Anti-pollutant effect of oleic acid against urban particulate matter is mediated via regulation of AhR- and TRPV1-mediated signaling in vitro.

Urban Particulate Matter (UPM) induces skin aging and inflammatory responses by regulating skin cells through the transient receptor potential vanilloid 1 (TRPV1). Although oleic acid, an unsaturated free fatty acid (FFA), has some functional activities, its effect on UPM-induced skin damage has not been elucidated. Here, we investigated signaling pathways on how oleic acid is involved in attenuating UPM induced cell damage. UPM treatment increased XRE-promoter luciferase activity and increased translocation of AhR to the nucleus, resulting in the upregulation of CYP1A1 gene. However, oleic acid treatment attenuated the UPM effects on AhR signaling. Furthermore, while UPM induced activation of TRPV1 and MAPKs signaling which activated the downstream molecules NFκB and AP-1, these effects were reduced by cotreatment with oleic acid. UPM-dependent generation of reactive oxygen species (ROS) and reduction of cellular proliferation were also attenuated by the treatment of oleic acid. These data reveal that cell damage induced by UPM treatment occurs through AhR signaling and TRPV1 activation which in turn activates ERK and JNK, ultimately inducing NFκB and AP-1 activation. These effects were reduced by the cotreatment of oleic acid on HaCaT cells. These suggest that oleic acid reduces UPM-induced cell damage through inhibiting both the AhR signaling and activation of TRPV1 and its downstream molecules, leading to a reduction of pro-inflammatory cytokine and recovery of cell proliferation.

Prediction of intradialytic hypotension using pre-dialysis features-a deep learning-based artificial intelligence model.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) that is associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning-based artificial intelligence (AI) model to predict IDH using pre-dialysis features. METHODS: Data from 2007 patients with 943 220 HD sessions at seven university hospitals were used. The performance of the deep learning model was compared with three machine learning models (logistic regression, random forest and XGBoost). RESULTS: IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared with non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared with non-IDH sessions. Matthews correlation coefficient and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session. CONCLUSIONS: Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.

Focality in Febrile Seizures: A Retrospective Assessment Using Arterial Spin Labeling MRI.

PURPOSE: Defining focality of febrile seizures (FS) in clinical practice remains controversial. We investigated focality issues in FS with a postictal arterial spin labeling (ASL) sequence. METHODS: We retrospectively reviewed 77 children (median: 19.0 months, range: 15.0-33.0 months) who consecutively visited our emergency room for FS and underwent brain magnetic resonance imaging (MRI), including the ASL sequence, within 24 hours of seizure onset. ASL data were visually analyzed to assess perfusion changes. Factors related to the perfusion changes were investigated. RESULTS: The mean time to ASL acquisition was 7.0 (interquartile range: 4.0-11.0) hours. The most common seizure classification was unknown-onset seizures (n = 37, 48%), followed by focal-onset (n = 26, 34%) and generalized-onset seizures (n = 14, 18%). Perfusion changes were observed in 43 (57%) patients: most were hypoperfusion (n = 35, 83%). The temporal regions were the most common location of perfusion changes (n = 26, 60%); the majority of these were distributed in the unilateral hemisphere. Perfusion changes were independently associated with seizure classification (focal-onset seizures, adjusted odds ratio [aOR]: 9.6, p = 0.01; unknown-onset seizures aOR: 10.4, p < 0.01), and prolonged seizures (aOR: 3.1, p = 0.04), but not with other factors (age, sex, time to MRI acquisition, previous FS, repeated FS within 24 hour, family history of FS, structural abnormality on MRI, and developmental delay). The focality scale of seizure semiology positively correlated with perfusion changes (R = 0.334, p < 0.01). CONCLUSION: Focality in FS may be common, and its primary origin might be the temporal regions. ASL can be useful for assessing focality in FS, particularly when seizure onset is unknown.

Reflex and Spontaneous Movements in Pediatric Patients with Brain Death.

BACKGROUND: Reflex and spontaneous movements are not uncommon in brain death patients. However, most studies have been conducted in adults, while reports in infants and children are rare. Thus, we aimed to evaluate the frequency and characteristics of these movements in pediatric patients declared as brain death. METHODS: Records of pediatric patients who were diagnosed as brain death from 15 hospitals in the Yeongnam region, South Korea, between January 2013 and September 2016 were analyzed. All body movements in patients who met the criteria for brain death as established by the Korea Medical Association were assessed by medical doctors and trained organ transplant coordinators. The frequency and characteristics of these movements were identified. Additionally, the demographic and clinical factors of the brain death patients with and without these movements were compared. RESULTS: A total of 31 patients who met the criteria for brain death were enrolled. Seven patients (22.6%) showed either reflex or spontaneous movements; six of them (85.7%) showed reflex movements only, and one patient (14.3%) showed both types of movements. The most common types of reflex movements were the flexor/extensor plantar response and isolated finger jerk. Four of seven patients (57.1%) showed a single movement pattern, while three (42.9%) showed two different movement patterns. CONCLUSION: It is essential for physicians who perform pediatric brain death examinations to recognize the frequency and characteristics of reflex and spontaneous movements, and this article may help in the accurate and prompt diagnosis of brain death.

Neurodevelopmental Outcomes of Neonatal Rotavirus-Associated Leukoencephalopathy.

Rotavirus infection has been reported to be associated with neonatal seizures with a diffuse and symmetrical diffusion restriction of periventricular white matter, namely, neonatal rotavirus-associated leukoencephalopathy. The extensive white matter injury seen in this cohort raises concerns about the long-term neurodevelopmental outcomes. In the present study, we prospectively assessed the neurodevelopmental outcomes of 13 patients with neonatal rotavirus-associated leukoencephalopathy at a median age of 26 months (range, 23-68 months). Neurodevelopmental outcomes were evaluated using a neurological examination, developmental evaluations, and magnetic resonance imaging (MRI) of the brain. Overall, 6 of the 13 patients (46%) had abnormal neurodevelopmental outcomes: 1 patient had mental retardation, visual-motor integration (VMI) dysfunction, cerebral palsy, and epilepsy; 1 patient had cerebral palsy and VMI dysfunction; remaining 4 patients had VMI dysfunction. Follow-up MRI in 12 of 13 patients showed an increased signal intensity on periventricular white matter in all patients. These findings suggested that neonatal rotavirus-associated leukoencephalopathy could not be assumed to be benign in long-term neurodevelopment, particularly in VMI function. Early intervention and long-term follow-up are necessary for these patients. Our findings raise caution for rotavirus infection in this vulnerable population for infants.

Revisited Arterial Supply of the Anterior Ear.

BACKGROUND: Since arterial supply of the anterior ear was described in 1992 by Park et al, various anatomical studies and surgical techniques have been published in the literatures. Although anatomic studies about the vascular pattern of the ear have been previously reported, most were incomplete to understand the vascular anatomy of the ear and its surgical outcomes. In this report, the authors defined further detailed vascular pattern of the arterial networks and of the main perforators of the anterior ear. METHODS: The authors dissected in a total of 11 auricles that had been fixed in 10% formalin solution. Prior to dissection, a red latex solution was injected into the common carotid artery. The anteroauricular and postauricular skin was dissected to expose the arterial network under ×10 microscope magnification. RESULTS: There are 2 arterial networks in the anteroauricular surface of the ear: triangular-scapha fossa and concha network. In this study, triangular-scapha fossa network has 2 vascular patterns by a dominant arterial supply: the superficial temporal artery (STA) type (6/11, 54.5%) and the posterior auricular artery (PAA) type (5/11, 45.4%). The STA type is distributed by a subbranch of the ascending helical artery of the STA, whereas the dominant arterial supply of the PAA type is a perforator of the triangular fossa from the PAA. We describe an important inflow to the triangular-scapha fossa network as blood supply from the middle division of the PAA, which directly emerges from the posterior to the anterior surface over the cartilage border at midhelix. CONCLUSIONS: The detailed vascular anatomy of this report allows surgeons to perform surgical procedures safely and to develop various flaps in the field of the ear reconstruction.

Mulberry Component Kuwanon C Exerts Potent Therapeutic Efficacy In Vitro against COVID-19 by Blocking the SARS-CoV-2 Spike S1 RBD:ACE2 Receptor Interaction.

There has been an immense effort by global pharmaceutical companies to develop anti-COVID-19 drugs, including small molecule-based RNA replication inhibitors via drug repositioning and antibody-based spike protein blockers related to cell entry by SARS-CoV-2. However, several limitations to their clinical use have emerged in addition to a lack of progress in the development of small molecule-based cell entry inhibitors from natural products. In this study, we tested the effectiveness of kuwanon C (KC), which has mainly been researched using in silico docking simulation and can serve as an effective building block for developing anti-COVID-19 drugs, in blocking the spike S1 RBD:ACE2 receptor interaction. KC is a natural product derived from Morus alba L., commonly known as mulberry, which has known antiviral efficacy. Molecular interaction studies using competitive ELISA and the BLItz system revealed that KC targets both the spike S1 RBD and the ACE2 receptor, successfully disrupting their interaction, as supported by the in silico docking simulation. Furthermore, we established a mechanism of action by observing how KC prevents the infection of SARS-CoV-2 spike pseudotyped virus in ACE2/TPRSS2-overexpressing HEK293T cells. Finally, we demonstrated that KC inhibits clinical isolates of SARS-CoV-2 in Vero cells. Future combinations of small molecule-based cell entry inhibitors, such as KC, with the currently prescribed RNA replication inhibitors are anticipated to significantly enhance the efficacy of COVID-19 therapies.

Undaria pinnatifida extract feeding increases exercise endurance and skeletal muscle mass by promoting oxidative muscle remodeling in mice.

Dietary habits can alter the skeletal muscle performance and mass, and Undaria pinnatifida extracts are considered a potent candidate for improving the muscle mass and function. Therefore, in this study, we aimed to assess the effect of U pinnatifida extracts on exercise endurance and skeletal muscle mass. C57BL/6 mice were fed a 0.25% U pinnatifida extract-containing diet for 8 weeks. U pinnatifida extract-fed mice showed increased running distance, total running time, and extensor digitorum longus and gastrocnemius muscle weights. U pinnatifida extract supplementation upregulated the expression of myocyte enhancer factor 2C, oxidative muscle fiber markers such as myosin heavy chain 1 (MHC1), and oxidative biomarkers in the gastrocnemius muscles. Compared to the controls, U pinnatifida extract-fed mice showed larger mitochondria and increased gene and protein expression of molecules involved in mitochondrial biogenesis and oxidative phosphorylation, including nuclear respiratory factor 2 and mitochondrial transcription factor A. U pinnatifida extract supplementation also increased the mRNA expression of angiogenesis markers, including VEGFa, VEGFb, FGF1, angiopoietin 1, and angiopoietin 2, in the gastrocnemius muscles. Importantly, U pinnatifida extracts upregulated the estrogen-related receptor γ and peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α)/AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) networks, which are partially increased by fucoxanthin, hesperetin, and caffeic acid treatments. Collectively, U pinnatifida extracts enhance mitochondrial biogenesis, increase oxidative muscle fiber, and promote angiogenesis in skeletal muscles, resulting in improved exercise capacity and skeletal muscle mass. These effects are attributable to fucoxanthin, hesperetin, and caffeic acid, bioactive components of U pinnatifida extracts.

Sex differences in seizure effects on social anxiety in persons with epilepsy.

PURPOSE: We investigated sex differences in the effect of seizures on social anxiety in persons with epilepsy. METHOD: In this cross-sectional multicenter study, social anxiety was measured using the short forms of the Social Phobia Scale (SPS-6) and Social Interaction Anxiety Scale (SIAS-6). SPS-6 scores ≥ 9 and SIAS-6 scores ≥ 12 were considered to indicate social phobia and social interaction anxiety, respectively. The Patient Health Questionnaire-9, Stigma Scale-Revised, and Family Adaptation-Partnership-Growth-Affection-Resolve scale were also completed. A logistic regression analysis with an interaction term was used to analyze the data. RESULTS: Out of 285 participants, a SPS-6 score ≥ 9 and a SIAS-6 score ≥ 12 were noted in 62 (21.8%) and 36 (12.6%) of participants, respectively. There was no difference in the prevalence of social anxiety between men and women. Intractable seizures and lack of seizure freedom were associated with a SPS-6 score ≥ 9 and a SIAS-6 score ≥ 12, but statistical significance was lost in the adjusted models. However, intractable seizures and lack of seizure freedom significantly interacted with sex for a SPS-6 score ≥ 9 (p = 0.018) and a SIAS-6 score ≥ 12 (p = 0.048) in both the separate and adjusted models. Specifically, intractable seizures tended to be positively associated with SPS-6 scores ≥ 9 than non-intractable seizures in men only (odds ratio = 2.602, p = 0.068), whereas lack of seizure freedom tended to be negatively associated with SIAS-6 scores ≥ 12 than seizure freedom in women only (odds ratio = 4.804, p = 0.053). CONCLUSION: We found significant sex differences in seizure effects on social anxiety. Intractable seizures were associated with social phobia in men, whereas lack of seizure freedom in the last year was associated with social interaction anxiety in women.

Geraniin Inhibits the Entry of SARS-CoV-2 by Blocking the Interaction between Spike Protein RBD and Human ACE2 Receptor.

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the development of vaccines, the emergence of SARS-CoV-2 variants and the absence of effective therapeutics demand the continual investigation of COVID-19. Natural products containing active ingredients may be good therapeutic candidates. Here, we investigated the effectiveness of geraniin, the main ingredient in medical plants Elaeocarpus sylvestris var. ellipticus and Nephelium lappaceum, for treating COVID-19. The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (hACE2) receptor to initiate virus entry into cells; viral entry may be an important target of COVID-19 therapeutics. Geraniin was found to effectively block the binding between the SARS-CoV-2 spike protein and hACE2 receptor in competitive enzyme-linked immunosorbent assay, suggesting that geraniin might inhibit the entry of SARS-CoV-2 into human epithelial cells. Geraniin also demonstrated a high affinity to both proteins despite a relatively lower equilibrium dissociation constant (KD) for the spike protein (0.63 µM) than hACE2 receptor (1.12 µM), according to biolayer interferometry-based analysis. In silico analysis indicated geraniin's interaction with the residues functionally important in the binding between the two proteins. Thus, geraniin is a promising therapeutic agent for COVID-19 by blocking SARS-CoV-2's entry into human cells.

8-O-(E-p-methoxycinnamoyl)harpagide Inhibits Influenza A Virus Infection by Suppressing Intracellular Calcium.

Calcium (Ca2+) dependent signaling circuit plays a critical role in influenza A virus (IAV) infection. The 8-O-(E-p-methoxycinnamoyl)harpagide (MCH) exhibits pharmacological activities that exert neuroprotective, hepatoprotective, anti-inflammatory and other biological effects. However, not have reports of antiviral effects. To investigate the antiviral activity of MCH on IAV-infected human lung cells mediated by calcium regulation. We examined the inhibitory effect of MCH on IAV infections and measured the level of viral proteins upon MCH treatment using Western blotting. We also performed molecular docking simulation with MCH and IAV M2 protein. Finally, we analyzed MCH's suppression of intracellular calcium and ROS (reactive oxygen species) in IAV-infected human lung cells using a flow cytometer. The results shown that MCH inhibited the infection of IAV and increased the survival of the infected human lung cells. The levels of IAV protein M1, M2, NS1 and PA were inhibited in MCH-treated human lung cells compared to that in infected and untreated cells. Also, docking simulation suggest that MCH interacted with M2 on its hydrophobic wall (L40 and I42) and polar amino acids (D44 and R45), which formed intermolecular contacts and were a crucial part of the channel gate along with W41. Lastly, MCH inhibited IAV infection by reducing intracellular calcium and mitochondrial Ca2+/ROS levels in infected human lung cells. Taken together, these data suggest that MCH inhibits IAV infection and increases the survival of infected human lung cells by suppressing calcium levels. These results indicate that MCH is useful for developing IAV treatments.

Divergence of metabolites in three phylogenetically close Monascus species (M. pilosus, M. ruber, and M. purpureus) based on secondary metabolite biosynthetic gene clusters.

BACKGROUND: Species of the genus Monascus are considered to be economically important and have been widely used in the production of yellow and red food colorants. In particular, three Monascus species, namely, M. pilosus, M. purpureus, and M. ruber, are used for food fermentation in the cuisine of East Asian countries such as China, Japan, and Korea. These species have also been utilized in the production of various kinds of natural pigments. However, there is a paucity of information on the genomes and secondary metabolites of these strains. Here, we report the genomic analysis and secondary metabolites produced by M. pilosus NBRC4520, M. purpureus NBRC4478 and M. ruber NBRC4483, which are NBRC standard strains. We believe that this report will lead to a better understanding of red yeast rice food. RESULTS: We examined the diversity of secondary metabolite production in three Monascus species (M. pilosus, M. purpureus, and M. ruber) at both the metabolome level by LCMS analysis and at the genome level. Specifically, M. pilosus NBRC4520, M. purpureus NBRC4478 and M. ruber NBRC4483 strains were used in this study. Illumina MiSeq 300 bp paired-end sequencing generated 17 million high-quality short reads in each species, corresponding to 200 times the genome size. We measured the pigments and their related metabolites using LCMS analysis. The colors in the liquid media corresponding to the pigments and their related metabolites produced by the three species were very different from each other. The gene clusters for secondary metabolite biosynthesis of the three Monascus species also diverged, confirming that M. pilosus and M. purpureus are chemotaxonomically different. M. ruber has similar biosynthetic and secondary metabolite gene clusters to M. pilosus. The comparison of secondary metabolites produced also revealed divergence in the three species. CONCLUSIONS: Our findings are important for improving the utilization of Monascus species in the food industry and industrial field. However, in view of food safety, we need to determine if the toxins produced by some Monascus strains exist in the genome or in the metabolome.

Development of the clinical assessment scale in autoimmune encephalitis.

OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92). INTERPRETATION: CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352-358.

Elevated plasma biomarkers of inflammation in acute ischemic stroke patients with underlying dementia.

BACKGROUND: The blood-brain barrier has been a hindrance to developing blood-based diagnostic tests for dementias, as it limits the appearance of brain biomarkers in the blood. Our aim was to see if the natural opening of the blood-brain barrier induced by ischemic stroke would increase serum levels of inflammatory biomarkers known to be elevated in the brains of patients with Alzheimer's disease and other neurodegenerative dementias. METHODS: Forty-three patients with acute ischemic stroke presenting to Stony Brook University Hospital were prospectively enrolled in the study. Eight of these patients were clinically diagnosed as having an underlying neurodegenerative dementia. Blood was drawn acutely within 72 h of stroke symptom onset, and serum levels of the classic inflammatory biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP) were measured, along with levels of S100B protein (S100B) and complement C3 (CC3). RESULTS: Serum levels of IL-6 and CRP in patients with acute ischemic stroke and underlying dementia (AIS + D) were significantly higher (p = 0.002 and 0.003, respectively) than in patients with acute ischemic stroke alone (AIS). Serum levels of S100B and CC3 did not differ significantly between the groups. CONCLUSIONS: This study supports the possibility that opening of the blood-brain barrier may enhance the blood appearance of brain tissue markers of inflammation associated with neurodegenerative dementia. Further study is warranted to test this possibility, given the recent emergence of methods to open the blood-brain barrier for diagnostic or therapeutic purposes.

Does the new Korean term for epilepsy reduce the stigma for Korean adults with epilepsy?

PURPOSE: The purpose of this study was to evaluate differences in stigma, disclosure management of epilepsy, and knowledge about epilepsy between patients with epilepsy who recognized and did not recognize the new Korean term for epilepsy. METHODS: This was a cross-sectional, multicenter study. The Stigma Scale-Revised, the Disclosure Management Scale, the Patient Health Questionnaire-9, and a questionnaire assessing knowledge about epilepsy were used. The set of questionnaires had two versions, using either the old or new name for epilepsy. Multivariate logistic regression analyses were used. RESULTS: A total of 341 patients with epilepsy and 509 family members were recruited. Approximately 62% of patients felt some degree of epilepsy-related stigma. Mild stigma, severe concealment of epilepsy diagnosis, and increased knowledge about epilepsy were independently identified as factors associated with recognition of the new term in patients. Recognition of the new term was more prevalent in patients and family members with higher education, female family members, and family members having patients with younger age at seizure onset and shorter duration of epilepsy. There were no significant differences between the two types of questionnaires. About 81% of patients and 93% of family members had a positive attitude about renaming epilepsy. CONCLUSION: The use of the new Korean term for epilepsy (cerebroelectric disorder) increased knowledge about epilepsy but did not reduce stigma and concealment of epilepsy diagnosis in Korean adults with epilepsy. Higher education may be an important factor for knowing the new term in patients and family members.

Factors associated with stigma and depressive symptoms in family members of patients with epilepsy.

PURPOSE: Literature regarding family stigma related to epilepsy is scarce. This study investigated the prevalence of family stigma and depressive symptoms and the associated factors among the family members of patients with epilepsy. METHODS: In a cross-sectional study, Stigma Scale-Revised score ≥ 4 and Patient Health Questionnaire-9 score ≥ 10 were considered indicative of moderate-to-severe stigma and depressive symptoms, respectively. Stepwise logistic regression analyses were performed. RESULTS: Of the 482 family members, a mean age was 47.1 ±â€¯9.4 years, and 73.4% were female. Of the patients, a mean age was 25.5 ±â€¯16.7 years, and 45.0% were female. Idiopathic generalized epilepsy and focal epilepsy were noted in 22.4% and 65.6% of patients, respectively. Family stigma and depressive symptoms were noted in 10.0% and 11.2% of family members, respectively. Family stigma was significantly associated with high seizure frequency and being a sibling or offspring of a patient independent of their depressive symptoms. By contrast, depressive symptoms in family members were significantly associated with polytherapy, being parents of a patient, and neurological comorbidities independent of family stigma. In a subset of patients and their family, patients had higher proportion of stigma and depressive symptoms than their family. Depressive symptoms and stigma among patients were significantly correlated with those among parents, but not spouse. CONCLUSION: Family stigma is common in families with epilepsy and is closely related to depressive symptoms. Frequent seizures, polytherapy, neurological comorbidities, and the relationship to a patient may be factors that are independently associated with family stigma and depressive symptoms in family members.

Association between Blood Pressure and Renal Progression in Korean Adults with Normal Renal Function.

BACKGROUND: Although hypertension (HTN) is a well-established major risk factor for renal progression in patients with chronic kidney disease (CKD), few studies investigating its role in renal deterioration in the general population with normal renal function (NRF) have been published. Here, we analyzed the correlation between blood pressure (BP) and impaired renal function (IRF) in Korean adults with NRF. METHODS: Data for the study were collected from the national health screening database of the Korean National Health Insurance Service. Patients whose baseline estimated glomerular filtration rate (eGFR) was less than 60 mL/min/1.73 m² or whose baseline urinalysis showed evidence of proteinuria were excluded. IRF was defined as an eGFR below 60 mL/min/1.73 m². We performed follow up for eGFR for 6 years from 2009 to 2015 and investigated IRF incidence according to baseline BP status. We categorized our study population into two groups of IRF and NRF according to eGFR level in 2015. RESULTS: During 6 years of follow-up examinations, IRF developed in 161,044 (2.86%) of 5,638,320 subjects. The IRF group was largely older, and the incidence was higher in females and patients with low income, HTN, diabetes mellitus, dyslipidemia, and obesity compared with the NRF group. Subjects whose systolic BP was more than 120 mmHg or whose diastolic BP was more than 70 mmHg had an increased risk of developing IRF compared with subjects with lower BP (odds ratio [OR], 1.037; 95% confidence interval [CI], 1.014-1.061 vs. OR, 1.021; 95% CI, 1.004-1.038). CONCLUSION: BP played a major role in renal progression in the general population with NRF. Strict BP control may help prevent CKD in the general population.

Reflex and Spontaneous Movements in Adult Patients during the Process of Determining Brain Death in Korea.

BACKGROUND: Brain death is a clinical diagnosis that implies irreversible loss of function of the entire brain, including the brainstem and both hemispheres. Based on previous reports, it is not rare for reflex and spontaneous movements to occur in patients during the process of determining brain death. However, reports of the frequency and common types of these movements vary from study to study. Thus, we evaluated adult patients with impending brain death in Korea to determine the frequency and characteristics of reflex and spontaneous movements. METHODS: Brain dead patients who were admitted to 15 hospitals in the Yeongnam region (Southeast) of Korea were recruited prospectively from January 2013 to September 2016. All patients met the criteria for brain death as established by the Korea Medical Association. All body movements occurred during the process of diagnosing brain death and were assessed by physicians and trained organ transplant coordinators. The frequency and characteristics of these movements were identified and the demographic and clinical factors of impending brain dead patients with and without these movements were compared. RESULTS: A total of 436 patients who met the criteria for brain death were enrolled during the study period. Of these patients, 74 (17.0%) exhibited either reflex or spontaneous movements. Of this subset, 45 (60.8%) exhibited reflex movements only, 18 (24.3%) exhibited spontaneous movements only, and 11 (14.9%) exhibited both reflex and spontaneous movements. The most common reflex movements were the flexor/extensor plantar response and spinal myoclonus. Of the 74 patients, 52 (70.3%) exhibited one movement of the same pattern and 22 (29.7%) exhibited two or more different movement patterns. In addition, 45 (60.8%) exhibited these movements only on a limited area of the body with the leg being most common (n = 26, 57.8%). Patients with hypoxic brain damage and a higher systolic blood pressure exhibited significantly more reflex or spontaneous movements. CONCLUSION: Movements associated with brain dead patients are not rare and thus an awareness of these movements is important to brain death diagnosis. Physicians who perform brain death examinations should understand the frequency and characteristics of these movements to reduce delays in determining brain death.

Is frozen shoulder completely resolved at 2 years after the onset of disease?

BACKGROUND: Although numerous studies have suggested that frozen shoulder (FS) is a self-limiting disease with most patients recovering within 2 years, its long-term outcome is still controversial. The aims of this study were to evaluate the clinical outcomes after conservative treatment for FS and to determine the predictors of its clinical outcome. METHODS: This study included 234 shoulders of 215 patients who received conservative treatment for FS. The mean follow-up period was 41.8 months (range 27-117 months). Initial evaluation included demographics, detailed medical history, and clinical assessments of shoulder status. Questionnaires, which included the Visual Analogue Scale (VAS) pain score, American Shoulder and Elbow Surgeons (ASES) score, Subjective Shoulder Value (SSV) and satisfaction grading for the current shoulder status were assessed at the final follow-up. RESULTS: The mean VAS pain score, ASES score, and SSV significantly improved from 6.7, 37.0, and 40.1% at the time of initial evaluation to 1.5, 87.6, and 85.0% at the final follow-up evaluation (all p < 0.001). According to satisfaction grading, the shoulder status at the final follow-up was very satisfied in 101 shoulders (43.2%), satisfied in 68 (29.1%), fair in 37 (15.8%), unsatisfied in 20 (8.5%), and very unsatisfied in 8 (3.4%). Univariate analysis revealed that gender, diabetes, simultaneous bilateral involvement, overall bilateral involvement and duration of symptoms were associated with clinical outcomes at the final follow-up. Multivariate analysis revealed that duration of symptoms (p = 0.002) was an independent risk factor for unsuccessful outcome. CONCLUSIONS: At the mean follow-up period of 41.8 months, 72.3% of patients revealed subjective satisfaction for the current shoulder status. Duration of symptoms was an independent risk factor for poor prognosis.

Kaempferol and Its Glycoside, Kaempferol 7-O-Rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro.

Kaempferol (KO) and kaempferol 7-O-rhamnoside (KR) are natural products from various oriental herbs such as Geranii Herba. Previous studies have reported some biological activities of KO and KR; however, their effects on PD-1/PD-L1 interaction have not been reported yet. To elucidate their inhibitory activities on PD-1/PD-L1 protein-protein interaction (PPI), biochemical assays including competitive ELISA and biolayer interferometry (BLI) systems were performed. Cellular PD-1/PD-L1 blocking activity was measured in a co-culture system with PD-1 Jurkat and PD-L1/aAPC CHO-K1 cells by T-cell receptor (TCR) activation-induced nuclear factor of activated T cells (NFAT)-luciferase reporter assay. The detailed binding mode of action was simulated by an in silico docking study and pharmacophore analysis. Competitive ELISA revealed that KO and its glycoside KR significantly inhibited PD-1/PD-L1 interaction. Cellular PD-1/PD-L1 blocking activity was monitored by KO and KR at non-cytotoxic concentration. Surface plasmon resonance (SPR) and biolayer interferometry (BLI) analysis suggested the binding affinity and direct inhibition of KR against PD-1/PD-L1. An in silico docking simulation determined the detailed mode of binding of KR to PD-1/PD-L1. Collectively, these results suggest that KR could be developed as a potent small molecule inhibitor for PD-1/PD-L1 blockade.