bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Survivorship of Total Hip Arthroplasty with Highly Cross-Linked Polyethylene for Osteonecrosis
Authors: Hart Adam , Janz Viktor , Trousdale Robert T. , Sierra Rafael J. , Berry Daniel J. , Abdel Matthew P. 
Published: September 2019

Background:Osteonecrosis of the hip is the underlying etiology for 3% to 12% of total hip arthroplasties (THAs). Compared with patients who undergo THA because of osteoarthritis, those who do so because of osteonecrosis typically are younger, have a greater number of underlying diagnoses, and have inferior clinical outcomes and implant survivorship. The purpose of this study was to compare the long-term implant survivorship (median follow-up, 10 years), functional outcomes, and radiographic results of contemporary THAs with a highly cross-linked polyethylene (HXLPE) liner between patients with osteonecrosis and those with osteoarthritis.Methods:All patients who underwent primary THA with an HXLPE liner from 1999 to 2007 were identified from our institutional total joint registry. Patients with a primary diagnosis of osteonecrosis were matched 1:1, on the basis of age, sex, and body mass index (BMI), to patients with a diagnosis of osteoarthritis. This resulted in 461 hips in 413 patients with osteonecrosis matched to 461 hips in 427 patients with osteoarthritis (mean age, 59 years; 47% female; and mean BMI, 29 kg/m2). Long-term implant survivorship, patient-reported outcomes, and radiographic findings were compared. In addition, a subgroup analysis of the osteonecrosis group was performed to see whether certain underlying etiologies portended poor outcomes. The median follow-up was 10 years.Results:The 15-year cumulative rates of revision were 6.6% and 4.5% in the osteonecrosis and osteoarthritis groups, respectively (hazard ratio [HR] = 1.8, p = 0.09). The 15-year cumulative rates of any reoperation were 10.5% and 6.4% in the osteonecrosis and osteoarthritis groups, respectively (HR = 2.2, p = 0.008). There were no radiographic signs of component loosening or osteolysis in the entire cohort. Despite a lower median preoperative Harris hip score (HHS) for patients with osteonecrosis, both groups had marked improvements in their scores, which were similar at all time points after surgery. The cumulative rate of reoperations at 15 years was 0% for hips with radiation-induced osteonecrosis, 6.3% for those with alcohol-induced osteonecrosis, 9.0% for those with posttraumatic osteonecrosis, 12.1% for those with steroid-induced osteonecrosis, and 25% for those with idiopathic osteonecrosis.Conclusions:Contemporary THA with an HXLPE liner offers excellent long-term implant survivorship and functional outcomes for patients with osteonecrosis; however, the risk of a reoperation is higher when compared with patients with osteoarthritis.Level of Evidence:PrognosticLevel III. See Instructions for Authors for a complete description of levels of evidence.
“Found Down” Compartment Syndrome
Authors: Parzych Lydia , Jo Jacob , Diwan Amna , Swart Eric 
Published: September 2019

Background:
With the worsening of the opioid epidemic, there has been an increasing number of cases in which patients are “found down” following a drug overdose and develop a crush injury resulting in muscle necrosis, rhabdomyolysis, and elevated compartment pressures in a unique presentation of compartment syndrome. The purpose of the present study is to summarize our experience at a trauma center in a region with a high endemic rate of opiate abuse to provide guidance for the management of patients with “found down” compartment syndrome.

Methods:
We performed a retrospective review of the records of patients who had been found unconscious as the result of overdose, with findings that were concerning for compartment syndrome, and had been managed with fasciotomy or observation at the discretion of the surgeon. The patients were divided into 3 groups based on presentation (partial deficits, complete deficits, or unexaminable), and the operative findings, hospital course, laboratory values, and functional status were compared between the groups.

Results:
Over 12 years, we identified 30 “found down” patients who had an examination that was concerning for compartment syndrome. Twenty-five patients were managed with fasciotomy; this group required an average of 4.2 operations and had a 20% infection rate and a 12% amputation rate. Lactate, creatine phosphokinase, and creatinine levels typically were elevated but did not correspond with muscle viability or return of function. At the time of initial debridement, 56% of patients had muscle that appeared nonviable, although muscle function returned in 28% of the patients who had questionable viability. Four patients had no motor or neurological function on initial examination, and none had meaningful return of function at the time of the latest follow-up. Of the 10 patients who had partial neurological deficits at the time of presentation and underwent fasciotomy, over half (70%) had some improvement in ultimate function.

Conclusions:
Patients who are “found down” following an opiate overdose with crush injuries resulting in compartment syndrome have a high surgical complication rate and poor recovery of function. The limited data from the present study suggest that those with absent function at the time of presentation are unlikely to gain function after fasciotomy, and the risk-benefit ratio of fasciotomy in this patient population may be different from that for patients with traumatic compartment syndrome.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Patient-Reported Outcome Measures and Health-Related Quality-of-Life Scores of Patients Undergoing Anatomic Total Shoulder Arthroplasty [RETRACTED]
Authors: Jain Sukrit S. , DeFroda Steven F. , Paxton E. Scott , Green Andrew 
Published: September 2019

Background:
Health-related quality-of-life (HRQoL) scores are required for cost-effectiveness and health-care value analysis. We evaluated HRQoL scores and patient-reported outcome measures (PROMs) in patients with advanced glenohumeral osteoarthritis treated with anatomic total shoulder arthroplasty to establish values of HRQoL scores that can be used for cost-effectiveness and value analysis and to assess relationships between HRQoL scores and shoulder and upper-extremity PROMs.

Methods:
We analyzed 145 patients (145 shoulders) with glenohumeral osteoarthritis treated with anatomic total shoulder arthroplasty; 93 patients had 1-year follow-up. Preoperative and postoperative functional outcomes were assessed with the Disabilities of the Arm, Shoulder and Hand (DASH) score, the American Shoulder and Elbow Surgeons (ASES) score, the Simple Shoulder Test (SST), and a visual analog scale (VAS) for shoulder pain and function. Health utility was assessed with the EuroQol-5 Dimensions (EQ-5D), Short Form-6 Dimensions (SF-6D), and VAS Quality of Life (VAS QoL). HRQoL score validity was determined through correlations between the PROMs and HRQoL scores. The responsiveness of HRQoL scores was measured through the effect size and the standardized response mean.

Results:
There were significant improvements in all PROMs and HRQoL scores (p < 0.001) at 1 year after the surgical procedure. The changes in VAS QoL and EQ-5D were significantly correlated (weak to moderate) with the changes in all PROMs except the SST, demonstrating comparably acceptable validity. The VAS QoL had a large effect size (1.833) and standardized response mean (1.603), and the EQ-5D also had a large effect size (1.163) and standardized response mean (1.228), demonstrating responsiveness. The effect sizes of all PROMs were larger than those of the HRQoL scores. The change in SF-6D had only a moderate effect size and standardized response mean and was not significantly correlated with the change in any of the PROMs.

Conclusions:
PROMs and HRQoL scores are not interchangeable, and studies of the cost-effectiveness and value of shoulder arthroplasty should incorporate both shoulder and upper-extremity PROMs and HRQoL scores. The findings of this study provide data on HRQoL scores that are specific to the treatment of advanced glenohumeral osteoarthritis with anatomic total shoulder replacement and can be used for future cost-effectiveness and value analysis studies.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Functional Results and Photic Phenomena with new Extended-Depth-of-Focus Intraocular Lens
Authors: Giers Bert C. , Khoramnia Ramin , Varadi Dorottya , Wallek Hannah , Son Hyeck Soo , Attia Mary S. , Auffarth Gerd U. 
Published: September 2019

Abstract
Background: Evaluation of clinical and functional results of a new extended depth of focus intraocular lens (EDOF-IOL).

Methods: Fourteen cataract patients (twenty-eight bilateral implantations) were assessed for uncorrected (UDVA) and corrected (CDVA) distance visual acuities; uncorrected (UNVA), distance-corrected (DCNVA) and best corrected (CNVA) near visual acuities; and uncorrected (UIVA) and distance-corrected (DCIVA) intermediate visual acuities - as well as binocular defocus curves. Photopic and mesopic contrast sensitivity was recorded. Reading acuity was evaluated using an electronic reading desk at fixed distances and at the patient’s preferred near and intermediate distances. Visual symptoms were assessed with a halo and glare simulator plus a patient questionnaire which also recorded quality of life.

Results: Median postoperative monocular UDVA was 0.13logMAR (range -0.08 to 0.42logMAR), median CDVA was -0.01logMAR (range -0.20 to 0.22logMAR), median UIVA at 80 cm was -0.05logMAR (range -0.18 to 0.58logMAR) and median UNVA at 40 cm was 0.14logMAR (range -0.10 to 0.64logMAR). Binocular uncorrected reading acuity was 0.10logMAR at 40 cm and 0.11logMAR at 80 cm. Patients preferred a median intermediate reading distance of 62.8 cm over the predetermined 80 cm, which allowed them to read smaller letter size but did not improve reading acuity. Patients reported a high rate of spectacle independence and satisfaction in everyday life and little to no dysphotopsia.

Conclusion: The Mini WELL Ready IOL provided good postoperative functional results at far and intermediate distances and improved the visual and reading acuity at reading distance. The lens caused little to no dysphotopsia.
An automated high throughput solution for DNA extraction and bisulfite-conversion from high volume liquid biopsy specimens – sample preparation for epigenetic analysis
Authors: Rausch Sebastian , Hasinger Oliver , König Thomas , Schlegel Anne , Weiss Gunter 
Published: September 2019

Abstract
Objective: DNA methylation analysis via real-time PCR or other analytical techniques requires purified bisulfite converted DNA. We report on an automated high throughput solution for DNA extraction, bisulfite-conversion, and purification of 96 samples with an input volume of up to 3.5mL of plasma or urine, using reagents from the commercially available Epi BisKit. Results: Magnetic bead-based DNA extraction, bisulfite conversion at high temperature, and efficient DNA purification was conducted on a customized commercially available liquid-handling platform. A highly interlaced 4x24 sample protocol was implemented for DNA extraction, elution in a 96-well plate, efficient bisulfite-conversion and extensive purification. The resulting bisulfite-converted DNA was stored in a 96-well format, ready for PCR set-up or other down-stream applications. The automated method is a walk-away solution for processing 96 samples in 7h30min. Performance of the method was validated by comparison with the standard manual method of the Epi BiSKit using technical and biological samples. Overall DNA yield was assessed with a standardized ß-actin assay. The automated workflow demonstrated equivalent performance to the manual method for technical, plasma and urine samples. It may provide a new standard for effective high-throughput preparation of bisulfite-converted DNA from a variety of high volume liquid biopsy specimens.
Developing a High-Performance Liquid Chromatography Fast and Accurate Method for Quantification of Silibinin In-Vitro
Authors: Bakhshi Faezeh , Molavi Ommoleila , Rashidi Mohammad Reza , Shayanfar Ali , Amini Hassan 
Published: September 2019

Abstract
Objective : Silibinin is an antioxidant agent and is shown to have anticancer effects in different cancers including lung, breast, colorectal, liver, prostate, and kidney. There are challenges in the clinical use of Silibinin. The main limitation is low solubility, poor oral absorption, and extensive hepatic metabolism. We developed a High-Performance Liquid Chromatography sensitive method for quantification of Silibinin in in-vitro samples to quantify in different formulations. We applied HPLC set, C18 column as stationary phase and the mixture of methanol (90%) and water (10%) as mobile phase. Utilized solutions were daily prepared through serial dilution of stock solution to make specific concentrations ranged between 10 μg/ml to 100 μg/ml. The developed method was validated by credible guidelines. Results : The calibration curve was drawn according to the height peaks of different concentrations and the established method demonstrated a linear ranged from 10 to 100 µg/ml, with a correlation coefficient of 0.996 for in-vitro samples. The retention time was 2.97 min, and the accuracy and precision (inter-day and intra-day) of the developed method was in the range of 88-105.9%. These results demonstrate that the developed method can be a fast and accurate method for quantification of Silibinin in in-vitro samples.
Heterogeneity of Microglia Phenotypes: Developmental, Functional and Some Therapeutic Considerations
Authors: Yuan Yun , Wu Chunyun , Ling Eng-Ang 
Published: September 2019

Background:Microglia play a pivotal role in maintaining homeostasis in complex brain environment. They first exist as amoeboid microglial cells (AMCs) in the developing brain, but with brain maturation, they transform into ramified microglial cells (RMCs). In pathological conditions, microglia are activated and have been classified into M1 and M2 phenotypes. The roles of AMCs, RMCs and M1/M2 microglia phenotypes especially in pathological conditions have been the focus of many recent studies.Methods:Here, we review the early development of the AMCs and RMCs and discuss their specific functions with reference to their anatomic locations, immunochemical coding etc. M1 and M2 microglia phenotypes in different neuropathological conditions are also reviewed.Results:Activated microglia are engaged in phagocytosis, production of proinflammatory mediators, trophic factors and synaptogenesis etc. Prolonged microglia activation, however, can cause damage to neurons and oligodendrocytes. The M1 and M2 phenotypes featured prominently in pathological conditions are discussed in depth. Experimental evidence suggests that microglia phenotype is being modulated by multiple factors including external and internal stimuli, local demands, epigenetic regulation, and herbal compounds.Conclusion:Prevailing views converge that M2 polarization is neuroprotective. Thus, proper therapeutic designs including the use of anti-inflammatory drugs, herbal agents may be beneficial in suppression of microglial activation, especially M1 phenotype, for amelioration of neuroinflammation in different neuropathological conditions. Finally, recent development of radioligands targeting 18 kDa translocator protein (TSPO) in activated microglia may hold great promises clinically for early detection of brain lesion with the positron emission tomography.
The Evolution of Population Pharmacokinetic Model of Oral Phenytoin for Early Seizure Prophylaxis Post-Craniotomy
Authors: Li Zhongdong , Wang Chuan , Ji Shuangmin , Jin Hao , Song Guiqin 
Published: September 2019

Background:
This study aimed to re-establish a Population Pharmacokinetic (PPK) model of oral phenytoin
to further optimize the individualized medication regimen based on our previous research.

Methods:
Patients with intracranial malignant tumor requiring craniotomy were prospectively enrolled according to
the inclusion criteria. Genotypes of CYP2C9*1 or *3 and CYP2C19*1, *2 or *3 were determined by real time PCR
(TaqMan probe) method. Serum concentrations of phenytoin on the 4th and 7th day after oral administration were
determined using fluorescence polarization immunoassay. The PPK parameters were estimated using Nonlinear
Mixed Effects Models (NONMEM) and internal validation was performed using bootstraps. The predictive performance
of the final model was evaluated by Normalized Predictive Distribution Errors (NPDEs) and diagnostic goodness-
of-fit plots.

Results:
A total of 390 serum samples were collected from 170 patients in PPK model building group. The population
typical values for Vm, Km and the apparent volume of distribution (V) in the final model were 17.5 mg/h, 6.41
mg/L and 54.8 L, respectively. Internal validation by bootstraps showed that the final model was stable and reliable.
NPDEs with a normal distribution and a scatterplot with symmetrical distribution showed that the final model had
good predictive capability. Individualized dose regimens of additional 40 patients in the external validation group
were designed by the present final PPK model. The percentages of patients with serum concentrations within the
therapeutic range were 61.53% (24/39) on the 4th day and 94.87% (37/39) on the 7th day, which were higher than the
39.33% (59/150) and 52.10% (87/167) of above 170 patients (P < 0.0001).

Conclusion:
The present PPK final model for oral phenytoin may be used to further optimize phenytoin individualized
dose regimen to prevent early seizure in patients after brain injury if patient characteristics meet those of the
population studied.
Design, Synthesis, Docking Studies and Biological Activities Novel 2,3- Diaryl-4-Quinazolinone Derivatives as Anti-HIV-1 Agents
Authors: Hajimahdi Zahra , Zabihollahi Rezvan , Aghasadeghi Mohamad Reza , Zarghi Afshin 
Published: September 2019

Background:
Although major efforts have been devoted to the effective treatment of
HIV-1 infection, it has remained one of the leading causes of deaths around the world. So, development
of anti-HIV-1 agents featuring novel structure is essential.

Objective:
To synthesize novel quinazolinone derivatives and evaluate their anti-HIV-1 activity.

Method:
In this study, we designed and synthesized a series of novel 2,3-diaryl-4-quinazolinone derivatives
using a one-pot multicomponent reaction. Then, the resulting derivatives were evaluated
for anti-HIV-1 activity using Hela cell-based single-cycle replication assay.

Results:
Most of the compounds showed efficacy against HIV-1 replication and the compound 9c
exhibited the highest activity with EC50 value of 37 μM. Docking studies indicated that synthesized
compounds can interact with the key residues of the HIV-1 integrase active site. Binding of the most
active compound was consistent with the HIV-1 integrase inhibitors.

Conclusion:
Based on our results, these derivatives represent novel lead compounds for the development
of new promising anti-HIV-1 agents.
Effect of Statin Supplementation on Pulmonary Function and Inflammatory Markers in Patients of Chronic Obstructive Pulmonary Disease
Authors: Daga Mradul K. , Chhoda Ankit , Singh Shashank , Mawari Govind , Kumar Naresh , Mishra Tarun K. , Hira Harmanjit S. 
Published: September 2019

Background:COPD being a systemic inflammatory disease is accompanied by alteration of various inflammatory cytokines which affect the metabolic equilibrium of body. Some therapeutic options, mainly statins via their wide range of pharmacologic actions alter the level of proinflammatory cytokines hence, helpful in attenuating various extra-pulmonary consequences of COPD. We did a randomised case-control study to study the effect of statin supplementation on pulmonary function and inflammatory markers in patients of COPD.Methods:We included 40 stable COPD subjects & randomized them in two groups, Intervention & Non-intervention. Intervention group received 40 mg atorvastatin once daily for 3 months in addition to the conventional treatment of COPD similar to the prior one. We studied levels of IL-6 & CRP and correlated them with disease severity before and after the aforementioned intervention.Results:We observed that CRP levels decreased in both the groups after a follow up of 3 months, but neither of them was statistically significant (p=0.57 & 0.63 respectively) nor the mean of their difference (p=0.969). IL-6 levels showed a persistent decline in intervention group but, was not significant (p=0.91). In this study, we noticed statistically significant improvement in FEV1 (p=0.008) in the intervention group which was in contrast to non-intervention group. Similarly, the exercise capacity also statistically increased in the intervention group (p=0.002). There was also evident negative correlation between exercise capacity and IL-6 as well CRP levels. FEV1 also showed statistically significant negative correlation with IL-6 levels (p=0.023).Conclusion:We can improve the disease outcome and alter its natural progression by altering the levels of inflammatory markers with the aid of some additional pharmacological interventions i.e., in this study was atorvastatin.
In silico and in vitro Study of the Inhibitory Effect of Antiinflammatory Drug Betamethasone on Two Lipases
Authors: Samira Nia , Khedidja Benarous , Zahra Abdelalim Fatima , Elyakine Chellali Khadidja Nour , Mohamed Yousfi 
Published: September 2019

Background:For the first time, the anti-inflammatory drug betamethasone is investigated for its inhibitory activity against lipase.Objective:This work aims to demonstrate the in vitro and in silico inhibitory effect of the anti-inflammatory drug betamethasone on the enzymatic activity of two lipases.Methods:In vitro study using p-nitrophenyllaurate as lipase substrate is used to determine inhibition potency. Molecular Docking is performed using the Autodock Vina for drug molecule and two enzymes Candida rugosa lipase and human pancreatic lipase.Results:Betamethasone represents a moderate inhibition effect with a value of IC50 of 0.36±0.01 mg/ml. Molecular docking allowed us to understand inhibitory – enzyme interactions and to confirm in vitro obtained results.Conclusion:These experiments showed that betamethasone can be used in the treatment of diseases related to lipase activity.