bluuebunny/crossref_metadata_2025 huggingface dataset:
Moving exercise research in multiple sclerosis forward (the MoXFo initiative): Developing consensus statements for research
Authors: Dalgas Ulrik , Hvid Lars G , Kwakkel Gert , Motl Robert W , de Groot Vincent , Feys Peter , Op’t Eijnde Bert , Coote Susan , Beckerman Heleen , Pfeifer Klaus , Streber René , Peters Stefan , Riemann-Lorenz Karin , Rosenkranz Sina Cathérine , Centonze Diego , Van Asch Paul , Bansi Jens , Sandroff Brian M , Pilutti Lara A , Ploughman Michelle , Freeman Jennifer , Paul Lorna , Dawes Helen , Romberg Anders , Kalron Alon , Stellmann Jan-Patrick , Friese Manuel A , Heesen Christoph
Published: March 2020

Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleotropic effects. There is an exponential increase in the quantity of research on exercise in MS, yet a number of barriers associated with study content and quality hamper rapid progress in the field. To address these barriers and accelerate discovery, a new international partnership of MS-related experts in exercise has emerged with the goal of advancing the research agenda. As a first step, the expert panel met in May 2018 and identified the most urgent areas for moving the field forward, and discussed the framework for such a process. This led to identification of five themes, namely “Definitions and terminology,” “Study methodology,” “Reporting and outcomes,” “Adherence to exercise,” and “Mechanisms of action.” Based on the identified themes, five expert groups have been formed, that will further (a) outline the challenges per theme and (b) provide recommendations for moving forward. We aim to involve and collaborate with people with MS/MS organizations (e.g. Multiple Sclerosis International Federation (MSIF) and European Multiple Sclerosis Platform (EMSP)) in all of these five themes. The generation of this thematic framework with multi-expert perspectives can bolster the quality and scope of exercise studies in MS that may ultimately improve the daily lives of people with MS.
Comorbid disease burden among MS patients 1968–2012: A Swedish register–based cohort study
Authors: Smith Kelsi A , Burkill Sarah , Hiyoshi Ayako , Olsson Tomas , Bahmanyar Shahram , Wormser David , Geissbühler Yvonne , Moore Alan , Kharat Vineetkumar , Montgomery Scott
Published: March 2020

Background:

People with multiple sclerosis (pwMS) have increased comorbid disease (CMD) risk. Most previous studies have not considered overall CMD burden.

Objective:

To describe lifetime CMD burden among pwMS.

Methods:

PwMS identified using Swedish registers between 1968 and 2012 ( n = 25,476) were matched by sex, age, and county of residence with general-population comparators ( n = 251,170). Prevalence, prevalence ratios (PRs), survival functions, and hazard ratios by MS status, age, and time period compared seven CMD: autoimmune, cardiovascular, depression, diabetes, respiratory, renal, and seizures.

Results:

The magnitude of the PRs for each CMD and age group decreased across time, with higher PRs in earlier time periods. Before 1990, younger age groups had higher PRs, and after 1990, older age groups had higher PRs. Male pwMS had higher burden compared with females. Overall, renal, respiratory, and seizures had the highest PRs. Before 2001, 50% of pwMS received a first/additional CMD diagnosis 20 years prior to people without MS, which reduced to 4 years after 2001. PwMS had four times higher rates of first/additional diagnoses in earlier time periods, which reduced to less than two times higher in recent time periods compared to people without MS.

Conclusion:

Swedish pwMS have increased CMD burden compared with the general population, but this has reduced over time.
Infection prevention and chronic disease management in cystic fibrosis and noncystic fibrosis bronchiectasis
Authors: Lommatzsch Sherstin T.
Published: March 2020

Bronchiectasis is a chronic lung disease (CLD) characterized by irreversible bronchial dilatation noted on computed tomography associated with chronic cough, ongoing viscid sputum production, and recurrent pulmonary infections. Patients with bronchiectasis can be classified into two groups: those with cystic fibrosis and those without cystic fibrosis. Individuals with either cystic fibrosis related bronchiectasis (CFRB) or noncystic fibrosis related bronchiectasis (NCFRB) experience continuous airway inflammation and suffer airway architectural changes that foster the acquisition of a unique polymicrobial community. The presence of microorganisms increases airway inflammation, triggers pulmonary exacerbations (PEx), reduces quality of life (QOL), and, in some cases, is an independent risk factor for increased mortality. As there is no cure for either condition, prevention and control of infection is paramount. Such an undertaking incorporates patient/family and healthcare team education, immunoprophylaxis, microorganism source control, antimicrobial chemoprophylaxis, organism eradication, daily pulmonary disease management, and, in some cases, thoracic surgery. This review is a summary of recommendations aimed to thwart patient acquisition of pathologic organisms, and those therapies known to mitigate the effects of chronic airway infection. A thorough discussion of airway clearance techniques and treatment of or screening for nontuberculous mycobacteria (NTM) is beyond the scope of this discussion.
Disliked but Free to Speak: Cognitive Ability Is Related to Supporting Freedom of Speech for Groups Across the Ideological Spectrum
Authors: De keersmaecker Jonas , Bostyn Dries H. , Van Hiel Alain , Roets Arne
Published: March 2020

Freedom of speech for all citizens is often considered as a cornerstone of democratic societies. In three studies, we examined the relationship between cognitive ability and support for freedom of speech for a variety of social groups across the ideological spectrum ( N 1 varies between 1,373 and 18,719, N 2 = 298, N 3 = 395). Corroborating our theoretical expectations, although cognitive ability was related to more affective prejudice toward relatively conservative groups and less affective prejudice toward relatively liberal groups (Study 2), people with higher levels of cognitive ability were more in favor of freedom of speech for all target groups (Studies 1–3). The relationship between cognitive ability and freedom of speech support was mediated by intellectual humility (preregistered Study 3). These results indicate that cognitive ability contributes to support for the democratic right of freedom of speech for all social–ideological groups.
School Pathways to the Juvenile Justice System
Authors: Hughes Tammy , Raines Tara , Malone Celeste
Published: March 2020

School policies have increasingly criminalized students for common developmentally appropriate behaviors, such as talking back, public displays of affection, or repeated tardiness. Although their behaviors are no more problematic than their peers, children of color and children of color with disabilities are punished at higher rates. The increasing number of police in schools has also increased the number of arrests. In some cities, schools are the primary referral source to juvenile court. The literature on implicit bias, decision-making, and discipline disparities suggests new policy approaches: Evidence-based measures can disrupt these pathways to the justice system. A range of solutions could fortify efforts to protect all students and promote positive school climate.
Comparing febrile children presenting on and off antibiotics to the emergency department: a retrospective cohort study
Authors: Sawaya R. D. , El Zahran T. , Mrad S. , Abdul Massih C. , Shaya S. , Makki M. , Tamim H. , Majdalani M.
Published: March 2020

Background

It is not yet known how antibiotics may affect Serious Bacterial Infections (SBI). Our aim is to describe the presentation, management, and serious bacterial infections (SBI) of febrile children on or off antibiotics.

Methods

Retrospective, cohort study of febrile Emergency Department patients, 0–36 months of age, at a single institution, between 2009and 2012.

Results

Seven hundred fifty-three patients were included: 584 in the No-Antibiotics group and 169 (22%) in the Antibiotics group. Age and abnormal lung sounds were predictors for being on antibiotics (OR 2.00 [95% CI 1.23–3.25] and OR 1.04 [95% CI 1.02–1.06] respectively) while female gender, and lower temperatures were negative predictors (OR 0.68 [95%0.47–0.98] and OR 0.47 [95% CI 0.32–0.67] respectively). Antibiotics were prescribed by a physician 89% of the time; the most common one being Amoxicillin/Clavulanic Acid (39%). The antibiotic group got more blood tests (57% vs 45%) and Chest X-Rays (37% vs 25%). Overall, the percent of SBIs (and pneumonias) was statistically the same in both groups (6.5% in the No-antibiotic group VS 3.6%).

Conclusions

Children presenting on antibiotics and off antibiotics were significantly different in their presentation and management, although the overall percentages of SBI were similar in each group. Further investigations into this subgroup of febrile children are needed.
Survival and mortality of elderly men with localized prostate cancer managed with primary androgen deprivation therapy or by primary observation
Authors: Seikkula Heikki , Boström Peter J. , Seppä Karri , Pitkäniemi Janne , Malila Nea , Kaipia Antti
Published: March 2020

Background

Androgen deprivation therapy (ADT) remains a primary treatment for localized prostate cancer (PCa) even though there is no evidence that its use is beneficial in the absence of curative treatment.

Methods

Men aged ≥70 years (n = 16,534) diagnosed with localized PCa from 1985 to 2014 and managed either with primary observation or ADT in the absence of curative treatment were included. The cases were identified from the population-based Finnish Cancer Registry. We estimated the standardized mortality ratios (SMR) for overall mortality by treatment group. We determined the relative risk (RR) of PCa-specific mortality (PCSM) and other-cause mortality between the two treatment groups. Survival was determined using the life table method. Two age groups (70–79 years and ≥ 80 years) and three calendar time cohorts (1985–1994, 1995–2004, and 2005–2014) were compared following adjustment of propensity score matching between the treatment groups with four covariates (age, year of diagnosis, educational level, and hospital district). Follow-up continued until death or until December 31, 2015.

Results

Patients in the observation group had lower overall SMRs than those in the ADT group in both age cohorts over the entire study period. PCSM was higher in men aged 70–79 years undergoing primary ADT compared to those managed by observation only (RR: 1.70, 95% confidence interval [CI]: 1.29–2.23 [1985–1994]; RR 1.55, 95% CI: 1.35–1.84 [1995–2004]; and RR 2.71, 95% CI: 2.08–3.53 [2005–2014]); p = 0.005 for periodic trend. A similar trend over time was also observed in men aged > 80 years; (p for age–period interaction = 0.237). Overall survival was also higher among men in their 70’s managed by observation compared to those undergoing ADT.

Conclusions

Primary ADT within four months period from diagnosis is not associated with improved long-term overall survival or decreased PCSM compared to primary conservative management for men with localized PCa. However, this observational study’s conclusions should be weighted with confounding factors related to cancer aggressiveness and comorbidities.
Life-threatening acute water intoxication in a woman undergoing hysteroscopic myomectomy: a case report and review of the literature
Authors: Liao Chen-Yi , Lo Chang-Han , Yu Mu-Xian , Chan Wei-Hung , Wei Kuang-yu , Tseng Min-Feng , Wu Chia-Chao
Published: March 2020

Background

Acute water intoxication after hysteroscopy is a rare, life-threatening condition, often accompanied with delayed diagnosis owing to masked symptoms because of general anesthesia.

Case presentation

Herein we presented a 39-year-old female who presented with cardiac arrest after hysteroscopic myomectomy because of acute water intoxication and survived after extracorporeal membrane oxygenation, continuous venous–venous hemofiltration, and aggressive high sodium fluid resuscitation.

Conclusion

Failure to recognize and treat this condition appropriately may lead to potentially lethal cardiopulmonary complications.
Natural resources used as folk cosmeceuticals among rural communities in Vhembe district municipality, Limpopo province, South Africa
Authors: Setshego Mamokete Venolia , Aremu Adeyemi Oladapo , Mooki Obakeng , Otang-Mbeng Wilfred
Published: March 2020

Background

Skin-related diseases affect every individual irrespective of age, gender or social status. Since time immemorial, humans have explored natural resources from their environment for the maintenance of the skin. This explorative survey was conducted to document the natural resources (plant and non-plant materials) used for folk cosmeceuticals by rural communities in Vhembe district municipality, Limpopo province, South Africa.

Methods

The research was conducted in six communities namely: Tshakuma, Shigalo, Tshamutilikwa, Luvhimbi (Masikhwa), Khakhanwa, and Folovhodwe in Vhembe district. Random and convenient sampling was used to access the target population. Semi-structured questionnaires were used to interview 71 participants that comprised traditional practitioners, herbalists and laypeople from the study area. Collected data were analysed using both quantitative (for e.g. frequency, use-value and relative frequency of citation) and qualitative (thematic) analytical methods.

Results

A total of 52 plants from 27 families and 22 non-plant materials were used as folk cosmeceuticals in the study area. The most cited plants includedDicerocaryum zanguebarium(Pedaliaceae),Ricinus communis(Euphorbiaceae)and Helinus integrifolius(Rhamnaceae).Trees and shrubs were the most common plant-life form while leaves were the most popular plant part. Pig fats, red ochre (Luvhundi soil) and ashes were the most cited non-plant materials. These documented natural resources are frequently prepared by crushing and mostly used to heal wounds.

Conclusion

Traditional knowledge concerning folk cosmeceuticals is mostly held by elders. The high number of natural resources documented is an indication that Vhembe district is rich in ethnopharmacological knowledge. Scientific investigation of the efficacies and safety of these natural resources is highly recommended as a drive aimed at innovations with benefits to the rural communities who are the custodians of this valuable knowledge.
Responsive evaluation of stakeholder dialogue as a worksite health promotion intervention to contribute to the reduction of SEP related health inequalities: a study protocol
Authors: van Heijster Hanneke , van Berkel Jantien , Abma Tineke , Boot Cécile R. L. , de Vet Emely
Published: March 2020

Background

Large health inequalities exist in the Netherlands among individuals with a high compared to a low socioeconomic position. Worksite health promotion interventions are considered promising to reduce these inequalities, however, current interventions seem not to have the desired effects. This study proposes ‘moral case deliberation’, a form of stakeholder dialogue on moral dilemmas, as an integrated and inclusive intervention for worksite health promotion. This intervention takes into account three factors that are considered possible underlying causes of low effectiveness of current interventions, namely the lack of deliberate attention to: 1) the diverging values and interests of stakeholders in worksite health promotion, 2) the ethical issues of worksite health promotion, and 3) the connection with the lived experience (lifeworld) of lower SEP employees. Moral case deliberation will help to gain insight in the conflicting values in worksite health promotion, which contributes to the development of a vision for worksite health promotion that is supported by all parties.

Methods

The intervention will be evaluated through Responsive Evaluation, a form of participatory research. Key to Responsive Evaluation is that stakeholders are consulted to determine relevant changes as a result of the intervention. The intervention will be evaluated yearly at both fixed moments (baseline and annual evaluation(s)) and continuously. Mixed methods will be used, including interviews, participatory observations, analyses of HRM-data and short questionnaires. In addition, the intervention will be evaluated economically, on both monetary and non-monetary outcomes.

Discussion

This protocol proposes an innovative intervention and a novel participatory evaluation in the context of worksite health promotion. The study aims to gain understanding in how dialogue on moral dilemmas on health and health promotion can contribute to heightened personal and mutual understanding among stakeholders and practice improvements in the work context. By evaluating the intervention in more than one setting, findings of this study will provide knowledge about how MCD can be adapted to specific work settings and what changes it may lead to in these settings.

Trial registration

Netherlands Trial Register (NRT): NL8051. Registration date: 28/09/2019, retrospectively registered. https://www.trialregister.nl/
Cigarette smoke and electronic cigarettes differentially activate bronchial epithelial cells
Authors: Herr Christian , Tsitouras Konstantinos , Niederstraßer Julia , Backes Christina , Beisswenger Christoph , Dong Li , Guillot Loïc , Keller Andreas , Bals Robert
Published: March 2020

Background

The use of electronic cigarettes (ECIGs) is increasing, but the impact of ECIG-vapor on cellular processes like inflammation or host defense are less understood. The aim of the present study was to compare the acute effects of traditional cigarettes (TCIGs) and ECIG-exposure on host defense, inflammation, and cellular activation of cell lines and primary differentiated human airway epithelial cells (pHBE).

Methods

We exposed pHBEs and several cell lines to TCIG-smoke or ECIG-vapor. Epithelial host defense and barrier integrity were determined. The transcriptome of airway epithelial cells was compared by gene expression array analysis. Gene interaction networks were constructed and differential gene expression over all groups analyzed. The expression of several candidate genes was validated by qRT-PCR.

Results

Bacterial killing, barrier integrity and the expression of antimicrobial peptides were not affected by ECIG-vapor compared to control samples. In contrast, TCIGs negatively affected host defense and reduced barrier integrity in a significant way. Furthermore ECIG-exposure significantly induced IL-8 secretion from Calu-3 cells but had no effect on NCI-H292 or primary cells. The gene expression based on array analysis distinguished TCIG-exposed cells from ECIG and room air-exposed samples.

Conclusion

The transcriptome patterns of host defense and inflammatory genes are significantly distinct between ECIG-exposed and TCIG-treated cells. The overall effects of ECIGs on epithelial cells are less in comparison to TCIG, and ECIG-vapor does not affect host defense. Nevertheless, although acute exposure to ECIG-vapor induces inflammation, and the expression of S100 proteins, long term in vivo data is needed to evaluate the chronic effects of ECIG use.
Glycopyrrolate/formoterol fumarate metered dose inhaler for maintenance-naïve patients with chronic obstructive pulmonary disease: a post-hoc analysis of the randomized PINNACLE trials
Authors: Zheng Jinping , Xu Jin-fu , Jenkins Martin , Assam Pryseley Nkouibert , Wang Lijiao , Lipworth Brian J.
Published: March 2020

Background

Glycopyrrolate (GP)/formoterol fumarate (FF; GFF) metered dose inhaler is a fixed-dose combination dual bronchodilator for patients with chronic obstructive pulmonary disease (COPD); however, whether the efficacy in patients without current maintenance treatment is consistent with currently maintenance-treated patients is unclear.

Methods

Data from patients who were not maintenance-treated at screening (NMT) (n = 1943) and patients who were maintenance-treated at screening (MT) patients (n = 3040) receiving GFF, FF, GP, or placebo were pooled from the Phase III PINNACLE studies (NCT01854645, NCT01854658, NCT02343458) for post-hoc analysis. MT patients had received long-acting bronchodilators and/or inhaled corticosteroids in the 30 days prior to screening, and/or prior to randomization. NMT patients had received short-acting bronchodilators or no treatment. Outcomes included forced expiratory volume over 1 s (FEV1), clinically important deterioration (CID), rescue medication use, and safety.

Results

GFF provided significant lung function improvements at Week 24 versus placebo, GP, and FF for NMT patients, with pre-dose trough FEV1 treatment differences of 152 (117–188) mL, 73 (45–100) mL, and 56 (29–84) mL, respectively (least squares mean change from baseline versus comparators [95% CI]; all P < 0.0001). GFF reduced the risk of CID by 17–43% in NMT (P ≤ 0.0157) and 18–52% (P ≤ 0.0012) in MT patients compared with monotherapy and placebo, and reduced rescue medication use by 1.5 puffs/day over 24 weeks for both cohorts. Safety profiles for all cohorts were consistent with each other and the parent studies.

Conclusions

NMT patients achieved better lung function with GFF versus monotherapy and placebo, without increased safety risk. Dual bronchodilator therapy may offer better outcomes than monotherapy for COPD patients when administered as first-line treatment.
Knocking-out the Siah2 E3 ubiquitin ligase prevents mitochondrial NCX3 degradation, regulates mitochondrial fission and fusion, and restores mitochondrial function in hypoxic neurons
Authors: Sisalli Maria Josè , Ianniello Gaetano , Savoia Claudia , Cuomo Ornella , Annunziato Lucio , Scorziello Antonella
Published: March 2020

Background

Na+/Ca2+ exchanger isoform 3 (NCX3) regulates mitochondrial Ca2+handling through the outer mitochondrial membrane (OMM) and promotes neuronal survival during oxygen and glucose deprivation (OGD). Conversely, Seven In-Absentia Homolog 2 (Siah2), an E3-ubiquitin ligase, which is activated under hypoxic conditions, causes proteolysis of mitochondrial and cellular proteins.

In the present study, we investigated whether siah2, upon its activation during hypoxia, interacts with NCX3 and whether such interaction could regulate the molecular events underlying changes in mitochondrial morphology, i.e., fusion and fission, and function, in neurons exposed to anoxia and anoxia/reoxygenation.

Methods

To answer these questions, after exposing cortical neurons from siah2 KO mice (siah2 −/−) to OGD and OGD/Reoxygenation, we monitored the changes in mitochondrial fusion and fission protein expression, mitochondrial membrane potential (ΔΨm), and mitochondrial calcium concentration ([Ca2+]m) by using specific fluorescent probes, confocal microscopy, and Western Blot analysis.

Results

As opposed to congenic wild-type neurons, in neurons from siah2−/− mice exposed to OGD, form factor (FF), an index of the complexity and branching aspect of mitochondria, and aspect ratio (AR), an index reflecting the “length-to-width ratio” of mitochondria, maintained low expression. In KO siah2 neurons exposed to OGD, downregulation of mitofusin 1 (Mfn1), a protein involved in mitochondrial fusion and upregulation of dynamin-related protein 1 (Drp1), a protein involved in the mitochondrial fission, were prevented. Furthermore, under OGD conditions, whereas [Ca2+]mwas reduced, ΔΨm, mitochondrial oxidative capacity and ATP production were improved. Interestingly, our immunoprecipitation assay revealed that Siah2 interacted with NCX3. Indeed, siah2 knock-out prevented NCX3 degradation in neurons exposed to OGD. Finally, when siah2−/− neurons were exposed to OGD/reoxygenation, FF, AR, and Mfn1 expression increased, and mitochondrial function improved compared to siah2+/+ neurons.

Conclusions

Collectively, these findings indicate that hypoxia-induced SIAH2-E3 ligase activation influences mitochondrial fusion and fission, as well as function, by inducing NCX3 degradation.
Determinants of suicidal ideation among patients with mental disorders visiting psychiatry outpatient unit in Mekelle town, psychiatric clinics, Tigray, Northern Ethiopia: a case–control study
Authors: Tsegay Abreha , Damte Ashenafi , Kiros Adam
Published: March 2020

Background

Globally, more than 450 million people suffer from a mental or behavioral disorder. Psychiatric disorder and its duration, physical illness, family history of mental illness, previous suicidal attempt, unemployment, poor social support, and psychotic symptoms are of the main reasons enabling patients to be suicidal ideates. The purpose of this study is to identify the determinants of suicidal ideation among patients with mental disorders in Mekelle, Ethiopia.

Methods

Case–control study design was employed with a total of 221 study subjects (74 cases and 147 controls) in Mekelle, Ethiopia. Suicidal ideation was measured by the Suicidal Behavior Questionnaire-Revised (SBQ-R) scale. Bivariate and multiple logistic regression analyses were performed to determine between the independent and dependent variables.

Results

This study revealed that family suicide history (AOR = 6.87, 95% CI [1.138–41.531, P = 0.036), previous attempts history (AOR = 27.457, 95% CI 10.417–72.368, P = 0.0001), family mental illness history (AOR = 3.029, 95% CI 1.088–8.431, P = 0.034), major depressive disorders (AOR = 11.182, 95% CI 2.382–52.501, P = 0.002), and psychiatric comorbid disorders (AOR = 12.245, 95% CI 1.898–78.986, P = 0.008) were significant factors of suicidal ideation.

Conclusion

Family mental illness history, family suicide history, previous suicide attempt history, major depressive disorders, and psychiatric comorbid disorders were significant factors of suicidal ideation.
Cell-free DNA screening for sex chromosome aneuploidies by non-invasive prenatal testing in maternal plasma
Authors: Wang Yipeng , Li Shanshan , Wang Wei , Dong Yuan , Zhang Meng , Wang Xin , Yin Chenghong
Published: March 2020

Background

Non-invasive prenatal testing (NIPT) has been confirmed as the most accurate screening test for trisomies 21, 18, and 13. However, reports on NIPT performance in sex chromosome aneuploidies (SCA) based on real clinical data are still limited.

Methods

High-throughput massively parallel genomic sequencing (MPS) technique was used to screen for fetal SCAs as part of the research to determine the potential value of NIPT in detecting fetal SCAs in the second trimester. A number of 12,243 consecutive cases from a single center were included in this study.

Results

The positive predictive value (PPV) of NIPT in the present study was 57.6%, which was divided and categorized by individual SCAs as follows: 21.4% for Turner syndrome (45,X), 75.0% for Triple X syndrome (47,XXX), 90.9% for Klinefelter syndrome (47,XXY), and 75.0% for XYY syndrome (47,XYY).

Conclusion

The NIPT-based SCA test cannot be used as a diagnostic method, and performing an invasive confirmation test on NIPT-based SCA-positive cases is strongly recommended.
Impact of blunt chest trauma on outcome after traumatic brain injury– a matched-pair analysis of the TraumaRegister DGU®
Authors: Schieren Mark , Wappler Frank , Wafaisade Arasch , Lefering Rolf , Sakka Samir G. , Kaufmann Jost , Heiroth Hi-Jae , Defosse Jerome , Böhmer Andreas B.
Published: March 2020

Background

Traumatic brain injury (TBI) is associated with high rates of long-term disability and mortality. Our aim was to investigate the effects of thoracic trauma on the in-hospital course and outcome of patients with TBI.

Methods

We performed a matched pair analysis of the multicenter trauma database TraumaRegisterDGU® (TR-DGU) in the 5-year period from 2012 to 2016. We included adult patients (≥18 years of age) with moderate to severe TBI (abbreviated injury scale (AIS)= 3–5). Patients with isolated TBI (group 1) were compared to patients with TBI and varying degrees of additional blunt thoracic trauma (AISThorax= 2–5) (group 2). Matching criteria were gender, age, severity of TBI, initial GCS and presence/absence of shock. The χ2-test was used for comparing categorical variables and the Mann-Whitney-U-test was chosen for continuous parameters. Statistical significance was defined by a p-value < 0.05.

Results

A total of 5414 matched pairs (10,828 patients) were included. The presence of additional thoracic injuries in patients with TBI was associated with a longer duration of mechanical ventilation and a prolonged ICU and hospital length of stay. Additional thoracic trauma was also associated with higher mortality rates. These effects were most pronounced in thoracic AIS subgroups 4 and 5. Additional thoracic trauma, regardless of its severity (AISThorax ≥2) was associated with significantly decreased rates of good neurologic recovery (GOS = 5) after TBI.

Conclusions

Chest trauma in general, regardless of its initial severity (AISThorax= 2–5), is associated with decreased chance of good neurologic recovery after TBI. Affected patients should be considered “at risk” and vigilance for the maintenance of optimal neuro-protective measures should be high.
Correction to: ESR1 mutations are frequent in newly diagnosed metastatic and loco-regional recurrence of endocrine-treated breast cancer and carry worse prognosis
Authors: Zundelevich Adi , Dadiani Maya , Kahana-Edwin Smadar , Itay Amit , Sella Tal , Gadot Moran , Cesarkas Karen , Farage-Barhom Sarit , Saar Efrat Glick , Eyal Eran , Kol Nitzan , Pavlovski Anya , Balint-Lahat Nora , Dick-Necula Daniela , Barshack Iris , Kaufman Bella , Gal-Yam Einav Nili
Published: March 2020

After the publication of the original article [1], we were notified the upper panel of the Fig. 1, where the patients’ codes are listed, was cropped by mistake so the patients 1–8 are repeated.
Highly-selective µ-opioid receptor antagonism does not block L-DOPA-induced dyskinesia in a rodent model
Authors: Bartlett Mitchell J. , So Lisa Y. , Szabò Lajos , Skinner David P. , Parent Kate L. , Heien Michael L. , Vanderah Todd W. , Polt Robin , Sherman Scott J. , Falk Torsten
Published: March 2020

Objectives

Dopamine-replacement utilizing L-DOPA is still the mainstay treatment for Parkinson’s disease (PD), but often leads to development of L-DOPA-induced dyskinesia (LID), which can be as debilitating as the motor deficits. There is currently no satisfactory pharmacological adjunct therapy. The endogenous opioid peptides enkephalin and dynorphin are important co-transmitters in the direct and indirect striatofugal pathways and have been implicated in genesis and expression of LID. Opioid receptor antagonists and agonists with different selectivity profiles have been investigated for anti-dyskinetic potential in preclinical models. In this study we investigated effects of the highly-selective μ-opioid receptor antagonist CTAP (> 1200-fold selectivity for μ- over δ-opioid receptors) and a novel glycopeptide congener (gCTAP5) that was glycosylated to increase stability, in the standard rat LID model.

Results

Intraperitoneal administration (i.p.) of either 0.5 mg/kg or 1 mg/kg CTAP and gCTAP5 completely blocked morphine’s antinociceptive effect (10 mg/kg; i.p.) in the warm water tail-flick test, showing in vivo activity in rats after systemic injection. Neither treatment with CTAP (10 mg/kg; i.p.), nor gCTAP5 (5 mg/kg; i.p.) had any effect on L-DOPA-induced limb, axial, orolingual, or locomotor abnormal involuntary movements. The data indicate that highly-selective μ-opioid receptor antagonism alone might not be sufficient to be anti-dyskinetic.
Estimating breast tissue-specific DNA methylation age using next-generation sequencing data
Authors: Castle James R. , Lin Nan , Liu Jinpeng , Storniolo Anna Maria V. , Shendre Aditi , Hou Lifang , Horvath Steve , Liu Yunlong , Wang Chi , He Chunyan
Published: March 2020

Background

DNA methylation (DNAm) age has been widely accepted as an epigenetic biomarker for biological aging. Emerging evidence suggests that DNAm age can be tissue-specific and female breast tissue ages faster than other parts of the body. The Horvath clock, which estimates DNAm age across multiple tissues, has been shown to be poorly calibrated in breast issue. We aim to develop a model to estimate breast tissue-specific DNAm age.

Methods

Genome-wide DNA methylation sequencing data were generated for 459 normal, 107 tumor, and 45 paired adjacent-normal breast tissue samples. We determined a novel set of 286 breast tissue-specific clock CpGs using penalized linear regression and developed a model to estimate breast tissue-specific DNAm age. The model was applied to estimate breast tissue-specific DNAm age in different breast tissue types and in tumors with distinct clinical characteristics to investigate cancer-related aging effects.

Results

Our estimated breast tissue-specific DNAm age was highly correlated with chronological age (r = 0.88; p = 2.9 × 10−31) in normal breast tissue. Breast tumor tissue samples exhibited a positive epigenetic age acceleration, where DNAm age was on average 7 years older than respective chronological age (p = 1.8 × 10−8). In age-matched analyses, tumor breast tissue appeared 12 and 13 years older in DNAm age than adjacent-normal and normal breast tissue (p = 4.0 × 10−6 and 1.0 × 10−6, respectively). Both HER2+ and hormone-receptor positive subtypes demonstrated significant acceleration in DNAm ages (p = 0.04 and 3.8 × 10−6, respectively), while no apparent DNAm age acceleration was observed for triple-negative breast tumors. We observed a non-linear pattern of epigenetic age acceleration with breast tumor grade. In addition, early-staged tumors showed a positive epigenetic age acceleration (p = 0.003) while late-staged tumors exhibited a non-significant negative epigenetic age acceleration (p = 0.10).

Conclusions

The intended applications for this model are wide-spread and have been shown to provide biologically meaningful results for cancer-related aging effects in breast tumor tissue. Future studies are warranted to explore whether breast tissue-specific epigenetic age acceleration is predictive of breast cancer development, treatment response, and survival as well as the clinical utility of whether this model can be extended to blood samples.
Emergency laparoscopic repair of coitus-induced vaginal cuff dehiscence: a case report
Authors: Agrawal Ajay , Huang Kuan-Gen , Mendoza Marie Christine Valerie
Published: March 2020

Background

Vaginal cuff dehiscence is a rare but potentially grave complication after total hysterectomy. Abdominal or pelvic contents are at risk of evisceration through the vaginal opening. It is associated with significant risk for patient morbidity, such as peritonitis, bowel injury, and sepsis.

Case presentation

We report a case of vaginal cuff dehiscence in a 45-year-old multiparous Taiwanese woman who had undergone abdominal total hysterectomy and presented with vaginal cuff dehiscence precipitated by sexual intercourse. Immediate laparoscopic repair was done. Few authors have reported the utilization of the laparoscopic approach. It allows thorough inspection, visualization, and irrigation of the abdominal cavity. It is also associated with fewer intraoperative and postoperative complications.

Conclusion

Laparoscopic repair is a safe treatment option to manage vaginal cuff dehiscence after total hysterectomy.
Expression and function of cartilage-derived pluripotent cells in joint development and repair
Authors: Jiang Zhou , Yu Sijing , Lin Hengyi , Bi Ruiye
Published: March 2020

Cartilage-derived pluripotent cells reside in hyaline cartilage and fibrocartilage. These cells have the potential for multidirectional differentiation; can undergo adipogenesis, osteogenesis, and chondrogenesis; and have been classified as mesenchymal stem cells (MSCs) conforming to the minimal criteria of the International Society for Cellular Therapy. Cartilage tissue is prone to injury and is difficult to repair. As cartilage-derived pluripotent cells are the closest cell source to cartilage tissue, they are expected to have the strongest ability to differentiate into cartilage compared to other MSCs. This review focuses on the organizational distribution, expression, and function of cartilage-derived pluripotent cells in joint development and repair to help explore the therapeutic potential of in situ cartilage-derived pluripotent cells for joint cartilage repair.
The influence of a swab type on the results of point-of-care tests
Authors: Zasada Aleksandra Anna , Zacharczuk Katarzyna , Woźnica Katarzyna , Główka Małgorzata , Ziółkowski Robert , Malinowska Elżbieta
Published: March 2020

Most point-of-care tests (POCT) use swabs for sampling and/or for applying a sample on the test. A variety of swabs differing in tip materials is commercially available. Different tip materials have different chemical and physical characteristics which might influence the specimen collection and release. We investigated properties of various types of swabs used in clinical diagnostics with focusing on two kinds of analytes, DNA and proteins, which are most often used targets in POCT. As the model samples we used diphtheria toxoid NIBSC 69/017 for investigating recovery of protein analytes such as antigens and bacterial strains of Escherichia coli ATCC 25922, diphtheria toxin-producing Corynebacterium diphtheriae NCTC 10648, and the clinical isolate nontoxigenic C. diphtheriae 5820/15 for investigating the recovery of nucleic acids. We investigated four types of swabs most commonly used in clinical diagnostics in terms of absorption capacity and efficiency of release of nucleic acids and proteins. Volume uptake was measured in milligrams. For DNA release various washing out buffers were used and the amount of released DNA was measured spectrophotometrically. The amount of protein released from the swabs were examined using the Lowry assay. We observed statistically significant differences (p < 0.05) in the mean weights of absorbed liquid, in the DNA recovery and protein recovery by the four variety of swab examined. However, the efficiency of DNA and protein release was not correlated to the absorbed volume of a sample, but rather to the properties of swabs. The swab composition and structure can have a significant impact on the collection and release efficiency of a sample. Therefore, validation of POCT in relation to the used swabs for sampling is really important. The use of inappropriate swabs could lead to false negative or misleading analysis results.
On the feasibility of a secondary service transmission over an existent satellite infrastructure: design and analysis
Authors: da Silva Luciano Barros Cardoso , Benaddi Tarik , Franck Laurent
Published: March 2020

In this paper, we present a realistic use case in order to investigate the feasibility of a secondary service transmission over an existent satellite infrastructure. By introducing the overlay cognitive radio paradigm towards satellite communications, we compute a theoretical achievable data rate greater than 16 kbps for the secondary service, which is suitable for most M2M applications. Using simulation results, we show that this can be achieved while preserving the primary service performance. In addition, a system design framework is discussed in order to dimension such systems.
The health-related determinants of eating pattern of high school athletes in Goiás, Brazil
Authors: Noll Matias , Rodrigues Ana Paula Santos , Silveira Erika Aparecida
Published: March 2020

Background

Athletes put their health at short- and long-term risk and a detailed investigation of health outcomes is important because it should allow the development of more specific interventions. This study aimed to evaluate the health-related determinants of eating pattern of high school athletes.

Methods

The study enrolled 248 Brazilian athletes aged 14–20 years. Eating pattern outcomes included skipping breakfast, vegetable and fruit consumption, and sweets consumption. The following factors were considered as independent variables: sociodemographic, economic, anthropometry, body weight control, psychosocial, sedentary behavior, sleeping time, meals, alcohol and smoking, and strength variables. Data were analyzed using Poisson regression model and the effect measure was the prevalence ratio (PR).

Results

The results showed that 45.6% of the athletes skipped breakfast, 29.8% ate sweets regularly, and only 8.9% consumed vegetables and fruit regularly. Multiple analysis revealed the following positive associations: breakfast skipping and vomiting or using laxatives to lose weight (PR, 1.12; 95% CI, 1.01–1.26); low fruit and vegetable consumption and using pills to lose weight (PR, 1.05; 95% CI, 1.02–1.07); high sweets consumption and female athletes (PR, 1.32; 95% CI, 1.12–1.55); high sweets consumption and more than 2 h spent watching TV (PR, 1.19; 95% CI, 1.02–1.39).

Conclusions

Our findings indicated that sociodemographic, body weight control and sedentary factors are determinants on eating patterns of high school athletes.
Prominent amyloid plaque pathology and cerebral amyloid angiopathy in APP V717I (London) carrier – phenotypic variability in autosomal dominant Alzheimer’s disease
Authors: Lloyd Grace M. , Trejo-Lopez Jorge A. , Xia Yuxing , McFarland Karen N. , Lincoln Sarah J. , Ertekin-Taner Nilüfer , Giasson Benoit I. , Yachnis Anthony T. , Prokop Stefan
Published: March 2020

The discovery of mutations associated with familial forms of Alzheimer’s disease (AD), has brought imperative insights into basic mechanisms of disease pathogenesis and progression and has allowed researchers to create animal models that assist in the elucidation of the molecular pathways and development of therapeutic interventions. Position 717 in the amyloid precursor protein (APP) is a hotspot for mutations associated with autosomal dominant AD (ADAD) and the valine to isoleucine amino acid substitution (V717I) at this position was among the first ADAD mutations identified, spearheading the formulation of the amyloid cascade hypothesis of AD pathogenesis. While this mutation is well described in multiple kindreds and has served as the basis for the generation of widely used animal models of disease, neuropathologic data on patients carrying this mutation are scarce. Here we present the detailed clinical and neuropathologic characterization of an APP V717I carrier, which reveals important novel insights into the phenotypic variability of ADAD cases. While age at onset, clinical presentation and widespread parenchymal beta-amyloid (Aβ) deposition are in line with previous reports, our case also shows widespread and severe cerebral amyloid angiopathy (CAA). This patient also presented with TDP-43 pathology in the hippocampus and amygdala, consistent with limbic predominant age-related TDP-43 proteinopathy (LATE). The APOE ε2/ε3 genotype may have been a major driver of the prominent vascular pathology seen in our case. These findings highlight the importance of neuropathologic examinations of genetically determined AD cases and demonstrate striking phenotypic variability in ADAD cases.
Designing a range of mentalizing interventions for young people using a clinical staging approach to borderline pathology
Authors: Hutsebaut Joost , Debbané Martin , Sharp Carla
Published: March 2020

Borderline personality disorder (BPD) can have a long-lasting impact on social and professional functioning, even when core symptoms of BPD are in remission. Adolescence may be a critical developmental period to change the potential long-term functional outcome of BPD. This paper presents a range of mentalizing interventions to alter the course and outcome of BPD, based upon a model of clinical staging. Mentalizing interventions have in common a focus on strengthening self-regulatory and interpersonal capacities, aiming to improve adaptive social learning. This paper argues that these interventions should be dosed and organized according to the stage of progression of BPD, which is illustrated by discussing different specific formats for mentalization-based interventions, including an early-intervention program for BPD and a standard program for full BPD.
Preliminary results of PI3Kδ inhibitor idelalisib (GS-1101) treatment in combination with everolimus, bortezomib, or bendamustine/rituximab in patients with previously treated mantle cell lymphoma (MCL).
Authors: Wagner-Johnston Nina D. , De Vos Sven , Leonard John , Sharman Jeff Porter , Schreeder Marshall T. , Boccia Ralph V. , Barrientos Jacqueline Claudia , Coutre Steven E. , Flinn Ian , Boyd Thomas E. , Holes Leanne , Johnson David Michael , Kim Yeonhee , Dansey Roger D. , Godfrey Wayne R. , Fowler Nathan Hale
Published: March 2020

8501

Background: PI3K-delta is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that has shown monotherapy activity in recurrent MCL (Kahl, ICML 2011). Methods: This phase 1 study is evaluating the activity of continuous idelalisib (Id), 150 mg BID, in combination with everolimus (E) (10 mg PO qD) (Id+E regimen), with bortezomib (V) (1.3 mg/m2 SC day 1, 8, 15 per 28 day cycle) (Id+V regimen), or with rituximab (R) (375 mg/m2, on Day 1) and bendamustine (B) (90 mg/m2x 2), for 6 cycles (Id+BR regimen). Investigators assessed response according to standard criteria (Cheson 2007). Results: Study enrolled 22 patients with relapsed/refractory MCL. Results are from 14 Jan 2013 data cutoff. The 3 cohorts included Id+E (N=12), Id+V (N=6), and Id+BR (N=4). Patients were 73% male, median age [range] of 68 [47E79] years, 32% with refractory disease and 73% stage III/IV. The median [range] number of prior therapies was 3 [1E7]. The median [range] duration of treatment was 2.5 [0.5-8.3+] months. Overall response rate (ORR) was 10/22 (46%), with 2 CR (9%). The ORR/CR for Id+E, was 25%/0%, Id+V was 50%/0%, and Id+BR was 100%/50%. The median duration of response (mDOR) and median PFS (mPFS) were not reached. Most common adverse events included (total%/≥G3%) diarrhea (41/9), fatigue (41/0), rash (27/14), cough (27/0), decreased appetite (23/0), and epistaxis (23/0). Lab abnormalities included (total%/≥G3%) thrombocytopenia (82/27), neutropenia (32/14), and ALT/AST elevations (50/5). Conclusions: Preliminary data indicates idelalisib-based combination therapy is active in patients with relapsed/refractory MCL. All combinations were tolerable. These data support further clinical development in larger trials to further characterize safety and response duration. Clinical trial information: NCT01088048.