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This paper presents a membrane computation error-minimized mixed-mode spiking neural network (SNN) crossbar array. Our approach involves imple-menting an embedded dummy switch scheme and a mid-node pre-charge scheme to construct a high-precision current-mode synapse. We effectively suppressed charge sharing between membrane capacitors and the parasitic capacitance of synapses that results in membrane computation error. A 400 X 20 SNN crossbar prototype chip is fabricated via a 28-nm FDSOI CMOS process, and 20 MNIST patterns with their sizes reduced to 20 X 20 pixels are successfully recognized under 411 μW of power consumed. Moreover, the peak-to-peak deviation of the normalized output spike count measured from the 21 fabricated SNN prototype chips is within 16.5% from the ideal value, including sample-wise random variations.

To expand the scale of spiking neural networks (SNNs), an interface circuit that supports multiple SNN cores is essential. This circuit should be designed using an asynchronous approach to leverage characteristics of SNNs similar to those of the human brain. However, the absence of a global clock presents tim-ing issues during implementation. Hence, we propose an intermediate latching template to establish asynchronous nonlinear connectivity with multipipeline processing between multiple SNN cores. We design arbitration and distribu-tion blocks in the interface circuit based on the proposed template and fabri-cate an interface circuit that supports four SNN cores using a full-custom approach in a 28-nm CMOS (complementary metal-oxide-semiconductor) FDSOI (fully depleted silicon on insulator) process. The proposed template can enhance throughput in the interface circuit by up to 53% compared with the conventional asynchronous template. The interface circuit transmits spikes while consuming 1.7 and 3.7 pJ of power, supporting 606 and 59 Mevent/s in intrachip and interchip communications, respectively.

Background/Aims Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF). Methods We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high. Results Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps

During an economic recession, the gaps between community service demands and available resources for nonprofits widen. Nonprofits with financial vulnerability cut back on their services or activities when facing a turbulent economic downturn. To make sense of such situations, drawn from organizational ecology theory, we examine the relationships between environmental factors and a nonprofit’s financial health and the moderating role of the Great Recession of 2008 on their relationship. Employing IRS 990 and US census data (2007–2012) on counties, our longitudinal analysis finds that: 1) nonprofits’ county-level environmental factors, i.e., service demand and available resources, are associated with their financial health; 2) the impact of economic recession on nonprofits’ financial health is particularly severe in communities with greater racial diversity; and 3) nonprofits located in communities with more resources are more likely to be financially healthy and are less affected by the economic recession in the long term.

Background and Objectives: Chronic hepatitis C (CHC) can be cured with direct-acting antiviral (DAA) therapy. In Korea, sofosbuvir (SOF) and ledipasvir (LDV)/SOF were launched in 2016. Patients who achieve a sustained virologic response (SVR) following DAA treatment are predicted to have a favorable prognosis. Nevertheless, little is known regarding the prognosis of Korean CHC patients who receive SOF-based treatment and achieve SVR. Therefore, the purpose of this study was to look into the long-term outcomes for these patients. Materials and Methods: This was a prospective, multicenter observational study. CHC patients were enrolled who, following SOF or LDV/SOF treatment, had achieved SVR. The last day for follow-up was December 2023. The primary endpoint was HCC occurrence, which was checked at least once per year. Results: A total of 516 patients were included in this analysis, with a median follow-up duration of 39.0 months. Among them, 231 were male patients (44.8%), with a median age of 62.0 years. Genotypes were 1 (90, 17.4%), 2 (423, 82.0%), and 3 (3, 0.6%). The combination of SOF plus ribavirin was the most common treatment (394, 76.4%). In total, 160 patients were cirrhotic (31.0%), and the mean Child–Pugh score was 5.1. Within a maximum of 7 years, 21 patients (4.1%) developed HCC. Patients with HCC were older (69 vs. 61 years, p = 0.013) and had a higher cirrhosis incidence (81.0 vs. 28.9%, p < 0.001), higher AFP (6.0 vs. 3.3, p = 0.003) and higher APRI (0.8 vs. 0.5, p = 0.005). Age over 65 (p = 0.016) and cirrhosis (p = 0.005) were found to be significant risk factors for HCC by Cox regression analysis. Conclusions: Patients who achieved SVR with SOF-based treatment had a relatively favorable prognosis. However, the risk of HCC was not eliminated, especially in older and cirrhotic patients. Therefore, routine follow-up, surveillance, and early treatment are required.

This paper presents a low-power and lightweight human body communication (HBC) receiver with an embedded dummy electrode for improved signal acquisition. The clock data recovery (CDR) circuit in the receiver operates with a low supply voltage and utilizes a clock phase inversion scheme. The receiver is equipped with a main electrode and dummy electrode that strengthen the capacitive-coupled signal at the receiver frontend. The receiver CDR circuit exploits a clock inversion scheme to allow 0.9-V operation while achieving a shorter lock time than at 3.3-V operation. In experiments, a receiver chip fabricated using 130-nm complementary metal–oxide–semiconductor technology was demonstrated to successfully receive the transmitted signal when the transmitter and receiver are placed separately on each hand of the user while consuming only 4.98 mW at a 0.9-V supply voltage.

This study presents a novel approach to modeling linearized inertia constraints of generators, considering frequency stability, and applies it to the unit commitment (UC). Specifically, we modeled the average rate of change of frequency (RoCoF) constraint and the minimum frequency constraint using the analytical expression derived from the reduced frequency response (RFR) model. We also considered the load-damping constant as a variable. As the power system has different nonlinear characteristics according to its operating status, the system can be expressed as several different systems. Each subsystem, with its own properties at a given operating point, is modeled as a single-machine system, categorized by pumped storage hydropower (PSH) status. The minimum frequency of each subsystem is determined by its individual machine time constant. We incorporated an additional constraint to ensure the quasi steady-state performance of frequency. This constraint can be omitted when it is not necessary. The proposed concepts have been validated on the Korean Power System. The UC, with the proposed inertia constraints, can secure system inertia and primary frequency response (PFR) that satisfies frequency stability. Our proposed method is more efficient in securing inertia and PFRs and more economical in terms of generation cost compared to existing methods.

Background: The European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium suggested that the clinical courses after acute decompensation (AD) stratify the long-term prognosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre acute-on-chronic liver failure (pre ACLF), and ACLF. However, previous studies included patients with a history of previous AD and had limitations associated with identifying the clinical factors related to prognosis after the first AD. Method: The prospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort included cirrhotic patients who were hospitalised with first AD between July 2015 and August 2018. We analysed the factors associated with readmission after the first AD and compared the characteristics and prognosis among each subgroup to evaluate the risk factors for the occurrence of pre ACLF after AD. Result: A total of 746 cirrhotic patients who were hospitalised with first AD were enrolled. The subgroups consisted of SDC (n = 565), UDC (n = 29), pre ACLF (n = 28), and ACLF (n = 124). Of note, pre ACLF showed a poorer prognosis than ACLF. The risk factors associated with readmission within 3 months of first AD were non-variceal gastrointestinal (GI) bleeding, hepatic encephalopathy (HE), and high MELD score. Viral aetiology was associated with the occurrence of pre ACLF compared with alcohol aetiology regardless of baseline liver function status. Conclusion: Cirrhotic patients with first AD who present as non-variceal GI bleeding and HE can easily relapse. Interestingly, the occurrence of AD with organ failure within 3 months of first AD (pre ACLF) has worse prognosis compared with the occurrence of organ failure at first AD (ACLF). In particular, cirrhotic patients with viral hepatitis with/without alcohol consumption showed poor prognosis compared to other aetiologies. Therefore, patients with ACLF after AD within 3 months should be treated more carefully and definitive treatment through LT should be considered.

This study aimed to identify the level of stress in teenagers from multicultural families in Korea and examine the factors influencing this stress. This cross-sectional study utilized the 15th (2019) Korea Youth Risk Bsehavior Web-based Survey. Of the 57,303 survey participants, 749 reported that their father, mother, or both parents were born outside of Korea. These 749 multicultural individuals were selected as study participants. We examined general characteristics (sex, grade, parental education level, academic performance level, foreign nationality, residence type, economic status, exposure to violence, and frequency of physical activity), health risk behaviors (sexual activity, drug use, and drinking), and mental health factors (sleep, depression, and presence of suicidal thoughts) to determine whether these factors may contribute to multicultural adolescent stress. Multicultural adolescents who reported insufficient sleep, depression, or suicidal thoughts were more likely to experience stress than those who did not report these factors. Moreover, participants with insufficient sleep were 3.73 times more likely to feel stress than those with good sleep. Among general characteristics, health risk behaviors, and mental health factors, mental health factors were observed to significantly predict an increase in multicultural adolescents’ stress levels. Considering the increase in the number of multicultural adolescents in Korea, it is important to address the difficulties they experience to provide appropriate interventional programs. Such programs should include techniques to help with the management of stress.

It is important to make a differential diagnosis between inflammatory diseases of the bowel with similar clinical and endoscopic features. The profiling of immune cells could be helpful for accurately diagnosing inflammatory bowel diseases. We compared immune marker expression between Crohn’s disease (CD), intestinal Behcet’s disease (BD), and intestinal tuberculosis (TB) and evaluated the usefulness of immune profiling in differentiating between these diseases. Biopsy specimens were acquired around ulcerations on the terminal ileum or cecum from five patients with each disease. Panel 1 included multiplex immunohistochemistry staining for CD8, CD4, Foxp3, CD20, programmed death-1, and granzyme B. CD56, CD68, CD163, CD11c, and HLA-DR were analyzed in panel 2. The differences in cytotoxic T cells (CD8+CD4−Fopx3−CD20−), helper T cells (CD8−CD4+Fopx3−CD20−), and regulatory T cells (CD8−CD4+Fopx3+CD20−) were also not significant. However, M1 macrophage (CD68+CD163−HLA−DR−) cell densities were significantly higher in intestinal BD than in other diseases. The expression level of dendritic cells (CD56−CD68−CD163−CD11c+HLA-DR+) was highest in intestinal TB and lowest in intestinal BD. The expression of immune cells, including M1 macrophages and dendritic cells, was different between CD, intestinal BD, and intestinal TB. Immune profiling can be helpful for establishing differential diagnoses of inflammatory bowel diseases.

Treatment of osteoarthritis (OA) by administration of corticosteroids is a commonly used method in clinics using anti-inflammatory medicine. Oral administration or intra-articular injection of corticosteroids can reduce the pain and progress of cartilage degeneration, but they are usually insufficient to show local and long-term anti-inflammatory effects because of their fast clearance in the body. In this study, we suggest an injectable anti-OA drug depot system for sustained drug release that provides long-term effective therapeutic advantages. Amphiphilic poly(organophosphazene), which has temperature-dependent nanoparticle forming and sol-gel transition behaviors when dissolved in aqueous solution, was synthesized for triamcinolone acetonide (TCA) delivery. Because hydrophobic parts of the polymer can interact with hydrophobic parts of the TCA, the TCA was encapsulated into the self-assembled polymeric nanoparticles. The TCA-encapsulated polymeric nanoparticles (TePNs) were well dispersed in an aqueous solution below room temperature so that they can be easily injected as a sol state into an intra-articular region. However, the TePNs solution transforms immediately to a viscose 3D hydrogel like a synovial fluid in the intra-articular region via the conducted body temperature. An in vitro TCA release study showed sustained TCA release for six weeks. One-time injection of the TePN hydrogel system in an early stage of OA-induced rat model showed a great inhibition effect against further OA progression. The OA-induced knees completely recovered as a healthy cartilage without any abnormal symptoms.

Abstract Background Alendronate (Alen) is promising material used for bone-targeted drug delivery due to its high bone affinity and therapeutic effects on bone diseases. In addition, Alen can enhance the osteogenic differentiation of osteoblastic cell. Recently, nanodiamonds (NDs) with hardness, non-toxicity, and excellent biocompatibility are employed as promising materials for carrier systems and osteogenic differentiation. Therefore, we prepared Alen-conjugated NDs (Alen-NDs) and evaluated their osteogenic differentiation performances. Methods Alen-NDs were synthesized using DMTMM as a coupling reagent. Morphological change of Mouse calvaria-derived preosteoblast (MC3T3-E1) treated with Alen-NDs was observed using the confocal microscope. The osteogenic differentiation was confirmed by cell proliferation, alkaline phosphatase (ALP), calcium deposition, and real-time polymerase chain reaction assay. Results Alen-NDs were prepared to evaluate their effect on the proliferation and differentiation of osteoblastic MC3T3-E1 cells. The Alen-NDs had a size of about 100 nm, and no cytotoxicity at less than 100 μg/mL of concentration. The treatment of NDs and Alen-NDs reduced the proliferation rate of MC3T3-E1 cells without cell death. Confocal microscopy images confirmed that the treatment of NDs and Alen-NDs changed the cellular morphology from a fibroblastic shape to a cuboidal shape. Flow cytometry, alkaline phosphatase (ALP) activity, calcium deposition, and real-time polymerase chain reaction (RT-PCR) confirmed the higher differentiation of MC3T3-E1 cells treated by Alen-NDs, compared to the groups treated by osteogenic medium and NDs. The higher concentration of Alen-ND treated in MC3T3-E1 resulted in a higher differentiation level. Conclusions Alen-NDs can be used as potential therapeutic agents for osteoporosis treatment by inducing osteogenic differentiation.

Aim and Objectives: Direct-acting antiviral (DAA) therapy can cure chronic hepatitis C (CHC), and daclatasvir (DCV)/asunaprevir (ASV) was the first interferon-free DAA therapy introduced in Korea. Patients who achieve sustained virologic response (SVR) after DAA treatment are expected to have good prognoses. Therefore, in this study, we aimed to investigate the prognosis of these patients. Materials and Methods: This multicenter prospective observational study included patients with CHC who achieved SVR after DCV/ASV treatment. The primary endpoint was hepatocellular carcinoma (HCC) occurrence, which was reviewed annually. Results: We included 302 patients (median follow-up duration: 38 [16.5–60.0] months; median age: 58 [49–67] years) in the study. Cirrhosis was observed in 103 patients (34.1%), and the median Child–Pugh score was 5.0. HCC occurred in 16 patients (5.3%) within six years post-SVR; these patients were older and had higher cirrhosis prevalence, alpha-fetoprotein levels, and fibrosis-4 index scores than did those without HCC development. Cox proportional hazards analysis revealed that age > 71 years (p = 0.005) and cirrhosis (p = 0.035) were significant risk factors for HCC occurrence. Conclusions: Although the prognoses of patients who achieved SVR with DCV/ASV therapy were generally good, the risk for HCC was present, especially in older patients and in those with cirrhosis. Hence, early treatment at younger ages and regular follow-up surveillance after achieving SVR are warranted.

Alcoholic liver disease (ALD) involves a wide spectrum of diseases, including asymptomatic hepatic steatosis, alcoholic hepatitis, hepatic fibrosis, and cirrhosis, which leads to morbidity and mortality and is responsible for 0.9% of global deaths. Alcohol consumption induces bacterial translocation and alteration of the gut microbiota composition. These changes in gut microbiota aggravate hepatic inflammation and fibrosis. Alteration of the gut microbiota leads to a weakened gut barrier and changes host immunity and metabolic function, especially related to bile acid metabolism. Modulation and treatment for the gut microbiota in ALD has been studied using probiotics, prebiotics, synbiotics, and fecal microbial transplantation with meaningful results. In this review, we focused on the interaction between alcohol and gut dysbiosis in ALD. Additionally, treatment approaches for gut dysbiosis, such as abstinence, diet, pro-, pre-, and synbiotics, antibiotics, and fecal microbial transplantation, are covered here under ALD. However, further research through human clinical trials is warranted to evaluate the appropriate gut microbiota-modulating agents for each condition related to ALD.

Evaluation of hepatic fibrosis is essential to prevent liver-related morbidity and mortality. Although various types of ultrasound shear wave elastography (SWE) have been used and validated, there are limited studies on the relatively newer technique, two-dimensional SWE (2D-SWE). Therefore, this study aimed to compare the diagnostic performances of 2D-SWE and point SWE (p-SWE) for evaluating liver fibrosis using histology as the reference standard. To measure liver stiffness (LS) values, 87 patients underwent 2D-SWE and p-SWE using the same machine. Technical failures and unreliable measurements were also evaluated. The diagnostic performances of 2D-SWE and p-SWE were compared using area under the receiver operating characteristic (AUROC) curve analysis. No technical failures were observed in either method; however, unreliable measurements were less frequent in 2D-SWE (1/87 [1.1%]) than in p-SWE (8/87 [9.2%]) (p < 0.001). The AUROC of the LS values of 2D-SWE were significantly higher than those of p-SWE for diagnosing significant fibrosis (0.965 vs. 0.872, p = 0.022) and cirrhosis (0.994 vs. 0.886, p = 0.042). In conclusion, 2D-SWE is more reliable and accurate than p-SWE for diagnosing hepatic fibrosis.

Background Eye measurements in Koreans have been studied extensively, but researchers have reported widely differing values, even for the same parameters. These discrepancies are likely due to inconsistencies in the proportions of subjects with double eyelids included in their studies. We retrospectively studied eye measurements according to the presence or absence of double eyelids, and compared the results to those of previous studies. Methods We conducted anthropometric measurements of eyes in young (20–29 years) Korean women with no congenital malformation, trauma, or surgery of the eyelids. The participants were dichotomized according to the presence of double eyelids, resulting in 116 eyes with single eyelids and 124 with double eyelids. We measured the palpebral fissure length (PFL), palpebral fissure height (PFH), margin reflex distance 1 (MRD1), intercanthal distance (ICD), interpupillary distance (IPD), outer canthal distance (OCD), and inclination of the palpebral fissure in each eye. Results The mean PFL was 24.1 mm in the single-eyelid group and 25.5 mm in the double-eyelid group. The other mean values for the two groups were as follows: PFH, 8.0 mm and 9.9 mm, respectively; MRD1, 2.8 mm and 4.1 mm, respectively; IPD, 61.6 mm and 62.8 mm, respectively; and OCD, 85.3 mm and 87.9 mm, respectively. Conclusions In the double-eyelid group, the horizontal and vertical length of the eye was greater than in the single-eyelid group, and the mean values of IPD, OCD, PFL, PFH, and MRD1 were statistically significantly higher.

Extramammary Paget disease (EMPD) is an uncommon malignancy that occurs in apocrine gland-rich areas of the body. EMPD of the axilla is rare, but a few cases have been reported. Some cases of EMPD have been reported with underlying apocrine adenocarcinoma; rarely, mammary-type ductal carcinoma can accompany EMPD. Here, we report a very rare case of EMPD with apocrine adenocarcinoma and invasive mammary-type ductal carcinoma. A 55-year-old woman was referred with a brownish pigmented plaque accompanying an area of ulceration in the left axilla. A preoperative biopsy indicated Paget disease, and an additional evaluation was performed to determine whether it was of primary or secondary origin. A wide excision was made, and the axilla was reconstructed using a thoracodorsal artery perforator flap. The biopsy showed apocrine adenocarcinoma and invasive mammary-type ductal carcinoma with pagetoid spreading. The patient had no evidence of recurrence or other postoperative complications.

Peptidyl arginine deiminases (PAD) enzymes have been investigated in various cancers. Recently, PAD enzyme, in particular PAD2, has been further implicated in cancers. Although the expression of PAD2 was significantly higher in hepatocellular carcinoma (HCC) tissue, its diagnostic or prognostic role of PAD2 in HCC patients is unknown. This study investigated whether the expression of PAD2 affects recurrence and survival in HCC patients who underwent hepatic resection. One hundred and twenty-two HCC patients after hepatic resection were enrolled. The median follow-up was 41 months (range 1–213 months) in enrolled patients. To investigate an association between PAD2 expression level and the clinical characteristics of enrolled patients, the recurrence of HCC following surgical resection and survival of the patients were examined. Ninety-eight cases (80.3%) of HCC demonstrated a higher expression of PAD2. The expression of PAD2 was correlated with age, hepatitis B virus positivity, hypertension, and higher alpha-fetoprotein level. There was no association between PAD2 expression and sex, diabetes mellitus, Child–Pugh class, major portal vein invasion, HCC size or number. The recurrence rates in patients with lower PAD2 expression were higher than those with higher PAD2 expression. The cumulative survival rates of patients with higher PAD2 expression were better than those of patients with lower PAD2 expression, but it was not statistically significant. In conclusion, PAD2 expression is closely associated with recurrence of HCC patients following surgical resection.

Hepatic encephalopathy (HE) is one of the main complications of liver cirrhosis (LC) and is classified into minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy (overt HE). S100B is expressed mainly in astrocytes and other glial cells, and S100B has been reported to be associated with various neurological disorders. The present study aimed to investigate the diagnostic ability of serum S100B to discriminate the grade of HE and the parameters correlated with serum S100B levels. Additionally, we investigated whether serum S100B levels can be used to predict 1-year mortality in cirrhotic patients. In total, 95 cirrhotic patients were consecutively enrolled and divided into the following three groups: (i) without any types of HEs; (ii) with MHE; and (iii) with overt HE. The diagnosis of MHE was made by the Mini-Mental State Examination (MMSE) and Psychometric Hepatic Encephalopathy Score (PHES). Among the three groups, there were no significant differences in serum S100B levels regardless of HE severity. The clinical parameters correlated with serum S100B levels were age, serum bilirubin, and creatinine levels. The Model for End-Stage Liver Disease (MELD) score showed a significant positive correlation with serum S100B levels. The relationship between serum S100B levels and MELD score was maintained in 48 patients without any type of HE. Additionally, hyperammonemia, low cholesterol levels, and the combination of serum S100B levels ≥ 35 pg/mL with MELD score ≥ 13 were factors for predicting 1- year mortality. In conclusion, serum S100B level was not useful for differentiating the severity of HE. However, we found that serum S100B levels can be affected by age, serum bilirubin, and creatinine in cirrhotic patients and are associated with MELD scores. Additionally, serum S100B levels showed the possibility of predicting 1-year mortality in cirrhotic patients. These findings suggest that serum S100B levels may reflect liver dysfunction and prognosis in liver disease.

Sonic hedgehog (Shh) signaling regulates multiple morphogenetic processes during embryonic neurogenesis and craniofacial skeletal development. Gpr161 is a known negative regulator of Shh signaling. Nullizygous Gpr161 mice are embryonic lethal, presenting with structural defects involving the neural tube and the craniofacies. However, the lineage specific role of Gpr161 in later embryonic development has not been thoroughly investigated. We studied the Wnt1-Cre lineage specific role of Gpr161 during mouse embryonic development. We observed three major gross morphological phenotypes in Gpr161 cKO (Gpr161 f/f; Wnt1-Cre) fetuses; protrusive tectum defect, encephalocele, and craniofacial skeletal defect. The overall midbrain tissues were expanded and cell proliferation in ventricular zones of midbrain was increased in Gpr161 cKO fetuses, suggesting that protrusive tectal defects in Gpr161 cKO are secondary to the increased proliferation of midbrain neural progenitor cells. Shh signaling activity as well as upstream Wnt signaling activity were increased in midbrain tissues of Gpr161 cKO fetuses. RNA sequencing further suggested that genes in the Shh, Wnt, Fgf and Notch signaling pathways were differentially regulated in the midbrain of Gpr161 cKO fetuses. Finally, we determined that cranial neural crest derived craniofacial bone formation was significantly inhibited in Gpr161 cKO fetuses, which partly explains the development of encephalocele. Our results suggest that Gpr161 plays a distinct role in midbrain development and in the formation of the craniofacial skeleton during mouse embryogenesis.

The platelet-to-white blood cell ratio (PWR) has been reported to predict the severity of patients with various diseases. However, no previous studies have assessed the use of the PWR as a prognostic marker for pyogenic liver abscesses (PLA). This observational retrospective study was performed between January 2008 and December 2017, including 833 patients with PLA from multiple centers. The enrolled patients, on average, had a PWR of 17.05, and 416 patients had a PWR lower than 17.05. A total of 260 patients (31.2%) with PLA showed complications of metastatic infection, pleural effusion and abscess rupture. A low PWR level was identified as a strong risk factor for metastatic infection and pleural effusion. The low PWR group also had a longer hospital stay. In the multivariate analysis, old age, anemia, albumin and CRP levels and unidentified pathogens were significant factors for low PWR levels. A low PWR, old age, male sex, abscess size, albumin, ALP and unidentified causative pathogens showed significant associations with a hospital stay longer than 28 days. As a result, PLA patients presenting with a low PWR were shown to have more complications and a poor prognosis. Considering its cost-effectiveness, PWR could be a novel biomarker used to predict a prognosis of PLA.

Implant-based breast reconstruction is the most commonly used reconstruction technique after mastectomy. This is because skin-sparing mastectomy has become possible with advancements in oncology. In addition, the development of breast implants and the advent of acellular dermal matrices have reduced postoperative complications and resulted in superior cosmetic results. The most frequently performed surgical breast reconstruction procedure for the past 20 years was the insertion of an implant under the pectoralis major muscle by means of the dual plane approach. However, some patients suffered from pain and animation deformity caused by muscle manipulation. Recently, a prepectoral approach has been used to solve the above problems in select patients, and the results are similar to subpectoral results. However, this technique is not always chosen due to the number of considerations for successful surgery. In this article, we will discuss the emergence of prepectoral breast reconstruction, indications and contraindications, surgical procedures, and outcomes.

Abstract Background More than half of the adult population worldwide is overweight or obese, while excess adiposity has been linked to chronic low-grade inflammation, contributing to the development of chronic diseases. Recent studies have showed that diet-induced alterations to the gut microbiota composition play a pivotal role in the development of obesity. However, the cause-effect relationship between obesity and gut microbiota composition is not yet fully understood. In this study, we investigated the short-term responses of gut microbiota composition to diets with different fat contents and their associations with inflammatory biomarkers. Results Sixty male C57BL/6 J mice were fed a normal diet (ND; 15% fat) or a high-fat diet (HFD; 45% fat) for 10 or 20 weeks. The relative proportion of the phylum Actinobacteria was elevated by the HFD and was positively associated with body weight and proinflammatory cytokines including TNF-α, IL-1β, and IL-6. The proportion of the phylum Firmicutes increased with aging and was also positively correlated with proinflammatory cytokines. The proportions of Actinobacteria and Firmicutes were inversely associated with tight junction proteins claudin-1 and E-cadherin, respectively. The proportions of the class Clostridia and the family Ruminococcaceae within the phylum Firmicutes were affected by both diet and age. In addition, the proportions of the phylum Bacteroidetes, the family Bacteroidaceae, and the genus Bacteroides decreased with aging and were inversely correlated with colonic proinflammatory cytokines representing a positive association with tight junction proteins. Conclusions Host age and dietary fat intake are important elements that induce proportional changes in gut microbiota, and these changes are also associated with systemic inflammation. This study provides evidence that diet affects the gut microbiota composition within a short period of time.

Background Barbed thread lifting is known to be a minimally invasive procedure compared with standard incisional surgery for facial rejuvenation. However, some studies have pointed out that the effects of thread lifting do not last long and disappear after several months. Therefore, the aim of this study was to evaluate the efficiency and duration of anchoring-type absorbable thread lifting combined with liposuction for facial rejuvenation. Methods A retrospective review of 27 cosmetic patients who underwent absorbable barbed thread lifting with liposuction between July 2013 and December 2015 was undertaken. The efficiency of facial rejuvenation was evaluated through a patient satisfaction score and the global aesthetic improvement scale (GAIS). Results Subjects were divided into two groups: thread lifting only and thread lifting combined with liposuction. The mean follow-up period of each group was 8.5 and 9.3 months, respectively. In the thread lifting–only group, the average patient satisfaction score was 2.36 (1=unsatisfied to 4=very satisfied), and the average GAIS score was 2.54 (1=very much improved to 5=worsen). In the thread lifting with liposuction group, the average patient satisfaction score was 3.06, and the average GAIS score was 1.85. Conclusions Thread lifting combined with liposuction showed better patient satisfaction and GAIS results than thread lifting alone, even over a long follow-up period.

Purpose To assess clinical and angiographic outcomes after endovascular treatment (EVT) in ischemic stroke patients according to anesthesia types (general anesthesia vs. conscious sedation).Materials and Methods A systematic literature review through an online data base between January 1990 and September 2017 was performed. A fixed effect model was used in cases of

Background Blepharoptosis is the drooping of the margin of the upper eyelid, which narrows the palpebral fissure and makes it difficult to open the eye. Various surgical methods are used to correct blepharoptosis and have been investigated in different studies. After surgery, blepharoptosis can relapse over time, which affects a patient’s satisfaction with the operation. However, few studies have investigated the long-term outcomes of patients after blepharoptosis surgery. Methods From 1991 to 2013, 325 patients (480 eyelids) underwent frontalis muscle transfer or Müller- aponeurosis composite flap advancement in our clinic. We analyzed 12 patients (13 eyelids) with severe ptosis who had been followed-up for more than 5 years. Six patients underwent frontalis muscle transfer for the correction of seven eyelids, while Müller-aponeurosis composite flap advancement was performed on six patients (six eyelids). The marginal reflex distance (MRD1), area of corneal exposure (ACE), and height of the eyebrow were used to analyze the objective outcomes, and the Glasgow Benefit Inventory questionnaire was used for the analysis of subjective patient satisfaction. Results There were no significant differences in the MRD1, ACE, and eyebrow height between the two methods used to correct ptosis. However, over the long-term (>5 years), the MRD1, ACE, and eyebrow height were better maintained in patients who underwent Müller-aponeurosis composite flap advancement than in patients who received frontalis muscle transfer. Conclusions Both surgeries were effective for blepharoptosis correction. However, Müller-aponeurosis composite flap advancement was better for long-term maintenance after surgery than frontalis muscle transfer.

The cellular prion protein (PrPC) is known to play a role in cancer proliferation and metastasis. However, the role of PrPC expression in hepatocellular carcinoma (HCC) is unknown. This study investigated whether overexpression of PrPC affects recurrence after surgical resection and survival in HCC. A total of 110 HCC patients who underwent hepatic resection were included. They were followed up for a median of 42 months (range 1–213 months) after hepatectomy. The relationships between PrPC expression and the HCC histologic features, recurrence of HCC following surgical resection, and survival of the patients were examined. Seventy-one cases (64.5%) of HCC demonstrated higher expression of PrPC. The expression of PrPC was only correlated with diabetes mellitus. There was no association between PrPC expression and age, sex, hypertension, hepatitis B virus positivity, alcohol consumption, Child–Pugh class, major portal vein invasion, serum alpha-fetoprotein, and HCC size or number. The 1-year recurrence rates in patients with higher PrPC expression were higher than those with lower PrPC expression. The cumulative survival rates of patients with higher PrPC expression were significantly shorter than those of patients with lower PrPC expression. In conclusion, PrPC expression is closely associated with early recurrence and poor survival of HCC patients following surgical resection.

Inflammatory bowel disease (IBD) is characterized by chronic intestinal-tract inflammation with dysregulated immune responses, which are partly attributable to dysbiosis. Given that diet plays a critical role in IBD pathogenesis and progression, we elucidated the effects of a high-fat diet (HFD) feeding on IBD development in relation to immune dysfunction and the gut microbiota. Five-week-old male C57BL/6J mice were fed either a normal diet (ND) or HFD for 14 weeks. The animals were further divided into ND, ND+ dextran sulfate sodium (DSS), HFD, and HFD+DSS treatment groups. The HFD+DSS mice exhibited lower body weight loss, lower disease activity index, longer colon length, and increased tight-junction protein expression and goblet-cell proportions compared with the ND+DSS mice. The T helper (h)1 and Th17 cell populations and pro-inflammatory cytokines involved in colitis pathogenesis were significantly more reduced in the HFD+DSS mice than in the ND+DSS mice. The HFD+DSS mice showed significantly increased serum leptin concentrations, colonic leptin receptor expression, enhanced anti-apoptotic AKT expression, and reduced pro-apoptotic MAPK and Bax expression compared with the ND+DSS mice, suggesting the involvement of the leptin-mediated pathway in intestinal epithelial cell apoptosis. The alterations in the gut-microbiota composition in the HFD+DSS group were the opposite of those in the ND+DSS group and rather similar to those of the ND group, indicating that the protective effects of HFD feeding against DSS-induced colitis are associated with changes in gut-microbiota composition. Overall, HFD feeding ameliorates DSS-induced colitis and colonic mucosal damage by reinforcing colonic barrier function and regulating immune responses in association with changes in gut-microbiota composition.

Human structural congenital malformations are the leading cause of infant mortality in the United States. Estimates from the United States Center for Disease Control and Prevention (CDC) determine that close to 3% of all United States newborns present with birth defects; the worldwide estimate approaches 6% of infants presenting with congenital anomalies. The scientific community has recognized for decades that the majority of birth defects have undetermined etiologies, although we propose that environmental agents interacting with inherited susceptibility genes are the major contributing factors. Neural tube defects (NTDs) are among the most prevalent human birth defects and as such, these malformations will be the primary focus of this review. NTDs result from failures in embryonic central nervous system development and are classified by their anatomical locations. Defects in the posterior portion of the neural tube are referred to as meningomyeloceles (spina bifida), while the more anterior defects are differentiated as anencephaly, encephalocele, or iniencephaly. Craniorachischisis involves a failure of the neural folds to elevate and thus disrupt the entire length of the neural tube. Worldwide NTDs have a prevalence of approximately 18.6 per 10,000 live births. It is widely believed that genetic factors are responsible for some 70% of NTDs, while the intrauterine environment tips the balance toward neurulation failure in at risk individuals. Despite aggressive educational campaigns to inform the public about folic acid supplementation and the benefits of providing mandatory folic acid food fortification in the United States, NTDs still affect up to 2,300 United States births annually and some 166,000 spina bifida patients currently live in the United States, more than half of whom are now adults. Within the context of this review, we will consider the role of maternal nutritional status (deficiency states involving B vitamins and one carbon analytes) and the potential modifiers of NTD risk beyond folic acid. There are several well-established human teratogens that contribute to the population burden of NTDs, including: industrial waste and pollutants [e.g., arsenic, pesticides, and polycyclic aromatic hydrocarbons (PAHs)], pharmaceuticals (e.g., anti-epileptic medications), and maternal hyperthermia during the first trimester. Animal models for these teratogens are described with attention focused on valproic acid (VPA; Depakote). Genetic interrogation of model systems involving VPA will be used as a model approach to discerning susceptibility factors that define the gene-environment interactions contributing to the etiology of NTDs.

Cholangiopathies encompass various biliary diseases affecting the biliary epithelium, resulting in cholestasis, inflammation, fibrosis, and ultimately liver cirrhosis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the most important progressive cholangiopathies in adults. Much research has broadened the scope of disease biology to genetic risk, epigenetic changes, dysregulated mucosal immunity, altered biliary epithelial cell function, and dysbiosis, all of which interact and arise in the context of ill-defined environmental triggers. An in-depth understanding of the molecular pathogenesis of these cholestatic diseases will help clinicians better prevent and treat diseases. In this review, we focus on the main underlying mechanisms of disease initiation and progression, and novel targeted therapeutics beyond currently approved treatments.

The mechanical properties of polyamide 6 glass fiber (PA6/GF) long-fiber-reinforced thermoplastic (LFT) composites were characterized by studying the process conditions in terms of manufacturing methods (direct extrusion and pultrusion) and material characteristics (void content and fiber volume fraction). The LFT composites prepared through the pultrusion process have higher mechanical properties than those prepared via the direct extrusion process. The PA6/GF composite prepared via pultrusion had the tensile and flexural strengths of 233 MPa and 338 MPa, respectively. The impact strength measured using the Izod method was 296 J/m, which is 64% higher than that of the composite fabricated via the direct process. The optical microscope images showed that the glass fiber length of the pultruded composites is longer than the fiber length of the direct composites, leading to higher mechanical properties of the LFT composites prepared through the pultrusion process. Moreover, the interfacial shear strength between the resin and the fiber, measured via single fiber pullout tests, can account for the higher fiber reinforcing efficiency. If the void content of a composite is sufficiently small to not be detrimental to the composites, the mechanical properties are observed to be proportional to the fiber volume fraction of the composites.

Purpose Multiple sclerosis is an autoimmune disease that affects the central nerve system, resulting in cumulative loss of motor function. Multiple sclerosis is induced through multiple mechanisms and is caused by inflammation and demyelination. This study aims to evaluate the neuroprotective effect of swimming exercise in experimental autoimmune encephalomyelitis (EAE) rats, an animal model of multiple sclerosis. Methods EAE was induced by an intradermal injection of 50-μg purified myelin oligodendrocyte glycoprotein 33–55 (MOG33-55) dissolved in 200-μL saline at the base of the tail. The rats in the swimming exercise group were made to swim for 30 minutes once pert a day for 26 consecutive days, starting 5 days after induction of EAE. To compare the effect of swimming exercise with interferon-β, a drug for multiple sclerosis, interferon-β was injected intraperitoneally into rats of the EAE-induced and interferon-β-treated group during the exercise period. Results Injection of MOG33-55 caused weight loss, decreased clinical disability score, and increased level of pro-inflammatory cytokines and inflammatory mediators in the lumbar spinal cord. Loss of motor function and weakness increased demyelination score. Swimming exercise suppressed demyelination and expression of pro-inflammatory cytokines and inflammatory mediators. These changes promoted recovery of EAE symptoms such as body weight loss, motor dysfunction, and weakness. Swimming exercise caused the same level of improvement as interferon-β treatment. Conclusions The results of this experiment suggest the possibility of swimming exercise in urological diseases that are difficult to treat. Swimming exercises can be considered for relief of symptom in incurable multiple sclerosis.

Background Current guidelines recommend bismuth-containing quadruple therapy (BQT) and quinolone-containing therapy after failure of first-line Helicobacter pylori eradication therapy. However, the optimum regimen of second-line eradication therapy remains elusive. We conducted a network meta-analysis to compare the relative efficacy of 16 second-line H. pylori eradication regimens.Methods Three major bibliographic databases were reviewed to enrol relevant randomised controlled trials between January 2000 and September 2018. Network meta-analysis was conducted by STATA software and we performed subgroup analysis in countries with high clarithromycin resistance and high levofloxacin resistance, and in patients with documented failure of first-line triple therapy.Results Fifty-four studies totalling 8752 participants who received 16 regimens were eligible for analysis. Compared with a 7-day BQT, use of probiotic add-on therapy during, before, and after second-line antibiotic regimens, quinolone-based sequential therapy for 10–14 days, quinolone-based bismuth quadruple therapy for 10–14 days, bismuth quadruple therapy for 10–14 days, and quinolone-based triple therapy for 10–14 days were significantly superior to the other regimens. Subgroup analysis of countries with high clarithromycin resistance and high levofloxacin resistance revealed that the ranking of second-line eradication regimens was distributed similarly in each group, as well as in patients with failure of first-line triple therapy.Conclusion We conducted a detailed comparison of second-line H. pylori regimens according to different antibiotic resistance rates and the results suggest alternative treatment choices with potential benefits beyond those that could be achieved using salvage therapies recommended by guidelines.

Background: Blood pressure (BP) variability has been associated with stroke risk. We elucidated the association between systolic BP (SBP) variation and outcomes in patients with nonlobar intracerebral hemorrhage (ICH) following intensive antihypertensive treatment upfront. Methods: We screened consecutive patients with spontaneous ICH who underwent intensive antihypertensive treatments targeting BP

Androgen deprivation therapy, also known as chemical castration, has been used as an adjunct to psychotherapy for sex offenders. Goserelin and bicalutamide are drugs used for chemical castration. Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter involved in mood changes, such as depression. We investigated the effects of surgical and chemical castration on depressive symptoms in rats. Surgical castration was performed through a bilateral orchiectomy. Bicalutamide was administrated orally once a day for 84 consecutive days. Goserelin acetate was implanted subcutaneously into the anterior abdominal wall, and this implantation was repeated 3 times at 28-day intervals. Testosterone levels were detected by enzyme-linked immunosorbent assays. Sexual behaviors were analyzed by measuring mount latency, mount frequency, intromission latency, and intromission frequency. The forced swimming test was performed to evaluate rats’ depression status. To detect 5-HT and tryptophan hydroxylase (TPH)-positive cells in the dorsal raphe, immunohistochemistry for 5-HT and TPH and western blotting for 5-HT1A receptors and TPH were performed. Surgical castration and goserelin decreased testosterone levels and suppressed sexual behaviors. However, bicalutamide did not inhibit sexual behaviors, although it reduced testosterone levels to a limited extent. Both surgical and chemical castration induced depression in rats. The expression of 5-HT, TPH, and 5-HT1A receptors in the dorsal raphe was significantly decreased by both surgical castration and chemical castration via bicalutamide and goserelin. The present results showed that surgical and chemical castration for 12 weeks induced a depressive state in rats by inhibiting serotonergic function through 5-HT1A receptors.

Abstract Background Risk scoring systems are used to evaluate patients with upper gastrointestinal bleeding (UGIB). We compared Glasgow-Blatchford score (GBS), modified GBS (mGBS), and Pre-endoscopy Rockall score (Pre-E RS) for immediate application without endoscopic findings in predicting the need of interventions and the 30-day mortality in patients with UGIB. Methods Patients who visited the emergency room with UGIB from January 2007 to June 2016 were included. GBS, mGBS, and Pre-E RS were obtained for all patients. The area under the receiver-operating characteristic curves (AUC) was used to assess the accuracy of the scoring systems to determine the need for interventions and 30-day mortality. Also, we investigated the potential cutoff scores for predicting 30-day mortality and the need for interventions. Results In predicting the need for interventions, GBS (AUC = 0.727) and mGBS (AUC = 0.733) outperformed Pre-E RS (AUC = 0.564, P

In recent years, the need for generation mixes that consider the inertial constraints in unit commitment (UC) has increased because the inertia of these systems has decreased with the increased use of renewable energy. In these circumstances, single-machine models can calculate the minimum frequency and rate of change of frequency (RoCoF) at a high speed in terms of the characteristics of the changes in the generation mix, in order to identify the generation mixes that can satisfy inertial constraints. This study proposed methods to determine the parameters of the reduced frequency response (RFR) model, which is a single-machine model that considers the nonlinearity caused by restrictions on the generator’s output power, in order to apply inertial constraints to UC. The RFR models can include various forms of governor models and consider the nonlinear response characteristics of restrictions on the generator’s output power that change according to the scales of contingencies, system inertia, and changes in load characteristics through these parameters. From the simulations of real systems, it was observed that the parameters determined through the proposed methods achieved considerable accuracy in calculating the minimum frequency and RoCoF with the RFR model.

In the current study, we fabricated tannic acid-alendronate (TA-ALN) nanocomplexes (NPXs) via self-assembly. These TA-ALNs were characterized by dynamic light scattering, zeta potential, transmission electron microscopy, and FT-IR spectroscopy. The TA-ALNs were evaluated for antioxidant, anti-inflammatory, and osteogenesis-accelerating abilities in osteoblast-like cells (MC3T3-E1 cells). All TA-ALNs displayed nano-sized beads that were circular in form. Treatment with TA-ALN (1:0.1) efficiently removed reactive oxygen species in cells and protected osteoblast-like cells from toxic hydrogen peroxide conditions. Moreover, TA-ALN (1:0.1) could markedly decrease the mRNA levels of pro-inflammatory mediators in lipopolysaccharide-stimulated cells. Furthermore, cells treated with TA-ALN (1:1) exhibited not only significantly greater alkaline phosphatase activity and calcium collection, but also outstandingly higher mRNA levels of osteogenesis-related elements such as collagen type I and osteocalcin. These outcomes indicate that the prepared TA-ALNs are excellent for antioxidant, anti-inflammatory, and osteogenic acceleration. Accordingly, TA-ALN can be used latently for bone renovation and regeneration in people with bone fractures, diseases, or disorders.

Background Various surgical methods for repairing medial orbital wall fractures have been introduced. The conventional technique requires total separation of the displaced orbital bones from the orbital soft tissues. However, subperiosteal dissection around the fracture can cause additional damage. The aim of the present study is to introduce a method of reconstructing medial orbital wall fractures without subperiosteal dissection named the “push-out” technique. Methods Six patients with post-traumatic enophthalmos resulting from an old medial orbital wall fracture and 10 patients with an acute medial orbital wall fracture were included. All were treated with the push-out technique. Postoperative computed tomography (CT) was performed to assess the correct positioning of the implants. The Hertel scale and a comparison between preoperative and postoperative orbital volume were used to assess the surgical results. Results Restoration of the normal orbital cavity shape was confirmed by examining the postoperative CT scans. In the old fracture group, the median orbital volume of the fractured side was 29.22 cm3 preoperatively, and significantly improved postoperatively to a value of 25.13 cm3. In the acute fracture group, the median orbital volume of the fractured side was 28.73 cm3 preoperatively, and significantly improved postoperatively to a value of 24.90 cm3. Differences on the Hertel scale also improved, from 2.13 mm preoperatively to 0.25 mm postoperatively in the old fracture group and from 1.67 mm preoperatively to 0.33 mm postoperatively in the acute fracture group. Conclusions The push-out technique can be considered a good alternative choice for old medial orbital wall fractures with posttraumatic enophthalmos, acute medial orbital wall fractures including large fractured bone segments, and single-hinged greenstick fractures.

Purpose The functions of the lower urinary tract (LUT), such as voiding and storing urine, are dependent on complex central neural networks located in the brain, spinal cord, and peripheral ganglia. Thus, the functions of the LUT are susceptible to various neurologic disorders including spinal cord injury (SCI). SCI at the cervical or thoracic levels disrupts voluntary control of voiding and the normal reflex pathways coordinating bladder and sphincter functions. In this context, it is noteworthy that α1-adrenoceptor blockers have been reported to relieve voiding symptoms and storage symptoms in elderly men with benign prostatic hyperplasia (BPH). Tamsulosin, an α1-adrenoceptor blocker, is also considered the most effective regimen for patients with LUT symptoms such as BPH and overactive bladder (OAB). Methods In the present study, the effects of tamsulosin on the expression of c-Fos, nerve growth factor (NGF), and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the afferent micturition areas, including the pontine micturition center (PMC), the ventrolateral periaqueductal gray matter (vlPAG), and the spinal cord (L5), of rats with an SCI were investigated. Results SCI was found to remarkably upregulate the expression of c-Fos, NGF, and NADPH-d in the afferent pathway of micturition, the dorsal horn of L5, the vlPAG, and the PMC, resulting in the symptoms of OAB. In contrast, tamsulosin treatment significantly suppressed these neural activities and the production of nitric oxide in the afferent pathways of micturition, and consequently, attenuated the symptoms of OAB. Conclusions Based on these results, tamsulosin, an α1-adrenoceptor antagonist, could be used to attenuate bladder dysfunction following SCI. However, further studies are needed to elucidate the exact mechanism and effects of tamsulosin on the afferent pathways of micturition.

d-Psicose, a rare sugar, not only has very low caloric value but possesses anti-adipogenic properties. Here, we identified target genes in adipose tissue affected by d-psicose by transcriptomic analysis and provided mechanistic explanations for the anti-adipogenic effect. C57BL/6J ob/ob mice were fed with a control or 5% d-psicose diet for 12 weeks. d-Psicose decreased final body weight, adipose tissue mass, adipocyte size, and serum total cholesterol levels. We identified 103 differentially expressed genes involved in inflammatory response, molecular transport, and lipid metabolism consequent to d-psicose administration. Genes related to inflammation and adipo/lipogenesis were significantly down-regulated, whereas those associated with β-oxidation were up-regulated by d-psicose. Our data suggest that Fos, Mmp3, Fgf21, and Abcd2 might be key target genes associated with d-psicose-induced changes in lipid metabolism and subsequent chronic inflammatory responses. d-Psicose is thus a promising sugar substitute possessing a direct gene-regulatory function related to the suppression of body fat deposition.

Background Skin erosion is a dire complication of implantable cardiac pacemakers and defibrillators. Classical treatments involve removal of the entire generator and lead systems, however, these may result in fatal complications. In this study, we present our experience with a simplified salvage technique for exposed implantable cardiac electronic devices (ICEDs) without removing the implanted device, in an attempt to reduce the risks and complication rates associated with this condition. Methods The records of 10 patients who experienced direct ICED exposure between January 2012 and December 2015 were retrospectively reviewed. The following surgical procedure was performed in all patients: removal of skin erosion and capsule, creation of a new pocket at least 1.0–1.5 cm inferior to its original position, migration of the ICED to the new pocket, and insertion of closed-suction drainage. Patients with gross local sepsis or septicemia were excluded from this study. Results Seven patients had cardiac pacemakers and the other 3 had implantable cardiac defibrillators. The time from primary ICED placement to exposure ranged from 0.3 to 151 months (mean, 29 months. Postoperative follow-up in this series ranged from 8 to 31 months (mean follow-up, 22 months). Among the 10 patients, none presented with any signs of overt infection or cutaneous lesions, except 1 patient with hematoma on postoperative day 5. The hematoma was successfully treated by surgical removal and repositioning of the closed-suction drainage. Conclusions Based on our experience, salvage of exposed ICEDs is possible without removing the device in selected patients.

Purpose Circadian rhythm affects learning process, memory consolidation, and long-term memory. In this study, the alleviating effect of exercise on circadian rhythm disruption-induced memory deficits was investigated. Methods BMAL1 knockdown transgenic mice (BMAL1 TG) were used as the BMAL1-TG group and the BMAL1-TG with treadmill exercise group. Female C57BL/6J mice of the same age were used as the wildtype group and the wildtype with treadmill exercise group. The mice in the treadmill exercise groups performed running on a motorized treadmill under the dark-dark conditions for 8 weeks. Short-term memory, nonspatial object memory, and spatial learning memory were determined using stepdown avoidance test, novel object-recognition test, and radial 8-arm maze test. Immunohistochemistry for doublecortin and 5-bromo-2’-deoxyuridine was conducted for the determination of hippocampal neurogenesis. Using the western blot analysis, we determined the expressions of glucocorticoid receptor (GR) and factors related to the neurogenesis and memory consolidation, such as brain-derived neurotrophic factor, tyrosine kinase B, p44/42 mitogen-activated protein kinase, cyclic AMP-responsive element binding protein, phosphatidylinositol 3-kinase, protein kinas B, protein kinase C alpha, early-growth-response gene 1. Results Circadian rhythm disruption impaired memory function through inhibiting the expressions of GR and the factors related to neurogenesis and memory consolidation. Treadmill exercise improved memory function via enhancing the expressions of GR and above-mentioned factors. Conclusions Treadmill exercise acts as the zeitgeber that improves memory function under the circadian rhythm disrupted conditions.

We evaluated whether the pupillary light reflex is altered in benign essential blepharospasm patients. Twenty-three patients with benign essential blepharospasm, 47 with reflex blepharospasm, and 29 dry eye disease controls were included. Pupillary light reflex-related parameters were measured under mesopic (10 lux) and photopic illuminance (200 lux) using an infrared pupillometer. Additionally, we assessed photophobia grade, eyelid function, and dry eye disease-related parameters. There were no differences in age, sex predominance, or dry eye disease-related parameters among the three groups, or in photophobia grade and eyelid function between benign essential blepharospasm and reflex groups. Constriction velocity and maximum constriction velocity in the mesopic condition were significantly greater in the benign essential blepharospasm group (3.26 ± 0.56 and 5.27 ± 0.90 mm/s) than in reflex (2.86 ± 0.62 and 4.59 ± 1.00 mm/s) or dry eye disease groups (2.96 ± 0.46 and 4.72 ± 0.67 mm/s). Constriction velocity and maximum constriction velocity in the mesopic condition positively correlated with photophobia grade (r = 0.525 and 0.617, P = 0.025 and 0.006) in the benign essential blepharospasm group. Pupillary light reflex may be related to the pathophysiology of benign essential blepharospasm with photophobia. Further studies are required to reveal connections among pupillary light reflex, photophobia, and focal dystonia in benign essential blepharospasm patients with photophobia.

Purpose Sleep deprivation induces depressive symptoms. Dexmedetomidine is a α2-adrenoreceptor agonist and this drug possesses sedative, anxiolytic, analgesic, and anesthetic-sparing effect. In this study, the action of dexmedetomidine on sleep deprivation-induced depressive behaviors was investigated using mice. Methods For the inducing of sleep deprivation, the mice were placed inside a water cage containing 15 platforms and filled with water up to 1 cm below the platform surface for 7 days. One day after sleep deprivation, dexmedetomidine at the respective dosage (0.5, 1, and 2 μg/kg) was intraperitoneally treated into the mice, one time per a day during 6 days. Then, forced swimming test and tail suspension test were conducted. Immunohistochemistry for tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT; serotonin), tryptophan hydroxylase (TPH) and western blot for D1 dopamine receptor were also performed. Results Sleep deprivation increased the immobility latency in the forced swimming test and tail suspension test. The expressions of TPH, 5-HT, and D1 dopamine receptor were decreased, whereas, TH expression was increased by sleep deprivation. Dexmedetomidine decreased the immobility latency and increased the expressions of TPH, 5-HT, and D1 dopamine receptor, whereas, HT expression was decreased by dexmedetomidine treatment. Conclusions In our results, dexmedetomidine alleviated sleep deprivation-induced depressive behaviors by increasing 5-HT synthesis and by decreasing dopamine production with up-regulation of D1 dopamine receptor.

Hepatic stellate cells (HSCs) play pivotal roles in hepatic fibrosis as they synthesize glial fibrillary acidic protein (GFAP), which is increased in activated HSCs. GFAP-expressing HSCs and myofibroblasts accumulate in and around hepatic fibrosis lesions. Peptidylarginine deiminase 2 (PAD2) is responsible for the citrullination of GFAP (cit-GFAP). However, the involvement of PAD2 and cit-GFAP in hepatic fibrosis remains unclear. To determine the expression of PAD2 and cit-GFAP in hepatic fibrosis, C57BL/6 mice underwent bile duct ligation (BDL) or a sham operation. In BDL livers, the expression of PAD2 and its enzyme activity were significantly increased compared with controls. In addition, PAD2-postitive cells were rarely observed in only the portal vein and the small bile duct in sham-operated livers, whereas an increased number of PAD2-positive cells were detected in the bile duct and Glisson's sheath in BDL livers. Interestingly, PAD2 was colocalized with α-SMA-positive cells and CK19-positive cells in BDL livers, indicating upregulated PAD2 in activated HSCs and portal fibroblasts of the livers of BDL mice. We also found that citrullinated proteins were highly accumulated in the livers of BDL mice compared with controls. Moreover, the expression level of GFAP and the amount of cit-GFAP were higher in BDL livers than in control livers. In correlation with PAD2 localization, cit-GFAP was observed in α-SMA-positive and CK19-positive cells in the livers of BDL mice. These results suggest that the increased expression and activation of PAD2 along with increased citrullinated proteins, specifically cit-GFAP, may play important roles in the pathogenesis of hepatic fibrosis.