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Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
Multiple neurotrophic factors, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2, nerve growth factor (NGF) and insulin-like growth factor(IGF)-1, have been shown to play important roles in the pathophysiology of mood disorders. However, insufficient clinical data supporting the importance of these neurotrophic factors in mood disorders, especially manic episode, have made inconclusive to make a connection between these factors and the disorder.
This study intended to investigate possible peripheral biomarkers in serum of manic episode of bipolar disorder.
We aimed to investigate whether or not serum levels of VEGF, FGF-2, NGF and IGF-1 varied in manic state.
Serum levels of VEGF, FGF-2, NGF and IGF-1 were examined in 70 drug-naïve patients with manic episode of bipolar disorder (BM) as well as 50 healthy controls, using an ELISA method.
The mean serum levels of VEGF, FGF-2, NGF and IGF-1 were 168.13±225.61pg/ml, 279.09±378.62pg/ml, 61.38±171.67pg/ml and 162.01±72.00ng/ml in BM patients, and 140.80±143.71pg/ml, 275.46±235.29pg/ml, 36.34±15.14pg/ml and 138.90±80.11ng/ml in healthy controls, respectively. Serum levels of FGF-2, NGF and IGF-1 in patients were significantly higher than those in healthy controls (Z=−2.896, P=0.004; Z=− 2.050, P=0.040; Z=−2.188, P=0.029; respectively), although there was no statistical difference in the serum levels of VEGF between two groups (Z=-0.468, P=0.639). Moreover, serum levels of NGF in patients correlated with the duration of disorder (rs=−0.241, P=0.044).
The increase in serum levels of FGF-2, NGF and IGF-1 in manic state may reflect a neuroprotective role for these factors, and these factors may be considered biological markers for manic episode.
Lethality of the chosen method during a suicide attempt is a strong risk factor for completion of suicide. We examined whether annual changes in the pattern of suicide methods is related to annual changes in suicide rates among older adults in South Korea and the United States. We analyzed annual the World Health Organization data on rates and methods of suicide from 2000 to 2011 in South Korea, and from 2000 to 2010 in the United States. We found that. for both Korean male and female older adults, there was a significant positive correlation between suicide rate and the rate of hanging, and a significant negative correlation between suicide rate and the rate of poisoning. Among older adults in the U.S., annual changes in the suicide rate and the pattern of suicide methods were less conspicuous, and no correlation was found between them.
The results of the present study suggest that the increasing use of lethal suicide methods has contributed to the rise in suicide rates among older adults in South Korea. Targeted efforts to reduce the social acceptability and accessibility of lethal suicide methods might lead to lower suicide rate among older adults in South Korea.
Chlamydia trachomatis (CT) infection has been a major public health threat globally. Monitoring and prediction of CT epidemic status and trends are important for programme planning, allocating resources and assessing impact; however, such activities are limited in China. In this study, we aimed to apply a seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence of CT infection in Shenzhen city, China. The monthly incidence of CT between January 2008 and June 2019 in Shenzhen was used to fit and validate the SARIMA model. A seasonal fluctuation and a slightly increasing pattern of a long-term trend were revealed in the time series of CT incidence. The monthly CT incidence ranged from 4.80/100 000 to 21.56/100 000. The mean absolute percentage error value of the optimal model was 8.08%. The SARIMA model could be applied to effectively predict the short-term CT incidence in Shenzhen and provide support for the development of interventions for disease control and prevention.
India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25–65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (−0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.
We study the inverse boundary value problem for fractional diffusion in a multilayer composite medium. Given data in the right boundary of the second layer, the problem is to recover the temperature distribution in the first layer, which is inaccessible for measurement. The problem is ill-posed and we propose a Fourier spectral approach to achieve Hölder approximations. The convergence analysis is performed in both the
Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.
To determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis.
We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum.
Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD.
Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.
Declaration of interest
D.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.
Based on the data from the Next Generation Virgo cluster Survey (NGVS), we statistically study the photometric properties of globular clusters (GCs), ultra-compact dwarfs (UCDs) and dwarf nuclei in the Virgo core (M87) region. We found an obvious negative color (g - z) gradient in GC system associate with M87, i.e. GCs in the outer regions are bluer. However, such color gradient does not exist in UCD system, neither in dwarf nuclei system around M87. In addition, we found that many UCDs are surrounded by extended, low surface brightness envelopes. The dwarf nuclei and UCDs show different spatial distributions from GCs, with dwarf nuclei and UCDs (especially for the UCDs with visible envelopes) lying at larger distances to the Virgo center. These results support the view that UCDs (at least for a fraction of UCDs) are more tied to dwarf nuclei than to GCs.
We have searched optical u′g′r′i′z′ imaging of 22 deg2 centred on the nearby giant elliptical galaxy NGC 5128 for new dwarf galaxies in the Centaurus A group. We report 45 promising new candidates, which are broadly consistent with the properties of nearby dwarf spheroidal galaxies and extend the size-luminosity relation toward fainter total luminosities and smaller sizes for known dwarf galaxies outside the Local Group (LG). Altogether, these new results show NGC 5128 to be the host of a large reservoir of low-mass dwarf galaxies that is at least as rich as that of the LG and is ripe for detailed follow-up observations.
Thermal plasma wind tunnels with power of 0.4 MW and 2.4 MW have been constructed at Chonbuk National University (CBNU) in Korea. This facility is capable of producing a heat flux greater than 10 MW/m2, a level that is relevant for testing thermal protection materials that are used for re-entry vehicles in space transportation. A segmented arc plasma torch was adopted as a plasma source; this was designed to have high thermal efficiency and long life, and to produce a supersonic plasma flow with enthalpy greater than 10 MJ/kg. We investigated the characteristics of the supersonic plasma flow using intrusive and non-intrusive diagnostic systems. Ablation characteristics of potential thermal protection materials such as carbon/carbon composites and graphite were investigated with the plasma wind tunnel. Cracks and pores in the materials accelerated the erosion. For carbon/carbon composites, the pores grew and the cracks which occurred at the interfaces between the carbon fibres and the matrix propagated, while for the graphite, the erosion started at the pores and peeled off the surface.
Relativistic collisionless shock charged particle acceleration is considered as a possible origin of high-energy cosmic rays. However, it is hard to explore the nature of relativistic collisionless shock due to its low occurring frequency and remote detecting distance. Recently, there are some works attempt to solve this problem by generating relativistic collisionless shock in laboratory conditions. In laboratory, the scheme of generation of relativistic collisionless shock is that two electron–positron pair plasmas knock each other. However, in laboratory, the appropriate pair plasmas have been not generated. The 10 PW laser pulse maybe generates the pair plasmas that satisfy the formation condition of relativistic collisionless shock due to its ultrahigh intensity and energy. In this paper, we study the positron production by ultraintense laser high Z target interaction using numerical simulations, which consider quantum electrodynamics effect. The simulation results show that the forward positron beam up to 1013/kJ can be generated by 10 PW laser pulse interacting with lead target. The estimation of relativistic collisionless shock formation shows that the positron yield satisfies formation condition and the positron divergence needs to be controlled. Our results indicate that the generation of relativistic collisionless shock by 10 PW laser facilities in laboratory is possible.
Claims that adult attachment differences across cultures are associated with individual differences in individualism and collectivism have seldom been evaluated. This study investigates how individualism and collectivism may relate to adult attachment orientations (anxiety and avoidance) and whether they moderate the attachment–psychological health link. In samples of young adults from Western (Australians, n = 143) and Eastern (Singaporeans, n = 146) locations, individual differences in individualism and collectivism were significantly associated with attachment avoidance but not anxiety. As predicted, attachment anxiety predicted worse negative symptoms more strongly among individuals higher in collectivism across cultures. However, individualism and collectivism did not moderate the relation between avoidance and negative symptoms. Results suggest there are other factors leading to the differential moderating effect of individualism and collectivism in the attachment–wellbeing link across cultures. The current study highlights the need to look beyond cultural stereotypes in clinical practice.
We comment on the proposition “that lower temperatures and especially greater seasonal variation in temperature call for individuals and societies to adopt … a greater degree of self-control” (Van Lange et al., sect. 3, para. 4) for which we cannot find empirical support in a large data set with data-driven analyses. After providing greater nuance in our theoretical review, we suggest that Van Lange et al. revisit their model with an eye toward the social determinants of self-control.
We studied neuroinflammation in individuals with late-life, depression, as a
risk factor for dementia, using [11C]PK11195 positron emission
tomography (PET). Five older participants with major depression and 13
controls underwent PET and multimodal 3T magnetic resonance imaging (MRI),
with blood taken to measure C-reactive protein (CRP). We found significantly
higher CRP levels in those with late-life depression and raised
[11C]PK11195 binding compared with controls in brain regions
associated with depression, including subgenual anterior cingulate cortex,
and significant hippocampal subfield atrophy in cornu ammonis 1 and
subiculum. Our findings suggest neuroinflammation requires further
investigation in late-life depression, both as a possible aetiological
factor and a potential therapeutic target.
A semitransparent CuO film was applied for photoelectrochemical (PEC) cell to produce the record-high photocurrent (6.4 mA/cm2) for nanocrystalline monoclinic CuO photocathode. Large-scale affordable reactive-sputtering method was effectively formed Cu oxide films and sequential thermal processes efficiently controlled the Cu oxide phases with enhanced optical-transparency of Cu oxide films. Structural, physical, optical, and electrical properties of various Cu oxide films (CuO, Cu4O3, and Cu2O) were systematically investigated according to the sputtering condition and thermal processes. It was found that the energy band gap of CuO can be tuned from 1.7 to 1.9 eV by modulating the oxygen flow for reactive sputtering. Mott–Schottky analyses revealed the flat band potential close to the 0.96 V versus reversible hydrogen electrode and energy band edges of Cu oxide films. This state-of-the-art CuO photocathode would provide a strong potential for wide applications of the transparent PEC system of on-site energy generation.
Although the strong coupling of polarization to spontaneous strain in ferroelectrics would impart a flux-closure with severe disclination strains, recent studies have successfully stabilized such a domain via a nano-scaled multi-layer growth. Nonetheless, the detailed distributions of polarizations in three-dimensions (3D) and how the strains inside a flux closure affect the structures of domain walls are still less understood. Here we report a 3D polarization texture of a 4-fold flux closure domain identified in tensile strained ferroelectric PbTiO3/SrTiO3 multilayer films. Ferroelectric displacement analysis based on aberration-corrected scanning transmission electron microscopic imaging reveals highly inhomogeneous strains with strain gradient above 107/m. These giant disclination strains significantly broaden the 90° domain walls, while the flexoelectric coupling at 180° domain wall is less affected. The present observations are helpful for understanding the basics of topological dipole textures and indicate novel applications of ferroelectrics through engineering strains.
Maintaining healthy eating habits in college is challenging. Interventions focused on nutrition education can assist in reversing these trends of poor eating habits among college students. The purpose of the study was to identify factors affecting the dietary habits, food choices and BMI of college females majoring in nutrition (NMs) compared with non-nutrition majors (OMs). A questionnaire-based cross-sectional survey study of dietary behaviour and food frequency of 202 college females was conducted at San Diego State University. Data were analysed by using t tests, χ2 tests and regression analysis in SPSS. NMs exhibited a lower BMI than OMs (P < 0·01); however, BMI values for both groups were within a healthy range. Interestingly, 3 % of NMs had a BMI in the range of overweight or obese; however, prevalence was three times higher for OMs, being 9·2 %. A healthier meal option was the most influential factor in NMs’ meal choices whereas convenience and weight control were influential factors in OMs’ meal choices. Most NMs read nutrition labels and reported that this affects their food choices. NMs exercised longer than OMs in the <120 min/week category. Exercise affected healthy meal conception in NMs only (P < 0·001). Taking dietary supplements influenced healthy meal awareness in OMs only (P < 0·05). University-level nutrition education is strongly associated with healthier eating habits and superior food choices among young adult females. More regular meal patterns, healthier snack choice and adherence to dietary guidelines may contribute to the lower BMI values observed among NMs compared with OMs.
This study evaluated whether primary tumour characteristics are associated with specific features of metastatic lymph nodes in papillary thyroid carcinoma patients.
A retrospective review of 411 patients with pathologically diagnosed cervical lymph node metastasis was conducted.
A metastatic lymph node focus size of at least 2 mm was independently associated with a primary tumour size of at least 1 cm (hazard ratio 1.962) and with male sex (hazard ratio 1.947). A number of at least five lymph node metastases was independently associated with a primary tumour size of at least 1 cm (hazard ratio 2.863), extrathyroidal extension (hazard ratio 1.737) and male sex (hazard ratio 1.689). Extranodal extension was independently associated with a primary tumour size of at least 1 cm (hazard ratio 2.288), extrathyroidal extension (2.201) and male sex (hazard ratio 1.733).
Primary papillary thyroid carcinoma characteristics are related to the pathological features of lymph node metastases.
We determined the prevalence and seasonality of infections by Fasciola of goats and bovine species (cattle and water buffalo) in Hubei and Anhui provinces of China. Faecal samples were collected at 2- to 3-month intervals from 200 goats in Hubei province and from 152 bovine species in Anhui province. All faecal samples were examined for the presence of parasites. We determined the nucleotide sequences of the first and second internal transcribed spacers (ITS-1 and ITS-2) of the nuclear ribosomal DNA (rDNA) of 39 Fasciola worms from Anhui province. The prevalence of Fasciola infection in goats ranged between 3.5 and 37.0%, with mean eggs per gram (EPG) ranging between 29.0 and 166.0. Prevalence and EPG exhibited downward trends over time with significant differences. The prevalence of Fasciola infection in cattle ranged between 13.3 and 46.2% (mean EPG, 36.4–100.0), and that of water buffalo ranged between 10.3 and 35.4% (mean EPG, 25.0–89.6), with a higher prevalence of infection and EPG from June to October compared with December to March. Analysis of ITS-1 and ITS-2 sequences revealed that F. hepatica and F. gigantica were present in all bovine species of Anhui province and that F. gigantica mainly infected water buffalo. This is the first demonstration of Fasciola infection in Hubei province and detection of F. hepatica and F. gigantica in Anhui province. The present study of Hubei province shows that mass treatment of livestock with closantel sodium injections in April and August/September controlled Fasciola infection effectively.