Abstract This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer ...drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967–2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC 0.25 : 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy.
Alzheimer’s disease (AD), a common form of dementia, is caused in part by the aggregation and accumulation in the brain of amyloid β (Aβ), a product of the proteolytic cleavage of amyloid precursor ...protein (APP) in endosomes. Trafficking of APP, such as surface-intracellular recycling, is an early critical step required for Aβ generation. Less is known, however, about the molecular mechanism regulating APP trafficking. This study investigated the mechanism by which SPIN90, along with Rab11, modulates APP trafficking, Aβ motility and accumulation, and synaptic functionality. Brain Aβ deposition was lower in the progeny of 5xFAD-SPIN90KO mice than in 5xFAD-SPIN90WT mice. Analysis of APP distribution and trafficking showed that the surface fraction of APP was locally distinct in axons and dendrites, with these distributions differing significantly in 5xFAD-SPIN90WT and 5xFAD-SPIN90KO mice, and that neural activity-driven APP trafficking to the surface and intracellular recycling were more actively mobilized in 5xFAD-SPIN90KO neurons. In addition, SPIN90 was found to be cotrafficked with APP via axons, with ablation of SPIN90 reducing the intracellular accumulation of APP in axons. Finally, synaptic transmission was restored over time in 5xFAD-SPIN90KO but not in 5xFAD-SPIN90WT neurons, suggesting SPIN90 is implicated in Aβ production through the regulation of APP trafficking.
Legionella pneumophila is the cause of Legionnaires' disease, a life-threatening pneumonia that occurs after inhalation of aerosolized water containing the bacteria. Legionella growth occurs in ...stagnant, warm-to-hot water (77°F-113°F) that is inadequately disinfected. Piped hot spring water in Hot Springs National Park, Arkansas, USA, has naturally high temperatures (>135°F) that prevent Legionella growth, and Legionnaires' disease has not previously been associated with the park or other hot springs in the United States. During 2018-2019, Legionnaires' disease occurred in 5 persons after they visited the park; 3 of these persons were potentially exposed in spa facilities that used untreated hot spring water. Environmental testing revealed Legionella bacteria in piped spring water, including 134°F stagnant pipe water. These findings underscore the importance of water management programs to reduce Legionella growth in plumbing through control activities such as maintaining hot water temperatures, reducing stored water age, and ensuring adequate water flow.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
: Aortic arch calcification (AoAC) is associated with a variety of cardiovascular complications. The measurement and grading of AoAC using posteroanterior (PA) chest X-rays are well established. The ...cardiothoracic ratio (CTR) can be simultaneously measured with PA chest X-rays and used as an index of cardiomegaly. The genetic and environmental contributions to the degree of the AoAC and CTR are not well understood. The purpose of this study was to investigate the effect of genetics and environmental factors on the AoAC and CTR.
: A total of 684 twins from the South Korean twin registry (261 monozygotic, MZ and 81 dizygotic, DZ pairs; mean age 38.6 ± 7.9 years, male/female = 264/420) underwent PA chest X-rays. Cardiovascular risk factors and anthropometric data were also collected. The AoAC and CTR were measured and graded using a standardized method. A structural equation method was used to calculate the proportion of variance explained by genetic and environmental factors behind AoAC and CTR.
: The within-pair differences were low regarding the grade of AoAC, with only a few twin pairs showing large intra-pair differences. We found that the thoracic width showed high heritability (0.67, 95% CI: 0.59-0.73,
= 1). Moderate heritability was detected regarding cardiac width (0.54, 95% CI: 0.45-0.62,
= 0.572) and CTR (0.54, 95% CI: 0.44-0.62,
= 0.701).
: The heritable component was significant regarding thoracic width, cardiac width, and the CTR.
Hallux valgus (HV) is a common foot deformity of multifactorial etiology, but knowledge about the relative importance of genetics and environments on HV has been limited. In order to estimate genetic ...influences on HV, 1,265 adults, including 175 monozygotic twin (MZ) pairs, 31 dizygotic twin (DZ) pairs, and 853 first-degree singleton family members of the twins were included from the Healthy Twin study, a population-based twin-family cohort in Korea. All participants underwent foot examination and weight-bearing radiographic assessment (anterior-posterior and lateral) in addition to a general health survey. Of the subjects, 208 (16.4%) were classified as HV (as HV angle >20°). The genetic influence on HV was estimated to be substantial; the heritability of HV was 0.51 (95% CI 0.42-0.59) and the heritability of HV angle was 0.47 (0.38-0.56), while contributions from shared environmental effects were negligible. These findings suggest that genetic factors play an important role in determining HV deformity.
Abscisic acid (ABA) plays an important role in seed germination, stomatal closure, and seedling growth inhibition in plants. Among downstream genes whose expression levels are regulated by AFA1 ...(Arabidopsis F-box Protein Hypersensitive to ABA 1), one gene, AtHAD1 upregulated by ABA was selected from Arabidopsis. AtHAD1 was induced by drought and salt stresses as well as by ABA and was found in dry seeds. Its loss-of-function mutants exhibited increased ABA-sensitivity in germination, seedling growth, and stomatal closure. In addition, the mutants displayed a lower water loss rate and higher survival rate under drought stress than the wild-type plants, indicating that a loss of AtHAD1 leads to enhanced drought tolerance. These results show that AtHAD1 has an inhibitory role in the ABA response and ABA-mediated drought tolerance. The expression levels of several ABA-responsive genes in athad1 were higher than those in the wild-type under the ABA treatment, suggesting that AtHAD1, as a negative regulator in the ABA response, could be associated with the downregulation of the ABA-responsive genes. The phosphatase assay showed that AtHAD1 exhibits phosphatase activity. Monitoring of the subcellular localization of GFP-fused AtHAD1 proteins indicated that AtHAD1 exists in the nucleus and cytoplasm. Overall, this study shows that Arabidopsis HAD1 as an intracellular phosphatase negatively functions in the ABA-mediated cellular responses. This research could serve as a research basis to understand the functional link between ABA signaling and the regulation process of the cellular phosphate level.
•AtHAD1 is positively regulated by AFA1.•AtHAD1 is upregulated by ABA and ABA-related abiotic stresses.•Functional defects of AtHAD1 lead to ABA-hypersensitivity in various plant processes.•AtHAD1 functions as an active phosphatase.•AtHAD1 plays a negative role in ABA-mediated cellular responses in Arabidopsis.
Kawasaki disease (KD) is a self-limited febrile disease predominantly affecting infants and children under 5 years old. Coronary artery lesions (CAL) are a prevalent complication, highlighting the ...necessity for swift diagnosis and treatment. A comprehensive review of biomarkers applicable for the diagnosis and treatment of Kawasaki disease (KD) in clinical settings is imperative. To provide a comprehensive review and analysis of biomarkers for diagnosis of KD, incidence of CAL, and intravenous immunoglobulin (IVIG) resistance. The data included in our study were sourced from searches conducted in PubMed/MEDLINE, Embase, EBSCO, and Google Scholar until March 15, 2024. Studies investigating the association with KD or evaluating diagnostic value were included in our study. Eligibility was independently assessed by two authors, with conflicts resolved through discussion. Data extraction was performed by 2 independent authors, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guideline. Data were pooled using a random-effects model. We assess biomarkers relevant to KD, categorizing them into three groups: diagnostic, associated with CAL incidence, and linked to IVIG resistance. For studies focusing solely on association, we present standardized mean differences (SMD). For those reporting sensitivity and specificity as diagnostic measures, we calculate the diagnostic odds ratio (DOR) to compare their efficacy. We identified 14 meta-analyses on biomarkers related to KD. 11 biomarkers exhibited diagnostic value for KD, while 21 were associated with its progression. Four biomarkers, including non-coding RNAs (DOR, 19.35 95% CI, 13.58-27.56), Serum ferritin (DOR, 24.90 11.67-53.12), N terminal proBNP (DOR, 21.03 9.03-49.00), and micro RNAs (DOR, 45.28 6.30-325.52), have significant diagnostic value for the diagnosis of KD. Seven biomarkers showed significant association with the incidence of CAL. Twenty biomarkers were for the prediction of IVIG resistance, including prognostic nutritional index (DOR, 7.72 95% CI, 2.37-25.09), non-coding RNAs (DOR, 14.63 3.24-66.14), neutrophil to lymphocyte ratio (DOR, 6.62 4.05-10.81), platelet to lymphocyte ratio (DOR, 3.30 2.10-5.19), and C reactive protein (DOR, 6.58 3.69-11.74). Based on the evidence, we have proposed various biomarkers associated with KD. Our aim is for these biomarkers to have wide applicability in both diagnostic and therapeutic settings.Kawasaki disease (KD) is a self-limited febrile disease predominantly affecting infants and children under 5 years old. Coronary artery lesions (CAL) are a prevalent complication, highlighting the necessity for swift diagnosis and treatment. A comprehensive review of biomarkers applicable for the diagnosis and treatment of Kawasaki disease (KD) in clinical settings is imperative. To provide a comprehensive review and analysis of biomarkers for diagnosis of KD, incidence of CAL, and intravenous immunoglobulin (IVIG) resistance. The data included in our study were sourced from searches conducted in PubMed/MEDLINE, Embase, EBSCO, and Google Scholar until March 15, 2024. Studies investigating the association with KD or evaluating diagnostic value were included in our study. Eligibility was independently assessed by two authors, with conflicts resolved through discussion. Data extraction was performed by 2 independent authors, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guideline. Data were pooled using a random-effects model. We assess biomarkers relevant to KD, categorizing them into three groups: diagnostic, associated with CAL incidence, and linked to IVIG resistance. For studies focusing solely on association, we present standardized mean differences (SMD). For those reporting sensitivity and specificity as diagnostic measures, we calculate the diagnostic odds ratio (DOR) to compare their efficacy. We identified 14 meta-analyses on biomarkers related to KD. 11 biomarkers exhibited diagnostic value for KD, while 21 were associated with its progression. Four biomarkers, including non-coding RNAs (DOR, 19.35 95% CI, 13.58-27.56), Serum ferritin (DOR, 24.90 11.67-53.12), N terminal proBNP (DOR, 21.03 9.03-49.00), and micro RNAs (DOR, 45.28 6.30-325.52), have significant diagnostic value for the diagnosis of KD. Seven biomarkers showed significant association with the incidence of CAL. Twenty biomarkers were for the prediction of IVIG resistance, including prognostic nutritional index (DOR, 7.72 95% CI, 2.37-25.09), non-coding RNAs (DOR, 14.63 3.24-66.14), neutrophil to lymphocyte ratio (DOR, 6.62 4.05-10.81), platelet to lymphocyte ratio (DOR, 3.30 2.10-5.19), and C reactive protein (DOR, 6.58 3.69-11.74). Based on the evidence, we have proposed various biomarkers associated with KD. Our aim is for these biomarkers to have wide applicability in both diagnostic and therapeutic settings.
The scarce and conflicting data on vaccine‐associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of ...vaccine‐associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine‐associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine‐associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 40.11%) of vaccine‐associated facial paralysis from 49 537 reports of all‐cause facial paralysis. Vaccine‐associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID‐19) pandemic, which is attributable to the COVID‐19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID‐19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 95% confidence interval, 27.60–29.03; IC, 3.37 IC0.25, 3.35), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella‐zoster, meningococcal, Ad‐5 vectored COVID‐19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole‐virus COVID‐19 vaccines. Concerning age‐ and sex‐specific risks, vaccine‐associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine‐associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine‐induced facial paralysis, primarily owing to COVID‐19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine‐associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.
Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID‐19 vaccines, literature on such ADRs with other vaccines is limited, ...particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine‐associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine‐associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC0.25, the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine‐associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra‐abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID‐19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR 95% CI: 10.30 9.65–10.99; IC IC0.25: 3.33 3.22), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5‐vectored and mRNA COVID‐19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 11.45–11.80; 3.05 3.03) and typhoid (11.02 10.66–11.39; 3.00 2.96). Pancreas and bile duct injury were associated with COVID‐19 mRNA (1.99 1.89–2.09; 0.90 0.83), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra‐abdominal hemorrhage, inactivated whole‐virus COVID‐19 vaccines (3.93 1.86–8.27; 1.71 0.41) had the highest association, followed by COVID‐19 mRNA (1.81 1.42–2.29; 0.77 0.39). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers' vigilant monitoring and timely management.
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