Lipid-modifying agents and risk of all-cause, natural and suicide mortality in schizophrenia: nationwide cohort study.

BACKGROUND: Individuals with schizophrenia face high mortality risks. The effects of lipid-modifying agents on this risk remain understudied. AIM: This study was conducted to investigate the effects of lipid-modifying agents on mortality risk in people with schizophrenia. METHOD: This nationwide cohort study collected the data of people with schizophrenia from Taiwan's National Health Insurance Research Database for the period between 1 January 2001 and 31 December 2019. Multivariable Cox proportional hazards regression with a time-dependent model was used to estimate the hazard ratio for mortality associated with each lipid-modifying agent. RESULTS: This study included 110 300 people with schizophrenia. Of them, 22 528 died (19 754 from natural causes and 1606 from suicide) during the study period, as confirmed using data from Taiwan's national mortality database. The use of lipid-modifying agents was associated with reduced risks of all-cause (adjusted hazard ratio [aHR]:0.37; P < 0.001) and natural (aHR:0.37; P < 0.001) mortality during a 5-year period. Among the lipid-modifying agents, statins and fibrates were associated with reduced risks of all-cause mortality (aHRs:0.37 and 0.39, respectively; P < 0.001 for both) and natural mortality (aHRs: 0.37 and 0.42, respectively; P < 0.001 for both). Notably, although our univariate analysis indicated an association between the use of lipid-modifying agents and a reduced risk of suicide mortality, the multivariate analysis revealed no significant association. CONCLUSIONS: Lipid-modifying agents, particularly statins and fibrates, reduce the risk of mortality in people with schizophrenia. Appropriate use of lipid-modifying agents may bridge the mortality gap between these individuals and the general population.

Comparative efficacy of brolucizumab, half-dose photodynamic therapy, and aflibercept in managing chronic central serous chorioretinopathy.

PURPOSE: To compare the efficacy of brolucizumab, half-dose PDT, and aflibercept in treating chronic central serous chorioretinopathy (CSC). METHODS: A retrospective cohort study with chronic CSC patients who underwent intravitreal injection of one shot of brolucizumab or aflibercept in the first 3 months, followed by pro re nata regimens or a single session of half-dose PDT, was retrospectively reviewed. The primary outcome measure was the proportion of eyes that achieved complete absorption of retinal fluid without requiring any rescue treatment. Secondary outcomes included changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and central choroidal thickness (CCT). RESULTS: A total of 54 consecutive patients were included in this study with 18 patients in each group. At months 1 and 2, the brolucizumab group exhibited the highest rate of complete retinal fluid resolution (61% and 77%), followed by the half-dose PDT group (56% and 72%), and lowest in the aflibercept group (28% and 33%), with statistically significant differences noted at month 2 (P = 0.012). The brolucizumab group also demonstrated the most significant reduction in CCT at months 1 and 2 among the three groups (P = 0.007 and 0.001). Recurrence of retinal fluid in the brolucizumab groups was predominantly observed at month 3. Conversely, the half-dose PDT group exhibited the most favorable anatomical results starting from month 3. Notably, mild vitritis was observed in one case from the brolucizumab group. CONCLUSIONS: Single injection of brolucizumab demonstrates trends of faster regression of persistent residual retinal fluid, greater CCT and CRT decline, and matched BCVA compared to half-dose PDT in the short term.

Antipsychotic medications and severe sepsis in schizophrenia: A nested case-control study.

BACKGROUND: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case-control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies. METHODS: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000-2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic-severe sepsis associations. RESULTS: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin-angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk. CONCLUSION: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients.

Mood stabilizers and risk of all-cause, natural, and suicide mortality in bipolar disorder: A nationwide cohort study.

OBJECTIVES: People with bipolar disorder have an elevated risk of mortality. This study evaluated associations between the use of mood stabilizers and the risks of all-cause mortality, suicide, and natural mortality in a national cohort of people with bipolar disorder. METHODS: In this nationwide cohort study, we used data from January 1, 2000, to December 31, 2016, collected from Taiwan's National Health Insurance Research Database and included 25,787 patients with bipolar disorder. Of these patients, 4000 died during the study period (including 760 and 2947 from suicide and natural causes, respectively). Each standardized mortality ratio (SMR) was calculated as the ratio of observed mortality in the bipolar cohort to the number of expected deaths in the general population. Multivariable Cox proportional hazards regression with a time-dependent model was performed to estimate the hazard ratio (HR) of each mood stabilizer with each mortality outcome. RESULTS: The SMRs of all-cause mortality, suicide, and natural mortality in the bipolar disorder cohort were 5.26, 26.02, and 4.68, respectively. The use of mood stabilizers was significantly associated with decreased risks of all-cause mortality (adjusted HR [aHR] = 0.58, p< 0.001), suicide (aHR = 0.60, p < 0.001), and natural mortality (aHR = 0.55, p < 0.001) within a 5-year follow-up period after index admission. Among the individual mood stabilizers, lithium was associated with the lowest risks of all-cause mortality (aHR = 0.38, p < 0.001), suicide (aHR = 0.39, p < 0.001), and natural mortality (aHR = 0.37, p < 0.001). CONCLUSION: In addition to having protective effects against suicide and all-cause mortality, mood stabilizers also exert a substantial protective effect against natural mortality, with lithium associated with the lowest risk of mortality.

Incidence of and risk factors for alcohol dependence in bipolar disorder: A population-based cohort and nested case-control study.

OBJECTIVES: Although alcohol dependence is highly prevalent in patients with bipolar disorder, the causal relationship is not yet well-established. This study estimated the incidence of alcohol dependence in a nationwide bipolar disorder cohort and examined risk factors for alcohol dependence. METHODS: Patients aged 15-65 years with consistent bipolar disorder who had their first psychiatric admission between 1999 and 2012 (n = 21,791) were enrolled from the National Health Insurance Research Database in Taiwan. We calculated the adjusted incidence rate ratio of alcohol dependence in the bipolar cohort relative to the general population after stratification by age and sex. In the nested case-control study, we included patients with incident alcohol dependence as cases and four age- and sex-matched controls for each case to analyze health care utilization, comorbidities and concomitant medications between them. RESULTS: We identified 1261 patients with bipolar disorder with incident alcohol dependence. Relative to the general population, the adjusted incidence rate ratio of alcohol dependence was 9.20 in the bipolar cohort. All adjusted incidence rate ratios were high across all age subgroups. Cases had higher psychiatric and nonpsychiatric health care utilization than did controls. Multivariate analysis revealed that cases tended to have cardiovascular disease, diabetes mellitus, chronic hepatic disease, pneumonia and delirium before alcohol dependence diagnosis. Cases had higher psychiatric comorbidities, namely drug-induced mental disorders, anxiety disorder, personality disorder, adjustment disorder and sleep disorder. CONCLUSION: The bipolar cohort had a higher incidence of alcohol dependence. We identified specific groups with a high risk of alcohol dependence. Additional strategies for early detection, treatment and intervention for alcohol dependence should be developed.

Viral dynamics of SARS-CoV-2 Omicron infections in a previously low COVID-19 prevalence region: Effects of vaccination status, antiviral agents, and age.

BACKGROUND: In Taiwan, the prevalence of COVID-19 was low before April 2022. The low SARS-CoV-2 seroprevalence in the population of Taiwan provides an opportunity for comparison with fewer confounding factors than other populations globally. Cycle threshold (Ct) value is an easily accessible method for modeling SARS-CoV-2 dynamics. In this study, we used clinical samples collected from hospitalized patients to explore the Ct value dynamics of the Omicron variant infection. METHODS: From Jan 2022 to May 2022, we retrospectively included hospitalized patients tested positive by nasopharyngeal SARS-CoV-2 PCR. We categorized the test-positive subjects into different groups according to age, vaccination status, and use of antiviral agents. To investigate the nonlinear relationship between symptom onset days and Ct value, a fractional polynomial model was applied to draw a regression line. RESULTS: We collected 1718 SARS-CoV-2 viral samples from 812 individuals. The Ct values of unvaccinated individuals were lower than those of vaccinated persons from Day 4 to Day 10 after symptom onset. The Ct value increased more rapidly in those individuals with antiviral drug treatment from Day 2 to Day 7. In elderly individuals, the Ct values increased slowly from Day 5 to Day 10, and the increasing trend was unique compared with that in children and adults. CONCLUSION: Our study demonstrated the primary viral infection dynamics of the Omicron variant in hospitalized patients. Vaccination significantly affected viral dynamics, and antiviral agents modified viral dynamics irrespective of vaccination status. In elderly individuals, viral clearance is slower than that in adults and children.

Heparan sulfate is essential for thymus growth.

Thymus organogenesis and T cell development are coordinated by various soluble and cell-bound molecules. Heparan sulfate (HS) proteoglycans can interact with and immobilize many soluble mediators, creating fields or gradients of secreted ligands. While the role of HS in the development of many organs has been studied extensively, little is known about its function in the thymus. Here, we examined the distribution of HS in the thymus and the effect of its absence on thymus organogenesis and T cell development. We found that HS was expressed most abundantly on the thymic fibroblasts and at lower levels on endothelial, epithelial, and hematopoietic cells. To study the function of HS in the thymus, we eliminated most of HS in this organ by genetically disrupting the glycosyltransferase Ext1 that is essential for its synthesis. The absence of HS greatly reduced the size of the thymus in fetal thymic organ cultures and in vivo, in mice, and decreased the production of T cells. However, no specific blocks in T cell development were observed. Wild-type thymic fibroblasts were able to physically bind the homeostatic chemokines CCL19, CCL21, and CXCL12 ex vivo. However, this binding was abolished upon HS degradation, disrupting the CCL19/CCL21 chemokine gradients and causing impaired migration of dendritic cells in thymic slices. Thus, our results show that HS plays an essential role in the development and growth of the thymus and in regulating interstitial cell migration.

Ring-Opening Polymerization of ε-Caprolactone by Using Aluminum Complexes Bearing Aryl Thioether Phenolates: Labile Thioether Chelation.

In this study, aluminum complexes bearing ferrocene-based and arylthiomethylphenolate ligands were synthesized, and their catalytic activity for ε-caprolactone (CL) polymerization was investigated. The catalytic activity of the reduced form of Al complexes was higher than that of the oxidized form. The CL polymerization rate of the reduced form fcO2AlMe (75 min, conversion = 100%) was higher than that of the oxidized form fcoxO2AlMe (4320 min, conversion = 45%), and the CL polymerization rate of fc(OAlMe2)2 (40 min, conversion = 100%) was higher than that of fcox(OAlMe2)2 (60 min, conversion = 97%). Electron deficiency substituents on phenolate decreased the catalytic activity of Al complexes bearing arylthiomethylphenolate ligands. Density functional theory calculations revealed that thioether coordination stabilized the transition state (TS1) and that the oxidized form fcox(OAlMe2)2 exhibited weaker thioether coordination and higher activation energy in TS1 compared with those of the reduced form fcO2AlMe. In addition, our study determined that the thioether group is a suitable chelating group for Al catalysts in CL polymerization due to its labile nature.

Orexin-a elevation in antipsychotic-treated compared to drug-free patients with schizophrenia: A medication effect independent of metabolic syndrome.

BACKGROUND/PURPOSE: Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-free group for comparison, or related to drug-induced metabolic abnormalities. METHODS: Blood orexin-A levels and metabolic profiles were compared between 37 drug-free, 45 aripiprazole-treated, and 156 clozapine-treated patients with schizophrenia. The association between orexin-A and metabolic outcomes were examined. We explored the effects of APDs treatment and metabolic status on orexin-A levels by linear regression. RESULTS: Patients under APDs treatment had increased orexin-A levels compared to drug-free patients, with aripiprazole-treated group having higher orexin-A levels than clozapine-treated group. Higher orexin-A levels reduced the risks of metabolic syndrome (MS) and type 2 diabetes mellitus, indicating a relationship between orexin-A levels and metabolic problems. After adjusting the effect from metabolic problems, we found APD treatment is still associated with orexin-A regulation, with aripiprazole more significantly than clozapine. CONCLUSION: With the inclusion of drug-free patients rather than healthy controls for comparison, we demonstrated that orexin-A is upregulated following APD treatment even after we controlled the potential effect from MS, suggesting an independent effect of APDs on orexin-A levels. Furthermore, the effect differed between APDs with dissimilar obesogenicity, i.e. less obesogenicity likely associated with higher orexin-A levels. Future prospective studies exploring the causal relationship between APDs treatment and orexin-A elevation as well as the underlying mechanisms are warranted.

Enhancement of the Modulation Response of Quantum-Dot-Based Down-Converted Light through Surface Plasmon Coupling.

In this paper, we first elaborate on the effects of surface plasmon (SP) coupling on the modulation responses of the emission of a light-emitting diode (LED) and its down-converted lights through colloidal quantum dots (QDs). The results of our past efforts for this subject are briefly discussed. The discussions lay the foundation for the presentation of the new experimental data of such down-converted lights in this paper. In particular, the enhancement of the modulation bandwidth (MB) of a QD-based converted light through SP coupling is demonstrated. By linking green-emitting QDs (GQDs) and/or red-emitting QDs (RQDs) with synthesized Ag nano-plates via surface modifications and placing them on a blue-emitting LED, the MBs of the converted green and red emissions are significantly increased through the induced SP coupling of the Ag nano-plates. When both GQD and RQD exist and are closely spaced in a sample, the energy transfer processes of emission-reabsorption and Förster resonance energy transfer from GQD into RQD occur, leading to the increase (decrease) in the MB of green (red) light. With SP coupling, the MB of a mixed light is significantly enhanced.

Increased risk of Parkinson's disease among patients with age-related macular degeneration.

BACKGROUND: This study aimed to investigate the risk of Parkinson's disease (PD) among patients with age-related macular degeneration (AMD) and its association with confounding comorbidities. METHODS: A population-based retrospective cohort study was conducted using Longitudinal Health Insurance Database 2000 (LHID2000). We established AMD and non-AMD cohorts from January 1, 2000 to December 31, 2012 to determine the diagnosis of PD. A total of 20,848 patients were enrolled, with 10,424 AMD patients and 10,424 controls matched for age, sex, and index year at a 1:1 ratio. The follow-up period was from the index date of AMD diagnosis to the diagnosis of PD, death, withdrawal from the insurance program, or end of 2013. Multivariable Cox regression analysis was performed to examine the hazard ratio (HR) and 95% confidence interval (CI) for the risk of PD between the AMD and non-AMD cohorts. RESULT: After adjusting for potential confounders, there was a higher risk of developing PD in the AMD cohort than in the non-AMD cohort (adjusted HR = 1.35, 95% CI = 1.16-1.58). A significant association could be observed in both female (aHR = 1.42, 95% CI = 1.13-1.80) and male (aHR = 1.28, 95% CI = 1.05-1.57) patients, aged more than 60 years (60-69: aHR = 1.51, 95% CI = 1.09-2.09, 70-79: aHR = 1.30, 95% CI = 1.05-1.60; 80-100: aHR = 1.40, 95% CI = 1.01-1.95), and with more than one comorbidity (aHR = 1.40, 95% CI = 1.20-1.64). A significant association between increased risk of PD and AMD was observed among patients with comorbidities of osteoporosis (aHR = 1.68, 95% CI = 1.22-2.33), diabetes (aHR = 1.41, 95% CI = 1.12-1.78) and hypertension (aHR = 1.36, 95% CI = 1.15-1.62) and medications of statin (aHR = 1.42, 95% CI = 1.19-1.69) and calcium channel blocker (CCB) (aHR = 1.32, 95% CI = 1.11-1.58). The cumulative incidence of PD was significantly higher over the 12-year follow-up period in AMD cohort (log-rank test, p < 0.001). CONCLUSIONS: Patients with AMD may exhibit a higher risk of PD than those without AMD.

Efficacy and Safety of Ablative Resurfacing With A High-Energy 1,064 Nd-YAG Picosecond-domain Laser for the Treatment of Facial Acne Scars in Asians.

OBJECTIVES: There have been few studies regarding the use of a picosecond-domain laser for acne scars in Asians. This prospective study evaluated the efficacy and safety of a high-energy 1,064 nm Nd:YAG picosecond-domain laser for ablation and resurfacing of facial acne scars in Asians. METHODS: Subjects were treated with a 1,064 nm picosecond laser (8 mm spot, 0.7-1.0 J/cm2 , 5 Hz) every 4 weeks for three sessions. Two blinded dermatologists evaluated the pre- and 3-month post-treatment images with a 10-point improvement scale. Subject pain, global improvement, and satisfaction were also assessed. The Facial Acne Scar Quality of Life (FASQoL) questionnaire was used to evaluate the subjects' quality of life. RESULTS: Twenty subjects aged 18-50 years with Fitzpatrick skin type III-V were enrolled. The median dermatologist-rated improvement score was 3 out of 10. Subjects were satisfied to very satisfied with global improvement. Subjects' quality of life significantly improved with a median FASQoL score of 10 after treatment compared with 21 before treatment (P < 0.001). Adverse effects were limited to erythema, pain, and edema without postinflammatory hyperpigmentation. CONCLUSIONS: The 1,064 nm picosecond-domain laser with ablative resurfacing parameters is safe and effective for the treatment of acne scars in Asians. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Color conversion efficiency enhancement of colloidal quantum dot through its linkage with synthesized metal nanoparticle on a blue light-emitting diode.

Four surface-modified and, hence, positively charged metal nanoparticles (NPs) of different localized surface plasmon (LSP) resonance wavelengths are synthesized for linking with negatively charged, red-emitting colloidal CdZnSeS/ZnS quantum dots (QDs) on the top surface of a blue-emitting InGaN/GaN quantum well (QW) light-emitting diode (LED) through electro-static force. The metal NP-QD linkage leads to a short distance between them for producing their strong surface plasmon (SP) coupling, such that QD absorption and emission can be enhanced. Meanwhile, the small p-GaN thickness in the LED results in strong SP coupling between the LSP resonance of metal NP and the QWs of the LED, leading to enhanced QW emission and, hence, stronger QD excitation. All those factors together result in the increase of the color conversion efficiency of the QD.

Orexin-A Levels in Relation to the Risk of Metabolic Syndrome in Patients with Schizophrenia Taking Antipsychotics.

Background: The role of orexin-A in regulating metabolic homeostasis has been recognized, but its association with antipsychotic-induced metabolic abnormalities remains unclear. We investigated the association between orexin-A levels and metabolic syndrome in patients with schizophrenia treated with clozapine or less obesogenic antipsychotics compared with nonpsychiatric controls. Methods: Plasma orexin-A levels and metabolic parameters were determined in 159 patients with schizophrenia: 109 taking clozapine; 50 taking aripiprazole, amisulpride, ziprasidone, or haloperidol; and 60 nonpsychiatric controls. Results: Orexin-A levels were significantly higher in the group taking less obesogenic antipsychotics, followed by the clozapine group and the controls (F=104.6, P<.01). Higher orexin-A levels were correlated with better metabolic profiles in the patient groups but not in the controls. Regression analyses revealed that the patients with higher orexin-A levels had significantly lower risk of metabolic syndrome (adjusted odds ratio [OR]=0.04, 95% CI: 0.01-0.38 for the 2nd tertile; OR=0.04, 95% CI: 0.01-0.36 for the 3rd tertile, compared with the first tertile), after adjustment for age, sex, smoking history, types of antipsychotics (clozapine vs less obesogenic antipsychotics), duration of antipsychotic treatment, and disease severity. Conclusions: Our results revealed that the orexin-A level was upregulated in patients with schizophrenia treated with antipsychotics, especially for the group taking less obesogenic antipsychotics. Furthermore, higher orexin-A levels were independently associated with better metabolic profiles. These observations suggest that an upregulation of orexin-A has a protective effect against the development of metabolic abnormalities in patients with schizophrenia receiving antipsychotic treatment.

Outcomes of necrotic immature open-apex central incisors treated by MTA apexification using poly(ε-caprolactone) fiber mesh as an apical barrier.

BACKGROUND/PURPOSE: Although unset mineral trioxide aggregate (MTA) has some cytotoxicity, MTA is still a biocompatible material suitable for doing apexification. This study assessed the outcomes for 8 necrotic immature open-apex permanent maxillary central incisors treated by MTA apexification using poly(ε-caprolactone) fiber mesh (PCL-FM) as an apical barrier (so-called PCL-FM/MTA apexification) to prevent extrusion of MTA materials into the periapical tissues of open-apex teeth. METHODS: Eight necrotic immature open-apex permanent maxillary central incisors with the open apices measuring 2.5 mm-3.5 mm in diameter in 8 patients (6 boys and 2 girls; age range, 8-10 years) were first cleaned using ultrasonic activated irrigation with 2.5% sodium hypochlorite solution and then treated by PCL-FM/MTA apexification procedure. RESULTS: All the 8 permanent maxillary central incisors showed successful outcomes after PCL-FM/MTA apexification procedure. The mean duration for apical hard tissue barrier formation of the 8 incisors was 6.8 ± 0.5 weeks (range 6-7 weeks). The mean increased root length was 1.8 ± 0.7 mm (range 1-3 mm) at 7 weeks and 3.1 ± 0.6 mm (range 2-4 mm) at 3 months. The mean increased dentinal wall thickness at the most apical portion of the root was 1.3 ± 0.5 mm (range 1-2 mm) at 7 weeks and 2.4 ± 0.6 mm (range 1.5-3 mm) at 3 months. None of the teeth treated by PCL-FM/MTA apexification showed tooth discoloration after a follow-up period of 3 months. CONCLUSION: PCL-FM/MTA apexification is an excellent technique for treatment of necrotic immature open-apex permanent maxillary central incisors.

Inositol polyphosphate multikinase is a coactivator for serum response factor-dependent induction of immediate early genes.

Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic protein. It displays both inositol phosphate kinase and phosphatidylinositol kinase catalytic activities. Noncatalytically, IPMK stabilizes the mammalian target of rapamycin complex 1 and acts as a transcriptional coactivator for CREB-binding protein/E1A binding protein p300 and tumor suppressor protein p53. Serum response factor (SRF) is a major transcription factor for a wide range of immediate early genes. We report that IPMK, in a noncatalytic role, is a transcriptional coactivator for SRF mediating the transcription of immediate early genes. Stimulation by serum of many immediate early genes is greatly reduced by IPMK deletion. IPMK stimulates expression of these genes, an influence also displayed by catalytically inactive IPMK. IPMK acts by binding directly to SRF and thereby enhancing interactions of SRF with the serum response element of diverse genes.

Experimentally-implemented genetic algorithm (Exp-GA): toward fully optimal photovoltaics.

The geometry and dimension design is the most critical part for the success in nano-photonic devices. The choices of the geometrical parameters dramatically affect the device performance. Most of the time, simulation is conducted to locate the suitable geometry, but in many cases simulation can be ineffective. The most pronounced examples are large-area randomized patterns for solar cells, light emitting diode (LED), and thermophtovoltaics (TPV). The large random pattern is nearly impossible to calculate and optimize due to the extended CPU runtime and the memory limitation. Other scenarios that numerical simulations become ineffective include three-dimensional complex structures with anisotropic dielectric response. This leads to extended simulation time especially for the repeated runs during its geometry optimization. In this paper, we show that by incorporating genetic algorithm (GA) into real-world experiments, shortened trial-and-error time can be achieved. More importantly, this scheme can be used for many photonic design problems that are unsuitable for simulation-based optimizations. Moreover, the experimentally implemented genetic algorithm (Exp-GA) has the additional advantage that the resultant objective value is a real one rather than a theoretical one. This prevents the gaps between the modeling and the fabrication due to the process variation or inaccurate numerical models. Using TPV emitters as an example, 22% enhancement in the mean objective value is achieved.

The Relationships of Obesity-Related Genetic Variants With Metabolic Profiles and Response to Metformin in Clozapine-Treated Patients With Schizophrenia.

Obesity-related genetic variants, including TMEM18 (rs6548238), SH2B1 (rs7498665), and GNPDA2 (rs10938397), have been shown to be associated with obesity in the general population. Our study aimed to test whether these genetic variants are associated with metabolic profiles and metformin treatment response in clozapine-treated schizophrenic patients. We recruited 107 clozapine-treated patients who were genotyped and measured their metabolic profiles. Fifty-five subjects, who had at least 1 metabolic abnormality in a range of measures, were subsequently randomized to a 24-week trial of metformin (n = 28) or placebo (n = 27). We examined the associations between TMEM18, SH2B1, GNPDA2 genetic variants and metabolic profiles at baseline in all patients and metabolic changes in the trial groups. We found a significant association between SH2B1 and blood pressure at baseline in all patients. In the metformin group, TMEM18 minor allele carriers had a greater reduction in insulin levels (P = 0.04). A significantly higher proportion of TMEM18 and GNPDA2 minor allele carriers (60% and 40%) lost more than 7% of their body weight after metformin treatment as compared with their homozygous counterparts (21.7% and 15.4%, P = 0.02 and 0.004, respectively).There were trends toward favorable metabolic changes in minor allele carrier groups. In the placebo group, no association between genetic variants and changes in metabolic profiles was found. In conclusion, the study results suggest that these genes might be associated with metabolic abnormalities and response to metformin in clozapine-treated patients with schizophrenia.

Transcriptome profiling of genes and pathways associated with arsenic toxicity and tolerance in Arabidopsis.

BACKGROUND: Arsenic (As) is a toxic metalloid found ubiquitously in the environment and widely considered an acute poison and carcinogen. However, the molecular mechanisms of the plant response to As and ensuing tolerance have not been extensively characterized. Here, we report on transcriptional changes with As treatment in two Arabidopsis accessions, Col-0 and Ws-2. RESULTS: The root elongation rate was greater for Col-0 than Ws-2 with As exposure. Accumulation of As was lower in the more tolerant accession Col-0 than in Ws-2. We compared the effect of As exposure on genome-wide gene expression in the two accessions by comparative microarray assay. The genes related to heat response and oxidative stresses were common to both accessions, which indicates conserved As stress-associated responses for the two accessions. Most of the specific response genes encoded heat shock proteins, heat shock factors, ubiquitin and aquaporin transporters. Genes coding for ethylene-signalling components were enriched in As-tolerant Col-0 with As exposure. A tolerance-associated gene candidate encoding Leucine-Rich Repeat receptor-like kinase VIII (LRR-RLK VIII) was selected for functional characterization. Genetic loss-of-function analysis of the LRR-RLK VIII gene revealed altered As sensitivity and the metal accumulation in roots. CONCLUSIONS: Thus, ethylene-related pathways, maintenance of protein structure and LRR-RLK VIII-mediated signalling may be important mechanisms for toxicity and tolerance to As in the species. Here, we provide a comprehensive survey of global transcriptional regulation for As and identify stress- and tolerance-associated genes responding to As.