Assessment of resting cerebral perfusion between methamphetamine-associated psychosis and schizophrenia through arterial spin labeling MRI.

OBJECTIVE: The clinical manifestations of methamphetamine (METH)-associated psychosis (MAP) and acute paranoid schizophrenia (SCZ) are similar. This study aims to assess regional cerebral blood flow (rCBF) in individuals who use METH and in those with SCZ using the MRI arterial spin labeling (ASL) technique. METHODS: We prospectively recruited 68 participants and divided them into four groups: MAP (N = 15), SCZ (N = 13), METH users with no psychosis (MNP; N = 22), and normal healthy controls (CRL; N = 18). We measured rCBF using an MRI three-dimensional pseudo-continuous ASL sequence. Clinical variables were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS). Group-level rCBF differences were analyzed using a two-sample t-test. RESULTS: Decreased rCBF was found in the precuneus, premotor cortex, caudate nucleus, dorsolateral prefrontal cortex, and thalamus in the MNP group compared with the CRL group. The MAP group had significantly decreased rCBF in the precuneus, hippocampus, anterior insula, inferior temporal gyrus, inferior orbitofrontal gyrus, and superior occipital gyrus compared with the MNP group. Increased rCBF in the precuneus and premotor cortex was seen in the MAP group compared with the SCZ group. rCBF in the precuneus and premotor cortex significantly correlated negatively with the PANSS but correlated positively with BACS scores in the MAP and SCZ groups. CONCLUSION: METH exposure was associated with decreased rCBF in the precuneus and premotor cortex. Patients with MAP exhibited higher rCBF than those with SCZ, implying preserved insight and favorable outcomes. rCBF can therefore potentially serve as a diagnostic approach to differentiate patients with MAP from those with SCZ.

Defective recovery of QT dispersion due to no-reflow following acute interventional therapy in patients with ST-segment elevation myocardial infarction.

Background: Previous studies have suggested that adequate myocardial reperfusion after percutaneous coronary intervention (PCI) can improve the inhomogeneity of myocardial repolarization. However, it remains unclear whether no-reflow (NR) following emergency PCI involves disadvantages related to ventricular repolarization indices. The present study aimed to determine the effect of NR on QT dispersion (QTd) in patients with ST-segment elevation myocardial infarction (STEMI) and to evaluate the prognostic value of the relative reduction of QTd on ventricular arrhythmia events (VAEs). Methods: A prospective case-control study was conducted. According to the inclusion criteria, 275 patients with STEMI who underwent primary PCI treatment at the First People's Hospital of Anqing affiliated to Anhui Medical University from January 2020 to May 2023 were enrolled. According to whether NR occurred during PCI, these patients were divided into two groups: an NR group and a non-NR group. Subsequently, the QT intervals were measured before and at 12 hours after PCI. Afterward, the QTd, corrected QTd (QTcd), and the relative reduction of QTd and QTcd 12 hours pre- and postprocedure (ΔQTd-R and ΔQTcd-R, respectively) were calculated. Finally, multivariable logistic regression analysis was performed to predict the risk of VAE occurrence. Results: In the non-NR group, there was a significant decrease from baseline in postprocedure QTd (48±17 vs. 73±22 ms; P=0.009) and QTcd (54±19 vs. 80±23 ms; P=0.01); in contrast, the NR group showed no significant difference in QTd (64±20 vs. 75±23 ms; P=0.58) or QTd (70±22 vs. 82±26 ms; P=0.45). Furthermore, the ΔQTd-R and ΔQTcd-R were both lower in the NR group than in the non-NR group (P<0.05); however, the rate of VAEs was higher in the NR group than in the non-NR group (15.2% vs. 6.2%; P=0.02). The multivariable logistic regression analysis results revealed that each increase of 12% in ΔQTcd-R was an independent predictor of VAEs (odds ratio: 0.547; 95% confidence interval: 0.228-0.976). Conclusions: The NR phenomenon following primary PCI in patients with STEMI leads to the defective recovery of QTd and QTcd. Furthermore, ΔQTcd-R can be viewed as an effective indicator for evaluating the myocardial repolarization inhomogeneity, and short-term clinical outcomes.

mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer's disease in an APOE genotype-dependent manner.

Apolipoprotein ε4 (APOE4) carriers develop brain metabolic dysfunctions decades before the onset of Alzheimer's disease (AD). A goal of the study is to identify if rapamycin, an inhibitor for the mammalian target of rapamycin (mTOR) inhibitor, would enhance synaptic and mitochondrial function in asymptomatic mice with human APOE4 gene (E4FAD) before they showed metabolic deficits. A second goal is to determine whether there may be genetic-dependent responses to rapamycin when compared to mice with human APOE3 alleles (E3FAD), a neutral AD genetic risk factor. We fed asymptomatic E4FAD and E3FAD mice with control or rapamycin diets for 16 weeks from starting from 3 months of age. Neuronal mitochondrial oxidative metabolism and excitatory neurotransmission rates were measured using in vivo 1H-[13C] proton-observed carbon-edited magnetic resonance spectroscopy, and isolated mitochondrial bioenergetic measurements using Seahorse. We found that rapamycin enhanced neuronal mitochondrial function, glutamate-glutamine cycling, and TCA cycle rates in the asymptomatic E4FAD mice. In contrast, rapamycin enhances glycolysis, non-neuronal activities, and inhibitory neurotransmission of the E3FAD mice. These findings indicate that rapamycin might be able to mitigate the risk for AD by enhancing brain metabolic functions for cognitively intact APOE4 carriers, and the responses to rapamycin are varied by APOE genotypes. Consideration of precision medicine may be needed for future rapamycin therapeutics.

Changes in the epidemiology and antimicrobial resistance patterns of Streptococcus pneumoniae from pediatric community acquired pneumonia patients attended in a Chinese hospital during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic has altered the infection dynamics of numerous pathogens. This study aimed to elucidate its impact on Streptococcus pneumoniae (S. pneumoniae) infections in children with community acquired pneumonia (CAP). METHODS: A retrospective analysis was conducted in pediatric CAP patients admitted before (2018-2019) and during (2020-2022) the COVID-19 pandemic. The epidemiology and antimicrobial resistance (AMR) patterns of S. pneumoniae were compared to reveal the impact of the pandemic. RESULTS: A total of 968 S. pneumoniae-associated pediatric CAP patients were enrolled. Although the positivity rate and gender of patients were stable across both periods, the age notably increased in 2021 and 2022. Additionally, significant changes were observed in the co-infections with several pathogens and the resistance rates to certain antibiotics during the COVID-19 pandemic. The resistance rate to clindamycin and quinupristin-dalfopristin increased, whereas the resistance rate to tetracycline, trimethoprim-sulfamethoxazole, telithromycin, and proportion of multi-drug resistant isolates decreased. The number of S. pneumoniae strains and resistant isolates exhibited similar seasonal patterns in 2018 and 2019, peaking in November or December with another minor peak in March or April. During the COVID-19 pandemic, there was a sharp decrease in February 2020 and no resurgence was observed at the end of 2022. Additionally, the minor peak was absent in 2020 and shifted to other months in 2021 and 2022. CONCLUSIONS: The COVID-19 pandemic has markedly altered the infection spectrum of S. pneumoniae in pediatric CAP patients, as evidenced by shifts in the age of patients, respiratory co-infections, AMR patterns, and seasonal trends.

Factors associated with perceived cognitive function in breast cancer patients treated with chemotherapy: A multicenter cross-sectional study.

PURPOSE: This study aimed to investigate the factors associated with perceived cognitive function among breast cancer patients treated with chemotherapy in China. METHODS: The study was a multicenter cross-sectional design. Data were collected from 10 public hospitals in China between April 2022 and February 2023. A total of 741 participants completed questionnaires assessing sociodemographic and medical characteristics, perceived cognitive function, sleep quality, fatigue, anxiety, and depression. Hierarchical multiple regression analysis was used to assess the determinants of cognitive function. RESULTS: The hierarchical multiple regression model accounted for 31.5% of variation in perceived cognitive function (sociodemographic 4.5%; medical 6.6%; exercise frequency 6.6%; sleep quality 2.1%; fatigue 2.8%; anxiety combined with depression 9.0%). Education level, chemotherapy type, number of chemotherapy cycles, and cyclophosphamide drug use were significant predisposing factors of perceived cognitive function (p < 0.001). Exercising ≥3 times/week (p < 0.001) was a significant factor positively influencing perceived cognitive function, meanwhile, anxiety (p < 0.001) and depression (p < 0 0.001) were negative factors. CONCLUSION: Our findings suggest that patients with low education levels, postoperative chemotherapy, cyclophosphamide treatment, and a greater number of chemotherapy cycles need more assessment. Sedentary patients, those who have never exercised, and those with anxiety or depression all showed greater cognitive decline. By identifying susceptible populations, encouraging regular exercise, and addressing anxiety and depression, healthcare professionals can contribute significantly to prevent patients' cognitive decline throughout chemotherapy.

The third PLeuralEffusion And Symptom Evaluation (PLEASE-3) study: Bendopnoea in patients with pleural effusion.

Background: Pleural effusions often cause disabling breathlessness, however the mechanism is unknown. Patients with pleural effusions are subjected to pleural fluid drainage on a 'trial and error' basis, as symptom relief varies. This population commonly complain of bendopnoea (breathlessness on bending forward) which has not been investigated. Our pilot data found bendopnoea was significantly associated with presence of pleural effusion. The PLEASE-3 study will evaluate bendopnoea as a screening test for effusion-related breathlessness, its predictive value of symptomatic benefits from fluid drainage and explore its underlying physiological mechanism. Methods: PLEASE-3 is a multi-centre prospective study. Eligible patients are assessed at baseline (pre-drainage) and for patients undergoing drainage, up to 72 h post-procedure. Outcome measures include the prevalence of bendopnoea, its correlation with size of effusion and its predictive value of breathlessness relief after drainage. The relationship of bendopnoea with breathlessness, physiological parameters, functional capacity and diaphragmatic characteristics will be assessed. The study will recruit 200 participants. Discussion: This is the first study to investigate bendopnoea in patients with pleural effusion. It has minimal exclusion criteria to ensure that the results are generalisable. The presence and clinical significance of bendopnoea in the context of pleural effusion requires thorough investigation. The post assessment of patients undergoing pleural fluid drainage will provide insight into whether the presence of bendopnoea is able to predict clinical outcomes. Trial Registration: Name of the registry: Australia New Zealand Clinical Trial Registry Trial registration number: ACTRN12622000465752. URL of the trial registry record for this trial: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383639&isReview=true Date of registration: Registered on 24 March 2022. Funding of the trial: This study has received funding from the Sir Charles Gairdner Research Advisory Council research project grant. The study is sponsored by the Institute for Respiratory Health, a not-for-profit organisation. Name and contact information for the trial sponsor: Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands WA 6009. t‖ + 61 8 6151 0877 e‖ bi.lam@resphealth.uwa.edu.au Role of sponsor : The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript.

Distinct effects of phyllosphere and rhizosphere microbes on invader Ageratina adenophora during its early life stages.

Microbes strongly affect invasive plant growth. However, how phyllosphere and rhizosphere soil microbes distinctively affect seedling mortality and growth of invaders across ontogeny under varying soil nutrient levels remains unclear. In this study, we used the invader Ageratina adenophora to evaluate these effects. We found that higher proportions of potential pathogens were detected in core microbial taxa in leaf litter than rhizosphere soil and thus leaf inoculation had more adverse effects on seed germination and seedling survival than soil inoculation. Microbial inoculation at different growth stages altered the microbial community and functions of seedlings, and earlier inoculation had a more adverse effect on seedling survival and growth. The soil nutrient level did not affect microbe-mediated seedling growth and the relative abundance of the microbial community and functions involved in seedling growth. The effects of some microbial genera on seedling survival are distinct from those on growth. Moreover, the A. adenophora seedling-killing effects of fungal strains isolated from dead seedlings by non-sterile leaf inoculation exhibited significant phylogenetic signals, by which strains of Allophoma and Alternaria generally caused high seedling mortality. Our study stresses the essential role of A. adenophora litter microbes in population establishment by regulating seedling density and growth.

Impact of the COVID-19 pandemic on Haemophilus influenzae infections in pediatric patients hospitalized with community acquired pneumonia.

The COVID-19 pandemic has altered the infection landscape for many pathogens. This retrospective study aimed to compare Haemophilus influenzae (H. influenzae) infections in pediatric CAP patients hospitalized before (2018-2019) and during (2020-2022) the COVID-19 pandemic. We analyzed the clinical epidemiology and antimicrobial resistance (AMR) patterns of H. influenzae from a tertiary hospital in southwest China. A total of 986 pediatric CAP patients with H. influenzae-associated infections were included. Compared to 2018, the positivity rate increased in 2019 but dropped significantly in 2020. Although it rose in the following 2 years, the rate in 2022 remained significantly lower than in 2019. Patients' age during the pandemic was significantly higher than in 2018 and 2019, while gender composition remained similar across both periods. Notably, there were significant changes in co-infections with several respiratory pathogens during the pandemic. Resistance rates of H. influenzae isolates to antibiotics varied, with the highest resistance observed for ampicillin (85.9%) and the lowest for cefotaxime (0.0%). Resistance profiles to various antibiotics underwent dramatic changes during the COVID-19 pandemic. Resistance to amoxicillin-clavulanate, cefaclor, cefuroxime, trimethoprim-sulfamethoxazole, and the proportion of multi-drug resistant (MDR) isolates significantly decreased. Additionally, MDR isolates, alongside isolates resistant to specific drugs, were notably prevalent in ampicillin-resistant and ß-lactamase-positive isolates. The number of pediatric CAP patients, H. influenzae infections, and isolates resistant to certain antibiotics exhibited seasonal patterns, peaking in the winter of 2018 and 2019. During the COVID-19 pandemic, sharp decreases were observed in February 2020, and there was no resurgence in December 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection spectrum of H. influenzae in pediatric CAP patients, as evidenced by shifts in positivity rate, demographic characteristics, respiratory co-infections, AMR patterns, and seasonal trends.

Influence and mechanism of typical transition metal ions on the denitrification performance of heterotrophic nitrification-aerobic denitrification bacteria.

To investigate the inhibitory effects of various transition metal ions on nitrogen removal and their underlying mechanisms, the single and combined effects of Cu2+ Ni2+ and Zn2+ on Heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria Acinetobacter sp. TAC-1 were studied in a batch experiment system. The results revealed that increasing concentrations of Cu2+ and Ni2+ had a detrimental effect on the removal of ammonium nitrogen (NH4+-N) and total nitrogen (TN). Specifically, Cu2+ concentration of 10 mg/L, the TN degradation rate was 55.09%, compared to 77.60% in the control group. Cu2+ exhibited a pronounced inhibitory effect. In contrast, Zn2+ showed no apparent inhibitory effect on NH4+-N removal and even enhanced TN removal at lower concentrations. However, when the mixed ion concentration of Zn2++Ni2+ exceeded 5 mg/L, the removal rates of NH4+-N and TN were significantly reduced. Moreover, transition metal ions did not significantly impact the removal rates of chemical oxygen demand (COD). The inhibition model fitting results indicated that the inhibition sequence was Cu2+ > Zn2+ > Ni2+. Transcriptome analysis demonstrated that metal ions influence TAC-1 activity by modulating the expression of pivotal genes, including zinc ABC transporter substrate binding protein (znuA), ribosomal protein (rpsM), and chromosome replication initiation protein (dnaA) and DNA replication of TAC-1 under metal ion stress, leading to disruptions in transcription, translation, and cell membrane structure. Finally, a conceptual model was proposed by us to summarize the inhibition mechanism and possible response strategies of TAC-1 bacteria under metal ion stress, and to address the lack of understanding regarding the influence mechanism of TAC-1 on nitrogen removal in wastewater co-polluted by metal and ammonia nitrogen. The results provided practical guidance for the management of transition metal and ammonia nitrogen co-polluted water bodies, as well as the removal of high nitrogen.

Oxytocin infusion dose-response to maintain uterine tone in obese elective cesarean patients: a randomized controlled trial.

Background: For cesarean delivery (CD), the 90% effective dosage (ED90) of oxytocin for a first bolus has been established. It is not yet known how much oxytocin to inject into obese women undergoing elective discectomy to keep their uterine tone (UT) appropriate. We hypothesized that patients who are overweight need a greater dose of oxytocin infusion; thus, we aimed to determine how the dose-response curve for oxytocin infusion changes following an initial 1 international unit (IU) bolus in obese women undergoing elective CD. Methods: One hundred parturients with a body mass index (BMI) greater than 30 kg/m2 were randomly assigned to receive an infusion rate of 14, 18, 22, or 26 IU/h of oxytocin. When the uterine palpation is as hard as touching the forehead or tip of the nose, it is considered sufficient UT according to the criteria used by obstetricians. The median effective dose (ED50) and ED90 values were determined using probit analysis. Results: We found the ED50 and ED90 values for the infusion dose of oxytocin were around 11.0 IU/h and 19.1 IU/h, respectively. Each group had a different number of parturients who needed rescued oxytocin: 14 IU/h for six, 18 IU/h for three, one for 22 IU/h, and none for 26 IU/h. The correlation between the frequency of rescued oxytocin administration and the amount of oxytocin infusion needed to avoid uterine atony was statistically significant (p = 0.02). Conclusion: The present research showed that the most effective dosage of oxytocin infusion for obese parturients undergoing elective CD is 19.1 IU/h, following an initial loading dose of 1 IU. Patients with obesity should receive a greater dosage of prophylactic oxytocin, and further studies comparing patients with and without obesity (with higher BMI) are required. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=159951, identifier ChiCTR2200059582.

Evidence-based screening, clinical care and health education recommendations for Alaska Native peoples with prediabetes living in southcentral Alaska: findings from the Alaska EARTH follow-up study.

Pre-diabetes (pre-DM) is a strong predictor of diabetes (DM) over time. This study investigated how much of the recent increase in pre-DM identified among Alaska Native (AN) peoples living in urban southcentral Alaska may be due to changes in diagnostic methods. We used clinical and demographic data collected at baseline between 2004 and 2006 and at follow-up collected between 2015 and 2017 from the urban southcentral Alaska Education and Research Towards Health (EARTH) cohort. We used descriptive statistics and logistic regression to explore differences in demographic and clinical variables among the identified pre-DM groups. Of 388 participants in the follow-up study, 243 had A1c levels indicating pre-DM with only 20 demonstrating pre-DM also by fasting blood glucose (FBG). Current smoking was the sole predictor for pre-DM by A1c alone while abdominal obesity and elevated FBG-predicted pre-DM by A1c+FBG. No participants had an elevated FBG without an A1c elevation. A substantial portion of the rise in pre-DM found among urban southcentral AN peoples in the EARTH follow-up study was due to the addition of A1c testing. Pre-DM by A1c alone should be used to motivate behavioural changes that address modifiable risk factors, including smoking cessation, physical activity and weight management.

Living well with diabetes in Alaska.

Many people with diabetes mellitus experience minimal or no complications. Our objective was to determine the proportion of Alaska Native people who experienced four major complications or mortality and to identify factors that may be associated with these outcomes. We used records in a diabetes registry and clinical and demographic variables in our analyses. We used logistic regression and Cox Proportional Hazards models to evaluate associations of these parameters with death and complications that occurred prior to 2013. The study included 591 Alaska Native people with non-type 1 diabetes mellitus, diagnosed between 1986 and 1992. Over 60% of people in this study remained free of four major diabetes-related complications for the remainder of life or throughout the approximately 20-year study period. Lower BMI, higher age at diagnosis of diabetes, and use of at least one diabetes medication were associated with death and a composite of four complications. A majority of Alaska Native people with DM had none of four major complications over a 20-year period. Lower BMI and use of diabetes medications were associated with higher hazard for some deleterious outcomes. This suggests that goals in care of elders should be carefully individualised. In addition, we discuss several programme factors that we believe contributed to favourable outcomes.

Use of tumor markers in distinguishing lung adenocarcinoma-associated malignant pleural effusion from tuberculous pleural effusion.

BACKGROUND: The distinction between lung adenocarcinoma-associated malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) continues to pose a challenge. This study sought to assess the supplementary value of tumor markers in enabling a differential diagnosis. METHODS: Data concerning tumor markers, which included carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), neuron-specific enolase (NSE), cytokeratin19 fragment (Cyfra21-1), and squamous cell carcinoma antigen (SCCA), in both serum and pleural effusion samples, were retrospectively compiled from lung adenocarcinoma-associated MPE and TPE patients. A comparative analysis of tumor marker concentrations between the two groups was performed to assess diagnostic utility, followed by a multiple logistic regression to control for confounding variables. RESULTS: While gender, serum CA125 and SCCA, and pleural effusion SCCA manifested comparability between the groups, distinctions were noted in patient age and the concentration of other tumor markers in serum and pleural effusion, which were notably elevated in the MPE group. Multiple logistic regression demonstrated a positive association between the risk of lung adenocarcinoma-associated MPE and levels of CEA and CA153 in serum and pleural effusion, as well as Cyfra21-1 in serum (P < 0.05). The odds ratio for CEA surpassed that of CA153 and Cyfra21-1. CONCLUSIONS: CEA and CA153 in serum and pleural effusion, and Cyfra21-1 in serum emerge as biomarkers possessing supplementary diagnostic value in distinguishing lung adenocarcinoma-associated MPE from TPE. The diagnostic efficacy of CEA is superior to CA153 and Cyfra21-1. Conversely, the utility of CA125, CA724, NSE, and SCCA appears constrained.

Comparison of Mycoplasma pneumoniae infection in children admitted with community acquired pneumonia before and during the COVID-19 pandemic: a retrospective study at a tertiary hospital of southwest China.

PURPOSE: The COVID-19 pandemic has notably altered the infection dynamics of various pathogens. This study aimed to evaluate the pandemic's impact on the infection spectrum of Mycoplasma pneumoniae (M. pneumoniae) among children with community acquired pneumonia (CAP). METHODS: We enrolled pediatric CAP patients admitted to a tertiary hospital in southwest China to compare the prevalence and characteristics of M. pneumoniae infections before (2018-2019) and during (2020-2022) the COVID-19 pandemic. Detection of M. pneumoniae IgM antibodies in serum were conducted using either indirect immunofluorescence or passive agglutination methods. RESULTS: The study included 1505 M. pneumoniae-positive and 3160 M. pneumoniae-negative CAP patients. Notable findings were the higher age and frequency of pneumonia-associated symptoms in M. pneumoniae-positive patients, alongside a lower male proportion and fewer respiratory co-infections. The year 2019 saw a notable increase in M. pneumoniae infections compared to 2018, followed by a decline from 2020 to 2022. The COVID-19 pandemic period witnessed significant alterations in age distribution, male proportion, and co-infections with specific pathogens in both M. pneumoniae-positive and negative patients. The M. pneumoniae infections were predominantly seasonal, peaking in autumn and winter during 2018 and 2019. Although there was a sharp drop in February 2020, the infection still peaked in cold months of 2020 and 2021. However, the typical seasonal pattern was nearly absent in 2022. CONCLUSIONS: The COVID-19 pandemic has markedly changed the infection landscape of M. pneumoniae in pediatric CAP patients, with shifts observed in infection rates, demographic profiles, co-infections, and seasonal patterns.

Phenylbutyric acid inhibits hypoxia-induced trophoblast apoptosis and autophagy in preeclampsia via the PERK/ATF-4/CHOP pathway.

Preeclampsia (PE) is a common pregnancy complication with a high mortality rate. Abnormally activated endoplasmic reticulum stress (ERS) is believed to be responsible for the destruction of key placental cells-trophoblasts. Phenylbutyric acid (4-PBA), an ERS inhibitor, is involved in regulating the development of ERS-related diseases. At present, how 4-PBA affects trophoblasts and its mechanisms is still unclear. In this study, PE cell models were established by stimulating HTR-8/SVneo cells with hypoxia. To verify the underlying mechanisms of 4-PBA on PE, CCT020312, an activator of PERK, was also used. The results showed that 4-PBA restored hypoxia-induced trophoblast viability, inhibited HIF-1α protein expression, inflammation, and PERK/ATF-4/CHOP pathway. Hoechst 33342 staining and flow cytometry results confirmed that 4-PBA decreased hypoxia-induced apoptosis in trophoblasts. The results of the JC-1 analysis and apoptosis initiation enzyme activity assay also demonstrated that 4-PBA inhibited apoptosis related to the mitochondrial pathway. Furthermore, by detecting autophagy in trophoblasts, an increased number of autophagic vesicles, damaged mitochondria, enhanced dansylcadaverine fluorescence, enhanced levels of autophagy proteins Beclin-1, LC3II, and decreased p62 were seen in hypoxia-stimulated cells. These changes were reversed by 4-PBA. Furthermore, it was observed that CCT020312 reversed the effects of 4-PBA on the viability, apoptosis, and autophagosome number of hypoxia-induced trophoblasts. In summary, 4-PBA reduces autophagy and apoptosis via the PERK/ATF-4/CHOP pathway and mitochondrial pathway, thereby restoring the viability of hypoxic trophoblasts. These findings provide a solid evidence base for the use of 4-PBA in PE treatment and guide a new direction for improving the outcomes of patients with PE.

Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Short-term responses of soil enzyme activities and stoichiometry to litter input in Castanopsis carlesii and Cunninghamia lanceolata plantations.

Litter input triggers the secretion of soil extracellular enzymes and facilitates the release of carbon (C), nitrogen (N), and phosphorus (P) from decomposing litter. However, how soil extracellular enzyme activities were controlled by litter input with various substrates is not fully understood. We examined the activities and stoichiometry of five enzymes including ß-1,4-glucosidase, ß-D-cellobiosidase, ß-1,4-N-acetyl-glucosaminidase, leucine aminopeptidase and acidic phosphatase (AP) with and without litter input in 10-year-old Castanopsis carlesii and Cunninghamia lanceolata plantations monthly during April to August, in October, and in December 2021 by using an in situ microcosm experiment. The results showed that: 1) There was no significant effect of short-term litter input on soil enzyme activity, stoichiometry, and vector properties in C. carlesii plantation. In contrast, short-term litter input significantly increased the AP activity by 1.7% in May and decreased the enzymatic C/N ratio by 3.8% in August, and decreased enzymatic C/P and N/P ratios by 11.7% and 10.3%, respectively, in October in C. lanceolata plantation. Meanwhile, litter input increased the soil enzymatic vector angle to 53.8° in October in C. lanceolata plantations, suggesting a significant P limitation for soil microorganisms. 2) Results from partial least squares regression analyses showed that soil dissolved organic matter and microbial biomass C and N were the primary factors in explaining the responses of soil enzymatic activity to short-term litter input in both plantations. Overall, input of low-quality (high C/N) litter stimulates the secretion of soil extracellular enzymes and accelerates litter decomposition. There is a P limitation for soil microorganisms in the study area.