bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis-associated aplastic anemia from workout supplement: Rare but potentially fatal entity
Authors: Bastola Sanjog , Kc Ojbindra , Khanal Sumesh , Halalau Alexandra
Published: January 2020

Hepatitis-associated aplastic anemia (HAAA) is a rare clinical syndrome characterized by bone marrow failure 1–3 months after development of hepatitis. Untreated, hepatitis-associated aplastic anemia has poor outcome and the mainstay of treatment remains either bone marrow transplant or immunosuppressive therapy. A previously healthy 21-year-old man presented with a 1-week history of right upper quadrant pain and jaundice. Admission labs revealed mixed hyperbilirubinemia and elevated transaminases ranging in 2000s IU/dl. Extensive workup for etiologies of acute hepatitis including viruses, autoimmune, toxins etc. were negative. He admitted to taking “Dust V2,” a workout supplement, for 4 months prior to the presentation. His liver function tests started to improve after conservative treatment. Two months after his discharge, he was found to have severe pancytopenia on routine labs. Bone marrow biopsy revealed hypocellular marrow consistent with aplastic anemia. Extensive workup for etiologies of aplastic anemia were negative. On literature review, none of the components of the supplement were found to cause aplastic anemia. A diagnosis of hepatitis-associated aplastic anemia was made as there was a lag time before development of anemia. His counts failed to improve despite treatment with filgrastim and he was referred for hematopoietic cell transplant.
CT imaging of the Eustachian tube using focal contrast medium administration: a feasibility study in humans
Authors: Falkenberg-Jensen Benedicte , Jablonski Greg E , Silvola Juha T , Kristiansen Joanna F , Hopp Einar
Published: January 2020

Background

Several methods of imaging the Eustachian tube have been tested in the last century, although neither has led to an established method. The introduction of balloon Eustachian tuboplasty (BET) has revived the request for Eustachian tube (ET) visualization in patients with chronic Eustachian tube dysfunction. Many institutions perform preoperative computed tomography (CT) scans of the temporal bone and epipharynx before BET. Purpose We hypothesize that the injection of a contrast medium into the tympanic cavity is safe and feasible and can evolve the CT scan by visualizing the ET lumen and, potentially, the level of obstruction. This study is the initial feasibility study for such a human application. Material and Methods Ten minutes before a CT scan, diluted iodixanol was injected into the middle ear in 18 patients planned for BET due to otitis media with effusion. Five patients with Meniere’s disease were controls. Any immediate or delayed adverse events were recorded. Masking of adjacent bony structures in the middle ear on the CT images was evaluated and the most caudally visible contrast medium between the middle ear and epipharynx recorded. Results There were no serious adverse events. One patient reported transitory vertigo. The contrast medium did not mask middle ear structures, apart from the tympanic membrane. The level of contrast medium passage could be assessed. Conclusion Visualizing the ET lumen in humans using intratympanic contrast medium is feasible and safe and does not obscure other valuable image information in a preoperative CT scan.
Implementation and Evaluation of a Standardized Non–Vitamin K Oral Anticoagulant (NOAC) Patient Safety Alert Card Across the Northern Region of England
Authors: Thomas Honey , Smyth Louise
Published: January 2020

Many patients are prescribed anticoagulants. Newer non–vitamin K oral anticoagulants, NOACs, were launched in 2008 and are increasingly commonly used. However, they may still be unfamiliar to patients and health care professionals. It is mandated by the National Patient Safety Agency and European Society of Cardiology to provide written safety information for patients receiving anticoagulants. We developed a standard patient alert card with the support of the North of England Strategic Clinical network (NESCN) to clearly provide key safety information for patients and health care professionals. This is the only card in the United Kingdom that is used over such a wide geographical area. We recognized that this would avoid duplication of work devising a similar card across all the sites in primary and secondary care. Given that staff and patients commonly move about the region it would also lead to better ease of recognition. The NESCN card was developed with input from all the key stakeholders, including cardiology, stroke, hematology, acute medicine, primary care, and patient groups. It was launched in 2015 across the Northern region, which includes over 3 million people. It was distributed to general practitioners (GPs), primary and secondary care pharmacists. Electronic and face-to-face education was carried out alongside to pharmacists, GPs, and hospital physicians. We gathered patient and clinical staff feedback regarding the card and found the alert card was widely embedded within practice across the region and patient feedback was good. The evaluation shows a simple and inexpensive intervention delivered with no formal funding can address this patient safety concern. We have engaged with Clinical Commissioning Groups and secondary care trusts in the region to ensure the legacy of the project. In response to requests from other regions and organizations, the card has been widely shared and implemented across many areas of the United Kingdom.
A Prospective 2-Year Clinical Evaluation of Augmented Hip Abductor Tendon Repair
Authors: Ebert Jay R. , Brogan Kit , Janes Gregory C.
Published: January 2020

Background:

Hip abductor tendon (HAT) tearing is commonly implicated in greater trochanteric pain syndrome. Studies reporting surgical outcomes are often on small cohorts and with limited information on functional improvement.

Purpose:

To report the 2-year clinical and functional outcomes in a series of patients undergoing HAT repair augmented with a ligament augmentation and reconstruction system (LARS) ligament.

Study Design:

Case series; Level of evidence, 4.

Methods:

Between October 2012 and December 2016, a total of 142 patients with symptomatic HAT tears underwent open bursectomy, V-Y lengthening, and reattachment of the tendon with suture anchors augmented with a LARS ligament. This included 132 women (93%) with a mean age of 64.3 years (range, 43-84 years), a mean body mass index of 28.2 kg/m2 (range, 20.0-41.3 kg/m2), and an average duration of symptoms of 4.0 years (range, 6 months-20 years). Following surgery, patients underwent a graduated rehabilitation program consisting of hydrotherapy and land-based exercises. Patient-reported outcome measures (PROMs) were evaluated preoperatively and at 3, 6, 12, and 24 months postoperatively with the Harris Hip Score, Oxford Hip Score, 12-item Short Form Health Survey, and visual analog scale (VAS) for pain. Hip range of motion, hip abduction strength, 30-s single-leg stance (SLS), and 6-minute walk test (6MWT) capacity were evaluated. Patient satisfaction and perceived global rating of change were evaluated postsurgery. Analysis of variance was employed to evaluate clinical improvement over time.

Results:

A significant improvement ( P < .05) was demonstrated up to 24 months in all PROMs and clinical scores, including hip range of motion in all planes, hip abductor strength limb symmetry indices (mean ± SD; presurgery, 90.1% ± 42.5%; 24 months, 102.6% ± 15.0%), and the 6MWT (presurgery, 421.8 ± 91.9 m; 24 months, 509.7 ± 105.1 m). Furthermore, several variables, including pain (VAS and pain scores during the 6MWT and 30-s SLS) and patient-perceived improvement (global rating of change), continued to improve from 12 to 24 months. At 24 months, 95.7% of patients were satisfied with their surgical outcome (excluding 3 patients who underwent reoperation within the 24-month period). There was a 5.6% (n = 8) failure rate over the study period.

Conclusion:

HAT repair augmented with a synthetic ligament demonstrated significantly improved clinical and functional outcomes, high levels of patient satisfaction, and a relatively low failure rate up to 24 months postsurgery.

Registration:

ACTRN12616001655437 (Australian New Zealand Clinical Trials Registry).
Precommissural and postcommissural fornix microstructure in healthy aging and cognition
Authors: Coad Bethany M. , Craig Emma , Louch Rebecca , Aggleton John P. , Vann Seralynne D. , Metzler-Baddeley Claudia
Published: January 2020

The fornix is a key tract of the hippocampal formation, whose status is presumed to contribute to age-related cognitive decline. The precommissural and postcommissural fornix subdivisions form respective basal forebrain/frontal and diencephalic networks that may differentially affect aging and cognition. We employed multi-parametric magnetic resonance imaging (MRI) including neurite orientation density and dispersion imaging, quantitative magnetization transfer (qMT), and T1-relaxometry MRI to investigate the microstructural properties of these fornix subdivisions and their relationship with aging and cognition in 149 asymptomatic participants (38–71 years). Aging was associated with increased free water signal and reductions in myelin-sensitive R1and qMT indices but no apparent axon density differences in both precommissural and postcommissural fibers. Precommissural relative to postcommissural fibers showed a distinct microstructural pattern characterised by larger free water signal and axon orientation dispersion, with lower apparent myelin and axon density. Furthermore, differences in postcommissural microstructure were related to performance differences in object-location paired-associate learning. These results provide novel in vivo neuroimaging evidence for distinct microstructural properties of precommissural and postcommissural fibers that are consistent with their anatomy as found in axonal tracer studies, as well as for a contribution of postcommissural fibers to the learning of spatial configurations.
Changes in preoperative corneal measurements following same-day intraocular pressure testing with rebound tonometry
Authors: Beckman Kenneth A. , Luchs Jodi I. , Milner Mark S. , Yee Richard W.
Published: January 2020

Purpose:

To evaluate the extent to which rebound tonometry affects corneal surface properties and preoperative corneal measurements.

Setting:

Four cornea specialty private practices.

Design:

Prospective case series.

Methods:

Visual acuity testing, corneal topography, keratometry, and grading of corneal staining were performed on both eyes of 60 randomly selected, previously scheduled patients. Technicians then performed rebound tonometry on one randomly selected eye only. Immediately following, intraocular pressure measurement, corneal topography, keratometry, and corneal staining were repeated on both eyes.

Results:

None of the 60 study eyes developed increased staining scores following intraocular pressure testing with the Icare ic100. For corneal staining, mean keratometry, and total corneal cylinder, no statistically significant difference was found from the first measurement to the second measurement between the study eyes and control eyes.

Conclusion:

Rebound tonometry with the Icare ic100 may be used on any patient at any time during the exam without affecting the results of other tests, allowing clinicians to test intraocular pressure prior to preoperative cataract or refractive surgery measurements on the same day. This may allow for significant improvement in patient flow in the office and save patients from the cost and time of extra visits.
Double Morphology of Co9S8 Coated by N, S Co-doped Carbon as Efficient Anode Materials for Sodium-Ion Batteries
Authors: Zhang Xuzi , Shang Chaoqun , Wang Xin , Zhou Guofu
Published: January 2020

Co9S8 is a potential anode material for its high sodium storage performance, easy accessibility, and thermostability. However, the volume expansion is a great hindrance to its development. Herein, a composite containing Co9S8 nanofibers and hollow Co9S8 nanospheres with N, S co-doped carbon layer (Co9S8@NSC) is successfully synthesized through a facile solvothermal process and a high-temperature carbonization. Ascribed to the carbon coating and the large specific surface area, severe volume stress can be effectively alleviated. In particular, with N and S heteroatoms introduced into the carbon layer, which is conducive to the Na+ adsorption and diffusion on the carbon surface, Co9S8@NSC can perform more capacitive sodium storage mechanism. As a result, the electrode can exhibit a favorable reversible capacity of 226 mA h g−1 at 5 A g−1 and a favorable capacity retention of 83.1% at 1 A g−1 after 800 cycles. The unique design provides an innovative thought for enhancing the sodium storage performance.
CRISPR/Cas9-mediated precise genome modification by a long ssDNA template in zebrafish
Authors: Bai Haipeng , Liu Lijun , An Ke , Lu Xiaochan , Harrison Michael , Zhao Yanqiu , Yan Ruibin , Lu Zhijie , Li Song , Lin Shuo , Liang Fang , Qin Wei
Published: January 2020

Background

Gene targeting by homology-directed repair (HDR) can precisely edit the genome and is a versatile tool for biomedical research. However, the efficiency of HDR-based modification is still low in many model organisms including zebrafish. Recently, long single-stranded DNA (lssDNA) molecules have been developed as efficient alternative donor templates to mediate HDR for the generation of conditional mouse alleles. Here we report a method, zLOST (zebrafish long single-stranded DNA template), which utilises HDR with a long single-stranded DNA template to produce more efficient and precise mutations in zebrafish.

Results

The efficiency of knock-ins was assessed by phenotypic rescue at the tyrosinase (tyr) locus and confirmed by sequencing. zLOST was found to be a successful optimised rescue strategy: using zLOST containing a tyr repair site, we restored pigmentation in at least one melanocyte in close to 98% of albino tyr25del/25del embryos, although more than half of the larvae had only a small number of pigmented cells. Sequence analysis showed that there was precise HDR dependent repair of the tyr locus in these rescued pigmented embryos. Furthermore, quantification of zLOST knock-in efficiency at the rps14, nop56 and th loci by next generation sequencing demonstrated that zLOST showed a clear improvement. We utilised the HDR efficiency of zLOST to precisely model specific human disease mutations in zebrafish with ease. Finally, we determined that this method can achieve a germline transmission rate of up to 31.8%.

Conclusions

In summary, these results show that zLOST is a useful method of zebrafish genome editing, particularly for generating desired mutations by targeted DNA knock-in through HDR.
Carbonyl-protein content increases in brain and blood of female rats after chronic oxycodone treatment
Authors: Fan Ruping , Schrott Lisa M. , Snelling Stephen , Felty John , Graham Derrel , McGauly Patrick L. , Arnold Thomas , Korneeva Nadejda L.
Published: January 2020

Background

Opioids are the most effective drugs commonly prescribed to treat pain. Due to their addictive nature, opioid pain relievers are now second to marijuana, ahead of cocaine with respect to dependence. Ours and other studies suggest potential toxic effects of chronic opioid administration leading to neuronal degeneration. It has been suggested that protein carbonylation may represent a sensitive biomarker of cellular degeneration. To evaluate whether prolonged oxycodone administration is associated with accumulation of protein aggregates that may contribute to neuronal degeneration we measured protein carbonylation levels in brain and also in blood plasma of rats after 30-days of 15 mg/kg daily oxycodone administration.

Results

We observed a significant increase in the level of carbonylated proteins in rat brain cortex after 30-days of oxycodone treatment compare to that in water treated animals. Also, oxycodone treated rats demonstrated accumulation of insoluble carbonyl-protein aggregates in blood plasma.

Conclusions

Our data suggests that tests detecting insoluble carbonyl-protein aggregates in blood may serve as an inexpensive and minimally invasive method to monitor neuronal degeneration in patients with a history of chronic opioid use. Such methods could be used to detect toxic side effects of other medications and monitor progression of aging and neurodegenerative diseases.
Cryptococcal meningitis and immune reconstitution inflammatory syndrome in a pediatric patient with HIV after switching to second line antiretroviral therapy: a case report
Authors: Otto Ssegujja Boniface Joseph , George Paul E. , Mercedes Rebecca , Nabukeera-Barungi Nicolette
Published: January 2020

Background

Cryptococcal meningitis (CCM) is a common and deadly disease among HIV-infected patients. Notable about CCM is its association with the immune reconstitution inflammatory syndrome (IRIS). Though it has been posited a switch from first to second-line antiretroviral therapy (ART) can induce CCM IRIS, a case presentation of CCM IRIS has not been published.

Case presentation

A 10-year-old, HIV-infected girl who initially presented with severe headache and new-onset seizures, with cerebrospinal fluid that returned antigen, India Ink, and culture positive forCryptococcus neoformans. Notably, 8 weeks prior to seizures, she had switched from first line to second-line ART (abacavir-lamivudine-efavirenz to zidovudine-lamivudine-lopinavir/ritonavir) due to virologic failure, with a viral load of 224,000 copies/milliliter. At time of seizures and 8 weeks on second-line ART, her viral load had reduced to 262 copies/milliliter.

Her hospital course was prolonged, as she had ongoing headaches and developed bilateral cranial nerve VI palsies despite clearance ofCryptococcusfrom cerebrospinal fluid on antifungal therapy and therapeutic lumbar punctures. However, symptoms stabilized, and she was discharged with oral fluconazole. Cranial nerve palsies resolved 10 weeks post discharge and she has remained disease free.

Conclusions

We describe a case of CCM IRIS in a 10-year-old HIV infected child after changing to second-line ART. This case provides evidence that screening for cryptococcal antigenaemia prior to switch from first-line to second-line ART could be an important measure to prevent cryptococcal disease.
Thrombocytopenia and endocarditis in a patient with Whipple’s disease: case report
Authors: Olivier Maxim , Licitra Carmelo , Field Zachary , Ge Li , Hill Dustin , Madruga Mario , Carlan S. J.
Published: January 2020

Background

Whipple’s disease (WD) is a rare multisystem infectious disorder that is caused by the actinomycete Tropheryma whipplei. It presents with joint pain followed by abdominal pain, diarrhea, malabsorption and finally failure to thrive. Diagnosis requires tissue sampling and histology with periodic acid-Schiff [PAS] staining. Thrombocytopenia associated with endocarditis associated with WD has been reported twice.

Case presentation

A 56 year old Caucasian male presented with years of steroid treated joint pain and recent onset diarrhea, weight loss and abdominal pain. Ultimately he was found to have a platelet count of 4000 with concomitant endocarditis and embolic stroke. Small bowel biopsy confirmed the diagnosis of WD approximately 1 year after his first visit. His platelets improved with antibiotic treatment but he eventually expired 16 months after his initial consult and 5 months after his definitive diagnosis.

Conclusion

WD can remain undiagnosed and untreated until late in the course of the illness. A high index of suspicion is recognized as necessary for early diagnosis to begin treatment. Critical thrombocytopenia associated with endocarditis is a rare and potentially poor prognostic sign in late stage Whipple’s disease.
Systemic treatment of hormone receptor positive, human epidermal growth factor 2 negative metastatic breast cancer: retrospective analysis from Leeds Cancer Centre
Authors: Twelves Chris , Cheeseman Sue , Sopwith Will , Thompson Matthew , Riaz Majid , Ahat-Donker Necibe , Myland Melissa , Lee Adam , Przybysz Raymond , Turner Stuart , Hall Geoff , Perren Tim
Published: January 2020

Background

Study aimed to characterise treatment and outcomes for patients with hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (MBC) within a large regional cancer centre, as a benchmark for evaluating real-world impact of novel therapies.

Methods

Retrospective longitudinal cohort, using electronic patient records of adult females with a first diagnosis of HR+/HER2- MBC January 2012–March 2018.

Results

One hundred ninety-six women were identified with HR+/HER2- MBC. Median age was 67 years, 85.2% were post-menopausal and median time between primary diagnosis and metastasis was 5.4 years. Most (75.1%) patients received endocrine therapy as first line systemic treatment (1st LoT); use of 1st LoT chemotherapy halved between 2012 and 2017. Patients receiving 1st LoT chemotherapy were younger and more likely to have visceral metastasis (p < 0.01). Median OS was 29.5 months and significantly greater for patients with exclusively non-visceral metastasis (p < 0.01). The adjusted hazard ratio for death of patients with visceral (or CNS) metastasis was 1.91 relative to those with exclusively non-visceral metastasis.

Conclusions

Diverse endocrine therapies predominate as 1st LoT for patients with HR+/HER2- MBC, chemotherapy being associated with more aggressive disease in younger patients, emphasising the importance of using effective and tolerable therapies early.
Early intervention and follow-up programs among children with cerebral palsy in Moldova: potential impact on impairments?
Authors: Bufteac Ecaterina Gincota , Andersen Guro L. , Spinei Larisa , Jahnsen Reidun Birgitta
Published: January 2020

Aim

To study whether early intervention services (EI) and a follow-up program (FU) influence outcomes of children with cerebral palsy (CP) in Moldova.

Methods

Records from 351 children with CP in Moldova born during 2009 and 2010 were retrieved from hospital and orphanage archives between 1 July 2016 and 30 September 2017. We investigated the proportion enrolled in EI and FU at the Early Intervention Centre Voinicel and at the Institute of Mother and Child in 2009–2012. Logistic regression analyses were applied to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) for outcomes in children enrolled and not enrolled.

Results

Among all children with CP, 166 (47%) were enrolled in EI and FU. Of the 51 children born extremely preterm (gestational age ≤ 31 weeks), 46 (90%) were enrolled, compared to 97 (39%) of the 250 children born at term. Among 110 non-walking children with CP, 82 (74%) were enrolled into EI and FU, compared to 84 (35%) of 241 able to walk.

There was no difference in outcomes of cognition, communication, vision and hearing impairments between those enrolled or not enrolled in EI and FU. However, the subgroup analyses showed that the risk of contractures was 11 times higher among non-walking children who were not enrolled in EI and FU programs (OR = 10.931, 95% CI 2.328–51.328, p = 0.002).

Conclusion

In Moldova, EI and FU seem to be offered mostly to extremely preterm and non-walking children with CP. The results indicate a decreased risk for contractures in these children.
Relationship between sleep and obesity among U.S. and South Korean college students
Authors: Sa Jaesin , Choe Siyoung , Cho Beom-young , Chaput Jean-Philippe , Kim Gyurin , Park Chae-Hee , Chung Joon , Choi Yoojin , Nelson Beatrice , Kim Yongkyu
Published: January 2020

Background

Little is known about the relationship between sleep and obesity in young adults, particularly college students. This study examined the relationship between sleep (i.e., sleep duration and quality) and obesity in a large and diverse binational sample of college students.

Methods

Analyses were based on a 40-item paper survey from 2016/2017 to 2017/2018 academic years, with a 72% response rate. The samples were 1578 college students aged 18–25 years from five universities (two in the U.S. and three in South Korea). Weight and height were measured objectively; other measures (e.g., health behaviors) were self-reported. Multinomial logistic regression was used to assess the association between sleep duration and independent variables (race/nationality, gender, and BMI). Poisson regression was used to examine the relationship between sleep quality and independent variables.

Results

Overall, blacks had a higher adjusted odds ratio (AOR) of short sleep (< 7 h/night) than whites (AOR = 1.74, P < .01); overweight participants had a higher AOR of short sleep than normal weight participants (AOR = 1.52, P < .01); and obese participants had a higher AORs of both short and long sleep (> 9 h/night) (AOR = 1.67, P < .01; AOR = 1.79, P < .05, respectively). Among men, being black, overweight, and obesity were associated with short sleep (P < .05), whereas only obesity was related to short sleep among women (P < .05). In analyses stratified by race and nationality, overweight and obesity were related to short sleep among blacks only (P < .05). Overall, sleep quality (getting enough sleep to feel rested in the morning in the past 7 days) was worse in blacks and South Koreans than whites (P < .05), worse in women than men (P < .05), and worse in participants with obesity than normal weight participants (P < .05).

Conclusions

Obesity was associated with both short (< 7 h/night) and long sleep duration (> 9 h/night) and poor sleep quality among all participants. In comparison with whites, blacks were more like to have short sleep, and blacks and South Koreans had worse sleep quality. Further investigations using a larger sample of college students in multiple countries may be helpful to identify target populations who are at a greater risk of obesity and sleep problems.
Malignant fibrous neoplasms of long bones: analysis of the surveillance, epidemiology, and end results database from 1973 to 2015
Authors: Huang Yiting , Hong Jianqiao , Meng Jiahong , Wu Haobo , Shi Mingmin , Yan Shigui , Wang Wei
Published: January 2020

Background

Malignant fibrous neoplasms (MFN) of long bones are rare lesions. Moreover, the prognostic determinants of MFN of long bones have not been reported. This study aimed to present epidemiological data and analyse the prognostic factors for survival in patients with MFN.

Materials and methods

The Surveillance, Epidemiology, and End Results (SEER) programme database was used to screen patients with malignant fibrous neoplasms (MFN) of long bones from 1973 to 2015, with attention to fibrosarcoma, fibromyxosarcoma, periosteal fibrosarcoma and malignant fibrous histiocytoma. The prognostic values of overall survival (OS) and cancer-specific survival (CSS) were assessed using the Cox proportional hazards regression model with univariate and multivariate analyses. The Kaplan–Meier method was used to obtain OS and CSS curves.

Results

A total of 237 cases were selected from the SEER database. Malignant fibrous histiocytoma was the most common form of lesion in long bones. Multivariate analysis revealed that independent predictors of OS included age, stage, tumour size and surgery. Age, stage, tumour size and surgery were also independent predictors of CSS. Additionally, the most significant prognostic factor was whether metastasis had occurred at the time of initial diagnosis.

Conclusion

Among patients with MFN of long bones, age (> 60 years), tumour size (> 10 cm), distant stage, and non-surgical treatment are factors for poor survival.
Correction to: Healthcare professionals’ perspectives on working conditions, leadership, and safety climate: a cross-sectional study
Authors:   on behalf of the WorkSafeMed Consortium, Wagner Anke , Rieger Monika A. , Manser Tanja , Sturm Heidrun , Hardt Juliane , Martus Peter , Lessing Constanze , Hammer Antje
Published: January 2020

In the original publication of this article [1], the authors missed that reverse coding was necessary for the item “Do you work separate from your colleagues?” before calculating the scale ‘social relations’. So they corrected the analysis accordingly. The results with the revised scale show that there are no longer any significant differences between nurses and physicians with regard to this scale.
The prevalence of Dichelobacter nodosus in clinically footrot-free sheep flocks: a comparative field study on elimination strategies
Authors: Kraft A. F. , Strobel H. , Hilke J. , Steiner A. , Kuhnert P.
Published: January 2020

Background

Ovine footrot caused by Dichelobacter nodosus (D nodosus) is an infectious disease affecting sheep worldwide. Switzerland plans a nationwide footrot eradication program, based on PCR-testing of interdigital swab samples. The aim of this study was to test for the presence of D nodosus in clinically footrot-free sheep flocks which had been subjected to different treatment strategies, to assess whether they were feasible for the eradication process, especially focussing on antimicrobial flock treatments. Clinical scoring and PCR-results were compared. Ten farms had used hoof bathing and hoof trimming without causing bleeding, ten had used individual treatments and flock vaccines to gain the free status and ten had become free through whole-flock systemic macrolide treatment. For every farm, three risk-based collected pool samples were analysed for the occurrence of virulent and benign D nodosus by PCR detection of aprV2/aprB2.

Results

Six flocks from any treatment group tested positive for aprB2 in all pools. Clinical signs were absent at the time of sampling, but some flocks had experienced non-progressive interdigital inflammation previously. Two flocks tested aprV2-positive in the high-risk pool. One of them underwent a progressive footrot outbreak shortly after sampling. Individual retesting indicated, that virulent D nodosus most likely was reintroduced by a recently purchased ram. In the second flock, a ram was tested positive and treated before clinical signs occurred.

Conclusions

All treatment strategies eliminated the causative agent and were found to be suitable for implementation in the PCR-based eradication process. PCR-testing proved to be more sensitive than visual scoring, as it also detected clinically healthy carriers. It will be of benefit as a diagnostic tool in elimination and surveillance programs.
SMAD6, positively regulated by the DNM3OS-miR-134-5p axis, confers promoting effects to cell proliferation, migration and EMT process in retinoblastoma
Authors: Wang Hui , Ji Xiang
Published: January 2020

Background

Retinoblastoma (RB) is acknowledged to be the commonest intraocular malignancy in infants and children and the outcome of RB patients is unfavorable due to limited early diagnosis and effective therapy. SMAD family member 6 (SMAD6) has been reported in the initiation and progression of human cancers by acting as a biological participant. However, the role of SMAD6 in RB has not been illustrated yet.

Methods

The expression of SMAD6 mRNA, miR-134-5p and DNM3OS was measured by RT-qPCR. SMAD6 protein levels were measured by western blot. The effects of SMAD6 depletion on RB cells were analyzed using CCK-8 and transwell assays. The key proteins related to epithelial-mesenchymal transition (EMT) was determined by western blot. The localization of DNM3OS was detected by nuclear/cytoplasmic assay. In addition, the direct interaction between miR-134-5p and SMAD6 or DNM3OS was confirmed with the application of dual-luciferase reporter assay.

Results

SMAD6 was upregulated in RB tissue samples and cell lines, and silencing SMAD6 suppressed cell proliferation, migration and EMT in RB. Mechanically, SMAD6 was positively regulated by lncRNA DNM3OS through competitively interacting with miR-134-5p. DNM3OS contributed to RB progression by SMAD6-mediated manner.

Conclusions

This research unmasked a novel DNM3OS/miR-134-5p/SMAD6 pathway in RB, which might make contribution to treatment of RB.
Predictors of Beta-Hexachlorocyclohexane blood levels among people living close to a chemical plant and an illegal dumping site
Authors: Narduzzi S. , Fantini F. , Blasetti F. , Rantakokko P. , Kiviranta H. , Forastiere F. , Michelozzi P. , Porta D.
Published: January 2020

Background

Hexachlorocyclohexane is a synthetic chemical with several isomers, including β-Hexachlorocyclohexane (β-HCH). In 2005, a large contamination of crude milk from some bovine farms along the Sacco River (Central Italy) was detected; it was related to the illegal disposal of large quantities of processing waste by a chemical industry of the area. A biomonitoring study, conducted in 2007 on a sample of the residing population, found high values of β-HCH in people living close to the river. These results led to the establishment of a clinical and epidemiological surveillance program on all the exposed population.

The aim of the study was to evaluate the determinants of β-HCH blood levels in people living within 1 Km of the Sacco River, focusing on the role of specific foods, body mass index and risk factors not yet identified.

Methods

The program involved all people living within 1 km of the river. A descriptive analysis of β-HCH blood levels was done in relation to the potential determinants including specific foods. Regression analysis was used to study the association between potential determinants and (natural log) β-HCH haematic concentration. The results were expressed as geometric mean ratios (GMR). To take into account similarities within the families we adjusted for family clustering.

Results

A total of 602 subjects (87.2%) agreed to participate in the surveillance. The β-HCH geometric mean serum concentration was 72 ng/g lipid. The regression analysis showed that being female (GMR: 1.32, 95%CI: 1.14–1.53), elderly (GMR> 70yy: 10.04, 95%CI: 6.65–15.15), obese (GMR: 1.63, 95%CI: 1.28–2.08), eating food of local/own production (GMR 1.47, 95%CI: 1.15–1.88) and using water from private wells (GMRdrink:1.47, 95%CI: 1.00–2.14 and GMRwash: 1.48, 95%CI: 1.17–1.87) were associated with higher β-HCH values. There was inverse association with breastfeeding (GMR: 0.64, 95%CI: 0.47–0.86). The focus on specific foods showed that the most important factors were eggs and beef.

Conclusions

The study indicated a greater contamination for older people, and those drinking and washing with water from private wells and consuming locally produced food, especially eggs and beef.
Pharmacokinetics of plasma lopinavir and ritonavir in tuberculosis–HIV co-infected African adult patients also receiving rifabutin 150 or 300 mg three times per week
Authors: Ouedraogo Henri Gautier , Matteelli Alberto , Sulis Giorgia , Compaore Tegwinde Rebeca , Diagbouga Serge , Tiendrebeogo Simon , Roggi Alberto , Cisse Kadari , Giorgetti Pier Francesco , Villani Paola , Sangare Lassana , Simpore Jacques , Regazzi Mario , Kouanda Seni
Published: January 2020

Background

To evaluate the pharmacokinetic of plasma lopinavir (LPV) and ritonavir (RTV) when co-administered with three times weekly (TPW) rifabutin (RBT) at a dose of either 150 or 300 mg in African tuberculosis (TB) and HIV co-infected adult patients.

Methods

This is a pharmacokinetic study conducted in Ouagadougou among patients treated with a standard dosage of LPV/RTV 400/100 mg twice daily and RBT 150 mg TPW (arm A = 9 patients) or rifabutin 300 mg TPW (arm B = 7 patients) based regimens. Patients were recruited from the Bogodogo and Kossodo district hospitals in Ouagadougou from May 2013 to December 2015. Study inclusion criteria were that the patients were between 18 and 60 years of age, HIV-1 infected with pulmonary tuberculosis confirmed or suspected. Subsequent blood samples for pharmacokinetic monitoring were collected at 1, 2, 3, 4, 6, 8 and 12 h after combined drug ingestion for plasma drug monitoring using HPLC/MS assays.

Results

The medians LPV Cmaxand Tmaxwere respectively, 20 μg/mL and 4 h for the RBT 150 mg group (arm A) and 7.7 μg/mL and 3 h for the RBT 300 mg group (arm B). The AUC0–12of LPV was 111.8 μg h/mL in patients belonging to arm A versus 69.9 μg/mL for those in arm B (p = 0.313). The C0of LPV was lower than 4 μg/mL in three patients receiving RBT 300 mg. Of note, the RTV plasma concentrations were nearly halved among patients on RBT 300 mg compared to those on lower RBT doses. The AUC0–12of RTV in arm A was 12.7 μg h/mL versus 6.6 μg h/ml in arm B (p = 0.313).

Conclusion

In our study, the pharmacokinetic of LPV and RTV was found to be highly variable when coadministrated with RBT 150 mg or 300 mg three times per week. There is a need for specific large study to verify clinical and virological effects of this variation, especially when coadministrated with RBT of 300 mg TPW, and to prevent viral resistance in response to under-dosing of LPV.

Trial registrationPACTR201310000629390. Registered 28 October 2013,http://www.pactr.org/
Autophagy and autophagy-related proteins in cancer
Authors: Li Xiaohua , He Shikun , Ma Binyun
Published: January 2020

Autophagy, as a type II programmed cell death, plays crucial roles with autophagy-related (ATG) proteins in cancer. Up to now, the dual role of autophagy both in cancer progression and inhibition remains controversial, in which the numerous ATG proteins and their core complexes including ULK1/2 kinase core complex, autophagy-specific class III PI3K complex, ATG9A trafficking system, ATG12 and LC3 ubiquitin-like conjugation systems, give multiple activities of autophagy pathway and are involved in autophagy initiation, nucleation, elongation, maturation, fusion and degradation. Autophagy plays a dynamic tumor-suppressive or tumor-promoting role in different contexts and stages of cancer development. In the early tumorigenesis, autophagy, as a survival pathway and quality-control mechanism, prevents tumor initiation and suppresses cancer progression. Once the tumors progress to late stage and are established and subjected to the environmental stresses, autophagy, as a dynamic degradation and recycling system, contributes to the survival and growth of the established tumors and promotes aggressiveness of the cancers by facilitating metastasis. This indicates that regulation of autophagy can be used as effective interventional strategies for cancer therapy.
Proteomic and lipidomic analysis of exosomes derived from ovarian cancer cells and ovarian surface epithelial cells
Authors: Cheng Lin , Zhang Kun , Qing Yunan , Li Dong , Cui Manhua , Jin Peng , Xu Tianmin
Published: January 2020

Background

The limitation of current biomarker of early stage ovarian cancer and the anatomical location of ovarian (depths of the pelvic) make ovarian cancer difficult to be detected in early stage. Growing evidence shows exosomes as key information transmitters, it carried molecules, such as miRNAs, proteins, lipids, double-stranded DNA have been reported as promising biomarkers in many diseases. However, little is known about the protein and lipid composition of ovarian cancer.

Methods

Here, we report proteomic and lipidomic analysis of exosomes derived from ovarian cancer cells (SKOV-3) and ovarian surface epithelial cells (HOSEPiC).

Results

A total of 1433 proteins and 1227 lipid species were identified from two cell line derived exosomes. Several lipid species and proteins significantly differ in SKOV-3 derived exosomes compared to those from HOSEPiC. For example, we noted that ChE and ZyE species were in general more abundant in exosomes from SKOV-3 than from HOSEPiC; Collagen type V alpha 2 chain (COL5A2) and lipoprotein lipase (LPL) were significantly higher in SKOV-3 derived exosomes than HOSEpic (p < 0.05).

Conclusions

Our research indicates the promising role of exosomal proteins and lipids in the early diagnosis of ovarian cancer.
Cross-sectoral rehabilitation intervention for patients with intermittent claudication versus usual care for patients in non-operative management - the CIPIC Rehab Study: study protocol for a randomised controlled trial
Authors: Siercke Maj , Jørgensen Lise Pyndt , Missel Malene , Thygesen Lau Caspar , Blach Pernille Peppercorn , Sillesen Henrik , Berg Selina Kikkenborg
Published: January 2020

Introduction

Intermittent claudication (IC) caused by peripheral artery disease (PAD) is a common cardiovascular disease. Patients with IC have reduced walking capacity, restricted activity levels and mobility, and reduced health-related quality of life. The disease leads to social isolation, the risk of cardiovascular morbidity, and mortality. Non-operative management of IC requires exercise therapy and studies show that supervised exercise training is more effective than unsupervised training, yet many patients with IC lack motivation for changes in health behaviour.

No studies investigating the effects of existing cardiac rehabilitation targeted patients with IC have been published. The aim of this article is to present the rationale and design of the CIPIC Rehab Study, which examines the effect of a cross-sectoral rehabilitation programme versus usual care for patients in non-operative management for IC.

Methods and analysis

A randomised clinical trial aims to investigate whether cardiac rehabilitation for patients with IC in non-operative management versus usual care is superior to treatment as usual. The trial will allocate 118 patients, with a 1:1 individual randomisation to either the intervention or control group.

The primary outcome is maximal walking distance measured by the standardised treadmill walking test. The secondary outcome is pain-free walking distance measured by the standardised treadmill walking test, healthy diet measured by a fat-fish-fruit-green score, and level of physical activity measured by an activity score within official recommendations. Statistical analyses will be blinded.

Several exploratory analyses will be performed. A mixed-method design is used to evaluate qualitative and quantitative findings. A qualitative and a survey-based complementary study will be undertaken to investigate patients’ post-discharge experiences. A qualitative post-intervention study will explore experiences of participation in rehabilitation.

Discussion

The study is the first to assess the effect of a cardiac rehabilitation programme designed for patients with IC. The study will describe how to monitor and improve rehabilitation programmes for patients with IC in a real-world setting. Mixed-method strategies can allow for both exploration and generalisation in the same study, but the research design is a complex intervention and any effects found cannot be awarded a specific component.

Trial Registration

Retrospectively registered inClinicaltrials.govidentifier: NCT03730623.
Pharmacokinetics and pharmacodynamic effect of crenezumab on plasma and cerebrospinal fluid beta-amyloid in patients with mild-to-moderate Alzheimer’s disease
Authors: Yoshida Kenta , Moein Anita , Bittner Tobias , Ostrowitzki Susanne , Lin Helen , Honigberg Lee , Jin Jin Y. , Quartino Angelica
Published: January 2020

Background

Crenezumab, a fully humanized anti-beta-amyloid (Aβ) immunoglobulin G4 (IgG4) monoclonal antibody, binds to both monomeric and aggregated forms of Aβ. We assessed the pharmacokinetics (PK)/pharmacodynamics (PD) of crenezumab and its interaction with monomeric Aβ(1–40) and Aβ(1–42) peptides in serum/plasma and cerebrospinal fluid (CSF) samples from the phase II ABBY and BLAZE studies and the phase Ib GN29632 study.

Methods

In ABBY, BLAZE, and GN29632 studies, patients with mild-to-moderate AD were treated with either placebo or crenezumab (300 mg subcutaneously every 2 weeks [q2w], or 15 mg/kg, 30 mg/kg, 45 mg/kg, 60 mg/kg, or 120 mg/kg intravenously q4w). Serum/plasma PK/PD analyses included samples from 131 patients who received crenezumab in all three studies. CSF PK/PD analyses included samples from 76 patients who received crenezumab in ABBY or BLAZE. The impact of baseline patient factors on Aβ profiles was also evaluated.

Results

The serum concentration of crenezumab increased in a dose-proportional manner between 15 and 120 mg/kg q4w. Total monomeric plasma Aβ(1–40) and Aβ(1–42) levels significantly increased after crenezumab administration. The mean crenezumab CSF to serum ratio was ~ 0.3% and was similar across dosing cohorts/routes of administration. No clear correlation was observed between crenezumab concentration and Aβ(1–42) increase in CSF at week 69. The target-mediated drug disposition (TMDD) model described the observed plasma concentration–time profiles of crenezumab and Aβ well. Elimination clearance (CLel) and central volume of distribution (Vcent) of crenezumab were estimated at 0.159 L/day and 2.89 L, respectively, corresponding to a half-life of ~ 20 days. Subcutaneous bioavailability was estimated at 66.2%.

Conclusions

Crenezumab PK was dose proportional up to 120 mg/kg, with a half-life consistent with IgG monoclonal antibodies. Our findings provide evidence for peripheral target engagement in patients with mild-to-moderate AD. The study also showed that a model-based approach is useful in making inference on PK/PD relationship with unmeasured species such as free plasma Aβ levels.

Trial registrations

ABBY: ClinicalTrials.gov,NCT01343966. Registered April 28, 2011. BLAZE: ClinicalTrials.gov,NCT01397578. Registered July 19, 2011. GN29632: ClinicalTrials.gov,NCT02353598. Registered February 3, 2015.
Age-variant and age-invariant features of functional brain organization in middle-aged and older autistic adults
Authors: Bathelt Joe , Koolschijn P. Cédric , Geurts Hilde M.
Published: January 2020

Background

The majority of research effort into autism has been dedicated to understanding mechanisms during early development. As a consequence, research on the broader life course of an autism spectrum condition (ASC) has largely been neglected and almost nothing is known about ASC beyond middle age. Differences in brain connectivity that arise during early development may be maintained across the lifespan and may play protective or detrimental roles in older age.

Method

This study explored age-related differences in functional connectivity across middle and older age in clinically diagnosed autistic adults (n = 44, 30–73 years) and in an age-matched typical comparison group (n = 45).

Results

The results indicated parallel age-related associations in ASC and typical aging for the local efficiency and connection strength of the default mode network and for the segregation of the frontoparietal control network. In contrast, group differences in visual network connectivity are compatible with a safeguarding interpretation of less age-related decline in brain function in ASC. This divergence was mirrored in different associations between visual network connectivity and reaction time variability in the ASC and comparison group.

Limitations

The study is cross-sectional and may be affected by cohort effects. As all participants received their autism diagnosis in adulthood, this might hinder generalizability.

Conclusion

These results highlight the complexity of aging in ASC with both parallel and divergent trajectories across different aspects of functional network organization.
Associations between HLA and autoimmune neurological diseases with autoantibodies
Authors: Muñiz-Castrillo Sergio , Vogrig Alberto , Honnorat Jérôme
Published: January 2020

Recently, several autoimmune neurological diseases have been defined by the presence of autoantibodies against different antigens of the nervous system. These autoantibodies have been demonstrated to be specific and useful biomarkers, and most of them are also pathogenic. These aspects have increased the value of autoantibodies in neurological practice, as they enable to establish more accurate diagnosis and to better understand the underlying mechanisms of the autoimmune neurological diseases when they are compared to those lacking them. Nevertheless, the exact mechanisms leading to the autoimmune response are still obscure. Genetic predisposition is likely to play a role in autoimmunity, HLA being the most reported genetic factor. Herein, we review the current knowledge about associations between HLA and autoimmune neurological diseases with autoantibodies. We report the main alleles and haplotypes, and discuss the clinical and pathogenic implications of these findings.