Emergence of Stable Meron Quartets in Twisted Magnets.

The investigation of twist engineering in easy-axis magnetic systems has revealed remarkable potential for generating topological spin textures. Implementing twist engineering in easy-plane magnets, we introduce a novel approach to achieving fractional topological spin textures, such as merons. Through atomistic spin simulations on twisted bilayer magnets, we demonstrate the formation of a stable double Meron pair, which we refer to as the "Meron Quartet" (MQ). Unlike a single pair, the merons within the MQ exhibit exceptional stability against pair annihilation due to the protective localization mechanism induced by the twist that prevents collision of the Meron cores. Furthermore, we showcase that the stability of the MQ can be enhanced by adjusting the twist angle, resulting in an increased resistance to external perturbations such as external magnetic fields. Our findings highlight the twisted magnet as a promising platform for achieving merons as stable magnetic quasiparticles in van der Waals magnets.

Network Structure and Clustering Analysis Relating to Individual Symptoms of Problematic Internet Use in a Community Adolescent Population.

INTRODUCTION: Problematic internet use (PIU) is a psychopathology that includes multiple symptoms and psychological constructs. Because no studies have considered both network structures and clusters among individual symptoms in the context of PIU in a Korean adolescent population, this study aimed to investigate network structures and clustering in relation to PIU symptoms in adolescents. METHODS: Overall, 73,238 adolescents were included. PIU severity was assessed using a self-rating scale comprising 20 items and 6 subscales, namely, the Internet Addiction Proneness Scale for Youth-Short Form; KS scale. Network structures and clusters among symptoms were analyzed using a Gaussian graphical model and exploratory graph analysis, respectively. Centrality of strength, closeness, and betweenness scores was also calculated. RESULTS: Our study identified four clusters: disturbance in adaptive functioning, virtual interpersonal relationships, withdrawal, and tolerance. The symptom of confidence served as a node bridging the cluster of virtual interpersonal relationships and other clusters of withdrawal and disturbances of adaptive function. The symptom of craving served as a bridge between the clusters of withdrawal and tolerance with high betweenness centrality. CONCLUSION: This study identified network structures and clustering among PIU symptoms in adolescents and revealed that positive experiences derived from online interpersonal relationships were an important mechanism underlying PIU. These are novel insights concerning the interconnection among multiple symptoms and related clustering for the mechanism of adolescent PIU in terms of KS-scale PIU assessment.

Ab Initio Spin Hamiltonian and Topological Noncentrosymmetric Magnetism in Twisted Bilayer CrI3.

Twist engineering of van der Waals magnets has emerged as an outstanding platform for manipulating exotic magnetic states. However, the complicated form of spin interactions in the large moiré superlattice obstructs a concrete understanding of such spin systems. To tackle this problem, for the first time, we developed a generic ab initio spin Hamiltonian for twisted bilayer magnets. Our atomistic model reveals that strong AB sublattice symmetry breaking due to the twist introduces a promising route to realize the novel noncentrosymmetric magnetism. Several unprecedented features and phases are uncovered including the peculiar domain structure and skyrmion phase induced by noncentrosymmetricity. The diagram of those distinctive magnetic phases has been constructed, and the detailed nature of their transitions analyzed. Further, we established the topological band theory of moiré magnons relevant to each of these phases. By respecting the full lattice structure, our theory provides the characteristic features that can be detected in experiments.

Gastric ulcer and duodenitis associated with coinfection of human herpesvirus-8 and cytomegalovirus in a renal transplant recipient: a case report.

BACKGROUND: The coinfection between cytomegalovirus (CMV) and either human herpesvirus-6 (HHV-6) or HHV-7 in renal transplant recipients is well known; however, there have been few reports of coinfection of CMV associated with HHV-8. This paper presents a first case of acute gastric ulcer and duodenitis associated with CMV and HHV-8 coinfection after renal transplantation. CASE PRESENTATION: A 33-year-old male with a history of kidney transplantation was admitted to hospital because of postural epigastric pain. The recipient was CMV seropositive prior to transplantation and received trimethoprim-sulfamethoxazole without universal prophylaxis. Approximately 5 months after renal transplant, the recipient complained postural epigastric pain. An endoscopy revealed diffuse ulcerative lesions in the lower body and in the antrum of the stomach, as well as several erythematous mucosal lesions in the duodenum. Histopathologic examination identified CMV inclusions consistent with invasive CMV disease and immunohistochemical staining showed positive results for HHV-8 and CMV. No tumorous diseases such as Kaposi's sarcoma were detected. After 3 weeks of intravenous ganciclovir treatment, we observed that serum CMV PCR remained within the normal range and clinical symptoms improved. A follow-up endoscopy performed 3 weeks later showed that the severity of the above mentioned lesions had improved. CONCLUSIONS: We report the first case of a renal transplant recipient diagnosed with acute gastric ulcer and duodenitis associated with coinfection of CMV and HHV-8. Ganciclovir appears to be effective in diseases associated with coinfection of CMV and HHV-8.

Emotional and Behavioral Correlates of Exposure to Electronic Media in School-Aged Children: A Prospective Study.

BACKGROUND: Exposure to electronic media is increasing from early childhood. This study aimed to examine the association between screen time and behavioral outcomes in school-aged children with a prospective birth-cohort. METHODS: We examined the association between screen time and behavioral outcomes in school-aged children with a Korean birth-cohort study. Participants were 2,150 children, recruited during their fetal period, assessed annually for developmental outcomes. Media exposure was assessed at T4 (3.2 y/o), T8 (7.3 y/o), and T10 (9.4 y/o). After exclusions for missing data, 1,368 children were categorized into four groups (Low-Low, Low-High, High-Low, and High-High) based on average daily media time in early childhood and during schooldays, respectively. Children's temperament was assessed from T1 (0.5 y/o) to T4. Emotional and behavioral outcomes were assessed using the Child Behavior Checklist (DSM-oriented subscales) at T8 and T10. RESULTS: We found that early-years temperament was generally similar between the media-time groups: they only differed significantly on Activity at T1 and Emotionality at T2 (1.2 y/o). However, compared to the Low-Low group, the Low-High group had significantly higher odds of high-risk scores for Conduct Problems (increased odds ratios [ORs] of 1.82 at T8 and 1.83 at T10) and Anxiety Problems (increased ORs of 1.60 at T8 and 1.82 at T10). Self-rated self-esteem and overall happiness at T10 also significantly differed among the four groups. CONCLUSION: Our findings suggest the negative impacts of media exposure on the emotional and behavioral development of school-aged children, which substantiates the guidelines that restrict media exposure during childhood.

The Relationship Between Posttraumatic Embitterment Disorder and Stress, Depression, Self-Esteem, Impulsiveness, and Suicidal Ideation in Korea Soldiers in the Local Area.

BACKGROUND: The purpose of this study was to identify the prevalence of posttraumatic embitterment disorder (PTED) among soldiers, and examine its relation to stress, depression, self-esteem, impulsiveness, and suicidal ideation. METHODS: The subjects of this study were 200 soldiers and 197 control subjects, a total of 397 persons. Measurement tools used included the PTED self-rating scale, Stress Response Inventory, Beck Depression Inventory, Rosenberg Self-Esteem Inventory, Barratt Impulsiveness Scale, and Beck Scale of Suicide Ideation. RESULT: The major findings of the analysis are as follows: first, 11.5% of the soldiers were in the risk group for PTED, and 4% of them had PTED. Second, PTED in the soldiers was significantly associated with a number of variables such as their educational background, stress, depression, self-esteem, impulsiveness, and suicidal ideation, while it was not significantly associated with age. Third, through the hierarchical multiple regression analysis, it was found that academic background, stress, and depression had a statistically significant positive effect on the incidence of PTED in the soldiers. CONCLUSION: In order to prevent and effectively intervene in PTED in soldiers, there is a need for interventional efforts focused on depression and stress related to negative life events.

Clinical significance of p53 protein expression and TP53 variation status in colorectal cancer.

In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the variational status of TP53. Recently, next-generation sequencing (NGS) of the TP53 gene has increased. However, to our knowledge, a comparison between TP53 status evaluated by IHC and NGS has not been studied. Therefore, the primary aim of this study was to compare the clinical effect of TP53 status evaluated by IHC and NGS in patients with CRC. The secondary aim was to investigate the correlation between expression of p53 by IHC and variational status of TP53 by NGS. We performed immunohistochemical staining of p53 and sequencing of TP53 by NGS in 204 human samples of CRC. We then analyzed the correlation between variational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 variation, TP53 variation and higher N stage, and positive p53 expression and higher N stage. Positive IHC expression of p53 was significantly associated with overall survival (OS) of CRC patients by univariate analysis and was revealed as an independent prognostic factor by multivariate analysis. Additionally, the nonsense/frameshift p53 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the variational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with variation status of TP53 and expression of p53 protein rather than variation status of TP53 has more significant impact on the OS of CRC patients.

Efficacy of bisphosphonate therapy on postmenopausal osteoporotic women with and without diabetes: a prospective trial.

BACKGROUND: The co-occurrence of diabetes and osteoporosis is common in postmenopausal women. For the treatment of postmenopausal osteoporosis, current guidelines recommend initial treatment with bisphosphonates, but it is unclear whether bisphosphonates provide a similar degree of therapeutic efficacy in patients with diabetes. This study sought to compare the efficacy of monthly oral ibandronate for retaining bone mineral density (BMD) in diabetic and non-diabetic postmenopausal women with osteoporosis. METHODS: Postmenopausal osteoporotic women with or without diabetes were enrolled in this study from three hospitals in an open-label approach from 2018 to 2020. Each group of patients received oral ibandronate 150 mg once monthly for 1 year. BMD, trabecular bone score (TBS), serum C-terminal telopeptide of type I collagen (CTx) and procollagen type 1 N-terminal propeptide (P1NP) were evaluated prospectively. Treatment-emergent adverse events and changes in glucose metabolism during drug use were also monitored. RESULTS: Among the 120 study participants, 104 (86.7%) completed the study. Following 1 year of treatment, BMD increased by 3.41% vs. 3.71% in the lumbar spine, 1.30% vs. 1.18% in the femur neck, and 1.51% vs. 1.58% in the total hip in the non-diabetes and diabetes groups, respectively. There were no significant differences in BMD changes between the groups, and the differences in CTx or P1NP changes between groups were not significant. We did not observe any significant differences in baseline TBS values or the degree of change between before and after 1 year of ibandronate treatment in either group in this study. A total of 11 adverse events (9.2%) that recovered without sequelae occurred among the 120 included patients, and there was no significant difference in the frequency of adverse events between the groups (p = 0.862). The changes in fasting glucose and glycated hemoglobin levels between before and after treatment were not significant in the diabetic group. CONCLUSIONS: Bisphosphonate therapy showed similar increases in BMD and decreases in CTx and P1NP of postmenopausal women with and without diabetes. Monthly oral ibandronate can be a safe and effective therapeutic option in postmenopausal osteoporosis patients with type 2 diabetes. TRIAL REGISTRATION: NCT number: NCT05266261, Date of registration: 04 March 2022.

Recent fall and high imminent risk of fracture in older men and women.

BACKGROUND: despite fall history being a well-known risk factor for falls and fractures, the association between very recent falls and imminent fracture risk is not clearly elucidated. OBJECTIVE: to study the very recent (<4 months) fall-related absolute risk of fractures in the following year. METHODS: two large prospective cohort studies of women (Study of Osteoporotic Fractures [SOF]) and men (Osteoporotic Fractures in Men Study [MrOS]) aged 65 years or older were included. Data on falls were collected every 4 months, and the primary outcomes were any non-spine and hip fractures in the next 12 months. RESULTS: a total of 9,704 women contributed 419,149, and 5,994 men contributed 223,885 four-monthly periods of observations during the 14.8-year SOF and 12.6-year MrOS follow-up. Falls within 4 months indicated a high risk of non-spine and hip fractures in the following year for both sexes; in women, a recent fall indicated an 8.1% absolute risk of a non-spine fracture within 1 year, a 2.5-fold higher risk than that in women without falls, a 2.5% absolute risk of hip fracture, and a 3.1-fold increased risk. Falls increased the risk of fractures regardless of whether a fracture occurred or not. Men had similar risk patterns, albeit with a lower absolute risk of fracture. CONCLUSIONS: in older people, a fall within 4 months indicates a high risk of fracture in the next year, regardless of fracture occurrence. A recent fall warrants urgent evaluation and consideration of treatments to reduce the imminent risk of fractures.

Calibration of BRDF Based on the Field Goniometer System Using a UAV Multispectral Camera.

The bidirectional reflectance distribution function (BRDF) is important for estimating the physical properties of a surface in remote sensing. In the laboratory, the BRDF can be estimated quickly and accurately using a goniometer, but it is very difficult to operate in the field. The purpose of this study was to evaluate whether estimating the BRDF with reasonable accuracy using an unmanned aerial vehicle (UAV) with a multispectral camera is possible in the field. Hemispherical reflectance was created from images taken using an UAV multispectral camera. The ground targets were four calibrated reference tarps (CRTs) of different reflectance, and the UAV was operated five times. Down-welling irradiance for reflectance calculation was measured in two ways: a sunlight sensor was mounted on a UAV, and a spectroradiometer with a remote cosine receptor (RCR) was installed on the ground. The BRDF was assessed through the anisotropy factor (ANIF) of the CRT reflectance derived from the collected data. As a result, the irradiance data for the reflectance calculation were more effective from the spectroradiometer with RCR on the ground than from the sunlight sensor mounted on an UAV. Furthermore, the high reflectance CRTs, ANIF, and BRDF had similar results. Therefore, when analyzing the BRDF, the effectiveness can be guaranteed when the reflectance of the target is over 21~46%, because a low reflectance tendency differs due to the adjacency effect. In addition, weather affects irradiance, so it is more effective to conduct fieldwork in clear weather.

Breast Arterial Calcification: A Potential Biomarker for Atherosclerotic Cardiovascular Disease Risk?

PURPOSE OF REVIEW: We aimed to summarize the current evidence regarding the association between breast arterial calcification (BAC) and atherosclerotic cardiovascular disease (ASCVD) in women and discuss the potential role of BAC in the risk stratification and preventive approaches for ASCVD. RECENT FINDINGS: BAC has emerged as a potential women-specific risk marker for ASCVD. Although BAC presents as a medial calcification of the arteries, notably different from the intimal atherosclerotic process, current evidence supports a correlation between BAC and ASCVD risk factors or subclinical and clinical ASCVD, such as coronary artery disease or stroke. As millions of women undergo mammograms each year, the potential clinical application of BAC in enhanced ASCVD risk estimation, with no additional cost or radiation, has tremendous appeal. Although further research regarding optimal risk assessment and management in women with BAC is required, the presence of BAC should prompt healthy cardiovascular lifestyle modifications.

Effect of chitinase-3-like protein 1 on glucose metabolism: In vitro skeletal muscle and human genetic association study.

We investigated the effect of chitinase-3-like protein 1 (CHI3L1) on glucose metabolism and its underlying mechanisms in skeletal muscle cells, and evaluated whether the observed effects are relevant in humans. CHI3L1 was associated with increased glucose uptake in skeletal muscles in an AMP-activated protein kinase (AMPK)-dependent manner, and with increased intracellular calcium levels via PAR2. The improvement in glucose metabolism observed in an intraperitoneal glucose tolerance test on male C57BL/6J mice supported this association. Inhibition of the CaMKK was associated with suppression of CHI3L1-mediated glucose uptake. Additionally, CHI3L1 was found to influence glucose uptake through the PI3K/AKT pathway. Results suggested that CHI3L1 stimulated the phosphorylation of AS160 and p38 MAPK downstream of AMPK and AKT, and the resultant GLUT4 translocation. In primary myoblast cells, stimulation of AMPK and AKT was observed in response to CHI3L1, underscoring the biological relevance of CHI3L1. CHI3L1 levels were elevated in cells under conditions that mimic exercise in vitro and in exercised mice in vivo, indicating that CHI3L1 is secreted during muscle contraction. Finally, similar associations between CHI3L1 and metabolic parameters were observed in humans alongside genotype associations between CHI3L1 and diabetes at the population level. CHI3L1 may be a potential therapeutic target for the treatment of diabetes.

FAM83H and Nectin1 expression are related with survival and relapse of bladder urothelial carcinoma patients.

BACKGROUND: FAM83H was originally reported to be essential for dental enamel formation. However, FAM83H has recently been implicated in tumorigenesis and tumor progression. Analysis of a publicly available gene expression database revealed a significant correlation between FAM83H and Nectin1 mRNA expression and bladder urothelial carcinoma (BUC). Therefore, we investigated the association between FAM83H and Nectin1 expression levels and the survival and recurrence of BUC in BUC patients using a tissue microarray. METHODS: We performed immunohistochemical staining of FAM83H and Nectin1 in 165 human BUC tissue sections, and analyzed the prognostic significance of FAM83H and Nectin1 expression. RESULTS: Both FAM83H and Nectin1 were mainly expressed in the cytoplasm, and their expression was significantly associated. FAM83H expression was significantly correlated with higher histologic grade, higher T stage, higher TNM stage, and recurrence. Nectin1 expression was significantly associated with higher histologic grade and recurrence. Univariate analysis showed FAM83H expression and Nectin1 expression were significantly associated with worse overall survival (OS) and shorter relapse-free survival (RFS) of BUC patients. In multivariate analysis, levels of FAM83H and Nectin1 were independent indicators of shorter survival of BUC patients. CONCLUSIONS: Our results suggest that FAM83H and Nectin1 are important in the progression of BUC, and that expression patterns of these two proteins can be used as prognostic indicators of survival in BUC patients.

Associations among exposure to television or video, language development, and school achievement in childhood: a prospective birth cohort study.

PURPOSE: Exposure to electronic media, which begins in early childhood, has been gradually increasing. This study investigated the associations between time watching television or video (TV time), children's language development, and school achievement using a large prospective design. METHODS: The participants underwent annual assessment from birth (T1; 5.5 months) to T8 (87.9 months). We used a parental questionnaire to evaluate TV time annually from T3 (2.2 years) to T8 (7.3 years), by the item asking "How many hours does your child usually spend a day watching TV or videos?". Children were grouped by TV time using group-based trajectory analysis. Among 2150 participants, 1087 were included in the final analysis. The Korean version of the Denver II and the Korean-Ages and Stages questionnaires were administered to evaluate early childhood development (T1 to T3). The Receptive and Expressive Vocabulary Test was used to assess children's language development at T8. Questionnaires completed by both parents and teachers were used to evaluate school achievement at T8. RESULTS: Participants were divided into "Low Descending" (LD), "Medium Flat" (MF), "High Ascending" (HA), and "Extremely High Descending" (XHD) groups. Early language development at T1 and T2 did not significantly differ among all groups. However, language development at T3 and T8, and school achievement at T8 differed significantly, and were the highest in LD and lowest in HA. CONCLUSION: We found a negative association between greater TV time and children's language and cognitive development. Thus, unchecked TV exposure could be detrimental to childhood cognitive development.

What makes adolescents psychologically distressed? Life events as risk factors for depression and suicide.

Adolescence is a vulnerable period for psychological distress. This study aimed to comprehensively investigate the distribution of major stress-causing factors and their correlates in a large population of adolescents. A computerized self-report questionnaire was completed by 291,110 participating adolescents over a 4-year period using a cross-sectional study design. The questionnaire included items assessing demographic variables, major stressors, severity of perceived stress, and mental health outcomes such as depressed mood, suicidal ideation, and attempts. Among the major stressors, schoolwork/career was the most predominant (54.7%). However, the odds ratios for depressed mood and suicidal ideation were the highest in the stressor of conflict with peers (OR = 1.97 for depressed mood and OR = 2.00 for suicidal ideation), followed by family circumstances (OR = 1.77 and 1.94 for depressed mood and suicidal ideation, respectively). Conversely, schoolwork/career presented significantly lower odds ratios of 0.87 and 0.87 for depressed mood and suicidal ideation, respectively. This study provides important information on psychological distress related to adolescents' mental health. Although school/career was the most prevalent source of psychological stress, the odds ratios for negative health outcomes of adolescents were higher in interpersonal problems such as conflicts with parents and peers and family circumstances. The present findings might help parents and clinicians understand the psychological distress of adolescents and improve their mental health.

Dietary patterns and smartphone use in adolescents in Korea: A nationally representative cross-sectional study.

BACKGROUND AND OBJECTIVES: Diet and smartphone use are daily routines that can affect adolescents' mental health. This study investigated whether the frequency of the consumption of certain foods is associated with the duration of smartphone use and problems caused by smartphone overuse in adolescents. METHODS AND STUDY DESIGN: Food consumption and smartphone use were investigated in 62,276 Korean adolescents aged 12-18 years by using a nationwide self-report survey. Food intake was assessed on a seven-point scale ("never" to "1, 2, and 3 or more times per day") for nine items: fruits, vegetables, milk, soda, energy drinks, sweetened beverages, fast food, instant noodles, and snacks. The durations of smartphone use and problematic use were determined using self-report items. RESULTS: Most respondents (66.5%) used smartphones over 2 hours per day. Higher consumption levels of fruits (F=151.8; p<0.001), vegetables (F=119.9; p<0.001), and milk (F=33.0; p<0.001) were associated with significantly lower smartphone usage, whereas higher consumption levels of soda (F=292.5; p<0.001), energy drinks (F=24.0; p<0.001), sweetened beverages (F=224.8; p<0.001), fast food (F=192.1; p<0.001), instant noodles (F=196.2; p<0.001), and snacks (F=131.6; p<0.001) were positively associated with higher smartphone usage. CONCLUSIONS: Our findings provide useful clinical information regarding the association between dietary habits and smartphone use in adolescents. Future studies should investigate underlying mechanisms and examine the efficacy of dietary interventions for adolescents with excessive smartphone use.

Effects of the methanol fraction of modified Seonghyangjeongki-san water extract on transient ischaemic brain injury in mice.

CONTEXT: Recently in Korean medicine, the antioxidant and anti-inflammatory activities of Seonghyangjeongki-san (SHJKS) were reported. However, studies on the specific mechanisms of action of SHJKS for the treatment of ischaemic stroke are still lacking. OBJECTIVE: This study investigates the mechanism of action of the water extract methanol fraction of modified SHJKS (SHJKSmex) on cerebral ischaemic injury. MATERIALS AND METHODS: C57BL/6 male mice were orally administered SHJKSmex (30, 100, or 300 mg/kg) for 3 consecutive days (2 days, 1 day, and 1 h, respectively) before middle cerebral artery occlusion (MCAO). Twenty-four hours after MCAO, the infarct volumes were measured, brain edoema indices were calculated, and neurological deficit scores were determined. Inflammation-related substances in the ipsilateral hemisphere were determined by western blotting, dichlorofluorescin diacetate, thiobarbituric acid-reactive substances assay, and enzyme-linked immunosorbent assay. RESULTS: SHJKSmex pre-treatment at 300 mg/kg decreased infarct volume by 87% and mean brain water content by 90% of the MCAO control group. Moreover, SHJKSmex effectively suppressed the expression of inducible nitric oxide synthase, reactive oxygen species, interleukin 1, and caspases-8 and -9 and increased the B-cell lymphoma 2/Bcl-2-associated X protein ratio (Bcl-2/Bax) in ischaemic mouse brain. The hippocampal pyramidal cell densities were significantly increased in the 300 mg/kg SHJKSmex-administered group compared to the MCAO control group. DISCUSSION AND CONCLUSIONS: SHJKSmex protected the brain from ischaemic stroke in mice through its antioxidant, anti-inflammatory, and antiapoptotic activities. Our findings suggest that SHJKSmex is a promising therapeutic candidate for the development of a new formulation for ischaemia-induced brain damage.

Recurrent KRAS mutations identified in papillary renal neoplasm with reverse polarity-a comparative study with papillary renal cell carcinoma.

Comprehensive molecular analyses revealed that papillary renal cell carcinoma (PRCC) is a heterogenous entity. Papillary renal neoplasm with reverse polarity (PRNRP) is a subset of PRCC with characteristic histomorphologies such as low-grade nuclear features, inverted nuclear location, eosinophilic cytoplasm, and indolent clinical behavior. We tried to define the molecular, clinicopathological, histologic, and immunohistochemical features of PRNRP by comparing them with type 1 PRCC (PRCC1) and type 2 PRCC (PRCC2). A cohort of 30 PRNRP, 23 PRCC1, and 26 PRCC2 cases was used. Targeted sequencing of 90 cancer-related genes including KRAS was performed in 26 PRNRP tumor samples. PNA-mediated clamping PCR of KRAS was performed using paired normal and tumor DNA from 30 PRNRP, 23 PRCC1, and 26 PRCC2 cases. Tissue microarray slides were made in three cores per tumor, which were stained with cytokeratin 7 (CK7), alpha-methylacyl-CoA racemase (AMACR), epithelial membrane antigen (EMA), E-cadherin, vimentin, and CD10. Recurrent mutations in KRAS were detected in 28 of the 30 PRNRPs. However, there were no KRAS mutations in any PRCC1 or PRCC2 cases. PRNRP exhibited distinct clinicopathological features: small tumor size, lower pathologic T stage, and no disease-specific death during the follow-up period. Histologically, peritumoral lymphoid aggregation, prominent papillary architecture (>80% of tumor), hyalinized papillae, inverted nuclear location, and lower nuclear grade were observed. PRNRP was usually positive for CK7, AMACR, EMA, and E-cadherin, and negative for CD10. The findings suggest that PRNRP is a subtype of papillary renal neoplasm that is different from PRCC1 or PRCC2 in terms of molecular, clinicopathological, histological, and immunohistochemical features.

ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways.

ATPase inhibitory factor 1 (IF1) is an ATP synthase-interacting protein that suppresses the hydrolysis activity of ATP synthase. In this study, we observed that the expression of IF1 was up-regulated in response to electrical pulse stimulation of skeletal muscle cells and in exercized mice and healthy men. IF1 stimulates glucose uptake via AMPK in skeletal muscle cells and primary cultured myoblasts. Reactive oxygen species and Rac family small GTPase 1 (Rac1) function in the upstream and downstream of AMPK, respectively, in IF1-mediated glucose uptake. In diabetic animal models, the administration of recombinant IF1 improved glucose tolerance and down-regulated blood glucose level. In addition, IF1 inhibits ATP hydrolysis by ß-F1-ATPase in plasma membrane, thereby increasing extracellular ATP and activating the protein kinase B (Akt) pathway, ultimately leading to glucose uptake. Thus, we suggest that IF1 is a novel myokine and propose a mechanism by which AMPK and Akt contribute independently to IF1-mediated improvement of glucose tolerance impairment. These results demonstrate the importance of IF1 as a potential antidiabetic agent.-Lee, H. J., Moon, J., Chung, I., Chung, J. H., Park, C., Lee, J. O., Han, J. A., Kang, M. J., Yoo, E. H., Kwak, S.-Y., Jo, G., Park, W., Park, J., Kim, K. M., Lim, S., Ngoei, K. R. W., Ling, N. X. Y., Oakhill, J. S., Galic, S., Murray-Segal, L., Kemp, B. E., Mantzoros, C. S., Krauss, R. M., Shin, M.-J., Kim, H. S. ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways.

Interaction between lead and noradrenergic genotypes affects neurocognitive functions in attention-deficit/hyperactivity disorder: a case control study.

BACKGROUND: Lead is known to be associated with attention-deficit/hyperactivity disorder (ADHD) even at low concentrations. We aimed to evaluate neurocognitive functions associated with lead in the blood and the interactions between lead and dopaminergic or noradrenergic pathway-related genotypes in youths with ADHD. METHODS: A total of 259 youths with ADHD and 96 healthy controls (aged 5-18 years) enrolled in this study. The Korean Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version was conducted for psychiatric diagnostic evaluation. Blood lead levels were measured, and their interaction with dopaminergic or noradrenergic genotypes for ADHD; namely, the dopamine transporter (DAT1), dopamine receptor D4 (DRD4), and alpha-2A-adrenergic receptor (ADRA2A) genotypes were investigated. All participants were assessed using the ADHD Rating Scale-IV (ADHD-RS). Participants also completed the continuous performance test (CPT) and Stroop Color-Word Test (SCWT). Analysis of covariance was used for comparison of blood lead levels between ADHD and control groups. A multivariable linear regression model was used to evaluate the associations of blood lead levels with the results of ADHD-RS, CPT, and SCWT; adjusted for intelligence quotient (IQ), age, and sex. A path analysis model was used to identify the mediating effects of neurocognitive functions on the effects of blood lead on ADHD symptoms. To evaluate the effect of the interaction between blood lead and genes on neuropsychological functions, hierarchical regression analyses were performed. RESULTS: There was a significant difference in blood lead levels between the ADHD and control groups (1.4 ± 0.5 vs. 1.3 ± 0.5 µg/dL, p = .005). Blood lead levels showed a positive correlation with scores on omission errors(r = .158, p = .003) and response time variability (r = .136, p = .010) of CPT. In the multivariable linear regression model, blood lead levels were associated with omission errors (B = 3.748, p = .045). Regarding the effects of lead on ADHD symptoms, hyperactivity-impulsivity was mediated by omission errors. An interaction effect was detected between ADRA2A DraI genotype and lead levels on omission errors (B = 5.066, p = .041). CONCLUSIONS: Our results indicate that neurocognitive functions at least partly mediate the association between blood lead levels and ADHD symptoms, and that neurocognitive functions are affected by the interaction between blood lead levels and noradrenergic genotype.