Background: Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by duplication of the 17p12 region including PMP22 gene. In CMT1A patients, anticipation showing increased severity by generations has been reported in the CMT1A patients. It has also been reported that severity increases in the non-de novo cases than in the de novo cases. This study was performed to examine epigenetic differences between CMT1A cases and controls as well as between de novo cases and non-de novo cases. Methods: This study examined 40 Korean CMT1A patients and 11 controls. Methylation level was determined using the SureSelect XT Methyl-Seq reagent kit and bisulfite sequence mapping program. Results: Many differentially methylated CpG sites (DMCs) were identified in the comparisonbetween cases and controls and between de novo cases and non-de novo cases. Most DMCs were located within or nearby genes related to the nervous system, mental stress, and motor ability. Conclusions This study is the first epigenetic study to uncover the mechanism of clinical heterogeneity among CMT1A patients. We suggest that weak severity in the de novo cases than the non-de novo cases may be related to the epigenomic differences in the nerve and stress-related genes.

Background: The use of acellular dermal matrix in implant-based breast reconstruction immediately after mastectomy has attracted attention in recent years because it yields good outcomes. Herein, we analyzed the usefulness of meshed SurgiMend in direct-to-implant (DTI) breast reconstruction. Methods: In this retrospective single-center analysis, 44 one-stage breast reconstructions using SurgiMend were performed in 42 patients from May 2016 to December 2017. The implant was inserted into the subpectoral plane and SurgiMend was applied to the inferolateral part that lacked tissues to wrap the silicone implant. In 19 patients (20 breasts), fenestration was performed with SurgiMend, while in the remaining 23 patients (24 breasts), SurgiMend that was meshed at a ratio of 1:1.5 was used. We analyzed the frequency of complications. Patient satisfaction was compared and analyzed using a five-item questionnaire (shape, texture, symmetry, pain, and overall outcome). Results: The average age of the patients was 43.2 years, and their mean body mass index was 21.1 kg/m2. The average follow-up period was 24.0 months. In the control (fenestrated SurgiMend) and experimental (meshed SurgiMend) groups, major seroma occurred in five of the 20 breasts (25.0%) and two of the 24 breasts (8.3%), respectively. Minor complications were resolved with conservative treatment. The patient satisfaction score for shape, texture, symmetry, pain, and overall satisfaction was 4.3, 4.1, 4.7, 4.5, and 4.4, respectively. Conclusions Applying meshed SurgiMend in DTI breast reconstruction is a useful surgical technique.

Decision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality. Materials and Methods The validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)–free survival, cancer-specific survival (CSS), and overall survival (OS). Results Excellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation. Conclusion The SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.

Stroke causes systemic immunosuppression. T lymphocytes are involved in infarct size in the early stages of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well analyzed in the acute and chronic phases of stroke. Here, we investigated pathological phenotypic alterations in the systemic immune response, especially changes in T lymphocytes, from one day to six months after ischemic stroke in mice. Impairment in thymocyte numbers, development, proliferation, and apoptosis were observed for up to two weeks. The number of mature T cells in the spleen and blood decreased and showed reduced interferon-γ production. Increased numbers of CD4-CD8-CD3+ double-negative T cells were observed in the mouse brain during the early stages of stroke, whereas interleukin (IL)-10+Foxp3+ regulatory T lymphocytes increased from two weeks during the chronic phase. These phenotypes correlated with body weight and neurological severity scores. The recovery of T lymphocyte numbers and increases in IL-10+Foxp3+ regulatory T lymphocytes may be important for long-term neurological outcomes. Dynamic changes in T lymphocytes between the acute and chronic phases may play different roles in pathogenesis and recovery. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs following stroke.

Background: The use of acellular dermal matrix in implant-based breast reconstruction immediately after mastectomy has attracted attention in recent years because it yields good outcomes. Herein, we analyzed the usefulness of meshed SurgiMend in direct-to-implant (DTI) breast reconstruction. Methods: In this retrospective single-center analysis, 44 one-stage breast reconstructions using SurgiMend were performed in 42 patients from May 2016 to December 2017. The implant was inserted into the subpectoral plane and SurgiMend was applied to the inferolateral part that lacked tissues to wrap the silicone implant. In 19 patients (20 breasts), fenestration was performed with SurgiMend, while in the remaining 23 patients (24 breasts), SurgiMend that was meshed at a ratio of 1:1.5 was used. We analyzed the frequency of complications. Patient satisfaction was compared and analyzed using a five-item questionnaire (shape, texture, symmetry, pain, and overall outcome). Results: The average age of the patients was 43.2 years, and their mean body mass index was 21.1 kg/m2. The average follow-up period was 24.0 months. In the control (fenestrated SurgiMend) and experimental (meshed SurgiMend) groups, major seroma occurred in five of the 20 breasts (25.0%) and two of the 24 breasts (8.3%), respectively. Minor complications were resolved with conservative treatment. The patient satisfaction score for shape, texture, symmetry, pain, and overall satisfaction was 4.3, 4.1, 4.7, 4.5, and 4.4, respectively. Conclusions Applying meshed SurgiMend in DTI breast reconstruction is a useful surgical technique.

Decision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality. Materials and Methods The validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)–free survival, cancer-specific survival (CSS), and overall survival (OS). Results Excellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation. Conclusion The SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.

Stroke causes systemic immunosuppression. T lymphocytes are involved in infarct size in the early stages of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well analyzed in the acute and chronic phases of stroke. Here, we investigated pathological phenotypic alterations in the systemic immune response, especially changes in T lymphocytes, from one day to six months after ischemic stroke in mice. Impairment in thymocyte numbers, development, proliferation, and apoptosis were observed for up to two weeks. The number of mature T cells in the spleen and blood decreased and showed reduced interferon-γ production. Increased numbers of CD4-CD8-CD3+ double-negative T cells were observed in the mouse brain during the early stages of stroke, whereas interleukin (IL)-10+Foxp3+ regulatory T lymphocytes increased from two weeks during the chronic phase. These phenotypes correlated with body weight and neurological severity scores. The recovery of T lymphocyte numbers and increases in IL-10+Foxp3+ regulatory T lymphocytes may be important for long-term neurological outcomes. Dynamic changes in T lymphocytes between the acute and chronic phases may play different roles in pathogenesis and recovery. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs following stroke.

BACKGROUND: Chronic exposure to elevated levels of free fatty acids contributes to pancreatic β-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic β-cells. We therefore examined the effects of metformin on pancreatic β-cells under lipotoxic stress.METHODS: NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis.RESULTS: We found that metformin has protective effects on palmitate-induced β-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK.CONCLUSION: This study suggests that the action of metformin on β-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic β-cell dysfunction through inhibition of oxidative stress and ER stress.
Adenosine Triphosphate ; AMP-Activated Protein Kinases ; Animals ; Blotting, Western ; Cell Survival ; Electron Transport ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Fatty Acids, Nonesterified ; Insulin ; Insulin-Secreting Cells ; Metformin ; Mice ; NADPH Oxidase ; Oxidative Stress ; Phosphorylation ; Polymerase Chain Reaction ; Reactive Oxygen Species ; rho-Associated Kinases ; RNA, Messenger

In recent years, there has been a notable increase in the rate of refractory donor site seroma, defined as seroma that persists for at least 3 months postoperatively, as the number of breast reconstructions using a latissimus dorsi (LD) musculocutaneous flap has increased. Various factors have been proposed to be related, including smoking, obesity, flap mass, and body weight, and several studies have been conducted to explore treatment methods. Typically, surgical treatment, such as capsulectomy, has been considered for refractory seroma, but in this case report, we describe positive outcomes achieved by using Abnobaviscum to treat three female patients who developed a donor site seroma at least 3 months after breast reconstruction using an LD flap.
Body Weight ; Breast ; Female ; Humans ; Mammaplasty ; Myocutaneous Flap ; Obesity ; Seroma ; Smoke ; Smoking ; Superficial Back Muscles ; Tissue Donors

BACKGROUND: Recently, younger prostate cancer (PCa) patients have been reported to harbour more favourable disease characteristics after radical prostatectomy (RP) than older men. We analysed young men (< 50 years) with PCa among the Korean population, paying attention to pathological characteristics on RP specimen and biochemical recurrence (BCR). METHODS: The multi-centre, Severance Urological Oncology Group registry was utilized to identify 622 patients with clinically localized or locally advanced PCa, who were treated with RP between 2001 and 2017. Patients were dichotomized into two groups according to age (< 50-year-old [n = 75] and ≥ 50-year-old [n = 547]), and clinicopathological characteristics were analysed. Propensity score matching was used when assessing BCR between the two groups. RESULTS: Although biopsy Gleason score (GS) was lower in younger patients (P = 0.033), distribution of pathologic GS was similar between the two groups (13.3% vs. 13.9% for GS ≥ 8, P = 0.191). There was no significant difference in pathologic T stage between the < 50- and ≥ 50-year-old groups (69.3% vs. 68.0% in T2 and 30.7% vs. 32.0% in ≥ T3, P = 0.203). The positive surgical margin rates were similar between the two groups (20.0% vs. 27.6%, P = 0.178). BCR-free survival rates were also similar (P = 0.644) between the two groups, after propensity matching. CONCLUSION: Contrary to prior reports, younger PCa patients did not have more favourable pathologic features on RP specimen and showed similar BCR rates compared to older men. These findings should be considered when making treatment decisions for young Korean patients with PCa.
Biopsy ; Humans ; Korea ; Male ; Middle Aged ; Neoplasm Grading ; Passive Cutaneous Anaphylaxis ; Prognosis ; Propensity Score ; Prostate ; Prostatectomy ; Prostatic Neoplasms ; Recurrence ; Survival Rate ; Young Adult