bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of direct oral anticoagulants versus vitamin K antagonist in atrial fibrillation
Authors: Hernández Rojas Zojaina , Dalmau Llorca Maria Rosa , Aguilar Martín Carina , Gonçalves Alessandra Queiroga , Casajuana Marc , Fernández-Sáez José , Rodríguez Cumplido Dolores , Forcadell Drago Emma , Carrasco-Querol Noèlia , Pepió Vilaubí Josep Maria , Alegret Josep M.
Published: September 2020

Background:

Anticoagulant therapy is used for stroke prevention and proved to be effective and safe in the long term. The study aims to analyse the cost-effectiveness relationship of using of direct-acting oral anticoagulants vs vitamin K antagonists to prevent ischaemic stroke in patients with nonvalvular atrial fibrillation, including all the active ingredients marketed in Spain, prescribed for 2 years in the Primary Care service of the Institut Català de la Salut.

Methods:

Population-based cohort study, in which the cost of the 2 treatment groups will be evaluated. Direct costs (pharmacy, primary care, emergency and hospitalization) and indirect costs (lost productivity) will be included from a social perspective. Effectiveness (assessed as the occurrence of a health event, the 1 of primary interest being stroke) will be determined, with a 2-year time horizon and a 3% discount rate. The average cost of the 2 groups of drugs will be compared using a regression model to determine the factors with the greatest influence on determining costs. We will carry out a univariate (‘one-way’) deterministic sensitivity analysis.

Discussion:

We hope to provide relevant information about direct and indirect costs of oral anticoagulants, which, together with aspects of effectiveness and safety, could help shape the consensual decision-making of evaluating bodies.
Molecular evidence of parvovirus B19 in the cutaneous polyarteritis nodosa tissue from a patient with parvovirus-associated hemophagocytic syndrome
Authors: Jeong Ji Yun , Park Ji Young , Ham Ji Yeon , Kwon Ki Tae , Han Seungwoo
Published: September 2020

Rationale:

Parvovirus B19 has been linked to polyarteritis nodosa (PAN), but there is some controversy about its pathogenesis regarding whether it is triggered by the immune complex or by the activated immune cells that phagocytose viruses.

Patient concerns:

A 38-year-old woman was admitted with fever and bicytopenia. She also complained of a painful palpable nodule in the left forearm.

Diagnosis:

Her bone marrow aspirate revealed erythroblasts in abnormal megaloblastic changes, some of which presented with pseudopods, and parvovirus B19 was positive in a PCR analysis of her blood, which was compatible with parvovirus B19-induced hemophagocytic syndrome. Skin excisional biopsy of the nodule on the left forearm revealed a heavy inflammatory cell infiltrate throughout whole layers of a medium-sized vessel, the characteristic feature of PAN. PCR analysis of the vasculitis tissue showed a positive result for parvovirus B19.

Interventions:

Her symptoms spontaneously resolved with supportive care.

Outcomes:

She underwent regular follow-up without recurrence of vasculitis-associated symptoms.

Lessons:

This case highlights the presence of parvovirus B19 DNA in vasculitis tissues, which can support the role of cellular immune response in the pathogenesis of parvovirus-associated PAN.
Hemichorea-hemiballismus as the initial manifestation of symptomatic middle cerebral artery dissection
Authors: Chen Hanfeng , Xu Ziqi
Published: September 2020

Introduction:

Hemichorea-hemiballismus, which spans a spectrum of involuntary, continuous, nonpatterned movement involving one side of the body, can emerge as the initial manifestation of acute ischemic stroke. However, because of its rarity in the community, the diagnosis and treatment are often delayed.

Patient concerns:

We report a unique case of a 47-year-old female who presented with acute onset hemichorea-hemiballismus. No obvious focal sign apart from involuntary, continuous, nonpatterned movement of her left arm and leg was presented.

Diagnosis:

Initial diffusion-weighted magnetic resonance imaging (MRI) was negative but significant increase of blood flow velocity in the right middle cerebral artery (MCA) stem was revealed by transcranial doppler sonography. Repeated MRI showed acute infarction in the contralateral globus pallidus. Isolated dissection of the right MCA typified by intimal flap with double lumen was identified by digital subtraction angiography and high-resolution magnetic resonance imaging (HR-MRI).

Interventions:

The patient was initially treated with dual antiplatelet agents but the uncontrollable movement deteriorated during hospitalization. Antithrombotic therapy was then intensified with combination of tirofiban and low-molecular-weight heparin. Other symptomatic treatment included volume expansion with colloidal fluid to improve cerebral perfusion. Her involuntary movement gradually diminished and the patient was discharged with rivaroxaban 15 mg/daily.

Outcomes:

The patient had recovered with significant reduction in her hemichorea-hemiballismus. Three-month follow-up HR-MRI showed complete resolution of the MCA dissection lesions.

Conclusion:

Prompt recognition of acute onset hemichorea-hemiballismus as the manifestation of acute ischemic stroke in appropriate clinical setting may reduce diagnostic delay. Multiple imaging techniques including cerebral digital subtraction angiography and HR-MRI can be applied to diagnosis and further clarify the mechanism of stroke, which facilitate in selection of secondary prevention therapies.
Exophiala lecanii-corni keratitis presenting as a serpiginous pigmented superficial lesion: a case report
Authors: Miyakubo Tomoko , Todokoro Daisuke , Satake Yoshiyuki , Makimura Koichi , Miyakubo Sumiko , Akiyama Hideo
Published: September 2020

Rationale:

Patients with bullous keratopathy (BK) treated by Descemet stripping automated endothelial keratoplasty (DSAEK) have a compromised cornea, due to the administration of topical steroid, postsurgical use of contact lenses, and impaired barrier function of the corneal epithelium by BK. We report a case of Exophiala lecanii-corni (E lecanii-corni) keratitis presenting as a serpiginous pigmented superficial lesion after DSAEK.

Patient concerns:

An 81-year-old woman who had undergone cataract surgeries, suffered from decreased vision in the left eye. She was diagnosed BK and she underwent DSAEK. Two months after DSAEK, a pigmented superficial lesion developed on the left cornea. The lesion migrated and recurred repeatedly and she was referred to our department. Best corrected vision was 20/220.

Diagnoses:

Light microscopy of a corneal scraping revealed branching fungal hyphae. Fungal culture showed growth of a black colony, identified as E lecanii-corni by ribosomal DNA sequencing.

Interventions:

We started topical treatment with 1% voriconazole and 1.5% levofloxacin. Antifungal susceptibility testing showed that the minimum inhibitory concentration of voriconazole was 0.06 μg/mL.

Outcomes:

The lesion scarred after treatment for 3 months, and left best corrected vision improved to 20/40.

Lessons:

Genus Exophiala is known as 1 of the “black molds” and a cause of chromomycosis. This is the first description of E lecanii-corni keratitis, and pigmented corneal epithelial lesions may be characteristic of this fungal genus.
Assessment of the efficacy of α-lipoic acid in treatment of diabetes mellitus patients with erectile dysfunction
Authors: Cai Jiawei , Chen Junmin , Zeng Qianqian , Liu Jie , Zhang Yanli , Cheng Haiping , Yao Shasha , Chen Qiu
Published: September 2020

Background:

Diabetes mellitus with erectile dysfunction (DMED) is one of the most common causes of disability in diabetic population, and its pathogenesis is related to a variety of factors. Because its pathogenesis is complex and the existing treatment methods have limitations, DMED is difficult to treat in clinical. Recently, some studies have shown that α-lipoic acid (ALA) is associated with DMED, but there is no systematic review and meta-analysis on the relationship between ALA and DMED.

Methods:

We will search each database from the built-in until July 2020. The English literature mainly searches Cochrane Library, PubMed, EMBASE, and Web of Science, while the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Simultaneously we will retrieve clinical registration tests and grey literatures. This study only screen the clinical randomized controlled trials (RCTs) about ALA for DMED to assess its efficacy. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on whether or not heterogeneity exists. Erectile dysfunction (ED) will be diagnosed by the International Index of Erectile Function 5 (IIEF-5) score. Finally, meta-analysis was conducted by RevMan software version 5.3.

Results:

This study will synthesize and provide high quality to evaluate the effectiveness of ALA supplementation for the treatment of DMED.

Conclusion:

This systematic review aims to provide new options for ALA supplementation treatment of DMED in terms of its efficacy and safety.

PROSPERO registration number:

INPLASY202070130.
Ethical decision-making in simultaneous heart–liver transplantation
Authors: Cheng Xinxing S. , Wall Anji , Teuteberg Jeffrey
Published: September 2020

Purpose of review

Simultaneous heart–liver (SHL) transplants are only a small proportion of overall heart and liver transplantation, they have been increasing in frequency and thus challenge the equitable allocation of organs.

Recent findings

The incidence of SHL transplants is reviewed along with the outcomes of SHL transplants and their impact on the waitlist, particularly in the context of solitary heart and liver transplantation. The ethical implications, most importantly the principles of utility and equity, of SHL transplant are addressed. In the context of utility, the distinction of a transplant being life-saving versus life-enhancing is investigated. The risk of hepatic decompensation for those awaiting both solitary and combined organ transplantation is an important consideration for the principle of equity. Lastly, the lack of standardization of programmatic approaches to SHL transplant candidates, the national approach to allocation, and the criteria by which programs are evaluated are reviewed.

As with all multiorgan transplantation, SHL transplantation raises ethical issues of utility and equity. Given the unique patient population, good outcomes, lack of alternatives, and overall small numbers, we feel there is continued ethical justification for SHL, but a more standardized nationwide approach to the evaluation, listing, and allocation of organs is warranted.
Home Healthcare Workers' Occupational Exposures
Authors: Bien Elizabeth , Davis Kermit , Gillespie Gordon
Published: September 2020

Home healthcare workers (HHCWs) belong to one of the fastest growing industries and have an unpredictable work environment, potentiating their risk of exposures to occupational hazards. More patients seeking care for chronic health conditions, and improvements in technology and medical advancements are allowing more complex patient care to be provided at home. A comprehensive integrative review was completed, identifying nine articles that provide an overview of the occupational hazards HHCWs face. Analysis of the articles indicates occupational hazards are similar across studies. Occupational exposures reported by HHCWs align within all the studies and include exposures to blood, saliva, dangerous conditions walking to and within the home, secondhand smoke, aggressive pets, violence, and ergonomic concerns. These studies have been methodologically limited to self-reports, including surveys, interviews, and focus groups but include quantitative and qualitative data. Future research can further describe and identify specific occupational exposures and health hazards, subsequently leading to modifications to protect the health and safety of HHCWs, personal care workers, and the informal caregivers who provide care in the home.
The Home Health Aide Experience
Authors: Mindlina Julia , O'Brien Shirley , Simpkins Leah
Published: September 2020

Little is known about how home health aides (HHAs) perceive the daily physical challenges and risks of injury they face in their line of work. The objectives of this study were to 1) gain detailed information about the daily experiences of HHAs, 2) identify physical challenges of their work, and 3) determine if there is a role for occupational therapists (OTs) in injury prevention through education. A qualitative descriptive approach using semistructured phone interviews that were recorded and transcribed was used. Colaizzi's descriptive phenomenological method was used to guide data analysis. Participants were recruited through convenience sampling and included eight female HHAs with an age range of 35 to 65 years. The following themes were identified: HHAs valued the use of a client-centered approach with their clients (Know the rules and know your clients even better), HHAs assisted their patients with a wide range of activities of daily living and instrumental activities of daily living to support their independence within their home (More than Activities of Daily Living), transferring clients was considered the most physically demanding task (Would you like a hand with your transfer?), and participants believed new HHAs could benefit from training in patient positioning, appropriate use of adaptive equipment, and proper lifting mechanics in various contexts (Let's get physical!). The areas of overlap between HHAs' needs and OTs' skills provide an opportunity for OTs to consult with home care agencies as educators.
Reinnervation of the Diaphragm After Bilateral Phrenic Nerve Resection and Immediate Reconstruction Using a Contralateral Phrenic Nerve Autograft
Authors: Brunetti Beniamino , Morelli Coppola Marco , Crucitti Pierfilippo , Spinelli Francesco , Stilo Francesco , Longo Filippo , Cortese Livio , Tenna Stefania , Persichetti Paolo
Published: September 2020

A patient affected by a voluminous synovial sarcoma of mediastinum received radical surgery, resulting in injury of both phrenic nerves. Because of the cancer location, reconstruction of the left phrenic nerve was not possible, so to prevent the patient's ventilator dependence, the right phrenic nerve was reconstructed via an autograft from the residual proximal stump of the contralateral one. In 3 months, the right hemidiaphragm function showed a full recovery, documented by ultrasonographic and radiographic assessment of diaphragmatic excursion, and the patient was weaned from mechanical ventilation. When a nerve autograft is indicated, the sural nerve still remains the criterion standard, because of the low morbidity of the donor site and ease of harvesting; however, in particular situations, such as in this unique case, the choice of an orthotopic graft may offer promising results.
Error Analysis of Robot-Assisted Orthognathic Surgery
Authors: Wu Jinyang , Hui Wenyu , Chen Shihang , Niu Jindong , Lin Yanping , Luan Nan , Zhang Shilei , Shen Steve G.F.
Published: September 2020

Objective:

Orthognathic surgery is an effective method to correct the dentomaxillofacial deformities. The aim of the study is to introduce the robot-assisted orthognathic surgery and demonstrate the accuracy and feasibility of robot-assisted osteotomy in transferring the preoperative virtual surgical planning (VSP) into the intraoperative phase.

Methods:

The CMF robot system, a craniomaxillofacial surgical robot system was developed, consisted of a robotic arm with 6 degrees of freedom, a self-developed end-effector, and an optical localizer. The individualized end-effector was installed with reciprocating saw so that it could perform osteotomy. The study included control and experimental groups. In control group, under the guidance of navigation system, surgeon performed the osteotomies on 3 skull models. In experimental group, according to the preoperative VSP, the robot completed the osteotomies on 3 skull models automatically with assistance of navigation. Statistical analysis was carried out to evaluate the accuracy and feasibility of robot-assisted orthognathic surgery and compare the errors between robot-assisted automatic osteotomy and navigation-assisted manual osteotomy.

Results:

All the osteotomies were successfully completed. The overall osteotomy error was 1.07 ± 0.19 mm in the control group, and 1.12 ± 0.20 mm in the experimental group. No significant difference in osteotomy errors was found in the robot-assisted osteotomy groups (P = 0.353). There was consistence of errors between robot-assisted automatic osteotomy and navigation-assisted manual osteotomy.

Conclusion:

In robot-assisted orthognathic surgery, the robot can complete an osteotomy according to the preoperative VSP and transfer a preoperative VSP into the actual surgical operation with good accuracy and feasibility.
Prediction Models for Recurrence of Chronic Subdural Hematoma in Patients Underwent Twist-Drill Craniostomy Combined With Urokinase Instillation
Authors: Zhuo Jianwei , Xu Yinong , Zhang Jing , Zhang Wenwen , Ji Meng , Wang Yuhai
Published: September 2020

The recurrence of chronic subdural hematoma (CSDH) is high post-treatment. In this study, we aimed to construct individualized models for prediction of the postoperative recurrence of CSDH in patients underwent twist-drill craniostomy combined with urokinase (UK) instillation. In total, 183 patients with CSDH were retrospectively enrolled. In summary, 21 candidate factors were retrieved from past medical records. The least absolute shrinkage and selection operator regression was adopted to reduce the high dimensionality of data. Four predictors: preoperative hematoma volume, encephalatrophy, brain re-expansion, and UK instillation frequency were filtered from the 21 candidate factors using the least absolute shrinkage and selection operator method. Binary logistic regression model was employed to establish preoperative and postoperative prediction models. The preoperative model included preoperative hematoma volume and encephalatrophy whereas the postoperative model included brain re-expansion and UK instillation frequency. The predictive performance of the nomograms was evaluated by the receiver operating characteristic curve and calibration chart. Area under curve of the preoperative and postoperative models were 0.755 (95% confidence interval: 0.690–0.889) and 0.782 (95% confidence interval: 0.720–0.936), respectively, indicating good discrimination ability. The calibration results showed good fitting between the predicted probability and the actual probability. Finally, a decision curve analysis revealed excellent clinical performance of the proposed nomograms. Functionally, the preoperative model was used to identify high-risk patients with CSDH and application of UK, while the postoperative model was applied to guide physician-patients communication during follow-up. These 2 prediction models provide a basis for further clinical and experimental studies.
Osteogenesis Differences Around Titanium Implant and in Bone Defect Between Jaw Bones and Long Bones
Authors: Liu Li-Nan , Zhang Xiao-Hui , Liu Hang-Hang , Li Ke-Han , Wu Qiong-Hui , Liu Yao , Luo En
Published: September 2020

The aim of this study is to evaluate the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones in ovariectomized (OVX) animal models. The literature on the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones was reviewed with charts. Fourty-eight rats were randomly divided into OVX group with ovariectomy and SHAM (sham-surgery) group with sham surgery. Titanium implants were inserted in the right mandibles and tibiae; bone defects were created in the left mandibles and tibiae. Two-week postoperatively, mandibles and tibiae of 8 rats were harvested and examined by hematoxylin and eosin staining and histological analysis; 4-week postoperatively, all mandibles and tibiae were harvested and examined by Micro-CT and histological analysis. A total of 52 articles were included in this literature review. Tibial osteogenesis around titanium implant and in bone defect in OVX group were significantly decreased compared with SHAM group. However, osteogenesis differences in the mandible both around titanium implant and in bone defect between groups were not statistically significant. OVX-induced osteoporosis suppresses osteogenesis around titanium implant and in the bone defect or fracture in long bones significantly while has less effect on that in the jaw bones.
Repeated unpredictable stress blunts alcohol-induced memory deficit in adolescent rat
Authors: Sircar Ratna
Published: September 2020

Objective

There exists a complex interaction between alcohol and stress on brain and behavior. Alcohol and stress are both known to affect memory. Whether stress and alcohol together can modulate memory functions in adolescent rats is not known. In the present study, effects of repeated unpredictable stress (RUPS) on contextual fear conditioning, a hippocampus-related memory function, were investigated in alcohol-treated adolescent rats.

Methods

Rats were divided into four experimental groups: group i – saline-treated non-stressed rats (sal no stress), group ii – alcohol-treated non-stressed rats (alc no stress), group iii – saline-treated rats subjected to stress (sal + RUPS), group iv – alcohol-treated rats subjected to stress (alc + RUPS). All rats were trained in the fear conditioning paradigm, and 24 h later were tested for contextual fear conditioning in the conditioning chamber, and nonspecific fear memory in a modified chamber.

Results

Stress, in the presence or absence of alcohol, did not alter nonspecific fear. RUPS exposure did not affect contextual freezing in vehicle-treated adolescent rats. Compared to vehicle-treated non-stressed rats, alcohol-treated non-stressed rats showed significant impairments in contextual freezing. Alcohol-treated RUPS rats performed better in the contextual freezing task than alcohol-treated non-stressed rats.

Conclusion

RUPS exposure did not alter contextual fear conditioning in adolescent rats. Alcohol significantly reduced contextual fear memory in non-stressed rats. Alcohol-treated RUPS rats showed significantly better memory than alcohol-treated non-stressed rats. Together, these data suggest resiliency to stress-induced memory impairment in adolescent rats, and RUPS exposure causes blunting of alcohol’s negative effects on contextual fear conditioning.
Factors Associated With Seizure Adequacy Along the Course of Electroconvulsive Therapy
Authors: Tedeschi Eduardo Antonio , Patusco Lucas Mohr , Zahler Sofia , Martini Murilo , Chiavaro da Fonseca Rodrigo , Magalhães Pedro V.S.
Published: September 2020

Objectives

Eliciting a generalized seizure is essential to electroconvulsive therapy (ECT), but there is still a need to understand how patient and session variables interact to generate a seizure of adequate quality. Here, we investigate factors associated with motor seizure length as a measure of quality in a large database of patients who underwent ECT.

Methods

This is a retrospective cohort including data from all adult inpatients who underwent ECT at a university hospital in Brazil from 2009 to 2015. We used linear mixed models to investigate the effects of patient, session, and medication on seizure length.

Results

Session information was available for 387 patients, a total of 3544 sessions and 4167 individual stimulations. Multiple stimulations were necessary in 12.4% of sessions. Median seizure length was 30 seconds. Seizure length was directly correlated with stimulus dosage and inversely correlated with the session number, patient age, prescription of anticonvulsants in the day before and β-blockers during the session, and the thiopental dose. Use of benzodiazepines was not associated with a shorter seizure duration, irrespective of dose.

Conclusions

We demonstrate here how motor seizure length evolves during a course of ECT. With a large number of sessions, we are able to integrate a host of factors in a prediction model. Seizure quality was influenced by a number of the studied factors, many of which are potentially modifiable and could be assessed before initiating and handled during treatment.
Sir Michael Atiyah OM. 22 April 1929–11 January 2019
Authors: Hitchin Nigel
Published: September 2020

Michael Atiyah was the dominant figure in UK mathematics in the latter half of
the twentieth century. He made outstanding contributions to geometry, topology,
global analysis and, particularly over the last 30 years, to theoretical
physics. Not only was he held in high esteem at a worldwide level, winning a
Fields Medal in 1966, the Abel Prize in 2004 and innumerable other international
awards, but his irrepressible energy and broad interests led him to take on many
national roles too, including the presidency of the Royal Society, the
mastership of Trinity College, Cambridge, and the founding directorship of the
Isaac Newton Institute for Mathematical Sciences. His most notable mathematical
achievement, with Isadore Singer, is the index theorem, which occupied him for
over 20 years, generating results in topology, geometry and number theory using
the analysis of elliptic differential operators. Then, in mid life, he learned
that theoretical physicists also needed the theorem and this opened the door to
an interaction between the two disciplines that he pursued energetically until
the end of his life. It led him not only to mathematical results on the
Yang--Mills equations that the physicists were seeking, but also to encouraging
the importation of concepts from quantum field theory into pure mathematics.
County-level exposures to greenness and associations with COVID-19 incidence and mortality in the United States
Authors: Klompmaker Jochem O , Hart Jaime E , Holland Isabel , Sabath M Benjamin , Wu Xiao , Laden Francine , Dominici Francesca , James Peter
Published: September 2020

Background

COVID-19 is an infectious disease that has killed more than 175,000 people in the US. During a time of social distancing measures and increasing social isolation, green spaces may be a crucial factor to maintain a physically and socially active lifestyle while not increasing risk of infection.

Objectives

We evaluated whether greenness is related to COVID-19 incidence and mortality in the United States.

Methods

We downloaded data on COVID-19 cases and deaths for each US county up through June 7, 2020, from Johns Hopkins University, Center for Systems Science and Engineering Coronavirus Resource Center. We used April-May 2020 Normalized Difference Vegetation Index (NDVI) data, to represent the greenness exposure during the initial COVID-19 outbreak in the US. We fitted negative binomial mixed models to evaluate associations of NDVI with COVID-19 incidence and mortality, adjusting for potential confounders such as county-level demographics, epidemic stage, and other environmental factors. We evaluated whether the associations were modified by population density, proportion of Black residents, median home value, and issuance of stay-at-home order.

Results

An increase of 0.1 in NDVI was associated with a 6% (95% Confidence Interval: 3%, 10%) decrease in COVID-19 incidence rate after adjustment for potential confounders. Associations with COVID-19 incidence were stronger in counties with high population density and high median home values, and in counties with stay-at-home orders. Greenness was not associated with COVID-19 mortality in all counties; however, it was protective in counties with high percentages of Black residents, high median home value, and higher population density.

Discussion

Exposures to NDVI had beneficial impacts on county-level incidence of COVID-19 in the US and may have reduced county-level COVID-19 mortality rates, especially in densely populated counties.
Neurological manifestations of coronavirus infections – a systematic review
Authors: Almqvist Jesper , Granberg Tobias , Tzortzakakis Antonios , Klironomos Stefanos , Kollia Evangelia , Öhberg Claes , Martin Roland , Piehl Fredrik , Ouellette Russell , Ineichen Benjamin V.
Published: September 2020

In order to optimize diagnostic workup of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we systematically reviewed neurological and neuroradiological manifestations of SARS-CoV-2 and all other known human coronavirus species (HCoV). Which lessons can we learn? We identified relevant publications (until July 26th2020) using systematic searches in PubMed, Web of Science and Ovid EMBASE with predefined search strings. A total of 4571 unique publications were retrieved, out of which 378 publications were selected for in-depth analysis by two raters, including a total of 17549 (out of which were 14418 SARS-CoV-2) patients. Neurological complications and associated neuroradiological manifestations are prevalent for all HCoVs (HCoV-229E, HKU1, NL63, OC43, Middle East respiratory syndrome (MERS)-CoV, SARS-CoV-1 and SARS-CoV-2). Moreover, there are similarities in symptomatology across different HCoVs, particularly between SARS-CoV-1 and SARS-CoV-2. Common neurological manifestations include fatigue, headache and smell/taste disorders. Additionally, clinicians need to be attentive for at least five classes of neurological complications: (1) Cerebrovascular disorders including ischemic stroke and macro/micro-hemorrhages, (2) encephalopathies, (3) para-/postinfectious immune-mediated complications such as Guillain–Barré syndrome and acute disseminated encephalomyelitis, (4) (meningo-)encephalitis, potentially with concomitant seizures and (5) neuropsychiatric complications such as psychosis and mood disorders. Our systematic review highlights the need for vigilance regarding neurological complications in patients infected by SARS-CoV-2 and other HCoVs, especially since some complications may result in chronic disability. Neuroimaging protocols should be designed to specifically screen for these complications. Therefore, we propose practical imaging guidelines to facilitate the diagnostic workup and monitoring of patients infected with HCoVs.
Prevalence and risk factors of disability and anxiety in a retrospective cohort of 432 survivors of Coronavirus Disease-2019 (Covid-19) from China
Authors: Zhu Siyi , Gao Qiang , Yang Lin , Yang Yonghong , Xia Wenguang , Cai Xiguo , Hui Yanping , Zhu Di , Zhang Yanyan , Zhang Guiqing , Wu Shuang , Wang Yiliang , Zhou Zhiqiang , Liu Hongfei , Zhang Changjie , Zhang Bo , Yang Jianrong , Feng Mei , Ni Zhong , Chen Baoyu , Du Chunping , He Hongchen , Qu Yun , Wei Quan , He Chengqi , Reinhardt Jan D.
Published: September 2020

Objective

To estimate the prevalence of disability and anxiety in Covid-19 survivors at discharge from hospital and analyze relative risk by exposures.

Design

Multi-center retrospective cohort study.

Setting

Twenty-eight hospitals located in eight provinces of China.

Methods

A total of 432 survivors with laboratory-confirmed SARS CoV-2 infection participated in this study. At discharge, we assessed instrumental activities of daily living (IADL) with Lawton’s IADL scale, dependence in activities of daily living (ADL) with the Barthel Index, and anxiety with Zung’s self-reported anxiety scale. Exposures included comorbidity, smoking, setting (Hubei vs. others), disease severity, symptoms, and length of hospital stay. Other risk factors considered were age, gender, and ethnicity (Han vs. Tibetan).

Results

Prevalence of at least one IADL problem was 36.81% (95% CI: 32.39-41.46). ADL dependence was present in 16.44% (95% CI: 13.23-20.23) and 28.70% (95% CI: 24.63-33.15) were screened positive for clinical anxiety. Adjusted risk ratio (RR) of IADL limitations (RR 2.48, 95% CI: 1.80-3.40), ADL dependence (RR 2.07, 95% CI 1.15-3.76), and probable clinical anxiety (RR 2.53, 95% CI 1.69-3.79) were consistently elevated in survivors with severe Covid-19. Age was an additional independent risk factor for IADL limitations and ADL dependence; and setting (Hubei) for IADL limitations and anxiety. Tibetan ethnicity was a protective factor for anxiety but a risk factor for IADL limitations.

Conclusion

A significant proportion of Covid-19 survivors had disability and anxiety at discharge from hospital. Health systems need to be prepared for an additional burden resulting from rehabilitation needs of Covid-19 survivors.
On Statistical Power for Case-Control Host Genomic Studies of COVID-19
Authors: Lin Yu-Chung , Brooks Jennifer D. , Bull Shelley B. , Gagnon France , Greenwood Celia M.T. , Hung Rayjean J. , Lawless Jerald , Paterson Andrew , Sun Lei , Strug Lisa
Published: September 2020

The identification of genetic variation that directly impacts infection susceptibility and disease severity of COVID-19 is an important step towards risk stratification, personalized treatment plans, therapeutic and vaccine development and deployment. Given the importance of study design in infectious disease genetic epidemiology, we use simulation and draw on current estimates of exposure, infectivity and test accuracy of COVID-19 to demonstrate the feasibility of detecting host genetic factors associated with susceptibility and severity with published COVID-19 study designs. We demonstrate why studying susceptibility to SARS-CoV-2 infection could be futile at the early stages of the pandemic. Our insights can aid in the interpretation of genetic findings emerging in the literature and guide the design of future host genetic studies.
Overexpression of HIF-2α in Protected Regions of Alzheimer’s disease Resilient Cases
Authors: Mitri Vivianne
Published: September 2020

Alzheimer’s disease (AD) Resilient individuals are characterized by having a degree of amyloid plaques at level with that of demented individuals, but a reduced amount of abnormal neurofibrillary protein “tangles” (NFTs). NFTs, also known to be upregulated under hypoxic conditions, become clinically relevant when involved in the stratum radiatum. In this paper, we show this region and more to have significant increases of hypoxic adaptive protein, HIF-2α, within AD resilient cases. Pericyte staining was present in the stratum lacunosum and radiatum of all cases affected by AD pathology (n = 4) but in AD resilient cases were increased by 12-fold (n=3) p<.0001. No staining was detected in normal cases (n=2). HIF-2α was also only present in hippocampal neuronal nuclei of AD resilient cases, including the dentate gyrus and CA1. Cytoplasmic staining of pyramidal neurons within the subiculum was seen in all cases affected by AD pathology. The intensity of HIF-2α appears to be specific to known regions of protection in AD resilience and to increase on a gradient that corresponds to protection against dementia. These results also highlight the stratum lacunosum and radiatum as regions critically impacted by hypoxic insult among AD cases.

Significance

HIF-2α directly regulates expression of erythropoietin (EPO), a neuroprotective glycoprotein that in brain pericytes is completely dependent upon activation of HIF-2α. To date, only indirect evidence exists that shows that brain pericyte-derived EPO can reach the bloodstream via HIF-2α expression (Urrutia et al, 2016). In this study, we provide novel preliminary findings that directly show HIF-2α expression in pericytes of human brains. Additionally, its localization is specific to the CA1 of the hippocampus, a region critical for hypoxic adaptation and the progression of Alzheimer’s disease. Finally, we present evidence of neuronal expression of HIF-2α in other critical regions of protection within AD resilient cases.
The Potential Role of Extracellular Vesicles in COVID-19 Associated Endothelial injury and Pro-inflammation
Authors: Krishnamachary Balaji , Cook Christine , Spikes Leslie , Chalise Prabhakar , Dhillon Navneet K.
Published: September 2020

COVID-19 infection caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic with the number of deaths growing exponentially. Early evidence points to significant endothelial dysfunction, micro-thromboses, pro-inflammation as well as a dysregulated immune response in the pathogenesis of this disease. In this study, we analyzed the cargo of EVs isolated from the plasma of patients with COVID-19 for the identifiction of potential biomarkers of disease severity and to explore their role in disease pathogenesis. Plasma-derived EVs were isolated from 53 hospitalized patients with COVID infection and compared according to the severity of the disease. Analysis of inflammatory and cardiovascular protein cargo of large EVs revealed significantly differentially expressed proteins for each disease sub-group. Notably, members of the TNF superfamily and IL-6 family were up-regulated in patients on oxygen support with severe and moderate disease. EVs from the severe group were also enhanced with pro-thrombotic/endothelial injury factors (TF, t-PA, vWF) and proteins associated with cardiovascular pathology (MB, PRSS8, REN, HGF). Significantly higher levels of TF, CD163, and EN-RAGE were observed in EVs from severe patients when compared to patients with a moderate disease requiring supplemental O2. Importantly, we also observed increased caspase 3/7 activity and decreased cell survival in human pulmonary microvascular endothelial cells exposed to EVs from the plasma of patients with severe disease compared to asymptomatic group. In conclusion, our findings indicate alterations in pro-inflammatory, coagulopathy, and endothelial injury protein cargo in large EVs in response to SARS-CoV-2 infection that may be a causative agent in severe illness.
Analysis and validation of a highly sensitive one-step nested quantitative real-time polymerase chain reaction assay for specific detection of severe acute respiratory syndrome coronavirus 2
Authors: Zhang Yang , Dai Chunyang , Wang Huiyan , Gao Yong , Li Tuantuan , Fang Yan , Shen Zuojun , Chen Lichang , Chen Zhaowu , Ma Xuejun , Li Ming
Published: September 2020

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is posing a serious threat to global public health. Reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. Due to technical limitations, the reported positive rates of qRT-PCR assay of throat swab samples vary from 30%–60%. Therefore, the evaluation of alternative strategies to overcome the limitations of qRT-PCR is required. A previous study reported that one-step nested (OSN)-qRT-PCR revealed better suitability for detecting SARS-CoV-2. However, information on the analytical performance of OSN-qRT-PCR is insufficient. In this study, we aimed to analyze OSN-qRT-PCR by comparing it with droplet digital PCR (ddPCR) and qRT-PCR by using a dilution series of SARS-CoV-2 pseudoviral RNA and a quality assessment panel. The clinical performance of OSN-qRT-PCR was also validated and compared with ddPCR and qRT-PCR using specimens from COVID-19 patients. The LoD (copies/ml) of qRT-PCR, ddPCR, and OSN-qRT-PCR were 520.1 (95% CI): 363.23–1145.69) for ORF1ab and 528.1 (95% CI: 347.7–1248.7) for N, 401.8 (95% CI: 284.8–938.3) for ORF1ab and 336.8 (95% CI: 244.6–792.5) for N, and 194.74 (95% CI: 139.7–430.9) for ORF1ab and 189.1 (95% CI: 130.9–433.9) for N, respectively. Of the 34 clinical samples from COVID-19 patients, the positive rates of OSN-qRT-PCR, ddPCR, and qRT-PCR were 82.35% (28/34), 67.65% (23/34), and 58.82% (20/34), respectively. In conclusion, the highly sensitive and specific OSN-qRT-PCR assay is superior to ddPCR and qRT-PCR assays, showing great potential as a technique for detection of SARS-CoV-2 in patients with low viral loads.
Aerosols created by dental procedures in a primary care setting
Authors: Hobson R S , Pabary S B , Alamani K , Badminton K
Published: September 2020

The study was undertaken to record the amount of dental aerosol created using 3-in-1 syringe, air rotor, and ultrasonic scaler using high volume suction (HVS) in 5 primary care dental surgeries. The time for the aerosol to dissipate following completion of the procedure was also recorded. The amount of aerosol created above the background level for the surgery corresponding to the operating positions of the nurse, dentist, and patient was recorded using particle meters measuring the number of 2.5µm (PM2.5) and 10µm (PM10) particles respectively. The procedures were recorded in triplicate for each surgery and average change calculated for each procedure, lasting 90 seconds.

PM2.5 remained at or very near background readings during all procedures, whereas PM10 increased with use of the air rotor and to a much lower extent with both 3-in-1, and ultrasonic scaler. The means time to return to background reading level was 2.5 minutes.

It was concluded that PM2.5 levels did not rise and although PM10 increased for all procedures the increase was low and with a return to background readings within 2m:50s (95% CI: 2:34 to 3:37) of completing the procedures that a minimum fallow period of 5minutes would allow be more than ample to be safe.
Acute kidney injury in patients with severe COVID-19
Authors: Casas-Aparicio Gustavo A. , León-Rodríguez Isabel , González-Navarro Mauricio , Alvarado-de la Barrera Claudia , Ávila-Ríos Santiago , Peralta-Prado Amy , Luna-Villalobos Yara , Velasco-Morales Alejandro , Calderón-Dávila Natalia
Published: September 2020

Introduction

Some patients with COVID-19 pneumonia present systemic disease involving multiple systems. There is limited information about the clinical characteristics and events leading to acute kidney injury (AKI). We described the factors associated with the development of AKI and explored the relation of AKI and mortality in Mexican population with severe COVID-19.

Methods

We retrospectively reviewed the medical records of individuals with severe pneumonia caused by SARS-CoV-2 hospitalized at the largest third-level reference institution for COVID-19 care in Mexico between March and April 2020. Demographic information, comorbidities, clinical and laboratory data, dates of mechanical ventilation and hospitalization, mechanical-ventilator settings and use of vasoactive drugs were recorded.

Results

Of 99 patients studied, 58 developed AKI (58.6%). The group with AKI had higher body mass index (p=0.0003) and frequency of obesity (p=0.001); a higher requirement of invasive mechanical ventilation (p=0.008) and vasoactive drugs (p=0.004); greater levels of serum creatinine (p<0.001) and D-dimer on admission (p<0.001); and lower lymphocyte counts (p=0.001) than the non-AKI group. The multivariate analysis indicated that risk factors for AKI were obesity (adjusted hazard ratio (HR)=2.71, 95% confidence interval (CI)=1.33-5.51, p=0.005); higher serum creatinine (HR=1.44, CI=1.02- 2.02, p=0.035) and D-dimer levels on admission (HR=1.14, CI=1.06-1.23, p<0.001). Inhospital mortality was higher in the AKI group than in the non-AKI group (65.5% vs. 14.6%; p=0.001).

Conclusions

AKI was common in our cohort of patients with severe COVID-19 and it was associated with mortality. The risk factors for AKI were obesity, elevated creatinine levels and higher D-dimer levels on admission.
Inactivation of posterior but not anterior dorsomedial caudate-putamen impedes learning with self-administered nicotine stimulus
Authors: Robison Christopher L. , Kazan Theodore , Miller Rikki , Cova Nicole , Charntikov Sergios
Published: September 2020

The rodent caudate-putamen is a large heterogeneous neural structure with distinct anatomical connections that differ in their control of learning processes. Previous research suggests that the anterior and posterior dorsomedial caudate-putamen (a- and p-dmCPu) differentially regulate associative learning with a non-contingent nicotine stimulus. The current study used bilateral NMDA-induced excitotoxic lesions to the a-dmCPu and p-dmCPu to determine the functional involvement of a-dmCPu and p-dmCPu in appetitive learning with contingent nicotine stimulus. Rats with a-dmCPu, p-dmCPu, or sham lesions were trained to lever-press for intravenous nicotine (0.03 mg/kg/inf) followed by access to sucrose 30 s later. After 1, 3, 9, and 20 nicotine-sucrose training sessions, appetitive learning in the form of a goal-tracking response was assessed using a non-contingent nicotine-alone test. All rats acquired nicotine self-administration and learned to retrieve sucrose from a receptacle at equal rates. However, rats with lesions to p-dmCPu demonstrated blunted learning of the nicotine-sucrose association. Our primary findings show that rats with lesions to p-dmCPu had a blunted goal-tracking response to a non-contingent nicotine administration after 20 consecutive days of nicotine-sucrose pairing. Our findings extend previous reports to a contingent model of nicotine self-administration and show that p-dmCPu is involved in associative learning with nicotine stimulus using a paradigm where rats voluntarily self-administer nicotine infusions that are paired with access to sucrose—a paradigm that closely resembles learning processes observed in humans.
The Contribution of Brain Structural and Functional Variance in Predicting Age, Sex and Treatment
Authors: Chen Ning-Xuan , Fu Gui , Chen Xiao , Li Le , Milham Michael P. , Lui Su , Yan Chao-Gan
Published: September 2020

Structural and functional neuroimaging have been widely used to track and predict demographic and clinical variables, including treatment outcomes. However, it is often difficult to directly establish and compare the respective weights and contributions of brain structure and function in prediction studies. The present study aimed to directly investigate respective roles of brain structural and functional indices, along with their contributions in the prediction of demographic variables (age/sex) and clinical changes of schizophrenia patients. The present study enrolled 492 healthy people from Southwest University Adult Lifespan Dataset (SALD) for demographic variables analysis and 42 patients with schizophrenia from West China Hospital for treatment analysis. We conducted a model fit test with two variables (one voxel-based structural metric and another voxel-based functional metric) and then performed a variance partitioning on the voxels that can be predicted sufficiently. Permutation tests were applied to compare the contribution difference between each pair of structural and functional measurements. We found that voxel-based structural indices had stronger predictive value for age and sex, while voxel-based functional metrics showed stronger predictive value for treatment. Therefore, through variance partitioning, we could clearly and directly explore and compare the voxel-based structural and functional indices on particular variables. In sum, for long-term change variable (age) and constant biological feature (sex), the voxel-based structural metrics would contribute more than voxel-based functional metrics; but for short-term change variable (schizophrenia treatment), the functional metrics could contribute more.