bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between ambulatory blood pressure variability and frailty among older hypertensive patients
Authors: Zhu Yingqian , Chen Xin , Geng ShaSha , Li QingQing , Yuan Huixiao , Zhou Xi , Li Huan , Li Jinglan , Jiang Hua
Published: August 2020

Frailty and hypertension often coexist and are increasingly prevalent with advancing age. Although hypertension is independently associated with frailty, whether high blood pressure variability affecting frailty is unclear. In this retrospective study, we consecutively enrolled elderly patients with essential hypertension undergoing 24‐hour ABPM. The frailty was assessed by a 38‐item frailty index. The parameters of blood pressure variability of ABPM, including ARV, coefficient of CV, SD, and weighed SD were calculated. Ordinal logistic regression was used to investigate the association between blood pressure variability and frailty. A total of 242 hypertensive patients were recruited and divided into the frail group, pre‐frail group, and non‐frail group. The overall magnitudes of BP variability, assessed by ARV, CV, SD, and weighed SD, were significantly greater in patients with frailty than those with pre‐frailty and non‐frailty. With adjustment for covariates, ARV of 24‐hour, diurnal, and nocturnal SBP were independently associated with frailty (24 hours, OR: 2.48, 95% CI: 2.01‐3.07; daytime, OR: 1.83, 95% CI: 1.60‐2.10; nighttime, OR: 1.19, 95% CI: 1.12‐1.27). The CV of 24‐hour, diurnal, and nocturnal SBP was independently associated with frailty in the study (24 hours, OR: 1.2, 95% CI: 1.05–3.07; daytime, OR: 1.19, 95% CI: 1.05‐1.34; nighttime, OR: 1.13, 95% CI: 1.03‐1.24). For SD and weighed SD, only 24‐hour systolic SD was independent risk factor associated with frailty (OR: 1.12, 95% CI: 1.01‐1.23). The greater blood pressure variability of SBP, particular ARV and CV, were independent risk factors associated with higher‐order frailty status. Longitudinal studies are needed to investigate the causality associations between hypertension and frailty.
METTL3 potentiates resistance to cisplatin through m6A modification of TFAP2C in seminoma
Authors: Wei Jingchao , Yin Yinghao , Zhou Jun , Chen Hanfei , Peng Jingxuan , Yang Jianfu , Tang Yuxin
Published: August 2020

Testicular germ cell tumours (TGCTs) rank as the most common malignancy in men aged 20‐34 years, and seminomas are the most type of TGCTs. As a crucial anti‐tumour agent with explicit toxicity, cisplatin may render resistance through intertwined mechanisms, even in disease entities with high curative ratio, such as seminoma. Previously, we established cisplatin‐resistant seminoma TCam‐2 (TCam‐2/CDDP) cells and showed that epigenetic regulations, such as non‐coding RNA (ncRNA) interactions, might orchestrate cell fate decisions in the cisplatin treatment context in seminoma. N6‐methyladenosine (m6A) is the most prevalent internal modification in mRNA. In the present study, we assessed cisplatin resistance in seminoma from the perspective of m6A, another manner of epigenetic modification. The global m6A enrichment of TCam‐2 and TCam‐2/CDDP was depicted. Then, we elucidated whether transcription factor‐activating enhancer‐binding protein 2C (TFAP2C) was functionally m6A‐modified by methyltransferase‐like protein 3 (METTL3), which acted as an m6A ‘writer’, and insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1), which acted as an m6A ‘reader’. Enhanced stability of TFAP2C mRNA promoted seminoma cell survival under cisplatin treatment burden probably through up‐regulation of DNA repair‐related genes. Hopefully, this study will help improve our understanding of the subtleties of the tumour cellular coping strategy in response to chemotherapy. Targeting factors that are involved in m6A methylation may be an effective strategy for circumventing cisplatin resistance in seminoma.
CircPSMC3 alleviates the symptoms of PCOS by sponging miR‐296‐3p and regulating PTEN expression
Authors: Liu Jun , Ding Jinli , Qu Bing , Liu Jiuying , Song Xiaojie , Suo Qingli , Zhou Aifen , Yang Jing
Published: August 2020

Polycystic ovary syndrome (PCOS), the most common female endocrine disease that causes anovulatory infertility, still lacks promising strategy for the accurate diagnosis and effective therapeutics of PCOS attributed to its unclear aetiology. In this study, we determined the abnormal reduction in circPSMC3 expression by comparing the ovarian tissue samples of PCOS patients and normal individuals. The symptom relief caused by up‐regulation of circPSMC3 in PCOS model mice suggested the potential for further study. In vitro functional experiments confirmed that circPSMC3 can inhibit cell proliferation and promote apoptosis by blocking the cell cycle in human‐like granular tumour cell lines. Mechanism study revealed that circPSMC3 may play its role through sponging miR‐296‐3p to regulate PTEN expression. Collectively, we preliminarily characterized the role and possible insights of circPSMC3/miR‐296‐3p/PTEN axis in the proliferation and apoptosis of KGN cells. We hope that this work provides some original and valuable information for the research of circRNAs in PCOS, not only to better understand the pathogenesis but also to help provide new clues for seeking for the future therapeutic target of PCOS.
EU Trade and Non‐trade Objectives: New Survey Evidence on Policy Design and Effectiveness
Authors: Yildirim Aydin , Basedow Robert , Fiorini Matteo , Hoekman Bernard
Published: August 2020

EU trade policy increasingly focuses on the achievement of non‐trade policy objectives (NTPOs) such as the promotion of human rights or environmental protection, motivating research on the political economy determinants and effectiveness of linking trade policy and NTPOs. This research reports selected findings from a new expert survey of stakeholder perceptions of trade–NTPO linkages. These suggest that the views of EU institutions align with those of civil society organizations more than with business, but also reveal significant differences in the perceived effectiveness of trade–NTPO linkage strategies. Many stakeholder groups believe that policy instruments other than trade agreements are more effective tools to pursue NTPOs. These findings suggest that further research on EU trade policy and non‐trade issues should consider the broader range of external policy tools available to the EU in pursuit of NTPOs and the determinants of differences in preferences for alternative policy instruments.
Editorial: Something special – the scientific challenges of rare risks
Authors: Oldehinkel Albertine J.
Published: August 2020

Globalization has sparked international collaboration in our field, and this trend is expected to continue in the years to come. This offers excellent opportunities to learn more about the influence of children’s sociocultural environments on their development and mental health. A particular challenge when studying risk factors across cultures and populations is that the risk associated with a particular exposure may depend on its prevalence: rarity tends to aggravate impact. This phenomenon complicates not only comparisons across cultures, but also those across subpopulations and time periods within a population. Moreover, it may counteract the effectiveness of risk‐reducing public health efforts. On the bright side, the extent to which the impact of a risk factor is determined by its rarity provides researchers with valuable tools to deepen and sharpen theories about the nature and working mechanisms of that risk factor, with prevention and treatment strategies that also benefit youth in exceptional conditions as a likely consequence.
Elevated incubation temperature improves later‐life swimming endurance in juvenile Chinook salmon, Oncorhynchus tshawytscha
Authors: Lim Dan Dohyung , Milligan C. Louise , Morbey Yolanda E.
Published: August 2020

The effect of incubation and rearing temperature on muscle development and swimming endurance under a high‐intensity swimming test was investigated in juvenile Chinook salmon (Oncorhynchus tshawytscha) in a hatchery experiment. After controlling for the effects of fork length (LF) and parental identity, times to fatigue of fish were higher when fish were incubated or reared at warmer temperatures. Significant differences among combinations of pre‐ and post‐emergence temperatures conformed to 15–15°C > 15–9°C > 9–9°C > 7–9°C > 7–7°C in 2011 when swimming tests were conducted at 300 accumulated temperature units post‐emergence and 15–9°C > (7–9°C = 7–7°C) in 2012 when swimming tests were conducted at an LF of c. 40 mm. The combination of pre‐ and post‐emergence temperatures also affected the number and size of muscle fibres, with differences among temperature treatments in mean fibre cross‐sectional area persisting after controlling for LF and parental effects. Nonetheless, neither fibre number nor fibre size accounted for significant variation in swimming endurance. Thus, thermal carryover effects on swimming endurance were not mediated by thermal imprinting of muscle structure. This is the first study to test how temperature, body size and muscle structure interact to affect swimming endurance during early development in salmon.
Determining the usefulness of Capsule Scoring of Ulcerative Colitis in predicting relapse of inactive ulcerative colitis
Authors: Matsubayashi Mao , Kobayashi Taku , Okabayashi Shinji , Nakano Masaru , Sagami Shintaro , Ozaki Ryo , Kiyohara Hiroki , Morikubo Hiromu , Asonuma Kunio , Miyatani Yusuke , Maeda Shin , Hibi Toshifumi
Published: August 2020

Background and Aim

The usefulness of second‐generation colon capsule endoscopy (CCE2) in ulcerative colitis (UC), especially in clinically inactive patients, has been reported. Capsule Scoring of Ulcerative Colitis (CSUC) was developed as a severity index for UC. We aimed to determine whether CSUC is useful for predicting relapse during clinical remission.

Methods

Forty‐one UC patients in clinical remission who underwent CCE2 were prospectively registered from April 2016 to August 2019. Patients' CSUC score was obtained; those with subsequent relapse were followed up retrospectively. The correlation of CSUC with white blood cell count, platelet count, albumin, C‐reactive protein, fecal calprotectin and fecal lactoferrin levels, and fecal immunochemical test results was evaluated; their predictive values for future relapse were compared.

Results

The correlations of CSUC with white blood cell, platelet, albumin, C‐reactive protein, fecal calprotectin, fecal immunochemical test, and fecal lactoferrin values were rs = 0.13, 0.27, −0.25, 0.15, 0.50, 0.43, and 0.50, respectively. CSUC was higher in 12 patients who relapsed within 1 year than in 29 patients who remained in clinical remission (2.83 ± 1.95 vs 0.72 ± 1.00, P < 0.01). Receiver operator characteristic curve analysis showed that CSUC ≥ 1 was a predictor of relapse (area under the curve of 0.82, sensitivity of 83.3%, specificity of 58.6%) and maybe superior to fecal biomarkers. In the univariate analysis, patients with CSUC of 0 had a lower relapse rate than those with CSUC of ≧ 1 (P = 0.03, log–rank test). After analyzing patients who underwent CCE2 within 6 months after the successful induction treatment, results showed that those with CSUC of ≤ 1 remained in clinical remission for a year.

Conclusion

CSUC predicts relapse within 1 year in UC patients in clinical remission, especially when used 6 months after induction treatment.
Design and Methodology of the Longitudinal Aging Study in India‐Diagnostic Assessment of Dementia (LASI‐DAD)
Authors: Lee Jinkook , Khobragade Pranali Y. , Banerjee Joyita , Chien Sandy , Angrisani Marco , Perianayagam Arokiasamy , Bloom David E. , Dey Aparajit B.
Published: August 2020

BACKGROUND/OBJECTIVES

To provide high‐quality data on older adults in India that will enable an in‐depth study of late‐life cognition and dementia in India and cross‐country analysis of risk factors for cognitive aging and dementia.

DESIGN

The Longitudinal Aging Study in India (LASI) is a nationally representative survey of health, economic, and social well‐being of the Indian population aged 45 and older. Its large sample of more than 70,000 older adults represents not only the country as a whole but also each state. LASI‐Diagnostic Assessment of Dementia (DAD) is an in‐depth study of late‐life cognition and dementia, drawing a subsample of over 3,000 LASI respondents aged 60 and older.

SETTING

Participants were interviewed at home or in a participating hospital according to their preferences.

PARTICIPANTS

Adults aged 60 and older (N = 3,224), along with 3,191 informants.

MEASUREMENTS

Respondents underwent a battery of cognitive tests, and informants were interviewed about their cognitive and health conditions. A common set of cognitive tests was selected to enable international comparisons, and additional cognitive tests suitable for illiterate and innumerate populations were also selected. Rich data on risk factors of dementia were collected through health examination, venous blood assays, and genotyping.

RESULTS

The response rate was 82.9%, varying across sex, education, and urbanicity. Data are available to other researchers.

CONCLUSION

LASI‐DAD provides an opportunity to study late‐life cognition and dementia and their risk factors in the older population in India and to gain further insights through cross‐country analysis by pooling data from its international sister studies. J Am Geriatr Soc 68:S5‐S10, 2020.
Statin Discontinuation and Life‐Limiting Illness in Non–Skilled Stay Nursing Homes at Admission
Authors: Mack Deborah S. , Baek Jonggyu , Tjia Jennifer , Lapane Kate L.
Published: August 2020

OBJECTIVES

To estimate 30‐day statin discontinuation among newly admitted nursing home residents overall and within categories of life‐limiting illness.

DESIGN

Retrospective cohort using Minimum Data Set 3.0 nursing home admission assessments from 2015 to 2016 merged to Medicare administrative data files.

SETTING

U.S. Medicare‐ and Medicaid‐certified nursing home facilities (n = 13,092).

PARTICIPANTS

Medicare fee‐for‐service beneficiaries, aged 65 years and older, newly admitted to nursing homes for non–skilled nursing facility stays on statin pharmacotherapy at the time of admission (n = 73,247).

MEASUREMENTS

Residents were categorized using evidence‐based criteria to identify progressive, terminal conditions or limited prognoses (<6 months). Discontinuation was defined as the absence of a new Medicare Part D claim for statin pharmacotherapy in the 30 days following nursing home admission.

RESULTS

Overall, 19.9% discontinued statins within 30 days of nursing home admission, with rates that varied by life‐limiting illness classification (no life‐limiting illness: 20.5%; serious illness: 18.6%; receipt of palliative care consult: 34.5%; clinician designated as end‐of‐life: 45.0%). Relative to those with no life‐limiting illness, risk of 30‐day statin discontinuation increased with life‐limiting illness severity (serious illness: adjusted risk ratio (aRR) = 1.06; 95% confidence interval (CI) = 1.02–1.10; palliative care index diagnosis: aRR = 1.15; 95% CI = 1.10–1.21; palliative care consultation: aRR = 1.58; 95% CI = 1.43–1.74; clinician designated as end of life: aRR = 1.59; 95% CI = 1.42–1.79). Nevertheless, most remained on statins after entering the nursing home regardless of life‐limiting illness status.

CONCLUSION

Statin use continues in a large proportion of Medicare beneficiaries after admission to a nursing home. Additional deprescribing research, which identifies how to engage nursing home residents and healthcare providers in a process to safely and effectively discontinue medications with questionable benefits, is warranted.
Anatectic melt inclusions in ultra high temperature granulites
Authors: Gianola Omar , Bartoli Omar , Ferri Fabio , Galli Andrea , Ferrero Silvio , Capizzi Luca S. , Liebske Christian , Remusat Laurent , Poli Stefano , Cesare Bernardo
Published: August 2020

Partial melting up to ultra high temperature (UHT) conditions is one of the major processes for the geochemical differentiation and reworking of the mid‐ to lower continental crust, with relevant implications on its rheological behaviour. UHT granulites from the Gruf Complex (European Central Alps) display garnet and sapphirine porphyroblasts containing a variety of primary melt inclusions (MI). Typically, MI in garnet occur as glassy and polycrystalline inclusions (i.e. nanogranitoids), the latter commonly organized in mm‐sized clusters associated with primary fluid inclusions (FI). Nanogranitoids are characterized by an elliptical faceted shape, with variable sizes ranging from 2 to 115 µm, while glassy inclusions show negative crystal shapes that usually never exceed 15 µm in diameter and present CO2‐rich shrinkage bubbles. The characteristic mineral assemblage observed in nanogranitoids consists of quartz, biotite, muscovite, plagioclase, K‐feldspar, kokchetavite and rarely aluminosilicates. Glassy and re‐homogenized MI are peraluminous and rhyolitic in composition, with SiO2 = 69 − 80 wt% and Na2O + K2O = 5 − 12 wt%. Commonly, the analysed MI have very high K2O (>6 wt%) and very low Na2O (<2 wt%) contents, indicative for potassic to ultrapotassic melts. Measured H2O contents of the melts range from 2.9 to 8.8 wt%, whereas CO2concentrations are between 160 and 1738 ppm. Accordingly, calculated viscosities for re‐homogenized MI vary between 104and 105 Pa·s. Related primary FI mainly contain CO2, with rare occurrence of CO and N2, and are commonly associated with quartz, as well as different carbonates and phyllosilicates. It is assumed that the source for the carbonic fluid was external and probably related to the degassing lithospheric mantle. Consequently, it is argued that anatexis was initially triggered by incongruent dehydration melting reactions involving biotite breakdown and proceeded in the presence of an externally derived COH‐bearing fluid. The coexistence of COH‐bearing fluid and MI indicates that partial melting occurred under conditions of fluid − melt immiscibility. Potassic to ultrapotassic MI in UHT granulites suggests that lower crustal anatexis may play a significant role in the redistribution of heat‐producing elements (such as K2O), potentially influencing the thermal structure of the continental crust.
Ataxia pancytopenia syndrome due to SAMD9L mutation presenting as demyelinating neuropathy
Authors: Vaughan David , Bogdanova‐Mihaylova Petya , Costello Daniel J. , Sweeney Brian J. , McNamara Brian , Walsh Richard A. , Murphy Sinéad M.
Published: August 2020

Ataxia pancytopenia (ATXPC) syndrome due to gain‐of‐function pathogenic variants in the SAMD9L gene has been described in 38 patients to date. It is characterized by variable neurological and hematological phenotypes including ataxia, pyramidal signs, cytopenias, and hematological malignancies. Peripheral neuropathy with slowing of conduction velocities has been reported in only two affected individuals. We describe a female with childhood onset neuropathy diagnosed as Charcot‐Marie‐Tooth disease type 1 with onset of cerebellar ataxia in her 50s. Cerebellar, pyramidal, and neuropathic features were found on examination. Additionally, she also had conjunctival telangiectasia. Nerve conduction studies confirmed a demyelinating neuropathy. MRI brain showed cerebellar atrophy with diffuse white matter hyperintensities. OCT demonstrated global thinning of the retinal nerve fiber layer (RNFL). Full blood count has always been normal. A previously described pathogenic variant in SAMD9L [c.2956C>T p.(Arg986Cys)] was identified on whole exome sequencing. This case extends the previously described phenotype to include conjunctival telangiectasia and RNFL thinning and suggests that ATXPC syndrome should be considered in the differential for inherited demyelinating neuropathies.
Intrauterine transplantation of autologous menstrual blood stem cells increases endometrial thickness and pregnancy potential in patients with refractory intrauterine adhesion
Authors: Ma Hailan , Liu Mengting , Li Yufeng , Wang Wei , Yang Keqin , Lu Lanying , He Mei , Deng Taoran , Li Meiling , Wu Dongcheng
Published: August 2020

Aim

This study was designed to evaluate the effects of intrauterine transplantation of menstrual blood stem cells (MenSCs) on endometrial thickness and pregnancy outcomes in patients with refractory intrauterine adhesion (IUA).

Methods

This study included a group of infertile women (n = 12, age 22–40 years), with refractory IUA. Autologous MenSCs isolated from the women's menstrual blood were expanded in vitro and transplanted into their uteruses, followed by hormone replacement therapy. Transvaginal ultrasound examination was performed to assess the endometrial thickness. Transabdominal ultrasound was conducted to detect pregnancy outcome.

Results

Autologous MenSCs were successfully isolated and expanded from menstrual blood and transplanted into the uterus of each patient. A significant improvement of the endometrial thickness was observed from 3.9 ± 0.9 to 7.5 ± 0.6 mm (P < 0.001). No adverse reaction was observed. The duration of menstruation was increased from 2.4 ± 0.7 to 5.3 ± 0.6 days (P < 0.001). Five out of 12 patients achieved clinical pregnancy and the pregnancy rate was 41.7%.

Conclusions

Intrauterine transplantation of autologous MenSCs results in regeneration of endometrium, a prolongation of menstrual duration and an increase rate of pregnancy in patients with refractory IUA.
Brain Morphological Alterations Are Detected in Early‐Stage Parkinson's Disease with MRI Morphometry
Authors: Fu Tong , Klietz Martin , Nösel Patrick , Wegner Florian , Schrader Christoph , Höglinger Günter U. , Dadak Mete , Mahmoudi Nima , Lanfermann Heinrich , Ding Xiao‐Qi
Published: August 2020

BACKGROUND AND PURPOSE

To detect brain morphological alterations in patients with early Parkinson's disease (PD) by using magnetic resonance imaging (MRI) morphometry under radiological diagnostic conditions.

METHODS

T1‐weighted brain images of 18 early PD patients and 18 age‐sex‐matched healthy controls (HCs) were analyzed with free software Computational Anatomy Toolbox (CAT12). Regional cortical thickness (rCTh) in 68 atlas‐defined regions‐of‐interest (ROIs) and subcortical gray matter volume (SGMV) in 14 atlas‐defined ROIs were determined and compared between patients and HCs by paired comparison using both ROI‐wise and voxel‐wise analyses. False‐discovery rate (FDR) was used multiple comparison correction. Possible correlations between brain morphological changes in patients and clinical observations were also analyzed.

RESULTS

Comparing to the HCs, the ROI‐wise analysis revealed rCTh thinning significantly in left medial orbitofrontal (P = .001), by trend (P < .05 but not significant after FDR correction) in four other ROIs located in frontal and temporal lobes, and a volume decreasing trend in left pallidum of the PD patients, while the voxel‐wise analysis revealed one cluster with rCTh thinning trend located between left insula and superior temporal region of the patients. In addition, the patients showed more distinct rCTh thinning in ipsilateral hemisphere and SGMV deceasing trends in contralateral hemisphere in respect of the symptom‐onset body side.

CONCLUSION

Brain morphological alterations in early PD patients are evident despite of their inconspicuous findings in standard MRI. Quantitative morphological measurements with CAT12 may be an applicable add‐on tool for clinical diagnosis of early PD. These results have to be verified in future studies with larger patient samples.
Effect of Milling Protocols on Trueness and Precision of Ceramic Crowns
Authors: Al Hamad Khaled Q. , Al‐Rashdan Rama B. , Al‐Rashdan Bashar A. , Baba Nadim Z.
Published: August 2020

Purpose

To investigate the effect of different milling protocols for different ceramic materials on the trueness and precision of milled ceramic crowns.

Materials and Methods

A definitive impression from a patient requiring a ceramic crown was used to fabricate forty glass ceramic crowns (VITABLOCS mark II, Vita Zahnfabrik) milled with wet, hard milling protocol, and 40 zirconia crowns (inCoris TZI, Dentsply, Sirona) milled with dry, soft milling protocol, using a 5‐axis milling machine (inLab MC X5; Dentsply Sirona). Trueness and precision for different crown areas were evaluated with a 3D evaluation software (Geomagic Control X, 3D systems). Statistical analysis was performed between the 2 crown types with independent t‐test, and analysis of variances followed by Bonferroni tests among crown areas for each crown.

Results

All areas of the glass ceramic crowns had higher trueness than the zirconia crown areas (p < 0.05). Crown areas of each crown type had significantly different trueness values (p < 0.001, F = 175.17 for glass crowns, p < 0.001, F = 35.04 for zirconia crowns). Glass crowns had 3.78 µm precision, while zirconia crowns had 4.12 µm precision, with a precision difference range between the 2 types of crowns from 0.32 µm for the inner surface to 6.5 µm for the marginal surface.

Conclusions

Type of ceramic material and milling protocol affected trueness of the milled crown, with higher trueness for the hardmilled glass crowns than the soft milled zirconia crowns. Soft milled zirconia crowns were generally overmilled in comparison with the reference design and glass crowns. However, glass crowns exhibited more undermilling in thin and deep areas. The crown area affected trueness, with external areas having better trueness than internal areas. The 5‐axis milling machine had high precision, which was minimally affected by the ceramic type, milling protocol, or crown area.
Hospitalised infants due to falls aged less 12 months in New South Wales from 2002 to 2013
Authors: Cooray Nipuna , Adams Susan , Zeltzer Justin , Nassar Natasha , Brown Julie
Published: August 2020

Aim

Falls are the most common injury mechanism of children <12 months in Australia. We aimed to determine the prevalence of hospital admission following a fall among New South Wales (NSW) infants and changes in admission rate over time. Secondary aims were to examine demographics, nature of injury and trends by age groups associated with developmental milestones and fall mechanism.

Methods

This was a retrospective, population‐based study across NSW from 2002 to 2013 using the NSW Admitted Patient Data collection. Infants with recorded falls, external causes of morbidity and mortality and activity codes were assessed. Main outcome measures were absolute numbers, rates and proportions by year, age group, socio‐demographics, fall mechanism, injury type, body region affected and admission outcome.

Results

A total of 4380 cases were identified. Numbers increased over years (342 in 2002 to 469 in 2013). Rate of admissions per 10 000 population were 40.37 in 2002 and 47.18 in 2013 (average increase 0.9% per year, P = 0.25). 76% resided in a major city, 23% resided in the least disadvantaged areas and 18% in the most disadvantaged. Falls from furniture and falls while being carried were most common. 85% suffered a head injury, 70% of which had a traumatic brain injury (TBI). There were seven deaths and one quarter of surviving infants were admitted for 2 or more days.

Conclusions

Hospital admission following a fall is a long‐standing problem with no improvement among infants in NSW, commonly leading to head injury and traumatic brain injury. Effective prevention interventions are needed.
Berberine, a natural alkaloid sensitizes human hepatocarcinoma to ionizing radiation by blocking autophagy and cell cycle arrest resulting in senescence
Authors: Ramesh Gautham , Das Shubhankar , Bola Sadashiva Satish Rao
Published: August 2020

Objective

To study the radiosensitizing potential of Berberine and the underlying mechanism in human hepatocarcinoma (HepG2) cells.

Methods

HepG2 cells were challenged with X-rays in combination with Berberine treatment and several in vitro assays were performed. Alteration in cell viability was determined by MTT assay. Changes in intracellular ROS levels, mitochondrial membrane potential/mass, intracellular acidic vesicular organelles as well as cell cycle arrest and apoptotic cell death were analysed by flow cytometry. Induction of autophagy was assessed by staining the cells with Monodansylcadaverine/Lysotracker red dyes and immunoblotting for LC3I/II and p62 proteins. Phase-contrast/fluorescence microscopy was employed to study mitotic catastrophe and senescence. Cellular senescence was confirmed by immunoblotting for p21 levels and ELISA for Interleukin-6.

Key findings

X-rays + Berberine had a synergistic effect in reducing cell proliferation accompanied by a robust G2/M arrest. Berberine-mediated radiosensitization was associated with elevated levels of LC3II and p62 suggesting blocked autophagy that was followed by mitotic catastrophe and senescence. Treatment of cells with X-rays + Berberine resulted in increased oxidative stress, hyperpolarized mitochondria with increased mitochondrial mass and reduced ATP levels.

Conclusions

The study expands the understanding of the pharmacological properties of Berberine and its applicability as a radiosensitizer towards treating liver cancer.
Recombinant ling zhi-8 enhances Tregs function to restore glycemic control in streptozocin-induced diabetic rats
Authors: Xiao Hongyu , Fang Zhi , He Xueling , Ding Ping , Cao Yongkai , Chan Shamyuen , Hou Shaozhen , Liang Jian
Published: August 2020

Objectives

To explore the effect of recombinant LZ-8 (rLZ-8) on streptozocin (STZ)-induced diabetic rats and further illustrate its underlying mechanism.

Methods

Rats were intraperitoneally injected with single-dose STZ 50 mg/kg for induction of type 1 diabetes (T1D), and then, the diabetic rats were treated with rLZ-8 for 3 months. The clinical symptoms, fasting blood glucose, insulin, cytokines, histopathology, flow cytometry and immunofluorescence were used to evaluate the therapeutic effect and underlying mechanism of rLZ-8 on alleviating diabetes mellitus (DM).

Key findings

Treatment with rLZ-8 obviously alleviated the clinical symptoms of T1D and dose-dependently reduced the levels of blood glucose, blood lipid and haemoglobin A1c (HbA1c) in diabetic rat model. Meanwhile, rLZ-8 markedly increased insulin secretion and protected against STZ-induced pancreatic tissue injury. Additionally, rLZ-8 dramatically inhibited the levels of TNF-α and IL-1β, and obviously increased the level of IL-10 in serum and pancreas. Further investigation indicated that rLZ-8 treatment significantly increased the number of regulatory T cells (Tregs) and up-regulated the expression of Foxp3 to restore balance between anti-inflammatory and inflammatory cytokines.

Conclusions

These data suggest that rLZ-8 can antagonize STZ-induced T1D, and its mechanism may be related to inhibit inflammation and enhance Tregs generation.
Metabolome modulatory effects of Kigelia africana (Lam.) Benth. fruit extracts on oxidative stress, hyperlipidaemic biomarkers in STZ-induced diabetic rats and antidiabetic effects in 3T3 L1 adipocytes
Authors: Fagbohun Oladapo F , Olawoye Babatunde , Ademakinwa Adedeji N , Jolayemi Kehinde A , Msagati Titus A M
Published: August 2020

Objectives

The management of diabetes is considered a global problem, and a cure is yet to be discovered. This study investigated the modulatory effect of Kigelia africana fruit on oxidative stress and hyperlipidaemic biomarkers in STZ-induced diabetic rats, profiled phytoconstituents using GC-TOF-MS and evaluated antidiabetic effects on 3T3 L1 adipocytes.

Methods

Thirty male Wistar rats (120–150 g) were divided into six groups (n = 5). Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) and treated with 100, 200 and 400 of hexane fraction of KA for 28 days. Immunohistochemical evaluation was carried out using avidin-biotin immunoperoxidase (ABI) method. Catalase and SOD activities as well as the levels of total protein, albumin, bilirubin, triglyceride, cholesterol, and high-density lipoprotein were measured.

Key findings

The expressions of oxidative stress and hyperlipidaemic biomarkers alongside fasting blood glucose concentrations were remarkedly decreased in KA-treated diabetic rats. Moreover, there was a significant increase in endocrine cell distribution, area covered with increase in β-cell mass, composition and morphology of KA-treated animals. Additionally, there was constant up-regulation in 3T3 L1 adipocytes due to the presence of phytoconstituents.

Conclusion

Kigelia africana fruit can act as a modulatory agent due to its ameliorative effects against oxidative stress.
Peripheral neutrophil phenotypes during management of periodontitis
Authors: Medara Nidhi , Lenzo Jason C. , Walsh Katrina A. , Reynolds Eric C. , O’Brien‐Simpson Neil M. , Darby Ivan B.
Published: August 2020

Background and Objectives

Neutrophils are emerging as a key player in periodontal pathogenesis. The surface expression of cellular markers enables functional phenotyping of neutrophils which have distinct roles in disease states. This study aimed to evaluate the effect of periodontal management on neutrophil phenotypes in peripheral blood in periodontitis patients over one year.

Materials and Methods

Peripheral blood and the periodontal parameters, mean probing depth and percentage of sites with bleeding on probing (%BOP), were collected from 40 healthy controls and 54 periodontitis patients at baseline and 3‐, 6‐ and 12‐ months post‐treatment. Flow cytometry was used to identify CD11b+, CD16b+, CD62L− and CD66b+ expression on neutrophils, neutrophil maturation stages as promyelocytes (CD11b−CD16b−), metamyelocytes (CD11b+CD16b−) and mature neutrophils (CD11b+CD16b+), and suppressive neutrophil phenotype as bands (CD16dimCD62Lbright), normal neutrophils (CD16brightCD62Lbright) and suppressive neutrophils (CD16brightCD62Ldim).

Results

CD62L− expression decreased with treatment. No differences were observed in neutrophil maturation stages in health or disease upon treatment. Suppressive and normal neutrophils showed a reciprocal relationship, where suppressive neutrophils decreased with treatment and normal neutrophils increased with treatment. In addition, %BOP was associated with suppressive neutrophils.

Conclusion

This study demonstrates that management of periodontitis significantly modifies distinct neutrophil phenotypes in peripheral blood. Suppressive neutrophils may play a role in the pathogenesis of periodontitis. However, their exact role is unclear and requires further investigation.
Efficacy of intramuscular hydroxocobalamin supplementation in cats with cobalamin deficiency and gastrointestinal disease
Authors: Kook Peter H. , Melliger Roger H. , Hersberger Martin
Published: August 2020

Background

In humans, absorption and tissue retention rates of intramuscularly administered hydroxocobalamin (OH‐Cbl) are superior compared to cyanocobalamin (CN‐Cbl). Supplementation with OH‐Cbl has not been described in cats.

Objectives

To evaluate effects of parenteral OH‐Cbl supplementation on clinical signs, serum Cbl and methylmalonic acid (MMA) concentrations in hypocobalaminemic cats with gastrointestinal disease.

Animals

Twenty‐three client‐owned cats.

Methods

Prospective study. Serum Cbl and MMA concentrations were determined at enrollment (t0), immediately before the 4th OH‐Cbl IM injection (300 μg, given q2 weeks) (t1), and 4 weeks after the 4th injection (t2). Severity of clinical signs (activity, appetite, vomiting, diarrhea, body weight) was graded at each time point and expressed as clinical disease activity score.

Results

Median clinical disease activity score decreased significantly from t0 (6; range, 2‐10) to t1 (1; range, 0‐6) and t2 (1; range, 0‐9). Median serum Cbl concentration increased significantly from 111 pmol/L (range, 111‐218; reference range, 225‐1451 pmol/L) at t0 to 1612 pmol/L (range, 526‐14 756) (P < .001) at t1, and decreased again significantly to 712 pmol/L (range, 205‐4265) (P < .01) at t2. Median baseline serum MMA concentration at t0 (802 nmol/L; range, 238‐151 000; reference range, 120‐420 nmol/L) decreased significantly (P < .001) to 199 nmol/L (range, 29‐478) at t1, and was 205 nmol/L (range, 88‐734) at t2. Serum MMA concentrations normalized in 22/23 cats at t1, and were not significantly higher at t2 compared to t1.

Conclusions and Clinical Importance

The herein described OH‐Cbl injection scheme appears efficacious for normalization of cellular Cbl deficiency in cats with gastrointestinal disease.
Effect of ketoprofen co‐administration on pharmacokinetics of cefquinome following repeated administration in goats
Authors: Tekeli Ibrahim Ozan , Turk Erdinc , Durna Corum Duygu , Corum Orhan , Kirgiz Fatma Ceren , Sakin Fatih , Uney Kamil
Published: August 2020

The pharmacokinetics of cefquinome (2 mg/kg every 24 hr for 5 days) was determined following intramuscular administration alone and co‐administration with ketoprofen (3 mg/kg every 24 hr for 5 days) in goats. Six goats were used for the study. In the study, the crossover pharmacokinetics design with 20‐day washout period was performed in two periods. Plasma concentrations of cefquinome were assayed using high‐performance liquid chromatography by ultraviolet detection. The mean terminal elimination half‐life (t1/2ʎz), area under the concentration–time curve (AUC0–24), peak concentration (Cmax), apparent volume of distribution (Vdarea/F), and total body clearance (CL/F) of cefquinome after the administration alone were 4.85 hr, 11.06 hr*µg/ml, 2.37 µg/mL, 1.23 L/kg, and 0.17 L/h/kg after the first dose, and 5.88 hr, 17.01 hr*µg/mL, 3.04 µg/mL, 0.95 L/kg, and 0.11 L/h/kg after the last dose. Ketoprofen significantly prolonged t1/2ʎz of cefquinome, increased AUC0–24 and Cmax, and decreased Vdarea/F and CL/F. Cefquinome exhibited low accumulation after the administration alone and in combination with ketoprofen. These results indicated that ketoprofen prolonged the elimination of cefquinome in goats. The 24‐hr dosing intervals at 2 mg/kg dose of cefquinome, which co‐administered with ketoprofen, may maintain T> minimum inhibitory concentration (MIC) values above 40% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 μg/ml in goats with an inflammatory condition.
Do regeneration traits vary according to vegetation structure? A case study for savannas
Authors: Escobar Diego F E , Silveira Fernando A O , Morellato Leonor Patricia C
Published: August 2020

Aim

Regeneration traits are crucial for understanding patterns and processes in plant communities. However, regeneration traits are not reported much in community ecology, preventing a better assessment of trait‐based community assembly. Here we assessed habitat‐related regeneration traits by comparing species from open (grassland and shrubland) and closed (woodland) Brazilian savannas (cerrado).

Location

Our study site comprised two cerrado areas in southeastern Brazil that range from open to closed vegetation types, as examples of an ecological gradient of resources and environmental conditions.

Methods

We classified 82 species according to dormancy (non‐dormant, physiological, physical, physiophysical, morphological, and morphophysiological dormancy), dispersal syndrome (autochory, anemochory, exozoochory, endozoochory), and dispersal season (rainy, dry, rainy‐to‐dry and dry‐to‐rainy transitions). We determined seed mass, germination percentage, mean germination time and coefficient of variation of germination time in conditions of optimal temperatures. Principal coordinates Analysis (PCoA) was used to explore the relationships between regeneration traits and vegetation types.

Results

The two main axes of the PCoA explained 38% of the total variance. The first axis was related to germination traits (germination percentage, mean gemination time, and coefficient of variation of gemination time) and separated dormant from non‐dormant species, whereas the second axis was related to seed mass, growth form, and dispersal syndromes which sharply separated open‐ and closed‐savanna species. Unexpectedly, seed germination and dormancy traits did not differ among open‐ and closed‐savanna species.

Conclusions

Seasonality is a strong filter for both germination and seedling establishment that shapes germination strategies regardless of vegetation type. The dominant strategy was dispersal of non‐dormant seeds in the rainy season, while the least common strategy was dispersal of dormant seeds during the rainy‐to‐dry season transition. Habitat‐related germination strategies were related to growth form and seed mass, improving our understanding of community assembly in species‐rich Brazilian savannas.
Changes in thermal quality of the environment along an elevational gradient affect investment in thermoregulation by Yarrow’s spiny lizards
Authors: Lymburner A.H. , Blouin‐Demers G.
Published: August 2020

Body temperature affects physiological processes and, consequently, is assumed to have a large impact on fitness. Lizards need to thermoregulate behaviourally to maintain their body temperature within a range that maximizes performance, but there are costs associated with thermoregulation. The thermal quality of an environment directly affects the amount of time and energy that must be invested by an individual to maintain an optimal body temperature for performance; time and energy are major costs of thermoregulation. According to Huey and Slatkin’s (Q. Rev. Biol. 1976, 363) cost–benefit model of thermoregulation, lizards should only thermoregulate when the benefits outweigh the costs. Thus, in habitats of poor thermal quality, lizards should invest less into thermoregulation. We tested the hypothesis that the thermal quality of an environment dictates investment in thermoregulation across an elevational gradient. Increases in elevation are accompanied by decreases in temperature and therefore thermal quality. We recorded body temperatures of Yarrow’s spiny lizards (Sceloporus jarrovii) at ten talus slopes along an elevational gradient of over 1000 m. We found a significant positive relationship between elevation and effectiveness of thermoregulation, opposite to the prediction of the cost–benefit model of thermoregulation. This suggests that the disadvantages of thermoconformity may be greater than the costs of thermoregulating as habitats become more thermally challenging.
‘Filamentary relations’: Virginia Woolf and India
Authors: Chaudhuri Supriya
Published: August 2020

Woolf's own phrase, ‘filamentary relations’, referring to threads or filaments, ‘webs of nerve’, that reach out and touch, but may also snap and break, offers a better metaphor for Woolf's links with India than notions of filiation or affiliation. This essay traces the phrase ‘filaments of the nerve’ to Alexander Bain's The Senses and the Intellect (1855), the first text to mention a ‘stream of consciousness’. I use the trope of the filament to explore the references to India that contextualize characters and histories in Woolf's work, the transnational modernist and anti‐imperial print networks within which she was placed and the threads of connection that Indian writers work into their own texts. But just as the affective range of Woolf's textual filaments is limited by location and ideology, there are breaks and ruptures, too, in the networks of transnational modernism. Nevertheless, postcolonial Indian writers can be seen to look back at Woolf through lines of textual relation, filaments that form a postmodern web of connections. The essay offers a reading of responses to Woolf by Indian novelists across three generations: Jyotirmoyee Devi, Anita Desai and Sunetra Gupta.
Macroeconomic Effects of Non‐Standard Monetary Policy Measures in the Euro Area: The Role of Corporate Bond Purchases
Authors: Bartocci A. , Burlon L. , Notarpietro A. , Pisani M.
Published: August 2020

This paper evaluates the macroeconomic effects of the European Central Bank’s Corporate Sector Purchase Programme (CSPP) when the monetary policy rate hits the zero lower bound (ZLB). To this purpose, we calibrate and simulate a monetary union dynamic general equilibrium model of the euro area (EA). We assume that entrepreneurs can finance their spending by issuing corporate bonds or through banking loans. Our results are as follows. First, the CSPP boosts GDP in both EA regions by about 0.3 percentage points (ppt) relative to the ZLB scenario. Inflation rises as well. Given the improvement in economic conditions, the EA monetary policy rate stays at the ZLB for a shorter amount of time. Second, the CSPP indirectly stimulates banking activity. Third, the two regions benefit in a similar way from the CSPP. Fourth, the duration of the program is relevant for its effectiveness. Finally, results are robust to changes in key parameters.
Association between the maternal protein nutrition status during pregnancy and the risk of preterm birth
Authors: Xiong Ting , Wu Yuanjue , Huang Li , Chen Xi , Zhang Yu , Zhong Chunrong , Gao Qin , Hong Miao , Hu Xingwen , Yang Xuefeng , Yang Nianhong , Hao Liping
Published: August 2020

We aimed to assess protein nutrition status during pregnancy by maternal plasma total protein (MTP) levels in urban pregnant women and to explore the association between the trimester‐specific MTP levels and risk of preterm birth (PTB).

A prospective design was conducted in 3,382 mother‐newborn pairs with the second‐trimester maternal MTP information and in 3,478 mother‐newborn pairs with the third‐trimester MTP information. Multiple Cox proportional hazard regression and multiple linear regression were used to analyse the associations between MTP levels and PTB risk as well as gestational duration, respectively.

Nearly all the second‐trimester MTP levels were within the clinical reference range, but more than 40% of the third‐trimester MTP levels were less than the lower limit of normal. No significant association was found between the second‐trimester MTP level and PTB risk. However, the adjusted hazard ratios (HRs) of PTB across increasing quartiles of the third‐trimester MTP levels were 1.00 (reference), 0.59 (0.36, 0.95), 0.35 (0.20, 0.60), and 0.32 (0.19, 0.53) (p for trend < 0.001), respectively. Each standard deviations increment of the third‐trimester MTP was associated with increase of 0.13 weeks in gestational duration. Moreover, stratified analyses showed that the effects of third‐trimester MTP on PTB risk and gestational duration were stronger in pregnant women carrying female offspring than those carrying male offspring (p for interaction < 0.05).

The third‐trimester MTP level was inversely associated with PTB risk and was positively associated with gestational duration. Improving third‐trimester MTP level may be helpful for preventing PTB.