null hypothesis that the model fits the data well. Fewer vegetable consumption (OR = 15.08, p < 0.001), higher soda consumption (OR = 0.06, p < 0.001), severe household hardships (OR = 5.82, p < 0.01), and maternal substance use problems (OR = 6.81, p < 0.05) predicted a higher likelihood of a history of diabetes. Conclusions: Our study calls attention to the need to reevaluate interventions for hardships and substance use in diabetes management, particularly in poor neighborhoods and among minority families. Full article

Medium and variable vessel vasculitides are a heterogeneous group of rare, immune-mediated vascular disorders that are associated with significant morbidity and mortality. The standard treatment approach involves glucocorticoids and immunosuppressive agents. However, many patients exhibit poor tolerance or respond inadequately to these medications. Recent advances in biologic therapies and Janus Kinase inhibitors (JAKis) offer promising alternatives. This review consolidates current knowledge on the pathogenesis, immunology, and therapeutic efficacy of biologics and JAKis in the management of medium and variable vessel vasculitis. While further research is needed to establish long-term safety and optimize treatment protocols, biologics and JAKis represent emerging therapeutic strategies with the potential to improve outcomes. Full article

The use of hormonal contraceptives is essential to ensure effective and safe contraception. However, factors such as inadequate prescription, poor adherence, or lack of information can lead to drug-related problems (DRPs) and negative outcomes associated with medication (NOMs). Methods: An observational, descriptive, cross-sectional study was conducted between January and June 2024 in two community pharmacies in Tenerife. It included 316 users of hormonal contraceptives over the age of 18. The main instrument was a structured questionnaire, administered through individual interviews conducted in the Personalized Care Area (PCA). Results: Combined Oral Contraceptives (COCs) were the most frequently used method (72.2%). Adverse reactions were reported by 47.2% of participants, mainly psychiatric disorders (28.1%). Emergency contraception had been used at least once by 43.8% of the respondents. Among COC users, 68.9% reported difficulties with daily adherence, and only 36.7% had adequate knowledge in case of missed doses. Conclusions: Community pharmacists may play a key role in reproductive health by providing personalized counselling, referring patients to other levels of care, and promoting the rational and safe use of hormonal contraceptives. Full article

Background: This study explored the dynamics of sustainability literacy among industry professionals to advance the adoption of sustainability initiatives within the Malawi construction industry. Specifically, it examined the key attitudinal indicators (KAIs), driving factors, and barriers influencing sustainability literacy. Method: A quantitative research approach was employed, utilizing a well-structured questionnaire for data collection with a sample size of seventy-five (75) and built environment professionals as respondents. The collected data were analyzed using two inferential statistical methods: the Mean Item Score (MIS) and Exploratory Factor Analysis (EFA). Results: The EFA results identified two key components of KAIs that affect sustainability literacy: an inertia mindset and psychosocial inertia. Two primary driving factors were revealed: Perceived Benefits and Integrated Digital Capacity-Building Initiatives. This study also highlighted two major categories of barriers: inter- and intra-institutional barriers and Poor Sustainability Governance. Based on the research findings, this study proposes six policy recommendations: (1) development of a Green Paper on sustainable practices, (2) mandatory SLP on sustainable and green building practices, (3) continuous professional development (CPD) incentives for sustainability literacy, (4) economic incentives for sustainability adoption, (5) establishment of sustainability learning hubs, and (6) leveraging Fourth Industrial Revolution (4IR) technologies to enhance practical sustainability training. Conclusions: The study concludes that achieving meaningful progress in sustainability literacy requires transformational leadership to drive change across the industry. Full article

Background/Objectives:: Right ventricular (RV) pressure assessment is crucial in both the diagnosis and follow-up of patients with chronic thromboembolic pulmonary hypertension (CTEPH). While right heart catheterization (RHC) and pulmonary angiography (PA) are gold-standard invasive methods, transthoracic echocardiography (TTE) offers a safer and more accessible alternative. This study aimed to evaluate the reliability of echocardiographic RV pressure estimation compared to invasive techniques and to identify clinical predictors of response to balloon pulmonary angioplasty (BPA). Methods: In this prospective study, 17 patients with confirmed CTEPH underwent RV pressure assessment via TTE, RHC (Swan-Ganz catheterization), and PA within the same hospitalization period. BPA responders were defined based on clinical improvement and were compared to poor responders using pre- and post-treatment parameters. Results: A strong correlation was found between Swan-Ganz and PA-derived pressures (r = 0.96), with a slightly lower correlation between TTE and PA (r = 0.84), and the lowest between TTE and Swan-Ganz (r = 0.78). In the well-responding group, the 6 min walk distance (6MWD) increased by 60 ± 18 m, compared to 12 ± 10 m in poor responders (p < 0.01). NT-proBNP levels decreased by 40% in responders versus 10% in non-responders (p < 0.01). TAPSE improved significantly in responders (from 16.0 ± 2.0 mm to 19.5 ± 2.5 mm, p < 0.01), while RV basal diameter decreased by 15% (p < 0.05). No significant echocardiographic improvement was observed in poor responders. Conclusions: TTE provides a reliable estimate of RV pressure in CTEPH when standardized protocols are followed. NT-proBNP levels and RV size may serve as useful predictors of BPA response. Full article

Tropical regions experience intense and highly variable solar radiation, often resulting in excessive indoor illuminance, uneven daylight distribution, and visual discomfort in high-rise residential buildings. This study investigates the daylighting performance of various external horizontal slat configurations as a shading strategy for east- and south-facing rooms in a typical high-rise apartment under both intermediate sky with sun and overcast sky conditions. Using IESVE simulations, ten shading device (SD) configurations (SD 1–SD 10) were evaluated for their impact on daylight illuminance and distribution uniformity. Results show that high-rise apartment room with a commonly used overhang provided poor daylighting quality, with excessive illuminance and low distribution uniformity. SD 10 and SD 9 achieved the best performance at 09:00 and 12:00, respectively, for east-facing rooms across design days, while SD 10 was optimal for south-facing rooms on both 21 March and 22 December. Under overcast sky conditions, SD 9 demonstrated superior performance. This study proposes a novel adaptive external shading device featuring adjustable horizontal slats that can be reconfigured throughout the day to respond to changing solar positions and sky conditions. This approach overcomes the limitations of fixed shading systems by adapting to dynamic tropical sky conditions, offering a practical solution for enhancing daylight quality in tropical high-rise apartments. The findings provide design guidance for the development of energy-efficient shading, climate-responsive shading systems tailored to tropical environments. Full article

Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders. Methods: This prospective single-center study included 33 adult patients with R/R AML treated with VEN plus either azacitidine (AZA) or decitabine (DEC) from 2018 to 2021. The primary endpoint was the composite complete remission (cCR) rate and the rate of early and late response, respectively, occurring within two cycles of therapy or later; secondary endpoints included overall survival (OS), relapse-free survival (RFS), time to relapse (TTR), and safety. Results: The cCR was 58%, with complete remission (CR) or CR with incomplete recovery (CRi) achieved in 52% of patients. Median OS was 9 months. No significant differences in OS or TTR were observed between early (≤2 cycles) and late (>2 cycles) responders. Eight responders (42%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), with comparable transplant rates in both groups of responders. Toxicity was manageable. Grade 3–4 neutropenia occurred in all patients, and febrile neutropenia occurred in 44% of patients. An Eastern Cooperative Oncology Group (ECOG) score >2 was associated with inferior response and shorter treatment duration. Conclusions: HMA-VEN therapy is effective and safe in R/R AML, including for patients with delayed responses. The absence of a prognostic disadvantage for late responders supports flexible treatment schedules and suggests that the continuation of therapy may be beneficial even without early blast clearance. Tailored approaches based on performance status and comorbidities are warranted, and future studies should incorporate minimal residual disease (MRD)-based monitoring to refine response assessment. Full article

Gut microbiota plays a vital role in host resilience but may be disrupted under environmental antibiotic pressure. The goitered gazelle (Gazella subgutturosa), a keystone ungulate in the Qaidam Basin, is crucial for ecosystem stability. We aimed to investigate how this species responds to antibiotic pressure through gut microbial adaptation. Using 16S rRNA sequencing and weighted gene co-expression network analysis (WGCNA) on fecal and soil samples from six regions, we identified 18 microbial modules, of which three were strongly associated with antibiotics (|r| ≥ 0.75, p < 0.05). Gut microbial α-diversity was lowest in the antibiotic-rich, vegetation-poor TGL region and highest in XRH, where diverse vegetation appeared to buffer antibiotic impact. Antibiotic pressure can reshape gut microbial communities, exerting both adaptive benefits and adverse effects. High-quality habitats may alleviate the negative impacts of antibiotic pressure. Full article

T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin’s lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring. Full article

Autologous therapies are currently being studied to determine if they can modulate the course of knee osteoarthritis symptoms and/or disease progression. One potential therapeutic target is the polarization of pro-inflammatory M1 macrophages to pro-healing M2 macrophages. The autologous therapy, Autologous Protein Solution (APS), was incubated with donor-matched human peripheral-derived macrophages for 10 days. M1 pro-inflammatory macrophages were determined by the percentage of CD80+ and M2 pro-healing macrophages were determined by CD68+ and CD163+ by epifluorescent microscopy. To determine clinical effectiveness, an APS-specific minimal clinically important improvement (MCII) using an anchor-based method was calculated in a randomized controlled trial of APS (n = 46) and then applied to a real-world registry study (n = 78) to determine the percentage of pain responders. Compared to control media, APS statistically increased the percentage of M2 macrophages and decreased the percentage of M1 macrophages, while platelet-poor plasma had no effect on polarization. In the randomized controlled trial (RCT), the MCII at the 12-month follow-up visit was calculated as 2.0 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and 7.5 points on the WOMAC function scale. Applying this MCII to the real-world registry data, 62.5% of patients met the MCII with an average of 4.7 ± 2.5 points of improvement in pain. Autologous therapies can influence macrophage polarization and have demonstrated clinical effectiveness in a real-world patient setting. Full article

Background: Eating disorders (EDs) and self-harm (SH) are both associated with distress, poor psychosocial functioning, and increased risk of mortality. Much of the literature discusses the complex interplay between SH and ED behaviours where co-occurrence is common. The onset of both is typically seen during teenage years into early adulthood. A better understanding of the functions of these behaviours is needed to guide effective prevention and treatment, particularly during the crucial developmental years. An earlier review has explored the functions of self-harm, but an equivalent review for eating disorder behaviours does not appear to have been completed. Objectives: This evidence synthesis had two objectives. First, to identify and synthesise published first-hand accounts of the reasons why people engage in eating disorder behaviours with the view to develop a broad theoretical framework of functions. Second, to draw comparisons between the functions of eating disorder behaviours and self-harm. Methods: A qualitative evidence synthesis reporting first-hand accounts of the reasons for engaging in eating disorder behaviours. A ‘best fit’ framework synthesis, using the a priori framework from the review of self-harm functions, was undertaken with thematic analysis to categorise responses. Results: Following a systematic search and rigorous screening process, 144 studies were included in the final review. The most commonly reported functions of eating disorder behaviours were distress management (affect regulation) and interpersonal influence. This review identified significant overlap in functions between self-harm and eating disorder behaviours. Gender identity, responding to food insecurity, to delay growing up and responding to weight, shape, and body ideals were identified as functions more salient to eating disorder behaviours. Similarly, some self-harm functions were not identified in the eating disorder literature. These were experimenting, averting suicide, personal language, and exploring/maintaining boundaries. Conclusions: This evidence synthesis identified a prominent overlap between psychological functions of eating disorder behaviours and self-harm, specifically in relation to distress management (affect regulation). Despite clear overlap in certain areas, some functions were found to be distinct to each behaviour. The implications for delivering and adapting targeted interventions are discussed. Full article

Background/Objectives: Pancreatic cancer (PC) is the seventh leading cause of cancer-related deaths worldwide, with its incidence rising each year. Despite its relatively low incidence, the aggressiveness of pancreatic cancer results in high mortality, with only 12% of patients surviving five years post-diagnosis. Surgical resection remains the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage. The goal of this work is to identify vulnerabilities that can affect the efficacy of treatments and improve the efficacy of therapy. Methods: MAP17 overexpression in pancreatic cancer cell lines, RT-qPCR analysis, xenografts, in vitro and in vivo treatments, analysis of data from pancreatic tumors in transcriptomic patient databases. Results: We studied the prognostic and predictive value of MAP17 (PDZK1IP1) expression in pancreatic cancer, and we found that high MAP17 mRNA expression was associated with poor prognosis. In addition, single-cell analysis revealed that high MAP17 expression was present only in tumor cells. We investigated whether the response to various antitumor agents depended on MAP17 expression. In 2D culture, MAP17-expressing pancreatic cancer cells responded better to gemcitabine and 5-fluorouracil. However, in vivo xenograft tumors with MAP17 expression showed resistance to all treatments. Additionally, MAP17-expressing cells had a high NAD pool, which seems to be effectively depleted in vivo by NAMPT inhibitors, the primary enzyme for NAD biosynthesis. Conclusions: Our findings suggest that MAP17 expression could enhance the prognostic stratification of pancreatic cancer patients. Moreover, the coadministration of NAMPT inhibitors with current treatments may sensitize tumors with high MAP17 expression to chemotherapy and improve the efficacy of chemotherapy. Full article

Background: Angiosarcomas (ASs) represent a heterogeneous and highly aggressive subset of tumors that respond poorly to systemic treatments and are associated with short progression-free survival (PFS) and overall survival (OS). The aim of this study was to develop and validate an immune-related prognostic model—termed the AS score—using data from two independent sarcoma cohorts. Methods: A prognostic model was developed using a previously characterized cohort of 25 angiosarcoma samples. Candidate genes were identified via the Maxstat algorithm (Maxstat v0.7-25 for R), combined with log-rank testing. The AS score was then computed by weighing normalized gene expression levels according to Cox regression coefficients. For external validation, transcriptomic data from TCGA Sarcoma cohort (n = 253) were analyzed. The Immunoscore—which reflects the tumor immune microenvironment—was inferred using the ESTIMATE package (v1.0.13) in R. All statistical analyses were performed in RStudio (v 4.0.3). Results: Four genes—IGF1R, MAP2K1, SERPINE1, and TCF12—were ultimately selected to construct the prognostic model. The resulting AS score enabled the classification of angiosarcoma cases into two prognostically distinct groups (p = 0.00012). Cases with high AS score values, which included both cutaneous and non-cutaneous forms, exhibited significantly poorer outcomes, whereas cases with low AS scores were predominantly cutaneous. A significant association was observed between the AS score and the Immunoscore (p = 0.025), with higher Immunoscore values found in high-AS score tumors. Validation using TCGA sarcoma cohort confirmed the prognostic value of both the AS score (p = 0.0066) and the Immunoscore (p = 0.0029), with a strong correlation between their continuous values (p = 2.9 × 10⁻⁸). Further survival analysis, integrating categorized scores into four groups, demonstrated robust prognostic significance (p = 0.00021). Notably, in tumors with a low Immunoscore, AS score stratification was not prognostic. In contrast, among cases with a high Immunoscore, the AS score effectively distinguished outcomes (p < 0.0001), identifying a subgroup with poor prognosis but potential sensitivity to immunotherapy. Conclusions: This combined classification using the AS score and Immunoscore has prognostic relevance in sarcoma, suggesting that angiosarcomas with an immunologically active microenvironment (high Immunoscore) and poor prognosis (high AS score) may be prime candidates for immunotherapy and this approach warrants prospective validation. Full article

Background/Objectives: Sarcopenia is defined by the progressive loss of muscle mass, strength, and/or physical performance associated with aging. Radiofrequency ablation (RFA) of the medial branch nerves is a well-established and effective treatment for lumbar facetogenic pain. While sarcopenia is associated with poor outcomes following epidural steroid injections and lumbar spine surgeries, its impact on clinical outcomes in patients undergoing RFA for facetogenic pain remains unexplored. This study aims to evaluate the influence of sarcopenia on treatment outcomes in this patient cohort. Methods: Patients were classified into sarcopenia (n = 35) and non-sarcopenia groups (n = 67) based on predefined psoas muscle index (PMI) thresholds. The primary outcomes included changes in back pain intensity and the proportion of responders at 1, 3, and 6 months following RFA. The secondary outcome was to identify demographic, clinical, and sarcopenia-related factors predictive of treatment response at each follow-up interval. Results: Both groups demonstrated statistically significant improvements in pain scores compared to baseline at all follow-up points. However, the median pain scores at 3 months post-RFA remained significantly higher in the sarcopenia group. Despite this, the proportion of responders did not differ significantly between the two groups at any time point. At 3 months, the absence of prior spinal surgery was identified as a significant predictor of treatment response. At 6 months, favorable outcomes were significantly associated with the absence of diabetes, no history of spinal surgery, and a higher PMI. Conclusions: Sarcopenia may influence the extent of pain improvement following medial branch nerve RFA. Additionally, patient-specific factors, such as diabetes, prior spinal surgery, and PMI, should be considered when predicting treatment outcomes. Full article