Impact of Infection Prevention Programs on Catheter-Associated Urinary Tract Infections Analyzed in Multicenter Study.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) account for a large proportion of healthcare-associated infections and have a significant impact on morbidity, length of hospital stay, and mortality. Adherence to the recommended infection prevention practices can effectively reduce the incidence of CAUTIs. This study aimed to assess the characteristics of CAUTIs and the efficacy of prevention programs across hospitals of various sizes. METHODS: Intervention programs, including training, surveillance, and monitoring, were implemented. Data on the microorganisms responsible for CAUTIs, urinary catheter utilization ratio, rate of CAUTIs per 1,000 device days, and factors associated with the use of indwelling catheters were collected from 2017 to 2019. The incidence of CAUTIs and associated data were compared between university hospitals and small- and medium-sized hospitals. RESULTS: Thirty-two hospitals participated in the study, including 21 university hospitals and 11 small- and medium-sized hospitals. The microorganisms responsible for CAUTIs and their resistance rates did not differ between the two groups. In the first quarter of 2018, the incidence rate was 2.05 infections/1,000 device-days in university hospitals and 1.44 infections/1,000 device-days in small- and medium-sized hospitals. After implementing interventions, the rate gradually decreased in the first quarter of 2019, with 1.18 infections/1,000 device-days in university hospitals and 0.79 infections/1,000 device-days in small- and medium-sized hospitals. However, by the end of the study, the infection rate increased to 1.74 infections/1,000 device-days in university hospitals and 1.80 infections/1,000 device-days in small- and medium-sized hospitals. CONCLUSION: We implemented interventions to prevent CAUTIs and evaluated their outcomes. The incidence of these infections decreased in the initial phases of the intervention when adequate support and personnel were present. The rate of these infections may be reduced by implementing active interventions such as consistent monitoring and adherence to guidelines for preventing infections.

Eucommia ulmoides Leaves Alleviate Cognitive Dysfunction in Dextran Sulfate Sodium (DSS)-Induced Colitis Mice through Regulating JNK/TLR4 Signaling Pathway.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that is characterized by systemic immune system activation. This study was performed to assess the alleviative effect of administering an aqueous extract of Eucommia ulmoides leaves (AEEL) on cognitive dysfunction in mice with dextran sulfate sodium (DSS)-induced colitis. The major bioactive compounds of AEEL were identified as a quinic acid derivative, caffeic acid-O-hexoside, and 3-O-caffeoylquinic acid using UPLC Q-TOF/MSE. AEEL administration alleviated colitis symptoms, which are bodyweight change and colon shortening. Moreover, AEEL administration protected intestinal barrier integrity by increasing the tight junction protein expression levels in colon tissues. Likewise, AEEL improved behavioral dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. Additionally, AEEL improved short-chain fatty acid (SCFA) content in the feces of DSS-induced mice. In addition, AEEL improved damaged cholinergic systems in brain tissue and damaged mitochondrial and antioxidant functions in colon and brain tissues caused by DSS. Also, AEEL protected against DSS-induced cytotoxicity and inflammation in colon and brain tissues by c-Jun N-terminal kinase (JNK) and the toll-like receptor 4 (TLR4) signaling pathway. Therefore, these results suggest that AEEL is a natural material that alleviates DSS-induced cognitive dysfunction with the modulation of gut-brain interaction.

The Plasmodium vivax MSP1P-19 is involved in binding of reticulocytes through interactions with the membrane proteins band3 and CD71.

The parasite Plasmodium vivax preferentially invades human reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region (PvMSP1P-19), has been shown to bind to reticulocytes, and this binding can be inhibited by antisera obtained by PvMSP1P-19 immunization. The molecular mechanism of interactions between PvMSP1P-19 and reticulocytes during P. vivax invasion, however, remains unclear. In this study, we analyzed the ability of MSP1P-19 to bind to different concentrations of reticulocytes and confirmed its reticulocyte preference. LC-MS analysis was used to identify two potential reticulocyte receptors, band3 and CD71, that interact with MSP1P-19. Both PvMSP1P-19 and its sister taxon Plasmodium cynomolgi MSP1P-19 were found to bind to the extracellular loop (loop 5) of band3, where the interaction of MSP1P-19 with band3 was chymotrypsin sensitive. Antibodies against band3-P5, CD71, and MSP1P-19 reduced the binding activity of PvMSP1P-19 and Plasmodium cynomolgi MSP1P-19 to reticulocytes, while MSP1P-19 proteins inhibited Plasmodium falciparum invasion in vitro in a concentration-dependent manner. To sum up, identification and characterization of the reticulocyte receptor is important for understanding the binding of reticulocytes by MSP1P-19.

[Spatial Distribution Characteristics of PM2.5 and O3 in Beijing-Tianjin-Hebei Region Based on Time Series Decomposition].

Notably, clear spatial differences occur in the distribution of air pollution among cities in the Beijing-Tianjin-Hebei (BTH) Region. Clarifying the concentration distribution of PM2.5 and O3 at different time scales is helpful to formulate scientific and effective pollution prevention and control measures. Here, the concentrations of PM2.5 and O3 were decomposed using a seasonal-trend decomposition procedure based on the loess (STL) method; their long-term, seasonal, and short-term components were obtained; and their temporal and spatial distribution characteristics were studied. The results showed that the decrease in PM2.5 concentration in the BTH Region from 2017 to 2021 was higher than that of O3. There was a positive correlation between PM2.5 and O3 concentrations in spring and summer and a negative correlation in autumn and winter. The short-term component and seasonal component had the greatest contribution to PM2.5 and O3 concentrations, respectively. There were two principal components in the seasonal and short-term components of PM2.5 and the long-term and short-term components of O3, corresponding to the central and southern part of Hebei Province and the northern part of the BTH Region. Sub-regional distribution of PM2.5 and O3 in the BTH Region at different time scales were found. Compared with that in the original series, the long-term component could better reflect the evolution trend of PM2.5 and O3 concentrations, and the standard deviation (SD) of the seasonal component and short-term component could be used to measure the fluctuation in PM2.5 and O3 concentrations in various cities. The SD of the seasonal and short-term components of the PM2.5 concentration in every city in front of Taihang Mountain was higher, and the SD of the short-term component of the O3 concentration in Tangshan was the highest.

[Source and Cause Analysis of High Concentration of Inorganic Aerosol During Two Typical Pollution Processes in Winter over Tianjin].

Inorganic aerosol is the main component of haze days in winter over Tianjin. In this study, two typical high concentrations of secondary inorganic aerosol (SIA) processes, defined as CASE1 and CASE2, were selected during polluted days in January 2020 over Tianjin, and the effects of meteorological factors, regional transport, and chemical processes were comprehensively investigated combined with observations and numerical models (WRF-NAQPMS). The average SIA concentrations in CASE1 and CASE2 were 76.8 µg·m-3 and 66.0 µg·m-3, respectively, and the nitrate concentration was higher than that of sulfate and ammonium, which were typical nitrate-dominated pollution processes. Meteorological conditions played a role in inorganic aerosol formation. The temperature of approximately -6-0℃ and 2-4℃ and the relative humidity of 50%-60% and 80%-100% would be suitable conditions for the high SIA concentration (>80 µg·m-3) in CASE1, whereas the temperature of approximately 2-4℃ and the relative humidity of 60%-70% would be suitable in CASE2. The average contribution rates of external sources to SIA in the CASE1 and CASE2 processes were 62.3% and 22.1%, which were regional transport-dominant processes and local emission-dominant processes, respectively. The contribution of the local emission of CASE1 to nitrate and sulfate was 16.2 µg·m-3 and 8.2 µg·m-3, respectively, higher than that of external sources (31.7 µg·m-3 and 8.8 µg·m-3). the local contribution of CASE2 to nitrate and sulfate was 29.3 µg·m-3 and 25.1 µg·m-3, respectively, whereas the contribution from external sources was 8.1 µg·m-3 and 9.4 µg·m-3, respectively. The quantitative result indicated that local formation and regional transport resulted in higher nitrate concentration than sulfate in CASE1, in contrast to only local sources in CASE2. The gas phase reaction was the main source of inorganic aerosol formation, contributing 48.9% and 57.8% in CASE1 and CASE2, respectively, whereas the heterogeneous reactions were also important processes, with contribution rates of 48.1% and 42.2% to SIA. The effect of aqueous phase reaction was negligible.

Exploration of the Amino Acid Metabolic Profiling and Pathway in Clonorchis sinensis-Infected Rats Revealed by the Targeted Metabolomic Analysis.

Background: Clonorchiasis remains a serious public health problem. However, the molecular mechanism underlying clonorchiasis remains largely unknown. Amino acid (AA) metabolism plays key roles in protein synthesis and energy sources, and improves immunity in pathological conditions. Therefore, this study aimed to explore the AA profiles of spleen in clonorchiasis and speculate the interaction between the host and parasite. Methods: Here targeted ultrahigh performance liquid chromatography multiple reaction monitoring mass spectrometry was applied to discover the AA profiles in spleen of rats infected with Clonorchis sinensis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (KEGG) was performed to characterize the dysregulated metabolic pathways. Results: Pathway analysis revealed that phenylalanine, tyrosine, and tryptophan biosynthesis and ß-alanine metabolism were significantly altered in clonorchiasis. There were no significant correlations between 14 significant differential AAs and interleukin (IL)-1ß. Although arginine, asparagine, histidine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine were positively correlated with IL-6, IL-10, tumor necrosis factor (TNF)-α as well as aspartate aminotransferase and alanine aminotransferase; ß-alanine and 4-hydroxyproline were negatively correlated with IL-6, IL-10, and TNF-α. Conclusion: This study reveals the dysregulation of AA metabolism in clonorchiasis and provides a useful insight of metabolic mechanisms at the molecular level.

Microbiomic association between the saliva and salivary stone in patients with sialolithiasis.

Salivary stones, known as sialoliths, form within the salivary ducts due to abnormal salivary composition and cause painful symptoms, for which surgical removal is the primary treatment. This study explored the role of the salivary microbial communities in the formation of sialoliths. We conducted a comparative analysis of microbial communities present in the saliva and salivary stones, and sequenced the 16S rRNA gene in samples obtained from patients with sialoliths and from healthy individuals. Although the diversity in the saliva was high, the essential features of the microbial environment in sialoliths were low diversity and evenness. The association of microbial abundance between stones and saliva revealed a positive correlation between Peptostreptococcus and Porphyromonas, and a negative correlation for Pseudomonas in saliva. The functional potential differences between saliva and stones Bacterial chemotaxis and the citrate cycle were negatively correlated with most genera found in salivary stone samples. However, the functions required for organic compound degradation did not differ between the saliva samples. Although some microbes were shared between the sialoliths and saliva, their compositions differed significantly. Our study presents a novel comparison between salivary stones and salivary microbiomes, suggesting potential preventive strategies against sialolithiasis.

Plasmodium yoelii surface-related antigen (PySRA) modulates the host pro-inflammatory responses via binding to CD68 on macrophage membrane.

Malaria, one of the major infectious diseases in the world, is caused by the Plasmodium parasite. Plasmodium antigens could modulate the inflammatory response by binding to macrophage membrane receptors. As an export protein on the infected erythrocyte membrane, Plasmodium surface-related antigen (SRA) participates in the erythrocyte invasion and regulates the immune response of the host. This study found that the F2 segment of P. yoelii SRA activated downstream MAPK and NF-κB signaling pathways by binding to CD68 on the surface of the macrophage membrane and regulating the inflammatory response. The anti-PySRA-F2 antibody can protect mice against P. yoelii, and the pro-inflammatory responses such as IL-1ß, TNF-α, and IL-6 after infection with P. yoelii are attenuated. These findings will be helpful for understanding the involvement of the pathogenic mechanism of malaria with the exported protein SRA.

Anti-pollutant effect of oleic acid against urban particulate matter is mediated via regulation of AhR- and TRPV1-mediated signaling in vitro.

Urban Particulate Matter (UPM) induces skin aging and inflammatory responses by regulating skin cells through the transient receptor potential vanilloid 1 (TRPV1). Although oleic acid, an unsaturated free fatty acid (FFA), has some functional activities, its effect on UPM-induced skin damage has not been elucidated. Here, we investigated signaling pathways on how oleic acid is involved in attenuating UPM induced cell damage. UPM treatment increased XRE-promoter luciferase activity and increased translocation of AhR to the nucleus, resulting in the upregulation of CYP1A1 gene. However, oleic acid treatment attenuated the UPM effects on AhR signaling. Furthermore, while UPM induced activation of TRPV1 and MAPKs signaling which activated the downstream molecules NFκB and AP-1, these effects were reduced by cotreatment with oleic acid. UPM-dependent generation of reactive oxygen species (ROS) and reduction of cellular proliferation were also attenuated by the treatment of oleic acid. These data reveal that cell damage induced by UPM treatment occurs through AhR signaling and TRPV1 activation which in turn activates ERK and JNK, ultimately inducing NFκB and AP-1 activation. These effects were reduced by the cotreatment of oleic acid on HaCaT cells. These suggest that oleic acid reduces UPM-induced cell damage through inhibiting both the AhR signaling and activation of TRPV1 and its downstream molecules, leading to a reduction of pro-inflammatory cytokine and recovery of cell proliferation.

Hepatoprotective Effect of Allium ochotense Extracts on Chronic Alcohol-Induced Fatty Liver and Hepatic Inflammation in C57BL/6 Mice.

This study was performed to investigate the protective effects of Allium ochotense on fatty liver and hepatitis in chronic alcohol-induced hepatotoxicity. The physiological compounds of a mixture of aqueous and 60% ethanol (2:8, w/w) extracts of A. ochotense (EA) were identified as kestose, raffinose, kaempferol and quercetin glucoside, and kaempferol di-glucoside by UPLC Q-TOF MSE. The EA regulated the levels of lipid metabolism-related biomarkers such as total cholesterol, triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)-cholesterol in serum. Also, EA ameliorated the levels of liver toxicity-related biomarkers such as glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and total bilirubin in serum. EA improved the antioxidant system by reducing malondialdehyde contents and increasing superoxide dismutase (SOD) levels and reduced glutathione content. EA improved the alcohol metabolizing enzymes such as alcohol dehydrogenase, acetaldehyde dehydrogenase, and cytochrome P450 2E1 (CYP2E1). Treatment with EA alleviated lipid accumulation-related protein expression by improving phosphorylation of AMP-activated protein kinase (p-AMPK) expression levels. Especially, EA reduced inflammatory response by regulating the toll-like receptor-4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR-4/NF-κB) signaling pathway. EA showed an anti-apoptotic effect by regulating the expression levels of B-cell lymphoma 2 (BCl-2), BCl-2-associated X protein (BAX), and caspase 3. Treatment with EA also ameliorated liver fibrosis via inhibition of transforming growth factor-beta 1/suppressor of mothers against decapentaplegic (TGF-ß1/Smad) pathway and alpha-smooth muscle actin (α-SMA). Therefore, these results suggest that EA might be a potential prophylactic agent for the treatment of alcoholic liver disease.

A descriptive study of stroke types, risk factors, clinical features, and outcomes in a tertiary hospital in Myanmar.

BACKGROUND: Stroke is a leading cause of death in the world, and the burden of stroke is higher in low- and middle-income countries. Understanding the risk factors, complications, and outcomes of stroke are useful for healthcare planning and resource allocation. Little information on stroke is available for many low- and middle-income Asian countries; including Myanmar, which is the focus of this study. METHODS: A review was conducted of medical records for stroke admissions during 2017 in a tertiary hospital in Myanmar. The final diagnoses, risk factors, clinical features, complications, and outcomes were systematically collected from computer- and paper-based medical records. RESULTS: Of 908 cases analysed, haemorrhagic stroke was the most common type (49%), followed by ischaemic stroke (43%). Unimproved cases were 32%. Identified risk factors of unimproved cases were 'haemorrhagic stroke' [adjusted odds ratio (aOR): 1.73], 'having fever during hospitalization' [aOR: 2.49], 'Glasgow Coma Scale (GCS) at the admission between 9 and 14' [aOR: 4.33], and GCS less than 9 [aOR: 42.86]. CONCLUSION: This study is based on hospital medical records to assess stroke types, risk factors, clinical features, and outcomes in a tertiary hospital, in Nay Pyi Daw, Myanmar. The findings indicated that early case admission, improved hospital care management, and increased awareness of the modifiable risk factors within populations are crucial for preventing stroke incidents.

Evaluation of the Ejection Pressure for Tracking Internal Cracks during Compaction in Bilayer Tablet Formulations Using Experimental and Finite Element Methods.

This study aimed to evaluate the ejection pressure and the correlation of the findings with the occurrence of internal cracks within bilayer tablets (BLTs) consisting of metformin HCl (MF) and evogliptin tartrate (EG). Then, the mechanism of tablet failure was provided by the finite element method (FEM). The ejection pressure and the difference in diameter depending on MAIN-P were evaluated to understand the correlation between ejection pressure and change in the BLT internal structure. The ejection pressure and the difference in diameter increased as the MAIN-P increased, then steeply decreased from 350 MPa to 375 MPa of MAIN-P, despite there being no pattern in compaction breaking force and porosity. The mechanical integrity at the BLT interface was weakened by internal cracks, reducing ejection pressure. The stress distribution analysis during the compression revealed that crack formation caused by entrapped air located at the center of the BLT interface may not propagate due to concentrated stress, which promotes a tight bond at the edge of the BLT. Furthermore, complete delamination can occur in the ejection process due to localized and intensive shear stresses at the BLT interface. These findings indicate that the mechanisms of internal cracking and delamination were successfully confirmed by FEM simulation. Moreover, measuring ejection pressure before BLT manufacturing can prevent invisible tablet cracks without damaging the tablets.

Associations of trajectories in body roundness index with incident cardiovascular disease: a prospective cohort study in rural China.

Aims: The body roundness index (BRI) has good predictive ability for both body fat and visceral adipose tissue. Longitudinal BRI trajectories can reveal the potential dynamic patterns of change over time. This prospective study assessed potential associations between BRI trajectories and incident cardiovascular disease (CVD) in rural regions of Northeast China. Methods: In total, 13,209 participants (mean age: 49.0 ± 10.3 years, 6,856 [51.9%] male) were enrolled with three repeated times of BRI measurements at baseline (2004-2006), 2008, and 2010, and followed up until 2017 in this prospective study. Using latent mixture model, the BRI trajectories were determined based on the data from baseline, 2008 and 2010. Composite CVD events (myocardial infarction, stroke, and CVD death combined) was the primary endpoint. Cox proportional-hazards models were used to analyze the longitudinal associations between BRI trajectories and incident CVD. Results: Three distinct BRI trajectories were identified: high-stable (n = 538), moderate-stable (n = 1,542), and low-stable (n = 11,129). In total, 1,382 CVD events were recorded during follow-up. After adjustment for confounders, the moderate-stable and high-stable BRI groups had a higher CVD risk than did the low-stable BRI group, and the HR (95%CI) were 1.346 (1.154, 1.571) and 1.751 (1.398, 2.194), respectively. Similar associations were observed between the trajectories of BRI and the risk of stroke and CVD death. The high-stable group was also significantly and independently associated with CVD, myocardial infarction, stroke, and CVD death in participants aged <50 years. Conclusion: BRI trajectory was positively associated with incident CVD, providing a novel possibility for the primary prevention of CVD in rural regions of China.

Fermented Protaetia brevitarsis Larvae Improves Neurotoxicity in Chronic Ethanol-Induced-Dementia Mice via Suppressing AKT and NF-κB Signaling Pathway.

This study was investigated to examine the neuroprotective effect of fermented Protaetia brevitarsis larvae (FPB) in ethanol-induced-dementia mice. Consumption of FPB by mice resulted in improved memory dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. FPB significantly decreased oxidative stress by regulating levels of malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) in brain tissues. In addition, FPB restored cerebral mitochondrial dysfunction by modulating levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP. In addition, FPB enhanced the cholinergic system via the regulation of acetylcholine (ACh) content, acetylcholinesterase (AChE) activity, and expressions of AChE and choline acetyltransferase (ChAT) in brain tissues. FPB ameliorated neuronal apoptosis through modulation of the protein kinase B (AKT)/B-cell lymphoma (BCL)-2 signaling pathway. Also, FPB improved inflammation response by down-regulating the toll-like receptor (TLR)-4/nuclear factor (NF)-κB pathway. Additionally, FPB ameliorated synaptic plasticity via the increase of the expressions of synaptophysin (SYP), postsynaptic density protein (PSD)-95, and growth-associated protein (GAP)-43. Treatment with FPB also reinforced the blood-brain barrier by increasing tight junctions including zonula occludens (ZO)-1, occludin, and claudin-1. In conclusion, these results show that FPB can improve cognitive impairment via AKT/NF-κB pathways in ethanol-induced-dementia mice.

Antibiotic prophylaxis for leptospirosis.

BACKGROUND: Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in particular in travellers and high-risk groups. However, the clinical benefits are unknown, especially when considering possible treatment-associated adverse effects. This review assesses the use of antibiotic prophylaxis in leptospirosis and is an update of a previously published review in the Cochrane Library (2009, Issue 3). OBJECTIVES: To evaluate the benefits and harms of antibiotic prophylaxis for human leptospirosis. SEARCH METHODS: We identified randomised clinical trials through electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and other resources. We searched online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The last date of search was 17 April 2023. SELECTION CRITERIA: We included ⁠⁠randomised clinical trials of any trial design, assessing antibiotics for prevention of leptospirosis, and with no restrictions on age, sex, occupation, or comorbidity of trial participants. We looked for trials assessing antibiotics irrespective of route of administration, dosage, and schedule versus placebo or no intervention. We also included trials assessing antibiotics versus other antibiotics using these criteria, or the same antibiotic but with another dose or schedule. DATA COLLECTION AND ANALYSIS: We followed Cochrane methodology. The primary outcomes were all-cause mortality, laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases), clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation, clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases), and serious adverse events. The secondary outcomes were quality of life and the proportion of people with non-serious adverse events. We assessed the risk of bias of the included trials using the RoB 2 tool and the certainty of evidence using GRADE. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD), with their 95% confidence intervals (CI). We used a random-effects model for our main analyses and the fixed-effect model for sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up. MAIN RESULTS: We identified five randomised clinical trials comprising 2593 participants that compared antibiotics (doxycycline, azithromycin, or penicillin) with placebo, or one antibiotic compared with another. Four trials assessed doxycycline with different durations, one trial assessed azithromycin, and one trial assessed penicillin. One trial had three intervention groups: doxycycline, azithromycin, and placebo. Three trials assessed pre-exposure prophylaxis, one trial assessed postexposure prophylaxis, and one did not report this clearly. Four trials recruited residents in endemic areas, and one trial recruited soldiers who experienced limited time exposure. The participants' ages in the included trials were 10 to 80 years. Follow-up ranged from one to three months. Antibiotics versus placebo Doxycycline compared with placebo may result in little to no difference in all-cause mortality (RR 0.15, 95% CI 0.01 to 2.83; 1 trial, 782 participants; low-certainty evidence). Prophylactic antibiotics may have little to no effect on laboratory-confirmed leptospirosis, but the evidence is very uncertain (RR 0.56, 95% CI 0.25 to 1.26; 5 trials, 2593 participants; very low-certainty evidence). Antibiotics may result in little to no difference in the clinical diagnosis of leptospirosis regardless of laboratory confirmation (RR 0.76, 95% CI 0.53 to 1.08; 4 trials, 1653 participants; low-certainty evidence) and the clinical diagnosis of leptospirosis with laboratory confirmation (RR 0.57, 95% CI 0.26 to 1.26; 4 trials, 1653 participants; low-certainty evidence). Antibiotics compared with placebo may increase non-serious adverse events, but the evidence is very uncertain (RR 10.13, 95% CI 2.40 to 42.71; 3 trials, 1909 participants; very low-certainty evidence). One antibiotic versus another antibiotic One trial assessed doxycycline versus azithromycin but did not report mortality. Compared to azithromycin, doxycycline may have little to no effect on laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (RR 1.49, 95% CI 0.51 to 4.32; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), and on non-serious adverse events (RR 1.12, 95% CI 0.36 to 3.48; 1 trial, 137 participants), but the evidence is very uncertain. The certainty of evidence for all the outcomes was very low. None of the five included trials reported serious adverse events or assessed quality of life. One study is awaiting classification. Funding Four of the five trials included statements disclosing their funding/supporting sources, and the remaining trial did not include this. Three of the four trials that disclosed their supporting sources received the supply of trial drugs directly from the same pharmaceutical company, and the remaining trial received financial support from a governmental source. AUTHORS' CONCLUSIONS: We do not know if antibiotics versus placebo or another antibiotic has little or have no effect on all-cause mortality or leptospirosis infection because the certainty of evidence is low or very low. We do not know if antibiotics versus placebo may increase the overall risk of non-serious adverse events because of very low-certainty evidence. We lack definitive rigorous data from randomised trials to support the use of antibiotics for the prophylaxis of leptospirosis infection. We lack trials reporting data on clinically relevant outcomes.

Antibiotics for treatment of leptospirosis.

BACKGROUND: Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review. OBJECTIVES: To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis. SEARCH METHODS: We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023. SELECTION CRITERIA: We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported. DATA COLLECTION AND ANALYSIS: During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period. MAIN RESULTS: We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I2 = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I2 = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I2 = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies. AUTHORS' CONCLUSIONS: As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation.

Sodium butyrate ameliorates high glucose-suppressed neuronal mitophagy by restoring PRKN expression via inhibiting the RELA-HDAC8 complex.

Damaged mitochondria accumulation in diabetes is one of the main features that contribute to increased incidence of cognitive impairment by inducing apoptosis. Butyrate is a major metabolite produced by microbiota that has neuroprotective effects by regulating mitochondrial function. However, detailed mechanisms underlying how butyrate can regulate neuronal mitophagy remain unclear. Here, we examined the regulatory effects of sodium butyrate (NaB) on high glucose-induced mitophagy dysregulation, neuronal apoptosis, and cognitive impairment and its underlying mechanisms in human-induced pluripotent stem cell-derived neurons, SH-SY5Ys, and streptozotocin (STZ)-induced diabetic mice. In our results, diabetic mice showed gut-microbiota dysbiosis, especially a decreased number of butyrate-producing bacteria and reduced NaB plasma concentration. NaB ameliorated high glucose-induced neuronal mitochondrial dysfunction by recovering PRKN/Parkin-mediated mitophagy. High glucose-induced reactive oxygen species (ROS) and -inhibited PRKAA/AMPKα stimulated the RELA/p65-HDAC8 complex, which downregulated PRKN protein expression by binding to the PRKN promoter region. NaB restored PRKN expression by blocking RELA nuclear translocation and directly inhibiting HDAC8 in the nucleus. In addition, HDAC8 overexpression inhibited the positive effect of NaB on high glucose-induced mitophagy dysfunction and neuronal apoptosis. Oral administration of NaB improved cognitive impairment in diabetic mice by restoring mitophagy in the hippocampus. Taken together, NaB ameliorates neuronal mitophagy through PRKN restoration by inhibiting RELA-HDAC8 complexes, suggesting that NaB is an important substance for protecting neuronal apoptosis in diabetes-associated cognitive impairment.

Simultaneous Detection of Exosomal microRNAs Isolated from Cancer Cells Using Surface Acoustic Wave Sensor Array with High Sensitivity and Reproducibility.

We present a surface acoustic wave (SAW) sensor array for microRNA (miRNA) detection that utilizes photocatalytic silver staining on titanium dioxide (TiO2) nanoparticles as a signal enhancement technique for high sensitivity with an internal reference sensor for high reproducibility. A sandwich hybridization was performed on working sensors of the SAW sensor array that could simultaneously capture and detect three miRNAs (miRNA-21, miRNA-106b, and miRNA-155) known to be upregulated in cancer. Sensor responses due to signal amplification varied depending on the concentration of synthetic miRNAs. It was confirmed that normalization (a ratio of working sensor response to reference sensor response) screened out background interferences by manipulating data and minimized non-uniformity in the photocatalytic silver staining step by suppressing disturbances to both working sensor signal and reference sensor signal. Finally, we were able to successfully detect target miRNAs in cancer cell-derived exosomal miRNAs with performance comparable to the detection of synthetic miRNAs.

Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression.

BACKGROUND/AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. METHODS: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. RESULTS: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. CONCLUSION: We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Long-term Recordings of Arcuate Nucleus Kisspeptin Neurons Across the Mouse Estrous Cycle.

The arcuate nucleus kisspeptin (ARNKISS) neurons represent the GnRH pulse generator that likely drives pulsatile gonadotropin secretion in all mammals. Using an improved GCaMP fiber photometry system enabling long-term continuous recordings, we aimed to establish a definitive profile of ARNKISS neuronal activity across the murine estrous cycle. As noted previously, a substantial reduction in the frequency of ARNKISS neuron synchronization events (SEs) occurs on late proestrus and extends into estrus. The SE amplitude remains constant throughout the cycle. During metestrus, we unexpectedly detected many multipeak SEs where many SEs occurred rapidly, within 160 seconds of each other. By applying a machine learning-based, k-means clustering analysis, we were further able to detect substantial within-stage variability in the patterns of pulse generator activity. Estrous cycle-dependent changes in SE activity occurred around the time of lights on and off. We also find that a mild stressor such as vaginal lavage reduces ARNKISS neuron SE frequency for up to 3 hours. These observations provide a comprehensive account of ARNKISS neuron activity across the estrous cycle, highlight a new pattern of multipeak SE activity, and introduce a new k-means clustering approach for analyzing ARNKISS neuron population behavior.