bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of acute-on-chronic liver failure and decompensated liver cirrhosis on psychosocial burden and quality of life of patients and their close relatives
Authors: Nagel Michael , Labenz Christian , Wörns Marcus A. , Marquardt J. U. , Galle Peter R. , Schattenberg Jörn M. , Nguyen-Tat Marc
Published: January 2020

Background

Patients with liver cirrhosis often suffer from complications such as ascites, gastrointestinal bleeding, and infections, resulting in impaired quality of life. Frequently, the close relatives of patients also suffer from a lower quality of life in chronic diseases. In recent years, acute-to-chronic liver failure has been defined as a separate entity with high mortality. Often several organs are affected which makes intensive care therapy necessary. Little is known about the influence of acute-on-chronic-liver failure (ACLF) on the quality of life of patients and the psychosocial burden on close relatives.

Aim

The purpose of this prospective study is to investigate the influence of decompensated liver cirrhosis and the onset of ACLF of the patient’s’ quality of life and the psychosocial burden of close relatives.

Method

In this non – randomized prospective cohort study a total of 63 patients with acute decompensation of liver cirrhosis and hospital admission were enrolled in the study. To assess the quality of life of patients, the disease specific CLDQ questionnaire was assessed. In addition. Quality of life and psychosocial burden of first degree relatives was measured using the generic SF-36 questionnaire as well as the Zarit Burden Score.

Results

21 of the 63 patients suffered from ACLF. Patients with ACLF showed a lower quality of life in terms of worries compared to patients with only decompensated liver cirrhosis (3,57 ± 1,17 vs. 4,48 ± 1,27; p value: 0,008) and increased systemic symptoms (3,29 ± 1,19 vs. 4,48 ± 1,58; p value: 0,004). The univariate analysis confirmed the link between the existence of an ACLF and the concerns of patients. (p value: 0,001). The organ failure score was significantly associated with overall CLDQ scores, especially with worries and systemic symptoms of patients. Interestingly the psychosocial burden and quality of life of close relative correlates with patient’s quality of life and was influenced by the onset of an acute-on-chronic liver failure.

Conclusion

Patients with decompensated liver cirrhosis suffer from impaired quality of life. In particular, patients with ACLF have a significantly reduced quality of life. The extent of the psychosocial burden on close relative correlates with poor quality of life in patients with decompensated liver disease and is influenced by the existence of ACLF.
The importance of synchronicity in the management of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
Authors: Wong Jolene Si Min , Tan Grace Hwei Ching , Chia Claramae Shulyn , Ong Johnny , Ng Wai Yee , Teo Melissa Ching Ching
Published: January 2020

Background

Colorectal peritoneal metastases (CPM) occur in up to 13% of patients with colorectal cancer, presenting either synchronously or metachronously. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) have been increasingly utilised for selected CPM patients with favourable outcomes, though its benefits may differ for synchronous (s-CPM) and metachronous CPM (m-CPM).

Methods

A retrospective analysis of CPM patients treated with CRS and HIPEC at the National Cancer Centre Singapore over 15 years was performed. In the s-CPM group, CPM was diagnosed at primary presentation with CRS and HIPEC performed at the time of or within 6 months from primary surgery. In the m-CPM group, patients developed CPM > 6 months after primary curative surgery.

Results

One hundred two patients with CPM were treated with CRS and HIPEC. Twenty (19.6%) patients had s-CPM and 82 (80.4%) had m-CPM. Recurrences occurred in 45% of s-CPM and in 54% of m-CPM (p= 0.619). Median overall survival was significantly prolonged in patients with m-CPM (45.2 versus 26.9 months,p= 0.025). In a subset of m-CPM patients with limited PCI in whom ICU stay was not required, a survival advantage was seen (p= 0.031).

Conclusion

A survival advantage was seen a subset of m-CPM patients, possibly representing differences in disease biology.
Translational research of temporomandibular joint pathology: a preliminary biomarker and fMRI study
Authors: Barkhordarian Andre , Demerjian Gary , Chiappelli Francesco
Published: January 2020

Background

The temporomandibular joint (TMJ) is well innervated by braches of the trigeminal nerve. The temporomandibular joint disorders (TMD) can cause neural-inflammation in the peripheral nervous system (PNS) at the site of injury, or compression, and may have systemic effects on the central nervous system (CNS). Neural-inflammation causes elevations in cytokine expression and microglia activation. When the site of injury, or compression is treated, or relieved, neural inflammation is reduced. These changes can be seen and measured with fMRI brain activities.

Methods

For this study, patients with comorbid TMD and systemic/neurologic conditions were compared using clinical diagnostic markers, inflammatory, pain, tissue destruction enzymatic biomarkers, and functional magnetic resonance imaging (fMRI) activity of the brain, with and without a custom-made dental orthotic.

Results

Our results showed a correlation between the clinical diagnosis of the pathological TMJ, biomarkers and the fMRI study. There was a marked elevation of biomarkers in samples taken from TMJ of patients who were clinically diagnosed with TMD. The fMRI study of TMD patients showed an abnormal hyper-connected salience network and a diminished blood flow to the anterior frontal lobes when they did not wear their customized dental orthotics.

Conclusions

Our findings highlight the importance of TMJ-CNS connections and use of fMRI as an investigative tool for understanding TMD and its related neurological pathologies.
Blast traumatic brain injury and serum inflammatory cytokines: a repeated measures case-control study among U.S. military service members
Authors: Rusiecki Jennifer , Levin Lynn I. , Wang Li , Byrne Celia , Krishnamurthy Jayasree , Chen Ligong , Galdzicki Zygmunt , French Louis M.
Published: January 2020

Background

There is a paucity of human data on exposure to blast traumatic brain injury (bTBI) and the corresponding systemic cytokine immune response at later time points (i.e., months, years) post-injury.

Methods

We conducted a repeated measures, case-control study, examining associations of serum levels of pro- and anti-inflammatory cytokines, measured both pre- and post-deployment with having mild and moderate/severe bTBI. Utilizing serum from the Department of Defense Serum Repository cytokines were measured via an ELISA-based array for 15 cytokines. We compared pre- vs. post-levels among mild cases, moderate/severe cases, and controls and carried out case-control comparisons, using paired t- tests and generalized linear models.

Results

The average time between bTBI and post-deployment/bTBI serum among cases was 315.8 days. From pre- to post-deployment/bTBI, levels of interleukin 8 (IL-8) were decreased among both mild cases (μ = − 83.43 pg/ml; s.e. = 21.66) and moderate/severe cases (μ = − 107.67 pg/ml; s.e. = 28.74 pg/ml), while levels increased among controls (μ = 32.86 pg/ml; s.e. = 30.29). The same pattern occurred for matrix metallopeptidase 3 (MMP3), with levels decreasing for moderate/severe cases (μ = − 3369.24 pg/ml; s.e. = 1701.68) and increasing for controls (μ = 1859.60 pg/ml; s.e. = 1737.51) from pre- to post-deployment/bTBI. Evidence was also suggestive of case-control differences, from pre- to post-deployment/bTBI for interleukin 1 alpha (IL-1α), interleukin 4 (IL-4), and interleukin 6 (IL-6) among moderate/severe cases.

Conclusion

The findings of this longitudinal study indicate that in the chronic phase of bTBI, levels of IL-8 and MMP3 may be substantially lower than pre-injury. These results need confirmation in other studies, potentially those that account for treatment differences, which was not possible in our study.
BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis
Authors: Ding Honglu , Chen Jialiang , Su Minzhi , Lin Zhijun , Zhan Hailun , Yang Fei , Li Wenbiao , Xie Juncong , Huang Yong , Liu Xianguo , Liu Bolong , Zhou Xiangfu
Published: January 2020

Background

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) often grieve over a low quality of life brought about by chronic pain. In our previous studies, we determined that neuroinflammation of the spinal dorsal horn (SDH) was associated with mechanisms of interstitial cystitis. Moreover, it has been shown that brain-derived neurotrophic factor (BDNF) participates in the regulation of neuroinflammation and pathological pain through BDNF-TrkB signaling; however, whether it plays a role in cyclophosphamide (CYP)-induced cystitis remains unclear. This study aimed to confirm whether BDNF-TrkB signaling modulates neuroinflammation and mechanical allodynia in CYP-induced cystitis and determine how it occurs.

Methods

Systemic intraperitoneal injection of CYP was performed to establish a rat cystitis model. BDNF-TrkB signaling was modulated by intraperitoneal injection of the TrkB receptor antagonist, ANA-12, or intrathecal injection of exogenous BDNF. Mechanical allodynia in the suprapubic region was assessed using the von Frey filaments test. The expression of BDNF, TrkB, p-TrkB, Iba1, GFAP, p-p38, p-JNK, IL-1β, and TNF-α in the L6-S1 SDH was measured by Western blotting and immunofluorescence analysis.

Results

BDNF-TrkB signaling was upregulated significantly in the SDH after CYP was injected. Similarly, the expressions of Iba1, GFAP, p-p38, p-JNK, IL-1β, and TNF-α in the SDH were all upregulated. Treatment with ANA-12 could attenuate mechanical allodynia, restrain activation of astrocytes and microglia and alleviate neuroinflammation. Besides, the intrathecal injection of exogenous BDNF further decreased the mechanical withdrawal threshold, promoted activation of astrocytes and microglia, and increased the release of TNF-α and IL-1β in the SDH of our CYP-induced cystitis model.

Conclusions

In our CYP-induced cystitis model, BDNF promoted the activation of astrocytes and microglia to release TNF-α and IL-1β, aggravating neuroinflammation and leading to mechanical allodynia through BDNF-TrkB-p38/JNK signaling.
Using the theory of planned behavior to explain birth in health facility intention among expecting couples in a rural setting Rukwa Tanzania: a cross-sectional survey
Authors: Moshi Fabiola V. , Kibusi Stephen M. , Fabian Flora
Published: January 2020

Background

According to the theory of planned behavior, an intention to carry out a certain behavior facilitates action. In the context of birth in health facility, the intention to use health facilities for childbirth may better ensure better maternal and neonatal survival. Little is known on the influence of the domains of theory of planned behavior on birth in health facility intention. The study aimed to determine the influence of the domains of theory of planned behavior on birth in health facility intention among expecting couples in the rural Southern Highlands of Tanzania.

Methods

A community based cross-sectional study targeting pregnant women and their partners was performed from June until October 2017. A three-stage probability sampling technique was employed to obtain a sample of 546 couples (making a total of 1092 study participants). A structured questionnaire based upon the Theory of Planned Behavior was used. The questionnaire explored three main domains of birth in health facility intentions. These three domains included; 1) attitudes towards maternal services utilization, 2) perceived subjective norms towards maternal services utilization and 3) perceived behavior control towards maternal services utilization.

Results

The vast majority of study participants had birth in health facility intention. This included 499(91.2%) of pregnant women and 488(89.7%%) of their male partners partner. Only perceived subjective norms showed a significant higher mean score among pregnant women (M = 30.21, SD = 3.928) compared to their male partners (M = 29.72, SD = 4.349) t (1090) = − 1.965 at 95% CI = -0.985 to − 0.002; p < 0.049. After adjusting for the confounders, no intention to use health facility for childbirth decreased as the attitude [pregnant women (B = − 0.091; p = 0.453); male partners (B = − 0.084; p = 0.489)] and perceived behavior control [pregnant women (B = − 0.138; p = 0.244); male partners (B = − 0.155; p = 0.205)] scores increase among both pregnant women and their male partners.

Conclusion

Despite the fact that majority of study respondents had birth in health facility intention, the likelihood of this intention resulting into practice is weak because none of the domains of theory of planned behavior showed a significant influence. Innovative interventional strategies geared towards improving domains of intention is highly recommended in order to elicit strong intention to use health facilities for childbirth.
Effects of bodyweight support and guidance force on muscle activation during Locomat walking in people with stroke: a cross-sectional study
Authors: Lin Jianhua , Hu Guojiong , Ran Jun , Chen Linyu , Zhang Xian , Zhang Yanxin
Published: January 2020

Background

Locomat is a robotic exoskeleton providing guidance force and bodyweight support to facilitate intensive walking training for people with stroke. Although the Locomat has been reported to be effective in improving walking performance, the effects of training parameters on the neuromuscular control remain unclear. This study aimed to compare the muscle activities between Locomat walking and treadmill walking at a normal speed, as well as to investigate the effects of varying bodyweight support and guidance force on muscle activation patterns during Locomat walking in people with stroke.

Methods

A cross-sectional study design was employed. Participants first performed an unrestrained walking on a treadmill and then walked in the Locomat with different levels of bodyweight support (30% or 50%) and guidance force (40% or 70%) at the same speed (1.2 m/s). Surface electromyography (sEMG) of seven muscles of the affected leg was recorded. The sEMG envelope was time-normalised and averaged over gait cycles. Mean sEMG amplitude was then calculated by normalising the sEMG amplitude with respect to the peak amplitude during treadmill walking for statistical analysis. A series of Non-parametric test and post hoc analysis were performed with a significance level of 0.05.

Results

Fourteen participants with stroke were recruited at the Yangzhi Affiliated Rehabilitation Hospital of Tongji University (female n = 1; mean age 46.1 ± 11.1 years). Only the mean sEMG amplitude of vastus medialis oblique during Locomat walking (50% bodyweight support and 70% guidance force) was significantly lower than that during treadmill walking. Reducing both bodyweight and guidance increased muscle activity of gluteus medius and tibialis anterior. Activity of vastus medialis oblique muscle increased as bodyweight support reduced, while that of rectus femoris increased as guidance force decreased.

Conclusions

The effects of Locomat on reducing muscle activity in people with stroke were minimized when walking at a normal speed. Reducing bodyweight support and guidance force increased the activity of specific muscles during Locomat walking. Effects of bodyweight support, guidance force and speed should be taken into account when developing individualized Locomat training protocols for clients with stroke.
Insoluble dietary fibre intake is associated with lower prevalence of newly-diagnosed non-alcoholic fatty liver disease in Chinese men: a large population-based cross-sectional study
Authors: Xia Yang , Zhang Shunming , Zhang Qing , Liu Li , Meng Ge , Wu Hongmei , Bao Xue , Gu Yeqing , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Song Kun , Wu Qijun , Niu Kaijun , Zhao Yuhong
Published: January 2020

Background

The health benefits of dietary fibre (DF) intake on non-alcoholic fatty liver disease (NAFLD) are controversial. Thus, this large cross-sectional study aimed to determine the associations between DF intake and the prevalence of newly-diagnosed NAFLD in a large general population.

Methods

A total of 23,529 participants were enrolled in the analyses. Newly-diagnosed NAFLD was diagnosed according to liver ultrasonography and history of alcohol intake.DF intake was assessed using a validated self-administered food frequency questionnaire. Logistic regression analysis was applied to estimate the associations between DF intake and NAFLD.

Results

In total, 18.81% (n = 4426) of the participants were newly diagnosed with NAFLD. Compared with the participants in the lowest quartile of DF intake, the ORs (95% CI) for the participants in the highest quartile were 0.81 (0.67, 0.97), 0.78 (0.62, 0.99), and 0.85 (0.62, 1.17) for all participants, men, and women, respectively. Compared with the participants in the lowest quartile of insoluble DF intake, the ORs (95% CI) for the participants in the highest quartile were 0.70 (0.58, 0.85), 0.60 (0.47, 0.76), and 0.95 (0.68, 1.32) in all participants, men, and women, respectively. No association was observed between soluble DF intake and NAFLD. DF from whole grain, soy foods, vegetables, and nuts but not fruits were negatively associated with NAFLD.

Conclusions

A higher intake of insoluble DF is associated with lower prevalence of newly-diagnosed NAFLD in men. Moreover, intake DF from whole grain, soy foods, vegetables, and nuts, but not fruits have favorable effect on the prevalence of newly diagnosed NAFLD. Further cohort studies and randomized controlled trials are needed to validate this finding.
Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model
Authors: Wang Hai-meng , Wu Chao , Jiang Yan-yun , Wang Wen-ming , Jin Hong-zhong
Published: January 2020

Background

Psoriasis is a common chronic inflammatory skin disease that features the abnormal proliferation of keratinocytes. This proliferation could partly result from disturbances in vitamin A metabolism. Changes in psoriasis patients of the levels of retinol-binding protein 4 (RBP4), a carrier of retinol (vitamin A); transmembrane protein stimulated by retinoic acid 6 (STRA6); and other retinol metabolic molecules have not yet been fully established. Therefore, we investigated vitamin A-related proteins in mice with imiquimod (IMQ)-induced psoriasis.

Methods

Thirty mice were divided into four study groups: two groups underwent IMQ application for 3 or 6 days (groups A and B, respectively), and two groups underwent Vaseline application for 3 or 6 days (groups C and D, respectively). Blood and skin samples from both lesional and non-lesional areas of the mice were analyzed using enzyme-linked immunosorbent assays, hematoxylin and eosin staining, immunochemistry, real-time reverse transcription polymerase chain reaction, and RNA sequencing.

Results

IMQ-treated mice developed erythema, scales, and skin thickening. Compared with the control groups, IMQ-treated groups had the following changes: 1) interleukin (IL)-17A, IL-23, and tumor necrosis factor (TNF)-α levels were raised significantly in both serum and lesional skin (allp < 0.001); 2) retinol levels in lesional skin increased slightly (p = 0.364), but no change was evident in serum retinol levels; 3) STRA6 was upregulated in both lesional skin (p = 0.021) and serum (p = 0.034); 4) RBP4 levels were elevated in serum (p = 0.042), but exhibited only an increasing trend (p = 0.273) in lesional skin; and 5) proteins and enzymes that mediate retinoic acid formation and transformation were upregulated in lesional skin.

Conclusions

As the demand for vitamin A in psoriatic mice increased, retinol underwent relocation from the circulation to target tissues. RBP4, STRA6, and the transformation from retinol to retinoic acid were upregulated, which may be part of the mechanism of psoriasis skin lesion formation. We propose that a positive feedback mechanism was formed that maintained the severity of psoriasis.
Aggressive prostate cancer with somatic loss of the homologous recombination repair gene FANCA: a case report
Authors: Hongo Hiroshi , Kosaka Takeo , Aimono Eriko , Nishihara Hiroshi , Oya Mototsugu
Published: January 2020

Background

Precision medicine based on genomic analysis of germline or tumor tissue is attracting attention. However, there is no consensus on how to apply the results of genomic analysis to treatment.

Case presentation

A 59-year-old man diagnosed with metastatic prostate cancer was diagnosed with castration-resistant prostate cancer. Although he was sequentially treated with enzalutamide and abiraterone, bone metastasis progression was identified by skeletal scintigraphy. Therefore, we sequentially performed docetaxel therapy followed by cabazitaxel. After the third cycle of cabazitaxel, his prostate-specific antigen level was stable at < 10 ng/mL, and no radiological progression was detected.

The patient’s formalin-fixed paraffin-embedded tumor biopsy specimen underwent multiple-gene testing by next-generation sequencing, which identified a FANCA homodeletion. No significant germline mutation was observed.

Conclusions

We describe a case of aggressive, castration-resistant prostate cancer with FANCA homodeletion. Genomic analysis of prostate cancer tissue can be useful to determine optimal treatment of such cancers.
A rapid access to addiction medicine clinic facilitates treatment of substance use disorder and reduces substance use
Authors: Wiercigroch David , Sheikh Hasan , Hulme Jennifer
Published: January 2020

Background

Substance use is prevalent in Canada, yet treatment is inaccessible. The Rapid Access to Addiction Medicine (RAAM) clinic opened at the University Health Network (UHN) in January 2018 as part of a larger network of addictions clinics in Toronto, Ontario, to enable timely, low barrier access to medical treatment for substance use disorder (SUD). Patients attend on a walk-in basis without requiring an appointment or referral. We describe the RAAM clinic model, including referral patterns, patient demographics and substance use patterns. Secondary outcomes include retention in treatment and changes in both self-reported and objective substance use.

Methods

The Electronic Medical Record at the clinic was reviewed for the first 26 weeks of the clinic’s operation. We identified SUD diagnoses, referral source, medications prescribed, retention in care and self-reported substance use.

Results

The clinic saw 64 unique patients: 66% had alcohol use disorder (AUD), 39% had opiate use disorder (OUD) and 20% had stimulant use disorder. Fifty-five percent of patients were referred from primary care providers, 30% from the emergency department and 11% from withdrawal management services. Forty-two percent remained on-going patients, 23% were discharged to other care and 34% were lost to follow-up. Gabapentin (39%), naltrexone (39%), and acamprosate (15%) were most frequently prescribed for AUD. Patients with AUD reported a significant decrease in alcohol consumption at their most recent visit. Most patients (65%) with OUD were prescribed buprenorphine, and most patients with OUD (65%) had a negative urine screen at their most recent visit.

Conclusion

The RAAM model provides low-barrier, accessible outpatient care for patients with substance use disorder and facilitates the prescription of evidence-based pharmacotherapy for AUD and OUD. Patients referred by their primary care physician and the emergency department demonstrated a reduction in median alcohol consumption and high rates of opioid abstinence.
Dosimetric benefit of an adaptive treatment by means of plan selection for rectal cancer patients in both short and long course radiation therapy
Authors: de Jong R. , Visser J. , Crama K. F. , van Wieringen N. , Wiersma J. , Geijsen E. D. , Bel A.
Published: January 2020

Background

To compare target coverage and dose to the organs at risk in two approaches to rectal cancer: a clinically implemented adaptive radiotherapy (ART) strategy using plan selection, and a non-adaptive (non-ART) strategy.

Methods

The inclusion of the first 20 patients receiving adaptive radiotherapy produced 10 patients with a long treatment schedule (25x2Gy) and 10 patients with a short schedule (5X5Gy). We prepared a library of three plans with different anterior PTV margins to the upper mesorectum, and selected the most appropriate plan on daily Conebeam CT scans (CBCT). We also created a non-adaptive treatment plan with a 20 mm margin. Bowel bag, bladder and target volume were delineated on CBCT. Daily DHVs were calculated based on the dose distribution of the selected and non-adaptive plans. Coverage of the target volume was compared per fraction between the ART and non-ART plans, as was the dose to the bladder and small bowel, assessing the following dose levels: V15Gy, V30Gy, V40Gy, V15Gy and V95% for long treatment schedules, and V15Gy and V95% for short ones.

Results

Target volume coverage was maintained from 98.3% (non-ART) to 99.0% (ART)(p = 0.878). In the small bowel, ART appeared to have produced significant reductions in the long treatment schedule at V15Gy, V40Gy, V45Gy and V95% (p <  0.05), but with small absolute differences. The DVH parameters tested for the short treatment schedule did not differ significantly. In the bladder, all DVH parameters in both schedules showed significant reductions (p <  0.05), also with small absolute differences.

Conclusions

The adaptive treatment maintained target coverage and reduced dose to the organs at risk.

Trial registration

Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center, W19_194 # 19.233.
Long-term outcomes in major trauma patients and correlations with the acute phase
Authors: Martino Costanza , Russo Emanuele , Santonastaso Domenico Pietro , Gamberini Emiliano , Bertoni Silvia , Padovani Emanuele , Tosatto Luigino , Ansaloni Luca , Agnoletti Vanni
Published: January 2020

Background

Major trauma patients experience a 20% mortality rate overall, and many survivors remain permanently disabled.

In order to monitor the quality of trauma care in the Trauma System, outcomes assessment is essential. Quality indicators on outcome can be expressed as quality of life, functional outcome, and others.

The trauma follow-up system was created within the Romagna Trauma System (Italy) in order to monitor the trauma network and assess its long-term outcomes.

The aim of this paper is firstly to evaluate the existence of correlations between epidemiological data, severity of injury, and clinical assessment characterizing the acute phase and the long-term outcomes in trauma patients and secondly, to explore the association between outcome variables have been modified.

Methods

We conducted a cross-sectional study over a 10-year period, including patients with severe trauma who survived and were discharged from the intensive care unit. The outcome measures were assessed with the use of the Extended Glasgow Outcome Scale and the Euro Quality of Life scale 5 dimension.

Demographic data and clinical severity descriptors versus functional outcome were tested in a binary logistic regression model.

Results

In all, 428 major trauma patients participated in the study. At 1 year, 50.8% of trauma patients included had a good recovery and 49.2% had some degree of disability. The median value of quality of life was 0.725.

At the multivariate analysis, variables showing significant impact on functional outcome were age (p = 0.052, OR 1.025), injury severity score (p = 0.001, OR 1.025), and Glasgow coma scale ≤ 8 (p = 0.001, OR 3.509)

The Spearman’s Rank correlation coefficient showed a strong correlation between the global level of function variables and quality of life at one year (Spearman’s Rho Correlation Coefficient 0.760 (p < 0.0001)).

Conclusions

Increased age, increased injury severity score, and severe traumatic brain injury are predictors of long-term disability.

Most of these trauma patients show impairments that affect not only the level of functional state but also the quality of life. The degree of functional independence has the greatest positive impact on quality of life.

According to our results, after the recovery a prompt recognition of physical and psychological problems with systematic follow-up screening programs can help patients and doctors in defining specific therapeutic-rehabilitation pathways tailored to meet individual requirements.
N-terminal pro-brain natriuretic peptide levels in patients with anomalous left coronary artery from pulmonary artery
Authors: Yunfei Ling , Qiang Fan , Yue Wang , Yongjun Qian
Published: January 2020

Introduction

N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is used as an important biomarker for heart failure in children and adults. Previous researches have shown the value of NT-pro-BNP in various congenital heart defects (CHD). However, the level of NT-pro-BNP in patients with anomalous left coronary artery from the pulmonary artery (ALCAPA) has not been determined.

Materials and methods

Plasma NT-pro-BNP was measured in 23 patients diagnosed with ALCAPA before operation. Echocardiogram was also recorded for each patient.

Results

Patients with NT-pro-BNP above 300 pg/mL showed a statistically significant decrease in LVEF (p < 0.0001) and in age (p < 0.0001) compared to patients with NT-pro-BNP below 300 pg/mL. Age (r = 0.399, p = 0.012) and LVEF (r = 0.403, p = 0.011) showed a statistically significant correlation with NT-pro-BNP in linear regression when NT-pro-BNP more than 300 pg/mL. A negative correlation was shown between NT-pro-BNP and LVEF (r = 0.570, p < 0.0001) in all the patients. No significant correlation was observed between mitral regurgitation (MR) grade and NT-pro-BNP in a Spearman correlation test (r = 0.383; P = 0.071).

Conclusions

In patients with ALCAPA, NT-pro-BNP levels showed a negative correlation with age and LVEF when NT-pro-BNP above 300 pg/mL and no correlation with age and LVEF when NT-pro-BNP under 300 pg/ml. Further studies are needed to determine whether there is a correlation between MR grade and NT-pro-BNP levels.
Extended use of extra corporeal membrane oxygenation as bridge to lung transplantation in two patients
Authors: Skansebo Elin , Broomé Michael , Magnusson Jesper , Riise Gerdt C. , Dellgren Göran
Published: January 2020

Background

We have previously reported our outcome after extra-corporeal membrane oxygenation as bridge-to-lung transplantation, which initially was considered controversial, but over time have gained acceptance and now is performed in most high-volume institutions.

Case presentation

We now report two “extreme” extra-corporeal membrane oxygenation (ECMO) bridge-to-lung transplantation cases, on ECMO > 200 days prior to lung transplantation. One patient survived long-term and the other one did not, and clinical cause and morbidity is outlined in this case-report.

Conclusion

We believe these two cases highlight the medical, ethical and resource allocation difficulties involved with saving patients in very dire circumstances. We have shown that a patient can survive extremely long duration of ECMO bridge to lung transplantation, but selection remains crucial to achieve a reasonable cost-benefit.
Adult ALCAPA: from histological picture to clinical features
Authors: Kubota Hiroshi , Endo Hidehito , Ishii Hikaru , Tsuchiya Hiroshi , Inaba Yusuke , Terakawa Katsunari , Takahashi Yu , Noma Mio , Takemoto Kazuya , Taniai Seiichi , Sakata Konomi , Soejima Kyoko , Shimoyamada Hiroaki , Kamma Hiroshi , Kawakami Hayato , Kaneko Yukihiro , Hirono Satoru , Izumi Daisuke , Ozaki Kazuyuki , Minamino Tohru , Yoshino Hideaki , Sudo Kenichi
Published: January 2020

Background

Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary anomaly that results in high mortality if left untreated. Our aim was to extend our knowledge of the histological, angiographic, and clinical characteristics of ALCAPA in order to deepen our understanding of this rare entity.

Case presentation

We were involved in the assessment, treatment, and pathological evaluation of two adult ALCAPA patients who were rescued from ventricular fibrillation and then surgically treated to establish a dual coronary artery system. Histological studies indicated various chronic ischemic changes in the myocardium, patchy fibrosis, and severely thickened arteriolar walls in both ventricles. The first patient is alive and well 11.5 years after surgical correction without any implantable cardioverter defibrillator (ICD) activations. The second patient required re-do surgery 9 months after the initial operation but subsequently died. Histologically, chronic ischemic alteration of the myocardium and thickened arteriolar walls persisted even after surgical correction, and coronary angiography (CAG) showed an extremely slow flow phenomenon even after surgical correction in both patients. The average postoperative opacification rate in the first case was 7.36 + 1.12 (n = 2) in the RCA, 3.81 + 0.51 (n = 3) in the left anterior descending (LAD) artery, and 4.08 + 0.27 (n = 4) in the left circumflex (LCx) artery. The slow flow phenomenon may represent persistent high arteriolar resistance in both ventricles.

Conclusions

Seldom reported or new findings in adult ALCAPA were identified in two cases. More frequent diagnosis of adult ALCAPA can be expected because of the widespread availability of resuscitation and more advanced diagnostic modalities. Accumulation of pathological and clinical findings and confirmation of the long-term follow-up results after treatment may contribute to expanding our knowledge of this rare entity and establishing optimal treatment.
Giant right coronary artery aneurysm mimicking a right intra-ventricular mass: a case report
Authors: Teng Peng , Ni Chengyao , Sun Qianhui , Ni Yiming
Published: January 2020

Background

Coronary artery aneurysm is a rare condition which constitutes a small proportion of coronary artery disease. Such condition mimicking an intra-cardiac mass is extremely rare and poorly understood.

Case presentation

We present an unusual case of a 53-year-old female with decreased exercise tolerance and lower extremity edema for 3 months. The echocardiography showed moderate tricuspid regurgitation and a right intra-ventricular mass below the tricuspid valve. No ventricular wall akinesia or ST segment change was found on echocardiography or electrocardiogram. Coronary computed tomographic angiography confirmed the diagnosis of intra-ventricular mass with feeding vessel originated from the right coronary artery. The patient was scheduled for tumor resection, and the mass turned out to be a thrombosed giant right coronary artery aneurysm. The patient received successful aneurysm resection and had an uneventful postoperative recovery. Unfortunately, a fistula between right coronary artery and right ventricle was detected on follow-up three months later by echocardiography.

Conclusions

Coronary artery aneurysms presenting as intra-cardiac masses are extremely rare. Comprehensive preoperative evaluation is highly recommended because the surgical strategies for tumor and aneurysm are completely different. Aneurysm resection with bypass surgery is preferred rather than aneurysm repair. To our best knowledge, coronary artery aneurysms presenting as intra-ventricular masses have seldom been reported.
Prevalence of Fabry disease in dialysis patients: Western Australia Fabry disease screening study - the FoRWARD study
Authors: Jahan Sadia , Sarathchandran Subashini , Akhter Shamina , Goldblatt Jack , Stark Samantha , Crawford Douglas , Mallett Andrew , Thomas Mark
Published: January 2020

Aim

To determine the prevalence of undiagnosed Fabry Disease (FD) in Western Australian (WA) patients undergoing dialysis.

Background

FD is a multisystem X-linked lysosomal storage disease caused by deficient activity of alpha-galactosidase-A (α-GAL-A). Affected individuals are at risk of developing small-fibre neuropathy, rash, progressive kidney disease, hypertrophic cardiomyopathy and ischaemic stroke. Diagnosis is often delayed by years or even decades. Screening high risk population such as dialysis patients may identify patients with undiagnosed Fabry disease.

Methods

A cross-sectional study was undertaken of all adult patients receiving dialysis in WA, without previously known FD. After informed consent they were screened for α-GAL-A activity by dried blood spot samples. Low or inconclusive activity were repeated via Centogene in Rostock, Germany with GLA genetic analysis. Ethics approval was granted by Royal Perth Hospital Human Research Ethic Committee REG 14–136; site-specific approval was granted from appropriate authorities; ANZ Clinical Trials Registry U1111–1163-7629.

Results

Between February 2015 & September 2017, α-GAL-A activity was performed on 526 patients at 16 dialysis sites. Twenty-nine patients had initial low α-GAL-A; repeat testing & GLA genotyping showed no confirmed FD cases. The causes of false positive rates were thought to be secondary to impaired protein synthesis due to patient malnutrition and chronic inflammation, which is common among dialysis patients, in addition to poor sampling handling.

Conclusion

Analysis of this dialysis population has shown a prevalence of 0% undiagnosed FD. False positives results may occur through impaired protein synthesis and sample handling.
The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease
Authors: Bevilacqua Jorge A. , Guecaimburu Ehuletche Maria del Rosario , Perna Abayuba , Dubrovsky Alberto , Franca Marcondes C. , Vargas Steven , Hegde Madhuri , Claeys Kristl G. , Straub Volker , Daba Nadia , Faria Roberta , Periquet Magali , Sparks Susan , Thibault Nathan , Araujo Roberto
Published: January 2020

Background

Limb-girdle muscular dystrophy (LGMD) is a group of neuromuscular disorders of heterogeneous genetic etiology with more than 30 directly related genes. LGMD is characterized by progressive muscle weakness involving the shoulder and pelvic girdles. An important differential diagnosis among patients presenting with proximal muscle weakness (PMW) is late-onset Pompe disease (LOPD), a rare neuromuscular glycogen storage disorder, which often presents with early respiratory insufficiency in addition to PMW. Patients with PMW, with or without respiratory symptoms, were included in this study of Latin American patients to evaluate the profile of variants for the included genes related to LGMD recessive (R) and LOPD and the frequency of variants in each gene among this patient population.

Results

Over 20 institutions across Latin America (Brazil, Argentina, Peru, Ecuador, Mexico, and Chile) enrolled 2103 individuals during 2016 and 2017. Nine autosomal recessive LGMDs and Pompe disease were investigated in a 10-gene panel (ANO5, CAPN3, DYSF, FKRP, GAA, SGCA, SGCB, SGCD, SGCG, TCAP) based on reported disease frequency in Latin America. Sequencing was performed with Illumina’s NextSeq500 and variants were classified according to ACMG guidelines; pathogenic and likely pathogenic were treated as one category (P) and variants of unknown significance (VUS) are described. Genetic variants were identified in 55.8% of patients, with 16% receiving a definitive molecular diagnosis; 39.8% had VUS. Nine patients were identified with Pompe disease.

Conclusions

The results demonstrate the effectiveness of this targeted genetic panel and the importance of including Pompe disease in the differential diagnosis for patients presenting with PMW.
Alpha-synuclein-induced mitochondrial dysfunction is mediated via a sirtuin 3-dependent pathway
Authors: Park Jae-Hyeon , Burgess Jeremy D. , Faroqi Ayman H. , DeMeo Natasha N. , Fiesel Fabienne C. , Springer Wolfdieter , Delenclos Marion , McLean Pamela J.
Published: January 2020

Background

Misfolding and aggregation of the presynaptic protein alpha-synuclein (αsyn) is a hallmark of Parkinson’s disease (PD) and related synucleinopathies. Although predominantly localized in the cytosol, a body of evidence has shown that αsyn localizes to mitochondria and contributes to the disruption of key mitochondrial processes. Mitochondrial dysfunction is central to the progression of PD and mutations in mitochondrial-associated proteins are found in familial cases of PD. The sirtuins are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent enzymes that play a broad role in cellular metabolism and aging. Interestingly, mitochondrial sirtuin 3 (SIRT3) plays a major role in maintaining mitochondrial function and preventing oxidative stress, and is downregulated in aging and age-associated diseases such as neurodegenerative disorders. Herein, we hypothesize that αsyn is associated with decreased SIRT3 levels contributing to impaired mitochondrial dynamics and biogenesis in PD.

Methods

The level of mitochondrial SIRT3 was assessed in cells expressing oligomeric αsyn within the cytosolic and mitochondrial-enriched fractions. Mitochondrial integrity, respiration, and health were examined using several markers of mitochondrial dynamics and stress response and by measuring the rate of oxygen consumption (OCR). Our findings were validated in a rodent model of PD as well as in human post-mortem Lewy body disease (LBD) brain tissue.

Results

Here, we demonstrate that αsyn associates with mitochondria and induces a decrease in mitochondrial SIRT3 levels and mitochondrial biogenesis. We show that SIRT3 downregulation is accompanied by decreased phosphorylation of AMPK and cAMP-response element binding protein (CREB), as well as increased phosphorylation of dynamin-related protein 1 (DRP1), indicative of impaired mitochondrial dynamics. OCR was significantly decreased suggesting a mitochondria respiratory deficit. Interestingly treatment with AMPK agonist 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) restores SIRT3 expression, improves mitochondrial function, and decreases αsyn oligomer formation in a SIRT3-dependent manner.

Conclusions

Together, our findings suggest that pharmacologically increasing SIRT3 levels can counteract αsyn-induced mitochondrial dysfunction by reducing αsyn oligomers and normalizing mitochondrial bioenergetics. These data support a protective role for SIRT3 in PD-associated pathways and contribute significant mechanistic insight into the interplay of SIRT3 and αsyn.
SELEX tool: a novel and convenient gel-based diffusion method for monitoring of aptamer-target binding
Authors: Liu Qingxiu , Zhang Wei , Chen Siying , Zhuang Zhenjing , Zhang Yi , Jiang Lingli , LIN Jun Sheng
Published: January 2020

Background

Aptamers, single-stranded DNAs or RNAs, can be selected from a library containing random sequences using a method called Systematic Evolution of Ligands by EXponential Enrichment (SELEX). In SELEX, monitoring the enriching statuses of aptamer candidates during the process is a key step until today. Conformational change of an aptamer caused by target-binding in gel can be used to indicate its statuses of binding.

Results

In this study, an easy-to-implement gel-based diffusion method (GBDM) was developed to monitor the interaction between enriched aptamer candidates and their targets. In order to prove the concept, characterization of aptamers targeting their targets including protein (thrombin) and non-protein molecules (acetamiprid, ATP, atrazine, profenofos and roxithromycin), respectively, were performed using mini gels. Our method has advantages over the common methods including easy performed with labor- and time- saving in experimental operation. The concept has been proven by monitoring enrichment of dynamic aptamer candidate libraries targeting a small molecule 2,2-bis(4-chlorophenyl) acetic acid (DDA) during SELEX process. A mini gel cassette was designed and fabricated by our laboratory to make mini agarose gels for diffusion with different directions.

Conclusions

These results indicate that GBDM, in particular, chasing diffusion is suitable for monitoring the interaction between enriched aptamer candidates and their targets. These pioneering efforts are helpful for novel aptamer selection by breaking through the technical bottleneck of aptamer development and helpful for development of novel aptasensors.
High-brightness anterograde transneuronal HSV1 H129 tracer modified using a Trojan horse-like strategy
Authors: Su Peng , Ying Min , Han Zengpeng , Xia Jinjin , Jin Sen , Li Yingli , Wang Huadong , Xu Fuqiang
Published: January 2020

Neurotropic viral transsynaptic tracing is an increasingly powerful technique for dissecting the structure and function of neural circuits. Herpes simplex virus type 1 strain H129 has been widely used as an anterograde tracer. However, HSV tracers still have several shortcomings, including high toxicity, low sensitivity and non-specific retrograde labeling. Here, we aimed to construct high-brightness HSV anterograde tracers by increasing the expression of exogenous genes carried by H129 viruses. Using a Trojan horse-like strategy, a HSV/AAV (adeno-associated virus) chimaera termed H8 was generated to enhance the expression of a fluorescent marker. In vitro and in vivo assays showed that the exogenous gene was efficiently replicated and amplified by the synergism of the HSV vector and introduced AAV replication system. H8 reporting fluorescence was brighter than that of currently available H129 tracers, and H8 could be used for fast and effective anterograde tracing without additional immunostaining. These results indicated that foreign gene expression in HSV tracers could be enhanced by integrating HSV with AAV replication system. This approach may be useful as a general enhanced expression strategy for HSV-based tracing tools or gene delivery vectors.
Circular RNA circRHOBTB3 acts as a sponge for miR-654-3p inhibiting gastric cancer growth
Authors: Deng Guangxu , Mou Tingyu , He Jiayong , Chen Da , Lv Daojun , Liu Hao , Yu Jiang , Wang Shuang , Li Guoxin
Published: January 2020

Background

Circular RNAs (circRNAs) have recently emerged as a new family of noncoding RNAs that are involved in the causation and progression of various cancers. However, the roles of circRNAs in the tumorigenesis of gastric cancer (GC) are still largely unknown.

Methods

The expression profiles of circRNAs in GC were identified in open GEO database and were evaluated at the mRNA level in clinical GC samples compared with paired non-tumorous tissues. Kaplan-Meier survival curve was used to analyze the correlation of circRNA and patients’ prognosis. Subsequently, the circular structures of candidate circRNAs were validated by Sanger sequencing, divergent primer PCR, and RNase R treatments. Gain- and loss-of-function analyses were performed to evaluate the functional significance of it in GC initiation and progression. Dual-luciferase reporter and RNA pull-down assays were used to identify the microRNA (miRNA) sponge mechanism of circRNAs.

Results

The expression of circRHOBTB3 was lower in GC tissues and cell lines. Downregulation of circRHOBTB3 was significantly correlated with poor differentiation and unfavorable prognosis in patients with GC. Overexpression of circRHOBTB3 in GC cells led to decreased proliferation and induced G1/S arrest in vitro, accompanied with inhibited xenograft tumor growth in vivo, while the opposite effects were achieved in circRHOBTB3-silenced cells. Furthermore, we demonstrated that circRHOBTB3 acts as a sponge for miR-654-3p and verified that p21 is a novel target of miR-654-3p.

Conclusion

Taken together, this study revealed that circRHOBTB3 might function as competing endogenous RNA (ceRNA) for miR-654-3p, which could contribute to growth inhibition of GC through activating p21 signaling pathway. Our data suggested that circRHOBTB3 would serve as a novel promising diagnosis marker and therapeutic target for GC.