Regulation of Glandular Size and Phytoalexin Biosynthesis by a Negative Feedback Loop in Cotton.

Plants have evolved diverse defense mechanisms encompassing physical and chemical barriers. Cotton pigment glands are known for containing various defense metabolites, but the precise regulation of gland size to modulate defense compound levels remains enigmatic. Here, it is discovered that the VQ domain-containing protein JAVL negatively regulates pigment gland size and the biosynthesis of defense compounds, while the MYC2-like transcription factor GoPGF has the opposite effect. Notably, GoPGF directly activates the expression of JAVL, whereas JAVL suppresses GoPGF transcription, establishing a negative feedback loop that maintains the expression homeostasis between GoPGF and JAVL. Furthermore, it is observed that JAVL negatively regulates jasmonate levels by inhibiting the expression of jasmonate biosynthetic genes and interacting with GoPGF to attenuate its activation effects, thereby maintaining homeostatic regulation of jasmonate levels. The increased expression ratio of GoPGF to JAVL leads to enlarged pigment glands and elevated jasmonates and defense compounds, enhancing insect and pathogen resistance in cotton. These findings unveil a new mechanism for regulating gland size and secondary metabolites biosynthesis, providing innovative strategies for strengthening plant defense.

Impact of coordinated care on adherence to antihypertensive medicines among adults experiencing polypharmacy in Australia.

BACKGROUND: Adherence to antihypertensives is key for blood pressure control. Most people with hypertension have several comorbidities and require multiple medicines, leading to complex care pathways. Strategies for coordinating medicine use can improve adherence, but cumulative benefits of multiple strategies are unknown. METHODS: Using dispensing claims for a 10% sample of eligible Australians, we identified adult users of antihypertensives during July 2018-June 2019 who experienced polypharmacy (≥5 unique medicines). We measured medicine use reflecting coordinated medicine management in 3 months before and including first observed dispensing, including: use of simple regimens for each cardiovascular medicine; prescriber continuity; and coordination of dispensings at the pharmacy. We measured adherence (proportion of days covered) to antihypertensive medicines in the following 12 months, and used logistic regression to assess independent associations and interactions of adherence with these measures of care. RESULTS: We identified 202 708 people, of which two-thirds (66.6%) had simple cardiovascular medicine regimens (one tablet per day for each medicine), two-thirds (63.3%) were prescribed >75% of medicines from the same prescriber, and two-thirds (65.5%) filled >50% of their medicine on the same day. One-third (28.4%) of people experienced all three measures of coordinated care. Although all measures were significantly associated with higher adherence, adherence was greatest among people experiencing all three measures (odds ratio = 1.63; 95% confidence interval: 1.55-1.72). This interaction was driven primarily by effects of prescriber continuity and dispensing coordination. CONCLUSIONS: Coordinating both prescribing and dispensing of medicines can improve adherence to antihypertensives, which supports strategies consolidating both prescribing and supply of patients' medicines.

Geographic variation in sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide-1 receptor agonist use in people with type 2 diabetes in New South Wales, Australia.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and cardio-renal outcomes for people with type 2 diabetes (T2D). However, geographic and socio-economic variation in use is not well understood. METHODS: We identified 367 829 New South Wales residents aged ≥40 years who dispensed metformin in 2020 as a proxy for T2D. We estimated the prevalence of use of other glucose-lowering medicines among people with T2D and the prevalence of SGLT2i and GLP-1RA use among people using concomitant T2D therapy (i.e. metformin + another glucose-lowering medicine). We measured the prevalence by small-level geography, stratified by age group, and characterized by remoteness and socio-economic status. RESULTS: The prevalence of SGLT2i (29.7%) and GLP-1RA (8.3%) use in people with T2D aged 40-64 increased with geographic remoteness and in areas of greater socio-economic disadvantage, similar to other glucose-lowering medicines. The prevalence of SGLT2i (55.4%) and GLP-1RA (15.4%) among people using concomitant T2D therapy varied across geographic areas, with lower SGLT2i use in more disadvantaged areas and localized areas of high GLP-1RA use (2.5 times the median). Compared with people aged 40-64 years, the prevalence of SGLT2i and GLP-1RA use was lower in older age groups, but with similar patterns of variation across geographic areas. CONCLUSIONS: The prevalence of SGLT2i and GLP-1RA use varied by geography, probably reflecting a combination of system- and prescriber-level factors. Socio-economic variation in GLP-1RA use was overshadowed by localized patterns of prescribing. Continued monitoring of variation can help shape interventions to optimize use among people who would benefit the most.

A latent class analysis of family resilience and its relationship with fear of recurrence in lung cancer patients: a cross-sectional study.

PURPOSE: Family resilience helps cancer-affected families overcome challenges and may influence an individual's fear of cancer recurrence (FCR). Identifying distinct classes of family resilience among lung cancer patients is crucial for tailored interventions. This study aimed to identify latent classes of family resilience in lung cancer patients and explore their relationships with FCR. METHODS: Three hundred ten lung cancer patients from three hospitals in Fujian were recruited from June to September 2021. Clinical data were extracted from medical records, while sociodemographic details, family resilience, and FCR were self-reported. A latent class analysis was performed to identify family resilience classes. RESULTS: A 4-class solution showed the best fit. Compared to Class 1, the patients who had no comorbidities (ORs = 3.480-16.005) had an increased likelihood of belonging to Class 2 and 3, while those who were not family breadwinners (ORs = 0.118-0.176) had a decreased likelihood. Further, the patients who (1) did not lack interest/pleasure in doing things during the past 2-week period (OR = 7.057), (2) were never smokers (OR = 6.230), and (3) were urban residents (OR = 8.985) had an increased likelihood of belonging to Class 4, while those who were (1) male (OR = 0.167), (2) not the family breadwinner (OR = 0.152), and (3) had none or only one child (OR = 0.203) had a decreased likelihood of belonging to Class 4. The FCR level differed significantly among these four classes. CONCLUSION: Our study identified four distinct classes of family resilience among Chinese lung cancer patients. FCR severity decreased with increasing levels of family resilience.

Promoting Lung Cancer Screen Decision-Making and Early Detection Behaviors: A Systematic Review and Meta-analysis.

BACKGROUND: Promoting lung cancer screening (LCS) is complex. Previous studies have overlooked that LCS behaviors are stage based and thus did not identify the characteristics of LCS interventions at different screening stages. OBJECTIVE: The aims of this study were to explore the characteristics and efficacy of interventions in promoting LCS decision making and behaviors and to evaluate these interventions. METHODS: We conducted a study search from the inception of each bibliographic database to April 8, 2023. The precaution adoption process model was used to synthesize and classify the evidence. The RE-AIM framework was used to evaluate the effectiveness of LCS programs. Heterogeneity tests and meta-analysis were performed using RevMan 5.4 software. RESULTS: We included 31 studies that covered 4 LCS topics: knowledge of lung cancer, knowledge of LCS, value clarification exercises, and LCS supportive resources. Patient decision aids outperformed educational materials in improving knowledge and decision outcomes with a significant reduction in decision conflict (standardized mean difference, 0.81; 95% confidence interval, -1.15 to -0.47; P < .001). Completion rates of LCS ranged from 3.6% to 98.8%. Interventions that included screening resources outperformed interventions that used patient decision aids alone in improving LCS completion. The proportions of reported RE-AIM indicators were highest for reach (69.59%), followed by adoption (43.87%), effectiveness (36.13%), implementation (33.33%), and maintenance (9.68%). CONCLUSION: Evidence from 31 studies identified intervention characteristics and effectiveness of LCS interventions based on different stages of decision making. IMPLICATIONS FOR PRACTICE: It is crucial to develop targeted and systematic interventions based on the characteristics of each stage of LCS to maximize intervention effectiveness and reduce the burden of lung cancer.

Medicine utilization studies in Australian individual-level dispensing data: A blinded, multi-center replicated analysis.

PURPOSE: Medicine dispensing data require extensive preparation when used for research and decisions during this process may lead to results that do not replicate between independent studies. We conducted an experiment to examine the impact of these decisions on results of a study measuring discontinuation, intensification, and switching in a cohort of patients initiating metformin. METHODS: Four Australian sites independently developed a HARmonized Protocol template to Enhance Reproducibility (HARPER) protocol and executed their analyses using the Australian Pharmaceutical Benefits Scheme 10% sample dataset. Each site calculated cohort size and demographics and measured treatment events including discontinuation, switch to another diabetes medicine, and intensification (addition of another diabetes medicine). Time to event and hazard ratios for associations between cohort characteristics and each event were also calculated. Concordance was assessed by measuring deviations from the calculated median of each value across the sites. RESULTS: Good agreement was found across sites for the number of initiators (median: 53 127, range: 51 848-55 273), gender (56.9% female, range: 56.8%-57.1%) and age group. Each site employed different methods for estimating days supply and used different operational definitions for the treatment events. Consequently, poor agreement was found for incidence of discontinuation (median 55%, range: 34%-67%), switching (median 3.5%, range: 1%-7%), intensification (median 8%, range: 5%-12%), time to event estimates and hazard ratios. CONCLUSIONS: Differences in analytical decisions when deriving exposure from dispensing data affect replicability. Detailed analytical protocols, such as HARPER, are critical for transparency of operational definitions and interpretations of key study parameters.

The effects of art-making intervention on mind-body and quality of life in adults with cancer: a systematic review and meta-analysis.

PURPOSE: To investigate the effectiveness of art-making interventions on physical and psychological outcomes, as well as quality of life (QOL), in adult patients with cancer. METHODS: Seven English-language databases (PubMed, Academic Search Premier, EMBASE, CINAHL, PsycINFO, The Cochrane Library, and Web of Science) and three Chinese-language databases (CNKI, WanFang, and VIP) were searched up to and including May 1, 2023. We used the Cochrane Risk of Bias tool 2.0 and the Risk of Bias in Non-Randomized Studies-of Interventions to evaluate the certainty of evidence. The data were analyzed using Review Manager software 5.4. The study protocol was registered with PROSPERO (CRD42022321471). RESULTS: The studies predominantly focused on visual art (n = 21), two specifically used performing art (n = 2), and five integrated both forms of art-making (n = 5). The pooled results showed that art-making significantly improved anxiety (SMD = - 1.12, 95% CI [- 1.43, - 0.81], p < 0.01), depression (SMD = - 0.91, 95% CI [- 1.16, - 0.65], p < 0.01), distress (SMD = - 1.19, 95% CI [- 1.43, - 0.95], p < 0.01), psychological well-being (SMD = 0.41, 95% CI [0.02, 0.80], p = 0.04), societal well-being (SMD = 0.29, 95% CI [0.04, 0.54], p = 0.03), nausea (SMD = - 1.81, 95% CI [- 2.84, - 0.78], p < 0.01), physical well-being (SMD = 0.11, 95% CI [0.02, 0.20], p = 0.02), and QOL (SMD = 0.81, 95% CI [0.29, 1.33], p < 0.01). However, it did not significantly improve fatigue (SMD = - 0.28, 95% CI [- 0.75, 0.19], p = 0.24) and pain (SMD = - 0.18, 95% CI [- 1.97, 1.60], p = 0.84) in patients with cancer. CONCLUSIONS: Art-making interventions may boost psychological well-being, physical symptoms, and QOL among patients with cancer. More robust studies are necessary to overcome methodological limitations and promote wider adoption of these interventions. TRIAL REGISTRATION: Prospero registration number: CRD42022321471.

Graphene enhances artemisinin production in the traditional medicinal plant Artemisia annua via dynamic physiological processes and miRNA regulation.

We investigated the effects of graphene on the model herb Artemisia annua, which is renowned for producing artemisinin, a widely used pharmacological compound. Seedling growth and biomass were promoted when A. annua was cultivated with low concentrations of graphene, an effect which was attributed to a 1.4-fold increase in nitrogen uptake, a 15%-22% increase in chlorophyll fluorescence, and greater abundance of carbon cycling-related bacteria. Exposure to 10 or 20 mg/L graphene resulted in a âˆ¼60% increase in H2O2, and graphene could act as a catalyst accelerator, leading to a 9-fold increase in catalase (CAT) activity in vitro and thereby maintaining reactive oxygen species (ROS) homeostasis. Importantly, graphene exposure led to an 80% increase in the density of glandular secreting trichomes (GSTs), in which artemisinin is biosynthesized and stored. This contributed to a 5% increase in artemisinin content in mature leaves. Interestingly, expression of miR828 was reduced by both graphene and H2O2 treatments, resulting in induction of its target gene AaMYB17, a positive regulator of GST initiation. Subsequent molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA (miRNA) biogenesis through Dicers and regulates the miR828-AaMYB17 module, thus affecting GST density. Our results suggest that graphene may contribute to yield improvement in A. annua via dynamic physiological processes together with miRNA regulation, and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.

Fear of recurrence in postoperative lung cancer patients: Trajectories, influencing factors and impacts on quality of life.

AIMS: To investigate the trajectory, influencing factors and dynamic relationships between fear of cancer recurrence (FCR) and quality of life (QOL) in lung cancer patients. DESIGN: Prospective longitudinal study. METHODS: Longitudinal data from 310 lung cancer patients across three hospitals in China were assessed at 1, 3, 6 and 12 months postoperatively (T1 -T4 ). Descriptive statistics characterised patient demographics, clinical characteristics, levels of FCR and QOL. A linear mixed-effects model was employed to analyse FCR trajectories, identify influencing factors on these trajectories, and predict the impact of FCR on QOL. RESULTS: FCR changed significantly over time, with a slight decrease during T1 -T2 , an increase at T3 and gradual decline at T4 . Higher fear levels were associated with female sex, suburban or rural residency, being a family breadwinner, presence of comorbidities and negative coping behaviours, and low family resilience. QOL negatively correlated with FCR, and FCR predicted lower QOL. CONCLUSIONS: At 3 and 6 months postoperatively, lung cancer patients, especially women, suburban or rural residents, family breadwinners, those with comorbidities, negative coping behaviours and low family resilience, reported high levels of FCR. Healthcare providers should pay special attention to lung cancer patients especially during the period of 3-6 months post-surgery and offer tailored interventions to improve their QOL. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Understanding the FCR trajectories, its influencing factors and its negative impacts on QOL can guide the development of targeted interventions to reduce fear and enhance well-being in patients with cancer. IMPACT: Identifying the trajectories and influencing factors of fear of lung cancer recurrence in patients at different time points informs future research on targeted interventions to improve QOL. REPORTING METHOD: The study adhered to the guidelines outlined in the Statement on Reporting Observational Longitudinal Research.

The dyadic relationship of supportive care needs with quality of life in lung cancer survivor and spousal caregiver couples.

Objective: This study aimed to explore the dyadic interrelationships between supportive care needs (SCNs) and quality of life (QOL) among lung cancer (LC) survivors and their spousal caregivers. Methods: In this cross-sectional study, 443 dyads were recruited from three tertiary hospitals in two cities (Fuzhou and Putian) in Fujian Province, China, between May 2020 and May 2021. The study shows that participants completed a sociodemographic information sheet, the SCNs survey, and answered the Chinese version of the World Health Organization Quality of Life-BREF questionnaire by telephone. The data were analyzed using descriptive statistics and Pearson's correlations. This study used the actor-partner interdependence model (APIM) with dyad analysis to examine the effect of LC survivors and spouses unmet SCNs on QOL. Results: LC survivor's and spouse's QOL levels were influenced by the level of unmet SCNs (the actor effect). LC survivors unmet SCNs were significantly negatively associated with their spouse's QOL (the partner effect). There were no partner effects between the spouse's unmet SCNs and the LC survivor's QOL. The APIM model produced an acceptable model fit [χ2/df = 2.84 (147), comparative fit index (CFI) = 0.94, Tucker-Lewis index (TLI) = 0.93, root mean square error of approximation (RMSEA) = 0.07]. Conclusions: The level of unmet SCNs significantly affected QOL in survivor and spouse dyads. Although partner effects were weaker than actor effects, healthcare providers should develop tailored LC dyadic self- and family-management interventions to provide SCN-driven care to LC survivors and their spouses.

Single-cell RNA sequencing reveals a hierarchical transcriptional regulatory network of terpenoid biosynthesis in cotton secretory glandular cells.

Plants can synthesize a wide range of terpenoids in response to various environmental cues. However, the specific regulatory mechanisms governing terpenoid biosynthesis at the cellular level remain largely elusive. In this study, we employed single-cell RNA sequencing to comprehensively characterize the transcriptome profile of cotton leaves and established a hierarchical transcriptional network regulating cell-specific terpenoid production. We observed substantial expression levels of genes associated with the biosynthesis of both volatile terpenes (such as ß-caryophyllene and ß-myrcene) and non-volatile gossypol-type terpenoids in secretory glandular cells. Moreover, two novel transcription factors, namely GoHSFA4a and GoNAC42, are identified to function downstream of the Gossypium PIGMENT GLAND FORMATION genes. Both transcription factors could directly regulate the expression of terpenoid biosynthetic genes in secretory glandular cells in response to developmental and environmental stimuli. For convenient retrieval of the single-cell RNA sequencing data generated in this study, we developed a user-friendly web server . Our findings not only offer valuable insights into the precise regulation of terpenoid biosynthesis genes in cotton leaves but also provide potential targets for cotton breeding endeavors.

Dyadic effects of family resilience on quality of life in patients with lung cancer and spousal caregivers: The mediating role of dyadic coping.

PURPOSE: This study explored the effects of family resilience on quality of life (QOL) and examined whether dyadic coping mediates these effects in patients with lung cancer and their spousal caregivers. METHODS: In total, 313 dyads were recruited from three tertiary hospitals in Fujian Province, China, between March and July 2022. Study participants independently completed sociodemographic and clinical characteristics questionnaires, the Shortened Chinese version of the Family Resilience Assessment Scale, the Dyadic Coping Inventory, and the 8-Item Short-Form Health Survey. Data analysis utilized the actor-partner interdependence mediation model (APIMeM). RESULTS: Family resilience of both patients with lung cancer and their spouses were positively and directly associated with their own QOL, which was mediated by dyadic coping. Family resilience did not significantly influence the partners' QOL. The APIMeM model produced acceptable fit (χ2/df = 2.857, RMSEA = 0.077, CFI = 0.992, TLI = 0.941, and NFI = 0.998). CONCLUSION: Dyadic coping mediated both actor and partner effects between family resilience and QOL, and there was no significant direct partner effect between individual family resilience and their partner's QOL. The development of efficient family- or dyad-based interventions is essential to improve family resilience and encourage dyadic coping strategies among patients with lung cancer and their spousal caregivers who experience poor family resilience and low dyadic coping. Such interventions have the potential to enhance QOL for both parties.

Association between proton pump inhibitor use and neurological or psychiatric disorders: a systematic review protocol.

OBJECTIVE: The objective of this review is to examine the association between proton pump inhibitors (PPIs) and neurological and/or psychiatric disorders in adults. INTRODUCTION: The association between PPIs and neurological and/or psychiatric disorders remains unclear, despite the widespread use of the medications. A systematic review is required to investigate the risk of developing neurological and/or psychiatric disorders following the use of PPIs. INCLUSION CRITERIA: Studies including participants aged ≥18 years and using any PPIs, including participants with comorbid conditions or using other medications, will be considered for inclusion. Randomized controlled trials, quasi-experimental studies, and observational studies examining the association of neurological and/or psychiatric disorders with the use of PPIs among adults will be included. METHODS: MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL databases will be searched from inception until the present. Two authors will independently screen and review the titles, abstracts, and full texts. The methodological quality of included studies will be assessed using the JBI critical appraisal checklists. Study characteristics, populations, type and duration of PPI usage, status of existing neurological and/or psychiatric disorders, comorbidity conditions, use of other medications, identification of neurological and/or psychiatric disorders (International Classification of Diseases codes vs others), and estimation of the associated neurological and/or psychiatric disorders will be extracted. Studies will be pooled using statistical meta-analysis where available; otherwise, the findings will be presented in narrative format. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for grading the certainty of evidence will be followed. REVIEW REGISTRATION: PROSPERO CRD42022355543.

Trends in use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in Australia in the era of increased evidence of their cardiovascular benefits (2014-2022).

PURPOSE: To investigate trends in SGLT2i and GLP-1RA use in Australia in the era of increased evidence of their cardiovascular benefits. METHODS: We used national dispensing claims for a 10% random sample of Australians to estimate the number of prevalent and new users (no dispensing in the prior year) of SGLT2i or GLP-1RA per month from January 2014 to July 2022. We assessed prescriber specialty and prior use of other antidiabetic and cardiovascular medicines as a proxy for evidence of type 2 diabetes (T2D) and cardiovascular conditions, respectively. RESULTS: We found a large increase in the number of prevalent users (216-fold for SGLT2i; 11-fold for GLP-1RA); in July 2022 approximately 250,000 Australians were dispensed SGLT2i and 120,000 GLP-1RA. Most new users of SGLT2i or GLP-1RA had evidence of both T2D and cardiovascular conditions, although from 2022 onwards, approximately one in five new users of SGLT2i did not have T2D. The proportion of new users initiating SGLT2i by cardiologists increased after 2021, reaching 10.0% of initiations in July 2022. Among new users with evidence of cardiovascular conditions, empagliflozin was the most commonly prescribed SGLT2i, while dulaglutide or semaglutide was the most common GLP-1RA. CONCLUSION: SGLT2i and GLP-1RA use is increasing in Australia, particularly in populations with higher cardiovascular risk. The increased use of SGLT2i among people without evidence of T2D suggests that best-evidence medicines are adopted in Australia across specialties, aligning with new evidence and expanding indications.

Involvement of iNOS-induced reactive enteric glia cells in gastrointestinal motility disorders of postoperative Ileus mice.

Postoperative ileus (POI) is the cessation or reduction of gastrointestinal (GI) motility after surgery. Reactive enteric glial cells (EGCs) are critical for maintaining bowel function. However, the triggering mechanisms and downstream effects of reactive EGCs in POI were poorly understood. The goal of this current study was to investigate whether the inducible nitric oxide synthase (iNOS)-driven reactive EGCs participated in GI motility disorders and mechanisms underlying altered GI motility in POI. Intestinal manipulation (IM)-induced POI mice and iNOS-/- mice were used in the study. Longitudinal muscle and myenteric plexuses (LMMPs) from the distal small intestine were stained by immunofluorescence. Our results found that the GI motility disorders occurred in the IM-induced POI mice, and reactive EGCs were observed in LMMPs. Glial metabolic inhibitor gliotoxin fluorocitrate (FC) treatment or iNOS gene knockout attenuated GI motility dysfunction. In addition, we also found that FC treatment or iNOS gene knockout significantly inhibited the fluorescence intensity macrophage colony-stimulating factor (M-CSF), which reduced M2 phenotype macrophages activation in LMMPs of IM-induced POI mice. Our findings demonstrated that iNOS-driven reactive EGCs played a key role and were tightly linked to the MMs homeostasis in the POI mice. EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target.

Persistence and Adherence to Cardiovascular Medicines in Australia.

Background The burden of cardiovascular disease is increasing, with many people treated for multiple cardiovascular conditions. We examined persistence and adherence to medicines for cardiovascular disease treatment or prevention in Australia. Methods and Results Using national dispensing claims for a 10% random sample of people, we identified adults (≥18 years) initiating antihypertensives, statins, oral anticoagulants, or antiplatelets in 2018. We measured persistence to therapy using a 60-day permissible gap, and adherence using the proportion of days covered up to 3 years from initiation, and from first to last dispensing. We reported outcomes by age, sex, and cardiovascular multimedicine use. We identified 83 687 people initiating antihypertensives (n=37 941), statins (n=34 582), oral anticoagulants (n=15 435), or antiplatelets (n=7726). Around one-fifth of people discontinued therapy within 90 days, with 50% discontinuing within the first year. Although many people achieved high adherence (proportion of days covered ≥80%) within the first year, these rates were higher when measured from first to last dispensing (40.5% and 53.2% for statins; 55.6% and 80.5% for antiplatelets, respectively). Persistence was low at 3 years (17.5% antiplatelets to 37.3% anticoagulants). Persistence and adherence increased with age, with minor differences by sex. Over one-third of people had cardiovascular multimedicine use (reaching 92% among antiplatelet users): they had higher persistence and adherence than people using medicines from only 1 cardiovascular group. Conclusions Persistence to cardiovascular medicines decreases substantially following initiation, but adherence remains high while people are using therapy. Cardiovascular multimedicine use is common, and people using multiple cardiovascular medicines have higher rates of persistence and adherence.

Activation of astrocytes in the basal forebrain in mice facilitates isoflurane-induced loss of consciousness and prolongs recovery.

OBJECTIVES: General anesthesia results in a state of unconsciousness that is similar to sleep. In recent years, increasing evidence has reported that astrocytes play a crucial role in regulating sleep. However, whether astrocytes are involved in general anesthesia is unknown. METHODS: In the present study, the designer receptors exclusively activated by designer drugs (DREADDs) approach was utilized to specifically activate astrocytes in the basal forebrain (BF) and observed its effect on isoflurane anesthesia. One the other side, L-α-aminoadipic acid was used to selectively inhibit astrocytes in the BF and investigated its influence on isoflurane-induced hypnotic effect. During the anesthesia experiment, cortical electroencephalography (EEG) signals were recorded as well. RESULTS: The chemogenetic activation group had a significantly shorter isoflurane induction time, longer recovery time, and higher delta power of EEG during anesthesia maintenance and recovery periods than the control group. Inhibition of astrocytes in the BF delayed isoflurane-induced loss of consciousness, promoted recovery, decreased delta power and increased beta and gamma power during maintenance and recovery periods. CONCLUSIONS: The present study suggests that astrocytes in the BF region are involved in isoflurane anesthesia and may be a potential target for regulating the consciousness state of anesthesia.

Comparison of the Clinical Efficacy and Safety of Standard and Ultrasound-Assisted Thrombolysis for Pulmonary Embolism: A Systematic Review and Meta-Analysis.

PURPOSE: Catheter-directed therapy has been increasingly used in acute pulmonary embolism (PE). Whether ultrasound-assisted thrombolysis (USAT) is superior to standard catheter-directed thrombolysis (SCDT) remains unclear. This is a systemic review and meta-analysis of comparative trials on USAT and SCDT for PE to determine whether either modality yielded better clinical efficacy and safety. MATERIALS AND METHOD: Major databases including PubMed, Embase, Cochrane Central, and Web of Science were searched through March 16, 2023. Studies that reported outcomes of SCDT and USAT for acute PE were included. Studies reported data on therapeutic efficacy (a reduction in the right ventricle [RV]/left ventricle [LV] ratio, a reduction in the systolic pulmonary artery pressure [mm Hg], change in Miller index, length of intensive care unit [ICU] and hospital stay) and safety outcomes (in-hospital mortality, overall and major bleeding events). RESULTS: A total of 9 studies with 2610 patients were included in the meta-analysis. The analysis showed significantly greater improvement in the RV/LV ratio in the SCDT group than in the USAT group (mean difference [MD]: -0.155; 95% confidence interval [CI]: -0.249 to -0.006). No statistically significant differences were found between groups comparing change in systolic pulmonary artery pressure (MD: 0.592 mm Hg; 95% CI: -2.623 to 3.807), change in Miller index (MD: -4.1%; 95% CI: -9.5 to 1.3%), hospital stay (MD: 0.372 days; 95% CI: -0.972 to 1.717), and ICU stay (MD: -0.073.038 days; 95% CI: -1.184 to 1). No significant difference was noted in safety outcomes, including in-hospital mortality (pooled odds ratio: 0.984; 95% CI: 0.597 to 1.622), and major bleeding (pooled odds ratio: 1.162; 95% CI: 0.714 to 1.894). CONCLUSIONS: In our meta-analysis of observational and randomized studies, USAT is not superior to SCDT in patients with acute PE.INSPLAY registration number: INPLASY202240082. CLINICAL IMPACT: This study compared SCDT and USAT in patients with acute pulmonary embolism. We found no additional benefit in PA pressure change, thrombus reduction, hospital stay, mortality and major bleeding rate. Additional study using consistent treatment protocol is necessary for further investigation.