bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of sarcopenia on short- and long-term outcomes in patients with gastric neuroendocrine neoplasms after radical gastrectomy: results from a large, two-institution series
Authors: Wang Jia-bin , Xue Zhen , Lu Jun , He Qing-liang , Zheng Zhi-fang , Xu Bin-bin , Xie Jian-wei , Li Ping , Xu Yu , Lin Jian-xian , Chen Qi-yue , Cao Long-long , Lin Mi , Tu Ru-hong , Huang Ze-ning , Lin Ju-li , Huang Chang-ming , Zheng Chao-hui
Published: October 2020

Background

The relationship between sarcopenia and the prognoses of patients with gastric neuroendocrine neoplasms (g-NENs) is unclear. This study was designed to explore the effects of sarcopenia on short-term and long-term outcomes of patients with g-NENs after radical gastrectomy.

Methods

This study retrospectively collected data from 138 patients with g-NENs after radical gastrectomy. The skeletal muscle index (SMI) diagnostic threshold for sarcopenia was determined using X-tile software. Cox regression analyses were performed to determine the independent risk factors for 3-year overall survival (OS) and 3-year recurrence-free survival (RFS).

Results

In this study, 59 patients (42.8%) were diagnosed with sarcopenia. Among patients in the sarcopenia group and nonsarcopenia group, the incidences of total postoperative complications were 33.9 and 30.4%, incidences of serious postoperative complications were 0 and 3.7%, incidences of postoperative surgical complications were 13.6 and 15.2%, and incidences of postoperative systemic complications were 20.3 and 15.2%, respectively (allp > 0.05). The 3-year OS and RFS rates were significantly worse in the sarcopenia group than in the nonsarcopenia group (OS: 42.37% vs 65.82%,p = 0.004; RFS: 52.54% vs 68.35%,p = 0.036). The multivariate analysis revealed a relation between sarcopenia and the long-term prognoses of patients with g-NENs. A stratified analysis based on the pathological type revealed that the Kaplan-Meier curve was only significantly different in patients with gastric mixed adenoneuroendocrine carcinoma (gMANEC) (OS: 40.00% vs 71.79%,p = 0.007; RFS: 51.43% vs 74.36%,p = 0.026); furthermore, the multivariate analysis identified sarcopenia as an independent risk factor for patients with gMANEC (p < 0.05).

Conclusions

Sarcopenia is not related to the short-term prognoses of patients with g-NENs. Sarcopenia is an independent risk factor for patients with gMANEC after radical surgery.
Biomarker exploration of microRNA-203 as a promising substrate for predicting poor survival outcome in colorectal cancer
Authors: Peng Qiliang , Shen Yi , Zhao Peifeng , Cai Shang , Feng Zhengyang , Cheng Ming , Wu Yongyou , Zhu Yaqun
Published: October 2020

Background

Increasing studies indicated that microRNA-203 (miR-203) may play an important part in the prognosis of CRC. Nevertheless, the prognostic and influential mechanism of miR-203 expression in CRC remains to be inconclusive. Accordingly, we conducted the current study to investigate the biomarker performance of miR-203 in CRC.

Methods

In the present study, we conducted an evidence synthesis of the published literatures to identify the prognostic roles of miR-203 in patients with CRC. Moreover, several bioinformatics methods were applied for exploring the biomarker roles of miR-203.

Results

It was demonstrated that elevated miR-203 expression was clearly related to worse overall survival (HR: 1.55, 95% CI: 1.07–2.24, P = 0.021) for CRC. The gene Ontology (GO) analysis indicated that miR-203 targets were primarily involved in a series of GO items closely associated with the molecular pathogenesis of CRC. The pathway analysis exhibited the potential signal pathways of miR-203 involved in CRC including pathways in cancer, wnt pathway, prolactin signaling pathway, proteoglycans in cancer, FoxO pathway, focal adhesion and Ras pathway. By constructing a protein-protein interaction (PPI) network of the targets of miR-203, ten crucial proteins and a significant network module were retrieved and found to serve important roles in the molecular pathogenesis of CRC.

Conclusions

Our results indicated that miR-203 may function as a promising biomarker to monitor CRC survival outcomes and progression. Notably, large-scale prospective cohort studies and biological experiments are required to confirm our conclusions.
Adjuvant chemotherapy could not bring survival benefit to HR-positive, HER2-negative, pT1b-c/N0–1/M0 invasive lobular carcinoma of the breast: a propensity score matching study based on SEER database
Authors: Hu Guangfu , Hu Guangxia , Zhang Chengjiao , Lin Xiaoyan , Shan Ming , Yu Yanmin , Lu Yongwei , Niu Ruijie , Ye Hui , Wang Cheng , Xu Cheng
Published: October 2020

Background

The benefit of adjuvant chemotherapy in invasive lobular carcinoma (ILC) is still unclear. The objective of the current study was to elucidate the effectiveness of adjuvant chemotherapy in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1b-c/N0–1/M0 ILC.

Methods

Based on Surveillance, Epidemiology, and End-Results (SEER) database, we identified original 12,334 HR-positive, HER2-negative, pT1b-c/N0–1/M0 ILC patients, who were then divided into adjuvant chemotherapy group and control group. End-points were overall survival (OS) and breast cancer-specific mortality (BCSM). Aiming to minimize the selection bias of baseline characteristics, Propensity Score Matching (PSM) method was used.

Results

In a total of 12,334 patients with HR-positive, HER2-negative, pT1b-c/N0–1/M0 ILC, 1785 patients (14.5%) were allocated into adjuvant chemotherapy group and 10,549 (85.5%) into control group. Used PSM, the 1785 patients in adjuvant chemotherapy group matched to the 1785 patients in control group. By Kaplan-Meier survival analyses, we observed no beneficial effect of adjuvant chemotherapy on OS in both original samples (P = 0.639) and matched samples (P = 0.962), however, ineffective or even contrary results of adjuvant chemotherapy on BCSM both in original samples (P = 0.001) and in matched samples (P = 0.002). In both original and matched multivariate Cox models, we observed ineffectiveness of adjuvant chemotherapy on OS (hazard ratio (HR) for overall survival = 0.82, 95% confidence interval (CI) [0.62–1.09]; P = 0.172 and HR = 0.90, 95%CI [0.65–1.26]; P = 0.553, respectively), unexpectedly promoting effect of adjuvant chemotherapy on BCSM (HR = 2.33, 95%CI [1.47–3.67]; P = 0.001 and HR = 2.41, 95%CI [1.32–4.39]; P = 0.004, respectively). Standard surgery was beneficial to the survival of patients. Lymph node metastasis was detrimental to survival and radiotherapy brought survival benefit in original samples, but two issues had unobvious effect in matched samples.

Conclusion

In this study, adjuvant chemotherapy did not improve survival for patients with HR-positive, HER2-negative pT1b-c/N0–1/M0 ILC.
Prevalence of gout and asymptomatic hyperuricemia in the pediatric population: a cross-sectional study of a Japanese health insurance database
Authors: Ito Shuichi , Torii Tomoko , Nakajima Akihiro , Iijima Takeshi , Murano Hiroshi , Horiuchi Hideki , Yamanaka Hisashi , Honda Masataka
Published: October 2020

Background

Although gout is rare in children, chronic sustained hyperuricemia can lead to monosodium urate deposits progressing to gout, just as in adults. This study assessed prevalence and characteristics of gout and asymptomatic hyperuricemia, and incidence of gouty arthritis in the pediatric population, using data from Japanese health insurance claims. The diagnosis and treatment of pediatric gout and hyperuricemia were analyzed, and specific characteristics of those patients were assessed. Since Japanese guidelines recommend treatment with uric acid lowering drugs for asymptomatic hyperuricemia as well as for gout, these data were also used to investigate the real-world use of uric acid lowering drugs in a pediatric population.

Methods

This cross-sectional study was based on a 2016–2017 Japanese health insurance claims database, one of the largest epidemiology claims databases available in Japan, which included 356,790 males and 339,487 females 0–18 years of age. Outcomes were measured for prevalence, patient characteristics, treatment with uric acid lowering drugs for gout and asymptomatic hyperuricemia, and prevalence and incidence of gouty arthritis. Because uric acid can be elevated by some forms of chemotherapy, data from patients under treatment for malignancies were excluded from consideration.

Results

Total prevalence of gout and asymptomatic hyperuricemia in 0–18 year-olds was 0.040% (276/696,277 patients), with gout prevalence at 0.007% (48/696,277) and asymptomatic hyperuricemia at 0.033% (228/696,277). Prevalence of gout and asymptomatic hyperuricemia was highest in adolescent males, at 0.135% (176/130,823). The most common comorbidities for gout and asymptomatic hyperuricemia were metabolic syndrome at 42.8% (118/276) and kidney disease at 34.8% (96/276). Of the patients diagnosed with gout or asymptomatic hyperuricemia, 35.1% (97/276) were treated with uric acid lowering drugs. Gouty arthritis developed in 43.8% (21/48) of gout patients during the study, at an incidence of 0.65 flares/person-year.

Conclusions

Even the pediatric population could be affected by asymptomatic hyperuricemia, gout, and gouty arthritis, and uric acid lowering drugs are being used in this population even though those drugs have not been approved for pediatric indications. Such off-label use may indicate a potential need for therapeutic agents in this population.

Trial registration

UMIN000036029.
Comprehensive pathogen detection in sera of Kawasaki disease patients by high-throughput sequencing: a retrospective exploratory study
Authors: Torii Yuka , Horiba Kazuhiro , Hayano Satoshi , Kato Taichi , Suzuki Takako , Kawada Jun-ichi , Takahashi Yoshiyuki , Kojima Seiji , Okuno Yusuke , Ogi Tomoo , Ito Yoshinori
Published: October 2020

Background

Kawasaki disease (KD) is an idiopathic systemic vasculitis that predominantly damages coronary arteries in children. Various pathogens have been investigated as triggers for KD, but no definitive causative pathogen has been determined. As KD is diagnosed by symptoms, several days are needed for diagnosis. Therefore, at the time of diagnosis of KD, the pathogen of the trigger may already be diminished. The aim of this study was to explore comprehensive pathogens in the sera at the acute stage of KD using high-throughput sequencing (HTS).

Methods

Sera of 12 patients at an extremely early stage of KD and 12 controls were investigated. DNA and RNA sequences were read separately using HTS. Sequence data were imported into the home-brew meta-genomic analysis pipeline, PATHDET, to identify the pathogen sequences.

Results

No RNA virus reads were detected in any KD case except for that of equine infectious anemia, which is known as a contaminant of commercial reverse transcriptase. Concerning DNA viruses, human herpesvirus 6B (HHV-6B, two cases) andAnelloviridae(eight cases) were detected among KD cases as well as controls. Multiple bacterial reads were obtained from KD and controls. Bacteria of the generaAcinetobacter,Pseudomonas,Delfita,Roseomonas, andRhodocyclaceaeappeared to be more common in KD sera than in the controls.

Conclusion

No single pathogen was identified in serum samples of patients at the acute phase of KD. With multiple bacteria detected in the serum samples, it is difficult to exclude the possibility of contamination; however, it is possible that these bacteria might stimulate the immune system and induce KD.
A day in the life of people with severe mental illness living in supported housing
Authors: Tjörnstrand Carina , Eklund Mona , Bejerholm Ulrika , Argentzell Elisabeth , Brunt David
Published: October 2020

Background

People with severe mental illness (SMI) living in supported housing (SH) struggle in everyday life and we currently lack a comprehensive body of knowledge concerning how the residents experience their day. This paper aimed to gain knowledge about how people with SMI describe a day in SH in Sweden, in particular the activities they most frequently engage in and how they experience what they do in or outside their home. Furthermore, it is important to gain knowledge of which activities motivate residents to leave the housing facility and to participate in the community. This new knowledge can help staff to encourage a recovery process among the residents.

Methods

One hundred thirty-three people living in SH completed a time-use diary and a mixed-methods approach was applied, including calculations of what activity that was most frequently performed and a manifest content analysis addressing experiences of activity.

Results

The residents had a low activity level and were often alone. Approximately one-half of the reported activities were performed in their own apartments, and generally unaccompanied. A quarter of the activities were performed in the common areas and a further quarter outside the SH. The most frequently performed activities were quiet and tranquil ones, e.g. listening to music and resting. Doing errands and group activities with staff and residents were the main activities that motivated leaving the facility. The participant experience of a day is presented in three categories: “Experiences of chosen and enforced togetherness and overcoming loneliness”, “Environmental change and emotional balance can generate activity”, and “Met and unmet needs for support, friendship and security”.

Conclusions

The residents were generally satisfied with their quiet and tranquil lifestyle and appeared to demand little of life, which may relate to previous experiences of institutional life and can constitute a challenge for staff. The findings highlight experiences that can help to improve SH. Services need to support individually adjusted contextual stimuli and individualize the support to help residents find a good balance and motivate them to be active in and outside SH, which can support a recovery process.
Disparities in emergency department use between Italians and migrants residing in Rome, Italy: the Rome Dynamic Longitudinal Study from 2005 to 2015
Authors: Trappolini Eleonora , Marino Claudia , Agabiti Nera , Giudici Cristina , Davoli Marina , Cacciani Laura
Published: October 2020

Background

The Emergency Department (ED) can be considered an indicator of accessibility and quality and can be influenced in period of economic downturns. In the last fifteen years, the number of migrants in Italy has doubled (from 2.4 million in 2005 to 5.2 in 2019, 4.1 and 8.7% of the total population, respectively). However, evidence about migrants’ healthcare use is poor, and no studies focused on the ED utilisation rate during the Great Recession are available. This study aims to analyse trends in all-cause and cause-specific ED utilisation among migrants and Italians residing in Rome, Italy, before and after 2008.

Methods

Longitudinal study based on data from the Municipal Register of Rome linked to the Emergency Department Register from 2005 to 2015. We analysed 2,184,467 individuals, aged 25–64 in each year. We applied a Hurdle model to estimate the propensity to use the ED and to model how often individuals accessed the ED.

Results

Migrants were less likely to be ED users than Italians, except for Africans (RR = 1.46, 95%CI 1.40–1.52) and Latin Americans (RR = 1.04, 95%CI 1.00–1.08) who had higher all-cause utilisation rates than non-migrants. Compared to the pre-2008 period, in the post-2008 we found an increase in the likelihood of being an ED user (OR = 1.34, 95%CI 1.34–1.35), and a decrease in ED utilisation rates (RR = 0.96, 95%CI 0.96–0.97) for the whole population, with differences among migrant subgroups, regardless of cause.

Conclusions

This study shows differences in the ED utilisation between migrants and Italians, and within the migrant population, during the Great Recession. The findings may reflect differentials in the health status, and barriers to access primary and secondary care among migrants. In this regard, health policies and cuts in health spending measures may have played a key role, and interventions to tackle health and access disparities should include policy measures addressing the underlying factors, adopting a Health in All Policies perspective. Further researches focusing on specific groups of migrants, and on the causes and diagnoses related to the ED utilisation, may help to explain the differences observed.
Associations between the number of children, age at childbirths and prevalence of chronic low back pain: the Nord-Trøndelag Health Study
Authors: Heuch Ingrid , Heuch Ivar , Hagen Knut , Storheim Kjersti , Zwart John-Anker
Published: October 2020

Background

Associations between childbirths and subsequent risk of low back pain (LBP) have not been clarified. Changes in sex hormone levels or lumbar posture during pregnancy may have an impact on LBP later in life. The purpose of this study was to explore associations between the number of childbirths, age at childbirths and prevalence of chronic LBP in a general population of women.

Methods

Data were obtained from the Norwegian community-based Nord-Trøndelag Health Study, HUNT2 (1995–1997). Women aged 20–69 years indicated whether they suffered from chronic LBP, defined as LBP persisting at least 3 months continuously during last year. Information about LBP was collected from 3936 women who had experienced no childbirths, 3143 women who had delivered one child only and 20,584 women who had delivered 2 or more children. Of these, 7339 women reported chronic LBP. The 595 women who were pregnant when information was collected were considered separately, regardless of previous births, with 80 women reporting chronic LBP. Associations with prevalence of chronic LBP were examined by generalised linear modelling with adjustment for potential confounders in a cross-sectional design.

Results

Women who had delivered one child only showed a higher prevalence of chronic LBP than women with no childbirths (prevalence ratio (PR) 1.11; 95% CI: 1.01–1.22). Among women with one or more childbirths, no overall change in prevalence could be demonstrated with an increasing number of children in analyses adjusted for age at first delivery. In women with at least two childbirths, an age less than 20 years at first childbirth was associated with an increased prevalence of chronic LBP (PR 1.36; 95% CI: 1.25–1.49; compared with age 25–29 years). No association was observed between age at last delivery and chronic LBP. The lowest prevalence of chronic LBP was found among women who were currently pregnant (PR 0.80; 95% CI: 0.63–1.00; compared with women with no childbirths).

Conclusions

Having experienced at least one childbirth seems to be associated with a higher prevalence of chronic LBP later in life. A young age at first childbirth is also associated with a long-lasting increased prevalence.
Social and environmental risk factors for the accidental drowning of children under five in China
Authors: Wang Meixian , Liu Yuxi , Kang Leni , He Chunhua , Miao Lei , Huang Jianwen , He Xiaoyan , Zhu Jun , Liang Juan , Li Qi , Wang Yanping , Liu Hanmin
Published: October 2020

Background

Accidental drowning of children under five is a serious problem in China. The present study analyzed data on environmental and sociodemographic factors and on primary caregivers of drowned children to understand factors that may contribute to this problem.

Methods

The present study collected information on 563 cases of drowning in children under five from October 1, 2015, to September 30, 2016, in 334 sampling districts in China. Primary caregivers were interviewed individually using the Drowning Mortality among Children under 5 Questionnaire.

Results

Most drowned children under 5 years old were boys, and 71.6% lived within 100 m of a body of water. The drownings primarily occurred in ponds, canals, rivers, and wells, and over 90% of these water bodies had no safety measures. There were 28.1% of primary caregivers who did not provide full-time care for the children, and 83.1% of them had no knowledge of first aid skills for drowning.

Conclusion

Encouraging kindergarten enrollment and providing safety education for children may reduce drowning in children under 5 years of age. Public water body protection measures should be strengthened to prevent children from drowning. Encouraging primary caregivers to care full-time for the children and learning first aid skills for drowning may also help reduce fatalities.
High-density surface electromyography maps after computer-aided training in individual with congenital transverse deficiency: a case study
Authors: Kisiel-Sajewicz Katarzyna , Marusiak Jarosław , Rojas-Martínez Mónica , Janecki Damian , Chomiak Sławomir , Kamiński Łukasz , Mencel Joanna , Mañanas Miguel Ángel , Jaskólski Artur , Jaskólska Anna
Published: October 2020

Background

The aim of this study was to determine whether computer-aided training (CAT) of motor tasks would increase muscle activity and change its spatial distribution in a patient with a bilateral upper-limb congenital transverse deficiency. We believe that our study makes a significant contribution to the literature because it demonstrates the usefulness of CAT in promoting the neuromuscular adaptation in people with congenital limb deficiencies and altered body image.

Case presentation

The patient with bilateral upper-limb congenital transverse deficiency and the healthy control subject performed 12 weeks of the CAT. The subject’s task was to imagine reaching and grasping a book with the hand. Subjects were provided a visual animation of that movement and sensory feedback to facilitate the mental engagement to accomplish the task. High-density electromyography (HD-EMG; 64-electrode) were collected from the trapezius muscle during a shrug isometric contraction before and after 4, 8, 12 weeks of the training. After training, we observed in our patient changes in the spatial distribution of the activation, and the increased average intensity of the EMG maps and maximal force.

Conclusions

These results, although from only one patient, suggest that mental training supported by computer-generated visual and sensory stimuli leads to beneficial changes in muscle strength and activity. The increased muscle activation and changed spatial distribution of the EMG activity after mental training may indicate the training-induced functional plasticity of the motor activation strategy within the trapezius muscle in individual with bilateral upper-limb congenital transverse deficiency. Marked changes in spatial distribution during the submaximal contraction in the patient after training could be associated with changes of the neural drive to the muscle, which corresponds with specific (unfamiliar for patient) motor task.

These findings are relevant to neuromuscular functional rehabilitation in patients with a bilateral upper-limb congenital transverse deficiency especially before and after upper limb transplantation and to development of the EMG based prostheses.
A mixed-method evaluation of a volunteer navigation intervention for older persons living with chronic illness (Nav-CARE): findings from a knowledge translation study
Authors: Pesut Barbara , Duggleby Wendy , Warner Grace , Bruce Paxton , Ghosh Sunita , Holroyd-Leduc Jayna , Nekolaichuk Cheryl , Parmar Jasneet
Published: October 2020

Background

Volunteer navigation is an innovative way to help older persons get connected to resources in their community that they may not know about or have difficulty accessing. Nav-CARE is an intervention in which volunteers, who are trained in navigation, provide services for older persons living at home with chronic illness to improve their quality of life. The goal of this study was to evaluate the impact of Nav-CARE on volunteers, older persons, and family participating across eight Canadian sites.

Methods

Nav-CARE was implemented using a knowledge translation approach in eight sites using a 12- or 18-month intervention period. A mixed method evaluation was used to understand the outcomes upon older person engagement; volunteer self-efficacy; and older person, family, and volunteer quality of life and satisfaction with the intervention.

Results

Older persons and family were highly satisfied with the intervention, citing benefits of social connection and support, help with negotiating the social aspects of healthcare, access to cost-effective resources, and family respite. They were less satisfied with the practical help available for transportation and errands. Older persons self-reported knowledge of the services available to them and confidence in making decisions about their healthcare showed statistically significant improvements (P < .05) over 12–18 months. Volunteers reported satisfaction with their role, particularly as it related to building relationships over time, and good self-efficacy. Volunteer attrition was a result of not recruiting older persons in a timely manner. There was no statistically significant improvement in quality of life for older persons, family or volunteers from baseline to study completion.

Conclusions

Findings from this study support a developing body of evidence showing the contributions volunteers make to enhanced older person and family well-being in the context of chronic illness. Statistically significant improvements were documented in aspects of client engagement. However, there were no statistically significant improvements in quality of life scores even though qualitative data illustrated very specific positive outcomes of the intervention. Similar findings in other volunteer-led intervention studies raise the question of whether there is a need for targeted volunteer-sensitive outcome measures.
Multiple use applicator for vaginal tablets/vaginal inserts: compliance verification and suitability studies
Authors: Brunner Heiko , Theodor Rudolf A.
Published: October 2020

Background

A newly developed multiple use applicator for vaginal tablets/vaginal inserts* was evaluated for its general suitability. There are no standard procedures described in guidelines or general accepted publications as to how this kind of product should be tested for suitability of purpose.

Methods

Due to the lack of existing standard procedures, three separate tests were designed and successful executed: (a) First, a patient acceptability evaluation was carried out as part of a phase III trial (registered in EudraCT on 9 Jan 2017, number 2017-000142-22 2. https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number%3A2017-000142-22). (b) Secondly, a cleaning procedure for the applicator after simulated multiple use was developed and verified in order to prove a minimized risk of microbiological contamination of the device. A newly developed vaginal fluid to simulate multiple applications was applied for this trial. (c) Lastly, a third trial evaluated the mechanical stability and proper functionality of the applicator after multiple simulated uses. Even potential abrasion of material of the device was checked.

Results

Acceptable patient compliance of the new multiple use applicator was verified after 2 weeks of daily use. Furthermore, diary data assessments of patients participating in the Pharmacodynamic part of the trial were evaluated as well. Overall, patient acceptability of the new applicator was proven.
The easy-to-use cleaning procedure for the applicator, which can even be carried out in a domestic environment, was developed and successfully verified for effectiveness, meeting all microbiological acceptance criteria for vaginal products of the European Pharmacopeia. The mechanical stability and proper functionality of the applicator after 50 simulated uses was also evaluated. All tested applicator batches (fresh and aged) passed the final evaluation, with no limitations in functionality.

Conclusion

The tests developed and executed consider various compliance aspects of the newly developed applicator. Results of these individual tests met the expectations and/or the predefined acceptance criteria. All included trials performed produced results justifying and qualifying the applicator for the intended multiple-use. The procedures outlined may also be a guide as to how this kind of medical device can be tested for suitability.

Trial registration Registered in EudraCT, number 2017-000142-22, start date 24 May 2017.
Glycosylation of anthocyanins enhances the apoptosis of colon cancer cells by handicapping energy metabolism
Authors: Jing Nan , Song Jiaxing , Liu Zheng , Wang Luoyang , Jiang Guoqiang
Published: October 2020

Background

While anthocyanins are proven to be effective in inhibiting tumour cell proliferation, the underlying mechanisms remain unclear. This research aims to explore the glycosylation of anthocyanins in the tumour inhibitory effects and the potential mechanism.

Methods

The tumour inhibitory effect on mouse colon cancer cells (MC38) was examined by MTT and flow cytometric analyses. The inhibitory pathway of anthocyanin was explored by assessment of tumour cell mitochondrial membrane potential (MMP), the caspase-3 and caspase-9 activity, as well as the cell energy metabolism in terms of the glucose uptake, the NAD+/NADH ratio and the ATP level.

Results

We found that 500 μM bilberry anthocyanins extract (BAE) induced 48.1% mitochondrial damage, activated the downstream caspase cascade to form apoptotic bodies (caspase-3 activity increased by 169%, caspase-9 activity increased by 186%), and inhibited cell proliferation (survival rate: 55.97%, 24 h). In contrast, the same concentration of anthocyanidin (cyanidin) led to marginal mitochondrial damage (only 9.85%) and resulted in little inhibition of MC38 cells (survival rate: 86.84%, 24 h). For cells incubated with 500 μM BAE, reactive oxygen species (ROS) decreased by 53.8%, but the ratio of NAD+/NADH increased to 3.67, demonstrating that the mitochondrial damage was induced by blocking energy metabolism. Furthermore, cell energy metabolism is related to glucose uptake since the presence of 200 μM GLUT1 inhibitor substantially enhanced the inhibitory effects of cyanidin-3-O-glucoside (Cy-3-Glu) at 500 μM (survival rate: 51.08%, 24 h).

Conclusions

The study suggested that the glycosides of anthocyanins might handicap glucose transport and inhibit energy metabolism, which, in turn, led to mitochondrial damage and apoptosis of tumour cells.
Development and preliminary evaluation of a communication skills training programme for hospital physicians by a specialized palliative care service: the ‘Teach to Talk’ programme
Authors: Tanzi S. , De Panfilis L. , Costantini M. , Artioli G. , Alquati S. , Di Leo S.
Published: October 2020

Background

There is widespread agreement about the importance of communication skills training (CST) for healthcare professionals caring for cancer patients. Communication can be effectively learned and improved through specific CST. Existing CSTs have some limitations with regard to transferring the learning to the workplace. The aim of the study is developing, piloting, and preliminarily assessing a CST programme for hospital physicians caring for advanced cancer patients to improve communication competences.

Methods

This is a Phase 0-I study that follows the Medical Research Council framework; this paper describes the following sections: a literature review on CST, the development of the Teach to Talk training programme (TtT), the development of a procedure for assessing the quality of the implementation process and assessing the feasibility of the implementation process, and the pilot programme. The study was performed at a 900-bed public hospital. The programme was implemented by the Specialized Palliative Care Service. The programme was proposed to 19 physicians from 2 departments.

Results

The different components of the training course were identified, and a set of quality indicators was developed. The TtT programme was implemented; all the physicians attended the lesson, videos, and role-playing sessions. Only 25% of the physicians participated in the bedside training. It was more challenging to involve Haematology physicians in the programme.

Conclusions

The programme was completed as established for one of the two departments in which it was piloted. Thus, in spite of the good feedback from the trainees, a re-piloting of a different training program will be developed, considering in particular the bed side component.

The program should be tailored on specific communication attitude and believes, probably different between different specialties.
Effect of a high value care curriculum on standardized patient exam in the Core Clerkship in Internal Medicine
Authors: Pahwa Amit K. , Eaton Kevin , Apfel Ariella , Bertram Amanda , Ridell Rebecca , Cayea Danelle
Published: October 2020

Background

With almost 20% unnecessary spending on healthcare, there has been increasing interest in high value care defined as the best care for the patient, with the optimal result for the circumstances, delivered at the right price. The American Association of Medical Colleges recommend that medical students are proficient in concepts of cost-effective clinical practice by graduation, thus leading to curricula on high value care. However little is published on the effectiveness of these curricula on medical students’ ability to practice high value care.

Methods

In addition to the standard curriculum, the intervention group received two classroom sessions and three virtual patients focused on the concepts of high value care. The primary outcome was number of tests and charges for tests on standardized patients.

Results

136 students enrolled in the Core Clerkship in Internal Medicine and 70 completed the high value care curriculum. There were no significant differences in ordering of appropriate tests (3.1 vs. 3.2 tests/students, p = 0.55) and inappropriate tests (1.8 vs. 2.2, p = 0.13) between the intervention and control. Students in the intervention group had significantly lower median Medicare charges ($287.59 vs. $500.86, p = 0.04) and felt their education in high value care was appropriate (81% vs. 56%, p = 0.02).

Conclusions

This is the first study to describe the impact of a high value care curriculum on medical students’ ordering practices. While number of inappropriate tests was not significantly different, students in the intervention group refrained from ordering expensive tests.
Pelvic organ prolapse and treatment decisions– developing an online preference-sensitive tool to support shared decisions
Authors: Hulbaek Mette , Knutz Eva , Ebbesen Niels Teglhus , Primdahl Jette , Nielsen Jesper Bo , Birkelund Regner
Published: October 2020

Background

Female patients with pelvic organ prolapse and clinicians need to take decisions regarding treatment that are often unpredictable in relation to how they impact the future everyday lives of the patients.

This study formed the developmental phase of a larger study to develop and test an online tool to support shared decision-making.

Methods

Patients, health care professionals and other stakeholders participated in the development and evaluation process of this tool. The collected data was generated from observational studies, exploratory interviews with prompt cards and workshops with end users from four Danish gynecology outpatient clinics.

Results

Content analysis led to important themes. For the patients three themes emerged: 1) how the impact of symptoms on everyday life affected the need for relief, 2) their bodily perception and sex life and 3) their worries about the future. For clinicians the different symptoms and their severity was a main theme.

Conclusions

This article provides an overall description and discussion of the development methodology. It demonstrates how user involvement informed the prototyping process and how patients’ preferences were included in the final prototype. Whether the tool actually increases SDM, remains to be tested in a pilot feasibility study.
Health care utilisation among older people with Down syndrome compared to specific medical guidelines for health surveillance: a Swedish national register study
Authors: Ahlström G. , Axmon A. , Sandberg M. , Flygare Wallén E.
Published: October 2020

Background

Specific medical guidelines for health surveillance exist for people with Down syndrome (DS) since 25 years but knowledge of adherence to the guidelines is lacking. The guidelines were developed to avoid unnecessary suffering from preventable conditions. The aims of the study were to investigate 1) planned health care visits in relation to the co-morbidities described in specific medical guidelines as a measure of adherence, 2) unplanned health care visits as a measure of potentially unmet health care needs and 3) gender differences in health care utilisation among older people with DS.

Methods

This register-based study includes people with DS (n = 472) from a Swedish national cohort of people with intellectual disability (n = 7936), aged 55 years or more, and with at least one support according to the disability law, in 2012. Data on inpatient and outpatient specialist health care utilisation were collected from the National Patient Register for 2002–2012.

Results

A total of 3854 inpatient and outpatient specialist health care visits were recorded during the 11 years, of which 54.6% (n = 2103) were planned, 44.0% (n = 1695) unplanned and 1.4% (n = 56) lacked information. More than half of the visits, 67.0% (n = 2582) were outpatient health care thus inpatient 33% (n = 1272). Most planned visits (29.4%, n = 618) were to an ophthalmology clinic, and most unplanned visits to an internal medicine clinic (36.6%, n = 621). The most common cause for planned visits was cataract, found at least once for 32.8% in this cohort, followed by arthrosis (8.9%), epilepsy (8.9%) and dementia (6.6%). Pneumonia, pain, fractures and epilepsy each accounted for at least one unplanned visit for approximately one-fourth of the population (27.1, 26.9, 26.3 and 19.7% respectively). Men and women had similar numbers of unplanned visits. However, women were more likely to have visits for epilepsy or fractures, and men more likely for pneumonia.

Conclusions

Increased awareness of existing specific medical guidelines for people with DS is vital for preventive measures. The relatively few planned health care visits according to the medical guidelines together with a high number of unplanned visits caused by conditions which potentially can be prevented suggest a need of improved adherence to medical guidelines.
‘There are no more secrets’: acceptability of a family-centered model of care for HIV positive children in Eswatini
Authors: Khumalo Philisiwe N. , Katirayi Leila , Ashburn Kim , Chouraya Caspian , Mpango Lydia , Mthethwa Nobuhle , Mofenson Lynne M.
Published: October 2020

Background

HIV-positive children have lagged adults on retention in HIV care and viral suppression. To address this gap, Eswatini’s Ministry of Health started a pilot family-centered HIV care model (FCCM) targeting HIV-positive children under 20 years old and their families.

Methods

We conducted semi-structured in-depth interviews with 25 caregivers and 17 healthcare workers (HCWs) to assess acceptability of FCCM in four pilot FCCM health facilities in Hhohho region of Eswatini. Thematic analysis with inductive and deductive codes was used to identify salient themes.

Results

Caregivers and HCWs reported FCCM benefits including strengthening the family bond, encouragement for family members to disclose their HIV status and supporting each other in taking antiretroviral drugs. Caregivers reported that they spent fewer days in clinic, experienced shorter waiting times, and received better counseling services in FCCM compared to the standard-of-care services. FCCM implementation challenges included difficulty for families to attend clinic visits together (e.g., due to scheduling conflicts with weekend Teen Support Club meetings and weekday FCCM appointments). Both HCWs and caregivers mentioned difficulty in sharing sensitive health information in the presence of other family members. HCWs also had challenges with supporting caregivers to disclose HIV status to children and managing the larger group during clinic visits.

Conclusions

FCCM for HIV-positive children was acceptable to both caregivers and HCWs, and they supported scaling-up FCCM implementation nationally. However, special considerations should be made to address the challenges experienced by participants in attending clinic visits together as a family in order to achieve the full benefits of FCCM for HIV positive children.
The mono-ADP-ribosyltransferase ARTD10 regulates the voltage-gated K+ channel Kv1.1 through protein kinase C delta
Authors: Tian Yuemin , Korn Patricia , Tripathi Priyanka , Komnig Daniel , Wiemuth Dominik , Nikouee Azadeh , Classen Arno , Bolm Carsten , Falkenburger Björn H. , Lüscher Bernhard , Gründer Stefan
Published: October 2020

Background

ADP-ribosylation is a ubiquitous post-translational modification that involves both mono- and poly-ADP-ribosylation. ARTD10, also known as PARP10, mediates mono-ADP-ribosylation (MARylation) of substrate proteins. A previous screen identified protein kinase C delta (PKCδ) as a potential ARTD10 substrate, among several other kinases. The voltage-gated K+ channel Kv1.1 constitutes one of the dominant Kv channels in neurons of the central nervous system and the inactivation properties of Kv1.1 are modulated by PKC. In this study, we addressed the role of ARTD10-PKCδ as a regulator of Kv1.1.

Results

We found that ARTD10 inhibited PKCδ, which increased Kv1.1 current amplitude and the proportion of the inactivating current component in HeLa cells, indicating that ARTD10 regulates Kv1.1 in living cells. An inhibitor of ARTD10, OUL35, significantly decreased peak amplitude together with the proportion of the inactivating current component of Kv1.1-containing channels in primary hippocampal neurons, demonstrating that the ARTD10-PKCδ signaling cascade regulates native Kv1.1. Moreover, we show that the pharmacological blockade of ARTD10 increases excitability of hippocampal neurons.

Conclusions

Our results, for the first time, suggest that MARylation by ARTD10 controls neuronal excitability.
Are the energy matrix values of the different feed additives in broiler chicken diets could be summed?
Authors: Metwally Abdallah E. , Abdel-Wareth Ahmed A. A. , Saleh Ahmed A. , Amer Shimaa A.
Published: October 2020

Background

The aim of this study is to investigate whether the energy matrix values of the nonstarch polysaccharide- (NSP-) degrading enzymes, bioemulsifier (LYSOFORTE®), guanidinoacetic acid (CreAMINO®), or their combinations could be summed. The effects of these additives on the growth performance, carcass traits, and economic value of the broiler chicken diets were evaluated. A total of 525-one-day-old Ross chicks with an initial body weight of 42.96 ± 0.87 g were haphazardly allocated into seven groups with five replicates. The seven experimental treatments are as follows: (1) basal diet with no additives (breeder recommendation), which is the control group, (2) basal diet minus 100 kcal/kg supplemented with 0.02% NSP-degrading enzymes (NSP), (3) basal diet minus 50 kcal/kg supplemented with 0.025% emulsifier (LYSOFORTE®), (4) basal diet minus 50 kcal/kg supplemented with 0.06% guanidinoacetic acid (CreAMINO®), (5) basal diet minus 150 kcal/kg supplemented with a mixture of NSP and LYSOFORTE®(NSPL), (6) basal diet minus 100 kcal/kg supplemented with a mixture of NSP and CreAMINO®(NSPC), and (7) basal diet minus 200 kcal/kg supplemented with a mixture of NSP, LYSO, and CreAMINO®(NSPLC). The experiment lasted for 35 days.

Results

It was found that the final body weight, body weight gain, and relative growth rate were significantly higher in birds fed diets supplemented with NSPL, NSPC, CreAMINO, and LYSO with the reduced energy matrix value. The overall feed conversion ratio was significantly improved due to the supplementation of NSPC, CreAMINO, NSPL, and LYSO with the reduced energy matrix value compared to the control group. Moreover, no significant effect on the carcass criteria was observed by the different treatments. As a result of the dietary supplementation with NSPL, NSPC, CreAMINO®, and LYSO with the reduced energy matrix value, the net profit, total return, economic efficiency, and performance index were increased and the cost of feed per kg of body weight gain was decreased.

Conclusion

The energy matrix value of NSPL, NSPC, CreAMINO®, and LYSOFORTE could be established in the diets of broiler chickens to improve the growth performance and economic efficiency.
Unmet need in severe, uncontrolled asthma: can anti-TSLP therapy with tezepelumab provide a valuable new treatment option?
Authors: Menzies-Gow Andrew , Wechsler Michael E. , Brightling Chris E.
Published: October 2020

Despite treatment with standard-of-care medications, including currently available biologic therapies, many patients with severe asthma have uncontrolled disease, which is associated with a high risk of hospitalization and high healthcare costs. Biologic therapies approved for severe asthma have indications limited to patients with either eosinophilic or allergic phenotypes; there are currently no approved biologics for patients with eosinophil-low asthma. Furthermore, existing biologic treatments decrease exacerbation rates by approximately 50% only, which may be because they target individual, downstream elements of the asthma inflammatory response, leaving other components untreated. Targeting an upstream mediator of the inflammatory response may have a broader effect on airway inflammation and provide more effective asthma control. One such potential target is thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine released in response to multiple triggers associated with asthma exacerbations, such as viruses, allergens, pollutants and other airborne irritants. Mechanistic studies indicate that TSLP drives eosinophilic (including allergic) inflammation, neutrophilic inflammation and structural changes to the airway in asthma through actions on a wide variety of adaptive and innate immune cells and structural cells. Tezepelumab is a first-in-class human monoclonal antibody that blocks the activity of TSLP. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced asthma exacerbations by up to 71% compared with placebo in patients with severe, uncontrolled asthma across the spectrum of inflammatory phenotypes, and improved lung function and asthma control. Phase 3 trials of tezepelumab are underway. NAVIGATOR (NCT03347279), a pivotal exacerbation study, aims to assess the potential efficacy of tezepelumab further in patients with a broad range of severe asthma phenotypes, including those with low blood eosinophil counts. SOURCE (NCT03406078) aims to evaluate the oral corticosteroid-sparing potential of tezepelumab. DESTINATION (NCT03706079) is a long-term extension study. In addition, an ongoing phase 2 bronchoscopy study, CASCADE (NCT03688074), aims to evaluate the effect of tezepelumab on airway inflammation and airway remodelling in patients across the spectrum of type 2 airway inflammation. Here, we summarize the unmet therapeutic need in severe asthma and the current treatment landscape, discuss the rationale for targeting TSLP in severe asthma therapy and describe the current development status of tezepelumab.