PCSK9 dysregulates cholesterol homeostasis and triglyceride metabolism in olanzapine-induced hepatic steatosis via both receptor-dependent and receptor-independent pathways.

Schizophrenia, affecting approximately 1% of the global population, is often treated with olanzapine. Despite its efficacy, olanzapine's prolonged use has been associated with an increased risk of cardiovascular diseases and nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanism remains unclear. Proprotein convertase subtilisin kexin type 9 (PCSK9) plays a crucial role in lipid metabolism and is involved in NAFLD pathogenesis via an unknown mechanism. This study aims to investigate the role of PCSK9 in olanzapine-induced NAFLD. C57BL/6J mice and HepG2 and AML12 cell lines were treated with varying concentrations of olanzapine to examine the effects of olanzapine on PCSK9 and lipid metabolism. PCSK9 levels were manipulated using recombinant proteins, plasmids, and small interfering RNAs in vitro, and the effects on hepatic lipid accumulation and gene expression related to lipid metabolism were assessed. Olanzapine treatment significantly increased PCSK9 levels in both animal and cell line models, correlating with elevated lipid accumulation. PCSK9 manipulation demonstrated its central role in mediating hepatic steatosis through both receptor-dependent pathways (impacting NPC1L1) and receptor-independent pathways (affecting lipid synthesis, uptake, and cholesterol biosynthesis). Interestingly, upregulation of SREBP-1c, rather than SREBP-2, was identified as a key driver of PCSK9 increase in olanzapine-induced NAFLD. Our findings establish PCSK9 as a pivotal factor in olanzapine-induced NAFLD, influencing both receptor-related and metabolic pathways. This highlights PCSK9 inhibitors as potential therapeutic agents for managing NAFLD in schizophrenia patients treated with olanzapine.

Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

Sheehan's syndrome (SS) is a rare but well-characterized cause of hypopituitarism. Data on skeletal health is limited and on microarchitecture is lacking in SS patients. PURPOSE: We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. METHODS: Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. RESULTS: The mean age of the patients was 45.5 ± 9.3 years with a lag of 8.3 ± 7.2 years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. CONCLUSION: Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

Lignocellulosic materials valorization in second generation biorefineries: an opportunity to produce fungal biopigments.

Second generation biorefineries play an important role in the production of renewable energy and fuels, utilizing forest and agro-industrial residues and by-products as raw materials. The integration of novel bioproducts, such as: xylitol, ß-carotene, xylooligosaccharides, and biopigments into the biorefinery's portfolio can offer economic benefits in the valorization of lignocellulosic materials, particularly cellulosic and hemicellulosic fractions. Fungal biopigments, known for their additional antioxidant and antimicrobial properties, are appealing to consumers and can have applications in various industrial sectors, including food and pharmaceuticals. The use of lignocellulosic materials as carbon and nutrient sources for the growth medium helps to reduce production costs, increasing the competitiveness of fungal biopigments in the market. In addition, the implementation of biopigment production in biorefineries allows the utilization of underutilized fractions, such as hemicellulose, for value-added bioproducts. This study deals with the potential of fungal biopigments production in second generation biorefineries in order to diversify the produced biomolecules together with energy generation. A comprehensive and critical review of the recent literature on this topic has been conducted, covering the major possible raw materials, general aspects of second generation biorefineries, the fungal biopigments and their potential for incorporation into biorefineries.

Enhancing xylose-fermentation capacity of engineered Saccharomyces cerevisiae by multistep evolutionary engineering in inhibitor-rich lignocellulose hydrolysate.

Major progress in developing Saccharomyces cerevisiae strains that utilize the pentose sugar xylose has been achieved. However, the high inhibitor content of lignocellulose hydrolysates still hinders efficient xylose fermentation, which remains a major obstacle for commercially viable second-generation bioethanol production. Further improvement of xylose utilization in inhibitor-rich lignocellulose hydrolysates remains highly challenging. In this work, we have developed a robust industrial S. cerevisiae strain able to efficiently ferment xylose in concentrated undetoxified lignocellulose hydrolysates. This was accomplished with novel multistep evolutionary engineering. First, a tetraploid strain was generated and evolved in xylose-enriched pretreated spruce biomass. The best evolved strain was sporulated to obtain a genetically diverse diploid population. The diploid strains were then screened in industrially relevant conditions. The best performing strain, MDS130, showed superior fermentation performance in three different lignocellulose hydrolysates. In concentrated corncob hydrolysate, with initial cell density of 1 g DW/l, at 35°C, MDS130 completely coconsumed glucose and xylose, producing ± 7% v/v ethanol with a yield of 91% of the maximum theoretical value and an overall productivity of 1.22 g/l/h. MDS130 has been developed from previous industrial yeast strains without applying external mutagenesis, minimizing the risk of negative side-effects on other commercially important properties and maximizing its potential for industrial application.

Zero-Emission Cement Plants with Advanced Amine-Based CO2 Capture.

Decarbonization of the cement sector is essentially required to achieve carbon neutrality to combat climate change. Amine-based CO2 capture is a leading and practical technology to deeply remove CO2 from the cement industry, owing to its high retrofittability to existing cement plants and extensive engineering experience in industrial flue gas decarbonization. While research efforts have been made to achieve low-carbon cement with 90% CO2 removal, a net-zero-emission cement plant that will be required for a carbon neutrality society has not yet been investigated. The present study proposed an advanced amine-based CO2 capture system integrated with a cement plant to achieve net-zero CO2 emission by pushing the CO2 capture efficiency to 99.7%. Monoethanomaine (MEA) and piperazine/2-amino-2-methyl-1-propanol (PZ-AMP) amine systems, which are considered to be the first- and second-generation capture agents, respectively, were detailed investigated to deeply decarbonize the cement plant. Compared to MEA, the advanced PZ-AMP system exhibited excellent energy performance with a regeneration duty of ∼2.6 GJ/tonne CO2 at 99.7% capture, 39% lower than the MEA process. This enabled a low CO2 avoided cost of $72.0/tonne CO2, which was 18% lower than that of the MEA-based zero-emission process and even 16.2% lower than the standard 90% MEA process. Sensitivity analysis revealed that the zero-emission capture cost of the PZ-AMP system would be further reduced to below $56/tonne CO2 at a $4/GJ steam production cost, indicating its economic competitiveness among various CO2 capture technologies to achieve a zero-emission cement plant.

Multiple Adverse Reactions Associated With the Use of Second-Generation Antipsychotics in People With Alzheimer's Disease: A Pharmacovigilance Analysis Based on the FDA Adverse Event Reporting System.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition leading to memory loss, cognitive impairment, and neuropsychiatric symptoms. Second-generation antipsychotics (SGAs) are commonly used to manage these neuropsychiatric symptoms, but their safety profile in patients with AD requires further investigation. OBJECTIVE: The objective was to evaluate the safety of SGAs in patients with AD by analyzing adverse drug reactions (ADRs) using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: This study conducted a comprehensive analysis of FAERS data from 2014 to 2023, focusing on ADRs in patients with AD treated with SGAs such as risperidone, quetiapine, olanzapine, clozapine, and aripiprazole. Descriptive, disproportionality, time, and dose analysis were performed using the Bayesian confidence propagation neural network, Weibull, and physiologically based pharmacokinetic model. RESULTS: Out of 1289 patients with AD treated with SGAs, the most common ADRs involved the nervous system, gastrointestinal system, and cardiac disorders. Disproportionality analysis identified significant positive signals in cardiac, renal, and vascular systems. Quetiapine, risperidone, and olanzapine showed more positive signals compared with clozapine and aripiprazole. Time analysis indicated that cardiovascular ADRs occurred randomly, whereas renal ADRs increased with prolonged use. Dose analysis suggested that small doses of SGAs did not elevate the risk of multiple cardiac, renal, or vascular ADRs. CONCLUSION AND RELEVANCE: The study underscores the importance of monitoring for ADRs, particularly in the cardiac and renal systems, when using SGAs in patients with AD. Future research incorporating more comprehensive clinical data is warranted to support safe and rational drug utilization.

Adjunctive cariprazine for major depressive disorder: a systematic review and meta-analysis.

Converging evidence has suggested that treatment augmentation with a second-generation atypical antipsychotic (SGA) may improve treatment outcomes in major depressive disorder (MDD) patients after an incomplete response to a first-line antidepressant. Cariprazine is a recently approved SGA for MDD augmentation. Herein, we evaluate both continuous (ie, change in depressive symptom severity scores over time) and categorical (ie, remission and response rates) outcomes. Following a full-text review, four randomized controlled trials (RCTs) were included in our meta-analysis, while five studies were included for a qualitative review. Risk ratios (RRs) were calculated for all included randomized controlled studies to determine the relative response and remission rates of cariprazine compared to placebo augmentation. The RR for all-cause dropout was also determined as a proxy for overall acceptability. Two studies found a statistically significant treatment response using cariprazine augmentation. One study observed depressive symptom remission for cariprazine compared to placebo. Our random-effects model revealed moderate antidepressant effects of cariprazine, with a standardized mean difference (SMD) in Montgomery-Åsberg Depression Rating Scale (MADRS) scores of -1.79 (95% CI): -2.89, -0.69). Our pooled response RR and remission RR were calculated as 1.21 (95% CI: 1.05, 1.39, P=0.008) and 0.99 (95% CI: 0.84, 1.17, P=0.91), respectively. The RR for response was statistically significant (P<0.05). However, the RR for remission was not statistically significant. The findings from our meta-analysis include a variable magnitude of effects. Evidence suggests cariprazine may be an effective treatment for MDD; however, further results are needed to clarify this relation.

Human papillomavirus-16 E6-positive cervical cancer attenuated by potent 2-(4-biphenylyl)-N-(1-ethyl-4-piperidinyl) acetamide second-generation analogs with improved binding affinity.

Human papillomavirus (HPV) infection, particularly HPV16, is a major contributor to the development of cervical cancer. Given the urgent need for novel therapeutic strategies targeting HPV-associated cancers, this study focuses on characterizing second-generation analogs of a lead compound, as a potential inhibitor of HPV16-E6. Protein-ligand docking, Gibbs binding free energy estimation, and molecular dynamics simulations were conducted. HPV16-infected SiHa and CaSki cell lines were used. MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay for proliferation and flow cytometry for target inhibition and apoptosis were employed. Computational and cell proliferation analyses revealed that modifications to E6-855, particularly in the piperidinyl group, enhanced binding affinities against HPV16-E6, with E6-272 demonstrating superior binding properties. Molecular dynamics simulations confirmed the stable binding of E6-272 to HPV16-E6, supported by favorable binding energy estimates. E6-272 inhibited the proliferation of SiHa and CaSki cells with GI50 values of 32.56 and 62.09 nM, respectively. The compound reduced HPV16-E6-positive population, while inducing the early and late phase apoptosis in these cells. Structural alterations at the piperidinyl group of E6-855 identified E6-272 as a promising inhibitor of HPV16-E6 with improved efficacy against HPV16-E6. Further experimental validation of E6-272 and its analogs warrant to advance its clinical utility in combating HPV-associated cancers.

Ultrasound Appearance of the Endometrium Post-Radiofrequency Ablation.

OBJECTIVE: To describe the ultrasonographic appearance of the post-ablative endometrium to improve knowledge of its sonographic findings. METHODS: This was an Institutional Review Board approved prospective study of patients who underwent second-generation endometrial ablation from 2016 to 2019 at a single health system. Patients had postoperative transvaginal ultrasounds at 2, 6, and 12 months. Ultrasound reports were analyzed for endometrial thickness, description of the endometrium and myometrium, presence of uterine fibroids, and uterine size. Statistical tests for repeated measures were utilized. RESULTS: There were 68 patients with the average age of 42 (SD 6) years and a BMI of 33 (SD 8). Preoperatively the average endometrial thickness was 10 mm, uterine length was 9.7 cm, and 38.2% had leiomyoma. The average endometrial thickness decreased at each ultrasound: 8.4 mm (SD 3.4), 7.2 mm (SD 3.0), and 5.8 mm (SD 2.5) at 2, 6, and 12 months, respectively. When comparing endometrial thickness postoperatively there was a significant difference at 2 and 12 months (P = .041), and 6 and 12 months (P = .031). There was no change during the postoperative period in the presence of leiomyoma, hyperechoic endometrium, hypoechoic endometrium, heterogeneous endometrium, and cystic endometrium on the ultrasounds. CONCLUSION: After ablation with a second-generation device, the endometrial thickness on ultrasound decreases with time following surgery. Additional studies correlating these findings to clinical outcomes would be useful.

Global profiling of protein S-palmitoylation in the second-generation merozoites of Eimeria tenella.

The intracellular protozoan Eimeria tenella is responsible for avian coccidiosis which is characterized by host intestinal damage. During developmental cycle, E. tenella undergoes versatile transitional stages such as oocyst, sporozoites, merozoites, and gametocytes. These developmental transitions involve changes in cell shape and cell size requiring cytoskeletal remodeling and changes in membrane proteins, which may require transcriptional and translational regulations as well as post-translational modification of proteins. Palmitoylation is a post-translational modification (PTM) of protein that orchestrates protein targeting, folding, stability, regulated enzymatic activity and even epigenetic regulation of gene expression. Previous research revealed that protein palmitoylation play essential role in Toxoplasma gondii, Trypanosoma cruzi, Trichomonas vaginalis, and several Plasmodium parasites. Until now, there is little information on the enzymes related to palmitoylation and role of protein acylation or palmitoylation in E. tenella. Therefore, palmitome of the second-generation merozoite of E. tenella was investigated. We identified a total of 2569 palmitoyl-sites that were assigned to 2145 palmitoyl-peptides belonging to 1561 protein-groups that participated in biological processes including parasite morphology, motility and host cell invasion. In addition, RNA biosynthesis, protein biosynthesis, folding, proteasome-ubiquitin degradation, and enzymes involved in PTMs, carbohydrate metabolism, glycan biosynthesis, and mitochondrial respiratory chain as well as vesicle trafficking were identified. The study allowed us to decipher the broad influence of palmitoylation in E. tenella biology, and its potential roles in the pathobiology of E. tenella infection. Raw data are publicly available at iProX with the dataset identifier PXD045061.

Efficient recycling pathway of bio-based composite polyurethane foams via sustainable diamine.

Aminolysis is widely recognized as a valuable chemical route for depolymerizing polymeric materials containing ester, amide, or urethane functional groups, including polyurethane foams. Bio-based polyurethane foams, pristine and reinforced with 40 wt% of sustainable fillers, were depolymerized in the presence of bio-derived butane-1,4-diamine, BDA. A process comparison was made using fossil-derived ethane-1,2-diamine, EDA, by varying amine/polyurethane ratio (F/A, 1:1 and 1:0.6). The obtained depolymerized systems were analyzed by FTIR and NMR characterizations to understand the effect of both diamines on the degradation pathway. The use of bio-based BDA seemed to be more effective with respect to conventional EDA, owing to its stronger basicity (and thus higher nucleophilicity), corresponding to faster depolymerization rates. BDA-based depolymerized systems were then employed to prepare second-generation bio-based composite polyurethane foams by partial replacement of isocyanate components (20 wt%). The morphological, mechanical, and thermal conductivity properties of the second-generation polyurethane foams were evaluated. The best performances (σ10 %=71 ± 9 kPa, λ = 0.042 ± 0.015 W∙ m-1 ∙K-1) were attained by employing the lowest F/A ratio (1:0.6); this demonstrates their potential application in different sectors such as packaging or construction, fulfilling the paradigm of the circular economy.

Evaluation of Global Dystonia Rating Scale as a predictor of unfavorable outcomes among acute antipsychotics poisoned patients.

Worldwide, acute antipsychotic poisoning results in high morbidities and mortalities. Though extrapyramidal syndromes are commonly associated, the extent of extrapyramidal syndromes in relation to the severity of antipsychotic poisoning has not been addressed yet. Thus, this study aimed to assess the Global Dystonia Rating Scale (GDRS) as an unfavorable outcomes predictive tool in acute antipsychotic poisoning. A cross-sectional study included 506 antipsychotic-poisoned patients admitted to Tanta University Poison Control Center, Egypt, over three years was conducted. The mean GDRS was 9.1 ± 16.7 in typical antipsychotic poisoning, which was significantly higher than that of atypical antipsychotics (4.2 ± 11.5) (p = 0.003). Patients with GDRS> 20 showed significantly higher liability for all adverse outcomes (p < 0.05). However, poisoning with typical antipsychotics was associated with significantly more cardiotoxicity (p = 0.042), particularly prolonged QRS (p = 0.005), and intensive care unit (ICU) admission (p = 0.000). In contrary to the PSS, which failed to predict the studied adverse outcomes, GDRS significantly predicted all adverse outcomes (p < 0.000) for all antipsychotic generations. In atypical antipsychotics, GDRS above three accurately predicted cardiotoxicities, prolonged QTc interval, and respiratory failure with Area under curves (AUC) of 0.937, 0.963, and 0.941, respectively. In typical antipsychotic poisoning, at higher cutoffs (7.5, 27.5, 18, and 7.5), cardiotoxicities, prolonged QTc interval, and respiratory failure were accurately predicted (AUC were 0.974, 0.961, and 0.960, respectively). GDRS is an objective, substantially useful tool that quantifies dystonia and can be used as an early reliable predictor of potential toxicity in acute antipsychotic poisoning.

Perceived discrimination and multiple indicators of positive development among second-generation Chinese-American youth: The moderating role of ethnic identity.

BACKGROUND: The present study examined the associations among ethnic identity, perceived discrimination and multiple indicators of positive youth development (PYD; i.e., intrapersonal-oriented competence, interpersonal-oriented competence, confidence, caring, character, family connection, peer connection, school and community connection, positive attitudes towards diversity and cultural pride) that were specifically identified among second-generation Chinese-American youth. METHODS: Participants were 196 second-generation Chinese-American youth (N girl = 93; M age = 14.56, SD age = 1.75) primarily from the greater Boston area in MA, United States. Multivariate regression models were estimated to examine the associations between ethnic identity, perceived discrimination, and each potential indicator of PYD, as well as the moderating role of ethnic identity, controlling for key demographics. RESULTS: (1) Ethnic identity was positively related to all PYD indicators, ßs = .32 to .72, ps < .01; (2) perceived discrimination was negatively associated with all indicators of PYD (ßs = -.15 to -.32, ps < .05), except for interpersonal-oriented competence and caring; and (3) ethnic identity significantly moderated the relationship between perceived discrimination and family connection (ß = .23, p < .01). CONCLUSIONS: Findings indicate that whereas discrimination has potential negative effects on the positive development of second-generation Chinese-American youth, ethnic identity may be a key strength that should be considered in PYD promotion practices for these youth.

Clinical characteristics of 14 cases of Chlamydia psittaci pneumonia.

Among 14 patients with C. psittaci pneumonia, there were 9 critical and 5 non-critical cases. Ten patients improved clinically and were discharged to home; however, four patients died. Seven patients had a history of contact with birds or poultry. All 14 patients had a high fever as the presenting symptom, but most had a normal white blood cell count. Most of the patients had a significant increase in high-sensitivity C-reactive protein and procalcitonin levels. The lymphocyte count in the critical group was considerably lower than in the non-critical group. Patients in the critical group were more advanced in age than in the non-critical group. In addition, serum urea nitrogen, creatinine, procalcitonin, and lactate dehydrogenase levels were significantly higher in the critical group than in the non-critical group (P<0.05). The 4 patients who died had significantly increased procalcitonin levels compared to the 10 patients who survived (P<0.05). In summary, a high fever is usually the presenting complaint of patients with C. psittaci pneumonia. Such patients often progress to severe disease; however, early diagnostic confirmation by mNGS and appropriate treatment dramatically improve the prognosis. Age, lymphocyte count, procalcitonin, blood urea nitrogen, creatinine, and lactate dehydrogenase levels were shown to predict disease severity.

Revision Total Knee Arthroplasty With an Imageless, Second-Generation Robotic System.

BACKGROUND: Robotic-assisted total knee arthroplasty is increasingly used in revision total knee arthroplasty (rTKA), with imageless systems recently receiving Food and Drug Administration (FDA) approval. However, there remains a paucity of literature on the use of robotic assistance in revision total knee arthroplasty (TKA). This paper describes the imageless surgical technique for robotic revision TKA using a second-generation robotic system and details both intraoperative and 90-day outcomes. METHODS: This was a retrospective review of 115 robotic revision TKAs from March 2021 to May 2023 at 3 tertiary academic centers. Patient demographics, perioperative surgical data, and 90-day outcomes were collected. Pain and Patient-Reported Outcomes Measurement Information System scores preoperatively and postoperatively were recorded. All-cause reoperations at the final follow-up were detailed. The mean patient age was 65 years (range, 43 to 88), and 58% were women. The mean follow-up time was 13 months (range, 3 to 51). RESULTS: The most common indications for rTKA were instability (n = 37, 32%) and aseptic loosening (n = 42, 37%). There were 83 rTKAs to a posterior-stabilized liner, 22 to a varus-valgus constrained liner, and 5 to a hinged construct. The median polyethylene size was 11 (interquartile range, 10 to 13), and 93% of patients had their joint line restored within 5 millimeters of the native contralateral knee. Within the 90-day postoperative window, there were 8 emergency department visits and 2 readmissions. At the final follow-up, there were 5 reoperations and 2 manipulations under anesthesia. There were 4 patients who required irrigation and debridement after superficial wound dehiscence, and one had an arthrotomy disruption after a fall. CONCLUSIONS: This review demonstrates favorable intraoperative and 90-day outcomes and suggests that imageless robotic surgery is a promising modality in rTKA. Further studies comparing the longitudinal outcomes after robotic and conventional rTKA are warranted.

Current-Mode Shadow Filter with Single-Input Multiple-Output Using Current-Controlled Current Conveyors with Controlled Current Gain.

In this paper, a novel current-mode shadow filter employing current-controlled current conveyors (CCCIIs) with controlled current gains is presented. The CCCII-based current-mode shadow filters are resistorless and can offer a number of advantages such as circuit simplicity and electronic tuning capability. The proposed shadow filters offer five filtering functions, i.e., low-pass, high-pass, band-pass, band-stop, and all-pass functions, in the same topology. Furthermore, no component matching condition is required to realize all the transfer functions. The natural frequency and quality factor adjustment is possible by using the CCCII current gains without the need to use external amplifiers, all capacitors are grounded, and the filter terminals offer low-input and high-output impedance. To verify the functionality and feasibility of the new topologies, the proposed circuits were simulated using SPICE and the transistor model process parameters NR100N (NPN) and PR100N (PNP) from AT&T's bipolar arrays ALA400-CBIC-R. The simulation results are consistent with the theory. The CCCII experimental setup was designed using commercially available 2N3904 (NPN) and 2N3906 (PNP) transistors with a supply voltage of ±2.5 V. The measurement results confirm the performance of the designed filters.

1 V Electronically Tunable Differential Difference Current Conveyors Using Multiple-Input Operational Transconductance Amplifiers.

This paper presents electronically tunable current conveyors using low-voltage, low-power, multiple-input operational transconductance amplifiers (MI-OTAs). The MI-OTA is realized using the multiple-input bulk-driven Metal Oxide Semiconductor transistor (MIBD-MOST) technique to achieve minimum power consumption. The MI-OTA also features high linearity, a wide input range, and a simple Complementary Metal Oxide Semiconductor (CMOS). Thus, high-performance electronically tunable current conveyors are obtained. With the MI-OTA-based current conveyor, both an electronically tunable differential difference current conveyor (EDDCC) and a second-generation electronically tunable current conveyor (ECCII) are available. Unlike the conventional differential difference current conveyor (DDCC) and second-generation current conveyor (CCII), the current gains of the EDDCC and ECCII can be controlled by adjusting the transconductance ratio of the current conveyors. The proposed EDDCC has been used to realize a voltage-to-current converter and current-mode universal filter to show the advantages of the current gain of the EDDCC. The proposed current conveyors and their applications are designed and simulated in the Cadence environment using 0.18 µm TSMC (Taiwan Semiconductor Manufacturing Company) CMOS technology. The proposed circuit uses ±0.5 V of power supply and consumes 90 µW of power. The simulation results are presented and confirm the functionality of the proposed circuit and the filter application. Furthermore, the experimental measurement of the EDDCC implemented in the form of a breadboard connection using a commercially available LM13700 device is presented.

The Effect of Neuropsychiatric Drugs on the Oxidation-Reduction Balance in Therapy.

The effectiveness of available neuropsychiatric drugs in the era of an increasing number of patients is not sufficient, and the complexity of neuropsychiatric disease entities that are difficult to diagnose and therapeutically is increasing. Also, discoveries about the pathophysiology of neuropsychiatric diseases are promising, including those initiating a new round of innovations in the role of oxidative stress in the etiology of neuropsychiatric diseases. Oxidative stress is highly related to mental disorders, in the treatment of which the most frequently used are first- and second-generation antipsychotics, mood stabilizers, and antidepressants. Literature reports on the effect of neuropsychiatric drugs on oxidative stress are divergent. They are starting with those proving their protective effect and ending with those confirming disturbances in the oxidation-reduction balance. The presented publication reviews the state of knowledge on the role of oxidative stress in the most frequently used therapies for neuropsychiatric diseases using first- and second-generation antipsychotic drugs, i.e., haloperidol, clozapine, risperidone, olanzapine, quetiapine, or aripiprazole, mood stabilizers: lithium, carbamazepine, valproic acid, oxcarbazepine, and antidepressants: citalopram, sertraline, and venlafaxine, along with a brief pharmacological characteristic, preclinical and clinical studies effects.

Considering context: Current relationship satisfaction in a second-generation model of men's physical intimate partner violence.

Despite a half-century of scholarship devoted to explicating and disrupting the intergenerational transmission of family violence, it remains a prominent and destructive social force in the United States. Theoretical models have posited a variety of historical and concurrent risk and protective factors implicated in the trajectory from childhood violence exposure to adult perpetration. Using a second-generation model of intimate partner violence (IPV), we integrated social learning and attachment conceptualizations to examine pathways from family-of-origin violence to IPV perpetration among adult men. A sample of mixed-sex couples (N = 233) completed self-report measures related to social learning and attachment-based factors (e.g., violence in past relationships, child exposure, IPV attitudes, adult attachment) and participated in a 10-min conversation about a desired area for change in their relationship. Following, each partner participated in a video-mediated-recall procedure assessing their anger volatility and eliciting attributions of their partners' behavior. We tested mediation pathways (consistent with social learning and attachment theories) between violence in men's families of origin and their adult IPV perpetration as a function of relationship satisfaction. The proposed model fit the data well (CFI = 0.95) but had notable modifications from the hypothesized model. Generally, social-learning pathways were more consistent with the data. Relationship satisfaction interacted with some parameters. Results support theoretical advances in understanding IPV. Although exposure to violence in men's family of origin confers risk for later IPV, and a social learning developmental pathway is consistent with results, some of these effects are altered by relationship context.

Explaining the attainment of the second-generation: When does parental relative education matter?

How can we understand unexplained variation in the educational outcomes of the children of immigrants? A growing literature posits that standard educational transmission models fail to explain national origin differences in attainment because they ignore immigrant selectivity - the degree to which immigrants differ from non-migrants in their sending countries. The immigrant selectivity hypothesis is usually tested using indicators of parents' relative or "contextual" educational attainment, measuring their rank in the educational attainment distribution of their country of origin. However, using this proxy, current support for the hypothesis is mixed. We outline three conditions for the use of educational selectivity as a proxy for relative social positioning among the children of immigrants. We test our conditions using an adult and a youth sample from a large household panel survey in the UK. We supplement our analyses by exploring relative education data from prior research on Italy, France and the United States. Triangulating these varied sources, we illustrate cases when our three conditions do and do not hold, providing evidence from the UK and other contexts. We provide guidelines on the use of relative education as a measure of relative social standing in cross-national research as well as an assessment of the immigrant selectivity hypothesis in explaining second-generation educational outcomes.