bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of colloid preload on the incidence of hypotension in spinal anesthesia for cesarean section: a systematic review and meta-analysis
Authors: Gong Rui-Song , Liu Xiao-Wen , Li Wei-Xia , Zhao Jing
Published: April 2021

Background:

Hypotension is a common complication caused by spinal anesthesia (SA), which may have adverse impacts on the condition of the parturient and fetus. Liquid infusion was found to be relatively effective for reducing the incidence of hypotension. However, the question of whether colloid preload can optimize hemodynamic variables in the cesarean section remains controversial. This study aims to determine the effects of colloid preload on the incidence of hypotension induced by SA in elective cesarean section.

Methods:

Related keywords were searched on PubMed, EMBASE, and Cochrane Library from inception dates to May 2020. Studies included were evaluated for eligibility and quality. The primary outcome was the intra-operative incidence of hypotension and severe hypotension. The secondary outcomes included the lowest intra-operative systolic blood pressure, the maximal intra-operative heart rate, the intra-operative needs of ephedrine and phenylephrine, the incidence of maternal nausea and/or vomiting, and neonatal outcomes (umbilical artery pH and Apgar scores). Apart from the above, RevMan 5.3 was used for the data analysis.

Results:

Altogether nine randomized controlled trials were included in the meta-analysis. There were no significant differences in the incidence of intra-operative hypotension, severe hypotension, or neonatal outcomes between the colloid preload group and control group, except for the umbilical artery pH.

Conclusion:

This meta-analysis suggests that colloid preload does not significantly reduce the incidence of hypotension associated with SA in elective cesarean section.
Role of osteopontin in diet-induced brown gallstone formation in rats
Authors: Jin Chang-Guo , Jiang Feng-Ru , Zhang Jie , Ma Jun-Ren , Ling Xiao-Feng
Published: April 2021

Background:

Although osteopontin (OPN) is expressed in the liver and pigment gallstones of patients with hepatolithiasis, its role in pigment gallstone formation remains unclear. This study aimed to explore the function of OPN in pigment gallstone formation.

Methods:

Rats were fed a chow diet (CD) or lithogenic diet (LD) for 10 consecutive weeks; blocking tests were then performed using an OPN antibody (OPN-Ab). Incidence of gallstones and levels of several bile components, OPN, tumor necrosis factor alpha (TNF-α), and cholesterol 7 alpha-hydroxylase (CYP7A1) were analyzed. To determine TNF-α expression in hepatic macrophages and both CYP7A1 and bile acid (BA) expression in liver cells, recombinant rat OPN and recombinant rat TNF-α were used to treat rat hepatic macrophages and rat liver cells, respectively. Chi-square or Fisher exact tests were used to analyze qualitative data, Student t-test or one-way analysis of variance were used to analyze qualitative data.

Results:

Incidence of gallstones was higher in LD-fed rats than in CD-fed rats (80% vs. 10%, P < 0.05). BA content significantly decreased in bile (t = −36.08, P < 0.01) and liver tissue (t = −16.16, P < 0.01) of LD-fed rats. Both hepatic OPN protein expression (t = 9.78, P < 0.01) and TNF-α level (t = 8.83, P < 0.01) distinctly increased in the LD group; what's more, CYP7A1 mRNA and protein levels (t = −12.35, P < 0.01) were markedly down-regulated in the LD group. Following OPN-Ab pretreatment, gallstone formation decreased (85% vs. 25%, χ
2 = 14.55, P < 0.01), liver TNF-α expression (F = 20.36, P < 0.01) was down-regulated in the LD group, and CYP7A1 expression (F = 17.51, P < 0.01) was up-regulated. Through CD44 and integrin receptors, OPN promoted TNF-α production in macrophage (F = 1041, P < 0.01), which suppressed CYP7A1 expression (F = 48.08, P < 0.01) and reduced liver BA synthesis (F = 119.4, P < 0.01).

Conclusions:

We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.
The Plastic Surgery Workforce and Its Role in Low-income Countries
Authors: Truche Paul , Moeller Ellie , Wurdeman Taylor , Zimmerman Kathrin , Cruz Norma , Nakarmi Kiran , Rai Shankar M. , Eado Yegeremu , Pompermaier Laura , Meara John G. , Corlew D. Scott
Published: April 2021

Background:

Plastic surgery varies in scope, especially in different settings. This study aimed to quantify the plastic surgery workforce in low-income countries (LICs), understand commonly treated conditions by plastic surgeons working in these settings, and assess the impact on reducing global disease burden.

Methods:

We queried national and international surgery societies, plastic surgery societies, and non-governmental organizations to identify surgeons living and working in LICs who provide plastic surgical care using a cross-sectional survey. Respondents reported practice setting, training experience, income sources, and perceived barriers to care. Surgeons ranked commonly treated conditions and reported which of the Disease Control Priorities-3 essential surgery procedures they perform.

Results:

An estimated 63 surgeons who consider themselves plastic surgeons were identified from 15 LICs, with no surgeons identified in the remaining 16 LICs. Responses were obtained from 43 surgeons (70.5%). The 3 most commonly reported conditions treated were burns, trauma, and cleft deformities. Of the 44 “Essential Surgical Package'' procedures, 37 were performed by respondents, with the most common being skin graft (73% of surgeons performing), cleft lip/palate repair (66%), and amputations/escharotomy (61%). The most commonly cited barrier to care was insufficient equipment. Only 9% and 5% of surgeons believed that there are enough plastic surgeons to handle the burden in their local region and country, respectively.

Conclusions:

Plastic surgery plays a significant role in the coverage of essential surgical conditions in LICs. Continued expansion of the plastic surgical workforce and accompanying infrastructure is critical to meet unmet surgical burden in low- and middle-income countries.
Efficacy and safety of pharmacological, physical, and psychological interventions for the management of chronic pain in children: a WHO systematic review and meta-analysis
Authors: Fisher Emma , Villanueva Gemma , Henschke Nicholas , Nevitt Sarah J. , Zempsky William , Probyn Katrin , Buckley Brian , Cooper Tess E. , Sethna Navil , Eccleston Christopher
Published: April 2021

Chronic pain in childhood is an international public health problem. We conducted a systematic review and meta-analysis to provide a summary of the published evidence of pharmacological, physical, and psychological therapies for children with chronic pain conditions. We searched CENTRAL, MEDLINE, EMBASE, and PsycINFO from inception to April 2020; clinical trial registries; and other sources for randomised controlled trials or comparative observational trials. We extracted critical outcomes of pain intensity, quality of life, physical functioning, role functioning, emotional functioning, sleep, and adverse events. We assessed studies for risk of bias and certainty of the evidence using GRADE. We included 34 pharmacological (4091 participants), 25 physical therapy (1470 participants), and 63 psychological trials (5025 participants). Participants reported a range of chronic pain conditions. Most studies were assessed to have unclear or high risk of bias across multiple domains. Pharmacological, physical, and psychological therapies showed some benefit for reducing pain, posttreatment, but only physical and psychological therapies improved physical functioning. We found no benefit of any treatment modality for health-related quality of life, role functioning, emotional functioning, or sleep. Adverse events were poorly reported, particularly for psychological and physical interventions. The largest evidence base for the management of chronic pain in children supports the use of psychological therapies, followed by pharmacological and physical therapies. However, we rated most outcomes as low or very low certainty, meaning further evidence is likely to change our confidence in the estimates of effects. This protocol was registered on PROSPERO (CRD42020172451).
Pandemic analysis of infection and death correlated with genomic open reading frame 10 mutation in severe acute respiratory syndrome coronavirus 2 victims
Authors: Yang De-Ming , Lin Fan-Chi , Tsai Pin-Hsing , Chien Yueh , Wang Mong-Lien , Yang Yi-Ping , Chang Tai-Jay
Published: April 2021

Background:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues the pandemic spread of the coronavirus disease 2019 (COVID-19), over 60 million people confirmed infected and at least 1.8 million dead. One of the most known features of this RNA virus is its easiness to be mutated. In late 2020, almost no region of this SARS-CoV-2 genome can be found completely conserved within the original Wuhan coronavirus. Any information of the SARS-CoV-2 variants emerged through as time being will be evaluated for diagnosis, treatment, and prevention of COVID-19.

Methods:

We extracted more than two million data of SARS-CoV-2 infected patients from the open COVID-19 dashboard. The sequences of the 38-amino acid putative open reading frame 10 (Orf10) protein within infected patients were gathered output through from National Center for Biotechnology Information and the mutation rates in each position were analyzed and presented in each month of 2020. The mutation rates of A8 and V30 within Orf10 are displayed in selected counties: United States, India, German, and Japan.

Results:

The numbers of COVID-19 patients are correlated to the death numbers, but not with the death rates (stable and <3%). The amino acid positions locating at A8(F/G/L), I13, and V30(L) within the Orf10 sequence stay the highest mutation rate; N5, N25, and N36 rank at the lowest one. A8F expressed highly dominant in Japan (over 80%) and German (around 40%) coming to the end of 2020, but no significant finding in other countries.

Conclusion:

The results demonstrate via mutation analysis of Orf10 can be further combined with advanced tools such as molecular simulation, artificial intelligence, and biosensors that can practically revealed for protein interactions and thus to imply the authentic Orf10 function of SARS-CoV-2 in the future.
Carbohydrate intake and circadian synchronicity in the regulation of glucose homeostasis
Authors: Zhao Lijun , Hutchison Amy T. , Heilbronn Leonie K.
Published: April 2021

Purpose of review

Glucose metabolism is under circadian regulation, with insulin secretion and sensitivity being highest in the morning as compared to the evening. The present review will discuss the existing evidence for the role of meal and macronutrient timing to improve glucose metabolism and reset circadian clocks, with a focus on the evidence in humans.

Recent findings

Shortening the daily eating window (also known as time-restricted eating), or skewing food intake towards breakfast and away from the evening meal both improve glucose control in people with impaired glucose metabolism. Insulin is recently purported to be a zeitgeber and thus an important reset signal for peripheral circadian clocks in vitro and in mice. Although few studies have tested the impact of macronutrient timing in humans, eating a greater proportion of carbohydrates earlier, rather than later, in the day is associated with better glucose control.

The impact of carbohydrate intake timing on endogenous central and peripheral clocks, and its potential to optimize circadian regulation and improve glycaemic control, are not well understood but are currently under intense exploration.
Treatment of Dyspnea in Advanced Disease and at the End of Life
Authors: Campbell Margaret L. , Donesky DorAnne , Sarkozy Alexandra , Reinke Lynn F.
Published: April 2021

Dyspnea is a subjective experience of breathing discomfort that consists of qualitatively distinct sensations, varies in intensity, and can only be known through the patient's report. Dyspnea is akin to suffocation and is one of the most distressing symptoms experienced by patients with advanced illness and at the end of life. Common approaches to dyspnea management, such as pulmonary rehabilitation, breathing strategies, or supplemental oxygen, have become accepted through pragmatic use or because studies do not include dyspnea as a measured outcome. Patients and clinicians urgently need evidence-based treatments to alleviate this frightening symptom. To fill this gap, a group of dyspnea researchers with expertise to conduct a literature review of evidence-based interventions for dyspnea in patients with serious illness produced these guidelines. We present the evidence from the strongest recommendations for practice to the weakest recommendations and include practical considerations for clinical nurses.
A Randomized Prospective Time and Motion Comparison of Techniques to Process Autologous Fat Grafts
Authors: Hanson Summer E. , Garvey Patrick B. , Chang Edward I. , Reece Gregory P. , Liu Jun , Baumann Donald P. , Butler Charles E.
Published: April 2021

Background:

Time and motion studies provide a reliable methodology to quantify efficiency and establish recommendations for best practices in autologous fat grafting. The purpose of this study was to compare the rate of graft processing of three frequently used systems for graft preparation.

Methods:

The authors conducted a prospective randomized comparison of three methods to prepare adipose tissue for autologous fat grafting: an active filtration system (Revolve; LifeCell Corporation, Branchburg, N.J.), a passive filtration system (PureGraft 250; Cytori Therapeutics, San Diego, Calif.), and centrifugation. An independent observer collected data according to the study’s behavioral checklist. The primary outcome measure was rate of adipose tissue processed.

Results:

Forty-six patients (mean age, 54 years; mean body mass index, 28.6 kg/m2) were included in the study (15 per arm; one patient was included with intention to treat after a failed screening). The rate of adipose tissue preparation was greater for the active filtration system compared with the others (active filtration: 9.98 ml/min versus passive filtration: 5.66 ml/min versus centrifugation: 2.47 ml/min). Similarly, there was a significant difference in total grafting time (active: 82.7 ± 8.51 minutes versus passive: 152 ± 13.1 minutes,p= 0.0005; versus centrifugation: 209.9 ± 28.5 minutes,p= 0.0005); however, there was no difference in total operative time (p= 0.82, 0.60).

Conclusions:

As the number of fat grafting procedures increases, there is interest in developing techniques to harvest, process, and inject fat to improve clinical outcomes and operative efficiency. The results of this study indicate that an active fat processing system is more time efficient at graft preparation than a passive system or centrifugation.
Nile Tilapia Fish Skin–Based Wound Dressing Improves Pain and Treatment-Related Costs of Superficial Partial-Thickness Burns: A Phase III Randomized Controlled Trial
Authors: Lima Júnior Edmar Maciel , de Moraes Filho Manoel Odorico , Costa Bruno Almeida , Fechine Francisco Vagnaldo , Vale Mariana Lima , Diógenes Ana Kely de Loyola , Neves Kelly Rose Tavares , Uchôa Alex Marques do Nascimento , Soares Maria Flaviane Araújo do Nascimento , de Moraes Maria Elisabete Amaral
Published: April 2021

Background:

In a phase II study comparing Nile tilapia fish skin to silver sulfadiazine cream for outpatient management of superficial partial-thickness burns, the fish skin decreased reepithelialization time (average reduction, 1.43 days), dressing changes (average reduction, 3.72 dressings), and visual analogue scale pain scores. The present study aimed to further evaluate Nile tilapia fish skin efficacy for superficial partial-thickness burns. Unlike silver sulfadiazine cream, the fish skin has good adherence to the wound bed, which may prevent infections and decrease need for dressing changes. Thus, it could be a low-cost alternative to hasten healing and improve pain of burn patients.

Methods:

A phase III randomized controlled trial was conducted from April of 2017 to October of 2018 in Fortaleza, Brazil, and included 115 outpatients aged 18 to 70 years with superficial partial-thickness burns affecting 15 percent or less of body surface area and no previous treatment. Fifty-seven patients were treated with the glycerolized fish skin and 58 with silver sulfadiazine cream 1%. Primary outcomes were reepithelialization time, number of dressings, treatment-related costs, and pain intensity, assessed by means of visual analogue scale, Electronic von Frey, Burns Specific Pain Anxiety Scale, and analgesic use. Patients were evaluated every 48 hours.

Results:

Patients treated with fish skin required fewer days for reepithelialization (9.7 ± 0.6 days versus 10.2 ± 0.9 days; p = 0.001) and fewer dressings (1.6 ± 0.7 versus 4.9 ± 0.5; p < 0.001). They also had decreased analgesic needs and visual analogue scale, Burns Specific Pain Anxiety Scale, and Electronic von Frey measurements. Finally, fish skin use reduced the final average treatment-related cost per patient by 42.1 percent.

Conclusion:

By hastening reepithelialization, improving burn-related pain, and decreasing treatment-related costs, Nile tilapia fish skin could benefit the resource-poor public health systems of developing countries.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Is Therapeutic Exercise Clinically Effective in Reducing Pain Intensity in Patients With Knee Osteoarthritis? A Systematic Review
Authors: Beydağı Muharrem Gökhan , Bazancir Zilan , Bozgeyik Sibel , Ulger Ozlem
Published: April 2021

Objective:

This systematic review aimed to evaluate and summarize the effects of therapeutic exercise clinically in reducing pain intensity in patients with knee osteoarthritis.

Methods:

A search of PubMed, Web of Science, Scopus, EBSCO, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from the date of inception to December 15, 2019, was conducted. Primary outcome of interest was pain measurement using the visual analog scale. The methodological quality of the studies was assessed using the Physiotherapy Evidence Database (PEDro) scale.

Results:

Sixteen studies were included in this systematic review. These studies reported that therapeutic exercise is clinically effective in reducing pain intensity in patients with knee osteoarthritis. In addition, compared with a short-term and low-intensity therapeutic exercise, there was strong evidence that therapeutic exercise, in combination with pain inhibition interventions, may play a significant role in reducing pain intensity.

Conclusion:

The systematic review provides evidence for the use of therapeutic exercises, which is high-intensity, long-term, and combined with other interventions, for reducing pain intensity clinically.
Effect of Submental Surface Neuromuscular Stimulation on Laryngeal Vestibule Opening in Healthy Volunteers at Rest and During Swallowing
Authors: Safi Mohammed F. , Mohamud Mohamud S.
Published: April 2021

Objective:

The aim of this study was to determine (a) whether submental electrical stimulation could induce hyolaryngeal movement in healthy adults, (b) the effect of submental surface electrical stimulation on hyolaryngeal movement during stimulated swallows in comparison to nonstimulated swallows, and (c) the effect of submental surface electrical stimulation on vestibular closing both during stimulated swallows and stimulation at rest.

Methods:

Seven healthy participants with a mean age was 51 ± 5.6 years were included in this study. Each participant received submental neuromuscular electrical stimulation and was given 5 mL of liquid barium to swallow both with and without stimulation. Six randomized trials were recorded—3 with submental surface stimulation and 3 without stimulation with at least one sham stimulation swallow trial at rest. Trials were recorded via videofluoroscopy.

Results:

A total of 82 trails were recorded. The results of this study indicated (a) there was a hyoid movement as a result of submental stimulation, (b) no laryngeal movement occurred as a result of stimulation, and (c) the vestibule opening size was larger during stimulated swallows as compared with nonstimulated swallows.

Conclusion:

This study shows that there is increased risk of aspiration with submental stimulation as a result of increased vestibular opening following submental neuromuscular electrical stimulation.
The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children
Authors: Bernaldo-de-Quirós Esther , López-Abente Jacobo , Camino Manuela , Gil Nuria , Panadero Esther , López-Esteban Rocío , Martínez-Bonet Marta , Pion Marjorie , Correa-Rocha Rafael
Published: April 2021

Background.

Regulatory T cells (Treg) are crucial for the induction and maintenance of graft tolerance. In pediatric heart transplant procedures, the thymus is routinely excised, removing the primary source of T-cell replenishment. Consequently, thymectomy joined to the effects of immunosuppression on the T-cell compartment may have a detrimental impact on Treg values, compromising the intrinsic tolerance mechanisms and the protective role of Treg preventing graft rejection in heart transplant children.

Methods.

A prospective study including 7 heart transplant children was performed, and immune cell populations were evaluated periodically in fresh peripheral blood at different time points before and up to 3 y posttransplant.

Results.

Treg counts decreased significantly from the seventh-month posttransplant. Furthermore, there was a significant increase in effector memory and terminally differentiated effector memory T cells coinciding with the fall of Treg counts. The Treg/Teffector ratio, a valuable marker of the tolerance/rejection balance, reached values around 90% lower than pretransplant values. Additionally, a negative correlation between Treg count and T effector frequency was observed. Particularly, when Treg count decreases below 50 or 75 cells/μL in the patients, the increase in the frequency of T effector CD4+ and CD8+, respectively, experiences a tipping point, and the proportion of T-effector cells increases dramatically.

Conclusions.

These results reveal that interventions employed in pediatric heart transplantation (immunosuppression and thymectomy) could induce, as an inevitable consequence, a dysregulation in the immunologic status characterized by a marked imbalance between Treg and T effector, which could jeopardize the preservation of tolerance during the period with the higher incidence of acute rejection.
Genomics reveals the novel species placement of industrial contaminant isolates incorrectly identified as Burkholderia lata
Authors: Cunningham-Oakes Edward , Pointon Tom , Murphy Barry , Campbell-Lee Stuart , Webster Gordon , Connor Thomas R. , Mahenthiralingam Eshwar
Published: April 2021

The

Burkholderia cepacia

complex (Bcc) is a closely related group of bacteria, composed of at least 20 different species, the accurate identification of which is essential in the context of infectious diseases. In industry, they can contaminate non-food products, including home and personal care products and cosmetics. The Bcc are problematic contaminants due to their ubiquitous presence and intrinsic antimicrobial resistance, which enables them to occasionally overcome preservation systems in non-sterile products.

Burkholderia lata

and

Burkholderia contaminans

are amongst the Bcc bacteria encountered most frequently as industrial contaminants, but their identification is not straightforward. Both species were historically established as a part of a group known collectively as taxon K, based upon analysis of the recA gene and multilocus sequence typing (MLST). Here, we deploy a straightforward genomics-based workflow for accurate Bcc classification using average nucleotide identity (ANI) and core-gene analysis. The workflow was used to examine a panel of 23

Burkholderia

taxon K industrial strains, which, based on MLST, comprised 13 B. lata, 4

B. contaminans

and 6 unclassified Bcc strains. Our genomic identification showed that the

B. contaminans

strains retained their classification, whilst the remaining strains were reclassified as

Burkholderia aenigmatica

sp. nov. Incorrect taxonomic identification of industrial contaminants is a problematic issue. Application and testing of our genomic workflow allowed the correct classification of 23 Bcc industrial strains, and also indicated that

B. aenigmatica

sp. nov. may have greater importance than

B. lata

as a contaminant species. Our study illustrates how the non-food manufacturing industry can harness whole-genome sequencing to better understand antimicrobial-resistant bacteria affecting their products.
COVID-19 risk assessment for the Tokyo Olympic Games
Authors: Zhu Wenhui , Feng Jie , Li Cheng , Wang Huimin , Zhong Yang , Zhang Xingyu , Zhang Tao
Published: April 2021

Objectives

To explore effective prevention and control measures for Coronavirus Disease 2019 (COVID-19) in large international events through simulations of different interventions according to risk assessment.

Methods

We used random model to calculate the number of initial infected patients. And Poisson distribution was used to determine the number of initial infected patients based on the number of countries involved. Further, to simulate the COVID-19 transmission, the susceptible-exposed-symptomatic-asymptomatic-recovered-hospitalized (SEIARH) model was established based on susceptible-exposed-infectious-recovered (SEIR) mathematical model of epidemic diseases. According to risk assessment indicators produced by different scenarios of the simulated interventions, the risk of COVID-19 transmission in Tokyo Olympic Games was assessed.

Results

The large-scale vaccination will effectively control the spread of COVID-19. If the effective rate of vaccine is 100%, and the vaccination rate of athletes reaches 80%, an epidemic prevention barrier can be established.

Conclusions

The current COVID-19 prevention measures proposed by the Japan Olympic Committee were needed to be enhanced. For the vaccination intervention had the best control effect, a mass vaccination serves was an effective way to control COVID-19.
Adherence to the EAT-Lancet diet and risk of stroke and stroke subtypes: A Danish cohort study
Authors: Ibsen Daniel B. , Christiansen Anne H. , Olsen Anja , Tjønneland Anne , Overvad Kim , Wolk Alicja , Mortensen Janne K. , Dahm Christina C.
Published: April 2021

Objective

To investigate the association between adherence to the EAT-Lancet diet, a sustainable and mostly plant-based diet, and risk of stroke and subtypes of stroke in a Danish population. For comparison, we also investigated the Alternate Healthy Eating Index-2010 (AHEI).

Methods

We used the Danish Diet, Cancer and Health cohort (n=55,016) including adults aged 50-64 years at baseline (1993-1997). A food frequency questionnaire was used to assess dietary intake and group participants according to adherence to the diets. Stroke cases were identified using a national registry and subsequently validated by review of medical records (n=2253). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations with the EAT-Lancet diet or the AHEI and risk of stroke and stroke subtypes.

Results

Adherence to the EAT-Lancet diet was associated with a lower risk of stroke, although not statistically significant (highest vs lowest adherence: HR 0.91; 95% CI 0.76, 1.09). A lower risk was observed for the AHEI (0.75; 0.64, 0.87). For stroke subtypes we found that adherence to the EAT-Lancet diet was associated with a lower risk of subarachnoid hemorrhage (0.30; 0.12, 0.73) and the AHEI was associated with a lower risk of ischemic stroke (0.76; 0.64, 0.90) and intracerebral hemorrhage (0.58; 0.36, 0.93).

Conclusions

Adherence to the EAT-Lancet diet was associated with a lower risk of subarachnoid stroke and the AHEI was associated with a lower risk of total stroke, mainly ischemic stroke and intracerebral hemorrhage.
Association of in-hospital use of ACE-I/ARB and COVID-19 outcomes in African American population
Authors: Li Shilong , Sarangarajan Rangaprasad , Jun Tomi , Kao Yu-Han , Wang Zichen , Schadt Emilio , Kiebish Michael A. , Granger Elder , Narain Niven R. , Chen Rong , Schadt Eric E. , Li Li
Published: April 2021

Importance

The ACE D allele is more prevalent among African Americans (AA) compared to other races/ethnicities and has previously been associated with severe COVID-19 pathogenesis through excessive ACE1 activity. ACE-I/ARBs may counteract this mechanism, but their association with COVID-19 outcomes has not been specifically tested in the AA population.

Objectives

To determine whether the use of ACE-I/ARBs is associated with COVID-19 in-hospital mortality in AA compared with non-AA population.

Design, Setting, and Participants

In this observational, retrospective study, patient-level data were extracted from the Mount Sinai Health System’s (MSHS) electronic medical record (EMR) database, and 6,218 patients with a laboratory-confirmed COVID-19 diagnosis from February 24 to May 31, 2020 were identified as ACE-I/ARB users.

Exposures

Patients with an active prescription from January 1, 2019 up to the date of admission for ACE-I/ARB (outpatient use) and patients administered ACE-I/ARB during hospitalization (in-hospital use) were identified.

Main Outcomes and Measures

The primary outcome was in-hospital mortality, assessed in the entire, AA, and non-AA population.

Results

Of the 6,218 COVID-19 patients, 1,138 (18.3%) were ACE-I/ARB users. In a multivariate logistic regression model, ACE-I/ARB use was independently associated with reduced risk of in-hospital mortality in the entire population (OR, 0.655; 95% CI, 0.505-0.850; P=0.001), AA population (OR, 0.44; 95% CI, 0.249-0.779; P=0.005), and non-AA population (OR, 0.748, 95% CI, 0.553-1.012, P=0.06). In the AA population, in-hospital use of ACE-I/ARBs was associated with improved mortality (OR, 0.378; 95% CI, 0.188-0.766; P=0.006) while outpatient use was not (OR, 0.889; 95% CI, 0.375-2.158; P=0.812). When analyzing each medication class separately, ARB in-hospital use was significantly associated with reduced in-hospital mortality in the AA population (OR, 0.196; 95% CI, 0.074-0.516; P=0.001), while ACE-I use was not associated with impact on mortality in any population.

Conclusion and Relevance

In-hospital use of ARBs was associated with a significant reduction in in-hospital mortality among COVID-19-positive AA patients. These results support further investigation of ARBs to improve outcomes in AA patients at high risk for COVID-19-related mortality.
Specific concussion curriculum: Does it improve residents’ comfort, knowledge, and In-Training Examination scores? A pilot study
Authors: Saleem Sandal , Jary Jessica , Levasseur Kelly
Published: April 2021

Background

Concussion is defined as aberrant brain function consequent to traumatic injury characterized by disorientation or loss of consciousness or memory. If concussions are not recognized and treated appropriately, they can cause significant morbidity. Because ∼20% of sports-related concussions occur in juveniles, pediatricians must be able to treat this injury. Our primary objective was to assess the comfort and competence of pediatric residents in managing patients with concussions. Secondary objective was to assess the change in the In-Training Examination (ITE) scores after instituting a novel multimodal concussion curriculum.

Method

From February to June 2019, all pediatric residents (N = 24) were required to complete a multimodal concussion curriculum, including board review-style questions, lectures, and rotation in a concussion clinic. Residents voluntarily participated in a pre-and post-curriculum survey. ITE scores from 2018 and 2019 were compared.

Results

Twenty-three of 24 (96%) residents completed both pre- and post-curriculum surveys; of those, 17 (74%) had matched identifiers. Most residents (82%) want more education about concussion management. Residents’ scores on knowledge-based questions increased an average of 0.64 questions, with PGY-1 showing the most improvement. The proportion of residents who correctly answered the ITE head injury/concussion questions increased from 0.33 to 0.88. The concussion clinic was identified as the most helpful tool.

Conclusion

To better educate pediatric residents about concussions, we propose a unique multimodal curriculum. We found improved self-assessed comfort and performance on knowledge-based questions and the ITE. We recommend that pediatric and other residency training programs consider implementing this type of curriculum.
Using Whole Genome Sequencing to Characterize Clinically Significant Blood Groups Among Healthy Older Australians
Authors: Jadhao Sudhir , Davison Candice , Roulis Eileen V. , Lee Simon , Lacaze Paul , Riaz Moeen , McNeil John J , Thomas David M , Pecheniuk Natalie M. , Hyland Catherine A. , Flower Robert L. , Nagaraj Shivashankar H.
Published: April 2021

There have been no comprehensive studies of a full range of blood group polymorphisms within the Australian population. The problem is compounded by the absence of any databases carrying genomic information on chronically transfused patients and low frequency blood group antigens in Australia. Here, we use RBCeq, a web server-based blood group genotyping software, to identify unique blood group variants among Australians and compare the variation detected versus global data. Whole genome sequencing data was analysed from for 2796 healthy older Australians from the Medical Genome Reference Bank and compared with data from 1000G phase 3 (1KGP3) databases comprising 661 African, 347 American, 503 European, 504 East Asian, and 489 South Asian participants. There were 688 rare variants detected in this Australian sample population, including nine variants that had clinical associations. Notably, we identified 149 variants that were computationally predicted to be novel and deleterious. No clinically significant rare or novel variants were found associated with the genetically complex ABO blood group system. For the Rh blood group system, one novel and 16 rare variants were found. Our detailed blood group profiling results provide a starting point for the creation of an Australian blood group variant database.

Key points

We identified unique blood group variants among the healthy older Australian population compared with global data using RBCeq software.

Our detailed blood group profiling result may be a starting point for the creation of an Australian blood group variant database.
Effect of asymptomatic transmission and emergence time on multi-strain viral disease severity
Authors: Alizad-Rahvar A. R. , Sadeghi M.
Published: April 2021

Background

In a viral epidemic, the emergence of a novel strain with increased transmissibility (larger value of basic reproduction numberR0) sparks the fear that the increase in transmissibility is likely to lead to an increase in disease severity. It is required to investigate if a new, more contagious strain will be necessarily dominant in the population and resulting in more disease severity.

Methods

The impact of the asymptomatic transmission and the emergence time of a more transmissible variant of a multi-strain viral disease on the disease prevalence, disease severity, and the dominant variant in an epidemic was investigated by a proposed 2-strain epidemic model, called 2-SEICARD model, that is an extension of the SEIRD model.

Results

The simulation results showed that considering onlyR0, is insufficient to predict the outcome of a new, more contagious strain in the population. A more transmissible strain with a high fraction of asymptomatic cases can substantially reduce the mortality rate. If the emergence time of the new strain is closer to the start of the epidemic, the new, more contagious variant has more chance to win the viral competition and be the dominant strain; otherwise, despite being more contagious, it cannot dominate previous strains.

Conclusions

Three factors ofR0, the fraction of asymptomatic transmission, and the emergence time of the new strain are required to correctly determine the prevalence, disease severity, and the winner of the viral competition.
Cell environment shapes TDP-43 function: implications in neuronal and muscle disease
Authors: Šušnjar Urša , Škrabar Neva , Brown Anna-Leigh , Abbassi Yasmine ,   NYGC ALS Consortium, Phatnani Hemali , Cortese Andrea , Cereda Cristina , Bugiardini Enrico , Cardani Rosanna , Meola Giovanni , Ripolone Michela , Moggio Maurizio , Romano Maurizio , Secrier Maria , Fratta Pietro , Buratti Emanuele
Published: April 2021

TDP-43 aggregation and redistribution have been recognised as a hallmark of amyotrophic lateral sclerosis, frontotemporal dementia and other neurological disorders. While TDP-43 has been studied extensively in neuronal tissues, TDP-43 inclusions have also been described in the muscle of inclusion body myositis patients, highlighting the need to understand the role of TDP-43 beyond the central nervous system. Using RNA-seq we performed the first direct comparison of TDP-43-mediated transcription and alternative splicing in muscle (C2C12) and neuronal (NSC34) mouse cells. Our results clearly show that TDP-43 displays a tissue-characteristic behaviour targeting unique transcripts in each cell type. This is not due to variable transcript abundance but rather due to cell-specific expression of RNA-binding proteins, which influences TDP-43 performance. Among splicing events commonly dysregulated in both cell lines, we identified some that are TDP-43-dependent also in human cells and show that inclusion levels of these alternative exons appear to be differentially altered in affected tissues of FTLD and IBM patients. We therefore propose that TDP-43 dysfunction, reflected in aberrant splicing, contributes to disease development but it does so in a tissue- and disease-specific manner.
Socio-demographic and knowledge-related determinants of vitamin D supplementation in the context of the COVID-19 pandemic: assessment of an educational intervention
Authors: Žmitek Katja , Hribar Maša , Lavriša Živa , Hristov Hristo , Kušar Anita , Pravst Igor
Published: April 2021

Vitamin D is a pro-hormone, essential for musculo-skeletal health, normal immune system, and numerous other body functions. Vitamin D deficiency is considered a risk factor in many conditions, and there is growing evidence of its potential role in the severity of COVID-19 outcomes. However, an alarmingly high prevalence of vitamin D deficiency is reported in many regions, and vitamin D supplementation is commonly recommended, particularly during wintertime. To reduce the risk for vitamin D deficiency in the Slovenian population during the COVID-19 pandemic, we conducted mass media intervention with an educational campaign. The objective of this study was to investigate vitamin D supplementation practices in Slovenia before and during the COVID-19 pandemic, and to determine the effects of the educational intervention on supplementation practices. Two data collections were conducted using an online panel with quota sampling for age, sex, and geographical location. A pre-intervention (N=602, April 2020) and post-intervention (N=606) sampling were done during the first and second COVID-19 lockdown, respectively. We also focused on the identification of different factors connected to vitamin D supplementation, with a particular emphasis on vitamin D-related knowledge. Study results showed significant changes in vitamin D supplementation in the population. Penetration of the supplementation increased from 33% in April to 56% in December 2020. The median daily vitamin D intake in supplement users was 25 µg, with about 95% of supplement users taking safe intake levels below 100 µg/daily. Vitamin D-related knowledge (particularly about dietary sources of vitamin D, the health-related impact of vitamin D, and the prevalence of deficiency) was identified as a key independent predictor of vitamin D supplementation. Based on the study findings, we prepared recommendations, which will enable the development of effective awareness campaigns for increasing supplementation of vitamin D.
Saliva Is Comparable to Nasopharyngeal Swabs for Molecular Detection of SARS-CoV-2
Authors: Callahan Cody , Ditelberg Sarah , Dutta Sanjucta , Littlehale Nancy , Cheng Annie , Kupczewski Kristin , McVay Danielle , Riedel Stefan , Kirby James E. , Arnaout Ramy
Published: April 2021

Background

The continued need for molecular testing for SARS-CoV-2 and potential for self-collected saliva as an alternative to nasopharyngeal (NP) swabs for sample acquisition led us to compare saliva to NP swabs in an outpatient setting, without restrictions to avoid food, drink, smoking, or tooth-brushing.

Methods

A total of 385 pairs of NP and saliva specimens were obtained, the majority from individuals presenting for initial evaluation, and were tested on two high-sensitivity RT-PCR platforms: the Abbott m2000 and Abbott Alinity m (both with limits of detection [LoD] of 100 copies of viral RNA/mL).

Results

Concordance between saliva and NP was excellent overall (Cohen’s κ=0.93), for both initial and followup testing, for both platforms, and for specimens treated with guanidinium transport medium as preservative as well as for untreated saliva (κ=0.88-0.95). Viral loads were on average 16x higher in NP specimens than saliva specimens, suggesting that only the relatively small fraction of outpatients (∼8% in this study) who present with very low viral loads (<1,600 copies/mL from NP swabs) would be missed by testing saliva instead of NP swabs, when using sensitive testing platforms. Special attention was necessary to ensure leak-resistant specimen collection and transport.

Conclusions

The advantages of self-collection of saliva, without behavioral restrictions, will likely outweigh a minor potential decrease in clinical sensitivity in individuals less likely to pose an infectious risk to others for many real-world scenarios, especially for initial testing.

Key points

Saliva has comparable sensitivity and specificity to nasopharyngeal swabs for RT-PCR-based COVID-19 testing (concordance, κ=0.93; n=385 participants), albeit with slightly lower recovery of viral RNA. Treatment with a readily available guanidinium preservative within 24 hours of sample collection improves recovery.
Assessing genetic overlap and causality between blood plasma proteins and Alzheimer’s Disease
Authors: Handy Alex , Lord Jodie , Green Rebecca , Xu Jin , Aarsland Dag , Velayudhan Latha , Hye Abdul , Dobson Richard , Proitsi Petroula ,   Add NeuroMed, and the GERAD1 Consortium
Published: April 2021

Background

Blood plasma proteins are modifiable and have been associated with Alzheimer’s disease (AD), but understanding which proteins are on the causal pathway remains challenging.

Objective

Investigate the genetic overlap between candidate proteins and AD using polygenic risk scores (PRS) and interrogate their causal relationship using bi-directional Mendelian Randomization (MR).

Methods

Following a literature review, 31 proteins were selected for PRS analysis. PRS were constructed for prioritised proteins with and without the apolipoprotein E region (APOE+/- PRS) and tested for association with AD status across three cohorts (n=6244). An AD PRS was also tested for association with protein levels in one cohort (n=410). Proteins showing association with AD were taken forward for MR.

Results

For APOE e3, apolipoprotein B-100, and C-reactive protein (CRP), protein APOE+ PRS were associated with AD below Bonferroni significance (pBonf, p-value <0.00017). No protein APOE-PRS or AD PRS (APOE+/-) passed pBonf. However, vitamin D-binding protein (protein PRS APOE-, p-value=0.009) and insulin-like growth factor-binding protein 2 (AD APOE- PRS p-value=0.025, protein APOE-PRS p-value=0.045) displayed suggestive signals and were selected for MR. In bi-directional MR, none of the 5 proteins demonstrated a causal association (p-value<0.05) in either direction.

Conclusion

Apolipoproteins and CRP PRS are associated with AD and provide a genetic signal linked to a specific, modifiable risk factor. Whilst evidence of causality was limited, this study was conducted in a moderate sample size and provides a framework for larger samples with greater statistical power.
Golgi-localized GALT7 and GALT8 participate in cellulose biosynthesis
Authors: Nibbering Pieter , Castilleux Romain , Wingsle Gunnar , Niittylä Totte
Published: April 2021

Arabinogalactan protein (AGP) glycan biosynthesis in the Golgi apparatus contributes to plant cell wall assembly, but the mechanisms underlying this process are largely unknown. Here, we show that two putative galactosyltransferases -named GALT7 and GALT8 -from the glycosyltransferase family 31 (GT31) ofArabidopsis thalianaparticipate in cellulose biosynthesis.galt7galt8mutants show primary cell wall defects manifesting as impaired growth and cell expansion in seedlings and etiolated hypocotyls, along with secondary cell wall defects, apparent as collapsed xylem vessels and reduced xylem wall thickness in the inflorescence stem. These phenotypes were associated with a ∼30% reduction in cellulose content, a ∼50% reduction in secondary cell wall CELLULOSE SYNTHASE (CESA) protein levels and reduced cellulose biosynthesis rate.CESAtranscript levels were not significantly altered ingalt7galt8mutants, suggesting that the reduction in CESA levels was caused by a post-transcriptional mechanism. We provide evidence that both GALT7 and GALT8 localise to the Golgi apparatus, while quantitative proteomics experiments revealed reduced levels of the entire FLA subgroup B in thegalt7galt8mutants. This leads us to hypothesize that a defect in FLA subgroup B glycan biosynthesis reduces cellulose biosynthesis rate ingalt7galt8mutants.
InterARTIC:an interactive web application for whole-genome nanopore sequencing analysis of SARS-CoV-2 and other viruses
Authors: Ferguson James M. , Gamaarachchi Hasindu , Nguyen Thanh , Gollon Alyne , Tong Stephanie , Aquilina-Reid Chiara , Bowen-James Rachel , Deveson Ira W.
Published: April 2021

Motivation

InterARTICis an interactive web application for the analysis of viral whole-genome sequencing (WGS) data generated on Oxford Nanopore Technologies (ONT) devices. A graphical interface enables users with no bioinformatics expertise to analyse WGS experiments and reconstruct consensus genome sequences from individual isolates of viruses, such as SARS-CoV-2.InterARTICis intended to facilitate widespread adoption and standardisation of ONT sequencing for viral surveillance and molecular epidemiology.

Worked example

We demonstrate the use ofInterARTICfor the analysis of ONT viral WGS data from SARS-CoV-2 and Ebola virus, using a laptop computer or the internal computer on an ONT GridION sequencing device. We showcase the intuitive graphical interface, workflow customisation capabilities and job-scheduling system that facilitate execution of small- and large-scale WGS projects on any common virus.

Implementation

InterARTICis a free, open-source web application implemented in Python. The application can be downloaded as a set of pre-compiled binaries that are compatible with all common Ubuntu distributions, or built from source. For further details please visit:https://github.com/Psy-Fer/interARTIC/.