bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity, diabetes and the risk of colorectal adenoma and cancer
Authors: Soltani Ghodratollah , Poursheikhani Arash , Yassi Maryam , Hayatbakhsh Abdorasool , Kerachian Matin , Kerachian Mohammad Amin
Published: October 2019

Background

Colorectal cancer (CRC) is the fourth most commonly diagnosed gastrointestinal (GI) malignancy and the third leading cause of cancer-related death worldwide. In the current case-control study, an association between diagnosis of CRC, obesity and diabetes was investigated.

Methods

Demographic characteristics, colonoscopy reports, history of drug, smoking, and medical history were collected from patients referred to a colonoscopy unit. The location, size and number of the polyps were recorded during the colonoscopy. Statistically, t-test was conducted for mean comparison for the groups. Pearson’s chi-squared test (χ2) was applied to categorize variables. Five classification methods based on the important clinicopathological characteristics such as age, BMI, diabetes, family history of colon cancer was performed to predict the results of colonoscopy.

Results

Overall, 693 patients participated in this study. In the present study, 115 and 515 patients were evaluated for adenoma/adenocarcinoma and normal colonoscopy, respectively. The mean age of patients positive for adenoma or adenocarcinoma were significantly higher than the negative groups (p value < 0.001). Incidence of overweight and/or obesity (BMI > 25 kg/m2) were significantly higher in adenoma positive patients as compared to controls (49.9 and 0.9% respectively, p value = 0.04). The results also demonstrated a significant association between suffering from diabetes and having colon adenoma (OR = 1.831, 95%CI = 1.058–3.169, p value = 0.023). The experimental results of 5 classification methods on higher risk factors between colon adenoma and normal colonoscopy data were more than 82% and less than 0.42 for the percentage of classification accuracy and root mean squared error, respectively.

Conclusions

In the current study, the occurrence of obesity measured based on BMI and diabetes in the adenoma positive patient group was significantly higher than the control group although there was no notable association between obesity, diabetes and adenocarcinoma.
A pilot study of the in vitro antimicrobial activity and in vivo residual activity of chlorhexidine and acetic acid/boric acid impregnated cleansing wipes
Authors: Rafferty Rebecca , Robinson Victoria H. , Harris Jennifer , Argyle Sally A. , Nuttall Tim J.
Published: October 2019

Background

Topical antimicrobials are recommended for first line treatment of surface and superficial infections in dogs. This is especially important given the increasing prevalence of antimicrobial resistant infections. Antimicrobial wipes have become popular, but there are a lack of controlled studies assessing their in vitro antimicrobial and in vivo residual activity. We aimed to assess the antimicrobial efficacy of two commercial antimicrobial wipes against frequently isolated pathogens.

Ten clinical and one reference isolate each of meticillin-susceptibleStaphylococcus pseudintermedius(MSSP), meticillin-resistantS. pseudintermedius(MRSP),Escherichia coli(EC), extended spectrum beta-lactamase (ESBL) producingE. coli(ESBL-EC),Pseudomonas aeruginosa(PA) andMalassezia pachydermatis(MP) were tested using a modified Kirby-Bauer technique. Each isolate was tested against 6 mm discs of chlorhexidine (CHX) and acetic acid/boric acid (AABA) wipes, and positive and negative controls either overnight (bacteria) or for 3 days (Malassezia).

Healthy dogs were treated with the wipes and distilled water on a randomised flank (n = 5 each). Hair samples (1 cm; 0.1 g) taken at days 0, 1 and 3 were inoculated with an isolate of each organism. Zones of inhibition (ZI) were measured.

Results

All isolates produced confluent growth with AABA and control wipes, except for the cleansing wipes and MP (median ZI 12 mm; 95% CI 8.2–15.8). The median (95% CI) CHX wipe ZIs (mm) were: MP 48.0 (47.0–49.0), MSSP 15.6 (14.2–17.0), MRSP 14.0 (13.6–14.4), EC 13.6 (12.0–15.2) and ESBL-EC 10.0 (9.4–10.6). PA showed confluent growth. The differences between the bacterial isolates was significant (Kruskal-Wallisp < 0.0001; post-tests MSSP = MRSP = EC > EBSL-EC > PA). Confluent growth was visible with all the hair samples.

Conclusion

CHX but not AABA showed in vitro efficacy against MSSP, MRSP, EC and MP. ESBL-EC were less susceptible and there was no activity against PA. There was no residual activity on hair. Additional studies are required to determine efficacy of these products in clinically affected patients.
Haemostatic, fibrinolytic and inflammatory profiles in West Highland white terriers with canine idiopathic pulmonary fibrosis and controls
Authors: Roels Elodie , Bauer Natali , Lecut Christelle , Moritz Andreas , Gothot André , Clercx Cécile
Published: October 2019

Background

Canine idiopathic pulmonary fibrosis (CIPF) is a progressive interstitial lung disease mainly affecting old West Highland white terriers (WHWTs). The aetiology of CIPF is currently unknown and pathogenesis poorly understood. A genetic basis is strongly suspected based on the breed predisposition. CIPF shares clinical and pathological features with human IPF. In human IPF, coagulation disorders favouring a local and systemic pro-thrombotic state have been demonstrated in association with disease severity and outcome. The aim of this study was to compare the systemic haemostatic, fibrinolytic and inflammatory profiles of WHWTs affected with CIPF with breed-matched controls (CTRLs). Additionally, data collected in both groups were interpreted with regard to the reference intervals (when available) to assess possible pro-thrombotic features of the WHWT breed that may be related to CIPF predisposition. A total of 14 WHWTs affected with CIPF and 20 CTRLs were included.

Results

WHWTs affected with CIPF had prolonged activated partial thromboplastine time in comparison with CTRLs (12.2 ± 0.9 s vs. 11.5 ± 0.7 s, P = 0.028), whereas results obtained in both groups were all within reference ranges. There was no significant difference between groups for the other factors assessed including plasmatic concentrations of fibrinogen, D-dimers concentration, antithrombin III activity, protein S and protein C activities, anti-factor Xa activity, activated protein C ratio, serum C-reactive protein concentration, and rotational thromboelastometry indices. Platelet count and plasmatic fibrinogen concentration were found to be above the upper limit of the reference range in almost half of the WHWTs included, independently of the disease status.

Conclusions

Results of this study provide no clear evidence of an altered systemic haemostatic, fibrinolytic or inflammatory state in WHWTs affected with CIPF compared with CTRLs. The higher platelet counts and fibrinogen concentrations found in the WHWT breed may serve as predisposing factors for CIPF or simply reflect biological variation in this breed.
Gene expression profiling in blood from cerebral malaria patients and mild malaria patients living in Senegal
Authors: Thiam Alassane , Sanka Michel , Ndiaye Diallo Rokhaya , Torres Magali , Mbengue Babacar , Nunez Nicolas Fernandez , Thiam Fatou , Diop Gora , Victorero Geneviève , Nguyen Catherine , Dieye Alioune , Rihet Pascal
Published: October 2019

Background

Plasmodium falciparum malaria remains a major health problem in Africa. The mechanisms of pathogenesis are not fully understood. Transcriptomic studies may provide new insights into molecular pathways involved in the severe form of the disease.

Methods

Blood transcriptional levels were assessed in patients with cerebral malaria, non-cerebral malaria, or mild malaria by using microarray technology to look for gene expression profiles associated with clinical status. Multi-way ANOVA was used to extract differentially expressed genes. Network and pathways analyses were used to detect enrichment for biological pathways.

Results

We identified a set of 443 genes that were differentially expressed in the three patient groups after applying a false discovery rate of 10%. Since the cerebral patients displayed a particular transcriptional pattern, we focused our analysis on the differences between cerebral malaria patients and mild malaria patients. We further found 842 differentially expressed genes after applying a false discovery rate of 10%. Unsupervised hierarchical clustering of cerebral malaria-informative genes led to clustering of the cerebral malaria patients. The support vector machine method allowed us to correctly classify five out of six cerebral malaria patients and six of six mild malaria patients. Furthermore, the products of the differentially expressed genes were mapped onto a human protein-protein network. This led to the identification of the proteins with the highest number of interactions, including GSK3B, RELA, and APP. The enrichment analysis of the gene functional annotation indicates that genes involved in immune signalling pathways play a role in the occurrence of cerebral malaria. These include BCR-, TCR-, TLR-, cytokine-, FcεRI-, and FCGR- signalling pathways and natural killer cell cytotoxicity pathways, which are involved in the activation of immune cells. In addition, our results revealed an enrichment of genes involved in Alzheimer’s disease.

Conclusions

In the present study, we examine a set of genes whose expression differed in cerebral malaria patients and mild malaria patients. Moreover, our results provide new insights into the potential effect of the dysregulation of gene expression in immune pathways. Host genetic variation may partly explain such alteration of gene expression. Further studies are required to investigate this in African populations.
Enhanced uptake, high selective and microtubule disrupting activity of carbohydrate fused pyrano-pyranones derived from natural coumarins attributes to its anti-malarial potential
Authors: Gupta Sonal , Khan Juveria , Kumari Priti , Narayana Chintam , Ayana R. , Chakrabarti Malabika , Sagar Ram , Singh Shailja
Published: October 2019

Background

Malaria is one of the deadliest infectious diseases caused by protozoan parasite ofPlasmodiumspp. Increasing resistance to anti-malarials has become global threat in control of the disease and demands for novel anti-malarial interventions. Naturally-occurring coumarins, which belong to a class of benzo-α-pyrones, found in higher plants and some essential oils, exhibit therapeutic potential against various diseases. However, their limited uptake and non-specificity has restricted their wide spread use as potential drug candidates.

Methods

Two series of carbohydrate fused pyrano[3,2-c]pyranone carbohybrids which were synthesized by combination of 2-C-formyl galactal and 2-C-formyl glucal, with various freshly prepared 4-hydroxycoumarins were screened againstPlasmodium falciparum. The anti-malarial activity of these carbohybrids was determined by growth inhibition assay onP. falciparum3D7 strain using SYBR green based fluorescence assay. Haemolytic activity of carbohybrid12, which showed maximal anti-malarial activity, was determined by haemocompatibility assay. The uptake of the carbohybrid12by parasitized erythrocytes was determined using confocal microscopy. Growth progression assays were performed to determine the stage specific effect of carbohybrid12treatment on Pf3D7. In silico studies were conducted to explore the mechanism of action of carbohybrid12on parasite microtubule dynamics. These findings were further validated by immunofluorescence assay and drug combination assay.

Results

2-C-formyl galactal fused pyrano[3,2-c]pyranone carbohybrid12exhibited maximum growth inhibitory potential againstPlasmodiumwith IC50value of 5.861 µM and no toxicity on HepG2 cells as well as no haemolysis of erythrocytes. An enhanced uptake of this carbohybrid compound was observed by parasitized erythrocytes as compared to uninfected erythrocytes. Further study revealed that carbohybrid12arrests the growth of parasite at trophozoite and schizonts stage during course of progression through asexual blood stages. Mechanistically, it was shown that the carbohybrid12binds to α,β-heterodimer of tubulin and affects microtubule dynamics.

Conclusion

These findings show carbohydrate group fusion to 4-hydroxycoumarin precursor resulted in pyrano-pyranones derivatives with better solubility, enhanced uptake and improved selectivity. This data confirms that, carbohydrate fused pyrano[3,2-c]pyranones carbohybrids are effective candidates for anti-malarial interventions againstP. falciparum.
Reduced expression of PD-L1 in autoimmune thyroiditis attenuate trophoblast invasion through ERK/MMP pathway
Authors: Chen Mengya , Gilbert Nduwimana , Liu Haixia
Published: October 2019

Background

Autoimmune thyroiditis (AIT) with euthyroid is associated with miscarriage. But the exact mechanism remains unclear. Studies have shown that the programmed cell death-1 (PD-1)/programmed cell death -ligand 1 (PD-L1) pathway is essential for normal pregnancy. However, the expression of PD-L1 in gestational trophoblasts in mice with autoimmune thyroiditis and the mechanisms leading to miscarriage have not been fully investigated.

Methods

Immunofluorescence and Western blot were used to detect the expression of PD-L1, p-ERK, MMP-2 and MMP-9 in embryonic trophoblast cells of pregnant mice with AIT. The expression of PD-L1 in HTR-8/SVneo cells were silenced, and the expression of PD-L1, MMP-2, MMP-9, ERK and p-ERK1/2 was detected by Western blot analyses and immunofluorescence assays. Invasive assays were performed in PD-L1 silenced HTR-8/SVneo cells using a Transwell chamber.

Results

Compared with normal pregnancy, the expression of PD-L1, ERK, p-ERK, MMP-2 and MMP-9 in embryonic trophoblast cells was significantly lower in pregnant mice with AIT. Compared with the negative control (NC) group (cells transfected with negative control siRNA), phosphorylation of MMP-2, MMP-9 and P-ERK1/2 proteins was significantly reduced in HTR-8/SVneo cells transfected with PD-L1 siRNA, and the number of cells penetrating the membrane was reduced.

Conclusion

AIT inhibits ERK/MMP-2 and MMP-9 pathways through PD-L1 reduction, attenuates embryonic trophoblast invasion and ultimalely induces miscarriage ultimately.
A systematic review and meta-analysis of the overall effects of school-based obesity prevention interventions and effect differences by intervention components
Authors: Liu Zheng , Xu Han-Meng , Wen Li-Ming , Peng Yuan-Zhou , Lin Li-Zi , Zhou Shuang , Li Wen-Hao , Wang Hai-Jun
Published: October 2019

Background

Childhood obesity is a serious public health concern. School-based interventions hold great promise to combat the rising trend of childhood obesity. This systematic review aimed to assess the overall effects of school-based obesity prevention interventions, and to investigate characteristics of intervention components that are potentially effective for preventing childhood obesity.

Methods

We systematically searched MEDLINE, CENTRAL and Embase databases to identify randomized- or cluster randomized- controlled trials of school-based obesity interventions published between 1990 and 2019. We conducted meta-analyses and subgroup analyses to determine the overall effects of obesity prevention programs and effect differences by various characteristics of intervention components on body mass index (BMI) or BMI Z-score of children.

Results

This systematic review included a total of 50 trials (reported by 56 publications). Significant differences were found between groups on BMI (− 0.14 kg/m2 (95% confidence interval: − 0.21, − 0.06)) and BMI Z-score (− 0.05 (− 0.10, − 0.01)) for single-component interventions; significant differences were also found between groups on BMI (− 0.32 (− 0.54, − 0.09) kg/m2) and BMI Z-score (− 0.07 (− 0.14, − 0.001)) for multi-component interventions. Subgroup analyses consistently demonstrated that effects of single-component (physical activity) interventions including curricular sessions (− 0.30 (− 0.51, − 0.10) kg/m2 in BMI) were stronger than those without curricular sessions (− 0.04 (− 0.17, 0.09) kg/m2 in BMI); effects of single-component (physical activity) interventions were also strengthened if physical activity sessions emphasized participants’ enjoyment (− 0.19 (− 0.33, − 0.05) kg/m2 in BMI for those emphasizing participants’ enjoyment; − 0.004 (− 0.10, 0.09) kg/m2 in BMI for those not emphasizing participants’ enjoyment). The current body of evidence did not find specific characteristics of intervention components that were consistently associated with improved efficacy for multi-component interventions (P > 0.05).

Conclusions

School-based interventions are generally effective in reducing excessive weight gain of children. Our findings contribute to increased understandings of potentially effective intervention characteristics for single-component (physical activity) interventions. The impact of combined components on effectiveness of multi-component interventions should be the topic of further research. More high-quality studies are also needed to confirm findings of this review.
Cyclooxygenase-2 (COX-2) inhibitors: future therapeutic strategies for epilepsy management
Authors: Rawat Chitra , Kukal Samiksha , Dahiya Ujjwal Ranjan , Kukreti Ritushree
Published: October 2019

Epilepsy, a common multifactorial neurological disease, affects about 69 million people worldwide constituting nearly 1% of the world population. Despite decades of extensive research on understanding its underlying mechanism and developing the pharmacological treatment, very little is known about the biological alterations leading to epileptogenesis. Due to this gap, the currently available antiepileptic drug therapy is symptomatic in nature and is ineffective in 30% of the cases. Mounting evidences revealed the pathophysiological role of neuroinflammation in epilepsy which has shifted the focus of epilepsy researchers towards the development of neuroinflammation-targeted therapeutics for epilepsy management. Markedly increased expression of key inflammatory mediators in the brain and blood-brain barrier may affect neuronal function and excitability and thus may increase seizure susceptibility in preclinical and clinical settings. Cyclooxygenase-2 (COX-2), an enzyme synthesizing the proinflammatory mediators, prostaglandins, has widely been reported to be induced during seizures and is considered to be a potential neurotherapeutic target for epilepsy management. However, the efficacy of such therapy involving COX-2 inhibition depends on various factors viz., therapeutic dose, time of administration, treatment duration, and selectivity of COX-2 inhibitors. This article reviews the preclinical and clinical evidences supporting the role of COX-2 in seizure-associated neuroinflammation in epilepsy and the potential clinical use of COX-2 inhibitors as a future strategy for epilepsy treatment.
Factors influencing decision-making power regarding reproductive health and rights among married women in Mettu rural district, south-west, Ethiopia
Authors: Tadele Afework , Tesfay Amanuel , Kebede Alemi
Published: October 2019

Background

Women’s decision-making power regarding reproductive health and rights (RHR) was the central component to achieve reproductive well-being. Literatures agree that a women having higher domestic decision-making power regarding their health care were more likely to utilize health services. More than 80% of women in Ethiopia reside in rural areas where they considered as the subordinates of their husbands. This would restrict women to fully exercise their RHR. Thus, this study aims to determine the factors influencing the women’s decision-making power regarding RHR in Mettu rural district, South West Ethiopia.

Methods

A community based cross-sectional study was done among 415 by using randomly selected married women of reproductive age from March to April 2017. Data was entered by using Epi-data manger 1.4 and analyzed by SPSS version 21. Descriptive and multivariate logistic regression analysis was carried out.

Result

One hundred sixty-eight (41.5%) of the women had greater decision-making power regarding RHR. Woman’s primary education AOR 2.62[95% C. I 1.15, 5.97], secondary (9+) education AOR 3.18[95% C. I 1.16, 8.73] and husband’s primary education AOR 4.0[95% C. I 1.53, 10.42], secondary (9+) education AOR 3.95 [95% C. I 1.38, 11.26], being knowledgeable about RHR AOR 3.57 [95% C. I 1.58, 8.09], marriage duration of more than 10 years AOR 2.95 [95% C. I 1.19, 7.26], access to micro-credit enterprises AOR 4.26[95% C. I 2.06, 8.80], having gender equitable attitude AOR 6.38 [95% C. I 2.52, 12.45] and good qualities of spousal relation AOR 2.95 [95% C. I 1.30, 6.64] were positively influencing women’s decision-making power regarding RHR.

Conclusion

More than four in ten rural women had greater decision-making power regarding RHR. External pressures (qualities of spousal relation, gender equitable attitude) and knowledge about RHR were found to influence women’s decision-making power. Public health interventions targeting women’s RHR should take into account strengthening rural micro-credit enterprises, qualities of spousal relations and priority should be given to women with no formal education of husband or herself and marriage duration of < 5 years.
Safer-by-design flame-sprayed silicon dioxide nanoparticles: the role of silanol content on ROS generation, surface activity and cytotoxicity
Authors: Rubio Laura , Pyrgiotakis Georgios , Beltran-Huarac Juan , Zhang Yipei , Gaurav Joshi , Deloid Glen , Spyrogianni Anastasia , Sarosiek Kristopher A. , Bello Dhimiter , Demokritou Philip
Published: October 2019

Background

Amorphous silica nanoparticles (SiO2 NPs) have been regarded as relatively benign nanomaterials, however, this widely held opinion has been questioned in recent years by several reports on in vitro and in vivo toxicity. Surface chemistry, more specifically the surface silanol content, has been identified as an important toxicity modulator for SiO2 NPs. Here, quantitative relationships between the silanol content on SiO2 NPs, free radical generation and toxicity have been identified, with the purpose of synthesizing safer-by-design fumed silica nanoparticles.

Results

Consistent and statistically significant trends were seen between the total silanol content, cell membrane damage, and cell viability, but not with intracellular reactive oxygen species (ROS), in the macrophages RAW264.7. SiO2 NPs with lower total silanol content exhibited larger adverse cellular effects. The SAEC epithelial cell line did not show any sign of toxicity by any of the nanoparticles. Free radical generation and surface reactivity of these nanoparticles were also influenced by the temperature of combustion and total silanol content.

Conclusion

Surface silanol content plays an important role in cellular toxicity and surface reactivity, although it might not be the sole factor influencing fumed silica NP toxicity. It was demonstrated that synthesis conditions for SiO2 NPs influence the type and quantity of free radicals, oxidative stress, nanoparticle interaction with the biological milieu they come in contact with, and determine the specific mechanisms of toxicity. We demonstrate here that it is possible to produce much less toxic fumed silicas by modulating the synthesis conditions.
Hearing loss after radiosurgery-blame it on Cochlear dose or the radiation tool!
Authors: Deora Harsh , Tripathi Manjul
Published: October 2019

While sudden hearing loss after stereotactic radiosurgery has been demonstrated in some cases a recent article by Linge et al. and have demonstrated the need for further discussion on this topic. We attempt to delineate the fact that the type of dosing regimen or technology used will not affect the hearing or radio-graphical control outcomes and thus should not be a consideration while administering treatment. Also we discuss the role of location of the lesion and vascularity and potential new therapies for this unexpected outcome after radiosurgery.
Connecting the dots between different networks: miRNAs associated with bladder cancer risk and progression
Authors: Braicu Cornelia , Buiga Rares , Cojocneanu Roxana , Buse Mihail , Raduly Lajos , Pop Laura Ancuta , Chira Sergiu , Budisan Liviuta , Jurj Ancuta , Ciocan Cristina , Magdo Lorand , Irimie Alexandru , Dobrota Florentin , Petrut Bogdan , Berindan-Neagoe Ioana
Published: October 2019

Background

Bladder cancer (BC) is a common urothelial malignancy, characterized by a high recurrence rate. The biology of bladder cancer is complex and needs to be deciphered. The latest evidence reveals the critical role of the non-coding RNAs, particularly microRNAs (miRNAs), as vital regulatory elements in cancer.

Method

We performed a miRNAs microarray using paired tissues (tumor and adjacent normal bladder tissue), followed by the validation with qRT-PCR of five selected transcripts. Additional next-generation sequencing investigation established the interconnection among the altered miRNAs and mutated genes. Based on the overlapping between TCGA data and data obtained in the study, we focused on the systematic identification of altered miRNAs and genes mutated involved in bladder cancer tumorigenesis and progression.

Results

By overlapping the miRNAs expression data, the two patient cohorts, we identified 18 miRNAs downregulated and, 187 miRNAs upregulated. qRT-PCR validation was completed using a selected panel of two downregulated (miR-139-5p and miR-143-5p) and three up-regulated miRNAs (miR-141b, miR-200 s or miR-205). Altered miRNAs patterns are interrelated to bladder tumorigenesis, allowing them to be used for the development of novel diagnostic and prognostic biomarkers. Three EMT-related upregulated miRNAs have an essential role in the molecular mechanisms, specifically key processes underlying tumorigenesis, invasion and metastasis. Using the Ampliseq Cancer Panel kit and Ion Torrent PGM Next-Generation Sequencing an increased mutation rate for TP53, FGFR3, KDR, PIK3CA and ATM were observed, but the mutational status for only TP53 was correlated to the survival rate. The miRNAs pattern, along with the gene mutation pattern attained, can assist for better patient diagnosis.

Conclusion

This study thereby incorporates miRNAs as critical players in bladder cancer prognosis, where their altered gene expression profiles have a critical biological function in relationship with tumor molecular phenotype. The miRNA-mRNA regulatory networks identified in BC are ripe for exploitation as biomarkers or targeted therapeutic strategies.
European survey on national training activities in clinical research
Authors: Magnin A. , Iversen V. Cabral , Calvo G. , Čečetková B. , Dale O. , Demlova R. , Blasko Gy. , Keane F. , Kovacs G. L. , Levy-Marchal C. , Monteiro E. C. , Palmisano L. , Pella D. , Portolés Pérez A. , Rascol O. , Schmid C. , Tay F. , von der Leyen H. , Ohmann C.
Published: October 2019

Background

Investigator-initiated clinical studies (IITs) are crucial to generate reliable evidence that answers questions of day-to-day clinical practice. Many challenges make IITs a complex endeavour, for example, IITs often need to be multinational in order to recruit a sufficient number of patients. Recent studies highlighted that well-trained study personnel are a major factor to conduct such complex IITs successfully. As of today, however, no overview of the European training activities, requirements and career options for clinical study personnel exists.

Methods

To fill this knowledge gap, a survey was performed in all 11 member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardised questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the landscape of academic training opportunities, to facilitate the exchange of expertise and experience among countries and to identify new fields of action.

Results

The survey found that training for Good Clinical Practice (GCP) and investigator training is offered in all but one country. A specific training for study nurses or study coordinators is also either provided or planned in ten out of eleven countries. A majority of countries train in monitoring and clinical pharmacovigilance and offer specific training for principal investigators but only few countries also train operators of clinical research organisations (CRO) or provide training for methodology and quality management systems (QMS). Minimal requirements for study-specific functions cover GCP in ten countries. Only three countries issued no requirements or recommendations regarding the continuous training of study personnel. Yet, only four countries developed a national strategy for training in clinical research and the career options for clinical researchers are still limited in the majority of countries.

Conclusions

There is a substantial and impressive investment in training and education of clinical research in the individual ECRIN countries. But so far, a systematic approach for (top-down) strategic and overarching considerations and cross-network exchange is missing. Exchange of available curricula and sets of core competencies between countries could be a starting point for improving the situation.
Identifying important barriers to recruitment of patients in randomised clinical studies using a questionnaire for study personnel
Authors: Isaksson Eva , Wester Per , Laska Ann Charlotte , Näsman Per , Lundström Erik
Published: October 2019

Background

Many randomised controlled trials (RCT) fail to meet their recruitment goals. Study personnel play a key role in recruitment. The aim of this study was to identify successful strategies that study personnel consider to be important in patient recruitment to RCT.

Methods

We constructed a questionnaire based on the literature, discussions with colleagues and our own experience as trialists. The survey was named “What is Important for Making a Study Successful questionnaire” (WIMSS-q). Our target group was the study personnel in the ongoing EFFECTS study. The questionnaire was sent out electronically to all physicians and nurses (n = 148). Success factors and barriers were divided according to patient, centre and study level, respectively.

Results

Responses were received from 94% of the study personnel (139/148). The five most important factors at centre level for enhancing recruitment were that the research question was important (97%), a simple procedure for providing information and gaining consent (92%), a highly engaged local principal investigator and research nurse (both 87%), and that study-related follow-ups are practically feasible and possible to coordinate with the clinical follow-up (87%). The most significant barrier at the local centre was lack of time and resources devoted to research (72%). Important patient-related barriers were fear of side effects (35%) and language problems (30%).

Conclusions

For recruitment in an RCT to be successful, the research question must be relevant, and the protocol must be simple and easy to implement in the daily routine.

Trial registration

The protocol for this study was registered at the Northern Ireland Hub for trials methodology research (SWAT ID 64). The EFFECTS study has EudraCT number 2011–006130-16 and was registered 17 February 2016 at ClinicalTrials.gov number NCT02683213.
Two new species of Acanthocotyle Monticelli, 1888 (Monogenea: Acanthocotylidae), parasites of two deep-sea skates (Elasmobranchii: Rajiformes) in the South-East Pacific
Authors: Ñacari Luis A. , Sepúlveda Fabiola A. , Escribano Ruben , Oliva Marcelo E.
Published: October 2019

Background

Parasites of deep-sea fishes from the South-East Pacific (SPO) are poorly known. Of c.1030 species of fish found in this area, 100–150 inhabit the deep-sea (deeper than 200 m). Only six articles concerning metazoan parasites of fish from deep-waters of SOP are known, and nine monogenean species have been reported. Currently, ten species are known in Acanthocotyle Monticelli, 1888 (Monogenea) and when stated, all of them are found in shallow waters (10–100 m). Acanthocotyle gurgesiella Ñacari, Sepulveda, Escribano & Oliva, 2018 is the only known species parasitizing deep-sea skates (350–450 m) in the SPO. The aim of this study was the description of two new species of Acanthocotyle from two Rajiformes.

Methods

In September 2017, we examined specimens of two species of deep-sea skates (Rajiformes), Amblyraja frerichsi (Krefft) and Bathyraja peruana McEachran & Myyake, caught at c.1500 m depth off Tocopilla, northern Chile, as a by-catch of the Patagonian tooth fish Dissostichus eleginoides Smitt fishery. Specimens of Acanthocotyle were collected from the skin of the skates. Morphometric (including multivariate analysis of proportional measurements, standardized by total length), morphological and molecular analyses (LSU rRNA and cox1 genes) were performed in order to identify the collected specimens.

Results

The three approaches used in this study strongly suggest the presence of two new species in the genus Acanthocotyle: Acanthocotyle imo n. sp. and Acanthocotyle atacamensis n. sp. parasitizing the skin of the thickbody skate Amblyraja frerichsi and the Peruvian skate Bathyraja peruana, respectively. The main morphological differences from the closely related species Acanthocotyle verrilli Goto, 1899 include the number of radial rows of sclerites, the non-discrete vitelline follicles and the number of testes.

Conclusions

The two species of monogeneans described here are the only recorded parasites from their respective host species in the SPO. Assessing host specificity for members of Acanthocotyle requires clarifying the systematics of Rajiformes.
Prevalence and genotyping identification of Cryptosporidium in adult ruminants in central Iran
Authors: Firoozi Zohre , Sazmand Alireza , Zahedi Alireza , Astani Akram , Fattahi-Bafghi Ali , Kiani-Salmi Narges , Ebrahimi Behnam , Dehghani-Tafti Arefeh , Ryan Una , Akrami-Mohajeri Fateme
Published: October 2019

Background

Apicomplexan parasites of the genus Cryptosporidium infect a wide range of animal species as well as humans. Cryptosporidium spp. can cause life threatening diarrhea especially in young animals, children, immunocompromised patients and malnourished individuals. Asymptomatic cryptosporidial infections in animals can also occur, making these animals potential reservoirs of infection.

Methods

In the present study, a molecular survey of Cryptosporidium spp. in ruminants that were slaughtered for human consumption in Yazd Province, located in central Iran was conducted. Faeces were collected per-rectum from 484 animals including 192 cattle, 192 sheep and 100 goats. DNA was extracted from all samples and screened for Cryptosporidium by PCR amplification of the 18S rRNA gene. Positives were Sanger sequenced and further subtyped by sequence analysis of the 60 kDa glycoprotein (gp60) locus.

Results

In total, Cryptosporidium spp. were detected in 22 animals: C. andersoni and C. bovis in seven and two cattle faecal samples, respectively, C. ubiquitum in five sheep, and C. xiaoi in six sheep and two goat samples, respectively. To our knowledge, this study provides for the first time, molecular information concerning Cryptosporidium species infecting goats in Iran, and is also the first report of C. ubiquitum and C. xiaoi from ruminants in Iran.

Conclusion

The presence of potentially zoonotic species of Cryptosporidium in ruminants in this region may suggest that livestock could potentially contribute to human cryptosporidiosis, in particular among farmers and slaughterhouse workers, in the area. Further molecular studies on local human populations are required to more accurately understand the epidemiology and transmission dynamics of Cryptosporidium spp. in this region.
Efficacy of sarolaner (Simparica®) against induced infestations of Haemaphysalis longicornis on dogs
Authors: Oda Kenji , Yonetake Wakako , Fujii Takeshi , Hodge Andrew , Six Robert H. , Maeder Steven , Rugg Douglas
Published: October 2019

Background

Haemaphysalis longicornis is the major tick affecting dogs in most of the East Asia/Pacific region and has recently been detected in a number of areas of the USA. This tick is a vector for a number of pathogens of dogs, other mammals and humans. In this study, the efficacy of a single oral administration of sarolaner (Simparica®, Zoetis) at the minimum label dosage (2 mg/kg) was evaluated against an existing infestation of H. longicornis and subsequent weekly reinfestations for 5 weeks after treatment.

Methods

Sixteen dogs were ranked on pretreatment tick counts and randomly allocated to treatment on Day 0 with sarolaner at 2 mg/kg or a placebo. The dogs were infested with H. longicornis nymphs on Days − 2, 5, 12, 19, 26 and 33. Efficacy was determined at 48 hours after treatment and subsequent re-infestations based on live tick counts relative to placebo-treated dogs.

Results

There were no adverse reactions to treatment. A single dose of sarolaner provided 100% efficacy on Days 2, 7, 14 and 21; and ≥ 97.4% efficacy on Days 28 and 35. Considering only attached, live ticks, efficacy was 100% for the entire 35 days of the study. Geometric mean live tick counts for sarolaner were significantly lower than those for placebo on all days (11.62 ≤ t(df) ≤ 59.99, where 13.0 ≤ df ≤ 14.1, P < 0.0001).

Conclusions

In this study, a single oral administration of sarolaner at 2 mg/kg provided 100% efficacy against an existing infestation of H. longicornis nymphs and ≥ 97.4% efficacy (100% against attached ticks) against weekly reinfestation for at least 35 days after treatment.
Patterns of genetic divergence among populations of Aedes aegypti L. (Diptera: Culicidae) in the southeastern USA
Authors: Hopperstad Kristen A. , Reiskind Michael H. , Labadie Paul E. , Burford Reiskind Martha O.
Published: October 2019

Background

The yellow fever mosquito,Aedes aegyptiis a public health concern in the USA, especially in the wake of emergent diseases such as Zika and chikungunya.Aedes aegyptipopulations dwindled after the invasion ofAedes albopictusin the 1980s and many populations were extirpated. However, in some areasAe. aegyptipersisted in small populations and there are reports of recent resurgences ofAe. aegyptiin Florida, Louisiana, Nevada and California. We assessed the population genetic structure ofAe. aegyptiin Florida and Georgia, which has concomitant consequences related to mosquito dispersal, pesticide resistance and vectorial capacity.

Methods

We collectedAe. aegyptiacross Florida and in Georgia using ovitraps. We hatched the eggs and reared them to adults, and after sacrifice we extracted their DNA. We then probed each individual for variation in 6 microsatellite markers, which we used to address population genetic characteristics.

Results

We collectedAe. aegyptiand genotyped seven Florida populations and one Georgia population using microsatellite markers. We found evidence of isolation by distance model of gene flow supported by driving distance among cities within Florida and two theoretic genetic clusters.

Conclusions

Significant genetic structure between some populations with substantial gene flow between geographically distant cities suggests regional genetic structuring ofAe. aegyptiin Florida. This study provides information on the genetic exchange between populations ofAe. aegyptiin the southeastern USA and suggests potential routes of spread of this species.
Prevalence of antenatal depression and associated factors among pregnant women in Aneded woreda, North West Ethiopia: a community based cross-sectional study
Authors: Habtamu Belete Abebe , Alemayehu Assega Mulunesh , Alemu Abajobir Amanuel , Abebe Belay Yihalem , Kassahun Tariku Mengistie
Published: October 2019

Objectives

To assess the prevalence of antenatal depression and factors associated with antenatal depression among pregnant women in Aneded woreda, Northwest Ethiopia, 2019. A community based- cross sectional study was conducted in Aneded woreda among 7 kebles’ of North-West, Ethiopia from March 16 to April 23, 2019. A total of 342 pregnant women were recruited using simple random sampling.

Result

The prevalence of antenatal depression was 15.20%. Urban residence [AOR = 6.8; 95% CI (1.97, 23.32)], marital status of being unmarried [AOR = 5.1; 95% CI (1.79, 14.63)], occupation of being government employee [AOR = 8.8; 95% CI (2.06, 37.12)] and merchant [AOR = 3.7; 95% CI (1.27, 10.91)], prim gravid [AOR = 5.3; 95% CI (2.03, 13.82)], not attend ANC follow up [AOR = 8.7; 95% CI (3.46, 21.79)], intimate partner violence [AOR = 4.5; 95% CI (1.28, 15.52)], unplanned pregnancy [AOR = 6.2; 95% CI (2.37, 16.06)], and substance use [AOR = 5.6; 95% CI (2.12, 14.92)] were significantly factors. Strengthen the risk prevention activities so important to tackle the problem of antenatal depression.
Assessment of liver marker enzymes and its association with type 2 diabetes mellitus in Northwest Ethiopia
Authors: Shibabaw Tewodros , Dessie Gashaw , Molla Meseret Derbew , Zerihun Muluken Fekadie , Ayelign Birhanu
Published: October 2019

Objective

This study aimed to assess the level of aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) and gamma-glutamyltransferase (GGT), and their association with type 2 diabetes mellitus in Northwest Ethiopia.

Results

Using a cross-sectional study, blood samples were collected from 192 Type 2 diabetes mellitus (T2DM) participants and 192 healthy age and sex-matched volunteers. The study was carried out from May to August 2017. The serum concentration of aspartate aminotransaminase, alanine aminotransaminase, and gamma-glutamyltransferase were measured using A25 Bio-system fully automatic chemistry analyzer and using the manufacturer’s kit of the machine. Liver function test results of T2DM participant were significantly higher than those of the control group, serum ALT (46.06 ± 22. 38 IU/L) and serum AST (42.94 ± 19. 08 IU/L), P < 0.001, while the level of GGT in both study groups was not significantly associated (P = 0.065). In conclusion, the evaluation of liver marker enzymes showed a significant association with Type 2 diabetes participants compared with the controls.
Smoking index, lifestyle factors, and genomic instability assessed by single-cell gel electrophoresis: a cross-sectional study in subjects from Yucatan, Mexico
Authors: Locken-Castilla Alejandra , Pacheco-Pantoja Elda Leonor , Rodríguez-Brito Fátima , May-Kim Sherlin , López-Rivas Victor , Ceballos-Cruz Angel
Published: October 2019

Background

It is widely accepted that genomic instability is associated with several mechanisms involving oxidative stress, which can increase the rate of DNA breaks. Such factors include smoking, impairments in body composition, an unhealthy lifestyle, and a hereditary history of cancer. The aim was to evaluate the degree of association of genomic instability in smokers and non-smokers, and how the risk could change depending on the lifestyle and other causes. For this purpose, a survey of tobacco consumption, dietary patterns, physical activity, antecedents of cancer, and body composition assessment was carried out. Genomic instability was evaluated through a single-cell gel electrophoresis using peripheral blood mononuclear cells in three different conditions of oxidative stress. The analysis of genomic damage degree was performed through a dimension reduction procedure (principal component analysis) from 16 parameters per treatment (adding up 48 parameters of genomic damage per subject) and a binary logistic regression model for DNA fragmentation risk.

Results

The sample consisted of 82 participants, divided into three age groups: young adults (18–35 years), adults (36–59 years), and older adults (60–95 years). As expected, the results showed a significant positive correlation of age with genomic damage rates, represented by 2 PCA groups (p = 0.027,p = 0.004). There were consistent significant positive associations of genomic damage rates with smoking index and three PCA groups (p = 0.007,p = 0.004,p = 0.009). The smoking status and age group analysis revealed that there were significant differences for adult smokers with the same aforementioned PCA groups (p = 0.002,p = 0.001,p = 0.010). In addition, higher DNA damage rates were found in subjects with incorrect diet patterns, long sitting hours, and previous exposure to radiation. The analysis with binary logistic regression displayed two models in which lifestyles (age, diet, and/or sedentarism) did not change the significance of smoking index for DNA fragmentation risk; however, when physical activity was present in the model, the smoking index was not a significant factor for DNA damage risk.

Conclusions

Although it is well known that smoking affects human health in different ways, DNA fragmentation can be analyzed by a damage phenotypic analysis and integrate a risk analysis reshaped by diet and lifestyle in general.
Successful pregnancy for primary amenorrhea and recurrent implantation failure and the role of hysteroscopic adhesiolysis: a case report
Authors: Khrait Zakwan
Published: October 2019

Background

Infertility continues to be an enigmatic and emerging problem. Although in vitro fertilization has proved to be revolutionary and immensely beneficial to many people, it is far from perfect, and many women experience recurrent in vitro fertilization failures. There can be a multitude of factors involved in recurrent in vitro fertilization failures. The aim of this report was to explore the role of hysteroscopy in determining potential causes of in vitro fertilization failure and how the relevant hysteroscopic findings can address the issue of infertility in terms of a subsequent successful in vitro fertilization.

Case presentation

A 37-year-old white Arab woman with a history of eight in vitro fertilization failures and one curettage performed for a blighted ovum presented to our hospital because of inability to conceive. Her past medical history was significant for hypothyroidism and positive factor V Leiden. She underwent hystero contrast sonography, which revealed a normal uterine cavity with irregular fillings in the right corner. To explore this further, hysteroscopy was performed, which showed dense adhesions in the right upper corner and first-degree adhesions in the lower half of the uterus. After undergoing adhesiolysis and a cycle of estradiol valerate and progesterone, the patient successfully conceived twins.

Conclusions

Hysteroscopy may play an important role before or in conjunction with assisted reproductive techniques to help infertile women and couples achieve their goals of pregnancy and live birth of a child.