A latent profile analysis on adolescents' Non-Suicidal Self-Injury related to intrapersonal and interpersonal factors.

Non-suicidal self-injury (NSSI) among adolescents continues to be a significant public health concern worldwide. A recent systematic review and meta-analysis found that the global prevalence of NSSI in adolescents aged 12-18 years was 17.2%, with higher rates reported among females (19.7%) than males (14.8%). This behavior has been linked to several negative outcomes, such as depression, anxiety, substance abuse, and suicidal ideation. The present study aimed to classify adolescents based on intrapersonal and interpersonal factors associated with NSSI proposed in Nock's (2009) integrated model of NSSI, to identify distinct clusters targeting specific risk factors. This encompassed negative cognition, emotional vulnerability, poor coping skill, peer-victimization, family adaptability, and perceived stress. A total of 881 adolescents aged 11-16 years in South Korea completed self-reported questionnaires on automatic thoughts, depression, emotional regulation, peer victimization, family adaptability and perceived stress. Latent profile analysis (LPA) revealed three distinct classes: "the severe group", "the moderate group", "the mild group". Class 3 ("severe group": N = 127) exhibited greater severity related to NSSI, including negative cognition, emotional vulnerability, poor coping skills, peer victimization, and perceived stress, with weaker levels of factors that can prevent NSSI compared to class 1 ("mild group": N = 416) and class 2 ("moderated group": N = 338). The present study emphasizes the importance of considering both intrapersonal (e.g., negative automatic thoughts & emotional dysregulation) and interpersonal factors (i.e., peer victimization) when understanding NSSI - among adolescents. These findings can be utilized to develop interventions aimed at reducing the prevalence and severity of NSSI among adolescents.

Preventing Donepezil-Induced Adverse Effects Through N-acetylcysteine Co-Administration.

Background: Drug-induced adverse symptoms affect patients' quality of life (QoL) during treatment. Understanding the underlying mechanisms of drug-induced adverse effects could help prevent them. As current drugs have limited effects in halting the progress of Alzheimer's disease (AD), patients are required to take these drugs over a long period. The main obstacles to long-term compliance are drug-elicited side effects that deteriorate patient QoL. Objective: Donepezil, the most popular acetylcholinesterase inhibitor (AChEI) drug for AD, induces various side effects, especially at high doses. This study aimed to identify a drug that can attenuate the side effects of donepezil and investigate the underlying mechanisms. Methods: Five-week-old Sprague-Dawley rats received daily oral donepezil and N-acetylcysteine (NAC) for four weeks. General symptoms following administration were monitored daily to address drug-related adverse effects. Cytosolic calcium influx and generation of reactive oxygen species (ROS) after drug treatment were measured in vitro using C2C12 myotubes. Results: High-dose donepezil induced numerous adverse symptoms in male and female rats, which were markedly attenuated by co-treatment with NAC. NAC significantly reduced both acute and chronic muscle-related symptoms caused by donepezil. Additionally, in vitro studies showed that high-dose donepezil increased ROS and intracellular calcium ([Ca2 +]i) levels in muscle cells, contributing to these adverse effects. NAC co-treatment dramatically reduced ROS and [Ca2 +]i levels in muscle cells. Conclusions: Combined treatment with NAC effectively diminishes the adverse effects elicited by donepezil by regulating ROS and [Ca2 +]i levels in the skeletal muscle, which could contribute to improving donepezil treatment in patients.

Facile Size Tunable Skin-Adaptive Patch for Accelerating Wound Healing.

Owing to the moist and curved interfaces of skin wounds, enhancing the adhesiveness while maintaining delivery efficacy of biomolecules has drawn significant attention in advanced wound dressings. Despite tremendous trials to load biomolecules with sound adhesiveness, the complicated fabricating processes and abnormal allergic responses that are attributed to chemical moiety-based adhesives remain as major problems. To this end, in this study a one-step fabrication process is developed to manufacture microstructures with both a therapeutic (cylindrical structure for embossed structure human adipose-derived stem cell sheet, ESS) and an adhesive part (octopi-inspired structure of adhesive, OIA), which ESOIA is called. OIA showed the highest adhesion strength in both dry (1.48 N cm-2) and wet pig skin conditions (0.81 N cm-2), maintaining the adhesive properties after repeated attach-detach trials. ESS from the therapeutic part of ESOIA also showed an enhanced angiogenic effect compared with the ones that are normally cultured in vitro. ESS also showed improved in vivo wound healing outcomes following enhanced cell engraftment compared to the cell injection group by means of intact cell-extracellular matrix interactions.

Dual function of PHF16 in reinstating homeostasis of murine intestinal epithelium after crypt regeneration.

Intestinal stem cells (ISCs) are highly vulnerable to damage, being in a constant state of proliferation. Reserve stem cells repair the intestinal epithelium following damage-induced ablation of ISCs. Here, we report that the epigenetic regulator plant homology domain (PHD) finger protein 16 (PHF16) restores homeostasis of the intestinal epithelium after initial damage-induced repair. In Phf16-/Y mice, revival stem cells (revSCs) showed defects in exiting the regenerative state, and intestinal crypt regeneration failed even though revSCs were still induced in response to tissue damage, as observed by single-cell RNA sequencing (scRNA-seq). Analysis of Phf16-/Y intestinal organoids by RNA sequencing (RNA-seq) and ATAC sequencing identified that PHF16 restores homeostasis of the intestinal epithelium by inducing retinoic acid receptor (RAR)/retinoic X receptor (RXR) target genes through HBO1-mediated histone H3K14 acetylation, while at the same time counteracting YAP/TAZ activity by ubiquitination of CDC73. Together, our findings demonstrate the importance of timely suppression of regenerative activity by PHF16 for the restoration of gut homeostasis after acute tissue injury.

Weight gain, new-onset overweight or obesity, and their influencing factors during the social distancing era of the COVID-19 pandemic.

The prevalence of obesity is gradually increasing in South Korea, and the coronavirus disease 2019 (COVID-19) pandemic has accelerated the weight gain. In response to COVID-19, South Korea implemented targeted distancing measures based on the number of COVID-19 cases, rather than a full lockdown. This study focused on two subgroups that influence the rise in obesity prevalence during the early stages of the COVID-19 pandemic and explored the factors contributing to rapid weight gain in this group during this period. This cross-sectional study involved 3,462 participants recruited through the MicroEmbrain Inc. Online survey panel. Participation emails were sent by the research company to the online survey panel, and individuals who voluntarily agreed to participate responded to the survey. The participants consisted of residents aged 19 and above from Seoul, with sample distribution taking considering sex, age, and region. Height, and weight before and during the COVID-19 pandemic were self-reported. The analysis revealed that compared with that of pre-COVID-19 statistics, 11 % of all participants entered the overweight or obese categories post COVID-19, and among those who were overweight or obese before COVID-19, 42.5 % reported weight gain. Both groups had relatively younger individuals, higher stress levels, spent more time alone, and had increased usage of online platforms including online food purchasing. Post-COVID-19 wt gain among individuals with pre-existing overweight or obesity status was associated with a higher frequency of solitary drinking (odds ratio [OR] = 1.407, 95 % confidence interval [CI] = 1.024-1.932), increased online leisure time (OR = 1.336, 95 % CI = 1.063-1.678), and increased use of meal delivery services (OR = 1.307, 95 % CI = 1.026-1.664). The prevalence of obesity has continued to rise after COVID-19 pandemic, highlighting the need for interventions that mitigate the negative impact of the pandemic on health behavior.

Effect of air-frying on formation and correlations of polycyclic aromatic hydrocarbons, acrylamide, and heterocyclic aromatic amines in foods and risk assessment.

The levels of acrylamide (AA), four polycyclic aromatic hydrocarbons (PAH4), and heterocyclic aromatic amines (HAAs) in 184 air-fried agricultural, fishery, and animal products were measured using GC-MS and UPLC-MS/MS. Among the tested samples, sea algae exhibited the highest levels of PAH4 and eight specific HAAs (HAA8), while root and tuber crops had the greatest amount of AA. Agricultural and fisheries products had higher levels of all three contaminants, while livestock products had an inverse correlation between PAH4 and HAA8. The margin of exposure in the Korean population is considered "unlikely a concern" for all samples for PAH4 and HAA8, however, that for AA in cereal, vegetable, and root and tuber crops is deemed "may be a concern", with a value < 10,000 in all age groups. These findings suggest a need to evaluate dietary AA exposure in certain food categories and further research to minimize AA formation during air frying. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01639-4.

The effect of plum extracts and antioxidants on reduction of ethyl carbamate in plum liqueur.

Stone-fruit liqueurs contain high contents of the carcinogen ethyl carbamate (EC). In this study, we investigated the effect of plum fruit extract and single antioxidants present in plum fruit extracts on the reduction in the EC content during the macerating process in a plum liqueur model system and authentic plum liqueur. 30% ethanol model plum liqueur treated with 0.2% plum extract showed the lowest EC content with 55% reduction rate after the macerating process compared to the content in the control. Interestingly, neither 0.1% ascorbic acid nor 0.1% p-coumaric acid lowered the EC contents in the model liqueur, while they decreased the EC contents in authentic plum liqueur. This was possibly attributed to the synergistic effect of the plum fruit phenolics with the ascorbic acid and p-coumaric acid antioxidants. Thus, plum extracts can be applied to plum liqueurs to reduce the rate of EC formation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01585-1.

Reverse Intersystem Crossing Boosting Sensitizer for Ultra-High Efficiency Blue Organic Light-Emitting Diode.

In designing thermally activated delayed fluorescence (TADF) emitters, a high reverse intersystem crossing (RISC) rate with a high photoluminescence quantum yield is essential. Herein, two blue TADF molecules, 2',5'-di(9H-carbazol-9-yl)-3',6'-bis(3,6-ditert-butyl-9H-carbazol-9-yl)-[1,1':4',1″-terphenyl]-4,4″-dicarbonitrile (CzTCzPhBN) and 2',5'-bis(3,6-ditert-butyl-9H-carbazol-9-yl)-3',6'-bis(3,6-diphenyl-9H-carbazol-9-yl)-[1,1':4',1″-terphenyl]-4,4″-dicarbonitrile (PhCzTCzPhBN) with a high RISC rate, were developed through donor engineering. CzTCzPhBN and PhCzTCzPhBN showed a high RISC rate of 4.00 × 105 and 16.62 × 105 s-1, respectively, with a high photoluminescence quantum yield of 80.1 and 84.9%, which resulted in high external quantum efficiency of 27.0 and 27.8% with color coordinates (0.148, 0.170) and (0.150, 0.230) in blue TADF organic light-emitting diodes, respectively. The high RISC rate and device efficiency inspired two TADF molecules to be used as sensitizers in hyperfluorescence devices. The hyperfluorescence devices showed ultra-high external quantum efficiency of 30.7 and 36.4% with color coordinates (0.125, 0.164) and (0.127, 0.193), respectively.

Effect of high-flow nasal and buccal oxygenation on safe apnea time in children with open mouth: A randomized controlled trial.

BACKGROUND: High-flow nasal oxygenation is reported to prolong duration of apnea while maintaining adequate oxygen saturation with the mouth closed. Also, buccal oxygenation is known to have similar effects in obese adults. We compared the effect of these two methods on prolongation of acceptable apnea time in pediatric patients with their mouth open. METHODS: Thirty-eight patients, aged 0-10 years were randomly allocated to either the high-flow nasal oxygenation group (n = 17) or the buccal oxygenation group (n = 21). After induction of anesthesia including neuromuscular blockade, manual ventilation was initiated until the expiratory oxygen concentration reached 90%. Subsequently, ventilation was paused, and the patient's head was extended, and mouth was opened. The HFNO group received 2 L·min-1·kg-1 of oxygen, and the BO group received 0.5 L·min-1·kg-1 of oxygen. We set a target apnea time according to previous literature. When the apnea time reached the target, we defined the case as "success" in prolongation of safe apnea time and resumed ventilation. When the pulse oximetry decreased to 92% before the target apnea time, it was recorded as "failure" and rescue ventilation was given. RESULTS: The success rate of safe apnea prolongation was 100% in the high-flow nasal oxygenation group compared to 76% in the buccal oxygenation group (p = .04). Oxygen reserve index, end-tidal or transcutaneous carbon dioxide partial pressure, and pulse oximetry did not differ between groups. CONCLUSION: High-flow nasal oxygenation is effective in maintaining appropriate arterial oxygen saturation during apnea even in children with their mouth open and is superior to buccal oxygenation. Buccal oxygenation may be a good alternative when high-flow nasal oxygenation is not available.

Non-relevant segment recognition via hard example mining under sparsely distributed events.

We propose on/offline hard example mining (HEM) techniques to alleviate the degradation of the generalization performance in the sparse distribution of events in non-relevant segment (NRS) recognition and to examine their utility for long-duration surgery. Through on/offline HEM, higher recognition performance can be achieved by extracting hard examples that help train NRS events, for a given training dataset. Furthermore, we provide two performance measurement metrics to quantitatively evaluate NRS recognition in the clinical field. The existing precision and recall-based performance measurement method provides accurate quantitative statistics. However, it is not an efficient evaluation metric in tasks where false positive recognition errors are fatal, such as NRS recognition. We measured the false discovery rate (FDR) and threat score (TS) to provide quantitative values that meet the needs of the clinical setting. Finally, unlike previous studies, the utility of NRS recognition was improved by applying our model to long-duration surgeries, instead of short-length surgical operations such as cholecystectomy. In addition, the proposed training methodology was applied to robotic and laparoscopic surgery datasets to verify that it can be robustly applied to various clinical environments.

Charting Proficiency: The Learning Curve in Robotic Hysterectomy for Large Uteri Exceeding 1000 g.

Background/Objectives: This study evaluates the safety and surgical outcomes of performing robotic hysterectomy on uteri weighing over 1000 g, with a focus on the surgeon's learning curve. Methods: A retrospective analysis was conducted on 44 patients who underwent hysterectomy by a single surgeon from January 2020 to February 2024 using the DaVinci Xi System. Surgical procedures included total hysterectomy with bilateral salpingectomy, and specimens were removed via transvaginal manual morcellation. Operative times were segmented into docking, console, morcellation, and conversion times. Results: Results indicated an inflection point in the 20th case, suggesting proficiency after 20 surgeries. Comparison between early (Group A, cases 1-20) and later cases (Group B, cases 21-44) showed significant reductions in console time (CT) and morcellation time (MT) in Group B, leading to a shorter overall operative time (OT). Although estimated blood loss was higher in Group A, it was not statistically significant. Hemoglobin differences were significantly higher in Group B. No significant differences were observed in transfusion rates, postoperative analgesic usage, or complications between the groups. Conclusions: The study concludes that robotic hysterectomy for large uteri is safe and that surgical proficiency improves significantly after 20 cases, enhancing overall outcomes.

Genetic Differences between Male and Female Pattern Hair Loss in a Korean Population.

Studies on androgenetic alopecia (AGA or patterned hair loss (PHL)) have suggested different underlying pathological mechanisms between males and females. While many genetic factors for male hair loss have been identified through genome-wide association studies (GWASs), the genetic determinants of female hair loss remain unclear. In this study, we analyzed approximately 1000 individuals (436 males and 568 females) to identify sex-specific genetic factors. We conducted three independent GWASs for the total, male-only, and female-only groups, identifying three novel loci (rs7814359, rs2163085, and rs4793158 of the TSNARE1, FZD1, and GJC1 genes, respectively). rs7814359 showed a significant genome-wide association with AGA in the combined sex group and a weak association in both the male-only and female-only groups. The single nucleotide polymorphism (SNP) rs2163085 showed a significant genome-wide association with AGA in the combined group and notable significance in females. The rs4793158 SNP showed a suggestive association with AGA in both the combined and female-only groups. TSNARE1, related to rs7814359, is involved in vesicle transport. FZD1 is a key regulator of the Wnt signaling pathway. GJC1 is a gap junction protein. The associations of FZD1 and GJC1 with female-specific AGA suggest that sex hormones, such as estrogen, may influence FPHL through these genes. These findings will contribute to our understanding of the sex-specific pathophysiology of AGA.

Screening and Selection of Antibiotics for Enhanced Production of Astaxanthin by Haematococcus lacustris.

Haematococcus lacustris (Girod-Chantrans) Rostafinski (Chlorophyta) is the richest microalgal source of astaxanthin. Natural astaxanthin from H. lacustris has been widely studied and used for commercial production worldwide. In this study, we examined the effects of 11 antibiotics (dihydrostreptomycin sulphate, neomycin, chloramphenicol, penicillin, streptomycin, ampicillin, kanamycin, gentamycin, hygromycin B, tetracycline, and paromomycin) on the biomass dry weight, growth, and astaxanthin yield of H. lacustris using Jaworski's medium without a nitrogen source. Astaxanthin content in H. lacustris was improved in the presence of ampicillin (0.25 g/L, 0.5 g/L, 1 g/L), chloramphenicol (0.25 g/L), and penicillin (0.25 g/L, 0.5 g/L, 1 g/L) in comparison to the control on day 15. The greatest increase in astaxanthin content on day 15 (6.69-fold) was obtained with the addition of penicillin (0.5 g/L) in comparison to the control. Similarly, on day 15, the cell numbers were also the highest for the H. lacustris culture grown with the addition of penicillin (0.5 g/L).

Is It the Best Option? Robotic Surgery for Endometriosis.

Endometriosis is a chronic condition affecting approximately 10% of women of reproductive age, leading to significant physical and emotional stress. Treatments include medical management and surgical interventions, with laparoscopic surgery being the gold standard for removing endometrial tissue. The advent of robotic-assisted laparoscopic surgery (RALS) has enabled more complex procedures to be performed minimally invasively, increasing its use in high-difficulty surgeries. Developed in the late 20th century, systems like the Da Vinci Surgical System have revolutionized surgery by enhancing precision, dexterity, and visualization. The latest models, including the Da Vinci Xi and SP, offer advanced features such as enhanced arm mobility, fluorescence imaging, and single-port capabilities. Comparative studies of RALS and conventional laparoscopy (LPS) for endometriosis show mixed results. While some studies indicate no significant differences in complications or recovery outcomes, others highlight longer operative times and hospital stays for RALS. Despite these drawbacks, RALS is not inferior to LPS overall. The clinical benefits of RALS include greater precision and accuracy, reduced surgeon fatigue, and a faster learning curve, facilitated by advanced ergonomic and control systems. However, the high costs and extensive infrastructure requirements limit the accessibility and availability of robotic surgery, particularly in smaller or rural hospitals. The absence of tactile feedback remains a challenge, though upcoming advancements aim to address this. Continued research and development are essential to make robotic surgery more cost-effective and broadly accessible, ensuring its benefits can reach a wider patient population. This abstract encapsulates the key aspects of robotic surgery's development, comparative studies with conventional methods, and its clinical benefits and limitations, highlighting the need for ongoing improvements and research.

Oxygen reserve index versus conventional peripheral oxygen saturation for prevention of hypoxaemia: A randomised controlled trial.

BACKGROUND: Hypoxaemia occurs frequently during paediatric laryngeal microsurgery. OBJECTIVE: The oxygen reserve index is a noninvasive and continuous parameter to assess PaO2 levels in the range of 100 to 200 mmHg. It ranges from 0 to 1.0. We investigated whether monitoring the oxygen reserve index can reduce the incidence of SpO2 90% or less. DESIGN: Randomised controlled trial. SETTING: A tertiary care paediatric hospital. PARTICIPANTS: Paediatric patients aged 18 years or less scheduled to undergo laryngeal microsurgery. INTERVENTION: The patients were randomly allocated to the oxygen reserve index or control groups, and stratified based on the presence of a tracheostomy tube. Rescue intervention was performed when the oxygen reserve index was 0.2 or less and the SpO2 was 94% or less in the oxygen reserve index and control groups, respectively. MAIN OUTCOME MEASURE: The primary outcome was the incidence of SpO2 90% or less during the surgery. RESULTS: Data from 88 patients were analysed. The incidence of SpO2 ≤ 90% did not differ between the oxygen reserve index and control groups [P = 0.114; 11/44, 25% vs. 18/44, 40.9%; relative risk: 1.27; and 95% confidence interval (CI): 0.94 to 1.72]. Among the 128 rescue interventions, SpO2 ≤ 90% event developed in 18 out of 75 events (24%) and 42 out of 53 events (79.2%) in the oxygen reserve index and control groups, respectively (P < 0.001; difference: 55.2%; and 95% CI 38.5 to 67.2%). The number of SpO2 ≤ 90% events per patient in the oxygen reserve index group (median 0, maximum 3) was less than that in the control group (median 0, maximum 8, P = 0.031). CONCLUSION: Additional monitoring of the oxygen reserve index, with a target value of greater than 0.2 during paediatric airway surgery, alongside peripheral oxygen saturation, did not reduce the incidence of SpO2 ≤ 90%.

Genetic Deletion of Skeletal Muscle Inositol Polyphosphate Multikinase Disrupts Glucose Homeostasis and Impairs Exercise Tolerance.

Inositol phosphates are critical signaling messengers involved in a wide range of biological pathways in which inositol polyphosphate multikinase (IPMK) functions as a rate-limiting enzyme for inositol polyphosphate metabolism. IPMK has been implicated in cellular metabolism, but its function at the systemic level is still poorly understood. Since skeletal muscle is a major contributor to energy homeostasis, we have developed a mouse model in which skeletal muscle IPMK is specifically deleted and examined how a loss of IPMK affects whole-body metabolism. Here, we report that mice in which IPMK knockout is deleted, specifically in the skeletal muscle, displayed an increased body weight, disrupted glucose tolerance, and reduced exercise tolerance under the normal diet. Moreover, these changes were associated with an increased accumulation of triglyceride in skeletal muscle. Furthermore, we have confirmed that a loss of IPMK led to reduced beta-oxidation, increased triglyceride accumulation, and impaired insulin response in IPMK-deficient muscle cells. Thus, our results suggest that IPMK mediates the whole-body metabolism via regulating muscle metabolism and may be potentially targeted for the treatment of metabolic syndromes.

Real world prescription of beta-blockers in patients with asthma.

PURPOSE: This study aimed to investigate the prescription of beta-blockers (ß-blockers) for patients with asthma. METHODS: In this retrospective cross-sectional study using the National Patient Sample (NPS) of the Health Insurance Review and Assessment Service (HIRA) of South Korea, ß-blockers and asthma medications were investigated using generic name codes provided by HIRA. Concomitant administration was identified when a ß-blocker and an asthma medication were co-prescribed in one billing statement or when separate ß-blocker and asthma prescriptions had overlapping dates of use. RESULTS: In the 1027 patients with asthma who were prescribed non-selective ß-blockers (non-SBs), 3087 non-SB prescriptions were identified, of which 62.3% and 37.3% were for carvedilol and propranolol, respectively. Of the 906 patients with asthma prescribed selective ß-blockers (SBs), 2942 SB prescriptions were identified, of which 48.5%, 28.3%, and 20.3% were for bisoprolol, atenolol, and nebivolol, respectively. Overall, 2149 non-SB and 2124 SB prescriptions with overlapping use dates with asthma medications were identified, which were prescribed to 726 and 657 patients, accounting for 70.7% and 72.5% of the patients receiving non-SBs and SBs, respectively. ß2-agonists accounted for 39.9% of the concomitant asthma medications with overlapping dates of use with non-SBs. Co-prescribing of bronchodilators occurred at a rate of 38.7% and 45.1% for the 3087 non-SB prescriptions and 2942 SB prescriptions, respectively. CONCLUSIONS: Carvedilol and propranolol accounted for half of all ß-blockers prescribed to asthma patients. Prescribing ß-blockers to patients with asthma requires caution to prevent exacerbation of asthma and drug interactions between ß-blockers and co-prescribed asthma medications.

ALK5/VEGFR2 dual inhibitor TU2218 alone or in combination with immune checkpoint inhibitors enhances immune-mediated antitumor effects.

Transforming growth factor ß (TGFß) is present in blood of patients who do not respond to anti-programmed cell death (ligand) 1 [PD-(L)1] treatment, and through synergy with vascular endothelial growth factor (VEGF), it helps to create an environment that promotes tumor immune evasion and immune tolerance. Therefore, simultaneous inhibition of TGFß/VEGF is more effective than targeting TGFß alone. In this study, the dual inhibitory mechanism of TU2218 was identified through in vitro analysis mimicking the tumor microenvironment, and its antitumor effects were analyzed using mouse syngeneic tumor models. TU2218 directly restored the activity of damaged cytotoxic T lymphocytes (CTLs) and natural killer cells inhibited by TGFß and suppressed the activity and viability of regulatory T cells. The inactivation of endothelial cells induced by VEGF stimulation was completely ameliorated by TU2218, an effect not observed with vactosertib, which inhibits only TGFß signaling. The combination of TU2218 and anti-PD1 therapy had a significantly greater antitumor effect than either drug alone in the poorly immunogenic B16F10 syngeneic tumor model. The mechanism of tumor reduction was confirmed by flow cytometry, which showed upregulated VCAM-1 expression in vascular cells and increased influx of CD8 + CTLs into the tumor. As another strategy, combination of anti-CTLA4 therapy and TU2218 resulted in high complete regression (CR) rates in CT26 and WEHI-164 tumor models. In particular, immunological memory generated by the combination of anti-CTLA4 and TU2218 in the CT26 model prevented the development of tumors after additional tumor cell transplantation, suggesting that the TU2218-based combination has therapeutic potential in immunotherapy.

Territories of Nerve Endings of the Medial Plantar Nerve within the Abductor Hallucis Muscle: Clinical Implications for Potential Pain Management.

This study aimed to elucidate the intramuscular distribution pattern of the medial plantar nerve and determine its motor nerve ending territories within the abductor hallucis muscle using modified Sihler's staining and external anatomical landmarks. The study included 40 specimens of the abductor hallucis muscle (13 men and seven women) from formalin-fixed (ten cadavers) and fresh cadavers (ten cadavers), with a mean age of 77.6 years. The entry point of the medial plantar nerve into the muscle was examined, followed by Sihler's staining to analyze the intramuscular distribution pattern and motor nerve ending location within the abductor hallucis muscle. Ultrasound- and palpation-guided injections were performed to verify the applicability of motor nerve ending location-based injections. The areas with the highest concentrations of nerve entry points and nerve endings were identified in the central portion of the muscle. Ultrasound- and palpation-guided injections were safely positioned near the densest nerve ending region of the muscle. These detailed anatomical data and injection methods would be beneficial for proceeding with safe and effective injection treatments using various analgesic agents to alleviate abductor hallucis muscle-associated pain disorders.

Sihler's staining of the anterior belly of digastric muscle for botulinum toxin injection.

PURPOSE: The anterior belly of the digastric muscle (ABDM) is the target of botulinum toxin injection; however, anatomical considerations related to the injection point are absent. This study used Sihler's staining to analyze the intramuscular nerve distribution of ABDM to identify the most effective botulinum toxin injection points. METHODS: We used 12 specimens from 6 embalmed cadavers in this study. The specimens were manually dissected to preserve the mylohyoid nerve and subjected to Sihler's staining. From the gnathion to and hyoid bone, the ABDM was divided into three equal parts, distinguishing the anterior, middle, and posterior thirds. RESULTS: Only a branch of the mylohyoid nerve entered the ABDM, and its entry point was located in the middle-third region in all cases. The nerve endings were concentrated in the middle third (100%), followed by the anterior third (58.3%) and were not observed in the posterior third. CONCLUSION: The landmarks used in this study (gnathion and hyoid bone) are easily palpable on the skin surface, allowing clinicians to target the most effective injection site (middle third of ABDM). These results provide scientific and anatomic evidence for injection points, and will aid in the management of ABDM injection procedures in clinical practice.