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Advancing treatment to resolve human cognitive disorders requires a comprehensive understanding of the molecular signaling pathways underlying learning and memory. While most organ systems evolved to maintain homeostasis, the brain developed the capacity to perceive and adapt to environmental stimuli through the continuous modification of interactions within a gene network functioning within a broader neural network. This distinctive characteristic enables significant neural plasticity, but complicates experimental investigations. A thorough examination of the mechanisms underlying behavioral plasticity must integrate multiple levels of biological organization, encompassing genetic pathways within individual neurons, interactions among neural networks providing feedback on gene expression, and observable phenotypic behaviors. Model organisms, such as Drosophila melanogaster, which possess more simple and manipulable nervous systems and genomes than mammals, facilitate such investigations. The evolutionary conservation of behavioral phenotypes and the associated genetics and neural systems indicates that insights gained from flies are pertinent to understanding human cognition. Rather than providing a comprehensive review of the entire field of Drosophila memory research, we focus on olfactory associative reward memories and their related neural circuitry in fly brains, with the objective of elucidating the underlying neural mechanisms, thereby advancing our understanding of brain mechanisms linked to cognitive systems. [ABSTRACT FROM AUTHOR]

This article describes a partnership involving a college and its surrounding public high schools in order to offer a model for transforming professional development initiatives into collaborative, reciprocal community engagement opportunities. This ongoing partnership addresses the shared goal of improving the mathematical college readiness of high school students through a three-part program focused on teacher content knowledge. The partnership is based on sustained, open dialogue in which the expertise of all participants, collegiate mathematics professors and high school mathematics teachers, are equally valued and imperative to achieving program outcomes.

Temperature has a significant effect on all physiological processes of animals. Suitable temperatures promote responsiveness, movement, metabolism, growth, and reproduction in animals, whereas extreme temperatures can cause injury or even death. Thus, thermosensation is important for survival in all animals. However, mechanisms regulating thermosensation remain unexplored, mostly because of the complexity of mammalian neural circuits. The fruit fly Drosophila melanogaster achieves a desirable body temperature through ambient temperature fluctuations, sunlight exposure, and behavioral strategies. The availability of extensive genetic tools and resources for studying Drosophila have enabled scientists to unravel the mechanisms underlying their temperature preference. Over the past 20 years, Drosophila has become an ideal model for studying temperature-related genes and circuits. This review provides a comprehensive overview of our current understanding of thermosensation and temperature preference in Drosophila. It encompasses various aspects, such as the mechanisms by which flies sense temperature, the effects of internal and external factors on temperature preference, and the adaptive strategies employed by flies in extreme-temperature environments. Understanding the regulating mechanisms of thermosensation and temperature preference in Drosophila can provide fundamental insights into the underlying molecular and neural mechanisms that control body temperature and temperature-related behavioral changes in other animals. [ABSTRACT FROM AUTHOR]

Thermosensation is critical for the survival of animals. However, mechanisms through which nutritional status modulates thermosensation remain unclear. Herein, we showed that hungry Drosophila exhibit a strong hot avoidance behavior (HAB) compared to food-sated flies. We identified that hot stimulus increases the activity of α′β′ mushroom body neurons (MBns), with weak activity in the sated state and strong activity in the hungry state. Furthermore, we showed that α′β′ MBn receives the same level of hot input from the mALT projection neurons via cholinergic transmission in sated and hungry states. Differences in α′β′ MBn activity between food-sated and hungry flies following heat stimuli are regulated by distinct Drosophila insulin-like peptides (Dilps). Dilp2 is secreted by insulin-producing cells (IPCs) and regulates HAB during satiety, whereas Dilp6 is secreted by the fat body and regulates HAB during the hungry state. We observed that Dilp2 induces PI3K/AKT signaling, whereas Dilp6 induces Ras/ERK signaling in α′β′ MBn to regulate HAB in different feeding conditions. Finally, we showed that the 2 α′β′-related MB output neurons (MBONs), MBON-α′3 and MBON-β′1, are necessary for the output of integrated hot avoidance information from α′β′ MBn. Our results demonstrate the presence of dual insulin modulation pathways in α′β′ MBn, which are important for suitable behavioral responses in Drosophila during thermoregulation under different feeding states. Thermosensation is critical for the survival of animals, but the mechanisms by which nutritional status modulates thermosensation remain unclear. Behavioral and live brain imaging studies reveal why food-sated fruit flies prefer to stay at relatively higher temperatures compared to hungry flies. [ABSTRACT FROM AUTHOR]

Depression is a medical and social problem. Multiple metabolites and neuroinflammation regulate it. Modifying the gut microbiota with probiotics to reduce depression through the gut-brain axis is a potential treatment strategy. In this study, three anti-depressive potentials of Lactobacillus spp. (LAB), including L. rhamnosus GMNL-74, L. acidophilus GMNL-185 and L. plantarum GMNL-141, which combined to produce low dosage LAB (1.6 × 108 CFU/mouse, LABL) and high dosage LAB (4.8 × 108 CFU/mouse, LABH), were administered to C57BL/6 mice induced depression by ampicillin (Amp). A behavioral test of depression, 16S ribosomal RNA gene amplicon sequencing, bioinformatic analysis, and short-chain fatty acid (SCFA) content measurement were executed to investigate the gut microbiota composition, activation of nutrient metabolism pathways, levels of inflammatory factors, gut-derived 5-HT biosynthesis genes, and SCFA levels in C57BL/6 mice. Results showed that after mice were induced by Amp, both LAB groups recovered from depressive behaviors, decreased the abundance of Firmicutes, and increased the abundance of Actinobacteria and Bacteroidetes in the mouse ileum. The prediction of metabolism pathways of microbes revealed the activation of arginine and proline metabolism, cyanoamino acid metabolism, and nicotinate and nicotinamide metabolism were increased, and fatty acid synthesis was decreased in both LAB groups. The LABH groups showed increased levels of acetic acid, propanoic acid, and iso-butyric acid and decreased butyric acid levels in the cecum. LABH treatment increased claudin-5 and reduced IL-6 mRNA expression. Both LAB groups also reduced monoamine oxidase, and the LABH group increased vascular endothelial growth factor mRNA expression. These results showed that the composite of three LAB exerts antidepressant effects by regulating the gut microbiota and modifying the levels of depression-related metabolites in C57BL/6J Amp-treated mice. [ABSTRACT FROM AUTHOR]

Hyperuricemia is a well-known risk factor for chronic kidney disease (CKD). Little is known about whether a vegetarian diet is associated with a lower risk of CKD in patients with hyperuricemia. From 5 September 2005, to 31 December 2016, we retrospectively included clinically stable patients with hyperuricemia who received health check-ups at Taipei Tzu Chi Hospital. All participants completed a dietary habits questionnaire to determine whether they were omnivorous, lacto-ovo vegetarian, or vegan. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the presence of proteinuria. A total of 3618 patients with hyperuricemia were recruited for this cross-sectional study, consisting of 225 vegans, 509 lacto-ovo vegetarians, and 2884 omnivores. After adjusting for age and sex, vegans had a significantly lower odds ratio (OR) of CKD than omnivores (OR, 0.62; p = 0.006). The OR of CKD remained significantly lower in vegans after adjusting for additional confounders (OR, 0.69; p = 0.04). Additionally, age (per year OR, 1.06; p < 0.001), diabetes mellitus (OR, 2.12; p < 0.001), hypertension (OR, 1.73; p < 0.001), obesity (OR, 1.24; p = 0.02), smoking (OR, 2.05; p < 0.001), and very high uric acid levels (OR, 2.08; p < 0.001) were independent risk factors for CKD in patients with hyperuricemia. Moreover, structural equation modeling revealed that a vegan diet was associated with a lower OR of CKD (OR, 0.69; p < 0.05). A vegan diet is associated with a 31% lower risk of CKD in patients with hyperuricemia. A vegan diet may be beneficial in reducing the occurrence of CKD in patients with hyperuricemia. [ABSTRACT FROM AUTHOR]

Background: Creatinine is widely used to estimate renal function, but this is not practical in critical illness. Low creatinine has been associated with mortality in many clinical settings. However, the associations between predialysis creatinine level, Sepsis-related Organ Failure Assessment (SOFA) score, fluid overload, and mortality in acute kidney injury patients receiving dialysis therapy (AKI-D) has not been fully addressed. Methods: We extracted data for AKI-D patients in the eICU and MIMIC databases. We conducted a retrospective observational cohort study using the eICU dataset. The study cohort was divided into the high-creatine group and the low-creatinine group by the median value (4 mg/dL). The baseline patient information included demographic data, laboratory tests, medications, and comorbid conditions. The independent association of creatinine level with 30-day mortality was examined using multivariate logistic regression analysis. In sensitivity analyses, the associations between creatinine, SOFA score, and mortality were analyzed in patients with or without fluid overload. We also carried out an external validity using the MIMIC dataset. Results: In all 1,600 eICU participants, the 30-day mortality rate was 34.2%. The crude overall mortality rate in the low-creatinine group (44.9%) was significantly higher than that in the high-creatinine group (21.9%; P < 0.001). In the fully adjusted models, the low-creatinine group was associated with a higher risk of 30-day mortality (odds ratio, 1.77; 95% confidence interval, 1.29–2.42; P < 0.001) compared with the high-creatinine group. The low-creatinine group had higher SOFA and nonrenal SOFA scores. In sensitivity analyses, the low-creatinine group had a higher 30-day mortality rate with regard to the BMI or albumin level. Fluid overloaded patients were associated with a significantly worse survival in the low-creatinine group. The results were consistent when assessing the external validity using the MIMIC dataset. Conclusions: In patients with AKI-D, lower predialysis creatinine was associated with increased mortality risk. Moreover, the mortality rate was substantially higher in patients with lower predialysis creatinine with concomitant elevation of fluid overload status. [ABSTRACT FROM AUTHOR]

Background and aims: Vaccination for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is strongly recommended. The efficacy of SARS-CoV-2 vaccine for patients with end-stage renal disease is low. Indoxyl sulfate (IS) is a representative protein bound uremic toxin arousing immune dysfunction in CKD patients. It is unknown whether IS impairs the efficacy of vaccines for SARS-CoV-2. Materials and Methods: From 1 June 2021, to 31 December 2021, hemodialysis patients (n = 358) and a control group (n = 59) were eligible to receive the first dose of the ChAdOx1 COVID-19 vaccine. Titer measurements indicative of the humoral response (anti-S1 IgG and surrogate virus neutralization test (sVNT) results) and indoxyl sulfate concentration measurement were performed 4 weeks after ChAdOx1 vaccine injection. Results: The serum concentrations of anti-S1 IgG were 272 ± 1726 AU/mL and 2111 ± 4424 AU/mL in hemodialysis patients and control group (p < 0.05), respectively. The sVNT values were 26.8 ± 21.1% and 54.0 ± 20.2% in the hemodialysis and control groups (p < 0.05), respectively. There was a decreasing trend for the anti-S1 IgG titer from the lowest to highest quartile of IS (p < 0.001). The patients with higher concentrations of IS had lower sVNT (p for trend < 0.001). Conclusion: Hemodialysis patients had weaker humoral immunity after the first dose of the ChAdOx1 vaccine. Higher concentration of IS altered the development of anti-S1 antibodies and sVNT-measured neutralization. [ABSTRACT FROM AUTHOR]

An integrated high temperature ultrasonic transducer (HTUT) sensor has been utilized for diagnosis of gas-assisted hot embossing process to fabricate V-cut patterns real-time, nonintrusively and nondestructively. The progression of the process, including plastic plate soften, gas introducing, cooling, and plate detachment inside the chamber, was clearly observed using ultrasound. Ultrasonic velocity could not only indicate the four steps of process, but also evaluate the replicating degree of the V-cut patterns on surface of plastic plate under various temperature and gas pressure settings. The experimental results indicate that the heights of V-cut patterns increase with temperature and gas pressure. POLYM. ENG. SCI., 53:2175-2182, 2013. [c] 2013 Society of Plastics Engineers, INTRODUCTION Hot embossing is a productive method for the parallel replication of precision micro-features at low cost. With a single master or stamp, identical structures can be reproduced onto substrates. [...]

(1) Background/aims: Intragastric botulinum toxin A injection (IGBI) combined with diet control is a new and effective weight loss method for grade 2 obese patients. However, the application of IGIB on overweight or obese adults still needs further research to confirm its efficacy. (2) Methods: We retrospectively collected medical data from 1 July 2021 to 1 January 2022 from a total of 71 patients without diabetes who participated in the bariatric clinic with a body mass index (BMI) > 25 kg/m2. Forty-nine participants opted for intragastric botulinum injection (IGBI) using 300 units of botulinum injected into the antrum, body, and fundus, followed with a low-calorie high-protein diet course. Another 22 people participated only in the low-calorie high-protein diet course as a placebo group. This study analyzes the weight loss percentage of the two groups. Adverse events after IGBI are also reported in a safety assessment. (3) Results: In terms of the characteristics of the two groups, the mean BMI was 29.3 kg/m2 in the IGBI group and 28.0 kg/m in the placebo group (p = 0.63 without significant difference). Comparing the percent weight loss from baseline in the two groups after 12 weeks, the IGBI group lost 11.5% of their body weight and the placebo group lost 1.8%. In terms of group analysis, the percentages of participants with a weight reduction of at least 5% for the IGBI and placebo groups were 95% and 4%, respectively. For weight reduction of at least 10%, these values for the IGBI and placebo groups were 63% and 4%, respectively. In terms of adverse events after IGBI for 12 weeks, 12 participants (24.4%) had constipation, which was the main side effect. No serious adverse events were observed during the study period. (4) Conclusion: The combination of a low-calorie high-protein diet and IGBI is an effective and safe procedure in overweight or obese adults for weight reduction, but further larger studies are needed. [ABSTRACT FROM AUTHOR]

Background/aims: Entecavir (ETV) can suppress chronic hepatitis B (CHB) virus replication as a standard of treatment drugs. For the treatment of CHB, affordable generic drugs may be more widely used in developing and undeveloped countries. However, there is little real-world data regarding the clinical efficacy of switching from entecavir-brand-name drugs (ETV-Brand) to entecavir generic drugs (ETV-Generic) with 0.5 mg once daily. The aim of the study was to evaluate the antiviral activity and safety of ETV-Generic in comparison to ETV-Brand in CHB-patients.Methods: In this single-center, retrospective, 175 treatment-naïve-CHB-patients were assigned to receive 0.5 mg of ETV-Brand per day for a least 2 years and then switched to ETV-Generic for 6 months for analysis. The primary efficacy endpoint was a sustained virological response in comparison of the rate of undetectable serum Hepatitis B deoxyribonucleic acid (HBV DNA) as the sustained virologic response at baseline and 6 months after switching. Secondary efficacy endpoints were the comparison of the alanine aminotransferase (ALT) levels between before and after switching and ALT normalization. Renal safety consideration was reported on changing the estimated glomerular filtration rate.Results: From baseline to 6 months, the rate of undetectable HBV DNA and ALT levels remained stable as compared ETV-Brand period with ETV-Generic for 6 months. The rate of undetectable HBV DNA were 81.1%in ETV-Brand versus 88.0%in ETV-Generic (p = 0.05 CI 0.1-13.5%). ALT levels were 27.2 IU/L (CI 24.8-29.6 IU/L) in ETV-Brand versus 26.2 IU/L (CI 24.0-28.4 IU/L) in ETV-Generic (p = 0.55). Both endpoints were not significantly different between ETV-Brand and ETV-Generic treatments. Kidney function did not significantly differ from ETV-Brand (80.8, interquartile range [IQR]: 66.6-95.3 mL/min/1.73 m2) to ETV-Generic treatment period (80.3, IQR: 65.6-93.5 mL/min/1.73 m2).Conclusion: In treatment-naïve CHB-patients, the efficacy and safety profiles of switching from ETV-Brand to ETV-Generic showed no difference. Concluding the ETV-Generic comes to exciting virologic responses and rare adverse events. [ABSTRACT FROM AUTHOR]

Mounting evidence indicates that the gut microbiota is linked to several physiological processes and disease development in mammals; however, the underlying mechanisms remained unexplored mostly due to the complexity of the mammalian gut microbiome. The fruit fly, Drosophila melanogaster, is a valuable animal model for studying host-gut microbiota interactions in translational aspects. The availability of powerful genetic tools and resources in Drosophila allowed the scientists to unravel the mechanisms by which the gut microbes affect fitness, health, and behavior of their hosts. Drosophila models have been extensively used not only to study animal behaviors (i.e., courtship, aggression, sleep, and learning & memory), but also some human related neurodegenerative diseases (i.e., Alzheimer's disease and Parkinson's disease) in the past. This review comprehensively summarizes the current understanding of the gut microbiota of Drosophila and its impact on fly behavior, physiology, and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10–11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcers, and gastric cancer. Infection of cells with H. pylori is dependent on lipid rafts, which are cholesterol-rich microdomains located in the cell membrane. H. pylori cholesterol-α-glucosyltransferase (CGT) catalyzes the conversion of membrane cholesterol to cholesteryl glucosides, which can be incorporated into the bacterial cell wall, facilitating evasion from immune defense and colonization in the host. However, the detailed mechanisms underlying this process remain to be explored. In this study, we discovered for the first time that H. pylori CGT could promote adherence to gastric epithelial cells in a cholesterol-dependent manner. Externalization of cell membrane phosphatidylserine (PS) is crucial for enhancement of binding of H. pylori to cells by CGT and for cytotoxin-associated gene A (CagA)-induced pathogenesis. Furthermore, exogenous cholesterol interferes with the actions of H. pylori CGT to catalyze cellular cholesterol, which impedes bacterial binding to cells and attenuates subsequent inflammation, indicating that the initial attachment of H. pylori to cells is closely dependent on host cholesterol. These results provide evidence that CGT contributes to H. pylori infectivity and it may serve as a key target for the treatment of H. pylori-associated diseases. [ABSTRACT FROM AUTHOR]

Background/Aims: In a recent study, attenuation imaging (ATI) with ultrasound was used as a new approach for detecting liver steatosis. However, although there are many studies on ATI and controlled attenuation parameter (CAP) that prove their practicability, there are few studies comparing these two methods. As such, this study compared CAP and ATI for the detection and evaluation of liver steatosis. Methods: A prospective analysis of 28 chronic liver disease patients who underwent liver biopsy, FibroScan® imaging, and ATI with ultrasound was conducted. The presence and degree of steatosis, as measured with the FibroScan® device and ATI, were compared with the pathological results obtained using liver biopsy. Results: The areas under the receiver operating characteristic curve (AUROC) of ATI and CAP for differentiating between normal and hepatic steatosis were 0.97 (95% confidence interval [CI] 0.83–1.00) and 0.96 (95% CI 0.81–0.99), respectively. ATI has a higher AUROC than CAP does in liver steatosis, at 0.99 (95% CI, 0.86–1.00) versus 0.91 (95% CI, 0.74–0.98) in grade ≥ 2 and 0.97 (95% CI, 0.82–1.00) versus 0.88 (95% CI, 0.70–0.97) in grade = 3, respectively. Conclusion: The ATI and CAP results showed good consistency and accuracy for the steatosis grading when compared with the liver biopsy results. Moreover, ATI is even better than CAP in patients with moderate or severe steatosis. Therefore, ATI represents a non-invasive and novel diagnostic tool with which to support the diagnosis of liver steatosis in clinical practice. [ABSTRACT FROM AUTHOR]

Array‐based analytical platforms have a distinct advantage of being able to detect analytes rapidly and simultaneously with the use of very small quantities of reagents and samples. However, the analyses of enzyme activities using this technique remain challenging, as the heterogeneous interface between the enzyme in the solution and the probe on the array surface impede the efficient binding and the subsequent enzymatic reaction. In this paper, we showed that the combination of affinity‐switchable biotin (ASB) probes and a novel click‐chemistry based immobilization method can overcome this heterogeneity problem. Three ASB probes were synthesized for the detection of alkaline phosphatase, nitroreductase, and the fluoride ion. This approach can be applied to determine the relative levels of phosphatase in different cell lines. We believe that the new strategy holds great potential for the effective sensing of a wide range of biomolecules in the future. [ABSTRACT FROM AUTHOR]

Long-term memory (LTM) formation depends on the conversed cAMP response element-binding protein (CREB)-dependent gene transcription followed by de novo protein synthesis. Thirsty fruit flies can be trained to associate an odor with water reward to form water-reward LTM (wLTM), which can last for over 24 hours without a significant decline. The role of de novo protein synthesis and CREB-regulated gene expression changes in neural circuits that contribute to wLTM remains unclear. Here, we show that acute inhibition of protein synthesis in the mushroom body (MB) αβ or γ neurons during memory formation using a cold-sensitive ribosome-inactivating toxin disrupts wLTM. Furthermore, adult stage-specific expression of dCREB2b in αβ or γ neurons also disrupts wLTM. The MB αβ and γ neurons can be further classified into five different neuronal subsets including αβ core, αβ surface, αβ posterior, γ main, and γ dorsal. We observed that the neurotransmission from αβ surface and γ dorsal neuron subsets is required for wLTM retrieval, whereas the αβ core, αβ posterior, and γ main are dispensable. Adult stage-specific expression of dCREB2b in αβ surface and γ dorsal neurons inhibits wLTM formation. In vivo calcium imaging revealed that αβ surface and γ dorsal neurons form wLTM traces with different dynamic properties, and these memory traces are abolished by dCREB2b expression. Our results suggest that a small population of neurons within the MB circuits support long-term storage of water-reward memory in Drosophila. Author summary: Unlike short-term memory (STM), the formation of long-term memory (LTM) requires de novo protein synthesis and CREB-mediated gene transcription in many animals. To date, the mechanism underlying LTM formation remains poorly understood. Thirsty fruit flies can be trained to associate an odor with water to form a water-reward LTM (wLTM), which requires de novo protein synthesis and dCREB2 activity. In this study, we found that dCREB2 activity in the mushroom body (MB) αβ surface and γ dorsal neuron subsets is essential for wLTM formation. Neurotransmission from αβ surface and γ dorsal neurons is specifically required for retrieval, but not for acquisition or consolidation of wLTM. Moreover, wLTM traces are formed in the αβ surface and γ dorsal neurons with different neural dynamics, which require normal dCREB2 functions. These findings highlight that dCREB2-dependent wLTM is located within a specific brain circuitry in fruit flies. [ABSTRACT FROM AUTHOR]

Brain function has been implicated to control the aging process and modulate lifespan. However, continuous efforts remain for the identification of the minimal sufficient brain region and the underlying mechanism for neuronal regulation of longevity. Here, we show that the Drosophila lifespan is modulated by rab27 functioning in a small subset of neurons of the mushroom bodies (MB), a brain structure that shares analogous functions with mammalian hippocampus and hypothalamus. Depleting rab27 in the α/βp neurons of the MB is sufficient to extend lifespan, enhance systemic stress responses, and alter energy homeostasis, all without trade‐offs in major life functions. Within the α/βp neurons, rab27KO causes the mislocalization of phosphorylated S6K thus attenuates TOR signaling, resulting in decreased protein synthesis and reduced neuronal activity. Consistently, expression of dominant‐negative S6K in the α/βp neurons increases lifespan. Furthermore, the expression of phospho‐mimetic S6 in α/βp neurons of rab27KO rescued local protein synthesis and reversed lifespan extension. These findings demonstrate that inhibiting TOR‐mediated protein synthesis in α/βp neurons is sufficient to promote longevity. [ABSTRACT FROM AUTHOR]

Background: Accumulation of tau oligomers at the synapses in Alzheimer's disease (AD) disrupts neuronal activities and leads to neurodegeneration. Tau immunotherapy has been actively pursued as a treatment for tauopathies in the past decade. Despite several failed Phase 2 trials of N‐terminus binding antibodies a variety of tau epitopes are being investigated at different stages of clinical trials. APNmAb005 is a humanized monoclonal antibody designed to block synaptic toxicity elicited by tau oligomers. Method: APNmAb005 was selected as a clinical candidate from APRINOIA's antibody discovery platform based on its unique binding properties to pathological tau in vitro immunoassays as well in vivo efficacy studies in rTg4510 mice. Humanized APNmAb005 is in IgG4 backbone and the production was scaled up successfully with good stability and solubility to support preclinical and clinical development. GLP safety study was conducted in cynomolgus monkeys. A Phase 1a randomized, double‐blind, placebo‐controlled study of APNmAb005 in healthy subjects is underway. Result: Epitope‐mapping study reveals that APNmAb005 binds to a conformation‐dependent epitope in the mid‐region, which results in a preferable recognition of pathological tau in early Braak stage (III‐IV) AD brains as well as tau aggregates in astrocytes and oligodendrocytes in brains from progressive supranuclear palsy (PSP) patients but not monomeric tau in normal brains. APNmAb005 blocks in vitro tau seeding at nanomolar concentrations and rescues neuronal loss in rTG4510 mice. Four‐week repeat dosing toxicology study shows no observed adverse effects. Conclusion: APNmAb005 is a conformation selective antibody that binds to tau oligomers and aggregates preferentiually in synapses in pathological brain tissues and inhibits tau spreading. The mid‐region conformation dependent epitope is distinct from all other tau antibodies currently in clinical development. APNmAb005 offers a unique tau immunotherapy for neurodegenerative disorders and is currently in Phase 1 to evaluate its safety and tolerability. [ABSTRACT FROM AUTHOR]

Aim: Recombinant tissue plasminogen activator (rt‐PA) administration is the most prevalent treatment for acute ischemic within golden time. However, the effects of rt‐PA on the kidney function in such patients remain unknown. This study determined long‐term renal outcomes in patients with acute ischemic stroke receiving systemic rt‐PA. Methods: We enroled patients who were hospitalized for acute ischemic stroke from January 2001 to January 2017. We applied 1:2 propensity score matching to eliminate various confounding variables. We defined surrogate renal outcomes as declining of estimated glomerular filtration rate (eGFR) greater than 30% and 50%, and chronic kidney disease (CKD) with eGFR less than 60 mL/min. We then compared the 1‐year eGFR with paired t‐test in patients treated with or without rt‐PA. Results: Overall, 343 of 1739 patients received rt‐PA within golden time. After 1:2 propensity score matching, their baseline characteristics were grouped as treated with rt‐PA (n = 235) or not (n = 394). rt‐PA‐treated patients exhibited slower renal progression, including the risk of eGFR declining greater than 30% (hazard ratio (HR), 0.72; P = 0.03), risk of declining eGFR greater than 50% (HR, 0.63; P = 0.046) and risk of CKD (HR, 0.61; P = 0.005). After 1‐year cohort, the rt‐PA group exhibited an improved renal outcome by the paired t‐test (propensity match: ΔGFR = 9.1 (95% confidence interval: 6.3, 11.8), P < 0.001 in rt‐PA group; ΔGFR = −1.1 (95% confidence interval: −2.9, 0.7), P = 0.23 in non‐rt‐PA group). In patients with eGFR less than 45 mL/min (n = 34), intracerebral haemorrhage was not reported. Conclusion: Patients receiving rt‐PA for acute ischemic stroke exhibit favourable renal outcomes, and no increased incidence of intracerebral haemorrhage occurs in rt‐PA patients with advanced CKD. SUMMARY AT A GLANCE: The authors hypothesize that neuro‐hormonal responses to ischaemic brain injury in stroke may affect kidney function. They compared changes in kidney function over time in patients treated with thrombolysis to those who were not. In these observational data, kidney function deteriorated less in patients who received thrombolysis for stroke. [ABSTRACT FROM AUTHOR]

Background Numerous studies have shown that exposure to air pollution, especially particulate matter (PM) with a diameter <2.5 μm (PM2.5), was associated with various diseases. We tried to determine the impact of PM2.5 and other weather factors on acute lung edema in patients with Stage 5 nondialysis chronic kidney disease (CKD Stage 5-ND). Methods In total, 317 CKD Stage 5-ND (estimated glomerular filtration rate 6.79 ± 4.56 mL/min) patients residing in central Taiwan who developed acute lung edema and initiated long-term dialysis were included in this case-crossover study. Pearson's correlation test was used to examine the relationship of acute lung edema cases with PM2.5 levels and ambient temperature separately. Results The average PM2.5 level within the 7-day period correlated with acute lung edema incidence in the fall [adjusted odds ratio (OR) 3.23, P = 0.047] and winter (adjusted OR 1.99, P < 0.001). In winter, even a 3-day exposure to PM2.5 was associated with increased risk (adjusted OR 1.55, P < 0.001). The average temperatures within 3 days in spring and summer were correlated positively with the risk (adjusted OR 2.77 P < 0.001 and adjusted OR 2.72, P < 0.001, respectively). In the fall and winter, temperatures were correlated negatively with the risk (adjusted OR 0.36, P < 0.001 and adjusted OR 0.54, P < 0.001, respectively). Conclusions A high PM2.5 level was associated with an increased risk of acute lung edema. High ambient temperature in hot seasons and low ambient temperature in cold seasons were also associated with increased risk. It is essential to educate these patients to avoid areas with severe air pollution and extreme ambient temperature. [ABSTRACT FROM AUTHOR]