bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric provider perspectives and practices regarding health policy discussions with families: a mixed methods study
Authors: Vasan Aditi , Krass Polina , Seifu Leah , Hitt Talia A. , Ijaz Nadir , Villegas Leonela , Pallegedara Kathryn , Pandurangi Sindhu , Congdon Morgan , Rezet Beth , Kenyon Chén C.
Published: July 2020

Background

Advocacy regarding child health policy is a core tenet of pediatrics. Previous research has demonstrated that most pediatric providers believe collective advocacy and political involvement are essential aspects of their profession, but less is known about how pediatric providers engage with families about policy issues that impact child health. The objectives of this study were to examine providers’ perceptions and practices with regards to discussing health policy issues with families and to identify provider characteristics associated with having these discussions.

Methods

In this cross-sectional mixed methods study, pediatric resident physicians, attending physcians, and nurse practitioners at primary care clinics within a large academic health system were surveyed to assess (1) perceived importance of, (2) frequency of, and (3) barriers to and facilitators of health policy discussions with families. Multivariable ordinal regression was used to determine provider characteristics (including demographics, practice location, and extent of civic engagement) associated with frequency of these discussions. A subset of providers participated in subsequent focus groups designed to help interpret quantitative findings.

Results

The overall survey response rate was 155/394 (39%). The majority of respondents (76%) felt pediatricians should talk to families about health policy issues affecting children, but most providers (69%) reported never or rarely having these discussions. Factors associated with discussing policy issues included being an attending physician/nurse practitioner (OR 8.22, 95% CI 2.04–33.1) and urban practice setting (OR 3.85, 95% CI 1.03–14.3). Barriers included feeling uninformed about relevant issues and time constraints. In provider focus groups, four key themes emerged: (1) providers felt discussing policy issues would help inform and empower families; (2) providers frequently discussed social service programs, but rarely discussed policies governing these programs; (3) time constraints and concerns about partisan bias were a barrier to conversations; and (4) use of support staff and handouts with information about policy changes could help facilitate more frequent conversations.

Conclusions

Pediatric providers felt it was important to talk to families about child health policy issues, but few providers reported having such conversations in practice. Primary care practices should consider incorporating workflow changes that promote family engagement in relevant health policy discussions.
Neurodevelopmental outcome and respiratory management of congenital central hypoventilation syndrome: a retrospective study
Authors: Ogata Tomomi , Muramatsu Kazuhiro , Miyana Kaori , Ozawa Hiroshi , Iwasaki Motoki , Arakawa Hirokazu
Published: July 2020

Background

Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by sleep apnea. Anoxia often occurs soon after birth, and it is important to prevent anoxia-mediated central nervous system complications; however, data on the relationship between respiratory management and the prognosis for intellectual development of patients with CCHS is not well yet investigate.

Methods

We performed a retrospective chart review cohort study of patients with CCHS in Japan. We investigated the risk and prognostic factors for developmental outcomes and examined the disease in terms of its symptoms, diagnosis, complications, and treatment.

Results

Of the 123 patients with CCHS included in the survey, 88 patients were 6 years old and older. They were divided into two group based on their intelligence quotient. Those treated using positive-pressure ventilation via tracheostomy in the first three months of life had a better developmental prognosis than those managed via tracheostomy after three months of age and those treated by ventilation using mask (OR = 3.80; 95% CI: 1.00–14.37, OR = 4.65; 95% CI: 1.11–19.37). There was no significant difference in physical development (P = 0.64).

Conclusions

The best respiratory treatment for patients with CCHS is ventilation via tracheostomy, initiated ideally before the age of three months.
Distal locked versus unlocked intramedullary nailing for stable intertrochanteric fractures, a systematic review and meta-analysis
Authors: Li Yan-Hui , Yu Tiecheng , Shao Wenjing , Liu Yanwei , Zhu Dong , Tan Lei
Published: July 2020

Background

Intramedullary nails have become the main treatment for intertrochanteric fractures. However, a distal locking procedure during nailing gradually raised controversy. In this study, a systematic review and meta-analysis of clinical trials was performed to summarize existing evidence, aiming to determine the safety and efficacy of distal locking or unlocking in the nailing of stable intertrochanteric fractures.

Methods

Appropriate articles were identified using the most common public databases, such as PubMed, Embase, the Cochrane Library, and Google Scholar from the inception of each database to April 2019, without restriction of language, publication date, and considering ongoing trials. Eligible studies were represented by randomized controlled trials or retrospective cohort studies, comparing distal locking and unlocking for the treatment of acute stable intertrochanteric fractures in adult patients. Information regarding methodological quality, patient demographics, and clinical outcomes were extracted independently by two reviewers. Subsequently, patients were divided into a locking and unlocking group.

Results

This study included 9 articles, comprising a total of 1978 patients with a similar baseline. The results showed that the unlocking group had a shorter operation time, less intraoperative bleeding, lower transfusion rate, and less thigh pain after the treatment of femoral intertrochanteric fracture when compared with the distal locking group. No significant differences were observed in safety-related outcomes, including mortality, infection rate, cutting out, loss of reduction, backing out of lag screws, cephalic screw breakage, nail breakage, and peri-implant fractures between the two groups. In addition, efficacy-related outcomes including nonunion, delayed healing rates, and the Harris functional score were not significantly different between the two groups.

Conclusions

Our pooled analysis demonstrated that distal unlocking of stable intertrochanteric fractures can shorten the operation time, reduce intraoperative bleeding, and reduce the blood transfusion rate. The use of locked or unlocked intramedullary nailing does not affect long-term outcomes regarding complications and function.
Intravesical gemcitabine versus mitomycin for non-muscle invasive bladder cancer: a systematic review and meta-analysis of randomized controlled trial
Authors: Li Rongxin , Li Ye , Song Jun , Gao Ke , Chen Kangning , Yang Xiaogang , Ding Yongqiang , Ma Xinlong , Wang Yang , Li Weipeng , Wang Yanan , Wang Zhiping , Dong Zhilong
Published: July 2020

Background

Mitomycin (MMC) has been frequently used as the compound for intravesical treatment. The relatively new pyrimidine analog gemcitabine (GEM) has exhibited anticancer effect on various solid cancers, such as the advanced bladder cancer. In this study, the GEM and MMC in treating non-muscle invasive bladder cancer (NMIBC) cases was compared through systemic review.

Methods

In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the electronic databases, including Embase, PubMed, Chinese biomedicine literature database, the Cochrane Library, the National Institute for Health and Clinical Excellence, NHS Evidence, Chinese technological periodical full-text database, and Chinese periodical full-text database, were systemically reviewed from inception to October 2018. Then, the RevMan 5.0 software was applied for data analysis. Five randomized controlled trials (RCTs) involving a total of 335 patients were included.

Results

For MMC group, the recurrence rate in the mitomycin arm increased compared with that in GEM group (OR = 0.44 95% CI [0.24, 0.78]), and the difference was statistically significant between the two groups. GEM was associated with reduced incidence of chemical cystitis compared with that of MMC (OR = 0.23 95% CI [0.12, 0.44]). Differences in hematuria (OR = 0.46 95% CI [0.16, 1.31]), skin reaction (OR = 0.49 95% CI [0.14, 1.70]) and liver and kidney function damage (OR = 0.51 95% CI [0.09, 2.85]) displayed no statistical significance between the two groups.

Conclusion

Findings in our study demonstrate the superior efficacy of GEM over MMC in reducing the relapse rate among NMIBC patients following transurethral resection (TUR). In addition, GEM is associated with reduced local toxic effects on the bladder compared with those of MMC. However, more future studies are needed to examine GEM safety when used as the monotherapy or polytherapy for bladder patients. More RCTs with high quality are also required to validate our findings due to the limitations of the current meta-analysis.
A pilot evaluation of the Strengthening a Palliative Approach in Long-Term Care (SPA-LTC) program
Authors: Kaasalainen Sharon , Sussman Tamara , Thompson Genevieve , McCleary Lynn , Hunter Paulette V. , Venturato Lorraine , Wickson-Griffiths Abigail , Ploeg Jenny , Parker Deborah , Sinclair Shane , Dal Bello-Haas Vanina , Earl Marie , You John J. ,   the SPA-LTC team
Published: July 2020

Background

Despite increased annual mortality in long-term care (LTC) homes, research has shown that care of dying residents and their families is currently suboptimal in these settings. The purpose of this study was to evaluate resident and family outcomes associated with the Strengthening a Palliative Approach in LTC (SPA-LTC) program, developed to help encourage meaningful end of life discussions and planning.

Methods

The study employs a mixed method design in four LTC homes across Southern Ontario. Data were collected from residents and families of the LTC homes through chart reviews, interviews, and focus groups. Interviews with family who attended a Palliative Care Conference included both closed-ended and open-ended questions.

Results

In total, 39 residents/families agreed to participate in the study. Positive intervention outcomes included a reduction in the proportion of emergency department use at end of life and hospital deaths for those participating in SPA-LTC, improved support for families, and increased family involvement in the care of residents. For families who attended a Palliative Care Conference, both quantitative and qualitative findings revealed that families benefited from attending them. Residents stated that they appreciated learning about a palliative approach to care and being informed about their current status.

Conclusions

The benefits of SPA-LTC for residents and families justify its continued use within LTC. Study results also suggest that certain enhancements of the program could further promote future integration of best practices within a palliative approach to care within the LTC context. However, the generalizability of these results across LTC homes in different regions and countries is limited given the small sample size.
Perillyle alcohol and Quercetin ameliorate monocrotaline-induced pulmonary artery hypertension in rats through PARP1-mediated miR-204 down-regulation and its downstream pathway
Authors: Rajabi Soodeh , Najafipour Hamid , Jafarinejad Farsangi Saeideh , Joukar Siyavash , Beik Ahmad , Iranpour Maryam , Kordestani Zeinab
Published: July 2020

Background

Pulmonary artery hypertension (PAH) is a vascular disease in the lung characterized by elevated pulmonary arterial pressure (PAP). Many miRNAs play a role in the pathophysiology of PAH. Perillyle alcohol (PA) and Quercetin (QS) are plant derivatives with antioxidant and anti-proliferative properties. We investigated the effect of PA and QS on PAP, expression of PARP1, miR-204, and their targets, HIF1α and NFATc2, in experimental PAH.

Methods

Thirty rats were divided into control, MCT, MCT + Veh, MCT + PA and MCT + QS groups. MCT (60 mg/kg) was injected subcutaneously to induce PAH. PA (50 mg/kg daily) and QS (30 mg/kg daily) were administered for 3 weeks after inducing PAH. PAP, lung pathology, expression of miRNA and mRNA, and target proteins were evaluated through right ventricle cannulation, H&E staining, real-time qPCR, and western blotting, respectively.

Results

Inflammation and lung arteriole thickness in the MCT group increased compared to control group. PA and QS ameliorated inflammation and reduced arteriole thickness significantly. miR-204 expression decreased in PAH rats (p < 0.001). PA (p < 0.001) and QS (p < 0.01) significantly increased miR-204 expression. Expression of PARP1, HIF1α, NFATc2, and α-SMA mRNA increased significantly in MCT + veh rats (all p < 0.001), and these were reduced after treatment with PA and QS (both p < 0.01). PA and QS also decreased the expression of PARP1, HIF1α, and NFATc2 proteins that had increased in MCT + Veh group.

Conclusion

PA and QS improved PAH possibly by affecting the expression of PARP1 and miR-204 and their downstream targets, HIF1a and NFATc2. PA and QS may be therapeutic goals in the treatment of PAH.
Correction to: Sexual harassment against female nurses: a systematic review
Authors: Kahsay Woldegebriel Gebregziabher , Negarandeh Reza , Nayeri Nahid Dehghan , Hasanpour Marzieh
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Health systems efficiency in Eastern Mediterranean Region: a data envelopment analysis
Authors: Seddighi Hamed , Nosrati Nejad Farhad , Basakha Mehdi
Published: July 2020

Background

One of the most important issues in public policy and welfare state is health care. Poor management leads to the waste of resources, including money, human resources, facilities, and equipment.

Aims

This paper seeks to answer the question of which eastern Mediterranean countries are more effective in allocating their health resources, and does Iran, in relation to those countries, have an effective health system.

Methods

This study examined technical efficiency among eastern Mediterranean countries in 2018. Data were extracted from Global Health Observatory data World Health Organization. We applied input-oriented Data Envelopment Analysis (DEA) models to estimate efficiency scores. Inputs are Physicians density per 10,000 populations, Total hospital beds per 10,000 populations, Current expenditure on health, % of gross domestic product and outputs are infant survival rate and Life expectancy.

Results

The most efficient health systems in the eastern Mediterranean were Bahrain, Egypt, Iran, Lebanon, Morocco, Oman, Pakistan, Qatar, Tunisia and the United Arab Emirates. The inefficient countries are Iraq, Jordan, Kuwait, Libya, Palestine and Saudi Arabia.

Conclusions

Among the efficient countries, one category of high-entry countries such as Bahrain and Qatar with high input especially in health expenditure had higher output. The second group of countries with lower inputs such as Iran and Morocco has been able to produce similar output with other countries. Also, inefficiency in countries such as Saudi Arabia can be attributed to this with higher input such as health expenditure has lower output such life expectancy and infant survival rate.
Effects of interactive video-game–based exercise on balance in older adults with mild-to-moderate Parkinson’s disease
Authors: Yuan Rey-Yue , Chen Shih-Ching , Peng Chih-Wei , Lin Yen-Nung , Chang Yu-Tai , Lai Chien-Hung
Published: July 2020

Background

This study aimed to evaluate the effectiveness of a customized interactive video game-based (IVGB) training on balance in older adults with mild-to-moderate Parkinson’s disease (PD).

Methods

In this 12-week crossover trial, PD patients ≥65 years of age were randomly divided into Group A (a 6-week intervention phase followed by a 6-week control phase) and Group B (a 6-week control phase followed by a 6-week intervention phase). Participants received IVGB exercise training during the intervention phase and no exercise during the control phase. Functional outcomes were measured using behavioral evaluation scales and questionnaires at baseline, week 6 and week 12.

Results

Twenty-four PD patients were included in this study, and were evenly divided into two groups. After Bonferroni adjustment, the changes in Modified Falls Efficacy Scale (MFES) and two subscales of Multi-Directional Reach Test were significantly different between two groups in the first 6-week period. In addition, the changes in Berg Balance Scale, MFES, and two subscales of Maximum Step Length were significantly different between two groups in the second 6-week period. Compared to controls, 6-week IVGB exercise intervention significantly improved different but overlapping functional outcomes in two groups of PD patients.

Conclusions

The customized IVGB exercise training improves balance, postural stability and confidence in preventing falls in older adults with mild-to-moderate PD. However, this IVGB exercise doesn’t have a significant impact on quality of life.

Trial registration

ClinicalTrials.gov. NCT03689764. Registered 27 September 2018, retrospectively registered.
Prevalence of human papillomavirus genotypes and precancerous cervical lesions in a screening population in Beijing, China: analysis of results from China’s top 3 hospital, 2009–2019
Authors: Liu Yidi , Ang Qing , Wu Huan , Xu Jingjiang , Chen Defu , Zhao Hongyou , Liu Haolin , Guo Xianghuan , Gu Ying , Qiu Haixia
Published: July 2020

Background

Cervical cancer is the fourth most common cancer in women. Early detection and diagnosis play an important role in secondary prevention of cervical cancer. This study aims to provide more information to develop an effective strategy for the prevention and control of cervical cancer in northern China.

Methods

A retrospective single-centre descriptive cross-sectional study was conducted in Chinese PLA General Hospital located in Beijing, covering the period from January 2009 to June 2019. The patients who underwent a polymerase chain reaction (PCR)-based HPV genotyping test and cervical pathological diagnosis were included. Furthermore, we limited the interval between the two examination within 180 days for the purpose of making sure their correlation to analyse their relationship. Moreover, the relationship between different cervical lesions and age as well as single/multiple HPV infection was assessed.

Results

A total of 3134 patients were eligible in this study after HPV genotyping test and pathological diagnosis. Most of the patients (95%) were from northern China. Among the patients, 1745(55.68%) had high-grade squamous intraepithelial neoplasia (HSIL), 1354 (43.20%) had low-grade squamous intraepithelial neoplasia (LSIL) and 35 (1.12%) were Normal. The mean age was 42.06 ± 10.82(range, 17–79 years). The women aged 35–49 years accounted for the highest incidence rate. The top five most commonly identified HPV genotypes in each lesion class were as follows: HPV16, 58, 52, 31 and 51 in the class of HSIL; HPV16, 52, 58, 56 and 51 in the class of LSIL; HPV16, 31, 6,11, 52 and 58 in the class of normal. The frequencies of HPV single genotype infection and multiple genotypes infection were 55.26 and 34.18%, respectively. There was no difference in the attributable proportions of multiple genotypes infection amongst HSIL, LSIL and Normal.

Conclusions

In Northern China, HPV16 was the most dominant genotype in the patients with pathological examination. The peak age of the onset of HSIL was between 35 and 49 years of age. Infection with multiple HPV genotypes did not increase the risk of HSIL. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.
Voxel-level biological optimisation of prostate IMRT using patient-specific tumour location and clonogen density derived from mpMRI
Authors: Her E. J. , Haworth A. , Reynolds H. M. , Sun Y. , Kennedy A. , Panettieri V. , Bangert M. , Williams S. , Ebert M. A.
Published: July 2020

Aims

This study aimed to develop a framework for optimising prostate intensity-modulated radiotherapy (IMRT) based on patient-specific tumour biology, derived from multiparametric MRI (mpMRI). The framework included a probabilistic treatment planning technique in the effort to yield dose distributions with an improved expected treatment outcome compared with uniform-dose planning approaches.

Methods

IMRT plans were generated for five prostate cancer patients using two inverse planning methods: uniform-dose to the planning target volume and probabilistic biological optimisation for clinical target volume tumour control probability (TCP) maximisation. Patient-specific tumour location and clonogen density information were derived from mpMRI and geometric uncertainties were incorporated in the TCP calculation. Potential reduction in dose to sensitive structures was assessed by comparing dose metrics of uniform-dose plans with biologically-optimised plans of an equivalent level of expected tumour control.

Results

The planning study demonstrated biological optimisation has the potential to reduce expected normal tissue toxicity without sacrificing local control by shaping the dose distribution to the spatial distribution of tumour characteristics. On average, biologically-optimised plans achieved 38.6% (p-value: < 0.01) and 51.2% (p-value: < 0.01) reduction in expected rectum and bladder equivalent uniform dose, respectively, when compared with uniform-dose planning.

Conclusions

It was concluded that varying the dose distribution within the prostate to take account for each patient’s clonogen distribution was feasible. Lower doses to normal structures compared to uniform-dose plans was possible whilst providing robust plans against geometric uncertainties. Further validation in a larger cohort is warranted along with considerations for adaptive therapy and limiting urethral dose.
High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies
Authors: Yuan Shunling , Liu Zhaoping , Xu Zhenru , Liu Jing , Zhang Ji
Published: July 2020

High mobility group box 1 (HMGB1) is a nonhistone chromatin-associated protein that has been widely reported to play a pivotal role in the pathogenesis of hematopoietic malignancies. As a representative damage-associated molecular pattern (DAMP), HMGB1 normally exists inside cells but can be secreted into the extracellular environment through passive or active release. Extracellular HMGB1 binds with several different receptors and interactors to mediate the proliferation, differentiation, mobilization, and senescence of hematopoietic stem cells (HSCs). HMGB1 is also involved in the formation of the inflammatory bone marrow (BM) microenvironment by activating proinflammatory signaling pathways. Moreover, HMGB1-dependent autophagy induces chemotherapy resistance in leukemia and multiple myeloma. In this review, we systematically summarize the emerging roles of HMGB1 in carcinogenesis, progression, prognosis, and potential clinical applications in different hematopoietic malignancies. In summary, targeting the regulation of HMGB1 activity in HSCs and the BM microenvironment is highly beneficial in the diagnosis and treatment of various hematopoietic malignancies.
RETRACTED ARTICLE: M2 macrophage-derived extracellular vesicles promote gastric cancer progression via a microRNA-130b-3p/MLL3/GRHL2 signaling cascade
Authors: Zhang Yu , Meng Wenbo , Yue Ping , Li Xun
Published: July 2020

Background

Transfer of noncoding microRNAs (miRNAs) by extracellular vesicles (EVs) promotes the development of chemoresistance in many tumor types. Additionally, restoration or depletion of several miRNAs has been observed in multiple cancer types including gastric cancer (GC). In this present study, we aimed to investigate the mechanism of miR-130b-3p in M2 macrophage-derived EVs in the development of GC through regulation of mixed lineage leukemia 3 (MLL3) and grainyhead-like 2 (GRHL2).

Methods

Expression of miR-130b-3p and GRHL2 was quantified in 63 pairs of cancerous and noncancerous gastric tissues. The predicted binding between miR-130b-3p and MLL3, together with the enrichment of MLL3, H3K4me1, and H3K27ac in gene enhancer region, was verified by luciferase activity assay and chromatin immunoprecipitation. Effects of miR-130b-3p on GC cell proliferation, apoptosis, migration and invasion, as well as tube formation of human umbilical endothelial vein cells (HUEVCs) were further determined by gain- and loss-of function assays in vitro.

Results

miR-130b-3p was upregulated in GC tissues, and miR-130b-3p promoted survival, metastasis and angiogenesis of GC cells as well as enhanced tumor formation and angiogenesis in GC in vivo. Additionally, miR-130b-3p delivered in M2 macrophage-derived EVs promoted survival, migration, invasion, and angiogenesis of GC cells. Notably, MLL3 inhibited GC cell proliferation, migration, invasion, and vessel-like tube formation of HUEVCs by increasing GRHL2. Furthermore, downregulation of miR-130b-3p in M2 macrophage-derived EVs or upregulation of GRHL2 inhibited tumor formation and angiogenesis in GC.

Conclusion

This study highlights that EVs loaded with the specific miRNA cargo miR-130b-3p mediate communication between M2 macrophages and cancer cells in the tumor microenvironment through the modulation of MLL3 and GRHL2 in GC.
Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19
Authors: Ni Wentao , Yang Xiuwen , Yang Deqing , Bao Jing , Li Ran , Xiao Yongjiu , Hou Chang , Wang Haibin , Liu Jie , Yang Donghong , Xu Yu , Cao Zhaolong , Gao Zhancheng
Published: July 2020

An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1–7), and the ACE2/angiotensin-(1–7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1–7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1–7)/MAS may help attenuate organ injuries.

Graphical abstract

SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.
Preventive efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of Heartgard® Plus or Interceptor® Plus against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs
Authors: Kryda Kristina , Holzmer Susan , Everett William R. , McCall John W. , Mahabir Sean P. , McTier Tom L. , Maeder Steven J.
Published: July 2020

Background

Recent reports indicated that increasing the monthly oral dosage and the number of consecutive monthly doses of moxidectin improved the efficacy against macrocyclic lactone (ML)-resistant Dirofilaria immitis. The two laboratory studies reported here evaluated the efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis strains.

Methods

Dogs were inoculated 30 days prior to first treatment with 50 third-stage (L3) larvae of a ML-resistant strain of D. immitis, ZoeLA or JYD-34. In each study, dogs (six per group) were randomized to treatment with six monthly doses of placebo, four or six monthly doses of 24 µg/kg moxidectin, or six monthly doses of Heartgard® Plus or Interceptor® Plus at their label dose rates. Efficacy was evaluated by adult heartworm counts approximately nine months after L3 inoculation.

Results

All negative-control dogs were infected with adult heartworms (geometric mean, 35.6; range, 24–41) for ZoeLA and (geometric mean, 32.9; range, 30–37) for JYD-34. Efficacies against ZoeLA for moxidectin, Heartgard® Plus and Interceptor® Plus were ≥ 96.1%, 18.7% and 21.2%, respectively. Adult counts for both moxidectin-treated groups were significantly lower than negative control (P < 0.0001), significantly lower than Heartgard® Plus and Interceptor® Plus (P < 0.0001), but not significantly different from each other (P = 0.5876). Counts for Heartgard® Plus and Interceptor® Plus were not significantly different than negative control (P ≥ 0.2471). Efficacies against JYD-34 were ≥ 95.9%, 63.9% and 54.6% for moxidectin, Heartgard® Plus and Interceptor® Plus, respectively. Counts for all groups were significantly lower than negative control (P ≤ 0.0001). Counts for six monthly doses of moxidectin were significantly lower than those for four monthly doses (P = 0.0470), and the counts for both moxidectin-treated groups were significantly lower than Heartgard® Plus and Interceptor® Plus (P ≤ 0.0002).

Conclusions

Moxidectin administered orally at 24 µg/kg to dogs for four or six consecutive months was ≥ 95.9% effective in preventing the development of two ML-resistant heartworm strains and resulted in significantly fewer adult D. immitis than in dogs treated with Heartgard® Plus or Interceptor® Plus when administered for six consecutive months at their approved label dosages in two laboratory efficacy studies.
Highly accurate skin-specific methylome analysis algorithm as a platform to screen and validate therapeutics for healthy aging
Authors: Boroni Mariana , Zonari Alessandra , Reis de Oliveira Carolina , Alkatib Kallie , Ochoa Cruz Edgar Andres , Brace Lear E. , Lott de Carvalho Juliana
Published: July 2020

Background

DNA methylation (DNAm) age constitutes a powerful tool to assess the molecular age and overall health status of biological samples. Recently, it has been shown that tissue-specific DNAm age predictors may present superior performance compared to the pan- or multi-tissue counterparts. The skin is the largest organ in the body and bears important roles, such as body temperature control, barrier function, and protection from external insults. As a consequence of the constant and intimate interaction between the skin and the environment, current DNAm estimators, routinely trained using internal tissues which are influenced by other stimuli, are mostly inadequate to accurately predict skin DNAm age.

Results

In the present study, we developed a highly accurate skin-specific DNAm age predictor, using DNAm data obtained from 508 human skin samples. Based on the analysis of 2,266 CpG sites, we accurately calculated the DNAm age of cultured skin cells and human skin biopsies. Age estimation was sensitive to the biological age of the donor, cell passage, skin disease status, as well as treatment with senotherapeutic drugs.

Conclusions

This highly accurate skin-specific DNAm age predictor constitutes a holistic tool that will be of great use in the analysis of human skin health status/molecular aging, as well as in the analysis of the potential of established and novel compounds to alter DNAm age.
Quantification of the CM-Dil-labeled human umbilical cord mesenchymal stem cells migrated to the dual injured uterus in SD rat
Authors: Zheng Jia-Hua , Zhang Jing-Kun , Kong De-Sheng , Song Yan-Biao , Zhao Shuang-Dan , Qi Wen-Bo , Li Ya-Nan , Zhang Ming-le , Huang Xiang-Hua
Published: July 2020

Background

Human umbilical cord mesenchymal stem cell (hUC-MSC) therapy is considered as a promising approach in the treatment of intrauterine adhesions (IUAs). Considerable researches have already detected hUC-MSCs by diverse methods. This paper aims at exploring the quantitative distribution of CM-Dil-labeled hUC-MSCs in different regions of the uterus tissue of the dual injury-induced IUAs in rats and the underlying mechanism of restoration of fertility after implantation of hUC-MSCs in the IUA model.

Methods

In this study, we investigated the quantification of the CM-Dil-labeled hUC-MSCs migrated to the dual injured uterus in Sprague Dawley rats. Additionally, we investigated the differentiation of CM-Dil-labeled hUC-MSCs. The differentiation potential of epithelial cells, vascular endothelial cells, and estrogen receptor (ER) cells were assessed by an immunofluorescence method using CK7, CD31, and ERα. The therapeutic impact of hUC-MSCs in the IUA model was assessed by hematoxylin and eosin, Masson, immunohistochemistry staining, and reproductive function test. Finally, the expression of TGF-β1/Smad3 pathway in uterine tissues was determined by qRT-PCR and Western blotting.

Results

The CM-Dil-labeled cells in the stroma region were significantly higher than those in the superficial myometrium (SM) (71.67 ± 7.98 vs. 60.92 ± 3.96, p = 0.005), in the seroma (71.67 ± 7.98 vs. 23.67 ± 8.08, p = 0.000) and in the epithelium (71.67 ± 7.98 vs. 4.17 ± 1.19, p = 0.000). From the 2nd week of treatment, hUC-MSCs began to differentiate into epithelial cells, vascular endothelial cells, and ER cells. The therapeutic group treated with hUC-MSCs exhibited a significant decrease in fibrosis (TGF-β1/Smad3) as well as a significant increase in vascularization (CD31) compared with the untreated rats.

Conclusion

Our findings suggested that the distribution of the migrated hUC-MSCs in different regions of the uterine tissue was unequal. Most cells were in the stroma and less were in the epithelium of endometrium and gland. Injected hUC-MSCs had a capacity to differentiate into epithelial cells, vascular endothelial cells, and ER cells; increase blood supply; inhibit fibration; and then restore the fertility of the IUA model.
Radiobiological and dosimetric assessment of DNA-intercalated 99mTc-complexes bearing acridine orange derivatives
Authors: Belchior Ana , Di Maria Salvatore , Fernandes Célia , Vaz Pedro , Paulo António , Raposinho Paula
Published: July 2020

Background

Recently, a new family of 99mTc(I)-tricarbonyl complexes bearing an acridine orange (AO) DNA targeting unit and different linkers between the Auger emitter (99mTc) and the AO moiety was evaluated for Auger therapy. Among them, 99mTc-C3 places the corresponding radionuclide at a shortest distance to DNA and produces important double strand breaks (DSB) yields in plasmid DNA providing the first evidence that 99mTc can efficiently induce DNA damage when well positioned to the double helix. Here in, we have extended the studies to human prostate cancer PC3 cells using the 99mTc-C3 and 99mTc-C5 complexes, aiming to assess how the distance to DNA influences the radiation-induced biological effects in this tumoral cell line, namely, in which concerns early and late damage effects.

Results

Our results highlight the limited biological effectiveness of Auger electrons, as short path length radiation, with increasing distances to DNA. The evaluation of the radiation-induced biological effects was complemented with a comparative microdosimetric study based on intracellular dose values. The comparative study, between MIRD and Monte Carlo (MC) methods used to assess the cellular doses, revealed that efforts should be made in order to standardize the bioeffects modeling for DNA-incorporated Auger electron emitters.

Conclusions

99mTc might not be the ideal radionuclide for Auger therapy but can be useful to validate the design of new classes of Auger-electron emitting radioconjugates. In this context, our results highlight the crucial importance of the distance of Auger electron emitters to the target DNA and encourage the development of strategies for the fine tuning of the distance to DNA for other medical radionuclides (e.g., 111In or 161Tb) in order to enhance their radiotherapeutic effects within the Auger therapy of cancer.
FDG PET versus CT radiomics to predict outcome in malignant pleural mesothelioma patients
Authors: Pavic M. , Bogowicz M. , Kraft J. , Vuong D. , Mayinger M. , Kroeze S. G. C. , Friess M. , Frauenfelder T. , Andratschke N. , Huellner M. , Weder W. , Guckenberger M. , Tanadini-Lang S. , Opitz I.
Published: July 2020

Background

Careful selection of malignant pleural mesothelioma (MPM) patients for curative treatment is of highest importance, as the multimodal treatment regimen is challenging for patients and harbors a high risk of substantial toxicity. Radiomics—a quantitative method for image analysis—has shown its prognostic ability in different tumor entities and could therefore play an important role in optimizing patient selection for radical cancer treatment. So far, radiomics as a prognostic tool in MPM was not investigated.

Materials and methods

This study is based on 72 MPM patients treated with surgery in a curative intent at our institution between 2009 and 2017. Pre-treatment Fluorine-18 fluorodeoxyglucose (FDG) PET and CT scans were used for radiomics outcome modeling. After extraction of 1404 CT and 1410 FDG PET features from each image, a preselection by principal component analysis was performed to include only robust, non-redundant features for the cox regression to predict the progression-free survival (PFS) and the overall survival (OS). Results were validated on a separate cohort. Additionally, SUVmax and SUVmean, and volume were tested for their prognostic ability for PFS and OS.

Results

For the PFS a concordance index (c-index) of 0.67 (95% CI 0.52–0.82) and 0.66 (95% CI 0.57–0.78) for the training cohort (n = 36) and internal validation cohort (n = 36), respectively, were obtained for the PET radiomics model. The PFS advantage of the low-risk group translated also into an OS advantage. On CT images, no radiomics model could be trained. SUV max and SUV mean were also not prognostic in terms of PFS and OS.

Conclusion

We were able to build a successful FDG PET radiomics model for the prediction of PFS in MPM. Radiomics could serve as a tool to aid clinical decision support systems for treatment of MPM in future.
Recommendations for the surveillance of multidrug-resistant bacteria in Italian long-term care facilities by the GLISTer working group of the Italian Association of Clinical Microbiologists (AMCLI)
Authors: Aschbacher Richard , Pagani Leonardo , Migliavacca Roberta , Pagani Laura ,   the GLISTer (Gruppo di Lavoro per lo Studio delle Infezioni nelle Residenze Sanitarie Assistite e Strutture Assimilabili) working group, Confalonieri Massimo , Farina Claudio , Fazii Paolo , Luzzaro Francesco , Rigoli Roberto , Spalla Melissa
Published: July 2020

Long-term care facilities (LTCFs) are an important reservoir of multidrug-resistant organisms (MDROs). Colonization of LTCF residents by MDROs is generally higher in Italy compared to other European countries. The present review by the working group for the study of infections in LTCFs (GLISTer) of the Italian Association of Clinical Microbiologists (AMCLI) aims to propose criteria for a laboratory-based surveillance of MDROs in Italian LTCFs.

We recommend the adhesion to three levels of laboratory-based MDROs surveillance in LTCFs: i) mandatory MDRO surveillance by cumulative retrospective analysis of antimicrobial susceptibility data, obtained as part of routine care of clinical specimens. ii) strongly recommended surveillance by active rectal swab cultures or molecular screening to determine colonization with carbapenemase-producing Enterobacterales, should a resident be proven infected. iii) voluntary surveillance by prospective MDRO surveys, mainly based on point prevalence colonization studies, allowing to determine the MDROs baseline prevalence in the facility.

Laboratory-based surveillance of MDROs in LTCFs is aimed at providing useful epidemiological information to healthcare providers operating in the facility, but it is only effective if the collected data are used for infection prevention and control purposes, targeting the peculiar aspects of LTCFs.
Science-society dialogue from the start: Participatory research agenda-setting by Science Cafés
Authors: Balázs Bálint , Horváth Janka , Pataki György
Published: July 2020

This empirical paper presents a case of a participatory agenda-setting exercise for green care services in Hungary. Science Cafés were utilised as a participatory agenda-setting tool within the framework of the InSPIRES H2020 project. The objectives were to collect perceptions of research needs from key actors in the green care field in Hungary, to generate collaborative research projects on green care services and to initiate social dialogue around green care in Hungary. The main research question was as follows: how can we co-create a research agenda on green care by eliciting responses from concerned citizens and experts in a very open and democratic setting? While a growing body of evidence supports the need for, and benefits of, green care services, there is not much research in Hungary addressing diverse knowledge needs of the multiple social actors in the green care field. Science Café as developed for institutionalising an informal and lively dialogue between science and society proved to be a useful tool to co-generate a research agenda for such a relatively neglected but socially highly beneficial theme as green care.
Training or Synergizing? Complex Systems Principles Change the Understanding of Sport Processes
Authors: Pol Rafel , Balagué Natàlia , Ric Angel , Torrents Carlota , Kiely John , Hristovski Robert
Published: July 2020

There is a need to update scientific assumptions in sport to promote the critical thinking of scientists, coaches, and practitioners and improve their methodological decisions. On the basis of complex systems science and theories of biological evolution, a systematization and update of theoretical and methodological principles to transform the understanding of sports training is provided. The classical focus on learning/acquiring skills and fitness is replaced by the aim of increasing the diversity/unpredictability potential of teams/athletes through the development of synergies. This development is underpinned by the properties of hierarchical organization and circular causality of constraints, that is, the nestedness of constraints acting at different levels and timescales. These properties, that integrate bottom-up and top-down all dimensions and levels of performance (from social to genetic), apply to all types of sport, ages, or levels of expertise and can be transferred to other fields (e.g., education, health, management). The team as the main training unit of intervention, the dynamic concept of task representativeness, and the co-adaptive and synergic role of the agents are some few practical consequences of moving from training to synergizing.
Efficacy of different load intensity and time-under-tension calf loading protocols for Achilles tendinopathy (the LOADIT trial): protocol for a randomised pilot study
Authors: Hasani Fatmah , Haines Terry P. , Munteanu Shannon E. , Vicenzino Bill , Malliaras Peter
Published: July 2020

Background

Modifying variables in exercise prescription can produce specific effects on Achilles tendinopathy outcomes. This study aims to determine the feasibility of conducting an adequately powered randomised trial in the future to assess the efficacy of different load intensity and time-under-tension exercise parameters for improving pain and function in individuals with persistent midportion Achilles tendinopathy.

Methods

The trial is designed as prospective, four-armed feasibility and randomised pilot trial with 3 months follow-up. Interventions will be provided in a gym setting. The investigator, who will be blind to the allocation of participants, will conduct all pre- and post-intervention assessments. Forty-eight male participants with Achilles tendinopathy will be recruited from the community. We will use a 2 × 2 factorial design with factors of load intensity (six or eighteen repetitions maximum) and time-under-tension (two or six second repetitions). Participants will be randomised into one of the testing groups: six RM with two second repetitions, six RM with six second repetitions, eighteen RM with two second repetitions or eighteen RM with six second repetitions. Trial feasibility will be indicated by the rate of conversion, recruitment and retention, adherence to the interventions by participants, the utility of videoconferencing mode for weekly exercise supervision, incidence of adverse events, and feasibility of future economic evaluation. The secondary clinical outcomes will assess pain and disability, participant impression of change, satisfaction, health-related quality of life, physical activity, work absenteeism, psychological measures at baseline, 6 and 12 weeks, and plantarflexor contractile dysfunction (torque, rate of force development and muscle force steadiness) at baseline and 12 weeks. These clinical outcomes are primarily measured to provide information regarding potential treatment effects and trends.

Discussion

The proposed study and follow-up powered randomised trial will be a first step towards determining exercise dose parameters that may optimise outcomes for Achilles tendinopathy. We have chosen to focus on load intensity and time-under-tension, as these parameters are important for tendon adaptation. This work has the potential to lead to more effective exercise loading interventions for Achilles tendinopathy.

Trial registration

Australian New Zealand Clinical Trials Registry, ACTRN12618001315202. Registered retrospectively on August 6th, 2018.