EP4 receptor agonist CAY10598 upregulates ROS-dependent Hsp90 cleavage in colorectal cancer cells.

Prostaglandin E2 (PGE2) interacts with four specific G protein-coupled receptors, namely EP1, EP2, EP3, and EP4, playing a pivotal role in determining the fate of cells. Our previous findings highlighted that stimulating the EP4 receptor with its agonist, CAY10598, triggers apoptosis in colon cancer HCT116 cells via the production of reactive oxygen species (ROS). This process also reduces the phosphorylation of the oncogenic protein JAK2 and leads to its degradation in these cells. In this study, our goal was to explore the pathways through which CAY10598 leads to JAK2 degradation. We focused on Hsp90, a heat shock protein family member known for its role as a molecular chaperone maintaining the stability of several key proteins including EGFR, MET, Akt, and JAK2. Our results show that CAY10598 decreases the levels of client proteins of Hsp90 in HCT116 cells, an effect reversible by pretreatment with the ROS scavenger N-acetyl cysteine (NAC) or the proteasome inhibitor MG132, indicating that the degradation is likely driven by ROS. Furthermore, we observed that CAY10598 cleaves both α and ß isoforms of Hsp90, the process inhibited by NAC. Inhibition of EP4 with the antagonist GW627368x not only prevented the degradation of Hsp90 client proteins but also the cleavage of Hsp90 itself in CAY10598-treated HCT116 cells. Additionally, CAY10598 suppressed the growth of HCT116 cells implanted in mice. Our findings reveal that CAY10598 induces apoptosis in cancer cells by a novel mechanism involving the ROS-dependent cleavage of Hsp90, thereby inhibiting the function of crucial Hsp90 client proteins.

Identification of a new bovine picornavirus (Boosepivirus) in the Republic of Korea.

IMPORTANCE: Despite advancements in herd management, feeding, and pharmaceutical interventions, neonatal calf diarrhea (NCD) remains a major global health concern. Bacteria, viruses, and parasites are the major contributors to NCD. Although several pathogens have been identified in the Republic of Korea (ROK), the etiological agents of numerous NCD cases have not been identified. OBJECTIVES: To identify, for the first time, the prevalence and impact of Boosepivirus (BooV) on calf diarrhea in the ROK. METHODS: Here, the unknown cause of calf diarrhea was determined using metagenomics We then explored the prevalence of certain pathogens, including BooV, that cause NCD. Seventy diarrheal fecal samples from Hanwoo (Bos taurus coreanae) calves were analyzed using reverse transcriptase and quantitative real-time polymerase chain reaction for pathogen detection and BooV isolate sequencing. RESULTS: The complete genome of BooV was detected from unknown causes of calf diarrhea. And also, BooV was the most frequently detected pathogen (35.7%) among 8 pathogens in 70 diarrheic feces from Hanwoo calves. Co-infection analyses indicated that most BooV-positive samples were solely infected with BooV, indicating its significance in NCD in the ROK. All isolates were classified as BooV B in phylogenetic analysis. CONCLUSIONS AND RELEVANCE: This is the first study to determine the prevalence and molecular characteristics of BooV in calf diarrhea in the ROK, highlighting the potential importance of BooV as a causative agent of calf diarrhea and highlighting the need for further research on its epidemiology and pathogenicity.

Age-associated contraction of tumor-specific T cells impairs antitumor immunity.

Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses. By systematically mapping immune cell profiles within tumors, we identified loss of tumor antigen-specific CD8+ T cells as a primary feature accelerating the growth of tumors in aged mice and driving resistance to immunotherapy. When antigen-specific T cells from young adult mice were administered to aged mice, tumor outgrowth was delayed and the aged animals became sensitive to PD-1 blockade. These studies reveal how age-associated CD8+ T-cell dysfunction may license tumorigenesis in elderly patients and have important implications for the use of aged mice as pre-clinical models of aging and cancer.

Prevalence, Isolation, and Molecular Characterizationof Severe Fever with Thrombocytopenia Syndrome Virus in Cattle from the Republic of Korea.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by Bandavirus dabieense. Initially identified in China, this disease has spread throughout Asian countries via tick bites and animal-to-human transmission. However, reports of the prevalence of SFTS virus (SFTSV) in cattle in Korea are lacking. This study aimed to investigate SFTSV infections in grazing cattle in the Republic of Korea (ROK). Materials and Methods: In total, 845 grazing cattle serum samples were collected over 2 years (2019 and 2020) in the ROK, and viral RNA was extracted using a kit. One-step RT-nested PCR was performed to amplify the S-segment of SFTSV. Positive serum samples were used to isolate SFTSV in Vero E6 cells, and the full sequences were analyzed. A phylogenetic tree was constructed using the maximum-likelihood method with MEGA X. In addition, immunoglobulin G antibodies against SFTSV were investigated using an enzyme-linked immunosorbent assay. Results: Here, 4.0% of serum samples (34/845) were positive for SFTSV S-segments, and one virus isolate was cultured in Vero E6 cells. Phylogenetic analysis based on the partial S-segment classified 4 SFTSV isolates as the B-2 genotype, 9 as the B-3 genotype, 18 as an unclassified B genotype, and 3 as the D genotype. One cultured virus was classified as the B-2 genotype based on SFTSV L-, M-, and S-segments. Antibody detection results showed that 21.1% of serum samples (161/763) were positive for SFTSV. Conclusion: To the best of our knowledge, this is the first study performed to identify the prevalence of SFTSV in grazing cattle in the ROK. Our findings indicate the necessity for more intensive and continuous SFTSV monitoring, not only in cattle but also in other animals, to comprehend the genetic diversity of the virus and its potential eco-epidemiological impact on human health.

Molecular surveillance of zoonotic pathogens from wild rodents in the Republic of Korea.

BACKGROUND: Rodents are recognized as major reservoirs of numerous zoonotic pathogens and are involved in the transmission and maintenance of infectious diseases. Furthermore, despite their importance, diseases transmitted by rodents have been neglected. To date, there have been limited epidemiological studies on rodents, and information regarding their involvement in infectious diseases in the Republic of Korea (ROK) is still scarce. METHODOLOGY/PRINCIPAL FINDINGS: We investigated rodent-borne pathogens using nested PCR/RT-PCR from 156 rodents including 151 Apodemus agrarius and 5 Rattus norvegicus from 27 regions in eight provinces across the ROK between March 2019 and November 2020. Spleen, kidney, and blood samples were used to detect Anaplasma phagocytophilum, Bartonella spp., Borrelia burgdorferi sensu lato group, Coxiella burnetii, Leptospira interrogans, and severe fever with thrombocytopenia syndrome virus (SFTSV). Of the 156 rodents, 73 (46.8%) were infected with Bartonella spp., 25 (16.0%) with C. burnetii, 24 (15.4%) with L. interrogans, 21 (13.5%) with A. phagocytophilum, 9 (5.8%) with SFTSV, and 5 (3.2%) with Borrelia afzelii. Co-infections with two and three pathogens were detected in 33 (21.1%) and 11 rodents (7.1%), respectively. A. phagocytophilum was detected in all regions, showing a widespread occurrence in the ROK. The infection rates of Bartonella spp. were 83.3% for B. grahamii and 16.7% for B. taylorii. CONCLUSIONS/SIGNIFICANCE: To the best of our knowledge, this is the first report of C. burnetii and SFTSV infections in rodents in the ROK. This study also provides the first description of various rodent-borne pathogens through an extensive epidemiological survey in the ROK. These results suggest that rodents harbor various pathogens that pose a potential threat to public health in the ROK. Our findings provide useful information on the occurrence and distribution of zoonotic pathogens disseminated among rodents and emphasize the urgent need for rapid diagnosis, prevention, and control strategies for these zoonotic diseases.

Wound healing induced by new synthetic peptide, A7-1, in C57BL/6 mouse model.

The effects of the novel synthetic peptide, A7-1, on wound healing and skin grafts were evaluated in a C57BL/6 mouse model. Two 15-mm wide circular skin excisions were made on the backs of mice and to each excision, 100 µM A7-1 or normal saline was applied daily. The treatments were applied and sutured for skin graft analysis. Digital photos were acquired on days 4, 7, 11, and 14 and fluorescein angiography was conducted. Wound sizes were verified using stereoscopic microscopy. Histological analysis was performed via hematoxylin and eosin staining and Masson's trichrome staining. Western blotting was performed using vascular endothelial growth factor. Using a stereoscopic microscope, significantly faster wound healing (17.3%) and skin graft healing (16.5%) were observed in the A7-1 treatment group in comparison to that of the control. The angiogenesis was significantly faster in fluorescein angiography examination in wound healing (11%) and skin grafts (15%). However, the average completion of epithelization (overall time for wound healing), did not show any significant differences. In comparison to the control, the new protein, A7-1, led to significantly faster wound healing in the initial angiogenesis.

Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells.

Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase- 3, -7, and -9 cleavage. Domperidone decreased in formation of ß-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways, respectively. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.

GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans.

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are effective antiobesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to patients with obesity and observed a heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1 receptor (GLP-1R) neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic manipulation of DMHGLP-1R neurons caused satiation. Calcium imaging demonstrated that these neurons are actively involved in encoding preingestive satiation. GLP-1RA administration increased the activity of DMHGLP-1R neurons selectively during eating behavior. We further identified that an intricate interplay between DMHGLP-1R neurons and neuropeptide Y/agouti-related peptide neurons of the arcuate nucleus (ARCNPY/AgRP neurons) occurs to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering previously unexplored neural targets for obesity and metabolic diseases.

Effect of Pravastatin on Kidney Function in Patients with Dyslipidemia and Type 2 Diabetes Mellitus: A Multicenter Prospective Observational Study.

INTRODUCTION: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice. METHODS: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety. RESULTS: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks. CONCLUSION: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. TRIAL REGISTRATION NUMBER: NCT05107063 submitted October 27, 2021.

First detection of Bandavirus dabieense in ticks collected from migratory birds in the Republic of Korea.

The causative agent of severe fever with thrombocytopenia syndrome (SFTS) is Bandavirus dabieense, an emerging tick-borne zoonotic pathogen. Migratory birds have often been suggested as potential carriers of ticks that can transmit Bandavirus dabieense; however, their role remains unclear. The Republic of Korea (ROK) holds an important position as a stopover on the East Asian-Australasian Flyway. The present study aimed to investigate the potential involvement of migratory birds in the transmission of the SFTS virus (SFTSV) in the ROK. A total of 4,497 ticks were collected across various regions, including Heuksando and Daecheongdo, in the ROK, from bird migration seasons in 2022 and 2023. Genetic analysis of the SFTSV was performed for 96 ticks collected from 20 different species of migratory birds. Polymerase chain reaction (PCR) fragments of SFTSV were detected in one Haemaphysalis concinna nymph collected from a Black-faced Bunting (Emberiza spodocephala) and one Ixodes turdus nymph collected from an Olive-backed Pipit (Anthus hodgsoni) on Daecheongdo and Heuksando, respectively, during their northward migration in two spring seasons. This finding suggests that migratory birds can be considered as possible carriers and long-distance dispersers of ticks and associated tick-borne diseases. This study highlights the importance of clarifying the role and impact of migratory birds in the rapid expansion of tick-borne diseases, facilitating enhanced preparedness and the development of mitigation measures against emerging SFTS across and beyond East Asia.

A Late Presentation of Right Common Iliac Vein Stent Embolization to the Right Atrium: Important Management Considerations.

Stent migration is a rare but serious complication of venous stenting, often presenting with chest pain, shortness of breath, and signs of heart failure. Potential complications include arrhythmia, perforation, and valve destruction. Here we present an asymptomatic patient with a late presentation of right common iliac vein stent migration to the right atrium.

MicroRNA-135b-5p Is a Pathologic Biomarker in the Endothelial Cells of Arteriovenous Malformations.

Arteriovenous malformations (AVMs) are congenital vascular anomalies with a poor prognosis. AVMs are considered intractable diseases, as there is no established approach for early diagnosis and treatment. Therefore, this study aimed to provide new evidence by analyzing microRNAs (miRNAs) associated with AVM. We present fundamental evidence for the early diagnosis and treatment of AVM by analyzing miRNAs in the endothelial cells of AVMs. This study performed sequencing and validation of miRNAs in endothelial cells from normal and AVM tissues. Five upregulated and two downregulated miRNAs were subsequently analyzed under hypoxia and vascular endothelial growth factor (VEGF) treatment by one-way analysis of variance (ANOVA). Under hypoxic conditions, miR-135b-5p was significantly upregulated in the AVM compared to that under normal conditions, corresponding to increased endothelial activity (p-value = 0.0238). VEGF treatment showed no significant increase in miR-135b-5p under normal conditions, however, a surge in AVM was observed. Under both hypoxia and VEGF treatment, comparison indicated a downregulation of miR-135b-5p in AVM. Therefore, miR-135b-5p was assumed to affect the pathophysiological process of AVM and might play a vital role as a potential biomarker of AVMs for application related to diagnosis and treatment.

Effect of the sodium-glucose cotransporter-2 inhibitor, DWP16001, as an add-on therapy to insulin for diabetic dogs: A pilot study.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of anti-hyperglycaemic agents. OBJECTIVE: This study aimed to evaluate the safety and the adjuvant glycaemic control effect of an SGLT2 inhibitor, DWP16001, in diabetic dogs receiving insulin treatment. METHODS: Nineteen diabetic dogs receiving insulin treatment (NPH, porcine lente and glargine insulin) were divided into two groups according to dosing frequency: DWP TOD group (n = 10) and DWP SID group (n = 9). In the DWP TOD group, 0.025 mg/kg of DWP16001 was administered once every 3 days, whereas, in the DWP SID group, 0.025 mg/kg of DWP16001 was administered once a day. Food intake was maintained during the trial period. Hypoglycaemia, ketoacidosis or unexpected life-threatening reactions were assessed as adverse effects before and after DWP16001 administration. We compared insulin requirement reduction and blood glucose level control between two groups. RESULTS: No specific adverse effects were observed during the clinical trial, and haematological parameter remained unchanged. Moreover, the fasting glucose levels and daily insulin dose in the DWP TOD group were lower than the pre-administration values, but not significantly different for 8 weeks. Systolic blood pressure, fructosamine and insulin dose decreased significantly in the DWP SID group compared to the DWP TOD group at 8 weeks (p < 0.05) without affecting food consumption. Among these patients, 10 patients were monitored while receiving DWP16001 for 12 months (DWP TOD group n = 5, DWP SID group n = 5). The fasting glucose and fructosamine levels and daily insulin dose were reduced in both groups at 12 months compared with those before receiving DWP16001. CONCLUSION: When DWP16001, an SGLT2 inhibitor, was supplied to dogs with type 1 diabetes, no adverse effects were observed, and it was confirmed that the administered insulin dose can be reduced in controlling blood glucose.

Effect of Kaempferol on Modulation of Vascular Contractility Mainly through PKC and CPI-17 Inactivation.

In this study, we investigated the efficacy of kaempferol (a flavonoid found in plants and plant-derived foods such as kale, beans, tea, spinach and broccoli) on vascular contractibility and aimed to clarify the detailed mechanism underlying the relaxation. Isometric contractions of divested muscles were stored and linked with western blot analysis which was carried out to estimate the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to estimate the effect of kaempferol on the RhoA/ROCK/CPI-17 pathway. Kaempferol conspicuously impeded phorbol ester-, fluoride- and a thromboxane mimetic-derived contractions regardless of endothelial nitric oxide synthesis, indicating its direct effect on smooth muscles. It also conspicuously impeded the fluoride-derived elevation in phospho-MYPT1 rather than phospho-CPI-17 levels and phorbol 12,13-dibutyrate-derived increase in phospho-CPI-17 and phospho-ERK1/2 levels, suggesting the depression of PKC and MEK activities and subsequent phosphorylation of CPI-17 and ERK1/2. Taken together, these outcomes suggest that kaempferol-derived relaxation incorporates myosin phosphatase retrieval and calcium desensitization, which appear to be modulated by CPI-17 dephosphorylation mainly through PKC inactivation.

Vaccine Development for Severe Fever with Thrombocytopenia Syndrome Virus in Dogs.

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4 days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs.

Interpretation of Complete Tumor Response on MRI Following Chemoradiotherapy of Rectal Cancer: Inter-Reader Agreement and Associated Factors in Multi-Center Clinical Practice.

OBJECTIVE: To measure inter-reader agreement and identify associated factors in interpreting complete response (CR) on magnetic resonance imaging (MRI) following chemoradiotherapy (CRT) for rectal cancer. MATERIALS AND METHODS: This retrospective study involved 10 readers from seven hospitals with experience of 80-10210 cases, and 149 patients who underwent surgery after CRT for rectal cancer. Using MRI-based tumor regression grading (mrTRG) and methods employed in daily practice, the readers independently assessed mrTRG, CR on T2-weighted images (T2WI) denoted as mrCRT2W, and CR on all images including diffusion-weighted images (DWI) denoted as mrCRoverall. The readers described their interpretation patterns and how they utilized DWI. Inter-reader agreement was measured using multi-rater kappa, and associated factors were analyzed using multivariable regression. Correlation between sensitivity and specificity of each reader was analyzed using Spearman coefficient. RESULTS: The mrCRT2W and mrCRoverall rates varied widely among the readers, ranging 18.8%-40.3% and 18.1%-34.9%, respectively. Nine readers used DWI as a supplement sequence, which modified interpretations on T2WI in 2.7% of cases (36/1341 [149 patients × 9 readers]) and mostly (33/36) changed mrCRT2W to non-mrCRoverall. The kappa values for mrTRG, mrCRT2W, and mrCRoverall were 0.56 (95% confidence interval: 0.49, 0.62), 0.55 (0.52, 0.57), and 0.54 (0.51, 0.57), respectively. No use of rectal gel, larger initial tumor size, and higher initial cT stage exhibited significant association with a higher inter-reader agreement for assessing mrCRoverall (P ≤ 0.042). Strong negative correlations were observed between the sensitivity and specificity of individual readers (coefficient, -0.718 to -0.963; P ≤ 0.019). CONCLUSION: Inter-reader agreement was moderate for assessing CR on post-CRT MRI. Readers' varying standards on MRI interpretation (i.e., threshold effect), along with the use of rectal gel, initial tumor size, and initial cT stage, were significant factors associated with inter-reader agreement.

A Study on the Effectiveness of Helmet Therapy for Cranial Deformations According to Cranial Shape.

BACKGROUND: To investigate the effects of helmet therapy on plagiocephaly, according to head circumference, cephalic index (CI), and skull height. Plagiocephaly is a condition in which the skull is congenitally asymmetrical or affected by acquired factors such as compression in the womb or the habit of sleeping on one side. Although there are numerous studies on the effectiveness of helmet therapy for plagiocephaly, research on its effectiveness on skull shape is lacking. METHODS: We conducted a prospective study on 400 patients who underwent helmet therapy. The infants were enrolled and the therapy was explained to the caregiver when the child had positional plagiocephaly and had a cranial vault asymmetry (CVA) exceeding 10 mm or a CVA index (CVAI) exceeding 3.5%. The CVA and CVAI changes were compared to investigate the effectiveness of helmet therapy according to head circumference, CI, and skull height. RESULTS: A significant treatment effect was observed for CI values between 90 and 103. The treatment effect was found to increase with greater skull height. However, no significant difference was observed in the effectiveness of helmet therapy according to head circumference. CONCLUSIONS: According to the findings, the effectiveness of helmet therapy in children with positional plagiocephaly is greater for children with higher skulls and for those with CI values between 90 and 103; it is unrelated to head circumference. Based on these results, we can provide predictions of the effectiveness of helmet therapy to caregivers of children with positional plagiocephaly.

Postoperative Scar Management Using Laser Therapy for Breast Reconstruction With Latissimus Dorsi Flap.

BACKGROUND: Postoperative scar formation is inevitable, and a gold standard management has not been established to date. Due to the fact long and large scar formation occurs in reconstructive surgery, this study analyzed the relationship between various factors in patients who received breast reconstruction using latissimus dorsi (LD) flap to investigate appropriate and effective management approaches. PATIENTS AND METHODS: Twenty-seven patients who underwent breast reconstruction between June 2014 and January 2015 received laser therapy on their LD donor site at the Kyungpook National University Chilgok Hospital. Scar evaluation was performed on both the surgical scar and intact skin on the contralateral side. Scar evaluation was conducted at five specific points, 2 cm from the midpoint of the scar on each side. Laser treatment was performed at 4-week intervals, and patients were then followed-up for 6 months. To assess scars, gross images were taken using the same settings. In addition, spectrophotometry was used for color assessment, durometer for texture and pressure evaluation, and Vernier calipers and height gauges for a more precise and objective approach. RESULTS: The mean age of the participants was 45.7 years, and the mean body mass index was 22.1 kg/m2 The operator-evaluated scar scale scores were 107.2 and 97.3 in the experimental and control groups, respectively. In the patient-rated questionnaire, the scores were 62.3 and 59.4 in the experimental and control groups, respectively. CONCLUSION: When analyzing early-stage postoperative scars based on various factors, laser therapy is considered a very useful scar management approach. Additionally, when performing reconstructive surgery, tension force is regarded as a significant factor to take into account since it affects scar widening.

External Volume Expansion: Timing and Effects on the Rate of Fat Graft Retention in BALB/c Nude Mice.

BACKGROUND/AIM: Fat grafting has been widely used for soft-tissue augmentation. External volume expansion (EVE) is a favorable tool for improvement in the rate of fat graft retention. However, few studies have focused on the most appropriate time for its implementation. In this study, BALB/c nude mice were used to investigate the effective time for the implementation of external volume expansion to improve the rate of fat retention. MATERIALS AND METHODS: Sixteen mice were divided into four groups, and EVE was performed at different time points before or both before and after fat grafting. Fat tissue from a human donor was injected into the mice following EVE. Visual assessment, micro-computed tomography analysis, and histopathological evaluation were used to assess fat retention. RESULTS: After 10 weeks, the group that underwent EVE 5 days before fat grafting demonstrated a significantly higher preserved fat volume, as determined by micro-computed tomography (p<0.05). Moreover, the group that received additional EVE after fat grafting exhibited a higher retention rate compared to the groups receiving EVE only before grafting (p<0.05). Histopathological analysis indicated that swelling, edema, and inflammation were more pronounced in the group with EVE immediately before grafting, while angiogenesis and lipogenesis were more active in the group with additional EVE after grafting. CONCLUSION: EVE is a safe and effective approach for improving the rate of fat graft retentions. Furthermore, the timing of external tissue expansion plays a crucial role in fat retention. Based on our animal study, performing EVE immediately before and after fat grafting may be an effective strategy for enhancing the rate of fat graft retentions.

Extracranial Vascular Malformations Increase Cardiovascular Disease Risk: A Nationwide Population-Based Cohort Study.

BACKGROUND: Extracranial vascular malformations affect vessel inflammation, clotting, and ischemia. However, the relationship between extracranial vascular malformations and myocardial infarction (MI) or stroke has not been fully elucidated. Limited studies have investigated the association between extracranial vascular malformations and cardiovascular diseases. METHODS: A total of 48,701 patients with extracranial vascular malformations and a control cohort with 487,010 age- and sex-matched participants from the Korean National Health Insurance database were included. The incidence and risk of MI, ischemic stroke (IS), and hemorrhagic stroke (HS) between participants with extracranial vascular malformations and the control cohort was then compared. RESULTS: After adjusting for other cardiovascular disease risk factors, the adjusted hazard ratios (aHRs) for VMs, CMs, AVMs, and LMs in patients with acute MI were 1.25 [CI 1.04-1.50], 1.41 [CI 1.24-1.61], 1.68 [CI 1.18-2.37], and 1.40 [CI 1.31-1.48], respectively. For IS, the aHRs were 1.55 [CI 1.35-1.77], 1.92 [CI 1.74-2.11], 1.13 [CI 0.78-1.64], and 1.51 [CI 1.44-1.58], respectively. For HS, the aHRs were 1.51 [CI 1.12-2.05], 5.63 [CI 4.97-6.38], 2.93 [CI 1.82-4.72], and 1.34 [CI 1.20-1.50], respectively. CONCLUSIONS: Independent of cardiovascular risk factors, extracranial vascular malformations were associated with an increased risk of MI, IS, and HS. For patients with CMs and AVMs, intracerebral hemorrhage risk was particularly high, accounting for 563% and 293%, respectively. Therefore, even in patients with extracranial CMs or AVMs, performing diagnostic evaluations for cerebral AVMs and employing measures to prevent intracerebral hemorrhage are very crucial.