bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between motor proficiency and academic performance in mathematics and reading in year 1 school children: a cross-sectional study
Authors: Macdonald Kirstin , Milne Nikki , Orr Robin , Pope Rodney
Published: February 2020

Background

A key priority for learning during the early years of school is for children to develop skills in numeracy and literacy. Consequently, less time may be allocated in the curriculum to foster other important developmental areas, including the ongoing motor skill development of school children, which has been positively linked to academic performance. In order to promote holistic approaches to teaching and learning in the early years of school, it is necessary to further delineate the nature of associations between motor skills and foundation academic skills. The aim of this study was to examine associations between fine and gross motor proficiency and academic performance in mathematics and reading in Year 1 children.

Methods

A cross-sectional study was conducted with Year 1 children from two primary schools in New South Wales, Australia (N = 55; 25 boys, 30 girls; mean age 6.77 ± 0.40 years). The Bruininks-Oseretsky Test of Motor Proficiency (2nd Edition) and the Wechsler Individual Achievement Test II (Australian Edition) were used to assess motor proficiency and academic performance in mathematics and reading, respectively. Associations between the components of motor proficiency and academic outcomes were examined using Pearson’s and Spearman’s correlation analyses. Hierarchical multiple linear regression analyses were conducted to determine how much variance in mathematics and reading composite scores could be explained by motor proficiency after controlling for age.

Results

A significant moderate positive association was found between total motor composite and mathematics composite scores (r = .466, p < .001). Fine manual control composite scores were significantly associated with both mathematics (rs = .572, p < .001) and reading (rs = .476, p = .001) composite scores. After controlling for age, fine motor integration was the only component of motor proficiency that explained significant variance in mathematics and reading composite scores.

Conclusions

The results of the study revealed that Year 1 children’s overall motor proficiency was significantly related to their mathematical ability. Children’s fine motor integration skills were also predictive of mathematics and reading ability. These study findings may interest both early childhood educators and paediatric health professionals.
Predictors of outcome in early onset schizophrenia: a 10-year follow-up study
Authors: Xu Lingzi , Guo Yanqing , Cao Qingjiu , Li Xue , Mei Ting , Ma Zenghui , Tang Xinzhou , Ji Zhaozheng , Yang Liu , Liu Jing
Published: February 2020

Background

Younger age at onset is generally thought to be a predictor of poor outcome in Early Onset Schizophrenia (EOS), but there is a paucity of epidemiological data supporting this belief. This study aims to describe long-term outcomes and predictors of patient functioning in EOS, with a focus on the effect of age at onset.

Methods

We consecutively enrolled 118 EOS patients who were hospitalized in 2006. Mean age at baseline was 13.3 ± 2.3 years. Sixty-five subjects were successfully interviewed. Mean length of follow up was 10.4 ± 0.3 years. Baseline data were collected from inpatient medical records, while follow up was conducted primarily through telephone interviews of patient relatives. WHODAS 2.0 was used to measure global functioning at follow up. Outcomes included education, employment, marriage status, physical health, subsequent diagnoses and treatment, and patient functioning. Univariate and multivariate regression models were used to assess predictors of outcome, while propensity scores were used to adjust for confounding in analyzing the effect of age at onset on functional outcome.

Results

Of the 65 subjects where follow-up data were available, 3 were deceased at follow up. Five (8%) discontinued treatment. Diagnostic stability was 76%. Nearly a quarter (24%) were using clozapine at follow up. In male and female patients, 61 and 55% respectively were overweight, while 29 and 32% respectively were obese. Sixteen (26%) were economically self-sufficient, while 34 (55%) were unemployed. Thirteen (21%) patients had ever been married. The median WHODAS score was 15 (IQR 2 to 35), roughly corresponding to the 78th percentile on population norms. Extroverted personality (p = 0.01), suspicious personality (p = 0.02), and high level of education (p = 0.001) predicted better functioning. Age of onset was not associated with function in either the univariate model (p = 0.24), full model (p = 0.17) or the final risk factor model (p = 0.11), nor after using propensity scores to further adjust for confounders.

Conclusion

The long-term functional outcome of EOS is more optimistic than generally believed. Age at disease onset does not predict long-term functional outcome in EOS populations.
Loneliness and social isolation interventions for older adults: a scoping review of reviews
Authors: Fakoya Olujoke A. , McCorry Noleen K. , Donnelly Michael
Published: February 2020

Background

Loneliness and social isolation are growing public health concerns in our ageing society. Whilst these experiences occur across the life span, 50% of individuals aged over 60 are at risk of social isolation and one-third will experience some degree of loneliness later in life. The aim of this scoping review was to describe the range of interventions to reduce loneliness and social isolation among older adults that have been evaluated; in terms of intervention conceptualisation, categorisation, and components.

Methods

Three electronic databases (CINAHL, Embase and Medline) were systematically searched for relevant published reviews of interventions for loneliness and social isolation. Inclusion criteria were: review of any type, published in English, a target population of older people and reported data on the categorisation of loneliness and/or social isolation interventions. Data extracted included: categories of interventions and the reasoning underpinning this categorisation. The methodology framework proposed by Arskey and O’Malley and further developed by Levac, et al. was used to guide the scoping review process.

Results

A total of 33 reviews met the inclusion criteria, evaluating a range of interventions targeted at older people residing in the community or institutionalised settings. Authors of reviews included in this paper often used the same terms to categorise different intervention components and many did not provide a clear definition of these terms. There were inconsistent meanings attributed to intervention characteristics. Overall, interventions were commonly categorised on the basis of: 1) group or one-to-one delivery mode, 2) the goal of the intervention, and 3) the intervention type. Several authors replicated the categorisation system used in previous reviews.

Conclusion

Many interventions have been developed to combat loneliness and social isolation among older people. The individuality of the experience of loneliness and isolation may cause difficulty in the delivery of standardised interventions. There is no one-size-fits-all approach to addressing loneliness or social isolation, and hence the need to tailor interventions to suit the needs of individuals, specific groups or the degree of loneliness experienced. Therefore, future research should be aimed at discerning what intervention works for whom, in what particular context and how.
Biomechanical analysis of single-level interbody fusion with different internal fixation rod materials: a finite element analysis
Authors: Hsieh Yueh-Ying , Tsuang Fon-Yih , Kuo Yi-Jie , Chen Chia-Hsien , Chiang Chang-Jung , Lin Chun-Li
Published: February 2020

Background

Lumbar spinal fusion with rigid spinal fixators as one of the high risk factors related to adjacent-segment failure. The purpose of this study is to investigate how the material properties of spinal fixation rods influence the biomechanical behavior at the instrumented and adjacent levels through the use of the finite element method.

Methods

Five finite element models were constructed in our study to simulate the human spine pre- and post-surgery. For the four post-surgical models, the spines were implanted with rods made of three different materials: (i) titanium rod, (ii) PEEK rod with interbody PEEK cage, (iii) Biodegradable rod with interbody PEEK cage, and (iv) PEEK cage without pedicle screw fixation (no rods).

Results

Fusion of the lumbar spine using PEEK or biodegradable rods allowed a similar ROM at both the fusion and adjacent levels under all conditions. The models with PEEK and biodegradable rods also showed a similar increase in contact forces at adjacent facet joints, but both were less than the model with a titanium rod.

Conclusions

Flexible rods or cages with non-instrumented fusion can mitigate the increased contact forces on adjacent facet joints typically found following spinal fixation, and could also reduce the level of stress shielding at the bone graft.
Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis
Authors: Li Li , Li Zhenxing , Li Yuyan , Hu Xi , Zhang Yu , Fan Pei
Published: February 2020

Background

Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA.

Methods

Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale.

Results

Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores.

Conclusions

IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.
Design and baseline data in the BAriatic surgery SUbstitution and Nutrition study (BASUN): a 10-year prospective cohort study
Authors: Höskuldsdóttir Gudrún , Mossberg Karin , Wallenius Ville , Al Nimer Angelos , Björkvall Wiveka , Lundberg Sören , Behre Carl-Johan , Werling Malin , Eliasson Björn , Fändriks Lars
Published: February 2020

Background

There is still a lack of knowledge on long-term effects of surgical and non-surgical weight-lowering treatments. BASUN is a prospective study with 10 years of follow-up that will observe the effects and consequences of surgical and medical treatment of obesity. The aims are to cover areas where data on long-term outcomes are lacking, e.g., nutritional deficiencies, substance abuse, psychiatric health, as well as patient-reported outcomes.

Methods

BASUN is a cohort study that recruited study persons with obesity (BMI ≥ 35 kg/m2) referred to the Regional Obesity Centre of Region Västra Götaland. The interventions were Roux-en-Y gastric bypass (RYGB) or Sleeve gastrectomy (SG), or 12 months of structured, multi-professional medical treatment (MT), including very low energy diet, followed by diet and pharmaceutical treatment. The study is not randomized, but based on patients preferences and multidisciplinary assessments. The study persons are examined at baseline, 2, 5, and 10 years with blood tests, measurements and questionnaires. The recruitment period lasted from May 2015 to November 2017.

Results

One thousand one hundred twenty-seven patients were included (74% female). Three hundred eighty-two patients were accepted for medical treatment, 589 for surgical treatment (388 RYGB and 201 SG) and 156 patients left the study without treatment, leaving a final study population of 971 patients. There were slight differences between the treatment groups with regards to age and BMI. Pharmaceutical treatments, level of education, smoking and marital status were not significantly different between the groups.

Conclusion

This study will follow 971 obese subjects in clinical practice treated with the best surgical or medical methods currently available. It has the potential to evaluate outcomes usually not reported in short-term studies, and to assist in identifying factors that are of importance for the choices of treatment. The main limitations are non-randomization and differences in baseline characteristics. The large number of participants and the length of the prospective follow-up are major strengths of the study. BASUN is designed to identify both early and late benefits and adverse events of treatment of obesity.

Trial registration

This trial was prospectively registered on March 03, 2015; NCT03152617.
Understanding the association between self-reported poor oral health and exposure to adverse childhood experiences: a retrospective study
Authors: Ford Kat , Brocklehurst Paul , Hughes Karen , Sharp Catherine A. , Bellis Mark A.
Published: February 2020

Background

Adverse childhood experiences, including physical, sexual or emotional abuse, can have detrimental impacts on child and adult health. However, little research has explored the impact that such early life experiences have on oral health. This study examines whether experiencing adverse childhood experiences before the age of 18 years is associated with self-reported poor dental health in later life.

Methods

Using stratified random probability sampling, a household survey (N = 5307; age range 18–69 years) was conducted in the South of England (Hertfordshire, Luton and Northamptonshire). Data were collected at participants’ homes using face-to-face interviews. Measures included exposure to nine adverse childhood experiences, and two dental outcomes: tooth loss (> 8 teeth lost due to dental caries or damage) and missing or filled teeth (direct or indirect restorations; > 12 missing or filled teeth).

Results

Strong associations were found between exposure to childhood adversity and poor dental health. The prevalence of tooth loss was significantly higher (8.3%) in those with 4+ adverse childhood experiences compared to those who had experienced none (5.0%; p < 0.05). A similar relationship was found for levels of missing or filled teeth (13.4%, 4+ adverse childhood experiences; 8.1%, none; p < 0.001). Exposure to 4+ adverse childhood experiences was associated with a higher level of tooth loss and restorations at any age, compared to individuals who had not experienced adversity. Demographically adjusted means for tooth loss increased with adverse childhood experience count in all age groups, rising from 1.0% (18–29 years) and 13.0% (60–69 years) in those with none, to 3.0% and 26.0%, respectively in those reporting 4+.

Conclusions

Exposure to childhood adversity could be an important predictive factor for poor dental health. As oral health is an important part of a child’s overall health status, approaches that seek to improve dental health across the life-course should start with safe and nurturing childhoods free from abuse and neglect. Given the growing role that dental professionals have in identifying violence and abuse, it seems appropriate to raise awareness in the field of dentistry of the potential for individuals to have suffered adverse childhood experiences, and the mechanisms linking childhood adversity to poor dental health.
Impact of non-surgical periodontal therapy on serum Resistin and periodontal pathogen in periodontitis patients with obesity
Authors: Md Tahir Khairunnisa , Ab Malek Ainul Haliza , Vaithilingam Rathna Devi , Saub Roslan , Safii Syarida Hasnur , Rahman Mohammad Tariqur , Abdul Razak Fathilah , Alabsi Aied M , Baharuddin Nor Adinar
Published: February 2020

Background

Non-surgical periodontal therapy (NSPT) known as gold standard treatment in managing periodontitis. The aim of this study was to investigate the response of NSPT in periodontitis subjects who were obese. Clinical parameters of periodontitis, changes in serum resistin and periodontal pathogens in subgingival plaque were compared before and after NSPT in periodontitis subjects who were obese and with normal weight.

Methods

A total of 48 periodontitis subjects (obese, n = 18; normal weight, n = 30) were recruited (hereafter will be referred as participants) to participate into a prospective, before and after clinical trial. Obesity status is defined by body mass index (BMI) criteria (obese: ≥30 kg/ m2; normal weight < 25 kg/m2). Visible Plaque Index (VPI), Gingival Bleeding Index (GBI), Probing Pocket Depth (PPD) and Clinical Attachment Loss (CAL) were recorded; and serum and plaque were collected at baseline and following 12 weeks post-NSPT. Serum resistin level was analyzed using enzyme-linked immune-sorbant assay (ELISA), while detection of periodontal pathogens in dental plaque were carried out using real time PCR (qPCR).

Results

Following NSPT, means VPI and GBI showed significant improvement between obese and normal weight groups (p <  0.05), but no difference in means PPD and CAL was observed between groups. Obesity remained as a predictor for VPI and GBI after adjusting for smoking habit. No significant difference was observed in serum resistin level and mean counts for P. gingivalis, T. forsythia, and P. intermedia between obese and normal weight groups following NSPT.

Conclusions

Regardless of obesity status, NSPT has a significant impact on VPI and GBI in periodontitis subjects. However, the impact of NSPT towards serum resistin and periodontal pathogens was non-significant in those with periodontitis.

Trial registration

This study followed the Consolidation Standards of Reporting Trials Statement and retrospectively registered on 26/11/2015 at clinicaltrials.gov (No. NCT02618486).
Psychometric evaluation of the family caregiver ICU delirium knowledge questionnaire
Authors: Krewulak Karla D. , Bull Margaret J. , Ely E. Wesley , Stelfox Henry T. , Fiest Kirsten M.
Published: February 2020

Background

Delirium is a common condition in critically ill patients, affecting nearly half of all patients admitted to an intensive care unit (ICU). Family caregivers of critically ill patients can be partners in the early recognition, prevention and management of delirium provided they are aware of the signs/symptoms and appropriate non-pharmacological strategies that might be taken. Valid, reliable instruments that assess family caregiver knowledge are essential so that nurses can prepare family caregivers to be effective partners. The purpose of the current study was to (a) adapt an existing caregiver delirium knowledge questionnaire (CDKQ) for use by nurses to measure a family caregiver’s delirium knowledge in the ICU; and (b) examine the psychometric properties and structure of the adapted Caregiver ICU Delirium Knowledge Questionnaire (CIDKQ).

Methods

In this cross-sectional study, a multidisciplinary team developed the 21-item CIDKQ (possible score range: 0–21) and administered it to 158 family caregivers of critically ill patients. Descriptive statistics were examined for all variables. The CIDKQ was analyzed for face validity, content validity, reliability and internal consistency.

Results

The mean CIDKQ score was 14.1 (SD: 3.5, range = 2 to 21). Path analysis revealed that a family caregiver’s delirium knowledge in the actions and symptoms dimensions had a direct effect on knowledge of delirium risk factors. The CIDKQ was found to have face validity and reliability (Cronbach’s α = 0.79).

Conclusions

The findings indicated good validity and reliability of the CIDKQ as a measure of ICU delirium knowledge in family caregivers of critically ill patients.
Time-to-completed-imaging, survival and function in patients with spinal epidural abscess: Description of a series of 34 patients, 2015–2018
Authors: King Caroline , Fisher Cameron , Brown Patrick C. M. , Priest Kelsey C. , Tanski Mary , Sullivan Peter
Published: February 2020

Introduction

Spinal epidural abscess (SEA) is a rare and life-threatening infection with increasing incidence over the past two decades. Delays in diagnosis can cause significant morbidity and mortality among patients.

Objective

The objective of this study was to describe trends in time-to-imaging and intervention, risk factors, and outcomes among patients presenting to the emergency department with SEA at a single academic medical center in Portland, Oregon.

Methods

This retrospective cohort study analyzed data from patients with new SEA diagnosis at a single hospital from October 1, 2015 to April 1, 2018. We describe averages to time-to-imaging and interventions, and frequencies of risk factors and outcomes among patients presenting to the emergency department with SEA.

Results

Of the 34 patients included, 7 (20%) died or were discharged with plegia during the study period. Those who died or were discharged with plegia (n = 7) had shorter mean time-to-imaging order (20.8 h versus 29.2 h). Patients with a history of intravenous drug use had a longer mean time-to-imaging order (30.2 h versus 23.7 h) as compared to those without intravenous drug use. Patients who died or acquired plegia had longer times from imaging completed to final imaging read (20.9 h versus 7.1 h), but shorter times from final imaging read to surgical intervention among patients who received surgery (4.9 h versus 46.2 h). Further, only three (42.9%) of the seven patients who died or acquired plegia presented with the three-symptom classic triad of fever, neurologic symptoms, and neck or back pain.

Conclusions

SEA is a potentially deadly infection that requires prompt identification and treatment. This research provides baseline data for potential quality improvement work at the study site. Future research should evaluate multi-center approaches for identifying and intervening to treat SEA, particularly among patients with intravenous drug use.
End-of-life experience for older adults in Ireland: results from the Irish longitudinal study on ageing (TILDA)
Authors: May Peter , Roe Lorna , McGarrigle Christine A. , Kenny Rose Anne , Normand Charles
Published: February 2020

Background

End-of-life experience is a subject of significant policy interest. National longitudinal studies offer valuable opportunities to examine individual-level experiences. Ireland is an international leader in palliative and end-of-life care rankings. We aimed to describe the prevalence of modifiable problems (pain, falls, depression) in Ireland, and to evaluate associations with place of death, healthcare utilisation, and formal and informal costs in the last year of life.

Methods

The Irish Longitudinal Study on Ageing (TILDA) is a nationally representative sample of over-50-year-olds, recruited in Wave 1 (2009–2010) and participating in biannual assessment. In the event of a participant’s death, TILDA approaches a close relative or friend to complete a voluntary interview on end-of-life experience. We evaluated associations using multinomial logistic regression for place of death, ordinary least squares for utilisation, and generalised linear models for costs. We identified 14 independent variables for regressions from a rich set of potential predictors. Of 516 confirmed deaths between Waves 1 and 3, the analytic sample contained 375 (73%) decedents for whom proxies completed an interview.

Results

There was high prevalence of modifiable problems pain (50%), depression (45%) and falls (41%). Those with a cancer diagnosis were more likely to die at home (relative risk ratio: 2.5; 95% CI: 1.3–4.8) or in an inpatient hospice (10.2; 2.7–39.2) than those without. Place of death and patterns of health care use were determined not only by clinical need, but other factors including age and household structure. Unpaid care accounted for 37% of all care received but access to this care, as well as place of death, may be adversely affected by living alone or in a rural area. Deficits in unpaid care are not balanced by higher formal care use.

Conclusions

Despite Ireland’s well-established palliative care services, clinical need is not the sole determinant of end-of-life experience. Cancer diagnosis and access to family supports were additional key determinants. Future policy reforms should revisit persistent inequities by diagnosis, which may be mitigated through comprehensive geriatric assessment in hospitals. Further consideration of policies to support unpaid carers is also warranted.
Two-dimensional speckle tracking echocardiography in goats: repeatability, variability, and validation of the technique using an exercise test and an experimentally induced acute ischemic cardiomyopathy
Authors: Leroux Aurélia A. , Moonen Marie , Farnir Frédéric , Deleuze Stefan , Sandersen Charlotte , Amory Hélène
Published: February 2020

Background

Two-dimensional speckle tracking (2DST) technique has been validated in numerous animal species, but neither studies of repeatability nor measurements after exercise or in animals with cardiac disease have been reported in goats. Goats are an attractive candidate for animal models in human cardiology because they are easy to handle and have a body and heart size comparable to that of humans. Therefore, the aim of this study was to validate this technique in goats for further clinical and experimental applications in this species.

Results

This study was divided into several steps. First, a standardized echocardiographic protocol was performed and 5 cineloops of a right parasternal short-axis view at papillary muscles level were recorded three times at one-day intervals in ten healthy adult unsedated Saanen goats to test repeatability and variability of 2DST measurements. Then, the same measurements were performed immediately before and after a standardized exercise on treadmill in seven of the goats, and at 24 h after induction of an experimental ischemic cardiomyopathy in five of the goats, to test the reliability of the technique to assess physiological and pathological changes. Average and regional measurements of radial and circumferential strain and strain rate, radial displacement, rotation and rotation rate were obtained. Comparisons were performed using two-way ANOVA (p < 0.05). Caprine 2DST average measurements have demonstrated a good repeatability with a low to moderate variability for all measurements except for the diastolic peaks of the circumferential strain rate, radial strain rate and rotation rate. Segmental 2DST measurements were less repeatable than average measurements. Time effect of two-way ANOVA was significant for anteroseptal segment diastolic peaks measurements, rotation and rotation rate measurements. Overall variability of segmental measurements was moderate or high. Segmental and average peak values obtained after exercise and after myocardial ischemia were significantly different than curves obtained at baseline.

Conclusions

The results of this study are consistent with those previously described in other animal species and humans. 2DST echocardiography is a valid technique to evaluate physiological and pathological changes in myocardial function in goats, despite the technical limitations observed in this species.
“Point of no return” in unilateral renal ischemia reperfusion injury in mice
Authors: Holderied Alexander , Kraft Franziska , Marschner Julian Aurelio , Weidenbusch Marc , Anders Hans-Joachim
Published: February 2020

Background

In the past years evidence has been growing about the interconnection of chronic kidney disease and acute kidney injury. The underlying pathophysiological mechanisms remain unclear. We hypothesized, that a threshold ischemia time in unilateral ischemia/reperfusion injury sets an extent of ischemic tubule necrosis, which as “point of no return” leads to progressive injury. This progress is temporarily associated by increased markers of inflammation and results in fibrosis and atrophy of the ischemic kidney.

Methods

Acute tubule necrosis was induced by unilateral ischemia/reperfusion injury in male C57BL/6 N mice with different ischemia times (15, 25, 35, and 45 min). At multiple time points between 15 min and 5 weeks we assessed gene expression of markers for injury, inflammation, and fibrosis, histologically the injury of tubules, cell death (TUNEL), macrophages, neutrophil influx and kidney atrophy.

Results

Unilateral ischemia for 15 and 25 min induced upregulation of markers for injury after reperfusion for 24 h but no upregulation after 5 weeks. None of the markers for inflammation or fibrosis were upregulated after ischemia for 15 and 25 min at 24 h or 5 weeks on a gene expression level, except forIl-6. Ischemia for 35 and 45 min consistently induced upregulation of markers for inflammation, injury, and partially of fibrosis (Tgf-β1andCol1a1) at 24 h and 5 weeks. The threshold ischemia time for persistent injury of 35 min induced a temporal association of markers for inflammation and injury with peaks between 6 h and 7 d along the course of 10 d. This ischemia time also induced persistent cell death (TUNEL) throughout observation for 5 weeks with a peak at 6 h and progressing kidney atrophy beginning 7 d after ischemia.

Conclusions

This study confirms the evidence of a threshold extent of ischemic injury in which markers of injury, inflammation and fibrosis do not decline to baseline but remain upregulated assessed in long term outcome (5 weeks). Excess of this threshold as “point of no return” leads to persistent cell death and progressing atrophy and is characterized by a temporal association of markers for inflammation and injury.
Effects of metal cation substitution on hexavalent chromium reduction by green rust
Authors: Thomas Andrew N. , Eiche Elisabeth , Göttlicher Jörg , Steininger Ralph , Benning Liane G. , Freeman Helen M. , Tobler Dominique J. , Mangayayam Marco , Dideriksen Knud , Neumann Thomas
Published: February 2020

Chromium contamination is a serious environmental issue in areas affected by leather tanning and metal plating, and green rust sulfate has been tested extensively as a potential material for in situ chemical reduction of hexavalent chromium in groundwater. Reported products and mechanisms for the reaction have varied, most likely because of green rust’s layered structure, as reduction at outer and interlayer surfaces might produce different reaction products with variable stabilities. Based on studies of Cr(III) oxidation by biogenic Mn (IV) oxides, Cr mobility in oxic soils is controlled by the solubility of the Cr(III)-bearing phase. Therefore, careful engineering of green rust properties, i.e., crystal/particle size, morphology, structure, and electron availability, is essential for its optimization as a remediation reagent. In the present study, pure green rust sulfate and green rust sulfate with Al, Mg and Zn substitutions were synthesized and reacted with identical chromate (CrO42−) solutions. The reaction products were characterized by X-ray diffraction, pair distribution function analysis, X-ray absorption spectroscopy and transmission electron microscopy and treated with synthetic δ-MnO2 to assess how easily Cr(III) in the products could be oxidized. It was found that Mg substitution had the most beneficial effect on Cr lability in the product. Less than 2.5% of the Cr(III) present in the reacted Mg-GR was reoxidized by δ-MnO2 within 14 days, and the particle structure and Cr speciation observed during X-ray scattering and absorption analyses of this product suggested that Cr(VI) was reduced in its interlayer. Reduction in the interlayer lead to the linkage of newly-formed Cr(III) to hydroxyl groups in the adjacent octahedral layers, which resulted in increased structural coherency between these layers, distinctive rim domains, sequestration of Cr(III) in insoluble Fe oxide bonding environments resistant to reoxidation and partial transformation to Cr(III)-substituted feroxyhyte. Based on the results of this study of hexavalent chromium reduction by green rust sulfate and other studies, further improvements can also be made to this remediation technique by reacting chromate with a large excess of green rust sulfate, which provides excess Fe(II) that can catalyze transformation to more crystalline iron oxides, and synthesis of the reactant under alkaline conditions, which has been shown to favor chromium reduction in the interlayer of Fe(II)-bearing phyllosilicates.
An impedance threshold device did not improve carotid blood flow in a porcine model of prolonged cardiac arrest
Authors: Kjaergaard Benedict , Holdgaard Hans O. , Magnusdottir Sigridur O. , Lundbye-Christensen Søren , Christensen Erika F.
Published: February 2020

Background

An impedance threshold device (ITD) was developed to increase venous return to the heart and therefore increase cardiac output and organ blood flow during cardiopulmonary rescue (CPR). Basic CPR aims to maintain coronary and cerebral blood flow at the minimum level necessary for survival. The present study compared the effects of an ITD on cerebral blood flow assessed as blood flow in both carotid arteries to the blood flow of a control group during prolonged CPR.

Methods

Fourteen anaesthetized pigs were monitored during 60 min of CPR after induced ventricular fibrillation. The primary outcome was blood flow in both carotid arteries, and the secondary outcomes were blood pressure, acid–base parameters, plasma potassium, and plasma lactate. The pigs were randomized to mechanical compressions and ventilation with an ITD added to the ventilation or to a control group treated only with mechanical compressions and ventilation. The time course for the parameters was tested using analysis of variance.

Results

The cumulative carotid blood flow in the ITD group decreased from 64 to 42 ml/min, and it decreased from 69 to 51 ml/min in the control group during 60 min of CPR. The difference was not significant. The secondary outcome measures were also not significantly different.

Conclusions

This study did not show any beneficial effect of an ITD on carotid blood flow.
Comparison of clinical features and outcomes between HBV-related and non-B non-C hepatocellular carcinoma
Authors: Xue Xiulan , Liao Wei , Xing Yugang
Published: February 2020

Objective

To evaluate the difference between hepatitis B virus related hepatocellular carcinoma (HBV-HCC) and non-HBV non-HCV hepatocellular carcinoma (NBNC-HCC) patients based on clinical features and prognosis.

Methods

A total of 175 patients with HCC were enrolled. Patients’ characteristics were extracted from medical records. Among them, 107 patients were positive for HBsAg and negative for HCV-Ab while 68 patients were negative for HBsAg and HCV-Ab.

Results

The patients in the NBNC-HCC group were significantly older than those in the HBV-HCC group (P = 0.045). Moreover, vascular invasion was found in 23.4% of HBV-HCC patients, which was significantly higher than that in the NBNC-HCC patients with 10.3% (P = 0.029). Kaplan-Meier analysis revealed that HBV-HCC patients had significantly worse outcomes in terms of overall survival (P = 0.036). Compared with the NBNC-HCC patients, the HBV-HCC patients had a significantly worse disease-free survival (P = 0.0018). The multivariate analysis results indicated that TNM stage (HR = 1.541, 95%CI 1.072–2.412, P = 0.002) and HBV infection (HR = 1.087, 95%CI 1.012–1.655, P = 0.042) were independent risk variables for overall survival. While vascular invasion (HR = 1.562, 95%CI 1.013–2.815, P = 0.042) and HBV infection (HR = 1.650, 95%CI 1.017–2.676, P = 0.037) were independent risk factors associated with disease-free survival.

Conclusion

Our data revealed that HBV-HCC is more common in young males with vascular invasion, while NBNC-HCC occurs mostly in elderly patients, and overall survival rate is significantly better than that of HBV-HCC. Our study therefore provides evidence that patients with HBV-HCC require closer follow-up due to their poor prognosis.
Mutational signatures: experimental design and analytical framework
Authors: Koh Gene , Zou Xueqing , Nik-Zainal Serena
Published: February 2020

Mutational signatures provide a powerful alternative for understanding the pathophysiology of cancer. Currently, experimental efforts aimed at validating and understanding the etiologies of cancer-derived mutational signatures are underway. In this review, we highlight key aspects of mutational signature experimental design and describe the analytical framework. We suggest guidelines and quality control measures for handling whole-genome sequencing data for mutational signature analyses and discuss pitfalls in interpretation. We envision that improved next-generation sequencing technologies and molecular cell biology approaches will usher in the next generation of studies into the etiologies and mechanisms of mutational patterns uncovered in cancers.
Effects of the Informed Health Choices podcast on the ability of parents of primary school children in Uganda to assess the trustworthiness of claims about treatment effects: one-year follow up of a randomised trial
Authors: Semakula Daniel , Nsangi Allen , Oxman Andrew D. , Oxman Matt , Austvoll-Dahlgren Astrid , Rosenbaum Sarah , Morelli Angela , Glenton Claire , Lewin Simon , Nyirazinyoye Laetitia , Kaseje Margaret , Chalmers Iain , Fretheim Atle , Rose Christopher J. , Sewankambo Nelson K.
Published: February 2020

Introduction

Earlier, we designed and evaluated an educational mass media intervention for improving people’s ability to think more critically and to assess the trustworthiness of claims (assertions) about the benefits and harms (effects) of treatments. The overall aims of this follow-up study were to evaluate the impact of our intervention 1 year after it was administered, and to assess retention of learning and behaviour regarding claims about treatments.

Methods

We randomly allocated consenting parents to listen to either the Informed Health Choices podcast (intervention) or typical public service announcements about health issues (control) over 7–10 weeks. Each intervention episode explained how the trustworthiness of treatment claims can be assessed by using relevant key concepts of evidence-informed decision-making. Participants listened to two episodes per week, delivered by research assistants. We evaluated outcomes immediately, and a year after the intervention. Primary outcomes were mean score and the proportion with a score indicating a basic ability to apply the key concepts (> 11 out of 18 correct answers) on a tool measuring people’s ability to critically appraise the trustworthiness of treatment claims. Skills decay/retention was estimated by calculating the relative difference between the follow-up and initial results in the intervention group, adjusting for chance. Statistical analyses were performed using R (R Core Team, Vienna, Austria; version 3.4.3).

Results

After 1 year, the mean score for parents in the intervention group was 58.9% correct answers, compared to 52.6% in the control (adjusted mean difference of 6.7% (95% CI 3.3% to 10.1%)). In the intervention group, 47.2% of 267 parents had a score indicating a basic ability to assess treatment claims compared to 39.5% of 256 parents in the control (adjusted difference of 9.8% more parents (95% CI 0.9% to 18.9%). These represent relative reductions of 29% in the mean scores and 33% in the proportion of parents with a score indicating a basic ability to assess the trustworthiness of claims about treatment effects.

Conclusions

Although listening to the Informed Health Choices podcast initially led to a large improvement in the ability of parents to assess claims about the effects of treatments, our findings show that these skills decreased substantially over 1 year. More active practice could address the substantial skills decay observed over 1 year.

Trial registration

Pan African Clinical Trial Registry (www.pactr.org), PACTR201606001676150. Registered on 12 June 2016.
The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment
Authors: Shu Cindy C. , Zaki Sanaa , Ravi Varshini , Schiavinato Antonella , Smith Margaret M. , Little Christopher B.
Published: February 2020

Background

Synovitis is implicated in the severity and progression of pain and structural pathology of osteoarthritis (OA). Increases in inflammatory or immune cell subpopulations including macrophages and lymphocytes have been reported in OA synovium, but how the particular subpopulations influence symptomatic or structural OA disease progression is unclear. Two therapies, hyaluronan (HA) and mesenchymal stem cells (MSCs), have demonstrated efficacy in some clinical settings: HA acting as device to improve joint function and provide pain relief, while MSCs may have immunomodulatory and disease-modifying effects. We used these agents to investigate whether changes in pain sensitization or structural damage were linked to modulation of the synovial inflammatory response in post-traumatic OA.

Methods

Skeletally mature C57BL6 male mice underwent medial-meniscal destabilisation (DMM) surgery followed by intra-articular injection of saline, a hyaluronan hexadecylamide derivative (Hymovis), bone marrow-derived stem cells (MSCs), or MSC + Hymovis. We quantified the progression of OA-related cartilage, subchondral bone and synovial histopathology, and associated pain sensitization (tactile allodynia). Synovial lymphocytes, monocyte/macrophages and their subpopulations were quantified by fluorescent-activated cell sorting (FACS), and the expression of key inflammatory mediators and catabolic enzyme genes quantified by real-time polymerase chain reaction (PCR).

Results

MSC but not Hymovis significantly reduced late-stage (12-week post-DMM) cartilage proteoglycan loss and structural damage. Allodynia was initially reduced by both treatments but significantly better at 8 and 12 weeks by Hymovis. Chondroprotection by MSCs was not associated with specific changes in synovial inflammatory cell populations but rather regulation of post-injury synovial Adamts4, Adamts5, Mmp3, and Mmp9 expression. Reduced acute post-injury allodynia with all treatments coincided with decreased synovial macrophage and T cell numbers, while longer-term effect on pain sensitization with Hymovis was associated with increased M2c macrophages.

Conclusions

This therapeutic study in mice demonstrated a poor correlation between cartilage, bone or synovium (histo)pathology, and pain sensitization. Changes in the specific synovial inflammatory cell subpopulations may be associated with chronic OA pain sensitization, and a novel target for symptomatic treatment.
Balanced oral pathogenic bacteria and probiotics promoted wound healing via maintaining mesenchymal stem cell homeostasis
Authors: Han Nannan , Jia Lu , Guo Lijia , Su Yingying , Luo Zhenhua , Du Juan , Mei Shenghui , Liu Yi
Published: February 2020

Objectives

The homeostasis of oral pathogenic bacteria and probiotics plays a crucial role in maintaining the well-being and healthy status of human host. Our previous study confirmed that imbalanced oral microbiota could impair mesenchymal stem cell (MSC) proliferation capacity and delay wound healing. However, the effects of balanced oral pathogenic bacteria and probiotics on MSCs and wound healing are far from clear. Here, the balance of pathogenic bacteriaPorphyromonas gingivalisand probioticsLactobacillus reuteriextracts was used to investigate whether balanced oral microbiota modulate the physiological functions of MSCs and promote wound healing.

Methods

The effects of balanced pathogenic bacteriaP. gingivalisand probioticsL. reuteriextracts on gingival MSCs (GMSCs) were tested using the migration, alkaline phosphatase activity, alizarin red staining, cell counting kit-8, real-time PCR, and western blot assays. To investigate the role of balanced pathogenic bacteriaP. gingivalisand probioticsL. reuteriextracts in the wound of mice, the wounds were established in the mucosa of palate and were inoculated with bacteria every 2 days.

Results

We found that the balance between pathogenic bacteria and probiotics enhanced the migration, osteogenic differentiation, and cell proliferation of MSCs. Additionally, local inoculation of the mixture ofL. reuteriandP. gingivalispromoted the process of wound healing in mice. Mechanistically, we found that LPS inP. gingivaliscould activateNLRP3inflammasome and inhibit function of MSCs, thereby accelerating MSC dysfunction and delaying wound healing. Furthermore, we also found that reuterin was the effective ingredient inL. reuteriwhich maintained the balance of pathogenic bacteria and probiotics by neutralizing LPS inP. gingivalis, thus inhibiting inflammation and promoting wound healing.

Conclusions

This study revealed that the homeostasis of oral microbiomes played an indispensable role in maintaining oral heath, provided hopeful methods for the prevention and treatment of oral diseases, and had some referential value for other systemic diseases caused by dysfunction of microbiota and MSCs.
Early-onset impairment of the ubiquitin-proteasome system in dopaminergic neurons caused by α-synuclein
Authors: McKinnon Chris , De Snoo Mitchell L. , Gondard Elise , Neudorfer Clemens , Chau Hien , Ngana Sophie G. , O’Hara Darren M. , Brotchie Jonathan M. , Koprich James B. , Lozano Andres M. , Kalia Lorraine V. , Kalia Suneil K.
Published: February 2020

Parkinson’s disease is a progressive neurodegenerative disorder characterised by the accumulation of misfolded α-synuclein in selected brain regions, including the substantia nigra pars compacta (SNpc), where marked loss of dopaminergic neurons is also observed. Yet, the relationship between misfolded α-synuclein and neurotoxicity currently remains unclear. As the principal route for degradation of misfolded proteins in mammalian cells, the ubiquitin-proteasome system (UPS) is critical for maintenance of cellular proteostasis. Misfolded α-synuclein impairs UPS function and contributes to neuronal death in vitro. Here, we examine its effects in vivo using adeno-associated viruses to co-express A53T α-synuclein and the ubiquitinated reporter protein UbG76V-GFP in rat SNpc. We found that α-synuclein over-expression leads to early-onset catalytic impairment of the 26S proteasome with associated UPS dysfunction, preceding the onset of behavioural deficits and dopaminergic neurodegeneration. UPS failure in dopaminergic neurons was also associated with selective accumulation of α-synuclein phosphorylated at the serine 129 residue, which has previously been linked to increased neurotoxicity. Our study highlights a role for α-synuclein in disturbing proteostasis which may contribute to neurodegeneration in vivo.