Emotional abuse mediated by negative automatic thoughts impacts functional connectivity during adolescence.

Background: Emotional abuse during childhood and adolescence is thought to be associated with the brain; however, the neural mechanism underlying the cognitive process remains unknown. Therefore, we aimed to investigate the mediating effect of negative automatic thoughts on the relationship between emotional abuse and resting-state functional connectivity (rsFC) during adolescence. Method: Our community sample included 54 adolescents aged 13-17 years in the statistical analysis. Resting-state functional and structural magnetic resonance imaging (MRI) was performed, while emotional abuse and negative automatic thoughts were assessed using self-reported scales. A mediation analysis was used to assess the contributions of early traumatic events and negative automatic thoughts to resting functional connectivity. Result: Higher negative automatic thoughts were associated with lower connectivity in the context of greater emotional abuse (i.e., suppression effect). Thus, the relationships between emotional abuse and connectivity in the precuneus (pCun)-medial prefrontal cortex, parahippocampal cortex-extrastriate cortex, and temporal cortex-temporal pole were decreased by negative automatic thoughts. In contrast, functional connections in the pCun-pCun, pCun-precuneus/posterior cingulate cortex, and nucleus accumbens-somatomotor areas were strongly mediated when emotionally abused adolescents reported a high tendency for negative automatic thoughts. Conclusion: Negative automatic thoughts strengthened the relationship between emotional abuse and rsFC. These findings highlight the underlying cognitive processing of the traumatic event-neural system, supporting the use of cognitive therapy for post-traumatic symptoms.

Evaluating pain management from peripheral nerve block for geriatric patients following bipolar hemiarthroplasty for displaced femoral-neck fracture.

INTRODUCTION: The purpose of this study was to evaluate peripheral nerve block (PNB) effectiveness on postoperative pain management and surgical outcomes for displaced femoral-neck fracture in geriatric patients (>70 years) who underwent bipolar hemiarthroplasty (BHA). METHODS: From January 2017 to December 2021, 231 geriatric patients with displaced femoral-neck fracture who consecutively underwent BHA were retrospectively reviewed. Patients were divided into two groups: patient-controlled analgesia (PCA) group (n=132) who received only intravenous (IV) PCA for postoperative pain management, and all others who received PNB with IV PCA (PNB+PCA) such as femoral nerve block or fascia iliaca compartment block after surgery (n=99). Primary outcomes were postoperative visual analog scale (VAS) at rest and during activity at 6, 24, and 48 hours postoperatively. Secondary outcomes were postoperative complications, changes in hemoglobin (Hb), length of hospital stay, and total morphine usage after surgery. RESULTS: Postoperative resting VAS at 6 hours and 48 hours was significantly lower in the PNB+PCA group compared with the PCA group (p=0.075, p=0.0318, respectively). However, there was no significant difference in either resting VAS at 24 hours or active VAS. Complications of pneumonia and delirium until one month postoperative were significantly lower in the PNB + PCA group than the PCA group (p=0.0022, p=0.0055, respectively). CONCLUSION: PNB with IV PCA seems to have a beneficial effect on geriatric femoral-neck patients who underwent BHA with postoperative analgesia for reducing postoperative resting pain and complications, especially pneumonia and delirium.

Comparison of the pharmacokinetic characteristics and bioequivalence between two nanosuspension formulations of megestrol acetate in healthy Korean male subjects.

Megestrol is commonly used to address appetite loss, cachexia, and significant weight loss in cancer or acquired immune deficiency syndrome patients. This study aimed to assess the pharmacokinetics and determine the bioequivalence of two orally administered megestrol acetate suspensions (625 mg/5 mL) in healthy Korean male subjects. A randomized, open-label, single-dose crossover study was conducted involving fifty-four healthy male subjects who were randomized into two sequence groups. Each subject received either a test or reference drug formulation of 625 mg/5 mL megestrol acetate with a two-week washout period between treatments. Plasma samples were collected before and up to 120 hours after administration, and their plasma drug concentrations were analyzed using validated liquid chromatography-mass spectrometry/mass spectrometry. The pharmacokinetic parameters were calculated, and bioequivalence was confirmed if the 90% confidence intervals of the geometric mean ratios were within the specified bounds of 80.00% to 125.00%. In total, fifty-two subjects completed the study, contributing to the pharmacokinetic analysis. The 90% confidence intervals for the geometric mean ratios of the test formulation compared to the reference formulation were 93.85% to 108.90% for maximum plasma concentration and 91.60% to 101.78% for area under the concentration-time curve from the point of administration to last time point of blood sampling. Throughout the study, no serious or unexpected adverse events were observed. The pharmacokinetic profiles of both formulations of megestrol acetate (625 mg) were comparable and well tolerated in healthy Korean male adult subjects. The test formulation met regulatory criteria for bioequivalence. Trial Registration: ClinicalTrials.gov Identifier: NCT06147908.

Low-Power Phototransistor with Enhanced Visible-Light Photoresponse and Electrical Performances Using an IGZO/IZO Heterostructure.

In this study, we demonstrated the effective separation of charge carriers within the IGZO/IZO heterostructure by incorporating IZO. We have chosen IGZO for its high mobility and excellent on-off switching behavior in the front channel of our oxide-oxide heterostructure. Similarly, for an additional oxide layer, we have selected IZO due to its outstanding electrical properties. The optimized optoelectronic characteristics of the IGZO/IZO phototransistors were identified by adjusting the ratio of In:Zn in the IZO layer. As a result, the most remarkable traits were observed at the ratio of In:Zn = 8:2. Compared to the IGZO single-layer phototransistor, the IGZO/IZO(8:2) phototransistor showed improved photoresponse characteristics, with photosensitivity and photoresponsivity values of 1.00 × 107 and 89.1 AW-1, respectively, under visible light wavelength illumination. Moreover, the electrical characteristics of the IGZO/IZO(8:2) transistor, such as field effect mobility (µsat) and current on/off ratio (Ion/Ioff), were highly enhanced compared to the IGZO transistor. The µsat and Ion/Ioff were increased by about 2.1 times and 2.3 times, respectively, compared to the IGZO transistor. This work provides an approach for fabricating visible-light phototransistors with elevated optoelectronic properties and low power consumption based on an oxide-oxide heterostructure. The phototransistor with improved performance can be applied to applications such as color-selective visible-light image sensors and biometric sensors interacting with human-machine interfaces.

Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia.

Background: The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. Purpose: This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. Methods: This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. Results: A total 150 children (66 females) aged 7.7 years (6.4-9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%-75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P<0.05). The median z scores of FEV1, FEV1/ FVC, and FEF25%-75% among asymptomatic patients were also significantly lower in the severe versus non/mild BPD group (-0.82 vs. 0.09, -1.68 vs. -0.87, -1.59 vs. -0.61, respectively; all P<0.05). The severe BPD group had a higher median (range) CT score than the non/mild BPD group (6 [0-12] vs. 1 [0-10], P<0.001). Prenatal oligohydramnios was strongly associated with both low pulmonary function (FEV1/FVC

Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics.

BACKGROUND: To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). METHODS: This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. RESULTS: Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. CONCLUSIONS: Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn's disease.

BACKGROUND: Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn's disease (CD). Anti-tumor necrotic factor (TNF) therapy combined with drainage procedure is effective as well. However, previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure. AIM: This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn's perianal fistula (CPF) closure rates after stem cell transplantation with and without anti-TNF therapy, and to identify the factors affecting CPF closure and recurrence. METHODS: The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled. Clinical data were compared according to anti-TNF therapy and CPF closure. RESULTS: A total of 65 patients were included. The median age of females was 26 years (range: 21-31) and that of males was 29 (44.6%). The mean follow-up duration was 65.88 ± 32.65 months, and complete closure was observed in 50 (76.9%) patients. The closure rates were similar after stem cell transplantation with and without anti-TNF therapy (66.7% vs 81.6% at 3 year, P = 0.098). The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture (P = 0.027, 0.002, and 0.008, respectively). Clinical factors such as complexity, number of fistulas, presence of concurrent abscess, and medication were not significant for closure. The cumulative 1-, 2-, and 3-year closure rates were 66.2%, 73.8%, and 75.4%, respectively. CONCLUSION: Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation. However, both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy. Fistulous tract length, proctitis, and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

Aesthetic doctors' perception and attitudes toward tolerance in botulinum toxin.

BACKGROUND: Botulinum toxin is a crucial therapeutic tool with broad indications in both cosmetic and medical fields. However, the expanding cosmetic use and increased dosages of botulinum toxin have raised concerns about resistance, making it essential to study the awareness and management practices among healthcare professionals. METHODS: A survey was conducted among clinical physicians using botulinum toxin. The study investigated their experiences, awareness, and management practices related to toxin resistance. Real-time mobile app-based surveys were administered to clinicians attending the 45th International Academic Conference of the Korean Academy of Laser and Dermatology (KALDAT) on December 3, 2023. RESULTS: Among 3140 participants, 673 clinical physicians completed the survey. Of these, 363 clinicians (53.9%) reported experiencing botulinum toxin resistance. Regarding the resistance rate, 59.4% indicated less than 1%, 36% reported approximately 1%-25%, and 95.4% reported less than 25%. Efforts to prevent resistance included maintaining intervals of over 3 months (54.8%), using products with lower resistance potential (47.0%), employing minimal effective doses (28.2%), and minimizing re-administration (14.9%). CONCLUSION: In the South Korean aesthetic medicine community, a majority of clinical physician's report encountering botulinum toxin resistance. Given the potential loss of various benefits associated with resistance, there is a need to establish appropriate guidelines based on mechanistic studies and current status assessments. Educating clinicians on applicable guidelines is crucial.

Functional and esthetic outcomes of redundante rhinoplasty for internal nasal valve dysfunction in Asian patients.

OBJECTIVE: This study aimed to use validated measures to evaluate the functional and esthetic outcomes in patients who underwent functional rhinoplasty for Internal Nasal Valve Dysfunction (INVD) in Korea. METHODS: A retrospective review of consecutive patients who underwent functional rhinoplasty for INVD confirmed by endoscopic findings and the modified Cottle test between 2016 and 2018 was performed. Nasal obstruction was assessed with the Visual Analog Scale (VAS) and nasal obstruction symptom evaluation (NOSE) scale. Acoustic rhinometry was performed pre- and post-operatively. The Minimal Cross-Sectional Area (MCA) of the nose was measured. Objective assessment of the esthetic outcomes was performed with the Objective Rhinoplasty Outcome Score (OROS), which assesses tip rotation, projection, width, dorsal height, width, length, symmetry, and the overall result. RESULTS: Fifty-seven patients (46 men and 11 women; mean age, 30.5 ±â€¯12.3 years) who underwent functional rhinoplasty were included in this study. The VAS and NOSE scores indicated functional improvement in all cases (all p < 0.001). There were no significant between-group differences (VAS score, p = 0.274; NOSE score, p = 0.952). The objective functional outcomes evaluated using MCA on the concave (p = 0.478) and convex (p = 0.631) sides did not differ significantly pre- and post-operatively. The subjective evaluation of esthetic satisfaction revealed no between-group difference. Moreover, 31 out of 44 patients (70.5%) with static INVD and nine out of 14 patients (64.3%) with dynamic or combined INVD showed excellent outcomes. Regarding objective esthetic outcomes, scores for the eight factors were >3, and there was no significant difference between the two groups (all p > 0.05). CONCLUSIONS: Functional rhinoplasty, including extracorporeal septoplasty and spreader grafting, may be a viable option for correcting INVD with functional and esthetic improvement. Dynamic INVD is less prevalent among Asians, and there was no significant difference in the surgical outcomes compared with those of static INVD. LEVEL OF EVIDENCE: Level 4.

Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss.

Multiple genome sequencing studies have identified genetic abnormalities as major causes of severe intellectual disability (ID). However, many children affected by mild ID and borderline intellectual functioning (BIF) lack a genetic diagnosis because known causative ID genetic mutations have not been identified or the role of genetic variants in mild cases is less understood. Genetic variant testing in mild cases is necessary to provide information on prognosis and risk of occurrence. In this study, we report two sibling patients who were 5 years 9 months old and 3 years 3 months old and presented to the hospital due to developmental delay. Clinical assessment and chromosomal microarray analysis were performed. The patients were diagnosed with mild intellectual disability (ID) and borderline intellectual functioning (BIF). Genetic analysis identified a loss of 12p11.22, including the OVCH1-AS1, OVCH1, and TMTC1 genes, which was the only variant that occurred in both sisters. Identical variants were found in their father with probable BIF. Neither patient presented any brain structural abnormalities or dysmorphism, and no exogenous factors or parenting problems were reported. Thus, loss of 12p11.22 may be associated with our patients' cognitive impairment. The OVCH1, OVCH1-AS1 and TMTC1 variants identified in this study are the most likely disease-causing genes in the sisters. Our findings may expand as yet limited knowledge on mild ID and BIF causative variants, which would further support the diagnosis even if the severity is mild.

The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium-glucose cotransporter-2 inhibitor, in type 2 diabetes.

AIMS: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). RESULTS: A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438). CONCLUSIONS: Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study.

Performance of ECG-Derived Digital Biomarker for Screening Coronary Occlusion in Resuscitated Out-of-Hospital Cardiac Arrest Patients: A Comparative Study between Artificial Intelligence and a Group of Experts.

Acute coronary syndrome is a significant part of cardiac etiology contributing to out-of-hospital cardiac arrest (OHCA), and immediate coronary angiography has been proposed to improve survival. This study evaluated the effectiveness of an AI algorithm in diagnosing near-total or total occlusion of coronary arteries in OHCA patients who regained spontaneous circulation. Conducted from 1 July 2019 to 30 June 2022 at a tertiary university hospital emergency department, it involved 82 OHCA patients, with 58 qualifying after exclusions. The AI used was the Quantitative ECG (QCG™) system, which provides a STEMI diagnostic score ranging from 0 to 100. The QCG score's diagnostic performance was compared to assessments by two emergency physicians and three cardiologists. Among the patients, coronary occlusion was identified in 24. The QCG score showed a significant difference between occlusion and non-occlusion groups, with the former scoring higher. The QCG biomarker had an area under the curve (AUC) of 0.770, outperforming the expert group's AUC of 0.676. It demonstrated 70.8% sensitivity and 79.4% specificity. These findings suggest that the AI-based ECG biomarker could predict coronary occlusion in resuscitated OHCA patients, and it was non-inferior to the consensus of the expert group.

Incidence and Presenting Characteristics of Angiosarcoma in the US, 2001-2020.

Importance: Angiosarcoma is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed. Objective: To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US. Design, Setting, and Participants: This retrospective cross-sectional study used data from the US Cancer Statistics (USCS) National Program of Cancer Registries-Surveillance, Epidemiology, and End Results Combined Database, which captures more than 99% of newly diagnosed cancers in the US. The study included all 19 289 patients in the US with a new diagnosis of angiosarcoma between 2001 and 2020 captured in the USCS database. Statistical analysis was performed from June to September 2023. Main Outcomes and Measures: Incidence of angiosarcoma, demographics of patients with angiosarcoma, and extent of disease at presentation. Results: The study included 19 289 patients (median age, 71 years [IQR, 59-80 years]; 10 506 women [54.5%]) with a new diagnosis of angiosarcoma. The US incidence of angiosarcoma doubled between 2001 (657 cases) and 2019 (1312 cases), reflecting both an increase in the adjusted incidence rate of 1.6% per year (P = .001), to 3.3 cases per 1 000 000 person-years (95% CI, 3.1-3.5 cases per 1 000 000 person-years), and an increase in the population at risk. In 2020, the reported incidence rate (3.0 cases per 1 000 000 person-years) and cases of angiosarcoma (n = 1159) were modestly lower than in 2019. Overall, 72.3% of cases of angiosarcoma (n = 13 955) were cutaneous, subcutaneous, or breast angiosarcomas; 24.4% were visceral (n = 4701); and 3.3% were located in unknown or rare primary sites (n = 633). Secondary breast and chest wall angiosarcomas among women represented the largest contribution to increasing incidence. Among breast angiosarcomas, 99.2% (2684 of 2705) were in women and 71.9% (1944 of 2705) were secondary. A total of 80.4% of chest wall or thorax cases among women (1861 of 2316) were secondary vs 26.5% among men (112 of 422), and 63.9% of upper extremity cases among women (205 of 321) were secondary vs 26.8% (56 of 209) among men (P = .001). Rates of secondary angiosarcoma in the abdomen and lower extremities were similar between men and women. The incidence rate of visceral angiosarcoma was also found to be increasing (1.5% per year; P = .001). Conclusions and Relevance: This cross-sectional study describes angiosarcoma presentation patterns and incidence rates in the US over a 20-year period and shows that the number of cases in men and women increased, with the greatest increase among women with secondary angiosarcoma of the chest, breast, and upper extremity. These data increase awareness of a rare but highly morbid disease and highlight the need for improved early detection of angiosarcoma among patients at high risk, such as women with a history of breast cancer.

Long-term outcomes of very low birth weight infants with intraventricular hemorrhage: a nationwide population study from 2011 to 2019.

BACKGROUND: Advancements in neonatal care have increased preterm infant survival but paradoxically raised intraventricular hemorrhage (IVH) rates. This study explores IVH prevalence and long-term outcomes of very low birth weight (VLBW) infants in Korea over a decade. METHODS: Using Korean National Health Insurance data (NHIS, 2010-2019), we identified 3372 VLBW infants with IVH among 4,129,808 live births. Health-related claims data, encompassing diagnostic codes, diagnostic test costs, and administered procedures were sourced from the NHIS database. The results of the developmental assessments  are categorized into four groups based on standard deviation (SD) scores. Neonatal characteristics and complications were compared among the groups. Logistic regression models were employed to identify significant changes in the incidence of complications and to calculate odds ratios with corresponding 95% confidence intervals for each risk factor associated with mortality and morbidity in IVH. Long-term growth and development were compared between the two groups (years 2010-2013 and 2014-2017). RESULTS: IVH prevalence was 12% in VLBW and 16% in extremely low birth weight (ELBW) infants. Over the past decade, IVH rates increased significantly in ELBW infants (P = 0.0113), while mortality decreased (P = 0.0225). Major improvements in certain neurodevelopmental outcomes and reductions in early morbidities have been observed among VLBW infants with IVH. Ten percent of the population received surgical treatments such as external ventricular drainage (EVD) or a ventriculoperitoneal (VP) shunt, with the choice of treatment methods remaining consistent over time. The IVH with surgical intervention group exhibited higher incidences of delayed development, cerebral palsy, seizure disorder, and growth failure (height, weight, and head circumference) up to 72 months of age (P < 0.0001). Surgical treatments were also significantly associated with abnormal developmental screening test results. CONCLUSIONS: The neurodevelopmental outcomes of infants with IVH, especially those subjected to surgical treatments, continue to be a matter of concern. It is imperative to prioritize specialized care for patients receiving surgical treatments and closely monitor their growth and development after discharge to improve developmental prognosis. Supplementary file2 (MP4 77987 kb).

Comparison study between single enzyme and multienzyme complex in distiller's dred grains with soluble supplemented diet in broiler chicken.

Upregulation of the nutritional value of feed is the major target of various studies in the livestock industry, and dietary enzyme supplementation could aid in digesting the nondegrading nutrients of grains in feed ingredients. Dried distillers' grains with solubles (DDGS) is a byproduct of the fermentation process in the beverage industry and can be used as a large supply source of fiber in feed. Therefore, we conducted an experiment with male broiler chickens to investigate the effect of various types of enzymes on DDGS and compare the efficacy of single enzyme and multienzyme complexes on growth performance and gut environments in broiler chickens. We used 420 1-day-old broiler chickens (Ross 308), and they were allotted into 4 dietary treatments with seven replications (CON, corn-soybean meal [SBM] diet; NC, DDGS supplemented diet; SE, 0.05 % of mannanase supplemented DDGS-based diet; MC, 0.10% of multienzyme complex (mannanase and xylanase, glucanase) supplemented DDGS-based diet. The dietary exogenous enzyme in the DDGS-supplemented diet could improve growth performance as much as the growth of the control group, and digestibility of dry matter, crude protein, and gross energy were significantly increased by enzyme addition in groups of chicks fed DDGS-supplementation diet. Moreover, the populations of pathogenic bacteria, coliforms, and Bacteroidetes were significantly decreased by enzyme supplementation, which might lead to improved gut mucus-secreting cells and inflammatory cytokines in the jejunum. Collectively, dietary single enzyme and multienzyme complexes could improve gut environments, including intestinal immune responses and gut microbial population, and lead to improvement of growth performance in broiler chickens.

A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure.

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses. We hypothesized that amlexanox, an anti-inflammatory drug and non-selective PDE4 inhibitor, could offer neuroprotection by addressing lysosomal dysfunction and mitigating neuroinflammation, ultimately preventing neuronal death in epileptic conditions. Our research utilized a pilocarpine-induced epilepsy animal model to investigate amlexanox's potential benefits. Administered intraperitoneally at a dose of 100 â€‹mg/kg daily following the onset of a seizure, we monitored its effects on lysosomal function, inflammation, neuronal death, and cognitive performance in the brain. Tissue samples from various brain regions were collected at predetermined intervals for a comprehensive analysis. The study's results were significant. Amlexanox effectively improved lysosomal function, which we attribute to the modulation of zinc's influx into the lysosomes, subsequently enhancing autophagic processes and decreasing the release of inflammatory factors. Notably, this led to the attenuation of neuronal death in the hippocampal region. Additionally, cognitive function, assessed through the modified neurological severity score (mNSS) and the Barnes maze test, showed substantial improvements after treatment with amlexanox. These promising outcomes indicate that amlexanox has potential as a therapeutic agent in the treatment of epilepsy and related brain disorders. Its ability to combat lysosomal dysfunction and neuroinflammation positions it as a potential neuroprotective intervention. While these findings are encouraging, further research and clinical trials are essential to fully explore and validate the therapeutic efficacy of amlexanox in epilepsy management.

IL4 receptor targeting enables nab-paclitaxel to enhance reprogramming of M2-type macrophages into M1-like phenotype via ROS-HMGB1-TLR4 axis and inhibition of tumor growth and metastasis.

Rationale: Nab-paclitaxel (Abx) is widely employed in malignant tumor therapy. In tumor cells and pro-tumoral M2-type macrophages, the IL4 receptor (IL4R) is upregulated. This study aimed to elucidate the selective delivery of Abx to M2-type macrophages by targeting IL4R and reprogramming them into an anti-tumoral M1-type. Methods: Abx was conjugated with the IL4R-binding IL4RPep-1 peptide using click chemistry (IL4R-Abx). Cellular internalization, macrophage reprogramming and signal pathways, and tumor growth and metastasis by IL4R-Abx were examined. Results: IL4R-Abx was internalized into M2 macrophages more efficiently compared to the unmodified Abx and control peptide-conjugated Abx (Ctrl-Abx), which was primarily inhibited using an anti-IL4R antibody and a receptor-mediated endocytosis inhibitor compared with a macropinocytosis inhibitor. IL4R-Abx reprogrammed the M2-type macrophages into M1-like phenotype and increased reactive oxygen species (ROS) levels and extracellular release of high mobility group box 1 (HMGB1) in M2 macrophages at higher levels than Abx and Ctrl-Abx. The conditioned medium of IL4R-Abx-treated M2 macrophages skewed M2 macrophages into the M1-like phenotype, in which an anti-HMGB1 antibody and a toll-like receptor 4 (TLR4) inhibitor induced a blockade. IL4R-Abx accumulated at tumors, heightened immune-stimulatory cells while reducing immune-suppressing cells, and hampered tumor growth and metastasis in mice more efficiently than Abx and Ctrl-Abx. Conclusions: These results indicate that IL4R-targeting allows enhancement of M2-macrophage shaping into M1-like phenotype by Abx through the ROS-HMGB1-TLR4 axis, improvement of antitumor immunity, and thereby inhibition of tumor growth and metastasis, presenting a new approach to cancer immunotherapy.

Effect of the probiotic Weissella cibaria CMS1 on the immune response and the oral microbiome: a randomized, double-blind, placebo-controlled, parallel study.

The oral cavity connects the external environment and the respiratory and digestive systems, and the oral microbial ecosystem is complex and plays a crucial role in overall health and immune defense against external threats. Recently, the potential use of probiotics for disease prevention and treatment has gained attention. This study aimed to assess the effect of Weissella cibaria CMS1 (W. cibaria CMS1) consumption on the oral microbiome and immune function in healthy individuals through a 12-week clinical trial. This randomized, double-blind, placebo-controlled, parallel trial enrolled 90 healthy subjects. The consumption of W. cibaria CMS1 significantly increased salivary immunoglobulin A (p = 0.046) and decreased tumor necrosis factor-α (TNF-α) levels (p = 0.008). Analysis of the oral microbiota revealed changes in beta diversity, increased abundance of Firmicutes and Actinobacteria, and decreased abundance of Bacteroidetes and Fusobacteria after 12 weeks of consuming W. cibaria CMS1. Significant increases in various strains, including Lactobacillales, Bacilli, Streptococcaceae, Streptococcus, and Firmicutes, were observed in the W. cibaria CMS1 group after 12 weeks of intake. Additionally, Fusobacteriia Fusobacteriales Fusobacteriaceae and Fusobacteriia Fusobacteriales Fusobacteriaceae Fusobacterium exhibited a positive correlation with TNF-α. These findings demonstrate the positive effect of W. cibaria CMS1 on the oral environment and immune function.

Baseline glycated albumin level and risk of type 2 diabetes mellitus in Healthy individuals: a retrospective longitudinal observation in Korea.

Glycated albumin (GA) reflects glycemic status for the past three weeks. GA level demonstrates a strong correlation with HbA1c level and is used as an adjunctive biomarker for diagnosis and monitoring of type 2 diabetes mellitus (T2DM). In this study, we validated the predictive performance of baseline GA for development of T2DM in healthy individuals in Korea. From August 2013 to September 2014, the medical records of 3,771 healthy Koreans were retrospectively reviewed. Each participant was categorized into tertiles based on initial GA level. During the follow-up period through May 2020, study participants were evaluated for T2DM using HbA1c, fasting glucose level, and a self-reported diagnosis history. Baseline GA level by tertile (T1 to T3) was 10.4 ± 0.8% (mean ± SD), 12.1 ± 0.3%, and 13.7 ± 0.9%, respectively. The median follow-up was 5.97 years, during which 4.9% (186 of 3,771) of the participants developed T2DM. After adjusting for confounding factors, the hazard ratio for the development of T2DM in the highest GA level group (T3) compared to the reference group (T1) was 2.46 (95% CI, 1.7 to 3.58, p < 0.001 for trend) with a Harrell's C index of 0.80 (95% CI, 0.76 to 0.83). Also, within highest group of baseline HbA1c and FG levels, higher GA levels were associated with an increased HRs for T2DM. In conclusion, Our study confirms that the risk of T2DM increases with baseline GA level. Additional follow-up of the cohort is warranted to investigate the correlations between GA and other clinical indicators including diabetic complications.

Managing Vascular Pedicle Exposure in Free Tissue Transfer Using a Reprocessed Micronized Dermal Substitute in Lower Extremity Reconstructions.

Lower extremity reconstruction is challenging because of its intricate anatomy and dynamic biomechanics. Although microsurgical free tissue transfer offers pivotal solutions to limited local tissue availability, vascular pedicle exposure after free tissue transfer is common. We evaluated a novel method of managing pedicle exposure after free tissue transfer using a reprocessed micronized dermal substitute. Ten patients who underwent lower-extremity reconstruction using free tissue transfer and micronized dermal substitute between January and December 2023 were retrospectively reviewed. When native tissue could not be closed over the pedicle, reprocessed micronized artificial dermal matrix (rmADM) was cut and stacked to protect and stabilize it. Epithelialization was achieved by secondary skin grafting or healing by secondary intention. Flap dimensions, recipient artery and vein, ADM size, time required for granulation tissue maturation and complete epithelialization, and flap outcomes were analyzed. The mean age was 55.80 ± 20.70 years, and six patients (60%) were diabetic. The mean rmADM coverage area was 8.70 ± 8.41 cm2, and the average time required for complete epithelialization was 50.89 ± 14.21 days. Except for one total necrosis due to bypass graft failure, nine limbs were successfully salvaged. Application of rmADM offers numerous advantages, including vascular collapse prevention, moisture maintenance, granulation tissue growth promotion, and pedicle stabilization.