bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Eccentric Strength Training on Elbow Flexor Spasticity and Muscle Weakness in People With Multiple Sclerosis: Proof-of-Concept Single-System Case Series
Authors: Manca Andrea , Martinez Gianluca , Aiello Elena , Ventura Lucia , Deriu Franca
Published: April 2020

Objective

To date, no attention has been devoted to the employment of eccentric contractions to manage spasticity in multiple sclerosis. This single-system case series aimed to explore the effects of eccentric training on spasticity-related resistance to passive motion in people with multiple sclerosis with elbow flexor spasticity.

Methods

Six people with multiple sclerosis (median Expanded Disability Status Scale score = 4.8, range = 2.0–5.5; Modified Ashworth Scale [MAS] score ≤ 3) underwent a 6-week eccentric strength training of the spastic muscles. Before and after the intervention, the following outcomes were assessed: resistive peak torque (RPT), isometric strength, resting limb position, passive range of motion and active range of motion, severity of hypertonia by MAS, and numerical rating scale. At baseline, the primary outcome (RPT) was tested over 3 time points to ensure a stable measurement. The 2-SD method was used to test pre-post training effects at individual level. Group-level analyses were also performed.

Results

Following the intervention RPT decreased by at least 2 SDs in all participants but 1, with a significant reduction at group level of 41.6 (29.6)%. Four people with multiple sclerosis reported a reduction in perceived spasticity severity. No changes in MAS score were detected. Group-level analyses revealed that maximal strength increased significantly in the trained elbow flexors (+30.9 [9.1]%). Elbow flexion at rest was found to be significantly reduced (−35.5 [12.4]%), whereas passive range of motion (+4.6%) and active range of motion (+11.8%) significantly increased.

Conclusion

Eccentric training is feasible and safe to manage spasticity in people with multiple sclerosis. Preliminary data showed that this protocol can reduce resistance to passive motion, also improving strength, spasticity-free range of motion, and limb positioning.

Impact

Patients with multiple sclerosis–related spasticity and moderate-to-severe disability can benefit from adding slow submaximal eccentric contractions to the conventional management of spasticity.
Blindness: behaviour in an epidemic†
Authors: Zatta Marta , Braut Beatrice
Published: April 2020

In ‘Blindness’ José Saramago transports us into a society in which an unexpected epidemic of blindness spreads quickly, disseminating chaos between citizens and institutions. This new reality acts as a magnifying glass highlighting the weaknesses and (few) forces of individuals and community. From this masterpiece we can learn many insights useful to understand the SARS-CoV-2 pandemic.
Evidence for Altered Metabolism of Sphingosine-1-Phosphate in the Corpus Callosum of Patients with Schizophrenia
Authors: Esaki Kayoko , Balan Shabeesh , Iwayama Yoshimi , Shimamoto-Mitsuyama Chie , Hirabayashi Yoshio , Dean Brian , Yoshikawa Takeo
Published: April 2020

The disturbed integrity of myelin and white matter, along with dysregulation of the lipid metabolism, may be involved in schizophrenia pathophysiology. Considering the crucial role of sphingolipids in neurodevelopment, particularly in oligodendrocyte differentiation and myelination, we examined the role of sphingolipid dynamics in the pathophysiology of schizophrenia. We performed targeted mass spectrometry-based analysis of sphingolipids from the cortical area and corpus callosum of postmortem brain samples from patients with schizophrenia and controls. We observed lower sphingosine-1-phosphate (S1P) levels, specifically in the corpus callosum of patients with schizophrenia, but not in major depressive disorder or bipolar disorder, when compared with the controls. Patient data and animal studies showed that antipsychotic intake did not contribute to the lowered S1P levels. We also found that lowered S1P levels in the corpus callosum of patients with schizophrenia may stem from the upregulation of genes for S1P-degrading enzymes; higher expression of genes for S1P receptors suggested a potential compensatory mechanism for the lowered S1P levels. A higher ratio of the sum of sphingosine and ceramide to S1P, which can induce apoptosis and cell-cycle arrest, was also observed in the samples of patients with schizophrenia than in controls. These results suggest that an altered S1P metabolism may underlie the deficits in oligodendrocyte differentiation and myelin formation, leading to the structural and molecular abnormalities of white matter reported in schizophrenia. Our findings may pave the way toward a novel therapeutic strategy.
Methods to Decrease Disparities in Age of Autism Diagnosis and Treatment Access among Latinx Children
Authors: Lopez Kristina , Marroquin Jessica M , Gutierrez Courtney
Published: April 2020

Autism spectrum disorder (ASD) affects a substantial number of individuals and their families. Early diagnosis followed by intensive behavioral services is critical to reducing social communication deficits and behavioral challenges. Research has continually demonstrated health disparities with Latinx families that perpetuate lower ASD prevalence rates, later ASD diagnosis, and limited access to treatment compared with white children. Moreover, Latinx children who are diagnosed with ASD receive less intense and fewer treatment services. Given the number of Latinx children and those with ASD, social workers are likely to encounter the intersection throughout their careers. Thus, it is critical for social workers to have general knowledge about autism and the complexity of accessing diagnostic and treatment services. In this article, the authors review the literature on Latinx children and ASD, and identify opportunities for social workers to be innovative in their use of frameworks, theories, and practice approaches to reduce disparities in ASD diagnosis and treatment among Latinx children.
Healing Justice, Transformative Justice, and Holistic Self-Care for Social Workers
Authors: Pyles Loretta
Published: April 2020

A self-care movement for social workers is beginning to embrace mindfulness and other forms of wellness. However, self-care is often framed as merely an individualistic pursuit and may be a tool of managerialism, reinforcing the social and economic structures and culture that are causing burnout and moral injury in the first place. Particularly for people who are marginalized, the self-care movement may ignore historical trauma and the ways that interlocking oppressions contribute to stress, trauma, moral injury, and burnout. Drawing from the evidence base on East–West mind–body practices and informed by a transformative practice lens, healing justice is presented as a framework and set of practices of the whole self. The whole self includes the physical, emotional, mental, spiritual, social, and ecological selves. A transformative approach to healing can be supported by enhancing the capabilities of mindfulness, compassion, curiosity, critical inquiry, effort, and equanimity. The concept of the healing justice organization is introduced as an opportunity for organizational change beginning with a set of inquiries for social work organizations to attend structurally and more purposefully to collective care.
Binaural Pitch Fusion in Children With Normal Hearing, Hearing Aids, and Cochlear Implants
Authors: Hartling Curtis L. , Fowler Jennifer R. , Stark Gemaine N. , Glickman Bess , Eddolls Morgan , Oh Yonghee , Ramsey Katrina , Reiss Lina A. J.
Published: April 2020

Objectives:

Binaural pitch fusion is the perceptual integration of stimuli that evoke different pitches between the ears into a single auditory image. Adults who use hearing aids (HAs) or cochlear implants (CIs) often experience abnormally broad binaural pitch fusion, such that sounds differing in pitch by as much as 3 to 4 octaves are fused across ears, leading to spectral averaging and speech perception interference. The main goal of this study was to measure binaural pitch fusion in children with different hearing device combinations and compare results across groups and with adults. A second goal was to examine the relationship of binaural pitch fusion to interaural pitch differences or pitch match range, a measure of sequential pitch discriminability.

Design:

Binaural pitch fusion was measured in children between the ages of 6.1 and 11.1 years with bilateral HAs (n = 9), bimodal CI (n = 10), bilateral CIs (n = 17), as well as normal-hearing (NH) children (n = 21). Depending on device combination, stimuli were pure tones or electric pulse trains delivered to individual electrodes. Fusion ranges were measured using simultaneous, dichotic presentation of reference and comparison stimuli in opposite ears, and varying the comparison stimulus to find the range that fused with the reference stimulus. Interaural pitch match functions were measured using sequential presentation of reference and comparison stimuli, and varying the comparison stimulus to find the pitch match center and range.

Results:

Children with bilateral HAs had significantly broader binaural pitch fusion than children with NH, bimodal CI, or bilateral CIs. Children with NH and bilateral HAs, but not children with bimodal or bilateral CIs, had significantly broader fusion than adults with the same hearing status and device configuration. In children with bilateral CIs, fusion range was correlated with several variables that were also correlated with each other: pure-tone average in the second implanted ear before CI, and duration of prior bilateral HA, bimodal CI, or bilateral CI experience. No relationship was observed between fusion range and pitch match differences or range.

Conclusions:

The findings suggest that binaural pitch fusion is still developing in this age range and depends on hearing device combination but not on interaural pitch differences or discriminability.
“Nailable” External Fixation of the Tibia: A Novel Technique to Accommodate Delayed Intramedullary Nailing of the Tibia
Authors: Savage-Elliott Ian , Wu Victor J. , Nguyen Lan N. , Martin Murphy P. , Gladden Paul B.
Published: April 2020

External fixation is often used for temporary stabilization of the tibia in several clinical scenarios. Conventional placement of external fixation pins may impede instrumentation with intramedullary nailing, thus requiring pin removal, loss of reduction, and increased operative time during definite fixation. In this article, we describe a strategic pin placement routinely used at our institution in which we create a medially based inverted triangular construct that allows for pins to remain in place during definitive fixation.
Evaluation and Management of Hemorrhoids
Authors: Jakubauskas Matas , Poskus Tomas
Published: April 2020

Case Summary:

A 46-year-old otherwise healthy female patient presents with bright red blood during defecation and a lump protruding on defecation that requires manual reduction. She is the mother of 2 children and has a long history of constipation.
Improving outcomes in retinal detachment: the potential role of rho-kinase inhibitors
Authors: Halász Éva , Townes-Anderson Ellen , Zarbin Marco A.
Published: April 2020

Purpose of review

Retinal detachment initiates a series of events that lead to degenerative changes in retinal synaptic architecture as well as the well-known phenomena of gliosis and photoreceptor apoptosis. Retinal reattachment does not always result in complete visual recovery, even if the fovea is not directly involved in the detachment. Rho-kinase (ROCK) inhibitors may mitigate some of these deleterious changes including disruption of synaptic architecture, photoreceptor apoptosis, and initiation of the epithelial-mesenchymal transition that characterizes proliferative vitreoretinopathy (PVR). This review focuses on the use of ROCK inhibitors to modulate synaptic disjunction.

Recent findings

ROCK inhibition prevents retinal detachment-induced photoreceptor synaptic terminal retraction (i.e., synaptic disjunction), thereby diminishing the damage of the first synapse in the visual pathway. ROCK inhibition also reduces retinal detachment-induced photoreceptor apoptosis and suppresses PVR progression in preclinical models.

Inhibition of ROCK may help to optimize visual recovery after retinal detachment surgery or iatrogenic detachments during cell transplantation or viral subretinal injection and might play a role in reducing the risk of PVR after retinal detachment surgery.
Clinical comparison of 27-gauge and 23-gauge instruments on the outcomes of pars plana vitrectomy surgery for the treatment of vitreoretinal diseases
Authors: Charles Steve , Ho Allen C. , Dugel Pravin U. , Riemann Chris D. , Berrocal María H. , Gupta Sunil , Hamilton Cody , Abulon Dina Joy K.
Published: April 2020

Purpose of review

To compare outcomes of 27-gauge and 23-gauge pars plana vitrectomy (PPV) for treatment of vitreoretinal diseases.

Recent findings

Sixty-eight patients undergoing microincisional PPV for treatment of vitreoretinal diseases were randomized 1 : 1 to 27-gauge or 23-gauge surgery with a 7500 cuts-per-minute vitrectomy probe. The most common reasons for vitrectomy were epiretinal membrane (49%) and vitreous hemorrhage (24%). Mean ± standard deviation (SD) changes from immediate preoperative to immediate postoperative intraocular pressure were −0.40 ± 6.60 mmHg in the 27-gauge and −3.05 ± 7.64 mmHg in the 23-gauge group (adjusted mean difference 2.42 mmHg, 95% lower confidence limit 0.64, P = 0.013), but these changes were not associated with primary reason for vitrectomy (P = 0.065). Mean ± SD conjunctival edema grades in the 27-gauge and 23-gauge groups 1 week after surgery were 0.02 ± 0.124 and 0.10 ± 0.246, respectively (least squares mean difference −0.09, 95% upper confidence limit −0.03, P = 0.004), and were 0.01 ± 0.122 and 0.12 ± 0.338, respectively, at the probe incision site. Conjunctival edema grades were similar in both groups at 1 and 3 months. Mean ± SD pain ratings on postoperative day 1 – an indicator of patient comfort – were similar in the two groups.

Smaller diameter vitrectomy instruments are associated with smaller reductions in immediate postoperative intraocular pressure.
Paradoxical Antibiotic Effect of Ampicillin
Authors: Ericson Jessica E. , Hornik Christoph P. , Greenberg Rachel G. , Clark Reese H. , Tremoulet Adriana H. , Le Jennifer , Cohen-Wolkowiez Michael , Smith P. Brian , Benjamin Daniel K. ,   on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network
Published: April 2020

Background:

High doses of ampicillin are often used to achieve therapeutic drug concentrations in infants. A paradoxical antibiotic effect, often called the Eagle effect, occurs when increasing concentrations of antibiotic above a threshold results in decreased efficacy. It is unknown if infants treated with ampicillin are at risk for this paradoxical effect.

Methods:

We identified infants <28 days of age with Escherichia coli, Enterococcus or Streptococcus agalactiae (group B streptococcus) bloodstream infections from 1997 to 2012 and previously included in an ampicillin pharmacokinetic (PK) modeling study. We compared the odds of death for ampicillin dose, estimated time above the minimum inhibitory concentration (T > MIC) and PK parameters using separate logistic regression models. Adjusted logistic regression and Poisson models were used to calculate the odds of prolonged bacteremia ≥3 days and the duration of bacteremia, respectively, for dose, T > MIC and multiple PK parameters.

Results:

Among 1272 infants meeting inclusion criteria, odds of death 7 or 30 days after the positive blood culture were not consistent with a paradoxical effect across any of the dosing regimens or PK parameters evaluated. The odds of prolonged bacteremia was lowest at the lowest dose category and the lowest daily dose category but not associated with the area-under-the-concentration time curve from 0 to 24 hours, or the maximum or minimum concentrations at steady state. T > MIC of ≥50% of the dosing interval was associated with decreased duration of bacteremia and odds of prolonged bacteremia.

Conclusions:

It is unlikely that a paradoxical antibiotic effect will have a clinical correlate when ampicillin is used for neonatal bacteremia. A T > MIC ≥50% decreased both duration of bacteremia and odds of prolonged bacteremia.
Respiratory Syncytial Virus Prophylaxis in Immunocompromised Children
Authors: Paes Bosco A. , Saleem Mahwesh , Li Abby , Lanctôt Krista L. , Mitchell Ian ,   for the CARESS Investigators
Published: April 2020

Background:

Immunocompromised children are at increased risk for respiratory syncytial virus (RSV) infection with associated morbidity and mortality. Prophylaxis is usually provided to these children on a case-by-case basis.

Methods:

Immunocompromised children who received ≥1 injection of palivizumab were prospectively enrolled across 32 Canadian sites, between 2005 and 2017, during the RSV season. We assessed respiratory illness hospitalization (RIH) and RSV-related hospitalization (RSVH) hazard ratios (HRs) in immunocompromised children versus infants’ prophylaxed for standard indications (SI: prematurity ≤35 weeks’ gestation, bronchopulmonary dysplasia, and congenital heart disease) and complex medical disorders (CMD). Data were analyzed using t-tests, χ2 and Cox proportional hazards adjusted for confounders.

Results:

A total of 25,003 infants were recruited; 214 immunocompromised, 4283 CMD, 20,506 SI. On average, children received 4.4 ± 1.3 injections. A total of 16,231 children were perfectly adherent (58.4% immunodeficiency, 68.9% CMD, 64.2% SI; P < 0.0005). A higher proportion of immunocompromised children were aboriginal and exposed to smoking compared with CMD and SI. Immunocompromised children also had a higher median; gestational and enrollment age and birth weight compared with CMD and SI. Immunodeficient children had a higher RIH risk compared with SI (HR = 2.4, 95% confidence interval, 1.3–4.7, P = 0.009) but were similar to CMD (HR = 1.7, 95% confidence interval, 0.9–3.4, P = 0.118). RSVH in prophylaxed, immunocompromised children was similar to CMD (HR < 0.005, P = 0.955) and SI (HR < 0.005, P = 0.953).

Conclusions:

Immunocompromised children who received palivizumab had an increased RIH hazard compared with the SI group. Similar RSVH hazard between the 3 groups suggests that immunocompromised children may benefit from palivizumab during the RSV season.
A Narrative Review of Current Challenges in the Diagnosis and Management of Bacterial Vaginosis
Authors: Muzny Christina A. , Kardas Przemyslaw
Published: April 2020

Despite the availability of a number of oral and intravaginal antibiotic medications for the treatment of bacterial vaginosis (BV), management of this condition remains challenging. Recurrent BV occurs in >50% of patients receiving guideline-recommended treatments. This may be due to persistence or resurgence of the BV biofilm after treatment cessation, failure to reestablish an optimal vaginal microbiome after treatment, reinfection from an untreated sexual partner, or a combination of these factors. Nonadherence to multidose BV therapies may potentially contribute to recurrent BV, although there are no published data that directly assess the role of nonadherence to poor treatment outcomes and recurrent BV. There is a need for studies of BV treatment adherence in real-world settings as well as studies to explore the relationship between treatment adherence and recurrence. This review explores challenges associated with diagnosing and treating BV, current multidose antibiotic treatment options, newer single-dose treatment options, and ways to potentially maximize treatment success for this common vaginal infection.
Invasive Stratified Mucin-producing Carcinoma (ISMC) of the Cervix
Authors: Stolnicu Simona , Segura Sheila , Parra-Herran Carlos , Horn Lars-Christian , Hoang Lynn , Terinte Cristina , Pesci Anna , Aviel-Ronen Sarit , Kyokawa Takako , Alvarado-Cabrero Isabel , Oliva Esther , Soslow Robert A. , Park Kay J.
Published: April 2020

Invasive stratified mucin-producing carcinoma (ISMC) is a recently described tumor with similar morphology to the stratified mucin-producing intraepithelial lesion. Stratified mucin-producing intraepithelial lesion and ISMC likely arise from human papillomavirus (HPV)-infected reserve cells in the cervical transformation zone that retain their pluripotential ability to differentiate into various architectural and cytologic patterns. This is important, as small studies have suggested that ISMC may be a morphologic pattern associated with more aggressive behavior than usual HPV-associated adenocarcinoma. We sought to study the morphologic spectrum of this entity and its associations with other, more conventional patterns of HPV-associated carcinomas. Full slide sets from 52 cases of ISMC were reviewed by an international panel of gynecologic pathologists and classified according to the new International Endocervical Criteria and Classification system. Tumors were categorized as ISMC if they demonstrated stromal invasion by solid nests of neoplastic cells with at least focal areas of mucin stratified throughout the entire thickness, as opposed to conventional tall columnar cells with luminal gland formation. Tumors comprising pure ISMC, and those mixed with other morphologic patterns, were included in the analysis. Twenty-nine pure ISMCs (56%) and 23 ISMCs mixed with other components (44%) were identified. Other components included 13 cases of usual-type adenocarcinoma, 6 adenosquamous carcinoma, 3 mucinous-type adenocarcinoma, 1 high-grade neuroendocrine carcinoma. ISMC displayed architectural diversity (insular, lumen-forming, solid, papillary, trabecular, micropapillary, single cells) and variable cytologic appearance (eosinophilic cytoplasm, cytoplasmic clearing, histiocytoid features, glassy cell-like features, signet ring-like features, bizarre nuclei, squamoid differentiation). Awareness of the spectrum of morphologies in ISMC is important for accurate and reproducible diagnosis so that future studies to determine the clinical significance of ISMC can be conducted.
Needling Policy Makers and Sharpening the Debate: Do Syringe Exchange Programs Improve Health at the Population Level?
Authors: Motie Ian , Carretta Henry J. , Beitsch Leslie M.
Published: April 2020

Context:

In the midst of the current opioid epidemic, states have selected differing legislative routes implementing pathways to ensure access to clean needles and syringes.

Objective:

To determine whether states that implemented laws supporting syringe exchange programs (SEPs) had reductions in transmission rates of hepatitis B, hepatitis C, and HIV infection compared with states without such laws.

Design and Setting:

Utilizing a longitudinal panel design, we determined the legal status of SEPs in each state for years 1983-2016. Disease transmission rates for this period were estimated via a simple Poisson regression, with transmitted cases as the dependent variable, law categories as the predictor variables, and the log of state population as the exposure. The mean number of incident cases per state-year was also calculated.

Participants:

US states were utilized as the unit of analysis.

Results:

Hepatitis B and hepatitis C mean transmission rate per 100 000 population declined in states with local ordinances/decriminalized statutes and legalized SEPs (hepatitis B: 71% and 81%, respectively, differences P < .001; hepatitis C: 8% and 38%, respectively, differences P < .001). Reductions in mean incident cases per state-year mirrored these findings. HIV infection among injection drug users yielded inconsistent results.

Conclusions:

Hepatitis B and hepatitis C transmission were reduced at the population level in states with SEP laws in a pattern reflecting the degree of legal intervention. HIV infection, based upon a smaller data set, showed a mixed impact.

Policy Implications:

The results show promise that SEPs have population-level effects on disease transmission. States lacking SEPs should reconsider current policies.
Decreasing Usage of Lights and Sirens in an Urban Environment: A Quality Improvement Project
Authors: Westley Laura , Nokes Janice , Rozenfeld Ranna A.
Published: April 2020

Introduction:

The risk of lights and sirens use in emergency medical services has been well documented. Our critical care transport team performs over 1,800 interfacility nonemergency medical services transports annually into a dense urban environment. Historically, we have utilized lights and sirens to navigate traffic patterns. The use exceeded industry standards. This quality improvement project was undertaken to decrease the use of lights and sirens.

Methods/Results:

The baseline use of lights and sirens in 2011 was 76% en route and 73% on return to the facility. We revised the internal policy guiding the appropriate usage of lights and sirens. In 2012, without an improvement in usage, a use justification process was implemented. By 2013, the use of lights and sirens was still high en route, but had decreased to 53% on the return trip. In 2014, we added accountability measures requiring justification, with a subsequent drop in 2015 to 14% en route and 13% on return. In the following 3 years, the transport teams have sustained lights and sirens use to 20% or below.

Conclusions:

This quality improvement initiative impacted team behavior and decreased the use of lights and sirens over 5 years, with sustained improvement at or below 20%. This improvement was accomplished through ongoing evaluation, education, data gathering, and open communication. There was no negative impact on patient outcomes during this time. Lights and sirens continue to be used when indicated.
Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes
Authors: Jackson Kyle R. , Long Jane , Motter Jennifer , Bowring Mary G. , Chen Jennifer , Waldram Madeleine M. , Orandi Babak J. , Montgomery Robert A. , Stegall Mark D. , Jordan Stanley C. , Benedetti Enrico , Dunn Ty B. , Ratner Lloyd E. , Kapur Sandip , Pelletier Ronald P. , Roberts John P. , Melcher Marc L. , Singh Pooja , Sudan Debra L. , Posner Marc P. , El-Amm Jose M. , Shapiro Ron , Cooper Matthew , Verbesey Jennifer E. , Lipkowitz George S. , Rees Michael A. , Marsh Christopher L. , Sankari Bashir R. , Gerber David A. , Wellen Jason , Bozorgzadeh Adel , Gaber A. Osama , Heher Eliot , Weng Francis L. , Djamali Arjang , Helderman J. Harold , Concepcion Beatrice P. , Brayman Kenneth L. , Oberholzer Jose , Kozlowski Tomasz , Covarrubias Karina , Desai Niraj , Massie Allan B. , Segev Dorry L. , Garonzik-Wang Jacqueline
Published: April 2020

Background.

Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown.

Methods.

We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes.

Results.

After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates.

Conclusions.

Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.
Stroke Rate, Subtype, and Cardiovascular Risk Factors in Nonarteritic Anterior Ischemic Optic Neuropathy: A Population-Based Study
Authors: Foster Robert C. , Bhatti M. Tariq , Crum Olivia M. , Lesser Elizabeth R. , Hodge David O. , Klaas James P. , Chen John J.
Published: April 2020

Background:

Nonarteritic anterior ischemic optic neuropathy (NAION) is a common cause of acute optic neuropathy in adults and is associated with vascular risk factors. Owing to the overlapping risk factor profiles between NAION and cerebral stroke, previous studies have produced conflicting results with regard to NAION as an independent risk factor for stroke.

Methods:

A retrospective chart review was conducted using the Rochester Epidemiology Project database to identify all cases of NAION occurring among Olmsted County, Minnesota residents from January 1, 1990, through December 31, 2016. Stroke events were characterized using clinical and radiologic data. Comparison was made to an age- and sex-matched control group with similar vascular risk factors.

Results:

One-hundred four patients with NAION and 104 control subjects were analyzed. Median age at diagnosis was 65 years (range, 40–90 years). Thirteen patients (13%) with NAION and 10 controls (10%) had symptomatic strokes after the age of 40 years. Among patients with NAION, 6 (46%) suffered a stroke before the diagnosis of NAION, 5 (39%) at least 5 months after the NAION diagnosis, and 2 patients (15%) suffered strokes both before and after the NAION. The cumulative probability of symptomatic strokes for patients with NAION was not significantly different than for controls (hazard ratio = 1.50, 95% confidence interval: 0.66–3.42; P = 0.34). There were no cardioembolic strokes within 1 month of the NAION diagnosis. The mechanism of symptomatic strokes did not differ between the 2 groups.

Conclusions:

NAION does not confer an increased risk of symptomatic stroke beyond the risk posed by age and existing vascular risk factors.
Dimensionality, symmetry and the Inverse Square Law
Authors: Gatzia Dimitria Electra , Ramsier Rex D.
Published: April 2020

Kant suggested that Newton's Inverse Square Law (ISL) determines the dimensions of space to be three. Much has been written in the philosophical literature about Kant's suggestion, including specific arguments attempting to link the ISL to three-dimensionality. In this article, we explore one such argument and demonstrate that it fails to support the link Kant purports to make between the ISL and the three-dimensionality of space. At best, the link that can be made is between the ISL and symmetry.
Detection of New Delhi metallo-beta-lactamase enzyme gene bla
NDM-1 associated with the Int-1 gene in Gram-negative bacteria collected from the effluent treatment plant of a tuberculosis care hospital in Delhi, India
Authors: Aggarwal Amit , Bhalla Manpreet , Fatima Khan Hena
Published: April 2020

Background. Organisms possessing the bla
NDM-1 gene (responsible for carbapenem resistance) with a class-1 integron can acquire many other antibiotic resistance genes from the community sewage pool and become multidrug-resistant superbugs. In this regard, hospital sewage, which contains a large quantity of residual antibiotics, metals and disinfectants, is being recognized as a significant cause of antimicrobial resistance (AMR) origination and spread across the major centres of the world and is thus routinely investigated as a marker for tracing the origin of drug resistance. Therefore, in this study, an attempt has been made to identify and characterize the carbapenem-resistant microbes associated with integron genes amongst the organisms isolated from the effluent treatment plant (ETP) installed in a tertiary respiratory care hospital in Delhi, India.

Methods. One hundred and thirty-eight organisms belonging to

Escherichia

,

Klebsiella

,

Pseudomonas

and

Acinetobacter

spp. were collected from the incoming and outgoing sewage lines of the ETP. Carbapenem sensitivity and characterization was performed by the imipenem and imipenem-EDTA disc diffusion method. Later DNA extraction and PCR steps were performed for the Int-1 and bla
NDM-1 genes.

Results. Of the 138 organisms, 86 (62.3 %) were imipenem-resistant (P<0.05). One hundred and twenty-four (89.9 %) organisms had one or both of the genes. Overall, the bla
NDM-1 gene (genotypic resistance) was present in 71 % (98/138) of organisms. 53.6 % (74/138) organisms were double gene-positive (bla
NDM-1 + Int-1), of which 40 were producing the metallo-beta-lactamase enzyme, making up almost 28.9 % (40/138) of the collected organisms.

Conclusion. The current study strengthens the hypothesis that Carbapenem resistant organisms are in a high-circulation burden through the human gut and hospital ETPs are providing an environment for resistance origination and amplification.
Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes
Authors: Jain Neha , Shankar Uma , Majee Prativa , Kumar Amit
Published: April 2020

Novel SARS coronavirus (SARS-CoV-2) has caused a pandemic condition world-wide and has been declared as public health emergency of International concern by WHO in a very short span of time. The community transmission of this highly infectious virus has severely affected various parts of China, Italy, Spain and USA among others. The prophylactic solution against SARS-CoV-2 infection is challenging due to the high mutation rate of its RNA genome. Herein, we exploited a next generation vaccinology approach to construct a multi-epitope vaccine candidate against SARS-CoV-2 with high antigenicity, safety and efficacy to combat this deadly infectious agent. The whole proteome was scrutinized for the screening of highly conserved, antigenic, non-allergen and non-toxic epitopes having high population coverage that can elicit both humoral and cellular mediated immune response against COVID-19 infection. These epitopes along with four different adjuvants were utilized to construct a multi-epitope vaccine candidate that can generate strong immunological memory response having high efficacy in humans. Various physiochemical analyses revealed the formation of a stable vaccine product having a high propensity to form a protective solution against the detrimental SARS-CoV-2 strain with high efficacy. The vaccine candidate interacted with immunological receptor TLR3 with high affinity depicting the generation of innate immunity. Further, the codon optimization and in silico expression show the plausibility of the high expression and easy purification of the vaccine product. Thus, this present study provides an initial platform of the rapid generation of an efficacious protective vaccine for combating COVID-19.
Perception of emergent epidemic of COVID-2019 / SARS CoV-2 on the Polish Internet
Authors: Jarynowski Andrzej , Wójta-Kempa Monika , Belik Vitaly
Published: April 2020

Problem

Due to the spread of SARS CoV-2 virus infection and COVID-2019 disease, there is an urgent need to analyze COVID-2019 epidemic perception in Poland. This would enable authorities for preparation of specific actions minimizing public health and economic risks.

Methods

We study the perception of COVID-2019 epidemic in Polish society using quantitative analysis of its digital footprints on the Internet (onTwitter, Google, YouTube, Wikipediaand electronic media represented byEvent Registry) from January 2020 to 12.03.2020 (before and after official introduction to Poland on 04.03.2020). To this end we utilize data mining, social network analysis, natural language processing techniques. Each examined internet platform was analyzed for representativeness and composition of the target group.

Results

We identified three temporal major cluster of the interest before disease introduction on the topic COVID-2019: China- and Italy-related peaks on all platforms, as well as a peak on social media related to the recent special law on combating COVID-2019. Besides, there was a peak in interest on the day of officially confirmed introduction as well as an exponential increase of interest when the Polish government “declared war against disease” with a massive mitigation program. From sociolingistic perspective, we found that concepts and issues of threat, fear and prevention prevailed before introduction. After introduction, practical concepts about disease and epidemic dominate. We have found out that Twitter reflected the structural division of the Polish political sphere. We were able to identify clear communities of governing party, mainstream oppostition and a protestant group and potential sources of disinformation. We have also detected bluring boundaries between comminities after disease introduction.

Conclusions

Traditional and social media do not only reflect reality, but also create it. Due to filter “bubbles” observed on Twitter, public information campaigns might have less impact on society than expected. For greater penetration, it might be necessary to diversify information channels to reach as many people as possible which might already be happening. Moreover, it might be necessary to prevent the spread of disinformation, which is now possible in Poland due to the special law on combating COVID-2019.
SARS-CoV-2 infection in health care workers: a retrospective analysis and model study
Authors: Bai Yansen , Wang Xuan , Huang Qimin , Wang Han , Gurarie David , Ndeffo-Mbah Martial , Fan Fei , Fu Peng , Horn Mary Ann , Xu Shuai , Mondal Anirban , Jiang Xiaobing , Zhao Hongyang
Published: April 2020

Background

There had been a preliminary occurrence of human-to-human transmissions between healthcare workers (HCWs), but risk factors in the susceptibility for COVID-19, and infection patterns among HCWs have largely remained unknown.

Methods

Retrospective data collection on demographics, lifestyles, contact status with infected subjects for 118 HCWs (include 12 COVID-19 HCWs) from a single-center. Sleep quality and working pressure were evaluated by Pittsburgh Sleep Quality Index (PSQI) and The Nurse Stress Index (NSI), respectively. Follow-up duration was from Dec 25, 2019, to Feb 15, 2020. Risk factors and transmission models of COVID-19 among HCWs were analyzed and constructed.

Findings

A high proportion of COVID-19 HCWs had engaged in night shift-work (75.0% vs. 40.6%) and felt they were working under pressure (66.7% vs. 32.1%) than uninfected HCWs. COVID-19 HCWs had higher total scores of PSQI and NSI than uninfected HCWs. Furthermore, these scores were both positively associated with COVID-19 risk. An individual-based model (IBM) estimated the outbreak duration among HCWs in a non-typical COVID-19 ward at 62-80 days and the basic reproduction numberR0=1.27 [1.06, 1.61]. By reducing the average contact rate per HCW by a 1.35 factor and susceptibility by a 1.40 factor, we can avoid an outbreak of the basic case among HCWs.

Interpretation

Poor sleep quality and high working pressure were positively associated with high risks of COVID-19. A novel IBM of COVID-19 transmission is suitable for simulating different outbreak patterns in a hospital setting.

Funding

Fundamental Research Funds for the Central Universities
Multiscale ATUM-FIB microscopy enables targeted ultrastructural analysis at isotropic resolution
Authors: Kislinger Georg , Gnägi Helmut , Kerschensteiner Martin , Simons Mikael , Misgeld Thomas , Schifferer Martina
Published: April 2020

Volume electron microscopy enables the ultrastructural analysis of biological tissues and is essential for dense reconstructions e.g. of neuronal circuits. So far, three-dimensional analysis is based on either serial sectioning followed by sequential imaging (ATUM, ssTEM/SEM) or serial block-face imaging (SB-SEM, FIB-SEM), where imaging is intercalated with sectioning. Currently, the techniques involving ultramicrotomy allow scanning large fields of view, but afford only limited z-resolution determined by section thickness, while ion beam-milling approaches yield isotropic voxels, but are restricted in volume size. Now we present a hybrid method, named ATUM-FIB, which combines the advantages of both approaches: ATUM-FIB is based on serial sectioning of tissue into semithick (2-10 µm) resin sections that are collected onto transparent tape. 3D information obtained by serial light and electron microscopy allows identifying regions of interest that are then directly accessible for targeted FIB-SEM. The set of serial semithin sections thus represent a tissue ‘library’, which provides information about microscopic tissue context that can then be probed ‘on demand’ by local high resolution analysis. We demonstrate the potential of this technique to reveal the ultrastructure of rare but pathologically important events by identifying microglia contact sites with amyloid plaques in a mouse model for familial Alzheimer’s disease.
CeTF: an R package to Coexpression for Transcription Factors using Regulatory Impact Factors (RIF) and Partial Correlation and Information (PCIT) analysis
Authors: de Biagi Carlos Alberto Oliveira , Nociti Ricardo Perecin , Funicheli Breno Osvaldo , de Cássia Ruy Patrícia , Ximenez João Paulo Bianchi , Silva Wilson Araújo
Published: April 2020

Finding meaningful gene-gene associations and the main Transcription Factors (TFs) in co-expression networks is one of the most important challenges in gene expression data mining. CeTF is an R package that integrates the Partial Correlation with Information Theory (PCIT) and Regulatory Impact Factors (RIF) algorithms applied to gene expression data from microarray, RNA-seq, or single-cell RNA-seq platforms. This approach allows identifying the transcription factors most likely to regulate a given network in different biological systems — for example, regulation of gene pathways in tumor stromal cells and tumor cells of the same tumor. This pipeline can be easily integrated into the high-throughput analysis.

Availability

CeTF is available as R package in Bioconductor (https://bioconductor.org/packages/CeTF), GitHub (https://github.com/cbiagii/CeTF) and as docker image (https://hub.docker.com/r/biagii/cetf). More information on how to use the package can be found in the Supplemental File 1.
Maintained representations of the ipsilateral and contralateral limbs during bimanual control in primary motor cortex
Authors: Cross Kevin P. , Heming Ethan A. , Cook Douglas J. , Scott Stephen H.
Published: April 2020

Primary motor cortex (M1) almost exclusively controls the contralateral side of the body. However, M1 activity is also modulated during ipsilateral body movements. Previous work has shown that M1 activity related to the ipsilateral arm is independent of the M1 activity related to the contralateral arm. How do these patterns of activity interact when both arms move simultaneously? We explored this problem by training two monkeys (male, Macaca mulatta) in a postural perturbation task while recording from M1. Loads were applied to one arm at a time (unimanual) or both arms simultaneously (bimanual). We found 83% of neurons were responsive to both the unimanual and bimanual loads. We also observed a small reduction in activity magnitude during the bimanual loads for both limbs (25%). Across the unimanual and bimanual loads, neurons largely maintained their preferred load directions. However, there was a larger change in the preferred loads for the ipsilateral limb (~25%) than the contralateral limb (~9%). Lastly, we identified the contralateral and ipsilateral subspaces during the unimanual loads and found they captured a significant amount of the variance during the bimanual loads. However, the subspace captured more of the bimanual variance related to the contralateral limb (97%) than the ipsilateral limb (66%). Our results highlight that even during bimanual motor actions, M1 largely retains its representations of the contralateral and ipsilateral limbs.

Significance Statement

Previous work has shown that primary motor cortex (M1) reflects information related to the contralateral limb, its downstream target, but also reflects information related to the ipsilateral limb. Can M1 still reflect both sources of information when performing simultaneous movements of the limbs? Here we use a postural perturbation task to show that M1 activity maintains a similar representation for the contralateral limb during bimanual motor actions, while there is only a modest change in the representation of the ipsilateral limb. Our results indicate that two orthogonal representations can be maintained and expressed simultaneously in M1.
Biophysical characterization of the SARS-CoV-2 spike protein binding with the ACE2 receptor and implications for infectivity
Authors: Chowdhury Ratul , Maranas Costas D.
Published: April 2020

SARS-CoV-2 is a novel highly virulent pathogen which gains entry to human cells by binding with the cell surface receptor – angiotensin converting enzyme (ACE2). We computationally contrasted the binding interactions between human ACE2 and coronavirus spike protein receptor binding domain (RBD) of the 2002 epidemic-causing SARS-CoV-1, SARS-CoV-2, and bat coronavirus RaTG13 using the Rosetta energy function. We find that the RBD of the spike protein of SARS-CoV-2 is highly optimized to achieve very strong binding with human ACE2 (hACE2) which is consistent with its enhanced infectivity. SARS-CoV-2 forms the most stable complex with hACE2 compared to SARS-CoV-1 (23% less stable) or RaTG13 (11% less stable) while occupying the greatest number of residues in the ATR1 binding site. Notably, the SARS-CoV-2 RBD out-competes the angiotensin 2 receptor type I (ATR1) which is the native binding partner of ACE2 by 35% in terms of the calculated binding affinity. Strong binding is mediated through strong electrostatic attachments with every fourth residue on the N-terminus alpha-helix (starting from Ser19 to Asn53) as the turn of the helix makes these residues solvent accessible. By contrasting the spike protein SARS-CoV-2 Rosetta binding energy with ACE2 of different livestock and pet species we find strongest binding with bat ACE2 followed by human, feline, equine, canine and finally chicken. This is consistent with the hypothesis that bats are the viral origin and reservoir species. These results offer a computational explanation for the increased infectivity of SARS-CoV-2 and allude to therapeutic modalities by identifying and rank-ordering the ACE2 residues involved in binding with the virus.
High-resolution Structures of multiple 5-HT3AR-setron complexes reveal a novel mechanism of competitive inhibition
Authors: Basak Sandip , Kumar Arvind , Ramsey Steven , Gibbs Eric , Kapoor Abhijeet , Filizola Marta , Chakrapani Sudha
Published: April 2020

Serotonin receptors (5-HT3AR) play a crucial role in regulating gut movement, and are the principal target of setrons, a class of high-affinity competitive antagonists, used in the management of nausea and vomiting associated with radiation and chemotherapies. Structural insights into setron-binding poses and their inhibitory mechanisms are just beginning to emerge. Here, we present high-resolution cryo-EM structures of full-length 5-HT3AR in complex with palonosetron, ondansetron, and alosetron. Each structure reveals a distinct interaction fingerprint between the setron and binding-pocket residues that may underlie their diverse affinities. In addition, setrons elicit varying degrees of conformational change throughout the channel that, quite surprisingly, lie along the channel activation pathway, suggesting a novel mechanism of competitive inhibition. Molecular dynamic simulations were used to assess binding-poses and the drug-target interaction dynamics. Together, this study provides a molecular basis for setron binding affinities and their inhibitory effects.