bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive behavioral therapy for overactive bladder in women: study protocol for a randomized controlled trial
Authors: Funada Satoshi , Watanabe Norio , Goto Takayuki , Negoro Hiromitsu , Akamatsu Shusuke , Ueno Kentaro , Uozumi Ryuji , Ichioka Kentaro , Segawa Takehiko , Akechi Tatsuo , Furukawa Toshiaki A. , Ogawa Osamu
Published: August 2020

Background

Overactive bladder (OAB) symptoms affect daily life by decreasing health-related quality of life (HRQol). However, there remain no very effective treatment for OAB. Pharmacotherapy is one of the best treatments, but it is not always efficient and may incur adverse events. Although behavioral therapy is another effective treatment, there are very few structured treatment manuals on how to prescribe behavioral therapy to treat OAB for whom.

Cognitive behavioral therapy (CBT) is a psychotherapy consisting of structured sessions to solve problems with the collaborative empiricism between therapists and patients. OAB symptoms are supposed to worsen with cognitive distortion, and CBT is expected to be effective in treating OAB by modifying such cognitive processes. In this trial, we will evaluate the efficacy of CBT for OAB.

Methods

A randomized, controlled, open-label, multicenter parallel-group superiority trial will be conducted. Participants with moderate to severe OAB symptoms with or without pharmacotherapy will be recruited and will be randomly allocated 1:1 to two different groups by minimization (age, baseline OAB severity, treatment status, types of intervention, and treating institutions). The intervention group will be prescribed an individual CBT program covering six techniques in 4 sessions (30 min each), with or without pharmacotherapy. The primary outcome is the change scores in an OAB-questionnaire (OAB-q) from baseline to the end of the trial (week 13). Secondary outcomes will include other patient reported outcome measures and the frequency volume chart. All analyses will be conducted on an intention-to-treat principle.

Discussion

This trial will determine the efficacy of CBT to treat OAB using a rigorous methodology. The effectiveness of CBT with a structured manual may not only lead to a new treatment option for patients suffering from OAB symptoms, but may also reduce the social burden by OAB.

Trial registration

UMIN-CTR Clinical Trial, CTR-UMIN000038513. Registered on November 7, 2019.
The Porphyromonas gingivalis inhibitory effects, antioxidant effects and the safety of a Sri Lankan traditional betel quid - an in vitro study
Authors: Paranagama Madhavi Priyanka , Piyarathne Nadisha Sewwandi , Nandasena Tharanga Lakmali , Jayatilake Sumedha , Navaratne Ayanthi , Galhena Bandula Prasanna , Williams Senani , Rajapakse Jayantha , Kita Kiyoshi
Published: August 2020

Background

The Sri Lankan traditional betel quid (TBQ) which had been extensively used in the country before its colonization is claimed to have antiperiodontopathic effects in the Sri Lankan folklore. However, there is no reported scientific evidence to support the claimed antiperiodontopathic effects mediated by this TBQ. The present study was carried out to investigate the protective effect of the Sri Lankan TBQ in the pathogenesis of periodontitis.

Methods

We investigate the ethyl acetate extract of the Sri Lankan TBQ for its antibacterial effects against the keystone periodontopathic bacterium,P. gingivalisand also its antioxidant potential, which is important to protect the periodontium from oxidative stress. Further, its safety was analyzed using the cytokinesis block micronucleus assay on human peripheral blood lymphocytes (PBLs).

Results

Ethyl acetate extract of this TBQ inhibited the growth ofP. gingivaliswith a minimum bactericidal concentration (MBC) of 125 μg/ml. It was found to be a rich source of polyphenols and displayed considerable DPPH and ABTS radical scavenging activities and a strong ferric reducing antioxidant power. This extract could protect the cultured human gingival fibroblasts from H2O2induced oxidative stress. In addition, this TBQ extract was not genotoxic to human PBLs even at a concentration of 2.5 mg/ml. Moreover, it exhibited protective effects against bleomycin induced genotoxicity in PBLs.

Conclusion

Ethyl acetate extract of the Sri Lankan TBQ is a source of natural antibacterial compounds againstP. gingivalis. It is also a source of natural antioxidants which can protect human gingival fibroblasts from H2O2induced oxidative stress. These properties of the TBQ may have contributed to its claimed antiperiodontopathic effects. Besides, it was found to be relatively non-toxic to human cells. Thus this TBQ extract has a huge potential to be developed as a novel adjunctive therapeutic lead against periodontitis.
A randomised controlled trial of feedback to improve patient satisfaction and consultation skills in medical students
Authors: Lai Michelle M. Y. , Roberts Noel , Mohebbi Mohammadreza , Martin Jenepher
Published: August 2020

Background

The use of feedback has been integral to medical student learning, but rigorous evidence to evaluate its education effect is limited, especially in the role of patient feedback in clinical teaching and practice improvement. The aim of the Patient Teaching Associate (PTA) Feedback Study was to evaluate whether additional written consumer feedback on patient satisfaction improved consultation skills among medical students and whether multisource feedback (MSF) improved student performance.

Methods

In this single site, double-blinded randomised controlled trial, 71 eligible medical students from two universities in their first clinical year were allocated to intervention or control and followed up for one semester. They participated in five simulated student-led consultations in a teaching clinic with patient volunteers living with chronic illness. Students in the intervention group received additional written feedback on patient satisfaction combined with guided self-reflection. The control group received usual immediate formative multisource feedback from tutors, patients and peers. Student characteristics, baseline patient-rated satisfaction scores and tutor-rated consultation skills were measured.

Results

Follow-up assessments were complete in 70 students attending the MSF program. At the final consultation episodes, both groups improved patient-rated rapport (P = 0.002), tutor-rated patient-centeredness and tutor-rated overall consultation skills (P = 0.01). The intervention group showed significantly better tutor-rated patient-centeredness (P = 0.003) comparing with the control group. Distress relief, communication comfort, rapport reported by patients and tutor-rated clinical skills did not differ significantly between the two groups.

Conclusions

The innovative multisource feedback program effectively improved consultation skills in medical students. Structured written consumer feedback combined with guided student reflection further improved patient-centred practice and effectively enhanced the benefit of an MSF model. This strategy might provide a valuable adjunct to communication skills education for medical students.

Trial registration

Australian New Zealand Clinical Trials Registry Number ACTRN12613001055796.
In Defence of informed consent for health record research - why arguments from ‘easy rescue’, ‘no harm’ and ‘consent bias’ fail
Authors: Ploug Thomas
Published: August 2020

Background

Health data holds great potential for improved treatments. Big data research and machine learning models have been shown to hold great promise for improved diagnostics and treatment planning. The potential is tied, however, to the availability of personal health data. In recent years, it has been argued that data from health records should be available for health research, and that individuals have a duty to make the data available for such research. A central point of debate is whether such secondary use of health data requires informed consent.

Main body

In response to recent writings this paper argues that a requirement of informed consent for health record research must be upheld. It does so by exploring different contrasting notions of the duty of easy rescue and arguing that none of them entail aperfectduty to participate in health record research. In part because the costs of participation cannot be limited to 1) the threat of privacy breaches, but includes 2) the risk of reduced trust and 3) suboptimal treatment, 4) stigmatization and 5) medicalisation, 6) further stratification of solidarity and 7) increased inequality in access to treatment and medicine. And finally, it defends the requirement of informed consent by arguing that the mere possibility of consent bias provides a rather weak reason for making research participation mandatory, and that there are strong, independent reasons for making.

Conclusion

Arguments from the duty of easy rescue in combination with claims about little risk of harm and potential consent bias fail to establish not only aperfectduty to participate in health record research, but also that participation in such research should be mandatory. On the contrary, an analysis of these arguments indicates that the duty to participate in research is most adequately construed as animperfectduty, and reveals a number of strong reasons for insisting that participation in health records research is based on informed consent.
Using spatial genetics to quantify mosquito dispersal for control programs
Authors: Filipović Igor , Hapuarachchi Hapuarachchige Chanditha , Tien Wei-Ping , Razak Muhammad Aliff Bin Abdul , Lee Caleb , Tan Cheong Huat , Devine Gregor J. , Rašić Gordana
Published: August 2020

Background

Hundreds of millions of people get a mosquito-borne disease every year and nearly one million die. Transmission of these infections is primarily tackled through the control of mosquito vectors. The accurate quantification of mosquito dispersal is critical for the design and optimization of vector control programs, yet the measurement of dispersal using traditional mark-release-recapture (MRR) methods is logistically challenging and often unrepresentative of an insect’s true behavior. UsingAedes aegypti(a major arboviral vector) as a model and two study sites in Singapore, we show how mosquito dispersal can be characterized by the spatial analyses of genetic relatedness among individuals sampled over a short time span without interruption of their natural behaviors.

Results

Using simple oviposition traps, we captured adult femaleAe. aegyptiacross high-rise apartment blocks and genotyped them using genome-wide SNP markers. We developed a methodology that produces a dispersal kernel for distance which results from one generation of successful breeding (effective dispersal), using the distance separating full siblings and 2nd- and 3rd-degree relatives (close kin). The estimated dispersal distance kernel was exponential (Laplacian), with a mean dispersal distance (and dispersal kernel spread σ) of 45.2 m (95% CI 39.7–51.3 m), and 10% probability of a dispersal > 100 m (95% CI 92–117 m). Our genetically derived estimates matched the parametrized dispersal kernels from previous MRR experiments. If few close kin are captured, a conventional genetic isolation-by-distance analysis can be used, as it can produce σ estimates congruent with the close-kin method if effective population density is accurately estimated. Genetic patch size, estimated by spatial autocorrelation analysis, reflects the spatial extent of the dispersal kernel “tail” that influences, for example, the critical radii of release zones and the speed ofWolbachiaspread in mosquito replacement programs.

Conclusions

We demonstrate that spatial genetics can provide a robust characterization of mosquito dispersal. With the decreasing cost of next-generation sequencing, the production of spatial genetic data is increasingly accessible. Given the challenges of conventional MRR methods, and the importance of quantified dispersal in operational vector control decisions, we recommend genetic-based dispersal characterization as the more desirable means of parameterization.
Cluster analysis in 975 patients with current cough identifies a phenotype with several cough triggers, many background disorders, and low quality of life
Authors: Koskela Heikki O. , Selander Tuomas A. , Lätti Anne M.
Published: August 2020

Background

Recognition of disorder phenotypes may help to estimate prognosis and to guide the clinical management. Current cough management guidelines classify patients according to the duration of the cough episode. However, this classification is not based on phenotype analyses. The present study aimed to identify cough phenotypes by clustering.

Methods

An email survey among employed, working-age subjects identified 975 patients with current cough. All filled in a comprehensive 80-item questionnaire including the Leicester Cough Questionnaire. Phenotypes were identified utilizing K-means partitional clustering. A subgroup filled in a follow-up questionnaire 12 months later to investigate the possible differences in the prognosis between the phenotypes.

Results

Two clusters were found. The cluster A included 608 patients (62.4% of the population) and the cluster B 367 patients (37.6%). The three most important variables to separate the clusters were the number of the triggers of cough (mean 2.63 (SD 2.22) vs. 6.95 (2.30), respectively, p < 0.001), the number of the cough background disorders (chronic rhinosinusitis, current asthma, gastroesophageal reflux disease, 0.29 (0.50) vs. 1.28 (0.75), respectively, p < 0.001), and the Leicester Cough Questionnaire physical domain (5.33 (0.76) vs. 4.25 (0.84), respectively, p < 0.001). There were significant interrelationships between these three variables (each p < 0.001). Duration of the episode was not among the most important variables to separate the clusters. At 12 months, 27.0% of the patients of the cluster A and 46.1% of the patients of the cluster B suffered from cough that had continued without interruptions from the first survey (p < 0.001).

Conclusions

Two cough phenotypes could be identified. Cluster A represents phenotype A, which includes the majority of patients and has a tendency to heal by itself. The authors propose that cluster B represents phenotype TBQ (Triggers, Background disorders, Quality of life impairment). Given the poor prognosis of this phenotype, it urges a prompt and comprehensive clinical evaluation regardless of the duration of the cough episode.
Unspoken inequality: how COVID-19 has exacerbated existing vulnerabilities of asylum-seekers, refugees, and undocumented migrants in South Africa
Authors: Mukumbang Ferdinand C. , Ambe Anthony N. , Adebiyi Babatope O.
Published: August 2020

An estimated 2 million foreign-born migrants of working age (15–64) were living in South Africa (SA) in 2017. Structural and practical xenophobia has driven asylum-seekers, refugees, and undocumented migrants in SA to abject poverty and misery. The Coronavirus Disease 2019 (COVID-19) containment measures adopted by the SA government through the lockdown of the nation have tremendously deepened the unequal treatment of asylum-seekers and refugees in SA. This can be seen through the South African government’s lack of consideration of this marginalized population in economic, poverty, and hunger alleviation schemes. Leaving this category of our society out of the national response safety nets may lead to negative coping strategies causing mental health issues and secondary health concerns. An effective response to the socioeconomic challenges imposed by the COVID-19 pandemic should consider the economic and health impact of the pandemic on asylum-seekers, refugees, and undocumented migrants.
Comparison of inpatient distribution amongst different medical alliances in a county: a longitudinal study on a healthcare reform in rural China
Authors: Ran Yifan , Gao Hongxia , Han Dan , Hou Guilin , Chen Yingchun , Zhang Yan
Published: August 2020

Background

China has launched the medical alliances (MAs) reform to drive the development of primary medical institutions and decrease health inequality in rural areas. Three different types of MAs were built to promote township hospitals in Y County. This study aims to evaluate the actual effect of China’s MAs reform in rural areas on inpatient distribution especially amongst different types of MAs.

Methods

We obtain 2008–2015 claims data from the New Cooperative Medical Scheme (NCMS) in Y County, Hubei Province of China. We consider January 2008–December 2010 as the pre-reform period and January 2011–December 2015 as the post-reform period.

We use independent sample t-test and single-group interrupted time series analysis (ITSA) to compare the number of inpatients per month in the three MAs, including three county and 10 township hospitals before and after the reform. We use paired t-test and multiple-group ITSA between seven township hospitals within MAs and seven township hospitals outside MAs.

Results

The MAs reform in Y County increased the number of inpatients in county and township hospitals within MAs. After the reform, the number of inpatients per month in county hospitals had an upward trend, with a slope of 31.01 person/month (P < 0.000). Approximately 19.99 new inpatients were admitted to township hospitals monthly after the reform (P < 0.000). Furthermore, township hospitals within MAs had a substantial increase in the number of inpatients (10.45 new inpatients monthly) compared with those outside MAs.

Conclusion

The MAs reform in Y County significantly improved the capability of medical institutions within MAs. After the reform, township hospitals within MAs had greater development advantages than those outside MAs. However, it also caused further imbalance in the county region, which contained the new health inequality risk.
Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis
Authors: Yan Feili , Zhong Zhirong , Wang Yao , Feng Yue , Mei Zhiqiang , Li Hui , Chen Xiang , Cai Liang , Li Chunhong
Published: August 2020

Background

Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration, serious adverse reactions during long-term administration. To achieve better treatment, reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system.

Results

The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was − 22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo biodistribution experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility.

Conclusion

The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.
Myeloid Pannexin-1 mediates acute leukocyte infiltration and leads to worse outcomes after brain trauma
Authors: Seo Joon Ho , Dalal Miloni S. , Calderon Frances , Contreras Jorge E.
Published: August 2020

Background

Neuroinflammation is a major component of secondary damage after traumatic brain injury (TBI). We recently reported that pharmacological inhibition of Pannexin-1 (Panx1) channels markedly reduced the inflammatory response after TBI. Panx1 channels have been shown to be important conduits for adenosine 5′-triphosphate (ATP) release and are associated with leukocyte infiltration and pyroptosis. Because Panx1 blockers significantly decrease ATP release and migration of activated microglia and other myeloid cells (such as monocyte-derived macrophages and dendritic cells) in vitro, we hypothesized that myeloid Panx1 channels play a specific role in immune cell infiltration promoting tissue damage following TBI.

Methods

The murine-controlled cortical impact (CCI) model was used on myeloid-specific Panx1 conditional knockout (Cx3cr1-Cre::Panx1fl/fl) mice to determine whether myeloid Panx1 mediates neuroinflammation and brain damage. Immune cell infiltration was measured using flow cytometry. Locomotor and memory functions were measured using the rotarod and Barnes maze test, respectively. The levels of biomarkers for tissue damage and blood–brain barrier leakage were measured using western blot and magnetic resonance imaging. Panx1 channel activity was measured with ex vivo dye uptake assays, using flow cytometry and confocal microscopy.

Results

CCI-injured Cx3cr1-Cre::Panx1fl/fl mice showed markedly reduced immune cell infiltration to the brain parenchyma compared with Panx1fl/fl mice. As expected, Panx1 dependent activity, assessed by dye uptake, was markedly reduced only in myeloid cells from Cx3cr1-Cre::Panx1fl/fl mice. The expression of biomarkers of tissue damage was significantly reduced in the CCI-injured Cx3cr1-Cre::Panx1fl/fl mice compared with Panx1fl/fl mice. In line with this, magnetic resonance imaging showed reduced blood–brain barrier leakage in CCI-injured Cx3cr1-Cre::Panx1fl/fl mice. There was also a significant improvement in motor and memory function in Cx3cr1-Cre::Panx1fl/fl mice when compared with Panx1fl/fl mice within a week post-CCI injury.

Conclusion

Our data demonstrate that CCI-related outcomes correlate with Panx1 channel function in myeloid cells, indicating that activation of Panx1 channels in myeloid cells is a major contributor to acute brain inflammation following TBI. Importantly, our data indicate myeloid Panx1 channels could serve as an effective therapeutic target to improve outcome after TBI.
Virtual reality-based action observation facilitates the acquisition of body-powered prosthetic control skills
Authors: Yoshimura Manabu , Kurumadani Hiroshi , Hirata Junya , Osaka Hiroshi , Senoo Katsutoshi , Date Shota , Ueda Akio , Ishii Yosuke , Kinoshita Seiji , Hanayama Kozo , Sunagawa Toru
Published: August 2020

Background

Regular body-powered (BP) prosthesis training facilitates the acquisition of skills through repeated practice but requires adequate time and motivation. Therefore, auxiliary tools such as indirect training may improve the training experience and speed of skill acquisition. In this study, we examined the effects of action observation (AO) using virtual reality (VR) as an auxiliary tool. We used two modalities during AO: three-dimensional (3D) VR and two-dimensional (2D) computer tablet devices (Tablet). Each modality was tested from first- and third-person perspectives.

Methods

We studied 40 healthy right-handed participants wearing a BP prosthesis simulator on their non-dominant hands. The participants were divided into five groups based on combinations of the different modalities and perspectives: first-person perspective on VR (VR1), third-person perspective on VR (VR3), first-person perspective on a tablet (Tablet1), third-person perspective on a tablet (Tablet3), and a control group (Control). The intervention groups observed and imitated the video image of prosthesis operation for 10 min in each of two sessions. We evaluated the level of immersion during AO using the visual analogue scale. Prosthetic control skills were evaluated using the Box and Block Test (BBT) and a bowknot task (BKT).

Results

In the BBT, there were no significant differences in the amount of change in the skills between the five groups. In contrast, the relative changes in the BKT prosthetic control skills in VR1 (p < 0.001, d = 3.09) and VR3 (p < 0.001, d = 2.16) were significantly higher than those in the control group. Additionally, the immersion scores of VR1 (p < 0.05, d = 1.45) and VR3 (p < 0.05, d = 1.18) were higher than those of Tablet3. There was a significant negative correlation between the immersion scores and the relative change in the BKT scores (Spearman’s rs = − 0.47, p < 0.01).

Conclusions

Using the BKT of bilateral manual dexterity, VR-based AO significantly improved short-term prosthetic control acquisition. Additionally, it appeared that the higher the immersion score was, the shorter the execution time of the BKT task. Our findings suggest that VR-based AO training may be effective in acquiring bilateral BP prosthetic control, which requires more 3D-based operation.
Functional hyperemia drives fluid exchange in the paravascular space
Authors: Kedarasetti Ravi Teja , Turner Kevin L. , Echagarruga Christina , Gluckman Bruce J. , Drew Patrick J. , Costanzo Francesco
Published: August 2020

The brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that directional fluid movement through the arteriolar paravascular space (PVS) promotes metabolite clearance. We performed simulations to examine if arteriolar pulsations and dilations can drive directional CSF flow in the PVS and found that arteriolar wall movements do not drive directional CSF flow. We propose an alternative method of metabolite clearance from the PVS, namely fluid exchange between the PVS and the subarachnoid space (SAS). In simulations with compliant brain tissue, arteriolar pulsations did not drive appreciable fluid exchange between the PVS and the SAS. However, when the arteriole dilated, as seen during functional hyperemia, there was a marked exchange of fluid. Simulations suggest that functional hyperemia may serve to increase metabolite clearance from the PVS. We measured blood vessels and brain tissue displacement simultaneously in awake, head-fixed mice using two-photon microscopy. These measurements showed that brain deforms in response to pressure changes in PVS, consistent with our simulations. Our results show that the deformability of the brain tissue needs to be accounted for when studying fluid flow and metabolite transport.
Combined use of intravenous and topical tranexamic acid efficiently reduces blood loss in patients aged over 60 operated with a 2-level lumbar fusion
Authors: Li Jianjiang , Wang Long , Bai Tao , Liu Yanlu , Huang Yifei
Published: August 2020

Purpose

The current study was conducted to assess the efficacy and safety of the intravenous (IV) administration combined with topical administration of tranexamic acid (TXA)in patients (aged over 60) scheduled for a 2-level lumbar fusion surgery.

Methods

Two hundred eighty patients scheduled for a 2-level lumbar fusion surgery were randomized into four groups, including an IV group, a local group, a combined group, and a control group. Patients in the combined group, in the IV group, in the topical group, and in the control group were administrated with 15 mg/kg of IV-TXA + 2 g TXA in local, 15 mg/kg IV-TXA, 2 g TXA in local, and 100 ml IV, respectively. The results of total blood loss (TBL), maximum hemoglobin drop, the transfusion rate, and the number of allogeneic blood units were compared. Deep venous thrombosis (DVT) and pulmonary embolism (PE) events were monitored and recorded.

Results

The TBL was 635.49 ± 143.60, 892.62 ± 166.85, 901.11 ± 186.25, and 1225.11 ± 186.25 mL for the combined group, the IV group, the topical group, and the control group, respectively (p = 0.015, p = 0.001, respectively). The average maximum hemoglobin drop in the four above groups was 2.18 ± 0.24, 2.80 ± 0.37, 2.40 ± 0.64, and 3.40 ± 1.32 g/dL, respectively. No PE event was reported during the follow-up. Although asymptomatic DVT events were reported by 1, 2, and 2 patients in the combined group, topical group, and control group, respectively, there is no intergroup difference.

Conclusions

The combined use of TXA effectively reduced the total blood loss and blood transfusion rate in patients aged over 60 scheduled for a 2-level lumbar fusion, without increasing the incidence of DVT and PE formation.
Correction to: Treatment comparison of femoral shaft with femoral neck fracture: a meta-analysis
Authors: Lu Yao , Wang Yakang , Song Zhe , Wang Qian , Sun Liang , Ren Cheng , Xue Hanzhong , Li Zhong , Zhang Kun , Hao Dingjun , Zhao Yang , Ma Teng
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Systemic osteoprotective effects of Epimedii Folium and Ligustri Lucidi Fructus in senile osteoporosis rats by promoting the osteoblastogenesis and osteoclastogenesis based on MLP-ANN model
Authors: Tang Xiu-Feng , Ma Zi-Tong , Gao Ying-Ying , Wang Han , Li Xiao-Xi , Yu Ping , Liu Ren-Hui
Published: August 2020

Background

Senile osteoporosis (SOP), which is caused by unbalanced bone remodeling, leads to significant economic and societal burdens globally. The combination of Epimedii Folium (EF) and Ligustri Lucidi Fructus (LLF) serves as a commonly-used prescription for SOP in Traditional Chinese Medicine (TCM). This study aimed to evaluate the osteoprotective effects of EF and LLF in combination on SOP rats based on the constructed multilayer perception (MLP)-artificial neural network (ANN) model.

Methods

15 month old male Sprague–Dawley rats were administrated with EF, LLF or the combination of EF and LLF (EF&LLF) for 2 months, while 17 month old rats were used as the aging control group. All the rats were anesthetized with 25% ethyl carbamate, then their serum liver and bone tissues were taken. We detected bone mass, bone mineral density (BMD), biomechanics and the microstructure of bone trabecula by micro-CT and H&E staining to evaluate the degree of osteoporosis. Blood lipids and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) and liver pathology were use to assess the side effects of drugs. Levels of alkaline phosphatase (ALP) and Tartrate-resistant acid phosphatase (TRACP) and the ratio of ALP to TRACP both in serum and bone were measured for the evaluation of bone turnover rate. The bone mRNA and protein expression of osteoprotegerin (OPG), nuclear factor-kappa B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), d2 isoform of vacuolar (H+) ATPase (ATP6V0d2), insulin-like growth factor (IGF-1), bone morphogenetic protein-2 (BMP2), M-CSF, Wnt5a, transforming growth factor-β1 (TGF-β1) were detected for evaluating bone metabolism.

Results

The results showed that EF&LLF improved bone mass and bone quality by preventing bone loss, increasing maximal load as well as protecting the micro-structural retrogressive change of trabecular bone in SOP rats; ameliorated the steatosis in the liver and decreased blood lipids and serum ALT, AST and GGT; enhanced bone remodeling by stimulating the expression of ALP and TRACP. At the molecular levels, EF&LLF stimulated the osteoclastogenesis by upregulating the protein and mRNA expression of OPG, RANKL, M-CSF and ATP6V0d2; meanwhile, EF&LLF stimulated osteoblastogenesis by enhancing the expression of TGF-β1, BMP2, Wnt5a and IGF-1. According to our established MLP model, EF&LLF has a better effect on osteoclastogenesis or steoblastogenesis in SOP rats than EF or LLF.

Conclusions

These findings demonstrate that the systemic bone protective effects of EF&LLF by promoting bone remodeling in aging rats might be a substitute medicine for the treatment of SOP.
Chromosomal instability associated with adverse outcome: a case report of patient with Nijmegen breakage syndrome and rapidly developed T-NHL with complex karyotype
Authors: Włodarczyk Monika , Lejman Monika
Published: August 2020

Background

Nijmegen breakage syndrome (NBS) is a rare genetic disorder inherited in an autosomal recessive pattern associated with an increased risk of developing lymphoproliferative disorders, mainly non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). NBS patients are 50 times more likely to develop malignancy than healthy controls. Moreover, in NBS, mortality rate from cancers, mainly lymphomas, is the highest among all diseases associated with excessive fragility of chromosomes.

Case presentation

This work presents a patient previously diagnosed with Nijmegen breakage syndrome who rapidly developed T-NHL despite of constant medical supervision. Cytogenetic karyotype and microarray tests revealed complex aberrations, indicating enhanced chromosomal instability. Despite initial steroid therapy, the patient passed away due to multiorgan failure.

Conclusions

The lack of well-established diagnostic procedures in NBS patients make it difficult to determine any therapeutic target or predictive marker. Moreover, anticancer treatment is the biggest challenge in NBS patients due to therapy-related toxicity and immunodeficiency. Our case indicates the importance of identifying parameters useful in prognosis of disease outcome, as main risk factor affecting overall survival in NBS patients is an extremely high incidence of malignancy development.
Pediatric hypothermic submersion incident – should we do chest compressions on a beating heart?
Authors: Einvik Steinar , Kruger Andreas Jorstad , Gisvold Sven Erik
Published: August 2020

Background

Drowning is the third leading cause of unintentional injury death worldwide, with the highest rates of fatality among young children. To decide how to treat these patients prehospitally could be challenging in certain situations when uncertain about the adequacy of the patent’s circulation.

Methods/case report

We describe a 2 year old boy surviving a 15 min hypothermic submersion in a cold river. In spite of the presence of some vital signs, we decided to do full cardiopulmonary resuscitation to the hospital. The main reason was that we were uncertain about the adequacy of the spontaneous circulation, and the transport to hospital was fairly long. The patient suffered no obvious harm and the outcome was good.

Discussion

What is regarded as adequate circulation when accidentally hypothermic between 24 and 250 C? A weak pulse was felt in the femoral artery with a rate of about 40–50 per minute. There were shallow, but regular respiration, and point of care ultrasound revealed a slightly dilated left ventricle and weak, but organised cardiac contractions. Despite these findings a decision was made to continue ventilations and chest compressions during helicopter transport to the University hospital.

Conclusion

In an accidentally hypothermic pediatric submersion incident we decided to do full cardiopulmonary resuscitation to the hospital despite there were signs of circulation. We did no harm to the patient. Future guideline revisions should try to clarify how to handle situations with severly accidentally hypothermic patients like this, so the good outcome that is often seen in these patients could be even better.
Impact of a ketogenic diet intervention during radiotherapy on body composition: III—final results of the KETOCOMP study for breast cancer patients
Authors: Klement Rainer J. , Champ Colin E. , Kämmerer Ulrike , Koebrunner Petra S. , Krage Kelley , Schäfer Gabriele , Weigel M. , Sweeney Reinhart A.
Published: August 2020

Background

Obesity and low muscle mass are associated with worse outcomes of breast cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in breast cancer patients undergoing radiotherapy.

Methods

Patients with non-metastasized breast cancer were allocated to either the KD (N = 32) or the SD (N = 31) during radiotherapy. Body composition was measured weekly by bioimpedance analysis. Blood parameters and quality of life were assessed before, during, and at the end of radiotherapy.

Results

A total of 29 KD and 30 SD patients completed the study. During radiotherapy, mean and median fasting BHB concentrations in the KD group were 0.72 and 0.49 mmol/l (range 0.06–4.9) which was significantly higher than those in the SD group (p < 2.2 × 10−16). There was a very small and insignificant increase in body weight and fat mass in the SD group, as well as a decrease of fat free mass. In contrast, patients in the KD group lost body weight and fat free and skeletal muscle mass quickly after diet onset, which for the most part was related to water losses. The KD did not cause further substantial changes in fat free or skeletal muscle mass, but was associated with a gradual decrease of 0.4 kg body weight and fat mass per week (p < 0.0001). The KD significantly decreased free T3 levels by 0.06 pg/ml/week (p = 6.3 × 10−5). Global quality of life remained stable in the SD group but increased in the KD group from a score of 66.7 to 75.0 (p = 0.20).

Conclusions

In breast cancer patients undergoing curative radiotherapy, a KD based on natural foods is feasible. After initial water losses, the KD tends to reduce body weight and fat mass while preserving fat free and skeletal muscle mass.

Trial registration

ClinicalTrials.gov identifier: NCT02516501, registered on August 06, 2015.
The effect of on-site CT-derived fractional flow reserve on the management of decision making for patients with stable chest pain (TARGET trial): objective, rationale, and design
Authors: Yang Junjie , Shan Dongkai , Dong Mei , Wang Zhiqiang , Ma Xiang , Hu Xinyang , Zeng Hesong , Chen Yundai
Published: August 2020

Background

The diagnostic accuracy of CT-derived fractional flow reserve (CT-FFR) in clinical application has been well validated. This advanced technology focus on evaluating anatomical stenosis and functional ischemia simultaneously. However, the effect of CT-FFR on the management of decision making has not been fully evaluated in randomized controlled design.

Method/design

TARGET study is a pragmatic, multicenter, prospective, open-label, and randomized controlled trial evaluating the effect of a CCTA/CT-FFR strategy (group A) versus usual care (group B) on intermediate-to-high risk patients with suspected CAD who undergo clinically indicated diagnostic evaluation. A total sample size of 1216 subjects will be enrolled and followed up for 12 months. This study will be performed in 6 Chinese hospitals, and the primary endpoint is the planned ICA without significant obstructive CAD within 90 days. The secondary endpoints include MACE, quality of life, medical expenditure, and cumulative radiation exposure during 1-year follow-up.

Discussion

The study will provide information to patients, health care providers, and other stakeholders in China about which strategy could be more effective in the management of intermediate-to-high risk patients with suspect CAD.

Trial registration

ClinicalTrials.gov NCT03901326. Registered on 3 April 2019.
Integrative transcriptome and proteome analyses provide new insights into different stages of Akebia trifoliata fruit cracking during ripening
Authors: Niu Juan , Shi Yaliang , Huang Kunyong , Zhong Yicheng , Chen Jing , Sun Zhimin , Luan Mingbao , Chen Jianhua
Published: August 2020

Background

Akebia trifoliata (Thunb.) Koidz may have applications as a new potential source of biofuels owing to its high seed count, seed oil content, and in-field yields. However, the pericarp of A. trifoliata cracks longitudinally during fruit ripening, which increases the incidence of pests and diseases and can lead to fruit decay and deterioration, resulting in significant losses in yield. Few studies have evaluated the mechanisms underlying A. trifoliata fruit cracking.

Results

In this study, by observing the cell wall structure of the pericarp, we found that the cell wall became thinner and looser and showed substantial breakdown in the pericarp of cracking fruit compared with that in non-cracking fruit. Moreover, integrative analyses of transcriptome and proteome profiles at different stages of fruit ripening demonstrated changes in the expression of various genes and proteins after cracking. Furthermore, the mRNA levels of 20 differentially expressed genes were analyzed, and parallel reaction monitoring analysis of 20 differentially expressed proteins involved in cell wall metabolism was conducted. Among the molecular targets, pectate lyases and pectinesterase, which are involved in pentose and glucuronate interconversion, and β-galactosidase 2, which is involved in galactose metabolism, were significantly upregulated in cracking fruits than in non-cracking fruits. This suggested that they might play crucial roles in A. trifoliata fruit cracking.

Conclusions

Our findings provided new insights into potential genes influencing the fruit cracking trait in A. trifoliata and established a basis for further research on the breeding of cracking-resistant varieties to increase seed yields for biorefineries.
Anti-proliferative and cytotoxic effect of cannabidiol on human cancer cell lines in presence of serum
Authors: Sainz-Cort Alberto , Müller-Sánchez Claudia , Espel Enric
Published: August 2020

Objective

Cannabinoids are able to reduce tumor growth in xenograft models, but their therapeutic potential as anti-cancer drugs in humans is unclear yet. In vitro studies of the effect of cannabinoids on cancer cells are often carried out in absence of serum or in low serum concentration (i.e. 0.5% serum), conditions that limit cellular growth and therefore can increase the response of cells to additional challenges such as the presence of cannabinoids. However, the tumor microenvironment can be teaming with growth factors. In this study we assessed the viability and proliferation of cancer cells treated with cannabidiol in presence of a serum concentration that commonly sustains cell growth (10% serum).

Results

The results show that cannabidiol exerts a markedly different effect on the viability of the human HT-29 cancer cell line when cultured in presence of 0.5% serum in comparison to 10% serum, displaying a cytotoxic effect only in the former situation. In presence of 10% serum, no inhibitory effect of cannabidiol on DNA replication of HT-29 cells was detected, and a weak inhibition was observed for other cancer cell lines. These results indicate that the effect of cannabidiol is cell context-dependent being modulated by the presence of growth factors.
Comparison of ActiGraph GT9X Link with two Japanese accelerometers for assessments of free-living physical activity in junior high school students
Authors: Sasayama Kensaku , Adachi Minoru
Published: August 2020

Objective

This study compared the measurements of total steps and moderate-to-vigorous physical activity (MVPA) between ActiGraph and the Lifecorder and Active Style Pro accelerometers in junior high school students.

Results

The total steps and MVPA significantly differed between ActiGraph and Lifecorder measurements, whereas the intraclass correlation coefficients (ICCs) for total steps and MVPA between the two accelerometers were not significant. There was no significant difference between the total steps measured using ActiGraph and Active Style Pro, and moderate agreement was noted. Additionally, MVPA measured using ActiGraph and Active Style Pro significantly differed, whereas the ICC for MVPA measured using the two accelerometers was not significant. When comparing the total steps between ActiGraph and Lifecorder and MVPA between ActiGraph and Lifecorder or Active Style Pro, it should be noted that the accelerometer measurements are not compatible.
PRDM8 reveals aberrant DNA methylation in aging syndromes and is relevant for hematopoietic and neuronal differentiation
Authors: Cypris Olivia , Eipel Monika , Franzen Julia , Rösseler Corinna , Tharmapalan Vithurithra , Kuo Chao-Chung , Vieri Margherita , Nikolić Miloš , Kirschner Martin , Brümmendorf Tim H. , Zenke Martin , Lampert Angelika , Beier Fabian , Wagner Wolfgang
Published: August 2020

Background

Dyskeratosis congenita (DKC) and idiopathic aplastic anemia (AA) are bone marrow failure syndromes that share characteristics of premature aging with severe telomere attrition. Aging is also reflected by DNA methylation changes, which can be utilized to predict donor age. There is evidence that such epigenetic age predictions are accelerated in premature aging syndromes, but it is yet unclear how this is related to telomere length. DNA methylation analysis may support diagnosis of DKC and AA, which still remains a challenge for these rare diseases.

Results

In this study, we analyzed blood samples of 70 AA and 18 DKC patients to demonstrate that their epigenetic age predictions are overall increased, albeit not directly correlated with telomere length. Aberrant DNA methylation was observed in the genePRDM8in DKC and AA as well as in other diseases with premature aging phenotype, such as Down syndrome and Hutchinson-Gilford-Progeria syndrome. Aberrant DNA methylation patterns were particularly found within subsets of cell populations in DKC and AA samples as measured with barcoded bisulfite amplicon sequencing (BBA-seq). To gain insight into the functional relevance of PRDM8, we used CRISPR/Cas9 technology to generate induced pluripotent stem cells (iPSCs) with heterozygous and homozygous knockout. Loss of PRDM8 impaired hematopoietic and neuronal differentiation of iPSCs, even in the heterozygous knockout clone, but it did not impact on epigenetic age.

Conclusion

Taken together, our results demonstrate that epigenetic aging is accelerated in DKC and AA, independent from telomere attrition. Furthermore, aberrant DNA methylation inPRDM8provides another biomarker for bone marrow failure syndromes and modulation of this gene in cellular subsets may be related to the hematopoietic and neuronal phenotypes observed in premature aging syndromes.

Graphical abstract
Atomic ring invariant and Modified CANON extended connectivity algorithm for symmetry perception in molecular graphs and rigorous canonicalization of SMILES
Authors: Krotko Dmytro G.
Published: August 2020

We propose new invariant (the product of the corresponding primes for the ring size of each bond of an atom) as a simple unambiguous ring invariant of an atom that allows distinguishing symmetry classes in the highly symmetrical molecular graphs using traditional local and distance atom invariants. Also, we propose modifications of Weininger’s CANON algorithm to avoid its ambiguities (swapping and leveling ranks, incorrect determination of symmetry classes in non-aromatic annulenes, arbitrary selection of atom for breaking ties). The atomic ring invariant and the Modified CANON algorithm allow us to create a rigorous procedure for the generation of canonical SMILES which can be used for accurate and fast structural searching in large chemical databases.