bluuebunny/crossref_metadata_2025 huggingface dataset:
Attention/memory complaint is correlated with motor speech disorder in Parkinson’s disease
Authors: Liu Ying , Gui Yuchang , Hu Jincui , Liang Shanshan , Mo Sixia , Zhou Yuanfang , Li Yujian , Zhou Fengkun , Xu Jianwen
Published: December 2019

Background

The mechanisms underlying the online modulation of motor speech in Parkinson’s disease (PD) have not been determined. Moreover, medical and rehabilitation interventions for PD-associated motor speech disorder (MSD) have a poor long-term prognosis.

Methods

To compare risk factors in PD patients with MSD to those without MSD (non-MSD) and determine predictive independent risk factors correlated with the MSD phenotype, we enrolled 314 PD patients, including 250 with and 64 without MSD. We compared demographic, characteristic data, as well as PD-associated evaluations between the MSD group and non-MSD group.

Results

Univariate analysis showed that demographic characteristics, including occupation, educational level, monthly income and speaking background; clinical characteristics, including lesions in the frontal and temporal lobes, and concurrent dysphagia; and PD-associated evaluations, including the activity of daily living (ADL) score, non-motor symptoms scale (NMSS) domain 4 score (perceptual problem), and NMSS domain 5 score (attention/memory) were all significantly different between the MSD and non-MSD group (all P < 0.05). Multivariate logistic regression analysis showed that educational level, frontal lesions, and NMSS domain 5 score (attention/memory) were independent risk factors for PD-associated MSD (all P < 0.005).

Conclusions

We determined an association between MSD phenotype and cognitive impairment, reflected by low-level education and related clinical profiles. Moreover, attention and memory dysfunction may play key roles in the progression of MSD in PD patients. Further studies are required to detail the mechanism underlying abnormal speech motor modulation in PD patients. Early cognitive intervention may enhance rehabilitation management and motor speech function in patients with PD-associated MSD.
Comparison of family centered care with family integrated care and mobile technology (mFICare) on preterm infant and family outcomes: a multi-site quasi-experimental clinical trial protocol
Authors: Franck Linda S. , Kriz Rebecca M. , Bisgaard Robin , Cormier Diana M. , Joe Priscilla , Miller Pamela S. , Kim Jae H. , Lin Carol , Sun Yao
Published: December 2019

Background

Family Centered Care (FCC) has been widely adopted as the framework for caring for infants in the Neonatal Intensive Care Unit (NICU) but it is not uniformly defined or practiced, making it difficult to determine impact. Previous studies have shown that implementing the Family Integrated Care (FICare) intervention program for preterm infants in the NICU setting leads to significant improvements in infant and family outcomes. Further research is warranted to determine feasibility, acceptability and differential impact of FICare in the US context. The addition of a mobile application (app) may be effective in providing supplemental support for parent participation in the FICare program and provide detailed data on program component uptake and outcomes.

Methods

This exploratory multi-site quasi-experimental study will compare usual FCC with mobile enhanced FICare (mFICare) on growth and clinical outcomes of preterm infants born at or before 33 weeks gestational age, as well as the stress, competence and self-efficacy of their parents. The feasibility and acceptability of using mobile technology to gather data about parent involvement in the care of preterm infants receiving FCC or mFICare as well as of the mFICare intervention will be evaluated (Aim 1). The effect sizes for infant growth (primary outcome) and for secondary infant and parent outcomes at NICU discharge and three months after discharge will be estimated (Aim 2).

Discussion

This study will provide new data about the implementation of FICare in the US context within various hospital settings and identify important barriers, facilitators and key processes that may contribute to the effectiveness of FICare. It will also offer insights to clinicians on the feasibility of a new mobile application to support parent-focused research and promote integration of parents into the NICU care team in US hospital settings.

Trial registration

ClinicalTrials.gov, IDNCT03418870. Retrospectively registered on December 18, 2017.
A health care labyrinth: perspectives of caregivers on the journey to accessing timely cancer diagnosis and treatment for children in India
Authors: Faruqui Neha , Joshi Rohina , Martiniuk Alexandra , Lowe Jennifer , Arora Ramandeep , Anis Huma , Kalra Manas , Bakhshi Sameer , Mishra Ananya , Santa Ayyagari , Sinha Sudha , Siddaiahgari Sirisharani , Seth Rachna , Bernays Sarah
Published: December 2019

Background

Cure rates for children with cancer in India lag behind that of high-income countries. Various disease, treatment and socio-economic related factors contribute to this gap including barriers in timely access of diagnostic and therapeutic care. This study investigated barriers to accessing care from symptom onset to beginning of treatment, from perspectives of caregivers of children with cancer in India.

Methods

Semi-structured in-depth interviews were conducted with caregivers of children (< 18 years) diagnosed with cancer in seven tertiary care hospitals across New Delhi and Hyderabad. Purposive sampling to saturation was used to ensure adequate representation of the child’s gender, age, cancer type, geographical location and socioeconomic status. Interviews were audio recorded after obtaining informed consent. Thematic content analysis was conducted and organised using NVivo 11.

Results

Thirty-nine caregivers were interviewed, where three key themes emerged from the narratives: time intervals to definitive diagnosis and treatment, the importance of social supportive care and the overall accumulative impacts of the journey. There were two phases encapsulating the experiences of the family: referral pathways taken to reach the hospital and after reaching the hospital. Most caregivers, especially those from distant geographical areas had variable and inconsistent referral pathways partly due to poor availability of specialist doctors and diagnostic facilities outside major cities, influence from family or friends, and long travel times. Upon reaching the hospital, families mostly from public hospitals faced challenges navigating the hospital facilities, finding accommodation, and comprehending the diagnosis and treatment pathway. Throughout both phases, financial constraint was a recurring issue amongst low-income families. The caregiver’s knowledge and awareness of the disease and health system, religious and social factors were also common barriers.

Conclusion

This qualitative study highlights and explores some of the barriers to childhood cancer care in India. Our findings show that referral pathways are intrinsically linked to the treatment experience and there should be better recognition of the financial and emotional challenges faced by the family that occur prior to definitive diagnosis and treatment. This information would help inform various stakeholders and contribute to improved interventions addressing these barriers.
Indwelling pleural catheters for malignancy-associated pleural effusion: report on a single centre’s ten years of experience
Authors: Frost Nikolaj , Brünger Martin , Ruwwe-Glösenkamp Christoph , Raspe Matthias , Tessmer Antje , Temmesfeld-Wollbrück Bettina , Schürmann Dirk , Suttorp Norbert , Witzenrath Martin
Published: December 2019

Introduction

Recurrent pleural effusion is a common cause of dyspnoea, cough and chest pain during the course of malignant diseases. Chemical pleurodesis had been the only definitive treatment option until two decades ago. Indwelling pleural catheters (IPC) emerged as an alternative, not only assuring immediate symptom relief but also potentially leading to pleurodesis in the absence of sclerosing agents.

Methods

In this single-centre retrospective observational study patient characteristics, procedural variables and outcome in a large population of patients with IPC in malignancy were evaluated and prognostic factors for pleurodesis were identified.

Results

From 2006 to 2016, 395 patients received 448 IPC, of whom 121 (30.6%) had ovarian, 91 (23.0%) lung and 45 (11.4%) breast cancer. The median length of IPC remaining in place was 1.2 months (IQR, 0.5–2.6), the median survival time after insertion 2.0 months (IQR, 0.6–6.4). An adequate symptom relief was achieved in 94.9% of all patients, with no need for subsequent interventions until last visit or death. In patients surviving ≥30 days after IPC insertion, pleurodesis was observed in 44.5% and was more common in patients < 60 years (HR, 1.72; 95% CI, 1.05–2.78;p = 0.03). The use of an additional talc slurry via the IPC was highly predictive for pleurodesis (HR 6.68; 95% CI, 1.44–31.08;p = 0.02). Complications occurred in 13.4% of all procedures (n = 60), 41.8% concerning infections (local infections at the tunnel/exit site (n = 14) and empyema (n = 11)), and 98.3% being low or mild grade (n = 59). Complication rates were higher in men than women (18.6 vs. 12.4%,p = 0.023).

Conclusion

High efficacy in symptom relief and a favourable safety profile confirm IPC as suitable first line option in most malignant pleural effusions. The study presents the largest dataset on IPC in gynaecologic cancer to date. Gender-specific differences in complication rates warrant further study.
Dual consent? Donors’ and recipients’ views about involvement in decision-making on the use of embryos created by gamete donation in research
Authors: Baía I. , de Freitas C. , Samorinha C. , Provoost V. , Silva S.
Published: December 2019

Background

Reasonable disagreement about the role awarded to gamete donors in decision-making on the use of embryos created by gamete donation (EGDs) for research purposes emphasises the importance of considering the implementation of participatory, adaptive, and trustworthy policies and guidelines for consent procedures. However, the perspectives of gamete donors and recipients about decision-making regarding research with EGDs are still under-researched, which precludes the development of policies and guidelines informed by evidence. This study seeks to explore the views of donors and recipients about who should take part in consent processes for the use of EGDs in research.

Methods

From July 2017 to June 2018, 72 gamete donors and 175 recipients completed a self-report structured questionnaire at the Portuguese Public Bank of Gametes (response rate: 76%). Agreement with dual consent was defined as the belief that the use of EGDs in research should be consented by both donors and recipients.

Results

The majority of participants (74.6% of donors and 65.7% of recipients) were willing to donate embryos for research. Almost half of the donors (48.6%) and half of the recipients (46.9%) considered that a dual consent procedure is desirable. This view was more frequent among employed recipients (49.7%) than among non-employed (21.4%). Donors were less likely to believe that only recipients should be involved in giving consent for the use of EGDs in research (25.0% vs. 41.7% among recipients) and were more frequently favourable to the idea of exclusive donors’ consent (26.4% vs. 11.4% among recipients).

Conclusions

Divergent views on dual consent among donors and recipients indicate the need to develop evidence-based and ethically sustainable policies and guidelines to protect well-being, autonomy and reproductive rights of both stakeholder groups. More empirical research and further theoretical normative analyses are needed to inform people-centred policy and guidelines for shared decision-making concerning the use of EGDs for research.
DPF is a cell-density sensing factor, with cell-autonomous and non-autonomous functions during Dictyostelium growth and development
Authors: Meena Netra Pal , Jaiswal Pundrik , Chang Fu-Sheng , Brzostowski Joseph , Kimmel Alan R.
Published: December 2019

Background

Cellular functions can be regulated by cell-cell interactions that are influenced by extra-cellular, density-dependent signaling factors.Dictyosteliumgrow as individual cells in nutrient-rich sources, but, as nutrients become depleted, they initiate a multi-cell developmental program that is dependent upon a cell-density threshold. We hypothesized that novel secreted proteins may serve as density-sensing factors to promote multi-cell developmental fate decisions at a specific cell-density threshold, and useDictyosteliumin the identification of such a factor.

Results

We show that multi-cell developmental aggregation inDictyosteliumis lost upon minimal (2-fold) reduction in local cell density. Remarkably, developmental aggregation response at non-permissive cell densities is rescued by addition of conditioned media from high-density, developmentally competent cells. Using rescued aggregation of low-density cells as an assay, we purified a single, 150-kDa extra-cellular protein with density aggregation activity. MS/MS peptide sequence analysis identified the gene sequence, and cells that overexpress the full-length protein accumulate higher levels of a development promoting factor (DPF) activity than parental cells, allowing cells to aggregate at lower cell densities; cells deficient for thisDPFgene lack density-dependent developmental aggregation activity and require higher cell density for cell aggregation compared to WT. Density aggregation activity co-purifies with tagged versions of DPF and tag-affinity-purified DPF possesses density aggregation activity. In mixed development with WT, cells that overexpress DPF preferentially localize at centers for multi-cell aggregation and define cell-fate choice during cytodifferentiation. Finally, we show that DPF is synthesized as a larger precursor, single-pass transmembrane protein, with the p150 fragment released by proteolytic cleavage and ectodomain shedding. The TM/cytoplasmic domain of DPF possesses cell-autonomous activity for cell-substratum adhesion and for cellular growth.

Conclusions

We have purified a novel secreted protein, DPF, that acts as a density-sensing factor for development and functions to define local collective thresholds forDictyosteliumdevelopment and to facilitate cell-cell communication and multi-cell formation. Regions of high DPF expression are enriched at centers for cell-cell signal-response, multi-cell formation, and cell-fate determination. Additionally, DPF has separate cell-autonomous functions for regulation of cellular adhesion and growth.
Clinicopathologic features of remnant gastric cancer after curative distal gastrectomy according to previous reconstruction method: a retrospective cohort study
Authors: Park Yong-Eun , Kim Sang-Woon
Published: December 2019

Background

Survival rate of patients treated for gastric cancer has increased due to early detection and improvements of surgical technique and chemotherapy. Increase in survival rate has led to an increase in the risk for remnant gastric cancer (RGC). The purpose of this study was to investigate clinicopathologic features of RGC according to previous reconstruction method and factors affecting the interval from previous curative distal gastrectomy for gastric cancer to RGC occurrence.

Methods

Medical records of patients diagnosed with RGC at Yeungnam University Medical Center from January 2000 to December 2017 who had a history of distal gastrectomy with D2 LN dissection due to gastric cancer were reviewed retrospectively.

Results

Forty-eight patients were enrolled in this study. The mean interval of 48 RGC patients was 105.6 months (8.8 years). RGC after Billroth II reconstruction recurred more often at anastomosis site than RGC after Billroth I reconstruction (p = 0.001). The mean interval of RGC after Billroth I reconstruction was 67 months, shorter than 119 months of RGC after Billroth II reconstruction (p = 0.003). On the contrary, interval showed no difference according to stage of previous gastric cancer, remnant gastric cancer, or sex (p = 0.810, 0.145, and 0.372, respectively).

Conclusions

RGC after Billroth I reconstruction tends to arise earlier at non-anastomosis site than RGC after Billroth II. Therefore, we should examine non-anastomosis site carefully from the beginning of surveillance after gastric cancer surgery with Billroth I reconstruction for better outcome.
Association of pre-surgery to pre-radiotherapy lymphocyte counts ratio with disease-free survival in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy
Authors: Xu Hongen , You Guangxian , Zhang Minjun , Song Tao , Zhang Haibo , Yang Jia , Jia Yongshi , Tang Jianming , Liang Xiaodong
Published: December 2019

Background

Colorectal cancer is the fourth most common cancer globally and neoadjuvant concurrent chemoradiotherapy (nCRT) and surgery are the standard treatments for locally advanced colorectal carcinoma. This study investigated the association between dynamic changes in absolute lymphocyte counts (ALCs) and disease-free survival (DFS) in rectal cancer patients receiving nCRT and identified factors associated with these changes.

Methods

We retrospectively examined 34 patients with locally advanced rectal cancer who received nCRT followed by surgery and adjuvant chemotherapy. The association between ALCs and DFS and that between ALCs and downstaging were analyzed and potential clinical- and treatment-related factors related to dynamic changes in ALCs were subsequently evaluated. The patient eligibility criteria were as follows: pathologically confirmed rectal adenocarcinoma, clinical stages II–III, ≥ 18 years of age, and so on. Pre-RTL was defined as ALCs obtained before the initiation of nCRT and pre-SL was defined as ALCs obtained before surgery. We measured pre-SL to pre-RTL ratio (pre-SLR), DFS, and ALCs.

Results

The median ALC declined significantly during nCRT. A lower pre-SLR was associated with poorer DFS with statistical significance in Kaplan–Meier (p = 0.007), univariate regression (hazard ratio [HR] = 6.287, 95% confidence interval [CI] 1.374–28.781, p = 0.018), and multivariable regression (HR = 7.347, 95% CI 1.595–33.850, p = 0.011) analyses. Neither patient characteristics nor treatment-related factors were related to downstaging. The pelvic bone marrow (PBM) volume receiving at least 30 Gy (V30) was significantly associated with pre-SLR in the univariate (HR = 5.760, 95% CI 1.317–25.187, p = 0.020) and multivariable (HR = 5.760, 95% CI 1.317–25.187, p = 0.020) regression analyses.

Limitations

Our study had several limitations. The sample size was small and the study was performed in a selected population, which may limit the generalization of the findings.

Conclusions

Radiotherapy had a profound impact on the change in ALCs. A lower pre-SLR was significantly associated with poorer DFS in rectal cancer patients receiving nCRT. The V30 of PBM was a predictor of pre-SLR.
Individualized home-based exercise and nutrition interventions improve frailty in older adults: a randomized controlled trial
Authors: Hsieh Tsung-Jen , Su Shin-Chang , Chen Chun-Wei , Kang Yaw-Wen , Hu Ming-Hsia , Hsu Li-Lin , Wu Szu-Yun , Chen Likwang , Chang Hsing-Yi , Chuang Shao-Yuan , Pan Wen-Harn , Hsu Chih-Cheng
Published: December 2019

Background

Frail older adults are predisposed to multiple comorbidities and adverse events. Recent interventional studies have shown that frailty can be improved and managed. In this study, effective individualized home-based exercise and nutrition interventions were developed for reducing frailty in older adults.

Methods

This study was a four-arm, single-blind, randomized controlled trial conducted between October 2015 and June 2017 at Miaoli General Hospital in Taiwan. Overall, 319 pre-frail or frail older adults were randomly assigned into one of the four study groups (control, exercise, nutrition, and exercise plus nutrition [combination]) and followed up during a 3-month intervention period and 3-month self-maintenance period. Improvement in frailty scores was the primary outcome. Secondary outcomes included improvements in physical performance and mental health. The measurements were performed at baseline, 1 month, 3 months, and 6 months.

Results

At the 6-month measurement, the exercise (difference in frailty score change from baseline: − 0.23; 95% confidence interval [CI]: − 0.41, − 0.05; p = 0.012), nutrition (− 0.28; 95% CI: − 0.46, − 0.11; p = 0.002), and combination (− 0.34; 95% CI: − 0.52, − 0.16; p <  0.001) groups exhibited significantly greater improvements in the frailty scores than the control group. Significant improvements were also observed in several physical performance parameters in the exercise, nutrition, and combination groups, as well as in the 12-Item Short Form Health Survey mental component summary score for the nutrition group.

Conclusions

The designated home-based exercise and nutrition interventions can help pre-frail or frail older adults to improve their frailty score and physical performance.

Trial registration

Retrospectively registered at ClinicalTrials.gov (identifier: NCT03477097); registration date: March 26, 2018.
Apelin-13/APJ system attenuates early brain injury via suppression of endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation and oxidative stress in a AMPK-dependent manner after subarachnoid hemorrhage in rats
Authors: Xu Weilin , Li Tao , Gao Liansheng , Zheng Jingwei , Yan Jun , Zhang Jianmin , Shao Anwen
Published: December 2019

Background

Neuroinflammation and oxidative stress play important roles in early brain injury following subarachnoid hemorrhage (SAH). This study is the first to show that activation of apelin receptor (APJ) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-associated inflammation and oxidative stress after SAH.

Methods

Apelin-13, apelin siRNA, APJ siRNA, and adenosine monophosphate-activated protein kinase (AMPK) inhibitor-dorsomorphin were used to investigate if the activation of APJ could provide neuroprotective effects after SAH. Brain water content, neurological functions, blood-brain barrier (BBB) integrity, and inflammatory molecules were evaluated at 24 h after SAH. Western blotting and immunofluorescence staining were applied to assess the expression of target proteins.

Results

The results showed that endogenous apelin, APJ, and p-AMPK levels were significantly increased and peaked in the brain 24 h after SAH. In addition, administration of exogenous apelin-13 significantly alleviated neurological functions, attenuated brain edema, preserved BBB integrity, and also improved long-term spatial learning and memory abilities after SAH. The underlying mechanism of the neuroprotective effects of apelin-13 is that it suppresses microglia activation, prevents ER stress from overactivation, and reduces the levels of thioredoxin-interacting protein (TXNIP), NOD-like receptor pyrin domain-containing 3 protein (NLRP3), Bip, cleaved caspase-1, IL-1β, TNFα, myeloperoxidase (MPO), and reactive oxygen species (ROS). Furthermore, the use of APJ siRNA and dorsomorphin abolished the neuroprotective effects of apelin-13 on neuroinflammation and oxidative stress.

Conclusions

Exogenous apelin-13 binding to APJ attenuates early brain injury by reducing ER stress-mediated oxidative stress and neuroinflammation, which is at least partly mediated by the AMPK/TXNIP/NLRP3 signaling pathway.
The phosphodiesterase 10 inhibitor papaverine exerts anti-inflammatory and neuroprotective effects via the PKA signaling pathway in neuroinflammation and Parkinson’s disease mouse models
Authors: Lee Yu-Young , Park Jin-Sun , Leem Yea-Hyun , Park Jung-Eun , Kim Do-Yeon , Choi Youn-Hee , Park Eun-Mi , Kang Jihee Lee , Kim Hee-Sun
Published: December 2019

Background

Neuroinflammation plays a pivotal role in the pathogenesis of Parkinson’s disease (PD). Thus, the development of agents that can control neuroinflammation has been suggested as a promising therapeutic strategy for PD. In the present study, we investigated whether the phosphodiesterase (PDE) 10 inhibitor has anti-inflammatory and neuroprotective effects in neuroinflammation and PD mouse models.

Methods

Papaverine (PAP) was utilized as a selective inhibitor of PDE10. The effects of PAP on the expression of pro-inflammatory molecules were examined in lipopolysaccharide (LPS)–stimulated BV2 microglial cells by ELISA, RT-PCR, and Western blot analysis. The effects of PAP on transcription factors were analyzed by the electrophoretic mobility shift assay, the reporter gene assay, and Western blot analysis. Microglial activation and the expression of proinflammatory molecules were measured in the LPS- or MPTP-injected mouse brains by immunohistochemistry and RT-PCR analysis. The effect of PAP on dopaminergic neuronal cell death and neurotrophic factors were determined by immunohistochemistry and Western blot analysis. To assess mouse locomotor activity, rotarod and pole tests were performed in MPTP-injected mice.

Results

PAP inhibited the production of nitric oxide and proinflammatory cytokines in LPS-stimulated microglia by modulating various inflammatory signals. In addition, PAP elevated intracellular cAMP levels and CREB phosphorylation. Treatment with H89, a PKA inhibitor, reversed the anti-inflammatory effects of PAP, suggesting the critical role of PKA signaling in the anti-inflammatory effects of PAP. We verified the anti-inflammatory effects of PAP in the brains of mice with LPS-induced systemic inflammation. PAP suppressed microglial activation and proinflammatory gene expression in the brains of these mice, and these effects were reversed by H89 treatment. We further examined the effects of PAP on MPTP-injected PD model mice. MPTP-induced dopaminergic neuronal cell death and impaired locomotor activity were recovered by PAP. In addition, PAP suppressed microglial activation and proinflammatory mediators in the brains of MPTP-injected mice.

Conclusions

PAP has strong anti-inflammatory and neuroprotective effects and thus may be a potential candidate for treating neuroinflammatory disorders such as PD.
Antiviral activities of extremophilic actinomycetes extracts from Kazakhstan’s unique ecosystems against influenza viruses and paramyxoviruses
Authors: Berezin Vladimir , Abdukhakimova Diyora , Trenozhnikova Lyudmila , Bogoyavlenskiy Andrey , Turmagambetova Aizhan , Issanov Alpamys , Azizan Azliyati
Published: December 2019

Background

Commercially available antiviral drugs, when used in the treatment of viral infections, do not always result in success. This is an urgent problem currently that needs to be addressed because several viruses including influenza and paramyxoviruses are acquiring multi-drug resistance. A potential solution for this emerging issue is to create new antiviral drugs from available compounds of natural products. It is known that the majority of drugs have been developed using compounds derived from actinomycetes, which are naturally occurring gram-positive bacteria. The purpose of this study was to investigate the antiviral properties of extremophilic actinomycetes extracts from strains that were isolated from extreme environments in Kazakhstan.

Methods

Five strains of extremophilic actinomycetes isolated from the unique ecosystems of Kazakhstan were extracted and tested for antiviral activity against influenza viruses (strains H7N1, H5N3, H1N1 and H3N2) and paramyxoviruses (Sendai Virus and Newcastle Disease Virus). The antiviral activity of these selected extracts was tested by checking their effect on hemagglutination and neuraminidase activities of the studied viruses. Additionally, actinomycetes extracts were compared with commercially available antiviral drugs and some plant preparations that have been shown to exhibit antiviral properties.

Results

The main findings show that extracts from strains K-192, K-340, K-362, K-522 and K525 showed antiviral activities when tested using influenza viruses, Sendai Virus, and Newcastle Disease Virus. These activities were comparable to those shown by Rimantadine and Tamiflu drugs, and “Virospan” and “Flavovir” plant preparations.

Conclusions

We identified several extracts with antiviral activities against several strains of influenza viruses and paramyxoviruses. Our research findings can be applied towards characterization and development of new antiviral drugs from the active actinomycetes extracts.
Effect of platelet-rich plasma on the degenerative rotator cuff tendinopathy according to the compositions
Authors: Kim Sang Jun , Yeo Seung Mi , Noh Soo Jin , Ha Chul-Won , Lee Byung Chan , Lee Hyo Sun , Kim Sun Jeong
Published: December 2019

Background

There are controversies about platelet-rich plasma (PRP) as an established treatment option for rotator cuff (RC) tendinopathy. The purpose of the study was to find the relation of cellular component with clinical efficacy in RC tendinopathy and to find the composition of PRP in treating RC tendinopathy.

Methods

A total 30 patients were recruited and divided into PRP and control groups. In the PRP group, 2 ml of PRP solution was injected to the hypoechoic lesion of degenerative supraspinatus via 22-gauge syringe with peppering technique. Patients in the control group were taught rotator cuff strengthening exercises. American Shoulder and Elbow Surgeons (ASES), Constant-Murley score, and numeric rating scale (NRS) were measured before, 6 weeks after, 12 weeks after, and 24 weeks after the procedure. PRP compositions were analyzed using the 1 ml of PRP solution.

Results

Linear regression analysis showed no significant difference of ASES and Constant-Murley scores between the groups at 6 weeks (P= 0.582 and 0.258) and at 12 weeks (P= 0.969 and 0.795) but showed a significant difference at 24 weeks (P= 0.050 and 0.048). Independentttest showed significant group difference of NRS at 6 weeks (P= 0.031) but not at 12 and 24 weeks (P= 0.147 and 0.935). 5.19 pg/ml in IL-1β and 61.79 μg/ml in TGF-β1 were acquired as cutoff values to predict meaningful improvement. The PRP subgroup above IL-1β or TGF-β1 cutoff value showed significant differences in all clinical outcomes compared with the exercise group while the PRP subgroup below the cutoff value showed no significant differences in linear regression analysis.

Conclusions

Our study can help to find the optimal PRP condition and to enhance the effect of PRP on RC tendinopathy.

Trial registration

All the patients were registered in our Institutional Ethics Committee (approval number2014-05-009).
Atypical presentation of classic Kaposi sarcoma in circumcised penis presenting as an ulcerative nodule with human herpesvirus 8 (HHV8) positivity and successfully treated with only local excision
Authors: Alamri Abdulaziz , Adiga B. K.
Published: December 2019

Introduction

Although the Kaposi sarcoma (KS) is one of the AIDS defining entity and seen in almost one third of HIV infected patients with low CD4 cell counts, it is not uncommon in HIV seronegative persons, but genital KS is rare, particularly in people without risk factors for HIV infection. Isolated penile KS is an unusual manifestation, especially as solitary nodule with ulceration, in HIV seronegative patient.

Case presentation

We report such a case of Kaposi sarcoma showing HHV-8 positivity in an elderly male Arabian patient with a delay in prompt diagnosis, but treated successfully with 3 3 years follow-up after limited local surgical excision.

Conclusion

The general practitioners, venereologists and urologists should think of KS as a possibility in such lesion and consider early biopsy.
Ultrasound-based clinical profiles for predicting the risk of intradialytic hypotension in critically ill patients on intermittent dialysis: a prospective observational study
Authors: da Hora Passos Rogerio , Caldas Juliana , Ramos Joao Gabriel Rosa , dos Santos Galvão de Melo Erica Batista , Ribeiro Michel Por Deus , Alves Maria Fernanda Coelho , Batista Paulo Benigno Pena , Messeder Octavio Henrique Coelho , de Carvalho de Farias Augusto Manoel , Macedo Etienne , Rouby Jean Jacques
Published: December 2019

Background

Intradialytic hypotension, a complication of intermittent hemodialysis, decreases the efficacy of dialysis and increases long-term mortality. This study was aimed to determine whether different predialysis ultrasound cardiopulmonary profiles could predict intradialytic hypotension.

Methods

This prospective observational single-center study was performed in 248 critically ill patients with acute kidney injury undergoing intermittent hemodialysis. Immediately before hemodialysis, vena cava collapsibility was measured by vena cava ultrasound and pulmonary congestion by lung ultrasound. Factors predicting intradialytic hypotension were identified by multiple logistic regression analysis.

Results

Intradialytic hypotension was observed in 31.9% (n = 79) of the patients, interruption of dialysis because of intradialytic hypotension occurred in 6.8% (n = 31) of the sessions, and overall 28-day mortality was 20.1% (n = 50). Patients were classified in four ultrasound profiles: (A) 108 with B lines > 14 and vena cava collapsibility > 11.5 mm m−2, (B) 38 with B lines < 14 and vena cava collapsibility ≤ 11.5 mm m−2, (C) 36 with B lines > 14 and vena cava collapsibility Di ≤ 11.5 mm m−2, and (D) 66 with B lines < 14 and vena cava collapsibility > 11.5 mm m−2. There was an increased risk of intradialytic hypotension in patients receiving norepinephrine (odds ratios = 15, p = 0.001) and with profiles B (odds ratios = 12, p = 0.001) and C (odds ratios = 17, p = 0.001).

Conclusion

In critically ill patients on intermittent hemodialysis, the absence of hypervolemia as assessed by lung and vena cava ultrasound predisposes to intradialytic hypotension and suggests alternative techniques of hemodialysis to provide better hemodynamic stability.
Completeness of reporting in abstracts of randomized controlled trials in subscription and open access journals: cross-sectional study
Authors: Jerčić Martinić-Cezar Iva , Marušić Ana
Published: December 2019

Background

Open access (OA) journals are becoming a publication standard for health research, but it is not clear how they differ from traditional subscription journals in the quality of research reporting. We assessed the completeness of results reporting in abstracts of randomized controlled trials (RCTs) published in these journals.

Methods

We used the Consolidated Standards of Reporting Trials Checklist for Abstracts (CONSORT-A) to assess the completeness of reporting in abstracts of parallel-design RCTs published in subscription journals (n = 149; New England Journal of Medicine, Journal of the American Medical Association, Annals of Internal Medicine, and Lancet) and OA journals (n = 119; BioMedCentral series, PLoS journals) in 2016 and 2017.

Results

Abstracts in subscription journals completely reported 79% (95% confidence interval [CI], 77–81%) of 16 CONSORT-A items, compared with 65% (95% CI, 63–67%) of these items in abstracts from OA journals (P < 0.001, chi-square test). The median number of completely reported CONSORT-A items was 13 (95% CI, 12–13) in subscription journal articles and 11 (95% CI, 10–11) in OA journal articles. Subscription journal articles had significantly more complete reporting than OA journal articles for nine CONSORT-A items and did not differ in reporting for items trial design, outcome, randomization, blinding (masking), recruitment, and conclusions. OA journals were better than subscription journals in reporting randomized study design in the title.

Conclusion

Abstracts of randomized controlled trials published in subscription medical journals have greater completeness of reporting than abstracts published in OA journals. OA journals should take appropriate measures to ensure that published articles contain adequate detail to facilitate understanding and quality appraisal of research reports about RCTs.
Transcranial magnetic stimulation and amyloid markers in mild cognitive impairment: impact on diagnostic confidence and diagnostic accuracy
Authors: Padovani Alessandro , Benussi Alberto , Cotelli Maria Sofia , Ferrari Clarissa , Cantoni Valentina , Dell’Era Valentina , Turrone Rosanna , Paghera Barbara , Borroni Barbara
Published: December 2019

Background

The development of diagnostic tools capable of accurately identifying the pathophysiology of mild cognitive impairment (MCI) has become a crucial target considering the claim that disease-modifying treatments should be administered as early as possible in the disease course. Transcranial magnetic stimulation (TMS) protocols have demonstrated analytical validity in discriminating different forms of dementia; however, its value in daily clinical practice in MCI subjects is still unknown.

Objective

To evaluate the clinical value of TMS compared to amyloid markers on diagnostic confidence and accuracy in MCI subjects, considering clinicians’ expertise.

Methods

One hundred seven MCI subjects were included and classified as MCI-Alzheimer disease (MCI-AD), MCI-frontotemporal dementia (MCI-FTD), MCI-dementia with Lewy bodies (MCI-DLB), or MCI-other in a three-step process based on (i) demographic, clinical, and neuropsychological evaluation (clinical work-up); (ii) clinical work-up PLUS amyloidosis markers or clinical work-up PLUS TMS measures; and (iii) clinical work-up PLUS both markers. Two blinded neurologists with different clinical expertise were asked to express a diagnostic confidence for each MCI subgroup, and ROC curve analyses were performed at each step.

Results

The addition of TMS markers to clinical work-up significantly increased the diagnostic confidence for MCI-AD (p = 0.003), MCI-FTD (p = 0.044), and MCI-DLB (p = 0.033) compared to clinical work-up alone, but not for MCI-other (p > 0.05). No significant differences between the add-on effect of TMS and the add-on effect of amyloid markers to clinical work-up were observed (p > 0.732), while the diagnostic confidence further increased when both markers were available. The greater the clinical expertise, the greater the flexibility in considering alternative diagnosis, and the greater the ability to modify diagnostic confidence with TMS and amyloid markers.

Conclusions

TMS in addition to routine clinical assessment in MCI subjects has a significant effect on diagnostic accuracy and confidence, comparable to well-established biomarkers of amyloidosis.
Mutations in neuroligin-3 in male mice impact behavioral flexibility but not relational memory in a touchscreen test of visual transitive inference
Authors: Norris Rebecca H. C. , Churilov Leonid , Hannan Anthony J. , Nithianantharajah Jess
Published: December 2019

Cognitive dysfunction including disrupted behavioral flexibility is central to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). A cognitive measure that assesses relational memory, and the ability to flexibly assimilate and transfer learned information is transitive inference. Transitive inference is highly conserved across vertebrates and disrupted in cognitive disorders. Here, we examined how mutations in the synaptic cell-adhesion molecule neuroligin-3 (Nlgn3) that have been documented in ASD impact relational memory and behavioral flexibility. We first refined a rodent touchscreen assay to measure visual transitive inference, then assessed two mouse models ofNlgn3dysfunction (Nlgn3−/yandNlgn3R451C). Deep analysis of touchscreen behavioral data at a trial level established we could measure trajectories in flexible responding and changes in processing speed as cognitive load increased. We show that gene mutations inNlgn3do not disrupt relational memory, but significantly impact flexible responding. Our study presents the first analysis of reaction times in a rodent transitive inference test, highlighting response latencies from the touchscreen system are useful indicators of processing demands or decision-making processes. These findings expand our understanding of how dysfunction of key components of synaptic signaling complexes impact distinct cognitive processes disrupted in neurodevelopmental disorders, and advance our approaches for dissecting rodent behavioral assays to provide greater insights into clinically relevant cognitive symptoms.
Fibrodysplasia ossificans progressiva (stone man syndrome): a case report
Authors: Shah Zakir Ali , Rausch Sascha , Arif Uzma , El Yafawi Bilal
Published: December 2019

Background

Fibrodysplasia ossificans progressiva is an ultrarare autosomal dominant disorder and disabling syndrome characterized by postnatal progressive heterotopic ossification of the connective tissue and congenital malformation of the big toes. Fibrodysplasia ossificans progressiva has worldwide prevalence of about 1 in 2 million births. Nearly 90% of patients with fibrodysplasia ossificans progressiva are misdiagnosed and mismanaged and thus undergo unnecessarily interventions. So far, the number of reported existing cases worldwide is about 700. Clinical examination, radiological evaluation, and genetic analysis for mutation of the ACVR1 gene are considered confirmatory tools for early diagnosis of the disease. Association of fibrodysplasia ossificans progressiva with heterotopic ossification is well documented; however, postsurgical exaggerated response has never been reported previously, to the best of our knowledge.

Case presentation

We report a case of a 10-year-old Pakistani boy brought by his parents to our institution. He had clinical and radiological features of fibrodysplasia ossificans progressive and presented with multiple painful lumps on his back due to hard masses and stiffness of his shoulders, neck, and left hip. He underwent surgical excision of left hip ossification followed by an exaggerated response in ossification with early disability. Radiological examination revealed widespread heterotopic ossification. All of his laboratory blood test results were normal.

Conclusion

Fibrodysplasia ossificans progressiva is a very rare and disabling disorder that, if misdiagnosed, can lead to unnecessary surgical intervention and disastrous results of early disability. We need to spread knowledge to physicians and patients’ family members about the disease, as well as its features for early diagnosis and how to prevent flare-up of the disease to promote better quality of life in these patients.
Intervention for early diabetic nephropathy by mesenchymal stem cells in a preclinical nonhuman primate model
Authors: An Xingxing , Liao Guangneng , Chen Younan , Luo Ai , Liu Jingping , Yuan Yujia , Li Lan , Yang Lichuan , Wang Hong , Liu Fang , Yang Guang , Yi Shounan , Li Yuanmin , Cheng Jingqiu , Lu Yanrong
Published: December 2019

Background

Diabetic nephropathy (DN) is one of the most severe chronic diabetic complications and the main cause of end-stage renal disease. Chronic inflammation plays a key role in the development of DN. However, few treatment strategies are available; therefore, new and effective strategies to ameliorate DN at the early stage must be identified.

Methods

Mesenchymal stem cells (MSCs) are characterized by anti-inflammatory and immune regulatory abilities. We developed a rhesus macaque model of DN and administered MSCs four times over 2 months. We measured blood glucose level, HbA1c, and levels of renal function parameters in the blood and urine, and cytokine levels in the kidney and blood circulatory system of rhesus macaques. Also, we analyzed the renal pathological changes of rhesus macaques. In vitro, we treated tubular epithelial cells (HK2) with 30 mmol/L glucose and 10 ng/mL human recombinant TNF-alpha (rhTNF-α) and explored the effects of MSCs on inflammation and Na+-glucose cotransporter 2 (SGLT2) expression in HK2.

Results

We found that MSCs decreased the blood glucose level and daily insulin requirement of DN rhesus macaques. Furthermore, MSCs had a dominant function in improving renal function and decreasing SGLT2 expression on renal tubular epithelial cells. Also, renal pathological changes were ameliorated after MSC treatment. Moreover, MSCs powerfully reduced inflammation, especially decreased the level of pro-inflammatory cytokine interleukin-16 (IL-16), in the kidney and blood circulatory system.

Conclusions

Our study is an important step to explore the mechanism of MSCs in ameliorating the early stage of DN, potentially through influencing SGLT2 expression and resulting in improved glycemic control and anti-inflammation. We hope these findings would provide insights for the clinical application of MSCs in DN.
The role of pulmonary mesenchymal cells in airway epithelium regeneration during injury repair
Authors: Fang Suyun , Zhang Suhong , Dai Haiting , Hu Xiaoxiang , Li Changgong , Xing Yiming
Published: December 2019

Background

The airways of mammalian lung are lined with highly specialized cell types that are the target of airborne toxicants and injury. Several epithelial cell types and bone marrow-derived mesenchymal stem cells have been identified to serve as stem cells during injury repair. However, the contributions of endogenous mesenchymal cells to recruitment, expansion or differentiation of stem cells, and repair and reestablishment of the normal composition of airway epithelium following injury have not been addressed.

Methods

The role of mouse pulmonary mesenchymal cells was investigated by lineage tracing using Dermo1-Cre; ROSAmTmG mice. In experimental models of lung injury by lipopolysaccharide and naphthalene, GFP-labeled Dermo1+ mesenchymal cells were traced during injury repair. In vitro lung explant culture treated with or without lipopolysaccharide was also used to verify in vivo data.

Results

During injury repair, a subgroup of GFP-labeled Dermo1+ mesenchymal cells were found to contribute to normal repair of the airway epithelium and differentiated into Club cells, ciliated cells, and goblet cells. In Club cell-specific naphthalene injury model, the process of Dermo1+ stem cell regenerating epithelial cells was dissected. The Dermo1+ stem cells was migrated into the airway epithelium layer sooner after injury, and sequentially differentiated transitionally to epithelial stem cells, such as neuroendocrine cells, and finally to newly differentiated Club cells, ciliated cells, and goblet cells in injury repair.

Conclusion

In this study, a population of Dermo1+ mesenchymal stem cell was identified to serve as stem cells in airway epithelial cell regeneration during injury repair. The Dermo1+ mesenchymal stem cell differentiated into epithelial stem cells before reestablishing various epithelial cells. These findings have implications for understanding the regulation of lung repair and the potential for usage of mesenchymal stem cells in therapeutic strategies for lung diseases.
Evaluation of SUV normalized by lean body mass (SUL) in 68Ga-PSMA11 PET/CT: a bi-centric analysis
Authors: Gafita Andrei , Calais Jeremie , Franz Charlott , Rauscher Isabel , Wang Hui , Roberstson Andrew , Czernin Johannes , Weber Wolfgang A. , Eiber Matthias
Published: December 2019

Introduction

The aim of this analysis was to investigate whether the standardized uptake value (SUV) normalized by lean body mass (SUL) is a more appropriate quantitative parameter compared to the commonly used SUV normalized by patient’s weight in 68Ga-PSMA11 PET/CT.

Material and methods

68Ga-PSMA11 PET/CT scans of 121 patients with prostate cancer from two institutions were evaluated. Liver SUV was measured within a 3-cm volume-of-interest (VOI) in the right hepatic lobe and corrected for lean body mass using the Janmahasatian formula. SUV and SUL repeatability between baseline and follow-up scans of the same patients were assessed.

Results

SUV was significantly positively correlated with body weight (r = 0.35, p = 0.02). In contrast, SUL was not correlated with body weight (r = 0.23, p = 0.07). No significant differences were found between baseline and follow-up scan (p = 0.52).

Conclusion

The Janmahasatian formula annuls the positive correlations between SUV and body weight, suggesting that SUL is preferable to SUV for quantitative analyses of 68Ga-PSMA11 PET/CT scans.