bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized, Controlled Pilot Trial Comparing Platelet-Rich Plasma to Topical Minoxidil Foam for Treatment of Androgenic Alopecia in Women
Authors: Bruce Alison J. , Pincelli Thais P. , Heckman Michael G. , Desmond Cheryl M. , Arthurs Jennifer R. , Diehl Nancy N. , Douglass Erika J. , Bruce Charles J. , Shapiro Shane A.
Published: October 2019

BACKGROUND

Androgenic alopecia (AGA) is a common hair loss disorder. Studies have demonstrated successful treatment with platelet-rich plasma (PRP) in men, but studies in women are few.

OBJECTIVE

To evaluate PRP in the treatment of AGA in women, compared with topical minoxidil.

MATERIALS AND METHODS

Twenty women with AGA received topical minoxidil for 12 weeks and injectable PRP for 12 weeks in a randomized crossover design with an 8-week washout between treatments. Standardized TrichoScan analysis and quality-of-life questionnaires were assessed at baseline and 12-week follow-up for each treatment.

RESULTS

After PRP, significant increases from baseline to Week 12 in TrichoScan analysis hair count (p= .002) and vellus hair density (p= .009) occurred. However, minoxidil resulted in significant increases in hair count (p< .001), vellus hair density (p= .03), terminal hair density (p= .004), and cumulative thickness (p= .004). Several quality of life responses improved from baseline to Week 12 after PRP treatment, whereas no improvements were noted after minoxidil.

CONCLUSION

Platelet-rich plasma is an effective treatment for hair regrowth in female AGA, although not as effective as minoxidil. However, the improved quality of life responses after PRP, but not minoxidil, suggest a potential overall greater degree of satisfaction with PRP.

LEVELS OF EVIDENCE

I.

CLINICAL TRIAL REGISTRATION

NCT03488108.
Patterns and Variability of Endocrine-disrupting Chemicals During Pregnancy
Authors: Buck Louis Germaine M. , Yeung Edwina , Kannan Kurunthachalam , Maisog Joseph , Zhang Cuilin , Grantz Katherine L. , Sundaram Rajeshwari
Published: October 2019

Background:

The exposome is a novel research paradigm offering promise for understanding the complexity of human exposures, including endocrine-disrupting chemicals (EDCs) and pregnancy outcomes. The physiologically active state of pregnancy requires understanding temporal changes in EDCs to better inform the application of the exposome research paradigm and serve as the impetus for study.

Methods:

We randomly selected 50 healthy pregnant women with uncomplicated pregnancies from a pregnancy cohort who had available serum/urine samples in each trimester for measuring 144 persistent and 48 nonpersistent EDCs. We used unsupervised machine-learning techniques capable of handling hierarchical clustering of exposures to identify EDC patterns across pregnancy, and linear mixed-effects modeling with false-discovery rate correction to identify those that change over pregnancy trimesters. We estimated the percent variation in chemical concentrations accounted for by time (pregnancy trimester) using Akaike Information Criterion–based R
2 methods.

Results:

Four chemical clusters comprising 80 compounds, of which six consistently increased, 63 consistently decreased, and 11 reflected inconsistent patterns over pregnancy. Overall, concentrations tended to decrease over pregnancy for persistent EDCs; a reverse pattern was seen for many nonpersistent chemicals. Explained variance was highest for five persistent chemicals: polybrominated diphenyl ethers #191 (51%) and #126 (47%), hexachlorobenzene (46%), p,p’-dichloro-diphenyl-dichloroethylene (46%), and o,p’-dichloro-diphenyl-dichloroethane (36%).

Conclusions:

Concentrations of many EDCs are not stable across pregnancy and reflect varying patterns depending on their persistency underscoring the importance of timed biospecimen collection. Analytic techniques are available for assessing temporal patterns of EDCs during pregnancy apart from physiologic changes.
Use of Time-Dependent Propensity Scores to Adjust Hazard Ratio Estimates in Cohort Studies with Differential Depletion of Susceptibles
Authors: Wyss Richard , Gagne Joshua J. , Zhao Yueqin , Zhou Esther H. , Major Jacqueline M. , Wang Shirley V. , Desai Rishi J. , Franklin Jessica M. , Schneeweiss Sebastian , Toh Sengwee , Johnson Margaret , Fireman Bruce
Published: October 2019

Estimating hazard ratios (HR) presents challenges for propensity score (PS)-based analyses of cohorts with differential depletion of susceptibles. When the treatment effect is not null, cohorts that were balanced at baseline tend to become unbalanced on baseline characteristics over time as “susceptible” individuals drop out of the population at risk differentially across treatment groups due to having outcome events. This imbalance in baseline covariates causes marginal (population-averaged) HRs to diverge from conditional (covariate-adjusted) HRs over time and systematically move toward the null. Methods that condition on a baseline PS yield HR estimates that fall between the marginal and conditional HRs when these diverge. Unconditional methods that match on the PS or weight by a function of the PS can estimate the marginal HR consistently but are prone to misinterpretation when the marginal HR diverges toward the null. Here, we present results from a series of simulations to help analysts gain insight on these issues. We propose a novel approach that uses time-dependent PSs to consistently estimate conditional HRs, regardless of whether susceptibles have been depleted differentially. Simulations show that adjustment for time-dependent PSs can adjust for covariate imbalances over time that are caused by depletion of susceptibles. Updating the PS is unnecessary when outcome incidence is so low that depletion of susceptibles is negligible. But if incidence is high, and covariates and treatment affect risk, then covariate imbalances arise as susceptibles are depleted, and PS-based methods can consistently estimate the conditional HR only if the PS is periodically updated.
Acellular Dermal Matrix Performance Compared with Latissimus Dorsi Myocutaneous Flap in Expander-Based Breast Reconstruction
Authors: Patrinely James Randall , Farinas Angel , Al-Majed Bader , Forte Antonio Jorge , TerKonda Sarvam , Perdikis Galen
Published: October 2019

Background:

Latissimus dorsi myocutaneous flap (LDMF) with tissue expander provides excellent results in breast reconstruction. Acellular dermal matrix (ADM) has been used in expander-based reconstruction (EBR) with good results. This study assesses how ADM compares to LDMF in EBR.

Methods:

The cohorts comprised 124 patients (218 breasts) who had EBR using ADM between 2006 and 2012, and 242 patients (266 breasts) who had EBR using LDMF between 1994 and 2012. Postoperative complications, reoperations, Breast-Q scores, and objectively assessed aesthetic outcomes were compared.

Results:

Median age was 55 years for both ADM (range 23–84) and LDMF (range 26–88) groups. No statistically significant differences were noted between the groups in the rates of major postoperative complications (P > 0.3). Forty-nine of the 218 (22.5%) in the ADM group and 67 of 266 (25.2%) in the LDMF group had a total of 63 and 84 reoperations, respectively (P = 0.52), with no significant differences in the reoperations rate (P > 0.3). No significant differences were observed in the Breast-Q scores. Some categorical differences were noted in the aesthetic outcomes; however, the difference between the overall outcomes was not significant (P = 0.54).

Conclusion:

Our study revealed no statistically significant differences in the complications or reoperation rates, patient satisfaction, or overall aesthetic outcomes when comparing the use of ADM to LDMF in EBR. In conclusion, this study supports the hypothesis that ADM performs as well as LDMF in EBR.
Eyebrow Height Changes with Aging: A Systematic Review and Meta-analysis
Authors: Asaad Malke , Kelarji Ahmad Beshr , Jawhar Cham Shaban , Banuelos Joseph , Taslakian Editt , Wahood Waseem , Vyas Krishna S. , Sharaf Basel
Published: October 2019

Background:

The eyebrows play an important role in emotional facial expressions, nonverbal communication, and facial esthetics. A comprehensive understanding of the mechanisms underlying eyebrow aging is vital in allowing plastic surgeons to appropriately address these age-related changes and to recreate an aesthetically desirable outcome for patients seeking brow rejuvenation. The aim of this study is to summarize the current literature on eyebrow height changes with aging.

Methods:

A comprehensive search was conducted across several databases to identify all published studies that reported changes of eyebrow position or height with aging, from 1946 to January 2019. Studies that reported eyebrow position at the level of medial canthus, mid-pupil, and lateral canthus were included in a meta-analysis.

Results:

A total of 346 articles were initially identified, of which 19 met our inclusion criteria. Of 3,634 patients who were identified, 2,237 (64%) were females and 1,274 (36%) were males. Eyebrow height showed significant increase with aging at the level of medial canthus (mean difference 1.4 mm; 95% CI: 0.22–2.59; P = 0.02), and the level of mid-pupil (mean difference 1.17 mm; 95% CI: 0.54–1.8; P = 0.0002). However, no significant difference was found at the level of lateral canthus (mean difference 0.19 mm; 95% CI: −0.87 to 1.25; P = 0.72).

Conclusions:

Based on the reviewed literature to date, the medial eyebrow height increases with age, whereas it remains stable at the level of the lateral canthus. These results should be considered when considering eyebrow rejuvenation.
Nasal Skin Thickness Measurements Using Computed Tomography in an Adult Saudi Population
Authors: Jomah Jamal , Elsafi Rawan Adel , Ali Khaled Salah Abdel Elaleem , Abdullah Reem , Gelidan Adnan Ghazi
Published: October 2019

Background:

Rhinoplasty is one of the most challenging operations in plastic surgery, and nasal skin thickness is a significant factor in determining rhinoplasty success. Only a few studies have measured nasal skin thickness before rhinoplasty. The present study was designed to measure nasal skin thickness to shed light on its importance to successful rhinoplasty.

Methods:

Altogether, 60 patients underwent measurements of nasal skin thickness at 4 aesthetic points: nasion, rhinion, nasal tip, columella. The thickness was measured using computed tomography (CT), an objective, reliable tool for this purpose. Universally adopted Hounsfield unit measurement using in house software (Consultant Radiology Center, Riyadh, Saudi Arabia) was performed using CT scan.

Results:

The study group included 32 women and 28 men. Age range was 18–68 years, but most of the patients (53.3%) were within the 20–30-year age range. CT results showed that the mean nasal skin thickness was 3.96 ± 1.08 mm at the nasion, 1.86 ± 0.62 mm at the rhinion, 3.32 ± 0.78 mm at the nasal tip, and 3.32 ± 0.73 mm at the columella. When the nasal skin thicknesses were compared between men and women, a significant difference was observed only at the columella (P = 0.016).

Conclusions:

The nasal skin is thickest at the nasion, thinner at the rhinion, and again thicker at the nasal tip and columella. Our data could be useful for plastic surgeons who could take the patient’s own nasal area thickness into consideration when planning his or her rhinoplasty.
Epithelial Ingrowth Post Phacoemulsification in a Case of Recurrent Pterygium
Authors: Khurana Surbhi , Gupta Parul Chawla , R Balamurugan , Sharma Vijay Kumar , Ram Jagat
Published: October 2019

Purpose:

To report an unusual case of epithelial ingrowth after phacoemulsification with posterior chamber intraocular lens implantation in a patient with recurrent pterygium, along with confocal microscopy findings of epithelial ingrowth.

Methods:

This is a case report and review of the literature.

Results:

A healthy 68-year-old woman presented with epithelial ingrowth with a best-corrected visual acuity of 6/60 in the left eye (−4.0 × 85 DC). She underwent pterygium surgery a decade ago, followed by recurrence 7 years later and an uneventful phacoemulsification surgery with posterior chamber intraocular lens implantation in the previous year. Confocal microscopy showed vacuolated cells in the area of epithelial ingrowth, which were similar to conjunctival cells of the pterygium. The postoperative period after cataract surgery was uneventful.

Conclusions:

This is the first case report to document epithelial ingrowth after phacoemulsification in a patient with recurrent pterygium and that demonstrates confocal microscopy findings showing conjunctival cells of pterygium as the origin of epithelial ingrowth. We recommend making clear corneal side-port incisions during phacoemulsification away from the site of pterygium in such cases and to check for postoperative wound leaks and tissue incarceration.
Keratoconus Could Be Associated With Psoriasis: Novel Findings From a Comparative Study
Authors: Akcam Hanife Tuba , Karagun Ebru , Iritas Ilter , Eyup Yavuz
Published: October 2019

Purpose:

To explore the relationship between keratoconus (KC) and psoriasis.

Methods:

One hundred ten eyes of 55 patients with psoriasis (study group, SG) and 110 eyes of age–sex-matched 55 healthy volunteers (control group, CG) were included in the study. All cases underwent a detailed dermatological and ophthalmological examination including corneal topography. Moreover, Psoriasis Area and Severity Index (PASI) scoring of the patients was carried out in the SG. A thorough comparison of pachymetric, aberrometric, and topometric values between the groups was performed, and the results were interpreted. A χ2 test, Mann–Whitney U test, and Pearson correlation test were used for statistical assessment.

Results:

Although the average Kmax (44.6 in the SG; 44.5 in the CG; P = 0.613) and Belin/Ambrósio enhanced ectasia total deviation value (1.34 in SG; 1.20 in CG; P = 0.880) were similar between the groups, the mean index of vertical asymmetry value in the SG (0.14 mm) was significantly higher than that in the CG (0.11 mm) (P = 0.041). Moreover, 28 eyes from 16 patients with psoriasis were found to be associated with KC because 26 of those 28 eyes were KC suspects and 2 of them were definite KC. A positive correlation was found among topometric parameters, especially between duration of the disease and PASI score. A negative correlation was discovered between topometric parameters and the early beginning of psoriasis.

Conclusions:

Serious changes in topography maps may occur in psoriatic patients. The changes were found to be more evident in the presence of a higher PASI score and the early beginning and longer duration of the disease. The results hinted a potential relationship between psoriasis and KC.
Precision medicine in severe pediatric asthma: opportunities and challenges
Authors: Vijverberg Susanne J.H. , Brinkman Paul , Rutjes Niels W.P. , Maitland-van der Zee Anke H.
Published: October 2019

Purpose of review

Severe pediatric asthma exerts a substantial burden on patients, their families and society. This review provides an update on the latest insights and needs regarding the implementation of precision medicine in severe pediatric asthma.

Recent findings

Biologicals targeting underlying inflammatory pathways are increasingly available to treat children with severe asthma, holding the promise to enable precision medicine in this heterogeneous patient population with high unmet clinical needs. However, the current understanding of which child would benefit from which type or combination of biologicals is still limited, as most evidence comes from adult studies and might not be generalizable to the pediatric population. Studies in pediatric severe asthma are scarce due to the time-consuming effort to diagnose severe asthma and the challenge to recruit sufficient study participants. The application of innovative systems medicine approaches in international consortia might provide novel leads for – preferably noninvasive – new biomarkers to guide precision medicine in severe pediatric asthma.

Despite the increased availability of targeted treatments for severe pediatric asthma, clinical decision-making tools to guide these therapies are still lacking for the individual pediatric patient.
In patients with diabetic foot, improved left ventricular functions are detected by strain echocardiography after the diabetic foot treatment
Authors: Demirtas Derya , Kucukosmanoglu Mehmet
Published: October 2019

Diabetic foot is a macrovascular complication of diabetes mellitus (DM). In the literature, the relationship between diabetic foot and another macrovascular complication of DM is not clear. The aim of this study was to determine the current left ventricular (LV) systolic function in patients with diabetic foot and to investigate the effect of diabetic foot treatment on LV systolic functions.

In this study, 54 patients with diabetic foot and 22 patients without diabetic foot were included. Routine anamnesis, physical examination, echocardiography, and laboratory examinations were performed. In addition, LV global longitudinal strain (LV-GLS) was measured by strain echocardiography technique. LV ejection fraction (LV-EF) and LV-GLS measurements were repeated with echocardiography at the 3rd month of diabetic foot treatment.

The incidence of cardiovascular risk factors such as smoking, hypertension, and coronary artery disease was found to be higher in patients with diabetic foot. (P < .05 for each one). Similarly, in patients with diabetic foot, glucose, Hemoglobin A1c, neutrophil, sedimentation, urea, creatinine, potassium, uric acid, alanine aminotransferase, aspartate aminotransferase, C-reactive protein, and brain natriuretic protein were higher; high-density lipoprotein cholesterol level was found to be significantly lower. LV wall thicknesses and diameters were higher and LV-EF was lower in patients with diabetic foot (P < .05 each one). LV-GLS values were significantly lower in patients with diabetic foot (P < .05). Although no significant change was found in the LV-EF value at the 3rd-month follow-up echocardiography (48.6% ± 7.0% vs 48.5% ± 5.9% and P = .747), it was detected that LV-GLS values (17.3 ± 2.1 vs 18.4 ± 2.3) were significantly increased (P < .001).

LV systolic function was significantly affected in patients with diabetic foot. This may be related to the increased frequency of cardiovascular risk factors in these patients. However, the significant improvement in LV-GLS values after the diabetic foot treatment showed that diabetic foot itself was an important cause of LV systolic dysfunction.
Retropharyngeal hematoma following anterior cervical spine surgery
Authors: Ren Haiyong , Wang Jin , Yu Leijun
Published: October 2019

Rationale:

Retropharyngeal hematoma (RH) is an infrequent but potentially life-threatening complication of anterior cervical spine surgeries (ACSS). Challenging situations might be confronted and catastrophic events or even deaths still occurred occasionally during the treatment. Currently, no widely accepted protocol has been developed.

Patient concerns:

A 55 years old male underwent ACSS due to cervical myelopathy. Thirty-three hours after surgery the patient presented cervical swelling and obstructive dysphagia. Conservative treatment resulted in no recovery and cervical swelling progressed.

Diagnoses:

Emergent magnetic resonance imaging and plain radiograph established massive incisional and RHs. RH was shown to extend from the base of the skull to T1.

Interventions:

An emergent surgery was performed under local anesthesia and cervical hematoma was evacuated. Nonetheless, evacuation of the blood clots in the vision field resulted into incomplete recovery of throat blockage. A gloved finger was used to explore the retropharyngeal space and some hidden blood clots were found and evacuated, then the patient obtained complete relief of the symptoms.

Outcomes:

Normal respiration and swallowing functions were obtained after the surgery. Obviously, recovery of motor function was noted while no other complication was found at 3-month follow-up

Lessons:

Our case illustrated that dysphagia was an early symptom of RH. Posterior compression from RH could cause obstruction of the pharyngeal airway and lead to difficulty of intubation. Hematoma could spread through the retropharyngeal space, a hematoma exploration beyond the visual range might be necessary in some cases for fear of the hidden hematoma.
Standard median sternotomy, right minithoracotomy, totally thoracoscopic surgery, percutaneous closure, and transthoracic closure for atrial septal defects in children
Authors: Yi Kang , Guo Xujian , You Tao , Wang Yunfang , Ding Fan , Hou Xiaodong , Zhou Li
Published: October 2019

Background:

Atrial septal defect (ASD) is one of the most common congenital heart diseases, with an average of 1.64 per 1000 newborns with the ASD. Empirical studies suggest that surgery should be performed early in the presence of right atrium and or right ventricular enlargement, even for asymptomatic patients. Many surgical procedures can be used to treat ASD. But which method is the best choice remains unclear. This study aims to compare the efficacy and safety of standard median sternotomy, right minithoracotomy, totally thoracoscopic surgery, percutaneous closure, transcutaneous by echocardiography, and transcutaneous by radiotherapy for ASDs in children using Bayesian network meta-analysis (NMA).

Methods:

We will perform a comprehensive literature search using PubMed, EMBASE.com, the Cochrane Library, Web of Science, and Chinese Biomedical Literature Database to identify relevant studies from inception to April 2019. Randomized controlled trials, prospective or retrospective cohort studies that reported the efficacy and safety of surgical procedures for the treatment of atrial septal defects will be included. Risk of bias of the included randomized controlled trials and prospective or retrospective cohort studies will be evaluated according to the Cochrane Handbook 5.1.0 and the risk of bias in non-randomized studies of interventions, respectively. A Bayesian NMA will be performed using R 3.4.1.

Results:

The results of this NMA will be submitted to a peer-reviewed journal for publication.

Conclusion:

This NMA will summarize the direct and indirect evidence to assess the efficacy and safety of different surgical procedures for the treatment of ASDs.

Ethics and dissemination:

Ethics approval and patient consent are not required as this study is a network meta-analysis based on published trials.

PROSPERO registration number:

CRD42019130902.
Does cognitive-behavioral therapy reduce internet addiction? Protocol for a systematic review and meta-analysis
Authors: Zhang Junhua , Zhang Yu , Xu Fang
Published: October 2019

Background:

Cognitive-behavioral therapy has been considered as a means for internet addiction, but its long-term effect and the impact of internet addiction types and culture are still unclear.

Objective:

This study aims to assess the efficacy of cognitive-behavior therapy for internet addiction symptoms and associated other psychopathological symptoms.

Method and analysis:

We will search PubMed, Web of Knowledge, Ovid Medline, Chongqing Vip Database, Wanfang, and China National Knowledge Infrastructure database. Random-effects model in comprehensive meta-analysis software will be used to conduct main meta-analysis. Cochran Q and I
2 are be used to assess heterogeneity while funnel plots and the Egger test are used to assess publication bias. Risk of bias for each study included is assessed by using the Cochrane risk of bias tool. The primary outcome is internet addiction symptom while secondary outcomes are psychopathological symptoms, time spent online, and dropout.

Trials registration number:

PROSPERO CRD42019125667
Development and Psychometric Evaluation of the Patient Engagement in Health Care Questionnaire
Authors: Wu Qing , Ye Xuchun , Wu Yaping , Zhao Li
Published: October 2019

Background:

Patient engagement in health care can contribute to improving care quality and safety. A valid measurement is essential for promoting it.

Purpose:

The purpose was to develop the Patient Engagement in Health Care Questionnaire and test its psychometric properties.

Methods:

An item pool was generated based on a literature review and qualitative research, and was reviewed by 2 expert panels. Two rounds of survey, with 364 and 433 patients, respectively, were conducted to evaluate psychometric properties of the questionnaire.

Results:

The questionnaire consists of 33 items. Exploratory factor analysis revealed a 6-factor model, explaining 67.16% of the variance, which included communication and information exchange, engaging in treatment and care, engaging in decision-making, giving feedback about care quality, monitoring care safety, and choosing health care providers. Confirmatory factor analysis indicated that the 6-factor model fit the data well. The scale-level content validity index, Cronbach α, and test-retest reliability were 0.935, 0.928, 0.882, respectively.

Conclusions:

The Patient Engagement in Health Care Questionnaire is a reliable and valid tool to assess patient engagement.
Experience with instrumental methods in radiopharmacy as a tool of radiation protection optimization
Authors: Budinsky Michal , Kozakova Sarka
Published: October 2019

Background:

The purpose of our study is to evaluate the effect of instrumental methods in radiopharmacy on radiation exposure of the staff preparing radiopharmaceuticals.

Methods:

Instrumental methods in radiopharmacy are used since 2004 as a tool of radiation protection optimization for the pharmacists after positron-emission tomography (PET) introduction to the department of nuclear medicine of Masaryk Memorial Cancer Institute (MMCI) in 2003. During 14 years of providing PET radiopharmaceuticals, different equipment and processes were used—DDS-A, μDDS-A and KARl100 (all Tema Sinergie). The increase in a number of instrumental equipment—2 μDDS-A and 1 KARl100, allows preparing 3 different radiopharmaceutical for PET (either [18F]FDG, [18F]FLT, [18F]NaF, [18F]choline, [18F]Vizamyl, [18C]methionine) in 1 day. The radiation exposure to the radiopharmacists was evaluated from ring dosimeters.

Results:

The introduction of PET in 2003 led to rise of the radiation dose over legislation limits to the radiopharmacists with personal maximum of 814.4 mSv/y for hands. As a tool of optimization, instrumental preparing radiopharmaceuticals for PET using DDS-A was introduced. In 2004, rapid reduction of radiation dose was recorded to personal maximum of 106.97 mSv/y for hands. The increase of number and types of PET radiopharmaceuticals used during 1 day required upgrade of equipment used and increase in its number. In 2009, former DDS-A was replaced by 2 μDDS-A. Another tool, KARl100 was installed in 2016. This led to further significant reduction of radiation dose to personal maximum of 24.91 mSv/y for hands.

Conclusions:

Introduction of PET and the need to prepare several different types of radiopharmaceutical lead to rise of radiation exposure and received dose of radiopharmacists. Introduction of instrumental methods in radiopharmacy is a tool for radiation protection optimization. In conclusion, it is the possible to state that instrumental methods in radiopharmacy have a significant effect on radiation protection of the radiopharmacists.
Assessment of medication use process in adult oncology unit of Tikur Anbesa Specialized Hospital
Authors: Gessese Yohannes A. , Fenta Teferi G. , Weldegiorgis Mathewos A.
Published: October 2019

Background:

Chemotherapy errors affect several steps of medication-use process. A reduction of errors and toxicities, and an increase in error awareness, dose verification, proper documentation, and appropriateness of supportive care treatment are important. The present study was conducted to assess the medication-use process and dose-related errors in an outpatient adult oncology unit of Tikur Anbesa Specialized Hospital.

Methods:

An institutional-based cross-sectional study was conducted in an oncology outpatient adult oncology unit of Tikur Anbesa Specialized Hospital between May 1 and June 30, 2012. A total of 212 patient records for 583 chemotherapy administrations were reviewed during the study period.

Results:

The overall dose-related error rate was found to be 228 (39.1%). Specific rate of dose-related errors were (under dosing 58 (25.4%), overdosing 52 (22.8%), inaccurately reconstituted doses 106 (46.5%), and inappropriately adjusted doses 12 (5.3%). Dose labeling and documentation of appropriate time of administration for each chemotherapy preparation were not evident in the unit records. Only 3/14 dose verifications and 3 dose documentation processes were found. Supportive care treatment was not performed according to the recommended standards. Of the 23 equipment and supplies needed for chemotherapy preparation and administration, only 8 were available.

Conclusions:

The findings of our study indicate that the medication-use process in an outpatient adult oncology unit was below expected standards in 2012. The hospital and the school of pharmacy should give emphasis on the establishment of pharmacist run oncology pharmacy for chemotherapy preparation. Policies and guidelines for chemotherapy mixing and administration service and standardization of the process workflow should be developed.
Marjolin Ulcer
Authors: Chaturvedi Gaurav , Gupta Ashish Kumar , Das Saikat , Gohil Amish Jayantilal , Lamba Shashank
Published: October 2019

Introduction

Marjolin ulcer is a rare skin malignancy. Marjolin ulcer arises in zones of long-standing scars, inflammation, or chronic wounds.

Material and methods

The present study was conducted to assess the demographic profile and identify the predictors of recurrence in 55 patients with Marjolin ulcer admitted over 10 years. Patients underwent either wide local excision with 2-cm peripheral margin or amputation if clinically indicated due to joint involvement. Lymph nodes were dissected if found positive. Patients received adjuvant radiotherapy if tumor clearance was less than 4 mm or the draining lymph nodes were positive.

Results

Of the total 55 cases (mean age, 48.75 years; range, 24–74 years), 34 were men and 21 were women (male/female, 1.6:1). The most common cause of injury was flame burn (n = 32, 58%) followed by trauma (n = 10, 18%). The lower limb was frequently affected (n = 38, 69.1%). Twenty-six patients with resection margins less than 4 mm had received adjuvant radiotherapy. Among the 55 patients, 6 (11%) had undergone lymph node dissection. Local recurrence was noted within 18 months in 9 (16.35%) patients, of which 5 patients had a tumor-free margin of less than 4 mm. We found 2 predictors for local recurrence. First, moderately differentiated squamous cell carcinoma (P = 0.04) and, second, patients with lymph node involvement (P = 0.001).

Conclusion

Marjolin ulcer is a high-risk skin tumor. Patients with positive lymph node or with moderately differentiated squamous cell carcinoma have high chances of recurrence. Frequent and intense follow-up is required for at least 2 years.
Effects of the colour of photophase light on locomotor activity in a nocturnal and a diurnal South African rodent
Authors: van der Merwe Ingrid , Bennett Nigel C. , Haim Abraham , Oosthuizen Maria K.
Published: October 2019

Many physiological and behavioural responses to varying qualities of light, particularly during the night (scotophase), have been well documented in rodents. We used varying wavelengths of day-time (photophase) lighting to assess daily responses in locomotor activity in the nocturnal Namaqua rock mouse (
Micaelamys namaquensis
) and diurnal four-striped field mouse (
Rhabdomys pumilio
). Animals were exposed to three light–dark cycle regimes: a short-wavelength- (SWLC, blue), a medium-wavelength- (MWLC, green) and a long-wavelength light–dark cycle (LWLC, red). Overall, daily locomotor activity of both species changed according to different wavelengths of light: the diurnal species displayed most activity under the SWLC and the nocturnal species exhibited the highest levels of activity under the LWLC. Both species showed an increase in diurnal activity and a decrease in nocturnal activity under the LWLC. These results indicate an attenuated responsiveness to long-wavelength light in the nocturnal species, but this does not appear to be true for the diurnal species. These results emphasize that the effect of light on the locomotor activity of animals depends on both the properties of the light and the temporal organization of activity of a species.
Prediction pipeline for discovery of regulatory motifs associated with Brugia malayi molting
Authors: Grote Alexandra , Li Yichao , Liu Canhui , Voronin Denis , Geber Adam , Lustigman Sara , Unnasch Thomas R. , Welch Lonnie , Ghedin Elodie
Published: October 2019

Filarial nematodes can cause debilitating diseases in humans. They have complicated life cycles involving an insect vector and mammalian hosts, and they go through a number of developmental molts. While whole genome sequences of parasitic worms are now available, very little is known about transcription factor (TF) binding sites and their cognate transcription factors that play a role in regulating development. To address this gap, we developed a novel motif prediction pipeline, Emotif Alpha, that integrates ten different motif discovery algorithms, multiple statistical tests, and a comparative analysis of conserved elements between the filarial worms Brugia malayi and Onchocerca volvulus, and the free-living nematode Caenorhabditis elegans. We identified stage-specific TF binding motifs in B. malayi, with a particular focus on those potentially involved in the L3-L4 molt, a stage important for the establishment of infection in the mammalian host. Using an in vitro molting system, we tested and validated three of these motifs demonstrating the accuracy of the motif prediction pipeline.
Natural IgE promotes epithelial hyperplasia and inflammation-driven tumour growth
Authors: Hayes Mark David , Ward Sophie , Crawford Greg , Seoane Rocio Castro , Jackson William David , Kipling David , Voehringer David , Dunn-Walters Deborah , Strid Jessica
Published: October 2019

IgE is the least abundant circulating antibody class but is constitutively present in healthy tissues bound to resident cells via its high-affinity receptor, FcεRI. The physiological role of endogenous IgE is unclear but it is suggested to provide host protection against a variety of noxious environmental substances and parasitic infections at epithelial barrier surfaces. Here we show that skin inflammation enhances levels of IgE with natural specificities and with a similar repertoire, VDJ rearrangements and CDRH3 characteristics as in healthy tissue. IgE-bearing basophils are recruited to inflamed skin via CXCL12 and TSLP/IL-3-dependent upregulation of CXCR4. In the inflamed skin, IgE/FcεRI-signalling in basophils promotes epithelial cell growth and differentiation, partly through histamine engagement of H1R and H4R. Furthermore, this natural IgE response strongly drives tumour outgrowth of epithelial cells harbouring oncogenic mutation. These findings indicate that natural IgE support skin barrier defences however during chronic tissue inflammation this may be subverted to promote tumour growth.
ISG15/USP18/STAT2 is a molecular hub regulating autocrine IFN I-mediated control of Dengue and Zika virus replication
Authors: Espada Constanza Eleonora , da Rocha Edroaldo Lummertz , Ricciardi-Jorge Taissa , dos Santos Adara Aurea , Soares Zamira Guerra , Malaquias Greicy , Patrício Daniel Oliveira , Kozlova Edgar Gonzalez , dos Santos Paula Fernandes , Bordignon Juliano , Sanford Thomas J. , Fajardo Teodoro , Sweeney Trevor R. , Báfica André , Mansur Daniel Santos
Published: October 2019

The establishment of a virus infection is the result of the pathogen’s ability to replicate in a hostile environment generated by the host’s immune system. Here, we found that ISG15 restricts Dengue and Zika viruses’ replication through the stabilisation of its binding partner USP18. ISG15 expression was necessary to control DV replication driven by both autocrine and paracrine type one interferon (IFN-I) signalling. Moreover, USP18 competes with NS5-mediated STAT2 degradation, a major mechanism for establishment of flavivirus infection. Strikingly, reconstitution of USP18 in ISG15-deficient cells was sufficient to restore the STAT2’s stability and restrict virus growth, suggesting that the IFNAR-mediated ISG15 activity is also antiviral. Our results add a novel layer of complexity in the virus/host interaction interface and suggest that NS5 has a narrow window of opportunity to degrade STAT2, therefore suppressing host’s IFN-I mediated response and promoting virus replication.

IMPORTANCE

Disease is an emergent property that results from a microorganism’s ability to replicate in a given host and the latter’s immune response. Here we describe how the immunoregulatory function of ISG15 (an interferon stimulated gene) affects Dengue and Zika virus replication by occupying a niche used by the virus non-structural protein 5 (NS5) to evade host’s immunity. In the absence of ISG15, NS5 efficiently degrades a main signalling hub of innate immunity (STAT2), leading to cell immune suppression and consequently virus growth. This sheds light into how flaviviruses intimately interact with the host immune system and could lead to a host-based therapy target.
Transcriptomic changes due to early, chronic alcohol exposure during cortical development implicate regionalization, cell-type specification, synaptogenesis and WNT signaling as primary determinants of fetal alcohol Spectrum Disorders
Authors: Fischer Máté , Chander Praveen , Kang Huining , Weick Jason P.
Published: October 2019

Fetal alcohol spectrum disorders (FASD) are described by a cluster of deficits following in utero alcohol exposure, whose effects disproportionately target the cerebral cortex. In vitro and in vivo models of FASD have successfully recapitulated multiple facets of clinical presentations, including morphological and behavioral deficits, but far less is understood regarding the molecular and genetic bases of FASD. In this study, we utilize an in vitro human pluripotent stem cell-based (hPSC) model of corticogenesis to probe the effect of early, chronic alcohol exposure on the transcriptome of developing cortical neurons. We here identify a relatively limited number of significantly altered biological pathways, including regional patterning, cell-type specification, axon guidance and synaptic function. Significant upregulation of WNT signaling-related transcripts, to the exclusion of other secreted morphogens was also observed in alcohol exposed cultures. Lastly, an overall alcohol-associated shift towards an increased caudal profile, at the expense of rostral molecular identity was observed, representing a potentially previously underappreciated FASD phenotype.
Scaffold-free human mesenchymal stem cell construct geometry regulates long bone regeneration
Authors: Herberg Samuel , Varghai Daniel , Alt Daniel S. , Dang Phuong N. , Park Honghyun , Cheng Yuxuan , Shin Jung-Youn , Dikina Anna D. , Boerckel Joel D. , Rolle Marsha W. , Alsberg Eben
Published: October 2019

Scaffold-based bone tissue engineering approaches frequently induce repair processes dissimilar to normal developmental programs. In contrast, biomimetic strategies aim to recapitulate aspects of development through cellular self-organization, morphogenetic pathway activation, and mechanical cues. This may improve regenerative outcome in large long bone defects that cannot heal on their own; however, no study to date has investigated the role of scaffold-free construct geometry, in this case tubes mimicking long bone diaphyses, on bone regeneration. We hypothesized that microparticle-mediated in situ presentation of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) to engineered human mesenchymal stem cell (hMSC) tubes induces the endochondral cascade, and that TGF-β1 + BMP-2-presenting hMSC tubes facilitate enhanced endochondral healing of critical-sized femoral segmental defects under delayed in vivo mechanical loading conditions compared to loosely-packed hMSC sheets. Here, localized morphogen presentation imparted early chondrogenic lineage priming, and stimulated robust endochondral differentiation of hMSC tubes in vitro. In an ectopic environment, hMSC tubes formed a cartilage template that was actively remodeled into trabecular bone through endochondral ossification without lengthy predifferentiation. Similarly, hMSC tubes stimulated in vivo cartilage and bone formation and more robust healing in femoral defects compared to hMSC sheets. New bone was formed through endochondral ossification in both groups; however, only hMSC tubes induced regenerate tissue partially resembling normal growth plate architecture. Together, this study demonstrates the interaction between mesenchymal cell condensation geometry, bioavailability of multiple morphogens, and defined in vivo mechanical environment to recapitulate developmental programs for biomimetic bone tissue engineering.

Significance Statement

Engineered bone constructs must be capable of withstanding and adapting to harsh conditions in a defect site upon implantation, and can be designed to facilitate repair processes that resemble normal developmental programs. Self-assembled tubular human mesenchymal stem cell constructs were engineered to resemble the geometry of long bone diaphyses. By mimicking the cellular, biochemical, and mechanical environment of the endochondral ossification process during embryonic development, successful healing of large femoral segmental defects upon implantation was achieved and the extent was construct geometry dependent. Importantly, results were obtained without a supporting scaffold or lengthy predifferentiation of the tubular constructs. This indicates that adult stem/progenitor cells retain features of embryonic mesenchyme, and supports the concept of developmental engineering for bone regeneration approaches.
Multimodal Neuroimaging-based Prediction of Adult Outcomes in Childhood-onset ADHD using Ensemble Learning Techniques
Authors: Luo Yuyang , Alvarez Tara L. , Halperin Jeffrey M. , Li Xiaobo
Published: October 2019

Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent and heterogeneous neurodevelopmental disorder, currently relaying on subjective symptom observations for diagnosis. Machine learning classifiers have been utilized to assist the development of neuroimaging-based biomarkers for objective diagnosis of ADHD. However, the existing basic model-based studies in ADHD reported suboptimal classification performances and inconclusive results, mainly due to the limited flexibility for each type of basic classifiers to appropriately handle multi-dimensional source features with various properties. In this study, we proposed to apply ensemble learning techniques (ELTs) in multimodal neuroimaging data collected from 72 young adults, including 36 probands (18 remitters and 18 persisters of childhood ADHD) and 36 group-matched controls. All the currently available optimization strategies for ELTs (i.e., voting, bagging, boosting and stacking techniques) were tested in a pool of semi-final classification results generated by seven basic classifiers. The high-dimensional neuroimaging features for classification included regional cortical gray matter (GM) thickness and surface area, GM volume of subcortical structures, volume and fractional anisotropy of major white matter fiber tracts, pair-wise regional connectivity and global/nodal topological properties of the functional brain network for cue-evoked attention process. As a result, the bagging-based ELT with the base model of support vector machine achieved the best results, with the most significant improvement of the area under the receiver of operating characteristic curve (0.89 for ADHD vs. controls, and 0.9 for ADHD persisters vs. remitters). We found that features of nodal efficiency in right inferior frontal gyrus, right middle frontal (MFG)-inferior parietal (IPL) functional connectivity, and right amygdala volume significantly contributed to accurate discrimination between ADHD probands and controls; higher nodal efficiency of right MFG greatly contributed to inattentive and hyperactive/impulsive symptom remission, while higher right MFG-IPL functional connectivity strongly linked to symptom persistence in adults with childhood ADHD. Our study also suggested that considering their solidly improved robustness than the commonly implemented basic classifiers, ELTs may have the potential to identify more reliable neurobiological markers for severe brain disorders.
Records of RNA localization through covalent tagging
Authors: Medina-Muñoz Hugo C. , Lapointe Christopher P. , Porter Douglas F. , Wickens Marvin
Published: October 2019

RNA movements and localization pervade biology, from embryonic development to disease. To identify RNAs at specific subcellular locations, we anchored a uridine-adding enzyme at those sites, which then marked RNAs in its vicinity with 3’ terminal uridines. RNAs were tagged independent of their translation status, and included not only mRNAs, but also ncRNAs and ncRNA processing intermediates. A battery of RNAs, including the stress sensor,IRE1, were tagged at both ER and mitochondria, and reveal RNAs whose dual localization is conserved from yeast to human cells.
Eye movements as a readout of sensorimotor decision processes
Authors: Fooken Jolande , Spering Miriam
Published: October 2019

Real-world tasks, such as avoiding obstacles, require a sequence of interdependent decisions to reach accurate motor outcomes. Yet, most studies on primate decision making involve simple one-step choices. Here we investigate how sensorimotor decisions develop over time. In a go/no-go interception task human observers (n=42) judged whether a briefly-presented moving target would pass (interception required) or miss (no hand movement required) a strike box while their eye and hand movements were recorded. Go/no-go decision formation had to occur within the first few hundred milliseconds to allow time-critical interception. We found that the earliest time point at which eye movements started to differentiate decision outcome (go vs. no-go) coincided with hand movement onset. Moreover, eye movements were related to different stages of decision making. Whereas higher eye velocity during smooth pursuit initiation (prior to “whether” decision) was related to higher go/no-go decision accuracy, faster pursuit maintenance was associated with accurate interception timing (“when” decision). These results indicate that pursuit initiation and maintenance are continuously linked to ongoing sensorimotor decision formation.
The majority of histone acetylation is a consequence of transcription
Authors: Martin Benjamin J.E. , Brind’Amour Julie , Jensen Kristoffer N. , Kuzmin Anastasia , Liu Zhen Cheng , Lorincz Matthew , Howe LeAnn J.
Published: October 2019

Histone acetylation is a ubiquitous hallmark of transcriptional activity, but whether the link is of a causal or consequential nature is still a matter of debate. In this study we resolve this question. Using both immunoblot analysis and chromatin immunoprecipitation-sequencing (ChIP-seq) in S. cerevisiae, we show that the majority of histone acetylation is dependent on transcription. Loss of histone H4 acetylation upon transcription inhibition is partially explained by depletion of histone acetyltransferases (HATs) from gene bodies, implicating transcription in HAT targeting. Despite this, HAT occupancy alone poorly predicts histone acetylation, suggesting that HAT activity is regulated at a step post-recruitment. Collectively, these data show that the majority of histone acetylation is a consequence of RNAPII promoting both the recruitment and activity of histone acetyltransferases.