bluuebunny/crossref_metadata_2025 huggingface dataset:
Periconceptional and prenatal exposure to metal mixtures in relation to behavioral development at 3 years of age
Authors: Doherty Brett T. , Romano Megan E. , Gui Jiang , Punshon Tracy , Jackson Brian P. , Karagas Margaret R. , Korrick Susan A.
Published: July 2020

Background:

Behavioral effects of prenatal exposure to mixtures of essential and toxic metals are incompletely understood.

Methods:

We investigated neurodevelopmental effects of prenatal metal exposures in the New Hampshire Birth Cohort Study, a prospective birth cohort. We measured metals (As, Cu, Mn, Pb, Se, Zn) in maternal prenatal and postnatal toenails and infant toenails, reflecting exposures during periconception and early pregnancy, mid pregnancy, and late pregnancy and early neonatal life, respectively. Mothers completed the Social Responsiveness Scale, 2nd ed. (SRS-2) and the Behavior Assessment System for Children, 2nd ed. (BASC-2) to assess their child’s neurobehavior at 3 years. We used mean field variational Bayes for lagged kernel machine regression to investigate associations of toenail metal concentrations with SRS-2 Total Scores and BASC-2 composite scores (SRS-2: n = 371; BASC-2: n = 318).

Results:

Infant toenail Mn was associated with poorer performance on multiple BASC-2 composite scores. Maternal postnatal toenail As was associated with worse scores on the BASC-2 Internalizing Problems and Behavioral Symptoms Index. Associations with Mn were generally stronger in males, and associations with As were generally stronger in females. Other metals, including Pb, were weakly or inconsistently associated with BASC-2 outcomes, and there were no strong associations of individual metals and SRS-2 Total Scores. We observed suggestive evidence of interaction between As and Se for SRS-2 Total Scores and BASC-2 Adaptive Skills, though overall evidence of interactions between metals was weak.

Conclusion:

Our results support the hypothesis that exposure to Mn and As in mid to late pregnancy may be neurodevelopmentally harmful.
Baseline High Sensitivity Cardiac Troponin I Level Below Limit of Quantitation Rules Out Acute Myocardial Infarction in the Emergency Department
Authors: Cook Bernard , McCord James , Hudson Michael , Al-Darzi Waleed , Moyer Michele , Jacobsen Gordon , Nowak Richard
Published: July 2020

The objective of our study was to determine the utility of a baseline high sensitivity cardiac troponin (hs-cTnI) value below the limit of quantitation to rule-out acute myocardial infarction (AMI) in patients presenting to the emergency department (ED) with any suspicious symptoms of a cardiac etiology. We enrolled subjects presenting to the ED with symptoms suspicious for AMI. Blood specimens were collected within 1 hour after a triage electrocardiogram. Cardiac troponin I was measured using the Beckman Coulter Access hs-cTnI assay. The diagnosis of AMI was adjudicated by 2 cardiologists using the Third Universal Definition of AMI and Roche Diagnostics Troponin T Generation 5 assay with all available clinical data at 30 days after presentation. A total of 567 subjects had all data required for data analyses. AMI was diagnosed in 46 (8.1%) patients. Two hundred thirty-two (40.9%) individuals had presentation hs-cTnI results <4.0 ng/L. None of the patients with baseline hs-cTnI <4.0 ng/L had an AMI, yielding a negative predictive value of 100.0% and a sensitivity of 100%, and a good prognosis (no AMIs or cardiac-related deaths at 30 days). In this single-center ED study, a baseline presenting novel hs-cTnI value of <4.0 ng/L effectively ruled out AMI in 40.9% of all patients presenting to the ED and having any symptoms suspicious for AMI. Importantly all patients, not only those with chest pain, and those having symptoms for any duration or those with end-stage renal disease requiring dialysis were included.
ULTRA-WIDE FIELD FUNDUS AUTOFLUORESCENCE IMAGING OF EYES WITH STICKLER SYNDROME
Authors: Fujimoto Kazushi , Nagata Tatsuo , Matsushita Itsuka , Oku Kazuma , Imagawa Mamika , Kuniyoshi Kazuki , Hayashi Takaaki , Kimoto Kenichi , Ohji Masahito , Kusaka Shunji , Kondo Hiroyuki
Published: July 2020

Purpose:

To determine the characteristics of fundus autofluorescence (FAF) images and visual functions in eyes with Stickler syndrome using ultra-widefield FAF images.

Methods:

Forty-six eyes of 26 patients with mutations in the COL2A1 gene underwent ultra-widefield FAF imaging. The eyes were categorized into three types; no signs of abnormal AF, predominantly hyperfluorescent AF (hyper-AF), and predominantly hypofluorescent AF (hypo-AF). Goldmann perimetry was performed on 34 eyes, and line-scan images of the abnormal AF lesions were obtained by swept-source optical coherence tomography in 4 eyes.

Results:

Abnormal AF lesions were found in 37 eyes of 21 (80.7%) of the 26 patients. Hyper-AF was found in 15 eyes and hypo-AF was found in 22 eyes. The FAF changes corresponded with the funduscopically observed radial paravascular retinal degeneration. The average age at the examination was significantly younger in patients who had eyes with hyper-AF or no abnormal AF than in those with hypo-AF (12.8 vs. 28.4 years; P = 0.009). Abnormal AF-associated visual field defects were found in 5/10 (50%) eyes with hyper-AF and 17/18 (94%) eyes with hypo-AF. Hyper-AF changes tended to appear before retinal changes were detectable by fluorescein angiography. An absence of the ellipsoid zone and the outer nuclear layer and a thinning of the overall retinal thickness were found corresponding to the hypo-AF lesions in the swept source optical coherence tomography images.

Conclusion:

Abnormal FAF is characteristic of eyes with Stickler syndrome. Age-related alterations of the FAF was associated with visual field defects and disruption of the photoreceptors and retinal pigment epithelial cells.
Global Consensus on the Management of Limbal Stem Cell Deficiency
Authors: Deng Sophie X. , Kruse Friedrich , Gomes José A. P. , Chan Clara C. , Daya Sheraz , Dana Reza , Figueiredo Francisco C. , Kinoshita Shigeru , Rama Paolo , Sangwan Virender , Slomovic Allan R. , Tan Donald ,   and the International Limbal Stem Cell Deficiency Working Group
Published: July 2020

Purpose:

In recent decades, the medical and surgical treatment of limbal stem cell deficiency (LSCD) has evolved significantly through the incorporation of innovative pharmacological strategies, surgical techniques, bioengineering, and cell therapy. With such a wide variety of options, there is a need to establish a global consensus on the preferred approaches for the medical and surgical treatment of LSCD.

Methods:

An international LSCD Working Group was established by the Cornea Society in 2012 and divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to reach agreement on a strategic plan and methods after a comprehensive literature search. A writing group drafted the current study.

Results:

A consensus in the medical and surgical management of LSCD was reached by the Working Group. Optimization of the ocular surface by eyelid and conjunctival reconstruction, antiinflammatory therapy, dry eye and meibomian gland dysfunction treatment, minimization of ocular surface toxicity from medications, topical medications that promote epithelialization, and use of a scleral lens is considered essential before surgical treatment of LSCD. Depending on the laterality, cause, and stage of LSCD, surgical strategies including conjunctival epitheliectomy, amniotic membrane transplantation, transplantation of limbal stem cells using different techniques and sources (allogeneic vs. autologous vs. ex vivo–cultivated), transplantation of oral mucosal epithelium, and keratoprosthesis can be performed as treatment. A stepwise flowchart for use in treatment decision-making was established.

Conclusions:

This global consensus provides an up-to-date and comprehensive framework for the management of LSCD.
Congenital melanocytic nevi
Authors: Moustafa Danna , Blundell Andrew R. , Hawryluk Elena B.
Published: July 2020

Purpose of review

To update pediatric providers on new developments in our understanding of the clinical presentation, genetics, and systemic risks associated with congenital melanocytic nevi (CMN).

Recent findings

CMN are primarily caused by sporadic postzygotic somatic mutations, most frequently in NRAS, and studies of the genetic underpinnings of CMN have demonstrated a diverse array of genetic drivers. The primary complications of large and giant CMN include neurocutaneous melanocytosis and malignant melanoma. Abnormalities in CNS MRI may predict a worse clinical course for patients and increased risk of melanoma. Targeted therapies of the MEK pathway have begun to be studied for the treatment of CMN and prevention of associated complications.

Patients with large and giant CMN should be managed by an interdisciplinary care team for the monitoring of dermatologic, neurologic, and psychosocial concerns. Ongoing research is underway to better characterize the genetic drivers of CMN and to better guide development of targeted therapeutics.
Recent advances in addressing vaccine hesitancy
Authors: Braun Caroline , O’Leary Sean T.
Published: July 2020

Purpose of review

To offer healthcare providers current, evidence-based approaches for addressing vaccine hesitancy to increase vaccine coverage and reduce the frequency of vaccine-preventable disease outbreaks.

Recent findings

Vaccine hesitancy is a growing problem with profound societal, economic, and medical consequences. Understanding the complexity of vaccine hesitancy can inform approaches to increasing vaccine uptake on both the individual and population levels. Notably, pediatricians play a critical role in increasing vaccine uptake due to their relationships with families. This doctor–patient relationship establishes trust and allows evidence-based intervention strategies to be effective in the office. Understanding potential solutions outside the office, such as media campaigns and policy changes, also provide insight into vaccine hesitancy and potential directions for future research. While pediatricians’ attempts in the clinic to increase coverage remain crucial, vaccine hesitancy remains a formidable public health problem that requires attention on both the micro and macro levels to be addressed successfully.

Providers have an opportunity to increase both confidence in and uptake of vaccines. Public health interventions would effectively complement strategies in the clinic to increase overall coverage.
Influence of social media on mental health: a systematic review
Authors: Sharma Manoj Kumar , John Nisha , Sahu Maya
Published: July 2020

Purpose of review

Social media's role in a user's life has increased dramatically over the past decade. It is used increasingly as a leisure activity amongst young adults. The types of social media have also diversified with time and the ease of access is worrying. Aim of the current review is to find the effect of social media use on mental health.

Recent findings

Systematic search of articles was carried out from different database from 1991 to February 2020 across five databases. The PICO guidelines, PRISMA flow diagram and Rayyan software were used in identifying relevant studies which were assessed using the risk of bias. Cross-referencing was done with the co-authors. A total of 16 studies was finally included in the review. Social media role is far reaching both in terms of an individual's self-perception and mood but also on their social relationships. It is interesting to find its effect also in politics, organizations and even psychiatric illnesses. The 16 studies were divided into the positive, negative and neutral effects of social media.

Debate over social media's role on mental health will continue till a greater number of RCTs are conducted. Various variables amongst different age groups should be measured. It would also be beneficial if longitudinal research can be done.
The onset and accumulation of physical multimorbidity in severe and common mental disorders
Authors: Filipčić Ivona Šimunović , Bajić Žarko , Filipčić Igor
Published: July 2020

Purpose of review

Despite of the heightened risks and burdens of physical comorbidities across the entire spectrum of mental disorders, relatively little is known about physical multimorbidity in this population. The aim of this narrative review is to present recent data regarding the onset and accumulation of physical multimorbidity and to assess its impact on the onset, course, treatment, and outcomes of mental disorders.

Recent findings

A substantial body of literature shows increased risk of physical multimorbidity among people with mental disorders. The disparity in physical multimorbidity occurs even before the diagnosis of mental disorder, and the younger age group appears to be at particular risk. Numerous patterns of association between mental disorders and medical disorders involving multiple organ systems have been identified. Physical multimorbidity affects people with mental disorders across their life spans, is associated with a wide range of unfavorable outcomes and presents significant clinical and public health concerns.

To address physical health inequalities among people with mental disorders compared with the general population, we must focus on the physical health from the very first point of contact with a mental health service. Treatment of mental disorders must be customized to meet the needs of patients with different physical multimorbidity patterns. Future work is needed to clarify how physical multimorbidity influences mental disorder treatment outcomes.
Trapping of swimming microalgae in foam
Authors: Roveillo Quentin , Dervaux Julien , Wang Yuxuan , Rouyer Florence , Zanchi Drazen , Seuront Laurent , Elias Florence
Published: July 2020

Massive foam formation in aquatic environments is a seasonal event that has a significant impact on the stability of marine ecosystems. Liquid foams are known to filter passive solid particles, with large particles remaining trapped by confinement in the network of liquid channels and small particles being freely advected by the gravity-driven flow. By contrast, the potential role of a similar retention effect on biologically active particles such as phytoplankton cells is still relatively unknown. To assess if phytoplankton cells are passively advected through a foam, the model unicellular motile alga
Chlamydomonas reinhardtii
(CR) was incorporated in a bio-compatible foam, and the number of cells escaping the foam at the bottom was measured in time. Comparing the escape dynamics of living and dead CR cells, we found that dead cells are totally advected by the liquid flow towards the bottom of the foam, as expected since the diameter of CR remains smaller than the typical foam channel diameter. By contrast, living motile CR cells escape the foam at a significantly lower rate: after 2 hours, up to 60% of the injected cells may remain blocked in the foam, while 95% of the initial liquid volume in the foam has been drained out of the foam. Microscopic observation of the swimming CR cells in a chamber mimicking the cross-section of foam internal channels revealed that swimming CR cells accumulate near channels corners. A theoretical analysis based on the probability density measurements in the micro chambers has shown that this trapping at the microscopic scale contributes to explain the macroscopic retention of the microswimmers in the foam. At the crossroads of distinct fields including marine ecology of planktonic organisms, fluid dynamics of active particles in a confined environment and the physics of foam, this work represents a significant step in the fundamental understanding of the ecological consequences of aquatic foams in water bodies.
Bumblebee hairs as electric and air motion sensors: theoretical analysis of an isolated hair
Authors: Koh K. , Robert D.
Published: July 2020

Foraging bumblebees are electrically charged. Charge accumulation has been proposed to enable their ability to detect and react to electrical cues. One mechanism suggested for bumblebee electro-sensing is the interaction between external electric fields and electric charges accumulating on fine hairs on the cuticular body. Such hairs exhibit several functional adaptations, for example, thermal insulation, pollen capture and notably, the sensing of air motion such as flow currents or low frequency sound particle velocity. Both air motion and electric fields are ubiquitous in the sensory ecology of terrestrial arthropods, raising the question as to whether cuticular hairs respond to both stimuli. Here, a model-theoretical approach is taken to investigate the capacity of bumblebee filiform hairs as electric sensors and compare it to their response to air motion. We find that oscillating air motion and electric fields generate different mechanical responses, depending on stimulus frequency and body geometry. Further, hair morphology can enhance one sensing mode over the other; specifically, higher surface area favours electric sensitivity. Assuming a maximum stable charge on the hair that is limited only by electric breakdown of air, it is expected that an applied oscillating electric field strength of approximately 300 V m−1produces comparable mechanical response on the hair as a 35 mm s−1air flow oscillating at 130 Hz—an air disturbance signal similar to that produced by wingbeats of insects within a few bodylengths of the bumblebee. This analysis reveals that bumblebee filiform hairs can operate as bi-modal sensors, responding to both oscillating electric and air motion stimuli in the context of ecologically relevant scenarios.
Characteristics and outcomes of Acute Respiratory Distress Syndrome related to COVID-19 in Belgian and French Intensive Care Units according to antiviral strategies. The COVADIS multicenter observational study
Authors: Grimaldi David , Aissaoui Nadia , Blonz Gauthier , Carbutti Giuseppe , Courcelle Romain , Gaudry Stephane , D’hondt Alain , Higny Julien , Horlait Geoffrey , Hraiech Sami , Lefebvre Laurent , Lejeune Francois , Ly Andre , Piagnerelli Michael , Sauneuf Bertrand , Serck Nicolas , Soumagne Thibaud , Szychowiak Piotr , Textoris Julien , Vandenbunder Benoit , Vinsonneau Christophe , Lascarrou Jean-Baptiste ,   for the COVADIS study group
Published: July 2020

Background

Limited data are available for antiviral therapy efficacy especially for the most severe patients under mechanical ventilation suffering from Covid-19 related Acute Respiratory Distress Syndrome (ARDS).

Methods

Observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, comparing antiviral strategies (none, hydroxychloroquine (HCQ), lopinavir/ritonavir (L/R), others (combination or remdesivir). The primary end-point was the day-28 ventilator free days (VFD), patients which died before d28 were considered as having 0 VFD. The variable was dichotomized in patients still ventilated or dead at day 28 vs patients being extubated and alive at day 28 (VFD = or >0).

Results

We analyzed 376 patients (80 with standard of care (SOC), 49 treated with L/R, 197 with HCQ, and 50 others). The median number of d28-VFD was 0 (IQR 0-13) and was different across the different groups (P=0.01), the SOC patients having the highest d28-VFD. A multivariate logistic regression including antiviral strategies, showed that age (OR 0.95 CI95%:0.93-0.98), male gender (OR 0.53 CI95%:0.31-0.93), Charlson score (OR 0.85 CI95%:0.73-0.99) and plateau pressure (OR 0.94 CI95%:0.88-0.99) were associated with having 0 d28-VFD whereas P/F ratio (OR 1.005 CI95%:1.001-1.010) was associated with having ≥1 d28-VFD (ie. being extubated and alive). Acute kidney injury (AKI) was frequent (64%), its incidence was different across the patients’ groups (P=0.01). In a post-hoc logistic multivariate regression apart from demographics characteristics and comorbidities, the use of L/R (administered to 81 of 376 patients was associated with occurrence of AKI (OR 2.07 CI95%:1.17-3.66) and need for renal replacement therapy (RRT).

Conclusion

In this observational study of moderate to severe Covid-19 ARDS patients, we did not observed a benefit of treating patients with any specific antiviral treatment. We observed an association between L/R treatment and occurrence of AKI and need for RRT.

Take home message

Any specific COVID-19 antiviral treatment is associated with higher ventilator free days at day 28 as compared to no antiviral treatment for patient in ICU under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of acute kidney injury.

Tweet

COVID-19: Insights from ARDS cohort: no signal of efficacy for antiviral treatments. Lopinavir/ritonavir may be associated with AKI and need for RRT.
Prevalence of HIV in patients hospitalized for COVID-19 and associated outcomes: a systematic review and meta-analysis
Authors: Ssentongo Paddy , Heilbrunn Emily S. , Ssentongo Anna E. , Advani Shailesh , Chinchilli Vernon M. , Nunez Jonathan J. , Du Ping
Published: July 2020

Objective

To conduct a systematic review and meta-analysis of the prevalence of HIV in patients hospitalized for COVID-19 and delineating clinical outcomes including mortality.

Design/Methods

MEDLINE, SCOPUS, OVID, and Cochrane Library databases and medrxiv.org were searched from January 1st, 2020, to June 15th, 2020. Data were extracted from studies reporting the prevalence of HIV among hospitalized COVID-19 patients and their clinical outcomes.

Analyses were performed using random-effects models on log-transformed proportions and risk ratio estimates, and heterogeneity was quantified.

Results

A total of 144,795 hospitalized COVID-19 patients were identified from 14 studies in North America, Europe, and Asia. Median age was 55 years, and 66% were male. The pooled prevalence of HIV in COVID-19 patients was 1.22% [95% confidence interval (CI): 0.61%-2.43%)] translating to a 2-fold increase compared to the respective local-level pooled HIV prevalence in the general population of 0.65% (95% CI: 0.48%-0.89%). When stratified by country, the pooled HIV prevalence among COVID-19 patients in United States (1.43%, 95% CI: 0.98%–2.07%) was significantly higher compared to Spain (0.26%, 95% CI: 0.23%-0.29%) but was not different from China (0.99%, 95% CI: 0.25%-3.85%). The pooled mortality rate in HIV-positive patients hospitalized for COVID-19 was 14.1% (95% CI: 5.78%-30.50%) and was substantially higher in the United States compared to other countries.

Conclusions

The prevalence of HIV among COVID-19 patients appeared higher than the general population, suggesting a greater susceptibility to COVID-19 for PLWH. The pooled mortality rate is high, but the rates vary significantly across countries.

Suggested Reviewers

Nelson Sewankambo, MD, PhD

Makerere University College of Health Sciences

Opposed Reviewers
Echocardiographic and Laboratory Findings in Coronary Slow Flow Phenomenon: cross-sectional study and review
Authors: Mohammadzad Mir Hosein Seyyed , Gardeshkhah Salar , Khademvatani Kamal , Sedokani Amin
Published: July 2020

Background and aims

Coronary Slow flow is a phenomenon known as slow contrast flow that injected into the coronary arteries, without epicardial coronary arteries obstruction. The etiology of this disease is unknown. Endothelial dysfunction, known as a major cause of Coronary Slow flow syndrome (CSF).

Methods

This study was cross-sectional (descriptive-analytic), which was performed on patients admitted to Seyedoshohada Heart Center, during one year (2018-2019). Considering the inclusion and exclusion criteria, patients were divided into two groups of normal coronary arteries (NECA, as the control group) and with the Coronary slow-flow (CSF).

Results

In the present study, 124 patients were studied, 67.9% in the coronary slow flow group and 39.4% in the control group were men (p=0.001). In the coronary slow flow group, the mean age of patients was 52.18 ± 12.55 years and in the control group, the mean age was 51.77 ± 10.36 years (p=0.18). Mean BMI was significantly higher in the coronary slow flow group than the control group (p <0.05). The smoking, hypertension, and mean of Lymphocyte, Hb, Hct, Plt, MPV, RDW, BUN, FBS, TG, TC, LDL was significantly higher coronary slow flow group. Also, in echocardiography, the mean E wave, E/A ratio was significantly lower in the coronary slow flow group. The GLS was also significantly lower in the control group (p=0.01). LAD was the most common type of coronaries that involved with a slow flow.

Conclusion

The results of this study showed that there was a significant increase in the rate of coronary slow flow in men, smokers, high BMI, and hypertensive patients. Also, platelet count, MPV, LDL, FBS, and some laboratory variables were high in patients with CSF. Mild diastolic dysfunction and low GLS were observed in this group of patients.
Polyp bailout and reattachment of the abundant Caribbean octocoral Eunicea flexuosa
Authors: Wells Christopher D. , Tonra Kaitlyn J.
Published: July 2020

Anthozoans exhibit great plasticity in their responses to stressful conditions, including decreasing individual size, detaching from the substratum and relocating, and releasing endosymbiotic microalgae. Another response to stress used by some colonial anthozoans is polyp bailout, in which the coenenchyme breaks down and individual polyps detach from the colony. We observed polyp bailout in the common Caribbean gorgonian Eunicea flexuosa after eight hours of aerial exposure. After nine days, 28% of bailed-out polyps reattached, although none opened to resume feeding. Polyp bailout is a costly and high-risk escape response, but reattachment indicates that this can be a genet-saving behavior in cases where whole-colony mortality is likely. While it has been described in several species of scleractinians and two octocorals, we still do not know how widespread this behavior is in anthozoans.
Implementing a Negative Pressure Isolation Space within a Skilled Nursing Facility to Control SARS-CoV-2 Transmission
Authors: Miller Shelly , Mukherjee Debanjan , Wilson Joseph , Clements Nicholas , Steiner Cedric
Published: July 2020

Background

Isolation space must be expanded during pandemics involving airborne transmission. Little to no work has been done to establish optimal design strategies and implementation plans to ease surge capacity and expand isolation capacity over long periods in congregate living facilities. The COVID-19 pandemic has an airborne transmission component and requires isolation, which is difficult to accomplish in skilled nursing facilities.

Purpose

In this study we designed, implemented, and validated an isolation space at a skilled nursing facility in Lancaster, PA. The overall goal was to minimize disease transmission between residents and staff within the facility.

Basic Procedures

We created an isolation space by modifying an existing HVAC system of the SNF. We measured pressure on-site and performed computational fluid dynamics and Lagrangian particle-based modeling to test containment and possible transmission extent given the isolation space is considered negative rather than individual rooms.

Main Findings

Pressure data shows the isolation space maintained an average hourly value of (standard deviation) -2.3 Pa (0.12 Pa) pressure differential between it and the external hallway connected to the rest of the facility. No transmission of SARS-CoV-2 between residents isolated to the space occurred, nor did any transmission to the staff or other residents occur. The isolation space was successfully implemented and, as of writing, continues to be operational through the pandemic.

Highlights

Negative pressure isolation space is an effective method to meet needed surge capacity during the COVID-19 pandemic and future pandemics

Planning for how and where to rapidly create a negative pressure isolation space is needed in congregate living areas such as skilled nursing facilities

This demonstration shows the feasibility of using low-cost and in-house systems to quickly create negative pressure within a skilled nursing facility hallway and to maintain these conditions, minimizing disease transmission between residents and staff
Impact of opioid agonists on mental health in substitution treatment for opioid use disorder: A systematic review and Bayesian network meta-analysis of randomized clinical trials
Authors: Moazen-Zadeh Ehsan , Ziafat Kimia , Yazdani Kiana , Mamdouh Mostafa , Wong James , Modabbernia Amirhossein , Blanken Peter , Verthein Uwe , Schütz Christian G. , Jang Kerry , Akhondzadeh Shahin , Krausz R. Michael
Published: July 2020

Objective

There is a dearth of high-quality systematic evidence on the impact of opioid substitution medications on mental health. We compared mental health outcomes between opioid medications and placebo/waitlist, and between different opioids.

Methods

This systematic review and meta-analysis of randomized clinical trials (RCTs) was pre-registered at PROSPERO (CRD42018109375). Embase, MEDLINE, PsychInfo, CINAHL Complete, and Web of Science Core Collection were searched from inception to May 2020. RCTs were included if they compared opioid agonists with each other or with a placebo/waitlist in substitution treatment of patients with opioid use disorder, and reported at least one mental health outcome on a span of more than 1-month post baseline. Studies with psychiatric care, adjunct psychotropic medications, or unbalanced psychosocial services were excluded. Primary outcomes were comparison of depressive symptoms and overall mental health between opioids and placebo/waitlist. Random effects model was used for all the meta-analysis.

Results

Nineteen studies were included in the narrative synthesis and 15 in the quantitative synthesis. Hydromorphone, diacetylmorphine (DAM), methadone, slow-release oral morphine, buprenorphine, and placebo/waitlist were among the included interventions. Based on network meta-analysis for primary outcomes, buprenorphine (SMD (CI95%)= −0.61 (−1.20, −0.11)), DAM (−1.40 (−2.70, −0.23)), and methadone (−1.20 (−2.30, −0.11)) were superior to waitlist/placebo on overall mental health. Further direct pairwise meta-analysis indicated that overall mental health improved more in DAM compared to methadone (−0.23 (−0.34, −0.13)).

Conclusions

It appears that opioid medications improve mental health independent of psychosocial services. Potential contribution of other factors needs to be further investigated.
Nanoscale Organization of FasL on DNA Origami as a Versatile Platform to Tune Apoptosis Signaling in Cells
Authors: Berger Ricarda M. L. , Weck Johann M. , Kempe Simon M. , Liedl Tim , Rädler Joachim O. , Monzel Cornelia , Heuer-Jungemann Amelie
Published: July 2020

Nanoscale probes with fine-tunable properties are of key interest in cell biology and nanomedicine to elucidate and eventually control signaling processes in cells. A critical, still challenging issue is to conjugate these probes with molecules in a number- and spatially-controlled manner. Here, DNA origami-based nanoagents as nanometer precise scaffolds presenting Fas ligand (FasL) in well-defined arrangements to cells are reported. These nanoagents activate receptor molecules in the plasma membrane initiating apoptosis signaling in cells. Signaling for apoptosis depends sensitively on FasL geometry: fastest time-to-death kinetics are obtained for FasL nanoagents representing predicted structure models of hexagonal receptor ordering with 10 nm inter-molecular spacing. Slower kinetics are observed for one to two FasL on DNA origami or FasL coupled with higher flexibility. Nanoagents with FasL arranged in hexagons with small (5 nm) and large (30 nm) spacing impede signal transduction. Moreover, for predicted hexagonal FasL nanoagents, signaling efficiency is faster and 100× higher compared to naturally occurring soluble FasL. Incubation of the FasL-origami nanoagent in solution exhibited an EC50 value of only 90 pM. These studies present DNA origami as versatile signaling platforms to probe the significance of molecular number and nanoscale ordering for signal initiation in cells.
On the diversity of chemical power supply as a determinant of biological diversity
Authors: Diego David , Hannisdal Bjarte , Dahle Håkon
Published: July 2020

Understanding how environmental factors shape biological communities is a fundamental problem in microbial ecology. Patterns of microbial diversity have been characterized across a wide range of different environmental settings, but the mechanisms generating these patterns remain poorly understood. Here, we use mathematical modelling to investigate fundamental connections between chemical power supply to a system and its biological diversity and community structure. We reveal a strong mechanistic coupling between biological diversity and the diversity of chemical power supply, but also find that different properties of power supply, such as substrate fluxes and flow and Gibbs energies of reactions, affect community structure in fundamentally different ways. Moreover, we show how simple connections between power supply and growth can give rise to complex patterns of biodiversity across physicochemical gradients, such as pH gradients. Our findings demonstrate the importance of taking into account energy fluxes in order to reveal fundamental connections between community structure and environmental variability, and to obtain a better understanding of microbial population dynamics and diversity in natural environments.
Combined multi-modal assessment of glaucomatous damage with electroretinography and optical coherence tomography/angiography
Authors: Al-Nosairy Khaldoon O. , Prabhakaran Gokulraj , Pappelis Konstantinos , Thieme Hagen , Hoffmann Michael B.
Published: July 2020

Purpose

To compare the diagnostic performance and to evaluate the interrelationship of electroretinographical and structural and vascular measures in glaucoma.

Methods

For 14 eyes of 14 healthy controls and 15 eyes of 12 patients with glaucoma ranging from preperimetric to advanced stages OCT, OCT-A and electrophysiological measures [multifocal photopic negative response ratio (mfPhNR) and steady state pattern electroretinogram (ssPERG)] were applied to assess changes in retinal structure, microvasculature, and function, respectively. The diagnostic performance was assessed via area-under-curve (AUC) measures obtained from ROC analyses. The interrelation of the different measures was assessed with correlation analyses.

Results

mfPhNR and ssPERG amplitudes, parafoveal (pfVD) and peripapillary vessel density (pVD), macular ganglion cell inner plexiform layer thickness (mGCIPL) and peripapillary retinal nerve fibre layer thickness (pRNFL) were significantly reduced in glaucoma. The AUC for mfPhNR was highest among diagnostic modalities (AUC: 0.88, 95%-CI: 0.75-1.0, P< 0.001), albeit not statistically different from that for macular (mGCIPL: 0.76, 0.58-0.94, P< 0.05; pfVD: 0.81, .65-.97, P< 0.01) or peripapillary imaging (pRNFL: 0.85, 0.70-1.0, P< 0.01; pVD: 0.82, 0.68-0.97, P < 0.01). Combined functional/vascular measures yielded the highest AUC (mfPhNR-pfVD: 0.94, 0.85-1.0, P<0.001). The functional/structural measure correlation (mfPhNR-mGCIPL correlation coefficient (rs): 0.58, P = 0.001; mfPhNR-pRNFL rs: 0.66, P < 0.0001) was stronger than the functional-vascular correlation (mfPhNR-pfVD rs: 0.29, P = 0.13; mfPhNR-pVD rs: 0.54, P = 0.003).

Conclusions

The combination of ERG measures and OCT-A improved diagnostic performance in glaucoma. Combing ERG, structural and OCT-A parameters provides an enhanced understanding of the pathophysiology of glaucoma.
Characterization of prolonged COVID-19 symptoms and patient comorbidities in an outpatient telemedicine cohort
Authors: Cellai Michele , O’Keefe James B.
Published: July 2020

We identified patients with coronavirus disease 2019 (COVID-19) in a telemedicine clinic who requested ongoing follow-up 6 weeks after symptom onset. Patients with prolonged symptoms often have not returned to work or usual activity. Respiratory symptoms are most common, and underlying asthma and lung disease occur frequently.
PAK3 controls the tangential to radial migration switch of cortical interneurons by coordinating changes in cell shape and polarity
Authors: Viou Lucie , Launay Pierre , Rousseau Véronique , Masson Justine , Pace Clarisse , Adelstein Robert S. , Ma X. , Jia Zhengping , Murakami Fujio , Barnier Jean-Vianney , Métin Christine
Published: July 2020

During the embryonic development, cortical interneurons migrate a long distance tangentially and then re-orient radially to settle in the cortical plate where they contribute to cortical circuits. Migrating interneurons express PAK3, a p21-activated kinase that switches between active and inactive states and controls interneuron migration by unknown mechanism(s). Here we examined the role of the kinase activity of PAK3 to regulate the migration of cortical interneurons. We showed that interneurons expressing a constitutively active PAK3 mutant (PAK3-ca) oriented preferentially radially in the cortex, extended short leading processes and exhibited unstable polarity. On the contrary, interneurons expressing an inactive PAK3 mutant (PAK3-kd for kinase dead) extended branched leading processes, showed directed nuclear movements and remained in the tangential pathways. Results showed that PAK3 kinase activity controls the switch between the tangential and radial modes of migration of cortical interneurons and identified myosin 2B as an effector of this switch.
Is Boldness in Climbing Perch (Anabas testudineus) Sensitive to the Apparatus Used for Measurement?
Authors: Das Prantik , Binoy V V
Published: July 2020

Swimway and open field are the two popular apparatus used for measuring boldness - the propensity to take risky decisions - in various piscine species. The present study compared boldness exhibited by an air breathing freshwater fish climbing perch in a swimway, rectangular open field, intermediate stages between these two apparatus and circular open field. Impact of the modification of the start chamber by providing substratum made up of cobbles and covering the water surface using water plant hydrilla, alone and in combinations on the boldness was also tested. Our results revealed that the apparatus has a significant impact on the boldness in climbing perch. The presence of a shelter in the experimental arena (swimway) and cobble substratum in the start chamber of the apparatus were found to be reducing boldness in this fish, while hydrilla cover on the water surface neutralised the impact of cobble substratum. Repeated exposure and resultant familiarity with the arena increased boldness of climbing perch but the pattern of modification of this behavioural trait exhibited during the course of experiment was divergent across the instruments. These results point towards the need for critically analyzing the influence of instruments used for measuring various behavioural traits and considering biological needs of the subject species while designing the apparatus.
Adenosine tips the pathogenic Th1 and Th17 responses in experimental autoimmune uveitis (EAU)
Authors: Sun Deming , Ko Minhee , Shao Hui , Kaplan Henry J.
Published: July 2020

Various pathological conditions are accompanied by ATP release from the intracellular to the extracellular compartment, where it degrades into adenosine and modulates immune responses. Previous studies concluded that both ATP and its degradation product adenosine are important immune-regulatory molecules; ATP acted as a danger signal that promotes immune responses, but adenosine’s effect was inhibitory. In this study, we show that adenosine plays an important role in balancing Th1 and Th17 pathogenic T cell responses in autoimmune disease. While its effect on Th1 responses is inhibitory, its effect on Th17 responses is enhancing, thereby impacting the balance between Th1 and Th17 responses. Mechanistic studies showed that this effect is mediated via several immune cells, among which γδ T cell activation and dendritic cell differentiation are prominent; adenosine and γδ-mediated immunoregulation synergistically impact each other’s effect. Adenosine augments the activation of γδ T cells, which is an important promoter for Th17 responses and has a strong effect on DC differentiation tipping the balance from generation of DCs that stimulate Th1 responses to those that stimulate Th17 responses. The knowledge acquired in this study should improve our understanding of the immune-regulatory effect of extracellular ATP-adenosine metabolism and improve treatment for autoimmune diseases caused by both Th1 and Th17-type pathogenic T cells.
Analysis of genetic diversity and association of seed and mucilage yields with inter simple sequence repeats (ISSR) polymorphism in a collection ofPlantgaospecies
Authors: Motahareh Bagheri , Heidrai Bahram , Shahriari Zolfaghar , Dadkhodaie Ali , Heidari Zahra , Richards Christopher M
Published: July 2020

Analysis of genetic diversity in medicinal plants assists germplasm conservation and selection for use in breeding schemes. The aims of the present study were to assess genetic diversity and differentiation of severalPlantagospecies using Inter Simple Sequence Repeats (ISSR) markers and identify marker-trait associations (MTAs). Thirty-onePlantagoaccessions belonging to eight species with various mating system and chromosome number were collected from geographical regions of Iran environments. Polymorphism in the DNA ofPlantagoaccessions were analyzed using polymerase chain reaction (PCR) of 25 ISSR primers. The data for number of polymorphic bands were analyzed on the basis of several genetic diversity parameters. The results of gel analysis indicated that the ISSR primers amplified 5 to 21 polymorphic bands with 100 to 3000 bp size. The mean polymorphism was 83.83% and five primers showed 100% polymorphism amongPlantagoaccessions. The Polymorphism Information Content (PIC) for ISSR as a dominant marker ranged from 0.1103 to 0.3829 with the mean 0.2727 in the species tested. Accessions inP. amplexicaulisandP. pysillumspecies represented the highest Nei’s and Shannon’s genetic diversity whilst the lowest obtained forP. lagopus. Analysis of phylogenetic network generated by the Neighbor-Net Algorithm showed moderate split of the eight species tested and the network depicted moderate conflict. The principal coordinate analysis (PCoA) results showed lower conflict in separation of accessions of the eight species. Fifty-six significant MTAs were detected for the traits tested inPlantagoaccessions, of which six were shared between three seed and mucilage traits and 24 were common between two traits. The coefficient of determination (R2) for the identified MTAs varied between 32 and 73%. In conclusion, the results of genetic diversity analysis suggested that ISSR marker could efficiently differentiatePlantagospecies and the information of genetic diversity might assistPlantagoimprovement and conservation.
Identification of novel Rab46 effector proteins
Authors: Pedicini Lucia , Wiktor Sabina D , Simmons Katie J , McKeown Lynn
Published: July 2020

Rab46 is a novel Ca2+- sensing Rab GTPase shown to have important functions in endothelial and immune cells. The presence of functional Ca2+- binding, coiled-coil and Rab domains suggest that Rab46 will be important for coupling rapid responses to signalling in many cell types. The molecular mechanisms underlying Rab46 function are currently unknown. Here we provide the first resource for studying Rab46 interacting proteins. Using liquid chromatography mass spectrometry (LC-MS/MS) to identify affinity purified proteins that bind to constitutively active GFP-Rab46 or inactive GFP-Rab46 expressed in endothelial cells, we have revealed 922 possible interacting proteins. Further comparative analyses between nucleotide-locked Rab46 proteins enriched this dataset to confidently identify 29 effector proteins. Importantly, through biochemical and imaging approaches we have validated two potential effector proteins; dynein and the Na2+/ K+ATPase subunit alpha 1 (ATP1α1). Hence, our use of affinity purification and LC-MS/MS to identify Rab46 neighbouring proteins provides a valuable resource for detecting Rab46 effector proteins and analysing Rab46 functions.
Sick Bats Stay Home Alone: Social distancing during the acute phase response in Egyptian fruit bats (Rousettus aegyptiacus)
Authors: Moreno Kelsey R. , Weinberg Maya , Harten Lee , Ramos Valeria B. Salinas , Herrera M. L. Gerardo , Czirják Gábor Á. , Yovel Yossi
Published: July 2020

Along with its many advantages, social roosting imposes a major risk of pathogen transmission. How social animals, and especially free-ranging mammals, reduce this risk is poorly documented. We used lipopolysaccharide injection to imitate bacterial sickness in both a captive and a free-ranging colony of an extremely social, long lived mammal – the Egyptian fruit bat. We monitored behavioral and physiological responses using an arsenal of methods, including on-board GPS and acceleration, video, temperature and weight measurements, and blood samples. Sick-like bats exhibited an increased immune response, as well as classical illness symptoms including fever, weight loss, anorexia, and lethargy. Notably, they also isolated themselves from the group by leaving the social cluster and avoiding contact. Free-ranging individuals ceased foraging outdoors for at least two nights. Together, these sickness behaviors demonstrate a strong, integrative immune response which promotes recovery of infected individuals while protecting their group members from transmission of pathogens, and at the same time, reducing spillover events outside the roost.
The rice bundle sheath produces reactive oxygen species during high light stress via NADPH oxidase
Authors: Xiong Haiyan , Hua Lei , Reyna-Llorens Ivan , Shi Yi , Chen Kun-Ming , Smirnoff Nicholas , Kromdijk Johannes , Hibberd Julian M.
Published: July 2020

When exposed to high light plants produce reactive oxygen species (ROS). InArabidopsis thalianalocal accumulation of ROS preferentially takes place in bundle sheath strands, but little is known about how this response takes place. Using rice and the ROS probes diaminobenzidine and 2’,7’-dichlorodihydrofluorescein diacetate, we found that after exposure to high light, ROS were produced more rapidly in bundle sheath strands than mesophyll cells. This response was not affected either by CO2supply or photorespiration. Consistent with these findings, deep sequencing of mRNA isolated from mesophyll or bundle sheath strands indicated balanced accumulation of transcripts encoding all major components of the photosynthetic apparatus. However, transcripts encoding several isoforms of the superoxide/H2O2-producing enzyme NADPH oxidase were more abundant in bundle sheath strands than mesophyll cells. ROS production in bundle sheath strands was reduced by blocking NADPH oxidase activity pharmacologically, but increased when the bundle sheath preferentialRBOHAisoform of NADPH oxidase was over-expressed. NADPH oxidase mediated accumulation of ROS in the rice bundle sheath was detected in etiolated leaves lacking chlorophyll indicating that high light and NADPH oxidase-dependent ROS production is not dependent on photosynthesis.