arker trajectories and clinical outcomes in the era of near-universal adoption of electronic health records.BACKGROUND Prescription opioid overprescribing is a focal point for legislators, but little is known about opioid prescribing patterns of primary care nurse practitioners (NPs) and physician assistants (PAs). OBJECTIVE To identify prescription opioid overprescribers by comparing prescribing patterns of primary care physicians (MDs), nurse practitioners (NPs), and physician assistants (PAs). DESIGN Retrospective, cross-sectional analysis of Medicare Part D enrollee prescription data. PARTICIPANTS Twenty percent national sample of 2015 Medicare Part D enrollees. MAIN MEASURES We identified potential opioid overprescribing as providers who met at least one of the following (1) prescribed any opioid to > 50% of patients, (2) prescribed ≥ 100 morphine milligram equivalents (MME)/day to > 10% of patients, or (3) prescribed an opioid > 90 days to > 20% of patients. KEY RESULTS Among 222,689 primary care providers, 3.8% of MDs, 8.0% of NPs, and 9.8% of PAs met at least one definition of overprescribing. 1.3% of MDs, 6.3% of NPs, and 8.8% of PAs prescribed an opioid to at least 50% of patients. NPs/PAs practicing in states with independent prescription authority were > 20 times more likely to overprescribe opioids than NPs/PAs in prescription-restricted states. CONCLUSIONS Most NPs/PAs prescribed opioids in a pattern similar to MDs, but NPs/PAs had more outliers who prescribed high-frequency, high-dose opioids than did MDs. Efforts to reduce opioid overprescribing should include targeted provider education, risk stratification, and state legislation.INTRODUCTION N6-methyladenosine (m6A), the most prominent mRNA modification, plays a critical role in many physiological and pathological processes. However, the roles of m6A RNA modification in hepatocellular carcinoma (HCC) remain largely unknown. MATERIALS AND METHODS We investigated the mRNA expression and clinical significance of m6A-related genes using data from The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma cohort. Mutation, copy number variation (CNV), methylation, differential expression, and gene ontology analyses, gene set enrichment analysis and the construction of a competing endogenous RNA (ceRNA) regulatory network were performed to investigate the underlying mechanisms of the aberrant expression of m6A-related genes. RESULTS m6A-related genes were frequently dysregulated in cancers but with a cancer-specific pattern. METTL3, YTHDF2, and ZC3H13 were found to be independent prognostic factors of overall survival (OS); however, only METTL3 was found to be an independent prognostic factor of recurrence-free survival (RFS). Joint effects analysis showed the predictive capacity of combining METTL3, YTHDF2, and ZC3H13 for HCC OS. Then the potential mechanisms of METTL3 were further explored due to its prognostic role in both OS and RFS. CNV and DNA methylation, but not somatic mutations, might contribute to the abnormal upregulation of METTL3 in HCC. Significantly altered genes, microRNAs, and lncRNAs were identified, and a ceRNA regulatory network was constructed to explain the upregulation of METTL3 in HCC. CONCLUSIONS Our study identified several m6A-related genes, especially METTL3, that could be potential prognostic biomarkers in HCC.Cytochrome p450-mediated metabolism of GRS (indolinone antiaggregant) and its effects on activities of cytochrome p450 isoenzymes were studied. Inhibition of 6 isomers of cytochrome p450 in human liver microsomes was studied with the use of specific substrates. It was found that human liver cytochrome p450 enzymes could not induce degradation of GRS and that GRS was not an inductor or inhibitor of cytochrome p450 family members 1A2, 2C9, 2C19, 2D6, 2C8, and 3A4. Hence, clinical use of the prospective antiaggregant would not involve the risk of uncontrolled fluctuations in GRS concentrations in the organism because of interactions between the drugs.The specific features of interactions between megakaryocytic and granulocytic hematopoiesis lineages and myelofibrosis were studied in patients with active phase (before treatment) of chronic myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. In patients with chronic myeloid leukemia, a direct correlation was found between the severity of both early and advanced myelofibrosis and the number of megakaryocytes in the bone marrow irrespectively of the type of the bone marrow tumor. The parameters of granulocytic hematopoiesis lineage were higher in myelofibrosis. In patients with chronic lymphocytic leukemia and multiple myeloma, negative correlations between the severity of early and advanced myelofibrosis and the number of megakaryocytes in the bone marrow and platelets in the peripheral blood were found. In chronic lymphocytic leukemia, negative correlations between the severity of early and advanced myelofibrosis and the number of neutrophils in the bone marrow and peripheral blood were detected. In patients with multiple myeloma, negative correlations between the severity of advanced myelofibrosis and number of neutrophils in the bone marrow and peripheral blood were detected.We investigate biodistribution of gallium-labeled hydroxyethylidenediphosphonic acid (68Ga-HEDP) and diethylenetriaminepentakis(methylenephosphonic acid) (68Ga-DTPMP) in intact Wistar rats. It was shown that 68Ga-DTPMP accumulated mainly in the bone tissue providing high femur/blood and femur/muscle ratios and had high stability in vivo. In contrast, 68Ga-HEDP was characterized by low stability and high uptake of radioactivity in blood throughout the study. So 68Ga-DTPMP can be considered as a new prospective radiotracer in oncology for imaging bone tissue metastasis by positron emission tomography.We studied the possibility of developing an autism model based on chronic prenatal psychological stress caused by variable frequency ultrasound 20-45 kHz. The offspring of female rats stressed during pregnancy demonstrated reduced time of social contacts in the social interaction test, increased anxiety in the open-field test, and memory impairment in the Morris water maze test in comparison with the control (intact) rat offspring. We also found a reducing trend in the BDNF gene expression in the amygdala in males of the experimental group. The results showed the possibility of developing the animal autism model based on prenatal stress.Previously, we established a 1H NMR metabolomics method using reversed-phase solid-phase extraction column (RP-SPEC), and succeeded in distinguishing wild from cultivated samples of Saposhnikoviae radix (SR), and between SR and its substitute, Peucedanum ledebourielloides root (PR). Herein, we performed LC-HR/MS metabolomics using fractions obtained via RP-SPEC to identify characteristic components of SR and PR. One and three characteristic components were respectively found for SR and PR; these components were isolated with their m/z values and retention times as a guide. The characteristic component of SR was identified as 4′-O-β-D-glucosyl-5-O-methylvisamminol (1), an indicator component used to identify SR in the Japanese Pharmacopoeia. In contrast, the characteristic components of PR were identified as xanthalin (2), 4′-O-β-D-apiosyl (1 → 6)-β-D-glucosyl-5-O-methylvisamminol (3), and 3′-O-β-D-apiosyl (1 → 6)-β-D-glucosylhamaudol (4) based on spectroscopic data such as 1D- and 2D-NMR, MS, and specific optical rotation. Among them, 4 is a novel compound. For the correlation between the NMR metabolomics results in the present and our previous report, only 1 and 2 were found to correlate with the chemical shifts, and the other compounds had no correlation. As the chemical shifts for compounds 1, 3, and 4 were similar to each other, especially for the aglycone moiety, they could not be distinguished because of the sensitivity and resolution of 1H NMR. Accordingly, combining NMR and LC/MS metabolomics with their different advantages is considered useful for metabolomics of natural products. The series of methods used in our reports could aid in quality evaluations of natural products and surveying of marker components.Fragile X-related protein 1 (FXR1) is a member of the fragile X family of RNA-binding proteins, which regulates a number of neurological and neuropsychiatric disorders such as fragile X syndrome, and is expected as a novel therapeutic target for some psychiatric diseases. However, it is unknown how FXR1 changes and functions in post-traumatic stress disorder (PTSD), a common mental disorder related to trauma and stressor. In this study, we characterized the expression pattern of FXR1 in the pathophysiological process of PTSD and further investigated the possible mechanism underlying these changes by finding an upstream regulator, namely miRNA-132 (miR-132). Furthermore, we verified whether miR-132 silence had an effect on the PTSD-like behaviors of single prolonged stress (SPS) rats through open field test, forced swimming test, and water maze test. At last, we examined the expression levels of PSD95 and synapsin I in the hippocampus, which was one of the key brain regions associated with PTSD. We showed that the levels of FXR1 and fragile X mental retardation protein (FMRP), an autosomal homolog of FXR1, were decreased in the hippocampus of PTSD rats, but the levels of PSD95 and synapsin I were increased, which could be reversed by downregulation of miR-132. The results revealed that miR-132 could modulate PTSD-like behaviors in rats following SPS through regulating FXR1 and FMRP.The goal of the current study was to test associations between various ASD-related behavior problems and negative peer experiences in adolescents with ASD. Data were obtained from the Bullying and School Experiences of Children with ASD Survey completed by parents in the Interactive Autism Network (IAN). The current study focused on data from 279 parents of 7th-11th graders with ASD who spent at least half of the school day in a general education setting. Logistic regression analyses found that frequent meltdowns, poor hygiene, rigid rule-keeping, and self-injury were associated with negative peer experiences. Surprisingly, repetitive behaviors and verbal tics were associated with a lower likelihood of experiencing verbal victimization.Animal-Assisted Therapy (AAT) is an intervention for children with Autism Spectrum Disorder (ASD). This study explores parent perspectives of the impact of five AAT sessions involving trained dogs with their children with ASD. A phenomenological qualitative approach was used to explore first-hand perspectives of parents. In-depth, semi-structured interviews were conducted. Data were analyzed using thematic analysis. Seventeen parents reported that the presence of the dogs facilitated their children’s engagement, enjoyment, and motivation. Parents also reported that this contributed to gains in the child’s communication with others and the dog (n = 11, 64.7%), behavioral regulation (n = 12, 70.6%), and community participation (n = 14, 82.3%). These findings indicate that parents supported the use of AAT and that dogs facilitated therapeutic gains.Parents play a critical role in the early identification of ASD because of their experiential knowledge and frequent observations of their children. Being knowledgeable about ASD may help parents recognize early signs and symptoms, know to which professionals to express their concerns, and better navigate systems of care. An appropriate measure of ASD knowledge for parents is essential to further understand the importance of ASD knowledge in this population. This study sought to validate the Autism Spectrum Knowledge Scale-General Population Version (ASKSG) with a sample of parents with children under the age of 18 years in the United States. Results indicate that the ASKSG is a valid and reliable measure for use with parents.Executive functioning is thought to contribute to adaptive behavior skills development in individuals with autism spectrum disorder (ASD). However, supporting data are largely based on caregiver reports of executive functioning. The current study evaluated whether performance-based measures of executive functioning (working memory and inhibition) explained unique variance in parent-reported adaptive functioning among youth with ASD without an intellectual disability. Both spatial and verbal working memory were associated with adaptive functioning, particularly communication and daily living skills. Our findings demonstrate a robust relationship between working memory and adaptive functioning that translates across different measurement modalities. This preliminary study highlights that targeting executive functioning may be a critical component of an adaptive function training program.OBJECTIVE To assess challenges to optimal rheumatology care from the perspective of patients served by our institution’s rheumatology division. DESIGN SETTING AND PARTICIPANTS Focus group study of adult rheumatic disease patients who attend clinics at a university teaching hospital in Montreal, Canada. INTERVENTIONS Individuals participated in 1-h focus group discussions concerning their experiences and beliefs regarding rheumatology care. Sessions were recorded and transcripts generated. A thematic analysis approach was used by two individual analyzers. MAIN OUTCOME MEASURES AND RESULTS Eighteen patients participated in three focus groups (group one = 8 patients; group two = 5; group three = 5). Eleven patients had systemic lupus erythematosus, 6 had rheumatoid arthritis, and 1 patient had psoriatic arthritis. The average age (standard deviation) was 51.2 (14.0) years, disease duration 23.5 (14.5) years, and in the majority had at least a high school education. All participants were female and 72.2% were Cauions, our work provides recommendations that could improve patient experiences when seeking health care in a rheumatology setting.BACKGROUND LY393558 is a combined antagonist of serotonin (5-HT) 5-HT1B receptors and inhibitor of serotonin transporter (SERT). LY393558 reduces 5-HT-induced vasoconstriction and remodelling of rat and/or mouse pulmonary arteries. The aim of our study was to examine the effect of LY393558 on the 5-HT-stimulated vasoconstriction of human pulmonary arteries (hPAs) and to determine the underlying mechanism(s). METHODS Vascular effects of 5-HT receptor agonists, antagonists and a SERT inhibitor were examined in organ bath studies on intralobar hPAs obtained from patients during resection of lung carcinoma. RESULTS Serotonin and agonists of the 5-HT1B receptor (5-carboxamidotryptamine, 5-CT) and 5-HT2A receptor (α-methyl-5-HT) contracted endothelium-intact hPAs in a concentration-dependent fashion. The 5-HT1B antagonists SB224289 and GR55562 reduced responses induced by 5-HT and 5-CT and the 5-HT2A antagonist ketanserin inhibited the effects of 5-HT and α-methyl-5-HT. Administration of the SERT inhibitor citalopram (at a concentration that failed to modify the 5-HT-induced vasoconstriction) in combination with SB224289 or GR55562 was more effective in inhibiting the response to 5-HT than the 5-HT1B antagonists alone. LY393558 showed the greatest antagonistic effect against the vasoconstriction elicited by 5-HT, 5-CT and α-methyl-5-HT. CONCLUSIONS LY393558 reduces the 5-HT-induced contraction antagonizing 5-HT1B and 5-HT2A receptors probably due to synergic interaction between SERT inhibition and 5-HT1B receptor antagonism. Thus, it might represent a valuable future option in the pulmonary arterial hypertension therapy.Quorum sensing (QS) inhibition by metal-antibiotic complexes is a promising strategy for the management and control of multidrug resistant Pseudomonas aeruginosa infections. We investigated the anti-quorum sensing activity of sub-minimum inhibitory concentration (sub-MIC) of copper(II) sulfate pentahydrate-ciprofloxacin (Cu-CIP) complex and free ciprofloxacin (free-CIP) against P. aeruginosa PAO1. Copper-CIP complex was synthesized and its characterization was assessed using spectroscopic methods and single crystal X-ray analysis. The effect of sub-MIC (1/4 and 1/16 MIC) concentrations of Cu-CIP and free-CIP on cell growth, biofilm formation, motility, alginate and pyocyanin production, H2O2 susceptibility and expression of QS circuit genes lasI and lasR in PAO1 was determined. Minimum inhibitory concentration of Cu-CIP complex and free-CIP was determined as 0.125 µg/ml. Copper-CIP complex did not show significant effect on the cell growth at concentrations of 1/4 and 1/16 MIC. However, sub-MIC concentrations (1/4 and 1/16 MIC) of Cu-CIP showed the significant reduction in violacein production, motility, biofilm formation, alginate and pyocyanin production and sensitivity to H2O2 in a concentration dependent manner (P  less then  0.001). Copper-CIP at the concentration of 1/4 MIC showed the greatest reduction in lasI and lasR transcriptional expression (89.5% and 96.2% respectively). Considering the biological effects of Cu-CIP complex and its inhibitory activity on QS related virulence traits at low concentrations (0.03 and 0.007 µg/ml), it may be used as an effective approach in the management of infections caused by P. aeruginosa.PURPOSE BRCA2 mutation carriers are offered annual breast screening with MRI and mammography. The aim of this study was to investigate the supplemental value of mammographic screening over MRI screening alone. METHODS In this multicenter study, proven BRCA2 mutation carriers, who developed breast cancer during screening using both digital mammography and state-of-art breast MRI, were identified. Clinical data were reviewed to classify cases in screen-detected and interval cancers. Imaging was reviewed to assess the diagnostic value of mammography and MRI, using the Breast Imaging and Data System (BI-RADS) classification allocated at the time of diagnosis. RESULTS From January 2003 till March 2019, 62 invasive breast cancers and 23 ductal carcinomas in situ were diagnosed in 83 BRCA2 mutation carriers under surveillance. Overall screening sensitivity was 95.2% (81/85). Four interval cancers occurred (4.7% (4/85)). MRI detected 73 of 85 breast cancers (sensitivity 85.8%) and 42 mammography (sensitivity 49.9%) (p  less then  0.001). Eight mammography-only lesions occurred. In 1 of 17 women younger than 40 years, a 6-mm grade 3 DCIS, retrospectively visible on MRI, was detected with mammography only in a 38-year-old woman. The other 7 mammography-only breast cancers were diagnosed in women aged 50 years and older, increasing sensitivity in this subgroup from 79.5% (35/44) to 95.5% (42/44) (p ≤ 0.001). CONCLUSIONS In BRCA2 mutation carriers younger than 40 years, the benefit of mammographic screening over MRI was very small. In carriers of 50 years and older, mammographic screening contributed significantly. Hence, we propose to postpone mammographic screening in BRCA2 mutation carriers to at least age 40.The COVID-19 pandemic presents clinicians a unique set of challenges in managing breast cancer (BC) patients. As hospital resources and staff become more limited during the COVID-19 pandemic, it becomes critically important to define which BC patients require more urgent care and which patients can wait for treatment until the pandemic is over. In this Special Communication, we use expert opinion of representatives from multiple cancer care organizations to categorize BC patients into priority levels (A, B, C) for urgency of care across all specialties. Additionally, we provide treatment recommendations for each of these patient scenarios. Priority A patients have conditions that are immediately life threatening or symptomatic requiring urgent treatment. Priority B patients have conditions that do not require immediate treatment but should start treatment before the pandemic is over. Priority C patients have conditions that can be safely deferred until the pandemic is over. The implementation of these recommendations for patient triage, which are based on the highest level available evidence, must be adapted to current availability of hospital resources and severity of the COVID-19 pandemic in each region of the country. Additionally, the risk of disease progression and worse outcomes for patients need to be weighed against the risk of patient and staff exposure to SARS CoV-2 (virus associated with the COVID-19 pandemic). Physicians should use these recommendations to prioritize care for their BC patients and adapt treatment recommendations to the local context at their hospital.BACKGROUND Increasing numbers of reproductive-aged women are using attention-deficit/hyperactivity disorder (ADHD) medications. Findings from studies exploring the safety of these medications during pregnancy are mixed, and it is unclear whether associations reflect causal effects or could be partially or fully explained by other factors that differ between exposed and unexposed offspring. OBJECTIVES The aim of this systematic review was to evaluate the adverse pregnancy-related and offspring outcomes associated with exposure to prescribed ADHD medication during pregnancy with a focus on how studies to date have handled the influence of confounding. METHODS We searched PubMed, Embase, PsycINFO, and Web of Science up to 1 July 2019 without any restrictions on language or date of publication. We included all observational studies (e.g., cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) with pregnant women of any age or from any setting who were prvidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman’s specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate specific confounding factors, the potential impact of timing of exposure, and potential long-term outcomes in the offspring.PURPOSE A systematic review of the literature was conducted to determine the effects of early cognitive interventions on delirium outcomes in critically ill patients. SOURCE Search strategies were developed for MEDLINE, EMBASE, Joanna Briggs Institute, Cochrane, Scopus, and CINAHL databases. Eligible studies described the application of early cognitive interventions for delirium prevention or treatment within any intensive care setting. Study designs included randomized-controlled trials, quasi-experimental trials, and pre/post interventional trials. Two reviewers independently extracted data and assessed risk of bias using Cochrane methodology. PRINCIPAL FINDINGS Four hundred and four citations were found. Seven full-text articles were included in the final review. Six of the included studies had an overall serious, high, or critical risk of bias. After application of cognitive intervention protocols, a significant reduction in delirium incidence, duration, occurrence, and development was found in four studies. Feasibility of cognitive interventions was measured in three studies. Cognitive stimulation techniques were described in the majority of studies. CONCLUSION The study of early cognitive interventions in critically ill patients was identified in a small number of studies with limited sample sizes. An overall high risk of bias and variability within protocols limit the utility of the findings for widespread practice implications. This review may help to promote future large, multi-centre trials studying the addition of cognitive interventions to current delirium prevention practices. The need for robust data is essential to support the implementation of early cognitive interventions protocols.The present study assessed how the adaptation to American culture by United States (U.S.)-born and foreign-born Hispanics living in the U.S. may influence stress-related physiological aspects that may impair health. Data on 8,360 Hispanics living in the U.S. categorized as U.S.-born (n = 3347) and foreign-born (n = 5013) from NHANES 1999-2010 (ages 18-85) were used. Stress-related physiological impact was measured by the allostatic load index (ALoad). Adaptation to American culture was evaluated through three acculturation-related measures. The average age was 39.39 years in a sample where 51% were males. ALoad was classified as no load (15.41%), low load (55.33%), and high load (29.24%). The U.S.-born Hispanics showed higher ALoad compared to foreign-born Hispanics (p  less then  0.001). Among foreign-born Hispanics, length of residence (LOR) and age of arrival in the U.S. (AOA) were associated with higher ALoad scores (p  less then  0.05), and in U.S.-born Hispanics, age and sex were positively associated and education was negatively associated with ALoad scores (p  less then  0.05). Adaptation to American culture in foreign-born Hispanics living in the U.S. appears to influence levels of ALoad in this population.Anti-smoking norms and educational aspirations are established tobacco prevention targets for general United States (U.S.) adolescent populations but protective factors remain poorly characterized for Somali-American youth. Here we describe patterns of past 30-day tobacco use and associated protective factors among eighth, ninth, and eleventh grade Somali adolescent respondents (n = 2009) to the 2016 Minnesota Student Survey using multivariate logistic regressions. E-cigarette (5.7%) and hookah (5.0%) use were most prevalent. Male youth reported higher levels of tobacco use across products. Adjusted odds ratios showed that internal developmental assets (e.g., e-cigarettes aOR 0.37, 95% CI 0.37, 0.79) and parental anti-smoking norms (e.g., e-cigarettes aOR 0.19, 95% CI 0.09, 0.38) protected against use of all tobacco products. E-cigarettes and hookah are prevalent among U.S. Somali youth, highlighting the need for prevention efforts that address emerging tobacco products and leverage protective factors such as internal assets and parental anti-smoking norms.Recurrent respiratory tract infections (rRTIs), of which there are three main groups-otitis media, tonsillitis and sinusopathies-are very common in paediatric populations and are associated with significant morbidity and mortality due to complications. These infections substantially reduce quality of life for paediatric patients and their families and are a significant personal, medical and economic burden on the patients, the patients’ families and the healthcare system. Most rRTIs are of viral origin; however, indiscriminate use of antibiotics in their treatment has led to development of bacterial resistance. Effective management of rRTIs to reduce the burden of disease and to avoid overuse of antibiotics has become a great therapeutic challenge. New strategies for the management of paediatric rRTIs include focus on prevention using non-specific immunomodulators to boost the body’s natural defences against infection and to downregulate infection- and allergen-induced airway inflammation. The oral immunomodulator, OM-85, a bacterial lysate, acts on the innate and adaptive branches of the immune system, conferring protection against viral and bacterial infections, and controls inflammation, thereby reducing tissue damage. OM-85 has demonstrated good tolerability and clinical efficacy in reducing the number and duration of RTIs in children with recurrent airway infections. It has also been reported to reduce the use of concomitant medications, including antibiotics, time to cure and school absenteeism. OM-85 is efficacious and well tolerated when administered concomitantly with inactivated influenza vaccine (IIV) and has been shown to reduce wheezing attacks induced by RTI in young children. Clinical results show that the greater the risk of rRTIs, the greater the benefit with OM-85. OM-85 may be considered a promising tool to add to the limited armamentarium of the ear, nose and throat (ENT) physician dealing with rRTIs and their complications, such as recurrent wheeze and asthma inception.Coronavirus disease 2019 (COVID-19) has rapidly spread not only in China but throughout the world. Children with kidney failure (chronic kidney disease (CKD) stage 5) are at significant risk for COVID-19. In turn, a set of recommendations for the prevention and control of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 in pediatric hemodialysis (HD) centers and in home peritoneal dialysis (PD) settings have been proposed. The recommendations are based on the epidemiological features of the SARS-CoV-2 virus and COVID-19 disease, susceptibility factors, and preventive and control strategies. These recommendations will be updated as new information regarding SARS-CoV-2 and COVID-19 becomes available.BACKGROUND To evaluate impact of anemia on health-related quality of life (HRQOL) over time in a large pediatric cohort with mild-to-moderate chronic kidney disease (CKD). METHODS Participants were enrolled in the Chronic Kidney Disease in Children Study (CKiD), a multicenter, longitudinal cohort. HRQOL was measured using the Pediatric Quality of Life Inventory (PedsQL). Anemia was defined as hemoglobin less then  5th percentile for age, sex, and race. Two longitudinal analyses were conducted on consecutive visit pairs. Models examined effects of anemia status on both HRQOL score over time and change in HRQOL score between consecutive visits. The sample included 733 children with a median estimated GFR 54 ml/min/1.73 m2. Thirty percent of children had anemia at index visit. RESULTS Analysis of HRQOL scores revealed the presence of anemia was associated with significantly lower overall HRQOL (β = - 2.90 (95% CI = - 7.74, - 0.21), p = 0.04) and physical functioning (β = - 5.72 (- 9.49, - 2.25), p = 0.001) according to children. On parent ratings, the development of anemia was associated with lower emotional functioning scores (β = - 4.87 (- 8.72, - 0.11), p = 0.045). In the second model, children who developed anemia were rated by caregivers as having more decreased physical functioning than children who remained anemia-free (β = - 3.30 per year (- 5.83, - 0.76), p = 0.01). Caregivers did not observe declines in their children’s other PedsQL subscales in the presence of developed anemia. Children with resolved or persistence did not show improvement or decline in any aspect of HRQOL functioning relative to non-anemic subjects. CONCLUSIONS In children with CKD, anemia has an adverse effect on HRQOL which persists over time but does not appear to be progressive.OBJECTIVE To determine whether diabetes mellitus (DM) contributes to the drug resistance of carbamazepine (CBZ), we investigated the correlation between the blood glucose status and the CBZ resistance condition in patients with trigeminal neuralgia (TN). PATIENTS AND METHODS A total of 155 TN patients treated with the CBZ monotherapy were selected at Shanghai General Hospital and Shanghai Xinhua Hospital from September 2018 to January 2020. Among them, 15 were diagnosed with DM. Patients’ CBZ resistance levels were evaluated according to progression-free survival. We utilized ordered multiple classification logistic regression to determine the dominant factors leading to CBZ resistance. We analyzed the correlation between hemoglobin A1c (HbA1c) and progression-free survival using the Pearson correlation analysis. RESULTS The regression analysis showed that DM was the only factor affecting CBZ resistance (p = 0.035; OR = 0.327; 95% CI, 0.115-0.926). Progression-free survival was 28.5 ± 21.2 months in the DM group and 66.0 ± 33.2 months in the non-DM group. The concentration of HbA1c in the blood was negatively correlated with progression-free survival (r = - 0.197; p = 0.014). CONCLUSIONS This study shows that blood glucose status is a significant factor contributing to the CBZ resistance in the treatment of TN. The progression-free survival of patients is affected by the status of DM and blood HbAlc levels.BACKGROUND The aim of this work was to assess the robustness of cardiac SPECT radiomic features against changes in imaging settings, including acquisition, and reconstruction parameters. METHODS Four commercial SPECT and SPECT/CT cameras were used to acquire images of a static cardiac phantom mimicking typical myorcardial perfusion imaging using 185 MBq of 99mTc. The effects of different image acquisition and reconstruction parameters, including number of views, view matrix size, attenuation correction, as well as image reconstruction related parameters (algorithm, number of iterations, number of subsets, type of post-reconstruction filter, and its associated parameters, including filter order and cut-off frequency) were studied. In total, 5,063 transverse views were reconstructed by varying the aforementioned factors. Eighty-seven radiomic features including first-, second-, and high-order textures were extracted from these images. To assess reproducibility and repeatability, the coefficient of variation (CO reproducibility of SPECT/CT cardiac radiomic features under different imaging settings is feature-dependent. Different image acquisition and reconstruction protocols have variable effects on radiomic features. The radiomic features exhibiting low COV are potential candidates for future clinical studies.We present a case of a 40-year-old Spanish man with cardiac amyloidosis in which a Tc-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-99m-DPD) scintigraphy was strongly suggestive of cardiac amyloidosis by transthyretin (ATTR) but endomyocardial biopsy (EB) analyzed by immunohistochemistry demonstrated a light chain amyloidosis (AL). Even though the Tc-99m-DPD has proven in different published papers that has high sensibility and specificity for differentiating AL and ATTR cardiac amyloidosis, we present an unusual case of an AL cardiac amyloidosis with a Perugini grade 3 on the scintigraphy. Diagnostic approach of cardiac amyloidosis following consensus documents is discussed to avoid diagnostic mistakes based on imaging techniques.BACKGROUND Left bundle branch (LBB) pacing has emerged as a novel pacing modality. Left ventricular activation time (LVAT) was reported to be associated with the activation via LBB, but the value of LVAT for determining LBB pacing was unknown. We conducted a pilot study to determine if LVAT could define LBB capture by validating left ventricular (LV) mechanical synchrony. METHODS We analyzed LVAT in 68 bradycardia-indicated patients who received LBB pacing. LVAT was measured from the stimulus to R-wave peak in lead V5 and V6. LV mechanical synchrony assessed by SPECT MPI was compared according to the value of LVAT and the presence of LBB potential. RESULTS The mean LVAT was 75.4 ± 12.7 ms. LBB potential was recorded in 47 patients (69.1%). Patients with LVAT  less then  76 ms had better LV mechanical synchrony than those with LVAT ≥ 76 ms. Patients with LVAT  less then  76 ms or LBB potential had better mechanical synchrony than those with LVAT ≥ 76 ms and no potential. LVAT  less then  76 ms could predict the normal synchrony with a sensitivity of 88.9% and a specificity of 87.5%. CONCLUSION A short LVAT indicated favorable mechanical synchrony in SPECT imaging. LVAT  less then  76 ms might be a practical parameter for defining LBB capture.BACKGROUND Surgical treatment of lesions involving the ventral craniovertebral junction (CVJ) and the lower clivus, traditionally involved complex lateral or transoral approaches to the skull base. However, mid or upper clivus involvement requires more extensive lateral approaches. Recently, the endoscopic endonasal approach (EEA) has become the standard for upper CVJ lesions and medial clival, and a valuable alternative for those tumors extending in its upper third as well as laterally. However, the EEA is associated with an increased risk of post-operative CSF leakage and infection when the tumor is characterized by an intradural extension. Furthermore, whenever the tumor has significant lateral and/or inferior extension below the odontoid process, the chances for a complete resection decrease. METHOD To analyze the extent of exposure of a hybrid microscopic-endoscopic transcondylar antero-lateral approach to the CVJ and clival region, and to verify its effectiveness in terms of mid and upper clival access. Five silicone-injected cadaver heads were used. Following a standard antero-lateral approach, condylectomy and jugular tubercle drilling were performed, after which angled endoscopes were utilized to extend the bone resection to the clivus. A volumetric assessment of the amount of clival removal was carried out. A case of CVJ chordoma operated through this approach is presented. RESULTS The hybrid antero-lateral transcondylar approach provides adequate exposure of the ventral CVJ, up to the dorsum sellae and the sphenoid sinus, the contralateral petrous apex, and the contralateral paraclival internal carotid artery (ICA). Approximately 60% of the total clival volume can be removed with this approach. The main limitation is the limited visualization of the ipsilateral paraclival ICA and petrous apex. CONCLUSION The hybrid antero-lateral transcondylar approach is a valuable surgical option for CVJ tumor extending from C2 to the mid and upper clivus.BACKGROUND As the predictive role of many risk factors for parasagittal meningioma (PM) recurrence remains unclear, the objective of the meta-analysis was to make a comprehensive assessment of the predictive value of selected risk factors in these lesions. METHODS Studies including data on selected risk factors, such as histology, tumor and sinus resection, sinus invasion, tumor localization, and immediate postoperative radiotherapy for PMs recurrence, were searched in the NCBI/NLM PubMed/MEDLINE, EBM Reviews/Cochrane Central, ProQuest, and Scopus databases, and analyzed using random effects modeling. RESULTS Thirteen observational studies involving 1243 patients met the criteria for inclusion in the meta-analysis. WHO grading of meningiomas was identified as the most powerful risk factor for recurrence. WHO grade II meningiomas (OR 11.61; 95% CI 4.43-30.43; P  less then  .01; I2 = 31%) or composite group of WHO grades II and III (OR 14.84; 95% CI 5.10-43.19; P  less then  .01; I2 = 48%) had a significantly higher risk of recurrence than benign lesions. Moreover, an advanced sinus involvement (types IV-VI according to the Sindou classification) (OR 3.49; 95% CI 1.30-9.33; P = .01; I2 = 0%) and partial tumor resection (Simpson grades III-V) (OR 2.73; 95% CI 1.41-5.30; P = .03; I2 = 52%) were associated with a significantly higher risk of recurrence than their counterparts. CONCLUSION Among the selected risk factors, high-grade WHO lesions, advanced sinus invasion, and partial tumor resection were associated with a higher risk of PM recurrence, with WHO grading system being the most powerful risk factor.INTRODUCTION Cone beam computed tomography (CBCT) is used across all dental specialties and has a number of advantages compared to 2D images. The SEDENTEXCT guidelines provide a number of indications for the use, however there are currently no specific guidelines for paediatric dentistry. The aim of this study was to assess current practice of CBCT imaging within paediatric dental departments in England, audit compliance of CBCT justifications against the standards set by SEDENTEXCT and assess whether the use of CBCT affected the treatment plan for each individual patient. METHODS From the retrospective analysis of CBCT examinations taken over a 4-year period across three dental hospitals in the north of England, the following data were collected age at the time of exposure, clinical indication, region of interest (ROI) and diagnostic findings. Clinical notes were also used to identify whether the CBCT had an effect on the final treatment plan. RESULTS A total of 335 CBCT examinations were performed, mean age 11 years. The number of CBCTs increased each year with a twofold increase in the first 2 years. The main clinical indication in 46% of CBCT examinations was the assessment of localised developing dentition, 68% were in the upper anterior sextant and 61% of CBCT exams were in the mixed dentition age group. The investigations were justified in 100% of the cases. CONCLUSION The quantity of CBCT examination in paediatric dental patients is increasing to assist treatment planning but more often to enable improved surgical planning.Itraconazole is the first drug of choice for the treatment of sporotrichosis and it is available at different concentrations for veterinary patients. However, therapeutic failure has been reported, limiting clinical treatment. This study evaluated the in vitro efficacy of brand-name and compounded itraconazole formulations against Sporothrix brasiliensis and estimated the itraconazole content in each tested formulation. Oral capsules were acquired from two brand-name products for human (H-IND) and veterinary (V-IND) uses, and three from compounding pharmacies in Pelotas, RS, for human (H-COMP1/H-COMP2) and veterinary (V-COMP) uses. Capsule purity was analyzed by liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS). Antifungal activity was determined against 29 Sporothrix brasiliensis by the M38-A2 guideline of CLSI. H-IND/H-COMP1/H-COMP2 had high efficacy against S. brasiliensis (approximately 70% of total isolated susceptible), V-COMP showed moderate efficacy (51.7%), and V-IND was the least effective formulation (37.9%). Thirty-four percent of the total isolates were resistant to all formulations. Furthermore, itraconazole content did not match the concentration indicated by the manufacturers, ranging from 387.70 to 7.81 μg/mg (H-COMP2 > V-COMP > H-IND > H-COMP1 > V-IND). Therefore, it is possible that the formulations showed different in vitro efficacy due to the difference in their itraconazole contents. Given the emergence of antifungal resistance for all formulations, the choice product to be used must follow susceptibility testing. Stringent quality control measures are recommended for product manufactures to assure drug content uniformity.Fungi in the genus Trichoderma are notorious producers of secondary metabolites with diverse applications, such as antibacterial, antifungal, and plant growth-promoting properties. Peptaibols are linear peptides produced by such fungi, with more than 440 compounds described to date, including tricholongins, longibrachins, trichobrachins, and trichovirins. Peptaibols are synthesized by non-ribosomal peptide synthetases and they have several biological activities. Our research group isolated four peptaibols (6DP2, 6DP3, 6DP4, and 6DP5) with antifungal activity against the plant pathogen Colletotrichum gloeosporioides and the proteasome (a cancer chemotherapy target) from Trichoderma sp. P8BDA1F1, an endophytic fungus from Begonia venosa. The ethyl acetate extract of this endophyte showed activity of 6.01% and 75% against C. gloeosporioides and the proteasome, respectively. The isolated compounds were identified by MS/MS and compared to literature data, suggesting the presence of trilongins BI, BII, BIII, and BIV, which are peptaibols containing 20 amino acid residues. The minimum inhibitory concentration against C. gloeosporioides was 40 μM for trilongin BI, 320 μM for trilongin BII, 160 μM for trilongin BIII, and 310 μM for trilongin BIV. BI-BIV trilongins inhibited proteasome ChTL activity, with IC50 values of 6.5 ± 2.7; 4.7 ± 1.8; 6.3 ± 2.2; and 2.7 ± 0.5 μM, respectively. The compounds were tested ex vivo against the intracellular amastigotes of Leishmania (L.) infantum but showed no selectivity. It is the first report of trilongins BI-BIV with antifungal activity against C. gloeosporioides and the proteasome target.BACKGROUND Traumatic brain injury (TBI) is a frequent cause of mortality and acquired neurological impairment in children. It is hypothesized, that with the adequate treatment of SDH in children and adolescence, excellent clinical and functional outcomes can be achieved. The aim of this study was to present the severity and outcome of traumatic SDH in children and adolescence as well as to analyze differences between patients treated surgically and conservatively. METHODS In this study 47 infants and children with a subdural hematoma (SDH) were treated between 1992 and 2010 at a single level-one trauma center. Data regarding accident, treatment and outcomes were collected retrospectively. To classify the outcomes the Glasgow outcome scale (GOS) scores at hospital discharge and at follow-up visits were used. Severity of SDH was classified according to the Rotterdam score. RESULTS In total, 47 cases were treated (21 surgically, 26 conservatively), with 10 patients needing delayed surgery. Overall, 89% of the patients were able to leave hospital, 5 patients died, 2 patients (5%) within 24 h, another 2 (5%) after 48 h and 1 (2%) within 7 days. In 25 patients (53%) a good recovery was recorded at the last follow-up visit. Outcome was mainly influenced by the following factors age, severity of TBI, and neurological status. Overall, in 70% good clinical and neurological outcomes could be achieved. CONCLUSION The results of this study confirmed that pediatric SDH is a rare, but serious condition. Despite a poor prognosis, most patients could be treated with good outcomes, given that the choice of treatment is correct. TRIAL REGISTRATION Research registry 2686.PURPOSE Germline mutations in the aryl-hydrocarbon receptor interacting protein (AIP) have been identified often in the setting of familial isolated pituitary adenoma (FIPA). To date there is no strong evidence linking germline AIP mutations to other neoplasms apart from the pituitary. Our primary objective was to investigate the prevalence of AIP gene mutations and mutations in genes that have been associated with neuroendocrine tumors in series of tumors from patients presenting with both pituitary adenomas and differentiated thyroid carcinomas (DTCs). METHODS Pathology samples were retrieved from all pituitary adenomas in patients with concomitant DTCs, including one with a known germline AIP variant. Subsequently, two additional patients with known germline AIP variants were included, of which one presented only with a follicular thyroid carcinoma (FTC). RESULTS In total, 17 patients (14 DTCs and 15 pituitary adenomas) were investigated by targeted next generation sequencing (NGS). The pituitary tumor samples revealed no mutations, while among the thyroid tumor samples BRAF (6/14, 42.9%) was the most frequently mutated gene, followed by NRAS (3/11, 27.3%). In one AIP-mutated FIPA kindred, the AIP-variant c.853C>T; p.Q285* was confirmed in the FTC specimen, including evidence of loss of heterozygosity (LOH) at the AIP locus in the tumor DNA. CONCLUSION Although most observed variants in pituitary adenomas and DTCs were similar to those of sporadic DTCs, we confirmed in one AIP mutation-positive case the AIP-variant and LOH at this locus in an FTC specimen, which raises the potential role of the AIP mutation as a rare initiating event.PURPOSE Although quality of life (QoL) is improved in patients with acromegaly after disease control, QoL correlates only weakly with traditional biomarkers. Our objective is to investigate a potential relation between the new serum biomarker soluble Klotho (sKlotho), GH and insulin-like growth factor 1 (IGF-1) levels, and QoL. METHODS In this prospective cohort study, we investigated 54 acromegaly patients biochemically well-controlled on combination treatment with first-generation somatostatin receptor ligands (SRLs) and pegvisomant (PEGV) at baseline and 9 months after switching to pasireotide LAR (PAS-LAR; either as monotherapy, n = 28; or in combination with PEGV, n = 26). QoL was measured by the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) and Acromegaly Quality of Life (AcroQoL) questionnaire. RESULTS Switching to PAS-LAR treatment significantly improved QoL without altering IGF-1 levels. QoL did not correlate with GH or IGF-1 levels, but sKlotho correlated with the observed improvements in QoL by the AcroQoL global (r = -0.35, p = 0.012) and physical subdimension (r = -0.34, p = 0.017), and with PASQ headache (r = 0.28, p = 0.048), osteoarthralgia (r = 0.46, p = 0.00080) and soft tissue swelling score (r = 0.29, p = 0.041). Parallel changes in serum sKlotho and IGF-1 (r = 0.31, p = 0.023) suggest sKlotho and IGF-1 to be similarly dependent on GH. Comparing the PAS-LAR combination therapy and the monotherapy group we did not observe a significant difference in improvement of QoL. CONCLUSIONS Patients experienced improved QoL during PAS-LAR, either as monotherapy or in combination with PEGV. Soluble Klotho concentrations appear to be a useful marker of QoL in acromegaly patients but the underlying mechanisms remain to be investigated.PURPOSE Statins are the mainstay of treatment for patients with familial hypercholesterolaemia (FH). However, their efficacy and safety in children and adolescents with FH has not been well-documented. The purpose of this study was to systematically investigate and meta-analyze the best available evidence from randomized-controlled trials (RCTs) regarding the efficacy and safety of statins in this population. METHODS A comprehensive search was conducted in PubMed, Scopus and Cochrane, up to 10 January 2020. Data were expressed as mean differences with 95% confidence intervals (CI). The I2 index was employed for heterogeneity. RESULTS Ten RCTs were included in the qualitative and quantitative analysis (1191 patients, aged 13.3 ± 2.5 years). Compared with placebo, statins led to a mean relative reduction in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride and apolipoprotein B (apo-B) concentrations by -25.5% (95% CI -30.4%, -20.5%; I2 91%), -33.8% (95% CI -40.1%, -27.4%; I2 90%), -8.4% (95% CI -14.8%, -2.03%; I2 26%) and -28.8% (95% CI -33.9%, -23.6%; I2 83%), respectively. High-density lipoprotein cholesterol (HDL-C) was increased by 3.1% (95% CI 1.1%-5.2%; I2 0%). Statins were well-tolerated, with no significant differences in transaminase and creatine kinase levels or other adverse effects compared with placebo. Statins exerted no effect on growth or sexual development. CONCLUSION Statins are quite effective in reducing TC, LDL-C, TG and apo-B and increasing HDL-C concentrations in children and adolescents with FH. No safety issues were seen with statin use.