bluuebunny/crossref_metadata_2025 huggingface dataset:
Is clinical effect of autologous conditioned serum in spontaneously occurring equine articular lameness related to ACS cytokine profile?
Authors: Marques-Smith Patrick , Kallerud Anne S. , Johansen Grethe M. , Boysen Preben , Jacobsen Anna M. , Reitan Karoline M. , Henriksen Mia M. , Löfgren Maria , Fjordbakk Cathrine T.
Published: June 2020

Background

Biologic’ therapies, such as autologous conditioned serum (ACS), are gaining popularity in treating orthopaedic conditions in equine veterinary medicine. Evidence is scarce regarding ACS constituents, and large inter-individual differences in cytokine and growth factor content have been demonstrated. The objective of the current study was to investigate the potential association between cytokine and growth factor content of ACS and clinical effect in harness racehorses with spontaneously occurring low-grade articular lameness. Horses received 3 intra-articular injections of ACS administered at approximately 2-week intervals. Lameness evaluation consisting of a trot-up with subsequent flexions tests was performed at inclusion and approximately 2 weeks after the last treatment (re-evaluation); horses were classified as responders when there was no detectable lameness on trot-up and a minimum of 50% reduction in flexion test scores at re-evaluation. Association between clinical outcome (responders vs. non-responders) and age, lameness grades at inclusion (both initial trot-up and after flexion tests), treatment interval, follow-up time and the ACS content of IL-1Ra, IGF-1 and TGF-β was determined by regression modelling.

Results

Outcome analysis was available for 19 of 20 included horses; 11 responded to treatment whereas 8 did not. There was considerable inter-individual variability in cytokine/growth factor content of ACS, and in the majority of the horses, the level of IL-10, IL-1β and TNF-α was below the detection limit. In the final multivariate logistic regression model, ACS content of IGF-1 and IL-1Ra was significantly associated with clinical response (P = 0.01 andP = 0.03, respectively). No association with clinical response was found for the other tested variables.

Conclusions

The therapeutic benefit of ACS may be related to higher levels of IL-1Ra and IGF-1. Our study corroborates previous findings of considerable inter-individual variability of cytokine- and growth factor content in ACS.
Comparison of physiological demands in Warmblood show jumping horses over a standardized 1.10 m jumping course versus a standardized exercise test on a track
Authors: Léguillette Renaud , Bond Stephanie L. , Lawlor Kelda , Haan Tineke de , Weber Lauren M.
Published: June 2020

Background

A greater understanding of exercise physiology and biochemistry is required for the sport horse disciplines, including show jumping. Conditioning of horses for show jumping is empirical because they are primarily trained on flat ground, however the equivalent workload between jumping and flat work is currently unknown. The objectives of the study were therefore to compare the physiological demands of Warmblood show jumpers over a standardized 1.10 m course vs a 600 m standardized incremental exercise test on flat ground, and to report reference field test values for competitive show jumping horses. In this prospective field study, 21 healthy, actively competing Warmblood show jumping horses were assessed to determine physiological variables after a standardized jumping course at 6.4 m/s (average speed) and track standardized incremental exercise test at 5 m/s, 8 m/s and 11 m/s. Heart rate, velocity, blood lactate, blood pH, pCO2, bicarbonate, PCV and TP concentrations were recorded. V200, V170 and VLa4 were calculated. Parametric statistics were performed on analysis of all 21 horses’ variables.

Results

Contrary to exercise at 5 m/s and 11 m/s, cantering at 8 m/s did not induce any significant difference in blood lactate, mean heart rate or mean venous blood pH compared to after completion of the jumping course.

Conclusions

Jumping a 1.10 m course demands a statistically similar workload to cantering around a flat track at 8 m/s. This study will help to test fitness and design conditioning programs for Warmblood show jumping horses.
Evaluation of a rapid immunochromatographic test kit to the gold standard fluorescent antibody test for diagnosis of rabies in animals in Bhutan
Authors: Tenzin Tenzin , Lhamo Kelzang , Rai Purna B. , Tshering Dawa , Jamtsho Pema , Namgyal Jamyang , Wangdi Thrinang , Letho Sangay , Rai Tuku , Jamtsho Sonam , Dorji Chendu , Rinchen Sangay , Lungten Lungten , Wangmo Karma , Lungten Lungten , Wangchuk Pema , Gempo Tshewang , Jigme Kezang , Phuntshok Karma , Tenzinla Tenzinla , Gurung Ratna B. , Dukpa Kinzang
Published: June 2020

Background

Rabies kills approximately 59,000 people each year worldwide. Rapid and accurate diagnosis of rabies is important for instituting rapid containment measures and for advising the exposed people for postexposure treatment. The application of a rapid diagnostic tests in the field can greatly enhance disease surveillance and diagnostic activities, especially in resource poor settings. In this study, a total of 179 brain tissue samples collected from different rabies suspect animal species (113 dogs, 50 cattle, 10 cats, 3 goats, 2 horses, and 1 bear) were selected and tested using both rapid immunochromatographic kit and the reference standard fluorescent antibody test (FAT). We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a rapid antigen detection test kit produced by BioNote, Inc. (Hwaseong-si, Korea) relative to a FAT for its fit-for-purpose for confirmation of clinical cases of rabies for early response and enhancing rabies surveillance.

Results

Among 179 samples examined in this study, there was a concordance in results by the rapid test and FAT in 115 positive samples and 54 negative samples. Test results were discordant in 10 samples which were positive by FAT, but negative (false negative) by rapid kit. The rapid test kit showed a sensitivity of 92% (95% CI: 85.9–95.6) and specificity of 100% (95% CI: 93.4–100) using FAT as the reference standard. The positive and negative predictive values were found to be 100% (95% CI:96.7–100) and 84.4% (95% CI: 73.6–91.3), respectively. Overall, there was 94.4% (95% CI: 90–96.9) test agreement between rapid test and FAT (Kappa value = 0.874) with a positive percent agreement and negative percent agreement of 92 and 100%, respectively.

Conclusions

Our finding demonstrated that the rapid test kit (BioNote) can be used for rabies surveillance and confirming clinical case of rabies in animals for making rapid decisions particularly controlling rabies outbreaks in resource poor settings.
Highly enantioselective synthesis of (R)-1,3-butanediol via deracemization of the corresponding racemate by a whole-cell stereoinverting cascade system
Authors: Zu Han , Gu Jie , Zhang Hui , Fan Anwen , Nie Yao , Xu Yan
Published: June 2020

Background

Deracemization, the transformation of the racemate into a single stereoisomeric product in 100% theoretical yield, is an appealing but challenging option for the asymmetric synthesis of optically pure chiral compounds as important pharmaceutical intermediates. To enhance the synthesis of (R)-1,3-butanediol from the corresponding low-cost racemate with minimal substrate waste, we designed a stereoinverting cascade deracemization route and constructed the cascade reaction for the total conversion of racemic 1,3-butanediol into its (R)-enantiomer. This cascade reaction consisted of the absolutely enantioselective oxidation of (S)-1,3-butanediol by Candida parapsilosis QC-76 and the subsequent asymmetric reduction of the intermediate 4-hydroxy-2-butanone to (R)-1,3-butanediol by Pichia kudriavzevii QC-1.

Results

The key reaction conditions including choice of cosubstrate, pH, temperature, and rotation speed were optimized systematically and determined as follows: adding acetone as the cosubstrate at pH 8.0, a temperature of 30 °C, and rotation speed of 250 rpm for the first oxidation process; in the next reduction process, the optimal conditions were: adding glucose as the cosubstrate at pH 8.0, a temperature of 35 °C, and rotation speed of 200 rpm. By investigating the feasibility of the step-by-step method with one-pot experiment as a natural extension for performing the oxidation–reduction cascade, the step-by-step approach exhibited high efficiency for this cascade process from racemate to (R)-1,3-butanediol. Under optimal conditions, 20 g/L of the racemate transformed into 16.67 g/L of (R)-1,3-butanediol with 99.5% enantiomeric excess by the oxidation–reduction cascade system in a 200-mL bioreactor.

Conclusions

The step-by-step cascade reaction efficiently produced (R)-1,3-butanediol from the racemate by biosynthesis and shows promising application prospects.
Genetic diversity and genotype multiplicity of Plasmodium falciparum infection in patients with uncomplicated malaria in Chewaka district, Ethiopia
Authors: Abamecha Abdulhakim , El-Abid Hassan , Yilma Daniel , Addisu Wondimagegn , Ibenthal Achim , Bayih Abebe Genetu , Noedl Harald , Yewhalaw Delenasaw , Moumni Mohieddine , Abdissa Alemseged
Published: June 2020

Background

Genetic diversity in Plasmodium falciparum poses a major threat to malaria control and elimination interventions. Characterization of the genetic diversity of P. falciparum strains can be used to assess intensity of parasite transmission and identify potential deficiencies in malaria control programmes, which provides vital information to evaluating malaria elimination efforts. This study investigated the P. falciparum genetic diversity and genotype multiplicity of infection in parasite isolates from cases with uncomplicated P. falciparum malaria in Southwest Ethiopia.

Methods

A total of 80 P. falciparum microscopy and qPCR positive blood samples were collected from study participants aged 6 months to 60 years, who visited the health facilities during study evaluating the efficacy of artemether-lumefantrine from September–December, 2017. Polymorphic regions of the msp-1 and msp-2 were genotyped by nested polymerase chain reactions (nPCR) followed by gel electrophoresis for fragment analysis.

Results

Of 80 qPCR-positive samples analysed for polymorphisms on msp-1 and msp-2 genes, the efficiency of msp-1 and msp-2 gene amplification reactions with family-specific primers were 95% and 98.8%, respectively. Allelic variation of 90% (72/80) for msp-1 and 86.2% (69/80) for msp-2 were observed. K1 was the predominant msp-1 allelic family detected in 20.8% (15/72) of the samples followed by MAD20 and RO33. Within msp-2, allelic family FC27 showed a higher frequency (26.1%) compared to IC/3D7 (15.9%). Ten different alleles were observed in msp-1 with 6 alleles for K1, 3 alleles for MAD20 and 1 allele for RO33. In msp-2, 19 individual alleles were detected with 10 alleles for FC27 and 9 alleles for 3D7. Eighty percent (80%) of isolates had multiple genotypes and the overall mean multiplicity of infection was 3.2 (95% CI 2.87–3.46). The heterozygosity indices were 0.43 and 0.85 for msp-1 and msp-2, respectively. There was no significant association between multiplicity of infection and age or parasite density.

Conclusions

The study revealed high levels of genetic diversity and mixed-strain infections of P. falciparum populations in Chewaka district, Ethiopia, suggesting that both endemicity level and malaria transmission remain high and that strengthened control efforts are needed in Ethiopia.
Disseminating clinical study results to trial participants in Ethiopia: insights and lessons learned
Authors: Degaga Tamiru S. , Weston Sophie , Tego Tedla T. , Abate Dagimawie T. , Aseffa Ashenafi , Wayessa Adugna , Price Ric N. , Hailu Asrat , Thriemer Kamala
Published: June 2020

International regulatory authorities and funders require that research be disseminated promptly and appropriately to all involved stakeholders. However, following completion of clinical trials participants often either do not receive any feedback or materials provided are not appropriate for the context. The investigators of a multicentre anti-malarial clinical trial (the IMPROV study) conducted a dissemination meeting at one of the study sites in Ethiopia; trial participants and medical staff were provided feedback on the study results. This report summarizes the dissemination strategies adopted by the investigators, including a plain language visual aid and simple communication techniques. Lessons learned are reported with a discussion on the operational challenges to dissemination of clinical trials in resource limited settings.
Subgroup analysis of the influence of body mass index on the association between serum lipids and cognitive function in Chinese population
Authors: Li Jiang , Cao Yongtong , Xiao Cheng
Published: June 2020

Background

Previous studies reported that the association between lipid levels and cognitive function is related with gender, age and specific cognitive domains, but the influence of body mass index (BMI) on this association is limited. This triggered interest in exploring how serum lipids relate to cognitive function in different subgroups.

Methods

Data was collected from 2009 wave and 2015 wave of China Health and Nutrition Survey (CHNS). Multivariable linear regression analyses examined serum lipids level as predictors of sex- and age-specific measure of cognitive function in different BMI levels, which were adjusted for nationality, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), smoking status, alcohol consumption and education level.

Results

Cognitive function score have different concentration curves in serum lipids quartile levels in different BMI categories. After adjustment for confounding factors, serum TG was positively associated with cognitive function score in underweight (β ± SE: 2.06 ± 0.88, P = 0.023) and obese (β ± SE: 1.44 ± 0.71, P = 0.045) male group, and serum HDL-C was positively associated with cognitive function score in overweight (β ± SE: 1.89 ± 0.92, P = 0.041) and obese (β ± SE: 5.04 ± 1.62, P = 0.002) female group. Serum TC was negatively associated with cognitive function score in overweight (β ± SE: − 2.55 ± 1.26, P = 0.043) mid-life adults, and serum HDL-C was positively associated with cognitive function score in overweight (β ± SE: 2.15 ± 0.94, P = 0.022) and obese (β ± SE: 5.33 ± 2.07, P = 0.011) older adults.

Conclusion

The associations of serum lipids with cognitive function were related with BMI levels and differed between gender and age groups. This result indicated that better nutritional status has superior cognitive function performance.
Health-related quality of life (FACT-GP) in Sweden
Authors: Lindqvist Bagge Ann-Sophie , Carlander Anders , Fahlke Claudia , Olofsson Bagge Roger
Published: June 2020

Background

Many studies have used disease-specific instruments, such as the Functional Assessment of Cancer Therapy (FACT), when studying health-related quality of life (HRQOL) in patients. Few studies however, have described normative HRQOL values in the general population using FACT - General Population (FACT-GP). The general aim of the present study is thus to describe the normative HRQOL values in the general Swedish population by using the FACT-GP instrument and to investigate to what degree sociodemographic factors and status of self-rated health (SRH) correlate with HRQOL.

Methods

The participants consisted of a pre-stratified (gender, age and education) sample of Swedish citizens that previously had enrolled to be a part of a web panel hosted by a research institute (SOM Institute) at the University of Gothenburg in Sweden. The HRQOL was assessed by using the FACT-GP and SRH.

Results

A higher FACT-GP score was mainly associated with males, higher age, higher income and better SRH. The results showed that the Swedish sample scored lower on FACT-GP than previous studies.

Conclusions

Since HRQOL is frequently used as an important endpoint in healthcare research, there is an increasing need for normative data. The results from this study serve as a general population standard against which other studied HRQOL-data could be evaluated.
The plastic brain: neurotoxicity of micro- and nanoplastics
Authors: Prüst Minne , Meijer Jonelle , Westerink Remco H. S.
Published: June 2020

Given the global abundance and environmental persistence, exposure of humans and (aquatic) animals to micro- and nanoplastics is unavoidable. Current evidence indicates that micro- and nanoplastics can be taken up by aquatic organism as well as by mammals. Upon uptake, micro- and nanoplastics can reach the brain, although there is limited information regarding the number of particles that reaches the brain and the potential neurotoxicity of these small plastic particles.

Earlier studies indicated that metal and metal-oxide nanoparticles, such as gold (Au) and titanium dioxide (TiO2) nanoparticles, can also reach the brain to exert a range of neurotoxic effects. Given the similarities between these chemically inert metal(oxide) nanoparticles and plastic particles, this review aims to provide an overview of the reported neurotoxic effects of micro- and nanoplastics in different species and in vitro. The combined data, although fragmentary, indicate that exposure to micro- and nanoplastics can induce oxidative stress, potentially resulting in cellular damage and an increased vulnerability to develop neuronal disorders. Additionally, exposure to micro- and nanoplastics can result in inhibition of acetylcholinesterase activity and altered neurotransmitter levels, which both may contribute to the reported behavioral changes.

Currently, a systematic comparison of the neurotoxic effects of different particle types, shapes, sizes at different exposure concentrations and durations is lacking, but urgently needed to further elucidate the neurotoxic hazard and risk of exposure to micro- and nanoplastics.
Indigenous uses of wild and tended plant biodiversity maintain ecosystem services in agricultural landscapes of the Terai Plains of Nepal
Authors: Thorn Jessica P. R. , Thornton Thomas F. , Helfgott Ariella , Willis Kathy J.
Published: June 2020

Background

Despite a rapidly accumulating evidence base quantifying ecosystem services, the role of biodiversity in the maintenance of ecosystem services in shared human-nature environments is still understudied, as is how indigenous and agriculturally dependent communities perceive, use, and manage biodiversity. The present study aims to document traditional ethnobotanical knowledge of the ecosystem service benefits derived from wild and tended plants in rice-cultivated agroecosystems, compare this to botanical surveys, and analyze the extent to which ecosystem services contribute social-ecological resilience in the Terai Plains of Nepal.

Method

Sampling was carried out in four landscapes, 22 Village District Committees, and 40 wards in the monsoon season. Data collection was based on transects walks to collect plant specimens, structured and semi-structured interviews, and participatory fieldwork in and around home gardens, farms, and production landscapes. We asked 180 farmers to free-list vernacular names and describe use-value of wild and tended plants in rice-cultivated agroecosystems. Uses were categorized into eight broad groupings, and 61 biomedical ailment classifications. We assessed if knowledge of plant species diversity and abundance differed with regard to caste, age, and gender.

Results

Nepalese farmers have a deep knowledge of the use and management of the 391 vascular plant specimens identified, which provide key provisioning, regulating, supporting, and cultural ecosystem services. Altogether, plants belong to 76 distinct plant species from 49 phylogenetic families: 56 are used to cure 61 ailments, 27 for rituals, 25 for food, 20 for timber, 17 for fuel, 17 for fodder, 11 for soil enhancement, and eight for pesticides. Four caste groups have statistically different knowledge, and younger informants report a lower average number of useful plants.

Conclusion

Agricultural landscapes in Nepal are reservoirs of biodiversity. The knowledge of the use of wild and tended plant species in and around these farms differs by the caste and age group of land manager. Conducting research on agroecosystems will contribute to a deeper understanding of how nature is perceived by locals, to more efficient management and conservation of the breadbasket of Nepal, and to the conservation of valuable, but disappearing traditional knowledge and practice.
Prelacteal feeding practices in Pakistan: a mixed-methods study
Authors: Asim Muhammad , Ahmed Zarak Husain , Hayward Mark D. , Widen Elizabeth M.
Published: June 2020

Background

Prelacteal feeding, the feeding a newborn substances or liquids before breastfeeding, is a common cultural practice in Pakistan, but is associated with neonatal morbidity and mortality because it delays early initiation of breastfeeding. In this study, we sought to examine the social and cultural factors associated with prelacteal feeding in Pakistan.

Methods

This mixed-method study used data from the Pakistan Demographic and Health Survey (PDHS) 2012–13. Findings from the survey were complemented by qualitative interviews with mothers and healthcare providers. In a subset of PDHS dyads (n = 1361) with children (0–23 months), descriptive statistics and bivariate and multivariable logistic regression analysis examined factors associated with prelacteal feeding. The qualitative study included in-depth interviews with six mothers and six health care providers, which were analyzed using NVivo software version 10.

Results

In PDHS, a majority of children (64.7%) received prelacteal feeding. The most common prelacteal food was milk other than breast milk (24.5%), while over a fifth (21.8%) of mothers reported giving honey and sugar water. Factors associated with prelacteal feeding included: birth at public health facilities (AOR 0.46, 95% CI 0.02, 0.95), maternal primary education (AOR 2.28, 95% CI 1.35, 3.85), and delayed breastfeeding initiation (AOR 0.03, 95% CI 0.01, 0.61). In our qualitative study, the major themes found associated with prelacteal feedings included: easy access to prelacteal substances at health facilities, deliveries in private health facilities, prelacteals as a family tradition for socialization, insufficient breast milk, Sunna of Holy Prophet, and myths about colostrum.

Conclusions

These data indicate that prelacteal feeding is a well-established practice and social norm in Pakistan. Policies and interventions aimed at promoting breastfeeding need to take these customs into consideration to achieve the desired behavioral changes.
A novel three-dimensional template combined with MR-guided 125I brachytherapy for recurrent glioblastoma
Authors: He Xiangmeng , Liu Ming , Zhang Menglong , Sequeiros Roberto Blanco , Xu Yujun , Wang Ligang , Liu Chao , Wang Qingwen , Zhang Kai , Li Chengli
Published: June 2020

Background

At present, the treatment of recurrent glioblastoma is extremely challenging. In this study, we used a novel three-dimensional non-coplanar template (3DNPT) combined with open MR to guide 125I seed implantation for recurrent glioblastoma. The aim of this study was to evaluate the feasibility, accuracy, and effectiveness of this technique.

Methods

Twenty-four patients of recurrent glioblastoma underwent 3DNPT with open MR-guided 125I brachytherapy from August 2017 to January 2019. Preoperative treatment plan and 3DNPT were made according to enhanced isovoxel T1-weighted MR images. 125I seeds were implanted using 3DNPT and 1.0-T open MR imaging guidance. Dosimetry verification was performed after brachytherapy based on postoperative CT/MR fusion images. Preoperative and postoperative dosimetry parameters of D90, V100, V200, conformity index (CI), external index (EI) were compared. The objective response rate (ORR) at 6 months and 1-year survival rate were calculated. Median overall survival (OS) measured from the date of brachytherapy was estimated by Kaplan-Meier method.

Results

There were no significant differences between preoperative and postoperative dosimetry parameters of D90, V100, V200, CI, EI (P > 0.05). The ORR at 6 months was 75.0%. The 1-year survival rate was 58.3%. Median OS was 12.9 months. One case of small amount of epidural hemorrhage occurred during the procedure. There were 3 cases of symptomatic brain edema after brachytherapy treatment, including grade three toxicity in 1 case and grade two toxicity in 2 cases. The three patients were treated with corticosteroid for 2 to 4 weeks. The clinical symptoms related to brain edema were significantly alleviated thereafter.

Conclusions

3DNPT combined with open MR-guided 125I brachytherapy for circumscribed recurrent glioblastoma is feasible, effective, and with low risk of complications. Postoperative dosimetry matched the preoperative treatment plan. The described method can be used as a novel implantation technique for 125I brachytherapy in the treatment of recurrent gliomas.

Trial registration

The study was approved by the Institutional Review Board of Shandong Provincial Hospital Affiliated to Shandong University (NSFC:NO.2017–058), registered 1st July 2017.
Overlapping volumes in re-irradiation for head and neck cancer – an important factor for patient selection
Authors: Embring Anna , Onjukka Eva , Mercke Claes , Lax Ingmar , Berglund Anders , Bornedal Sara , Wennberg Berit , Friesland Signe
Published: June 2020

Background

There is a lack of consensus concerning the definition of re-irradiation and re-irradiation volumes in head and neck cancer (HNC). The aim of the present study is to introduce a more strict definition of the re-irradiated volume that might better predict the risk of serious side-effects from treatment.

Methods

Fifty-four consecutive patients re-irradiated for HNC cancer were retrospectively analysed. CT images were deformably registered and the dose distributions accumulated after conversion to EQD2. Patients with a cumulative dose of ≥100 Gy in the overlapping volume (V100) were included in the study. Survival data and radiation-related acute and late toxicities were recorded.

Results

The overall survival of all included patients at 2 and 5 years was 42.6 and 27.3% respectively and the progression free survival at 2 and 5 years was 32.5 and 28.5% respectively. The overall rate of any event of severe (grade ≥ 3) acute and late toxicity was 26 and 51%, respectively. We found that severe acute toxicity was more common in patients who had a larger overlapping volume (V100 > mean) where 43% of the patients experienced grade ≥ 3 acute toxicity, compared to the patients with smaller overlapping volumes (V100 < mean) where only 11% had severe toxicity (p = 0.02). The seemingly high rates of late toxicity in the present study could be due to the use of a more strict definition of re-irradiation. In previous studies also patients with low dose overlap are included and our results imply that there is a risk that previous studies might have overestimated the risk-benefit ratio in re-irradiation of HNC.

Conclusions

Our study describes the outcome of a patient material where a more strict definition of the re-irradiated volume is used. With this definition, which could better describe the volume of highest risk for serious complications, we found that larger such overlapping volumes result in an increase in severe acute side-effects. A clear definition of re-irradiation and re-irradiation volumes is of utmost importance for future studies of HNC to make results from different studies comparable.
Effect of Achilles tendon on kinematic coupling relationship between tarsal bones: a pilot finite element study
Authors: Li Song-Jian , Tang Lei , Zhao Li , Liu Cheng-Long , Liu Yu-Bin
Published: June 2020

Background

The procedure of percutaneous Achilles tenotomy (PAT) is an important component of the Ponseti method. However, few studies reported the influence of Achilles tendon on kinematic coupling relationship between tarsal bones. The purpose of present study was to demonstrate the effect of Achilles tendon on the kinematic coupling relationship between tarsal bones, and to illustrate how kinematic coupling relationship between tarsal bones works in term of finite element analysis.

Methods

A three-dimensional finite element model of foot and ankle was constructed based on the Chinese digital human girl No.1 (CDH-G1) image database using the software of mimics, Geomagic studio, HyperMesh, and Abaqus. The last manipulation of the Ponseti method before the procedure of PAT was simulated. The talus head and the proximal tibia and fibula bone were fixed in all six degrees of freedom, and the outward pressure was added on the first metatarsal head to investigate the kinematic coupling relationship between tarsal bones.

Results

The least relationship of kinematic coupling between tarsal bones was found in calcaneus. Stress concentration was mainly observed at the navicular, talus and the medial malleolus. The difference in displacement of the navicular was only found with the Achilles tendon stiffness of 0 N/mm and others. No difference in the navicular displacement was found in the stiffness of Achilles tendon between 40, 80, 200, 400, and 1000 N/mm. The maximum displacement of navicular was observed at the ankle position of PF-20° (plantar flexion-20°). The difference in displacement of the navicular was greater at the ankle position of PF-20° with the Achilles tendon stiffness of 0 N/mm than that at the ankle position of PF-40° with the Achilles tendon stiffness of 40 N/mm.

Conclusions

Based on the findings from this study, it was demonstrated that the Achilles tendon existence or not and ankle position had great influence, while increased stiffness of Achilles tendon had no influence on kinematic coupling relationship between tarsal bones. For the cases with severe equinus, earlier implementation of PAT procedure (with the purpose of release the Achilles tendon and reduce the degree of ankle plantar flexion) may be beneficial to the deformity correction.
Structural durability of early-generation Transcatheter aortic valve replacement valves compared with surgical aortic valve replacement valves in heart valve surgery: a systematic review and meta-analysis
Authors: Ler Ashlynn , Ying Yeo Jie , Sazzad Faizus , Choong Andrew M. T. L. , Kofidis Theo
Published: June 2020

Background

The current treatment for aortic stenosis includes open surgical aortic valve replacement (SAVR) as well as endovascular transcatheter aortic valve replacement (TAVR). This study aims to compare the 1-year, 2–3 year and 5-year structural durability of TAVR valves with that of SAVR valves.

Method

A systematic literature search was conducted in July 2019 on Medline (via PubMed), Embase and Cochrane electronic databases according to the PRISMA guidelines.

Results

Thirteen randomized controlled trials were included. From the meta-analysis, we observed higher rates of 1-year (OR: 7.65, CI: 4.57 to 12.79, p < 0.00001), 2–3-year (OR: 13.49, CI: 5.66 to 32.16, p < 0.00001) and 5-year paravalvular regurgitation (OR: 14.51, CI: 4.47 to 47.09, p < 0.00001) associated with the TAVR valves than the SAVR valves. There were also higher rates of 1-year (OR: 5.00, CI: 3.27 to 7.67, p < 0.00001), 2–3-year (OR: 8.14, CI: 3.58 to 18.50, p < 0.00001) and 5-year moderate or severe aortic regurgitation (MD: 14.65, CI: 4.55 to 47.19, p < 0.00001), and higher rates of 1-year (OR: 3.55, CI: 1.86 to 6.77, p = 0.0001), 2–3-year (OR: 3.55, CI: 1.86 to 6.77, p = 0.0001) and 5-year reintervention (OR: 3.55, CI: 1.22 to 10.38, p = 0.02) in the TAVR valves as compared to SAVR valves.

Conclusion

TAVR valves appear to be more susceptible to structural valve deterioration and thus potentially less structurally durable than SAVR valves, given that they may be associated with higher rates of moderate or severe aortic regurgitation, paravalvular regurgitation and reintervention in the 1-year-, 2–3 year, and 5-year period.
Barriers and challenges in the process of including critically ill patients in clinical studies
Authors: Dahlberg Jørgen , Eriksen Camilla , Robertsen Annette , Beitland Sigrid
Published: June 2020

Background

Clinical research in severely ill or injured patients is required to improve healthcare but may be challenging to perform in practice. The aim of this study was to analyse barriers and challenges in the process of including critically ill patients in clinical studies.

Methods

Data from critically ill patients considered for inclusion in an observational study of venous thromboembolism in Norway were analysed. This included quantitative and qualitative information from the screening log, consent forms and research notes.

Results

Among 279 eligible critically ill patients, 204 (73%) were omitted from the study due to challenges and barriers in the inclusion process. Reasons for omission were categorised as practical in 133 (65%), medical in 31 (15%), and legal or ethical in 40 (20%) of the patients. Among 70 included patients, 29 (41%) consents were from patients and 41 (59%) from their next of kin. Several challenges were described herein; these included whether patients were competent to give consent, and which next of kin that should represent the patient. Furthermore, some included patients were unable to recall what they have consented, and some appeared unable to separate research from treatment.

Conclusions

Barriers and challenges in the inclusion process led to the omission of near three out of four eligible patients. This analysis provided information about where the problem resides and may be solved. The majority of challenges among included patients were related to issues of autonomy and validity of consent.

Trial registration

ClinicalTrials.gov(NCT03405766).
Drug dosing in the critically ill obese patient—a focus on sedation, analgesia, and delirium
Authors: Erstad Brian L. , Barletta Jeffrey F.
Published: June 2020

Practice guidelines provide clear evidence-based recommendations for the use of drug therapy to manage pain, agitation, and delirium associated with critical illness. Dosing recommendations however are often based on strategies used in patients with normal body habitus. Recommendations specific to critically ill patients with extreme obesity are lacking. Nonetheless, clinicians must craft dosing regimens for this population. This paper is intended to help clinicians design initial dosing regimens for medications commonly used in the management of pain, agitation, and delirium in critically ill patients with extreme obesity. A detailed literature search was conducted with an emphasis on obesity, pharmacokinetics, and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided.
Whole-genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes
Authors: Sakthikumar Sharadha , Roy Ananya , Haseeb Lulu , Pettersson Mats E. , Sundström Elisabeth , Marinescu Voichita D. , Lindblad-Toh Kerstin , Forsberg-Nilsson Karin
Published: June 2020

Background

Glioblastoma (GBM) has one of the worst 5-year survival rates of all cancers. While genomic studies of the disease have been performed, alterations in the non-coding regulatory regions of GBM have largely remained unexplored. We apply whole-genome sequencing (WGS) to identify non-coding mutations, with regulatory potential in GBM, under the hypothesis that regions of evolutionary constraint are likely to be functional, and somatic mutations are likely more damaging than in unconstrained regions.

Results

We validate our GBM cohort, finding similar copy number aberrations and mutated genes based on coding mutations as previous studies. Performing analysis on non-coding constraint mutations and their position relative to nearby genes, we find a significant enrichment of non-coding constraint mutations in the neighborhood of 78 genes that have previously been implicated in GBM. Among them,SEMA3CandDYNC1I1show the highest frequencies of alterations, with multiple mutations overlapping transcription factor binding sites. We find that a non-coding constraint mutation in theSEMA3Cpromoter reduces the DNA binding capacity of the region. We also identify 1776 other genes enriched for non-coding constraint mutations with likely regulatory potential, providing additional candidate GBM genes. The mutations in the top four genes,DLX5,DLX6,FOXA1, andISL1, are distributed over promoters, UTRs, and multiple transcription factor binding sites.

Conclusions

These results suggest that non-coding constraint mutations could play an essential role in GBM, underscoring the need to connect non-coding genomic variation to biological function and disease pathology.
Beta-adrenergic antagonist for the healing of chronic diabetic foot ulcers: study protocol for a prospective, randomized, double-blinded, controlled and parallel-group study
Authors: Kaur Ramanjot , Tchanque-Fossuo Catherine , West Kaitlyn , Hadian Yasmin , Gallegos Anthony , Yoon Daniel , Ismailyan Ligia , Schaefer Saul , Dahle Sara E. , Isseroff R. Rivkah
Published: June 2020

Background

Diabetic foot ulcers (DFUs) are the most common cause of leg amputations and their management is extremely challenging. Despite many advances and expensive therapies, there has been little success in improving outcomes of DFUs. In prior work our laboratory has examined the effects of beta-adrenergic antagonists (βAAs) on skin and skin-derived cells. We have shown that βAAs enhance the rate of keratinocyte migration, promote angiogenesis, and hasten wound healing in scratch wounds in vitro, in animal wound models, and in anecdotally reported cases of chronic wounds that healed successfully after topical application of the βAA timolol. Thus, we propose to test timolol directly on DFUs to determine if it improves healing above the current standard of care (SOC). This study will examine the efficacy and safety of topically applied beta-antagonist Timoptic-XE® (timolol maleate ophthalmic gel forming solution) in subjects with DFUs.

Methods/design

This is a phase two, randomized, double-blinded, controlled, and parallel-group clinical trial with two treatment arms, SOC plus topical Timoptic-XE® and SOC plus a non-biologically active gel (hydrogel, as placebo drug). Study subjects with a DFU will be selected from the Veterans Affairs Northern California Health Care System (VANCHCS). Study duration is up to 31 weeks, with three phases (screening phase for two weeks, active phase for up to 12 weeks, with an additional second consecutive confirmatory visit after 2 weeks, and follow-up phase comprising monthly visits for 4 months). Subjects will apply daily either the topical study drug or the placebo on the foot ulcer for 12 weeks or until healed, whichever comes first. Measurements of wound size and other data will be collected at baseline, followed by weekly visits for 12 weeks, and then a monthly follow-up period.

Discussion

This is a clinical translation study, moving the investigators’ pre-clinical laboratory research into a translational study in which we will analyze clinical outcomes to assess for safety and estimate the efficacy of a topical beta-antagonist in healing of DFUs. The results from this trial may establish new treatment paradigms and safety profile for DFU treatment.

Trial registration

ClinicalTrials.gov, NCT03282981. Registered on June 14th, 2018.
Elbow hemiarthroplasty versus open reduction and internal fixation for AO/OTA type 13 C2 and C3 fractures of distal humerus in patients aged 50 years or above: a randomized controlled trial
Authors: Al-Hamdani Ali , Rasmussen Jeppe V. , Holtz Kenneth , Olsen Bo S.
Published: June 2020

Background

Intraarticular distal humeral fractures of AO/OTA type 13 C2 and C3 pose a surgical challenge despite the evolution of surgical implants and techniques. Open reduction and internal fixation (ORIF) is often preferred as the first choice of treatment, but the results vary and are sometimes disappointing. Total elbow arthroplasty (TEA) has been widely used for fractures that are not amenable to ORIF in elderly patients, but the mechanical complications remain a challenge, especially in active patients. Elbow hemiarthroplasty (EHA) provides a modern alternative that might avoid the mechanical complications and weight bearing restrictions related to the linked articulation in semi-constrained TEA. No studies have compared the results of EHA to that of ORIF, but case series have reported promising results.

Methods/design

This is a study protocol describing an investigator-initiated, non-blinded randomized controlled trial comparing the outcome of EHA with ORIF for AO/OTA type 13 C2 and C3 fractures of the distal humerus in patients who are 50 years or older. Forty-four patients with AO/OTA type 13 C2 and C3 fractures of distal humerus will be randomized to either EHA or ORIF. The Oxford Elbow Score (OES) will be used as primary outcome. Mayo Elbow Performance Score (MEPS), pain severity score (VAS), range of motion, and patient satisfaction will be used as secondary outcomes. Reoperations, complications, and the length of sick leave will be recorded. The patients will be examined after the operation and at 3 months and 1, 2, 5, and 10 years.

Discussion

The main objective of this study is to investigate the best treatment option for AO/OTA type 13 C2 and C3 fractures of distal humerus in patients aged 50 years or above. We hypothesize that EHA results in fewer complications and superior functional outcome compared with ORIF and that the mechanical complications related to the linked articulation of TEA can be avoided.

Trial registration

ClinicalTrials.gov, PRS, NCT04163172. Registered November 13, 2019. https://clinicaltrials.gov/ct2/results?cond=&term=evori&cntry=&state=&city=&dist= (Table 2).

The protocol has been approved by The Scientific Ethics Committee of the Capital Region of Denmark (Jr. no.: H− 19,035,590).

The processing of personal data has been approved by the Danish Data Protection Agency (Jr. no. P-2019-246). Inclusion started on February 1, 2020.
Implementation and evaluation of a nurse-led decision-coaching program for healthy breast cancer susceptibility gene (BRCA1/2) mutation carriers: a study protocol for the randomized controlled EDCP-BRCA study
Authors: Isselhard A. , Töpper M. , Berger-Höger B. , Steckelberg A. , Fischer H. , Vitinius F. , Beifus K. , Köberlein-Neu J. , Wiedemann R. , Rhiem K. , Schmutzler R. , Stock S.
Published: June 2020

Background

Female BRCA mutation carriers have an increased lifetime risk for breast and ovarian cancer compared to the general population. Women who carry this mutation have several options to deal with their cancer risk, such as risk-reducing surgeries or intensified breast cancer screening. Previous research has shown that preferences in this scenario are highly dependent on affected women’s personalities and value systems. To support these women in the decision-making process, a structured decision support consisting of decision coaching combined with a decision aid might be helpful.

Methods/design

A randomized controlled trial will be conducted in order to compare usual care with structured decision support alongside usual care. The decision support program entails nurse-led decision coaching as well as an evidence-based patient decision aid. Nurses are qualified by a 4-day training program in informed decision-making and decision coaching. Six centers for Familial Breast and Ovarian Cancer in Germany will be included in the study, with a planned sample size of 398 women.

The primary outcome is the congruence between the preferred and the actual played role in the decision-making process as measured by the Control Preferences Scale. It is hypothesized that the structured decision support will enable women to play the preferred role in the decision-making process. Secondary outcomes include the knowledge and attitudes about preventive options, decisional conflict, depression and anxiety, coping self-efficacy, impact of event, and self-concept. A process evaluation will accompany the study.

Discussion

The EDCP-BRCA study is the first study to implement and evaluate decision coaching combined with a decision aid for healthy BRCA mutation carriers worldwide.

Trial registration {2a}

DRKS-ID: DRKS00015527. Registered 30 October 2019.
Does internal limiting membrane peeling during epiretinal membrane surgery induce microscotomas on microperimetry? Study protocol for PEELING, a randomized controlled clinical trial
Authors: Ducloyer Jean-Baptiste , Ivan Juliette , Poinas Alexandra , Lebreton Olivier , Bonissent Alexandre , Fossum Paul , Volteau Christelle , Tadayoni Ramin , Creuzot-Garchet Catherine , Le Mer Yannick , Perol Julien , Fortin June , Chiffoleau Anne , Billaud Fanny , Ivan Catherine , Weber Michel
Published: June 2020

Background

The epiretinal membrane (ERM) is a degenerative condition associated with age, which can cause loss of vision and/or metamorphopsia. The treatment of symptomatic ERM involves surgical removal including a vitrectomy followed by peeling of the ERM using a microforceps. As the internal limiting membrane (ILM) is adherent to the ERM, it is sometimes removed with it (spontaneous peeling). If ILM remains in place, it can be removed to reduce ERM recurrence. However, it is important to clarify the safety of ILM peeling, while it increases surgical risks and cause histological disorganization of the retina that can lead to microscotomas, may be responsible for definitive visual discomfort.

Methods

PEELING is a prospective, randomized, controlled, single-blind, and multicentered trial with two parallel arms. This study investigates the benefit/risk ratio of active ILM peeling among individuals undergoing ERM surgery without spontaneous ILM peeling. Randomization is done in the operating room after ERM removal if ILM remains in place. After randomization, the two groups—“active peeling of the ILM” and “no peeling of the ILM”—are compared during a total of three follow-up visits scheduled at month 1, month 6, and month 12. Primary endpoint is the difference in microscotomas before surgery and 6 months after surgery. Patients with spontaneous peeling are not randomized and are included in the ancillary study with the same follow-up visits and the same examinations as the principal study.

Relevant inclusion criteria involve individuals aged > 18 years living with idiopathic symptomatic ERM, including pseudophakic patients with transparent posterior capsule or open capsule or lensed patients with age-related cataracts. The calculated sample size corresponds to 53 randomized eyes (one eye/patient) per arm that means 106 randomized eyes (106 randomized patients) in total and a maximum of 222 included patients (116 spontaneous peeling).

Discussion

ILM peeling is often practiced in ERM surgery to reduce ERM recurrence. It does not impair postoperative visual acuity, but it increases the surgical risks and causes anatomical damages. If active ILM peeling is significantly associated with more microscotomas, it may contraindicate the ILM peeling during primitive idiopathic ERM surgery.

Trial registration

ClinicalTrials.gov, NCT02146144. Registered on 22 May 2014. Recruitment is still ongoing.