A web-based video messaging intervention for suicide prevention in men: study protocol for a five-armed randomised controlled trial.

BACKGROUND: More than 50% of people who die by suicide have not been in contact with formal mental health services. The rate of people who fly 'under the radar' of mental health services is higher among men than women, indicating a need to improve engagement strategies targeted towards men who experience suicidal thoughts and/or behaviours. In Australia, a range of mental health support services exist, designed specifically for men, yet, a substantial proportion of men do not use these services. The aim of this study is to evaluate whether a brief online video-based messaging intervention is an effective approach for encouraging men with suicidal thoughts and/or behaviours to engage with existing support services. METHODS: Informed by a literature review, surveys, and consultation with men with a lived experience of suicidal thoughts and/or behaviours, we designed five video-based messages that will be used in this five-arm randomised controlled trial. A total of 380 (76 per arm) men aged 18 years or older with suicidal thoughts who are not currently accessing formal mental health services will be recruited online and randomly assigned to watch one of the five web-based video messages. After viewing the video, men will be presented with information about four existing Australian support services, along with links to these services. The primary outcome will be help-seeking, operationalised as a click on any one of the four support service links, immediately after viewing the video. Secondary outcomes include immediate self-reported help-seeking intentions in addition to self-reported use of the support services during a 1-week follow-up period. We will also use the Discrete Choice Experiment methodology to determine what aspects of support services (e.g. low cost, short appointment wait times) are most valued by this group of men. DISCUSSION: This study is the first to evaluate the effectiveness of a brief web-based video messaging intervention for promoting engagement with existing support services among men with suicidal thoughts who are not currently receiving formal help. If found to be effective, this would represent a scalable, cost-effective approach to promote help-seeking for this at-risk population. Limitations and strengths of this study design are discussed.

Novel magnetic compression technique for the treatment of postoperative anastomotic stenosis in rectal cancer: A case report.

BACKGROUND: The treatment of postoperative anastomotic stenosis after excision of rectal cancer is challenging. Endoscopic balloon dilation and radial incision are not effective in all patients. We present a new endoscopy-assisted magnetic compression technique (MCT) for the treatment of rectal anastomotic stenosis. We successfully applied this MCT to a patient who developed an anastomotic stricture after radical resection of rectal cancer. CASE SUMMARY: A 50-year-old man had undergone laparoscopic radical rectal cancer surgery at a local hospital 5 months ago. A colonoscopy performed 2 months ago indicated that the rectal anastomosis was narrow due to which ileostomy closure could not be performed. The patient came to the Magnetic Surgery Clinic of the First Affiliated Hospital of Xi'an Jiaotong University after learning that we had successfully treated patients with colorectal stenosis using MCT. We performed endoscopy-assisted magnetic compression surgery for rectal stenosis. The magnets were removed 16 d later. A follow-up colonoscopy performed after 4 months showed good anastomotic patency, following which, ileostomy closure surgery was performed. CONCLUSION: MCT is a simple, non-invasive technique for the treatment of anastomotic stricture after radical resection of rectal cancer. The technique can be widely used in clinical settings.

Acute treatment of bilateral rTMS combined with antidepressants on the plasma fatty acids for major depressive episodes.

Bilateral repetitive transcranial magnetic stimulation (B-rTMS) has been largely used in the treatment of major depressive disorder (MDD). Nonetheless, information on the acute treatment by B-rTMS combined with antidepressants (ADs) on the plasma fatty acids in MDD is limited. The present study focused on depressive symptoms; Plasma was obtained from 27 adult patients with MDD at baselinephase (MDD), after 2 weeks of treatment (MDD-2w), and 27 healthy controls (HC). Meanwhile, we evaluated the composition of short-chain fatty acids (SCFAs) and medium-and long-chain fatty acids (MLCFAs) in the plasma. Consequently, the levels of Isobutyric acid, Caproic acid, and Propionic acid were low both in the MDD and MDD-2w groups and negatively correlated with the scores of HAMD and HAMA. Besides, minimal changes were observed between the MDD and HC groups, whereas significant MLCFA levels were high in the MDD-2w group. Moreover, we developed combined panels that could effectively differentiate MDD from HCs (AUC=0.99), MDD-2w from HC (AUC=0.983), and MDD from MDD-2w (AUC=0.852). These findings may provide a reference for the use of B-rTMS combined with ADs against the acute phase of depressive episodes and shed light on the relationship between plasma FAs and MDD.

Gut microbes on the risk of advanced adenomas.

BACKGROUND: More than 90% of colorectal cancer (CRC) arises from advanced adenomas (AA) and gut microbes are closely associated with the initiation and progression of both AA and CRC. OBJECTIVE: To analyze the characteristic microbes in AA. METHODS: Fecal samples were collected from 92 AA and 184 negative control (NC). Illumina HiSeq X sequencing platform was used for high-throughput sequencing of microbial populations. The sequencing results were annotated and compared with NCBI RefSeq database to find the microbial characteristics of AA. R-vegan package was used to analyze α diversity and ß diversity. α diversity included box diagram, and ß diversity included Principal Component Analysis (PCA), principal co-ordinates analysis (PCoA), and non-metric multidimensional scaling (NMDS). The AA risk prediction models were constructed based on six kinds of machine learning algorithms. In addition, unsupervised clustering methods were used to classify bacteria and viruses. Finally, the characteristics of bacteria and viruses in different subtypes were analyzed. RESULTS: The abundance of Prevotella sp900557255, Alistipes putredinis, and Megamonas funiformis were higher in AA, while the abundance of Lilyvirus, Felixounavirus, and Drulisvirus were also higher in AA. The Catboost based model for predicting the risk of AA has the highest accuracy (bacteria test set: 87.27%; virus test set: 83.33%). In addition, 4 subtypes (B1V1, B1V2, B2V1, and B2V2) were distinguished based on the abundance of gut bacteria and enteroviruses (EVs). Escherichia coli D, Prevotella sp900557255, CAG-180 sp000432435, Phocaeicola plebeiuA, Teseptimavirus, Svunavirus, Felixounavirus, and Jiaodavirus are the characteristic bacteria and viruses of 4 subtypes. The results of Catboost model indicated that the accuracy of prediction improved after incorporating subtypes. The accuracy of discovery sets was 100%, 96.34%, 100%, and 98.46% in 4 subtypes, respectively. CONCLUSION: Prevotella sp900557255 and Felixounavirus have high value in early warning of AA. As promising non-invasive biomarkers, gut microbes can become potential diagnostic targets for AA, and the accuracy of predicting AA can be improved by typing.

16S rRNA gene sequencing reveals altered gut microbiota in young adults with schizophrenia and prominent negative symptoms.

BACKGROUND: Gut dysbiosis has been established as a characteristic of schizophrenia (SCH). However, the signatures regarding SCH patients with prominent negative symptoms (SCH-N) in young adults have been poorly elucidated. METHODS: Stool samples were obtained from 30 young adults with SCH-N, 32 SCH patients with prominent positive symptoms (SCH-P) along with 36 healthy controls (HCs). Microbial diversity and composition were analyzed by 16S rRNA gene sequencing. Meanwhile, psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). RESULTS: There is a significant difference in ß-diversity but not α-diversity indexes among the three groups. Moreover, we found a higher abundance of Fusobacteria and Proteobacteria phyla and a lower abundance of Firmicutes phyla in SCH-N when compared with HC. Besides, we identified a diagnostic potential panel comprising six genera (Coprococcus, Monoglobus, Prevotellaceae_NK3B31_group, Escherichia-Shigella, Dorea, and Butyricicoccus) that can distinguish SCH-N from HC (area under the curve = 0.939). However, the difference in microbial composition between the SCH-N and SCH-P is much less than that between SCH-N and the HC, and SCH-N and SCH-P cannot be effectively distinguished by gut microbiota. CONCLUSION: The composition of gut microbiota was changed in the patients with SCH-N, which may help in further understanding of pathogenesis in young adults with SCH-N.

[Characteristics and drivers of vegetation temporal dynamics in Hunan Province of China during 2002-2020]. / 湖南省2002­2020å¹´æ¤è¢«åŠ¨æ€æ¼”å˜ç‰¹å¾åŠå½±å“å› å­.

Understanding the influences of climate change and human activities on vegetation change is the foundation for effective ecosystem management. Based on the 250 m MODIS-NDVI data from 2002 to 2020, we employed Theil-Sen Median trend analysis and the Mann-Kendall test to quantify vegetation change in Hunan Province. By combining with meteorological, nighttime light index, land cover and other data, residual analysis and correlation analysis, we examined the impacts of human activities and climate change on vegetation dynamics at both the pixel level and the county level. The results showed that the normalized difference vegetation index (NDVI) in Hunan Province exhibited a spatial pattern of "overall improvement with localized degradation" during 2002-2020. Approximately 64.9% of the study area experienced significant vegetation improvement, mainly occurring in the western and central-southern parts of Hunan Province. 1.4% of the study area experienced significant vegetation degradation, mostly in the newly developed urban areas and the farmland in the Dongting Lake Plain. Human activities and climate change jointly promoted vegetation improvement in 67.9% of the study area. Human activities and climate contributed to 96% and 4% of the NDVI change, respectively. At the county level, human activities contributed to over 80% of the NDVI change in each district or county. The impacts of human activities on vegetation change exhibited significant spatial heterogeneity. Urban expansion led to vegetation degradation in the newly developed areas, while vegetation growth appeared in the old developed urban areas. The ecological restoration projects promoted vegetation restoration in the western part of Hunan Province. This study could help us better understand the spatiotemporal variations of vegetation and their responses to climate change and human activities, which would offer scientific basis for effective ecological restoration policy.

Neferine inhibits BMECs pyroptosis and maintains blood-brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α.

Blood-brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine (Nef) on IS have focused on neuroprotective effect. However, whether Nef attenuates BBB disruption during IS is unclear. We here used mice underwent transient middle cerebral artery occlusion (tMCAO) in vivo and bEnd.3 cells exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro to simulate cerebral ischemia. We showed that Nef reduced neurobehavioral dysfunction and protected brain microvascular endothelial cells and BBB integrity. Molecular docking, short interfering (Si) RNA and plasmid transfection results showed us that PGC-1α was the most binding affinity of biological activity protein for Nef. And verification experiments were showed that Nef upregulated PGC-1α expression to reduce mitochondrial oxidative stress and promote TJ proteins expression, further improves the integrity of BBB in mice. Intriguingly, our study showed that neferine is a natural PGC-1α activator and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated Nef reduced mitochondria oxidative damage and ameliorates endothelial inflammation by inhibiting pyroptosis to improve BBB permeability through triggering a cascade reaction of PGC-1α via regulation of PGC-1α/NLRP3/GSDMD signaling pathway to maintain the integrity of BBB in ischemia/reperfusion injury.

Design and Preparation Technology of Green Multiple Solid Waste Cementitious Materials.

For solid waste-based cementitious materials, most scholars focus their research on the hydration reaction of cementitious materials, but there is still a lack of solid waste design that comprehensively considers mechanical properties and durability. Therefore, this article focuses on exploring the mix of design and the microscopic and macroscopic properties of multi solid waste cementitious materials (MSWCMs), namely steel slag (SS), slag powder (SP), desulfurization gypsum (DG), fly ash (FA), and ordinary Portland cement (OPC). According to the orthogonal experimental results, the compressive strength of MSWCMs is optimal when the OPC content is 50% and the SS, SP, DG, and FA contents are 10%, 20%, 5%, and 15%, respectively. The MSWCMs group with an OPC content of 50% and SS, SP, DG, and FA contents of 5%, 15%, 5%, and 25% was selected as the control group. The pure OPC group was used as the blank group, and the optimal MSWCMs ratio group had a 28-day compressive strength of 50.7 megapascals, which was 14% and 7.6% higher than the control group and blank group, respectively. The drying shrinkage rate and resistance to chloride ions were also significantly improved, with maximum increases of 22.9%, 22.6%, and 8.9%, 9.8%, respectively. According to XRD, TG-DTG, and NMR testing, the improvement in macroscopic performance can be attributed to the synergistic effect between various solid wastes. This synergistic effect produces more ettringite (AFt) and C-(A)-S-H gel. This study provides a good theoretical basis for improving the comprehensive performance of MSWCMs and is conducive to reducing the use of cement, with significant economic and environmental benefits.

Drug-Drug Interactions and Actual Harm to Hospitalized Patients: A Multicentre Study Examining the Prevalence Pre- and Post-Electronic Medication System Implementation.

INTRODUCTION: Drug-drug interactions (DDIs) have potential to cause patient harm, including lowering therapeutic efficacy. This study aimed to (i) determine the prevalence of potential DDIs (pDDIs); clinically relevant DDIs (cDDIs), that is, DDIs that could lead to patient harm, taking into account a patient's individual clinical profile, drug effects and severity of potential harmful outcome; and subsequent actual harm among hospitalized patients and (ii) examine the impact of transitioning from paper-based medication charts to electronic medication management (eMM) on DDIs and patient harms. METHODS: This was a secondary analysis of the control arm of a controlled pre-post study. Patients were randomly selected from three Australian hospitals. Retrospective chart review was conducted before and after the implementation of an eMM system, without accompanying clinical decision support alerts for DDIs. Harm was assessed by an expert panel. RESULTS: Of 1186 patient admissions, 70.1% (n = 831) experienced a pDDI, 42.6% (n = 505) a cDDI and 0.9% (n = 11) an actual harm in hospital. Of 15,860 pDDIs identified, 27.0% (n = 4285) were classified as cDDIs. The median number of pDDIs and cDDIs per 10 drugs were 6 [interquartile range (IQR) 2-13] and 0 (IQR 0-2), respectively. In cases where a cDDI was identified, both drugs were 44% less likely to be co-administered following eMM (adjusted odds ratio 0.56, 95% confidence interval 0.46-0.73). CONCLUSION: Although most patients experienced a pDDI during their hospital stay, less than one-third of pDDIs were clinically relevant. The low prevalence of harm identified raises questions about the value of incorporating DDI decision support into systems given the potential negative impacts of DDI alerts.

Qualitative study of challenges with recruitment of hospitals into a cluster controlled trial of clinical decision support in Australia.

OBJECTIVE: To identify barriers to hospital participation in controlled cluster trials of clinical decision support (CDS) and potential strategies for addressing barriers. DESIGN: Qualitative descriptive design comprising semistructured interviews. SETTING: Five hospitals in New South Wales and one hospital in Queensland, Australia. PARTICIPANTS: Senior hospital staff, including department directors, chief information officers and those working in health informatics teams. RESULTS: 20 senior hospital staff took part. Barriers to hospital-level recruitment primarily related to perceptions of risk associated with not implementing CDS as a control site. Perceived risks included reductions in patient safety, reputational risk and increased likelihood that benefits would not be achieved following electronic medical record (EMR) implementation without CDS alerts in place. Senior staff recommended clear communication of trial information to all relevant stakeholders as a key strategy for boosting hospital-level participation in trials. CONCLUSION: Hospital participation in controlled cluster trials of CDS is hindered by perceptions that adopting an EMR without CDS is risky for both patients and organisations. The improvements in safety expected to follow CDS implementation makes it challenging and counterintuitive for hospitals to implement EMR without incorporating CDS alerts for the purposes of a research trial. To counteract these barriers, clear communication regarding the evidence base and rationale for a controlled trial is needed.

Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer.

Phosphatases can dephosphorylate phosphorylated kinases, leading to their inactivation, and ferroptosis is a type of cell death. Therefore, our aim is to identify phosphatases associated with ferroptosis by analyzing the differentially expressed genes (DEGs) of the Luminal A Breast Cancer (LumABC) cohort from the Cancer Genome Atlas (TCGA). An analysis of 260 phosphatase genes from the GeneCard database revealed that out of the 28 DEGs with high expression, only the expression of pyruvate dehydrogenase phosphatase 2 (PDP2) had a significant correlation with patient survival. In addition, an analysis of DEGs using gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis revealed a significant variation in the expression of ferroptosis-related genes. To further investigate this, we analyzed 34 ferroptosis-related genes from the TCGA-LumABC cohort. The expression of long-chain acyl-CoA synthetase 4 (ACSL4) was found to have the highest correlation with the expression of PDP2, and its expression was also inversely proportional to the survival rate of patients. Western blot experiments using the MCF-7 cell line showed that the phosphorylation level of ACSL4 was significantly lower in cells transfected with the HA-PDP2 plasmid, and ferroptosis was correspondingly reduced (p < 0.001), as indicated by data from flow cytometry detection of membrane-permeability cell death stained with 7-aminoactinomycin, lipid peroxidation, and Fe2+. Immunoprecipitation experiments further revealed that the phosphorylation level of ACSL4 was only significantly reduced in cells where PDP2 and ACSL4 co-precipitated. These findings suggest that PDP2 may act as a phosphatase to dephosphorylate and inhibit the activity of ACSL4, which had been phosphorylated and activated in LumABC cells. Further experiments are needed to confirm the molecular mechanism of PDP2 inhibiting ferroptosis.

Comparison of the Medium-term Outcomes of Anterior Lumbar Discectomy and Fusion with Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Retrospective Cohort Study.

OBJECTIVE: Lumbar degenerative diseases (LDDs) with huge herniation in the left lateral recess or central canal present challenges for oblique lateral lumbar interbody fusion (OLIF) or endoscope-assisted OLIF procedures. Currently, minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is the primary approach for this issue. This study aims to provide a standardized technical description of the anterior lumbar discectomy and fusion (ALDF) and evaluate the medium-term clinical effectiveness of both ALDF and MIS-TLIF techniques. METHODS: A retrospective review was performed on LDDs who underwent ALDF and MIS-TLIF surgery from January 2018 to January 2020. The evaluation encompassed various clinical outcomes, such as the visual analogue scale (VAS) scores for back pain and leg pain (VAS-back, VAS-leg), the Oswestry disability index (ODI), the 36-item short-form health survey mental component summary (SF-36 MCS), and the physical component summary (SF-36 PCS). Additionally, radiological parameters, including disc height (DH), segmental disk angle (SDA), lumbar lordosis (LL), and cross-sectional area (CSA), were assessed. Data including radiculopathy, estimated blood loss, operation time, time of getting out of bed, fusion rate, and complications were recorded. Student's independent samples t test and Pearson's chi-square test were used to compare the differences between groups. RESULTS: In total, 47 patients were treated by ALDF and 48 patients were treated by MIS-TLIF. The ALDF group exhibited statistically significant lower estimated blood loss and earlier time of getting out of bed compared to the MIS-TLIF group (p < 0.05). The ALDF group demonstrated lower VAS-back scores and a higher remission rate of low back pain 3 years after the surgery (p < 0.05). During the entire follow-up period, the ALDF group exhibited higher increases in DH and SDA compared to the MIS-TLIF group (p < 0.05). At 6 months, the fusion rate in the ALDF group was significantly higher than in the MIS-TLIF group (p < 0.05). The comparison revealed no statistically significant differences in complication rates between the two groups (p > 0.05). CONCLUSION: The ALDF could be considered as a viable surgical alternative for the treatment of LDDs that necessitate ventral neural direct decompression. ALDF exhibited favorable medium-term outcomes in patients with LDDs, displaying advantages in facilitating expedited recovery, enhancing radiographic outcomes, and elevating the remission rate of low back pain. Although ALDF presents slightly higher complication rates compared to MIS-TLIF, it does not adversely affect clinical outcomes.

The gut microbiome from middle-aged women with depression modulates depressive-like behaviors and plasma fatty acid metabolism in female middle-aged mice.

BACKGROUND: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD). OBJECTIVE: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT). METHODS: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated. RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice. CONCLUSIONS: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.

An Analysis of Incident Reports Related to Electronic Medication Management: How They Change Over Time.

OBJECTIVE: Electronic medication management (EMM) systems have been shown to introduce new patient safety risks that were not possible, or unlikely to occur, with the use of paper charts. Our aim was to examine the factors that contribute to EMM-related incidents and how these incidents change over time with ongoing EMM use. METHODS: Incidents reported at 3 hospitals between January 1, 2010, and December 31, 2019, were extracted using a keyword search and then screened to identify EMM-related reports. Data contained in EMM-related incident reports were then classified as unsafe acts made by users and the latent conditions contributing to each incident. RESULTS: In our sample, 444 incident reports were determined to be EMM related. Commission errors were the most frequent unsafe act reported by users (n = 298), whereas workarounds were reported in only 13 reports. User latent conditions (n = 207) were described in the highest number of incident reports, followed by conditions related to the organization (n = 200) and EMM design (n = 184). Over time, user unfamiliarity with the system remained a key contributor to reported incidents. Although fewer articles to electronic transfer errors were reported over time, incident reports related to the transfer of information between different computerized systems increased as hospitals adopted more clinical information systems. CONCLUSIONS: Electronic medication management-related incidents continue to occur years after EMM implementation and are driven by design, user, and organizational conditions. Although factors contribute to reported incidents in varying degrees over time, some factors are persistent and highlight the importance of continuously improving the EMM system and its use.

The endosymbiont Serratia symbiotica improves aphid fitness by disrupting the predation strategy of ladybeetle larvae.

Aphids, the important global agricultural pests, harbor abundant resources of symbionts that can improve the host adaptability to environmental conditions, also control the interactions between host aphid and natural enemy, resulting in a significant decrease in efficiency of biological control. The facultative symbiont Serratia symbiotica has a strong symbiotic association with its aphid hosts, a relationship that is known to interfere with host-parasitoid interactions. We hypothesized that Serratia may also influence other trophic interactions by interfering with the physiology and behavior of major predators to provide host aphid defense. To test this hypothesis, we investigated the effects of Serratia on the host aphid Acyrthosiphon pisum and its predator, the ladybeetle Propylaea japonica. First, the prevalence of Serratia in different A. pisum colonies was confirmed by amplicon sequencing. We then showed that harboring Serratia improved host aphid growth and fecundity but reduced longevity. Finally, our research demonstrated that Serratia defends aphids against P. japonica by impeding the predator's development and predation capacity, and modulating its foraging behavior. Our findings reveal that facultative symbiont Serratia improves aphid fitness by disrupting the predation strategy of ladybeetle larvae, offering new insight into the interactions between aphids and their predators, and providing the basis of a new biological control strategy for aphid pests involving the targeting of endosymbionts.

Effectiveness of fall prevention interventions in residential aged care and community settings: an umbrella review.

INTRODUCTION: Preventing falls is a priority for aged care providers. Research to date has focused on fall prevention strategies in single settings (e.g., residential aged care (RAC) or community settings). However, some aged care providers deliver care, including fall prevention interventions, across RAC and community settings. We conducted an umbrella review to identify what type of fall prevention interventions had the greatest impact on falls outcomes in RAC and community settings. METHODS: Five databases were searched for systematic reviews of falls prevention randomised control trials in older adults living in the community or RAC. Data extracted included systematic review methods, population characteristics, intervention characteristics, setting details (RAC or community), and fall-related outcomes (falls, people who have had a fall, fall-related hospitalisations, and fall-related fractures). Review quality was appraised using the Assessment of Multiple Systematic Reviews-2 tool. RESULTS: One-hundred and six systematic reviews were included; 63 and 19 of these stratified results by community and RAC settings respectively, the remainder looked at both settings. The most common intervention types discussed in reviews included 'exercise' (61%, n = 65), 'multifactorial' (two or more intervention types delivered together) (26%, n = 28), and 'vitamin D' (18%, n = 19). In RAC and community settings, 'exercise' interventions demonstrated the most consistent reduction in falls and people who have had a fall compared to other intervention types. 'Multifactorial' interventions were also beneficial in both settings however demonstrated more consistent reduction in falls and people who fall in RAC settings compared to community settings. 'Vitamin D' interventions may be beneficial in community-dwelling populations but not in RAC settings. It was not possible to stratify fall-related hospitalisation and fall-related fracture outcomes by setting due to limited number of RAC-specific reviews (n = 3 and 0 respectively). CONCLUSION: 'Exercise' interventions may be the most appropriate falls prevention intervention for older adults in RAC and community settings as it is beneficial for multiple fall-related outcomes (falls, fall-related fractures, and people who have had a fall). Augmenting 'exercise' interventions to become 'multifactorial' interventions may also improve the incidence of falls in both settings.

Peroxide derivatives as SARS-CoV-2 entry inhibitors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Host cell invasion is mediated by the interaction of the viral spike protein (S) with human angiotensin-converting enzyme 2 (ACE2) through the receptor-binding domain (RBD). In this work, bio-layer interferometry (BLI) was used to screen a series of fifty-two peroxides, including aminoperoxides and bridged 1,2,4 - trioxolanes (ozonides), with the aim of identifying small molecules that interfere with the RBD-ACE2 interaction. We found that two compounds, compound 21 and 29, exhibit the activity to inhibit RBD-ACE2. They are further demonstrated to inhibit SARS-CoV-2 cell entry, as shown in pseudovirus assay and experiment with authentic SARS-CoV-2. A comprehensive in silico analysis was carried out to study the physicochemical and pharmacokinetic properties, revealing that both compounds have good physicochemical properties as well as good bioavailability. Our results highlight the potential of small molecules targeting RBD inhibitors as potential therapeutic drugs for COVID-19.

Gankyrin inhibits ferroptosis through the p53/SLC7A11/GPX4 axis in triple-negative breast cancer cells.

Gankyrin is found in high levels in triple-negative breast cancer (TNBC) and has been established to form a complex with the E3 ubiquitin ligase MDM2 and p53, resulting in the degradation of p53 in hepatocarcinoma cells. Therefore, this study sought to determine whether gankyrin could inhibit ferroptosis through this mechanism in TNBC cells. The expression of gankyrin was investigated in relation to the prognosis of TNBC using bioinformatics. Co-immunoprecipitation and GST pull-down assays were then conducted to determine the presence of a gankyrin and MDM2 complex. RT-qPCR and immunoblotting were used to examine molecules related to ferroptosis, such as gankyrin, p53, MDM2, SLC7A11, and GPX4. Additionally, cell death was evaluated using flow cytometry detection of 7-AAD and a lactate dehydrogenase release assay, as well as lipid peroxide C11-BODIPY. Results showed that the expression of gankyrin is significantly higher in TNBC tissues and cell lines, and is associated with a poor prognosis for patients. Subsequent studies revealed that inhibiting gankyrin activity triggered ferroptosis in TNBC cells. Additionally, silencing gankyrin caused an increase in the expression of the p53 protein, without altering its mRNA expression. Co-immunoprecipitation and GST pull-down experiments indicated that gankyrin and MDM2 form a complex. In mouse embryonic fibroblasts lacking both MDM2 and p53, this gankyrin/MDM2 complex was observed to ubiquitinate p53, thus raising the expression of molecules inhibited by ferroptosis, such as SLC7A11 and GPX4. Furthermore, silencing gankyrin in TNBC cells disrupted the formation of the gankyrin/MDM2 complex, hindered the degradation of p53, increased SLC7A11 expression, impeded cysteine uptake, and decreased GPX4 production. Our findings suggest that TNBC cells are able to prevent cell ferroptosis through the gankyrin/p53/SLC7A11/GPX4 signaling pathway, indicating that gankyrin may be a useful biomarker for predicting TNBC prognosis or a potential therapeutic target.

Emergency medicine education via the micro-course and flipped classroom-reform of medical education during the COVID-19 pandemic.

The "micro-course" and "flipped classroom" are emerging tools for medical education but little is known about their utility for emergency medicine teaching. The suitability of the micro-course combined with flipped classroom is investigated for delivery of an emergency medicine course in West Anhui Health Vocational College. Students from Class A and Class B of the Clinical Department of West Anhui Health Vocational College, Grade 2000, were assigned to experimental (micro-course plus flipped classroom, n = 102) and control (traditional, didactic teaching, n = 104) groups, respectively. The effectiveness of teaching was assessed by theoretical tests and questionnaires at the end of the course. Theory test results were significantly better for the experimental group than for controls (t = 3.122, P < .01). General satisfaction of students who had participated in the micro-course plus flipped classroom exceeded that of those who had received traditional teaching. Enthusiasm, efficiency, and learning facility was self-reported to be enhanced by students in the experimental group relative to controls. Use of the micro-course combined with flipped classroom successfully increased the outcome of emergency medicine teaching and may be considered as an approach to reform emergency medicine teaching in medical colleges and universities.

The Application Value of Gemstone Spectral Imaging (GSI) Combined with an 80 mm Wide-body Detector in Head-neck CTA.

OBJECTIVE: This study aims to investigate the value of gemstone spectral imaging (GSI) combined with an 80 mm wide-body detector in head-neck CTA. METHODS: Ninety patients with head-neck CTA were prospectively selected and randomly divided into a control group and a test group, with 45 patients in each group. The control group was scanned conventionally. With a tube voltage of 100 kVp and detector width of 40 mm, a 70 ml contrast agent was injected at a flow rate of 5.0 ml/s. The test group used GSI. With a tube current fixed of 445 mAs and a detector width of 80 mm, the contrast agent was injected at a flow rate of 3.5 ml/s and 0.6 ml/kg body weight, and the 55 keV virtual monoenergetic images (VMIs) were automatically reconstructed. Finally, the target vessel CT values, background noise (BN), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), subjective scores, contrast agent dose, CT dose index volume (CTDIvol), and dose length product (DLP) were recorded. The DLP was converted to the effective dose (ED). RESULTS: The target vessel CT values, BN, SNR, CNR, and subjective scores of the two groups were not statistically significant (all P > 0.05), and the image quality of both groups was the same and met the diagnostic requirements. The contrast agent dose and effective dose (ED) in the test group were approximately 44% and 26% lower than that of the control group, respectively (all P < 0.05). CONCLUSION: In head-neck CTA examination, the Revolution CT GSI combined with an 80 mm wide-body detector can reduce the contrast agent dose and radiation dose while ensuring image quality.