Prostate Cancer, Pathophysiology and Recent Developments in Management: A Narrative Review.

PURPOSE OF REVIEW: Prostate cancer is the second most common cancer in men. The different stages of prostate cancer which include localised (low, intermediate, and high risk) disease, locally advanced, non-metastatic castration-resistant prostate cancer (M0 CRPCa), and metastatic disease. The main treatment of locally advanced disease is external beam radiotherapy with hormonal therapy which are associated with good prognosis. RECENT FINDINGS: Current treatments for M0 CRPCa include androgen deprivation therapy in combination with apalutamide, darolutamide or enzalutamide, all of which are associated with good metastatic-free survival rates in clinical trials. Hormone-naive metastatic prostate cancer comprises the same treatments as M0 CRPCa, whereas further treatment includes docetaxel and abiraterone. Metastatic castration-resistant prostate cancer treatments include sipuleucel-T, radium-223, abiraterone, enzalutamide and cabazitaxel, which aim to slow down the progression of the disease and to prolong life. This article also provides insight into the development of new drugs recently approved for metastatic castration prostate cancer, which include PARP inhibitors and Lutetium-177 which have shown to have significantly good overall survival and to improve radiographic progression-free survival. In addition, new clinical trials are ongoing to test new medications such as cabozantinb and chimeric-antigen receptor T-cell therapy for the treatment of advanced prostate cancer. With the aim to slow down the progression of the disease and to prolong life, new drug developments are underway to hopefully provide a positive impact on overall survival and improve progression-free survival, especially in advanced prostate cancer.

Structural and biochemical insights of xylose MFS and SWEET transporters in microbial cell factories: challenges to lignocellulosic hydrolysates fermentation.

The production of bioethanol from lignocellulosic biomass requires the efficient conversion of glucose and xylose to ethanol, a process that depends on the ability of microorganisms to internalize these sugars. Although glucose transporters exist in several species, xylose transporters are less common. Several types of transporters have been identified in diverse microorganisms, including members of the Major Facilitator Superfamily (MFS) and Sugars Will Eventually be Exported Transporter (SWEET) families. Considering that Saccharomyces cerevisiae lacks an effective xylose transport system, engineered yeast strains capable of efficiently consuming this sugar are critical for obtaining high ethanol yields. This article reviews the structure-function relationship of sugar transporters from the MFS and SWEET families. It provides information on several tools and approaches used to identify and characterize them to optimize xylose consumption and, consequently, second-generation ethanol production.

Comparative analysis of survival rate and quality of life in axial-flow pump left ventricular assist devices (LVADs).

BACKGROUND: The rising heart failure rates globally show the pressing demand for treatment progress, especially in Left Ventricular Assist Devices (LVADs). Axial-flow pump LVADs are gaining notice for their small size, few moving parts, and potential for miniaturization, providing a vital option for heart transplants during donor shortages. OBJECTIVES: Despite several studies on LVADs, there is a notable lack of research specifically comparing axial-flow pumps with similar technology. This gap hinders the identification of the most optimal technology to guide development efforts and meet patient needs. This study aims to comprehensively compare the most commonly used axial-flow pumps and provide a detailed analysis focusing on survival rates and quality of life parameters. METHODS: As a developer of axial-flow pumps (LVADs), our group conducted a systematic review of the current axial-flow pump LVADs. We analyzed studies comparing these devices, focusing on key metrics such as survival rates and quality of life. RESULTS: The HeartMate 2 and Jarvik 2000 show superior survival rates (up to 86.9 % at 6 months, 96.3 % at 3 years) and (6-month survival 67 %-91 %) respectively, compared to the other axial flow pumps LVAD. The results underscore the importance of choosing the optimal device and informing the direction of future developments. CONCLUSION: In this paper, we aim to inform future studies to enhance their effectiveness and advance the overall performance of these devices, ultimately benefiting patients and developers. This review furnishes evidence-based recommendations for the most appropriate axial-flow pumps based on survival rates and quality of life parameters.

Impact of second-generation antipsychotics monotherapy or combined therapy in cytokine, lymphocyte subtype, and thyroid antibodies for schizophrenia: a retrospective study.

BACKGROUND: Schizophrenia (SCZ) shares high clinical relevance with the immune system, and the potential interactions of psychopharmacological drugs with the immune system are still an overlooked area. Here, we aimed to identify whether the second-generation antipsychotics (SGA) monotherapy or combined therapy of SGA with other psychiatric medications influence the routine blood immunity biomarkers of patients with SCZ. METHODS: Medical records of inpatients with SCZ from January 2019 to June 2023 were retrospectively screened from June 2023 to August 2023. The demographic data and peripheral levels of cytokines (IL-2, IL-4, IL-6, TNF-α, INF-γ, and IL-17 A), lymphocyte subtype proportions (CD3+, CD4+, CD8 + T-cell, and natural killer (NK) cells), and thyroid autoimmune antibodies (thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb)) were collected and analyzed. RESULTS: 30 drug-naïve patients, 64 SGA monotherapy (20 for first-episode SCZ, 44 for recurrent SCZ) for at least one week, 39 combined therapies for recurrent SCZ (18 with antidepressant, 10 with benzodiazepine, and 11 with mood stabilizer) for at least two weeks, and 23 used to receive SGA monotherapy (had withdrawn for at least two weeks) were included despite specific medication. No difference in cytokines was found between the SGA monotherapy sub-groups (p > 0.05). Of note, SGA monotherapy appeared to induce a down-regulation of IFN-γ in both first (mean [95% confidence interval]: 1.08 [0.14-2.01] vs. 4.60 [2.11-7.08], p = 0.020) and recurrent (1.88 [0.71-3.05] vs. 4.60 [2.11-7.08], p = 0.027) episodes compared to drug-naïve patients. However, the lymphocyte proportions and thyroid autoimmune antibodies remained unchanged after at least two weeks of SGA monotherapy (p > 0.05). In combined therapy groups, results mainly resembled the SGA monotherapy for recurrent SCZ (p > 0.05). CONCLUSION: The study demonstrated that SGA monotherapy possibly achieved its comfort role via modulating IFN-γ, and SGA combined therapy showed an overall resemblance to monotherapy.

Gastric insufflation with and without an inserted gastric tube in second-generation laryngeal mask airways: A randomized controlled cross-over trial.

STUDY OBJECTIVE: Second-generation laryngeal mask airways are equipped with an additional lumen for a gastric tube, with the intention to reduce the risk of aspiration by draining gastric content. However, the effect of an inserted gastric tube through the gastric channel on gastric insufflation, a substantial part of the pathomechanism of aspiration, during positive-pressure ventilation is not clear. We hypothesized, that an inserted gastric tube increases the risk of gastric insufflation. DESIGN: Single center, prospective, randomized-controlled cross-over trial. SETTING: Tertiary academic hospital in Germany. PATIENTS: 152 patients, ASA I-III, scheduled for general anesthesia with a laryngeal mask airway. INTERVENTIONS: Gastric insufflation was investigated during an incremental pressure trial up to a maximum airway pressure of 30 cmH2O and during oropharyngeal leak pressure measurement with and without an inserted gastric tube while one of two laryngeal mask airways with different cuff designs (inflatable or thermoelastic) was used. MEASUREMENTS: Gastric insufflation was detected with real-time ultrasound. MAIN RESULTS: Frequency of gastric insufflation was higher with than without inserted gastric tube during the incremental pressure trial (10.9 % (16/147) vs. 2.7 % (4/147), p = 0.009) and during oropharyngeal leak pressure measurement (16.3 % (24/147) vs. 5.4 % (8/147), p = 0.004). Risk of gastric insufflation didn't differ between the two cuff-types (p = 0.100). Flow over the open gastric channel was associated with gastric insufflation during positive-pressure ventilation (p = 0.003) and during oropharyngeal leak pressure measurement (p = 0.049). Incidence of postoperative nausea and vomiting was higher in patients in which gastric insufflation was detected, compared to others (17.1 % (6/35) vs. 5.4 % (6/112), p = 0.037). CONCLUSION: Placement of a gastric tube through the gastric channel of a second-generation laryngeal mask airway, independent of the cuff-type, increases the risk of gastric insufflation. Flow over the gastric channel indicate a higher risk of gastric insufflation and gastric insufflation may increase the risk of postoperative nausea and vomiting.

Falls and fractures in men with prostate cancer taking second-generation androgen receptor antagonists: A retrospective chart review.

INTRODUCTION: Second-generation androgen receptor antagonists, including enzalutamide, apalutamide, and darolutamide, are commonly used to treat metastatic and non-metastatic prostate cancer. Although these medications are typically well-tolerated, falls were reported in 4.2-15.6% of patients and fractures in 4.2-11.7% of patients enrolled in the phase III clinical trials evaluating these drugs in prostate cancer. However, post-marketing studies have reported a lower incidence than reported in clinical trials. The objective of this study is to determine the prevalence of falls and fractures in patients with prostate cancer receiving second-generation androgen receptor antagonists at UConn Health and identify potential risk factors associated with falls and fractures in these patients. METHODS: A retrospective chart review involving patients with prostate cancer treated with darolutamide, enzalutamide, or apalutamide from March 1, 2022, to March 31, 2023, at UConn Health Carole & Ray Neag Comprehensive Cancer Center. Data recorded includes basic demographics, history of fall or fracture, presence of metastases, fall risk, history of osteoporosis, prescribed second-generation androgen receptor antagonist, and other comorbidities. Data was evaluated using descriptive statistics. RESULTS: Twenty-six men were included, all of whom were receiving enzalutamide. At baseline, 96.1% of patients had bone metastases, 15.4% had osteoporosis, 15.4% had osteopenia, and 34.6% had neuropathy. The incidence of falls was 19.2% and the incidence of fractures was 26.9%. The mean length of therapy at time of a fall was 19.44 months (range, 6-31 months). The mean length of therapy at time of a fracture was 19 months (range, 1-33 months). In patients experiencing fall, 100% had arthralgia, 60% had neuropathy, 40% had a gait problem, 40% had hypertension, and 80% of them were at risk of fall. In patients experiencing fracture, 28.6% had osteoporosis, 42.9% had osteopenia, 100% had bone metastases, and 57.1% were on denosumab at time of fracture. CONCLUSION: The prevalence of falls and fractures in patients receiving enzalutamide were higher in this retrospective chart review than reported in clinical trials and post-marketing studies. This could be due to the small patient population or the patient's comorbidities such as osteoporosis, bone metastases, or neuropathy. Fall/fracture risk with enzalutamide and other risk factors for fall and fracture should be considered when discussing treatment and developing a monitoring plan.

Psychopathological and Therapeutic Trajectories of Inpatients Affected by Mixed States and Bipolar Spectrum Disorders.

In clinical practice, mental health professionals face diagnostic and therapeutic challenges daily. The diagnostic identification of mixed states allows the management of diagnostic and therapeutic trajectories appropriately. In our study, we evaluated 484 patients at a psychiatric rehabilitation center. The initial pre-admission diagnosis of the mixed state of 3.71% (at baseline) increased to 32.23%. The observation period was three years. The therapeutic efficacy of the pharmacological association of Antidepressants (Ads) or Second Generation Antipsychotics (SGAs) with a mood stabilizer (sodium valproate, lithium, lamotrigine, gabapentin, and pregabalin) was evaluated. An improvement in psychopathological symptoms was observed in different groups analyzed. The most significant differences were observed with the association SGAs + mood stabilizer [olanzapine + valproate sodium (p=0.005); risperidone + pregabalin (p=0.072)] and SSRIs + mood stabilizer [escitalopram + valproate sodium (p=0.005), vortioxetine + mood stabilizers (valproate or gabapentin). However, these are preliminary data and are under evaluation.

Metabolic Syndrome and Its Associated Factors Among Patients With Schizophrenia Treated With Second-Generation Antipsychotics at Amanuel Mental Specialized Hospital, Ethiopia.

Background Metabolic syndrome (MetS) encompasses a group of risk factors that increase the likelihood of developing cardiovascular diseases, thereby increasing the mortality rate. Second-generation antipsychotics (SGAs) are known for these side effects. This study aimed to determine the prevalence of MetS and its associated factors at Amanuel Mental Specialized Hospital. Methods A cross-sectional study was conducted from October 3, 2022, to August 31, 2023. Fasting blood sugar and lipid analysis were performed using the Dimension® EXL™ 200 Integrated Chemistry System (Siemens Healthineers, Malvern, PA, USA). A diagnosis of MetS was established using the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) criteria. IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, NY, USA) was used for analysis. A binary logistic regression model was employed, and a p-value less than 0.05 was considered significant. Results A total of 271 participants were enrolled in the study. Most subjects were male (90%) and had a mean age of 34.2 years, with an SD of 10.5. Most participants (70.8%) had abnormal waist circumference, followed by lower high-density lipoprotein cholesterol (HDL-C) at 42.8%. The prevalence of MetS was 35.8%. Gender (being female) (adjusted odds ratio or AOR 3, 95% CI: 1.2-7.4; p = 0.02) and olanzapine use (AOR 2.2, 95% CI: 1.3-3.7; p = 0.005) were predictors of MetS. Conclusions MetS is highly prevalent in patients treated with SGAs. Being female and olanzapine use were predictors of MetS. Clinicians managing these patients should screen and monitor the metabolic components used to diagnose MetS.

Prognostic Outcomes and Predictive Factors in Non-Metastatic Castration-Resistant Prostate Cancer Patients Not Treated with Second-Generation Antiandrogens.

Background/Objectives: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and high-risk features frequently have progression to life-threatening metastasis without second-generation antiandrogens. This study investigated nmCRPC patients for the survival and prognostic factors from a cohort before the approved use of second-generation antiandrogens. Methods: From March 2016 to January 2021, 326 patients treated with second-generation antiandrogens for metastatic castration-resistant prostate cancer (mCRPC) or metastatic castration-sensitive prostate cancer were retrieved. Forty-four patients experiencing nmCRPC with no use of second-generation antiandrogens were reviewed. The prognostic factors, at initial diagnosis or at nmCRPC, associated with metastasis-free survival (MFS) and overall survival (OS) were analyzed. Results: The median follow-up time after nmCRPC was 46 months. The median PSA level at nmCRPC was 2.7 ng/mL. Thirty-eight of forty-four patients with nmCRPC had a PSA doubling time (PSADT) of 10 months or shorter, and the median PSADT was 4 months. The median OS from nmCRPC was 53 months, and the median interval for nmCRPC patients progressing to mCRPC was 20 months. Upon univariate analysis, PSADT < 10 months (p = 0.049) and the very-high-risk group at the initial diagnosis (p = 0.043) were associated with significantly shorter post-nmCRPC MFS. The very-high-risk group (p = 0.031) was associated with significantly worse post-nmCRPC OS. In terms of survivals from the initial diagnosis of prostate cancer, Gleason grade ≥ 8 was the only independent factor with MFS and OS. Conclusions: Without second-generation antiandrogens, nmCRPC patients with PSADT <10 months and in the initial very-high-risk group developed subsequent mCRPC in a significantly faster fashion. Patients of the very-high-risk group had shorter survival rates after nmCRPC.

A Rare Occurrence of Delayed Olanzapine-Induced Oculogyric Crisis in a Postpartum Patient: A Case Report.

Oculogyric crisis (OGC) is an acute dystonic reaction characterized by involuntary upward deviation of the eyes, often linked to the use of antipsychotic medications. While commonly associated with first-generation antipsychotics (FGAs) due to their higher propensity to cause extrapyramidal symptoms (EPS), OGC remains a rare but documented occurrence with second-generation antipsychotics (SGAs). SGAs, including olanzapine, are generally preferred in clinical practice due to their reduced risk of EPS; however, they are not completely devoid of such adverse effects. The emergence of OGC in the context of SGAs, particularly in unique clinical scenarios, highlights the importance of awareness and careful management of potential adverse effects in clinical practice. This case report presents a rare instance of OGC in a 25-year-old postpartum woman following an independent reduction in her olanzapine dosage, a medication usually associated with a low risk of dystonia. The patient, with no previous psychiatric history, had been treated with olanzapine for postpartum depression with psychotic features and demonstrated stability. The onset of OGC, occurring three months after the initiation of olanzapine and precipitated by stressors such as interpersonal conflicts and high-pressure situations, underscores the critical need for comprehensive patient education on the dangers of unsupervised medication adjustments. It also highlights the importance of vigilant monitoring, particularly in vulnerable populations, such as postpartum patients. This case underscores the necessity for individualized treatment approaches and highlights the rarity and clinical significance of OGC in patients on SGAs, contributing to the understanding of atypical presentations associated with these medications.

Second-generation biorefineries: single platform for the conversion of lignocellulosic wastes to environmentally important biofuels.

The continuously increasing demands for various fossil fuels to achieve the day-to-day needs of the human population are growing and causing adverse effects on the environment and leading to the depletion of their natural resources. To overcome such drastic problems and minimize the production of greenhouse gases, lignocellulose biomass, which is an abundant and bio-renewable source present on earth with excellent properties and composition, has been used for decades to develop biofuels that can easily take over the place of conventional fuels. Lignocellulose biomass comprises polymeric sugars, i.e., cellulose and hemicellulose, and aromatic polymer, lignin, which are responsible for producing various bio-based products. However, utilizing lignocellulosic wastes for such purposes is needed but their recalcitrant structure makes it difficult to achieve their full usage. For this, several pretreatment approaches are developed to loosen the complexity between sugars and lignin. In some way, few of the conventional pretreatment methods are expensive, non-eco-friendly, and produce undesired by-products, causing a lower yield and reusability of enzymes used in the reaction. Utilizing novel pretreatment strategies that are cost-effective, help in increasing the yield of products, and are environment-friendly is required. Thus, incorporating nanoparticles and nanomaterials in the development of pretreatment and other strategies for the production of bio-based products is currently thriving. This review is designed in such a way that the readers can easily get brief knowledge about the production of important biofuels developed within second-generation biorefineries using lignocellulosic biomass. It also summarizes the importance of nanotechnology in different steps of biofuel development.

Engineering cellular redox homeostasis to optimize ethanol production in xylose-fermenting Saccharomyces cerevisiae strains.

The transition from fossil fuels dependency to embracing renewable alternatives is pivotal for mitigating greenhouse gas emissions, with biorefineries playing a central role at the forefront of this transition. As a sustainable alternative, lignocellulosic feedstocks hold great promise for biofuels and biochemicals production. However, the effective utilization of complex sugars, such as xylose, remains a significant hurdle. To address this challenge, yeasts can be engineered as microbial platforms to convert the complex sugars derived from biomass. The efficient use of xylose by XR-XDH strains still poses a significant challenge due to redox imbalance limitations, leading to the accumulation of undesirable by-products. In this study, we focused on engineering the industrial S. cerevisiae strain PE-2, known for its robustness, and compared different strategies to balance cellular redox homeostasis, guided by a genome-scale metabolic model. Flux balance analysis guided the selection of four approaches: i. decoupling NADPH regeneration from CO2 production; ii. altering XDH cofactor affinity; iii. shifting XR cofactor preference; iv. incorporating alternate phosphoketolase and acetic acid conversion pathways. A comparative time-course targeted metabolic profile was conducted to assess the redox status of xylose-fermenting cells under anaerobic conditions. The main limitations of xylose-fermenting strains were tested and the replacement of xylose reductase with a NADH-preferred XR in the LVY142 strain proved to be the most effective strategy, resulting in an increase in ethanol yield and productivity, coupled with a reduction in by-products. Comparative analysis of various genetic approaches provided valuable insights into the complexities of redox engineering, highlighting the need for tailored strategies in yeast metabolic engineering for efficient biofuels and biochemicals production from lignocellulosic feedstocks.

Efficacy and safety of second­generation FLT3 inhibitors in acute myeloid leukemia: A systematic review and meta­analysis of randomized controlled trials.

Acute myeloid leukemia (AML) is one of the most frequent forms of acute leukemia and the second most common leukemia subtype in adults. In 2020, the incidence of AML in the United States was estimated to be ~4 cases per 100,000 adults. The FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutation are major prognostic indicators of AML. They are more frequently observed in younger AML patients (aged <60 years), likely due to their association with de novo. Additionally, these mutations have a stronger negative impact on survival in younger patients. Therefore, quizartinib and gilteritinib are second-generation FLT3 inhibitors that are frequently applied for treating patients with AML. However, to the best of our knowledge, few studies have compared the efficacy of second-generation FLT3 inhibitors for AML treatment. Therefore, the present study conducted a comprehensive search for studies on the efficacy and safety of FLT3 inhibitors across PubMed, Embase, the Cochrane Library and ClinicalTrials.gov. The search criteria were limited to randomized controlled trials (RCTs). Subsequently, a meta-analysis was performed on a total of five randomized controlled trials, involving 1,543 participants in total, using a random-effects model. In each RCT, compared to the salvage chemotherapy used in the control group, the groups that received second-generation FLT3 inhibitors experienced significant improvements in overall survival (hazard ratio, 0.717; 95% CI, 0.604-0.850; P<0.001). In addition, overall survival was found to be consistent across the different types of second-generation FLT3 inhibitors used and different types of AML. The risks associated with a prolonged heart-rate corrected QT interval (QTc) interval were next evaluated. Compared with the salvage chemotherapy used in the control group, the second-generation FLT3 inhibitor group exhibited a significantly higher risk of having a prolonged QTc interval (odds ratio, 6.311; 95% CI, 3.061-13.013; P<0.001). In conclusion, these findings suggest that second-generation FLT3 inhibitors can improve the overall survival of patients with AML. However, QTc prolongation is a potential adverse effect that should be monitored.

Impact of Demographics and Insurance Coverage on Schizophrenia Treatment and Healthcare Resource Utilization Within an Integrated Healthcare System.

Purpose: Little is known about the impact of health disparities on antipsychotic treatment and healthcare resource utilization (HRU) among patients with schizophrenia. The objective of this analysis is to examine treatment patterns and HRU by age, race/ethnicity, and insurance coverage among patients with schizophrenia in an integrated delivery network (IDN). Patients and Methods: This cross-sectional study used electronic health record data from MedStar Health, an IDN in the Baltimore-Washington, DC, area. Patients were aged ≥18 years and had ≥2 outpatient encounters or ≥1 hospitalization with a diagnosis of schizophrenia between January 1, 2017 and March 31, 2021. Outcomes assessed included oral antipsychotic prescriptions, long-acting injectable antipsychotic (LAI) utilization, hospitalizations, emergency department (ED) visits, and outpatient visits. Analyses compared subgroups based on age, race/ethnicity (non-Hispanic Black, non-Hispanic White, and other), and type of insurance coverage at index (Medicare, Medicaid, and other) during 12 months of follow-up. Results: A total of 78.1% of patients had ≥1 prescription for an antipsychotic and 69.1% received ≥1 second-generation antipsychotic. Second-generation long-acting injectables (SGA LAI) were utilized by 9.0% of patients, with the elderly and Medicaid beneficiaries having the lowest SGA LAI utilization. Overall, 61.7% of patients had ≥1 hospitalization, 56.4% had ≥1 outpatient visit, and 50.5% had ≥1 ED visit. Hospitalizations and ED visits were most common in those 18 to 24 years of age and in Medicaid beneficiaries, whereas outpatient visits were more common for the elderly and Medicare beneficiaries. Conclusion: At the population level, the results indicate widespread underprescription/underutilization of antipsychotics that have been shown to improve clinical and economic outcomes in patients with schizophrenia, particularly SGA LAI. Within specific subpopulations, disparities in treatment selection and HRU were observed, suggesting the need for increased attention to at-risk groups to ensure consistent quality of care regardless of age, race/ethnicity, or insurance coverage.

Usefulness of driver's eye movement measurement to detect potential risks under combined conditions of taking second-generation antihistamines and calling tasks.

BACKGROUND: Concerns persist regarding the potential reduction in driving performance due to taking second-generation antihistamines or performing hands-free calling. Previous studies have indicated a potential risk to driving performance under an emergency event when these two factors are combined, whereas a non-emergency event was operated effectively. Currently, there is a lack of a discriminative index capable of detecting the potential risks of driving performance impairment. This study aims to investigate the relationship between driving performance and eye movements under combined conditions of taking second-generation antihistamines and a calling task, and to assess the usefulness of eye movement measurements as a discriminative index for detecting potential risks of driving performance impairment. METHODS: Participants engaged in a simulated driving task, which included a calling task, both under taking or not taking second-generation antihistamines. Driving performance and eye movements were monitored during both emergency and non-emergency events, assessing their correlation between driving performance and eye movements. The study further evaluated the usefulness of eye movement as a discriminative index for potential driving impairment risk through receiver operating characteristic (ROC) analysis. RESULTS: In the case of a non-emergency event, no correlation was observed between driving performance and eye movement under the combined conditions. Conversely, a correlation was observed during an emergency event. The ROC analysis, conducted to assess the discriminative index capability of eye movements in detecting the potential risk of driving performance impairment, demonstrated a high discriminative power, with an area under the curve of 0.833. CONCLUSIONS: The findings of this study show the correlation between driving performance and eye movements under the concurrent influence of second-generation antihistamines and a calling task, suggesting the usefulness of eye movement measurement as a discriminant index for detecting potential risks of driving performance impairment.

Waste from the food industry: Innovations in biorefineries for sustainable use of resources and generation of value.

Biorefineries have attracted significant attention from the scientific community and various industrial sectors due to their use of unconventional biomass sources to produce biofuels and other value-added compounds. Various agro-industrial residues can be applied in biorefinery systems, making them economically and environmentally attractive. However, the cost, efficiency, and profitability of the process are directly affected by the choice of biomass, pre-treatments, and desired products. In biorefineries, the simultaneous production of different products during processing is a valuable approach. Chemical, physical, biological, or combined treatments can generate numerous compounds of high commercial interest, such as phenolic compounds. These treatments, in addition to modifying the biomass structure, are essential for the process's viability. Over the years, complex treatments with high costs and environmental impacts have been simplified and improved, becoming more specific in generating high-value resources as secondary outputs to the main process (generally related to the release of sugars from lignocelluloses to produce second-generation ethanol). Innovative methods involving microorganisms and enzymes are the most promising in terms of efficiency and lower environmental impact. Biorefineries enable the use of varied raw materials, such as different agro-industrial residues, allowing for more efficient resource utilization and reducing dependence on non-renewable sources. In addition to producing low-carbon biofuels, biorefineries generate a variety of high-value by-products, such as packaging materials, pharmaceuticals, and nutritional ingredients. This not only increases the profitability of biorefineries but also contributes to a circular economy.

Prescribing patterns for older-age bipolar disorder patients discharged from two public mental hospitals in Taiwan, 2006-2019.

BACKGROUND: Older-age bipolar disorder (OABD) is commonly defined as bipolar disorder in individuals aged 60 or more. There have been no studies to examine temporal trends in the pharmacological treatment of OABD. We aimed to investigate prescription changes among OABD patients discharged from two public mental hospitals in Taiwan from 2006 to 2019. METHODS: OABD patients discharged from the two study hospitals, from 1 January 2006 to 31 December 2019 (n = 1072), entered the analysis. Prescribed drugs at discharge, including mood stabilisers (i.e., lithium, valproate, carbamazepine, and lamotrigine), antipsychotics (i.e., second- and first-generation antipsychotics (SGAs and FGAs)), and antidepressants, were investigated. Complex polypharmacy was defined as the use of three or more agents among the prescribed drugs. Temporal trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. RESULTS: The most commonly prescribed drugs were SGAs (72.0%), followed by valproate (48.4%) and antidepressants (21.7%). The prescription rates of SGAs, antidepressants, antidepressants without mood stabilisers, and complex polypharmacy significantly increased over time, whereas the prescription rates of mood stabilisers, lithium, FGAs, and antidepressants plus mood stabilisers significantly decreased. CONCLUSIONS: Prescribing patterns changed remarkably for OABD patients over a 14-year period. The decreased use of lithium and increased use of antidepressants did not reflect bipolar treatment guidelines. Future research should examine whether such prescribing patterns are associated with adverse clinical outcomes.

Efficacy and safety of pasireotide treatment in acromegaly: A systematic review and single arm meta-analysis.

BACKGROUND: Acromegaly is a rare chronic endocrine disorder associated with significant comorbidities. Many patients fail to achieve biochemical control with current medical therapies, including surgery and first-generation somatostatin ligands (fg-SRLs). We aimed to perform a systematic review and single-arm meta-analysis to evaluate the efficacy of the multi-receptor somatostatin ligand pasireotide in patients with active or uncontrolled acromegaly. METHODS: We systematically searched PubMed, Embase, and Cochrane databases for studies that assessed the efficacy of pasireotide in patients with acromegaly and reported the outcomes of (1) biochemical control and its composite indicators; (2) normalized IGF-1 level and (3) low GH level. For the statistical analysis, we used R software. RESULTS: We included nine studies with a total of 590 patients: four clinical trials and five observational cohorts. 82.2% of the overall population consisted of inadequately controlled acromegaly patients. After a follow-up of 12 months, the pooled biochemical control rate was 26.50% (95% CI 14.87-42.66). The prevalence of normalized IGF-1 and low GH levels was 36.27% (95% CI 29.15-43.39) and 34.76% (95% CI 24.58-44.95), respectively. Additionally, biochemical response rates were sustained throughout the extension phase of these studies. In a pooled analysis including four studies with extension phase results, the prevalence of biochemical control rate was 29.03% (95% CI 11.49-46.58) with 76 events out of 281 patients. The most commonly reported adverse events were gastrointestinal disturbances in 31.26% (95% CI 7.44-72.01) and hyperglycemia in 29.55% (95% CI 21.80-37.29) of patients. The incidence of new-onset diabetes mellitus significantly increased after pasireotide treatment, with a rate of 23.36% (95% CI 19.58-27.13). CONCLUSION: Pasireotide demonstrates biochemical control in patients with active or uncontrolled acromegaly. Although a high rate of hyperglycemic adverse events and diabetes mellitus related to the treatment were observed, most of them were manageable.

Metabolic Syndrome among Patients Taking Atypical Antipsychotics: A Comparative Cross-Sectional Study at Erada and Mental Health Complex in Taif, Saudi Arabia.

Introduction: Second-Generation Antipsychotics (SGAs) are widely used for treating psychiatric disorders due to their favorable side effect profile compared to First-Generation Antipsychotics (FGAs). However, SGAs are associated with significant metabolic side effects. This study aims to explore the sociodemographic and health differences between individuals using SGAs and those not using them. Methods: A comparative cross-sectional study was conducted with 148 participants, including 102 SGA users and 46 non-users. Data were collected from patients and medical records, encompassing sociodemographic factors and health variables including diabetes mellitus, hypertension, cardiovascular disease, hyperlipidemia, waist circumference, fasting blood glucose, cholesterol, triglycerides, HDL, LDL, and BMI. Statistical analyses included chi-square and Fisher's exact tests to compare the two groups. Results: SGA users had higher rates of overweight and obesity compared to non-users (p = 0.000), with 30.4% overweight and 29.4% obese among SGA users versus 21.7% overweight and 4.3% obese among non-users. A higher prevalence of cardiovascular disease was observed in SGA users (11.8% vs. 2.2%, p = 0.076). Although not statistically significant, trends indicated higher rates of diabetes mellitus and hyperlipidemia in non-users (30.4% vs. 18.6%, p = 0.110 and 7% vs. 0%, p = 0.083, respectively). Conclusion: This study highlights significant differences in BMI and cardiovascular disease prevalence between SGA users and non-users, reinforcing the need for comprehensive metabolic monitoring in patients treated with SGAs. The findings underscore the importance of considering sociodemographic factors in managing the health risks associated with SGA use. Further research with larger sample sizes and longitudinal designs is warranted to better understand these associations and develop targeted interventions.

A novel secondary ALK gene mutation which resistant to second-generation TKIs: a case report and literature review.

Background: Adenocarcinoma with positive echinoderm microtubule-associated protein-like 4 gene and anaplastic lymphoma kinase (EML4-ALK) gene fusion accounts for 3-7% of lung cancer cases and can be targeted with ALK tyrosine kinase inhibitors (TKIs). Second-generation TKIs are the standard of care for targeted populations, especially those with central nervous system (CNS) metastasis. However, most patients eventually experience disease progression because of drug resistance caused by multiple mechanisms, predominantly secondary mutations. Case description: We present a female advanced non-small cell lung cancer (NSCLC) case with positive EML4-ALK gene fusion, in which disease progression occurred in only 3 months after first-line treatment with alectinib. Two secondary mutations were detected by next-generation sequencing; one was V1180L located in exon 23, and the other was E803Q located in exon 14, which was a novel mutation that had never been reported. Ensartinib and ceritinib were administered as second-line and third-line treatments. However, the response to these TKIs was poor, and her overall survival was only 7 months. Conclusion: The secondary mutation E803Q located in exon 14 seems resistant to most second-generation ALK-TKIs. If there is an opportunity, the efficacy of the third-generation ALK-TKI loratinib should be tested.