bluuebunny/crossref_metadata_2025 huggingface dataset:
THOR 42: A touchstone ∼24 Myr-old eclipsing binary spanning the fully-convective boundary
Authors: Murphy Simon J , Lawson Warrick A , Onken Christopher A , Yong David , Da Costa Gary S , Zhou George , Mamajek Eric E , Bell Cameron P M , Bessell Michael S , Feinstein Adina D
Published: November 2019

We present the characterization of CRTS J055255.7−004426 (=THOR 42), a young eclipsing binary comprising two pre-main sequence M dwarfs (combined spectral type M3.5). This nearby (103 pc), short-period (0.859 d) system was recently proposed as a member of the ∼24 Myr-old 32 Orionis Moving Group. Using ground- and space-based photometry in combination with medium- and high-resolution spectroscopy, we model the light and radial velocity curves to derive precise system parameters. The resulting component masses and radii are 0.497 ± 0.005 and 0.205 ± 0.002 $\rm {M}_{\odot }$, and 0.659 ± 0.003 and 0.424 ± 0.002 $\rm {R}_{\odot }$, respectively. With mass and radius uncertainties of ∼1 per cent and ∼0.5 per cent, respectively, THOR 42 is one of the most precisely characterized pre-main sequence eclipsing binaries known. Its systemic velocity, parallax, proper motion, colour–magnitude diagram placement and enlarged radii are all consistent with membership in the 32 Ori Group. The system provides a unique opportunity to test pre-main sequence evolutionary models at an age and mass range not well constrained by observation. From the radius and mass measurements we derive ages of 22–26 Myr using standard (non-magnetic) models, in excellent agreement with the age of the group. However, none of the models can simultaneously reproduce the observed mass, radius, temperature and luminosity of the coeval components. In particular, their H–R diagram ages are 2–4 times younger and we infer masses ∼50 per cent smaller than the dynamical values.
Conformation-dependent restraints for polynucleotides: the sugar moiety
Authors: Kowiel Marcin , Brzezinski Dariusz , Gilski Miroslaw , Jaskolski Mariusz
Published: November 2019

Stereochemical restraints are commonly used to aid the refinement of macromolecular structures obtained by experimental methods at lower resolution. The standard restraint library for nucleic acids has not been updated for over two decades and needs revision. In this paper, geometrical restraints for nucleic acids sugars are derived using information from high-resolution crystal structures in the Cambridge Structural Database. In contrast to the existing restraints, this work shows that different parts of the sugar moiety form groups of covalent geometry dependent on various chemical and conformational factors, such as the type of ribose or the attached nucleobase, and ring puckering or rotamers of the glycosidic (χ) or side-chain (γ) torsion angles. Moreover, the geometry of the glycosidic link and the endocyclic ribose bond angles are functionally dependent on χ and sugar pucker amplitude (τm), respectively. The proposed restraints have been positively validated against data from the Nucleic Acid Database, compared with an ultrahigh-resolution Z-DNA structure in the Protein Data Bank, and tested by re-refining hundreds of crystal structures in the Protein Data Bank. The conformation-dependent sugar restraints presented in this work are publicly available in REFMAC, PHENIX and SHELXL format through a dedicated RestraintLib web server with an API function.
Specialized Functions of Olive FAD2 Gene Family Members Related to Fruit Development and the Abiotic Stress Response
Authors: Luisa Hernández M , Dolores Sicardo M , Arjona Patricia M , Martínez-Rivas José M
Published: November 2019

Three different cDNA sequences, designated OepFAD2-3, OepFAD2-4 and OepFAD2-5, encoding three microsomal oleate desaturases (FAD2) have been isolated from olive (Olea europaea cv. Picual). Sequence analysis and functional expression in yeast of the corresponding cDNAs confirm that they encode microsomal oleate desaturases. Gene expression and lipid analysis indicate that these three genes are not involved in the linoleic acid present in seed lipids, while OeFAD2-5, together with OeFAD2-2, contributes mostly to the linoleic acid present in the mesocarp and, therefore, in the olive oil. Our results have also shown that olive FAD2-3, FAD2-4 and FAD2-5 gene expression is not only spatially and temporally regulated in olive fruit, but also is cultivar-dependent, as well as regulated by water regime, temperature, light and wounding. All these data suggest specialized physiological roles for the olive FAD2 gene family members with respect to both aspects of the biosynthesis of the linoleic acid, either present in storage lipids that constitute the olive oil or being part of membrane lipids, which are involved in the response to abiotic stresses, and highlight the differences on FAD2 gene regulation between oilseeds and oil fruits.
Untangling systematics of the Paramacrobiotus areolatus species complex by an integrative redescription of the nominal species for the group, with multilocus phylogeny and species delineation in the genus Paramacrobiotus
Authors: Stec Daniel , Krzywański Łukasz , Zawierucha Krzysztof , Michalczyk Łukasz
Published: November 2019

Incomplete descriptions of nominal taxa are one of the most significant obstacles in modern taxonomy, including the taxonomy of Tardigrada. Another major problem in tardigrade systematics is the lack of tests for the reliability of genetic markers in species delineation. Here, we employ an integrative taxonomy approach to redescribe the nominal taxon for the P. areolatus complex, Paramacrobiotus areolatus. Moreover, we obtained multilocus DNA sequences for another 16 populations representing 9–12 Paramacrobiotus species collected from Europe, North America, Africa and Australia, enabling us to reconstruct the most extensive phylogeny of the genus to date. The identification of a pair of potentially cryptic dioecious P. areolatus complex species with divergent genetic distances in ITS2 (1.4%) and COI (13.8%) provided an opportunity to test the biological species concept for the first time in the history of tardigrade taxonomy. Intra- and interpopulation crosses did not differ in reproductive success in terms of F1 offspring. However, because of the low F1 family sizes, we were unfortunately unable to test F1 hybrid fertility. Although our results are only partially conclusive, they offer a baseline not only for further taxonomic and phylogenetic research on the areolatus complex, but also for studies on species delineation in tardigrades in general.
A Light in the Darkness: Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat the Hedonic Dysregulation of Addiction
Authors: Pettorruso Mauro , di Giannantonio Massimo , De Risio Luisa , Martinotti Giovanni , Koob George F.
Published: November 2019

The present paper discusses the potential use of repetitive transcranial magnetic stimulation (rTMS) for the treatment of addiction, within a conceptual framework that includes the “dark side” of addiction. New findings suggest that rTMS may rescue specific reward system dysfunction that underlies the pathophysiology of addiction by exposing widely under-recognized and untreated key clinical and psychopathological aspects of addictive disorders. Our paper sheds light on the relevance of these hidden dimensions for the development of effective treatment interventions. In particular, we argue that rTMS may have an impact on craving by reversing the allostatic load of hedonic dysregulation.
Investigating Swallowing and Tracheostomy Following Critical Illness: A Scoping Review
Authors: Skoretz Stacey A. , Riopelle Stephanie J. , Wellman Leslie , Dawson Camilla
Published: November 2019

Objectives:

Tracheostomy and dysphagia often coexist during critical illness; however, given the patient’s medical complexity, understanding the evidence to optimize swallowing assessment and intervention is challenging. The objective of this scoping review is to describe and explore the literature surrounding swallowing and tracheostomy in the acute care setting.

Data Sources:

Eight electronic databases were searched from inception to May 2017 inclusive, using a search strategy designed by an information scientist. We conducted manual searching of 10 journals, nine gray literature repositories, and forward and backward citation chasing.

Study Selection:

Two blinded reviewers determined eligibility according to inclusion criteria: English-language studies reporting on swallowing or dysphagia in adults (≥ 17 yr old) who had undergone tracheostomy placement while in acute care. Patients with head and/or neck cancer diagnoses were excluded.

Data Extraction:

We extracted data using a form designed a priori and conducted descriptive analyses.

Data Synthesis:

We identified 6,396 citations, of which 725 articles were reviewed and 85 (N) met inclusion criteria. We stratified studies according to content domains with some featuring in multiple categories: dysphagia frequency (n = 38), swallowing physiology (n = 27), risk factors (n = 31), interventions (n = 21), and assessment comparisons (n = 12) and by patient etiology. Sample sizes (with tracheostomy) ranged from 10 to 3,320, and dysphagia frequency ranged from 11% to 93% in studies with consecutive sampling. Study design, sampling method, assessment methods, and interpretation approach varied significantly across studies.

Conclusions:

The evidence base surrounding this subject is diverse, complicated by heterogeneous patient selection methods, design, and reporting. We suggest ways the evidence base may be developed.
Functional and Aesthetic Osseous Free Flap Mandible Reconstruction Using a Low-cost Method: Long-term Results
Authors: Olvera-Caballero Carlos , Cortes-Aroche Sergio , Vazquez- de- Lara Luis G.
Published: November 2019

Background:

Mandibular segment loss due to tumoral resection or infectious sequelae causes functional alterations with disorders in mastication, swallowing, speech, and aesthetic alterations with facial asymmetry due to deformity secondary to soft tissue collapse. Reconstructive treatment should recover function and aesthetics. This paper presents a low-cost method of mandibular reconstruction in a series of 6 patients with different years of follow-up (average follow-up time of 11.6 years) using the fibula and scapula free flaps.

Methods:

Five female patients and 1 male patient received mandibular reconstruction using osseous free flaps, 5 with the fibula and 1 with the scapula osseous free flap. The patient’s ages at the time of surgery ranged from 8 to 62 years (mean 33.1 years). Stainless steel wire was used as the osteosynthesis material, with intermaxillary fixation for 40 days postoperatively and masticatory rehabilitation using mucodental-supported prostheses.

Results:

To evaluate the aesthetic result and the facial symmetry, a questionnaire and the photographs of all the cases were sent to 8 plastic surgeons. The functional result was evaluated in 5 of the 6 patients using the Spanish version of the Oral Health Impact Profile. All flaps survived, dental occlusion was achieved in all patients, no tumors recurred, masticatory function was normal without swallowing or speech alterations, and the transplanted bone hypertrophied and spontaneously remodeled, providing facial symmetry with good aesthetic results.

Conclusion:

We present a low-cost and universally applicable mandibular reconstruction method, with long-term follow-up and good aesthetic and functional results.
Quantitative 3-dimensional Geometry of the Aging Eyelids
Authors: Flores Cristina A. , Mundy Joseph L. , Byrne Margaret E. , Gonzalez Jose A. , Taylor Helena O.
Published: November 2019

Background:

Although facial aging is a well-known phenomenon, it has not been comprehensively characterized in 3 dimensions. This study introduces a novel technique for capturing periorbital structures across age groups using 3-dimensional (3D) imaging and point cloud data collection.

Methods:

Forty-six white women were divided into 3 age groups: 20–39 years, 40–59 years, and 60+ years. Patients were scanned with the Canfield 3D photogrammetry system, and data files were exported to the point cloud processing software CloudCompare. Manually selected points specifying eyelid margins, creases, and 5 key periorbital features provided the basis for a fitted model and principal component analysis (PCA). Potential statistical significance across age groups was assessed for PCA values corresponding to each subject's eyelid geometry.

Results:

Three tendencies emerged with respect to increasing age and eyelid anatomy: the width and height of the palpebral fissure decreases, with the width decreasing more rapidly; the depth of the lateral canthus relative to the medial canthus decreases; and the superior crease becomes more variable. Analyses of variance of PCA values across age groups show statistically significant differences between the youngest and oldest groups.

Conclusions:

Three-dimensional photogrammetry enables rigorous and reliable evaluation of the aging eyelid. Results suggest age-induced changes to eyelid margin, crease, and lateral canthus positions, which have been noted anecdotally but poorly quantified until now.
PHENOTYPE-GUIDED GENETIC TESTING OF PEDIATRIC INHERITED RETINAL DISEASE IN THE UNITED ARAB EMIRATES
Authors: Khan Arif O.
Published: November 2019

Purpose:

Inherited retinal disease is relatively common in the Arabian Gulf, but details regarding pediatric inherited retinal disease in the region are lacking. The purpose of this study is to report the experience of a regional Ocular Genetics Service with childhood-onset inherited retinal disease in the United Arab Emirates.

Methods:

Retrospective series of consecutive Emirati patients referred to the Ocular Genetics Service of Cleveland Clinic Abu Dhabi over a 3-year period (2016–2018) who were diagnosed with childhood-onset inherited retinal disease (onset before 16 years old) and underwent diagnostic genetic testing guided by clinical phenotype (single gene, next-generation panel, or exome sequencing).

Results:

Seventy-one probands were identified (38 male and 33 females), the majority of whom were symptomatic with visual problems within the first 5 years of life. All patients had disease causing mutations in 1 of 26 retinal disease genes. Recessive disease was frequently due to homozygous mutations. The most frequently mutated genes (and number of probands) were ABCA4 (14), KCNV2 (8), CRB1 (6), and CNGA3 (5). Recurrent specific gene mutations included ABCA4 p.Gly1961Glu/p.Leu857Pro, KCNV2 p.Glu143*, MERTK p.Cys738Trpfs*32, and RS1 c.52+3A>G. Some probands had mutations in syndromic genes and were confirmed to have extraocular findings.

Conclusion:

Phenotype-guided genetic testing had a remarkable yield for this patient population. Recessive disease is often from homozygous mutations. Cone-dominated phenotypes are common. There are apparent founder mutations for several genes that could be used in a targeted genetic testing strategy. Molecular diagnosis is particularly important in affected children when inherited retinal dystrophy could be a sign of syndromic disease as proper earlier diagnosis minimizes potential extraocular morbidity.
SELF-INFLICTED LASER-INDUCED MACULOPATHY MASQUERADING AS POSTERIOR UVEITIS IN A PATIENT WITH SUSPECTED IgG4-RELATED DISEASE
Authors: Agarwal Aniruddha , Jindal Ankur Kumar , Anjani Gummadi , Suri Deepti , Freund K. Bailey , Gupta Vishali
Published: November 2019

Purpose:

To report the clinical presentation and imaging features in a case of bilateral self-inflicted handheld laser-induced maculopathy which masqueraded as progressive posterior uveitis in a patient with suspected IgG4-related disease.

Methods:

Case report with clinical history, fundus photographs, fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography.

Results:

A young Asian Indian man presented with sudden progressive bilateral visual loss over the past 1 week. He was being treated with oral corticosteroids for multiple subcutaneous skin lesions believed to be due to IgG4-related disease. Findings included bilateral central areas of outer retinal disruption with eccentric linear and serpentine lesions showing hypoautofluorescence. Hyperreflective bands extending from the retinal pigment epithelium and interdigitation zone to the outer plexiform layer were present on swept-source optical coherence tomography. After careful history and evaluation of multimodal imaging, posterior uveitis was excluded, and a diagnosis of handheld laser-induced maculopathy was established.

Conclusion:

Pattern recognition is important in establishing a diagnosis of self-inflicted handheld laser-induced maculopathy which can masquerade as posterior uveitis. Increasing availability of powerful Class IIIb laser devices in both developed and developing countries will likely increase the incidence of this entity.
CONVERSION AND SPONTANEOUS REVERSION OF LAMELLAR HOLE FROM FULL-THICKNESS MACULAR HOLE
Authors: Ellis Michael , Yiu Glenn
Published: November 2019

Purpose:

To report the conversion and spontaneous reversion of a lamellar hole from full-thickness macular hole after vitrectomy surgery for retinal detachment repair.

Methods:

Case report of a patient with a preexisting lamellar hole who underwent retinal detachment repair.

Results:

A patient with a history of a lamellar hole developed a fovea-sparing retinal detachment that was repaired by vitrectomy surgery with gas tamponade. Two months after the surgery, he developed a full-thickness macular hole that spontaneously reverted back to a lamellar hole configuration over several months.

Conclusion:

Although spontaneous closure of full-thickness macular hole after retinal detachment repair has been reported, the conversion and spontaneous reversion of a lamellar hole from full-thickness macular hole after vitrectomy provide insight into the tractional forces involved in the pathophysiology of lamellar and full-thickness macular holes.
Durability of Hearing Preservation Following Microsurgical Resection of Vestibular Schwannoma
Authors: Dowling Eric M. , Patel Neil S. , Lohse Christine M. , Driscoll Colin L. W. , Neff Brian A. , Van Gompel Jamie J. , Link Michael J. , Carlson Matthew L.
Published: November 2019

Objective:

To ascertain long-term hearing outcomes in patients with serviceable hearing following microsurgical resection of sporadic vestibular schwannoma (VS).

Study Design:

Retrospective cohort.

Setting:

Tertiary academic referral center.

Patients:

Forty-three adult subjects with unilateral sporadic VS who had serviceable hearing (American Academy of Otolaryngology–Head and Neck Surgery [AAO-HNS] class A or B) on initial postoperative audiogram following microsurgical resection between 2003 and 2016 with a minimum of two postoperative audiograms available for review.

Intervention:

Surgical treatment with a retrosigmoid or middle cranial fossa approach.

Main Outcome Measure:

Rate of maintaining serviceable hearing, as estimated using the Kaplan–Meier method, in accordance with the 1995 and 2012 AAO-HNS guidelines on reporting hearing outcomes.

Results:

The median immediate postoperative pure-tone average (PTA) and word recognition score (WRS) were 31 dB and 95%, respectively. At last follow-up, the median PTA was 38 dB with a median change of 5 dB from initial postoperative audiogram, and the median WRS was 90% with a median change of 0% from initial postoperative audiogram. Eight patients developed non-serviceable hearing at a median of 4.1 years following microsurgical resection (interquartile range, 2.9–7.0). The median duration of hearing follow-up for the 35 patients who maintained serviceable hearing was 3.1 years (interquartile range, 2.2–7.5). Tumor control was achieved in 41 (95%) patients. The rate of maintaining serviceable hearing at 5 years was 81%.

Conclusion:

Microsurgical resection provides excellent tumor control and durable long-term hearing in those with AAO-HNS class A or B hearing postoperatively. The paradigm of proactive microsurgical resection—when the tumor is small and hearing is good—hinges on the surgeon's ability to preserve residual hearing in a very high percentage of cases at or near preoperative hearing levels to maintain an advantage over conservative observation with regard to long-term hearing preservation.
Antibiotic prescribing trends in a pediatric population in Lithuania in 2003–2012
Authors: Karinauske Egle , Kasciuskeviciute Skaiste , Morkuniene Vilma , Garuoliene Kristina , Kadusevicius Edmundas
Published: November 2019

The purpose of this study was to determine the trends in consumption of antibiotics and evaluate the antibiotic prescription rates in the pediatric population in Lithuania during 2003 to 2012.

A cross-sectional study. Data of systemic antibiotic use in pediatric population for outpatient treatment was derived from National Health Insurance Fund database. Consumption was expressed as WHO ATC defined daily dose (DDD)/1000 children/day and as a number of prescriptions written in the general population per year. Statistical analysis was performed using the SPSS/W 20.0 software (Statistical Product and Service Solutions for Windows).

Total utilization of antibiotics (expressed in DDD units) during study period increased by 8.40% (from 5.67 to 6.19 DDD/1000 children/day) and by 5.96% expressed in prescription rate (from 585.84 to 622.97 prescriptions/1000 children/year). The most popular antibiotic group was macrolides which showed the highest increase of utilization 5.9 times (from 0.27 DDD/1000 children/day in 2003 to 1.66 DDD/1000 children/day in 2012).

The most common indications for antibiotic prescribing for children in 2012 were acute bronchitis (25.6%), acute tonsillitis (21.7%) and acute pharyngitis (14.6%). Amoxicillin had the highest probability to be chosen to treat acute tonsillitis (prob. [probability] = .2875) and acute pharyngitis (prob. = .5553). Clarithromycin had the highest probability to be chosen to treat acute bronchitis (prob. = .4222).

Most of the diseases treated with antibiotics were viral infections. The most commonly prescribed antibiotics were broad-spectrum. The consumption of antibiotics was evenly increasing during 2003 to 2012 period, but the distribution of separate antibiotic group remained the same.
The association of endocannabinoid receptor genes (CNR1 and CNR2) polymorphisms with depression
Authors: Kong Xiangjuan , Miao Qingshan , Lu Xiaozi , Zhang Zeng , Chen Min , Zhang Jinxiang , Zhai Jinguo
Published: November 2019

Studies investigating the association between gene variants and depression susceptibility found inconsistent data. The present study aimed to clarify whether CNR1rs1049353, CNR1 AAT triplet repeat, and CNR2rs2501432 polymorphisms confer higher risk for depressive disorder.

Literature from PubMed, Medline, Embase, Scopus, Cochrance Library, and Wanfang databases was searched (up to August 20, 2018). Seven case–control studies with various comorbidities were eligible. We targeted CNR single-nucleotide polymorphisms (SNPs) that have been reported by 2 or more studies to be involved in the current meta-analysis, resulting in a final list of 3 SNPs: CNR1rs1049353, CNR1 AAT triplet repeat polymorphism, and CNR2rs2501432. Odds ratios (ORs) and 95% confidence intervals (CIs) for allele and homozygote comparisons, dominant and recessive models, and triplet repeat polymorphism ((AAT)n≥5, ≥5 vs (AAT)n<5, <5 or <5, ≥5) were assessed using a random effect model as measures of association. Heterogeneity among included studies was analyzed using sensitivity test. Publication bias was also explored by Egger and rank correlation test.

overall, no significant association was found between depression and CNR1rs1049353 (G vs A: OR [95% CI] = 1.09 [0.61–1.95]; GG vs AA: 1.29 [0.73–2.26]; GG vs GA+AA: 1.10 [0.57–2.10]; GG+GA vs AA: 1.25 [0.72–2.18]; and AAT triplet repeat polymorphism ((AAT)n≥5, ≥5 vs (AAT)n<5, <5 or <5, ≥5): 1.92 [0.59–6.27]. In contrast, a significant association between CNR2rs2501432 and depression was detected, and the ORs and 95% CIs are as follows: allele contrast (OR = 1.39, 95% CI = [1.12–1.72], P = .003); homozygous (OR = 2.19, 95% CI = [1.34–3.59], P = .002); dominant (OR = 1.93,95% CI = [1.23–3.04], P = .005); and recessive (OR = 1.41, 95% CI = [1.04–1.92], P = .03).

This meta-analysis revealed that CNR1rs1049353 or AAT triplet repeat polymorphism had no association with susceptibility to depression, while CNR2rs2501432 polymorphism was a remarkable mark for depression patients.
Assessment of sleep and obesity in adults and children
Authors: Bonanno Lilla , Metro Daniela , Papa Mattia , Finzi Giuseppa , Maviglia Antonia , Sottile Fabrizio , Corallo Francesco , Manasseri Luigi
Published: November 2019

The sleep allows many psychological processes, such as immune system activity, body metabolism and hormonal balance, emotional and mental health, learning, mnemonic processes. The lack of sleep could undermine mental and physical purposes, causing an alteration in cognitive functions or metabolic disorders. In our study, we have examined the irregular sleep effects with the overweight and obesity risk in children and adults.

The sample was composed of 199 subjects, of which 71 adults, (29 males and 42 females), and 128 children (73 males and 55 females). We have measured the weight and height with standard techniques; we also have measured the body mass index dividing the weight in kg with the height square expressed in meters (kg/m2). Subjects were divided into underweight, normal weight, overweight, and obese. Were administered some questionnaires to measure the quantity and quality of sleep, and eating habits and individual consumption of food.

Analysis of demographic variables not showed significant differences between male and female groups but highlighted a significant trend differences in normal-weight score. The clinical condition has a substantial impact on body mass index score and sleep hours were significant predictor on this.

Quantity and quality sleep can also represent a risk factor of overweight and obesity, so sufficient sleep is a factor that influence a normal weight. Adults and children that sleep less, have an increase in obesity and overweight risk with dysfunctional eating behaviors, decreased physical activity, and metabolic changes.
Heart rate variability in people with visual disability
Authors: Moreno Renaldo D. , Abreu Luiz C. , Morais Mauro J.D. , Oliveira Fabiano S. , Bezerra Italla M.P. , Valenti Vitor E. , Sato Monica A.
Published: November 2019

Introduction:

People with visual impairment (VI) have loss of vision that causes impact on their daily living activities. Synonymous of VI are blindness, low vision, subnormal vision, visual incapacity, although there are peculiarities among them. The autonomic nervous system (ANS) provides the body with dynamic adaptation, moment by moment, according to changes in the internal and/or external body environment. As VI is an adverse condition, it is expected to be associated with changes in systemic autonomic activity, such as heart rate (HR) variability.

Objective:

To analyze the blindness stress by monitoring the activity of the ANS in the heart in subjects submitted acutely to low vision and also in subjects with chronic visual deficiency.

Method:

This is a randomized trial experimental study. In this clinical trial, initially, patients will undergo an ophthalmologic medical evaluation, along with monitoring of HR and systolic blood pressure /diastolic blood pressure. Volunteers with normal vision (Group i); and people with VI (Group ii) will be evaluated, all of them inhabitants of Rio Branco City, capital of Acre State, Brazilian Amazon. The intervention will consist of simulating blindness by sealing both eyes of each participant with good eyesight, using a sleep mask and allowing maximum occlusion for 45 minutes, split into 3 periods of 15 minutes each. Still blindfolded, participants will be requested to perform different tasks as walking, serve themselves water and/or cookies, and engaging in playful-pedagogical activity. Identical procedure will be done with the group with VI. The HR will be recorded by the Polar RS800 HR monitor. All findings with a value of P < .05 will be considered statistically significant. As a risk measure the odds ratio will be calculated, adjusted, and not adjusted with their respective 95% confidence intervals. The odds ratio = 1 of lowest risk for the outcome of interest will be considered as the base category for each independent variable.

Ethics and dissemination:

This study will be carried out in accordance with the guidelines that regulate human research in Resolution No. 466/12 of the National Health Council. We obtained the approval of the Research Ethics Committee of the ABC Medical School/Faculdade de Medicina do ABC, with CAAE: 73945017.0.0000.0082, and Opinion No. 2,275,101. All individuals who agreed to participate in the study will sign the free and informed consent form (FICF). The FICF is also available in audio and Braille versions. The results will be disseminated through peer-reviewed journal articles and conferences. This study is registered in the Brazilian Registry of Clinical Trials under the number RBR-9sm9dp.
Treatment of multicentric Castleman disease through combination of tocilizumab, lenalidomide and glucocorticoids
Authors: Cai Sisi , Zhong Zhaodong , Li Xiang , Wang Hong Xiang , Wang Li , Zhang Min
Published: November 2019

Rationale:

Castleman's disease (CD) is a rare lymphoproliferative disease. Compared to unicentric CD, multicentric Castleman disease (MCD) displays poorer prognosis and great variance to different therapies. Though chemotherapy, immunization therapy, and glucocorticoids have been used in the treatment of MCD, its optimal treatment is still controversial.

Patient concerns:

A 47-year-old woman was admitted due to poor appetite, general fatigue, puffiness of face, systemic rash, and abdominal distension. On physical examination, the patient displayed as general lymphadenopathy, splenomegaly, hepatomegaly, and shifting dullness.

Diagnoses:

After biopsy of her swollen lymph node and laboratory tests, her initial diagnosis was hyaline vascular-CD.

Interventions:

She was treated with combination of tocilizumab, lenalidomide, and glucocorticoids.

Outcomes:

This patient achieved complete remission (CR) with all her indexes returned to be normal. Her blood routines and biochemical examinations were still normal during the following period.

Lessons:

We reported a case with multicentric Castleman's disease (MCD) which acquired quite good remission after combination treatment with tocilizumab, lenalidomide, and glucocorticoids. Our report provided powerful evidence for displaying the efficiency and safety of target therapy against unicentric Castleman disease.
Traditional Chinese medicine non-pharmaceutical therapies for chronic adult insomnia
Authors: Li Feizhou , Xu Bo , Wang Ping , Liu Ling
Published: November 2019

Background:

Traditional Chinese medicine (TCM) non-pharmaceutical therapies are frequently used for chronic insomnia in China, but in clinical practice, most practitioners choose appropriate treatments based on personal experience. In our study, Bayesian network meta-analysis will be used to identify differences in efficacy and safety between diverse non-pharmaceutical therapies for chronic adult insomnia.

Methods:

The authors will totally retrieve seven electronic databases from their establishment to August 2019 in accordance with relevant strategies. After a series of screening, the 2 researchers will employ the Aggregate Data Drug Information System (ADDIS) and R software to analyze the data extracted from enclosed Randomized Controlled Trials (RCTs). Ultimately, the evidentiary grade of the results will be evaluated.

Results:

This study will provide reliable evidence for different non-pharmaceutical therapies on chronic insomnia in adults.

Conclusions:

The findings will be an available reference to evaluate the efficacy and safety of different non-pharmaceutical therapies on chronic insomnia in adults and may provide decision-making reference on which method to choose for clinicians.

Trial registration number:

PROSPERO CRD42019141496.
Denosumab and Sunitinib in the treatment of giant-cell tumor of bone with pulmonary and bone metastases in an adolescent
Authors: Wang Guannan , Jiang Sujing , Li Zhouqi , Dong Ying
Published: November 2019

Introduction:

Giant cell tumor of bone with pulmonary and bone metastases is exceedingly rare in adolescents. Furthermore, Denosumab and Sunitinib in the treatment of giant cell tumor of bone has never been reported.

Patient concerns:

A 16-year-old boy complained of fever, chest tightness, and shortness of breath and back pain for 5 days.

Diagnosis:

Giant cell tumor of bone with pulmonary and bone metastases.

Interventions:

The patient underwent 2 surgeries for giant cell tumor of bone located in the spine and received Denosumab to reduce local recurrence and control the metastases. Then Sunitinib was added into treatment strategies after the progressing of metastases.

Outcomes:

Within 5 months of Denosumab and Sunitinib, lung metastases were shrinking (stable disease, response evaluation criteria in solid tumors version 1.1). Until now about 4 years into treatment the patient is still survival. Pulmonary and bone metastases are stable.

Conclusions:

This is a case of multi-center giant cell tumor of bone, it does not only provide a reference to the treatment of similar cases of the clinic but also reflects the limitations of the application of Denosumab in the real world.
Cardiovascular outcomes of liraglutide in patients with type 2 diabetes
Authors: Duan Chun-Mei , Wan Teng-Fei , Wang Yue , Yang Qing-Wu
Published: November 2019

Background:

Liraglutide is a novel, long-acting glucagon-like peptide-1 (GLP-1) analogue used to treat type 2 diabetes mellitus. However, the cardiovascular safety and benefits of liraglutide treatment on type 2 diabetes patients remain in debate. In this study, we aimed to examine the overall cardiovascular outcomes of liraglutide in patients with type 2 diabetes.

Methods:

In this systematic review and meta-analysis, we searched the PubMed, Embase, and Web of Knowledge databases up to September 1st, 2017 for randomized trials in which type 2 diabetes patients were assigned to liraglutide and placebo or other comparators groups.

Results:

Eight studies fulfilled the eligibility criteria for inclusion and 14,608 patients were analyzed in this systematic review and meta-analysis. We found patients in the liraglutide group had a lower risk of major cardiovascular events (MACE) (RR = 0.89, 95% CI: 0.82–0.96, P = .002), acute myocardial infarction (AMI) (RR = 0.85, 95% CI: 0.74–0.99, P = .036), all-cause death (RR = 0.84, 95% CI: 0.74–0.96, P = .009), and cardiovascular death (RR = 0.77, 95% CI: 0.65–0.91, P = .002) than all comparator groups. However, liraglutide treatment did not decrease incidence of stroke (RR = 0.86, 95% CI: 0.70–1.04, P = .124). But among the MACE subgroups analysis, a significant reduction of MACE with liraglutide was only observed in placebo-controlled trials (RR = 0.89, 95% CI: 0.83–0.96, P = .004) but not in studies concerning other comparators (RR = 0.58, 95% CI: 0.29–1.16, P = .122).

Conclusions:

In conclusion, our results suggest that liraglutide treatment decreases the risk of MACE, AMI, all-cause death and cardiovascular death among patients with type 2 diabetes.
Steroids in the treatment of nonarteritic anterior ischemic optic neuropathy
Authors: Chen Jun , Zhu Jie , Chen Li , Hu Chen , Du Yi
Published: November 2019

Background:

Non-arteritic anterior ischemic optic neuropathy (NAION) is the common cause of acute and subacute optic neuropathy in adults over the age of 50. Steroid administration in NAION seems to be in practice and is advised frequently by neurologists. The controversy regarding steroid usage in NAION is far from settled, with strong opinions on both sides. Despite a large amount of articles on this topic, but the results have not always been consistent. To address this gap, we decided to conduct a meta-analysis of all available published studies in order to better understand the effectiveness of steroids in treating NAION.

Objectives:

To identify the effectiveness of steroids in treating NAION.

Methods:

We performed a meta-analysis using databases, including PUBMED EMBASE, and the Cochrane library, to find relevant studies. The weighted mean difference (WMD) was determined for BCVA in steroid and nonsteroid groups.

Results:

Eight studies were included and summarized in this analysis. The studies included 720 eyes (392 NAION eyes and 328 eyes of normal controls). Heterogeneity among these studies was low (I
2 = 0%). Because of the presence of heterogeneity, we conducted a fixed effects model to assess the effect of steroids on visual acuity in patients with NAION. The meta-analysis clearly demonstrated that in NAION, steroids did not significantly improve visual acuity (WMD = −0.02 [95% CI: −0.10 to 0.06], Z = 0.40, P = .69). After sensitivity analysis via the leave-one-out method, WMD was not significantly changed.

Conclusions:

Our meta-analysis found that steroids do not significantly improve visual acuity in NAION. In view of their long list of side effects, attempts at reversing ischemia should not involve the use of steroids.
Acute ischemic stroke in a 7-month-old infant, risk factors, and diagnosis peculiarities
Authors: Meliţ Lorena Elena , Mărginean Cristina Oana , Simu Iunius , Bucur Gabriela
Published: November 2019

Introduction:

Ischemic stroke is an extremely rare disorder in children. The timely diagnosis is essential for the outcome of these children, but unfortunately, delays in diagnosis occur frequently.

Patient concerns:

We report the case of a 7-month-old infant admitted in our clinic for limited movements of the superior and inferior right limbs whose onset was 27 hours before with repeated clonic movements of the right hand associated with the same manifestations in the right oral commissure lasting approximately 10 seconds.

Diagnosis:

The laboratory tests revealed high D-dimers, and positive IgG anti-cardiolipin and anti-beta2 glycoproteins I antibodies, whereas the genetic profile for thrombophilia revealed heterozygote mutation in MTHFR C677T and A1298C genes. Brain imaging established the diagnosis of left frontal ischemic stroke, frontal ischemic stroke, hypoplasia of internal carotid artery, and agenesia of segment M1 of median cerebral artery and segment A1 of left anterior cerebral artery.

Intervention:

We administered low-molecular-weight heparin, antiplatelet therapy along with vasodilators and depletive treatment, wide-spectrum antibiotics, and anticonvulsant therapy.

Outcome:

The neurological deficit was greatly improved, especially in the inferior limb after 6 month from the incident of stroke, and all laboratory parameters were within normal limits including the antibodies mentioned above.

Conclusion:

Cerebral vascular malformation, excessive weight, and altered lipid profiles contributed to the development of acute ischemic stroke in our patient.
Uncommon erythema multiforme in small children: experience of a single Romanian pediatric unit
Authors: Mocanu Adriana , Ivanov Anca , Alecsa Mirabela , Lupu Vasile Valeriu , Lupu Ancuta , Starcea Iuliana Magdalena , Miron Oana Tatiana , Gavrilovici Cristina , Miron Ingrith Crenguta
Published: November 2019

Rationale:

Erythema multiforme (EM) is an immune-mediated disease with mucocutaneous localization and plurietiologic determinism. The term “multiforme” refers to the variety of aspects that the lesions can take from patient to patient and during evolution in a single patient.

Patient concerns:

We have selected 2 cases of small children diagnosed with different etiology of EM to illustrate the importance of a correct and fast diagnosis. Case 1 involves a 2-year-old girl from a rural area who presented with fever and pruritic erythematous papular eruption. The onset of the symptoms was 3 days before presentation with fever and ulcerative lesions on the oral and labial mucosa, followed by the appearance of erythematous macular lesions, with progressive confluence to intense pruritic patches. The 2nd involves a 2-year-old boy with fever, loss of appetite, productive cough, and petechiae. He had corticosensible immune thrombocytopenia from the age of 6 months, with many recurrences. The patient received treatment with ampicillin/sulbactam and symptomatics for an erythemato-pultaceous angina. During the 2nd day of treatment the patient developed an erythematous macular eruption on the face, scalp, trunk, and limbs, with bullae formation.

Diagnoses:

The 1st patient was diagnosed based on biologic findings: positive inflammatory syndrome, elevated level of anti-Mycoplasma pneumoniae immunoglobulin M antibodies and immunoglobulin E. Histopathologic examination described papillary dermal edema, inflammatory infiltrate, and lymphocyte exocytosis. In the 2nd case, the hemoleucogram identified 12,000/mm3 platelets and the medulogram aspect was normal. Serology for Epstein–Barr virus was negative. The diagnosis was EM secondary to M pneumoniae infection in case 1 and secondary to administration of ampicillin/sulbactam in case 2.

Interventions:

In both cases, etiopathogenic treatment consisting of steroidal antiinflammatory drugs, antihistamines was administered. Because of specific etiology, the 1st case received antibiotics.

Outcomes:

The evolution was favorable in 10 to 14 days; the patients were discharged after etiopathogenic treatment consisting of steroidal antiinflammatory drugs, antihistamines, and/or antibiotics.

Lessons:

Performing a detailed clinical examination, medical history of drug use, infection or general diseases can establish a good diagnosis of EM. Histopathologic examination can help. The treatment is etiologic, pathogenic, and symptomatic. EM usually has a self-limited evolution.
Childhood adrenocortical tumor
Authors: Wu Xiaohui , Xu Jun , Wang Jinhu , Gu Weizhong , Zou Chaochun
Published: November 2019

The aim of the study was to investigate the molecular mechanisms in childhood adrenocortical tumors (ACTs), which is still unclear.

A total of 9 girls and 4 boys with ACTs were enrolled. Relevant clinical features were obtained from records. Immunohistochemistry of vimentin, chromogranin A, S100, synaptophysin, cytokeratin (CK), type 2 3β-hydroxysteroid dehydrogenase (3βHSD), cytochrome P45017α, p53, p21, p27, cyclin D1, Ki-67, insulin growth facter-2 (IGF-2), and β-catenin were undertaken for 13 tumors and 3 adjacent normal tissues. TP53 mutations in exon 2-11 were analyzed for 6 tumors and 3 blood samples.

Virilization was the most common presentation (8/13, 61.5%). Immunohistochemically, p53 was positive in 8 of 13 ACTs and none in controls while p21 was positive in 12 of 13 ACTs and none in controls (P = .0036). Ki-67 was positive in 10 of 13 ACTs, but not in normal tissues (P = .0089). Although the expression of p27, cyclin D1, IGF-2 and β-catenin were similar between the ACTs and controls, β-catenin was noted in nuclear of 3 ACTs but not in controls. The difference of type 2 3βHSD and P450c17α was not significant (P > .05, respectively). Four variants of TP53 were identified in the 6 tumors. C215G variant was found in 5 of 6 while A701G and G743A variants were found in 1 case, respectively. A novel C680G variant was also noted in 1 case. It was notable that C215G variant was found in the blood mononuclear cell of 3 patients.

In conclusion, p53 variant and p21 overexpression, and abnormal β-catenin distribution may be involved in the etiology and mechanism of childhood ACTs.
Autologous platelet-rich gel and continuous vacuum sealing drainage for the treatment of patients with diabetic foot ulcer
Authors: Xu Jie , Wang Qiao-Yun , Li Wei
Published: November 2019

Background:

Research focusing on the efficacy of autologous platelet-rich gel (APRG) and continuous vacuum sealing drainage (CVSD) for diabetic foot ulcer (DFU) is increasing. Despite increasing knowledge on this theme, its results remain inconsistent. Thus, we will provide insight into the efficacy of APRG and CVSD for patients with DFU.

Methods:

We will search electronic databases of MEDILINE, EMBASE, Cochrane Library, CINAHL, AMED, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception to October 1, 2019. No language limitation is utilized to these databases. Two authors will independently perform study selection, data extraction, and risk of bias assessment. Disagreements between 2 authors will be solved through discussion with a third author.

Results:

The efficacy and safety of APRG and CVSD for patients with DFU will be assessed by the time to complete healing, proportion of ulcers healed within trial period, change of size of ulcer, health-related quality of life, patient length of hospital stay, and adverse events.

Conclusion:

The results of this study will provide helpful evidence of APRG and CVSD for patients with DFU.

Systematic review registration:

PROSPERO CRD42019153289.
The treatment modalities of masticatory muscle pain a network meta-analysis
Authors: Feng Jie , Luo Mengqi , Ma Jianbin , Tian Ye , Han Xianglong , Bai Ding
Published: November 2019

Background:

Numerous treatment modalities have been attempted for masticatory muscle pain in patients with temporomandibular disorders (TMD). To compare the treatment efficacy of more than 2 competing treatments, a network meta-analysis (NMA) was conducted.

Methods:

This study was reported with reference to the extended Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting of systematic reviews incorporating network meta-analyses. Medline via Pubmed, Embase via OVID, and Cochrane Library Central were searched (up to February 11, 2019). Axis I protocol of Diagnostic Criteria or Research Diagnostic Criteria for Temporomandibular Disorders (DC/TMD, RDC/TMD) were chosen as diagnostic standards. The PICOS (Problem/patient, Intervention, Comparison, Outcome, Study design) method was used to screen trials under eligibility criteria. And the NMA was performed with mvmeta commands in Stata (StataCorp, Tex).

Results:

Of 766 studies searched, 12 randomized clinical trials (RCTs) were finally included. Nineteen different therapies were found and further categorized into 9 treatment modalities. The general heterogeneity was not found among included trials. But predictive intervals (PrIs) were conspicuously wider than confidential intervals (CIs) of all pairwise comparisons, indicating that heterogeneity may exist between studies. Complementary therapy showed the greatest probability (42.7%) to be the best intervention. It also had the highest mean rank (2.3) in the rankogram and the biggest value of surface under the cumulative ranking (SUCRA, 84.1%).

Conclusions:

Based on the limited evidence of available trials, complementary therapy seemed to be slightly more effective than remaining treatment modalities for pain reduction in TMD patients with masticatory muscle pain. High-quality randomized controlled trials are expected to validate the findings.