Technology Usability for People Living With Dementia: Concept Analysis.

BACKGROUND: Usability is a key indicator of the quality of technology products. In tandem with technological advancements, potential use by individuals with dementia is increasing. However, defining the usability of technology for individuals with dementia remains an ongoing challenge. The diverse and progressive nature of dementia adds complexity to the creation of universal usability criteria, highlighting the need for focused deliberations. Technological interventions offer potential benefits for people living with dementia and caregivers. Amid COVID-19, technology's role in health care access is growing, especially among older adults. Enabling the diverse population of people living with dementia to enjoy the benefits of technologies requires particular attention to their needs, desires, capabilities, and vulnerabilities to potential harm from technologies. Successful technological interventions for dementia require meticulous consideration of technology usability. OBJECTIVE: This concept analysis aims to examine the usability of technology in the context of individuals living with dementia to establish a clear definition for usability within this specific demographic. METHODS: The framework by Walker and Avant was used to guide this concept analysis. We conducted a literature review spanning 1984 to 2024, exploring technology usability for people with dementia through the PubMed, Web of Science, and Google Scholar databases using the keywords "technology usability" and "dementia." We also incorporated clinical definitions and integrated interview data from 29 dyads comprising individuals with mild Alzheimer dementia and their respective care partners, resulting in a total of 58 older adults. This approach aimed to offer a more comprehensive portrayal of the usability needs of individuals living with dementia, emphasizing practical application. RESULTS: The evidence from the literature review unveiled that usability encompasses attributes such as acceptable learnability, efficiency, and satisfaction. The clinical perspective on dementia stages, subtypes, and symptoms underscores the importance of tailored technology usability assessment. Feedback from 29 dyads also emphasized the value of simplicity, clear navigation, age-sensitive design, personalized features, and audio support. Thus, design should prioritize personalized assistance for individuals living with dementia, moving away from standardized technological approaches. Synthesized from various sources, the defined usability attributes for individuals living with dementia not only encompass the general usability properties of effectiveness, efficiency, and satisfaction but also include other key factors: adaptability, personalization, intuitiveness, and simplicity, to ensure that technology is supportive and yields tangible benefits for this demographic. CONCLUSIONS: Usability is crucial for people living with dementia when designing technological interventions. It necessitates an understanding of user characteristics, dementia stages, symptoms, needs, and tasks, as well as consideration of varied physical requirements, potential sensory loss, and age-related changes. Disease progression requires adapting to evolving symptoms. Recommendations include versatile, multifunctional technology designs; accommodating diverse needs; and adjusting software functionalities for personalization. Product feature classification can be flexible based on user conditions.

Engaging adolescents in research: Home self-collection of biological samples and health questionnaires.

Adolescent health research with biomarker data collection is limited due to difficulties in recruiting and engaging this age group. Thus, successful recruitment, engagement, and retention of adolescents in translational research are necessary to elucidate factors influencing mental and physical health conditions, uncover novel biomarkers, and expand prevention and treatment options. This paper describes strategies for effective recruitment and retention of adolescents in a research study, using a project examining depressive symptoms and the microbiome to illustrate these approaches. This cross-sectional study collected electronic self-reported survey data and self-collected biospecimens (stool and salivary samples) from adolescents 13-19 years old. All but two participants completed the questionnaires, with few missing responses. 94% provided at least one salivary sample and 89% supplied a stool sample. Participants were able to adhere to the study instructions. Using a participant-centered approach, our study successfully recruited and engaged the targeted 90 participants in self-collection of electronic survey data and biospecimens. Successful strategies of recruitment and retention included: 1) on-site clinic recruitment by research team, 2) active involvement of parents as appropriate, 3) use of electronic surveys and self-collection of biospecimens to foster control and ease of participation while addressing privacy concerns, 4) noninvasive collection of data on biospecimen, 5) frequent texting to communicate with participants, 6) flexibility in the pickup and transferring of biospecimens to accommodate adolescent schedules, 7) developmentally appropriate research, 8) participant reimbursement, and 9) sensitivity toward discussing stool sample materials. As a result of these strategies, adolescent participation in the research proved feasible.

A simple and efficient gene functional analysis method for studying the growth and development of peach seedlings.

Stable genetic transformation of peach [Prunus persica (L.) Batsch] still faces many technical challenges, and existing transient expression methods are limited by tissue type or developmental stage, making it difficult to conduct functional analysis of genes regulating shoot growth. To overcome this dilemma, we developed a three-step method for efficient analysis of gene functions during peach seedling growth and development. This method resulted in transformation frequencies ranging from 48 to 87%, depending on the gene. From transformation of germinating seeds to phenotyping of young saplings took just 1.5 months and can be carried out any time of year. To test the applicability of this method, the function of three tree architecture-related genes, namely PpPDS, PpMAX4, and PpWEEP, and two lateral root-related genes, PpIAA14-1 and -2, were confirmed. Since functional redundancy can challenge gene functional analyses, tests were undertaken with the growth-repressor DELLA, which has three homologous genes, PpDGYLA (DG), PpDELLA1 (D1), and -2 (D2), in peach that are functionally redundant. Silencing using a triple-target vector (TRV2-DG-D1-D2) resulted in transgenic plants taller than those carrying just TRV2-DG or TRV2. Simultaneously silencing the three DELLA genes also attenuated the stature of two dwarf genotypes, 'FHSXT' and 'HSX', which normally accumulate DELLA proteins. Our study provides a method for the functional analysis of genes in peach and can be used for the study of root, stem, and leaf development. We believe this method can be replicated in other woody plants.

SFN promotes renal fibrosis via binding with MYH9 in chronic kidney disease.

Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on renal fibrosis. First, we found that SFN was highly expressed in patients with CKD, as well as in renal fibrosis animal and cell models. Next, transforming growth factor-beta 1 (TGF-ß1) induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated unilateral ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes renal fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD.

Urinary concerns among older adults: a qualitative analysis in the context of healthy aging.

BACKGROUND: Urinary concerns increase with age impacting health and quality of life. The aims of this study were to describe: (1) urinary concerns as an age-related change (ARC); (2) the challenges of urinary concerns; (3) adaptation strategies used to manage urinary concerns; and (4) the value of engaging with aging (EWA) as a framework to promote self-management of urinary concerns. METHODS: Data was used from semi-structured interviews with 29 older adults (mean age 77 years). An iterative coding process was used. A codebook was developed based on a-priori themes derived from the EWA framework, our previous publication, and a line-by-line coding of one of the transcripts. As the analysis progressed, additional codes emerged, enriching the codebook. RESULTS: Six themes emerged: (1) the participants' experiences; (2) responses to urinary concerns, (3) adaptation and management strategies; (4) knowledge and understanding of urinary concerns; (5) available capacities and resources; and (6) the impact of the COVID-19 pandemic on urinary concerns. Participants tended to address their urinary concerns by adjusting routines, medication schedules, or diet patterns. They tried to secure restroom locations or use tools or reminders to resolve their urinary concerns. COVID-19 led to increased inconvenience for older adults to engage in outdoor activities due to the closure of public restrooms. CONCLUSIONS: Our in-depth qualitative analysis found that participants developed personalized adjustments to address their needs and abilities to their urinary concerns. These findings offer insights into the individual aging experience, which will further enhance our understanding and advancement of person-centered care.

Associations of early retirement and mortality risk: a population-based study in Taiwan.

BACKGROUND: Early retirement is highly prevalent in Taiwan. This study assesses the association between early retirement and all-cause and cause-specific mortality risks while exploring the modifying effect of sociodemographic factors. METHODS: Using Taiwan's National Health Insurance Research Database between 2009 and 2019, 1 762 621 early retirees aged 45-64 and an equal number of employed comparators were included. The date and cause of death were identified using the National Death Registry. Cox regression models were used to estimate HRs of early retirement for all-cause mortality and cause-specific mortality. To explore modifying effects, we conducted subgroup analyses based on age groups, sexes, occupation types and general health status (Charlson Comorbid Index score). RESULTS: The analysis revealed that early retirees, compared with their concurrently employed counterparts, had a higher mortality risk (adjusted HR (aHR) 1.69, 95% CI (1.67 to 1.71)). Specifically, younger individuals (aged 45-54) (aHR 2.74 (95% CI 2.68 to 2.80)), males (aHR 1.78 (95% CI 1.76 to 1.81)), those in farming or fishing occupations (aHR 2.13 (95% CI 2.06 to 2.21)) or the private sector (aHR 1.92 (95% CI 1.89 to 1.96)), and those with the poorest health conditions (aHR 1.79 (95% CI 1.76 to 1.83)) had higher mortality risks of early retirement. Regarding specific causes of death, the top three highest risks were associated with gastrointestinal disorders, followed by suicide and neurological disorders. CONCLUSIONS: This study underscores the substantial mortality risk increase linked to early retirement, emphasising the importance of policy considerations, particularly regarding vulnerable populations and specific causes of death potentially linked to unhealthy lifestyles.

Teaching diagnostic radiology to radiology majors: Implementation and evaluation of a flipped classroom model.

PURPOSE: Radiology instruction focuses on cultivating medical students' diagnostic thinking skills and practical competence, and lecture-based learning (LBL) is the most commonly used teaching approach. While fact-based, this type of traditional instruction is often non-engaging, leading to a shift toward student-centered models, one of which is the flipped classroom (FC). However, studies involving a comprehensive evaluation of students' experiences using the FC approach and its effects on their learning are lacking. Therefore, this study analyzed the teaching efficacy of the FC approach based on data of large groups of radiology students, accumulated over time. METHODS: Data from 636 medical radiology students taught using the FC and LBL models from 2012 to 2021 were retrospectively collected and analyzed. RESULTS: The test scores of the FC group were significantly higher than those of the LBL group, and improvements in learning initiative and learning ability were notably higher in the FC than in the LBL group. The two groups showed no significant difference in the critical thinking disposition indicator, and the proportion of students with positive critical thinking tendencies was higher in the FC than in the LBL group. The academic and social self-perception scores of the FC group were significantly higher than those of the LBL group, and there was a significant difference in Kolb's learning style. CONCLUSIONS: Based on evidence of completing pre-, in-, and after-class work, the FC approach improved students' academic performance, learning initiative, diagnostic ability, and satisfaction with learning and the teaching institution. Our findings suggest that FC instruction promotes students' assimilation and convergence of learning styles, and cultivates positive critical thinking.

Comprehensive Investigation of the Temperature-Dependent Electromechanical Behaviors of Carbon Nanotube/Polymer Composites.

The performances of flexible piezoresistive sensors based on polymer nanocomposites are significantly affected by the environmental temperature; therefore, comprehensively investigating the temperature-dependent electromechanical response behaviors of conductive polymer nanocomposites is crucial for developing high-precision flexible piezoresistive sensors in a wide-temperature range. Herein, carbon nanotube (CNT)/polydimethylsiloxane (PDMS) composites widely used for flexible piezoresistive sensors were prepared, and then the temperature-dependent electrical, mechanical, and electromechanical properties of the optimized CNT/PDMS composite in the temperature range from -150 to 150 °C were systematically investigated. At a low temperature of -150 °C, the CNT/PDMS composite becomes brittle with a compressive modulus of ∼1.2 MPa and loses its elasticity and reversible sensing capability. At a high temperature (above 90 °C), the CNT/PDMS composite softens, shows a fluid-like mechanical property, and loses its reversible sensing capability. In the temperature range from -60 to 90 °C, the CNT/PDMS composite exhibits good elasticity and reversible sensing behaviors and its modulus, resistivity, and sensing sensitivity decrease with an increasing temperature. At room temperature (30 °C), the CNT/PDMS composite exhibits better mechanical and piezoresistive stability than those at low and high temperatures. Given that environmental temperature changes have significant effects on the sensing performances of conductive polymer composites, the effect of ambient temperature changes must be considered when flexible piezoresistive sensors are designed and fabricated.

Gentianamopanshanensis (Gentianaceae), a new species from Yunnan, southwest China.

Gentianamopanshanensis, a new species of the family Gentianaceae is here described and illustrated. This species is presently known only from the Mopanshan Mountain, Yunnan Province, southwest China. Phylogenetic analysis based on ITS sequence data has shown that this new species is a member of the series Fimbriatae of the section Chondrophyllae. Morphologically, it mostly resembles G.mairei and G.panthaica, but differs clearly from the latter two species in the shape and size of the leaves, and the characters of the corolla throat and plicae.

Isodonxiaoluzhiensis (Lamiaceae, Nepetoideae), a new species from Yunnan, southwest China.

Isodonxiaoluzhiensis, a new species of the tribe Ocimeae in family Lamiaceae, is described and illustrated. The new species is known only from the type locality, Xiaoluzhi village in Luzhijang dry-hot valley of Yimen County, central Yunnan, southwest China. It is characterized by having a procumbent habit, gracile stems and branches, relatively small leaves and flowers, and the phenology of flowering in winter. The morphological comparisons with its putative closest relatives (I.adenanthus and I.hsiwenii) are also presented.

Medium- and long-chain triglyceride propofol activates PI3K/AKT pathway and inhibits non-alcoholic fatty liver disease by inhibiting lipid accumulation.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. The mechanism by which medium- and long-chain triglyceride (MCT/LCT) propofol plays a role in promoting NAFLD remains unclear. In this study, we investigated the effect of MCT/LCT propofol on NAFLD progression and its mechanism of action. In Huh-7 and HepG3 cells induced by free fatty acids (FFA), propofol downregulated the expression levels of TG and lipid metabolism-related proteins by promoting the activation of the PI3K/AKT pathway and suppressing FFA-induced lipid metabolic disorders. In a high-fat diet (HFD) -induced NAFLD mouse model, we demonstrated that propofol significantly inhibited liver steatosis, inflammatory cell infiltration, and fibrosis. In conclusion, our results suggest that MCT/LCT propofol reduces liver lipid accumulation by activating the PI3K/AKT pathway and further suppressing the NAFLD process.

The Effect of Intranasal Dexmedetomidine on Emergence Delirium Prevention in Pediatric Ambulatory Dental Rehabilitation Under General Anesthesia: A Randomized Clinical Trial.

Purpose: Sevoflurane is the preferred anesthetic agent for induction and maintenance of ambulatory surgery due to its property of fast onset and recovery. However, it has been recognized as one of the major contributors of emergence delirium. The aim of this study was to evaluate the preventive effect of intranasal dexmedetomidine on the occurrence of emergence delirium in pediatric patients under general anesthesia with sevoflurane. Patients and Methods: Ninety pediatric patients undergoing dental rehabilitation under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=30 each in the 2 µg/kg dexmedetomidine, 1 µg/kg dexmedetomidine, and control with saline groups). The same volume (0.02mL/kg) of the mixed solution was dropped into the nasal cavity of the children 30 minutes before surgery. We used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level and incidence of delirium in the post-anesthesia care unit. Results: Compared with the control group, prophylactic use of different dosages of intranasal dexmedetomidine significantly reduces the incidence of ED and severe ED in PACU (P<0.001). Intranasal administration of 2 µg/kg dexmedetomidine was associated with a better acceptance of mask induction and a better tolerance of separation with parents. Conclusion: Both 2 µg/kg and 1 µg/kg intranasal dexmedetomidine can achieve ED preventive effects in PACU in dental rehabilitation under general anesthesia. A dosage of 2 µg/kg is more effective in preventing severe ED and providing better mask acceptance.

A Mobile Intervention Designed Specifically for Older Adults With Frailty to Support Healthy Eating: Pilot Randomized Controlled Trial.

BACKGROUND: Frailty, a common geriatric syndrome, predisposes older adults to functional decline. No medications can alter frailty's trajectory, but nutritional interventions may aid in supporting independence. OBJECTIVE: This paper presents a pilot randomized controlled trial to investigate the feasibility and efficacy of a mobile health intervention, "Olitor," designed to enhance adherence to the Mediterranean diet among older adults with frailty, requiring no external assistance. METHODS: The study sample consisted of 15 participants aged 66-77 (mean 70.5, SD 3.96) years randomized into intervention (n=8; 8 females; mean 72.4, SD 4.8 years) and control groups (n=7; 6 females, 1 male; mean 70.0, SD 3.9 years). The intervention involved a patient-facing mobile app called "Olitor" and a secure web-based administrative dashboard. Participants were instructed to use the app at least weekly for 3 months, which provided feedback on their food choices, personalized recipe recommendations, and an in-app messaging feature. Using Mann-Whitney tests to compare change scores and Hedges g statistics to estimate effect sizes, the primary efficacy outcomes were adherence to the Mediterranean diet score and insulin resistance measures. Secondary outcomes included retention as a measure of feasibility, engagement level and user app quality ratings for acceptability, and additional metrics to evaluate efficacy. Models were adjusted for multiple comparisons. RESULTS: The findings demonstrated a significant improvement in the Mediterranean diet adherence score in the intervention group compared to the control (W=50.5; adjusted P=.04) with median change scores of 2 (IQR 2-4.25) and 0 (IQR -0.50 to 0.50), respectively. There was a small and insignificant reduction in homeostasis model assessment of insulin resistance measure (W=23; adjusted P=.85). Additionally, there were significant increases in legume intake (W=54; adjusted P<.01). The intervention's effect size was large for several outcomes, such as Mediterranean diet adherence (Hedges g=1.58; 95% CI 0.34-2.67) and vegetable intake (Hedges g=1.14; 95% CI 0.08-2.21). The retention rate was 100%. The app's overall quality rating was favorable with an average interaction time of 12 minutes weekly. CONCLUSIONS: This pilot study revealed the potential of the mobile intervention "Olitor" in promoting healthier eating habits among older adults with frailty. It demonstrated high retention rates, significant improvement in adherence to the Mediterranean diet, and increased intake of recommended foods. Insulin resistance showed a minor nonsignificant improvement. Several secondary outcomes, such as lower extremity function and Mediterranean diet knowledge, had a large effect size. Although the app's behavior change features were similar to those of previous digital interventions, the distinctive focus on theory-informed mechanistic measures involved in behavioral change, such as self-regulation, self-efficacy, and expected negative outcomes, may have enhanced its potential. Further investigations in a more diverse and representative population, focusing on individuals with impaired insulin sensitivity, are warranted to validate these preliminary findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05236712; https://clinicaltrials.gov/study/NCT05236712.

Circ_0005015 upregulates BACH1 to promote aggressive behaviors in glioblastoma by sponging microRNA-382-5p.

To investigate the potential role and molecular mechanism of circ_0005015 in GBM progression. Circ_0005015, microRNA-382-5p (miR-382-5p), and BTB domain and CNC homolog 1 (BACH1) levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was determined by MTT, colony formation, and EdU assays. Cell apoptosis was analyzed using flow cytometry. Cell migration and invasion were assessed using wound healing and transwell assays. Glucose accumulation and lactate levels were examined by the corresponding kit. RNA pull-down and dual-luciferase reporter assays were performed to confirm the interaction between miR-382-5p and circ_0005015 or BACH1. Protein levels of MMP9, PCNA, and BACH1 were examined using western blot assay. Role of circ_0005015 on tumor growth in vivo was analyzed using a xenograft tumor model. Circ_0005015 content was up-regulated in GBM patients and cells, its knockdown restrained GBM cell proliferation, migration, invasion, glycolysis, and triggered apoptosis. Mechanistically, we found that circ_0005015 could directly interact with miR-382-5p and serve as a miRNA sponge to regulate BACH1 expression. In addition, circ_0005015 knockdown might repress tumor growth in vivo. Circ_0005015 boosted GBM progression via binding to miR-382-5p to up-regulate BACH1, which may offer new effective targets for GBM treatment.

[Determination of nine organic amine compounds in CO2 absorption liquid by hydrophilic interaction liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry].

Carbon dioxide (CO2) absorption and capture is an effective measure to achieve the "dual carbon" goal of carbon peak and carbon neutrality in China. Organic amine compounds are widely used in the industrial separation and recovery of CO2. Thus, the establishment of analytical methods for organic amine compounds is of great significance for the research and development of carbon capture and storage (CCS) technology and carbon capture, utilization and storage (CCUS) technology. In this study, a method was developed for the determination of nine organic amine compounds in CO2 absorption liquid by hydrophilic interaction liquid chromatography (HILIC)-electrostatic field orbitrap high resolution mass spectrometry. The sample was diluted with water and filtered through a 0.22 µm nylon membrane before sampling and analysis. An Accucore HILIC column (100 mm×2.1 mm, 2.6 µm) was used for separation at 30 ℃. Gradient elution was conducted using 90% acetonitrile aqueous solution containing 5 mmol/L ammonium formate and 0.1% formic acid as mobile phase A and 10% acetonitrile aqueous solution containing 5 mmol/L ammonium formate and 0.1% formic acid as mobile phase B. Determination was performed using an electrospray ion source (ESI) in the positive ion mode. The quantitative analysis was carried out by standard addition method. The chromatographic retention performance of different chromatographic columns and the influence of different mobile phases on the separation of the organic amine compounds were compared, and the method was validated. The results showed that the linear ranges of the nine organic amine compounds were 0.04-25000 ng/mL with the linear correlation coefficients (R2) greater than 0.9910. The limits of detection (LODs) of the method were in the range of 0.0004-0.0080 ng/mL, and the limits of quantification (LOQs) of the method were in the range of 0.0035-0.0400 ng/mL. The average recoveries of the method ranged from 85.30% to 104.26% with relative standard deviations (RSDs) of 0.04%-7.95% at the spiked levels of 1, 1.5 and 3 times sample concentration. The established method was applied to detect the absorption waste liquid of a cement plant, and nine organic amine compounds could be effectively detected. The stability of the actual sample was tested, and the RSDs were 0.10%-6.35% in 48 h at 4 ℃. The method is sensitive, rapid and accurate for the determination of the nine organic amine compounds in industrial waste water. It can provide reference for the detection of organic amine compounds, and provide strong technical support for the research and industrial application of CO2 capture technology.

Environmental DNA unveiling the fish community structure and diversity features in the Yangtze River basin.

Fish, as top predators in aquatic ecosystems, play an important role in maintaining the structure and functioning of these ecosystems, making their diversity a topic of great interest. This study focused on the Yangtze River Basin to investigate the fish community structure and diversity using environmental DNA (eDNA) technology. The results showed that a total of 71616 fish operational taxonomic units (OTUs) and 90 fish belonging to 23 families were detected, with the Cyprinidae family being the dominant group, followed by the Cobitidae, Amblycipitidae, etc. Compared to historical traditional morphological fish surveys, the quantity of fish detected using eDNA was relatively low, but the overall distribution pattern of fish communities was generally consistent. The highest fish Shannon-Wiener diversity index in the Yangtze River Basin sites reaches 2.60 with an average value of 1.25. The fish diversity index was higher in the downstream compared to the middle and upstream regions, and there were significant differences among different sampling sites. Significant environmental factors influencing α-diversity included chlorophyll-a, chemical oxygen demand, dissolved oxygen, total nitrogen, and elevation. Non-metric multidimensional scaling (NMDS) analysis revealed significant differences in fish community composition between the upstream and middle/lower reaches of the Yangtze River, while the composition of fish communities in the middle and lower reaches was more similar. Redundancy analysis (RDA) indicated that total organic carbon (TOC) was positively correlated with fish community distribution in the upstream, while water temperature and NO3-N were negatively correlated with fish distribution in the upstream. NH3-N and CODMn were negatively correlated with fish distribution in the middle and downstream regions, indicating a relatively severe water pollution in these areas. Additionally, fish communities in the Yangtze River displayed a typical distance decay pattern.

CDN1163, a SERCA activator, causes intracellular Ca2+ leak, mitochondrial hyperpolarization and cell cycle arrest in mouse neuronal N2A cells.

OBJECTIVE: Activity or expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) is diminished in some disease states such as cardiac failure and diabetes mellitus. A newly developed activator of SERCA, CDN1163, reportedly rescued or alleviated pathological conditions attributed to dysfunctional SERCA. We examined whether CDN1163 could relieve mouse neuronal N2A cell growth inhibition caused by cyclopiazonic acid (CPA, SERCA inhibitor). We also examined how CDN1163 affected cytosolic Ca2+, mitochondrial Ca2+ and mitochondrial membrane potential. METHODS: Cell viability was measured by MTT assay and trypan blue exclusion test. Cytosolic Ca2+, mitochondrial Ca2+ and mitochondrial membrane potential were measured using fura 2, Rhod-2 and JC-1, respectively, as fluorescent probes. RESULTS: CDN1163 (10 µM) itself suppressed cell proliferation, and did not alleviate CPA's inhibitory effect (and vice versa). Cell cycle was arrested at the G1 phase after CDN1163 treatment. CDN1163 treatment caused a slow yet persistent cytosolic [Ca2+] elevation partly due to Ca2+ release from an internal store other than the CPA-sensitive endoplasmic reticulum (ER). Treatment with CDN1163 for 3 h raised mitochondrial Ca2+ level and such increase was suppressed by MCU-i4 (an inhibitor of mitochondria Ca2+ uniporter, MCU), suggesting Ca2+ entered the mitochondrial matrix through MCU. Treatment of cells with CDN1163 up to 2 days resulted in mitochondrial hyperpolarization. CONCLUSION: CDN1163 caused internal Ca2+ leak, cytosolic Ca2+ overload, mitochondrial Ca2+ elevation and hyperpolarization, cell cycle arrest and cell growth inhibition.

Regional versus general anesthesia in older patients for hip fracture surgery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The optimal anesthesia technique for older patients undergoing hip fracture surgery remains controversial. We performed a systematic review and meta-analysis of updated randomized controlled trials (RCTs) to assess whether regional anesthesia was superior to general anesthesia in hip fracture surgery. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from January 2000 until April 2022. RCTs directly comparing regional and general anesthesia in hip fracture surgery were included in the analysis. The incidence of delirium and mortality were the primary outcomes and other perioperative outcomes including complications were secondary outcomes. RESULTS: Thirteen studies involving 3736 patients were included in this study. There was no significant difference in the incidence of delirium (odds ratio [OR] 1.09; 95% confidence interval [CI] 0.86, 1.37) and mortality (OR 1.08; 95% CI 0.71, 1.64) between the two groups. Patients receiving regional anesthesia in hip fracture surgery were associated with a reduction in operative time (weighted mean difference [WMD]: - 4.74; 95% CI - 8.85, - 0.63), intraoperative blood loss (WMD: - 0.25; 95% CI - 0.37, - 0.12), postoperative pain score (WMD: - 1.77; 95% CI - 2.79, - 0.74), length of stay (WMD: - 0.10; 95% CI - 0.18, - 0.02), and risk of acute kidney injury (AKI) (OR 0.56; 95% CI 0.36, 0.87). No significant difference was observed in the other perioperative outcomes. CONCLUSIONS: For older patients undergoing hip fracture surgery, RA did not significantly reduce the incidence of postoperative delirium and mortality compared to GA. Due to the limitations of this study, the evidence on delirium and mortality was still inconclusive and further high-quality studies are needed.

Targeting Ca2+-dependent pathways to promote corneal epithelial wound healing induced by CISD2 deficiency.

Chronic epithelial defects of the cornea, which are usually associated with severe dry eye disease, diabetes mellitus, chemical injuries or neurotrophic keratitis, as well as aging, are an unmet clinical need. CDGSH Iron Sulfur Domain 2 (CISD2) is the causative gene for Wolfram syndrome 2 (WFS2; MIM 604928). CISD2 protein is significantly decreased in the corneal epithelium of patients with various corneal epithelial diseases. Here we summarize the most updated publications and discuss the central role of CISD2 in corneal repair, as well as providing new results describing how targeting Ca2+-dependent pathways can improve corneal epithelial regeneration. This review mainly focuses on the following topics. Firstly, an overview of the cornea and of corneal epithelial wound healing. The key players involved in this process, such as Ca2+, various growth factors/cytokines, extracellular matrix remodeling, focal adhesions and proteinases, are briefly discussed. Secondly, it is well known that CISD2 plays an essential role in corneal epithelial regeneration via the maintenance of intracellular Ca2+ homeostasis. CISD2 deficiency dysregulates cytosolic Ca2+, impairs cell proliferation and migration, decreases mitochondrial function and increases oxidative stress. As a consequence, these abnormalities bring about poor epithelial wound healing and this, in turn, will lead to persistent corneal regeneration and limbal progenitor cell exhaustion. Thirdly, CISD2 deficiency induces three distinct Ca2+-dependent pathways, namely the calcineurin, CaMKII and PKCα signaling pathways. Intriguingly, inhibition of each of the Ca2+-dependent pathways seems to reverse cytosolic Ca2+ dysregulation and restore cell migration during corneal wound healing. Notably, cyclosporin, an inhibitor of calcineurin, appears to have a dual effect on both inflammatory and corneal epithelial cells. Finally, corneal transcriptomic analyses have revealed that there are six major functional groupings of differential expression genes when CISD2 deficiency is present: (1) inflammation and cell death; (2) cell proliferation, migration and differentiation; (3) cell adhesion, junction and interaction; (4) Ca2+ homeostasis; (5) wound healing and extracellular matrix; and (6) oxidative stress and aging. This review highlights the importance of CISD2 in corneal epithelial regeneration and identifies the potential of repurposing venerable FDA-approved drugs that target Ca2+-dependent pathways for new uses, namely treating chronic epithelial defects of the cornea.