Regional health priorities for dementia: a roadmap for the Western Pacific.

In the Western Pacific Region, the prevalence of dementia is expected to increase, however, the diversity of the region is expected to present unique challenges. The region has varying levels of preparedness, with a limited number of countries having a specific national dementia plan and awareness campaigns. Diversity of risk and healthcare services within the region is exerting impact on diagnosis, treatment, care, and support, with most countries being under resourced. Similarly, the ability to monitor dementia-related indicators and progress research, particularly relating to treatment and clinical trial access needs to be addressed. Countries require comprehensive national plans that lay out how resources will be allocated to improve dementia literacy, train, and support carers, mobilise resources to reduce risk factors and improve research capabilities. These plans need to be informed by consumers and tailored to the region to develop an inclusive society for people living with dementia and their families.

Comparison of remimazolam and midazolam for preventing intraoperative nausea and vomiting during cesarean section under spinal anesthesia: a randomized controlled trial.

Background: Preventing intraoperative nausea and vomiting (IONV) is crucial for maternal safety during cesarean section under spinal anesthesia. While midazolam is known to prevent IONV, we hypothesized that remimazolam would be superior due to its minimal hemodynamic effects. We compared the effects of the two drugs on IONV. Methods: Parturients scheduled for cesarean section were randomly assigned to receive either midazolam or remimazolam. They received midazolam 2 mg or remimazolam 5 mg, with additional doses administered upon request. The primary outcome measure was the incidence of newly developed IONV during sedation. Other outcomes included overall IONV, rescue antiemetic use, shivering, hemodynamic variables, sedation scale scores, and satisfaction scores. Results: Data from 80 participants were analyzed. Deeper sedation was induced in the remimazolam group (PGroup × Time < 0.001) despite comparable hemodynamic trends between the groups. The incidence of overall IONV was comparable between the two groups (27.5% in the midazolam group vs. 17.5% in the remimazolam group, absolute risk reduction [ARR]: 0.100, 95% confidence interval [CI] [-0.082, 0.282], P = 0.284); however, newly developed IONV during sedation was significantly reduced in the remimazolam group (20.0% vs. 5.0%, ARR: 0.150, 95% CI [0.009, 0.291], P = 0.043). The need for rescue antiemetics was also lower in the remimazolam group (15.0% vs. 2.5%, ARR: 0.125, 95% CI [0.004, 0.246], P = 0.048). Conclusion: Remimazolam significantly reduced the incidence and severity of newly developed IONV compared with midazolam, with minimal impact on hemodynamics, making it a useful sedative option for cesarean section.

Topology, dynamics, and control of a muscle-architected soft arm.

Muscular hydrostats, such as octopus arms or elephant trunks, lack bones entirely, endowing them with exceptional dexterity and reconfigurability. Key to their unmatched ability to control nearly infinite degrees of freedom is the architecture into which muscle fibers are weaved. Their arrangement is, effectively, the instantiation of a sophisticated mechanical program that mediates, and likely facilitates, the control and realization of complex, dynamic morphological reconfigurations. Here, by combining medical imaging, biomechanical data, live behavioral experiments, and numerical simulations, an octopus-inspired arm made of [Formula: see text]200 continuous muscle groups is synthesized, exposing "mechanically intelligent" design and control principles broadly pertinent to dynamics and robotics. Such principles are mathematically understood in terms of storage, transport, and conversion of topological quantities, effected into complex 3D motions via simple muscle activation templates. These are in turn composed into higher-level control strategies that, compounded by the arm's compliance, are demonstrated across challenging manipulation tasks, revealing surprising simplicity and robustness.

Time to Treat First Acute Attack of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Importance: A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion. Objective: To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus. Design, Setting, and Participants: This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration. Exposures: Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days). Main Outcomes and Measures: A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment. Results: Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not. Conclusions and Relevance: Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction in the proportion of relapsing disease course and an increase in the likelihood of MOG-IgG seronegative conversion. These data suggest that timing of acute phase treatment for the first MOGAD attack can be associated with the long-term prognosis and autoimmune status of patients.

Fructose 1,6-bisphosphate aldolase: A promising prognostic marker for oral cancer and its role in radiotherapy response.

Oral cancer remains a significant global health concern and its early detection plays a crucial role in improving patient outcomes. Identifying reliable prognostic markers is essential to guide treatment decisions and enhance survival rates. Fructose 1,6-bisphosphate aldolase (FBA), a glycolytic enzyme, has emerged as a promising candidate for prognostic assessment of oral cancer. This review highlights the role of FBA in tumorigenesis, its potential utility in predicting disease progression and patient survival, and its influence on response to radiotherapy. Recent studies have suggested that dysregulated metabolic pathways involving FBA may contribute to radiation resistance in oral cancer, emphasizing the need for further exploration of FBA-targeted therapeutic strategies. Understanding the role of FBA in oral cancer pathogenesis could pave the way for the development of personalized treatment strategies, including combined radiotherapy.

Hierarchically Micro- and Nanostructured Polymer via Crystallinity Alteration for Sustainable Environmental Cooling.

Cooling environments are a pervasive need in our society, with conventional air conditioners being the most popular approach. However, air conditioners rely heavily on electricity and Freon, a chemical that depletes ozone and contributes to greenhouse gas effects. To address this issue, passive daytime radiative coolers (PDRCs) have been proposed to achieve cooling by simultaneously reflecting sunlight and allowing internal heat to escape without electricity. Despite their potential, most high-performance PDRCs are composed of thick polymer films, which increases material costs during PDRC preparation and limits thermal transport. In this work, we introduced an economical and scalable solvent evaporation-based method to prepare a relatively thin hierarchically micro- and nanostructured poly(vinylidene fluoride-trifluoroethylene) via crystallinity alteration. Particularly, we find that the key to generating nanosized pores is to remove the water residual within the film without sample annealing, which significantly enhances the scattering efficiency across the solar spectrum. With our design, we demonstrate effective cooling of the outdoor environment, achieving a cooling temperature of Δ2.5 °C, with a film thickness of only 215 µm. Furthermore, our model suggested that applying this material could lead to annual energy savings of up to ∼39% in warmer climates across the country and up to 715 GJ nationwide. Developing effective PDRCs with reduced material thickness, such as the one discussed here, is imperative for implementing sustainable cooling solutions and reducing our carbon footprint.

Safeguarding Public Health: Advanced Detection of Food Adulteration Using Nanoparticle-Based Sensors.

Food adulteration, whether intentional or accidental, poses a significant public health risk. Traditional detection methods often lack the precision required to detect subtle adulterants that can be harmful. Although chromatographic and spectrometric techniques are effective, their high cost and complexity have limited their widespread use. To explore and validate the application of nanoparticle-based sensors for enhancing the detection of food adulteration, focusing on their specificity, sensitivity, and practical utility in the development of resilient food safety systems. This study integrates forensic principles with advanced nanomaterials to create a robust detection framework. Techniques include the development of nanoparticle-based assays designed to improve the detection specificity and sensitivity. In addition, sensor-based technologies, including electronic noses and tongues, have been assessed for their capacity to mimic and enhance human sensory detection, offering objective and reliable results. The use of nanomaterials, including functionalized nanoparticles, has significantly improved the detection of trace amounts of adulterants. Nanoparticle-based sensors demonstrate superior performance in terms of speed, sensitivity, and selectivity compared with traditional methods. Moreover, the integration of these sensors into food safety protocols shows promise for real-time and onsite detection of adulteration. Nanoparticle-based sensors represent a cutting-edge approach for detecting food adulteration, and offer enhanced sensitivity, specificity, and scalability. By integrating forensic principles and nanotechnology, this framework advances the development of more resilient food-safety systems. Future research should focus on optimizing these technologies for widespread application and adapting them to address emerging adulteration threats.

Long-term Outcomes of Bilateral Lateral Rectus Recession Using a Modified Normogram for Targeting Small Overcorrection in Intermittent Exotropia.

PURPOSE: To evaluate the surgical outcomes of a modified normogram for bilateral lateral rectus recession in the surgical management of intermittent exotropia, with a focus on achieving small overcorrection. METHODS: A retrospective medical chart review of 242 patients who underwent surgery for intermittent exotropia between October 2014 and June 2020 was performed. Our modified normogram reducing amount of recession targeted for small postoperative overcorrection within 5 prism diopters (PD). Patients were observed for at least 3 years. Esodeviation was denoted by negative numbers and positive values indicated exodeviation. A satisfactory outcome was defined as if distant angle of deviation ranged between ≤10 PD of exotropia and ≤5 PD of esotropia. Recurrence was defined as an exodeviation of >10 PD at distance. Overcorrection was defined as an esodeviation of >5 PD at distance. RESULTS: The mean preoperative deviation angles were 29.32 ± 3.92 PD at distance and 29.88 ± 4.41 PD at near. At postoperative day 1, the mean deviation angles at distance and near were -6.22 ± 1.44 and -6.22 ± 1.49 PD, respectively. Overcorrection within 6 PD of esodeviation was seen in 168 patients (69.42%), undercorrection with exophoria was noted in 11 patients (4.55%), and overcorrection by more than 6 PD of esodeviation was seen in 63 patients (26.03%) at postoperative day 1. The long-term success rate at postoperative 3 years was 77.27% (187 of 242), with a recurrence rate of 19.83% (48 of 242) and an overcorrection rate of 2.89% (7 of 242). A positive correlation between the angle of deviation at postoperative day 1 and 3 years was observed (r = 0.22, p = 0.001). The final success rate at the final examination after a mean follow-up of 38.60 ± 7.99 months was 83.06%. CONCLUSIONS: Our modified normogram for bilateral lateral rectus recession in intermittent exotropia surgery resulted in successful surgical outcomes with small overcorrection, reducing the risk of consecutive esotropia due to excessive overcorrection.

ALK5/VEGFR2 dual inhibitor TU2218 alone or in combination with immune checkpoint inhibitors enhances immune-mediated antitumor effects.

Transforming growth factor ß (TGFß) is present in blood of patients who do not respond to anti-programmed cell death (ligand) 1 [PD-(L)1] treatment, and through synergy with vascular endothelial growth factor (VEGF), it helps to create an environment that promotes tumor immune evasion and immune tolerance. Therefore, simultaneous inhibition of TGFß/VEGF is more effective than targeting TGFß alone. In this study, the dual inhibitory mechanism of TU2218 was identified through in vitro analysis mimicking the tumor microenvironment, and its antitumor effects were analyzed using mouse syngeneic tumor models. TU2218 directly restored the activity of damaged cytotoxic T lymphocytes (CTLs) and natural killer cells inhibited by TGFß and suppressed the activity and viability of regulatory T cells. The inactivation of endothelial cells induced by VEGF stimulation was completely ameliorated by TU2218, an effect not observed with vactosertib, which inhibits only TGFß signaling. The combination of TU2218 and anti-PD1 therapy had a significantly greater antitumor effect than either drug alone in the poorly immunogenic B16F10 syngeneic tumor model. The mechanism of tumor reduction was confirmed by flow cytometry, which showed upregulated VCAM-1 expression in vascular cells and increased influx of CD8 + CTLs into the tumor. As another strategy, combination of anti-CTLA4 therapy and TU2218 resulted in high complete regression (CR) rates in CT26 and WEHI-164 tumor models. In particular, immunological memory generated by the combination of anti-CTLA4 and TU2218 in the CT26 model prevented the development of tumors after additional tumor cell transplantation, suggesting that the TU2218-based combination has therapeutic potential in immunotherapy.

Crosslinking-induced anion transport control for enhancing linearity in organic synaptic devices.

Numerous studies on neuromorphic computing systems and their associated synaptic devices have been reported for the efficient processing of complex data. Among them, organic electrochemical transistors (OECTs) have attracted considerable attention owing to their advantages such as low cost, high scalability, and facile electrical modulation. However, the requirement of supplementary processing for ionic transport control to actualize or enhance synaptic attributes necessitates a compromise between their inherent benefits. Here, we developed a simple method, photoinduced crosslinking, which can control the structure of conjugated polymers in OECTs to improve ionic transport control. Crosslinked polymers increase the ion doping efficiency and allow sequential anion movements, which leads to high linearity in OECTs. The fabricated device also exhibited enhanced synaptic properties such as a long retention time, wide dynamic range, and high recognition accuracy. This innovative approach opens up new possibilities for the construction of next-generation artificial synapses.

Corrosion behavior of Ti-Pt-coated stainless steel for bipolar plates in polymer electrolyte membranes under water electrolysis conditions.

In this study, the corrosion behavior and degradation mechanism of Ti-Pt-coated stainless steel bipolar plates were investigated through electrochemical tests and surface analysis in a polymer electrolyte membrane water electrolysis (PEMWE) operating environment. The coated bipolar plate has a corrosion current density of only 1.68 × 10-8 A/cm2, which is an order of magnitude lower than that of the bare SS316L substrate (1.94 × 10-7 A/cm2), indicating that its corrosion resistance is superior to that of bare SS316L substrate. However, in the PEMWE operating environment, the protection efficiency of the coating and the corrosion resistance of the coated bipolar plate decreased. The degradation of the coated bipolar plate can be attributed to electrolyte penetration into the blistering areas of the coating layer with micro voids. Defects in the coating layer occur because of the pressure of oxygen gas generated within the coating layer under high-potential conditions, thereby exposing the substrate to the electrolyte and corrosion.

Surgical necrotizing enterocolitis risk factors in extremely preterm infants: a Korean nationwide cohort study.

BACKGROUND: The incidence of necrotizing enterocolitis (NEC) is significantly associated with gestational age (GA). This study aimed to investigate risk factors for surgically treated NEC (sNEC) in extremely preterm infants (EPIs) using nationwide cohort registry. METHODS: Data were collected from 16,338 very-low-birth-weight infants registered in the Korean neonatal network. Clinical data of 5310 EPIs were retrospectively analyzed. sNEC was defined as infants with diagnosis of NEC requiring surgical treatment, who underwent surgical intervention for NEC or died before surgery. Infants were categorized into three groups based on their NEC status: infants without NEC (control), medically treated NEC (mNEC), and sNEC. These groups were matched based on GA to investigate risk factors for NEC. RESULTS: In EPIs, small for gestational age (SGA; odds ratio 1.68, 95% confidence interval [CI], 1.17-2.36, p = 0.004), hypotension (1.49, 1.18-1.89, p = 0.001), and IVH (1.63, 1.30-2.05, p < 0.001) were identified as risk factors for sNEC. Complete administration of antenatal steroid reduced the risk of sNEC (0.80, 0.64-0.99, p = 0.044). CONCLUSION: Our study demonstrated that EPIs who are SGA, and experience hypotension and IVH may be at an increased risk of developing NEC requiring surgery. These groups require close attention and monitoring for any signs of surgical indications of NEC. IMPACT: This nationwide cohort study aimed to identify characteristics of infants with necrotizing enterocolitis (NEC) among extremely preterm infants (EPIs) and analyze the risk factors associated with NEC requiring surgical intervention. Small for gestational age (SGA), hypotension, and intraventricular hemorrhage (IVH) were identified as significant risk factors for surgically treated NEC (sNEC) in EPIs. The administration of antenatal steroids decreases the risk of sNEC. Close attention and monitoring for EPIs with early identifiable risk factors such as SGA, hypotension, and IVH should be considered to prevent and detect sNEC early, ultimately leading to improved long-term outcomes.

Comparative study for metabolomics, antioxidant activity, and molecular docking simulation of the newly bred Korean red rice accessions.

This study analyzed the metabolite profiles and antioxidant capacities of two waxy and non-waxy Korean red rice accessions newly bred. Fifteen phenolic compounds were detected in the rice samples. Accession1 had high fatty acids, phytosterols, and vitamin E; accession3 had high vitamin E and phytosterol; and accession4 had a high total flavonoid. The correlation analysis findings from this study validated the positive association between all the metabolites and antioxidant activity. in silico results revealed that protocatechuic acid had a docking score of -9.541, followed by luteolin, quercetin, and caffeic acid, all of which had significant docking scores and a significant number of contacts. Similarly, molecular dynamics simulations showed that phytochemicals had root mean square deviation values of <2.8 Å with Keap 1, indicating better stability. This study provides valuable insights into potential directions for future investigations and improvements in the functional qualities of other colored rice varieties.

Dynamic interplay of reactive oxygen and nitrogen species (ROS and RNS) in plant resilience: unveiling the signaling pathways and metabolic responses to biotic and abiotic stresses.

KEY MESSAGE: Plants respond to environmental challenges by producing reactive species such as ROS and RNS, which play critical roles in signaling pathways that lead to adaptation and survival strategies. Understanding these pathways, as well as their detection methods and effects on plant development and metabolism, provides insight into increasing crop tolerance to combined stresses. Plants encounter various environmental stresses (abiotic and biotic) that affect plant growth and development. Plants sense biotic and abiotic stresses by producing different molecules, including reactive species, that act as signaling molecules and stimulate secondary messengers and subsequent gene transcription. Reactive oxygen and nitrogen species (ROS and RNS) are produced in both physiological and pathological conditions in the plasma membranes, chloroplasts, mitochondria, and endoplasmic reticulum. Various techniques, including spectroscopy, chromatography, and fluorescence methods, are used to detect highly reactive, short-half-life ROS and RNS either directly or indirectly. In this review, we highlight the roles of ROS and RNS in seed germination, root development, senescence, mineral nutrition, and post-harvest control. In addition, we provide information on the specialized metabolism involved in plant growth and development. Secondary metabolites, including alkaloids, flavonoids, and terpenoids, are produced in low concentrations in plants for signaling and metabolism. Strategies for improving crop performance under combined drought and pathogen stress conditions are discussed in this review.

Predictive factors for perinatal bacterial transmission from colonized mothers to delivered very-low-birth-weight infants: a retrospective cohort study.

This study investigated the predictive factors for perinatal bacterial transmission in very-low-birth-weight infants (VLBWIs) born to mothers with a history of intrapartum colonization. We retrospectively reviewed the medical records of 173 VLBWIs, wherein pathogens were confirmed in maternal cultures obtained from the blood, urine, and vagina during the intrapartum period from 2013 to 2020. Newborns were categorized based on microbiological tests, including gastric aspirates, endotracheal aspirates, blood, and skin/nasal swab cultures collected immediately after birth. Infants whose cultures matched their maternal pathogens were categorized into the "transmission group" (n = 45), while those who tested negative were assigned to the "control group" (n = 128). The predominant maternal-colonizing pathogen observed was Escherichia coli (30.6%), which also emerged as the primary colonizing pathogen in neonates (35.6%). Transmission group had higher incidences of maternal leukocytosis, chorioamnionitis, and cervical cerclage. Regarding neonatal characteristics, the transmission group demonstrated lower initial base excesses (- 6.3 ± 3.9 vs. - 9.2 ± 4.9, P < 0.05) and higher C-reactive protein levels (0.1 ± 0.3 vs. 0.4 ± 0.8, P < 0.05). Notably, regarding major neonatal outcomes, transmission group had higher mortality rates and incidences of severe intraventricular hemorrhage. These findings may be useful for making decisions when considering antibiotic treatment for infants with a history of maternal colonization.

Brain-body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common form of human motor neuron disease. It is characterized by the progressive degeneration of upper and lower motor neurons, leading to generalized motor weakness and, ultimately, respiratory paralysis and death within 3-5 years. The disease is shaped by genetics, age, sex and environmental stressors, but no cure or routine biomarkers exist for the disease. Male individuals have a higher propensity to develop ALS, and a different manifestation of the disease phenotype, than female individuals. However, the mechanisms underlying these sex differences remain a mystery. In this Review, we summarize the epidemiology of ALS, examine the sexually dimorphic presentation of the disease and highlight the genetic variants and molecular pathways that might contribute to sex differences in humans and animal models of ALS. We advance the idea that sexual dimorphism in ALS arises from the interactions between the CNS and peripheral organs, involving vascular, metabolic, endocrine, musculoskeletal and immune systems, which are strikingly different between male and female individuals. Finally, we review the response to treatments in ALS and discuss the potential to implement future personalized therapeutic strategies for the disease.

Histopathologic Change in the Anterior Part of the Posterior Fixation Suture After a Faden Operation in an Animal Model.

PURPOSE: To observe postoperative histological changes in the anterior part of the posterior fixation suture after a Faden operation in an animal model. METHODS: A posterior fixation suture was placed at two points 6 mm posterior to the insertion of the extraocular muscle on the superior rectus muscle of the right eye in eight rabbits. The superior rectus muscle of the left eye was used as a control. The eyes were enucleated and the anterior portion of the posterior fixation suture, including the myoscleral junction, was extracted 4 weeks after surgery. Postoperative adhesion was graded from 0 to 4 based on histologic findings (hematoxylin-eosin and Masson's trichrome staining). RESULTS: Histological evaluation revealed diffuse fibrosis at the myoscleral junction and the anterior part of the posterior fixation suture after the Faden operation. The graded scores for fibrosis, acute inflammation, chronic inflammation, and foreign body reactions in the Faden operation group were significantly higher than those in the control group (P < .05). Postoperative diffuse fibrosis of the myoscleral junction and anterior-to-posterior fixation sutures were observed in an animal model. CONCLUSIONS: Histologic changes may affect ocular alignment and motility, making reoperation unpredictable after the Faden procedure. [J Pediatr Ophthalmol Strabismus. 2024;61(5):371-375.].

Systemic Treatment with siRNA Targeting Gamma-Secretase Activating Protein Inhibits Amyloid-ß Accumulation in Alzheimer's Disease.

Amyloid-ß (Aß) peptide aggregation in the brain is a key factor in Alzheimer's disease. However, direct inhibition of ß-secretase or γ-secretase proves ineffective in reducing Aß accumulation and improving cognition in Alzheimer's. Recent findings suggest that inhibiting gamma-secretase activating protein (GSAP) can decrease Aß generation without affecting crucial γ-secretase substrates. Dimerization of Lep9R3LC (diLep9R3LC) was confirmed by Ellman's test. The peptide-small interfering RNA (siRNA) complex ratio, particle size, and surface charge were analyzed using electrophoretic mobility shift assay, and dynamic light scattering, respectively. In a 3xTg mice model of Alzheimer's disease, diLep9R3LC:siRNA complexes were intravenously administered twice a week for 8 weeks. Assessments included gene silencing, protein expression, and behavioral improvement using reverse transcription polymerase chain reaction, quantitative polymerase chain reaction, western blotting, Y-maze, and object recognition tests. The efficacy of Lep9R3LC dimerization was ~80% after a 3-d reaction by Ellman's test. In N2a cells, diLep9R3LC:siGSAP complexes achieved ~70% silencing at 48 h posttransfection. In 7-month-old male 3xTg mice, GSAP knockdown was ~30% in the cortex and ~50% in the hippocampus. The behavior improved in mice treated with diLep9R3LC:siGSAP complexes, showing a 60% increase in entries and an 80% increase object recognition. A novel dipeptide, diLep9R3LC, complexed with siRNA targeting GSAP (siGSAP), efficiently delivers siRNA to the mouse brain, targeting the hippocampus. The treatment inhibits Aß accumulation, reduces GSK-3ß-associated with tau hyperphosphorylation, and improves Alzheimer's behavior. Our findings highlight diLep9R3LC:siGSAP's potential for Alzheimer's and as a siRNA carrier for central nervous system-related diseases.

Clinical, cognitive, and functional characteristics of recent-onset psychosis with autistic features: A 2-year longitudinal study.

Though categorized as separate illnesses, schizophrenia and autism are known to exhibit shared characteristics. This study explored the distinctions in clinical, cognitive, and functional characteristics among individuals with recent-onset psychosis, considering the severity of their autistic symptoms, involving longitudinal examinations. We analyzed 671 patients with recent-onset psychosis from Korean Early Psychosis Cohort Study (KEPS), and used the PANSS Autism Severity Score (PAUSS) to categorize patient into 'autistic', 'moderate', and 'non-autistic' groups. The autistic group had the highest rate of schizophrenia diagnosis, and the lowest incidence of comorbid psychiatric disorders. Schizophrenia diagnosis predicted membership of the autistic group. More severe autistic symptoms correlated with worse overall symptoms and functional outcomes, which significantly predicted membership of the autistic group. Cognitive impairments and emotional recognition difficulties increased with the severity of autistic symptoms. 2-year longitudinal assessments demonstrated that group differences in autistic features and overall symptoms, and functional outcomes remained consistent, and membership of the autistic group significantly predicted symptomatic remission and functional recovery. In conclusion, the presence of autistic symptoms has a significant impact on the overall symptomatology and functional capabilities. They are enduring attributes rather than temporary state variables, and serve as a significant predictor for both symptomatic and functional recovery.

Association between preoperative lumbar skeletal muscle index and postoperative nausea and vomiting in patients undergoing pylorus-preserving pancreatoduodenectomy: a retrospective study.

BACKGROUND: Sarcopenia is associated with postoperative complications; however, its impact on the quality of postoperative recovery, such as postoperative nausea and vomiting (PONV) and pain, remains unclear. We investigated the association of preoperative lumbar skeletal muscle mass index (LSMI) with PONV, postoperative pain, and complications. METHODS: Medical records of 756 patients who underwent pylorus-preserving pancreatoduodenectomy (PPPD) were retrospectively reviewed. The skeletal muscle areas were measured on abdominal computed tomography (CT) images. LSMI was calculated by dividing the skeletal muscle area by the square of the patient's height. We analyzed the correlations between preoperative LSMI calibrated with confounding variables and PONV scores, PONV occurrence, pain scores, rescue analgesic administration, postoperative complications, and length of hospital stay. RESULTS: The median (1Q, 3Q) LSMI was 47.72 (40.74, 53.41) cm2/m2. The incidence rates of PONV according to time period were as follows: post-anesthesia care unit, 42/756 (5.6%); 0-6 h, 54/756 (7.1%); 6-24 h, 120/756 (15.9%); 24-48 h, 46/756 (6.1%); and overall, 234/756 (31.0%). The incidence of PONV was inversely correlated with LSMI 24-48 h post-surgery and overall. LSMI and PONV scores were negatively associated 6-24 h and 24-48 h post-surgery. There was no association between LSMI and postoperative pain scores, rescue analgesic administration, complications, or length of hospital stay. CONCLUSIONS: Preoperative LSMI was associated with PONV in patients undergoing PPPD. Therefore, LSMI measured on preoperative abdominal CT can be a predictive indicator of PONV. Appropriate PONV prophylaxis is necessary in patients with low LSMI before PPPD.