Observation of perfect diamagnetism and interfacial effect on the electronic structures in infinite layer Nd0.8Sr0.2NiO2 superconductors.

Nickel-based complex oxides have served as a playground for decades in the quest for a copper-oxide analog of the high-temperature superconductivity. They may provide clues towards understanding the mechanism and an alternative route for high-temperature superconductors. The recent discovery of superconductivity in the infinite-layer nickelate thin films has fulfilled this pursuit. However, material synthesis remains challenging, direct demonstration of perfect diamagnetism is still missing, and understanding of the role of the interface and bulk to the superconducting properties is still lacking. Here, we show high-quality Nd0.8Sr0.2NiO2 thin films with different thicknesses and demonstrate the interface and strain effects on the electrical, magnetic and optical properties. Perfect diamagnetism is achieved, confirming the occurrence of superconductivity in the films. Unlike the thick films in which the normal-state Hall-coefficient changes signs as the temperature decreases, the Hall-coefficient of films thinner than 5.5 nm remains negative, suggesting a thickness-driven band structure modification. Moreover, X-ray absorption spectroscopy reveals the Ni-O hybridization nature in doped infinite-layer nickelates, and the hybridization is enhanced as the thickness decreases. Consistent with band structure calculations on the nickelate/SrTiO3 heterostructure, the interface and strain effect induce a dominating electron-like band in the ultrathin film, thus causing the sign-change of the Hall-coefficient.

[Hemodynamic changes in standing-up test of children and adolescents with postural tachycardia syndrome].

OBJECTIVE: To explore the hemodynamic changes in standing-up test of children and adolescents with postural tachycardia syndrome (POTS) and to compare hemodynamic parameters of POTS patients with decreased cardiac index (CI) and those with not-decreased CI. METHODS: A retrospective study was conducted to show the trends of CI, total peripheral vascular resistance index (TPVRI), heart rate and blood pressure in standing-up test of 26 POTS patients and 12 healthy controls, and to compare them between the two groups. The POTS patients were divided into two groups based on CI decreasing or not in standing-up test, namely decreased CI group (14 cases) and not-decreased CI group (12 cases). The trends of the above mentioned hemodynamic parameters in standing-up test were observed and compared between decreased CI group and not-decreased CI group. RESULTS: In standing-up test for all the POTS patients, CI (F=6.936, P=0.001) and systolic blood pressure (F=6.049, P<0.001) both decreased significantly, and heart rate increased obviously (F=113.926, P<0.001). However, TPVRI (F=2.031, P=0.138) and diastolic blood pressure (F=2.018, P=0.113) had no significant changes. For healthy controls, CI (F=3.646, P=0.016), heart rate (F=43.970, P<0.001), systolic blood pressure (F=4.043, P=0.020) and diastolic blood pressure (F=8.627, P<0.001) all increased significantly in standing-up test. TPVRI (F=1.688, P=0.190) did not change obviously. The changing trends of CI (F=6.221, P=0.001), heart rate (F=6.203, P<0.001) and systolic blood pressure (F=7.946, P<0.001) over time were significantly different between the patients and healthy controls, however, no difference was found in TPVRI and diastolic blood pressure (P > 0.05). Among the POTS patients, CI was significantly different between decreased CI group and not-decreased CI group (F=14.723, P<0.001). Systolic blood pressure of the former decreased obviously (F=8.010, P<0.001), but it did not change obviously in the latter (F=0.612, P=0.639). Furthermore, none of the changes of TPVRI, heart rate and diastolic blood pressure in standing-up test were significantly different between the two groups (P > 0.05). Age was an independent factor for decreased CI patients (P=0.013, OR=2.233; 95% CI, 1.183 to 4.216). CONCLUSION: POTS patients experience vital hemodynamic changes in standing-up test, part of them suffering from decreased CI, but others from not-decreased CI. Age is an independent factor for patients suffering from decreased CI.

Relative risks of Internet-related addictions and mood disturbances among college students: a 7-country/region comparison.

OBJECTIVES: This study aimed to determine the relative risks of addiction to the Internet, online gaming and online social networking of college students in six Asian countries/regions (Singapore, Hong Kong [HK]/Macau, China, South Korea, Taiwan and Japan) compared with students in the United States (US). It also explored the relative risks of depression and anxiety symptoms among students with Internet-related addictions from these countries/regions. STUDY DESIGN: This is a cross-sectional survey. METHODS: A convenience sample of 8067 college students aged between 18 and 30 years was recruited from seven countries/regions. Students completed a survey about their use of the Internet, online gaming and online social networking as well as the presence of depression and anxiety symptoms. RESULTS: For all students, the overall prevalence rates were 8.9% for Internet use addiction, 19.0% for online gaming addiction and 33.1% for online social networking addiction. Compared with the US students, Asian students showed higher risks of online social networking addiction but displayed lower risks of online gaming addiction (with the exception of students from HK/Macau). Chinese and Japanese students also showed higher risks of Internet addiction compared with the US students. In general, addicted Asian students were at higher risks of depression than the addicted US students, especially among Asian students who were addicted to online gaming. Addicted Asian students were at lower risks of anxiety than the addicted US students, especially among Asian students who were addicted to online social networking, and addicted students from HK/Macau and Japan were more likely to have higher relative risks of depression. CONCLUSIONS: There are country/regional differences in the risks of Internet-related addictions and psychiatric symptoms. It is suggested that country/region-specific health education programmes regarding Internet-related addictions are warranted to maximise the efficiency of prevention and intervention. These programmes should attempt to tackle not only problematic Internet-related behaviours but also mood disturbances among college students.

[Progress in diagnosis and management of syncope in children].

Syncope is a common emergency of children and adolescents, which has serious influence on the quality of life. Neurally-mediated syncope, including postural tachycardia syndrome, vasovagal syncope, orthostatic hypotension and orthostatic hypertension, is the main cause of syncope in children and adolescents. The main manifestations of neurally-mediated syncope are diverse, such as dizziness, headache, chest tightness, chest pain, pale complexion, fatigue, pre-syncope and syncope. Although the clinical manifestations are similar, each subtype of syncope has its hemodynamic feature and optimal treatment option. The diagnosis rate of syncope in children has been greatly improved on account of the development of the diagnostic procedures and methods. In recent years, with the promotion of head-up tilt test and drug-provocated head-up tilt test, the hemodynamic classification of neurally-mediated syncope gets continually refined. In recent years, with the effort of clinicians, an appropriate diagnostic protocol for children with syncope has been established. The initial evaluation consists of history taking, physical examination, standing test and standard electrocardiography. After the initial evaluation, some patients could be diagnosed definitely, such as postural tachycardia syndrome, orthostatic hypotension, and situational syncope. Those with a specific entity causing syncope need selective clinical and laboratory investigations. Patients for whom the cause of syncope remained undetermined should undergo head-up tilt test. The precise pathogenesis of neurally-mediated syncope is not entirely clear. In recent years, studies have shown that neurally-mediated syncope may be related to several factors, including hypovolemia, high catecholamine status, abnormal local vascular tension, decreased skeletal muscle pump activity and abnormal neurohumoral factors. Currently based on the possible pathogenesis, the individualized treatment of neurally-mediated syncope has also been studied in-depth. Generally, the management of neurally-mediated syncope includes non-pharmacological and pharmacological interventions. Patient education is the fundamental part above all. In addition to exercise training, the first-line treatments mainly include oral rehydration salts, beta adrenoreceptor blockers, and alpha adrenoreceptor agonists. By analyzing the patient's physiological indexes and biomarkers before treatment, the efficacy of medication could be well predicted. The individualized treatment will become the main direction in the future researches.

HLA-B*38:02:01 predicts carbimazole/methimazole-induced agranulocytosis.

Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.

Expression levels of urotensin II are associated with endoplasmic reticulum stress in patients with severe preeclampsia.

Hypertensive disorders in pregnancy remain a leading cause of maternal and perinatal mortality and morbidity. We aim to study urotensin II (UII) and its association with the markers of endoplasmic reticulum stress (ERS) in placentas of patients with severe preeclampsia (SPE). Thirty-three patients with hypertensive disorders in pregnancy and twenty-two healthy pregnant women designated as healthy controls were recruited. Expression levels of UII, UII receptor (GPR14) and the markers of ERS in placenta specimens of patients were performed. Plasma and urinary UII levels were measured by radioimmunoassay method. Our study showed that the plasma levels of UII in patients with hypertensive disorders during pregnancy were significantly higher than that of the healthy control group. However, the urinary levels of UII had no difference in two groups. The expression level of mRNA and protein of UII, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulation protein 78 in placentas of SPE was significantly increased. Immunohistochemical analyses show that the expression levels of UII and ERS markers were mainly located in the cytoplasm of placental trophoblastic cells. Moreover, expression level of UII mRNA and protein was positively correlated with that of the markers of ERS. The positive correlation between UII and ERS markers expression level also corresponded with the level of patient's systolic blood pressure and proteinuria. In conclusion, we first verify that expression of UII is associated with ERS in patients with SPE. Our results indicate that UII may trigger ERS in placental trophoblastic cells in patients with preeclampsia.

Survey on examining prevalence of paternal anxiety and its risk factors in perinatal period in Hong Kong: a longitudinal study.

BACKGROUND: There is emerging evidence of the significance of paternal mental health problems among the expectant fathers during the antenatal and postnatal period. The present study aims at determining the prevalence of paternal perinatal anxiety and identifying its risk factors among the fathers. METHODS: A total of 622 expectant fathers were recruited in Hong Kong. The expectant fathers were assessed using standardized and validated psychological instruments on three time points including early pregnancy, late pregnancy and 6 week postnatal. Independent samples t-test, one way ANOVA, Pearson's correlation and multiple linear regression were used to examine the effect of hypothesized risk factors. Hierarchical multiple regression and mixed effect model were also conducted with potential confounding factors controlled for. RESULTS: Results showed that a significant proportion of expectant fathers experienced anxiety during the perinatal period. Low self-esteem and poor social support were found to be risk factors of paternal anxiety across pregnancy to postnatal period. Work-family conflict could significantly predict paternal anxiety in the pregnancy period. CONCLUSIONS: The present study points to the need for greater research and clinical attention to paternal anxiety, given that it is a highly prevalent problem and could be detrimental to their partner's well-being and children development. The present findings contributes to the theoretical understanding of the prevalence and risk factors of paternal perinatal anxiety and have implications for the design of effective identification, prevention, and interventions of these clinical problems.

Effect of Treadmill Running on Apelin and APJ Expression in Adipose Tissue and Skeletal Muscle in Rats Fed a High-fat Diet.

Apelin, an adipokine and also a myokine, is involved in glucose homeostasis. In this study we investigated the effect of insulin resistance and exercise on the regulation of apelin and APJ in adipose tissue and skeletal muscle. After 20 weeks of a high-fat diet (HFD), rats showed severe insulin resistance, with increased fasting blood sugar and plasma insulin and impaired glucose tolerance. Plasma apelin immunoreactivity as well as apelin and APJ expression in adipose tissue and gastrocnemius muscle were significantly increased, with no difference in soleus muscle. Treadmill running completely ameliorated the HFD-induced insulin resistance, decreased plasma apelin level, and downregulated apelin and APJ expression in adipose tissue. However, apelin and APJ expression was upregulated in soleus and gastrocnemius muscle with treadmill training and a HFD. Exercise had a tissue-dependent effect on apelin and APJ expression in rats fed a HFD.

Superoxide anions in the paraventricular nucleus mediate cardiac sympathetic afferent reflex in insulin resistance rats.

AIM: Cardiac sympathetic afferent reflex (CSAR) participates in sympathetic over-excitation. Superoxide anions and angiotensin II (Ang II) mechanisms are associated with sympathetic outflow and CSAR in the paraventricular nucleus (PVN). This study was designed to investigate whether PVN superoxide anions mediate CSAR and Ang II-induced CSAR enhancement response in fructose-induced insulin resistance (IR) rats. METHODS: CSAR was evaluated with the changes of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to the epicardial application of capsaicin (CAP) in anaesthetized rats. RESULTS: Compared with Control rats, IR rats showed that CSAR, PVN NAD(P)H oxidase activity, superoxide anions, malondialdehyde (MDA), Ang II and AT1 receptor levels were significantly increased, whereas PVN superoxide dismutase (SOD) and catalase (CAT) activities were decreased. In Control and IR rats, PVN microinjection of superoxide anions scavengers tempol, tiron and PEG-SOD (an analogue of endogenous superoxide dismutase) or inhibition of PVN NAD(P)H oxidase with apocynin caused significant reduction of CSAR, respectively, but DETC (a superoxide dismutase inhibitor) strengthened the CSAR. PVN pre-treatment with tempol abolished, whereas DETC potentiated, Ang II-induced CSAR enhancement response. Moreover, PVN pre-treatment with tempol or losartan prevented superoxide anions increase caused by Ang II in IR rats. CONCLUSION: PVN superoxide anions mediate CSAR and Ang II-induced CSAR response in IR rats. In IR state, increased NAD(P)H oxidase activity and decreased SOD and CAT activities in the PVN promote superoxide anions increase to involve in CSAR enhancement. Ang II may increase NAD(P)H oxidase activity via AT1 receptor to induce superoxide anion production.

The Prevalence and Risk Factors of Paternal Depression from the Antenatal to the Postpartum Period and the Relationships between Antenatal and Postpartum Depression among Fathers in Hong Kong.

Introduction. Despite the fact that maternal perinatal mental health problems have been extensively studied and addressed to be a significant health problem, the literature on paternal perinatal mental health problems is relatively scarce. The present study aims at determining the prevalence of paternal perinatal depression and identifying the risk factors and the relationship between antenatal and postpartum depression. Methodology. 622 expectant fathers were recruited from regional maternal clinics. The expectant fathers were assessed using standardized and validated psychological instruments on 3 time points including early pregnancy, late pregnancy, and six weeks postpartum. Results. Results showed that a significant proportion of expectant fathers manifested depressive symptoms during the perinatal period. Paternal antenatal depression could significantly predict higher level of paternal postpartum depression. Psychosocial risk factors were consistently associated with paternal depression in different time points. Conclusions. The present study points to the need for greater research and clinical attention to paternal depression given that it is a highly prevalent problem and could be detrimental to their spouse and children development. The present findings contribute to theoretical basis of the prevalence and risk factors of paternal perinatal depression and have implications of the design of effective identification, prevention, and interventions of these clinical problems.

Serum tumour necrosis factor-alpha is associated with poor health-related quality of life and depressive symptoms in patients with systemic lupus erythematosus.

OBJECTIVES: While patients with systemic lupus erythematosus (SLE) have poorer health-related quality of life (HRQoL) and are more depressed than healthy people, the impact of proinflammatory cytokines, particularly tumour necrosis factor-alpha (TNFα), on these unfavourable psychosocial parameters is unclear. We aim to explore potential relationships between lupus-related proinflammatory cytokines, HRQoL and depressive symptoms in patients with SLE. METHODS: Patients with SLE and age-matched healthy subjects were assessed for HRQoL and depressive and anxiety symptoms by the Short Form Health Survey-36 (SF-36) and Hospital Anxiety and Depression Scale (HADS) respectively. Using multiplex immunoassay, a panel of serum proinflammatory cytokines including TNFα, interleukin (IL)-1ß, IL-6, IL-17, IL-23 and IL-33 were determined and compared between both groups. Independent associations between SF-36, serum proinflammatory cytokine levels and HADS scores were studied by regression models. RESULTS: In total, 54 patients and 54 healthy controls were studied. Lupus patients had significantly poorer HRQoL (p < 0.001) and were significantly more depressed (p = 0.006) and anxious (p = 0.022) than their healthy counterparts. Amongst the proinflammatory cytokines studied, serum TNFα was significantly higher in lupus patients (p < 0.001). After multivariate adjustment, higher serum TNFα (ß = -0.224, p = 0.047) remained significantly associated with lower SF-36, along with smoking (ß = -0.253, p = 0.014) and more severe depressive symptoms (ß = -0.433, p = 0.002). In healthy subjects, serum TNFα was associated with depressive symptoms but not with SF-36. CONCLUSIONS: Higher serum TNFα level is independently associated with poorer HRQoL and more severe depressive symptoms in SLE patients. These associations suggest a potential impact of inflammatory response on depressive symptoms and the quality of life in patients with SLE.

Adrenomedullin attenuates vascular calcification in fructose-induced insulin resistance rats.

AIM: To determine the therapeutic effects of adrenomedullin (ADM) on vascular calcification and related molecular mechanism in fructose-induced insulin resistance rats. METHODS: Rats received ordinary drinking water or 10% fructose in drinking water for 12 weeks and subcutaneous injection of normal saline or ADM (3.6 µg kg(-1) ) twice a day for the last 4 weeks. Levels of ADM, calcitonin receptor-like receptors (CRLR), receptor activity-modifying proteins (RAMP) as well as calcium content, alkaline phosphatase (ALP) activity, osteoblastic and contractile smooth muscle markers in aortic media were measured. RESULTS: The levels of ADM, CRLR, RAMP2 and RAMP3 in aortic media were increased in fructose-fed rats. ADM treatment attenuated the fructose-induced insulin resistance, increased blood pressure, fasting glucose, insulin, triglycerides and cholesterol levels. It improved VSMCs proliferation and disordered arrangement and hyperplasia of elastic fibres in fructose-fed rats. Calcium deposits, calcium content and ALP activity in the aortic media were increased in fructose-fed rats, which were attenuated by ADM treatment. The osteoblastic markers such as osteopontin (OPN), bone morphogenetic protein 2 (BMP2) proteins and core binding factor alpha-1 (Cbfα-1) protein and mRNA expressions were increased in fructose-fed rats. ADM treatment increased the OPN protein expression, but reduced the BMP2 protein, Cbfα-1 protein and mRNA expression. Contractile smooth muscle markers such as α-actin and smooth muscle 22α (SM-22α) were downregulated in fructose-fed rats, which were recovered by ADM treatment. CONCLUSION: Administration of ADM attenuates insulin resistance, calcium deposition and osteogenic transdifferentiation in aortic media in fructose-fed rats.

Chemical production in electrocautery smoke by a novel predictive model.

OBJECTIVES: The hazards of electrocautery smoke have been known for decades. However, few clinical studies have been conducted to analyze the responsible variables of the smoke production. This study collected clinical smoke samples and systematically analyzed all possible factors. METHODS: Thirty diathermy smoke samples were collected during mastectomy and abdominal cavity operations. Samples were analyzed using a gas chromatographer with a flame ionization detector. Data were applied to construct prediction models for chemical production from electrosurgeries to identify all possible factors that impact chemical production during electrosurgery. RESULTS: Toluene was detected in 27 smoke samples (90%) with concentrations of 0.003-0.463 mg/m(3) and production of 176.0-2,780.0 ng. Ethyl benzene and styrene were identified in very few cases. General linear regression analysis demonstrates that surgery type, patient age, electrocautery duration and imparted coagulation energy explained 67.63% of the variation in toluene production. CONCLUSION: Surgery type and patient age are known prior to surgery. In terms of risk precaution, the operating team should pay close attention to exposure when certain positive factors of increasing the chemical production are known in advance.

Fine mapping of the 9q31 Hirschsprung's disease locus.

Hirschsprung's disease (HSCR) is a congenital disorder characterised by the absence of ganglia along variable lengths of the intestine. The RET gene is the major HSCR gene. Reduced penetrance of RET mutations and phenotypic variability suggest the involvement of additional modifying genes in the disease. A RET-dependent modifier locus was mapped to 9q31 in families bearing no coding sequence (CDS) RET mutations. Yet, the 9q31 causative locus is to be identified. To fine-map the 9q31 region, we genotyped 301 tag-SNPs spanning 7 Mb on 137 HSCR Dutch trios. This revealed two HSCR-associated regions that were further investigated in 173 Chinese HSCR patients and 436 controls using the genotype data obtained from a genome-wide association study recently conducted. Within one of the two identified regions SVEP1 SNPs were found associated with Dutch HSCR patients in the absence of RET mutations. This ratifies the reported linkage to the 9q31 region in HSCR families with no RET CDS mutations. However, this finding could not be replicated. In Chinese, HSCR was found associated with IKBKAP. In contrast, this association was stronger in patients carrying RET CDS mutations with p = 5.10 x 10(-6) [OR = 3.32 (1.99, 5.59)] after replication. The HSCR-association found for IKBKAP in Chinese suggests population specificity and implies that RET mutation carriers may have an additional risk. Our finding is supported by the role of IKBKAP in the development of the nervous system.

Sulfur dioxide relaxes rat aorta by endothelium-dependent and -independent mechanisms.

This study aimed to investigate the vasoactivity of sulfur dioxide (SO2), a novel gas identified from vascular tissue, in rat thoracic aorta. The thoracic aorta was isolated, cut into rings, and mounted in organ-bath chambers. After equilibrium, the rings were gradually stretched to a resting tension. Isometric tension was recorded under the treatments with vasoconstrictors, SO2 derivatives, and various drugs as pharmacological interventions. In endothelium-intact aortic rings constricted by 1 microM phenylephrine (PE), SO2 derivatives (0.5-8 mM) caused a dose-dependent relaxation. Endothelium removal and a NOS inhibitor L-NAME reduced the relaxation to low doses of SO2 derivatives, but not that to relatively high doses (>or=2 mM). In endothelium-denuded rings, SO2 derivatives attenuated vasoconstriction induced by high K+ (60 mM) or CaCl2 (0.01-10 mM). The relaxation to SO2 derivatives in PE-constricted rings without endothelium was significantly inhibited by blockers of ATP-sensitive K+(KATP) and Ca2+-activated K+ (KCa) channels, but not by those of voltage-dependent K+ channels, Na+- K+-ATPase or Na+-Ca2+ exchanger. SO2 relaxed vessel tone via endothelium-dependent mechanisms associated with NOS activation, and via endothelium-independent mechanisms dependent on the inhibition of voltage-gated Ca2+ channels, and the opening of KATP and KCa channels.

An evaluation of the contributions by fresh gas flow rate, carbon dioxide concentration and desflurane partial pressure to carbon monoxide concentration during low fresh gas flows to a circle anaesthetic breathing system.

BACKGROUND AND OBJECTIVE: Numerous in vitro studies have shown that volatile anaesthetics react with desiccated carbon dioxide (CO2) absorbents to produce carbon monoxide (CO). The effects of anaesthetic concentration, fresh gas flow rate, and the hydration of absorbent or the excretion of CO2 by patients on CO production have also been investigated. This work aims to identify the most significant one of these factors on CO concentration in a low-flow anaesthesia system, without control of the hydration of the absorbents. METHODS: A simulated clinical circle anaesthetic breathing system was used to study the CO concentration under various conditions. Desflurane was used at three different concentrations. Two CO2 flow rates and three fresh gas flow rates were used. The absorbent temperatures and hydration were measured simultaneously. RESULTS: Desflurane degraded to produce CO in the breathing tube, when the CO2 absorbents were not dried beforehand. In this imitation clinical low-flow setting, fresh gas flow affected the CO production more than the CO2 did (31.7% vs. 9.5%). The actual desflurane partial pressure was not a significant factor. The CO2 flow rate explained 18.2% and 54.0% of the variation of the absorbent hydration changes (%) and temperature, respectively. CONCLUSIONS: In clinical practice, the CO2 production varies among patients and is uncontrollable, but markedly affects CO production. The only controllable factor is the fresh gas flow rate if the ultimate goal is to reduce the undesirable exposure of patients to CO from the breathing tube according to this bench model without counting the oxygen consumption.

Identification of C-glycoside flavonoids as potential mutagenic compounds in kava.

Kava (Piper methysticum) extract products have been implicated in a number of severe hepatotoxicity cases. However, systematic toxicological studies regarding kava consumption have not been reported. In this study, 6 major kavalactones and different solvent fractions of kava roots, leaves, and stem peelings were evaluated for their mutagenic potential. None of the kavalactones was found to be positive in the experimental concentration ranges tested by the umu test (a sensitive test for point mutations). However, among the different solvent fractions, the n-butanol fraction of kava leaves was positive. Further investigations using bioassay-directed isolation and analysis indicated that 2 C-glycoside flavonoid compounds accounted for the positive mutagenic results. Two isolated compounds were identified as 2''-O-rhamnosylvitexin and schaftoside by NMR and MS techniques.

A pilot study on tacrolimus treatment in membranous or quiescent lupus nephritis with proteinuria resistant to angiotensin inhibition or blockade.

Persistent proteinuria in patients with quiescent lupus can result from membranous lupus nephritis and/or glomerular scarring following previous flares. This pilot study examined the effects of tacrolimus over two years in six patients with membranous/inactive lupus nephritis and persistent proteinuria despite angiotensin inhibition/blockade. Tacrolimus treatment reduced proteinuria and increased serum albumin (time effect, P = 0.047 and 0.032 respectively). Compared with baseline levels, proteinuria improved by more than 50% in five patients (83.3%) and hypoalbuminaemia was corrected in four patients. The efficacy was most prominent in four patients with biopsy-proven membranous lupus nephritis, whose protienuria improved by over 80%. One patient developed biopsy-proven chronic nephrotoxicity after 10 months of tacrolimus treatment, despite non-excessive blood levels. These data suggest that tacrolimus is an effective treatment for proteinuria due to membranous lupus nephritis, but should probably be reserved for patients who are refractory to other non-nephrotoxic treatments, in view of the potential risk of subclinical nephrotoxicity.

Quality of life comparison between corticosteroid- and-mycofenolate mofetil and corticosteroid- and-oral cyclophosphamide in the treatment of severe lupus nephritis.

There is accumulating evidence that mycophenolate mofetil (MMF), when combined with corticosteroid, is an effective induction treatment for severe proliferative lupus nephritis and is associated with fewer adverse effects compared to cyclophosphamide (CTX), but the quality of life (QOL) associated with these regimens as perceived by the patient has not been compared. This study included patients who had experienced both treatment regimens, for distinct episodes of diffuse proliferative lupus nephritis. QOL parameters during the first six months of each treatment were assessed through SF36 and WHOQOL questionnaires. Twelve patients and 24 episodes of severe lupus nephritis were studied. CTX-treated and MMF-treated episodes showed comparable baseline characteristics and response rate, with complete remission occurring in 83.3%. MMF treatment was associated with higher numerical scores for all domains across both QOL instruments than CTX. MMF treatment was associated with significantly less fatigue, less impediment of physical and social functioning, and better psychological well being compared to CTX. When each patient served as her/his own control, most patients ascribed higher QOL domain scores to the MMF-treated episode. Seventy-five percent of patients found MMF treatment more acceptable and preferred when compared with CTX, and the complications that most concerned them included Cushingoid features, alopecia, menstrual disturbance and infections. These data showed that MMF-based induction immunosuppression for severe lupus nephritis was associated with better QOL than CTX as perceived by patients, which was most likely attributed to the reduced side-effects during MMF treatment.

Dynamic, electronically switchable surfaces for membrane protein microarrays.

Microarray technology is a powerful tool that provides a high throughput of bioanalytical information within a single experiment. These miniaturized and parallelized binding assays are highly sensitive and have found widespread popularity especially during the genomic era. However, as drug diagnostics studies are often targeted at membrane proteins, the current arraying technologies are ill-equipped to handle the fragile nature of the protein molecules. In addition, to understand the complex structure and functions of proteins, different strategies to immobilize the probe molecules selectively onto a platform for protein microarray are required. We propose a novel approach to create a (membrane) protein microarray by using an indium tin oxide (ITO) microelectrode array with an electronic multiplexing capability. A polycationic, protein- and vesicle-resistant copolymer, poly(l-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG), is exposed to and adsorbed uniformly onto the microelectrode array, as a passivating adlayer. An electronic stimulation is then applied onto the individual ITO microelectrodes resulting in the localized release of the polymer thus revealing a bare ITO surface. Different polymer and biological moieties are specifically immobilized onto the activated ITO microelectrodes while the other regions remain protein-resistant as they are unaffected by the induced electrical potential. The desorption process of the PLL-g-PEG is observed to be highly selective, rapid, and reversible without compromising on the integrity and performance of the conductive ITO microelectrodes. As such, we have successfully created a stable and heterogeneous microarray of biomolecules by using selective electronic addressing on ITO microelectrodes. Both pharmaceutical diagnostics and biomedical technology are expected to benefit directly from this unique method.