bluuebunny/crossref_metadata_2025 huggingface dataset:
Mayo Adhesive Probability (MAP) score of non-donated kidney aids in predicting post-operative renal function following donor nephrectomy
Authors: Cockerill Katherine J. , Kahn Amanda E. , Young Stacy M. , Ball Colleen T. , Mai Martin L. , Taner C. Burcin , Perry Dana K. , Thiel David D.
Published: August 2020

Background

To examine the association of preoperative Mayo Adhesive Probability (MAP) scores in the donor (MAPd) and non-donor kidneys (MAPnd) with post-donation renal function.

Methods

Three hundred thirty-one patients undergoing hand assisted laparoscopic donor nephrectomy (HALDN) were reviewed. MAPd and MAPnd were obtained. Estimated glomerular filtration rate (eGFR) was recorded preoperatively and at 1 day, 1 month, and 6 months postoperatively.

Results

Two hundred females and 131 males were evaluated with median BMI 26.4 kg/m2 (range 17.1–39.6) and median age 45 years (range 19–78). MAPd score was 0 for 231 patients (69.8%) and > 0 for 100 patients (30.2%). MAPnd score was 0 for 234 patients (70.7%) and > 0 for 97 patients (29.3%). The median preoperative eGFR was 86.6 ml/min/1.73m2 (range 48.8–138.4). After adjusting for preoperative eGFR, BMI, ASA score, and kidney sidedness, postoperative eGFR was associated with MAP score in the non-donated kidney (p = 0.014) but not in the donated kidney (p = 0.24). Compared to donors with MAPnd = 0, donors with a MAPnd > 0, mean eGFR was − 2.33 ml/min/1.73m2 lower at postoperative day 1 (95% CI − 4.24 to − 0.41, p = 0.018), − 3.02 ml/min/1.73m2 lower at 1 month (95% CI − 5.11 to − 0.93, p = 0.005), and − 2.63 ml/min/1.73m2 lower at 6 months postoperatively (95% CI − 5.01 to − 0.26, p = 0.030).

Conclusions

MAP score > 0 in the non-donated kidney is associated with worse renal function in the 6 months following HALDN.
Effect of concentrated growth factors on frequency of alveolar Osteitis following partially-erupted mandibular third molar surgery: a randomized controlled clinical study
Authors: Özveri Koyuncu Banu , Işık Gözde , Özden Yüce Meltem , Günbay Sevtap , Günbay Tayfun
Published: August 2020

Background

The aim of this prospective study was to assess the effectiveness of concentrated growth factors (CGF) in preventing the development of alveolar osteitis (AO) after the extraction of partially-erupted mandibular third molars.

Methods

Seventy patients (26 men and 44 women) 18 years or older (mean age 25.86; range 18–35) underwent 140 third molar extractions. All the patients presented with bilateral, partially-erupted mandibular third molars and underwent surgical extractions. In each case, one socket received CGF and the other served as a control. The predictor variable was the CGF application and the sides were categorized as ‘CGF’ and ‘non-CGF’. The outcome variable was the development of AO during the first postoperative week. Other study variables included age and gender. Data were analyzed using Cochran’s Q test with the significance level set at a P value less than 0.05.

Results

The overall frequency of AO was 11.4% for the control group. The frequency of AO in the CGF group was significantly lower than in the non-CGF group (p < 0.001).

Conclusions

Based on the results of this study, application of CGF fibrin gel may decrease the risk of AO development after mandibular third molar surgery.

Trial registration

This study was registered in ClinicalTrials.gov database on November 1, 2019 (ID: NCT04151147, retrospectively registered).
Theoretically designed interventions for colorectal cancer prevention: a case of the health belief model
Authors: Rakhshanderou Sakineh , Maghsoudloo Maryam , Safari-Moradabadi Ali , Ghaffari Mohtasham
Published: August 2020

Background

According to the WHO, most chronic diseases, including cancer, can be prevented by identifying their risk factors such as unhealthy diet, smoking and physical inactivity. This research examined the effectiveness of a theory-based educational intervention on colorectal cancer-related preventive nutritional behaviors among a sample of organizational staff.

Methods

In this interventional study, 110 employees of Shahid Beheshti University of Medical Sciences were randomly divided into two groups (intervention and control) with cluster sampling. The data gathering tool was a researcher-made questionnaire containing two parts of 10-dimensional information and health belief model constructs. The educational intervention was conducted for 1 month and in four sessions in the form of classroom lecture, pamphlet, educational text messages via mobile phones and educational pamphlets through the office automation system. Two groups were evaluated in two stages, pre-test and post-test. Data were analyzed using SPSS-18 software, analysis of Covariance (ANCOVA) and independent t-test (intergroup comparisons).

Results

Two groups were evaluated for variables such as age, sex, education level and family history of colorectal cancer, and there was no significant difference between the two groups (P < 0.05). After the 2 months since intervention, except for the mean score of perceived barriers, which was not significant after intervention, the mean scores of knowledge, perceived susceptibility, perceived severity, perceived benefits, perceived self-efficacy, behavioral intention, and preventive behaviors were significantly increased after the intervention in the intervention group compared to the control group (P > 0.05).

Conclusion

Implementation of educational intervention based on health belief model was effective for the personnel, and can enhance the preventative nutritional behaviors related to colorectal cancer.
Referrals to a pediatric emergency department of a tertiary care teaching hospital before and after introduction of a referral education module - a quality improvement study
Authors: Ezhumalai Gopalakrishnan , Jayashree Muralidharan , Nallasamy Karthi , Bansal Arun , Bharti Bhavneet
Published: August 2020

Background

Provision of timely care to critically ill children is essential for good outcome. Referral from smaller peripheral hospitals to higher centers for intensive care is common. However, lack of an organized referral and feedback system compromises optimal care. We studied the quality of referral letters coming to our Emergency Department (ED) with respect to their demography, association with severity of illness and mortality before and after referral education.

Methods

Our study was completed in three phases in the Pediatric ED; Pre-intervention, Intervention and Post intervention phases. Quality of referral letter was matched with a quality checklist proforma and graded as ‘good’, ‘fair’ and ‘poor’ if it scored > 7, 5–7 and < 5 points respectively. A peer reviewed referral education module was prepared using case studies, expert opinions, and lacunae observed in the first phase and administered to health care providers (HCP’s) of referring hospitals. Quality of referral letter was compared between pre and post intervention phases.

Results

Most referrals belonged to the neighboring states of Punjab (48.2%) and Haryana (22.4%). Major referring hospitals were from public sector (80.9%), of which the teaching hospitals topped the list (53.6%). Government run ambulance services (85.5%) was commonest mode of transport used and need for a PICU bed and/or mechanical ventilation (50.4%) was the commonest reason for referral. The post intervention phase saw a significant decline in the proportion of poor (93.2 vs.78.2%; p = 0.001) and a significant increase in the proportion of fair (6.1 vs 18%; p = 0.001) and good referral letters (0.7 vs 18%; p = 0.001). The proportion of children with physiological decompensation at triage had reduced significantly in the post intervention phase [513 out of 1403 (36.5%) vs. 310 out of 957 (32.3%); p = 0.001].

Conclusion

Referral education had significantly improved the quality of referral letters. Proportion of children with physiological decompensation at triage had decreased significantly after referral module. This change suggests sensitization of the peripheral hospitals towards a better referral process. Continued multifaceted approach will be required for sustained and increased benefits.
Epigenetic tuning of brain signal entropy in emergent human social behavior
Authors: Puglia Meghan H. , Krol Kathleen M. , Missana Manuela , Williams Cabell L. , Lillard Travis S. , Morris James P. , Connelly Jessica J. , Grossmann Tobias
Published: August 2020

Background

How the brain develops accurate models of the external world and generates appropriate behavioral responses is a vital question of widespread multidisciplinary interest. It is increasingly understood that brain signal variability—posited to enhance perception, facilitate flexible cognitive representations, and improve behavioral outcomes—plays an important role in neural and cognitive development. The ability to perceive, interpret, and respond to complex and dynamic social information is particularly critical for the development of adaptive learning and behavior. Social perception relies on oxytocin-regulated neural networks that emerge early in development.

Methods

We tested the hypothesis that individual differences in the endogenous oxytocinergic system early in life may influence social behavioral outcomes by regulating variability in brain signaling during social perception. In study 1, 55 infants provided a saliva sample at 5 months of age for analysis of individual differences in the oxytocinergic system and underwent electroencephalography (EEG) while listening to human vocalizations at 8 months of age for the assessment of brain signal variability. Infant behavior was assessed via parental report. In study 2, 60 infants provided a saliva sample and underwent EEG while viewing faces and objects and listening to human speech and water sounds at 4 months of age. Infant behavior was assessed via parental report and eye tracking.

Results

We show in two independent infant samples that increased brain signal entropy during social perception is in part explained by an epigenetic modification to the oxytocin receptor gene (OXTR) and accounts for significant individual differences in social behavior in the first year of life. These results are measure-, context-, and modality-specific: entropy, not standard deviation, linksOXTRmethylation and infant behavior; entropy evoked during social perception specifically explains social behavior only; and only entropy evoked during social auditory perception predicts infant vocalization behavior.

Conclusions

Demonstrating these associations in infancy is critical for elucidating the neurobiological mechanisms accounting for individual differences in cognition and behavior relevant to neurodevelopmental disorders. Our results suggest that an epigenetic modification to the oxytocin receptor gene and brain signal entropy are useful indicators of social development and may hold potential diagnostic, therapeutic, and prognostic value.
Non-invasive sampling in Itatiaia National Park, Brazil: wild mammal parasite detection
Authors: Dib Laís Verdan , Palmer João Pedro Siqueira , de Souza Carvalho Class Camila , Pinheiro Jessica Lima , Ramos Raissa Cristina Ferreira , dos Santos Claudijane Ramos , Fonseca Ana Beatriz Monteiro , Rodríguez-Castro Karen Gisele , Gonçalves Camila Francisco , Galetti Pedro Manoel , Bastos Otilio Machado Pereira , Uchôa Claudia Maria Antunes , Corrêa Laís Lisboa , Bastos Augusto Cezar Machado Pereira , Amendoeira Maria Regina Reis , da Silva Barbosa Alynne
Published: August 2020

Background

Non-invasive sampling through faecal collection is one of the most cost-effective alternatives for monitoring of free-living wild mammals, as it provides information on animal taxonomy as well as the dynamics of the gastrointestinal parasites that potentially infect these animals. In this context, this study aimed to perform an epidemiological survey of gastrointestinal parasites using non-invasive faecal samples from carnivores and artiodactyls identified by stool macroscopy, guard hair morphology and DNA sequencing in Itatiaia National Park. Between 2017 and 2018, faeces from carnivores and artiodactyls were collected along trails in the park. The host species were identified through macroscopic and trichological examinations and molecular biology. To investigate the parasites, the Faust, Lutz and modified Ritchie and Sheather techniques and enzyme immunoassays to detectCryptosporidiumsp. antigens were used.

Results

A total of 244 stool samples were collected. The species identified wereChrysocyon brachyurus,Leopardus guttulus,Canis familiaris,Cerdocyon thous,Puma yagouaroundi,Leopardus pardalis,Puma concolorandSus scrofa. There were 81.1% samples that were positive for parasites distributed mainly in the high part of the park. Helminths, especially eggs of the family Ascarididae, were more frequently detected in carnivore faeces (70.9%). Protozoa, especiallyCryptosporidiumsp., represented the highest frequency of infection in artiodactyl faeces (87.1%). This zoonotic protozoon was detected in eight mammalian species, including in a wild boar. High values of structural richness and Shannon and Simpson diversity indices were observed for the parasites, especially in the faeces ofC. brachyurus. Significant differences in parasite diversity were observed between wild and domestic animals, such asC. brachyurusandC. familiaris, respectively, and between taxonomically distant species, such asC. brachyurusandS. scrofa. The highest values for parasite similarity were found among the species that frequented similar areas of the park, such asC. brachyurusandL. guttulus.

Conclusions

The animals and parasite infections were identified through the combination of three techniques. High frequency parasite structures were diagnosed. Zoonotic protozoa were found and mainly occurred in samples from introduced species.
Amino acid-dependent control of mTORC1 signaling: a variety of regulatory modes
Authors: Takahara Terunao , Amemiya Yuna , Sugiyama Risa , Maki Masatoshi , Shibata Hideki
Published: August 2020

The mechanistic target of rapamycin complex 1 (mTORC1) is an essential regulator of cell growth and metabolism through the modulation of protein and lipid synthesis, lysosome biogenesis, and autophagy. The activity of mTORC1 is dynamically regulated by several environmental cues, including amino acid availability, growth factors, energy levels, and stresses, to coordinate cellular status with environmental conditions. Dysregulation of mTORC1 activity is closely associated with various diseases, including diabetes, cancer, and neurodegenerative disorders. The discovery of Rag GTPases has greatly expanded our understanding of the regulation of mTORC1 activity by amino acids, especially leucine and arginine. In addition to Rag GTPases, other factors that also contribute to the modulation of mTORC1 activity have been identified. In this review, we discuss the mechanisms of regulation of mTORC1 activity by particular amino acids.
Pericardial fat and its influence on cardiac diastolic function
Authors: de Wit-Verheggen Vera H. W. , Altintas Sibel , Spee Romy J. M. , Mihl Casper , van Kuijk Sander M. J. , Wildberger Joachim E. , Schrauwen-Hinderling Vera B. , Kietselaer Bas L. J. H. , van de Weijer Tineke
Published: August 2020

Background

Pericardial fat (PF) has been suggested to directly act on cardiomyocytes, leading to diastolic dysfunction. The aim of this study was to investigate whether a higher PF volume is associated with a lower diastolic function in healthy subjects.

Methods

254 adults (40–70 years, BMI 18–35 kg/m2, normal left ventricular ejection fraction), with (a)typical chest pain (otherwise healthy) from the cardiology outpatient clinic were retrospectively included in this study. All patients underwent a coronary computed tomographic angiography for the measurement of pericardial fat volume, as well as a transthoracic echocardiography for the assessment of diastolic function parameters. To assess the independent association of PF and diastolic function parameters, multivariable linear regression analysis was performed. To maximize differences in PF volume, the group was divided in low (lowest quartile of both sexes) and high (highest quartile of both sexes) PF volume. Multivariable binary logistic analysis was used to study the associations within the groups between PF and diastolic function, adjusted for age, BMI, and sex.

Results

Significant associations for all four diastolic parameters with the PF volume were found after adjusting for BMI, age, and sex. In addition, subjects with high pericardial fat had a reduced left atrial volume index (p = 0.02), lower E/e (p < 0.01) and E/A (p = 0.01), reduced e′ lateral (p < 0.01), reduced e′ septal p = 0.03), compared to subjects with low pericardial fat.

Conclusion

These findings confirm that pericardial fat volume, even in healthy subjects with normal cardiac function, is associated with diastolic function. Our results suggest that the mechanical effects of PF may limit the distensibility of the heart and thereby directly contribute to diastolic dysfunction.

Trial registration NCT01671930
High-intensity interval training and health-related quality of life in de novo heart transplant recipients – results from a randomized controlled trial
Authors: Rolid Katrine , Andreassen Arne K. , Yardley Marianne , Gude Einar , Bjørkelund Elisabeth , Authen Anne R. , Grov Ingelin , Pettersen Kjell I. , Dall Christian H. , Karason Kristjan , Broch Kaspar , Gullestad Lars , Nytrøen Kari
Published: August 2020

Background

Studies on the effect of high-intensity interval training (HIT) compared with moderate intensity continuous training (MICT) on health-related quality of life (HRQoL) after heart transplantation (HTx) is scarce. No available studies among de novo HTx recipients exists. This study aimed to investigate the effect of HIT vs. MICT on HRQoL in de novo recipients.

Methods

The HITTS study randomized eighty-one de novo HTx recipients to receive either HIT or MICT (1:1). The HIT intervention were performed with 2–4 interval bouts with an intensity of 85–95% of maximal effort. The MICT group exercised at an intensity of 60–80% of their maximal effort with a duration of 25 min. HRQoL was assessed by the Short Form-36 version 2 (SF-36v2) and the Hospital Anxiety and Depression Scale, mean 11 weeks after surgery and after a nine months’ intervention. The participants recorded their subjective effect of the interventions on their general health and well-being on a numeric visual analogue scale. Clinical examinations and physical tests were performed. Differences between groups were investigated with independent Student t-tests and with Mann-Whitney U tests where appropriate. Within-group differences were analyzed with Paired-Sample t-tests and Wilcoxon Signed Rank tests. Correlations between SF-36 scores and VO2peak were examined with Pearson’s correlations.

Results

Seventy-eight participants completed the intervention. Both exercise modes were associated with improved exercise capacity on the physical function scores of HRQoL. Mental health scores remained unchanged. No differences in the change in HRQoL between the groups occurred except for Role Emotional subscale with a larger increase in the HIT arm. Better self-reported physical function was associated with higher VO2peak and muscle strength.

Conclusion

HIT and MICT resulted in similar mean changes in HRQoL the first year after HTx. Both groups experienced significant improvements in the physical SF-36v2.

Trial registration

ClinicalTrials.gov number: NCT01796379 Registered 18 February 2013.
Cowden syndrome is a risk factor for multiple neoplasm: a case report
Authors: Miguelote Sofia , Silva Roberto , Fougo J. L. , Barbosa L. E. , Araújo Teixeira J. P.
Published: August 2020

Background

Cowden’s syndrome is an autosomal dominant disease with variable penetrance, involving the tumor suppressor phosphatase and tension homolog gene, located on chromosome 10q22-23, responsible for cell proliferation, migration, and cellular apoptosis. Its clinical presentation encompasses mucocutaneous lesions, which are present around 99% of the time; macrocephaly; and cognitive impairment, and it precedes the appearance of neoplasms such as thyroid carcinoma, breast cancer, among others.

In addition to these malformations, arteriovenous malformations of the brain and spine, endocrine abnormalities, skeletal defects, and cardiopulmonary lesions may also be found.

The relevance of the case is due to the fact that, through a certain phenotype, the patient’s genotype can be inferred and thus followed up closely.

Case representation

The clinical case concerns a 28-year-old Caucasian and Portuguese woman with palmar pits, macrocephaly, and cognitive impairment. She was diagnosed with papillary thyroid carcinoma at 22 years of age and proposed total thyroidectomy.

At age 27, a pregnancy was diagnosed with a Breast Imaging-Reporting and Data System 2-rated breast lump. After the histological verification, it was concluded that it was a high metastatic breast sarcoma, opting for palliative mastectomy. A genetic evaluation confirmed alteration in the phosphatase and tension homolog gene, confirming Cowden’s syndrome. The patient died at age 29 due to neoplastic pathology.

Conclusion

This report aims to alert to the clinical signs of this entity and the clinical supervision and follow-up of these patients. In order to prevent premature deaths and to improve patient’s quality of life, genetic diseases with cancer impact should be diagnosed as early as possible.
Effects of the KEIGAAF intervention on the BMI z-score and energy balance-related behaviors of primary school-aged children
Authors: Verjans-Janssen Sacha R. B. , Gerards Sanne M. P. L. , Kremers Stef P. J. , Vos Steven B. , Jansen Maria W. J. , Van Kann Dave H. H.
Published: August 2020

The aim of the current study was to evaluate the one- and two-year effectiveness of the KEIGAAF intervention, a school-based mutual adaptation intervention, on the BMI z-score (primary outcome), and energy balance-related behaviors (secondary outcomes) of children aged 7–10 years.

A quasi-experimental study was conducted including eight intervention schools and three control schools located in low socioeconomic neighborhoods in the Netherlands. Baseline measurements were conducted in March and April 2017 and repeated after one and 2 years. Data were collected on children’s BMI z-score, sedentary behavior (SB), physical activity (PA) behavior, and nutrition behavior through the use of anthropometric measurements, accelerometers, and questionnaires, respectively. All data were supplemented with demographics, and weather conditions data was added to the PA data. Based on the comprehensiveness of implemented physical activities, intervention schools were divided into schools having a comprehensive PA approach and schools having a less comprehensive approach. Intervention effects on continuous outcomes were analyzed using multiple linear mixed models and on binary outcome measures using generalized estimating equations. Intervention and control schools were compared, as well as comprehensive PA schools, less comprehensive PA schools, and control schools. Effect sizes (Cohen’s d) were calculated.

In total, 523 children participated. Children were on average 8.5 years old and 54% were girls. After 2 years, intervention children’s BMI z-score decreased (B = -0.05, 95% CI -0.11;0.01) significantly compared to the control group (B = 0.20, 95% CI 0.09;0.31). Additionally, the intervention prevented an age-related decline in moderate-to-vigorous PA (MVPA) (%MVPA: B = 0.95, 95% CI 0.13;1.76). Negative intervention effects were seen on sugar-sweetened beverages and water consumption at school, due to larger favorable changes in the control group compared to the intervention group. After 2 years, the comprehensive PA schools showed more favorable effects on BMI z-score, SB, and MVPA compared to the other two conditions.

This study shows that the KEIGAAF intervention is effective in improving children’s MVPA during school days and BMI z-score, especially in vulnerable children. Additionally, we advocate the implementation of a comprehensive approach to promote a healthy weight status, to stimulate children’s PA levels, and to prevent children from spending excessive time on sedentary behaviors.

Trial registration

Netherlands Trial Register, NTR6716 (NL6528), Registered 27 June 2017 – retrospectively registered.
Cortical priming strategies for gait training after stroke: a controlled, stratified trial
Authors: Madhavan Sangeetha , Cleland Brice T. , Sivaramakrishnan Anjali , Freels Sally , Lim Hyosok , Testai Fernando D. , Corcos Daniel M.
Published: August 2020

Background

Stroke survivors experience chronic gait impairments, so rehabilitation has focused on restoring ambulatory capacity. High-intensity speed-based treadmill training (HISTT) is one form of walking rehabilitation that can improve walking, but its effectiveness has not been thoroughly investigated. Additionally, cortical priming with transcranial direct current stimulation (tDCS) and movement may enhance HISTT-induced improvements in walking, but there have been no systematic investigations. The objective of this study was to determine if motor priming can augment the effects of HISTT on walking in chronic stroke survivors.

Methods

Eighty-one chronic stroke survivors participated in a controlled trial with stratification into four groups: 1) control–15 min of rest (n = 20), 2) tDCS–15 min of stimulation-based priming with transcranial direct current stimulation (n = 21), 3) ankle motor tracking (AMT)–15 min of movement-based priming with targeted movements of the ankle and sham tDCS (n = 20), and 4) tDCS+AMT–15 min of concurrent tDCS and AMT (n = 20). Participants performed 12 sessions of HISTT (40 min/day, 3 days/week, 4 weeks). Primary outcome measure was walking speed. Secondary outcome measures included corticomotor excitability (CME). Outcomes were measured at pre, post, and 3-month follow-up assessments.

Results

HISTT improved walking speed for all groups, which was partially maintained 3 months after training. No significant difference in walking speed was seen between groups. The tDCS+AMT group demonstrated greater changes in CME than other groups. Individuals who demonstrated up-regulation of CME after tDCS increased walking speed more than down-regulators.

Conclusions

Our results support the effectiveness of HISTT to improve walking; however, motor priming did not lead to additional improvements. Upregulation of CME in the tDCS+AMT group supports a potential role for priming in enhancing neural plasticity. Greater changes in walking were seen in tDCS up-regulators, suggesting that responsiveness to tDCS might play an important role in determining the capacity to respond to priming and HISTT.

Trial registration

ClinicalTrials.gov, NCT03492229. Registered 10 April 2018 – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03492229.
Iodine nutrition status and its association with microvascular complications in urban dwellers with type 2 diabetes
Authors: Chen Chi , Chen Yi , Zhai Hualing , Xia Fangzhen , Han Bing , Zhang Wen , Wang Yuying , Wan Heng , Wang Ningjian , Lu Yingli
Published: August 2020

Background

The principal function of iodine acts on thyroid function, but in recent years, the role of iodine deficiency in metabolism has also been gradually revealed. We aimed to investigate the current status of iodized salt consumption and urinary iodine concentration (UIC) in an urban Chinese population with type 2 diabetes, and to further explore whether UIC was associated with diabetic microvascular complications.

Methods

Four thousand five hundred fifty-nine subjects with diabetes from 7 communities in downtown Shanghai were enrolled in the cross-sectional Metal Study in 2018. UIC was detected using an inductively coupled plasma-mass spectrometer. Diabetic kidney disease (DKD) was defined as urinary albumin-to-creatinine ratio (UACR) > 30 mg/g or estimated glomerular filtration rate < 60 mL/min/1.73 m2. Diabetic retinopathy (DR) was evaluated by high-quality fundus photographs and was remotely read by ophthalmologist.

Results

The median UIC of subjects with diabetes was 115.4 μg/L (78.9–170.8) in downtown Shanghai. Among all the subjects, 52.7% consumed non-iodized salt and 40.4% were iodine deficient. Iodine deficiency (UIC < 100 μg/L) was associated with an increased odds of DKD (OR 1.17; 95%CI 1.01–1.37) after adjustment for age, sex, education, current smokers, BMI, HbA1c, duration of diabetes, dyslipidemia, thyroid-stimulating hormone and free thyroxine. No association was observed between UIC and DR after multivariable adjustment.

Conclusions

A concerning number of subjects with diabetes consumed non-iodized salt and suffered from iodine deficiency in coastal regions of China. Low UIC might be a risk factor for DKD, which should be further confirmed by longitudinal prospective studies.
Biomechanical analysis of fibular graft techniques for nontraumatic osteonecrosis of the femoral head: a finite element analysis
Authors: Xu Jian , Zhan Shi , Ling Ming , Jiang Dajun , Hu Hai , Sheng Jiagen , Zhang Changqing
Published: August 2020

Background

Free vascularized fibula graft (FVFG) techniques have most consistently demonstrated beneficial effects in young patients diagnosed with nontraumatic osteonecrosis of the femoral head (NONFH), and the core track technique (CTT) in particular is the most commonly used technique. As an alternative to CTT, the modified light bulb technique (LBT) has been reported to have a higher success rate. However, its biomechanical outcomes are poorly understood. This study aimed to compare the biomechanical properties of modified LBT with those of CTT in treating NONFH.

Methods

Two types (C1 and C2) of NONFH finite element models were established on the basis of a healthy subject and the Japanese Investigation Committee (JIC) classification system, and the CTT and LBT procedures were simulated in each type of model. The average von Mises stresses and stiffness of the proximal femur were calculated by applying a load of 250% of the body weight on the femoral head to simulate walking conditions. In addition, two patient-specific models were built and simulated under the same boundary conditions to further validate the LBT.

Results

In the healthy subject-derived models, both the LBT and CTT resulted in reduced stresses in the weight-bearing area, central femoral head, femoral neck, and trochanteric and subtrochanteric regions and increased structural stiffness after surgery. In the weight-bearing area, the CTT reduced the stress more than the LBT did (36.19% vs 31.45%) for type C1 NONFH and less than the LBT did (23.63% vs 26.76%) for type C2 NONFH. In the patient-specific models, the stiffness and stresses also increased and decreased, respectively, from before to after surgery, which is consistent with the results of healthy subject-derived models.

Conclusion

The biomechanical effects of the LBT and CTT differ by the JIC type of NONFH. In terms of preventing the collapse of the femoral head, the LBT may be more effective for JIC type C2 NONFH and may be a suitable alternative to the CTT, while for JIC type C1 NONFH, the CTT is still a better choice. Both techniques can improve the biomechanical properties of NONFH by reducing the proximal femoral stress and increasing the structural stiffness.
Correction to: Probiotics’ efficacy in paediatric diseases: which is the evidence? A critical review on behalf of the Italian Society of Pediatrics
Authors: Martinelli Massimo , Banderali Giuseppe , Bobbio Marisa , Civardi Elisa , Chiara Alberto , D’Elios Sofia , Lo Vecchio Andrea , Olivero Mattia , Peroni Diego , Romano Claudio , Stronati Mauro , Turra Renato , Viola Irene , Staiano Annamaria , Villani Alberto
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Correction to: PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas
Authors: Noorani Imran , de la Rosa Jorge , Choi Yoon Ha , Strong Alexander , Ponstingl Hannes , Vijayabaskar M. S. , Lee Jusung , Lee Eunmin , Richard-Londt Angela , Friedrich Mathias , Furlanetto Federica , Fuente Rocio , Banerjee Ruby , Yang Fengtang , Law Frances , Watts Colin , Rad Roland , Vassiliou George , Kim Jong Kyoung , Santarius Thomas , Brandner Sebastian , Bradley Allan
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
The efficacy of ball blankets on insomnia in depression in outpatient clinics: study protocol for a randomized crossover multicentre trial
Authors: Kristiansen Sanne Toft , Videbech Poul , Bjerrum Merete Bender , Larsen Erik Roj
Published: August 2020

Background

Depression affects approx. 4% of the global population and is often accompanied by insomnia. Medications used to treat insomnia can have side effects such as development of tolerance and addiction. The Protac Ball Blanket™ (PBB) is a non-pharmacological supplement to sedatives and hypnotics, but evidence for the efficacy of PBB is needed before the treatment is implemented. The objective of this trial is to test the efficacy of PBB on insomnia caused by depression in a randomized controlled design.

Methods

This study is a multicentre, randomized crossover trial with planned inclusion of 45 patients. The randomization procedure is permuted-block randomization with varying block sizes. Patients are allocated into either a sequence “AB” or “BA” each lasting 4 weeks (28 nights). Patients randomized to the “AB” sequence receive treatment A (Protac Ball Blanket™) in the first 2 weeks and switch to treatment B (treatment as usual) in the second period, whereas patients who are randomized to the BA sequence receive treatment B in the first period and treatment A in the second period. The participants will serve as their own control in this design. The primary outcome is changes in total sleep time. Secondary outcome measures are changes in sleep onset latency, number of awakenings, wake after sleep onset, and use of sedatives and hypnotics. Furthermore, quality of sleep, insomnia severity status, and self-reported symptoms of depression, anxiety, interpersonal sensitivity, and neurasthenia will be measured. A paired, two-sided t test to compare the means of the differences in the outcomes will be performed.

Discussion

This clinical trial will assess the effect of PBB on depression-related insomnia. The outcomes are of high interest as the PBB is a potential non-pharmacological supplement to medical treatment of patients with insomnia due to depression.

Trial registration

ClinicalTrials.gov Identifier: NCT03730974. Registered on 5 November 2018.
An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial
Authors: Randremanana Rindra Vatosoa , Raberahona Mihaja , Randria Mamy Jean de Dieu , Rajerison Minoarisoa , Andrianaivoarimanana Voahangy , Legrand Agathe , Rasoanaivo Tsinjo Fehizoro , Randriamparany Ravaka , Mayouya-Gamana Théodora , Mangahasimbola Reziky , Bourner Josie , Salam Alex , Gillesen Annelies , Edwards Tansy , Schoenhals Matthieu , Baril Laurence , Horby Peter , Olliaro Piero
Published: August 2020

Background

Bubonic plague is the primary manifestation of infection with Yersinia pestis, accounting for 90% of all plague cases and with 75% of global cases reported in Madagascar. All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The IMASOY trial intends to fill this knowledge gap by comparing two 10-day regimens included in the national guidelines in Madagascar. The primary objective of the trial is to test the hypothesis that ciprofloxacin monotherapy is non-inferior to streptomycin followed by ciprofloxacin for the treatment of bubonic plague, thus avoiding the need for injectable, potentially toxic, aminoglycosides.

Methods

A two-arm parallel-group randomized control trial will be conducted across peripheral health centres in Madagascar in five districts. Males and non-pregnant females of all ages with suspected bubonic or pneumonic plague will be recruited over the course of three plague ‘seasons’. The primary endpoint of the trial is to assess the proportion of patients with bubonic plague who have a therapeutic response to treatment (defined as alive, resolution of fever, 25% reduction in the size of measurable buboes, has not received an alternative treatment and no clinical decision to continue antibiotics) as assessed on day 11.

Discussion

If successful, the trial has the potential to inform the standard of care guidelines not just in Madagascar but in other countries afflicted by plague. The trial is currently ongoing and expected to complete recruitment in 2022.

Trial registration

ClinicalTrials.gov NCT04110340. Registered on 1 October 2019
Levobupivacaine inhibits proliferation and promotes apoptosis of breast cancer cells by suppressing the PI3K/Akt/mTOR signalling pathway
Authors: Kwakye Akosua Kotaa , Kampo Sylvanus , Lv Jiaxin , Ramzan Muhammad Noman , Richard Seidu A. , Falagán Aglais Arredondo , Agudogo Jerry , Atito-Narh Evans , Yan Qiu , Wen Qing-Ping
Published: August 2020

Objective

This study aimed to test the hypothesis that levobupivacaine has anti-tumour effects on breast cancer cells.

Results

Colony formation and transwell assay were used to determine breast cancer cells proliferation. Flow Cytometry (annexin V and PI staining) was used to investigate breast cancer cells apoptosis. The effects of levobupivacaine on cellular signalling and molecular response were studied with Quantitative Polymerase Chain Reaction and western blot. Induction of apoptosis was confirmed by cell viability, morphological changes showed cell shrinkage, rounding, and detachments from plates. The results of the western blot and Quantitative Polymerase Chain Reaction indicated activation of active caspase-3 and inhibition of FOXO1. The results of the flow Cytometry confirmed that levobupivacaine inhibited breast cancer cell proliferation and enhanced apoptosis of breast cancer cells. Quantitative Polymerase Chain Reaction and Western blot analysis showed increased p21 and decreased cyclin D. Quantitative Polymerase Chain Reaction and western blot analysis showed that levobupivacaine significantly increased Bax expression, accompanied by a significant decreased Bcl-2 expression and inhibition of PI3K/Akt/mTOR signalling pathway. These findings suggested that levobupivacaine inhibits proliferation and promotes breast cancer cells apoptosis in vitro.
Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B
Authors: Perets N. , Oron O. , Herman S. , Elliott E. , Offen D.
Published: August 2020

Background

Partial or an entire deletion of SHANK3 are considered as major drivers in the Phelan–McDermid syndrome, in which 75% of patients are diagnosed with autism spectrum disorder (ASD). During the recent years, there was an increasing interest in stem cell therapy in ASD, and specifically, mesenchymal stem cells (MSC). Moreover, it has been suggested that the therapeutic effect of the MSC is mediated mainly via the secretion of small extracellular vesicle that contains important molecular information of the cell and are used for cell-to-cell communication. Within the fraction of the extracellular vesicles, exosomes were highlighted as the most effective ones to convey the therapeutic effect.

Methods

Exosomes derived from MSC (MSC-exo) were purified, characterized, and given via intranasal administration to Shank3B KO mice (in the concentration of 107 particles/ml). Three weeks post treatment, the mice were tested for behavioral scoring, and their results were compared with saline-treated control and their wild-type littermates.

Results

Intranasal treatment with MSC-exo improves the social behavior deficit in multiple paradigms, increases vocalization, and reduces repetitive behaviors. We also observed an increase of GABARB1 in the prefrontal cortex.

Conclusions

Herein, we hypothesized that MSC-exo would have a direct beneficial effect on the behavioral autistic-like phenotype of the genetically modified Shank3B KO mouse model of autism. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of this mouse model of autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation.
The value of 2D speckle-tracking strain echocardiography in evaluating the relationship between carotid elasticity and left ventricular systolic function in patients with diabetic nephropathy
Authors: Li Xiuyun , Kou Hongju , Dong Yanyan , Zheng Chao , Wang Pengfei , Xu Maosheng , Zou Chunpeng , Wang Liang
Published: August 2020

Objective

To investigate the relationship between the elasticity of the carotid artery and the LV (left ventricle) systolic function in patients with diabetic nephropathy (DN) by using two-dimensional speckle-tracking strain echocardiography (2D-STE).

Methods

DN patients (n = 108) and control subjects (n = 112), all of whom underwent echocardiography and carotid ultrasound. Analysis of LV GLS (global longitudinal strain) from the apical two-chamber (2C), three-chamber (3C), and four-chamber (4C) views. Meanwhile, the circumferential strain (CS) of the carotid artery was obtained from the view of the short-axis right common carotid artery. The differences between the two groups were compared, and a correlation analysis between CS and GLS was performed.

Results

The 4CGLS, 2CGLS, 3CGLS, and CS of the DN group were significantly lower at significant levels in contrast to the control group (p < 0.05). There was a significantly positive correlation of CS with 4CGLS, 2CGLS, and 3CGLS in all subjects (r = 0.809, p = 0.000; r = 0.830, p = 0.000; r = 0.830, p = 0.000, respectively).

Conclusion

2D-STE is a relatively new technique for assessing the mechanical characteristics of the carotid artery in patients with DN. Reduced values of CS correlate with reduced LV systolic function as evaluated by strain measurements, which can predict the risk of systolic dysfunction of LV.
Traumatic and non-traumatic bone marrow edema in ankle MRI: a pictorial essay
Authors: Szaro Pawel , Geijer Mats , Solidakis Nektarios
Published: August 2020

Bone marrow edema (BME) is one of the most common findings on magnetic resonance imaging (MRI) after an ankle injury but can be present even without a history of trauma. This article will provide a systematic overview of the most common disorders in the ankle and foot associated with BME.

The presence of BME is an unspecific but sensitive sign of primary pathology and may act as a guide to correct and systematic interpretation of the MR examination. The distribution of BME allows for a determination of the trauma mechanism and a correct assessment of soft tissue injury. The BME pattern following an inversion injury involves the lateral malleolus, the medial part of the talar body, and the medial part of the distal tibia. In other cases, a consideration of the distribution of BME may indicate the mechanism of injury or impingement. Bone in direct contact with a tendon may lead to alterations in the bone marrow signal where BME may indicate tendinopathy or dynamic tendon dysfunction. Changed mechanical forces between bones in coalition may lead to BME. Degenerative changes or minor cartilage damage may lead to subchondral BME. Early avascular necrosis, inflammation, or stress fracture may lead to more diffuse BME; therefore, a detailed medical history is crucial for correct diagnosis.

A systematic analysis of BME on MRI can help to determine the trauma mechanism and thus assess soft tissue injuries and help to differentiate between different etiologies of nontraumatic BME.
A transcriptomic analysis of serial-cultured, tonsil-derived mesenchymal stem cells reveals decreased integrin α3 protein as a potential biomarker of senescent cells
Authors: Choi Da Hyeon , Oh Se-Young , Choi Ju Kwang , Lee Kyeong Eun , Lee Ju Yeon , Park Yoon Jeong , Jo Inho , Park Yoon Shin
Published: August 2020

Background

Mesenchymal stem cells (MSCs) have been widely used for stem cell therapy, and serial passage of stem cells is often required to obtain sufficient cell numbers for practical applications in regenerative medicine. A long-term serial cell expansion can potentially induce replicative senescence, which leads to a progressive decline in stem cell function and stemness, losing multipotent characteristics. To improve the therapeutic efficiency of stem cell therapy, it would be important to identify specific biomarkers for senescent cells.

Methods

Tonsil-derived mesenchymal stem cells (TMSCs) with 20–25 passages were designated as culture-aged TMSCs, and their mesodermal differentiation potentials as well as markers of senescence and stemness were compared with the control TMSCs passaged up to 8 times at the most (designated as young). A whole-genome analysis was used to identify novel regulatory factors that distinguish between the culture-aged and control TMSCs. The identified markers of replicative senescence were validated using Western blot analyses.

Results

The culture-aged TMSCs showed longer doubling time compared to control TMSCs and had higher expression of senescence-associated (SA)-β-gal staining but lower expression of the stemness protein markers, including Nanog, Oct4, and Sox2 with decreased adipogenic, osteogenic, and chondrogenic differentiation potentials. Microarray analyses identified a total of 18,614 differentially expressed genes between the culture-aged and control TMSCs. The differentially expressed genes were classified into the Gene Ontology categories of cellular component (CC), functional component (FC), and biological process (BP) using KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis. This analysis revealed that those genes associated with CC and BP showed the most significant difference between the culture-aged and control TMSCs. The genes related to extracellular matrix-receptor interactions were also shown to be significantly different (p < 0.001). We also found that culture-aged TMSCs had decreased expressions of integrin α3 (ITGA3) and phosphorylated AKT protein (p-AKT-Ser473) compared to the control TMSCs.

Conclusions

Our data suggest that activation of ECM-receptor signaling, specifically involved with integrin family-mediated activation of the intracellular cell survival-signaling molecule AKT, can regulate stem cell senescence in TMSCs. Among these identified factors, ITGA3 was found to be a representative biomarker of the senescent TMSCs. Exclusion of the TMSCs with the senescent TMSC markers in this study could potentially increase the therapeutic efficacy of TMSCs in clinical applications.