Search Results (1,453)

Blood transfusion is a routine yet resource-intensive medical procedure. Increasing global demand, limited donor availability, and logistical and ethical constraints have driven the search for adequate blood substitutes. Hemoglobin-based oxygen carriers (HBOCs) represent a promising class of therapeutics designed to mimic the oxygen transport function of red blood cells while overcoming the challenges of storage, compatibility, and infection risk. Despite decades of research, no HBOC has yet met all criteria for widespread clinical use. This review summarizes recent advances in the design and development of hemoglobin derivatives, with a focus on their biochemical properties, safety profiles, and oxygen delivery capabilities. We also discuss current limitations and translational barriers. The successful implementation of HBOCs could significantly improve transfusion strategies, especially in emergency medicine, military applications, and resource-limited settings. Continued innovation is essential to bring safe and effective oxygen therapeutics into routine clinical practice. Full article

(1) Background: Invasive micropapillary carcinoma (IMPC) is a rare, aggressive breast cancer subtype marked by high lymph node metastasis rates. While Oncotype DX recurrence score (RS) offers prognostic information for patients with hormone-receptor-positive (HR+) breast cancer, its utility in IMPC—a histology with distinct biologic behavior—remains unvalidated. This study evaluates whether Oncotype DX offers prognostic information with respect to overall survival (OS) in non-metastatic, early-stage patients with IMPC of the breast. (2) Methods: The National Cancer Database (2004–2020) was queried to select for women with ER+/HER2−, T1-T2N0-N1 IMPC who underwent Oncotype DX testing and received no neoadjuvant therapy. Patients were stratified by RS: low (≤11), intermediate (12–25), and high (>25). Kaplan–Meier survival curves and log-rank tests compared 5-year OS between groups. Multivariable Cox proportional hazards models assessed RS as an independent predictor, adjusting for age, race, comorbidities, grade, radiation, and insurance status. (3) Results: A total of 1325 women met the selection criteria. The cohort demonstrated significant survival disparities by RS (log-rank p = 0.017). Five-year OS rates were 97.5%, 97.5%, and 93.7% for low, intermediate, and high-risk patients, respectively. Adjusted multivariate analysis confirmed RS as an independent prognosticator: low (HR = 0.31, 95% CI: 0.15–0.75) and intermediate (HR = 0.32, 95% CI: 0.15–0.75) scores correlated with reduced mortality versus high RS. Omission of radiation therapy (HR = 2.68, 95% CI: 1.05–6.86) and higher comorbidity burden (0 comorbidities vs. ≥2: HR = 0.25, 95% CI: 0.10–0.61) were significantly associated with worse survival. (4) Conclusions: Oncotype DX is predictive for OS in IMPC, with high RS (>25) portending poorer outcomes. The survival detriment associated with RT omission aligns with prior studies demonstrating RT benefit in higher-risk cohorts. These findings validate RS as a prognostic tool in IMPC and underscore its potential to refine adjuvant therapy, particularly RT utilization. Future studies should explore RS-driven treatment personalization in IMPC, including comorbidity management and adjuvant radiation to improve outcomes in this distinct patient population. Full article

Background/Objectives: National Football League (NFL) American football players are exposed to osteoarthritis risk factors of obesity and high joint loads. We sought to examine the association between total body mass (TBM), lean body mass (LBM), body fat percentage (BF%), and normalized compressive knee joint reaction forces (JRFcomp), peak knee adductor moments (KAM), and vertical ground reaction forces (vGRF) in NFL draft-eligible players during a high-speed run. Methods: A total of 125 participants ran a single trial at 5.5–6.5 m/s for 5 s on an instrumented treadmill. Bilateral vGRF and knee joint kinetics were calculated using inverse dynamics. Body composition was assessed using bioelectrical impedance. Results: LBM demonstrated significant moderate associations with vGRF (left, r(123) = −0.56, p < 0.001; right, r(123) = −0.60, p < 0.001) and low-to-negligible associations with KAM (left, r(123) = −0.20, p = 0.026; right, r(123) = −0.30, p < 0.001) and JRFcomp (left, r(123) = −0.39, p = 0.020; right, r(123) = −0.38, p = 0.015), respectively. TBM showed significant moderate negative associations with vGRF (left, r(123) = −0.56, p < 0.001; right, r(123) = −0.61, p < 0.001) and low-to-negligible associations with KAM (left, r(123) = −0.21, p = 0.021; right, r(123) = −0.28, p = 0.002) and JRFcomp (left, r(123) = −0.39, p < 0.001; right, r(123) = −0.37, p < 0.001), respectively. BF% showed significant low-to-negligible negative associations with JRFcomp (left, r(123) = −0.21, p < 0.001; right, r(123) = −0.22, p < 0.001) and vGRF (left, r(123) = −0.39, p < 0.001; right, r(123) = −0.41, p < 0.001), respectively, and no significant associations with KAM, p > 0.05. The heavier group exhibited significantly lower normalized JRFcomp, and vGRF, p < 0.05. Conclusions: Heavier, but not fatter, players attenuate knee loads. Dampening may be a short-term protective strategy for joints of heavier players. Full article

Despite the health concerns regarding alcohol and its link to cancer, moderate consumption of red wine has been associated with healthy aging and longevity, defined as up to one drink per day for women and two drinks per day for men (approximately 142 mL or 5 oz per drink). Previous research has revealed the health benefits of red wine, particularly in relation to cardiovascular disease. However, the influence of genetic factors on these benefits remains to be elucidated. In this study, we explored genes linked to red wine and created a curated gene set that intersects with those related to centenarians, which are markers of exceptional longevity. By analyzing literature from over 190 databases, we identified and validated a curated list of 43 genes associated with red wine and centenarians. We conducted gene set enrichment analysis as well as enrichment analysis of diseases and their tissue distributions. The results suggest that these genes play a crucial role in stress response and apoptosis, which are essential for cell survival and renewal. Additionally, these genes were enriched in pathways associated with smooth muscle cell proliferation, neuroinflammation, nucleotide excision repair, and lipoprotein metabolism (false discovery rate, FDR < 3 × 10⁻⁷). Gene set enrichment analysis indicated significant tissue distribution in the gastrointestinal, cardiovascular, and respiratory systems. Furthermore, the disease–gene enrichment analysis pointed to associations with diseases related to tissues and organs, including cardiovascular disease (heart disease and stroke), type 2 diabetes, gastrointestinal diseases and metabolic diseases, immune diseases, and cancer (FDR < 9.37 × 10⁻⁶); notably, cardiovascular diseases, diabetes, and cancer are leading causes of death, suggesting that these genes may be protective against those diseases. Our review of the literature indicates that individuals who do not currently drink alcohol should not be encouraged to start. However, we propose that moderate consumption of red wine, especially for middle-aged to older adults after 40 years old, can provide significant health benefits due to its components and the positive effects of hormesis. Although further research is necessary to uncover additional genes, this study provides the first genetic overview of the health benefits of red wine, emphasizing its potential in supporting healthy aging and longevity. Full article

A systematic review of toxoplasmosis cases in patients receiving targeted immunotherapy with biologics or small molecules was performed. This systematic review searched for case reports, case series and observational studies in PubMed; last search was on 19 July 2025. The review identified 46 toxoplasmosis cases among patients receiving biologics (including CAR T-Cell Therapies) or small molecules for diverse autoimmune, oncologic and transplant conditions. These cases were reported from 18 countries, including the United States and several European countries. Most patients developed severe disease. Fifty percent (23/46) presented with cerebral toxoplasmosis, 33% (15/46) with ocular toxoplasmosis, 7% (3/46) with lymphadenopathy, 4% (2/46) with disseminated disease, 2% (1/46) with both cerebral and ocular disease, 2% (1/46) with pneumonic toxoplasmosis, and 2% (1/46) with severe fetal congenital toxoplasmosis. Among those were also four cases with fatal outcomes due to toxoplasmosis and eight cases with permanent ocular or neurological deficits. In addition, there was a case of fetal congenital toxoplasmosis that occurred despite maternal discontinuation of adalimumab five months before conception, resulting in elective pregnancy termination due to severe fetal cerebral disease. Overall, 44% (20/46) of cases were due to reactivation of chronic latent Toxoplasma infections and 39% (18/46) due to acute primary infections; 17% did not report this information. One case of disseminated acute toxoplasmosis was also identified after eating wild boar sausages, and two cases of severe acute ocular toxoplasmosis after eating undercooked venison meat, and undercooked unspecified type of meat respectively, while on small molecules or biologics. Details on the clinical presentations, management and clinical outcomes of these cases were reported. Recommendations for the management of toxoplasmosis in patients with targeted immunotherapies were also provided. Health care providers should consider toxoplasmosis in patients on biologics or small molecules who present with compatible clinical syndromes. Prompt diagnosis and treatment can be lifesaving. Full article

Elevated cholesterol levels play important mitogenic roles. Pseurotin A (PsA) is a fermentation product that has recently been reported as a dual inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion and protein-protein interaction (PPI) with the LDLR. PsA showed a high acute safety profile and therapeutic potential against metastatic castration-resistant prostate cancer (mCRPC). The study aims to uncover the chronic safety, distribution, and anti-mCRPC genomic and molecular mechanistic insights of PsA. A 90-day chronic safety assessment of PsA up to 80 mg/kg in Swiss albino mice showed no signs of hematological, biochemical, or major organ toxicity. PsA demonstrated rapid intravenous distribution and elimination in Swiss albino mice. PsA is biodistributed to multiple key organs but was not detected in the brain, indicating its inability to cross the blood-brain barrier. PsA effectively suppressed the recurrence of nude mice xenografted mCRPC, which was subjected to a neoadjuvant docetaxel and enzalutamide regimen, followed by surgical excision. Collected PsA and vehicle control-treated recurrent tumors were subjected to RNA-sequencing and pathway enrichment analysis (PEA) of differentially expressed genes (DEGs). PsA-treated tumors revealed multiple significantly enriched pathways associated with promoting tumor apoptosis and inhibiting both invasion and migration. The PPI network analyses for the downregulated DEGs displayed prominent networks of genes associated with the ubiquitin-proteasome system. Results provide comprehensive mechanistic and preclinical validations for PsA’s potential as a novel PC recurrence suppressive lead entity. Full article

Background: The Pharm2Home Initiative’s Community Health Arm adopts a health-equitable approach to chronic disease education and medication therapy management (MTM). We serve senior residents of Solano County, California, who live in affordable housing and have limited financial resources. Aim: This evaluation assesses the uptake of chronic disease management recommendations provided by clinical pharmacists during MTM sessions at community events. Methods: The program engaged clinical pharmacists to provide tailored education and healthcare interventions in senior housing facilities. The goal was to empower seniors to manage their health effectively. The sessions covered various topics, including expired or duplicated medications, incorrect medication use, consultations on medication management, immunizations, and lifestyle adjustments. Results: Over an 18-month period, from January 2022 to August 2023, the program involved 65 participants across ten community health events. These events provided approximately 65 h of direct intervention. Many participants reported significant improvements in understanding their treatment plans and navigating their health needs more confidently. Feedback from 60 seniors after the sessions indicated that 88% felt much better informed about their medications, and 75% expressed that their concerns were addressed extremely well. Conclusions: These outcomes demonstrate the importance of clinical pharmacist-led interventions in improving seniors’ medication use and chronic disease management. The initiative’s approach advocates for integrating clinical pharmacists into community health settings, suggesting a scalable model for enhancing person-centered care. However, further studies are necessary to assess the long-term impacts of these interventions and explore their effectiveness across diverse age groups and more complex conditions. Full article

Introduction: Evidence on orthodontic interventions for temporomandibular disorders (TMD) is fragmented and inconclusive, creating a gap in guidance for clinical decision-making. This study addresses that gap by evaluating current knowledge on these interventions. Methods: A PRISMA-ScR scoping review was conducted with a systematic search of PubMed, Scopus, and Web of Science (2018–2023). Eligible studies were peer-reviewed, English-language, human studies examining TMD treatment and/or etiology. Three independent reviewers screened records and extracted data and a fourth reviewer performed random audits. Results: Of 899 records, 10 studies met inclusion criteria (non-surgical, n = 7: 4 case reports, 2 prospective, 1 longitudinal; combined orthodontic–surgical, n = 3: 1 case report, 2 longitudinal; participant ages 15–71 years). Diagnostics included imaging, clinical examination, occlusal analysis, and questionnaires, although few used RDC/TMD or DC/TMD criteria. Non-surgical orthodontic modalities (fixed appliances, camouflage, TADs, stabilization splints) showed mixed results, with several studies reporting short-term symptom improvement, while others found no effect on TMD onset or progression. Combined orthodontic–surgical approaches (e.g., bilateral sagittal split osteotomy, Le Fort I) also showed variable outcomes. Conclusions: Low-to-moderate quality evidence suggests that orthodontic-surgical interventions may alleviate TMD symptoms in select patients; however, heterogeneity and limited use of standardized diagnostics constrain the certainty of these findings. Future research should prioritize DC/TMD-based diagnostics, core outcomes, comparative designs, and ≥12–24 months of follow-up to identify prognostic factors and responsive subgroups. Full article

Curcumin is a diarylheptanoid polyphenol compound derived from the plant species Curcuma longa. For thousands of years, it has been used as a dietary supplement, food coloring agent, and natural antibiotic in many Asian countries. Recent studies have also investigated its potential therapeutic role in a variety of inflammatory diseases, including osteoarthritis, asthma, chronic obstructive pulmonary disease, atherosclerosis, irritable bowel syndrome, sepsis, atopic dermatitis, and psoriasis. Although individual studies have reported beneficial effects, a comprehensive discussion on findings across these conditions has been lacking. This review systematically evaluates the therapeutic potential of curcumin in inflammatory diseases. Literature was sourced through a PubMed search using relevant terms such as curcumin, treatment, and the names of each targeted disease over the past two decades. We discussed the key findings on how curcumin administration was associated with improvements in disease markers, symptom relief, or progression delay. Despite promising research outcomes, the current evidence underscores the need for more robust, large-scale studies to confirm these effects and guide the clinical applications of curcumin in managing inflammatory disorders. Full article

Families in rural communities face a constellation of challenges that significantly hinder their ability to support adolescents. Our study aimed to explore family functioning as a protective factor for adolescent mental health from the perspective of parents in rural communities of southern Ecuador, using Photovoice as a participatory research tool. The research design corresponds to Participatory Action Research. Five Focus Group Discussions (FGDs) were conducted. A total of 29 parents of adolescents participated in the study. The research team employed qualitative content analysis for the interpretation phase. Through photographs and focus groups, parents commented on aspects of family life that they perceived as necessary for supporting adolescents, such as effective communication, cohesion, supervision, and expressions of care. The main conclusion indicated that the implementation of Photovoice converted participants from subjects to collaborators, allowing them to critically reflect on their behaviors while aiding or reinforcing in the co-creation of strategies. Full article

Background/Objectives: Microglia are the primary immune cells in the central nervous system (CNS) and are known as “resident” macrophages. The aim of this study was to determine the effect of acute ethanol (EtOH) on the microglia state and monocyte infiltration into the CNS, with particular attention to the role of peripheral and central dopamine (DA) D2 receptors (D2Rs) in mediating EtOH effects on peripheral and central substrates. We hypothesize that EtOH interacts with peripheral immune mediators via D2Rs including monocyte-derived macrophages (MDMs) to modulate midbrain neurons, DA transmission in the mesolimbic pathway from the ventral tegmental area (VTA) to nucleus accumbens (NAc), and the intoxicating effects of acute EtOH. Methods: Using the Macrophage FAS-Induced Apoptosis (MaFIA) mouse model (GFP+ on Csf1r promoter), we assessed the effects of three intraperitoneal (IP) doses of EtOH (1, 2, and 4 g/kg) at three time points (0.5, 1, and 2 h after injection) on D2R expression in blood leukocytes and microglia, as well as midbrain neuronal activity, DA release, and behavior. Results: Acute EtOH significantly enhanced lymphocyte and monocyte D2R expression at 1.0 g/kg by 2 h after injection in vivo but decreased D2R expression in vitro. Ethanol enhanced microglia D2R expression in the NAc, while not altering D2R expression in the VTA, but altered the microglia state in these areas, shifting them toward an inflammatory phenotype. Acute EtOH induced prolonged and progressive hypersensitivity of D2R activation of VTA GABA neurons. Intravenous injection of the macrophage depleter liposomal clodronate significantly reduced blood macrophages by 55.3% and blocked the typical inhibition of VTA GABA neurons by EtOH, as well as the enhancement of DA levels in the NAc, and the locomotor indices of intoxication produced by acute EtOH, but not choice place preference. Conclusions: These findings strongly suggest a neuroimmune peripheral connection for acute low-dose EtOH use and challenge the dogma that central actions of EtOH exclusively mediate its effect on DA neuronal activity and release. Full article

Organ transplantation has significantly progressed since the 1950s, with notable advancements in surgical procedures and immunosuppression. However, current organ preservation techniques, mainly static cold storage, have not evolved at the same pace and remain insufficient to prevent ischemic and oxidative damage. This damage, primarily caused by the cessation of aerobic metabolism, limits organ viability and transplant outcomes. In this study, we investigated whether supplementing a storage solution with a hemoglobin-based oxygen carrier (HBOC) could improve the condition of ex vivo rabbit kidneys by maintaining oxygenation and supporting aerobic metabolism. In a paired, randomized design, contralateral rabbit kidneys were preserved either in a Krebs-Ringer-based solution enriched with the polymerized hemoglobin OxyVita^®C (15 g/L, p50 4–6 mmHg, MW ≈ 17 MDa, pH adjusted to 7.4) or in an HBOC-free control solution. Physicochemical characterization of OxyVita^®C included oxygen equilibrium curves, zeta potential, polydispersity index, and dynamic light scattering. Biochemical markers (AST, ALT, LDH, K⁺, pH) and histopathological assessments were used to evaluate tissue integrity over 24 h. Histology was additionally stratified according to rinsing protocols (unwashed, NaCl single flush, triple flush), and tubular necrosis was scored by blinded pathologists. Group comparisons were analyzed using ANOVA with Tukey’s HSD test. The HBOC-enriched solution showed improved tissue preservation, higher cell survivability, and better histomorphological profiles, with significantly reduced tubular necrosis scores compared to controls. These findings suggest that active oxygen delivery via HBOCs offers a promising strategy to mitigate ischemic damage during ex vivo kidney storage. Limitations include the lack of transplantation outcomes and direct ROS quantification, which will be addressed in future work integrating hypothermic and normothermic machine perfusion. Full article

Background: The COVID-19 pandemic disrupted routine healthcare delivery, raising concerns about chronic disease management, particularly for individuals with type 2 diabetes mellitus (T2DM). This study evaluated the pandemic’s impact on glycemic control and telehealth utilization in an underserved outpatient population. Methods: A retrospective cohort analysis used de-identified electronic health record and claims data from a family medicine clinic in central Texas. The study included 387 adults with T2DM who had at least one A1c measurement in both the pre-pandemic period (1 March 2019–13 March 2020) and COVID-19 era (14 March 2020–31 March 2021). Outcomes included A1c control (<8.0%), prescription trends, and telehealth use. A case series examined individual-level patterns. Results: A significantly higher percentage of patients achieved A1c control during the COVID-19 era (75.2%) compared to the pre-pandemic period (68.7%, p < 0.05), despite a decline in prescriptions for diabetes medications and supplies. Telehealth visits increased substantially. Patients who maintained or improved glycemic control often had uninterrupted access to medications and telehealth. Conclusion: This study is novel in its focus on a safety-net outpatient clinic serving a predominantly low-income, diverse population in central Texas, an underserved group often underrepresented in diabetes research. By combining a retrospective cohort analysis with a descriptive case series, the study offers both population-level trends and individual-level insights into how medication access and telehealth engagement influenced glycemic control during the pandemic. These findings highlight the potential of telehealth to support diabetes management during healthcare disruptions and underscore the importance of maintaining medication access in vulnerable populations. Full article

Tuberculosis (TB) is a global health challenge caused by Mycobacterium tuberculosis, with drug resistance, treatment toxicity, and treatment adherence challenges continuing to impede control efforts. The objective of this review is to explore current advancements in TB treatment, for both drug-sensitive and drug-resistant TB, focusing on pharmacologic regimens, diagnostics, and adjunctive therapies. For drug-sensitive TB, a 4-month rifapentine–moxifloxacin regimen has been proven to be non-inferior to the traditional 6-month standard, while optimized pyrazinamide dosing or faropenem substitution may improve culture conversion and reduce adverse events. In drug-resistant TB, regimens such as the bedaquiline, pretomanid, linezolid, and moxifloxacin have demonstrated efficacy with substantially shorter treatment duration; however, incidents of hepatotoxicity and linezolid-related neuropathy require careful monitoring. Adjunctive therapies, such as metformin, N-Acetylcysteine, aspirin, and statins, show promising effects in modulating host immunity and reducing long-term lung damage. Advances in diagnostics, including whole genome sequencing and CRISPR-based methods, are enabling rapid detection of resistance mutations and directed therapy. Vaccine development has advanced beyond the BCG vaccine to explore vaccines with enhanced immunogenicity or ones that are safe for immunocompromised patients. Implementation strategies such as video directly observed therapy are improving adherence; additionally, community-based, technology-supported interventions significantly improve TB knowledge and compliance. An integrated approach that combines optimized pharmacologic regimens, host-directed therapies, advanced diagnostics, and patient-centered public health strategies is essential to reduce TB incidence, long-term morbidity, and mortality. Full article

N⁶-methyladenosine (m⁶A) is the most prevalent internal modification in eukaryotic messenger RNA (mRNA) and plays a vital role in post-transcriptional gene regulation. In recent years, m⁶A has emerged as a pivotal epitranscriptomic signal involved in neural development, synaptic remodeling, and the molecular pathophysiology of neuropsychiatric disorders. In this review, we summarize the mechanisms underlying the deposition, removal, and recognition of m⁶A by dedicated methyltransferases, demethylases, and RNA-binding proteins. We further explore how these dynamic modifications influence neuronal differentiation and memory formation. Recent studies have linked aberrant m⁶A regulation to psychiatric conditions such as depression, anxiety, schizophrenia, and bipolar disorder. Additionally, we discuss how pharmacological or genetic modulation of m⁶A pathways may promote adaptive neural plasticity and enhance cognitive and emotional resilience. Despite these promising findings, significant challenges remain in achieving spatial and temporal specificity while minimizing off-target effects in the brain. Therefore, we advocate for more in-depth investigations into m⁶A function within developmentally defined neural circuits to better understand its enduring role in maintaining neural homeostasis. Full article