bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-146a alleviates the apoptosis of hippocampal neurons induced by microglia activation via targeting TRAF6
Authors: Jia J , Liu C , Han Y , Han H , Zhong M , Gao Y
Published: July 2020

Objective:

To identify the role of miR-146a and tumor necrosis factor receptor-associated factor 6 (TRAF6) for improving the apoptosis of hippocampal neurons induced by microglia activation.

Methods:

Mouse microglial cell line (BV2 cell) was employed and treated with lipopolysaccharide. Mouse hippocampal nerve cell line (HT22 cell) was then grown in BV2 conditioned medium, and miR-146a overexpression and silencing cell lines were constructed. CCK8 and clone formation test were utilized to evaluate the proliferation ability of the transfected cells, and the level of inflammatory factors was measured by ELISA. Apoptosis was determined extensively by flow cytometry. The apoptosis-related protein and TRAF6 protein expressions were verified by Western blot. TRAF6 was identified to be the target gene of miR-146a based on double Luciferase Report. Finally, both TRAF6 and miR-146a were used to treat HT22 cells and the above indexes were detected repeatedly.

Results:

Interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 expressions in BV2 cells increased significantly. miR-146a overexpression distinctly increased the cell proliferation ability and B-cell lymphoma-2 expression ((Bcl-2, p < 0.05); meanwhile, the apoptosis rate of cells, apoptosis-related proteins (Bcl-2 associated X and cleaved caspase-3), and TRAF6 gene and protein expressions were significantly decreased ( p < 0.05). However, these above results were reversed for miR-146a silence. There is a targeting relationship between miR-146a and TRAF6. Silencing TRAF6 gene can promote HT22 cells’ proliferation and inhibit apoptosis. The effect of miR-146a on HT22 cells was reversed by adding TRAF6 mimics to miR-146a overexpression cells.

Conclusion:

miR-146a can inhibit the apoptosis of hippocampal neurons caused by microglia activation via targeting TRAF6 and down-regulating its expression.
Dendrobine attenuates isoniazid- and rifampicin-induced liver injury by inhibiting miR-295-5p
Authors: Ci R , Zhang K , Zhu A , Zang W
Published: July 2020

The present study aims to investigate the protective effects of Dendrobine and its underlying mechanisms on liver injury induced by isoniazid (INH) and rifampicin (RIF). A mouse model of liver injury was induced by intragastrically administration of 100 mg/kg INH and 100 mg/kg RIF for 14 days. The mice were intragastrically administrated with Dendrobine (50, 100, and 200 mg/kg) before the administration of INH and RIF. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Oxidative stress markers including glutathione, superoxide dismutase, and malondialdehyde in the liver were measured and liver histopathological examinations were performed. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were applied to determine the mRNA and protein expressions, respectively. Luciferase reporter assay was used to evaluate the interactions between miR-295-5p and CYP1A2. Dendrobine significantly decreased serum ALT and AST and inhibited the liver index and ameliorated the liver histological changes induced by INH and RIF. Besides, Dendrobine also regulated oxidative stress status in the liver by the regulation of CYP1A2. Moreover, mmu-miR-295-5p was identified to target CYP1A2 and to regulate the expression of CYP1A2. In summary, Dendrobine ameliorated INH and RIF induced mouse liver injury by miR-295-5p-mediated CYP1A2 expression.
Myocardial injury in systemic lupus erythematosus according to cardiac magnetic resonance tissue characterization: clinical and echocardiographic features
Authors: du Toit Riëtte , Herbst Phillip G , Ackerman Christelle , Pecoraro Alfonso JK , du Toit Rudolf HR , Hassan Karim , Joubert LLoyd H , Reuter Helmuth , Doubell Anton F
Published: July 2020

Objectives

To determine the prevalence of myocardial injury (MInj) in systemic lupus erythematosus (SLE) according to cardiac magnetic resonance (CMR) criteria. To compare clinical and echocardiographic features of patients with and without MInj and identify predictors of myocardial tissue characteristics according to CMR.

Methods

SLE inpatients underwent CMR screening for MInj based on the Lake Louise Criteria (LLC). Tissue characteristics included inflammation (increased T2-weighted signal or early gadolinium enhancement ratio (EGEr)) and necrosis or fibrosis (late gadolinium enhancement (LGE)). Echocardiographic parameters included left (left ventricular ejection fraction (LVEF)) and right ventricular function (tricuspid annular plane systolic excursion (TAPSE)), global longitudinal strain (GLS), wall motion score (WMSi) and left ventricular internal diameter index (LVIDi). Variables were compared with regards to the presence/absence of CMR criteria. Logistic regression identified variables predictive of CMR tissue characteristics.

Results

A hundred and six SLE patients were screened of whom 49 patients were included. Fifty-seven patients were excluded due to intolerance of or contraindication to CMR (27/57 due to renal impairment). Twenty-three patients had CMR evidence of MInj, of which 60.9% was subclinical. Inflammation occurred in 16/23 and necrosis/fibrosis in 12/23 patients. Patients with any evidence of MInj were more frequently anti-dsDNA positive ( p = 0.026) and patients fulfilling LLC for myocarditis had higher SLE disease activity ( p = 0.022). The LVIDi ( p = 0.005), LVEF ( p = 0.005) and TAPSE ( p = 0.011) were more abnormal in patients with an increased EGEr, whereas WMSi ( p = 0.002) and GLS (0.020) were more impaired in patients with LGE. On multivariable logistic regression analyses, TAPSE predicted inflammation (OR: 0.045, p = 0.006, CI: 0.005–0.415) and GLS predicted necrosis/fibrosis (OR: 1.329, p = 0.031, CI: 1.026–1.722). A model including lymphocyte count, TAPSE and LVIDi predicted an increased EGEr on CMR (receiver operating characteristic-curve analyses: area under the curve: 0.901, p < 0.001, sensitivity: 88.9%, specificity: 76.3%).

Conclusions

CMR evidence of MInj frequently occurs in SLE and is often subclinical. The utility of CMR in SLE is limited by a high exclusion rate, mainly due to renal involvement. Models including echocardiographic parameters (TAPSE, LVIDi and GLS) are predictive of CMR myocardial injury. Echocardiography can be used as a cost-effective screening tool with a high negative predictive value, in particular when CMR is contraindicated or unavailable.
Smearing time: Critical temporality and corporate ontology
Authors: Genosko Gary , Hegarty Paul
Published: July 2020

Since 1972 a leap second has been introduced into global time standardization systems, due to the discrepancy between Coordinated Universal Time and International Atomic Time. Until recently, the leap second has been a consensual, if mildly uncanny adjustment, a para-governmental temporal wobble. Google's explanation of its actions with regard to the insertion of a leap second smeared into its Network Time Protocol servers is couched in terms of a period extending initially over 20 h, ultimately reaching 24 h. Google is intent on taking ownership of the smear and transducing it into a technologically stabilised change. Although there are a number of different strategies of smearing time, Google advocates for its standard smear that it wants other digital giants like Bloomberg, Amazon and Microsoft to replicate. In this paper we first analyze Google's temporal strategy in terms of its affinities and departures from the classical view of time in Aristotle's core considerations in the Physics Book IV, in terms of a consonant enumeration but in our example at variable speeds/intervals, and then in terms of Wolfgang Ernst's conception of time-critical media. Leap seconds conform to Ernst's sense of kairotic time, an auspicious micro-moment that is both techno-mathematically pre-defined and decisive for ensuring operationality. Google executes smeared time-critical processes but wants to establish mastery over the measurement and manipulation of humanly imperceptible microtemporal events by inhabiting temporal ontology itself, proposing its practice, based on misleading its servers, as a model for other digital hegemons.
Comparison of commercial manual extraction kits for RNA isolation from canine whole blood
Authors: Tesfamichael Dahlia H. , Wood Michael W. , Pritchard Jessica C.
Published: July 2020

High quantities of quality RNA are necessary for many veterinary laboratory tests. Several commercial kits are available for RNA isolation from human whole blood; their resultant RNA yield and purity have not been reported for canine whole blood, to our knowledge. We assessed the performance of 4 RNA extraction kits (RiboPure, TRIzol, RNeasy Protect animal blood, and QIAamp RNA blood mini). Whole blood from a healthy dog was stored in the manufacturer-recommended RNA stabilizing buffer as directed. RNA isolation, including DNase treatment, was performed using each kit’s manufacturer’s protocol. Resultant RNA yield and purity were evaluated using spectrophotometric absorbance, capillary electrophoresis and electropherogram analysis, and a reverse-transcription real-time PCR (RT-rtPCR) assay. The RNeasy Protect animal blood kit extracted the highest, and RiboPure the lowest, concentration of nucleic acid. RNA integrity numbers classified extracted RNA as good quality or better for all kits except RNeasy Protect. All kits had evidence of genomic DNA contamination as assessed by RT-rtPCR. Overall, QIAamp RNA blood mini kit and TRIzol optimized both RNA yield and purity from canine whole blood. These kits extracted high quantities of good quality RNA as evidenced by high RNA integrity numbers and minimal contamination with proteins and solvents.
Opioids May be Appropriate for Chronic Pain
Authors: Christo Paul J.
Published: July 2020

Patients living with chronic pain require appropriate access to opioid therapy along with improved access to pain care and additional therapeutic options. It's both medically reasonable and ethical to consider opioid therapy as a treatment option in the management of chronic, non-cancer pain for a subset of patients with severe pain that is unresponsive to other therapies (e.g., injections, other medications, integrative strategies), negatively impacts function or quality of life, and will likely outweigh the potential harms. This paper will examine opioid therapy in the setting of the opioid epidemic, why critics feel that the CDC guideline has resulted in harsh consequences for patients and their physicians, and the rationale for opioid therapy as a means of providing ethical and compassionate pain care.
An Effective Intervention: Limiting Opioid Prescribing as a Means of Reducing Opioid Analgesic Misuse, and Overdose Deaths
Authors: Fink Brandi C. , Uyttebrouck Olivier , Larson Richard S.
Published: July 2020

Overdose deaths involving prescription opioids killed more than 17,000 Americans in 2017, marking a five-fold increase since 1999. High prescribing rates of opioid analgesics have been a substantial contributor to prescription opioid misuse, dependence, overdose and heroin use. There was recognition approximately ten years ago that opioid prescribing patterns were contributing to this startling increase in negative opioid-related outcomes, and federal actions, including Medicare reimbursement reform and regulatory actions, were initiated to restrict opioid prescribing. The current manuscript is a description of those actions, the effect of those actions on opioid prescribing and related patient outcomes. We also describe our proposal of methods of expanding these efforts as an important piece to further reduce opioid-related misuse, dependence, and overdose death.
A Matter of Intent: A Social Obligation to Improve Criminal Procedures for Individuals with Dementia
Authors: Arias Jalayne J. , Flicker Lauren S.
Published: July 2020

The relationship between dementia and criminal behavior perplexes legal and health care systems. Dementia is a progressive clinical syndrome defined by impairment in at least two cognitive domains that interferes with one's activities of daily. Dementia symptoms have been associated with behaviors that violate social norms and constitute criminal actions. A failure to address a gap in policies that support appropriate management of individuals with dementia reflects a failure in our social obligation to care for those who are most vulnerable amongst us. Categorical protections, informed by precedent models applied to juveniles and individuals with psychiatric illness, could help meet a social obligation to provide protections to individuals with dementia. We propose an approach that integrates affirmative defenses to mitigate criminal liability and sentencing restrictions to prevent cruel and unusual punishment.
Should I Stay or Should I Go? A Bioethical Analysis of Healthcare Professionals' and Healthcare Institutions' Moral Obligations During Active Shooter Incidents in Hospitals — A Narrative Review of the Literature
Authors: Giwa Al , Milsten Andrew , Vieira Dorice , Ogedegbe Chinwe , Kelly Kristen , Schwab Abraham
Published: July 2020

Active shooter incidents (ASI) have unfortunately become a common occurrence the world over. There is no country, city, or venue that is safe from these tragedies, and healthcare institutions are no exception. Healthcare facilities have been the targets of active shooters over the last several decades, with increasing incidents occurring over the last decade. People who work in healthcare have a professional and moral obligation to help patients. As concerns about the possibility of such incidents increase, how should healthcare institutions and healthcare professionals understand their responsibilities in preparation for and during ASI?
Coexisting systemic and organ-specific autoimmunity in MOG-IgG1-associated disorders versus AQP4-IgG+ NMOSD
Authors: Kunchok Amy , Flanagan Eoin P , Snyder Melissa , Saadeh Ruba , Chen John J , Weinshenker Brian G , McKeon Andrew , Pittock Sean J
Published: July 2020

Aquaporin-4 (AQP4) neuromyelitis optica spectrum disorder (NMOSD) has been demonstrated to be associated with non-organ and organ-specific autoantibodies (antinuclear antibody, extractable nuclear antibody, double-stranded DNA, muscle acetylcholine receptor antibody) and systemic autoimmune diseases. In this study, we evaluated whether a similar association with non-organ and organ-specifc autoantibodies occurs in patients with MOG-IgG1-associated disorders. We determined that MOG-IgG1 was not strongly associated with these organ and non-organ-specific autoantibodies. Systemic lupus erythematous (SLE) was significantly associated with AQP4-IgG+ NMOSD and not with MOGAD ( p = 0.037). These findings suggest differences in co-existing systemic and organ-specific autoimmunity between MOGAD and AQP4-IgG+ NMOSD.
Characterization and analysis of exhaust pipe (muffler) contact burns: An unsuspecting culprit
Authors: Hansen Trevor C , Patel Alap U , Pencek Megan E , Bell Derek E
Published: July 2020

Introduction

Thermal injury due to contact with engine exhaust systems represents a distinct subgroup of acute contact burns. Temperatures generated by motor vehicle, radiator, and lawn mower engines can exceed 250℃, at which point relatively deep tissue loss occurs with less than 0.06 seconds of cutaneous exposure. While prior studies have helped elucidate the demographic characteristics of exhaust pipe contact burns, our analysis was aimed at both demographics and burn severity, as indicated by rate of full-thickness injury and requirement for tangential excision and skin grafting.

Methods

Data were obtained from a retrospective review of admissions at a regional burn center between 1 July 2012 and 30 August 2016. Patients of all ages with muffler, exhaust, motorcycle, lawn mower, and radiator burn injuries were included. Extensive demographic information, percent total body surface area burned (TBSA), burn etiology and location, third-degree and fourth-degree burn percentage, and subsequent operative information were analyzed for patients who sustained exhaust pipe contact burns. These data were then compared with all contact burn injuries from the same time period, matched for %TBSA range, using Fisher exact and unpaired t-tests.

Results

A total of 110 patients suffered exhaust pipe contact burns during the study period; 65 (59%) were males, and mean age was 30. Nearly two thirds of the muffler burns were sustained from motorcycles with TBSA ranging from 0.05% to 3.14%; at least 61% had some third-degree burn. The average number of operating room visits per patient was 0.54, though this varied significantly, with 38 patients (35%) requiring 59 total surgeries (range 1–6). Muffler burn patients were older than the matched control group. The most common location of burn injury was the lower leg with no difference between adults and children. Pediatric patients understandably had smaller burn surface area but similar TBSA compared to adults. The majority of injuries occurred in May, June, and July.

Conclusions

Exhaust pipe contact burns comprise a specific subset of low %TBSA contact burns with relatively high morbidity, evidenced by a significantly higher proportion of full-thickness tissue loss and eventual need for skin grafting when compared with nonexhaust burn controls. Awareness of the increased severity of exhaust pipe contact burns may lead to more expedient surgical intervention as well as further education regarding preventative measures.
Reclassifying severity after 48 hours could better predict mortality in acute respiratory distress syndrome
Authors: Chiu Li-Chung , Lin Shih-Wei , Liu Pi-Hua , Chuang Li-Pang , Chang Chih-Hao , Hung Chen-Yiu , Li Shih-Hong , Lee Chung-Shu , Wu Huang-Pin , Huang Chung-Chi , Li Hsin-Hsien , Kao Kuo-Chin , Hu Han-Chung
Published: July 2020

Background:

Disease severity may change in the first week after acute respiratory distress syndrome (ARDS) onset. The aim of this study was to evaluate whether the reclassification of disease severity after 48 h (i.e. day 3) of ARDS onset could help in predicting mortality and determine factors associated with ARDS persistence and mortality.

Methods:

We performed a secondary analysis of a 3-year prospective, observational cohort study of ARDS in a tertiary care referral center. Disease severity was reclassified after 48 h of enrollment, and cases that still fulfilled the Berlin criteria were regarded as nonresolving ARDS.

Results:

A total of 1034 ARDS patients were analyzed. Overall hospital mortality was 57.7% (56.7%, 57.5%, and 58.6% for patients with initial mild, moderate, and severe ARDS, respectively, p = 0.189). On day 3 reclassification, the hospital mortality rates were as follows: resolved (42.1%), mild (47.9%), moderate (62.4%), and severe ARDS (76.1%) ( p < 0.001). Patients with improving severity on day 3 had lower mortality (48.8%), whereas patients with the same or worsening severity on day 3 had higher mortality (62.7% and 76.3%, respectively). Patients who were older, had lower PaO2/FiO2, or higher positive end-expiratory pressure on day 1 were significantly associated with nonresolving ARDS on day 3. A Cox regression model with ARDS severity as a time-dependent covariate and competing risk analysis demonstrated that ARDS severity was independently associated with hospital mortality, and nonresolving ARDS had significantly increased hazard of death than resolved ARDS ( p < 0.0001). Cumulative mortality curve for ARDS severity comparisons demonstrated significantly different (overall comparison, p < 0.001).

Conclusions:

Reclassification of disease severity after 48 h of ARDS onset could help to divide patients into subgroups with greater separation in terms of mortality. The reviews of this paper are available via the supplemental material section.
Origins and functions of climate-related relocation: An analytical review
Authors: Marter-Kenyon Jessica
Published: July 2020

Planned, state-led population relocation is advanced as an adaptation to climate change. Concerned that climate hazards will threaten settlement viability and provoke widespread, unplanned migration, global discourse overwhelmingly characterizes relocation as a voluntary, “last resort” effort to resettle and rebuild communities in safer areas. Over the past decade, scholars have investigated where and why climate-related relocation materializes and how it functions as an adaptation (or otherwise). This article systematically reviews the scientific literature, concluding that climate-related relocation is a more diverse and complex process than recognized within dominant research efforts and policy narratives. While climate-related relocation is sometimes a function of environmental migration pressures and adaptation imperatives, recent critical scholarship shows that climate-related relocation processes are embedded in historical responses to environment and development problems and unfold through political negotiation, discourse, and the social construction of risk and response. In practice, “adaptive relocation” frequently involves population redistribution (villagization and sedentarization) as well as resettlement, is often proactive and involuntary, and risks (re)producing maladaptive outcomes. Based on this analysis, I argue for an expanded research and policy agenda centered around a pluralistic conceptual framework that respects the diversity of relocation efforts undertaken as adaptation.
Randomized Pilot Trial of Acute Normovolemic Hemodilution in Pediatric Cardiac Surgery Patients
Authors: Harris Weronika M. , Treggiari Miriam M. , LeBlanc Ashleigh , Giacomuzzi Carmen , You Jayme J. , Muralidaran Ashok , Shen Irving
Published: July 2020

Background:

Due to the substantial improvement in survival among pediatric patients undergoing congenital heart surgery, reducing early and long-term morbidity is becoming the major focus of care. Blood transfusion is associated with worse postoperative outcomes after cardiac surgery. Acute normovolemic hemodilution (ANH) is a blood conservation strategy that aims to reduce allogenic blood transfusion during cardiac surgery. However, there are scant data regarding its efficacy for pediatric cardiac surgery patients.

Methods:

We designed a single-center, controlled, randomized, pilot trial in patients between 6 and 36 months old undergoing pediatric heart surgery. Patients were equally assigned to undergo ANH prior to initiation of cardiopulmonary bypass or to be managed per usual care. The primary end point was the amount of blood product transfused perioperatively. Secondary end points were markers of morbidity: postoperative bleeding, hematocrit, inotropic agents use, intensive care unit, and hospital stay. The analysis was by intention-to-treat. Estimates of differences between groups are presented with 95% CIs.

Results:

Twelve pediatric heart surgery patients were randomized to each group, ANH and usual care. Baseline characteristics were similar between groups. Acute normovolemic hemodilution implementation did not result in a reduction in the administration of blood product transfused (difference between ANH and usual care among patients transfused = −1.4 mL [−29.4 to 26.6], P = .92). Secondary end points were not different between groups.

Conclusions:

In this small trial of pediatric cardiac surgery patients, ANH as a strategy to reduce blood component therapy was safe; however, the study failed to show a reduction in perioperative transfusion or other postoperative outcomes.
Theoretical Reflections on the Underutilization of Employee Talents in the Workplace and the Consequences
Authors: Jessurun J. H. , Weggeman M. C. D. P. , Anthonio G. G. , Gelper S. E. C.
Published: July 2020

This article describes “chronic relative underperformance” (CRU)—a special example of P-E misfit. It investigates literature on giftedness, underachievement, underemployment, workplace boredom, and boreout, and connects these to clinical psychological views on mentalization. The intent is to develop thoughts that are useful in the understanding of why some employees fail to thrive, even though they are performing seemingly well enough as regards to the targets of the employer, and offer a frame of reference that can lead to further understanding of this condition. CRU is an issue that is hardly described within the literature. Recognizing CRU in the workforce and taking steps to counter its effects may lead to a more efficient and elegant way to reach organizational, and personal, goals.
Mindfulness as Relational: Participants’ Experience of Mindfulness-based Programs Are Critical to Fidelity Assessments
Authors: Monteiro Lynette M
Published: July 2020

Mindfulness outcome research has been criticized for issues in research design, precision of outcome measures, and reporting overoptimistically their power to effect change. Although mindfulness programs are a complex interaction of teachers, teachings, and participants, it is of some concern that current assessments of program fidelity focus primarily on teacher skills and program content delivery. Although ensuring that teachers are trained to criteria and adhere to program elements, the participants’ engagement, a critical parameter contributing to outcomes of mindfulness programs, has been neglected. Furthermore, the assessment measures are primarily actuarial even when assessing experiential or difficult-to-define aspects of teacher–participant interactions. The inclusion of the participants’ experience of the program as a component of fidelity assessments creates several opportunities to deepen our understanding of how mindfulness impacts the lives of practitioners. By investigating the teacher–participant relationship, determining how participants process the core elements, and exploring the implementation of the practices in their lives, a more nuanced understanding of the capacity of mindfulness-based programs to effect positive change may be possible.
Does Intramedullary Nailing for Distal Fibular Fractures Restore Anatomic Parameters and Syndesmotic Relationship?
Authors: Mikenberg Natalio R. Cuchacovich , Gallardo Francisco J. Bravo , Giannini Esteban , Astudillo Claudia , Pellegrini Manuel J. , Muñoz Gerardo , Melo Rodrigo , Cortes Aaron , Bastias Gonzalo F.
Published: July 2020

Category:

Trauma; Ankle

Introduction/Purpose:

Fibular nailing (FN) is a method of fixation that has proven to be useful for the treatment of distal fibular fractures (DF). FN minimizes soft tissue complications, provides similar stability compared to plating with less hardware related symptoms. Nevertheless, FN has been associated with syndesmotic malreduction and incapacity of restoring length and rotation of the fibula. We aimed to evaluate the fibular and syndesmotic reduction after fixation with FN compared to the uninjured ankle.

Methods:

Prospective cohort, cross-sectional study with a paired control group. Patients with DF fractures treated with FN between January 2017 and July 2019 were included. Immediate postoperative bilateral Ankle CT was obtained in all cases. Two independent radiologists performed all the measurements on both ankles (fibular rotation, length, translation, and syndesmotic diastasis. Statistical analysis was made using the Wilcoxon Test and Intraclass correlation coefficient (ICC). Considering a medium size sample effect, 95% confidence with .05 alpha error, a total sample of 26 subjects were needed to achieve a .80 of statistical power (G-Power 3.1). All analyses were performed using SPSS V20.

Results:

Twenty-six patients were included (14 Women). The mean age was 47 years (18-91). No statistically significant differences were identified considering fibular rotation (p:0,694), fibular length (p:0,585) and syndesmotic diastasis (p:0,078) between the injured and uninjured ankle. Fibular translation has statistical differences (p:0,043). The ICC shows an excellent concordance between radiologists except for Fibular translation (ICC 0,47)

Conclusion:

In this cohort, fixation of DF fractures with FN allows restoration of anatomical parameters of the ankle in terms of fibular rotation, length, and syndesmotic diastasis. However, Fibular translation had significant differences compared with the uninjured ankle.
Hindfoot Alignment after Total Ankle Replacement
Authors: Gross Christopher E. , Usuelli Federico Guiseppe , Indino Christian
Published: July 2020

Category:

Ankle Arthritis; Ankle

Introduction/Purpose:

End-stage ankle arthritis can involve misalignment of the ankle in both the coronal and sagittal planes as up to reported 33% to 44% of patients who present for total ankle replacement have greater than 10° of coronal plane deformity. Improvements in both the design and surgical technique for total ankle replacements (TAR) have allowed surgeons to tackle the most challenging of multiplanar ankle deformities. Normalization of the sagittal and coronal alignment is key in improving survivorship and functional outcomes in TAR. In the present study, we analyzed how both the ankle and hindfoot alignment for both a fixed-bearing and mobile bearing TAR system changes over time. Specifically, we measured coronal and sagittal alignment of both the ankle and hindfoot complex. We hypothesize that both significant differences would be seen between all time points and pre-operative radiographs, and that these differences would not change over time.

Methods:

A retrospective study performed by a single orthopaedic surgeon was performed on two independent groups of patients undergoing two different systems for total ankle replacement: Zimmer TAR (lateral-approach, fixed-bearing, n=89) and Hintegra (anterior approach, mobile-bearing, n=81). We noted specific demographic data and radiographic data were measured including: Hindfoot alignment view angle (HAV), Hindfoot alignment distance (HAVD), tibiotalar ratio, α angle and β angle. These were measured pre-operatively, and 6 months, 12 months, and 24 months post-operatively. Within-group comparisons were performed using one-way repeated-measures ANOVA (1-w rANOVA), analyzing temporal course of clinical data (comparisons between different time points, e.g. T0vsT6vsT12vsT24) within the Hintegra and Zimmer groups. To compare the time course of clinical measures between the two groups, 2-w rANOVAs were performed for SA, SD, TT ratio, α and β angle. Specifically, time*group interaction was tested.

Results:

At the ankle joint itself, as measured by the α and β angles (p>.05), the position of the components remains relatively similar in both the fixed and mobile bearing TAR over the course of 24 months. The sagittal alignment, as measured by the TT ratio, demonstrated a posterior shifting of the talus in the mobile bearing group (p=.036). Though the fixed and mobile- bearing TAR had both significant hindfoot alignment improvement between the pre-op radiographs and twenty-four months, over time, the fixed-bearing ankle had a significant increase in both the HAV and HAVD (p<.001), suggesting a dynamism of the hindfoot in the fixed-bearing ankle.

Conclusion:

Correcting coronal and sagittal alignment is important for the long-term survivorship of a TAR. The fixed and mobile-bearing implants had maintained coronal and sagittal alignment in the short term, the temporal course of the fixed-bearing ankle showed an increased in the valgus positioning of the hindfoot.
Effects of long-period processing on structural collapse predictions
Authors: Buyco Kenny , Roh Becky , Heaton Thomas H.
Published: July 2020

We investigate the extent to which applying high-pass filters to ground motion records affects the collapse capacity of building models. We consider 26 ground motion records from seven large earthquakes and high-pass filter them with corner periods, [Formula: see text], ranging from 10 to 60 s. We perform incremental dynamic analysis on 9-, 20-, and 55-story steel moment-frame building models with fundamental periods of 1.88, 3.50, and 6.10 seconds, respectively. Even though filters with [Formula: see text] have a minimal effect on the collapse capacities of the building models, we find that for a few motions, collapse capacities can increase by more than 50%, if Tc = 10 or 15 s, even for the 9-story models. We find that the collapse capacities with respect to raw, uncorrected records are generally similar to those of the tilt-corrected versions, indicating that removing long-period noise with high-pass filters can make collapse predictions less accurate, if Tc < 20 s.
Specific patterns of H3K79 methylation influence genetic interaction of oncogenes in AML
Authors: Kingsley Molly C. , Xie Hongbo M. , Chen Bo-Rui , Riedel Simone S. , Pastuer Taylor , Bollig Madelyn K. , Shank Tyler , Libbrecht Clara , Stabler Sally P. , Deshpande Aniruddha J. , Intlekofer Andrew M. , Bernt Kathrin M.
Published: July 2020

Understanding mechanisms of cooperation between oncogenes is critical for the development of novel therapies and rational combinations. Acute myeloid leukemia (AML) cells with KMT2A-fusions and KMT2A partial tandem duplications (KMT2APTD) are known to depend on the histone methyltransferase DOT1L, which methylates histone 3 lysine 79 (H3K79). About 30% of KMT2APTD AMLs carry mutations in IDH1/2 (mIDH1/2). Previous studies showed that 2-hydroxyglutarate produced by mIDH1/2 increases H3K79 methylation, and mIDH1/2 patient samples are sensitive to DOT1L inhibition. Together, these findings suggested that stabilization or increases in H3K79 methylation associated with IDH mutations support the proliferation of leukemias dependent on this mark. However, we found that mIDH1/2 and KMT2A alterations failed to cooperate in an experimental model. Instead, mIDH1/2 and 2-hydroxyglutarate exert toxic effects, specifically on KMT2A-rearranged AML cells (fusions/partial tandem duplications). Mechanistically, we uncover an epigenetic barrier to efficient cooperation; mIDH1/2 expression is associated with high global histone 3 lysine 79 dimethylation (H3K79me2) levels, whereas global H3K79me2 is obligate low in KMT2A-rearranged AML. Increasing H3K79me2 levels, specifically in KMT2A-rearrangement leukemias, resulted in transcriptional downregulation of KMT2A target genes and impaired leukemia cell growth. Our study details a complex genetic and epigenetic interaction of 2 classes of oncogenes, IDH1/2 mutations and KMT2A rearrangements, that is unexpected based on the high percentage of IDH mutations in KMT2APTD AML. KMT2A rearrangements are associated with a trend toward lower response rates to mIDH1/2 inhibitors. The substantial adaptation that has to occur for 2 initially counteracting mutations to be tolerated within the same leukemic cell may provide at least a partial explanation for this observation.
Reduced-intensity single-unit unrelated cord blood transplant with optional immune boost for nonmalignant disorders
Authors: Vander Lugt Mark T. , Chen Xiaohua , Escolar Maria L. , Carella Beth A. , Barnum Jessie L. , Windreich Randy M. , Hill Memphis J. , Poe Michelle , Marsh Rebecca A. , Stanczak Heather , Stenger Elizabeth O. , Szabolcs Paul
Published: July 2020

Children with many inherited nonmalignant disorders can be cured or their condition alleviated by hematopoietic stem cell transplantation (HSCT). Umbilical cord blood (UCB) units are a rapidly available stem cell source and offer great flexibility in HLA matching, allowing nearly uniform access to HSCT. Although reduced-intensity conditioning (RIC) regimens promise decreased treatment-related morbidity and mortality, graft failure and infections have limited their use in chemotherapy-naive patients. We prospectively evaluated a novel RIC regimen of alemtuzumab, hydroxyurea, fludarabine, melphalan, and thiotepa with a single-unit UCB graft in 44 consecutive patients with inborn errors of metabolism, immunity, or hematopoiesis. In addition, 5% of the UCB graft was re-cryopreserved and reserved for cord donor leukocyte infusion (cDLI) posttransplant. All patients engrafted at a median of 15 days posttransplant, and chimerism was >90% donor in the majority of patients at 1-year posttransplant with only 1 secondary graft failure. The incidence of grade II to IV graft-versus-host disease (GVHD) was 27% (95% confidence interval [CI], 17-43) with no extensive chronic GVHD. Overall survival was 95% (95% CI, 83-99) and 85% (95% CI, 64-93) at 1 and 5 years posttransplant, respectively. No significant end-organ toxicities were observed. The use of cDLI did not affect GVHD and showed signals of efficacy for infection control or donor chimerism. This RIC transplant regimen using single-unit UCB graft resulted in outstanding survival and remarkably low rates of graft failure. Implementation of the protocol not requiring pharmacokinetic monitoring would be feasible and applicable worldwide for children with inherited disorders of metabolism, immunity, or hematopoiesis. This trial was registered at www.clinicaltrials.gov as #NCT01962415.
Cumulative inactivated vaccine exposure and allergy development among children: a birth cohort from Japan
Authors: Yamamoto-Hanada Kiwako , Pak Kyongsun , Saito-Abe Mayako , Yang Limin , Sato Miori , Mezawa Hidetoshi , Sasaki Hatoko , Nishizato Minaho , Konishi Mizuho , Ishitsuka Kazue , Matsumoto Kenji , Saito Hirohisa , Ohya Yukihiro ,   Japan Environment and Children’s Study (JECS) Group, Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Ito Shuichi , Yamagata Zentaro , Inadera Hidekuni , Kamijima Michihiro , Nakayama Takeo , Iso Hiroyasu , Shima Masayuki , Kurozawa Youichi , Suganuma Narufumi , Kusuhara Koichi , Katoh Takahiko
Published: July 2020

Background

Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development.

Methods

We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children’s Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age.

Results

Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028–1.893) or four to five different inactivated vaccines (aOR 1.544, 95% CI 1.149–2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e. wheeze (aOR 1.238, 95% CI 1.094–1.401; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007–1.299; four or five vaccines vs. a single vaccine).

Conclusions

Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue.

Trial registration

UMIN000030786.
Inequalities in measles immunization coverage in Ethiopia: a cross-sectional analysis of demographic and health surveys 2000–2016
Authors: Shibre Gebretsadik , Zegeye Betregiorgis , Idriss-Wheeler Dina , Yaya Sanni
Published: July 2020

Background

Ethiopia has low measles immunization coverage and little is known about the disparities surrounding what coverage is provided. This study assessed disparities in measles immunization and its change over time using the four Ethiopia Demographic and Health Surveys conducted between 2000 and 2016.

Methods

This is a cross-sectional analysis of data using Ethiopia Demographic and Health Surveys (EDHS) conducted between 2000 and 2016. We used the World Health Organization’s (WHO) Health Equity Assessment Toolkit (HEAT) to present the inequalities. Four measures of inequality were calculated: Difference (D), Ratio (R), Population Attributable Fraction (PAF) and Population Attributable Risk (PAR). The results were disaggregated by wealth, education, residence, sex and sub-national regions and 95% Uncertainty Intervals (UIs) were computed for each point estimate to boost confidence of the findings.

Results

Measles immunization coverage was higher among the richest and secondary and above schools’ subgroup by nearly 30 to 31 percentage points based on point estimates (D = 31%; 95% CI; 19.48, 42.66) and 29.8 percentage points (D = 29.8%; 95% CI; 16.57, 43.06) as compared to the poorest and no education subgroup respectively in the 2016 survey. Still, in the 2016 survey, substantial economic status (PAF = 36.73; 95%CI: 29.78, 43.68), (R = 1.71; 95%CI: 1.35, 2.08), education status (PAF = 45.07; 95% CI: 41.95, 48.18), (R = 1.60; 95% CI: 1.30, 1.90), place of residence (PAF = 39.84, 95% CI: 38.40, 41.27), (R = 1.47, 95% CI: 1.20, 1. 74) and regional (PAF = 71.35, 95% CI: 31.76, 110.95), (R = 3.09, 95%CI: 2.01, 4.17) inequality were observed with both simple and complex measures. There was no statistically significant difference in the prevalence of measles immunization between male and female children in all the studied years, as indicated, for instance, by measures of PAF in 2000 (PAF = 0; 95%CI: − 6.79, 6.79), 2005 (PAF = 0; 95%CI: − 6.04, 6.04), 2011(PAF = 0; 95%CI: − 3.79, 3.79) and 2016 (PAF = 2.66; − 1.67; 6.99). Overall, the inequality of measles immunization narrowed significantly by at least some of the measures between the first and the last survey periods across all the studied subgroups.

Conclusions

National, regional and district levels of government should make a pledge to reduce inequalities in coverage of measles immunization. Equity-sensitive strategies, sufficient human and financial resources as well as continued research and monitoring of immunization coverage inequalities are necessary to achieve related sustainable development goals.
Mapping male circumcision for HIV prevention efforts in sub-Saharan Africa
Authors: Cork Michael A. , Wilson Kate F. , Perkins Samantha , Collison Michael L. , Deshpande Aniruddha , Eaton Jeffrey W. , Earl Lucas , Haeuser Emily , Justman Jessica E. , Kinyoki Damaris K. , Mayala Benjamin K. , Mosser Jonathan F. , Murray Christopher J. L. , Nkengasong John N. , Piot Peter , Sartorius Benn , Schaeffer Lauren E. , Serfes Audrey L. , Sligar Amber , Steuben Krista M. , Tanser Frank C. , VanderHeide John D. , Yang Mingyou , Wabiri Njeri , Hay Simon I. , Dwyer-Lindgren Laura
Published: July 2020

Background

HIV remains the largest cause of disease burden among men and women of reproductive age in sub-Saharan Africa. Voluntary medical male circumcision (VMMC) reduces the risk of female-to-male transmission of HIV by 50–60%. The World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) identified 14 priority countries for VMMC campaigns and set a coverage goal of 80% for men ages 15–49. From 2008 to 2017, over 18 million VMMCs were reported in priority countries. Nonetheless, relatively little is known about local variation in male circumcision (MC) prevalence.

Methods

We analyzed geo-located MC prevalence data from 109 household surveys using a Bayesian geostatistical modeling framework to estimate adult MC prevalence and the number of circumcised and uncircumcised men aged 15–49 in 38 countries in sub-Saharan Africa at a 5 × 5-km resolution and among first administrative level (typically provinces or states) and second administrative level (typically districts or counties) units.

Results

We found striking within-country and between-country variation in MC prevalence; most (12 of 14) priority countries had more than a twofold difference between their first administrative level units with the highest and lowest estimated prevalence in 2017. Although estimated national MC prevalence increased in all priority countries with the onset of VMMC campaigns, seven priority countries contained both subnational areas where estimated MC prevalence increased and areas where estimated MC prevalence decreased after the initiation of VMMC campaigns. In 2017, only three priority countries (Ethiopia, Kenya, and Tanzania) were likely to have reached the MC coverage target of 80% at the national level, and no priority country was likely to have reached this goal in all subnational areas.

Conclusions

Despite MC prevalence increases in all priority countries since the onset of VMMC campaigns in 2008, MC prevalence remains below the 80% coverage target in most subnational areas and is highly variable. These mapped results provide an actionable tool for understanding local needs and informing VMMC interventions for maximum impact in the continued effort towards ending the HIV epidemic in sub-Saharan Africa.
On the use of neural networks to evaluate performances of shell models for composites
Authors: Petrolo Marco , Carrera Erasmo
Published: July 2020

This paper presents a novel methodology to assess the accuracy of shell finite elements via neural networks. The proposed framework exploits the synergies among three well-established methods, namely, the Carrera Unified Formulation (CUF), the Finite Element Method (FE), and neural networks (NN). CUF generates the governing equations for any-order shell theories based on polynomial expansions over the thickness. FE provides numerical results feeding the NN for training. Multilayer NN have the generalized displacement variables, and the thickness ratio as inputs, and the target is the maximum transverse displacement. This work investigates the minimum requirements for the NN concerning the number of neurons and hidden layers, and the size of the training set. The results look promising as the NN requires a fraction of FE analyses for training, can evaluate the accuracy of any-order model, and can incorporate physical features, e.g., the thickness ratio, that drive the complexity of the mathematical model. In other words, NN can trigger fast informed decision-making on the structural model to use and the influence of design parameters without the need of modifying, rebuild, or rerun an FE model.
Correction to: Multi-criteria collaborative filtering recommender by fusing deep neural network and matrix factorization
Authors: Nassar Nour , Jafar Assef , Rahhal Yasser
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Study of bioaccessibility of cobalt species in berries and seeds by mass spectrometry techniques
Authors: Wojcieszek Justyna , Ruzik Lena
Published: July 2020

In recent years, açai berries (Euterpe Oleracea M.), goji berries (Lycium barbarum L.), bilberries (Vaccinium myrtillus L.), and chia seeds (Salvia hispanica L.) have increased interest worldwide due to their nutritional value and health benefits. In the present study, SEC-ICP-MS and μ-HPLC-ESI-MS/MS were used for the investigation of cobalt speciation and evaluation of its bioaccessibility in these products. Total cobalt content was determined, and açai berries (0.348 ± 0.042 μg g−1) and chia seeds (0.352 ± 0.036 μg g−1) were found as the best sources of this element. Different elution profiles of the extracts of examined berries and seeds obtained with the use of ammonium acetate, Tris-HCl, and SDS suggested that cobalt is bound by different bioligands in each biomatrix.

The bioaccessibility of cobalt species was evaluated by SEC-ICP-MS. On the chromatograms of extracts obtained after simulation of gastrointestinal digestion, peaks corresponding to low molecular mass (17.00–1.35 kDa) cobalt complexes were observed. In the case of goji berries, their intensities were significantly higher on chromatograms of gastrointestinal than gastric extract. In enzymatic extracts, different forms of vitamin B12 were identified by μ-HPLC-ESI-MS, including its natural forms—methylcobalamin (Me-Cbl) and adenosylcobalamin (Ado-Cbl).