bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-allodynic effect induced by curcumin in neuropathic rat is mediated through the NO-cyclic-GMP-ATP sensitive K+ channels pathway
Authors: Pastrana-Quintos Tracy , Salgado-Moreno Giovanna , Pérez-Ramos Julia , Coen Arrigo , Godínez-Chaparro Beatriz
Published: March 2020

Background

Recent studies pointed up that curcumin produces an anti-nociceptive effect in inflammatory and neuropathic pain. However, the possible mechanisms of action that underline the anti-allodynic effect induced by curcumin are not yet established. The purpose of this study was to determine the possible anti-allodynic effect of curcumin in rats with L5-L6 spinal nerve ligation (SNL). Furthermore, we study the possible participation of the NO-cyclic GMP-ATP-sensitive K+ channels pathway in the anti-allodynic effect induced by curcumin.

Methods

Tactile allodynia was measured using von Frey filaments by the up-down method in female Wistar rats subjected to SNL model of neuropathic pain.

Results

Intrathecal and oral administration of curcumin prevented, in a dose-dependent fashion, SNL-induced tactile allodynia. The anti-allodynic effect induced by curcumin was prevented by the intrathecal administration of L-NAME (100 μg/rat, a non-selective nitric oxide synthase inhibitor), ODQ (10 μg/rat, an inhibitor of guanylate-cyclase), and glibenclamide (50 μg/rat, channel blocker of ATP-sensitive K+ channels).

Conclusions

These data suggest that the anti-allodynic effect induced by curcumin is mediated, at least in part, by the NO-cyclic GMP-ATP-sensitive K+ channels pathway in the SNL model of neuropathic pain in rats.
Dasatinib reverses drug resistance by downregulating MDR1 and Survivin in Burkitt lymphoma cells
Authors: Tabata Mitsuki , Tsubaki Masanobu , Takeda Tomoya , Tateishi Keisuke , Tsurushima Katsumasa , Imano Motohiro , Satou Takao , Ishizaka Toshihiko , Nishida Shozo
Published: March 2020

Background

Current chemotherapies for Burkitt lymphoma (BL) have dramatically improved its clinical outcome. However, chemoresistance can lead to chemotherapy failure and very poor prognosis; thus, novel strategies are urgently required for patients with drug-resistant BL. To investigate the mechanisms underlying drug resistance in BL, we established drug-resistant BL cell lines: HS-Sultan/ADM (adriamycin-resistant), HS-Sultan/VCR (vincristine-resistant), HS-Sultan/DEX (dexamethasone-resistant), and HS-Sultan/L-PAM (melphalan-resistant).

Methods

Drug transporter and survival factor expression were investigated the using western blotting and real time polymerase chain reaction. Cell survival was analyzed by trypan blue dye exclusion method.

Results

The established cell lines acquired cross-resistance to adriamycin, vincristine, dexamethasone, and melphalan and exhibited 50% inhibitory concentration values 106-, 40-, 81-, and 45-fold higher than the parental cell lines, respectively. We found that protein and mRNA expression of MDR1 and Survivin were higher in drug-resistant BL cells than in the parent cells. Treatment with verapamil, an MDR1 inhibitor, or Survivin siRNA alongside each anti-cancer drug suppressed the proliferation of all drug-resistant BL cells. Src kinase activity was higher in all resistant cell lines than the parental cells; suppressing Src with dasatinib restored drug sensitivity by reducing MDR1 and Survivin expression.

Conclusions

MDR1 and Survivin upregulation are responsible for resistance to conventional drugs and dasatinib can restore drug sensitivity by reducing MDR1 and Survivin expression in drug-resistant BL cells. Src inhibitors could therefore be a novel treatment strategy for patients with drug resistant BL.
Learning clinical reasoning: how virtual patient case format and prior knowledge interact
Authors: Kiesewetter Jan , Sailer Michael , Jung Valentina M. , Schönberger Regina , Bauer Elisabeth , Zottmann Jan M. , Hege Inga , Zimmermann Hanna , Fischer Frank , Fischer Martin R.
Published: March 2020

Introduction

Clinical reasoning has been fostered with varying case formats including the use of virtual patients. Existing literature points to different conclusions regarding which format is most beneficial for learners with diverse levels of prior knowledge. We designed our study to better understand which case format affects clinical reasoning outcomes and cognitive load, dependent on medical students’ prior knowledge.

Methods

Overall, 142 medical students (3 rd to 6 th year) were randomly assigned to either a whole case or serial cue case format. Participants worked on eight virtual patients in their respective case format. Outcomes included diagnostic accuracy, knowledge, and cognitive load.

Results

We found no effect of case format on strategic knowledge scores pre- vs post-test (whole case learning gain = 3, 95% CI. -.01 to .01, serial cue learning gain = 3, 95% CI. -.06 to .00 p = .50). In both case formats, students with high baseline knowledge (determined by median split on the pre-test in conceptual knowledge) benefitted from learning with virtual patients (learning gain in strategic knowledge = 5, 95% CI .03 to .09, p = .01) while students with low prior knowledge did not (learning gain = 0, 95%CI −.02 to .02). We found no difference in diagnostic accuracy between experimental conditions (difference = .44, 95% CI −.96 to .08, p = .22), but diagnostic accuracy was higher for students with high prior knowledge compared to those with low prior knowledge (difference = .8, 95% CI 0.31 to 1.35, p < .01). Students with low prior knowledge experienced higher extraneous cognitive load than students with high prior knowledge (multiple measurements, p < .01).

Conclusions

The whole case and serial cue case formats alone did not affect students’ knowledge gain or diagnostic accuracy. Students with lower knowledge experienced increased cognitive load and appear to have learned less from their interaction with virtual patients. Cognitive load should be taken into account when attempting to help students learn clinical reasoning with virtual patients, especially for students with lower knowledge.
Developing a toolkit for engagement practice: sharing power with communities in priority-setting for global health research projects
Authors: Pratt Bridget
Published: March 2020

Background

Communities’ engagement in priority-setting is a key means for setting research topics and questions of relevance and benefit to them. However, without attention to dynamics of power and diversity, their engagement can be tokenistic. So far, there remains limited ethical guidance on how to share power with communities, particularly those considered disadvantaged and marginalised, in global health research priority-setting. This paper generates a comprehensive, empirically-based “ethical toolkit” to provide such guidance, further strengthening a previously proposed checklist version of the toolkit. The toolkit places community engagement and power-sharing at the heart of priority-setting for global health research projects.

Methods

A two part method was used to generate a revised toolkit. Part one was conceptual, consisting of novel analysis of empirical data (previously collected as part of the same overall project) to identify additional concepts relevant to power-sharing between researchers and communities in global health research priority-setting. Part two was empirical, seeking feedback on the initial checklist version of the toolkit in interviews with researchers, ethicists, community engagement practitioners, and community organisation staff.

Results

The conceptual process identified two additional components of engagement and six additional features that affect who defines, who participates, and who is heard in research priority-setting. New ethical considerations related to sharing power in global health research priority-setting are articulated in relation to those components and features. Interviewees provided suggestions for revising the toolkit’s content and language. The implications of these suggestions and the analytic process for the toolkit are described.

Conclusions

The resultant toolkit is a reflective project planning aid for researchers and their community partners to employ before priority-setting is undertaken for global health research projects. It consists of three worksheets (to be completed collectively) and a companion document detailing how to use them. It is more comprehensive than the initial toolkit, as worksheet questions for discussion cover all phases of priority-setting.
An evaluation of paediatric tinnitus services in UK National Health Service audiology departments
Authors: Smith Harriet , Fackrell Kathryn , Kennedy Veronica , Barry Johanna G. , Broomhead Emily , Hoare Derek J.
Published: March 2020

Background

Whilst evidence indicates many children experience troublesome tinnitus, specialist services for children are far less established than those available for adults. To date, there is limited understanding of how paediatric tinnitus is managed in the UK, and to what extent current practice reflects what is recommended. This service evaluation aimed to 1) profile how tinnitus in children is managed in UK clinical practice, and assess to what extent care provided by services reflects advice included in the British Society of Audiology (BSA) Tinnitus in Children Practice Guidance, 2) collate clinician opinions on how services may be optimised, and 3) identify common problems experienced by children who present with bothersome tinnitus in clinic.

Methods

As part of a larger survey, eight questions regarding services for paediatric tinnitus were distributed to UK NHS audiology services via email and social media. Representatives from eighty-seven services responded between July and September 2017.

Results

Fifty-three percent of respondents reported that their department provided a paediatric tinnitus service. Among these services, there was widespread use of most BSA recommended assessments and treatments. Less widely used practices were the assessment of mental health (42%), and the use of psychological treatment approaches; cognitive behavioural therapy (CBT) (28%), mindfulness (28%), and narrative therapy (14%). There was varied use of measurement tools to assess tinnitus in children, and a minority of respondents reported using adult tinnitus questionnaires with children. Frequently reported tinnitus-related problems presented by children were sleep difficulties, concentration difficulties at school, situation-specific concentration difficulties, and emotional distress.

Conclusions

Approaches used to manage children with troublesome tinnitus in UK NHS services are largely consistent and reflective of the current practice guidance. However, findings from this study indicate specialist staff training, access to child-specific tools, and the treatment and referral of children with tinnitus-related psychological problems represent key areas in need of optimisation.
Pain-related fear in adolescents with chronic musculoskeletal pain: process evaluation of an interdisciplinary graded exposure program
Authors: Dekker C. , van Haastregt J. C. M. , Verbunt J. A. M. C. F. , de Jong J. R. , van Meulenbroek T. , Pernot H. F. M. , van Velzen A. D. , Bastiaenen C. H. G. , Goossens M. E. J. B.
Published: March 2020

Background

For studying the effectiveness of treatment, it is important to check whether a new treatment is performed as originally described in the study-protocol.

Objectives

To evaluate whether an interdisciplinary graded exposure program, for adolescents with chronic musculoskeletal pain reporting pain-related fear, was performed according to protocol, and whether it is feasible to implement the program in rehabilitation care.

Methods

A process evaluation where quantitative and qualitative data on participant characteristics (adolescents, parents and therapists), attendance and participants’ opinion on the program were collected, by means of registration forms, questionnaires and group interviews. To evaluate treatment fidelity, audio and video recordings of program sessions were analyzed.

Results

Thirty adolescents were offered the program, of which 23 started the program. Adolescents attended on average 90% of the sessions. At least one parent per adolescent participated in the program. Analysis of 20 randomly selected recordings of treatment sessions revealed that treatment fidelity was high, since 81% of essential treatment elements were offered to the adolescents. The program was considered client-centered by adolescents and family-centered by parents. Treatment teams wished to continue offering the program in their center.

Conclusion

The interdisciplinary graded exposure program was performed largely according to protocol, and therapists, adolescents and their parents had a favorable opinion on the program. Implementation of the program in rehabilitation care is considered feasible.

Trial registration

Clinicaltrials.gov ID: NCT02181725 (7 February 2014).
Neurological and psychiatric safety of tafenoquine in Plasmodium vivax relapse prevention: a review
Authors: Duparc Stephan , Chalon Stephan , Miller Scott , Richardson Naomi , Toovey Stephen
Published: March 2020

Background

Tafenoquine is an 8-aminoquinoline anti-malarial drug recently approved as a single-dose (300 mg) therapy for Plasmodium vivax relapse prevention, when co-administered with 3-days of chloroquine or other blood schizonticide. Tafenoquine 200 mg weekly after a loading dose is also approved as travellers’ prophylaxis. The development of tafenoquine has been conducted over many years, using various dosing regimens in diverse populations.

Methods

This review brings together all the preclinical and clinical data concerning tafenoquine central nervous system safety. Data were assembled from published sources. The risk of neuropsychiatric adverse events (NPAEs) with single-dose tafenoquine (300 mg) in combination with chloroquine to achieve P. vivax relapse prevention is particularly examined.

Results

There was no evidence of neurotoxicity with tafenoquine in preclinical animal models. In clinical studies in P. vivax relapse prevention, nervous system adverse events, mainly headache and dizziness, occurred in 11.4% (36/317) of patients with tafenoquine (300 mg)/chloroquine versus 10.2% (19/187) with placebo/chloroquine; and in 15.5% (75/483) of patients with tafenoquine/chloroquine versus 13.3% (35/264) with primaquine (15 mg/day for 14 days)/chloroquine. Psychiatric adverse events, mainly insomnia, occurred in 3.8% (12/317) of patients with tafenoquine/chloroquine versus 2.7% (5/187) with placebo/chloroquine; and in 2.9% (14/483) of patients with tafenoquine/chloroquine versus 3.4% (9/264) for primaquine/chloroquine. There were no serious or severe NPAEs observed with tafenoquine (300 mg)/chloroquine in these studies.

Conclusions

The risk:benefit of single-dose tafenoquine/chloroquine in P. vivax relapse prevention is favourable in the presence of malaria, with a low risk of NPAEs, similar to that seen with chloroquine alone or primaquine/chloroquine.
Correction to: Exosomal miR-21 regulates the TETs/PTENp1/PTEN pathway to promote hepatocellular carcinoma growth
Authors: Cao Liang-qi , Yang Xue-wei , Chen Yu-bin , Zhang Da-wei , Jiang Xiao-Feng , Xue Ping
Published: March 2020

Following the publication of article [1], the authors found that the images of Transwell Matrigel invasion (Fig. 7d) are incorrect.
Fenobody and RANbody-based sandwich enzyme-linked immunosorbent assay to detect Newcastle disease virus
Authors: Ji Pinpin , Zhu Jiahong , Li Xiaoxuan , Fan Wenqi , Liu Qianqian , Wang Kun , Zhao Jiakai , Sun Yani , Liu Baoyuan , Zhou En-Min , Zhao Qin
Published: March 2020

Background

Traditional sandwich enzyme-linked immunosorbent assay (ELISA) using polyclonal and monoclonal antibodies as reagents presents several drawbacks, including limited amounts, difficulty in permanent storage, and required use of a secondary antibody. Nanobodies can be easily expressed with different systems and fused with several tags in their tertiary structure by recombinant technology, thus offering an effective detection method for diagnostic purposes. Recently, the fenobody (ferritin-fused nanobody) and RANbody (nanobody-fused reporter) have been designed and derived from the nanobody for developing the diagnostic immunoassays. However, there was no report about developing the sandwich ELISA using the fenobody and RANbody as pairing reagents.

Results

A platform for developing a sandwich ELISA utilizing fenobody as the capture antibody and RANbody as the detection antibody was firstly designed in the study. Newcastle disease virus (NDV) was selected as the antigen, from which 13 NDV-specific nanobodies were screened from an immunized Bactrian camel. Then, 5 nanobodies were selected to produce fenobodies and RANbodies. The best pairing of fenobodies (NDV-fenobody-4, 800 ng/well) and RANbodies (NDV-RANbody-49, 1:10) was determined to develop the sandwich ELISA for detecting NDV. The detection limits of the assay were determined to be 22of hemagglutination (HA) titers and 10 ng of purified NDV particles. Compared with two commercial assays, the developed assay shows higher sensitivity and specificity. Meanwhile, it exhibits 98.7% agreement with the HA test and can detect the reference NDV strains belonging to Class II but not Class I.

Conclusions

In the presented study, the 13 anti-NDV nanobodies binding the NDV particles were first produced. Then, for the first time, the sandwich ELISA to detect the NDV in the different samples has been developed using the fenobody and RANbody as reagents derived from the nanobodies. Considering the rapidly increasing generation of nanobodies, the platform can reduce the cost of production for the sandwich ELISA and be universally used to develop assays for detecting other antigens.
Surface chemistry governs the sub-organ transfer, clearance and toxicity of functional gold nanoparticles in the liver and kidney
Authors: Li Xue , Wang Bing , Zhou Shuang , Chen Wei , Chen Hanqing , Liang Shanshan , Zheng Lingna , Yu Hongyang , Chu Runxuan , Wang Meng , Chai Zhifang , Feng Weiyue
Published: March 2020

Background

To effectively applied nanomaterials (NMs) in medicine, one of the top priorities is to address a better understanding of the possible sub-organ transfer, clearance routes, and potential toxicity of the NMs in the liver and kidney.

Results

Here we explored how the surface chemistry of polyethylene glycol (PEG), chitosan (CS), and polyethylenimine (PEI) capped gold nanoparticles (GNPs) governs their sub-organ biodistribution, transfer, and clearance profiles in the liver and kidney after intravenous injection in mice. The PEG-GNPs maintained dispersion properties in vivo, facilitating passage through the liver sinusoidal endothelium and Disse space, and were captured by hepatocytes and eliminated via the hepatobiliary route. While, the agglomeration/aggregation of CS-GNPs and PEI-GNPs in hepatic Kupffer and endothelial cells led to their long-term accumulation, impeding their elimination. The gene microarray analysis shows that the accumulation of CS-GNPs and PEI-GNPs in the liver induced obvious down-regulation of Cyp4a or Cyp2b related genes, suggesting CS-GNP and PEI-GNP treatment impacted metabolic processes, while the PEI-GNP treatment is related with immune responses.

Conclusions

This study demonstrates that manipulation of nanoparticle surface chemistry can help NPs selectively access distinct cell types and elimination pathways, which help to clinical potential of non-biodegradable NPs.
Enhancement of sciatic nerve regeneration with dual delivery of vascular endothelial growth factor and nerve growth factor genes
Authors: Fang Zhiwei , Ge Xuemei , Chen Xuan , Xu Yang , Yuan Wei-En , Ouyang Yuanming
Published: March 2020

Background

Peripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomically the most challenging to regenerate given its length and large cross-sectional area. For the present, autologous nerve grafting remains to be the most ideal strategy when treating with sciatic nerve injury. However, this method sacrifices healthy nerves and requires highly intensive surgery, still calling for other advanced alternatives for nerve grafting.

Results

In this study, we utilized previously well-established gene delivery system to dually deliver plasmid DNA (pDNA) encoding vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), exploring therapeutics for sciatic nerve injury. Low-molecular-weight branched polyethylenimine (bPEI) was constructed as the backbone structure of gene vectors, and it was further crosslinked to synthesize degradable polycations via the conjugation of dialdehydes. Potential synergistic effect between VEGF and NGF proteins were observed on rat sciatic nerve crush injury model in this study.

Conclusions

We concluded that dual delivery of plasmid VEGF and NGF as gene therapy could enhance sciatic nerve regeneration.
Accelerometer-measured physical activity and sedentary time in a cohort of US adults followed for up to 13 years: the influence of removing early follow-up on associations with mortality
Authors: Tarp Jakob , Hansen Bjørge Herman , Fagerland Morten Wang , Steene-Johannessen Jostein , Anderssen Sigmund Alfred , Ekelund Ulf
Published: March 2020

Background

Observational studies linking physical activity with mortality are susceptible to reverse causation bias from undiagnosed and prevalent diseases. Researchers often attempt to deal with reverse causation bias by excluding deaths occurring within the first 1 or 2 years from the analysis, but it is unclear if excluding deaths within this time-frame is sufficient to remove bias.

Methods

We examined associations between total and intensity-specific physical activity and sedentary time with all-cause mortality in a prospective cohort of 3542 individuals from the 2003–2006 NHANES cycles. In order to yield measures of association hypothesized as minimally influenced by reverse causation bias the primary analysis excluded individuals with < 5 years of follow-up. Accelerometer-measured physical activity was linked with recently updated vital status from the National Death Index with a median follow-up of 10.8 years.

Results

Hazard ratios (95% confidence intervals) were 0.74 (0.53, 1.04), 0.52 (0.37, 0.73), and 0.61 (0.38, 1.01) for ascending quartiles of total physical activity against the least active reference. Hazard ratios for ascending moderate-to-vigorous physical activity quartiles against the reference were 0.67 (0.47, 1.96), 0.67 (0.47, 0.95), and 0.68 (0.39, 1.18). Associations for light intensity physical activity and sedentary time were smaller in magnitude and all confidence intervals included unity. Total activity and moderate-to-vigorous physical activity hazard ratios from analyses only excluding deaths within the first 2 years were inflated by 13 and 26% relative to analysis restricted to ≥5 years of follow-up.

Conclusions

The pattern of associations suggested total physical activity and moderate-to-vigorous physical activity were associated with lower mortality after more than 10 years of follow-up and excluding the first 5 years of observation time to minimize the impact of reverse causation bias. Excluding deaths within the first 2 years appeared insufficient to minimize the impact of reserve causation bias.
Gastrointestinal mixed adenoneuroendocrine carcinoma: a population level analysis of epidemiological trends
Authors: Wang Jiakun , He Aoxiao , Feng Qian , Hou Ping , Wu Junjun , Huang Zhihao , Xiao Zhouqing , Sun Chi , Liao Wenjun , Wu Linquan
Published: March 2020

Background

The rise in incidence and mortality of gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC) has not been well focused. The aim of our study was to examine epidemiological trends in incidence and incidence-based (IB) mortality of gastrointestinal MANEC at a population level.

Methods

The incidence and IB mortality of gastrointestinal MANEC as well as data on affected patients from 2000 to 2016 were obtained from the Surveillance, Epidemiology, and End Results database. Trends in incidence and IB mortality were assessed using Joinpoint regression. The Kaplan–Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression was used to identify independent predictors of mortality.

Results

581 patients diagnosed with gastrointestinal MANEC were enrolled. Gastrointestinal MANEC incidence was 0.23 cases per 1,000,000 individuals in 2000 and 1.16 cases per 1,000,000 individuals in 2016, with an annual percent change (APC) of 8.0% (95% CI 5.7–10.3%, P < 0.05). IB mortality also showed a sustained increase (APC 12.9%, 95% CI 9.0–16.8%, P < 0.05). In Cox regression analysis, age at diagnosis, tumor grade and stage, lymph node metastasis, surgery, and tumor size were independently associated with mortality. Median survival was 75 months (95% CI 60–128 months). Median survival of appendiceal MANEC was significantly longer than that of cecal MANEC (115 vs. 31 months; P < 0.001).

Conclusions

We found a sustained and rapid increase both in incidence and IB mortality of gastrointestinal MANEC, manifesting that there has been no significant improvement in patient outcomes, nor progress in prevention and treatment. Additional resources should be devoted to gastrointestinal MANEC research.
Quality of intrapartum care: direct observations in a low-resource tertiary hospital
Authors: Housseine Natasha , Punt Marieke C. , Mohamed Ali Gharib , Said Said Mzee , Maaløe Nanna , Zuithoff Nicolaas P. A. , Meguid Tarek , Franx Arie , Grobbee Diederick E. , Browne Joyce L. , Rijken Marcus J.
Published: March 2020

Background

The majority of the world’s perinatal deaths occur in low- and middle-income countries. A substantial proportion occurs intrapartum and is avoidable with better care. At a low-resource tertiary hospital, this study assessed the quality of intrapartum care and adherence to locally-tailored clinical guidelines.

Methods

A non-participatory, structured, direct observation study was held at Mnazi Mmoja Hospital, Zanzibar, Tanzania, between October and November 2016. Women in active labour were followed and structure, processes of labour care and outcomes of care systematically recorded. Descriptive analyses were performed on the labour observations and compared to local guidelines and supplemented by qualitative findings. A Poisson regression analysis assessed factors affecting foetal heart rate monitoring (FHRM) guidelines adherence.

Results

161 labouring women were observed. The nurse/midwife-to-labouring-women ratio of 1:4, resulted in doctors providing a significant part of intrapartum monitoring. Care during labour and two-thirds of deliveries was provided in a one-room labour ward with shared beds. Screening for privacy and communication of examination findings were done in 50 and 34%, respectively. For the majority, there was delayed recognition of labour progress and insufficient support in second stage of labour. While FHRM was generally performed suboptimally with a median interval of 105 (interquartile range 57–160) minutes, occurrence of an intrapartum risk event (non-reassuring FHR, oxytocin use or poor progress) increased assessment frequency significantly (rate ratio 1.32 (CI 1.09–1.58)).

Conclusions

Neither international nor locally-adapted standards of intrapartum routine care were optimally achieved. This was most likely due to a grossly inadequate capacity of birth attendants; without whom innovative interventions at birth are unlikely to succeed. This calls for international and local stakeholders to address the root causes of unsafe intrafacility care in low-resource settings, including the number of skilled birth attendants required for safe and respectful births.
First evidence for STING SNP R293Q being protective regarding obesity-associated cardiovascular disease in age-advanced subjects – a cohort study
Authors: Hamann Lutz , Szwed Malgorzata , Mossakowska Malgorzata , Chudek Jerzy , Puzianowska-Kuznicka Monika
Published: March 2020

Obesity is a risk factor for several aging-related diseases such as type 2 diabetes, cardiovascular disease, and cancer. Especially, cardiovascular disease is triggered by obesity by inducing vascular senescence and chronic low-grade systemic inflammation, also known as inflamm-aging. Released molecules from damaged cells and their recognition by the innate immune system is one of the mechanisms driving inflamm-aging. Obesity results in mitochondrial damage, leading to endothelial inflammation triggered by cytosolic mtDNA via the cGAS/STING pathway. Recently, we have shown STING SNP R293Q to be associated with a decreased risk for aging-related diseases in current smokers. Since current smoking triggers DNA damage that, similar to obesity, may result in the release of DNA into the cytoplasm, we hypothesized that the cGAS/STING pathway can modify the phenotype of aging also in obese subjects. Therefore, the objective of our study was to investigate whether STING R293Q is associated with aging-related diseases in obese individuals. We indeed show that STING 293Q is associated with protection from combined aging-related diseases (P = 0.014) and, in particular, cardiovascular disease in these subjects (P = 0.010). Therefore, we provide the first evidence that stratification for obesity may reveal new genetic loci determining the risk for aging-related diseases.
Dietary restriction of amino acids for Cancer therapy
Authors: Kang Jian-Sheng
Published: March 2020

Biosyntheses of proteins, nucleotides and fatty acids, are essential for the malignant proliferation and survival of cancer cells. Cumulating research findings show that amino acid restrictions are potential strategies for cancer interventions. Meanwhile, dietary strategies are popular among cancer patients. However, there is still lacking solid rationale to clarify what is the best strategy, why and how it is. Here, integrated analyses and comprehensive summaries for the abundances, signalling and functions of amino acids in proteomes, metabolism, immunity and food compositions, suggest that, intermittent dietary lysine restriction with normal maize as an intermittent staple food for days or weeks, might have the value and potential for cancer prevention or therapy. Moreover, dietary supplements were also discussed for cancer cachexia including dietary immunomodulatory.
A simple plant high-molecular-weight DNA extraction method suitable for single-molecule technologies
Authors: Li Zhigang , Parris Stephen , Saski Christopher A.
Published: March 2020

Background

High-molecular-weight and pure DNA is crucial for high-quality results from 3rd generation DNA Analyzers and optical mapping technologies. Conventional nuclei isolation methods for preparing high-molecular-weight genomic DNA from plant tissues include the preparation of protoplasts or embedding nuclei in an agarose matrix with subsequent manipulations via electro-elution or pulsed-field gel electrophoresis.

Results

In this method, plant nuclei are isolated by physically grinding tissues and reconstituting the intact nuclei in a unique Nuclear Isolation Buffer (NIB). The plastid DNAs are released from organelles and eliminated with an osmotic buffer by washing and centrifugation. The purified nuclei are then lysed and further cleaned by organic extraction, and the genomic DNA is precipitated with a high concentration of CTAB. The highly pure, high molecular weight gDNA is extracted from the nuclei, dissolved in a high pH buffer, allowing for stable long-term storage.

Conclusions

This method is unique and avoids the use of embedding in agarose, which dramatically reduces time (4–8 h versus days), complexity, and materials cost. This procedure can be used on essentially any plant species and tissue stage. Here we describe a case study and a simple method to rapidly prepare high molecular weight gDNA from Upland cotton, blackgrass, and strawberry suitable for single-molecule sequencing.
Radiation-induced lymphopenia correlates with survival in nasopharyngeal carcinoma: impact of treatment modality and the baseline lymphocyte count
Authors: Xie Xiaoxue , Gong Shenglan , Jin Hekun , Yang Pei , Xu Ting , Cai Yilong , Guo Chengxian , Zhang Rong , Lou Fan , Yang Wenjuan , Wang Hui
Published: March 2020

Background and purpose

We evaluated the relationship between patient-, tumor-, and treatment-related features and radiation-induced lymphopenia (RIL) and evaluated the correlation between RIL and survival outcome in NPC patients to help improve the treatment strategy.

Methods

This retrospective study included 374 patients with stage II-IVa NPC who had been treated with definitive RT and were enrolled from 2004 to 2015; The associations between the G3–4 RIL (absolute lymphocyte count, ALC <  0.5 × 109cells/L) during RT and patient-, tumor-, and treatment-related factors were assessed using Cox regression analyses. The correlation between ALC nadir and survival was examined using a Kaplan-Meier analysis, compared with the log-rank test, and confirmed by a Cox proportional hazards analysis.

Results

In the multivariate analysis, lower baseline ALC and intensity modulated radiation therapy (IMRT) (vs. 2 dimensional-conformal radiation therapy,2D-CRT) were identified as 2 independent factors that were associated with G3–4 RIL. In the multivariate survival analysis, patients with G3–4 ALC nadir had longer local recurrence-free survival durations (LRFS) (vs. G0–2 nadir, HR = 0.548,P = 0.005) and longer progression-free survival durations (PFS) (vs. G0–2 nadir, HR = 0.676,P = 0.022), while patients with G4 ALC nadir had a shorter distant-metastasis-free survival duration (DMFS) (vs. G0–2 nadir, hazard ratio [HR] = 2.567,P = 0.037).

Conclusions

In the study, lymphopenia during RT were affected by baseline ALC and RT modality independently. Moreover, G3–4 ALC nadir was independently linked with longer PFS and LRFS durations, while G4 ALC nadir was independently linked with a shorter DMFS duration.
Prevalence and factors associated with higher levels of perceived stigma among people with schizophrenia Addis Ababa, Ethiopia
Authors: Tesfaw Getachew , Kibru Boki , Ayano Getinet
Published: March 2020

Background

Schizophrenia is a severe and disabling chronic mental disorder and accompanied by different levels of a perceived stigma that affects almost all age groups. This perceived stigma negatively impacts the quality of life, physical, and mental well-being of people with schizophrenia. It is also linked with a poor level of functioning, poor adherence to drugs, and increased dropout rate. However, research into perceived stigma and associated factors among people with schizophrenia in low- and middle-income countries are limited. Therefore, this study aimed to explore the perceived stigma and correlates among people with schizophrenia in Ethiopia.

Methods

An institution based cross-sectional study was conducted from May to June 2018. A structured, pre-tested, and interviewer-administered questionnaire was used to collect data. The standardized perceived devaluation and discrimination questionnaire was used to assess perceived stigma. The systematic random sampling technique was used to select study participants. Binary logistic regression analysis was used to identify factors associated with perceived stigma. An odds ratio (OR) with a 95% confidence interval (CI) was computed to assess the strength of the association.

Results

The prevalence of high perceived stigma was found to be 62.6% [95% CI 58.3, 67.4]. In the multivariate logistic regression, female sex [AOR = 2.30, 95% CI 1.42, 3.71], age of onset of schizophrenia [AOR = 1.85, 95% CI 1.19, 2.89], multiple hospitalizations [AOR = 1.7, 95% CI 1.16, 3.27], and duration of illness 1–5 years [AOR = 2, 95% CI 1.01, 3.27], 6–10 years [AOR = 2.48, 95% CI 1.29, 4.74], and ˃10 years [AOR = 2.85, 95% CI 1.40, 5.79] were factors significantly associated with higher perceived stigma.

Conclusion

In the present study, the prevalence of high perceived stigma among people with schizophrenia was found to be 62.6%. Female sex, age of onset of schizophrenia, multiple hospitalizations, and duration of illness were factors significantly associated with higher perceived stigma. Measures to enhance the awareness of the patients, their families and their social networks about perceived stigma and associated factors, by the leading government and healthcare institutions are warranted.
The long-term residual effects of low-magnitude mechanical stimulation therapy on skeletal health
Authors: Bodnyk Kyle A. , Kuchynsky Kyle S. , Balgemann Megan , Stephens Brooke , Hart Richard T.
Published: March 2020

Background

Low-magnitude mechanical stimulation (LMMS) may improve skeletal health. The objective of this research was to investigate the long-term residual effects of LMMS on bone health. 10-week old female mice were given LMMS for 8 weeks; SHAM did not receive LMMS. Some groups remained on study for an additional 8 or 16 weeks post treatment (N = 17).

Results

Epiphyseal trabecular mineralizing surface to bone surface ratio (MS/BS) and bone formation rate (BFR/BS) were significantly greater in the LMMS group compared to the SHAM group at 8 weeks by 92 and 128% respectively. Mineral apposition rate (MAR) was significantly greater in the LMMS group 16 weeks post treatment by 14%.

Metaphyseal trabecular bone mineral density (BMD) increased by 18%, bone volume tissue volume ratio (BV/TV) increased by 37%, and trabecular thickness (Tb.Th.) increased by 10% with LMMS at 8 weeks post treatment. Significant effects 16 weeks post treatment were maintained for BV/TV and Tb.Th. The middle-cortical region bone volume (BV) increased by 4% and cortical thickness increased by 3% with 8-week LMMS.

Conclusions

LMMS improves bone morphological parameters immediately after and in some cases long-term post LMMS. Results from this work will be helpful in developing treatment strategies to increase bone health in younger individuals.
Vasculogenic mimicry in carcinogenesis and clinical applications
Authors: Luo Qingxi , Wang Jun , Zhao Wenyuan , Peng Zhenzi , Liu Xianyu , Li Bin , Zhang Heng , Shan Bin , Zhang Chunfang , Duan Chaojun
Published: March 2020

Distinct from classical tumor angiogenesis, vasculogenic mimicry (VM) provides a blood supply for tumor cells independent of endothelial cells. VM has two distinct types, namely tubular type and patterned matrix type. VM is associated with high tumor grade, tumor progression, invasion, metastasis, and poor prognosis in patients with malignant tumors. Herein, we discuss the recent studies on the role of VM in tumor progression and the diverse mechanisms and signaling pathways that regulate VM in tumors. Furthermore, we also summarize the latest findings of non-coding RNAs, such as lncRNAs and miRNAs in VM formation. In addition, we review application of molecular imaging technologies in detection of VM in malignant tumors. Increasing evidence suggests that VM is significantly associated with poor overall survival in patients with malignant tumors and could be a potential therapeutic target.
Different kinds of acupuncture treatments for knee osteoarthritis: a multicentre, randomized controlled trial
Authors: Zhang Qifei , Fang Jianqiao , Chen Lifang , Wu Jiayao , Ni Jing , Liu Fang , Sun Jing
Published: March 2020

Introduction

Knee osteoarthritis (KOA) is a chronic disease with symptoms of persistent pain or resting pain, joint stiffness, numbness, limitation of activity and even disability, with significant associated costs and effects on individuals’ life quality. The use of acupuncture for the management of chronic pain is receiving increasing recognition from both the public and professionals. The aim of this study is to identify the effects of three commonly used acupuncture treatments for KOA.

Methods/analysis

In a prospective trial involving six hospitals in Zhejiang Province (China), 360 patients with KOA will be included. Eligible patients will be randomized into six groups: Acupuncture, Electro-acupuncture, Mild moxibustion, Warm-needling, Sham acupuncture and Celebrex treatment. Twelve treatment sessions will be performed over a 4-week period. The primary outcome will be the visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function scores (the average of the past 3 days) at weeks 2 and 4 and at 3-month and 6-month follow-up. Secondary outcome measures will be as follows: the WOMAC pain score and WOMAC stiffness score (the average of the past 3 days); the Physical Activity Scale of the Elderly (PASE); knee joint swelling measurement; the WHO Quality Of Life-BREF (WHOQOL-BREF) life quality scale; and the incidence of adverse events.

Trial registration

ClinicalTrials.gov, NCT03563690. Registered on 2rd July 2018.
Treating anxiety in autistic adults: study protocol for the Personalised Anxiety Treatment–Autism (PAT-A©) pilot randomised controlled feasibility trial
Authors: Parr Jeremy R. , Brice Samuel , Welsh Patrick , Ingham Barry , Le Couteur Ann , Evans Gemma , Monaco Alexander , Freeston Mark , Rodgers Jacqui
Published: March 2020

Background

Anxiety is common in autistic adults and significantly limits everyday opportunities and quality of life. Evidence-based psychological therapies offered by mental health services often fail to meet the needs of autistic adults. The development of appropriate treatments for mental health conditions and, in particular, anxiety has been identified as a key priority by the autism community. The Personalised Anxiety Treatment–Autism (PAT-A©) trial aims to address this need by investigating the feasibility and acceptability of delivering an individualised psychological treatment for anxiety experienced by autistic adults.

Methods/design

This is a pilot randomised controlled feasibility trial. Up to 40 autistic adults with clinically diagnosed anxiety will be randomised into one of two groups (either the PAT-A© intervention or Current Clinical Services Plus two emotional literacy skills sessions). Before randomisation, participants will receive a detailed clinical assessment to inform formulation and guide anxiety treatment. As part of the baseline assessment participants will also identify two personally important ‘target situations’ that cause significant anxiety and impact upon their daily life. Based upon the formulation and identified target situations, participants randomised to the PAT-A© intervention will receive up to 12 individualised, one-to-one therapy sessions. Initial emotional literacy training sessions will be followed by a bespoke, modular, needs-based treatment approach utilising one or more of the following approaches: Mindfulness, Coping with Uncertainty in Everyday Situations (CUES), social anxiety and graded exposure within Virtual Reality Environments. Participants in the control arm will receive two psycho-educational sessions focussing on understanding and describing emotions and be signposted to healthcare provision as required. Data will be collected through quantitative and qualitative methods.

Discussion

This feasibility pilot trial serves as the first stage in the development and evaluation of a manualised personalised, evidence-based psychological therapy treatment for anxiety in autistic adults. Study outcomes will be used to inform an application for a fully powered multi-site intervention trial of adults and young people.

Trial registration

ISRCTN, ID: 15881562. Retrospectively registered on 9 August 2019.
Efficacy and safety of Shu-gan-qing-re formula for generalized anxiety disorder: study protocol for a multi-center, prospective, double-blind, double-dummy, randomized controlled trial
Authors: Chen Pei , Zhu Hong , Ning Yanzhe , Yin Dongqing , Jia Hongxiao
Published: March 2020

Background

Generalized anxiety disorder (GAD) is a persistent and common mental disorder that entails significant impairments in role functioning and quality of life. Currently available effective interventions include psychological therapies, self-help approaches, and pharmacological treatments, which do not quite meet clinical needs, and the ideal anxiolytic is still being sought. Shu-gan-qing-re (SGQR) formula, a Chinese patent medicine, has been well received by patients with GAD in Chinese clinical practice for years. The present prospective, double-blind, double-dummy, randomized controlled trial is designed to investigate the efficacy and safety of SGQR formula for GAD.

Methods/design

A total of 200 eligible participants will be recruited from four hospitals in different parts of China. They will be randomly assigned to either the study group or the control group in a ratio of 1:1. Participants allocated to the study group will receive SGQR formula and buspirone placebo, while buspirone and SGQR placebo will be applied in the control group. Six scheduled visits will be conducted over the course of 8 weeks. Outcome measurements include Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale-17 (HAMD-17), Clinical Global Impression-Improvement Scale (CGI-I), Traditional Chinese Medicine Syndrome Scale for GAD, and pro-inflammatory cytokine tests: interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha. Adverse reactions will be evaluated by using the Treatment Emergent Symptom Scale (TESS). Safety outcomes and adverse events will also be recorded.

Discussion

The study will provide scientific and objective assessments for the efficacy and safety of SGQR formula for patients with GAD, hopefully offering clinicians an alternative approach to GAD.

Trial registration

Chinese Clinical Trial Registry, ID: ChiCTR-IPR-17013058. Registered on October 20, 2017.
A review on quinoline derivatives as anti-methicillin resistant Staphylococcus aureus (MRSA) agents
Authors: Kumar Pradeep
Published: March 2020

Methicillin Resistant Staphylococcus aureus (MRSA) consists of strains of S. aureus which are resistant to methicillin. The resistance is due to the acquisition of mecA gene which encodes PBP2a unlike of any PBPs normally produced by S. aureus. PBP2a shows unusually low β-Lactam affinity and remains active to allow cell wall synthesis at normally lethal β-Lactam concentrations. MRSA can cause different types of infections like Healthcare associated MRSA, Community associated MRSA and Livestock associated MRSA infections. It causes skin lesions, osteomyelitis, endocarditis and furunculosis. To treat MRSA infections, only a few options are available like vancomycin, clindamycin, co-trimoxazole, fluoroquinolones or minocycline and there is a dire need of discovering new antibacterial agents that can effectively treat MRSA infections. In the current review, an attempt has been made to compile the data of quinoline derivatives possessing anti-MRSA potential reported to date.