bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-assessment of Competence in Endoscopy: Challenges and Insights
Authors: Scaffidi Michael A , Khan Rishad , Grover Samir C , Gimpaya Nikko , Walsh Catharine M
Published: May 2020

Background

Endoscopists use self-assessment to monitor the development and maintenance of their skills. The accuracy of these self-assessments, which reflects how closely one’s own rating corresponds to an external rating, is unclear.

Methods

In this narrative review, we critically examine the current literature on self-assessment in gastrointestinal endoscopy with the aim of informing training and practice and identifying opportunities to improve the methodological rigor of future studies.

Results

In the seven included studies, the evidence regarding self-assessment accuracy was mixed. When stratified by experience level, however, novice endoscopists were least accurate in their self-assessments and tended to overestimate their performance. Studies examining the utility of video-based interventions using observation of expert benchmark performances show promise as a mechanism to improve self-assessment accuracy among novices.

Conclusions

Based on the results of this review, we highlight problematic areas, identify opportunities to improve the methodological rigor of future studies on endoscopic self-assessment and outline potential avenues for further exploration.
An unexpected intraoperative finding of cystic adventitial degeneration of the common femoral artery
Authors: Esposito Davide , Masciello Fabrizio , Dorigo Walter , Alessi Innocenti Alessandro , Santi Raffaella , Nesi Gabriella , Pratesi Carlo
Published: May 2020

Herein we present a rare case of cystic adventitial degeneration involving the common femoral artery (CFA) of a 71-year-old patient, an unusual site of presentation of the disease. The most commonly affected district is the popliteal artery, and only a few cases of CFA involvement are described in literature. The history and comorbidities of the patient oriented us initially towards the diagnosis of an atherosclerotic obstructive disease. It was only intraoperatively indeed that a diagnosis of cystic adventitial arterial degeneration was made, subsequently confirmed by microscopic examination. Our case shows how both clinical and instrumental diagnosis of cystic adventitial disease can be challenging, given its non-specific presentation and low incidence. Suspicion of cystic adventitial degeneration is recommended in patients with sudden appearance of symptoms and with an isolated lesion of the affected artery without other involvement of the vascular tree.
Successful smallpox eradication: what can we learn to control COVID-19?
Authors: Heymann D L , Wilder-Smith Annelies
Published: May 2020

The public health community needs to learn from history and needs to regain its ability to do shoe-leather public health. If we come together collectively and use the public health tools that we have at hand, we will be successful in containing COVID-19 despite geopolitical tensions, just as we were successful in eradicating smallpox despite the Cold War at the time.
Dissolution-precipitation growth of uniform and clean two dimensional transition metal dichalcogenides
Authors: Cai Zhengyang , Lai Yongjue , Zhao Shilong , Zhang Rongjie , Tan Junyang , Feng Simin , Zou Jingyun , Tang Lei , Lin Junhao , Liu Bilu , Cheng Hui-Ming
Published: May 2020

Two dimensional transition metal dichalcogenides (TMDCs) have attracted much interest and shown promise in many applications. However, it is challenging to obtain uniform TMDCs with clean surfaces, because of the difficulties in controlling the way the reactants are supplied to the reaction in the current chemical vapor deposition growth process. Here, we report a new growth approach called ‘dissolution-precipitation’ (DP) growth, where the metal sources are sealed inside glass substrates to control their feeding to the reaction. Noteworthy, the diffusion of metal source inside glass to its surface provides a uniform metal source on the glass surface, and restricts the TMDC growth to only a surface reaction while eliminating unwanted gas-phase reaction. This feature gives rise to highly uniform monolayer TMDCs with a clean surface on centimeter-scale substrates. The DP growth works well for a large variety of TMDCs and their alloys, providing a solid foundation for the controlled growth of clean TMDCs by the fine control of the metal source.
A cohort-based analysis of labor force participation for advanced economies
Authors: Grigoli Francesco , Koczan Zsoka , Topalova Petia
Published: May 2020

Advanced economies are in the midst of a major demographic transition, with the number of elderly rising precipitously. Yet, advanced economies experienced different trajectories in labor force participation rates and workforce attachment of men and women. Using a cohort model for 17 advanced economies during 1985–2016, we document a significant role of common patterns of participation over the life cycle and shifts in these patterns across generations, especially for women. New cohorts of women led to upward shifts in the age participation profile. However, this process plateaued in most countries, with signs of reversal in some. We project sizable declines in participation rates over the next three decades, with aggregate participation forecast to decline by 5.5 percentage points for the median advanced economy. Illustrative simulations show that closing gender gaps, extending working lives, and implementing policies encouraging labor supply can help attenuate, but may not fully offset, demographic pressures.
Muscle deterioration due to rheumatoid arthritis: assessment by quantitative MRI and strength testing
Authors: Farrow Matthew , Biglands John , Tanner Steven , Hensor Elizabeth M A , Buch Maya H , Emery Paul , Tan Ai Lyn
Published: May 2020

Objectives

RA patients often present with low muscle mass and decreased strength. Quantitative MRI offers a non-invasive measurement of muscle status. This study assessed whether MRI-based measurements of T2, fat fraction, diffusion tensor imaging and muscle volume can detect differences between the thigh muscles of RA patients and healthy controls, and assessed the muscle phenotype of different disease stages.

Methods

Thirty-nine RA patients (13 ‘new RA’—newly diagnosed, treatment naïve, 13 ‘active RA’—persistent DAS28 >3.2 for >1 year, 13 ‘remission RA’—persistent DAS28 <2.6 for >1 year) and 13 age and gender directly matched healthy controls had an MRI scan of their dominant thigh. All participants had knee extension and flexion torque and grip strength measured.

Results

MRI T2 and fat fraction were higher in the three groups of RA patients compared with healthy controls in the thigh muscles. There were no clinically meaningful differences in the mean diffusivity. The muscle volume, handgrip strength, knee extension and flexion were lower in all three groups of RA patients compared with healthy controls.

Conclusion

Quantitative MRI and muscle strength measurements can potentially detect differences within the muscles between RA patients and healthy controls. These differences may be seen in RA patients who are yet to start treatment, those with persistent active disease, and those who were in clinical remission. This suggests that the muscles in RA patients are affected in the early stages of the disease and that signs of muscle pathology and muscle weakness are still observed in clinical remission.
Participation and weight loss in online National Diabetes Prevention Programs: a comparison of age and gender subgroups
Authors: Sauder Katherine A , Ritchie Natalie D , Crowe Byron , Cox Edith , Hudson Marissa , Wadhwa Sandeep
Published: May 2020

Early onset diabetes has adverse transgenerational effects, yet in-person National Diabetes Prevention Programs (NDPPs) have low reach among adults of peak reproductive age. We examined participation and weight loss with online NDPPs for younger versus older adults. Solera Health, Inc., collected data from 12,966 adults who enrolled in a yearlong online NDPP from 2015 to 2018. We used general linear models and logistic regression to assess differences between younger and older adults (<45 vs. ≥45 years) in session initiation (logging in), session completion (activities approximating intensity of in-person classes), and weight loss, overall and according to engagement thresholds. Almost all (N = 12,497, 96%) individuals who enrolled initiated ≥1 session(s), but fewer (N = 2,408, 19%) completed ≥4 sessions over ≥9 months, achieving 4.5% weight loss on average. Among all enrollees with ≥2 weights (N = 10,161), younger men and women lost less weight (1.8% and 1.7%, respectively) than older men (3.3%) and women (2.7%; all p < .05). Among all enrollees who completed ≥4 sessions over ≥9 months, weight loss did not differ between older men (4.3%), older women (4.0%), and younger men (3.5%), but younger women achieved less weight loss (3.0%) than older adults (all p < .001). Online programming supports NDPP reach and weight loss, although younger adults completed fewer sessions and young women achieved less weight loss than older adults. Efforts to increase ongoing engagement among younger adults are needed to prevent early onset of diabetes and adverse transgenerational effects.
RN to BSN Students’ Experiences With Asynchronous Audio-Video Discussion Responses
Authors: Denson Vicki L. , Shurts Leslie M.
Published: May 2020

Literature suggests use of audio-video (AV) technology enhances a sense of connectedness between students in online programs. In a previous quantitative study conducted by these authors, the use of AV discussion responses revealed that social presence was negatively impacted. This descriptive study explored RN to BSN students’ experiences with AV discussion formats. Participants found value related to forming distinct impressions of others but expressed feelings of distress; they described issues with technology and time as barriers. Implications suggest that AV format is not supported for use in every discussion forum but may be of value if limited to select discussion forums.
Using Universal Design Principles in a Fundamentals Course to Promote Student Transition to Nursing Education
Authors: Scheirer Tracy Fogarty
Published: May 2020

The transition to “thinking like a nurse” can present challenges to contemporary student nurses. Nurse educators are called to provide meaningful learning experiences to students with diverse learning needs and promote critical thinking application. Multiple stakeholders encourage nursing faculty to innovate their teaching practices and reflect on the process to promote the life-long learning necessary in professional nursing. Universal design for instruction uses multiple pedagogies, resources, and technologies to create accessible learning environments for all students. This article highlights the evolution of a case exemplar course design in a fundamentals nursing course that utilizes universal design for instruction principles in nursing education.
Faculty Perceptions in Facilitating Success for Accelerated BSN Student Veterans
Authors: Wiersma Gretchen , Cox Catherine Wilson , McNelis Angela M. , Schumann Mary Jean , Maring Joyce
Published: May 2020

Student veterans enrolled in nursing programs often experience challenges transitioning to higher education environments. This study investigated faculty perspectives regarding the strengths and challenges of student veterans in an accelerated bachelor’s of science in nursing program; faculty (N = 21) participated in focus groups. Four themes emerged: No Man Left Behind, Acclimating to the Higher Education Environment, Not Wanting to Be Different, and Professionalism/Maturity. Faculty perceived student veterans possess strengths and approaches to learning different from students without a military background. Integrating these strengths into the curriculum, with strategies such as team-based learning and group assignments, will leverage their skills and facilitate academic success.
Coagulopathy of Coronavirus Disease 2019
Authors: Iba Toshiaki , Levy Jerrold H. , Levi Marcel , Connors Jean Marie , Thachil Jecko
Published: May 2020

Objectives:

Recent studies have reported a high prevalence of thrombotic events in coronavirus disease 2019. However, the significance of thromboembolic complications has not been widely appreciated. The purpose of this review is to provide current knowledge of this serious problem.

Design:

Narrative review.

Data Sources:

Online search of published medical literature through PubMed using the term “COVID-19,” “SARS,” “acute respiratory distress syndrome,” “coronavirus,” “coagulopathy,” “thrombus,” and “anticoagulants.”

Study Selection and Data Extraction:

Articles were chosen for inclusion based on their relevance to coagulopathy and thrombosis in coronavirus disease 2019, and anticoagulant therapy. Reference lists were reviewed to identify additional relevant articles.

Data Synthesis:

Coronavirus disease 2019 is associated with a strikingly high prevalence of coagulopathy and venous thromboembolism that may contribute to respiratory deterioration. Monitoring coagulation variables is important, as abnormal coagulation tests are related to adverse outcomes and may necessitate adjuvant antithrombotic interventions. In the initial phase of the infection, d-dimer and fibrinogen levels are increased, while activated partial prothrombin time, prothrombin time, and platelet counts are often relatively normal. Increased d-dimer levels three times the upper limit of normal may trigger screening for venous thromboembolism. In all hospitalized patients, thromboprophylaxis using low-molecular-weight heparin is currently recommended. The etiology of the procoagulant responses is complex and thought to be a result of specific interactions between host defense mechanisms and the coagulation system. Although the coagulopathy is reminiscent of disseminated intravascular coagulation and thrombotic microangiopathy, it has features that are markedly distinct from these entities.

Conclusions:

Severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 frequently induces hypercoagulability with both microangiopathy and local thrombus formation, and a systemic coagulation defect that leads to large vessel thrombosis and major thromboembolic complications, including pulmonary embolism in critically ill hospitalized patients. d-dimers and fibrinogen levels should be monitored, and all hospitalized patients should undergo thromboembolism prophylaxis with an increase in therapeutic anticoagulation in certain clinical situations.
The Effect of Systemic Chemotherapy on Survival in Patients With Localized, Regional, or Metastatic Adenocarcinoma of the Urinary Bladder
Authors: Luzzago Stefano , Palumbo Carlotta , Rosiello Giuseppe , Pecoraro Angela , Deuker Marina , Mistretta Francesco A. , Tian Zhe , Musi Gennaro , Montanari Emanuele , Shariat Shahrokh F. , Saad Fred , Briganti Alberto , de Cobelli Ottavio , Karakiewicz Pierre I.
Published: May 2020

Objectives:

To test the effect of systemic chemotherapy on cancer-specific mortality (CSM) in patients with adenocarcinoma of the urinary bladder (ADKUB).

Materials and Methods:

Within the Surveillance, Epidemiology, and End Results registry (2004 to 2016), we identified patients with localized (T2-3N0M0), regional (T4N0M0/TanyN1-3M0), and metastatic (TanyNanyM1) ADKUB. Temporal trends, Kaplan-Meier plots, and multivariable Cox regression models were used before and after 1:1 propensity score matching and inverse probability of treatment weighting.

Results:

Of 1537 patients with ADKUB, 834 (54.0%), 363 (23.5%), and 340 (22.5%) harbored localized, regional, and metastatic disease, respectively. The rates of chemotherapy use increased in localized (estimated annual percentage change [EAPC]: +2.7%; P=0.03) and regional ADKUB (EAPC: +2.4%; P=0.04). Conversely, chemotherapy rates remained stable in metastatic patients (EAPC: +1.6%; P=0.4). In multivariable Cox regression models, chemotherapy use was associated with lower CSM in metastatic ADKUB (hazard ratio [HR]: 0.5; P=0.003), but not in either localized (HR: 0.8; P=0.2) or in regional ADKUB (HR: 1.0; P=0.9). In metastatic ADKUB, the benefit of chemotherapy on CSM persisted after 1:1 propensity score matching (HR: 0.6; P=0.002) and after inverse probability of treatment weighting (HR: 0.4; P<0.001).

Conclusions:

Chemotherapy improves survival in metastatic ADKUB. However, only one out of 2 such patients benefit from chemotherapy. In consequence, greater emphasis on chemotherapy use may be warranted in these patients. Conversely, no benefit was identified in localized or regional ADKUB.
CHOROIDAL GRANULOMAS VISUALIZED BY SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Pichi Francesco , Smith Scott D. , Neri Piergiorgio , Woodstock Elizabeth , Hay Steven , Parrulli Salvatore , Corvi Federico , Mapelli Chiara , Invernizzi Alessandro
Published: May 2020

Purpose:

To assess the visualization of choroidal granulomas with swept-source optical coherence tomography angiography (OCTA).

Methods:

Consecutive patients with granulomatous choroiditis due to tuberculosis, sarcoidosis, or Vogt–Koyanagi–Harada disease underwent baseline OCTA images using a 12 × 12-mm field of view, and the choroidal slabs were analyzed by two independent examiners who counted the oval areas of flow void. Simultaneously, indocyanine green angiography (ICGA) and enhanced-depth imaging OCT were performed to mark visible choroidal changes corresponding to granulomatous lesions. The lesion areas on OCTA and ICGA were assessed using the in-built caliper tool.

Results:

Three hundred and one round-shaped areas of flow void on OCTA, 209 hypofluorescent round lesions on ICGA, and 42 hyporeflective choroidal lesions on enhanced-depth imaging OCT were identified in 23 eyes from 14 patients. Of the 209 ICGA granulomas, 197 (94.3%) had a corresponding round area of flow void on OCTA that was interpreted as a granuloma. One hundred and four additional round flow voids were identified on OCTA that did not correspond to any hypofluorescent lesion on ICGA. The mean area of the 197 granulomas detected with both imaging modalities was significantly larger on ICGA (mean 0.33 mm2) than that on OCTA (mean 0.28 mm2).

Conclusion:

Optical coherence tomography angiography seems to be an optimal imaging method for the visualization of choroidal granulomas.
Combinations of Job Demands and Job Control and Future Trajectories of Sickness Absence and Disability Pension An 11-year Follow-up of Two Million Employees in Sweden
Authors: Salonen Laura , Alexanderson Kristina , Rugulies Reiner , Framke Elisabeth , Niemelä Mikko , Farrants Kristin
Published: May 2020

Objective:

The aim of this study was to examine the association between combinations of job demands/control and future sickness absence (SA) and disability pension (DP) trajectories over 11 years.

Methods:

A population-based prospective cohort study of female (n = 1,079,631) and male (n = 1,107,999) employees in 2001. With group-based trajectory analysis, we modeled the trajectories of annual mean SA/DP days in 2002 to 2012. We predicted trajectory memberships for job demands/control using multinomial regression.

Results:

We found three SA/DP trajectories for women (low stable, medium stable, and high increasing) and two for men (low stable and high increasing). Low demands/low control in women [odds ratio (OR) 1.42; 95% confidence interval (95% CI) 1.38 to 1.45], and low demands and medium/high control in men (equal OR of 1.23; 95% CI 1.18 to 1.28) were strongly associated with high increasing trajectory.

Conclusion:

The associations between job demands/control varied between SA/DP trajectories and between sexes.
Association Between Overtime-Working Environment and Psychological Distress Among Japanese Workers
Authors: Ishida Yoko , Murayama Hiroshi , Fukuda Yoshiharu
Published: May 2020

Objective:

The study aims to examine the association between overtime-working environment (OWE) and individual psychological distress among Japanese workers.

Methods:

Data of 7786 workers from 101 companies in Japan were analyzed. Psychological distress was assessed through a 29-item questionnaire. The OWE was evaluated by calculating the proportion of workers whose monthly overtime was 45 hours or more in a workplace. Multilevel logistic regression was used.

Results:

As 10% increase in the OWE was associated with a 16% higher risk of individual psychological distress after adjustment of individual covariates, including overtime working hours. Cross-level interaction showed that the risk was varied depending on individual overtime working hours.

Conclusions:

OWE was associated with the psychological distress of workers. It is necessary to create a non-OWE at workplaces to prevent psychological distress for workers.
Love in the Time of Corona
Authors: Levitt Danielle L.
Published: May 2020

Dealing with this dystopian time with a little rhyme.
Characterization of unexpected survivors following a prehospital plasma randomized trial
Authors: Gruen Danielle S. , Guyette Francis X. , Brown Joshua B. , Daley Brian J. , Miller Richard S. , Harbrecht Brian G. , Claridge Jeffrey A. , Phelan Herb A. , Yazer Mark H. , Neal Matthew D. , Zuckerbraun Brian S. , Sperry Jason L.
Published: May 2020

BACKGROUND

Prehospital plasma improves survival for severely injured trauma patients transported by air ambulance. We sought to characterize the unexpected survivors, patients who survived despite having high predicted mortality after traumatic injury.

METHODS

The Prehospital Air Medical Plasma trial randomized severely injured patients (n = 501) to receive either standard care (crystalloid) or two units of prehospital plasma followed by standard care fluid resuscitation. We built a generalized linear model to estimate patient mortality. Area under the receiver operating characteristic curve was used to evaluate model performance. We defined unexpected survivors as patients who had a predicted mortality greater than 50% and survived to 30 days. We characterized patient demographics, clinical features, and outcomes of the unexpected survivors. Observed to expected (O/E) ratios and Z-statistics were calculated using model-estimated mortality for each cohort.

RESULTS

Our model predicted mortality better than Injury Severity Score or Revised Trauma Score parameters and identified 36 unexpected survivors. Compared with expected survivors, unexpected survivors were younger (33 years [24, 52 years] vs. 47 years [32, 59 years], p = 0.013), were more severely injured (Injury Severity Score 34 [22, 50] vs. 18 [10, 27], p < 0.001), had worse organ dysfunction and hospital resource outcomes (multiple organ failure, intensive care unit, hospital length of stay, and ventilator days), and were more likely to receive prehospital plasma (67 vs. 46%, p = 0.031). Nonsurvivors with high predicted mortality were more likely to receive standard care resuscitation (p < 0.001). Unexpected survivors who received prehospital plasma had a lower observed to expected mortality than those that received standard care resuscitation (O/E 0.56 [0.33–0.84] vs. 1.0 [0.73–1.32]). The number of prehospital plasma survivors (24) exceeded the number of predicted survivors (n = 10) estimated by our model (p < 0.001).

CONCLUSION

Prehospital plasma is associated with an increase in the number of unexpected survivors following severe traumatic injury. Prehospital interventions may improve the probability of survival for injured patients with high predicted mortality based on early injury characteristics, vital signs, and resuscitation measures.

LEVEL OF EVIDENCE

Therapeutic Level III.
Cognitive Complaints in Motor Functional Neurological (Conversion) Disorders: A Focused Review and Clinical Perspective
Authors: Alluri Priyanka R. , Solit Juliet , Leveroni Catherine L. , Goldberg Katherine , Vehar Julia V. , Pollak Lauren E. , Colvin Mary K. , Perez David L.
Published: May 2020

Functional neurological (conversion) disorder (FND) is a neuropsychiatric condition characterized by sensorimotor symptoms exhibiting features incompatible with other neurologic diseases. Individuals with motor FND (mFND) typically present with limb weakness, nonepileptic seizures, and/or abnormal movements. However, this population also frequently reports clouded thinking, inattention, and memory difficulties. Cognitive complaints in individuals with mFND are important to evaluate as they may negatively impact quality of life and impede treatment engagement. We provide a narrative review of the neuropsychological testing literature detailing neurocognitive profiles of individuals with mFND. We also present three illustrative clinical cases at the intersection of mFND and cognitive concerns. Several studies and our case examples highlight that generally normal cognitive performance can be observed concurrently with subjective cognitive complaints in some individuals with mFND; this mismatch may be a possible “rule-in” sign of functional cognitive symptoms. Other studies have reported impairments in attention, memory, language, visuospatial, and executive functioning in individuals with mFND. These impairments could be related to medical-psychiatric comorbidities, psychotropic medication side effects, and intrinsic disease mechanisms. When evaluating individuals with mFND and their cognitive complaints, clinicians can use performance validity test and psychopathology findings to help them interpret the neuropsychological test results. Perceptual mismatches between intact objective cognitive performance and subjective cognitive complaints may reflect a negative attentional bias for cognitive abilities that can be targeted with cognitive retraining and cognitive behavioral therapy. Neuropsychological evaluations may provide a useful adjunctive tool clinicians can use to help assess individuals with mFND and cognitive concerns.
Relationship Between Abnormalities in Resting-State Quantitative Electroencephalogram Patterns and Poststroke Depression
Authors: Li Xinyuan , Yue Lang , Liu Jing , Lv Xiaomin , Lv Yang
Published: May 2020

Purpose:

Spectral power analysis of quantitative EEG has gained popularity in the assessment of depression, but findings across studies concerning poststroke depression (PSD) have been inconsistent. The goal of this study was to determine the extent to which abnormalities in quantitative EEG differentiate patients with PSD from poststroke nondepressed (PSND) subjects.

Methods:

Resting-state EEG signals of 34 participants (11 patients with PSD and 23 PSND subjects) were recorded, and then the spectral power analysis for six frequency bands (alpha1, alpha2, beta1, beta2, delta, and theta) was conducted at 16 electrodes. Pearson linear correlation analysis was used to investigate the association between depression severity measured with the Hamilton Depression Rating Scale (HDRS) total score and absolute power values. In addition, receiver operating characteristic curves were used to assess the sensitivity and specificity of quantitative EEG in discriminating PSD.

Results:

In comparison with PSND patients, PSD patients showed significantly higher alpha1 power in left temporal region and alpha2 power at left frontal pole. Higher theta power in central, temporal, and occipital regions was observed in patients with PSD. The results of Pearson linear correlation analysis showed significant association between HDRS total score and the absolute alpha1 power in frontal, temporal, and parietal regions.

Conclusions:

Absolute powers of alpha and theta bands significantly distinguish between PSD patients and PSND subjects. Besides, absolute alpha1 power is positively associated with the severity of depression.
HIV serology false positivity among expatriates from Africa: a screening dilemma
Authors: Al-Kindi Hanan , Al-Jardani Amina
Published: May 2020

HIV prevalence in Oman is low (<5 %); however, 45 % of the population are expatriates, including a portion originating from countries with high HIV prevalence (>5 %). HIV screening is performed at regional public health laboratories as part of a medical fitness programme for residency applicants. We conducted a retrospective evaluation of indeterminate serology results from 11 females of African origin, aged 21–43 years. Serology testing for HIV was conducted according to the national Oman algorithm: fourth-generation immunoassays (Bio-Rad GS HIV Combo Ag/Ab EIA, Siemens Enzygnost HIV Integral 4, Abbott ARCHITECT HIV Ag/Ab Combo, Roche Elecsys HIV Combi PT, bioMérieux VIDAS HIV DUO QUICK), confirmatory assays (Geenius HIV 1/2 Confirmatory, INNO-LIA HIV I/II Score) and PCR testing. Confirmatory testing to resolve indeterminate results was conducted with available samples for five patients using a combination of immunoassays, confirmatory assays, PCR/PERT and pro-viral DNA levels, at three external laboratories; Roche Diagnostics (Germany), Swiss National Laboratory (Switzerland) and Barts Health NHS Trust (UK). Nineteen serum, 15 plasma and two whole-blood samples were analysed. Nine of ten patients analysed on Bio-Rad and Siemens immunoassays were highly reactive; seven were highly reactive on the Abbott assay. Eight of nine patients tested with the Roche assay were negative. Three of four patients tested on the bioMérieux assay were negative. Five patients underwent confirmatory testing at external laboratories; all were negative by HIV-RNA or pro-viral DNA testing. In conclusion, HIV-RNA and pro-viral DNA testing is recommended for HIV screening of individuals from high-prevalence regions coming to low-prevalence regions.
Characterization of chondroitinase-induced lumbar intervertebral disc degeneration in a sheep model intended for assessing biomaterials
Authors: Borem Ryan , Walters Joshua , Madeline Allison , Madeline Lee , Gill Sanjitpal , Easley Jeremiah , Mercuri Jeremy
Published: May 2020

Intervertebral disc (IVD) degeneration (IVDD) leads to structural and functional changes. Biomaterials for restoring IVD function and promoting regeneration are currently being investigated; however, such approaches require validation using animal models that recapitulate clinical, biochemical, and biomechanical hallmarks of the human pathology. Herein, we comprehensively characterized a sheep model of chondroitinase-ABC (C-ABC) induced IVDD. Briefly, C-ABC (1U) was injected into the L1/2, L2/3, and L3/4IVDs. Degeneration was assessed via longitudinal magnetic resonance (MR) and radiographic imaging. Additionally, kinematic, biochemical, and histological analyses were performed on explanted functional spinal units (FSUs). At 17-weeks, C-ABC treated IVDs demonstrated significant reductions in MR index (p=0.030) and disc height (p=0.009) compared to pre-operative values. Additionally, C-ABC treated IVDs exhibited significantly increased creep displacement (p=0.004) and axial range of motion (p=0.007) concomitant with significant decreases in tensile (p=0.034) and torsional (p=0.021) stiffnesses and long-term viscoelastic properties (p=0.016). C-ABC treated IVDs also exhibited a significant decrease in NP glycosaminoglycan: hydroxyproline ratio (p=0.002) and changes in microarchitecture, particularly in the NP and endplates, compared to uninjured IVDs. Taken together, this study demonstrated that intradiscal injection of C-ABC induces significant degeneration in sheep lumbar IVDs and its potential for use in evaluating biomaterials for IVD repair.

Statement of Significance

Selecting the appropriate model for assessing biomaterials to repair and/or support regeneration of the intervertebral disc (IVD) has been controversial, leading to the use of many methods of simulating IVD degeneration (IVDD) in multiple species. Many of these models lack thorough characterization of their fidelity to human IVDD, which could hinder the translation of novel biomaterials and therapies due to unknown confounding factors. Herein, further investigation of one such model was performed using the matrix-degrading enzyme chondroitinase-ABC to induce degeneration in sheep lumbar IVDs. Degenerative changes were quantified using outcome measures relevant to human IVDD, and this dosage and method induces an aggressive degeneration environment that could be used to assess biomaterials that mimic the structure and function of the entire composite IVD. These findings may aid investigators in their selection of an appropriate animal model for preclinical testing of biomaterials and other therapeutics.
Exposure to the predator odor TMT induces early and late differential gene expression related to stress and excitatory synaptic function throughout the brain in male rats
Authors: Tyler Ryan E. , Weinberg Ben , Lovelock Dennis , Ornelas Laura , Besheer Joyce
Published: May 2020

Persistent changes in brain stress and glutamatergic function are associated with post-traumatic stress disorder (PTSD). Rodent exposure to the predator odor trimethylthiazoline (TMT) is an innate stressor that produces lasting behavioral consequences relevant to PTSD. As such, the goal of the present study was to assess early (6 hours and 2 days) and late (4 weeks) changes to gene expression (RT-PCR) related to stress and excitatory function following TMT exposure in male, Long-Evans rats. During TMT exposure, rats engaged in stress reactive behaviors, including digging and immobility. Further, the TMT group displayed enhanced exploration and mobility in the TMT-paired context one week after exposure, suggesting a lasting contextual reactivity. Gene expression analyses revealed upregulatedFKBP56 hours post-TMT in the hypothalamus and dorsal hippocampus. Two days after TMT,GRM3was downregulated in the prelimbic cortex and dorsal hippocampus, but upregulated in the nucleus accumbens. This may reflect an early stress response (FKBP5) that resulted in later glutamatergic adaptation (GRM3). Finally, four weeks after TMT exposure, several differentially expressed genes known to mediate excitatory tripartite synaptic function were observed. Specifically in the prelimbic cortex (GRM5, DLG4andSLC1A3upregulated), infralimbic cortex (GRM2downregulated,Homer1upregulated), nucleus accumbens (GRM7andSLC1A3downregulated), dorsal hippocampus (FKBP5andNR3C2upregulated,SHANK3downregulated) and ventral hippocampus (CNR1, GRM7, GRM5, SHANK3, andHomer1downregulated). These data demonstrate that TMT exposure stress induces early and late stress and excitatory molecular adaptations, which may help us understand the persistent glutamatergic dysfunction observed in PTSD.
Comparison of the NeuMoDX, Diasorin Simplexa, Cepheid and Roche CDC SARS-CoV 2 EUA assays using nasopharyngeal/nasal swabs in universal transport media (UTM) and sputum and tracheal aspirates
Authors: Tibbetts Robert , Callahan Kathy , Rofoo Kareem , Zarbo Richard J. , Samuel Linoj
Published: May 2020

In March 2019 the outbreak of SARS-CoV 2 was officially defined as a pandemic by the World Health Organization and shortly after, the United States Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) to the Centers for Disease Control (CDC) for reverse transcription polymerase chain reaction (rtPCR) molecular testing for the detection of the SARS-CoV-2 virus from NP swabs. Since then, EUA with relaxed regulations were granted to numerous manufacturers and clinical microbiology laboratories to implement in-house testing assays with nasopharyngeal swabs (NP) and subsequently additional specimen types. Because of supply chain shortages leading to competition for reagents, sustaining any significant volume of testing soon became problematic. As a countermeasure, within several weeks the Henry Ford Microbiology Laboratory validated 4 different rtPCR assays and multiple specimen types using NeuMoDX, Diasorin Simplexa, Cepheid and Roche platforms. The purpose of this study was to analyze the analytic sensitivity of these rtPCR assays with NP/nasal swabs and sputum/tracheal aspirates. Qualitative analytic agreement between the 4 platforms for NP/nasal swabs ranged 95% - 100% overall with no statistically significant difference in threshold cT values. Similar results were obtained with the sputum/tracheal aspirates. These data demonstrate the high accuracy and reproducibility in detection of SARS-CoV 2 between the rtPCR assays performed on 4 different platforms with numerous specimen types.
Modelling Capacity on London Underground Carriages in Light of UK Government Mandated Social Distancing Rules in Response to the Covid-19 Pandemic
Authors: Marley Justin
Published: May 2020

Consultant

The UK has been affected by the COVID-19 pandemic and London in particular has experienced a large number of cases. The London Underground is a key part of the transport for London. The UK Government has implemented social distancing rules meaning that people should be 2 metres from each other. The current paper models the impact of the social distancing on the carrying capacity of 10 different underground and overground carriages. The model determines the optimal standing and seating capacity for the different carriages and identifies logistical approaches to the seating and standing arrangements.
Extensive Healthy Donor Age/Gender Adjustments and Propensity Score Matching Reveal Physiology of Multiple Sclerosis through Immunophenotyping
Authors: Hannikainen Paavali A. , Kosa Peter , Barbour Christopher , Bielekova Bibiana
Published: May 2020

Quantifying cell subpopulations in biological fluids aids in diagnosis and understanding of the mechanisms of injury. Although much has been learned from cerebrospinal fluid (CSF) flow cytometry in neuroimmunological disorders such as multiple sclerosis (MS), previous studies did not contain enough healthy donors (HD) to derive age- and gender-related normative data and sufficient heterogeneity of other inflammatory neurological diseases (OIND) controls to identify MS specific changes.

The goals of this blinded, training and validation study of MS patients and embedded controls, representing 1240 prospectively-acquired paired CSF/blood samples from 588 subjects was: 1. To define physiological age/gender-related changes in CSF cells; 2. To define/validate cellular abnormalities in blood and CSF of untreated MS through disease duration (DD) and determine which are MS-specific; 3. To compare effect(s) of low-efficacy (i.e., interferon-beta [IFN-beta] and glatiramer acetate [GA]) and high-efficacy drugs (i.e., natalizumab, daclizumab and ocrelizumab) on MS-related cellular abnormalities using propensity score matching.

Physiological gender differences are less pronounced in the CSF compared to blood, while age- related changes suggest decreased immunosurveillance of CNS by activated, HLA-DR+ T cells associated with natural aging. Results from patient samples support concept of MS being immunologically single disease evolving in time. Initially, peripherally activated innate and adaptive immune cells migrate into CSF to form MS lesions. With progression, T cells (CD8+ > CD4+), NK cells and myeloid dendritic cells are depleted from blood as they continue to accumulate, together with B cells, in the CSF and migrate to CNS tissue forming compartmentalized inflammation. All MS drugs inhibit non-physiological accumulation of immune cells in the CSF. While low efficacy drugs tend to normalize it, high efficacy drugs overshoot some aspects of CSF physiology suggesting impairment of CNS immunosurveillance. Comparable inhibition of MS-related CSF abnormalities advocates changes within CNS parenchyma responsible for differences in drug’s efficacy on MS disability progression.

Video summarizing all results may become useful educational tool.
COVID-19 in Multiple Sclerosis Patients and Risk Factors for Severe Infection
Authors: Chaudhry Farhan , Bulka Helena , Rathnam Anirudha S. , Said Omar M , Lin Jia , Lorigan Holly , Bernitsas Eva , Rube Jacob , Korzeniewski Steven J , Memon Anza B , Levy Phillip D. , Javed Adil , Lisak Robert , Cerghet Mirela
Published: May 2020

Importance

Multiple sclerosis patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, no study has identified clinical characteristics of multiple sclerosis associated with worse COVID-19 outcomes.

Objective

To evaluate the clinical characteristics of multiple sclerosis, including staging, degree of disability, and disease-modifying therapy use that are associated with worse outcomes from COVID-19.

Design

Prospective cohort study looking at the outcomes of multiple sclerosis patients with COVID-19 between March 1stand May 18th2020.

Setting

This is a multicenter study of three distinct hospital systems within the U.S.

Participants

The study included 40 consecutive patients with nasopharyngeal/oropharyngeal PCR-confirmed COVID-19 infection.

Exposures

Multiple sclerosis staging, severe disability (based on baseline-extended disability status scale equal to or greater than 6.0) and disease-modifying therapy.

Main Outcomes and Measure

Severity of COVID-19 infection was based on hospital course, where a mild course was defined as the patient not requiring hospital admission, moderate severity was defined as the patient requiring hospital admission to the general floor only, and most severe was defined as requiring intensive care unit admission and/or death.

Results

For the 40 patients, the median age was 52(45.5-61) years, 16/40(40%) were male, and 21/40(52.5%) were African American. 19/40(47.5%) had mild courses, 15/40(37.5%) had moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57[50-63] years old and 66[58.8-69.5] years old vs 48[40-51.5] years old, P=0.0121, P=0.0373). There was differing prevalence of progressive multiple sclerosis staging in those with more severe courses (severe:2/6[33.3%]primary-progressing and 0/6[0%]secondary-progressing, moderate:1/14[7.14%] and 5/14[35.7%] vs mild:0/19[0%] and 1/19[5.26%], P=0.0075, 1 unknown). Significant disability was found in 1/19(5.26%) mild course-patients, but was in 9/15(60%, P=0.00435) of moderate course-patients and 2/6(33.3%, P=0.200) of severe course-patients. Disease-modifying therapy prevalence did not differ among courses (mild:17/19[89.5%], moderate:12/15[80%] and severe:3/6[50%], P=0.123).

Conclusions and Relevance

Multiple sclerosis patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive staging, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses.
Non-Invasive Single-Cell Morphometry in Living Bacterial Biofilms
Authors: Zhang Mingxing , Zhang Ji , Wang Yibo , Wang Jie , Achimovich Alecia M. , Acton Scott T. , Gahlmann Andreas
Published: May 2020

Fluorescence microscopy enables spatial and temporal measurements of live cells and cellular communities. However, this potential has not yet been fully realized for investigations of individual cell behaviors and phenotypic changes in dense, three-dimensional (3D) bacterial biofilms. Accurate cell detection and cellular shape measurement in densely packed biofilms are challenging because of the limited resolution and low signal to background ratios (SBRs) in fluorescence microscopy images. In this work, we present Bacterial Cell Morphometry 3D (BCM3D), an image analysis workflow that combines deep learning with mathematical image analysis to accurately segment and classify single bacterial cells in 3D fluorescence images. InBCM3D, deep convolutional neural networks (CNNs) are trained using simulated biofilm images with experimentally realistic SBRs, cell densities, labeling methods, and cell shapes. We systematically evaluate the segmentation accuracy ofBCM3Dusing both simulated and experimental images. Compared to state-of-the-art bacterial cell segmentation approaches,BCM3Dconsistently achieves higher segmentation accuracy and further enables automated morphometric cell classifications in multi-population biofilms.
“Monoclonal-type” plastic antibodies for SARS-CoV-2 based on Molecularly Imprinted Polymers
Authors: Parisi Ortensia Ilaria , Dattilo Marco , Patitucci Francesco , Malivindi Rocco , Pezzi Vincenzo , Perrotta Ida , Ruffo Mariarosa , Amone Fabio , Puoci Francesco
Published: May 2020

Summary of the idea

Our idea is focused on the development of “monoclonal-type” plastic antibodies based on Molecularly Imprinted Polymers (MIPs) able to selectively bind a portion of the novel coronavirus SARS-CoV-2 spike protein to block its function and, thus, the infection process. Molecular Imprinting, indeed, represents a very promising and attractive technology for the synthesis of MIPs characterized by specific recognition abilities for a target molecule. Given these characteristics, MIPs can be considered tailor-made synthetic antibodies obtained by a templating process.

In the present study, the developed imprinted polymeric nanoparticles were characterized in terms of particles size and distribution by Dynamic Light Scattering (DLS) and the imprinting effect and selectivity were investigated by performing binding experiments using the receptor-binding domain (RBD) of the novel coronavirus and the RBD of SARS-CoV spike protein, respectively. Finally, the hemocompatibility of the prepared MIP-based plastic antibodies was also evaluated.
Neurobiological underpinnings of rapid white matter plasticity during intensive reading instruction
Authors: Huber Elizabeth , Mezer Aviv , Yeatman Jason D.
Published: May 2020

Diffusion MRI is a powerful tool for imaging brain structure, but it is challenging to discern the biological underpinnings of plasticity inferred from these and other non-invasive MR measurements. Biophysical modeling of the diffusion signal aims to render a more biologically rich image of tissue microstructure, but the application of these models comes with important caveats. A separate approach for gaining biological specificity has been to seek converging evidence from multi-modal datasets. Here we use metrics derived from diffusion kurtosis imaging (DKI) and the white matter tract integrity (WMTI) model along with quantitative MRI measurements of T1 relaxation to characterize changes throughout the white matter during an 8-week, intensive reading intervention (160 total hours of instruction). Behavioral measures, multi-shell diffusion MRI data, and quantitative T1 data were collected at regular intervals during the intervention in a group of 33 children with reading difficulties (7-12 years old), and over the same period in an age-matched non-intervention control group. Throughout the white matter, mean ‘extra-axonal’ diffusivity was inversely related to intervention time. In contrast, model estimated axonal water fraction (AWF), overall diffusion kurtosis, and T1 relaxation time showed no significant change over the intervention period. Both diffusion and quantitative T1 based metrics were correlated with pre-intervention reading performance, albeit with distinct anatomical distributions. These results are consistent with the view that rapid changes in diffusion properties reflect phenomena other than widespread changes in myelin density. We discuss this result in light of recent work highlighting non-axonal factors in experience-dependent plasticity and learning.

Highlights

Diffusion MRI measurements in white matter show changes linked to an educational intervention.

Tissue modeling results point to changes within the extra-axonal space.

Complementary MRI measurements fail to suggest a widespread change in white matter in myelination over the intervention period.

Both diffusion and quantitative T1 measures correlate with pre-intervention reading skill.