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Colonic interposition is the main procedure used in esophageal reconstruction. We report a rare case of simultaneous treatment of an anastomotic site stricture and a neoplasm in the interpositioned colon. A 69-year-old female visited our outpatient clinic with symptoms of progressive dysphagia for 1 year. At the age of 30 years, the patient underwent esophagectomy with retrosternal colonic interposition because of severe esophageal burns after chemical ingestion. Upper gastrointestinal endoscopy revealed stricture at the anastomosis site and a 10-mm flat elevated high-grade dysplasia in the interpositioned colon. First, through-the-scope balloon dilatation was performed for strictures. However, stenosis was observed during the second upper gastrointestinal endoscopy session.Therefore, a second session of through-the-scope balloon dilatation was performed, and simultaneously, endoscopic submucosal dissection was also successfully performed. After 2 months of follow-up, stenosis persisted; consequently, balloon dilatation was performed. No recurrence of neoplasm was confirmed endoscopically. Through-the-scope balloon dilatation of the stricture site and simultaneous endoscopic submucosal dissection of the neoplasm in the interpositioned colon were successfully performed.
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Purpose@#This study aimed to compare and evaluate the shear bond strength between various temporary prostheses resin blocks fabricated by subtractive and additive manufacturing methods bonded to self-curing reline resin. @*Materials and methods@#The experimental groups were divided into 4 groups according to the manufacturing methods of the resin block specimens and each specimen was fabricated by subtractive manufacturing (SM), additive manufacturing stereolithography apparatus manufacturing (AMS), additive manufacturing digital light processing manufacturing (AMD) and conventional self-curing (CON). To bond the resin block specimens and self-curing resin, the reline resin was injected and polymerized into the same location of each resin block using a silicone mold. The shear bond strength was measured using a universal testing machine, and the surface of the adhesive interface was examined by scanning electron microscopy. To compare between groups, one-way ANOVA was done followed by Tukey post hoc test (α = 0.05). @*Results@#The shear bond strength showed higher values in the order of CON, SM, AMS, and AMD group. There were significant differences between CON and AMS groups, as well as between CON and AMD groups. but there were no significant differences between CON and SM groups (P > .05). There were significant differences between SM and AMD groups, but there were no significant differences between SM and AMS groups. The AMS group was significantly different from the AMD group (P < .001). The most frequent failure mode was mixed failures in CON and AMS groups, and adhesive failures in SM and AMD groups. @*Conclusion@#The shear bond strength of SM group showed lower but not significant bond strength compared to the CON group. The additive manufacturing method groups (AMS and AMD) showed significantly lower bond strength than the CON group, with the AMD group the lowest. There was also a significant difference between the AMD and SM group.
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Purpose@#The aim of this study was to evaluate the risk factors associated with glaucoma or ocular hypertension (OHT) in patients taking oral corticosteroids for extended periods, and to aid in managing intraocular pressure (IOP) in patients with these risk factors. @*Methods@#A cross-sectional study was performed involving 690 patients who visited a tertiary referral hospital and had been using oral corticosteroids for more than six months. Patients' demographics, tonometry results, drug type, dosage, duration, ophthalmic history, and the use of glaucoma eye drops were analyzed to determine the risk factors associated with glaucoma or OHT. @*Results@#In a generalized linear model analysis comparing patients' eyes diagnosed with glaucoma or ocular hypertension to those without such diagnoses, no statistical difference was observed between the two groups in terms of drug type, age, and duration of oral corticosteroid use. However, the dosage was found to be statistically significant (odds ratio 1.09, p = 0.0294). @*Conclusions@#No difference in the incidence of glaucoma or OHT was found based on the type of oral steroid, age, or duration of use. However, a higher incidence of glaucoma and OHT was observed among patients taking higher doses of oral steroids. Therefore, it is suggested that using lower doses of oral steroids may be more beneficial for managing IOP.
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The application of artificial intelligence (AI) and deep learning (DL) in radiology is rapidly evolving. AI in healthcare has benefits for image recognition, classification, and radiological workflows from a clinical perspective. Additionally, clinical triage AI can be applied to triage systems. This review aims to introduce the concept of DL and discuss its applications in the interpretation of magnetic resonance (MR) images and the DL-based reconstruction of accelerated MR images, with an emphasis on musculoskeletal radiology. The most recent developments and future directions are also discussed briefly.
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Purpose@#. This retrospective study was to investigate the survival and complication rates of posterior single implant according to the implant diameters, lengths and position. @*Materials and methods@#. Patients who had been restored single implant prosthesis in the posterior area by the three prosthodontists in the department of prosthodontics, Daejeon dental hospital of Wonkwang university, in the period from February 2014 to May 2018 were selected for the study. A total of 505 patients with 697 implants were observed. The survival and complications of implants were investigated using electronic medical records and radiographs. Fixture diameters, lengths, position, patient’s sex and age were assessed as possible factor affecting the survival and complications of implants. @*Results@#. 3-year cumulative survival rates of posterior single implants were 98.5% and 5-year cumulative survival rates were 94.4%. 5-year cumulative survival rates were higher in implants with diameter > 4.0 mm (97.0%) than implants with diameter ≤ 4.0 mm (89.5%), and in females (98.8%) than males (92.4%). There were statistically significant differences (P 4.0 mm than implants with diameter ≤ 4.0 mm and in females than males. Abutment screw loosening which was the most commonly occurring complication occurred more frequently in the lower molar region, in males than females, and in patients aged < 65 years than patients aged ≥ 65 years. There were statistically significant differences.
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Purpose@#Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy. @*Materials and Methods@#We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA. @*Results@#Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker. @*Conclusion@#Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.
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Background@#Recent studies suggest that MEK1/2 inhibitors, including binimetinib, significantly improve malignant melanoma (MM) patient survival. Growing evidence suggests that phytochemicals, especially curcumin, can overcome drug resistance in cancer cells through a variety of mechanisms. @*Objective@#This study aims to examine curcumin’s efficacy in vitro combined with binimetinib in human MM cells. @*Methods@#We used 2D monolayer and 3D spheroid human epidermal melanocyte culture models, HEMn-MP (human epidermal melanocytes, neonatal, moderately pigmented), and two human MM cell lines, G361 and SK-MEL-2, to evaluate cell viability, proliferation, migration, death, and reactive oxygen species (ROS) production following single therapy treatment, with either curcumin or binimetinib, or a combination of both. @*Results@#Compared to MM cells treated with single therapy, those with combination therapy showed significantly decreased cell viability and increased ROS production. We observed apoptosis following both single and combination therapies. However only those who had had combination therapy had necroptosis. @*Conclusion@#Collectively, our data demonstrates that curcumin exerts significant synergistic anticancer effects on MM cells by inducing ROS and necroptosis when combined with binimetinib. Therefore, a strategy of adding curcumin to conventional anticancer agents holds promise for treating MM.
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Objective@#Financial hardship influences depression risk, however, the pathway of the effect of financial hardship on depression and the role of self-esteem remain unclear. This study examined whether changes in financial hardship affected depression, and whether self-esteem mediated by this relationship. @*Methods@#Data from 99,588 observations of 15,331 individuals were extracted from 10 waves of the Korean Welfare Panel Study. The association between changes in financial hardship and depression was investigated using a generalized estimation equation, and the extent to which these associations were mediated by self-esteem was assessed. @*Results@#The results indicated that changes in financial hardship were associated with depression, with varying magnitude. Experiencing severe financial hardship over two consecutive years (odds ratio [OR]: 3.87, 95% confidence interval [CI]=3.09–4.85) or increased financial hardship over the previous year strongly influenced depression (e.g., OR: 3.88, 95% CI=3.09–4.86 for low financial hardship at t-1 year and high at t year). Self-esteem plays a mediating role in the relationship between changes in financial hardship and depression, where persistent financial hardship is associated with low self-esteem, leading to depression. @*Conclusion@#These findings highlighted the importance of monitoring and intervention for financial hardship and psychological problems to help manage depression.
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Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low:median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma.
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Objective@#Resuscitation-related gastric inflation is associated with inadequate ventilation and the risk of gastric regurgitation in out-of-hospital cardiac arrest (OHCA) patients. This study aims to estimate resuscitation-related gastric inflation values by using multi-detector computed tomography (MDCT) scanning. @*Methods@#MDCT imaging data were obtained from OHCA patients undergoing resuscitation from January 2014 to December 2020. Thirty age- and sex-matched healthy controls that underwent an MDCT scan were included. Gastric air volume (GAV), total gastric volume (TGV), and GAV/gastric content volume (GCV) ratio values were estimated. @*Results@#In healthy controls (n=30), GAV and TGV values were in the range 5.0-35.0 mL, and 202.0-1,002.0 mL, respectively. The mean GAV and TGV values of OHCA patients (n=97) were 251.0 mL (range, 55.5-896.0) and 878.0 mL (range, 430.5-1,696.0), respectively. Significant between-group differences were determined in the mean GCV, GAV, and GAV/GCV ratio values. In OHCA patients, the cut-off value for abnormal GAV was defined as 56.5 mL (mean value plus two times standard deviation). Patients with abnormal GAV findings on MDCT scans had a longer duration from arrest to the return of spontaneous circulation, low body mass index, and increased rates of lactic acidosis. @*Conclusion@#Our results indicate an association between gastric air accumulation after resuscitation with longer recovery from arrest to return of spontaneous circulation, low body mass index, and increased lactic acidosis.
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Objective@#Undifferentiated and dedifferentiated endometrial carcinoma is a rare type of uterine malignancy. This study assesses disease characteristics, treatment and survival outcomes in patients with undifferentiated and dedifferentiated endometrial carcinoma treated at BC Cancer. @*Methods@#All patients diagnosed with undifferentiated and dedifferentiated endometrial carcinoma between 2000 and 2019 at BC Cancer were reviewed centrally. Clinical, pathologic, treatment and outcomes were reviewed retrospectively. The Kaplan-Meier method was used to evaluate overall survival (OS) and disease-free survival (DFS). Multivariable analysis was performed using Cox regression analysis. @*Results@#Fifty-two patients were included, 33% had undifferentiated carcinoma and 67% dedifferentiated carcinoma. Sixty-nine percent of those who had mismatch repair (MMR) testing of their tumor had an abnormal profile. The 5-year DFS was 80% (95% confidence interval [CI]=71%–89%) for stage I/II, 29% (95% CI=28%–40%) for stage III and 10% (95% CI 1%–19%) for stage IV. The 5-year OS was 84% (95% CI=75%–92%) for stage I/II, 38% (95% CI=26%–50%) for stage III and 12% (95% CI=1%–24%) for stage IV. Multivariate analysis showed that receiving adjuvant chemotherapy, adjuvant radiotherapy, lower stage and better Eastern Cooperative Group performance status were associated with improved DFS (p<0.05). @*Conclusion@#Patients with stage I/II undifferentiated and dedifferentiated endometrial carcinoma had excellent survival outcomes, those with stage III/IV had worse outcomes, similar to previously reported. Adjuvant chemotherapy and radiotherapy were associated with improved DFS. MMR testing should be performed for these patients due to the high incidence of abnormal profiles.
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Purpose@#This study was to investigate the dentists’ experience and awareness of foreign body ingestion and aspiration during dental prosthetic treatment. @*Materials and Methods@#A survey of 157 dentists working at 108 dental institutions in Daejeon and Chungcheong provinces was carried out and frequency analysis was conducted. Chi-square test was conducted to find out the difference between the sociodemographic data and experience of foreign body ingestion and aspiration of patients and independent sample t-test was conducted to find out the difference in awareness depending on whether receiving related education. @*Results@#The percentage of dentists experiencing dropping foreign body into patients’ oral cavity was 99.4% and the percentage of dentists experiencing foreign body ingestion and aspiration of patients was 53.5%. There were more dentists who experienced foreign body ingestion and aspiration of patients in male than female, longer working career, and general practitioners than specialists (P < .05). 50.3% of the respondents received related education. When they receive related education, they had low degree of concern, high confidence in coping with situations, and low willingness to receive education in the future (P < .05). @*Conclusion@#The percentage of foreign body dropping was 16% higher in prosthetic treatment than general treatment. The percentage of dentists with experience of foreign body ingestion and aspiration of patients was 53.5%. Among them, 92.9% experienced foreign body ingestion of patients and 7.1% of them experienced foreign body aspiration of patients.
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Objectives@#We described the trends and epidemiological characteristics of varicella outbreaks from 2016 to 2020 in the Republic of Korea. @*Methods@#We investigated variables such as the outbreak setting, age of patients, vaccination status, and lesion count. The collected data were analyzed with the Cochrane-Armitage trend test and Kruskal-Wallis test. These statistical tests were performed using R ver. 4.0.3. @*Results@#The number of varicella outbreaks increased from 2016 to 2018; however, after a slight decrease in the number of outbreaks in 2019, the number fell sharply in 2020. The median size of outbreaks decreased from 8 to 9 cases during 2016−2019 to 6 cases in 2020. The median duration of outbreaks was 18 days during 2016−2017, 28 days in 2018, 29 days in 2019, and 15 days in 2020. Varicella outbreaks occurred most frequently in elementary schools, and vaccination coverage of patients increased from 89.4% in 2016 to 97.2% in 2019. The median age of patients with outbreak-related varicella decreased from 8 years in 2016 to 6 years in 2020. @*Conclusion@#Significant changes were observed in the age of patients with outbreak-related varicella. Ongoing monitoring of varicella outbreaks should be conducted. Further research will be needed to measure the disease burden of varicella and enable evidence-based policy decisions.
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Background@#Non-invasive painless signaling therapy (NPST) is an electro-cutaneous treatment that converts endogenous pain information into synthetic non-pain information. This study explored whether pain improvement by NPST in failed back surgery syndrome (FBSS) patients is related to cerebral modulation. @*Methods@#Electroencephalography (EEG) analysis was performed in 11 patients with FBSS. Subjects received daily NPST for 5 days. Before the first treatment, patients completed the Brief Pain Inventory (BPI) and Beck Depression Inventory and underwent baseline EEG. After the final treatment, they responded again to the BPI, reported the percent pain improvement (PPI), and then underwent post-treatment EEG. If the PPI grade was zero, they were assigned to the ineffective group, while all others were assigned to the effective group. We used standardized low-resolution brain electromagnetic tomography (sLORETA) to explore the EEG current-source distribution (CSD) associated with pain improvement by NPST. @*Results@#The 11 participants had a median age of 67.0 years, and 63.6% were female. The sLORETA images revealed a beta-2 CSD increment in 12 voxels of the right anterior cingulate gyrus (ACG) and the right medial frontal area. The point of maximal CSD changes was in the right ACG. The alpha band CSD increased in 2 voxels of the left transverse gyrus. @*Conclusions@#Pain improvement by NPST in FBSS patients was associated with increased cerebral activity, mainly in the right ACG. The change in afferent information induced by NPST seems to be associated with cerebral pain perception.
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Objectives@#This study analyzed trends in foodborne and waterborne diseases in South Korea between 2015 and 2019. @*Methods@#The data consisted of information on outbreaks of waterborne and foodborne infectious diseases reported through the Korea Centers for Disease Control and Prevention(KCDC) system. We analyzed the trends and epidemiological aspects of outbreaks by month, place of occurrence, and causative pathogens in this observational study. @*Results@#The number of outbreaks has steadily increased over the last 5 years, but the number of cases per outbreak has followed a decreasing trend. Incidence at daycare centers and preschools has been steadily increasing over consecutive years. @*Conclusion@#The steady number of patients and decreasing number of cases per outbreak,even as the number of outbreaks has been increasing, suggest that the KCDC’s professional management system is operating effectively. It is necessary to continue improving the objectivity and efficiency of the management system and to carefully examine the increasing number of outbreaks in smaller-scale group catering facilities, such as daycare centers and preschools. Outbreaks can be prevented by closely examining those caused by unidentified pathogens and group outbreaks caused by other diseases, identifying problems, and supplementing the management system.
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Objective@#To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). @*Methods@#We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. @*Results@#In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. @*Conclusion@#Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.
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Magnetic resonance imaging (MRI) plays an important role in diagnosing and classifying axial spondyloarthritis (SpA) and is also useful for appropriate evaluation of disease status owing to its ability to detect inflammation early and reveal structural changes.However, dedicated MRI for the anterior chest wall (ACW) is not routinely considered despite relatively frequent presence of ACW lesions. To date, no study has investigated the imaging findings and clinical features of ACW involvement in Korean SpA patients. Thus, we aimed to show ACW involvement in SpA patients using ACW lesions found by MRI. We describe 20 cases of ACW involvement in which MRI-detected manubriosternal joint lesions. The lesion types included subchondral bone marrow edema, marginal or central bone erosions, subchondral fat infiltration or deposition, and ankylosis, with erosions being the most prevalent finding. We also provide the literature review results describing MRI findings of ACW lesions in SpA patients.
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Background@#Little is known about the surgical discipline in North Korea from the perspective of the outside world. This study aimed to examine the disease entities covered by articles published in the major medical journal in North Korea, “Surgery.” @*Methods@#Content and frequency analyses of 2,132 articles published in “Surgery” from 2006 to 2017 were conducted. Two medical doctors who majored in Surgery and anesthesiology perused the articles and compiled the diseases being elucidated in each article. The diseases described in each article were stratified into 13 surgical subspecialties. @*Results@#Articles from “Surgery,” similar to articles from the Western surgical community, also covered a wide variety of surgical diseases from different subspecialties, and the number of publications continued to grow consistently. Moreover, a number of studies focused on the fields of orthopedics and general Surgery dealing with benign diseases. Some articles focused on minimally invasive surgeries using laparoscopy. @*Conclusion@#The studies published in the North Korean journal “Surgery” encompass various clinical areas, but their quality is unclear.
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Purpose@#(1) To evaluate the trabecular pattern at the femoral attachment of the posterior cruciate ligament (PCL) in patients with a PCL injury; (2) to analyze bone microarchitecture by applying gray level co-occurrence matrix (GLCM)-based texture analysis; and (3) to determine if there is a significant relationship between bone microarchitecture and posterior instability. @*Materials and Methods@#The study included 96 patients with PCL tears. Trabecular patterns were evaluated on T2-weighted MRI qualitatively, and were evaluated by GLCM texture analysis quantitatively. The grades of posterior drawer test (PDT) and the degrees of posterior displacement on stress radiographs were recorded. The 96 patients were classified into two groups: acute and chronic injury. And 27 patients with no PCL injury were enrolled for control. Pearson’s correlation coefficient and one-way ANOVA with Bonferroni test were conducted for statistical analyses. This protocol was approved by the Institutional Review Board. @*Results@#A thick and anisotropic trabecular bone pattern was apparent in normal or acute injury (n = 57/61;93.4%), but was not prominent in chronic injury and posterior instability (n = 31/35;88.6%). Grades of PDT and degrees of posterior displacement on stress radiograph were not correlated with texture parameters. However, the texture analysis parameters of chronic injury were significantly different from those of acute injury and control groups (P < 0.05). @*Conclusion@#The trabecular pattern and texture analysis parameters are useful in predicting posterior instability in patients with PCL injury. Evaluation of the bone microarchitecture resulting from altered biomechanics could advance the understanding of PCL function and improve the detection of PCL injury.
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The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.