bluuebunny/crossref_metadata_2025 huggingface dataset:
In silico analysis of gene expression in V3a and the superior occipital gyrus: Relevance for migraine
Authors: Lisicki Marco , Carpinella Mariela , Coppola Gianluca , Zamparella Tatiana Castro , Ruiz-Romagnoli Emiliano , Manise Maïté , de Noordhout Alain Maertens , Schoenen Jean , Magris Diego Conci
Published: October 2020

Introduction:

Visual manifestations are the most prominent non-painful features of migraine. During the last decades, visual area V3a has gathered attention of headache scientists because of its apparent implication on aura initiation, photophobia and cortical hyper-responsiveness related to visual motion perception. In this hypothesis-generating study, we performed an in silico analysis of gene expression in left V3a and the cerebral gyrus that harbours it (left superior occipital gyrus (lSOG)) searching for transcriptomic patterns that could be linked with migraine’s pathophysiology.

Materials and methods:

Neurotransmitter receptor gene expression levels in left V3a were extracted from validated brain mRNA expression models using a probabilistic volumetric mask of this region. The primary visual cortex and other sensory cortices (auditory, olfactory and somatosensory) were used as comparators. Genome-wide transcriptomic differences between the gyrus harbouring left V3a (lSOG) and the rest of the cerebral cortex were assessed using the Allen Brain Institute Human RNA micro array atlas/database.

Results:

Adrenergic receptor β1, dopaminergic receptor D3 and serotoninergic receptors 1B, 1F and 2A, which have been previously implicated in migraine’s pathophysiology and/or treatment, showed significantly higher expression levels on left V3a. Transcriptomic differences between the lSOG harbouring V3a and the rest of the cortex comprise genes whose products are involved in neuronal excitability (SLC17A6, KCNS1, KCNG1 and GABRQ), activation of multiple signal transduction pathways (MET) and cell metabolism (SPHKAP via its interaction with cAMP-dependent protein kinase).

Conclusions:

Focal gene expression analysis of V3a suggests some clues about its implication in migraine. Further studies are warranted.
Effects of γ-irradiation on the Cu2+ sorption behaviour of NaOH-modified Philippine natural zeolites
Authors: Gili Mon Bryan Z. , Olegario Eleanor M.
Published: October 2020

Adsorption kinetic and thermodynamic tests were conducted using non-irradiated and γ-irradiated (400 kGy) NaOH-modified Philippine natural zeolites for the removal of Cu2+ ions in aqueous solution. The effects of γ-radiation on zeolites were investigated. Samples were equilibrated with binary systems of Cu2+ ↔ 2Na+ at room temperature. There were no significant changes in the elemental composition of the irradiated zeolite. Irradiation primarily results in the shrinking of the zeolite framework and improvements in the crystallinity. The γ-irradiation increases the sorption uptake according to the kinetic study in which the adsorption kinetics followed a pseudo-second-order model. Thermodynamic tests show that the adsorption isotherms of the two samples are best described by the Langmuir model. The maximum adsorption capacities of the non-irradiated and γ-irradiated NaOH-modified zeolites are 33.00 and 43.22 mg Cu2+ g–1, respectively, suggesting that γ-irradiation might enhance the maximum adsorption capacity by up to 30.8%.
Dr Barbara S. Neumann: clay scientist and industrial pioneer; creator of Laponite®
Authors: Shafran Kirill , Jeans Christopher , Kemp Simon J. , Murphy Kevin
Published: October 2020

In 2019, BYK Additives (Widnes, UK; www.byk.com) marked the 55th anniversary of the discovery by Dr Barbara Zsusanna (Susanna) Neumann of the extraordinary product known as Laponite®. The range of Laponite® products developed in the UK during the early 1960s is one of the first examples of truly nanodimensional materials manufactured on an industrial scale, at a time when the field of nanotechnology was only being hinted at (Feynman, 1959). These hectorite-like synthetic nanoclays with very unusual properties have been an enduring commercial success for the UK company that first patented and introduced them to the market, Laporte Industries, which is now a part of the BYK company. The Laponite® brand has proved tremendously popular with academic and industrial scientists worldwide, being cited in >3000 patents and >2500 published academic articles.
Clinical MDR1 inhibitors enhance Smac-mimetic bioavailability to kill murine LSCs and improve survival in AML models
Authors: Morrish Emma , Copeland Anthony , Moujalled Donia M. , Powell Jason A. , Silke Natasha , Lin Ann , Jarman Kate E. , Sandow Jarrod J. , Ebert Gregor , Mackiewicz Liana , Beach Jessica A. , Christie Elizabeth L. , Lewis Alexander C. , Pomilio Giovanna , Fischer Karla C. , MacPherson Laura , Bowtell David D. L. , Webb Andrew I. , Pellegrini Marc , Dawson Mark A. , Pitson Stuart M. , Wei Andrew H. , Silke John , Brumatti Gabriela
Published: October 2020

The specific targeting of inhibitor of apoptosis (IAP) proteins by Smac-mimetic (SM) drugs, such as birinapant, has been tested in clinical trials of acute myeloid leukemia (AML) and certain solid cancers. Despite their promising safety profile, SMs have had variable and limited success. Using a library of more than 5700 bioactive compounds, we screened for approaches that could sensitize AML cells to birinapant and identified multidrug resistance protein 1 inhibitors (MDR1i) as a class of clinically approved drugs that can enhance the efficacy of SM therapy. Genetic or pharmacological inhibition of MDR1 increased intracellular levels of birinapant and sensitized AML cells from leukemia murine models, human leukemia cell lines, and primary AML samples to killing by birinapant. The combination of clinical MDR1 and IAP inhibitors was well tolerated in vivo and more effective against leukemic cells, compared with normal hematopoietic progenitors. Importantly, birinapant combined with third-generation MDR1i effectively killed murine leukemic stem cells (LSCs) and prolonged survival of AML-burdened mice, suggesting a therapeutic opportunity for AML. This study identified a drug combination strategy that, by efficiently killing LSCs, may have the potential to improve outcomes in patients with AML.
Novel Surface Design of Deployable Reflector Antenna Based on Polar Scissor Structures
Authors: Zhao Pengyuan , Liu Jinguo , Wu Chenchen , Li Yangmin , Chen Keli
Published: October 2020

Space-deployable mechanisms can be used as supporting structures for large-diameter antennas in space engineering. This study proposes a novel method for constructing the surface design of space reflector antennas based on polar scissor units. The concurrency and deployability equations of the space scissor unit with definite surface constraints are derived using the rod and vector methods. Constraint equations of the spatial transformation for space n-edge polar scissor units are summarized. A new closed-loop deployable structure, called the polar scissor deployable antenna (PSDA), is designed by combining planar polar scissor units with spatial polar scissor units. The over-constrained problem is solved by releasing the curve constraint that locates at the end-point of the planar scissor mechanism. Kinematics simulation and error analysis are performed. The results show that the PSDA can effectively fit the paraboloid of revolution. Finally, deployment experiments verify the validity and feasibility of the proposed design method, which provides a new idea for the construction of large space-reflector antennas.
Comparison of reliability evaluation methods between China and Canada standards for wood structures featuring duration of load
Authors: Wu Qiongyao , Niu Shuang , Zhu Enchun
Published: October 2020

Duration of load (DOL) is a key factor in design of wood structures, which makes the reliability analysis of wood structures more complicated. The importance of DOL is widely recognized, yet the methods and models through which it is incorporated into design codes vary substantially by country/region. Few investigations of the effect of different model assumptions of DOL and other random variables on the results of reliability analysis of wood structures can be found. In this paper, comparisons are made on the reliability analysis methods that underlie the China and the Canada standards for design of wood structures. Main characteristics of these two methods, especially the way how DOL is treated are investigated. Reliability analysis was carried out with the two methods employing the same set of material properties and load parameters. The resulted relationships between reliability index β and resistance partial factor γR* (the β–γR* curves) for four load combinations are compared to study the safety level indicated by the two methods. The comparison shows that the damage accumulation model (Foschi–Yao model) in the Canada analysis method is highly dependent on the type and duration of load, resulting in more conservative design than the China analysis method in loading cases dominated by dead load, but less conservative design in cases of high level of live loads. The characteristics of the load effect term of the performance function are also found to make considerable difference in reliability levels between the two methods. This study aims to provide references for researchers and standard developers in the field of wood structures.
Bio-economics of Indian hybrid Bt cotton and farmer suicides
Authors: Gutierrez Andrew Paul , Ponti Luigi , Kranthi Keshav R. , Baumgärtner Johann , Kenmore Peter. E. , Gilioli Gianni , Boggia Antonio , Cure Jose Ricardo , Rodríguez Daniel
Published: October 2020

Background

The implementation of hybrid Bt cotton unique to India has been heralded as a grand success by government agencies, seed companies and other proponents, and yet yields have stagnated at low levels and production costs have risen 2.5–3-fold. The low-yield hybrid cotton system of India contributes thousands of farmer suicides to the annual national toll. Conceptual and methodological barriers have hindered bioeconomic analysis of the ecological and social sustainability of such cross-scale agro-ecological problems in time and geographic space, under global technology and climate change. As a paradigm shift, we use conceptually simple, parameter-sparse, theoretically based, mechanistic, weather-driven physiologically based demographic models (PBDMs) to deconstruct the bio-economics of the Indian cotton system.

Results

Our analysis of Indian hybrid cotton system explains some extant ecological and economic problems, and suggests a viable solution. Specifically, the model accurately captured the age-stage mass dynamics of rainfed and irrigated cotton growth/development and the interactions with the key pest pink bollworm across five south-central Indian states, and enabled identification of proximate bioeconomic factors responsible for low yield and their relationship to farmer suicides. The results are reinforced by analysis of Ministry of Agriculture annual state-level data. We explain why short-season, high-density non-GM cotton is a highly viable solution for Indian cotton farmers in rainfed and irrigated cotton areas of the five states, and possibly nationally. The transition from a theoretical bioeconomic construct to a real-world regional bioeconomic analysis proved seamless.

Conclusions

The hybrid long-season Bt technology for rainfed and irrigated cotton is unique to India, and is a value capture mechanism. This technology is suboptimal leading to stagnant yields, high input costs, increased insecticide use, and low farmer incomes that increase economic distress that is a proximate cause of cotton farmer suicides. The current GM Bt technology adds costs in rainfed cotton without commensurate increases in yield. Non-GM pure-line high-density short-season varieties could double rainfed cotton yield, reduce costs, decrease insecticide use, and help ameliorate suicides. The GM hybrid technology is inappropriate for incorporation in short-season high-density varieties.
Bayesian splines versus fractional polynomials in network meta-analysis
Authors: Heinecke Andreas , Tallarita Marta , De Iorio Maria
Published: October 2020

Background

Network meta-analysis (NMA) provides a powerful tool for the simultaneous evaluation of multiple treatments by combining evidence from different studies, allowing for direct and indirect comparisons between treatments. In recent years, NMA is becoming increasingly popular in the medical literature and underlying statistical methodologies are evolving both in the frequentist and Bayesian framework. Traditional NMA models are often based on the comparison of two treatment arms per study. These individual studies may measure outcomes at multiple time points that are not necessarily homogeneous across studies.

Methods

In this article we present a Bayesian model based on B-splines for the simultaneous analysis of outcomes across time points, that allows for indirect comparison of treatments across different longitudinal studies.

Results

We illustrate the proposed approach in simulations as well as on real data examples available in the literature and compare it with a model based on P-splines and one based on fractional polynomials, showing that our approach is flexible and overcomes the limitations of the latter.

Conclusions

The proposed approach is computationally efficient and able to accommodate a large class of temporal treatment effect patterns, allowing for direct and indirect comparisons of widely varying shapes of longitudinal profiles.
Revisiting: “prevalence of and factors associated with sarcopenia among multi-ethnic ambulatory older Asians with type 2 diabetes mellitus in a primary care setting”
Authors: Li Xueting , Xu Fengqiang , Hu Longgang , Fang Hao , An Yi
Published: October 2020

Background

Sarcopenia is an age-related clinical syndrome characterized by loss of muscle mass and reduced muscle function. Diseases that contribute to sarcopenia include type 2 diabetes mellitus (T2DM), chronic obstructive pulmonary disease (COPD), heart failure, chronic kidney disease, and cancer and others. Fung FY et al. (BMC Geriatrics. 2019;19(1):122) conducted a single-center study aimed to determine the prevalence of sarcopenia among older patients with T2DM and to identify factors which mitigate sarcopenia. Their study entitled “Prevalence of and factors associated with sarcopenia among multi-ethnic ambulatory older Asians with type 2 diabetes mellitus in a primary care setting” suggested that the prevalence of sarcopenia in older patients with T2DM was 27.4%, and that Chinese ethnicity was associated with a greater risk of sarcopenia in the study population.

Discussion

Deficiency in scientific research and analysis of other diseases associated with sarcopenia such as COPD, may contribute to misestimation of the prevalence of sarcopenia in older patients with T2DM. We are concerned that the conclusions of this single-center study with a small study population might be unreliable.

The prevalence of sarcopenia in older patients with T2DM in a single-center study with a small sample size may be misestimated due to the lack of strict exclusion criteria and detailed analysis of other diseases that contribute to sarcopenia. In addition, it is inappropriate to draw the conclusion that Chinese ethnic group was associated with a greater risk of sarcopenia among the study population.
Urinary nitrate concentration as a marker for kidney transplant rejection
Authors: Riddell Amy , Kirkwood John , Smallwood Miranda , Winyard Paul , Knight Beatrice , Romanczuk Lidia , Shore Angela , Gilchrist Mark
Published: October 2020

Background

Early identification and treatment of kidney transplant rejection episodes is vital to limit loss of function and prolong the life of the transplanted kidney and recipient. Current practice depends on detecting a creatinine rise. A biomarker to diagnose transplant rejection at an earlier time point than current practice, or to inform earlier decision making to biopsy, could be transformative.

It has previously been shown that urinary nitrate concentration is elevated in renal transplant rejection. Nitrate is a nitric oxide (NO) oxidation product. Transplant rejection upregulates NO synthesis via inducible nitric oxide synthase leading to elevations in urinary nitrate concentration. We have recently validated a urinary nitrate concentration assay which could provide results in a clinically relevant timeframe. Our aim was to determine whether urinary nitrate concentration is a useful tool to predict renal transplant rejection in the context of contemporary clinical practice.

Methods

We conducted a prospective observational study, recruiting renal transplant participants over an 18-month period. We made no alterations to the patients’ clinical care including medications, immunosuppression, diet and frequency of visits. We collected urine samples from every clinical attendance. We assessed the urinary nitrate to creatinine ratio (uNCR) between patient groups: routine attendances, biopsy proven rejection, biopsy proven no rejection and other call backs. uNCR was examined over time for those with biopsy proven transplant rejection. These four groups were compared using an ANOVA test.

Results

A total of 2656 samples were collected. uNCR during biopsy proven rejection, n = 15 (median 49 μmol/mmol, IQR 23–61) was not significantly different from that of routine samples, n = 164 (median 55 μmol/mmol, IQR 37–82) (p = 0.55), or biopsy proven no rejection, n = 12 (median 39 μmol/mmol, IQR 21–89) (P = 0.77).

Overall uNCR was highly variable with no diagnostic threshold for kidney transplant rejection. Furthermore, within-patient uNCR was highly variable over time, and thus it was not possible to produce individualised patient thresholds to identify rejection. The total taking Tacrolimus was 204 patients, with no statistical difference between the uNCR of all those on Tacrolimus, against those not, p = 0.18.

Conclusion

The urinary nitrate to creatinine ratio is not a useful biomarker for renal transplant rejection.
Value of monitoring urine ammonia at time of biopsy in patients with lupus nephritis
Authors: Zhu Huanhuan , Wan Huiting , Duan Suyan , Zhang Chengning , Li Qing , Liu Simeng , Wu Lin , Zhang Bo , Xing Changying , Yuan Yanggang
Published: October 2020

Objective

Although lupus nephritis (LN) is mostly characterized by glomerular involvement, tubular injury is indispensable in its pathogenesis and progression. The purpose of this study is to examine associations between urinary acidification function and clinical and pathological features in LN.

Methods

A total of 103 patients with renal biopsy-proven LN were included, and clinical parameters and laboratory data were obtained from the medical records. Plasma samples, 24-h urine samples and the urinary acidification function, including urine pH, titratable acid, and ammonia, were collected within 3 days before the day of renal biopsy. The correlations between defects of acid excretion and clinical and pathological features were then assessed. Logistic regression analysis was used to assess factors associated with the presence of nephrotic range proteinuria.

Results

The urine ammonia level was inversely correlated with SLEDAI-2 K scores, rSLEDAI scores, serum creatinine levels and proteinuria, while it was positively correlated with eGFR. And urine titratable acid was only inversely correlated with rSLEDAI scores and proteinuria. Moreover, urine ammonia had significant negative correlations with AI scores, interstitial inflammatory cell infiltration, CI scores, glomerular sclerosis, fibrous crescents, tubular atrophy and interstitial fibrosis. And urine titratable acid was mainly inversely correlated with CI scores. Furthermore, univariate logistic analyses identified that both urine titratable acid and ammonia were correlated with the presence of nephrotic range proteinuria. After the adjustment for chronicity index and eGFR in a multivariate logistic analysis, only urine titratable acid was still identified as an independent risk factor for the occurrence of nephrotic range proteinuria.

Conclusions

Urine ammonia was associated with clinical and pathological features of chronicity and tubulointerstitial disease activity among patients with lupus nephritis. Furthermore, the strong association between urinary protein and titratable acid excretion at the time of kidney biopsy is significant even after adjusting for the chronicity index and eGFR at biopsy.
LncRNA SNHG10 is downregulated in non-small cell lung cancer and predicts poor survival
Authors: Liang Meng , Wang Linlin , Cao Chuanhua , Song Shimao , Wu Feng
Published: October 2020

Background

LncRNA SNHG10 has been reported to be an oncogenic lncRNA in liver cancer. However, its roles in non-small cell lung cancer (NSCLC) remains unknown.

Methods

Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. RT-qPCR was used to detect the expression of SNHG10 and miR-21 in tissues. Overexpression experiments were used to evaluate the interaction between SNHG10 and miR-21 in NSCLC cells. CCK-8 assay was used to detect the cell proliferation.

Results

We observed the expression of SNHG10 was down-regulated in non-small cell lung cancer (NSCLC) compared with that in non-tumor tissues. Moreover, we found that high expression levels of SNHG10 predicted favorable survival of NSCLC patients, and the expression of miR-21 were increased in NSCLC and inversely correlated with SNHG10 expression. In NSCLC cells, overexpression of SNHG10 resulted in increased miR-21 gene methylation and decreased miR-21 expression. Moreover, overexpression of SNHG10 attenuated the enhancing effect of miR-21 overexpression on cell proliferation.

Conclusions

SNHG10 may involve in NSCLC cell proliferation by regulating the miR-21 gene methylation.
The differences in whole-body sagittal alignment between different postures in young, healthy adults
Authors: Xue Rui , Liu Dai , Shen Yong
Published: October 2020

Study design

Prospective study.

Objective

To identify the radiographic differences between the standard upright position and the natural and comfortable upright position.

Methods

The radiographic data of 50 young and healthy adults were evaluated, and parameters including the global cervical angle (GCA), global thoracic angle (GTA), global lumbar angle (GLA) were used to depict the spine profile; the distance from the cranial center to the posterior corner of S1 (CSVA-S), the center of the hip (CSVA-H), the center of the knee (CSVA-K) and the center of the ankle (CSVA-A) were measured in both the standard and the natural and comfortable upright positions to assess whole-body balance.

Results

Significant differences were observed in the GCA (17.39 ± 6.90 vs. 10.90 ± 3.77, p < .001), GTA (25.63 ± 7.27 vs. 45.42 ± 8.15 p < .001), GLA (42.64 ± 8.05 vs. 20.21 ± 7.47 p < .001), CSVA-S (0.33 ± 2.76 cm vs. 8.54 ± 3.78 cm, p < 0.001), CSVA-H (1.53 ± 3.11 cm vs. 5.71 ± 3.26 cm, p < 0.001), CSVA-K (3.58 ± 2.47 cm vs. 5.22 ± 2.69 cm, p = 0.002) and CSVA-A (1.79 ± 1.92 cm vs. 4.79 ± 2.51 cm, p < 0.001) between the two different standing postures. Compared with the standard upright position, the natural and comfortable upright position results in a more kyphotic spine profile.

Conclusion

Significant differences in sagittal radiographic parameters were found between the standard upright position and the natural and comfortable upright position; the latter served as a marker for energy conservation during standing and revealed a more kyphotic spinal profile. The standard upright position and natural and comfortable upright position are equally important and should be addressed before a surgical plan is developed for patients who need surgery.
Caregiver’s perspectives on facilitators and barriers of active participation in cerebral palsy rehabilitation in North West Nigeria: a qualitative study
Authors: Abdullahi Auwal , Isah Auwal
Published: October 2020

Background

Cerebral Palsy (CP) refers to the permanent disorders involving postural and movement control as a result of injury to the developing brain. As a result of impairment in postural and movement control, children with CP usually have problems in carrying out activities of daily living (ADL). This makes them dependent on help from their caregivers. Thus, for effective rehabilitation of children with CP, active participation of their caregivers is important. This study seeks to explore the facilitators and barriers of active participation of caregivers in the rehabilitation of children with CP in Kano, Nigeria.

Methods

The study design used was qualitative in-depth interview. The participants were caregivers of children with CP at Hasiya Bayero Paediatric Specialists Hospital, Kano. The caregivers were interviewed face-to-face, and their responses were audio-recorded with a tape recorder, supplemented with note taking. The data generated was analyzed using constant comparative analysis.

Results

Forty young caregivers (mean age, 27.17 ± 4.46 years) participated in the study. They expressed encouragement from the therapist managing the child, family support, empathy, improvement in the conditions of other children with CP, cooperation of the child during home programs family support and improvement in the child’s condition as factors that facilitate their active participation in the rehabilitation of the children. However, they mentioned occupation, financial resources and the number of children the caregiver has are the barriers to their active participation in the rehabilitation of the children.

Conclusions

Both the facilitators and barriers of active participation of caregivers in the rehabilitation of children with CP need to be recognized in order to help caregivers reinforce or overcome them respectively. In addition, economically sustainable and accessible rehabilitation services are needed for all children with CP. Similarly, sharing caregiving rehabilitation tasks amongst family members could facilitate caregiver active participation.
Large-scale in silico mutagenesis experiments reveal optimization of genetic code and codon usage for protein mutational robustness
Authors: Schwersensky Martin , Rooman Marianne , Pucci Fabrizio
Published: October 2020

Background

How, and the extent to which, evolution acts on DNA and protein sequences to ensure mutational robustness and evolvability is a long-standing open question in the field of molecular evolution. We addressed this issue through the first structurome-scale computational investigation, in which we estimated the change in folding free energy upon all possible single-site mutations introduced in more than 20,000 protein structures, as well as through available experimental stability and fitness data.

Results

At the amino acid level, we found the protein surface to be more robust against random mutations than the core, this difference being stronger for small proteins. The destabilizing and neutral mutations are more numerous in the core and on the surface, respectively, whereas the stabilizing mutations are about 4% in both regions. At the genetic code level, we observed smallest destabilization for mutations that are due to substitutions of base III in the codon, followed by base I, bases I+III, base II, and other multiple base substitutions. This ranking highly anticorrelates with the codon-anticodon mispairing frequency in the translation process. This suggests that the standard genetic code is optimized to limit the impact of random mutations, but even more so to limit translation errors. At the codon level, both the codon usage and the usage bias appear to optimize mutational robustness and translation accuracy, especially for surface residues.

Conclusion

Our results highlight the non-universality of mutational robustness and its multiscale dependence on protein features, the structure of the genetic code, and the codon usage. Our analyses and approach are strongly supported by available experimental mutagenesis data.
Haematological and serum biochemical reference values in Chinese water deer (Hydropotes inermis): a preliminary study
Authors: Nie Dayi , Gui Jianfeng , Zhao Na , Lin Yi , Tang Haiming , Cai Feng , Shen Guoping , Liu Jiazhong , Zhang Endi , Chen Min
Published: October 2020

Background

A selection of haematological and serum biochemical profile was first presented from the 81 samples of Chinese water deer (Hydropotes inermis). The deer health assessment database was initially established, especially in relation to determining potential effects associated with diseases diagnosis.

Results

Blood samples were analyzed for different haematological parameters viz. white blood cells (WBC), red blood cells (RBC), haemoglobin (HGB), packed-cell volume (PCV), platelet count (PLT), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean red blood cells distribution width coefficient of variation (RDW) and different hematological parameters viz. total protein (TP), albumin (ALB), globulin (GLB), albumin to globulin ratio (A/G), total bilirubin (TBIL), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, creatinine, urea (BUN), uric acid, total cholesterol (TC), triglyceride, creatine kinase (CK), lactate dehydrogenase (LDH) and cortisol. The adult females had higher values than adult males in albumin, mean corpuscular volume, packed-cell volume, and hemoglobin content values. The deer from Shanghai had higher urea nitrogen values than those from Zhoushan.

Conclusion

To our knowledge this is the first report about the haematological and serum biochemical parameters in Chinese water deer. We had initially established a profile of Chinese water deer on haematological and serum biochemical parameters based on 81 samples we had collected. The findings can serve as a primary reference for health monitoring and disease prevention in this species.
Elasticity spectra as a tool to investigate actin cortex mechanics
Authors: Lüchtefeld Ines , Bartolozzi Alice , Mejía Morales Julián , Dobre Oana , Basso Michele , Zambelli Tomaso , Vassalli Massimo
Published: October 2020

Background

The mechanical properties of single living cells have proven to be a powerful marker of the cell physiological state. The use of nanoindentation-based single cell force spectroscopy provided a wealth of information on the elasticity of cells, which is still largely to be exploited. The simplest model to describe cell mechanics is to treat them as a homogeneous elastic material and describe it in terms of the Young’s modulus. Beside its simplicity, this approach proved to be extremely informative, allowing to assess the potential of this physical indicator towards high throughput phenotyping in diagnostic and prognostic applications.

Results

Here we propose an extension of this analysis to explicitly account for the properties of the actin cortex. We present a method, the Elasticity Spectra, to calculate the apparent stiffness of the cell as a function of the indentation depth and we suggest a simple phenomenological approach to measure the thickness and stiffness of the actin cortex, in addition to the standard Young’s modulus.

Conclusions

The Elasticity Spectra approach is tested and validated on a set of cells treated with cytoskeleton-affecting drugs, showing the potential to extend the current representation of cell mechanics, without introducing a detailed and complex description of the intracellular structure.
Health professional regulation in historical context: Canada, the USA and the UK (19th century to present)
Authors: Adams Tracey L.
Published: October 2020

Background

There is no widespread agreement over what form healthcare professional regulation should take, and the evidence base concerning the effectiveness and fairness of regulatory systems and practices is limited. Those urging policy change argue there is a need to modernize; however, there is much we can learn from reviewing the history of healthcare professional regulation.

Main body

An overview of the history of regulation in Canada, with consideration of the United States of America and the United Kingdom, is provided. Self-regulating professions emerged in the nineteenth century, influenced by a variety of stakeholders responding to local concerns for healthcare quality, access and professional training. Regulatory practices changed over the course of the twentieth and twenty-first centuries in response to changing stakeholders and shifting interests.

Conclusions

Reviewing the history of healthcare professional regulation reveals lessons to inform policy in a range of settings.
Where we eat is who we are: a survey of food-related travel patterns to Singapore’s hawker centers, food courts and coffee shops
Authors: Tan Shin Bin , Arcaya Mariana
Published: October 2020

Background

The development of empirically-grounded policies to change the obesogenic nature of urban environment has been impeded by limited, inconclusive evidence of the link between food environments, dietary behaviors, and health-related outcomes, in part due to inconsistent methods of classifying and analyzing food environments. This study explores how individual and built environment characteristics may be associated with how far and long people travel to food venues,that can serve as a starting point for further policy-oriented research to develop a more nuanced, context-specific delineations of ‘food environments’ in an urban Asian context.

Methods

Five hundred twenty nine diners in eight different neighborhoods in Singapore were surveyed about how far and long they travelled to their meal venues, and by what mode. We then examined how respondents’ food-related travel differed by socioeconomic characteristics, as well as objectively-measured built environment characteristics at travel origin and destination, using linear regression models.

Results

Low-income individuals expended more time traveling to meal destinations than high-income individuals, largely because they utilized slower modes like walking rather than driving. Those travelling from areas with high food outlet density travelled shorter distances and times than those from food-sparse areas, while those seeking meals away from their home and work anchor points had lower thresholds for travel. Respondents also travelled longer distances to food-dense locations, compared to food-sparse locations.

Conclusion

Those seeking to improve food environments of poor individuals should consider studying an intervention radius pegged to typical walking distances, or ways to improve their transport options as a starting point. Policy-focused research on food environments should also be sensitive to locational characteristics, such as food outlet densities and land use.
Allogeneic administration of human umbilical cord-derived mesenchymal stem/stromal cells for bronchopulmonary dysplasia: preliminary outcomes in four Vietnamese infants
Authors: Nguyen Liem Thanh , Trieu Thai T. H. , Bui Hue T. H. , Hoang Van T. , Nguyen Anh T. T. , Trinh Nhung T. H. , Nguyen Kien T. , Hoang Duc M.
Published: October 2020

Background

Bronchopulmonary dysplasia (BPD) is a severe condition in premature infants that compromises lung function and necessitates oxygen support. Despite major improvements in perinatal care minimizing the devastating effects, BPD remains the most frequent complication of extreme preterm birth. Our study reports the safety of the allogeneic administration of umbilical cord-derived mesenchymal stem/stromal cells (allo-UC-MSCs) and the progression of lung development in four infants with established BPD.

Methods

UC tissue was collected from a healthy donor, followed by propagation at the Stem Cell Core Facility at Vinmec Research Institute of Stem Cell and Gene Technology. UC-MSC culture was conducted under xeno- and serum-free conditions. Four patients with established BPD were enrolled in this study between May 25, 2018, and December 31, 2018. All four patients received two intravenous doses of allo-UC-MSCs (1 million cells/kg patient body weight (PBW) per dose) with an intervening interval of 7 days. Safety and patient conditions were evaluated during hospitalization and at 7 days and 1, 6 and 12 months postdischarge.

Results

No intervention-associated severe adverse events or prespecified adverse events were observed in the four patients throughout the study period. At the time of this report, all patients had recovered from BPD and were weaned off of oxygen support. Chest X-rays and CT scans confirmed the progressive reductions in fibrosis.

Conclusions

Allo-UC-MSC administration is safe in preterm infants with established BPD.

Trial registration This preliminary study was approved by the Vinmec International Hospital Ethics Board (approval number: 88/2019/QĐ-VMEC; retrospectively registered March 12, 2019).
Contrast-induced nephropathy and oxidative stress: mechanistic insights for better interventional approaches
Authors: Kusirisin Prit , Chattipakorn Siriporn C. , Chattipakorn Nipon
Published: October 2020

Contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI) is an iatrogenic acute kidney injury observed after intravascular administration of contrast media for intravascular diagnostic procedures or therapeutic angiographic intervention. High risk patients including those with chronic kidney disease (CKD), diabetes mellitus with impaired renal function, congestive heart failure, intraarterial intervention, higher volume of contrast, volume depletion, old age, multiple myeloma, hypertension, and hyperuricemia had increased prevalence of CIN. Although CIN is reversible by itself, some patients suffer this condition without renal recovery leading to CKD or even end-stage renal disease which required long term renal replacement therapy. In addition, both CIN and CKD have been associated with increasing of mortality. Three pathophysiological mechanisms have been proposed including direct tubular toxicity, intrarenal vasoconstriction, and excessive production of reactive oxygen species (ROS), all of which lead to impaired renal function. Reports from basic and clinical studies showing potential preventive strategies for CIN pathophysiology including low- or iso-osmolar contrast media are summarized and discussed. In addition, reports on pharmacological interventions to reduce ROS and attenuate CIN are summarized, highlighting potential for use in clinical practice. Understanding this contributory mechanism could pave ways to improve therapeutic strategies in combating CIN.
Emergence of T cell immunosenescence in diabetic chronic kidney disease
Authors: Chiu Yen-Ling , Tsai Wan-Chuan , Hung Ruo-Wei , Chen I-Yu , Shu Kai-Hsiang , Pan Szu-Yu , Yang Feng-Jung , Ting Te-Tien , Jiang Ju-Ying , Peng Yu-Sen , Chuang Yi-Fang
Published: October 2020

Background

Type 2 diabetes is an important challenge given the worldwide epidemic and is the most important cause of end-stage renal disease (ESRD) in developed countries. It is known that patients with ESRD and advanced renal failure suffer from immunosenescence and premature T cell aging, but whether such changes develop in patients with less severe chronic kidney disease (CKD) is unclear.

Method

523 adult patients with type 2 diabetes were recruited for this study. Demographic data and clinical information were obtained from medical chart review. Immunosenescence, or aging of the immune system was assessed by staining freshly-obtained peripheral blood with immunophenotyping panels and analyzing cells using multicolor flow cytometry.

Result

Consistent with previously observed in the general population, both T and monocyte immunosenescence in diabetic patients positively correlate with age. When compared to diabetic patients with preserved renal function (estimated glomerular filtration rate > 60 ml/min), patients with impaired renal function exhibit a significant decrease of total CD3+ and CD4+ T cells, but not CD8+ T cell and monocyte numbers. Immunosenescence was observed in patients with CKD stage 3 and in patients with more severe renal failure, especially of CD8+ T cells. However, immunosenescence was not associated with level of proteinuria level or glucose control. In age, sex and glucose level-adjusted regression models, stage 3 CKD patients exhibited significantly elevated percentages of CD28−, CD127−, and CD57+ cells among CD8+ T cells when compared to patients with preserved renal function. In contrast, no change was detected in monocyte subpopulations as renal function declined. In addition, higher body mass index (BMI) is associated with enhanced immunosenescence irrespective of CKD status.

Conclusion

The extent of immunosenescence is not significantly associated with proteinuria or glucose control in type 2 diabetic patients. T cells, especially the CD8+ subsets, exhibit aggravated characteristics of immunosenescence during renal function decline as early as stage 3 CKD. In addition, inflammation increases since stage 3 CKD and higher BMI drives the accumulation of CD8+CD57+ T cells. Our study indicates that therapeutic approaches such as weight loss may be used to prevent the emergence of immunosenescence in diabetes before stage 3 CKD.
Sufficience serum vitamin D before 20 weeks of pregnancy reduces the risk of gestational diabetes mellitus
Authors: Yue Chao-Yan , Ying Chun-Mei
Published: October 2020

Objective

Our aim was to evaluate the relationship between serum vitamin D levels before 20 weeks of pregnancy and the risk of gestational diabetes mellitus.

Methods

This study is a retrospective study. We analyzed the relationship between serum 25 (OH) D level before 20 weeks of pregnancy (first antenatal examination) and the risk of gestational diabetes mellitus. Age, parity and pre-pregnancy body mass index were used as confounding factors. 8468 pregnant women were enrolled in this study between January 2018 and March 2020 at the Obstetrics and Gynecology Hospital of Fudan University. Adjusted smoothing splinespline plots, subgroup analysis and multivariate logistic regression analysis was conducted to estimate the relative risk between 25(OH)D and gestational diabetes mellitus.

Results

After fully adjusting the confounding factors, serum vitamin D is a protective factor in gestational diabetes mellitus (OR = 0.90). Compared with vitamin D deficiency, vitamin D insufficiency (OR = 0.78), sufficience (OR = 0.82) are a protective factor for gestational diabetes mellitus.

Conclusion

Sufficience vitamin D before 20 weeks of pregnancy is a protective factor for gestational diabetes mellitus. Vitamin D > 20 ng/mL can reduce the risk of GDM, which is not much different from the effect of > 30 ng/mL. The protective effect of vitamin D is more significant in obese pregnant women.
Dietary iron intake and anemia: food frequency questionnaire in patients with hereditary hemorrhagic telangiectasia
Authors: Cavalcoli Federica , Gandini Alberto , Matelloni Irene Aglaia , Catalano Francesca , Alicante Saverio , Manfredi Guido , Brambilla Gianfranco , Menozzi Fernanda , Perolini Federica , Costi Egon , Bertè Roberto , Buscarini Elisabetta
Published: October 2020

Background

Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic inherited vascular disease characterized by a heterogeneous clinical presentation and prognosis. Dietary evaluation is relevant in HHT patients to provide adequate iron and nutrient intake. Additionally, different dietary items have been reported to precipitate epistaxis in this setting. Our primary aim was to investigate the dietary habits of HHT patients through a food-frequency questionnaire (FFQ) to evaluate the presence of precipitants and/or protective factors for epistaxis and the occurrence of possible dietary modifications. The secondary aims were to evaluate the nutritional intake of iron in HHT patients and the self-reported effect of iron treatments on epistaxis. From April 2018 to October 2018, a 138-item FFQ was provided to HHT patients followed up at the HHT Referral Center of Crema Maggiore Hospital. The relationship between food items and epistaxis was ascertained on a separate form. Daily iron intake was calculated to establish the mean iron content of food items reported in the FFQ.

Results

One hundred forty-nine questionnaires were evaluated [72 females, median age 54 years (12–76). Overall, 26 (18%) patients reported dietary items that improved epistaxis (mostly blueberries and red fruits, green vegetables and legumes), while 38 (26%) reported some dietary items that exacerbated epistaxis (spices, chocolate, alcohol, strawberries and ginger). Dietary modifications were reported in up to 58% of cases. In HHT patients, the mean daily iron intake was 8.46 ± 2.78 mg, and no differences were observed in the iron intake of patients reporting a diet modification and those who did not.

Conclusions

In the comprehensive management of HHT a healthy and balanced diet, with increased consumption of dietary items with a high iron content, should be encouraged.
Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response after Out-of-Hospital Cardiac Arrest (IMICA): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial
Authors: Meyer Martin A. S. , Wiberg Sebastian , Grand Johannes , Kjaergaard Jesper , Hassager Christian
Published: October 2020

Background

Resuscitated out-of-hospital cardiac arrest (OHCA) patients who remain comatose at admission are at high risk of morbidity and mortality. This has been attributed to the post-cardiac arrest syndrome (PCAS) which encompasses multiple interacting components, including systemic inflammation. Elevated levels of circulating interleukin-6 (IL-6), a pro-inflammatory cytokine, is associated with worse outcomes in OHCA patients, including higher vasopressor requirements and higher mortality rates. In this study, we aim to reduce systemic inflammation after OHCA by administering a single infusion of tocilizumab, an IL-6 receptor antibody approved for use for other indications.

Methods

Investigator-initiated, double-blinded, placebo-controlled, single-center, randomized clinical trial in comatose OHCA patients admitted to an intensive cardiac care unit. Brief inclusion criteria: OHCA of presumed cardiac cause, persistent unconsciousness, age ≥ 18 years. Intervention: 80 patients will be randomized in a 1:1 ratio to a single 1-h intravenous infusion of either tocilizumab or placebo (NaCl). During the study period, patients will receive standard of care, including sedation and targeted temperature management of 36 ° for at least 24 h, vasopressors and/or inotropes as/if needed, prophylactic antibiotics, and any additional treatment at the discretion of the treating physician. Blood samples are drawn for measurements of biomarkers included in the primary and secondary endpoints during the initial 72 h. Primary endpoint: reduction in C-reactive protein (CRP). Secondary endpoints (abbreviated): cytokine levels, markers of brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, adverse events, and follow-up assessment of cerebral function and mortality.

Discussion

We hypothesize that reducing the effect of circulating IL-6 by administering an IL-6 receptor antibody will mitigate the systemic inflammatory response and thereby modify the severity of PCAS, in turn leading to lessened vasopressor use, more normal hemodynamics, and better organ function. This will be assessed by primarily focusing on hemodynamics and biomarkers of organ damage during the initial 72 h.

In addition, pro-inflammatory and anti-inflammatory cytokines will be measured to assess if cytokine patterns are modulated by IL-6 receptor blockage.

Trial registration

ClinicalTrials.gov Identifier: NCT03863015; submitted February 22, 2019, first posted March 5, 2019.

EudraCT: 2018-002686-19; date study was authorized to proceed: November 7, 2018.