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Fluctuating risk of acute kidney injury-related mortality for four weeks after exposure to air pollution: A multi-country time-series study in 6 countries.
Get PDFBACKGROUND
Recent studies have reported that air pollution is related to kidney diseases. However, the global evidence on the risk of death from acute kidney injury (AKI) owing to air pollution is limited. Therefore, we investigated the association between short-term exposure to air pollution-particulate matter ≤ 2.5 μm (PM2.5), ozone (O3), and nitrogen dioxide (NO2)-and AKI-related mortality using a multi-country dataset.
METHODS
This study included 41,379 AKI-related deaths in 136 locations in six countries during 1987-2018. A novel case time-series design was applied to each air pollutant during 0-28 lag days to estimate the association between air pollution and AKI-related deaths. Moreover, we calculated AKI deaths attributable to non-compliance with the World Health Organization (WHO) air quality guidelines.
RESULTS
The relative risks (95% confidence interval) of AKI-related deaths are 1.052 (1.003, 1.103), 1.022 (0.994, 1.050), and 1.022 (0.982, 1.063) for 5, 10, and 10 µg/m3 increase in lag 0-28 days of PM2.5, warm-season O3, and NO2, respectively. The lag-distributed association showed that the risk appeared immediately on the day of exposure to air pollution, gradually decreased, and then increased again reaching the peak approximately 20 days after exposure to PM2.5 and O3. We also found that 1.9%, 6.3%, and 5.2% of AKI deaths were attributed to PM2.5, warm-season O3, and NO2 concentrations above the WHO guidelines.
CONCLUSIONS
This study provides evidence that public health policies to reduce air pollution may alleviate the burden of death from AKI and suggests the need to investigate the several pathways between air pollution and AKI death
Comparison between diaphragmatic-navigated and self-navigated coronary magnetic resonance angiography at 3T in pediatric patients with congenital coronary artery anomalies
Get PDFBackground: Coronary magnetic resonance angiography (CMRA) is being increasingly used in pediatric patients with congenital coronary artery anomalies (CAAs). However, the data on the free-breathing self-navigation technique, which has the potential to simplify the acquisition plan with a high success rate at 3T, remain scarce. This study investigated the clinical application value of self-navigated (sNAV) CMRA at 3T in pediatric patients with suspected CAAs and compared it to conventional diaphragmatic-navigated (dNAV) CMRA.
Methods: From April 2019 to March 2022, we enrolled 65 pediatric patients (38 males and 27 females; mean age 8.5±4.4 years) with suspected CAAs in this prospective study. All patients underwent both dNAV and sNAV sequences in random order with gradient recalled echo (GRE) sequence during free breathing, with 39 (20 males and 19 females; mean age 10.2±3.6 years) of them additionally undergoing coronary computed tomography angiography (CCTA) or invasive coronary angiography (ICA). We measured and compared the success rate, scan time, visual score of the 9 main coronary artery segments, vessel sharpness, and vessel length between the two sequences. The diagnostic accuracy was compared using CCTA or ICA as a reference.
Results: The success rate of sNAV-CMRA (65/65, 100%) was higher than that of dNAV-CMRA (61/65, 93.8%) (P0.050). The visual score and vessel sharpness of the right coronary artery and left anterior descending coronary artery (LAD) were significantly improved in dNAV-CMRA compared with sNAV-CMRA (all P values 0.050).
Conclusions: Our findings demonstrated that both sNAV and dNAV in CMRA provide clinical application value in pediatric patients with CAAs and have similar diagnostic performance. Although the image quality of sNAV-CMRA is slightly inferior compared to that of dNAV-CMRA, sNAV-CMRA allows for a simpler scanning procedure
The Bright and Dark Sides of a Central Bank's Financial Support to Local Banks after a Natural Disaster: Evidence from the Great Kanto Earthquake, 1923 Japan
No full textThe Great Kanto Earthquake of 1923 caused serious damage to firms and banks in Yokohama City. We explore the role of the financial support by the Bank of Japan (BoJ) through local banks in a firm's survival and recovery from the natural disaster. We find that the small- and medium-sized firms (SMEs) that had a relatively large correspondent bank with a large number of bills rediscounted by BoJ had a higher likelihood of survival but lower growth after the earthquake. Liquidity supply by the central bank for recovery from a negative shock can have both positive and negative impacts
The Theranostic Optimization of PSMA-GCK01 Does Not Compromise the Imaging Characteristics of [99mTc]Tc-PSMA-GCK01 Compared to Dedicated Diagnostic [99mTc]Tc-EDDA/HYNIC-iPSMA in Prostate Cancer.
Get PDFPURPOSE
Radiolabeled PSMA-ligands play a major role in today's nuclear medicine. Since approval of [177Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of 177Lu became bottleneck of supply due to the high demand. Recently, a theranostic PSMA-ligand, PSMA-GCK01, was developed which can be labeled either diagnostically with 99mTc or therapeutically with 188Re with both nuclides available from well-known generator systems. This novel tracer might aid to overcome aforementioned supply limitations. In this investigation, the biodistribution and general imaging characteristics of [99mTc]Tc-PSMA-GCK01 were compared with the diagnostic reference compound [99mTc]Tc-EDDA/HYNIC-iPSMA in patients with advanced stage prostate cancer. In addition, the binding of both ligands to PSMA was analyzed at the molecular level using molecular docking.
PROCEDURES
Two cohorts (n = 19 vs. n = 21) of patients with metastatic castration-resistant prostate cancer matched for age, tumor stage, and Gleason score underwent a planar gamma camera imaging with [99mTc]Tc-EDDA/HYNIC-iPSMA or [99mTc]Tc-PSMA-GCK01 prior to PSMA-ligand therapy for PSMA-phenotyping. The imaging data were retrospective analyzed for salivary gland, kidney, liver, soft tissue, and tumor uptake on a semi-automated ROI-analysis using HERMES Medical Solutions AB (HMS, Sweden).
RESULTS
The data sets were semi-automated quantified on a ROI-based analysis. The tumor-to-background presented equal results of [99mTc]Tc-PSMA-GCK01 compared to [99mTc]Tc-EDDA/HYNIC-iPSMA. The physiological PSMA-positive organs like salivary gland presented also equal uptake in counts/MBq (salivary gland median 9.48 [99mTc]Tc-PSMA-GCK01 vs. median 9.11 [99mTc]Tc-EDDA/HYNIC-iPSMA), while liver-to-kidney ratio presented a slight shift to the liver parenchyma using [99mTc]Tc-PSMA-GCK01 (0.83) compared to [99mTc]Tc-EDDA/HYNIC-iPSMA (0.55) with no statistical significance. This is in agreement with the results from the docking study revealing only a minor difference in the docking scores for both ligands.
CONCLUSIONS
The novel theranostic tracer [99mTc]Tc/[188Re]Re-PSMA-GCK01 demonstrates comparable general imaging characteristic with the reference compound [99mTc]Tc-EDDA/HYNIC-iPSMA. These results pave the way for the PSMA-targeting imaging and theranostic agents for a broader, rather low-cost, generator applied radio-ligand therapy utilization
Hyaluronic acid enhances cell migration, viability, and mineralized tissue-specific genes in cementoblasts.
Get PDFBACKGROUND/OBJECTIVES
It has been repeatedly demonstrated that cementum formation is a crucial step in periodontal regeneration. Hyaluronic acid (HA) is an important component of the extracellular matrix which regulates cells functions and cell-cell communication. Hyaluronic acid/derivatives have been used in regenerative periodontal therapy, but the cellular effects of HA are still unknown. To investigate the effects of HA on cementoblast functions, cell viability, migration, mineralization, differentiation, and mineralized tissue-associated genes and cementoblast-specific markers of the cementoblasts were tested.
MATERIALS AND METHODS
Cementoblasts (OCCM-30) were treated with various dilutions (0, 1:2, 1:4, 1:8, 1:16, 1:32, 1:64, 1:128) of HA and examined for cell viability, migration, mineralization, and gene expressions. The mRNA expressions of osteocalcin (OCN), runt-related transcription factor 2 (Runx2), bone sialoprotein (BSP), collagen type I (COL-I), alkaline phosphatase (ALP), cementum protein-1 (CEMP-1), cementum attachment protein (CAP), and small mothers against decapentaplegic (Smad) -1, 2, 3, 6, 7, β-catenin (Ctnnb1) were performed with real-time polymerase chain reaction (RT-PCR). Total RNA was isolated on days 3 and 8, and cell viability was determined using MTT assay on days 1 and 3. The cell mineralization was evaluated by von Kossa staining on day 8. Cell migration was assessed 2, 4, 6, and 24 hours following exposure to HA dilutions using an in vitro wound healing assay (0, 1:2, 1:4, 1:8).
RESULTS
At dilution of 1:2 to 1:128, HA importantly increased cell viability (p < .01). HA at a dilution of 1/2 increased wound healing rates after 4 h compared to the other dilutions and the untreated control group. Increased numbers of mineralized nodules were determined at dilutions of 1:2, 1:4, and 1:8 compared with control group. mRNA expressions of mineralized tissue marker including COL-I, BSP, RunX2, ALP, and OCN significantly improved by HA treatments compared with control group both on 3 days and on 8 days (p < .01). Smad 2, Smad 3, Smad 7, and β-catenin (Ctnnb1) mRNAs were up-regulated, while Smad1 and Smad 6 were not affected by HA administration. Additionally, HA at dilutions of 1:2, 1:4, and 1:8 remarkably enhanced CEMP-1 and CAP expressions in a dilution- and time-dependent manner (p < .01).
CONCLUSIONS
The present results have demonstrated that HA affected the expression of both mineralized tissue markers and cementoblast-specific genes. Positive effects of HA on the cementoblast functions demonstrated that HA application may play a key role in cementum regeneration
Impact of COVID-19 pandemic: increase in complicated upper respiratory tract infections requiring ENT surgery?
Get PDFPURPOSE
This study investigates the impact of the COVID-19 pandemic on complicated upper respiratory tract infections requiring surgical intervention in a tertiary referral center. The aim is to understand the consequences of pandemic-related measures and their subsequent relaxation on the incidence and characteristics of upper respiratory tract infection-related complications.
METHODS
Patients who underwent surgery as a complication of upper respiratory tract infections between December 2014 to February 2023 were included. Demographic information, surgical procedures, microbiological findings, and clinical outcomes were assessed and analyzed comparing pre-pandemic, pandemic and post-pandemic groups.
RESULTS
321 patients were enrolled, including 105 patients (32.7%) in the pediatric population. Comparison of pre-pandemic (n = 210), pandemic (n = 46) and post-pandemic periods (n = 65) revealed a statistically significant increase in complicated otologic infections requiring surgical intervention in the post-pandemic period compared to the pandemic period (p value = 0.03). No statistically significant differences in other surgical procedures or demographic parameters were observed. A statistically significant increase in urgent ear surgery in the pediatric population between the pandemic and the post-pandemic period (p value = 0.02) was observed. Beta-hemolytic group A streptococcal infections showed a statistically significant increase in the post-pandemic period compared with the pandemic period (p value = 0.02).
CONCLUSIONS
Relaxation of COVID-19-related restrictions was associated with an increase of upper respiratory tract infection-related otologic infections requiring surgical intervention with an increasing rate of beta-hemolytic group A streptococcal infections. These findings highlight the importance of considering the impact of the pandemic on upper respiratory tract infection complications and adapting management strategies accordingly
Prognostic Value of a Novel Artificial Intelligence-Based Coronary Computed Tomography Angiography-Derived Ischemia Algorithm for Patients with Suspected Coronary Artery Disease.
No full textAIMS
Coronary computed tomography angiography (CTA) imaging is used to diagnose patients with suspected coronary artery disease (CAD). A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCTischemia) aims to identify myocardial ischemia directly from CTA images and may be helpful to improve risk stratification. The aims were 1) the prognostic value of AI-QCTischemia among symptomatic patients with suspected CAD entering diagnostic imaging with coronary CTA, and 2) the prognostic value of AI-QCTischemia separately among patients with no/non-obstructive CAD (≤50% visual diameter stenosis) and obstructive CAD (>50% visual diameter stenosis).
METHODS AND RESULTS
For this cohort study, AI-QCTischemia was calculated by blinded analysts among patients with suspected CAD undergoing coronary CTA. The primary endpoint was the composite of death, myocardial infarction (MI), or unstable angina pectoris (uAP) (median follow-up 6.9 years). 1880/2271 (83%) patients were analyzable by AI-QCTischemia. Patients with an abnormal AI-QCTischemia result (n = 509/1880) vs. patients with a normal AI-QCTischemia result (n = 1371/1880) had significantly higher crude and adjusted rates of the primary endpoint (HRadj 1.96,95% CI 1.46-2.63, p < 0.001; covariates: age/sex/hypertension/diabetes/smoking/typical angina). An abnormal AI-QCTischemia result was associated with significantly higher crude and adjusted rates of the primary endpoint among patients with no/non-obstructive CAD (n = 1373/1847) (HRadj 1.81,95% CI 1.09-3.00, p = 0.022), but not among those with obstructive CAD (n = 474/1847) (HRadj 1.26,95% CI 0.75-2.12, p = 0.386) (p-interaction = 0.032).
CONCLUSION
Among patients with suspected CAD, an abnormal AI-QCTischemia result was associated with a 2-fold increased adjusted rate of long-term death, MI, or uAP. AI-QCTischemia may be useful to improve risk stratification, especially among patients with no/non-obstructive CAD on coronary CTA
Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.
Get PDFBACKGROUND
Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy.
SUMMARY
At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level.
KEY MESSAGES
The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders
Using Machine Learning to Predict the Antibacterial Activity of Ruthenium Complexes.
No full textRising antimicrobial resistance (AMR) and lack of innovation in the antibiotic pipeline necessitate novel approaches to discovering new drugs. Metal complexes have proven to be promising antimicrobial compounds, but the number of studied compounds is still low compared to the millions of organic molecules investigated so far. Lately, machine learning (ML) has emerged as a valuable tool for guiding the design of small organic molecules, potentially even in low-data scenarios. For the first time, we extend the application of ML to the discovery of metal-based medicines. Utilising 288 modularly synthesized ruthenium arene Schiff-base complexes and their antibacterial properties, a series of ML models were trained. The models perform well and are used to predict the activity of 54 new compounds. These displayed a 5.7x higher hit-rate (53.7%) against methicillin-resistant Staphylococcus aureus (MRSA) compared to the original library (9.4%), demonstrating that ML can be applied to improve the success-rates in the search of new metalloantibiotics. This work paves the way for more ambitious applications of ML in the field of metal-based drug discovery
EEG microstate D as psychosis-specific correlate in adolescents and young adults with clinical high risk for psychosis and first-episode psychosis
Get PDFResting-state electroencephalography (EEG) microstates are brief periods (60–120 ms) of quasi-stable scalp field
potentials, indicating simultaneous activity of large-scale networks. Microstates are assumed to reflect basic
neuronal information processing. A common finding in psychosis spectrum disorders is that microstates classes C
and D are altered. Whereas evidence in adults with schizophrenia is substantial, little is known about effects in
underage patients, particularly in those at clinical high risk for psychosis (CHR) and first-episode psychosis
(FEP). The present study used 74-channel EEG to investigate microstate effects in a large sample of patients with
CHR (n = 100) and FEP (n = 33), clinical controls (CC, n = 18), as well as age-matched healthy controls (HC, n =
68). Subjects span an age range from 9 to 35 years, thus, covering underage patients as well as the most
vulnerable period for the emergence of psychosis and its prodrome. Four EEG microstates classes were analyzed
(A-D). In class D, CHR and FEP patients showed a decrease compared to HC, and CHR patients also to CC. An
increase in class C was found in CHR and FEP compared to HC but not to CC. Results were independent of age
and no differences were found between the psychosis spectrum groups. The findings suggest an age-independent
decrease of microstate class D to be specific to the psychosis spectrum, whereas the increase in class C seems to
reflect unspecific psychopathology. Overall, present data strengthens the role of microstate D as potential
biomarker for psychosis, as early as in adolescence and already in CHR status
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