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Sodium-glucose cotransporter-2 (SGLT2) inhibitors regulate blood glucose levels in patients with type 2 diabetes mellitus and may also exert anti-inflammatory and anti-atherosclerotic effects by promoting M2 macrophage polarization. Although SGLT2 is expressed in brain regions that influence glucose balance and cognitive function, its roles in the central nervous system are unclear. This study investigated the effects of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic inflammation associated with metabolic diseases. Mice were subjected to a high-fat diet (HFD) for varying durations (3 d, 3 weeks, and 16 weeks) and treated with EMPA for 3 weeks (NFD, NFD + EMPA, HFD, HFD + EMPA; n = 5/group). EMPA regulated the expression of astrocyte markers and pro-inflammatory cytokine mRNA in the hypothalamus of HFD-induced mice, which was linked to regulation of the NF-κB pathway. Under hyperglycemic conditions, EMPA may mitigate hypothalamic inflammation by modulating astrocyte activation via the NF-κB pathway. Our findings demonstrated that EMPA possesses therapeutic potential beyond merely lowering blood glucose levels, opening new avenues for addressing inflammation and providing neuroprotection in metabolic disease management.

Sodium–glucose cotransporter 2 (SGLT2) inhibitors regulate plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) by inhibiting renal glucose reabsorption. This study investigated the impact of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic energy regulation. To directly investigate the role of SGLT2 inhibitors in the hypothalamus, we administered EMPA through intracerebroventricular (i.c.v.) injections into the murine ventricles. After dental cementing the i.c.v. cannula onto the skull, the mice were given 5 days to recover before receiving vehicle or EMPA (50 nM/2 μL) injections. In a high-fat diet (HFD)-induced obesity model, we determined the gene expression levels of agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) in the hypothalamus. Additionally, we assessed FoxO1 expression, which regulates AgRP and POMC gene transcription in hypothalamic cell lines. We found that EMPA directly influenced the expression of endogenous mRNA of POMC and AgRP, which are critical for energy homeostasis, and modulated their transcription in high-fat diet-induced obese mice. Additionally, EMPA affected the expression of FoxO1, a key transcriptional regulator of glucose homeostasis, thereby regulating the transcriptional activity of POMC and AgRP. These results indicate that EMPA significantly influences hypothalamic energy homeostasis, highlighting its potential as a regulator in obesity and T2DM management.

Background The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcystatin C/eGFRcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts. Methods We assessed whether the eGFRcystatin C/eGFRcreatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine. Results A total of 860 patients were stratified according to their eGFRcystatin C/eGFRcreatinine ratio (i.e., 1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the 1.1 group, 17.2%, P1.1 group, 1,494.0±252.2 cm/sec, P

Objectives: To investigate the association between serum uric acid (UA) and relative hand grip strength (HGS) in comparison with metabolic syndrome components. Methods: We analyzed the data of 5247 Korean adults aged ≥ 20 years (2422 men and 2825 women) who participated in the KNHNES VII (2018). Results: Among women, relative HGS was significantly lower in participants with hyperuricemia (1.65 ± 0.04) than in those without (1.95 ± 0.01) and was significantly decreased in the highest quartile (4Q: 1.77 ± 0.02) of serum UA compared with that in the lowest quartile (1Q: 1.98 ± 0.02). Among men, relative HGS was lower in participants with hyperuricemia (3.09 ± 0.04 vs. 3.16 ± 0.02) and decreased in 4Q (3.08 ± 0.03) of serum UA compared with that in 1Q (3.15 ± 0.03); however, these results were not statistically significant. In age- and multivariate-adjusted analyses in men, relative HGS was significantly lower in 4Q compared with that in 1Q in model 1 (adjusted for age), but there were no significant differences in model 2 (adjusted for age, BMI, and waist circumference) and model 3 (adjusted for age, BMI, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, triglycerides, and high-density lipoprotein cholesterol). Meanwhile, in women, relative HGS was significantly decreased in 4Q compared with that in 1Q in all models. Conclusions: A significant inverse correlation was observed between serum UA levels and relative HGS in women, and their significance was maintained even after adjusting for age and metabolic syndrome components.

Background The present study investigated the role of synergistic interaction between hyperuricemia and abdominal obesity as a risk factor for the components of metabolic syndrome. Methods We performed a cross-sectional study using the data of 16,094 individuals from the seventh Korean National Health and Nutrition Examination Survey (2016 to 2018). The adjusted odds ratios of metabolic syndrome and its components were analyzed by multivariate logistic regression analysis. The presence of synergistic interaction between hyperuricemia and abdominal obesity was evaluated by calculating the additive scales—the relative excess risk due to interaction, attributable proportion due to interaction, and synergy index (SI). Results There was a synergistic interaction between hyperuricemia and abdominal obesity in hypertriglyceridemia (men: SI, 1.39; 95% confidence interval [CI], 1.01 to 1.98; women: SI, 1.61; 95% CI, 1.02 to 2.69), and low high-density lipoprotein cholesterol (HDL-C) (men: SI, 2.03; 95% CI, 1.41 to 2.91; women: SI, 1.70; 95% CI, 1.05 to 2.95). There was no significant synergistic interaction between hyperuricemia and abdominal obesity for the risk of high blood pressure (men: SI, 1.22; 95% CI, 0.85 to 1.77; women: SI, 1.53; 95% CI, 0.79 to 2.97), and hyperglycemia (men: SI, 1.03; 95% CI, 0.72 to 1.47; women: SI, 1.39; 95% CI, 0.75 to 2.57). Conclusion Hyperuricemia and abdominal obesity synergistically increased the risk of hypertriglyceridemia and low HDL-C in both sexes.

Objective: Dystrophinopathy is an X-linked recessive muscular dystrophy caused by mutations in the DMD gene. Herein we describe the prenatal detection of DMD gene mutations in a patient with no family history, by multiplex ligation-dependent probe amplification (MLPA) after noninvasive prenatal screening (NIPS). Case report: A 41-year-old woman underwent NIPS owing to an advanced maternal age. A copy number variation was detected in the maternal X chromosome, and uninformative results were obtained for the fetal sex chromosomes. Following amniocentesis, a duplication was identified in exons 1–29 of the dystrophin gene by MLPA. After interviewing her family members it was confirmed that the patient is a de novo carrier of DMD duplications, and her daughter is a carrier of the same mutation. Conclusion: his is the first case report to describe the prenatal diagnosis of duplications in the DMD gene by MLPA following NIPS in a patient with no family history.

Abstract Background Twin pregnancies with uterine fibroid(s) (UFs) may not be at increased risk for obstetric complications compared to those without UFs. However, there was no reported comparison study with obstetric outcomes and complications of twin pregnancy after myomectomy. We aimed to compare the pregnancy outcomes in twin pregnancies with or without uterine fibroid(s), and also compared in patients with previous myomectomy history in Korean women. Methods A cohort of twin pregnancies delivered in a single institution between January 2011 and March 2019 were retrospectively analyzed. UFs group was defined by the presence of UFs during pregnancy (≥1 fibroid, measuring ≥2 cm or multiple fibroids regardless of the size). Previous myomectomy group included patients with history of abdominal or laparoscopic or hysteroscopic myomectomy of ≥1 fibroid, measuring ≥2 cm or multiple fibroids whatever the size. Patients with monochorionic monoamniotic twins, myoma less than 2 cm in size, missed abortion or intrauterine fetal death (IUFD) of one fetus before 14 weeks, history of previous conization, and uterine anomalies were excluded. Pregnancy outcomes and obstetric complications were compared. Result A total 1388 patients were included in this study, 191 (13.8%) had UFs and 89 (6.4%) had a history of myomectomy. Maternal age was younger in non-UFs group and primiparity was more common in UFs group (p

ObjectiveThis study investigated the association between relative hand grip strength (HGS) and glycemic status, such as impaired fasting glucose (IFG) and diabetes, using data from the Korea National Health and Nutrition Examination Survey (KNHANES).MethodsWe performed a cross-sectional study using the data from the KNHANES of 27,894 individuals from 2014 to 2019. Relative HGS was defined as the absolute HGS divided by body mass index and divided into quartiles in men and women. Odds ratios (OR) for diabetes and IFG were calculated using multivariate logistic regression analysis. All analyses were stratified by sex, and subgroup analysis was age-stratified.ResultsThe lowest relative HGS quartile had a significant increase in the risk for diabetes (men: OR 2.72, 95% confidence interval [CI] 2.12-3.50; women: OR 3.38, 95% CI 2.70-4.24) and IFG (men: OR 1.35, 95% CI 1.15-1.59; women: OR 1.60, 95% CI 1.40-1.84). The ORs for diabetes and IFG according to the decreasing quartiles of relative HGS gradually increased in both sexes (P for trend ConclusionLower relative HGS was associated with a higher risk of not only diabetes but also IFG in both sexes. These trends were stronger in younger adults than in older adults.

Crosstalk between T cells, dendritic cells, and macrophages in temporal leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. Activated T cells from these leukocyte clusters play critical roles in the efferent phase of allergic contact hypersensitivity (CHS). However, the cytokines driving maintenance and survival of pathogenic T cells during and following CHS remain mostly unknown. Upon epicutaneous allergen challenge, we here report that macrophages produce IL-27 which then induces IL-15 production from epidermal keratinocytes and dermal myeloid cells within leukocyte clusters. In agreement with the known role of IL-15 as a T cell survival factor and growth cytokine, this signaling axis enhances BCL2 and survival of skin T cells. Genetic depletion or pharmacological blockade of IL-27 in CHS mice leads to abrogated epidermal IL-15 production resulting in a decrease in BCL2 expression in T cells and a decline in dermal CD8+ T cells and T cell cluster numbers. These findings suggest that the IL-27 pathway is an important cytokine for regulating cutaneous T cell immunity.

Abstract Background Twin pregnancy has a high risk for developing uterine atony (UA). This study aimed to evaluate efficacy and clinical outcomes of prophylactic compression sutures to treat UA during twin cesarean section (CS). Methods All patient records of twin deliveries by CS after gestational age of 24 weeks in a large maternity hospital in South Korea between January 2013 and June 2018 were reviewed. Patients with monochorionic monoamniotic twins were excluded from data analysis. In total, 953 women were eligible for data analysis. Results Of the 953 patients, compression sutures were applied to 147 cases with postpartum bleeding that were refractory to uterine massage and uterotonics. Out of the 147, two patients (1.4%) proceeded to additional uterine artery ligation to achieve hemostasis, yielding a success rate of 98.6%. The rate of transfusion after the first 24 h of delivery in the suture group was not significantly different from that in the non-suture group, suggesting that both groups achieved hemostasis at an equal rate after the first 24 h of delivery. The difference in the operation time between the two groups was only 8.5 min. The rate of subsequent pregnancy among the patients who received compression sutures was 44.4%. Conclusions Overall, our findings suggest that with early and fast implementation of compression sutures, UA can be treated in the setting of twin cesarean delivery without significantly increasing maternal morbidity.

Objective: We present prenatal diagnosis of rec(18)dup(18q)inv(18)(p11.2q21.2)pat owing to paternal pericentric inversion in a fetus. Case report: A 37-year-old woman was diagnosed with multiple anomalies on a prenatal ultrasound scan at 17 weeks and 5 days of gestation. She underwent amniocentesis at 20 weeks and 2 days. Conventional karyotyping of amniocyte showed 46, XX, der(18). She was thus referred for genetic counseling; cytogenetic analysis revealed a 46, XY karyotype, inv(18)(p11.2q21.2), of the father. Therefore, based on the results of the father, the fetal karyotype was defined as 46, XX, rec(18)dup(18q)inv(18)(p11.2q21.2)pat. Array comparative genomic hybridization of amniocytes to obtain specific information showed a 3-Mb deletion of 18p11.31p11.32 (136227_3100353)x1 and a 23.7-Mb duplication of 18q21.31-q23 (54222717_77957375) × 3. Conclusion: Maternal serum screening produces normal results for 18p-/18q+ syndrome, but it can be diagnosed by fluorescent in situ hybridization, quantitative-fluorescent polymerase chain reaction, or array comparative genomic hybridization test by observing abnormal findings on ultrasound. Keywords: 18p deletion, 18q duplication, Chromosome 18 pericentric inversion, Recombinant chromosome 18

Abstract Background Cardiovascular disease (CVD) presents the most serious health problems and contributes to the increased mortality in young women with Turner syndrome. Arterial hypertension in Turner syndrome patients is significantly more prevalent than that in a general age-matched control group. The aetiology of hypertension in Turner syndrome varies, even in the absence of cardiac anomalies and obvious structural renal abnormalities. Pheochromocytoma is an extremely rare cause among various etiologies for hypertension in patients with Turner syndrome. Here, we reported a pheochromocytoma as a rare cause of hypertension in Turner syndrome patient. Case presentation A 21-year-old woman who has diagnosed with Turner syndrome with a karyotype of 46,X,i(X)(q10) visited for hypertension and mild headache. Transthoracic echography (TTE) showed no definite persistent ductus arteriosus shunt flow and cardiac valve abnormalities. Considering other important secondary causes like pheochromocytoma, hormonal studies were performed and the results showed increased serum norepinephrine, serum normetanephrine, and 24 h urine norepinephrine. We performed an abdominal computed tomography (CT) to confirm the location of pheochromocytoma. Abdominal CT showed a 1.9 cm right adrenal mass. I-131 meta-iodobenzylguanidine (MIBG) scintigraphy showed a right adrenal uptake. Laparoscopic adrenalectomy was performed and confirmed a pheochromocytoma. After surgery, blood pressure was within normal ranges and postoperative course was uneventful, and no recurrence developed via biochemical tests and abdominal CT until 24 months. Conclusion Our case and previous literatures suggest that hypertension caused by pheochromocytoma which is a rare but important and potentially lethal cause of hypertension in Turner syndrome. This case underlines the importance of early detection of pheochromocytoma in Turner syndrome. Clinicians should keep in mind that pheochromocytoma can be a cause of hypertension in patients with Turner syndrome.

Abstract Background Albuminuria is generally accepted as a sensitive marker of diabetic nephropathy but has limitations in predicting its progression. The aim of this study was to evaluate the use of nonalbumin proteinuria in addition to albuminuria for predicting the progression of type 2 diabetic nephropathy. Methods In this retrospective observational study, the urine albumin-to-creatinine ratio (ACR) and the nonalbumin protein-to-creatinine ratio (NAPCR) were measured in 325 patients with type 2 diabetes and estimated glomerular filtration rates (eGFR) ≥30 mL/min/1.73 m2. The patients were divided into four groups based on the cutoff points for the urinary ACR (30 mg/g) and NAPCR (120 mg/g). The renal outcomes were chronic kidney disease (CKD) progression and accelerated eGFR decline. Results During the 4.3-year follow-up period, 25 (7.7%) patients showed CKD progression and 69 (21.2%) patients showed accelerated eGFR decline. After adjusting for nine clinical parameters, the group with a NAPCR greater than 120 mg/g exhibited higher cumulative incidences of CKD progression (hazard ratio 6.84; P = 0.001) and accelerated eGFR decline (hazard ratio 1.95; P = 0.011) than the group with a NAPCR

The skin and intestine are active organs of the immune system that are constantly exposed to the outside environment. They support diverse microbiota, both commensal and pathogenic, which encompass bacteria, viruses, fungi, and parasites. The skin and intestine must maintain homeostasis with the diversity of commensal organisms present on epithelial surfaces. Here we review the current literature pertaining to epithelial barrier formation, microbial composition, and the complex regulatory mechanisms governing the interaction between the innate immune system and microbiota in the skin and intestine. We also compare and contrast the skin and intestine—two different organ systems responsible creating a protective barrier against the external environment, each of which has unique mechanisms for interaction with commensal populations and host repair.

Surgery in patients with craniosynostosis is a common treatment to correct the deformed skull shape, and it is necessary to verify the surgical effect of correction on the regional cranial bone. We propose a quantification method for evaluating surgical effects on regional cranial bones by comparing preoperative and postoperative skull shapes. To divide preoperative and postoperative skulls into two frontal bones, two parietal bones, and the occipital bone, and to estimate the shape deformation of regional cranial bones between the preoperative and postoperative skulls, an age-matched mean-normal skull surface model already divided into five bones is deformed into a preoperative skull, and a deformed mean-normal skull surface model is redeformed into a postoperative skull. To quantify the degree of the expansion and reduction of regional cranial bones after surgery, expansion and reduction indices of the five cranial bones are calculated using the deformable registration as deformation information. The proposed quantification method overcomes the quantification difficulty when using the traditional cephalic index(CI) by analyzing regional cranial bones and provides useful information for quantifying the surgical effects of craniosynostosis patients with symmetric and asymmetric deformities.

Extravillous trophoblast cells (EVTs) secreted by the uterine cavity may help overcome limitations associated with prenatal testing currently in use. EVTs are isolated using a routine safe liquid-based Pap test (called ThinPrep); however, the ThinPrep solution contains alcohol that hinders the isolation of intact EVTs. We compared the trophoblastic cell isolation efficiency of two different methods of fixation: Thinprep (pre-fixation method) and formalin (post-fixation method). We analyzed EVTs from 20 pregnant women (5–20 weeks of gestation) who underwent invasive prenatal testing. The percentages of placental β-human chorionic gonadotropin (β-hCG)-expressing cells were calculated. The presence of XY chromosomes were used to confirm pure trophoblast cells by fluorescence in situ hybridization. The β-hCG-positive cells obtained from pre- and post-fixation were 66.4 ± 13.3% and 83.2 ± 8.1% (p = 0.003), respectively, and fluorescence-positive cells were 11.1 ± 2.1% and 23.8 ± 4.8%, respectively (p = 0.001). Post-fixation was found to be more efficient in isolating non-trophoblast cells than pre-fixation. For the successful clinical application of trophoblast retrieval and isolation from the cervix in prenatal genetic testing, each step should be optimized for consistent and reliable results.

BackgroundAntithyroid drugs (ATDs) can lead to the development of agranulocytosis, which is the most serious adverse effect. Characteristics of ATD-induced agranulocytosis (AIA) have seldom been reported due to the rarity. In this study, we characterized the clinical features for AIA in Korean patients.MethodsWe retrospectively reviewed data from patients with AIA diagnosed between 1997 and 2014 at four tertiary hospitals. Agranulocytosis was defined as an absolute neutrophil count (ANC) below 500/mm3.ResultsThe mean age of the patients (11 males, 43 females) was 38.2±14.9 years. Forty-eight patients (88.9%) with AIA had fever and sore throat on initial presentation, 20.4% of patients developed AIA during the second course of treatment, and 75.9% of patients suffered AIA within 3 months after initiation of ATD. The patients taking methimazole (n=39) showed lower levels of ANC and more frequent use of granulocyte-macrophage colony-stimulating factor than propylthiouracil (n=15) users. The median duration of agranulocytosis was 5.5 days (range, 1 to 20). No differences were observed between the long (≥6 days) and short recovery time (≤5 days) groups in terms of age, gender, ATDs, duration of ATDs, or initial ANC levels. Four patients (7.4%) who were taking ATDs for less than 2 months died of sepsis on the first or second day of hospitalization.ConclusionThe majority of AIA incidents occur in the early treatment period. Considering the high fatality rate of AIA, an early aggressive therapeutic approach is critical and patients should be well informed regarding the warning symptoms of the disease.

Abstract Objectives Cardiopulmonary support has been used to treat the patients with refractory cardiogenic shock since 1950s. In advent of portable system its use has been widened considerably. In this retrospective study, we report our single center experience concerning possible indications, complications and outcomes of percutanous cardiopulmonary support (PCPS) Methods From January 2013 to March 2014, we searched the patients who were supported by PCPS system by reviewing the medical records in cardiology department at our Hospital. Infectious organism was limited to what was identified within 2 weeks after weaning of PCPS. Results A total of 9 patients were supported by PCPS with CAPIOX CX® system (Terumo inc., Tokyo, Japan) initially for ST-segment elevation myocardial infarction/non ST-segment elevation myocardial infarction in 4 patients, myocarditis in 3 patients, valvular heart disease in 1 patient, and acute respiratory distress syndrome in 1 patient. The mean duration of PCPS support was 79.1±76.6 hours and 5 of them were recovered and discharged alive. All the patients needed transfusions of various forms of blood products. And there was one major stroke and one hyperbilirubinemia in related to PCPS treatment. Conclusions PCPS treatment was a valuable means to treat the patients with cardiovascular collapse, but not without costs. Efforts to reduce its associated complications should be made to improve outcomes.

The best management strategy for angiographically intermediated coronary artery diseases remains controversial. Lesions, when coupled with spasm, can lead to catastrophic results and cardiogenic shock. We report a case of a 62-year-old man who had an intermediate coronary artery disease presenting with cardiogenic shock due to coronary spasm during a preoperative period.