Adjunctive mood stabilizer treatment for hospitalized schizophrenia patients: Asia psychotropic prescripton study (2001-2008)

Recent studies indicate relatively high international rates of adjunctive psychotropic medication, including mood stabilizers, for patients with schizophrenia. Since such treatments are little studied in Asia, we examined the frequency of mood-stabilizer use and its clinical correlates among hospitalized Asian patients diagnosed with schizophrenia in 2001-2008. We evaluated usage rates of mood stabilizers with antipsychotic drugs, and associated factors, for in-patients diagnosed with DSM-IV schizophrenia in 2001, 2004 and 2008 in nine Asian regions: China, Hong Kong, India, Korea, Japan, Malaysia, Taiwan, Thailand, and Singapore. Overall, mood stabilizers were given to 20.4% (n=1377/6761) of hospitalized schizophrenia patients, with increased usage over time. Mood-stabilizer use was significantly and independently associated in multivariate logistic modeling with: aggressive behaviour, disorganized speech, year sampled (2008 vs. earlier), multiple hospitalizations, less negative symptoms, younger age, with regional variation (Japan, Hong Kong, Singapore>Taiwan or China). Co-prescription of adjunctive mood stabilizers with antipsychotics for hospitalized Asian schizophrenia patients increased over the past decade, and was associated with specific clinical characteristics. This practice parallels findings in other countries and illustrates ongoing tension between evidence-based practice vs. individualized, empirical treatment of psychotic disorders.published_or_final_versio

Detection of transgene in early developmental stage by GFP monitoring enhances the efficiency of genetic transformation of pepper

In order to establish a reliable and highly efficient method for genetic transformation of pepper, a monitoring system featuring GFP (green fluorescent protein) as a report marker was applied to Agrobacterium-mediated transformation. A callus-induced transformation (CIT) system was used to transform the GFP gene. GFP expression was observed in all tissues of T0, T1 and T2 peppers, constituting the first instance in which the whole pepper plant has exhibited GFP fluorescence. A total of 38 T0 peppers were obtained from 4,200 explants. The transformation rate ranged from 0.47 to 1.83% depending on the genotype, which was higher than that obtained by CIT without the GFP monitoring system. This technique could enhance selection power by monitoring GFP expression at the early stage of callus in vitro. The detection of GFP expression in the callus led to successful identification of the shoot that contained the transgene. Thus, this technique saved lots of time and money for conducting the genetic transformation process of pepper. In addition, a co-transformation technique was applied to the target transgene, CaCS (encoding capsaicinoid synthetase of Capsicum) along with GFP. Paprika varieties were transformed by the CaCS::GFP construct, and GFP expression in callus tissues of paprika was monitored to select the right transformant

Identification of QTL genes for BMD variation using both linkage and gene-based association approaches

Low bone mineral density (BMD) is a risk factor for osteoporotic fracture with a high heritability. Previous large scale linkage study in Northern Chinese has identified four significant quantitative trait loci (QTL) for BMD variation on chromosome 2q24, 5q21, 7p21 and 13q21. We performed a replication study of these four QTL in 1,459 Southern Chinese from 306 pedigrees. Successful replication was observed on chromosome 5q21 for femoral neck BMD with a LOD score of 1.38 (nominal p value = 0.006). We have previously identified this locus in a genome scan meta-analysis of BMD variation in a white population. Subsequent QTL-wide gene-based association analysis in 800 subjects with extreme BMD identified CAST and ERAP1 as novel BMD candidate genes (empirical p value of 0.032 and 0.014, respectively). The associations were independently replicated in a Northern European population (empirical p value of 0.01 and 0.004 for CAST and ERAP1, respectively). These findings provide further evidence that 5q21 is a BMD QTL, and CAST and ERAP1 may be associated with femoral neck BMD variation

Obesity in total hip arthroplasty—does it really matter?: A meta-analysis

Discussion persists as to whether obesity negatively influences the outcome of hip arthroplasty. We performed a meta-analysis with the primary research question of whether obesity has a negative effect on short- and long-term outcome of total hip arthroplasty. We searched the literature and included studies comparing the outcome of hip arthroplasty in different weight groups. The methodology of the studies included was scored according to the Cochrane guidelines. We extracted and pooled the data. For continuous data, we calculated a weighted mean difference and for dichotomous variables we calculated a weighted odds ratio (OR). Heterogeneity was calculated using I(2) statistics. 15 studies were eligible for data extraction. In obese patients, dislocation of the hip (OR = 0.54, 95% CI: 0.38-0.75) (10 studies, n = 8,634), aseptic loosening (OR = 0.64, CI: 0.43-0.96) (6 studies, n = 5,137), infection (OR = 0.3, CI: 0.19-0.49) (10 studies, n = 7,500), and venous thromboembolism (OR = 0.56, CI: 0.32-0.98) (7 studies, n = 3,716) occurred more often. Concerning septic loosening and intraoperative fractures, no statistically significant differences were found, possibly due to low power. Subjective outcome measurements did not allow pooling because of high heterogeneity (I(2) = 68%). Obesity appears to have a negative influence on the outcome of total hip replacemen

CD36-mediated activation of endothelial cell apoptosis by an N-terminal recombinant fragment of thrombospondin-2 inhibits breast cancer growth and metastasis in vivo

Thus far the clinical benefits seen in breast cancer patients treated with drugs targeting the vascular endothelial growth factor (VEGF) pathway are only modest. Consequently, additional antiangiogenic approaches for treatment of breast cancer need to be investigated. Thrombospondin-2 (TSP-2) has been shown to inhibit tumor growth and angiogenesis with a greater potency than the related molecule TSP-1. The systemic effects of TSP-2 on tumor metastasis and the underlying molecular mechanisms of the antiangiogenic activity of TSP-2 have remained poorly understood. We generated a recombinant fusion protein consisting of the N-terminal region of TSP-2 and the IgG-Fc1 fragment (N-TSP2-Fc) and could demonstrate that the antiangiogenic activity of N-TSP2-Fc is dependent on the CD36 receptor. We found that N-TSP2-Fc inhibited VEGF-induced tube formation of human dermal microvascular endothelial cells (HDMEC) on matrigel in vitro and that concurrent incubation of anti-CD36 antibody with N-TSP2-Fc resulted in tube formation that was comparable to untreated control. N-TSP2-Fc potently induced apoptosis of HDMEC in vitro in a CD36-dependent manner. Moreover, we could demonstrate a CD36 receptor-mediated loss of mitochondrial membrane potential and activation of caspase-3 in HDMEC in vitro. Daily intraperitoneal injections of N-TSP2-Fc resulted in a significant inhibition of the growth of human MDA-MB-435 and MDA-MB-231 tumor cells grown in the mammary gland of immunodeficient nude mice and in reduced tumor vascularization. Finally, increased serum concentrations of N-TSP2-Fc significantly inhibited regional metastasis to lymph nodes and distant metastasis to lung as shown by quantitative real-time alu PCR. These results identify N-TSP2-Fc as a potent systemic inhibitor of tumor metastasis and provide strong evidence for an important role of the CD36 receptor in mediating the antiangiogenic activity of TSP-2

Molecular Mechanisms of Fiber Differential Development between G. barbadense and G. hirsutum Revealed by Genetical Genomics

Cotton fiber qualities including length, strength and fineness are known to be controlled by genes affecting cell elongation and secondary cell wall (SCW) biosynthesis, but the molecular mechanisms that govern development of fiber traits are largely unknown. Here, we evaluated an interspecific backcrossed population from G. barbadense cv. Hai7124 and G. hirsutum acc. TM-1 for fiber characteristics in four-year environments under field conditions, and detected 12 quantitative trait loci (QTL) and QTL-by-environment interactions by multi-QTL joint analysis. Further analysis of fiber growth and gene expression between TM-1 and Hai7124 showed greater differences at 10 and 25 days post-anthesis (DPA). In this two period important for fiber performances, we integrated genome-wide expression profiling with linkage analysis using the same genetic materials and identified in total 916 expression QTL (eQTL) significantly (P<0.05) affecting the expression of 394 differential genes. Many positional cis-/trans-acting eQTL and eQTL hotspots were detected across the genome. By comparative mapping of eQTL and fiber QTL, a dataset of candidate genes affecting fiber qualities was generated. Real-time quantitative RT-PCR (qRT-PCR) analysis confirmed the major differential genes regulating fiber cell elongation or SCW synthesis. These data collectively support molecular mechanism for G. hirsutum and G. barbadense through differential gene regulation causing difference of fiber qualities. The down-regulated expression of abscisic acid (ABA) and ethylene signaling pathway genes and high-level and long-term expression of positive regulators including auxin and cell wall enzyme genes for fiber cell elongation at the fiber developmental transition stage may account for superior fiber qualities

Forty years literature review of primary lung lymphoma

There are several unresolved issues through out the literature regarding the entity of primary lung lymphoma. Extensive literature review of this uncommon pathology is carried out

Polyploidization Altered Gene Functions in Cotton (Gossypium spp.)

Cotton (Gossypium spp.) is an important crop plant that is widely grown to produce both natural textile fibers and cottonseed oil. Cotton fibers, the economically more important product of the cotton plant, are seed trichomes derived from individual cells of the epidermal layer of the seed coat. It has been known for a long time that large numbers of genes determine the development of cotton fiber, and more recently it has been determined that these genes are distributed across At and Dt subgenomes of tetraploid AD cottons. In the present study, the organization and evolution of the fiber development genes were investigated through the construction of an integrated genetic and physical map of fiber development genes whose functions have been verified and confirmed. A total of 535 cotton fiber development genes, including 103 fiber transcription factors, 259 fiber development genes, and 173 SSR-contained fiber ESTs, were analyzed at the subgenome level. A total of 499 fiber related contigs were selected and assembled. Together these contigs covered about 151 Mb in physical length, or about 6.7% of the tetraploid cotton genome. Among the 499 contigs, 397 were anchored onto individual chromosomes. Results from our studies on the distribution patterns of the fiber development genes and transcription factors between the At and Dt subgenomes showed that more transcription factors were from Dt subgenome than At, whereas more fiber development genes were from At subgenome than Dt. Combining our mapping results with previous reports that more fiber QTLs were mapped in Dt subgenome than At subgenome, the results suggested a new functional hypothesis for tetraploid cotton. After the merging of the two diploid Gossypium genomes, the At subgenome has provided most of the genes for fiber development, because it continues to function similar to its fiber producing diploid A genome ancestor. On the other hand, the Dt subgenome, with its non-fiber producing D genome ancestor, provides more transcription factors that regulate the expression of the fiber genes in the At subgenome. This hypothesis would explain previously published mapping results. At the same time, this integrated map of fiber development genes would provide a framework to clone individual full-length fiber genes, to elucidate the physiological mechanisms of the fiber differentiation, elongation, and maturation, and to systematically study the functional network of these genes that interact during the process of fiber development in the tetraploid cottons

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. Copyright (C) 2021 World Health Organization; licensee Elsevier

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.