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In a conventional two-dimensional (2D) culture method, cells are attached to the bottom of the culture dish and grow into a monolayer. These 2D culture methods are easy to handle, cost-effective, reproducible, and adaptable to growing many different types of cells. However, monolayer 2D cell culture conditions are far from those of natural tissue, indicating the need for a threedimensional (3D) culture system. Various methods, such as hanging drop, scaffolds, hydrogels, microfluid systems, and bioreactor systems, have been utilized for 3D cell culture. Recently, external physical stimulation-based 3D cell culture platforms, such as acoustic and magnetic forces, were introduced. Acoustic waves can establish acoustic radiation force, which can induce suspended objects to gather in the pressure node region and aggregate to form clusters. Magnetic targeting consists of two components, a magnetically responsive carrier and a magnetic field gradient source. In a magnetic-based 3D cell culture platform, cells are aggregated by changing the magnetic force. Magnetic fields can manipulate cells through two different methods: positive magnetophoresis and negative magnetophoresis. Positive magnetophoresis is a way of imparting magnetic properties to cells by labeling them with magnetic nanoparticles. Negative magnetophoresis is a label-free principle-based method. 3D cell structures, such as spheroids, 3D network structures, and cell sheets, have been successfully fabricated using this acoustic and magnetic stimuli-based 3D cell culture platform. Additionally, fabricated 3D cell structures showed enhanced cell behavior, such as differentiation potential and tissue regeneration. Therefore, physical stimuli-based 3D cell culture platforms could be promising tools for tissue engineering.
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BACKGROUND@#To achieve optimal bone marrow engraftment during bone marrow transplantation, migration of donor bone marrow cells (BMCs) toward the recipient’s bone marrow is critical. Despite the enhanced engraftment of BMCs by co-administration of mesenchymal stem cells (MSCs), the efficiency can be variable depending on MSC donor. The purpose of this study is to examine the functional heterogeneity of tonsil-derived MSCs (TMSCs) and to identify a marker to evaluate efficacy for the enhancement of BMC migration. @*METHODS@#To examine the donor-to-donor variation of TMSCs in potentiating BMC migration, we isolated TMSCs from 25 independent donors. Transcriptome of TMSCs and proteome of conditioned medium derived from TMSC were analyzed. @*RESULTS@#Enhanced BMC migration by conditioned medium derived from TMSCs was variable depending on TMSC donor. The TMSCs derived from 25 donors showed distinct expression profiles compared with other cells, including fibroblasts, adipose-derived MSCs and bone marrow–derived MSCs. TMSCs were distributed in two categories: high- and low-efficacy groups for potentiating BMC migration. Transcriptome analysis of TMSCs and proteome profiles of conditioned medium derived from TMSCs revealed higher expression and secretion of matrix metalloproteinase (MMP) 1 in the high-efficacy group. MMP1 knockdown in TMSCs abrogated the supportive efficacy of conditioned medium derived from TMSC cultures in BMC migration. @*CONCLUSION@#These data suggest that secreted MMP1 can be used as a marker to evaluate the efficacy of TMSCs in enhancing BMC migration. Furthermore, the strategy of analyzing transcriptomes and proteomes of the MSCs may be useful to set the standard for donor variation.
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Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.
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Since the coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome-coronavirus-2 virus (SARS-CoV-2), various complications have been reported. Although most COVID-19 cases exhibited flu-like symptoms, COVID-19 may dysregulate the immune response and promote overwhelming levels of inflammation in some patients. Inflammatory bowel disease (IBD) is caused by dysregulated or inappropriate immune responses to environmental factors in a genetically susceptible host, and a SARS-CoV-2 infection may act as a possible cause of IBD. This paper describes two pediatric patients who developed Crohn’s disease following a SARS-CoV-2 infection. They were previously healthy before the SARS-CoV-2 infection. On the other hand, they started to develop fever and gastrointestinal symptoms several weeks after recovery from the infection. They were diagnosed with Crohn’s disease by imaging and endoscopic studies, and their symptoms improved after treatment with steroids and azathioprine. This paper suggests that a SARS-CoV-2 infection may trigger IBD in predisposed patients.
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Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T-cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.
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Background@#Bier’s spots represent a distinct pattern of speckled vascular mottling composed of small, irregular anemic macules. This phenomenon is common and easily reproducible by placing an extremity in a dependent position when mild venous stasis is created. @*Objective@#This study aimed to investigate the clinical manifestations of multiple anemic macules, Bier’s spots, and analyze its association with other underlying conditions in hospital outpatients. @*Methods@#Between 2015∼2020, we reviewed clinical data of 18 patients diagnosed with Bier’s spots at our hospital. Analysis was performed to assess patient’s demographics, presentation, and treatment. @*Results@#A total of 18 patients were included, and 10 (55.6%) were males. Lesions on both sides of the extremities were more common in 11 patients (61.1%), with four (22.2%) and two (11.1%) only on the upper and lower sides, respectively. Symptoms included itching in six patients (33.3%), numbness in two (11.1%), tenderness in one (5.6%), and asymptomatic in 11 (61.1%). The symptoms often accompanied hypertension, atopic dermatitis, and dyslipidemia. Histopathologic findings showed perivascular inflammation in six biopsy specimens, lymphocytic infiltration in four (66.7%), and papillary dermal vascular dilatation in three (50.0%). Calcium channel blockers and antihistamines were used for treatment in 13 patients (72.2%). @*Conclusion@#The result shows clinical manifestations of Bier’s spots and a possibility of association with various underlying diseases. Optimum treatment for Bier’s spots has not been defined, and because most cases are asymptomatic, no treatment is required. Therefore, this study will be a valuable data of Bier’s spots for dermatologists.
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Marjolin’s ulcer is a malignant skin tumor that arises at the site of scars, chronic ulcerations, inflammations, and fistulas after a long latent period. These tumors are mostly squamous cell carcinomas; however, other types of malignancies, such as basal cell carcinoma, malignant melanoma, and sarcoma rarely occur. Marjolin’s ulcer have aggressive characteristics, and local recurrence and lymph node metastasis rates are higher than those of cutaneous primary tumors. Herein, we report an unusual case of squamous cell carcinoma at the site of an arteriovenous fistula ulcer treated with repeated radical operation and skin graft.
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Background@#Various treatments exist for addressing volume loss in atrophic scars. Although laser therapy has gained traction in treating atrophic scars, it is associated with side effects, such as post-inflammatory hyperpigmentation or erythema. Additionally, not all types of atrophic scars respond optimally to laser therapy, even after multiple sessions. @*Objective@#This study aimed to evaluate the efficacy and safety of punch elevation for atrophic scars that yielded unsatisfactory outcomes after repeated laser treatment sessions. @*Methods@#Seven patients with atrophic scars on their facial area underwent punch elevation, concurrently supplemented by fractional CO2 laser application to the scar margins. Improvement in volume restoration of atrophic scars was assessed via investigator evaluation and 3-dimensional (3D) image analysis. @*Results@#After 1 month, median volume (interquartile range) of depression improved from 4.39 mm3 (2.23∼9.90 mm3 ) to 1.97 mm3 (1.46∼7.50 mm3 ), indicating a statistically significant difference post-punch elevation (p=0.018). No serious adverse events were reported during follow-up. @*Conclusion@#The efficacy of the punch elevation was objectively evaluated. Punch elevation is a safe and effective therapeutic avenue for atrophic scars that exhibit resistance to laser or alternative interventions.
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Pilomatricoma is a common benign tumor that originates from hair matrix cells. Bullous pilomatricoma (BP) is a rare variant that often occurs on the upper extremities. A 23-year-old male presented with a cyst on the left upper arm for 6 months. He received the BNT162b2 (Pfizer) mRNA COVID-19 vaccine in the same location approximately 6 months prior to presentation. The lesion appeared 1 week after inoculation and gradually enlarged.Physical examination revealed a 2.5-×2.0-cm-sized, pinkish cystic nodule on the left upper arm. The lesion was excised, and histopathological examination showed a well-circumscribed nodule composed of basophilic cells and eosinophilic shadow cells. Finally, the patient was diagnosed with BP. The exact cause of BP formation following vaccination is yet to be determined; however, this report presents the possibility of BP occurrence in individuals with chronic skin lesions at the site of vaccination.
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Purpose@#Several studies are concerned about the association between bone mineral density (BMD) and the risk of breast cancer in postmenopausal women, but it is controversial. Therefore, we evaluated whether BMD might be a risk factor for recurrences, or metastases in menopausal luminal A breast cancer patients. @*Methods@#In this retrospective study, data of 348 patients with luminal A breast cancer who received treatment at Pusan National University Yangsan Hospital between 2012 and 2016 were analyzed. Patients were divided into two groups: normal BMD and low BMD including osteopenia or osteoporosis in preoperative examination. Patients were also divided into three groups according to BMD changes: no change in BMD; improvement in BMD, and deterioration in BMD. Events were defined as recurrence, occurrence of contralateral breast cancer, and metastasis to any other organ. @*Results@#Preoperative examination revealed normal BMD in 129 of 348 patients and low BMD in 219 patients. During a median follow-up period of 78 months, only 14 patients (4.0%) experienced recurrences, distant metastases, or occurrences of contralateral breast cancer. Five-year disease-free survival rate was 98.2% for 219 patients with low BMD and 95.0% for 129 patients with normal BMD (P=0.33). Disease-free survival at 5 years was 97.0% for the no change in the BMD group, 94.6% for the BMD improvement group, and 98.4% for the BMD deterioration group (P=0.79). @*Conclusion@#In this study, BMD had no statistically significant associations on recurrences, metastases, or incidences of contralateral breast cancer in postmenopausal patients with luminal A breast cancer.
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Background@#Delayed emergence after general anesthesia may significantly affect a patient’s condition. We present the case of a patient who experienced prolonged delayed recovery of consciousness, language, and motor response due to catatonia after eight hours of total elbow arthroplasty under general anesthesia.Case: A 68-year-old woman with neuropsychiatric disorders and Parkinson’s disease did not respond adequately during recovery after more than eight hours of general anesthesia. Following the operation, the patient was semi-comatose and appeared to have nonconvulsive status epilepticus upon awakening from anesthesia. However, subsequent examinations did not reveal any organic causes. The patient was subsequently diagnosed with catatonia, treated, and discharged following gradual improvement. @*Conclusions@#Although rare, patients taking psychiatric drugs for an extended period may experience delayed emergence after prolonged general anesthesia without identifiable causes. Catatonia should be considered in the differential diagnoses of these patients.
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Background and Objectives@#In previous studies, high homocysteine levels were associated with high cardiovascular mortality. However, these results were inconsistent with those of randomized controlled trials. We aimed to evaluate the causal role of homocysteine on allcause and cardiovascular mortality using Mendelian randomization (MR) analysis. @*Methods@#This study included the 10,005 participants in the Namwon Study. In conventional observational analysis, age, sex, survey years, lifestyles, body mass index, comorbidities, and serum folate level were adjusted using multivariate Cox proportional regression. MR using 2-stage least squares regression was used to evaluate the association between genetically predicted plasma homocysteine levels and mortality. Age, sex, and survey years were adjusted for each stage. The methylenetetrahydrofolate reductase (MTHFR) polymorphism was used as an instrumental variable for predicting plasma homocysteine levels. @*Results@#Observed homocysteine levels were positively associated with all-cause (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.26–1.54) and cardiovascular (HR, 1.62; 95% CI, 1.28–2.06) mortality when plasma homocysteine levels doubled. However, these associations were not significant in MR analysis. The HRs of doubling genetically predicted plasma homocysteine levels for all-cause and cardiovascular mortality were 0.99 (95% CI, 0.62–1.57) and 1.76 (95% CI, 0.54–5.77), respectively. @*Conclusions@#This MR analysis did not support a causal role for elevated plasma homocysteine concentrations in premature deaths.
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Background and Objectives@#The association between bilirubin and atrial fibrillation (AF) has been evaluated previously in observational studies but with contradictory results. This study evaluated the causal association between serum bilirubin level and AF using Mendelian randomization (MR) analysis. @*Methods@#This cross-sectional study includes 8,977 participants from the Dong-gu Study.In the observational analysis, multivariate logistic regression was performed to evaluate the association between bilirubin and prevalent AF. To evaluate the causal association between bilirubin and AF, MR analysis was conducted by using the UGT1A1 rs11891311 and rs4148323 polymorphisms as instrumental variables. @*Results@#Elevated serum bilirubin levels were associated with an increased risk for AF in observational analysis (total bilirubin: odds ratio [OR], 1.31; 95% confidence interval [95% CI], 1.15–1.48 per 1 standard deviation [SD]; direct bilirubin: OR, 1.31; 95% CI, 1.18–1.46 per 1 SD), whereas the genetically predicted serum bilirubin levels in MR analysis did not show this association (total bilirubin: OR, 1.02; 95% CI, 0.67–1.53 per 1 SD; direct bilirubin: OR, 1.03; 95% CI, 0.61–1.73 per 1 SD). @*Conclusions@#Genetically predicted bilirubin levels were not associated with prevalent AF.Thus, the observational association between serum bilirubin levels and AF may be noncausal and affected by reverse causality or unmeasured confounding.
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An oroantral fistula (OAF) or oroantral communication (OAC) is an opening between the oral cavity and the maxillary sinus. If left untreated, these openings may cause chronic maxillary sinusitis. Although small defects (diameter <5 mm) may close spontaneously, larger communications require surgical intervention. Various studies have been conducted on OAC closure using a platelet-rich fibrin (PRF) membrane; most of these prior studies have involved simple direct application of PRF clots. This study introduces a new “double-barrier technique” using PRF for closure of an OAF involving sinus mucosal lifting and closure. The PRF material is inserted into the prepared maxillary sinus space, and the buccal advancement flap covers the oral side. This technique was successfully used to treat two patients with chronic OAF in the posterior maxillary region after implant removal or tooth extraction. The use of a PRF membrane in a double-barrier technique may have advantages in soft-tissue healing and could enable easy closure of chronic OAF with minimal trauma.
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Background and Objectives@#Turbinoplasty may be an option in patients with persistent symptoms of allergic rhinitis (AR) despite adequate medication. The two most frequently used surgical techniques for turbinoplasty are radiofrequency ablation and microdebriderassisted turbinoplasty. This study compared the outcomes of these two surgical techniques and assessed the long-term treatment effects. @*Methods@#This study included patients with AR who underwent turbinoplasty between January 2010 and June 2017. We examined the medication scores, overall treatment satisfaction scores, and medical records. Based on the type of surgery, patients were classified into microdebrider and coblator groups. A telephone survey was conducted to collect data on the 5-year post-treatment efficacy parameters. Scores for allergic symptoms, prescription medicines taken after surgery, and general satisfaction were compared. @*Results@#Of the total 241 patients, 192 (79.7%) and 49 (20.3%) underwent microdebrider-assisted turbinoplasty and radiofrequency ablation turbinoplasty, respectively. Both the microdebrider and coblator groups showed remarkable improvements in AR symptoms at the 5-year follow-up (p<0.001). Although the degree of symptom improvement did not differ significantly between the two groups, the coblator group did show significant improvements in medication scores when compared with the microdebrider group (p<0.05), and there were significant differences in postoperative satisfaction scores between the two groups. @*Conclusion@#In terms of 5-year postoperative outcomes, radiofrequency-ablation turbinoplasty and microdebrider-assisted turbinoplasty were equally beneficial for reducing nasal symptoms and enhancing medication ratings in patients with AR.
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Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.
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Background@#Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study. @*Methods@#Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53. @*Results@#CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history. @*Conclusions@#Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.
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Objective@#Lipoprotein(a) (Lp[a]) and the atherogenic index of plasma (AIP) have been reported as predictive markers of coronary artery calcium (CAC). However, previous studies demonstrated that the cardiovascular risk associations with Lp(a) are attenuated in patients with low-density lipoprotein cholesterol (LDL-C) levels ≤135 mg/dL. However, few articles have identified the risk factors of CAC in patients without high LDL-C. Therefore, we performed this study to investigate the association of Lp(a) and AIP with CAC in patients with LDL-C levels ≤135 mg/dL. @*Methods@#This study included 625 lipid-lowering agent naive patients with LDL-C levels ≤135 mg/dL who underwent coronary computed tomographic angiography. We performed multivariate logistic regression analysis to evaluate the risk factors for a coronary artery calcium score (CACS) >0, CACS ≥400, and CAC ≥90th percentile. @*Results@#The mean age of the patients was 55.0±7.9 years and their mean LDL-C level was 94.7 ±23.3 mg/dL. Multivariate regression analysis showed that age, male sex, diabetes, hypertension, Lp(a), and AIP were independent predictors of CAS>0. Age, male sex, and diabetes were independent predictors of CACS≥400. Diabetes, hypertension, and AIP were independent predictors of CAC ≥90th percentile (all p<0.05). Unlike Lp(a), higher AIP tertiles were associated with significantly higher CAC percentiles and greater proportions of patients with CACS ≥400 and CAC ≥90th percentile. @*Conclusion@#In patients without high LDL-C, AIP could be a more reliable predictor of CAC than Lp(a).
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Background@#The Gout Impact Scale (GIS), part of the Gout Assessment Questionnaire 2.0, measures gout-specific health-related quality of life (HRQOL). This study aimed to translate the GIS into Korean and validate the Korean version (K-GIS) using generic HRQOL measures. @*Methods@#The GIS was translated into Korean and back-translated into English. We asked patients aged 18 years or older who met the 2015 gout classification criteria to fill out the questionnaires (from January 2022 to June 2022); the K-GIS (5 scales [0–100 scores each]), along with the Korean version of Health Assessment Questionnaire (HAQ) and EuroQol-5 dimension (EQ-5D). We investigated the internal consistency, construct validity, and discriminative validity for gout characteristics of K-GIS. The K-GIS form was administrated to patients 4 weeks later to assess the test-retest reliability using the intraclass correlation coefficient (ICC). @*Results@#One hundred patients completed the questionnaire. The mean ± standard deviation age of the patients was 53.0 ± 15.1 years, and 99.0% of the patients were men. All scales had high degree of internal consistency (Cronbach’s α = 0.59 to 0.96) and test-retest reliability (n = 18, ICC = 0.83 to 0.94, all P 6 mg/dL, frequent gout flares in the past year, and fewer comorbidities. In contrast, neither the HAQ nor the EQ-5D could discern these subsets of patients. @*Conclusion@#The K-GIS is a reliable and valid HRQOL measure for patients with gout. Higher K-GIS scores were associated with clinical characteristics leading to unfavorable outcomes, which were not demonstrated by the HAQ and EQ-5D.
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Background@#We sought to identify the influence of prepregnancy glucose levels on obstetric complications in subsequent pregnancy. @*Methods@#Women in Republic of Korea who had given birth between January 1st, 2007 and December 31st, 2010 were enrolled. The database of the Health Insurance Review and Assessment Service and data from a national health screening program for infants and children were used. Subjects were divided into seven groups according to their fasting glucose levels. @*Results@#59,619 women were included for analysis, and 10.4%, 13.7%, 19.1%, 21.5%, 16.0%, 11.6%, and 7.5% women had glucose levels of 100 mg/dL. Each 5 mg/dL increase in prepregnancy fasting glucose levels was associated with increased risk of gestational diabetes and macrosomia in subsequent pregnancy. Adjusted risk ratio for gestational diabetes per standard deviation prepregnancy glucose > 100 mg/dL was 2.015 (95% confidence interval, 1.649–2.462) and for macrosomia an adjusted risk ratio 1.389 (95% confidence interval, 1.147–1.682). @*Conclusion@#Higher prepregnancy glucose level within normal range was related to gestational diabetes and macrosomia in following pregnancy. Our results may aid in the identification of women at future risk of obstetric complications and may guide to stratify women into normal and intensified care.Tweetable abstractHigher prepregnancy glucose in normal range is associated with gestational diabetes and macrosomia.