Pediatric case of mesalazine‐induced interstitial nephritis with literature review

We present the case of a 14‐year‐old boy with ulcerative colitis who was diagnosed with mesalazine‐induced interstitial nephritis ( M‐IIN ). Improvement in renal function occurred with discontinuation of mesalazine and corticosteroid therapy. We systematically searched the literature for pediatric cases of M‐IIN . There were eight cases. Majority of the cases were boys (75%) with ulcerative colitis (75%). Average duration of mesalazine use prior to the diagnosis of interstitial nephritis was 24 ± 18 months. The median dose was 1.5 g/day. M‐IIN appears to be an idiosyncratic reaction without any relation to dose or duration of mesalazine use. Although there are no guidelines to recommend routine surveillance of renal function, monitoring of serum creatinine in patients on mesalazine remains an inexpensive and non‐invasive test that may lead to early detection and treatment of renal injury.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98820/1/ped3745.pd

The RNA-binding protein HuR contributes to neuroinflammation by promoting C-C chemokine receptor 6 (CCR6) expression on Th17 cells.

In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C-C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). Whereas many cytokines and their receptors are potently regulated via post-transcriptional mechanisms in response to various stimuli, how CCR6 expression is post-transcriptionally regulated in Th17 cells is unknown. Here, using RNA-binding protein HuR conditional knock-out (KO) and wild-type (WT) mice, we present evidence that HuR post-transcriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation. We also found that HuR down-regulates several microRNA expressions, which could target the 3\u27-UTR of Ccr6 mRNA for decay. Accordingly, knock-out of HuR reduced CCR6 expression on Th17 cells and impaired their migration to CNS compared with the response of WT Th17 cells and thereby ameliorated EAE. Together, these findings highlight how HuR contributes to Th17 cell-mediated autoimmune neuroinflammation and support the notion that targeting HuR might be a potential therapeutic intervention for managing autoimmune disorders of the CNS

Strand and Statehood Predictors of Senior High School Graduates: A Tracer Study

Philippines has now graduated a couple of Senior High School (SHS) batches since its major education reform but not much was studied yet regarding its graduates. In view of tracing and learning of their status relative to the curriculum’s exits, this study is conceptualized. It aimed at profiling Aurora State College of Technology (ASCOT) SHS graduates and determining which of these profiles explain statehood and SHS strand. Alignment of respondents’ SHS strands to their college courses and the absorption rate of the college were also determined. A researcher-developed questionnaire was administered to 2018 and 2019 ASCOT SHS graduates. Responses received were screened, grouped according to strand then randomly sampled. A total of 523 responses remained for analysis. This corresponds to 2.87% margin for error which is within the traditional 5%. Results showed that majority of the graduates are within the ages 19-21, a huge majority of the respondents belong to the lower income categories and that the number of male graduates is at par with females. Out of all the respondents enrolled in college, only one-half have courses aligned to their SHS strands while ASCOT has an absorption rate 75.42%. Relative to their statehood, 90.82% pursued college education, 4.02% are employed, 1.15% are entrepreneurs and 4.02% are layabouts. Sex, age and monthly family income explained the respondents chosen strand. Both sex and monthly family income explained the statehood. Basic education schools should establish a career guidance program that help students choose their SHS strand aligned to the college degree they wish to earn. GAD trainers are also recommended to include in their campaign the non-exclusivity of SHS strands and college courses for the rich or poor, male or female. TVL courses must be offered and strengthened in education as this is where many poor students enroll in view of skills ready for employment and entrepreneurship

En masse nascent transcription analysis to elucidate regulatory transcription factors

Despite exhaustively informing about steady-state mRNA abundance, DNA microarrays have been used with limited success to identify regulatory transcription factors (TFs). The main limitation of this approach is that altered mRNA stability also strongly governs the patterns of expressed genes. Here, we used nuclear run-on assays and microarrays to systematically interrogate changes in nascent transcription in cells treated with the topoisomerase inhibitor camptothecin (CPT). Analysis of the promoters of coordinately transcribed genes after CPT treatment suggested the involvement of TFs c-Myb and Rfx1. The predicted CPT-dependent associations were subsequently confirmed by chromatin immunoprecipitation assays. Importantly, after RNAi-mediated knockdown of each TF, the CPT-elicited induction of c-Myb- and/or Rfx1-regulated mRNAs was diminished and the overall cellular response was impaired. The strategies described here permit the successful identification of the TFs responsible for implementing adaptive gene expression programs in response to cellular stimulation

Management approach for recurrent spontaneous pneumothorax in consecutive pregnancies based on clinical and radiographic findings

OBJECTIVE: To describe management and clinical features observed in a patient's seven spontaneous pneumothoraces that developed during two consecutive pregnancies involving both hemithoraces. MATERIALS AND METHODS: A 21 year old former smoker developed three spontaneous left pneumothoraces in the index pregnancy, having already experienced four right pneumothorax events in a prior pregnancy at age 19. RESULTS: Chest tubes were required in several (but not all) hospitalizations during these two pregnancies. Following her fourth right pneumothorax, thoracoscopic excision of right apical lung blebs and mechanical pleurodesis was performed. The series of left pneumothoraces culminated in mini-thoracotomy and thoracoscopically directed mechanical pleurodesis. For both pregnancies unassisted vaginal delivery was performed with no adverse perinatal sequelae. With the exception of multiple pneumothoraces, there were no additional pregnancy complications. CONCLUSION: Spontaneous pneumothorax in pregnancy is believed to be a rare phenomenon, yet the exact incidence is unknown. Here we present the first known case of multiple spontaneous pneumothoraces in two consecutive pregnancies involving both hemithoraces. Clinical management coordinated with obstetrics and surgical teams facilitated a satisfactory outcome for both pregnancies. The diagnosis of pneumothorax should be contemplated in any pregnant patient with dyspnea and chest pain, followed by radiographic confirmation

Translating Evidence-Based Falls Prevention into Clinical Practice in Nursing Facilities: Results and Lessons from a Quality Improvement Collaborative

OBJECTIVES—To describe the changes in process of care before and after an evidence-based fall reduction quality improvement collaborative in nursing facilities. DESIGN—Natural experiment with non-participating facilities serving as controls. SETTING—Community nursing homes. PARTICIPANTS—Thirty-six participating and 353 non-participating nursing facilities in North Carolina. INTERVENTION—Two in-person learning sessions, monthly teleconferences, and an e-mail discussion list over 9 months. The change package emphasized screening, labeling, and risk-factor reduction. MEASUREMENTS—Compliance was measured using facility self-report and chart abstraction (n = 832) before and after the intervention. Fall rates as measured using the Minimum Data Set (MDS) were compared with those of non-participating facilities as an exploratory outcome. RESULTS—Self-reported compliance with screening, labeling, and risk-factor reduction approached 100%. Chart abstraction revealed only modest improvements in screening (51% to 68%, P<.05), risk-factor reduction (4% to 7%, P = .30), and medication assessment (2% to 6%, P = .34). There was a significant increase in vitamin D prescriptions (40% to 48%, P = .03) and decrease in sedative-hypnotics (19% to 12%, P = .04) but no change in benzodiazepine, neuroleptic, or calcium use. No significant changes in proportions of fallers or fall rates were observed according to chart abstraction (28.6% to 37.5%, P = .17), MDS (18.2% to 15.4%, P = .56), or self-report (6.1–5.6 falls/1,000 bed days, P = .31). CONCLUSON—Multiple-risk-factor reduction tasks are infrequently implemented, whereas screening tasks appear more easily modifiable in a real-world setting. Substantial differences between self-reported practice and medical record documentation require that additional data sources be used to assess the change-in-care processes resulting from quality improvement programs. Interventions to improve interdisciplinary collaboration need to be developed

RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals

DNA Topoisomerases are essential to resolve topological problems during DNA metabolism in all species. However, the prevalence and function of RNA topoisomerases remain uncertain. Here, we show that RNA topoisomerase activity is prevalent in Type IA topoisomerases from bacteria, archaea, and eukarya. Moreover, this activity always requires the conserved Type IA core domains and the same catalytic residue used in DNA topoisomerase reaction; however, it does not absolutely require the non-conserved carboxyl-terminal domain (CTD), which is necessary for relaxation reactions of supercoiled DNA. The RNA topoisomerase activity of human Top3β differs from that of Escherichia coli topoisomerase I in that the former but not the latter requires the CTD, indicating that topoisomerases have developed distinct mechanisms during evolution to catalyze RNA topoisomerase reactions. Notably, Top3β proteins from several animals associate with polyribosomes, which are units of mRNA translation, whereas the Top3 homologs from E. coli and yeast lack the association. The Top3β-polyribosome association requires TDRD3, which directly interacts with Top3β and is present in animals but not bacteria or yeast. We propose that RNA topoisomerases arose in the early RNA world, and that they are retained through all domains of DNA-based life, where they mediate mRNA translation as part of polyribosomes in animals

Characterization of Novel Pathogenic Variants Leading to Caspase-8 Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome

Pathogenic RIPK1 variants have been described as the cause of two different inborn errors of immunity. Biallelic loss-of-function variants cause the recessively inherited RIPK1 deficiency, while monoallelic variants impairing the caspase-8-mediated RIPK1 cleavage provoke a novel autoinflammatory disease (AID) called cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome. The aim of this study was to characterize the pathogenicity of two novel RIPK1 variants located at the cleavage site of caspase-8 detected in patients with dominantly-inherited, early-onset undefined AID. RIPK1 genotyping was performed by Sanger and next-generation sequencing. Clinical and analytical data were collected from medical charts, and in silico and in vitro assays were performed to evaluate the functional consequences. Genetic analyses identified two novel heterozygous RIPK1 variants at the caspase-8 cleavage site (p.Leu321Arg and p.Asp324Gly), which displayed a perfect intrafamilial phenotype-genotype segregation following a dominant inheritance pattern. Structural analyses suggested that these variants disrupt the normal RIPK1 structure, probably making it less accessible to and/or less cleavable by caspase-8. In vitro experiments confirmed that the p.Leu321Arg and p.Asp324Gly RIPK1 variants were resistant to caspase-8-mediated cleavage and induced a constitutive activation of necroptotic pathway in a similar manner that previously characterized RIPK1 variants causing CRIA syndrome. All these results strongly supported the pathogenicity of the two novel RIPK1 variants and the diagnosis of CRIA syndrome in all enrolled patients. Moreover, the evidences here collected expand the phenotypic and genetic diversity of this recently described AID, and provide interesting data about effectiveness of treatments that may benefit future patients