bluuebunny/crossref_metadata_2025 huggingface dataset:
Obstructive sleep apnea is more severe in men but not women with refractory hypertension compared with controlled resistant hypertension
Authors: Thomas S. Justin , Siddiqui Mohammed , Judd Eric , Moore David , Harding Susan M. , Oparil Suzanne , Calhoun David
Published: October 2020

Objectives:

Obstructive sleep apnea (OSA) is associated with treatment-resistant hypertension (RHTN) and may contribute to refractory hypertension (RfHTN). The objective of the current study was to test the hypothesis that patients with RfHTN have more severe OSA compared with patients with controlled RHTN.

Methods:

Patients (n = 187) referred to the University of Alabama at Birmingham Hypertension Clinic for evaluation and treatment of RHTN, defined as uncontrolled blood pressure (BP) (SBP ≥ 130 mmHg or DBP ≥ 80 mmHg) despite the use of at least three antihypertensive medications including a diuretic, were enrolled following completion of at least three follow-up clinic visits. RfHTN was defined as uncontrolled high BP despite treatment with five or more antihypertensive agents of different classes, including a long-acting thiazide-type diuretic and a mineralocorticoid receptor antagonist. Following enrollment, all patients (n = 130) completed 24-h ambulatory BP measurement and overnight diagnostic polysomnography during normal nightly use of continuous positive airway pressure. Analyses examined the severity of OSA and related sleep characteristics among patients with RfHTN versus controlled RHTN.

Results:

Of the 130 evaluated patients, 37 (28.5%) had RfHTN and 93 (71.5%) had controlled RHTN. In unadjusted analyses, there was not a significant difference in OSA severity, oxygen saturation, or hypoxemia time in patients with RfHTN versus controlled RHTN (P > 0.05). Men with RfHTN had more severe OSA compared with men with controlled RHTN (P = 0.044). In adjusted analyses, OSA severity was associated with sex (P < 0.0001), but not hypertension phenotype (P = 0.17).

Conclusion:

The severity of OSA may contribute to RfHTN status in men but not women.
Methodological considerations for the measurement of arterial stiffness using applanation tonometry
Authors: Cooke Alexandra B. , Kuate Defo Alvin , Dasgupta Kaberi , Papaioannou Theodore G. , Lee Jeremy , Morin Suzanne N. , Murphy Jessica , Santosa Sylvia , Daskalopoulou Stella S.
Published: October 2020

Introduction:

Accurate comparisons of carotid--femoral pulse wave velocity (cfPWV) within and across studies require standardized procedures. Guidelines suggest reporting the average of at least two cfPWV measurements; if the difference exceeds 0.5 m/s, a third measurement should be taken, and the median reported. Another method involves repeating measurements until two values are within 0.5 m/s. However, in many studies, duplicate measurements are averaged irrespective of the difference between readings. We evaluated the impact of these methods on the reported cfPWV value.

Methods:

Measurements of cfPWV (SphygmoCor) from five studies included individuals spanning a wide age range, with or without comorbid conditions, and pregnant women. In participants with at least three high-quality measurements, differences between the median value (MED) and the average of the first two cfPWV measurements (AVG1) and the average of two cfPWV measurements within 0.5 m/s (AVG2) were evaluated using paired t-tests and Bland--Altman plots.

Results:

Participants’ mean age was 50 ± 14 years and BMI was 28.0 ± 5.5 kg/m2 (N = 306, 79% women). The overall mean difference was −0.10 m/s (95% CI 0.17 to −0.04) between MED and AVG1, and 0.11 m/s (95% CI 0.05--0.17) between MED and AVG2. The absolute difference exceeded 0.5 m/s in 34% (MED-AVG1) and 22% (MED-AVG2) of participants, and 1 m/s in 8% of participants (both MED-AVG1 and MED-AVG2). Scatter around the bias line increased with higher mean cfPWV values.

Conclusion:

Although the overall mean difference in cfPWV between protocols was not clinically relevant, large variation led to absolute differences exceeding 0.5 m/s in a large proportion of participants.
Combined Trabeculotomy-Trabeculectomy Versus Trabeculectomy for Treatment of Silicone Oil–induced Ocular Hypertension
Authors: El Maamoun Tarek A. , Shalaby Hisham S.
Published: October 2020

Précis:

Combined trabeculotomy-trabeculectomy (CTT) has a significantly better hypotensive effect than trabeculectomy and a higher success rate in cases of silicone oil–induced ocular hypertension.

Purpose:

To compare the ocular hypotensive effect of CTT with mitomycin-C (MMC) to that of trabeculectomy with MMC in cases of silicone oil–induced ocular hypertension.

Patients and Methods:

Thirty eyes of 30 patients with high intraocular pressure (IOP) after vitrectomy and silicone oil injection (followed by silicone oil removal) were randomly allocated to 2 groups in this randomized trial. Group A was composed of 15 cases who underwent combined CTT with MMC while group B cases contained 15 cases undergoing trabeculectomy with MMC. Patients were followed up for 12 months. We included patients above 18 years old, having performed vitrectomy and silicone oil injection followed by oil removal, and having IOP >21 mm Hg uncontrollable by antiglaucoma medications.

Results:

The postoperative IOP drop was significantly greater in group A than in group B at all follow up visits (P<0.05). Compared with preoperative IOP, both surgeries produced a significantly lower postoperative IOP at all follow-up visits (P<0.05). For group A, complete success rates (IOP≤21 mm Hg without ocular hypotensive medications) and qualified success rates (IOP≤21 mm Hg with or without ocular hypotensive medications) were both higher than for group B.

Conclusion:

Both surgeries effectively reduce IOP in cases of silicone oil–induced ocular hypertension, but CTT has a significantly better hypotensive effect and a higher success rate on the long-term.
Impact of COVID-19 Quarantine and School Cancelation on Other Common Infectious Diseases
Authors: McBride Joseph A. , Eickhoff Jens , Wald Ellen R.
Published: October 2020

Coronavirus disease 2019 lead to wide-spread quarantines and cancelations. The impact of these measures on other, noncoronavirus disease 2019, infectious diseases was analyzed within Dane County, Wisconsin. The incidence of streptococcal pharyngitis and acute otitis media decreased during quarantine while gonorrhea increased. Quarantine had the expected result for infections spread via the respiratory route but a different effect from those transmitted through sexual activity.
Children and Adolescents With SARS-CoV-2 Infection
Authors: Maltezou Helena C. , Magaziotou Ioanna , Dedoukou Xanthi , Eleftheriou Eirini , Raftopoulos Vasilios , Michos Athanasios , Lourida Athanasia , Panopoulou Maria , Stamoulis Konstantinos , Papaevangelou Vasiliki , Petinaki Efthimia , Mentis Andreas , Papa Anna , Tsakris Athanasios , Roilides Emmanuel , Syrogiannopoulos George A. , Tsolia Maria ,   for Greek Study Group on SARS-CoV-2 Infections in Children
Published: October 2020

Background:

There is limited information on severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection in children.

Methods:

We retrieved data from the national database on SARS-CoV-2 infections. We studied in-family transmission. The level of viral load was categorized as high, moderate, or low based on the cycle threshold values.

Results:

We studied 203 SARS-CoV-2-infected children (median age: 11 years; range: 6 days to 18.4 years); 111 (54.7%) had an asymptomatic infection. Among the 92 children (45.3%) with coronavirus disease 2019 (COVID-19), 24 (26.1%) were hospitalized. Infants <1 year were more likely to develop COVID-19 (19.5% of all COVID-19 cases) (P-value = 0.001). There was no significant difference between viral load and age, sex, underlying condition, fever and hospitalization, as well as between type of SARS-CoV-2 infection and age, sex, underlying condition and viral load. Transmission from a household member accounted for 132 of 178 (74.2%) children for whom the source of infection was identified. An adult member with COVID-19 was the first case in 125 (66.8%) family clusters. Child-to-adult transmission was found in one occasion only.

Conclusions:

SARS-CoV-2 infection is mainly asymptomatic or mild during childhood. Adults appear to play a key role in spread of the virus in families. Most children have moderate or high viral loads regardless of age, symptoms or severity of infection. Further studies are needed to elucidate the role of children in the ongoing pandemic and particularly in light of schools reopening and the need to prioritize groups for vaccination, when COVID-19 vaccines will be available.
The Impact of Nurse-Led Cardiac Rehabilitation on Quality of Life and Biophysiological Parameters in Patients With Heart Failure: A Randomized Clinical Trial
Authors: ARJUNAN Porkodi , TRICHUR Ramakrishnan Venkatakrishnan
Published: October 2020

Background

Cardiovascular diseases are the leading cause of mortality in the Indian subcontinent, accounting for 38% of deaths annually. One cardiovascular disease in particular, heart failure, is a growing public health problem both in India and worldwide.

Purpose

Heart failure is a chronic, progressive disease with increasing rates of incidence and prevalence. This study was conducted to determine the influence of a nurse-led cardiac rehabilitation program on quality of life and biophysiological parameters in patients with chronic heart failure. In this study, it was hypothesized that participants in the cardiac rehabilitation program would report significantly more-positive changes in quality of life and biophysiological parameters than their peers who did not participate in this program.

Methods

In this randomized controlled trial, the participants were patients with chronic heart failure who had been admitted to a tertiary care hospital in India. The participants assigned to the intervention group received both nurse-led cardiac rehabilitation and routine care. In addition, intervention group participants received a booklet on cardiac rehabilitation, Healthy Way to Healthy Heart, at discharge and fortnightly telephone reminders about good cardiac rehabilitation practices. A standard questionnaire was used to collect targeted information on participants' general and disease-specific quality of life at 1 and 3 months postintervention. Biophysiological parameters such as body mass index, blood pressure, and serum cholesterol values were also measured.

Results

Two thirds of the participants in each group (65% in the intervention group and 66% in the control group) were between 51 and 70 years old. The mean score for the mental component summary of generic quality of life steadily decreased in the control group and steadily increased in the intervention group at the first and second posttests.

Conclusions/Implications for Practice

Nurses working in cardiology units play a pivotal role in educating and managing the health status of patients with heart failure. Providing cardiac rehabilitation to patients with heart failure benefits the quality of life of these patients. Nurses working in cardiology units should encourage patients with heart failure to practice cardiac rehabilitation for a longer period to further improve their quality of life.
Decrease of Postchemotherapy Complications With the Use of Probiotics in Children With Acute Lymphoblastic Leukemia
Authors: Reyna-Figueroa Jesús , Bejarano-Juvera Arely Anahí , García-Parra Cecilia , Barrón-Calvillo Elsa E. , Queipo-Garcia Gloria E. , Galindo-Delgado Patricia
Published: October 2020

Introduction:

During the administration of antineoplastic drugs, acute complications because of toxicity occur, determining their hospital readmission, visits to the emergency department, use of antimicrobials, and possibilities of presenting systemic infections, impacting on their life quality.

Methods:

Through a prospective cohort, 60 children with acute lymphoblastic leukemia were followed-up for 30 days after the hospital discharge because of chemotherapy administration, those patients were previously included in a single-blinded study in which 30 (group 1) received Lactobacillus rhamnosus GG probiotic during the administration of chemotherapy. The remaining 30 patients did not receive probiotics (group 2). There were evaluated gastrointestinal symptoms, such as diarrhea, dyspepsia, abdominal distension, meteorism, constipation, nausea, and vomit, development of infections, antibiotic use, number of emergency department visits, number of hospitalizations, and sepsis diagnosis.

Statistical Analysis:

To assess the impact of the use of probiotics, the difference in proportions between both study groups was evaluated.

Results:

Gastrointestinal manifestations (nausea, vomiting, diarrhea, constipation) occurred in 30% of patients in group 1 versus 63% of group 2 (P=0.009). Nine of 30 patients (30.0%) in group 1 went to the emergency room, versus 33.3% of group 2 (P=0.7). Antimicrobials were used in 8 subjects (26.6%) in group 1 versus 6 subjects (53.3%) in group 2 (P=0.03) suspected of an infectious disease. Four (13.3%) group 1 patients were hospitalized versus 30% of group 2 (P=0.1). Two subjects (6.6%) in group 1 had sepsis versus 7 (23.3%) in group 2 (P=0.07).

Conclusions:

The results indicate that the use of probiotics can be a great alternative in the improvement of gastrointestinal symptoms and the adverse effects associated with chemotherapy.
Fatal Herpes Simplex Esophagitis of an Infant Case Report and Review of the Literature
Authors: Bissessar Randall , Kannan Rajesh P.
Published: October 2020

Herpes simplex virus esophagitis is a rare and not readily recognized condition which is often seen in immunocompromised individuals. This case highlights the rare complication of herpes simplex virus in an otherwise healthy male infant who presented with a possible seizure after listlessness, fever, and black stools for 1 day. The decedent died shortly after arrival to the hospital emergency department, and a complete autopsy was performed, which was remarkable for upper gastrointestinal bleeding due to esophageal ulcers secondary to viral infection (herpes simplex virus type 1). To our knowledge, this is the first reported case in which herpes simplex virus esophagitis resulted in ulcerations that extended through the esophagus and involved the adjacent wall of the aorta with subsequent upper gastrointestinal bleeding leading to the death of an infant.
Medicolegal Implications of Biphasic Anaphylaxis
Authors: Da Broi Ugo , Moreschi Carlo , Marega Giulia , Tse Rexson , Garland Jack , Ondruschka Benjamin , Palmiere Cristian
Published: October 2020

Biphasic anaphylaxis is an uncommon IgE-mediated condition whose pathophysiological mechanisms, risk factors, and predictive signs are not properly understood. Fortunately, the lethality of biphasic anaphylaxis, although probably underestimated, is low. Preventive clinical measures for biphasic anaphylaxis are neither standardized nor commonly applied. Furthermore, there are no laboratory protocols or anaphylactic markers to help identify the onset of biphasic anaphylaxis in clinical settings. The aim of this review is to highlight the medicolegal difficulties facing coroners and forensic pathologists in terms of the diagnosis and assessment of harm for victims and survivors of biphasic anaphylaxis.
Modification of Pediatric Sequential Organ Failure Assessment Score Using Acute Kidney Injury Diagnostic Criteria
Authors: Jhang Won Kyoung , Kim Da Hyun , Ha Eun Ju , Park Seong Jong
Published: October 2020

Objectives:

To develop a modified pediatric Sequential Organ Failure Assessment score using the acute kidney injury diagnostic criteria and evaluate its performance in predicting mortality.

Design:

A single-center retrospective study.

Setting:

Fourteen-bed PICU in a tertiary care academic children’s hospital.

Patients:

Critically ill children admitted to the PICU between January 2017 and September 2019 with at least more than two serum creatinine measurements—one for baseline and the other within the first 48 hours of PICU admission.

Interventions:

None.

Measurements and Main Results:

A total of 755 patients were included. Overall, 265 patients were diagnosed with acute kidney injury using the current acute kidney injury diagnostic criteria. The overall PICU mortality was 5.8%. Patients with acute kidney injury required more vasoactive-inotropic drugs and showed higher illness severity scores, including the Pediatric Risk of Mortality III, Pediatric Logistic Organ Dysfunction 2, pediatric Sequential Organ Failure Assessment, and modified pediatric Sequential Organ Failure Assessment scores, as well as higher PICU mortality than patients without acute kidney injury (p < 0.001). As acute kidney injury stages increase, PICU mortality also increased (p < 0.001). Based on multivariable logistic regression analysis adjusted for age and sex, the modified pediatric Sequential Organ Failure Assessment score was an independent prognostic factor of PICU mortality. The modified pediatric Sequential Organ Failure Assessment score showed better performance in predicting PICU mortality (area under the receiver operating characteristic curve, 0.821; 95% CI, 0.759–0.882) than other severity scores (area under the receiver operating characteristic curve [95% CI] of Pediatric Risk of Mortality III, Pediatric Logistic Organ Dysfunction 2, and pediatric Sequential Organ Failure Assessment scores: 0.788 [0.723–0.853], 0.735 [0.663–0.807], and 0.785 [0.718–0.853], respectively).

Conclusions:

Acute kidney injury is prevalent and associated with poor clinical outcomes in critically ill children. The modified pediatric Sequential Organ Failure Assessment score, based on the acute kidney injury diagnostic criteria, showed improved performance in predicting PICU mortality. The modified pediatric Sequential Organ Failure Assessment score could be a promising prognostic factor for critically ill children.
Rapid Transition of a PICU Space and Staff to Adult Coronavirus Disease 2019 ICU Care
Authors: Wasserman Emily , Toal Megan , Nellis Marianne E. , Traube Chani , Joyce Christine , Finkelstein Robert , Killinger James S. , Joashi Umesh , Harrington John S. , Torres Lisa K. , Greenwald Bruce M. , Howell Joy
Published: October 2020

Objectives:

We describe the process by which a PICU and a PICU care team were incorporated into a hospital-wide ICU care model during the coronavirus disease 2019 pandemic.

Design:

A descriptive, retrospective report from a single-center PICU.

Setting:

Twenty-three bed, quaternary PICU, within an 862-bed hospital.

Patients:

Critically ill adults, with coronavirus disease 2019-related disease.

Interventions:

ICU care provided by pediatric intensivists with training and support from medical intensivists.

Measurements and Main Results:

Within the context of the institution’s comprehensive effort to centralize and systematize care for adults with severe coronavirus disease 2019 disease, the PICU was transitioned to an adult coronavirus disease 2019 critical care unit. Nurses and physicians underwent just-in-time training over 3 days and 2 weeks, respectively. Medical ICU physicians and nurses provided oversight for care and designated hospital-based teams were available for procedures and common adult emergencies. Over a 7-week period, the PICU cared for 60 adults with coronavirus disease 2019-related critical illness. Fifty-three required intubation and mechanical ventilation for a median of 18 days. Eighteen required renal replacement therapy and 17 died.

Conclusions:

During the current and potentially in future pandemics, where critical care resources are limited, pediatric intensivists and staff can be readily utilized to meaningfully contribute to the care of critically ill adults.
The Structure of Research Questions in Randomized Controlled Trials in the Rehabilitation Field
Authors: Arienti Chiara , Lazzarini Stefano G. , Patrini Michele , Puljak Livia , Pollock Alex , Negrini Stefano
Published: October 2020

Objective

The aim of this study is to assess whether and how the PICO (Population, Intervention, Comparator, and Outcomes) format is described to frame research questions in randomized controlled trials looking at effectiveness of rehabilitation interventions.

Design

A methodological study was conducted. Randomized controlled trials in the rehabilitation field, published between July 1, 2019, and December 31, 2019, were included. The framing of the primary research question from each trial was evaluated.

Results

A total of 97 randomized controlled trials were included in the analysis. The most frequent framing of the primary research question was as an “objective” statement (55%), and in 33% of the articles, this was stated as an “objective” together with a “hypothesis” description. All PICO elements were present in 55% of research questions, but only 49% have used the statement suggested by Cochrane.

Conclusion

The findings of this study suggest that a specific item about the “research question” and the rationale that drove the proposed design following the form suggested by Cochrane should be included in the RCT Rehabilitation Checklist.
Thrombosis of the Iliac Vein Detected by 64Cu–Prostate-Specific Membrane Antigen (PSMA) PET/CT
Authors: Annunziata Salvatore , Rea Sandra , Romano Luisa , Mazzone Costanza , Di Traglia Silvia , Sciuto Rosa
Published: October 2020

An 82-year-old man had a diagnosis of prostate cancer and underwent curative radiotherapy. During the oncological follow-up, the patient showed biochemical relapse and underwent whole-body 64Cu–prostate-specific membrane antigen PET/CT for restaging purpose. 64Cu–prostate-specific membrane antigen PET/CT showed a pathological uptake in left iliac venous axis, subsequently confirmed as venous thrombosis.
Evaluation of the Therapeutic Response by 11C-Methionine PET in a Case of Neuro-Sweet Disease
Authors: Mitamura Katsuya , Yamamoto Yuka , Norikane Takashi , Takata Tadayuki , Nishiyama Yoshihiro
Published: October 2020

Sweet disease is a multisystem inflammatory disorder characterized by fever, cutaneous erythematous plaques, and aseptic neutrophilic infiltration of various organs. Neuro-Sweet disease is a known rare central nervous system complication of Sweet disease. A 67-year-old Japanese woman who was diagnosed with neuro-Sweet disease underwent 11C-methionine (11C-MET) PET. 11C-MET PET revealed increased accumulation in the affected brain tissues. After steroid therapy, she became asymptomatic, and a follow-up 11C-MET PET scan showed disappearance of the abnormal uptake of 11C-MET.
Is 0.6% Reasonable as the Minimum Requirement of the Graft-to-recipient Weight Ratio Regardless of Lobe Selection in Adult Living-donor Liver Transplantation?
Authors: Kusakabe Jiro , Yagi Shintaro , Sasaki Kazunari , Uozumi Ryuji , Abe Hiroyasu , Okamura Yusuke , Taura Kojiro , Kaido Toshimi , Uemoto Shinji
Published: October 2020

Background.

Several studies reported favorable outcomes of small-for-size grafts with graft-to-recipient weight ratio (GRWR) <0.8% in living-donor liver transplantation (LDLT). However, their indications should be carefully determined because they must have been indicated for low-risk cases over larger grafts with 0.8% ≤ GRWR. Furthermore, evidence for minimum requirements of GRWR remains inconclusive. We investigated the safety of small-for-size grafts against larger grafts by adjusting for confounding risk factors, and minimum requirement of graft volume in adult LDLT.

Methods.

We enrolled 417 cases of primary adult-to-adult LDLT in our center between 2006 and 2019. The outcomes of small grafts (0.6% ≤ GRWR < 0.8%, n = 113) and large grafts (0.8% ≤ GRWR, n = 289) were mainly compared using a multivariate analysis and Kaplan-Meier estimates.

Results.

The multivariate analysis showed that small grafts were not a significant risk factor for overall graft survival (GS). In the Kaplan-Meier analysis, small grafts did not significantly affect overall GS regardless of lobe selection (versus large grafts). However, GRWR < 0.6% was associated with poor overall GS. Although there were no significant differences between the 2 groups, unadjusted Kaplan-Meier curves of small grafts were inferior to those of large grafts in subcohorts with ABO incompatibility, and donor age ≥50 years.

Conclusions.

Similar outcomes were observed for small and large graft use regardless of lobe selection. 0.6% in GRWR was reasonable as the minimum requirement of graft volume in LDLT. However, small grafts should be indicated carefully for high-risk cases.
Personal protective equipment for reducing the risk of COVID-19 infection among healthcare workers involved in emergency trauma surgery during the pandemic: a systematic review protocol
Authors: Griswold Dylan P , Gempeler Andres , Kolias Angelos , Hutchinson Peter J. , Rubiano Andres M.
Published: October 2020

Objective

The objective of this broad evidence synthesis is to identify and summarize the available literature regarding the efficacy of different personal protective equipment (PPE) for reducing the risk of COVID-19 infection in health personnel caring for patients undergoing trauma surgery in low-resource environments (LREs).

Introduction

Many healthcare facilities in low-and middle-income countries are inadequately resourced and may lack optimal organization and governance, especially concerning surgical health systems. COVID-19 has the potential to decimate these already strained surgical healthcare services unless health systems take stringent measures to protect healthcare workers from viral exposure and ensure the continuity of specialized care for the patients.

Inclusion criteria

This review will preferentially consider systematic reviews of experimental and quasi-experimental studies, as well as individual studies of such designs, evaluating the effect of different PPE on the risk of COVID-19 infection in healthcare workers (HCWs) involved in emergency trauma surgery.

Methods

We will conduct several searches in the L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs automated regular searches in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and over thirty other sources. The search results will be presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Critical appraisal of the eligible studies for methodological quality will be conducted. Data will be extracted using the standardized data extraction tool in Covidence. Studies will, when possible, be pooled in a statistical meta-analysis using JBI SUMARI. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for grading the certainty of evidence will be followed, and a Summary of Findings (SoF) will be created.

Systematic review registration number

CRD42020198267
Connectivity for Rapid Synchronization in a Neural Pacemaker Network
Authors: Williams Ezekiel , Shifman Aaron R. , Lewis John E.
Published: October 2020

Synchronization is a fundamental property of biological neural networks, playing a mechanistic role in both healthy and disease brain states. The medullary pacemaker nucleus of the weakly electric fish is a synchronized network of high-frequency neurons, weakly coupled via gap junctions. Synchrony in the pacemaker is behaviourally modulated on millisecond timescales, but how gap junctional connectivity enables such rapid resynchronization speeds is poorly understood. Here, we use a computational model of the pacemaker, along with graph theory and predictive analyses, to investigate how network properties, such as randomness and the directionality of coupling (bidirectional/non-rectifying versus directional/rectifying gap junctions) characterize the fast synchronization of the pacemaker network. Our results provide predictions about connectivity in the pacemaker and insight into the relationship between structural network properties and synchronization dynamics in neural systems more generally.
Effects of Milk Fat Globule Epidermal Growth Factor VIII On Age-Associated Arterial Elastolysis, Fibrosis, and Calcification
Authors: Kim Soo Hyuk , Liu Lijuan , Ni Leng , Zhang Li , Zhang Jing , Wang Yushi , McGraw Kimberly R. , Monticone Robert , Telljohann Richard , Morrell Christopher H. , Lakatta Edward G. , Wang Mingyi
Published: October 2020

Milk fat globule-EGF factor 8 (MFG-E8) protein increases with age and is mainly secreted by vascular smooth muscle cells in the arterial wall. Here, we investigated the role of MFG-E8 signaling during proinflammation, elastolysis, fibrosis, and calcification within the aging arterial wall. In vivo studies indicated that (1) Elastic lamina breaks collagen deposition and calcium-phosphorus products were markedly increased in the aging arterial wall of rats; (2) MFG-E8 protein abundance was markedly increased while intact tropoelastin (TPELN), an element of repair of the elastic fibers, was markedly decreased in the aging arterial wall of rats; (3) The absence of MFG-E8 markedly alleviated age-associated increases in elastic lamina breaks, collagen deposition and calcium-phosphorus products in mice; and (4) MFG-E8 deficiency significantly decreased age-associated increases in matrix metalloproteinase type II (MMP-2) activation, alkaline phosphatase, and runt-related transcription factor 1 (Runx1) expression in the aortic walls of mice. The in vitro studies demonstrated that (1) treating either young or old rat VSMCs with recombinant human MFG-E8 protein (rhMFG-E8) significantly reduced TPELN levels while MFG-E8 gene silencing significantly increased TPELN levels; (2) rhMFG-E8 treatment activated MMP-2 levels in both young and old VSMCs; and (3) MMP-2 bound to and cleaved TPELN secreted from VSMCs. Thus, these findings suggest that MFG-E8 signaling promotes age-associated adverse structural remodeling, including elastolysis, fibrosis, and calcification; however, MFG-E8 deficiency markedly mitigates these adverse effects in mice.
Intradermal versus Intramuscular Administration of Influenza Vaccination: Rapid Review and Meta-analysis
Authors: Egunsola Oluwaseun , Clement Fiona , Taplin John , Mastikhina Liza , Li Joyce W. , Lorenzetti Diane L. , Dowsett Laura E. , Noseworthy Tom
Published: October 2020

Background

Vaccinations are essential for prevention of influenza. We synthesized the published literature on the immunogenicity and safety of the influenza vaccine at reduced or full intradermal doses compared with full intramuscular doses.

Methods

A rapid review of the literature was completed. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for studies published from 2010 until June 5th, 2020. All studies comparing intradermal and intramuscular influenza vaccinations were included. Random-effects meta-analyses of immunogenicity and safety outcomes were conducted.

Results

A total of 30 relevant studies were included. Seroconversion rates were equivalent between the 3 mcg, 6 mcg, 7.5 mcg, and 9 mcg intradermal vaccine doses and the 15 mcg intramuscular vaccine dose for each of the H1N1, H3N2, and B strains, but significantly higher with the 15 mcg intradermal compared with the 15 mcg intramuscular dose, for the H1N1 (RR 1.10, 95% CI: 1.01-1.20) and B strains (RR 1.40, 95% CI: 1.13-1.73). Seroprotection rates for the 9 mcg and 15 mcg intradermal doses were equivalent with the 15 mcg intramuscular dose for all the three strains, except for the 15 mcg intradermal dose for the H1N1 strain which was significantly higher (RR 1.05, 95% CI: 1.01-1.09). Local adverse events were significantly higher with intradermal doses. Fever and chills were significantly higher with the 9 mcg intradermal dose, while all other systemic adverse events were equivalent for all doses.

Conclusion

Reduced dose intradermal influenza vaccination appears to be a reasonable alternative to standard dose intramuscular vaccination because of the similarity in immunogenicity.
Misinformation on covid-19 origin and its relationship with perception and knowledge about social distancing: A cross-sectional study
Authors: Reyes Lenisse M. , Ortiz Lilibeth , Abedi Maxwell , Luciano Yenifel , Ramos Wilma , de Js. Reyes Pablo J.
Published: October 2020

Despite the vast scientific evidence obtained from the genomic sequencing of COVID-19, a controversy regarding its origin has been created in the mass media. This could potentially have a long-term influence on the behavior among individuals, such as failure to comply with proposed social distancing measures, leading to a consequent rise in the morbidity and mortality rates from COVID-19 infection. Several studies have collected information about knowledge, attitudes and practices regarding COVID-19; however, very little is known about the relationship of the perceptions of the individuals regarding the origin of the virus with the knowledge and perception about social distancing. This study aimed at ascertaining this relationship. For such purpose, a web-based cross-sectional study was conducted among a sample population from five provinces of the Dominican Republic within the period of June to July of 2020. The data collection instrument exploited in the study was a self-designed questionnaire distributed throughout different social media platforms. A purposive sampling strategy was implemented and a total of 1195 respondents completed the questionnaire. The collected data was analyzed using SPSS. Descriptive statistics, stepwise multiple linear regression and one-way multivariate analysis were implemented to test the hypotheses. The level of education was significantly associated (P = 0.017) with individuals’ perception about the origin of COVID-19, whilst only age (P = 0.032) and education level (P < 0.001) statistically significantly predicted ‘knowledge about social distancing’. Perception of COVID-19 origin was statistically significant associated (P = < 0.001) with the measures of the dependent variables (knowledge and perception on social distancing). The present study has established a possible link between the ‘perception of COVID-19 origin’ and ‘the perception and knowledge about social distancing’.
The Effect of Gender on Covid-19 Infections and Mortality in Germany: Insights From Age- and Sex-Specific Modelling of Contact Rates, Infections, and Deaths
Authors: Dörre Achim , Doblhammer Gabriele
Published: October 2020

Background

Recent research points towards age- and sex-specific transmission of COVID-19 infections and their outcomes. The effect of sex, however, has been overlooked in past modelling approaches of COVID-19 infections.

Aim

The aim of our study is to develop an age- and sex-specific model of COVID-19 transmission and to explore how contact changes effect COVID-19 infection and death rates.

Method

We consider a compartment model to establish forecasts of the COVID-19 epidemic, in which the compartments are subdivided into different age groups and genders. Estimated contact patterns, based on other studies, are incorporated to account for age- and sex-specific social behaviour. The model is fitted to real data and used for assessing hypothetical scenarios with regard to lockdown measures.

Results

Under current mitigation measures as of mid-August, active COVID-19 cases will double by the end of October 2020. Infection rates will be highest among the young and working ages, but will also rise among the old. Sex ratios reveal higher infection risks among women than men at working ages; the opposite holds true at old age. Death rates in all age groups are twice as high among men as women. Small changes in contact rates at working and young ages may have a considerable effect on infections and mortality at old age, with elderly men being always at higher risk of infection and mortality.

Discussion

Our results underline the high importance of the non-pharmaceutical mitigation measures in low-infection phases of the pandemic to prevent that an increase in contact rates leads to higher mortality among the elderly. Gender differences in contact rates, in addition to biological mechanisms related to the immune system, may contribute to sex-specific infection rates and their mortality outcome. To further explore possible pathways, more data on COVID-19 transmission is needed which includes socio-demographic information.
Misinterpretation of viral load in COVID-19
Authors: Miranda Renan Lyra , Guterres Alexandro , de Azeredo Lima Carlos Henrique , Filho Paulo Niemeyer , Gadelha Mônica R.
Published: October 2020

Knowledge of viral load is essential for formulating strategies for antiviral treatment, vaccination, and epidemiological control of COVID-19. Moreover, patients identification with high viral load could also be useful to understand risk factors such as age, comorbidities, severity of symptoms and hypoxia to decide the need for hospitalization. Several studies are evaluating the importance of analyzing viral load in different types of samples, clinical outcomes and viral transmission pathways. However, in a great number of emerging studies cycle threshold (Ct) values by itself is often used as a viral load indicator, which may be a mistake. In this study, we compared tracheal aspirate with nasopharyngeal samples obtained from critically ill COVID-19 patients and demonstrate how the raw Ct could lead to misinterpretation of results. Further, we analyzed nasopharyngeal swabs positive samples and propose a method to reduce evaluation error that could occur from using raw Ct. Based on these findings, we show the impact that normalization of Ct values has on interpretation of viral load data from different biological samples from patients with COVID-19, transmission and lastly in relations with clinical outcomes.

Importance

In a pandemic, prevention of disease transmission is key. Reliable data for profiles of viral load are needed and important to guide antiviral treatment, infection control and vaccination. The differential expression of SARS-CoV-2 viral RNA among patient groups is a current topic of interest and viral load has been associated with a diversity of outcomes. However, in a great number of emerging studies cycle threshold (Ct) values by itself is often used as a viral load indicator, which may be a mistake. In this study, we compared tracheal aspirate with nasopharyngeal samples obtained from critically ill COVID-19 patients and demonstrate how the raw Ct could lead to misinterpretation of results. Based on these findings, we show the impact that normalization of Ct values has on interpretation of viral load data from different biological samples from patients with COVID-19, transmission and lastly in relations with clinical outcomes.
FKBPL and SIRT-1, key angiogenesis proteins, are downregulated by diabetes in pregnancy
Authors: Alqudah Abdelrahim , Eastwood Kelly-Ann , Jerotic Djurdja , Todd Naomi , Hoch Denise , McNally Ross , Obradovic Danilo , Dugalic Stefan , Hunter Alyson J. , Holmes Valerie A. , McCance David R. , Young Ian S. , Watson Chris J , Robson Tracy , Desoye Gernot , Grieve David J , McClements Lana
Published: October 2020

Context

Diabetes in pregnancy is associated with numerous complications, however the mechanisms are still poorly understood.

Objective

To investigate the role of new angiogenesis markers, FKBPL and SIRT-1, in pre-gestational (type 1 diabetes, T1D) and gestational diabetes (GDM).

Design and intervention

Placental FKBPL, SIRT-1, PlGF and VEGF-R1 protein expression was determined from pregnant women with GDM or T1D, and in first trimester trophoblast cells exposed to high glucose and varying oxygen concentrations. Endothelial cell function was assessed in high glucose conditions and FKBPL overexpression.

Settings and Participants

Human placental samples from pregnant women with GDM (n=6) or T1D (n=8) were collected to assess FKBPL and SIRT-1 protein expression compared to non-diabetic controls.

Main outcome measures

To determine the role of placental FKBPL and/or SIRT-1 in diabetic pregnancies, in first trimester trophoblasts and endothelial cell function in high-glucose environment.

Results

Placental FKBPL protein expression was downregulated in T1D (FKBPL; p<0.05) whereas PlGF/VEGF-R1 were upregulated (p<0.05); correlations adjusted for gestational age were also significant. In the presence of GDM, only SIRT-1 (p<0.001) was significantly downregulated even when adjusted for gestational age (r=-0.92, p=0.001). FKBPL and SIRT-1 were also downregulated in ACH-3P cells in high glucose conditions and 6.5%/2.5% oxygen concentrations (p<0.05). FKBPL overexpression in HUVECs reduced tubule formation compared to empty vector control, in high glucose conditions (junctions; p<0.01, branches; p<0.05).

Conclusions

FKBPL and/or SIRT-1 downregulation in response to diabetes may have a role in the development of vascular dysfunction in pregnancy, and associated complications such as preeclampsia.
Single-cell data and correlation analysis support the independent double adder model in bothEscherichia coliandBacillus subtilis
Authors: Le Treut Guillaume , Si Fangwei , Li Dongyang , Jun Suckjoon
Published: October 2020

The reference point for cell-size control in the cell cycle is a fundamental biological question. We previously reported that we were unable to reproduce the conclusions of Witzet al.’seLifepaper (Witz, van Nimwegen, and Julou 2019) entitled, “Initiation of chromosome replication controls both division and replication cycles inE. colithrough a double-adder mechanism”, despite extensive efforts. In this ‘replication double adder’ (RDA) model, both replication and division cycles are determined via replication initiation as the sole implementation point of size control. Witzet al.justified the RDA model using a type of correlation analysis (the “I-value analysis”) that they developed. By contrast, we previously showed that, in bothEscherichia coliandBacillus subtilis,replication initiation and cell division are determined by balanced biosynthesis of key cell cycle proteins (e.g., DnaA for initiation and FtsZ for cell division) and their accumulation to their respective threshold numbers, which Witzet al.coined the ‘independent double adder’ (IDA) model. The adder phenotype is a natural quantitative consequence of these mechanistic principles. In a recentbioRxivresponse to our report, Witz and colleagues explicitly confirmed two important limitations of theI-value analysis: (1) it is only applicable to non-overlapping cell cycles, whereinE. coliis known to deviate from the adder principle, and (2) it is only applicable to select biological models and, for example, cannot evaluate the IDA model. These limitations of theI-value analysis were not explained in the originaleLifepaper and were overlooked during the review process. In this report, we show using data analysis, mathematical modeling, and experiments why theI-value analysis - in its current implementation - cannot compare different biological models. Furthermore, the RDA model is incompatible with the adder principle and is not broadly supported by experimental data. For completeness, we also provide a detailed point-by-point response to Witzet al.’s response (Witz, Julou, and van Nimwegen 2020) in the Supplemental Information.
The macaque brain ONPRC18 template with combined gray and white matter labelmap for multimodal neuroimaging studies of nonhuman primates
Authors: Weiss Alison R , Liu Zheng , Wang Xiaojie , Liguore William A , Kroenke Christopher D. , McBride Jodi L.
Published: October 2020

Macaques are the most common nonhuman primate (NHP) species used in neuroscience research. With the advancement of many neuroimaging techniques, new studies are beginning to apply multiple types of in vivo magnetic resonance imaging (MRI), such as structural imaging (sMRI) with T1 and T2 weighted contrasts alongside diffusion weighed (DW) imaging. In studies involving rhesus macaques, this approach can be used to better understand micro-structural changes that occur during development, in various disease states or with normative aging. However, many of the available rhesus brain atlases have been designed for only one imaging modality, making it difficult to consistently define the same brain regions across multiple imaging modalities in the same subject. To address this, we created a brain atlas from 18 adult rhesus macaques that includes co-registered templates constructed from images frequently used to characterize macroscopic brain structure (T2/SPACE and T1/MP-RAGE), and a diffusion tensor imaging (DTI) template. The DTI template was up-sampled from 1 mm isotropic resolution to resolution match to the T1 and T2-weighted images (0.5 mm isotropic), and the parameter map was derived for fractional anisotropy (FA). The labelmap volumes delineate 57 gray matter regions of interest (ROIs; 36 cortical regions and 21 subcortical structures), as well as 74 white matter tracts. Importantly, the labelmap overlays both the structural and diffusion templates, enabling the same regions to be consistently identified across imaging modalities. A specialized condensed version of the labelmap ROIs are also included to further extend the usefulness of this tool for imaging data with lower spatial resolution, such as functional MRI (fMRI) or positron emission tomography (PET).

Graphical Abstract
Ablation of Proliferating Osteoblast Lineage Cells After Fracture Leads to Atrophic Nonunion in a Mouse Model
Authors: Hixon Katherine R. , McKenzie Jennifer A. , Sykes David A.W. , Yoneda Susumu , Hensley Austin , Buettmann Evan G. , Zheng Hongjun , Skouteris Dimitrios , McAlinden Audrey , Miller Anna N. , Silva Matthew J.
Published: October 2020

Nonunion is defined as the permanent failure of a fractured bone to heal, often necessitating surgical intervention. Atrophic nonunions are a subtype that are particularly difficult to treat. Animal models of atrophic nonunion are available; however, these require surgical or radiation-induced trauma to disrupt periosteal healing. These methods are invasive and not representative of many clinical nonunions where osseous regeneration has been arrested by a “failure of biology”. We hypothesized that arresting osteoblast cell proliferation after fracture would lead to atrophic nonunion in mice. Using mice that express a thymidine kinase (tk) “suicide gene” driven by the 3.6Col1a1 promoter (Col1-tk), proliferating osteoblast lineage cells can be ablated upon exposure to the nucleoside analog ganciclovir (GCV). Wild-type (WT; control) and Col1-tk littermates were subjected to a full femur fracture and intramedullary fixation at 12 weeks age. We confirmed abundant tk+ cells in fracture callus of Col-tk mice dosed with water or GCV, specifically many osteoblasts, osteocytes, and chondrocytes at the cartilage-bone interface. Histologically, we observed altered callus composition in Col1-tk mice at 2 and 3 weeks post fracture, with significantly less bone and more fibrous tissue. Col1-tk mice, monitored for 12 weeks within vivoradiographs and microCT scans, had delayed bone bridging and reduced callus size. Following sacrifice,ex vivomicroCT and histology demonstrated failed union with residual bone fragments and fibrous tissue in Col1-tk mice. Biomechanical testing demonstrated a failure to recover torsional strength in Col1-tk mice, in contrast to WT. Our data indicates that suppression of proliferating osteoblast-lineage cells for at least 2 weeks after fracture blunts the formation and remodeling of a mineralized callus leading to a functional nonunion. We propose this as a new murine model of atrophic nonunion.