bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel ribonucleotide discrimination in the RNA polymerase-like two-barrel catalytic core of Family D DNA polymerases
Authors: Zatopek Kelly M , Alpaslan Ece , Evans Thomas C , Sauguet Ludovic , Gardner Andrew F
Published: October 2020

Family D DNA polymerase (PolD) is the essential replicative DNA polymerase for duplication of most archaeal genomes. PolD contains a unique two-barrel catalytic core absent from all other DNA polymerase families but found in RNA polymerases (RNAPs). While PolD has an ancestral RNA polymerase catalytic core, its active site has evolved the ability to discriminate against ribonucleotides. Until now, the mechanism evolved by PolD to prevent ribonucleotide incorporation was unknown. In all other DNA polymerase families, an active site steric gate residue prevents ribonucleotide incorporation. In this work, we identify two consensus active site acidic (a) and basic (b) motifs shared across the entire two-barrel nucleotide polymerase superfamily, and a nucleotide selectivity (s) motif specific to PolD versus RNAPs. A novel steric gate histidine residue (H931 in Thermococcus sp. 9°N PolD) in the PolD s-motif both prevents ribonucleotide incorporation and promotes efficient dNTP incorporation. Further, a PolD H931A steric gate mutant abolishes ribonucleotide discrimination and readily incorporates a variety of 2′ modified nucleotides. Taken together, we construct the first putative nucleotide bound PolD active site model and provide structural and functional evidence for the emergence of DNA replication through the evolution of an ancestral RNAP two-barrel catalytic core.
GRNdb: decoding the gene regulatory networks in diverse human and mouse conditions
Authors: Fang Li , Li Yunjin , Ma Lu , Xu Qiyue , Tan Fei , Chen Geng
Published: October 2020

Gene regulatory networks (GRNs) formed by transcription factors (TFs) and their downstream target genes play essential roles in gene expression regulation. Moreover, GRNs can be dynamic changing across different conditions, which are crucial for understanding the underlying mechanisms of disease pathogenesis. However, no existing database provides comprehensive GRN information for various human and mouse normal tissues and diseases at the single-cell level. Based on the known TF-target relationships and the large-scale single-cell RNA-seq data collected from public databases as well as the bulk data of The Cancer Genome Atlas and the Genotype-Tissue Expression project, we systematically predicted the GRNs of 184 different physiological and pathological conditions of human and mouse involving >633 000 cells and >27 700 bulk samples. We further developed GRNdb, a freely accessible and user-friendly database (http://www.grndb.com/) for searching, comparing, browsing, visualizing, and downloading the predicted information of 77 746 GRNs, 19 687 841 TF-target pairs, and related binding motifs at single-cell/bulk resolution. GRNdb also allows users to explore the gene expression profile, correlations, and the associations between expression levels and the patient survival of diverse cancers. Overall, GRNdb provides a valuable and timely resource to the scientific community to elucidate the functions and mechanisms of gene expression regulation in various conditions.
Sexually dimorphic radiogenomic models identify distinct imaging and biological pathways that are prognostic of overall survival in glioblastoma
Authors: Beig Niha , Singh Salendra , Bera Kaustav , Prasanna Prateek , Singh Gagandeep , Chen Jonathan , Saeed Bamashmos Anas , Barnett Addison , Hunter Kyle , Statsevych Volodymyr , Hill Virginia B , Varadan Vinay , Madabhushi Anant , Ahluwalia Manmeet S , Tiwari Pallavi
Published: October 2020

Background

Recent epidemiological studies have suggested that sexual dimorphism influences treatment response and prognostic outcome in glioblastoma (GBM). To this end, we sought to (i) identify distinct sex-specific radiomic phenotypes—from tumor subcompartments (peritumoral edema, enhancing tumor, and necrotic core) using pretreatment MRI scans—that are prognostic of overall survival (OS) in GBMs, and (ii) investigate radiogenomic associations of the MRI-based phenotypes with corresponding transcriptomic data, to identify the signaling pathways that drive sex-specific tumor biology and treatment response in GBM.

Methods

In a retrospective setting, 313 GBM patients (male = 196, female = 117) were curated from multiple institutions for radiomic analysis, where 130 were used for training and independently validated on a cohort of 183 patients. For the radiogenomic analysis, 147 GBM patients (male = 94, female = 53) were used, with 125 patients in training and 22 cases for independent validation.

Results

Cox regression models of radiomic features from gadolinium T1-weighted MRI allowed for developing more precise prognostic models, when trained separately on male and female cohorts. Our radiogenomic analysis revealed higher expression of Laws energy features that capture spots and ripple-like patterns (representative of increased heterogeneity) from the enhancing tumor region, as well as aggressive biological processes of cell adhesion and angiogenesis to be more enriched in the “high-risk” group of poor OS in the male population. In contrast, higher expressions of Laws energy features (which detect levels and edges) from the necrotic core with significant involvement of immune related signaling pathways was observed in the “low-risk” group of the female population.

Conclusions

Sexually dimorphic radiogenomic models could help risk-stratify GBM patients for personalized treatment decisions.
Prevalence and Factors Associated With Liver Fibrosis Among Adult HIV-Infected Patients Attending Urban and Rural Care Clinics in Uganda
Authors: Wekesa Clara , Kirk Gregory D , Aizire Jim , Benson Eve-Marie , Karabarinde Alex , Parkes-Ratanshi Rosalind , Ocama Ponsiano
Published: October 2020

Background

Liver fibrosis is common among HIV-infected patients. Risk factors vary by location. Understanding this variation may inform prevention strategies. We compared the prevalence and correlates of liver fibrosis among HIV-infected patients attending care clinics in Uganda.

Methods

This was a cross-sectional study involving 2030 HIV-infected patients attending care clinics in urban and rural Uganda. Liver fibrosis was defined as liver stiffness measurement (LSM) >7.1 KPa. Proportions and correlates of liver fibrosis were assessed and compared using logistic regression stratified by gender and site.

Results

Prevalence of liver fibrosis was higher among participants in the rural clinic (15% vs 11%; P = .017). History of tobacco use (urban P = .022; rural P = .035) and serologic evidence of hepatitis C infection (HCV; urban P = .028; rural P = .03) was associated with liver fibrosis in all men. Elevated liver transaminases (urban P = .002; rural P = .028) and increasing age (urban P = .008; rural P = .052) were risk factors among all women. Tobacco use among women was only a risk factor in those attending the rural clinic (P = .003), and detectable HIV viral load (P = .002) for men in the urban clinic.

Conclusions

Liver fibrosis is prevalent among HIV-infected persons in Uganda. HIV viral suppression and avoiding tobacco may be strategies to prevent liver fibrosis and cancer risk.
Cannabis Significantly Reduces the Use of Prescription Opioids and Improves Quality of Life in Authorized Patients: Results of a Large Prospective Study
Authors: Lucas Philippe , Boyd Susan , Milloy M.-J. , Walsh Zach
Published: October 2020

Objectives

This article presents findings from a large prospective examination of Canadian medical cannabis patients, with a focus on the impacts of cannabis on prescription opioid use and quality of life over a 6-month period.

Methods

The Tilray Observational Patient Study took place at 21 medical clinics throughout Canada. This analysis includes 1,145 patients who had at least one postbaseline visit, with follow-up at 1, 3, and 6 months. Instruments included a comprehensive cannabis use inventory, the World Health Organization Quality of Life Short Form (WHOQOL-BREF), and a detailed prescription drug questionnaire.

Results

Participants were 57.6% female, with a median age of 52 years. Baseline opioid use was reported by 28% of participants, dropping to 11% at 6 months. Daily opioid use went from 152 mg morphine milligram equivalent (MME) at baseline to 32.2 mg MME at 6 months, a 78% reduction in mean opioid dosage. Similar reductions were also seen in the other four primary prescription drug classes identified by participants, and statistically significant improvements were reported in all four domains of the WHOQOL-BREF.

Conclusions

This study provides an individual-level perspective of cannabis substitution for opioids and other prescription drugs, as well as associated improvement in quality of life over 6 months. The high rate of cannabis use for chronic pain and the subsequent reductions in opioid use suggest that cannabis may play a harm reduction role in the opioid overdose crisis, potentially improving the quality of life of patients and overall public health.
The protective effect of daytime sleep on planning and risk-related decision-making in emerging adults
Authors: Mark Lawrence Wong , Esther Yuet Ying Lau , Yeuk Ching Lam , Benjamin Rusak , Chia-huei Tseng , Tatia Mei Chun Lee , Yun Kwok Wing
Published: October 2020

We assessed the effect of a daytime sleep opportunity on planning and risk-related decision-making in emerging adults using multiple neurobehavioral assessments. A total of 136 healthy emerging adults (20.0 ± 1.5 years), 65% female, performed the Risky-Gains Task and the Tower of London test twice. Between these assessments, they were randomized to either have a sleep opportunity monitored by polysomnography (Sleep group, n = 101) or to stay awake (Wake group, n = 35). During Test 2, in comparison to the Sleep group, the Wake group showed increased sleepiness, worse planning ability and more decrease in reaction times when selecting risky choices. Changes in Tower of London test steps used and Risky-Gains Task response time correlated with the number of central and frontal fast sleep spindles, respectively. These results indicate that among emerging adults who commonly have poor sleep patterns, a daytime sleep opportunity was related to better planning ability, better psychomotor vigilance and stable response speeds in risk-related decision-making. Changes in planning and risk-related decision-making correlated with the number of sleep spindles during the nap, supporting a specific role for sleep in modulating planning and potentially other higher-order cognitive functions.
Individual differences in light sensitivity affect sleep and circadian rhythms
Authors: Chellappa Sarah L
Published: October 2020

Artificial lighting is omnipresent in contemporary society with disruptive consequences for human sleep and circadian rhythms because of overexposure to light, particularly in the evening/night hours. Recent evidence shows large individual variations in circadian photosensitivity, such as melatonin suppression, due to artificial light exposure. Despite the emerging body of research indicating that the effects of light on sleep and circadian rhythms vary dramatically across individuals, recommendations for appropriate light exposure in real-life settings rarely consider such individual effects. This review addresses recently identified links among individual traits, for example, age, sex, chronotype, genetic haplotypes, and the effects of evening/night light on sleep and circadian hallmarks, based on human laboratory and field studies. Target biological mechanisms for individual differences in light sensitivity include differences occurring within the retina and downstream, such as the central circadian clock. This review also highlights that there are wide gaps of uncertainty, despite the growing awareness that individual differences shape the effects of evening/night light on sleep and circadian physiology. These include (1) why do certain individual traits differentially affect the influence of light on sleep and circadian rhythms; (2) what is the translational value of individual differences in light sensitivity in populations typically exposed to light at night, such as night shift workers; and (3) what is the magnitude of individual differences in light sensitivity in population-based studies? Collectively, the current findings provide strong support for considering individual differences when defining optimal lighting specifications, thus allowing for personalized lighting solutions that promote quality of life and health.
Effects of coated and noncoated steroidal implants on growth performance, carcass characteristics, and serum estradiol-17β concentrations of finishing Holstein steers
Authors: Carvalho Pedro H V , Westphalen Mariana F , Campbell Jonathan A , Felix Tara L
Published: October 2020

The objectives of the study were to determine the effect of coated or noncoated hormone implants on growth performance, carcass characteristics, and serum estradiol-17β (E2) concentrations of Holstein steers fed a grain-based diet for 112 d. Seventy-nine Holstein steers [average initial body weight (BW) = 452 ± 5.5 kg] were stratified by BW and allotted to one of two treatments: 1) Holstein steers implanted with a coated implant containing 200 mg of trenbolone acetate (TBA) and 40 mg E2 (Revalor-XS (Merck Animal Health; Summit, NJ)] on day 0 (XS) or 2) Holstein steers implanted two times (days 0 and 56) with a noncoated implant containing 80 mg of TBA and 16 mg of E2 [(2IS) Revalor-IS (Merck Animal Health)]. Data were analyzed using the MIXED procedure of SAS (SAS Inst. Inc., Cary, NC). There was no effect (P ≥ 0.71) of implant strategy on initial, middle, and final BW. No effect (P ≥ 0.12) of implant strategy was observed on average daily gain, dry matter intake, or gain-to-feed ratio. There were no effects (P ≥ 0.11) of implant strategy on carcass characteristics. There was an implant × day interaction (P < 0.01) for the circulation of serum E2 concentrations. Serum E2 concentration increased similarly 14 d after Holstein steers were implanted, regardless of implant strategy. At 28 d, after steers were implanted, steers in the XS group had less serum E2 concentration than Holstein steers in the 2IS group. However, at 56 d after the first implantation, both groups, once again, had similar serum E2 concentrations and E2 concentrations were less on day 56 than day 28 for both strategies. Holstein steers implanted with 2IS had greater serum E2 concentration on day 70 and E2 concentrations remained greater than serum E2 of Holstein steers implanted XS for the duration of the trial (day 112). In summary, there was no effect of coated or two doses of noncoated implant on growth performance or carcass characteristics of Holstein steers.
Chromosome-Scale Genome Assembly of Talaromyces rugulosus W13939, a Mycoparasitic Fungus and Promising Biocontrol Agent
Authors: Wang Bo , Guo Li , Ye Kai , Wang Long
Published: October 2020

Here, we report a chromosome-level genome assembly of Talaromyces rugulosus (syn. Penicillium rugulosum) W13939 (six chromosomes; contig N50: 5.90 Mb), generated using a combination of PacBio long-read and Illumina paired-end data. T. rugulosus is not only a potent enzyme producer, but also a mycoparasite of Aspergillus flavus, which is a notorious plant pathogen and mycotoxin producer, making it a promising biocontrol agent. The T. rugulosus genome is rich in genes encoding proteases, carbohydrate-active enzymes, fungal cell wall–degrading enzymes, lectin, and secondary metabolite biosynthetic enzymes, reflecting its mycoparasitic life style and mycotoxigenic capability. This high-quality assembly of the T. rugulosus genome will be a valuable resource to assist us in the understanding of the molecular basis of mycoparasitism and facilitate the agricultural and biotechnological applications of Talaromyces spp.
Detection and Fitness of Dicarboximide-Resistant Isolates of Alternaria alternata from Dendrobium officinale, a Chinese Indigenous Medicinal Herb
Authors: Zhao Weicheng , Sun Chunxia , Wei Lingling , Chen Wenchan , Wang Bingran , Li Fengjie , Wei Mengdi , Lou Tiancheng , Zhang Pengcheng , Zheng Huanhuan , Chen Changjun , Xiang Zengxu
Published: October 2020

Black spot, caused by Alternaria alternata, poses a severe threat to the industry of Dendrobium officinale, a Chinese indigenous medicinal herb. Dicarboximide fungicides (DCFs) have been intensively used to control this disease for decades in China, and offer excellent efficacy. The resistance of phytopathogenic pathogens against DCFs are reportedly selected in fields; however, the DCF resistance of A. alternata from D. officinale is not well understood. The isolates of A. alternata with low procymidone resistance (ProLR) were detected in the commercial orchards of D. officinale in China in 2018 and biochemically characterized in this study. The result showed that the ProLR isolates were selected in the commercial orchards with a resistance frequency of 100%, and no significant difference in mycelial growth, sporulation, and virulence was observed among the ProLR and procymidone-sensitive (ProS) isolates. A positive cross-resistance pattern was exhibited between procymidone and iprodione. Results of amino acid sequence alignment of AaOS-1 from the tested isolates showed that all of the ProLR genotypes could be categorized into two groups, including group I (mutations at AaOs-1) and group II (no mutation). Under procymidone (5.0 µg/ml) treatment conditions, the AaOs-1 expression levels increased in the ProS isolates and ranged from approximately 2.94- to 3.69-fold higher than those under procymidone-free conditions, while the AaOs-1 expressions of the ProLR isolates were significantly lower than those in the ProS isolates under the same conditions. The data indicated that the mutations at AaOs-1 are involved in the DCF resistance of A. alternata selected in the D. officinale orchards.
Genetic Diversity and Population Structure ofPhyllosticta citriasianain China
Authors: Zeng Yibing , Xiong Tao , Liu Bei , Carstens Elma , Chen Xiangling , Xu Jianping , Li Hongye
Published: October 2020

Phyllosticta citriasiana is the causal agent of citrus tan spot, an important pomelo disease in Asia. At present, there is little or no information on the epidemiology or population structure of P. citriasiana. By using simple sequence repeat markers, we analyzed 94 isolates from three pomelo production regions in southern and southeastern China. The analyses showed high genetic diversity in each of the three geographic populations. A STRUCTURE analysis revealed two genetic clusters among the 94 isolates; one geographic population was dominated by genotypes in one cluster, and the other two geographic populations were dominated by genotypes of the second cluster. P. citriasiana has a heterothallic mating system with two idiomorphs, MAT1-1 and MAT1-2. Analyses using mating type–specific primers revealed that both mating types were present in all three geographic populations, and in all three populations the mating type ratios were in equilibrium. Although the sexual stage of the fungus has not been discovered yet, analyses of allelic associations indicated evidence for sexual and asexual reproduction within and between populations. Despite the observed genetic differentiation between the three geographic populations, evidence for long-distance gene flow was found.
Recognition of oral potentially malignant disorders and transformation to oral cancer
Authors: Vail Marianne , Robinson Sean , Condon Heather
Published: October 2020

Oral potentially malignant disorders refer to oral mucosal disorders with increased risk for malignant transformation, primarily to oral squamous cell carcinoma (SCC). Leukoplakia and erythroplakia are the most common of these disorders, but others have been identified. Transformation rates to oral cancer vary based on multiple factors. Healthcare providers should be aware of risk factors and clinical manifestations of these disorders and should intervene early to monitor and/or treat them to reduce the potential for malignant transformation.
Myocardial Dysfunction Is Independently Associated With Mortality in Pediatric Septic Shock
Authors: Lautz Andrew J. , Wong Hector R. , Ryan Thomas D. , Statile Christopher J.
Published: October 2020

Objectives:

Circulatory dysfunction has been associated with mortality in children with septic shock. However, the mortality risk attributable to myocardial dysfunction per se has not been established, and the association between myocardial dysfunction and mortality is confounded by illness severity. The objective was to determine if sepsis-associated myocardial dysfunction defined by low left ventricular ejection fraction or global longitudinal strain is associated with mortality in pediatric septic shock after adjusting for baseline mortality probability.

Design:

Retrospective, observational study.

Setting:

Single-center, quaternary-care PICU.

Patients:

Children less than 18 years old admitted to the PICU from 2003 to 2018 who had an echocardiogram performed within 48 hours of septic shock identification and Pediatric Sepsis Biomarker Risk Model II data available.

Interventions:

None.

Measurements and Main Results:

All echocardiograms were reread by a cardiologist blinded to patient data for left ventricular ejection fraction and global longitudinal strain. Low left ventricular ejection fraction was defined as less than 45%, and low global longitudinal strain was defined as greater than z score of –2 for body surface area. Multivariable logistic regression separately analyzed the associations of low left ventricular ejection fraction and low global longitudinal strain with mortality, adjusting for Pediatric Sepsis Biomarker Risk Model II mortality risk. A post hoc logistic regression analyzed the association of left ventricular ejection fraction as a continuous variable with mortality, where linearity was maintained for left ventricular ejection fraction less than 65%. Eighteen percent of 181 children had low left ventricular ejection fraction. After adjusting for baseline mortality risk, low left ventricular ejection fraction remained independently associated with mortality (odds ratio, 4.4 [1.0–19.8]; p = 0.0497). Likewise, left ventricular ejection fraction was associated with mortality (odds ratio, 0.96 [0.93–0.99]; p = 0.037) on multivariable analysis for left ventricular ejection fraction less than 65%. Thirty-six percent of 169 children had low global longitudinal strain, and low global longitudinal strain was also independently associated with mortality (odds ratio, 4.6 [1.2–18.0]; p = 0.027).

Conclusions:

Sepsis-associated myocardial dysfunction, whether defined by low left ventricular ejection fraction or low global longitudinal strain, is an independent risk factor for mortality in pediatric septic shock after accounting for the confounding effects of septic shock severity.
Effect of Nonsedation on Cognitive Function in Survivors of Critical Illness
Authors: Nedergaard Helene Korvenius , Jensen Hanne Irene , Stylsvig Mette , Olsen Hanne Tanghus , Korkmaz Serkan , Strøm Thomas , Toft Palle
Published: October 2020

Objectives:

Critical illness can cause severe cognitive impairments. The objective of this trial was to assess the effect of nonsedation versus sedation with a daily wake-up call during mechanical ventilation on cognitive function in adult survivors of critical illness.

Design:

Single-center substudy of the multicenter, randomized Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Mechanical Ventilation trial. Three months after ICU-discharge participants were tested for cognitive function by a neuropsychologist.

Setting:

Mixed 14-bed ICU in teaching hospital.

Patients:

A total of 205 critically ill, orally intubated, and mechanically ventilated adults.

Interventions:

Patients were randomized within the first 24 hours from intubation to either nonsedation with sufficient analgesia or light sedation with a daily wake-up call during mechanical ventilation.

Measurements and Main Results:

A total of 118 patients survived to follow-up and 89 participated (75%). The participating survivors in the two groups did not differ regarding baseline data or premorbid cognitive impairments. Sedated patients had received more sedatives, whereas doses of morphine and antipsychotics were equal. The primary outcome was that no significant difference was found in the number of patients with mild/moderate cognitive impairments (six nonsedated patients vs four sedated patients) or severe cognitive impairments (16 nonsedated patients vs 17 sedated patients; p = 0.71). Secondary outcomes were cognitive test scores, and no differences were found between the scores in nonsedated and sedated patients. Hypothetical worst case scenarios where all patients, who had not participated in follow-up assessment, were assumed to have severe cognitive impairments were analyzed, but still no difference between the groups was found. We found more patients with delirium in the sedated group (96% vs 69% of patients; p = 0.002) and increased duration of delirium in sedated patients (median 5 vs 1 d; p < 0.001). Delirium subtypes were equally distributed between the groups, with hypoactive delirium most frequent (61%), followed by mixed delirium (39%).

Conclusions:

Nonsedation did not affect cognitive function 3 months after ICU-discharge.
Effect of Nurse-Led Consultations on Post-Traumatic Stress and Sense of Coherence in Discharged ICU Patients With Clinically Relevant Post-Traumatic Stress Symptoms—A Randomized Controlled Trial
Authors: Valsø Åse , Rustøen Tone , Småstuen Milada Cvancarova , Ekeberg Øivind , Skogstad Laila , Schou-Bredal Inger , Myhren Hilde , Sunde Kjetil , Tøien Kirsti
Published: October 2020

Objectives:

To investigate the effect of nurse-led consultations on reducing post-traumatic stress symptoms and increasing sense of coherence in discharged ICU patients with clinically relevant post-traumatic stress symptoms and to identify variables associated with symptoms 12 months later.

Design:

A pragmatic nonblinded randomized controlled trial.

Settings:

Five surgical and medical ICUs at Oslo University Hospital.

Patients:

Adult patients treated in the ICU greater than or equal to 24 hours were screened with Post-Traumatic Stress Scale 10 intensive part B after ICU discharge. Those scoring greater than or equal to 25 were included in the study.

Intervention:

Patients randomized to intervention group were offered three nurse-led consultations within 2 months, and patients in the control group received standard care.

Measurements and Main Results:

Sense of Coherence Scale 13 and Post-Traumatic Stress Scale 10 intensive part B were completed after inclusion, and reevaluated after 3, 6, and 12 months. Linear mixed model for repeated measures and linear regression analyses were performed. Among 523 screened patients, 111 and 113 were randomized to intervention group and control group, respectively. Mean Post-Traumatic Stress Scale 10 intensive part B score was 37 (±10) before randomization. No differences in post-traumatic stress symptoms or sense of coherence were found between intervention group versus control group, with a mean Post-Traumatic Stress Scale 10 intensive part B score 39 (95% CI, 37–41) versus 37 (95% CI, 35–39), 32 (95% CI, 28–35) versus 32 (95% CI, 29–35), 31 (95% CI, 28–34) versus 30 (95% CI, 27–33), and 31 (95% CI, 28–34) versus 29 (95% CI, 26–33) at baseline, 3, 6, and 12 months, respectively. There was a significantly reduced Post-Traumatic Stress Scale 10 intensive part B score for both groups during the year (p= 0.001). Low sense of coherence, pain, and previous psychiatric problems were associated with increased level of post-traumatic stress symptoms at 12 months.

Conclusions:

Nurse-led consultations did not reveal any significant effect on post-traumatic stress symptoms or sense of coherence after ICU discharge in patients with clinically relevant symptoms.
The Effects of Melatonin Supplementation on Sleep Quality and Assessment of the Serum Melatonin in ICU Patients: A Randomized Controlled Trial
Authors: Gandolfi Joelma Villafanha , Di Bernardo Ana Paula Altimari , Chanes Débora Augusto Valverde , Martin Danilo Fernando , Joles Vanessa Bonafim , Amendola Cristina Prata , Sanches Luciana Coelho , Ciorlia Gustavo Larsen , Lobo Suzana Margareth
Published: October 2020

Objectives:

To evaluate whether the use of exogenous melatonin affects sleep, reduces the prevalence of delirium, and decreases the need for analgosedation and to assess whether serum melatonin indices correlate with exogenous administration in critically ill patients.

Design:

Double-blind, randomized, placebo-controlled study.

Setting:

Multicenter ICUs of two tertiary hospitals.

Patients:

A total of 203 adult patients who were admitted to the ICU and administered with analgesics and/or sedatives.

Interventions:

Oral melatonin (10 mg) or placebo for up to seven consecutive nights.

Measurements and Main Results:

The number of observed sleeping hours at night was assessed by the bedside nurse. Sleep quality was evaluated using the Richards Campbell Questionnaire Sleep (RCSQ). The prevalence of delirium, pain, anxiety, adverse reactions, duration of mechanical ventilation, length of ICU and hospital stays, and doses of sedative and analgesic drugs administered were recorded. The use of analgesics and sedatives was assessed daily. Melatonin levels were determined by enzyme-linked immunosorbent assay. Based on the RCSQ results, sleep quality was assessed to be better in the melatonin group than that in the placebo group with a mean (sd) of 69.7 (21.2) and 60.7 (26.3), respectively (p= 0.029). About 45.8% and 34.4% of participants in the melatonin and placebo groups had very good sleep (risk ratio, 1.33; 95% CI, 0.94–1.89), whereas 3.1% and 14.6% had very poor sleep (risk ratio, 0.21; 95% CI, 0.06–0.71), respectively. No significant difference was observed regarding the days free of analgesics or sedatives, the duration of night sleep, and the occurrence of delirium, pain, and anxiety. Melatonin serum peak levels at 2amwere 150 pg/mL (range, 125–2,125 pg/mL) in the melatonin group and 32.5 pg/mL (range, 18.5–35 pg/mL) in the placebo group (p< 0.001).

Conclusions:

Melatonin was associated with better sleep quality, which suggests its possible role in the routine care of critically ill patients in the future.
Prevalence of symptoms and associated factors across menopause status in Taiwanese women
Authors: Lee Pei-Shan , Lee Chyi-Long
Published: October 2020

Objective:

To investigate the prevalence of symptoms and associated factors in Taiwanese women calling a menopause hotline.

Methods:

A cross-sectional, descriptive, epidemiological study was performed on 20,882 women aged 40 to 89 years registered in the menopause consultation database of the nationwide toll-free consultation hotline for menopause-related issues from January 2006 to December 2016. The data included demography, sources of menopausal health care, and menopause/midlife symptoms scale.

Results:

The mean menopausal age was 49.6 ± 4 years. The prevalence of the symptoms increased with the progress of the menopausal stages, and the differences between stages were significant. The top five symptoms reported on a menopause hot line were memory loss (66.9%), fatigue (66.5%), insomnia (59.6%), depressed mood (58.5%), and back pain (58.2%). Of the women, 23.5% did visit a medical facility for menopausal problems mainly the department of gynecology. More than half of the women (56.4%) opted for medical personnel as the preferred channel for obtaining information concerning menopause. Women who had a higher education level, were single, had no children, were not experiencing the empty-nest phenomenon, were employed, had no chronic disease, were premenopausal, had never received hormone therapy, and had not visited medical facilities scored the lowest in menopause/midlife symptoms.

Conclusions:

Compared with premenopausal and perimenopausal women, postmenopausal women experience the most severe symptoms. Therefore, establishing a menopause consultation hotline answered by medical personnel and implementing support for postmenopausal women to obtain strategies to alleviate symptoms are required and necessary.

Video Summary:

http://links.lww.com/MENO/A651.
Investigation of the Role of Complementary Medicine on Anxiety of Patients Before and After Surgery
Authors: Ebrahimi Abed , Eslami Jamshid , Darvishi Isan , Momeni Khadijeh , Akbarzadeh Marzieh
Published: October 2020

Every year millions of patients undergo surgery worldwide. Anxiety is a common pre- and postoperative problem. Nonpharmacologic anxiety control has been demonstrated to be more suitable in patients. The objective of this study was to apprise the evidence of the effect of various complementary therapies on pre- and postoperative anxiety among patients. A comprehensive literature search was made on Web of Science, Scopus, Cochrane, PubMed Irandoc, SID Science, ScienceDirect, Ovid, Mag Iran, and Google Scholar for original research studies published between 1980 and 2019. Original articles that reported the effect of complementary therapies in patients undergoing surgery were included. Ninety-six studies were analyzed. All of the studies have documented the effects of complementary therapies on improving pre- and postoperative outcomes of patients. Although methods varied considerably, most of the studies included in this review reported positive results. Therefore, there is some evidence that complementary therapies can lead to positive pre- and postoperative outcomes. Therefore, the efficiency and use of complementary medicine, along with the use of therapeutic techniques in classical medicine, can provide a new model for reducing anxiety before and after surgery. It is recommended that nurses conduct additional reviews or clinical studies so that effective approaches to integrated medical care can be developed and patients' health enhanced.
Recurrent gelatinous Salzmann-like nodular lesion with prior history of astigmatic keratotomy: October consultation #1
Authors: Moshirfar Majid , Shmunes Margaret H.
Published: October 2020

A 67-year-old woman was referred to our facility with declining vision in the right eye that has been present since her cataract surgery in 2016. The patient has a history of an 8-cut radial keratotomy (RK) with 2-cut astigmatic keratotomy (AK) along the vertical meridian in both eyes since 1993. She underwent superficial keratectomy of the right eye 3 times in 3 consecutive years after her cataract extraction with toric intraocular lens (IOL) implantation. She is hoping to improve her vision in the right eye with a corrected distance visual acuity (CDVA) of 20/50 with a manifest refraction of +2.00 −5.50 × 65. Keratometry readings are 39.4 @ 87/43.3 @ 177. Slitlamp examination shows a persistent raised white gelatinous tissue overlying the inferior AK at the 6 o'clock position (Figures 1, 2, and 3

JOURNAL/jcrs/04.03/02158034-202010000-00021/figure1/v/2023-08-19T002554Z/r/image-tiff

JOURNAL/jcrs/04.03/02158034-202010000-00021/figure2/v/2023-08-19T002554Z/r/image-tiff

JOURNAL/jcrs/04.03/02158034-202010000-00021/figure3/v/2023-08-19T002554Z/r/image-tiff

). The patient had attempted several failed trials of scleral lens and rigid gas-permeable (RGP) lens-fitting after each corneal scraping with intolerance and lack of improvement in her vision. Her left eye is an asymptomatic pseudophakic eye with uncorrected distance visual acuity (UDVA) and CDVA of 20/25.

What would be your next step? Would you request additional diagnostic workup? What medical and surgical interventions would you recommend?
Nontraumatic Acute Hyperextension Myelopathy Associated With Weightlifting
Authors: Cipriano Kevin , Mansfield J. Taylor , Batal Hannie , Gosai Erika
Published: October 2020

We describe the clinical course of a 56-yr-old woman without a significant medical history presenting with nontraumatic paraplegia found to have an infarction of the conus medullaris after intensive lumbar hyperextension exercises. This condition, known as surfer’s myelopathy, has been described in multiple case reports that attributed a similar mechanism and presentation. We present a case of surfer’s myelopathy associated with weightlifting, which has not been previously reported. We conclude that this diagnosis should be considered in patients who present after spine hyperextension activity with nontraumatic paraplegia. Furthermore, we support the nomenclature change to “acute hyperextension myelopathy,” better reflecting the underlying pathophysiology.
Tuberculosis symptom screening for children and adolescents living with HIV in six high HIV/TB burden countries in Africa
Authors: Vonasek Bryan , Kay Alexander , Devezin Tara , Bacha Jason M. , Kazembe Peter , Dhillon Dilsher , Dlamini Sandile , Haq Heather , Thahane Lineo , Simon Katie , Matshaba Mogomotsi , Sanders Jill , Minde Mercy , Wanless Sebastian , Nyasulu Phoebe , Mandalakas Anna
Published: October 2020

Objectives:

The WHO recommends that children and adolescents living with HIV (CALHIV) complete TB symptom screening at every clinical encounter but evidence supporting this recommendation is limited. We evaluated the performance of the recommended TB symptom screening in six high-burden TB/HIV countries.

Design:

Retrospective longitudinal cohort.

Methods:

We extracted data from electronic medical records of CALHIV receiving care from clinics in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda from January 2014 to June 2017. We defined incident TB cases as those prescribed TB treatment within 30 days of TB diagnosis. We analyzed the most recent symptom screen preceding a TB diagnosis. In accordance with WHO guidelines, positive screens were defined as current fever, cough, poor weight gain, or recent TB contact. Odds of TB disease was modeled by screen result and age at which screening was conducted.

Results:

Twenty thousand seven hundred and six patients collectively had 316 740 clinic visits, of which 240 161 (75.8%) had documented TB symptom screens. There were 35 701 (14.9%) positive TB symptom screens, and 1212 incident TB diagnoses. Sensitivity and specificity of the TB symptom screen to diagnose TB were 61.2% (95% CI 58.4--64.0) and 88.8% (95% CI 88.7--88.9), respectively. Log odds of documented TB for positive or negative screens was statistically different only for screens conducted at ages 7--17.

Conclusion:

Although specificity was high, the sensitivity of the TB symptom screen to detect TB in CALHIV was low. More accurate screening approaches are needed to optimally identify TB disease in CALHIV.
Financial incentives to increase pediatric HIV testing: a randomized trial
Authors: Njuguna Irene N. , Wagner Anjuli D. , Neary Jillian , Omondi Vincent O. , Otieno Verlinda A. , Orimba Anita , Mugo Cyrus , Babigumira Joseph B. , Levin Carol , Richardson Barbra A. , Maleche-Obimbo Elizabeth , Wamalwa Dalton C. , John-Stewart Grace , Slyker Jennifer
Published: October 2020

Background:

Financial incentives can motivate desirable health behaviors, including adult HIV testing. Data regarding the effectiveness of financial incentives for HIV testing in children, who require urgent testing to prevent mortality, are lacking.

Methods:

In a five-arm unblinded randomized controlled trial, adults living with HIV attending 19 HIV clinics in Western Kenya, with children 0–12 years of unknown HIV status, were randomized with equal allocation to $0, $1.25, $2.50, $5 or $10. Payment was conditional on child HIV testing within 2 months. Block randomization with fixed block sizes was used; participants and study staff were unblinded at randomization. Primary analysis was intent-to-treat, with predefined primary outcomes of completing child HIV testing and time to testing.

Results:

Of 452 caregivers, 90, 89, 93, 92 and 88 were randomized to $0, $1.25, $2.50, $5.00, and $10.00, respectively. Of those, 31 (34%), 31 (35%), 44 (47%), 51 (55%), and 54 (61%) in the $0, $1.25, $2.50, $5.00, and $10.00 arms, respectively, completed child testing. Compared with the $0 arm, and adjusted for site, caregivers in the $10.00 arm had significantly higher uptake of testing [relative risk: 1.80 (95% CI 1.15--2.80), P = 0.010]. Compared with the $0 arm, and adjusted for site, time to testing was significantly faster in the $5.00 and $10.00 arms [hazard ratio: 1.95 (95% CI 1.24--3.07) P = 0.004, 2.42 (95% CI 1.55--3.79), P < 0.001, respectively).

Conclusion:

Financial incentives are effective in improving pediatric HIV testing among caregivers living with HIV.

Registration:

NCT03049917.
Endogenous spatial pattern formation from two intersecting ecological mechanisms: the dynamic coexistence of two noxious invasive ant species in Puerto Rico
Authors: Vandermeer John , Perfecto Ivette
Published: October 2020

Endogenous (or autonomous, or emergent) spatial pattern formation is a subject transcending a variety of sciences. In ecology, there is growing interest in how spatial patterns can ‘emerge’ from internal system processes and simultaneously affect those very processes. A classic situation emerges when a predator's focus on a dominant competitor releases competitive pressure on a subdominant competitor, allowing coexistence of the two. If this idea is formulated spatially, two interesting consequences immediately arise. First, a spatial predator/prey system may take the form of a Turing instability, in which an activator (the dispersing prey population) is contained by a repressor (the more rapidly dispersing predator population) generating a spatial pattern of clusters of prey and predators, and second, an indirect intransitive loop (where A beats B beats C beats A) emerges from the simple fact that the system is spatial. Two common invasive ant species,
Wasmannia auropunctata
and
Solenopsis invicta,
and the parasitic phorid flies of
S. invicta
commonly coexist in Puerto Rico. Emergent spatial patterns generated by the combination of the Turing mechanism and the indirect intransitive loop are likely to be common here. This theoretical framework and the realities of the natural history in the field could explain both the long-term coexistence of these two species, and the highly variable pattern of their occurrence across a large landscape.
Estimating epidemiologic dynamics from cross-sectional viral load distributions
Authors: Hay James A. , Kennedy-Shaffer Lee , Kanjilal Sanjat , Lennon Niall J. , Gabriel Stacey B. , Lipsitch Marc , Mina Michael J.
Published: October 2020

Estimating an epidemic’s trajectory is crucial for developing public health responses to infectious diseases, but incidence data used for such estimation are confounded by variable testing practices. We show instead that the population distribution of viral loads observed under random or symptom-based surveillance, in the form of cycle threshold (Ct) values, changes during an epidemic and that Ct values from even limited numbers of random samples can provide improved estimates of an epidemic’s trajectory. Combining multiple such samples and the fraction positive improves the precision and robustness of such estimation. We apply our methods to Ct values from surveillance conducted during the SARS-CoV-2 pandemic in a variety of settings and demonstrate new approaches for real-time estimates of epidemic trajectories for outbreak management and response.
An epigenetic proxy of chronic inflammation outperforms serum levels as a biomarker of brain ageing
Authors: Conole Eleanor L.S. , Stevenson Anna J. , Green Claire , Harris Sarah E. , Maniega Susana Muñoz , Valdés-Hernández María del. C , Harris Mathew A. , Bastin Mark E. , Wardlaw Joanna M. , Deary Ian J. , Miron Veronique E. , Whalley Heather C. , Marioni Riccardo E. , Cox Simon R.
Published: October 2020

Low-level chronic inflammation increases with age and is associated with cognitive decline. DNA methylation (DNAm) levels may provide more stable reflections of cumulative inflammatory burden than traditional serum approaches. Using structural and diffusion MRI data from 521 individuals aged 73, we demonstrate that a DNAm proxy of C-Reactive Protein (CRP) shows significantly (on average 6.4-fold) stronger associations with brain structural outcomes than serum CRP. We additionally find that DNAm CRP has an inverse association with global and domain-specific (speed, visuospatial and memory) cognitive functioning, and that brain structure partially mediates this CRP-cognitive association (up to 29.4%), dependent on lifestyle and health factors. These data support the hypothesis that chronic systemic inflammation may contribute to neurodegenerative brain changes which underlie differences in cognitive ability in later life. DNA methylation-based predictors could be used as proxies for chronic inflammatory status.
Estimating the Burden of COVID-19 Symptoms Among Participants at the 2020 USA Curling Club Nationals Tournament
Authors: Luethy Paul M.
Published: October 2020

The COVID-19 pandemic has been a significant cause of global morbidity and mortality, with evidence suggesting that activities involving heavier breathing, such as singing and exercise, can result in increased risk for disease transmission. The USA Curling Club Nationals is a week-long curling tournament to determine the men’s and women’s club-level champions. The 2020 tournament took place March 7-14 at the Potomac Curling Club in Laurel, MD, and featured teams from across the United States. Preventative measures, such as increased cleaning and disinfection of surfaces, single use and disposable food containers, and canceling traditional event banquets were implemented. Despite these measures, players, coaches, officials, volunteers, and spectators contracted the virus as a result of participation in the event. We surveyed participants to assess total positivity, potential days of transmission, and the burden of symptoms experienced among the participants. We found that 55.6% of all participants reported experiencing symptoms consistent with COVID-19, with nearly all experiencing more than one symptom. Although most participants’ symptoms resolved quickly, 9.6% of all participants experienced symptoms for at least one month and 12.6% of all participants reported taking at least 30 days before they felt they had returned to normal. As a result of this study, we believe curling tournaments have the potential to be high-risk events for the transmission of COVID-19. Further infection prevention measures that were not yet publicly implemented at the time of this tournament may be an effective method of lowering transmission risk, although further research is required.