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Convinced that he is cursed after the Great Mississippi Flood of 1927, 20-year-old Robert Chatham, who, constantly followed by trouble, has lost his will to live, finally shakes his demons until he is forced to make an impossible choice.

Background Complete healing of diabetic wounds continues to be a clinically unmet need. Although robust therapies such as stem cell therapy and growth factor treatment are clinically applied, these treatments are costly for most diabetic wound patients. Therefore, a cheaper alternative is needed. Cobalt protoporphyrin (CoPP) has recently been demonstrated to promote tissue regeneration. In this study, the therapeutic benefits of CoPP in diabetic wound healing were examined. Methods An in vitro wound healing model that mimics re-epithelialization was established to examine the effect of CoPP on the migratory capability of human keratinocytes (HaCaT) in either normal glucose (NG) or high glucose (HG) media, as well as in the presence of either H 2 O 2 or lipopolysaccharide (LPS). At the end of the migration assays, cells were collected and subjected to Western blotting analysis and immunostaining. Results HaCaT were found to migrate significantly more slowly in the HG media compared to the NG media. CoPP treatment was found to enhance cell migration in HG media, but was found to decrease cell migration and proliferation when HaCaT were cultured in NG media. CoPP treatment induced high levels of expression of Nrf-2/HO-1 and FoxO1 in HaCaT cultured in either glucose concentration, although the FoxO1 expression was found to be significantly higher in HaCaT that underwent the migration assay in NG media compared to those in HG media. The higher level of FoxO1 expression seen in CoPP-treated HaCaT cultured in NG media resulted in upregulation of CCL20 and downregulation of TGFβ1. In contrast, HaCaT migrated in HG media were found to have high levels of expression of TGFβ1, and low levels of expression of CCL20. Interestingly, in the presence of H 2 O 2 , CoPP-pretreated HaCaT cultured in either NG or HG media had similar expression level of Nrf-2/HO-1 and FoxO1 to each other. Moreover, the anti-apoptotic effect of CoPP pretreatment was noticed in HaCaT cultured in either glucose concentration. Additionally, CoPP pretreatment was shown to promote tight junction formation in HaCaT suffering from LPS-induced damage. Conclusions CoPP enhances cell migratory capacity under hyperglycemic conditions, and protects cells from oxidative and LPS-induced cellular damage in HG media containing either H 2 O 2 or LPS.

Using microfluidic flow for biological detection is a non-invasive method that can replace traditional invasive testing methods to achieve fast and accurate results. The design of the detection device and lab-on-a-disk (LoaD) can impact performance in accurately identifying biological features. Therefore, we created a novel device to extract cancer cells from a heterogeneous cell population by centrifugal-force-driven microfluidic flow and magnetic labeling. Two-stage centrifugal force and a specially designed LoaD were used to drive microfluidic flow and control its movement to designated areas. The purpose was to allow the CD44 antibody–magnetic bead complex (CD44 beads), which specifically binds to the abundantly present CD44 receptors on identifiable cancer cells, to flow into the reservoir well, while the biological mixture containing the cancer cells is retained in the capture well. Fluorescence imaging as well as flow cytometric analysis revealed the successful retention of the microbead-bound cancer cells in the magnetic area, while the remaining biological mixture was retained in the reservoir area. The entire separation process took less than 2 h.

Background and Objectives: Laparoscopic right hemicolectomy (LRHC) is commonly performed for patients with colon cancer, selecting between intracorporeal anastomosis (ICA) or extracorporeal anastomosis (ECA). However, the impact of ICA versus ECA on patient outcomes remains debatable. The varying levels of experience among surgeons may influence the outcomes. Therefore, this study sought to compare the short- and long-term outcomes of LRHC using ICA versus ECA. Materials and Methods: This retrospective study extracted patient data from the medical records database of Changhua Christian Hospital, Taiwan, from 2017 to 2020. Patients with colon cancer who underwent LRHC with either ICA or ECA were included. Primary outcomes were post-surgical outcomes and secondary outcomes were recurrence rate, overall survival (OS), and cancer-specific survival (CSS). Between-group differences were compared using chi-square, t-tests, and Fisher’s exact tests and Mann–Whitney U tests. Associations between study variables, OS, and CSS were determined using Cox analyses. Results: Data of 240 patients (61 of ICA and 179 of ECA) with a mean age of 65.0 years and median follow-up of 49.3 months were collected. No recognized difference was found in patient characteristics between these two groups. The ICA group had a significantly shorter operation duration (median (IQR): 120 (110–155) vs. 150 (130–180) min) and less blood loss (median (IQR): 30 (10–30) vs. 30 (30–50) mL) than the ECA group (p < 0.001). No significant differences were found in 30-day readmission (ICA vs. ECA: 1.6% vs. 2.2%, p > 0.999) or recurrence (18.0% vs. 13.4%, p = 0.377) between the two groups. Multivariable analyses revealed no significant differences in OS (adjusted hazard ratio (aHR): 0.65; 95% confidence interval (CI): 0.25–1.44) or CSS (adjusted sub-hazard ratio (aSHR): 0.41, 95% CI: 0.10–1.66) between groups. Conclusions: Both ICA and ECA in LRHC for colon cancer had similar outcomes without statistically significant differences in post-surgical complications, 30-day readmission rates, recurrence rate, and long-term survival outcomes. However, ICA may offer two advantages in terms of a shorter operative duration and reduced blood loss.

Background: Chinese-Australian adolescents face unique academic and cultural challenges that may impact their lifestyle and psychological well-being. Physical activity, screen time, and sleep are known to influence well-being. However, research on the adherence to the 24-Hour Movement Guidelines among Chinese-Australian adolescents remains limited and awaits further investigation. Objective: This study hypothesized a significant positive association between adherence to the 24-Hour Movement Guidelines for physical activity, screen time, and sleep, and the psychological well-being of Chinese-Australian adolescents. Methods: A self-reported questionnaire was distributed to two language schools in Brisbane, Australia, targeting high school students from grades 7 to 12 with Chinese-Australian backgrounds. This study used multiple linear regression modelling to examine the associations between meeting or not meeting recommendations. Meeting the 24-Hour Movement Guidelines was defined as ≥60 min/day of moderate to vigorous physical activity (MVPA), ≤2 h/day of recreational screen time, and 9–11 h/night of sleep. Results: Out of 251 participants (average age: 13.31 years; 58% female), only 20.3% met two or three recommendations, while 43.3% met one, and 36.2% met none. The most common compliance was meeting only the screen time guideline alone (48%), while 9.6% met either MVPA + screen time or screen time + sleep. The regression analysis showed that meeting at least MVPA (β = 1.41, 95% CI: 0.07 to 2.74) or at least sleep (β = 1.40, 95% CI: 0.19 to 2.60) was associated with better psychological well-being. Notably, meeting MVPA and sleep guidelines was significantly associated with higher well-being (β = 3.83, 95% CI: 1.06–6.60). From the results, adherence to additional 24-Hour Movement Guidelines was associated with improved psychosocial well-being. However, a small proportion of adolescents met all the guidelines. Conclusions: Greater adherence to physical activity and sleep guidelines is linked to better psychological well-being among Chinese-Australian adolescents. These results highlight the importance of promoting healthy behaviours and implementing public health strategies to enhance education on exercise and sleep, particularly at the school and family levels, to support adolescents’ psychological well-being.

Diabetic retinopathy is characterized by hyperglycemic retinal pigment epithelial cells that secrete excessive pro-inflammatory cytokines and VEGF, leading to retinal damage and vision loss. Cobalt protoporphyrin (CoPP) is a compound that can reduce inflammatory responses by inducing high levels of HO-1. In the present study, the therapeutic effects of CoPP were examined in ARPE-19 cells under hyperglycemia. ARPE-19 cells were incubated in culture media containing either 5.5 mM (NG) or 25 mM (HG) glucose, with or without the addition of 0.1 µM CoPP. Protein expressions in samples were determined by either Western blotting or immunostaining. A Seahorse metabolic analyzer was used to assess the impact of CoPP treatment on mitochondrial respiration in ARPE-19 cells in NG or HG media. ARPE-19 cells cultured in NG media displayed different cell morphology than those cultured in HG media. CoPP treatment induced high HO-1 expressions and significantly enhanced the viability of ARPE-19 cells under hyperglycemia. Moreover, CoPP significantly downregulated expressions of inflammatory and apoptotic markers and significantly upregulated mitochondrial respiration in APRPE-19 cells under hyperglycemia. CoPP treatment significantly enhanced cell viability in ARPE-19 cells under hyperglycemia. The treatment also downregulated the expressions of pro-inflammatory and upregulated mitochondrial respiration in the hyperglycemic cells.

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Cardiac inflammation is considered by many as the main driving force in prolonging the pathological condition in the heart after myocardial infarction. Immediately after cardiac ischemic injury, neutrophils are the first innate immune cells recruited to the ischemic myocardium within the first 24 h. Once they have infiltrated the injured myocardium, neutrophils would then secret proteases that promote cardiac remodeling and chemokines that enhance the recruitment of monocytes from the spleen, in which the recruitment peaks at 72 h after myocardial infarction. Monocytes would transdifferentiate into macrophages after transmigrating into the infarct area. Both neutrophils and monocytes-derived macrophages are known to release proteases and cytokines that are detrimental to the surviving cardiomyocytes. Paradoxically, these inflammatory cells also play critical roles in repairing the injured myocardium. Depletion of either neutrophils or monocytes do not improve overall cardiac function after myocardial infarction. Instead, the left ventricular function is further impaired and cardiac fibrosis persists. Moreover, the inflammatory microenvironment created by the infiltrated neutrophils and monocytes-derived macrophages is essential for the recruitment of cardiac progenitor cells. Recent studies also suggest that treatment with anti-inflammatory drugs may cause cardiac dysfunction after injury. Indeed, clinical studies have shown that traditional ant-inflammatory strategies are ineffective to improve cardiac function after infarction. Thus, the focus should be on how to harness these inflammatory events to either improve the efficacy of the delivered drugs or to favor the recruitment of cardiac progenitor cells.

We previously showed that injection of peptide nanofibers (NF) combined with autologous bone marrow mononuclear cells (MNC) immediately after coronary artery ligation improves cardiac performance in pigs. To evaluate the clinical feasibility, this study was performed to determine the therapeutic time window for NF/MNC therapy in acute myocardial infarction (MI). A total of 45 adult minipigs were randomly grouped into 7 groups: sham or MI plus treatment with NS (normal saline), or NF or MNC alone at 1 day (1D) post-MI, or NF/MNC at 1, 4, or 7 days post-MI (N≥6). Cardiac function was assessed by echocardiography and ventricular catheterization. Compared with the NS control, pigs treated with NF/MNC at 1 day post-MI (NF/MC-1D) had the greatest improvement in left ventricle ejection fraction (LVEF; 55.1±1.6%; P<0.01 vs. NS) 2 months after MI. In contrast, pigs treated with either NF/MNC-4D or NF/MNC-7D showed 48.9±0.8% (P<0.05 vs. NS) and 43.5±2.3% (n.s. vs. NS) improvements, respectively. The +dP/dt and -dP/dt, infarct size and interstitial collagen content were also improved in the NF/MNC-1D and -4D groups but not in the -7D group. Mechanistically, MNC quality and the states of systemic inflammation and damaged heart tissue influence the therapeutic efficiency of NF/MNC therapy, as revealed by another independent study using 16 pigs. Injection of NF/MNC at 1 or 4 days, but not at 7 days post-MI, improves cardiac performance and prevents ventricular remodeling, confirming the importance of early intervention when using this therapy for acute MI.

Striatal dopaminergic activity is significantly correlated with various cognitive activities, mood regulation, and even metabolic homeostasis, and is modulated by the dopamine transporter (DAT). The availability of DAT could be regulated by presynaptic autoreceptors, which are G-protein coupled receptors; however, whether functional variations in the common downstream signaling molecule, G-protein, could cause individual differences in presynaptic transporter availability remains unclear. To investigate this relationship, the DAT availability in seventy-eight healthy subjects was approximated using single photon emission computed tomography (SPECT) with [99mTc] TRODAT-1, a radio-labeled form of tropan derivative for the selective labeling of DAT. The C825T single nucleotide polymorphism (SNP) (rs5443) of the beta subunit of the G-protein second messenger (GNβ3) gene was genotyped, and analysis of variance showed a significant difference in striatal DAT when referenced to the entire occipital lobe among the three genotypes. Post hoc independent t tests were also performed, and showed that the striatal DAT availability of the CC genotype was higher than that of the other two genotypes. These results indicated that genetic variation in the common downstream signaling molecule of the dopamine autoreceptor could affect the functional status of the striatal dopamine system. These results together with the known role of the GNβ3 gene might provide further evidence to support the common effect of the striatal dopamine system on mood and metabolic regulation. ► G-protein variation causes individual dopamine transporter availabilities differences. ► The GNβ3 rs5443 polymorphism affects striatal dopamine transporter availabilities. ► GNβ3 gene may link common effects of dopamine system on mood and metabolic regulation.