bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles for the DNA-PK complex and 53BP1 in protecting ends from resection during DNA double-strand break repair
Authors: Shibata Atsushi , Jeggo Penny A
Published: August 2020

p53-binding protein 1 (53BP1) exerts distinct impacts in different situations involving DNA double-strand break (DSB) rejoining. Here we focus on how 53BP1 impacts upon the repair of ionising radiation-induced DSBs (IR-DSBs) and how it interfaces with Ku, the DNA end-binding component of canonical non-homologous end-joining (c-NHEJ), the major DSB repair pathway in mammalian cells. We delineate three forms of IR-DSB repair: resection-independent c-NHEJ, which rejoins most IR-DSBs with fast kinetics in G1 and G2, and Artemis and resection-dependent c-NHEJ and homologous recombination (HR), which repair IR-DSBs with slow kinetics in G1 and G2 phase, respectively. The fast component of DSB repair after X-ray exposure occurs via c-NHEJ with normal kinetics in the absence of 53BP1. Ku is highly abundant and has avid DNA end-binding capacity which restricts DNA end-resection and promotes resection-independent c-NHEJ at most IR-DSBs. Thus, 53BP1 is largely dispensable for resection-independent c-NHEJ. In contrast, 53BP1 is essential for the process of rejoining IR-DSBs with slow kinetics. This role requires 53BP1’s breast cancer susceptibility gene I (BRCA1) C-terminal (BRCT) 2 domain, persistent ataxia telangiectasia mutated (ATM) activation and potentially relaxation of compacted chromatin at heterochromatic-DSBs. In distinction, 53BP1 inhibits resection-dependent IR-DSB repair in G1 and G2, and this resection-inhibitory function can be counteracted by BRCA1. We discuss a model whereby most IR-DSBs are rapidly repaired by 53BP1-independent and resection-independent c-NHEJ due to the ability of Ku to inhibit resection, but, if delayed, then resection in the presence of Ku is triggered, the 53BP1 barrier comes into force and BRCA1 counteraction is required for resection.
Acute Myeloid Leukemia Case Harboring Unusual FLT3 Variant: Somatic vs Germline?
Authors: Singh Nirupama , Morlote Diana , Vnencak-Jones Cindy , Papadantonakis Nikolaos , Harada Shuko
Published: August 2020

FLT3 mutations are considered a prognostic and predictive marker. Here we report on a patient with a rare FLT3 germline variant in the context of relapsed acute myeloid leukemia (AML). A female patient aged 57 years presented with AML with mutations in the IDH2, ASXL1, and DNMT3A genes. She underwent allogenic hematopoietic stem cell transplant but relapsed 2 years posttransplant. Targeted next generation sequencing identified a new missense variant in the FLT3 tyrosine kinase domain c.2440G > T (p.A814S). The treating team considered the possibility of patient eligibility for an FLT3 inhibitor. Because both somatic and germline mutations can be identified in tumor tissue with high-throughput sequencing, it becomes important to distinguish the origin of these alterations when possible—especially, in this challenging case, to define the treatment modality. Simultaneous tumor/germline sequencing allows for the identification of rare germline mutations and may help in determining their significance in the pathogenesis of disease.
Spatial Transcriptomics of Nematodes Identifies Sperm Cells as a Source of Genomic Novelty and Rapid Evolution
Authors: Rödelsperger Christian , Ebbing Annabel , Sharma Devansh Raj , Okumura Misako , Sommer Ralf J , Korswagen Hendrik C
Published: August 2020

Divergence of gene function and expression during development can give rise to phenotypic differences at the level of cells, tissues, organs, and ultimately whole organisms. To gain insights into the evolution of gene expression and novel genes at spatial resolution, we compared the spatially resolved transcriptomes of two distantly related nematodes, Caenorhabditis elegans and Pristionchus pacificus, that diverged 60–90 Ma. The spatial transcriptomes of adult worms show little evidence for strong conservation at the level of single genes. Instead, regional expression is largely driven by recent duplication and emergence of novel genes. Estimation of gene ages across anatomical structures revealed an enrichment of novel genes in sperm-related regions. This provides first evidence in nematodes for the “out of testis” hypothesis that has been previously postulated based on studies in Drosophila and mammals. “Out of testis” genes represent a mix of products of pervasive transcription as well as fast evolving members of ancient gene families. Strikingly, numerous novel genes have known functions during meiosis in Caenorhabditis elegans indicating that even universal processes such as meiosis may be targets of rapid evolution. Our study highlights the importance of novel genes in generating phenotypic diversity and explicitly characterizes gene origination in sperm-related regions. Furthermore, it proposes new functions for previously uncharacterized genes and establishes the spatial transcriptome of Pristionchus pacificus as a catalog for future studies on the evolution of gene expression and function.
Frequent DNA methylation changes in cancerous and noncancerous lung tissues from smokers with non-small cell lung cancer
Authors: Daniunaite Kristina , Sestokaite Agne , Kubiliute Raimonda , Stuopelyte Kristina , Kettunen Eeva , Husgafvel-Pursiainen Kirsti , Jarmalaite Sonata
Published: August 2020

Cancer deaths account for nearly 10 million deaths worldwide each year, with lung cancer (LCa) as the leading cause of cancer-related death. Smoking is one of the major LCa risk factors, and tobacco-related carcinogens are potent mutagens and epi-mutagens. In the present study, we aimed to analyse smoking-related epigenetic changes in lung tissues from LCa cases. The study cohort consisted of paired LCa and noncancerous lung tissues (NLT) from 104 patients, 90 of whom were smokers or ex-smokers (i.e. ever smokers) at the time of diagnosis. DNA methylation status of tumour suppressor genes DAPK1, MGMT, p16, RASSF1 and RARB was screened by means of methylation-specific PCR (MSP) and further analysed quantitatively by pyrosequencing. Methylation of at least one gene was detected in 59% (61 of 104) of LCa samples and in 39% (41 of 104) of NLT. DAPK1 and RASSF1 were more frequently methylated in LCa than in NLT (P = 0.022 and P = 0.041, respectively). The levels of DNA methylation were higher in LCa than NLT at most of the analysed CpG positions. More frequent methylation of at least one gene was observed in LCa samples of ever smokers (63%, 57 of 90) as compared with never smokers (36%, 5 of 14; P = 0.019). In the ever smokers group, methylation of the genes also occurred in NLT, but was rare or absent in the samples of never smokers. Among the current smokers, RASSF1 methylation in LCa showed association with the number of cigarettes smoked per day (P = 0.017), whereas in NLT it was positively associated with the duration of smoking (P = 0.039). Similarly, p16 methylation in LCa of current smokers correlated with the larger number of cigarettes smoked per day (P = 0.047). Overall, DNA methylation changes were present in both cancerous and noncancerous tissues of LCa patients and showed associations with smoking-related parameters.
Topical nitroglycerin for management of peripheral extravasation of vasopressors: a case report
Authors: Shrestha Ninadini , Acharya Utsav , Shrestha Pramesh Sunder , Acharya Subhash Prasad , Karki Bipin , Dhakal Subodh Sagar
Published: August 2020

Peripheral route for administration of vasopressors is often opted due to resource limitations or as a rescue until central venous access is established. This, however, is not devoid of complications, the most common being extravasation and tissue injury. Phentolamine is the only drug approved for management of vasopressor extravasation; however, successful use of other agents has been reported. Here we report a case of peripheral extravasation of vasopressors, successfully managed with topical nitroglycerin in intensive care unit in Kathmandu. To our knowledge, this is the first report of such kind from Nepal.
Loneliness and COVID-19 preventive behaviours among Japanese adults
Authors: Stickley Andrew , Matsubayashi Tetsuya , Ueda Michiko
Published: August 2020

Background

There is some evidence that loneliness may be linked to poorer health behaviours. Despite this, there has been little research to date on the relationship between loneliness and COVID-19 preventive behaviours. We studied these associations in a sample of the Japanese population.

Methods

Data were analysed from an online survey of 2000 adults undertaken in April and May 2020. Loneliness was assessed with the Three-Item Loneliness Scale. Information was also collected on 13 COVID-19 preventive behaviours. Regression analyses were used to examine associations.

Results

In linear regression models adjusted for demographic and mental health variables, both dichotomous and continuous loneliness measures were negatively associated with engaging in COVID-19 preventive behaviours. Logistic regression analyses further showed that loneliness was also associated with reduced odds for a variety of individual preventive behaviours including wearing a mask (odds ratio [OR]: 0.77, 95% confidence interval [CI]: 0.62–0.95), disinfecting hands (OR: 0.80, 95% CI: 0.67–0.94) and social distancing when outdoors (OR: 0.75, 95% CI: 0.61–0.92).

Conclusions

Loneliness is associated with lower engagement in COVID-19 preventive behaviours. Interventions to prevent or ameliorate loneliness during the ongoing pandemic may be important in combating the spread of the coronavirus.
Mortality over 14 years in MTX-refractory patients randomized to a strategy of addition of infliximab or sulfasalazine and hydroxychloroquine
Authors: Miller Heather , Wallman Johan K , Petersson Ingemar F , Saevarsdottir Saedis , Söderling Jonas , Ernestam Sofia , Askling Johan , van Vollenhoven Ronald , Neovius Martin
Published: August 2020

Objective

To compare mortality risk over up to 14 years of follow-up in methotrexate-refractory patients with early RA randomized to a strategy starting with addition of infliximab vs addition of SSZ and HCQ.

Methods

Data was from the two-arm, parallel, randomized, active-controlled, open-label Swefot trial in which patients with early RA (symptom duration <1 y) were recruited from 15 rheumatology clinics in Sweden (2002–2005). Patients who did not achieve low disease activity after 3–4 months of MTX were randomized to addition of infliximab (n = 128) or SSZ and HCQ (n = 130). Participants were followed until death, emigration, or end of follow-up, whichever came first. Analyses were by intention-to-treat.

Results

Over an average follow-up of 13 years, there were 13 and 16 deaths, respectively [8.8 vs 10.6 deaths per 1000 person-years; mortality hazard ratio 1.2 (95% CI: 0.6, 2.5); P =0.62]. The 1-year mortality was 0.8% in both treatment arms, the 5-year mortality was 2.3% for the infliximab arm compared with 1.5% for the conventional combination treatment arm, while the 10-year mortality was 7.8% and 7.7%, respectively. After 5 years, ∼50% of patients in the conventional combination therapy arm had switched to biologic treatment, and 50% in the biologic arm had discontinued treatment with a biologic DMARD.

Conclusion

No difference in mortality risk could be observed over up to 14 years of follow-up between treatment strategy groups. At 5 years (3 years after trial cessation), 50% of patients remained on their assigned therapy, reflecting that DMARD combination is an adequate treatment strategy in 50% of patients.

Trial registration

clinicaltrials.gov, identifier: NCT00764725.
Successful management with Janus kinase inhibitor tofacitinib in refractory juvenile dermatomyositis: a pilot study and literature review
Authors: Yu Zhongxun , Wang Lin , Quan Meiying , Zhang Tiannan , Song Hongmei
Published: August 2020

Objectives

JDM is a rare autoimmune inflammatory muscle disease with a pronounced IFN signature. Treatment for children with JDM has improved over the years with the use of steroids and immunosuppressive agents. However, there remains a subset of children who have refractory disease. Janus kinase and type I IFN signalling production are suspected to contribute to the pathogenesis of JDM. Our pilot study investigated the use of tofacitinib, a Janus kinase inhibitor, in refractory JDM cases to provide new therapeutic options for better treatment.

Methods

Refractory JDM was defined as patients who failed two or more steroid sparing agents or high-dose steroids. Tofacitinib was given to three refractory JDM patients with a dose of 5 mg twice per day for at least 6 months. Core set measures defined by Pediatric Rheumatology International Trials Organization were evaluated at month 0, 3 and 6 along with other systemic evaluations. A literature review was conducted to identify all the cases using Janus kinase inhibitors in JDM.

Results

All three subjects tolerated and responded well to tofacitinib with significant improvement in Child Myositis Assessment Scale, manual muscle testing-8, physician global disease activity and inflammatory indices without occurrence of severe adverse events.

Conclusion

This pilot study showed improvement of muscle strength, resolution of cutaneous lesions, increased daily quality of life and successful tapering of steroids when tofacitinib used in selected cases. Tofacitinib can be considered with caution when treating refractory JDM cases. Further randomized controlled trials are warranted to assess its efficacy in JDM.
An Innovative Approach to Advancing Academic Success for Underrepresented Nursing Students Using the Collective Impact Model
Authors: Ackerman-Barger Kupiri , DeWitty Vernell P. , Cooper Jazmine , Anderson Maija R.
Published: August 2020

This article describes the application of the Collective Impact Model as an innovative conceptual framework for developing a pedagogical process for advancing academic success and retention for underrepresented nursing students. A more diverse nursing workforce is critical to promoting health equity and supporting a culture of health by providing access to culturally and linguistically appropriate care. By strategically applying this framework to a complex issue in nursing education, we discuss a process that may lead to increased academic success and NCLEX®RN pass rates for underrepresented students.
The Effects of a Deliberate Practice Debriefing During a Response to Rescue Patient Simulation With Undergraduate Nursing Students
Authors: Aronson Barbara , Bell Arleigh , Andrighetti Tia , Meyer Mary , Shepherd Karen , Bambini Deborah
Published: August 2020

The purpose of this multisite, randomized, pretest/posttest quasi-experimental study was to compare student nurse competency, learning retention, and perceived student support after exposure to a deliberate practice debriefing versus standardized debriefing. Fifty undergraduate students participated in the complex response to rescue simulation. The intervention group had significantly higher total mean and three subscale scores on the competency tool than the comparison group, although differences in learning retention and student support were not significant. This study provides preliminary support for the effectiveness of deliberate practice debriefing to enhance students’ mastery of skills and behaviors in complex simulations.
Pregnancy and Hymenoptera venom allergy
Authors: Bonadonna Patrizia , Mauro Marina , Preziosi Donatella , Pravettoni Valerio
Published: August 2020

Purpose of review

To evaluate the indication to perform venom immunotherapy (VIT) during pregnancy considering the risks of adverse events during the build-up phase or the maintenance phase and analyzing specific articles and guidelines on VIT.

Recent findings

Only few studies treat this argument and literature only counts one recent study on the topic, whereas recent guidelines state the behavior to keep in pregnancy.

Hymenoptera venom allergy (HVA) affects about 7.5% of the European population. VIT is the only effective disease-modifying treatment for patients presenting anaphylactic reactions. VIT counts several mechanisms of action, with the increase of IgG1 and IgG4 and a cytokine impairment inducing a Th2–Th1 shift. Pregnancy is a health condition where a Th2 profile is required to prevent fetal rejection, so VIT could be a problem for the fetus when started during pregnancy.
Volatile Anesthetics Activate a Leak Sodium Conductance in Retrotrapezoid Nucleus Neurons to Maintain Breathing during Anesthesia in Mice
Authors: Yang Yaoxin , Ou Mengchan , Liu Jin , Zhao Wenling , Zhuoma Lamu , Liang Yan , Zhu Tao , Mulkey Daniel K. , Zhou Cheng
Published: August 2020

Background

Volatile anesthetics moderately depress respiratory function at clinically relevant concentrations. Phox2b-expressing chemosensitive neurons in the retrotrapezoid nucleus, a respiratory control center, are activated by isoflurane, but the underlying mechanisms remain unclear. The hypothesis of this study was that the sodium leak channel contributes to the volatile anesthetics-induced modulation of retrotrapezoid nucleus neurons and to respiratory output.

Methods

The contribution of sodium leak channels to isoflurane-, sevoflurane-, and propofol-evoked activity of Phox2b-expressing retrotrapezoid nucleus neurons and respiratory output were evaluated in wild-type and genetically modified mice lacking sodium leak channels (both sexes). Patch-clamp recordings were performed in acute brain slices. Whole-body plethysmography was used to measure the respiratory activity.

Results

Isoflurane at 0.42 to 0.50 mM (~1.5 minimum alveolar concentration) increased the sodium leak channel–mediated holding currents and conductance from −75.0 ± 12.9 to −130.1 ± 34.9 pA (mean ± SD, P = 0.002, n = 6) and 1.8 ± 0.5 to 3.6 ± 1.0 nS (P = 0.001, n = 6), respectively. At these concentrations, isoflurane increased activity of Phox2b-expressing retrotrapezoid nucleus neurons from 1.1 ± 0.2 to 2.8 ± 0.2 Hz (P < 0.001, n = 5), which was eliminated by bath application of gadolinium or genetic silencing of sodium leak channel. Genetic silencing of sodium leak channel in the retrotrapezoid nucleus resulted in a diminished ventilatory response to carbon dioxide in mice under control conditions and during isoflurane anesthesia. Sevoflurane produced an effect comparable to that of isoflurane, whereas propofol did not activate sodium leak channel–mediated holding conductance.

Conclusions

Isoflurane and sevoflurane increase neuronal excitability of chemosensitive retrotrapezoid nucleus neurons partly by enhancing sodium leak channel conductance. Sodium leak channel expression in the retrotrapezoid nucleus is required for the ventilatory response to carbon dioxide during anesthesia by isoflurane and sevoflurane, thus identifying sodium leak channel as a requisite determinant of respiratory output during anesthesia of volatile anesthetics.

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Machine Learning Predicts Prolonged Acute Hypoxemic Respiratory Failure in Pediatric Severe Influenza
Authors: Sauthier Michaël S. , Jouvet Philippe A. , Newhams, Margaret M. , Randolph Adrienne G.
Published: August 2020

Background:

Influenza virus is a major cause of acute hypoxemic respiratory failure. Early identification of patients who will suffer severe complications can help stratify patients for clinical trials and plan for resource use in case of pandemic.

Objective:

We aimed to identify which clinical variables best predict prolonged acute hypoxemic respiratory failure in influenza-infected critically ill children. Acute hypoxemic respiratory failure was defined using hypoxemia cutoffs from international consensus definitions of acute respiratory distress syndrome in patients with ventilatory support. Prolonged acute hypoxemic respiratory failure was defined by acute hypoxemic respiratory failure criteria still present at PICU day 7.

Derivation Cohort:

In this prospective multicenter study across 34 PICUs from November 2009 to April 2018, we included children (< 18 yr) without comorbid risk factors for severe disease.

Validation Cohort:

We used a Monte Carlo cross validation method with N
2 random train-test splits at a 70–30% proportion per model.

Prediction Model:

Using clinical data at admission (day 1) and closest to 8 am on PICU day 2, we calculated the area under the receiver operating characteristic curve using random forests machine learning algorithms and logistic regression.

Results:

We included 258 children (median age = 6.5 yr) and 11 (4.2%) died. By day 2, 65% (n = 165) had acute hypoxemic respiratory failure dropping to 26% (n = 67) with prolonged acute hypoxemic respiratory failure by day 7. Those with prolonged acute hypoxemic respiratory failure had a longer ICU stay (16.5 vs 4.0 d; p < 0.001) and higher mortality (13.4% vs 1.0%). A multivariable model using random forests with 10 admission and eight day 2 variables performed best (0.93 area under the receiver operating characteristic curve; 95 CI%: 0.90–0.95) where respiratory rate, Fio
2, and pH on day 2 were the most important factors.

Conclusions:

In this prospective multicentric study, most children with influenza virus–related respiratory failure with prolonged acute hypoxemic respiratory failure can be identified early in their hospital course applying machine learning onto routine clinical data. Further validation is needed prior to bedside implementation.
Higher Intensity Thromboprophylaxis Regimens and Pulmonary Embolism in Critically Ill Coronavirus Disease 2019 Patients
Authors: Taccone Fabio Silvio , Gevenois Pierre Alain , Peluso Lorenzo , Pletchette Zoe , Lheureux Olivier , Brasseur Alexandre , Garufi Alessandra , Talamonti Marta , Motte Serge , Nobile Leda , Grimaldi David , Creteur Jacques , Vincent Jean-Louis
Published: August 2020

Objectives:

To assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients.

Design:

Retrospective analysis of prospectively collected data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020.

Setting:

ICU of an University Hospital in Belgium.

Patients and Interventions:

Critically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin).

Measurements and Main Results:

Of 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4–8 d) since ICU admission and 12 days (9–16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs: 0.78–1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%—odds ratio 0.13 [0.02–0.69]; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 [0.24–3.26]; p = 0.99).

Conclusions:

In this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication.
Usability and the Rapid Deployable Infectious Disease Decision Support System
Authors: Hoelscher Dwayne , McBride Susan
Published: August 2020

Health information technology–guided clinical decision support has demonstrated decreases in patient safety errors in the electronic health record. Unknown and re-emerging infectious diseases are a growing concern for many healthcare facilities. The purpose of this project was to develop a modular approach to integrate rapid deployment of clinical decision support for infectious diseases into the clinical workflow and evaluate the usability of the design. This article reports on the results of a quality improvement project to develop, implement, and evaluate rapid deployment of a clinical decision support module using a tuberculosis use case. Important lessons learned from the electronic health record build with previous Ebola and Zika decision support alert strategy are discussed as foundational in guiding the overall design, implementation, and evaluation of improvement strategies. Subject matter expert feedback was sought throughout the project for electronic health record design and build considerations. Usability evaluation was conducted using the classic Task, User, Representation, and Function unified framework of electronic health record usability. Usability satisfaction for both providers and nurses remained high. Tuberculosis cases pre-alert and post-alert had decreased order times for diagnostic studies. Results suggest satisfied clinicians coupled with usable systems create a more efficient workflow resulting in safer and timelier diagnostic testing.
Traffic-related Noise Exposure and Late-life Dementia and Cognitive Impairment in Mexican–Americans
Authors: Yu Yu , Mayeda Elizabeth Rose , Paul Kimberly C. , Lee Eunice , Jerrett Michael , Su Jason , Wu Jun , Shih I-Fan , Haan Mary , Ritz Beate
Published: August 2020

Background:

Recently, it has been suggested that environmental exposures from traffic sources including noise may play a role in cognitive impairment in the elderly. The objective of the study was to investigate the association between local traffic-related noise pollution and incident dementia or cognitive impairment without dementia (CIND) during a 10-year follow-up period.

Methods:

1612 Mexican–American participants from the Sacramento Area Latino Study on Aging (SALSA) were followed every 12–15 months via home visits from 1998 to 2007. We used the SoundPLAN software package to estimate noise originating from local traffic with the input of Annual Average Daily Traffic (AADT) data from Metropolitan Planning Organizations (MPO) based on geocoded residential addresses at baseline (1998–1999). We estimated the risks of incident dementia or CIND from 24-hour and nighttime noise exposure using Cox proportional hazard models.

Results:

During the follow-up, we identified 159 incident dementia or CIND cases in total. Per 11.6 dB (interquartile range width) increase in 24-hour noise, the hazard of developing dementia or CIND increased (hazard ratio = 1.3 [1.0, 1.6]) during follow-up; estimates were slightly lower (hazard ratio = 1.2 [0.97, 1.6]) when adjusting for modeled local air pollution exposure from traffic sources. Overall, the risk of dementia/CIND was elevated when 24-hour and nighttime noise were higher than 75 and 65 dB respectively. See video Abstract: http://links.lww.com/EDE/B728.

Conclusions:

In our study, traffic-related noise exposure was associated with increased risk of dementia or CIND in elderly Mexican–Americans. Future studies taking into account other noise sources and occupational noise exposure before retirement are needed.
Effect of vitamin D supplementation during pregnancy on mid-to-late gestational blood pressure in a randomized controlled trial in Bangladesh
Authors: Subramanian Anita , Korsiak Jill , Murphy Kellie E. , Al Mahmud Abdullah , Roth Daniel E. , Gernand Alison D.
Published: August 2020

Objective:

To examine the dose-dependent effect of maternal vitamin D during pregnancy on blood pressure from mid-to-late gestation within the context of a randomized, placebo-controlled trial of vitamin D supplementation in Bangladesh (n = 1298).

Methods:

Healthy women without hypertension were enrolled at 17–24 weeks gestation and randomized to one of four vitamin D doses during pregnancy: placebo, 4200, 16 800 or 28 000 IU/week. This substudy examined 1257 women with blood pressure measured at enrollment with at least one other timepoint (measurements included at 24 weeks, 30 weeks, and weekly from 36 weeks until delivery). Effects of vitamin D on SBP or DBP were analyzed using mixed-effects models.

Results:

Vitamin D did not have an effect on SBP or DBP at 24 or 30 weeks; blood pressure was higher at 36 weeks for the highest dose versus placebo [mean difference (95% CI) mmHg: SBP = 2.3 (0.9–3.7); DBP = 1.9 (0.7–3.0)]. The differences in changes in SBP and DBP between vitamin D groups and placebo across intervals were small (P > 0.10), but the difference for 28 000 IU/week versus placebo was the highest from 30 to 36 weeks [SBP 0.2 (−0.1 to 0.5) and DBP 0.2 (−0.0 to 0.4) mmHg].

Conclusion:

Vitamin D supplementation starting mid-pregnancy did not affect SBP or DBP until late gestation, and then only at the highest dose. These results do not support the clinical use of vitamin D in pregnancy to lower maternal blood pressure.
A European Study of the Performance and Safety of MINIject in Patients With Medically Uncontrolled Open-angle Glaucoma (STAR-II)
Authors: García Feijoó Julián , Denis Philippe , Hirneiß Christoph , Aptel Florent , Perucho González Lucía , Hussain Zubair , Lorenz Katrin , Pfeiffer Norbert
Published: August 2020

Precis:

In this European study (STAR-II), MINIject, a novel, ab-interno, supraciliary minimally invasive glaucoma surgery device, effectively lowered intraocular pressure (IOP) and the need for IOP-lowering medications in patients with primary open-angle glaucoma.

Purpose:

This study evaluates the safety and performance of a minimally invasive supraciliary glaucoma drainage device (MINIject DO627) for surgical treatment of primary open-angle glaucoma in patients refractory to topical hypotensive medications.

Methods:

In a prospective, interventional, single-arm, multicenter, European study (STAR-II), MINIject was successfully implanted in a stand-alone procedure in 29 of 31 patients in 8 sites in 3 countries. The primary endpoint was the success rate 6 months after surgery >60% (defined as diurnal IOP ≤21 and >5 mm Hg with ≥20% IOP reduction from baseline, with/without glaucoma hypotensive medication). ClinicalTrials.gov: NCT03624361.

Results:

At the 6-month follow-up, the primary endpoint was fulfilled, with 75.9% of patients reaching prospectively defined success. The mean IOP was reduced by 40.2% (9.9 mm Hg) to 14.7±6.0 mm Hg at 6 months from 24.6±3.8 mm Hg at baseline. The use of IOP-lowering medication ingredients was reduced by 63.4% from 2.9±1.2 at baseline to 1.0±1.3. Furthermore, 79.3% of the patients had mean IOP ≤18 mm Hg, 82.8% achieved a ≥20% IOP reduction, and 55.2% were medication free at 6 months. Six device-related serious adverse events were reported in the study eye: IOP increase (3/31 patients, 9.7%), and single reports of eye pain, corneal erosion, and chorioretinal folds (1/31, 3.2%), all of which resolved. There was minimal change to corneal endothelial cell density.

Conclusion:

Ab-interno supraciliary surgical implantation using MINIject DO627 in a stand-alone procedure significantly lowers IOP by 40% at the 6-month follow-up, while reducing the need for IOP-lowering medication.
Medically Attended Outpatient Coronavirus Infections in Ecuadorean Children During the 20 Months Preceding Countrywide Lockdown Related to the SARS-CoV-2 Pandemic of 2020
Authors: Sippy Rachel , Prado Esteban Ortiz , Pizarro Fajardo Freddy , Hidalgo Iván , Aguilar Guillermo Victoriano , Bonville Cynthia A. , Aponte Cinthya Cueva , Gómez Mariuxi Salazar , Aponte Jorge Luis Carrillo , Cordova Mercy Borbor , Polo Gladys Rincón , Suryadevara Manika , Domachowske Joseph B.
Published: August 2020

Background:

Human coronaviruses (HCoVs) cause respiratory tract infections during childhood manifesting as common colds, bronchiolitis, croup and pneumonia. In temperate geographies, HCoV activity peaks between December and March. The epidemiology and manifestations of HCoV infections have not been previously reported from Ecuador.

Methods:

Children <5 years who presented with ≥2 symptoms consistent with an acute respiratory tract infection were eligible for enrollment. After obtaining informed consent, demographic data and details regarding the acute illness were recorded. Secretions collected with a nasopharyngeal swab underwent diagnostic testing using multiplex polymerase chain reaction.

Results:

A total of 850 subjects were enrolled. A total of 677 (80%) tested positive for at least 1 pathogen, including 49 (7.2%) who tested positive for ≥1 HCoV type. HCoV-NL63 was the most frequent type detected (39%), followed by HCoV-OC43 (27%), 229E (22%) and HKU1 (12%). Nearly all subjects who tested positive for HCoV had nasal congestion or secretions (47/49; 96%). The most frequent syndromic diagnosis was common cold (41%), followed by bronchiolitis (27%). We found no association between the infecting HCoV type and subject’s syndromic diagnosis (P > 0.05) or anatomic location of infection (upper vs. lower respiratory tract; P > 0.05). The 2018–2019 peak HCoV activity occurred from October to November; the 2019–2020 peak occurred from January to February.

Conclusions:

HCoVs were detected in ~7% of outpatient Ecuadorean children <5 years of age with symptoms of acute respiratory tract infection. The most frequently detected HCoV types, and the period of peak HCoV activity differed for the 2018–2019 and 2019–2020 seasons.
Evaluation for Arboviral Infection Among Children Hospitalized in Colorado With Aseptic Meningitis and Encephalitis
Authors: Gould Carolyn V. , Messacar Kevin , Dominguez Samuel R. , Panella Amanda , Tobolowsky Farrell , Fischer Marc
Published: August 2020

Among 39 children hospitalized in Colorado with aseptic meningitis or encephalitis, 16 (41%) had an etiology identified, including 2 (5%) with West Nile virus infection. Despite extensive testing, no other arboviral infections were identified. Arboviral infection should be considered in children with neuroinvasive disease during arboviral season with testing directed toward viruses endemic to the region and type of exposure.
Identification of neural and psychophysical predictors of headache reduction after cognitive behavioral therapy in adolescents with migraine
Authors: Nahman-Averbuch Hadas , Schneider Victor J. , Chamberlin Leigh Ann , Kroon Van Diest Ashley M. , Peugh James L. , Lee Gregory R. , Radhakrishnan Rupa , Hershey Andrew D. , Powers Scott W. , Coghill Robert C. , King Christopher D.
Published: August 2020

Cognitive behavioral therapy (CBT) is a psychological intervention that involves development of coping strategies to reduce the experience of pain. Although CBT is a promising intervention to reduce headache days in patients with migraine, it may not be effective for all patients. Thus, there is a need to identify markers that could predict which patients will respond to CBT. We aimed to determine whether baseline brain function and amygdalar connectivity, assessed by functional magnetic resonance imaging, or pain modulation capacities, assessed by the conditioned pain modulation (CPM) response, can predict a reduction in headache days after CBT in adolescents with migraine. Patients with migraine (n = 20; age range 10-17 years) completed 8 weekly CBT sessions. The CPM response was examined in the trapezius and the leg. Headache days significantly decreased after CBT (P < 0.001). Greater functional connectivity before CBT between the right amygdala and frontal gyrus, anterior cingulate cortex, and precentral gyrus was related to greater headache reduction after CBT. Greater reduction in headache days after CBT was related with less efficient CPM response before CBT at the trapezius (r = −0.492, P = 0.028) but not at the leg. This study found that headache reduction after CBT was related to right amygdala connectivity with frontal and sensorimotor regions at baseline as well as baseline pain modulation capacities. These findings suggest that individual differences in brain function and pain modulation can be associated with clinical improvements and help with determination of CBT responsiveness.
Employers’ Role in Employee Health
Authors: Pfeffer Jeffrey , Vilendrer Stacie , Joseph Grace , Kim Jason , Singer Sara J.
Published: August 2020

Objective:

Employers affect the health of employees and their families through work environments and employee benefits. We sought to understand employer decisions around those topics.

Methods:

Interviews with 21 executives from diverse, purposely-sampled, progressive companies with transcripts analyzed using inductive and deductive methods.

Results:

Companies often viewed keeping employees healthy primarily as a means to profitability rather than an end in itself and rationalized stressful workplaces as necessary and non-changeable. Many possible actions including job redesign and changing benefits administrators were seen as infeasible. Even large, resource-rich organizations were strikingly non-agentic.

Conclusions:

Companies seem less committed to the goal of increasing employee health than they claim or than they should be, given the significant relationship between employee health and economic performance, and see external and internal barriers to improving health that are often self-created.
Nurses’ Mental Health During the Covid-19 Outbreak
Authors: Sampaio Francisco , Sequeira Carlos , Teixeira Laetitia
Published: August 2020

Objective:

To describe nurses’ mental health status during the Covid-19 outbreak and to explore the factors that might accentuate the negative consequences on their mental health.

Methods:

We conducted an online survey to evaluate demographic variables, working conditions, family dynamics, and mental health variables in nurses working in healthcare settings, in Portugal, during the Covid-19 outbreak.

Results:

Portuguese nurses presented higher depression, anxiety and stress levels, when compared to the Portuguese general population, during the outbreak. Overall, nurses who did not consider the quantity and quality of personal protective equipment as adequate presented significantly higher levels of depression, anxiety, and stress.

Conclusions:

Our results suggest that nurses’ mental health status seems to be particularly affected by the Covid-19 outbreak and that some modifiable elements might accentuate the impacts on their mental health.
Early Experience With Telemedicine in Patients Undergoing Otologic/Neurotologic Procedures
Authors: Shapiro Scott B. , Lipschitz Noga , Kemper Nathan , Zuccarello Mario , Breen Joseph T. , Pensak Myles L. , Samy Ravi N.
Published: August 2020

Objective:

Compare outcomes for patients who were seen via telemedicine visits after otology/neurotology surgical procedures with those who were seen in traditional office visits.

Study Design:

Retrospective case review.

Setting:

Tertiary care academic medical center.

Patients:

Inclusion criteria were patients who underwent otologic/neurotologic surgery and were seen in at least one telemedicine visit for postoperative care.

Intervention (s):

Telemedicine visit for postoperative care.

Main Outcome Measure (s):

Comparison of the number of patient calls, unplanned visits, and delayed complications between telemedicine patients and controls matched for age, procedure, and American Society of Anesthesiologists (ASA) status.

Results:

Eighteen patients were seen in telemedicine visits postoperatively after the following otologic/neurotologic surgical procedures: cochlear implant surgery (10), vestibular schwannoma resection (4), combined middle fossa and transmastoid cerebrospinal fluid (CSF) leak repair (2), middle fossa repair of superior canal dehiscence (1), and stapedectomy (1). All telehealth visits were for the second postoperative visit. The mean number of patient calls after surgery was 2.3 for the telemedicine group and 1.9 for matched controls which was not a statistically significant difference (p = 0.466). Both groups each had two patients who went to the emergency room, with one in each group being admitted. There was one delayed complication in the control group.

Conclusion:

Our preliminary experience suggests telemedicine may be used safely in caring for patients after otologic/neurotologic surgery, though it may be associated with more patient phone calls. Further study and experience, including assessing patient satisfaction, will clarify the future role of telemedicine in otology and neurotology.
Epigenetic-sensitive challenges of cardiohepatic interactions: clinical and therapeutic implications in heart failure patients
Authors: Benincasa Giuditta , Cuomo Oreste , Vasco Maria , Vennarecci Giovanni , Canonico Raffaele , Della Mura Nunzia , Alfano Roberto , Napoli Claudio
Published: August 2020

Heart failure and liver dysfunction can coexist owing to complex cardiohepatic interactions including the development of hypoxic hepatitis and congestive hepatopathy in patients with heart failure as well as ‘cirrhotic cardiomyopathy’ in advanced liver disease and following liver transplantation. The involvement of liver dysfunction in patients with heart failure reflects crucial systemic hemodynamic modifications occurring during the evolution of this syndrome. The arterial hypoperfusion and downstream hypoxia can lead to hypoxic hepatitis in acute heart failure patients whereas passive congestion is correlated with congestive hepatopathy occurring in patients with chronic heart failure. Nowadays, liquid biopsy strategies measuring liver function are well established in evaluating the prognosis of patients with heart failure. Large randomized clinical trials confirmed that gamma-glutamyltransferase, bilirubin, lactate deihydrogenase, and transaminases are useful prognostic biomarkers in patients with heart failure after transplantation. Deeper knowledge about the pathogenic mechanisms underlying cardiohepatic interactions would be useful to improve diagnosis, prognosis, and treatments of these comorbid patients. Epigenetic-sensitive modifications are heritable changes to gene expression without involving DNA sequence, comprising DNA methylation, histone modifications, and noncoding RNAs which seem to be relevant in the pathogenesis of heart failure and liver diseases when considered in a separate way. The goal of our review is to highlight the pertinence of detecting epigenetic modifications during the complex cardiohepatic interactions in clinical setting. Moreover, we propose a clinical research program which may be useful to identify epigenetic-sensitive biomarkers of cardiohepatic interactions and advance personalized therapy in these comorbid patients.
Emphysematous Cystitis Following Bone Marrow Transplant
Authors: Pringle Charlene , Brothers Elizabeth
Published: August 2020

Emphysematous cystitis is an exceedingly rare complication of urinary tract infection in children and adults. Characterized by air within the bladder wall, this life-threatening condition most often impacts diabetic women. The inciting pathogen is typically Escherichia coli or Klebsiella pneumoniae, though many other organisms have also been reported. Diagnosis is most commonly made via computed tomography scan; however, plain radiographs have also been described to be diagnostic. Medical management is the mainstay of therapy, consisting of bladder decompression and treatment of the underlying infection. Urologic surgery is required in 10% of cases. We report a 10-year-old child with a recent history of bone marrow transplantation complicated by gut-associated graft–versus-host disease who was diagnosed with emphysematous cystitis following a change in his abdominal pain.
Case Report: Long-term Structural and Functional Effects of Ethambutol Optic Neuropathy
Authors: Addy Laura K. , Harrison Wendy W.
Published: August 2020

SIGNIFICANCE

This case report demonstrates reduction in the retinal nerve fiber layer (RNFL) thickness and an abnormal electroretinogram after toxic optic neuropathy from ethambutol, more than 1 year after improvements in visual acuity (VA) and visual fields (VFs) were seen. Although many studies have described complications of ethambutol, continuing reduction in RNFL thickness 2 years after discontinuation has not been described elsewhere.

PURPOSE

It is well known that ethambutol can cause optic nerve toxicity, visual impairment, and VF loss. Visual acuity can be regained after stopping the drug; however, the amount and time frame are variable. There are few data on long-term follow-up of these cases to direct clinicians how to proceed once VA has stabilized. Here we present a case with 2 years of follow-up for a patient with ethambutol toxicity, showing the condition change even after VA becomes normal.

CASE REPORT

A 61-year-old man presented shortly after discontinuing ethambutol for Mycobacterium avium complex. Visual acuity values were 20/70 in the right eye and 20/125 in the left eye with cecocentral VF scotomas. Optical coherence tomography showed normal RNFL. Visual-evoked potentials were significantly reduced and delayed. Over the course of 2 years, the patient became asymptomatic as VA and VF returned to normal and visual-evoked potential improved. However, the optical coherence tomography RNFL was reduced from each visit to the next, and the electroretinogram showed decreased scotopic and photopic amplitudes.

CONCLUSIONS

Signs of ethambutol toxicity may remain or worsen years after discontinuation, even in the absence of patient symptoms and with normal VA and VF.
Three Cases of Karoshi Without the Typical Pathomorphological Features of Cardiovascular/Cerebrovascular Disease
Authors: Miao Qi , Li Jing , Pan Yu-Peng , Yu Yan-Geng , Zhang Fu , Xiao Ning , Li Dong-Ri
Published: August 2020

Karoshi is a term used to describe unexplained sudden death associated with overwork and has become a serious public health issue in China. Cases have occurred in physicians, university professors, engineers in high-tech companies, and blue-collar workers. The mechanisms associated with death by overwork are very complex. According to most researchers, karoshi is considered to be caused by an excessive workload that induces deterioration of underlying hypertension or atherosclerosis. These conditions inevitably lead to death from cardiovascular or cerebrovascular diseases. However, in our own experience, we have found that in some cases, the victims of karoshi were in a chronic state of overwork but without a history of cardiovascular or cerebrovascular diseases. In support of this, we have found that even autopsies have revealed few positive findings except for cardiac hypertrophy. In this article, we report 3 typical cases of karoshi but without the typical pathomorphological features of cardiovascular or cerebrovascular disease.