Nerve growth factor promote VCAM-1-dependent monocyte adhesion and M2 polarization in osteosarcoma microenvironment: Implications for larotrectinib therapy.

Osteosarcoma is the most prevalent form of primary malignant bone tumor, primarily affecting children and adolescents. The nerve growth factors (NGF) referred to as neurotrophins have been associated with cancer-induced bone pain; however, the role of NGF in osteosarcoma has yet to be elucidated. In osteosarcoma samples from the Genomic Data Commons data portal, we detected higher levels of NGF and M2 macrophage markers, but not M1 macrophage markers. In cellular experiments, NGF-stimulated osteosarcoma conditional medium was shown to facilitate macrophage polarization from the M0 to the M2 phenotype. NGF also enhanced VCAM-1-dependent monocyte adhesion within the osteosarcoma microenvironment by down-regulating miR-513c-5p levels through the FAK and c-Src cascades. In in vivo xenograft models, the overexpression of NGF was shown to enhance tumor growth, while the oral administration of the TrK inhibitor larotrectinib markedly antagonized NGF-promoted M2 macrophage expression and tumor progression. These results suggest that larotrectinib could potentially be used as a therapeutic agent aimed at mitigating NGF-mediated osteosarcoma progression.

Early prediction of platelet recovery with immature platelet fraction in patients receiving hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is pivotal in treating hematologic disorders, yet it poses the risk of post-transplantation pancytopenia. Prophylactic platelet transfusions are often administered to mitigate this risk. Utilizing practical markers, such as immature platelet fraction (IPF), to predict hematopoietic recovery in advance could reduce unnecessary prophylactic transfusions. Our prospective study, involving 53 HSCT patients at Taipei Veterans General Hospital between September 2022 and May 2023, utilized the Sysmex XN analyzer to assess peripheral blood cell parameters. We investigated whether IPF could predict platelet recovery early, determined the optimal cut-off value, and compared platelet usage. Neutrophil and platelet engraftment occurred 10 (median; range: 10-12) and 15 (median; range: 15-18) days post-HSCT. Notably, 71.7% of patients exhibited an IPF increase exceeding 2% before platelet recovery. The optimal cut-off IPF on day 10 for predicting platelet recovery within five days was 2.15% (specificity 0.89, sensitivity 0.65). On average, patients received 3.89 units of post-transplantation platelet transfusion. Our results indicate that IPF serves as a predictive marker for platelet engraftment, peaking before the increase in platelet count. This insight aids clinicians in assessing the need for prophylactic platelet transfusions. Integrating reference IPF values alongside platelet counts enhances the accuracy of evaluating a patient's hematopoietic recovery status. Anticipating the timing of platelet recovery optimizes blood product usage and mitigates transfusion reaction risks.

Mir221- and Mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3/PUMA pathway.

Epidemiology has shown a strong relationship between fine particulate matter (PM) exposure and cardiovascular disease. However, it remains unknown whether PM aggravates myocardial ischemia-reperfusion (I/R) injury, and the related mechanisms are unclear. Our previous study has shown that adipose stem cell-derived exosomes (ADSC-Exos) contain high levels of Mir221 and Mir222. The present study investigated the effects of PM exposure on I/R-induced cardiac injury through mitophagy and apoptosis, as well as the potential role of Mir221 and Mir222 in ADSC-Exos. Wild-type, mir221- and mir222-knockout (KO), and Mir221- and Mir222-overexpressing transgenic (TG) mice were intratracheally injected with PM (10 mg/kg). After 24 h, mice underwent left coronary artery ligation for 30 min, followed by 3 h of reperfusion (I/R). H9c2 cardiomyocytes were cultured under 1% O2 for 6 h, then reoxygenated for 12 h (hypoxia-reoxygenation [H/R]). PM aggravated I/R (or H/R) cardiac injury by increasing ROS levels and causing mitochondrial dysfunction, which increased the expression of mitochondrial fission-related proteins (DNM1L/Drp1 and MFF) and mitophagy-related proteins (BNIP3 and MAP1LC3B/LC3B) in vivo and in vitro. Treatment with ADSC-Exos or Mir221- and Mir222-mimics significantly reduced PM+I/R-induced cardiac injury. Importantly, ADSC-Exos contain Mir221 and Mir222, which directly targets BNIP3, MAP1LC3B/LC3B, and BBC3/PUMA, decreasing their expression and ultimately reducing cardiomyocyte mitophagy and apoptosis. The present data showed that ADSC-Exos treatment regulated mitophagy and apoptosis through the Mir221 and Mir222-BNIP3-MAP1LC3B-BBC3/PUMA pathway and significantly reduced the cardiac damage caused by PM+I/R. The present study revealed the novel therapeutic potential of ADSC-Exos in alleviating PM-induced exacerbation of myocardial I/R injury.Abbreviation: ADSC-Exos: adipose-derived stem cell exosomes; AL: autolysosome; ATP: adenosine triphosphate; BBC3/PUMA: BCL2 binding component 3; BNIP3: BCL2/adenovirus E1B interacting protein 3; CASP3: caspase 3; CASP9: caspase 9; CDKN1B/p27: cyclin dependent kinase inhibitor 1B; CVD: cardiovascular disease; DCFH-DA: 2',7'-dichlorodihydrofluorescein diacetate; DHE: dihydroethidium; DNM1L/Drp1: dynamin 1-like; EF: ejection fraction; FS: fractional shortening; H/R: hypoxia-reoxygenation; I/R: ischemia-reperfusion; LDH: lactate dehydrogenase; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MFF: mitochondrial fission factor; miRNA: microRNA; NAC: N-acetylcysteine; OCR: oxygen consumption rate; PIK3C3/Vps34: phosphatidylinositol 3-kinase catalytic subunit type 3; PM: particulate matter; PRKAA1/AMPK: protein kinase AMP-activated catalytic subunit alpha 1; ROS: reactive oxygen species; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TRP53/p53: transformation related protein 53; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling.

Efficacy of first-line combination therapies versus gemcitabine monotherapy for advanced pancreatic cancer: a systematic review and network meta-analysis.

Various first-line gemcitabine-based or fluorouracil-based combination regimens were approved in patients with advanced pancreatic cancer. Recent randomized clinical trials (RCTs) have investigated chemotherapy backbones in combination with novel investigational drugs, including chemotherapy agents or targeted drugs. However, the comparative efficacy of these different combination therapies remains limited. This systematic review and network meta-analysis aimed to assess the efficacy of first-line combination therapies for advanced pancreatic cancer. The study included 46 RCTs with 10,499 patients and 47 distinct regimens, using data sources from MEDLINE, EMBASE, Cochrane Clinical Trials, and ClinicalTrials.gov from January 1, 2010 to April 23, 2024. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included overall response rate (ORR) and disease control rate (DCR). The analysis revealed that gemcitabine+nab-paclitaxel (GA), GA with platinum and fluorouracil (GA+Plat+FU), gemcitabine with fluorouracil (G+FU), G+Plt+FU, and FOLFIRINOX were associated with superior OS and PFS compared to gemcitabine monotherapy. Triplet or quadruplet polychemotherapy combinations, such as GA+Plat+FU, G+Plt+FU, and FOLFIRINOX, demonstrated better OS benefit with hazard ratios of 0.42 (95% CI, 0.26-0.68), 0.41 (95% CI, 0.24-0.71), and 0.58 (95% CI, 0.48-0.71), respectively, compared to doublet regimens like GA and G+FU, which had hazard ratios of 0.70 (95% CI, 0.59-0.82) and 0.82 (95% CI, 0.72-0.95), respectively. Notably, no targeted drugs, monoclonal antibodies, or other medications showed improved survival when added to chemotherapy backbones. These findings support the use of gemcitabine-based or fluorouracil-based triplet or quadruplet regimens for better survival outcomes in patients with advanced pancreatic cancer. Further research is warranted to explore the potential benefits of adding chemotherapy agents, such as fluorouracil, to the GA doublet regimen.

Risk and impact of cytomegalovirus infection in lymphoma patients treated with bendamustine.

Bendamustine is used to treat lymphoma with excellent efficacy but is known for its immunosuppressive effect. Cytomegalovirus (CMV) reactivation after bendamustine use has been reported. We aim to address the impact of CMV infection in lymphoma patients treated with bendamustine-containing regimens. We retrospectively analyzed lymphoma patients at Taipei Veterans General Hospital in Taiwan between September 1, 2010, and April 30, 2022. Clinically significant CMV infection (CS-CMVi) was defined as the first CMV reactivation after bendamustine use necessitating CMV therapy. Patients' baseline characteristics and laboratory data were recorded. The primary endpoint of the study was CS-CMVi. A time-dependent covariate Cox regression model was used to estimate the risk factors of CS-CMVi and mortality. A total of 211 lymphoma patients treated with bendamustine were enrolled. Twenty-seven (12.8%) had CS-CMVi. The cumulative incidence was 10.1 per 100 person-years during the three-year follow-up period. In the multivariate analysis, lines of therapy before bendamustine ≥ 1 (95% CI 1.10-24.76), serum albumin < 3.5 g/dL (95% CI 2.63-52.93), and liver disease (95% CI 1.51-28.61) were risk factors for CS-CMVi. In conclusion, CS-CMVi (95% confidence interval [CI] 1.23-10.73) was one of the major independent risk factors of mortality. Lines of therapy before bendamustine ≥ 1, hypoalbuminemia, and liver disease were risk factors for CS-CMVi in lymphoma patients treated with bendamustine.

[The Efficacy of Joyful Learning on Exercise in Older Adults: The GAME Strategy].

Exercise can effectively slow aging and prevent the onset and reduce the complications of chronic diseases in the elderly. However, roughly one-third of older adults are inactive. Joyful learning is an effective method for promoting physical activity, while using games is a feasible strategy for achieving joyful learning that enables individuals to fully immerse themselves in and enjoy an activity. Therefore, exploring gaming strategies to enhance physical activity among the elderly is worthwhile. In this paper, a set of gaming strategies based on the literature and practical experience is proposed. The name of this strategy, GAME, is an acronym of the following: goal setting and educational content development (G), activity design and game content creation (A), mechanics and dynamics implementation (M), and evaluation of qualitative and quantitative health outcomes (E). This systematic descriptive approach helps clearly demonstrate how gamification strategies can promote physical activity and health in older adults. The aim of this paper is to provide a reference and guide for education, research, and clinical practice in health promotion programs targeting older adults.

Parylene Double-Layer Coated Screen-Printed Carbon Electrode for Label-Free and Reagentless Capacitive Aptasensing of Gliadin.

Celiac patients are required to strictly adhere to a gluten-free diet because even trace amounts of gluten can damage their small intestine and leading to serious complications. Despite increased awareness, gluten can still be present in products due to cross-contamination or hidden ingredients, making regular monitoring essential. With the goal of guaranteeing food safety for consuming labeled gluten-free products, a capacitive aptasensor was constructed to target gliadin, the main allergic gluten protein for celiac disease. The success of capacitive aptasensing was primarily realized by coating a Parylene double-layer (1000 nm Parylene C at the bottom with 400 nm Parylene AM on top) on the electrode surface to ensure both high insulation quality and abundant reactive amino functionalities. Under the optimal concentration of aptamer (5 µM) used for immobilization, a strong linear relationship exists between the amount of gliadin (0.01-1.0 mg/mL) and the corresponding ΔC response (total capacitance decrease during a 20 min monitoring period after sample introduction), with an R2 of 0.9843. The detection limit is 0.007 mg/mL (S/N > 5), equivalent to 0.014 mg/mL (14 ppm) of gluten content. Spike recovery tests identified this system is free from interferences in corn and cassava flour matrices. The analytical results of 24 commercial wheat flour samples correlated well with a gliadin ELISA assay (R2 = 0.9754). The proposed label-free and reagentless capacitive aptasensor offers advantages of simplicity, cost-effectiveness, ease of production, and speediness, making it a promising tool for verifying products labeled as gluten-free (gluten content <20 ppm).

The Clinical Impact of Different Types of Preoperative Biliary Intervention on Postoperative Biliary Tract Infection of Patients Undergoing Pancreaticoduodenectomy.

Background: For patients with obstructive jaundice and who are indicated for pancreaticoduodenectomy (PD) or biliary intervention, either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography and drainage (PTCD) may be indicated preoperatively. However, the possibility of procedure-related postoperative biliary tract infection (BTI) should be a concern. We tried to evaluate the impact of ERCP and PTCD on postoperative BTI. Methods: Patients diagnosed from June 2013 to March 2022 with periampullary lesions and with PD indicated were enrolled in this cohort. Patients without intraoperative bile culture and non-neoplastic lesions were excluded. Clinical information, including demographic and laboratory data, pathologic diagnosis, results of microbiologic tests, and relevant infectious outcomes, was extracted from medical records for analysis. Results: One-hundred-and-sixty-four patients from the cohort (164/689) underwent preoperative biliary intervention, either ERCP (n = 125) or PTCD (n = 39). The positive yield of intraoperative biliary culture was significantly higher in patients who underwent ERCP than in PTCD (90.4% vs. 41.0%, p < 0.001). Although there was no significance, a trend of higher postoperative BTI (13.8% vs. 2.7%) and BTI-related septic shock (5 vs. 0, 4.0% vs. 0%) in the ERCP group was noticed. While the risk factors for postoperative BTI have not been confirmed, a trend suggesting a higher incidence of BTI associated with ERCP procedures was observed, with a borderline p-value (p = 0.05, regarding ERCP biopsy). Conclusions: ERCP in patients undergoing PD increases the positive yield of intraoperative biliary culture. PTCD may be the favorable option if preoperative biliary intervention is indicated.

Impact of Vitamin D Receptor Genotypes on Taiwan Hallux Valgus.

BACKGROUND/AIM: Hallux valgus (HV) is the most prevalent deformity affecting the forefoot; however, its genetic etiology remains unclear. In the literature, vitamin D receptor (VDR) genotypes have been reported to be associated with the risk of skeletal malformations accompanied by inflammation. This study aimed to examine the hypothesis that VDR genotypes are associated with the risk of HV. MATERIALS AND METHODS: The VDR rs731236, rs1544410, rs2228570 and rs7975232 genotypes of 150 HV patients and 600 non-HV subjects were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology and examined regarding their associations with HV risk. RESULTS: The results showed that none of the genetic frequency distributions of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significant between the HV cases and non-HV controls (p for trend=0.4055, 0.2170, 0.7220, 0.5509, respectively). Additionally, allelic frequency analysis showed that none of the allelic frequencies of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significantly distributed (p=0.2285, 0.1572, 0.9278, and 0.5547, respectively). Furthermore, stratified analysis showed that no correlation was observed between VDR rs731236 and different age groups (either younger or older than 51) or sex (p=0.3953 and p=0.9576). Moreover, no correlation was found between VDR rs731236 genotype and the risk of HV in individuals within subgroups of height, weight, or body mass index (BMI) (p=0.8317, 0.5346, and p=0.8783, respectively). CONCLUSION: VDR rs731236, rs1544410, rs2228570, and rs7975232 may not serve as indicators for a higher risk of HV.

NAMPT enhances LOX expression and promotes metastasis in human chondrosarcoma cells by inhibiting miR-26b-5p synthesis.

Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX-dependent cell migration and invasion in chondrosarcoma by suppressing miR-26b-5p generation through the c-Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT-facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma.

Clinical Applications of Comprehensive Genomic Profiling in Advanced Non-Small-Cell Lung Cancer-A Case Series.

BACKGROUND: Advanced non-small-cell lung cancer (NSCLC) can be treated with novel targeted therapies that are tailored to the genetic characteristics of malignancy. While tissue-based genomic testing is considered the gold standard for the detection of oncogenic driver mutations, several challenges like inadequate tissue availability, the invasiveness of procuring tumors, and prolonged turnaround time of analysis are encountered. Considering these limitations, guidelines have recognized liquid biopsies using circulating cell-free DNA (cfDNA) as a useful tool to complement conventional tissue testing. Even though cfDNA next-generation sequencing (NGS) can have high sensitivity and specificity, optimal patient benefit requires the interpretation of the molecular profiling results in the context of clinical and diagnostic features to achieve the best outcomes. CASE DESCRIPTIONS: In this case series, we present six patients with advanced NSCLC whose plasma or tissue biopsy samples were analyzed with commercially available comprehensive NGS assays that elucidate the role of testing at various time points in the treatment journey. In all six cases, comprehensive genomic profiling (CGP) provided clinically useful information to guide treatment decisions. CONCLUSION: Adding to the existing real-world evidence, this case series reinforces that CGP-driven treatment strategies in advanced NSCLC, coupled with other available clinical information, can optimize treatment decisions.

Redefining aberrant P53 expression of gastric cancer and its distinct clinical significance among molecular-histologic subtypes.

BACKGROUND: Numerous studies have demonstrated a correlation between p53 overexpression and diminished survival in gastric cancer patients. However, conflicting findings exist, and we hypothesize that these discrepancies arise from the cancer's complexity and heterogeneity, coupled with a lack of consensus on aberrant p53 expression. METHODS: We enrolled a cohort of 187 patients with surgically resected gastric cancer. Patient categorization was based on Epstein-Barr virus (EBV), microsatellite instability (MSI), and Lauren classification (intestinal, diffuse and mixed). Utilizing an incremental algorithm, we evaluated p53 immunohistochemical (IHC) patterns in all 187 cases, while next-generation sequencing was successfully performed on 152 cases to identify TP53 mutations (mutTP53). RESULTS: MutTP53 was identified in 32 % of the 152 cases, comprising 36 missense, 5 nonsense, and 7 frameshift alterations. Missense mutations predominantly correlated with p53 overexpression, while nonsense and frameshifting alterations related to null expression. Trial calculations indicated that null expression and a p53 IHC cutoff at >40 % offered the best prediction of mutTP53 (kappa coefficient, 0.427), with the highest agreement (0.524) observed in diffuse type and the lowest (0.269) in intestinal type. Null expression and a p53 IHC cutoff at >10 %, but not mutTP53 per se, provided the optimal prediction of survival outcome (p = 0.043), particularly in diffuse type (p = 0.044). Multivariate analysis showed that aberrant p53 IHC expression was not an independent prognostic factor. CONCLUSIONS: P53 IHC patterns are predictive biomarkers for mutTP53 and gastric cancer outcomes, where a prerequisite involves a nuanced approach considering cutoff values and molecular-histologic subtyping.

Visfatin Facilitates VEGF-D-Induced Lymphangiogenesis through Activating HIF-1α and Suppressing miR-2277-3p in Human Chondrosarcoma.

Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Lymphangiogenesis plays an essential role in cancer metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with VEGF-D generation and lymphangiogenesis in chondrosarcoma remains undetermined. Our results from clinical samples reveal that VEGF-D levels are markedly higher in chondrosarcoma patients than in normal individuals. Visfatin stimulation promotes VEGF-D-dependent lymphatic endothelial cell lymphangiogenesis. We also found that visfatin induces VEGF-D production by activating HIF-1α and reducing miR-2277-3p generation through the Raf/MEK/ERK signaling cascade. Importantly, visfatin controls chondrosarcoma-related lymphangiogenesis in vivo. Therefore, visfatin is a promising target in the treatment of chondrosarcoma lymphangiogenesis.

Arthroscopic modified Broström may improve function while anatomic reconstructions could enhance stability for chronic lateral ankle instability: A network meta-analysis.

PURPOSE: The purpose of this systematic review and network meta-analysis was to compare the efficacy of different surgical treatments, including open and arthroscopic modified Broström procedures (MB), anatomical reconstructions, and suture tape augmentations (STA), for chronic lateral ankle instability (CLAI). METHODS: We conducted a systematic search for comparative studies that included adult patients with CLAI who underwent open MB, arthroscopic MB, reconstruction with autografts or allografts, and STA. We used a random-effects model to present the NMA results, with mean differences and 95 % confidence intervals (CI) for continuous measures and relative ratios with 95 % CI for dichotomous variables. Surface under the cumulative ranking curve analysis (SUCRA) was used for treatment ranking. RESULTS: The results, based on surface under the cumulative ranking curve analysis, showed that arthroscopic MB likely improves functional outcomes the most as measured by change in American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores. Anatomical graft reconstructions with allografts or autografts demonstrated greater reduction in anterior talar translation (ATT) and talar tilt angle (TTA). Arthroscopic MB and STA were associated with fewer complications. CONCLUSIONS: Arthroscopic MB may be associated with better functional outcomes, while anatomical reconstructions appear to provide greater improvements in stability for CLAI. Additionally, arthroscopic techniques seem to have lower complication risks compared to open procedures. These potential differences in outcomes and risks between techniques could help guide surgical decision-making.

Effect of Surgeon Volume on Mechanical Complications after Resection Arthroplasty with Articulating Spacer.

Two-stage revision with an antibiotic-loaded cement articulating spacer is a standard treatment for chronic prosthetic knee infection (PKI); however, mechanical complications can occur during the spacer period. There is limited evidence on the association between surgeon volume and mechanical complications after resection arthroplasty (RA) using an articulating spacer. This study aimed to compare the rates of mechanical complications and reoperation after RA with articulating spacers by surgeons with high volumes (HV) and low volumes (LV) of RA performed and analyzed the risk factors for mechanical failure. The retrospective study investigated 203 patients treated with PKIs who underwent RA with articulating spacers and were divided according to the number of RAs performed by the surgeons: HV (≥14 RAs/year) or LV (<14 RAs/year). Rates of mechanical complications and reoperations were compared. Risk factors for mechanical complications were analyzed. Of the 203 patients, 105 and 98 were treated by two HV and six LV surgeons, respectively. The mechanical complication rate was lower in HV surgeons (3.8%) than in LV surgeons (36.7%) (p < 0.001). The reoperation rate for mechanical complications was lower in HV surgeons (0.9%) than in LV surgeons (24.5%) (p < 0.001). Additionally, 47.2% of patients required hinge knees after mechanical spacer failure. Medial proximal tibial angle < 87°, recurvatum angle > 5°, and the use of a tibial spacer without a cement stem extension were risk factors for mechanical complications. Based on these findings, we made the following three conclusions: (1) HV surgeons had a lower rate of mechanical complications and reoperation than LV surgeons; (2) mechanical complications increased the level of constraint in final revision knee arthroplasty; and (3) all surgeons should avoid tibial spacer varus malalignment and recurvatum deformity and always use a cement stem extension with a tibial spacer.

Structural equation modeling of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in people with type 2 diabetes.

BACKGROUND: To achieve suitable diabetes care, understanding the factors that affect self-care behaviors is necessary. OBJECTIVE: To construct a model of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in people with diabetes. DESIGN AND METHODS: This cross-sectional study analyzed a convenience sample of 311 people with type 2 diabetes in Taiwan. Data were collected through questionnaires, including the Diabetes Symptoms Checklist, Emotional Distress Scale, Empowerment Process Scale, Interpersonal Communication Scale and Self-Care Behavior scale. RESULTS: Structural equation modeling indicated that a model of dispositional mindfulness, internal environmental factors, external environmental factors, and self-care behaviors in the patients with diabetes best fit the data. Dispositional mindfulness (ß = 0.39), internal environmental factors (ß = 0.52), and external environmental factors (ß = 0.71) directly influenced self-care behaviors in the patients with diabetes. Dispositional mindfulness significantly indirectly affected self-care behaviors via internal and external environmental factors. CONCLUSIONS: To improve self-care behaviors, interventions should consider mindfulness training, and also include internal environmental factors and external environmental factors in the mindfulness training.

Medicinal Chemistry Gone Wild.

Earth is currently experiencing a mass extinction event. The flora and fauna of our planet are experiencing mass die-offs from a multitude of factors, with wildlife disease emerging as one parameter where medicinal chemists are equipped to intervene. While contemporary medicinal chemistry focuses on human health, many traditional pharmaceutical companies have historic roots in human health, animal health, and plant health. This trifecta of health sciences perfectly maps to the current field of One Health, which recognizes that optimal health outcomes can only be achieved through the health of humans, plants, animals, and their shared environments. This Perspective imagines a world where state-of-the-art medicinal chemistry tactics are used to prevent the extinction of endangered species and points to preliminary work in the emerging area of conservation medicine.

MCP-1 controls IL-17-promoted monocyte migration and M1 polarization in osteoarthritis.

Osteoarthritis (OA) is a low-grade inflammatory joint illness in which monocytes migrate and infiltrate synovial tissue, differentiating into the pro-inflammatory M1 macrophage phenotype. IL-17 is a proinflammatory mediator principally generated by Th17 cells, which is elevated in OA patients; nevertheless, investigators have yet to elucidate the function of IL-17 in M1 polarization during OA development. Our analysis of clinical tissues and results from the open online dataset discovered that the level of M1 macrophage markers is elevated in human OA tissue samples than in normal tissue. High-throughput screening demonstrated that MCP-1 is a potential candidate factor after IL-17 treatment in OA synovial fibroblasts (OASFs). Immunohistochemistry data revealed that the level of MCP-1 is higher in humans and mice with OA than in normal tissues. IL-17 stimulation facilitates MCP-1-dependent macrophage polarization to the M1 phenotype. It also appears that IL-17 enhances MCP-1 synthesis in human OASFs, enhancing monocyte migration via the JAK and STAT3 signaling cascades. Our findings indicate the IL-17/MCP-1 axis as a novel strategy for the remedy of OA.

Unusual Coincidence: Concurrent Cast Nephropathy and Lymphoma Infiltration in an Influenza A-Associated Acute Kidney Injury.

Acute kidney injury (AKI) poses a substantial challenge in the management of lymphoma patients and is frequently associated with diverse causative factors. Herein, we report an illustrative case involving a 47-year-old male with influenza A infection who developed severe AKI, which was incongruent with his medical history. Laboratory investigations disclosed aberrant immunoglobulin levels and urinary protein excretion, prompting further evaluation. A renal biopsy revealed the presence of infiltrating lymphoid cells and cast nephropathy, raising suspicion of an underlying hematological disorder. A comprehensive diagnostic workup, including positron emission tomography imaging and bone marrow biopsy, culminated in the definitive diagnosis of splenic marginal zone lymphoma. This case highlights the crucial significance of including lymphoma-associated kidney disorders in the evaluation of unexplained AKI, particularly when encountering unconventional clinical and laboratory results. Swift and precise intervention is of utmost importance in attaining positive results in these rare and complex clinical situations. This study underscores the persistent concern of AKI in lymphoma patients, with lymphocytic infiltration and cast nephropathy as notable elements contributing to the intricate nature of this condition.