bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Liquid Chromatography-Tandem Mass Spectrometry Method for Quantifying Amisulpride in Human Plasma and Breast Milk, Applied to Measuring Drug Transfer to a Fully Breast-Fed Neonate
Authors: O'Halloran Sean J. , Wong Antonia , Joyce David A. 
Published: April 2016

Background:
Amisulpride is a second generation atypical antipsychotic drug. The management of psychosis exacerbation in late pregnancy or during lactation is often hampered by inadequate knowledge of risk to the baby from placental transfer or breast milk transfer of drugs. There is no specific information on adverse effects from amisulpride. To gather guiding information from one mother–baby pair, we conducted a drug concentration study on the fourth post-natal day and developed a novel liquid chromatography-tandem mass spectrometry method with application to the very small plasma volumes obtainable from a neonate, requiring 15 μL of plasma, and with application to human breast milk.

Methods:
Plasma and breast milk extracts, spiked with deuterated internal standard (amisulpride-d5) were separated isocratically with a buffered water–methanol–acetonitrile mobile phase. A tandem mass spectrometer in positive electrospray ionisation mode with multiple reaction monitoring was used for detection.

Results:
Method linearity, sensitivity, imprecision, matrix effects, recovery, and overall process efficiency were satisfactory for milk and plasma. No interferences were found from a broad range of psychotropic and general drugs. The breast milk area under the concentration–time curve for the interval 0–12 hours was 10,726 mcg·h·L−1, corresponding to a mean breast milk concentration of 894 mcg/L. Breast milk amisulpride was 12-fold higher than the simultaneous plasma concentration. The baby's plasma amisulpride concentration was 10.5% of the maternal plasma concentration.

Conclusions:
An assay was developed that is suitable for therapeutic drug monitoring of amisulpride. Its application to breast milk and neonate plasma showed that amisulpride partitioned strongly into breast milk and that the neonate reached plasma levels that were more than desirable for a psychotropic drug.
Primary ovarian insufficiency associated with autosomal abnormalities: from chromosome to genome-wide and beyond
Authors: Vichinsartvichai Patsama 
Published: April 2016

Abstract

Objective:
The pathophysiology of primary ovarian insufficiency (POI) is not well elucidated. Many candidate genetic aberrations are on the X-chromosome; on the contrary, many genetic perturbations are also on the autosomes. The aim of this review is to summarize the knowledge of genetic aberrations on autosomes from chromosomal rearrangement, gene abnormality, genome-wide association studies and epigenetics.

Methods:
Searches of electronic databases were performed. Articles and abstracts relevant to POI and genetic studies associated with autosomes were summarized in this interpretive literature review.

Results:
Various genetic aberrations located on the autosomes were found. These abnormalities are from chromosomal rearrangement, which might disrupt the critical region on chromosome loci or disturbance of the meiosis process. Specific gene aberrations are also identified. The genes that have functions in ovarian development, folliculogenesis, and steroidogenesis on autosomes are proposed to be involved from gene association studies. Gene-to-gene interaction or epistasis also might play a role in POI occurrence. Recently, genetic techniques to study the whole genome have emerged. Although no specific conclusion has been made, the studies using genome-wide association to find the specific aberration throughout the genome in POI have been published. Epigenetic mechanisms might also take part in the pathogenesis of POI.

Conclusions:
The considerably complex process of POI is still not well understood. Further research is needed for gene functional validation studies to confirm the contribution of genes in POI, or additional genome-wide association studies using novel clustered regularly interspaced short palindromic repeat/Cas9 technique might make these mechanisms more comprehensible.
Combined Use of the Latissimus Dorsi Musculocutaneous Flap and the Anterolateral Thigh Flap to Reconstruct an Extensive Shoulder Defect in an NF-1 Patient
Authors: Miyamoto Shimpei , Fujiki Masahide , Sakisaka Masanobu , Kawai Akira 
Published: April 2016

Summary:
Soft tissue coverage after the resection of a large malignant peripheral neural sheath tumor (MPNST) is a challenge. We report the successful reconstruction of an extensive shoulder defect after MPNST resection in a patient with a type 1 neurofibromatosis with a novel combination of flaps. A 70-year-old man with type 1 neurofibromatosis presented with a recurrent MPNST on his right shoulder. He underwent a wide excision of the tumor, which resulted in a huge soft tissue defect around the shoulder joint. The resultant defect was reconstructed with a pedicled latissimus dorsi musculocutaneous flap and a free anterolateral thigh flap. The flaps survived, and the wounds healed uneventfully. His affected arm was useful. The combination of a pedicled latissimus dorsi musculocutaneous flap and a free anterolateral thigh flap is a versatile option for the reconstruction of an extensive shoulder defect.
BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION: A CASE REPORT
Authors: Alasil Tarek , Coady Patrick A. , Koudsi Sirine , Mathur Mahan , Materin Miguel A. 
Published: April 2016

Purpose:
To report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) in the setting of metastatic ovarian cancer.

Methods:
In this observational case report, a 59-year-old woman presented with bilateral worsening vision and photophobia. She had been diagnosed with metastatic ovarian cancer 5 years prior for which she received Tamoxifen. Ophthalmic examination was completed followed by fluorescein angiography and optical coherence tomography (Spectralis OCT; Heidelberg Engineering).

Results:
The visual acuity was 20/150 in both eyes. Exam demonstrated an iris pigmented lesion in the right eye, bilateral nuclear sclerotic cataracts, multiple orange lesions in the fundus, elevated pigmented uveal melanocytic tumors with diffuse choroidal thickening and multifocal early hyperfluorescence of these lesions (giraffe-like pattern) on fluorescein angiography, and exudative retinal detachment on OCT. The patient was diagnosed with BDUMP in the setting of metastatic ovarian carcinoma. Further metastatic workup demonstrated enlarged lymphadenopathy in the right axilla and inguinal regions. The patient declined chemotherapy and was initiated on plasmapheresis.

Conclusions:
BDUMP is a peculiar paraneoplastic syndrome in the setting of metastatic ovarian cancer, where antigens from the retinal pigment epithelium, iris and choroidal melanocytes cross-react with ovarian tumor cell antibodies that are circulating in the serum. Plasmapheresis can decrease the concentrations of the antibodies, maintain reasonable functional vision and improve the quality of life.
PERSISTENT PLACOID MACULOPATHY IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Puche Nathalie , Hera Ruxandra , Terrada Celine , Souied Eric H. 
Published: April 2016

Purpose:
To describe the case of a patient presenting with persistent placoid maculopathy imaged with optical coherence tomography angiography.

Methods:
Case report of a 72-year-old man who presented with blurred vision in his right eye. fundus photography, fluorescein angiography, infracyanine green angiography, fundus autofluorescence imaging, spectral domain optical coherence tomography, optical coherence tomography angiography, and split spectrum amplitude decorrelation angiography were performed. The diagnosis was made based on ophthalmological manifestations and multimodal imaging.

Results:
The spectral domain optical coherence tomography image of the right eye revealed disruption of the ellipsoid layers, and an underlying sliver of hyporeflectance. In the left eye, there were no obvious changes on spectral domain optical coherence tomography. In both eyes, infracyanine green angiography showed hypocyanescence of the lesions, persisting throughout late phases. In optical coherence tomography angiography, imaging of the choroidal capillary layers revealed hyposignal lesions, topographically corresponding exactly to hypocyanescent lesions on infracyanine green angiography.

Conclusion:
In this patient, a distinct hyposignal on optical coherence tomography angiography, combined with hypocyanescence on infracyanine green angiography, was interpreted as indicating focal hypoperfusion of the choriocapillaris.
FLATTENING OF A TREATMENT-RESISTANT RETINAL PIGMENT EPITHELIAL DETACHMENT AFTER A SINGLE INTRAVITREAL INJECTION OF ZIV-AFLIBERCEPT
Authors: Yogi Rohit , Stewart Michael , Chhablani Jay 
Published: April 2016

Purpose:
To report flattening of a treatment-resistant retinal pigment epithelial detachment (PED) due to neovascular age-related macular degeneration after a single intravitreal injection of ziv-aflibercept (Zaltrap).

Methods:
A 67-year-old woman with a neovascular age-related macular degeneration–related PED was treated with intravitreal injections of bevacizumab and ranibizumab, and in combination with verteporfin photodynamic therapy, before receiving a single intravitreal injection of ziv-aflibercept (1.25 mg/0.05 mL).

Results:
The patient presented with a visual acuity of 20/30 in the right eye, a PED height of 581 μm, and a central macular thickness of 381 μm. She received eight intravitreal injections of bevacizumab and ranibizumab, one in combination with photodynamic therapy. The height of the PED and the central macular thickness varied over time, but 3 years later, they measured 382 μm and 418 μm, respectively. A single intravitreal injection of ziv-aflibercept resulted in a dramatic reduction in PED height to 140 μm, which was maintained 2 months later. The visual acuity remained stable, and there were no clinical signs of toxicity.

Conclusion:
Intravitreal ziv-aflibercept safely and effectively improved a treatment-resistant PED. Intravitreal ziv-aflibercept could become a treatment option for neovascular age-related macular degeneration in countries where aflibercept (Eylea) is not available or its cost is prohibitive, but further studies are necessary to establish efficacy and safety.
Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses
Authors: Low Lucie A. , Bauer Lucy C. , Pitcher Mark H. , Bushnell M. Catherine 
Published: April 2016

Abstract
With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the “nociceptive” central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli.
A Simple Dietary Questionnaire Correlates With Formal Dietitian Evaluation and Frequently Identifies Specific Clinical Interventions in an Outpatient Gastroenterology Clinic
Authors: Dubin Sterling M. , Vadivelu Jaya , Copur-Dahi Nedret , Miranda Leslie , Palermo Dana , Pandey Braj , Groessl Erik J. , Ho Samuel B. 
Published: April 2016

Background:
The spectrum of gastroenterology-related diseases related to obesity is growing. Few clinical tools exist to aid in clinician-guided dietary counseling.

Goals:
(1) Develop and validate a 1-page diet history form that would provide information on dietary factors that can contribute to gastrointestinal (GI) illness and to assess adherence to the Mediterranean diet; and (2) evaluate the form in a general GI clinic to determine its potential utility as a clinical tool.

Study:
A 1-page diet history form was developed and underwent qualitative and quantitative validation in comparison to a formal diet evaluation by a registered dietitian. The form was then evaluated in consecutive patients attending a general GI clinic, and analyzed for overall diet content, compliance with a Mediterranean diet, and presence of high-risk (red flag) dietary behaviors.

Results:
The form was evaluated in 134 patients. In a validation cohort (n=30) the qualitative dietary components measured were highly concordant with a formal dietary interview. Total daily calorie intake correlated with formal dietary review (R=0.61), but tended to underestimate total calories due to less precision in portion size. The prospective cohort (n=104) patients had a mean body mass index of 29.8. Overall, 52.9% were obese, 50% had metabolic syndrome, and 51% had a primary GI illness directly impacted by dietary factors (gastroesophageal reflux, irritable bowel, fatty liver). Overall, 85.6% of patients documented red flag behaviors. Patients with obesity trended for more red flags than overweight or normal body mass index groups.

Conclusion:
A 1-page diet questionnaire correlated well with formal dietary assessment and identified clinically relevant dietary interventions in a high percentage of GI patients.
Palliative Locoregional Treatment for Unresectable Nonmetastatic Klatskin Tumor
Authors: Liu Yanfeng , Sun Jingxian , Ma Dening , Jin Bin , Shao Zhenyu , Wang Jianbo , Zhang Zongli 
Published: April 2016

Purpose:
This study aimed to identify the effect of percutaneous transhepatic biliary drainage (PTBD) combined with 3-dimensional conformal radiotherapy (3D-CRT) in comparison with PTBD therapy only on the treatment of unresectable Klatskin tumors (KTs).

Materials and Methods:
Thirty-seven patients with unresectable KTs were included in the study. Twenty-six patients received PTBD and 3D-CRT successively, whereas the other 11 patients received PTBD only. Changes in the clinical symptoms after the PTBD treatment, the radiotherapy effect, and the survival time were recorded and analyzed.

Results:
The clinical symptoms of the 2 groups gradually decreased after the PTBD treatment. The radiotherapy effect showed an overall effective rate (complete response+partial response) of 17 (65.38%), and the serum carbohydrate antigen-19-9 levels before and after 3D-CRT were significantly different (P<0.001). The mean survival time of the PTBD group was 11.27 months; the 1- and 2-year cumulative survival rates were 36.4% and 9.1%, respectively. The mean survival time of the combined therapy group was 22.77 months; the 1-, 2-, and 3-year cumulative survival rates were 53.8%, 38.5%, and 11.5%, respectively. The log-rank test showed that the patients who received combined therapy had longer survival time than the patients who only received PTBD (P=0.001).

Conclusions:
Patients with unresectable KTs who underwent PTBD could relieve biliary obstruction effectively. Although this study is not a randomized trial, 3D-CRT combined with PTBD seems to be a promising and an effective method as a palliative treatment for unresectable KTs.
Gastric Activity and Gut Peptides in Patients With Functional Dyspepsia
Authors: Russo Francesco , Chimienti Guglielmina , Clemente Caterina , Riezzo Giuseppe , D’Attoma Benedetta , Martulli Manuela 
Published: April 2016

Goals:
The goals of the study were to investigate in both postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) the gastric electrical activity and the gastric emptying (GE) time together with the circulating concentrations of motilin, somatostatin, corticotrophin-releasing factor, and neurotensin, and to establish whether the genetic variability in the neurotensin system genes differs between these 2 categories of functional dyspepsia (FD).

Background:
The current FD classification is based on symptoms and it has been proven not to be completely satisfying because of a high degree of symptom overlap between subgroups.

Study:
Gastric electrical activity was evaluated by cutaneous electrogastrography: the GE time by 13C-octanoic acid breast test. Circulating concentrations of gut peptides were measured by a radioimmunoassay. NTS 479 A/G and NTSR1 rs6090453 SNPs were evaluated by PCR and endonuclease digestion.

Results:
Fifty-four FD patients (50 female/4 male) were studied. Using a symptom questionnaire, 42 patients were classified as PDS and 12 as EPS, although an overlap between the symptom profiles of the 2 subgroups was recorded. The electrogastrographic parameters (the postprandial instability coefficient of dominant frequency, the dominant power, and the power ratio) were significantly different between the subgroups, whereas the GE time did not differ significantly. In addition, EPS was characterized by a different gut peptide profile compared with PDS. Finally, neurotensin polymorphism was shown to be associated with neurotensin levels. This evidence deserves further studies in consideration of an analgesic role of neurotensin.

Conclusions:
Analysis of gut peptide profiles could represent an interesting tool to enhance FD diagnosis and overcome limitations due to a distinction based solely on symptoms.
Adolescent tracheal intubation in an adult urban emergency department: a retrospective, observational study
Authors: Hale James J. , Lynch Stephen , Ray David C. , Reid Lindsay A. 
Published: April 2016

Objectives
Tracheal intubation is the cornerstone of advanced emergency airway management in children and adults and there is good-quality data characterizing intubation in both groups. There are, however, few published studies on emergency tracheal intubation in adolescents. We carried out an observational study to characterize tracheal intubation in adolescents.

Methods
We analysed data from a previously collected Emergency Department Intubation Registry. We included all attempts at tracheal intubation performed in our adult emergency department between 1999 and 2011. We recorded the indication for intubation, the staff involved, the technique and drugs used, and the rates of successful intubation and adverse events. We classified patients into three age groups: 13–16 years (adolescent), 17–24 years (young adult) and at least 25 years (older adult).

Results
Trauma was the most common indication for intubation in adolescents, and rapid sequence induction was used in 88% of cases. Ninety-nine percent of tracheal intubations in adolescent patients were successful on the first or the second attempt, no adolescent underwent more than three attempts and none required a surgical airway. The initial intubation attempt in adolescents was more likely to be performed by an anaesthetist (P<0.005). The first attempt success rate was higher (P<0.01) and adverse event rate was lower (P<0.05) in adolescents than in adults. Hypotension was the only adverse event recorded in adolescents; this occurred in three patients (4.5%).

Conclusion
Our findings suggest that the airway in adolescent patients can be managed successfully and safely in an adult emergency department where there is close collaboration between anaesthetists and emergency physicians.
Claims-based Identification Methods and the Cost of Fall-related Injuries Among US Older Adults
Authors: Hoffman Geoffrey J. , Hays Ron D. , Shapiro Martin F. , Wallace Steven P. , Ettner Susan L. 
Published: April 2016

Objectives:
Compare expenditures of fall-related injuries (FRIs) using several methods to identify FRIs in administrative claims data.

Research Design:
Using 2007–2009 Medicare claims and 2008 Health and Retirement Survey data, FRIs were identified using external-cause-of-injury (e-codes 880/881/882/884/885/888) only, e-codes plus a broad set of primary diagnosis codes, and a newer approach using e-codes and diagnostic and procedural codes. Linear regression models adjusted for sociodemographic, health, and geographic characteristics were used to estimate per-FRI, service component, patient cost share, expenditures by type of initial FRI treatment (inpatient, emergency department only, outpatient), and total annual FRI-related Medicare expenditures.

Subjects:
The analysis included 5497 community-dwelling adults ≥65 (228 FRI, 5269 non-FRI individuals) with continuous Medicare coverage and alive during the 24-month study.

Results:
The 3 FRI identification methods produced differing distributions of index FRI type and varying estimated expenditures: $12,171 [95% confidence interval (CI), $4662–$19,680], $5648 (95% CI, $3819–$7476), and $9388 (95% CI, $5969–$12,808). In all models, most spending occurred in hospital, outpatient, and skilled nursing facility (SNF) settings, but greater proportions of SNF and outpatient spending were observed with commonly used FRI identification methods. Patient cost-sharing was estimated at $691–$1900 across the 3 methods. Inpatient-treated index FRIs were more expensive than emergency department and outpatient-treated FRIs across all methods, but were substantially higher when identifying FRI using only e-codes. Estimated total FRI-related Medicare expenditures were highly variable across methods.

Conclusions:
FRIs are costly, with implications for Medicare and its beneficiaries. However, expenditure estimates vary considerably based on the method used to identify FRIs.
Effects of melatonin on cardiovascular diseases: progress in the past year
Authors: Sun Hang , Gusdon Aaron M. , Qu Shen 
Published: April 2016

Purpose of reviewMelatonin is a neuroendocrine hormone synthesized primarily by the pineal gland. Numerous studies have suggested that melatonin plays an important role in various cardiovascular diseases. In this article, recent progress regarding melatonin's effects on cardiovascular diseases is reviewed.Recent findingsIn the past year, studies have focused on the mechanism of protection of melatonin on cardiovascular diseases, including myocardial ischemia-reperfusion injury, myocardial hypoxia-reoxygenation injury, pulmonary hypertension, hypertension, atherosclerosis, valvular heart diseases, and other cardiovascular diseases.SummaryStudies have demonstrated that melatonin has significant effects on ischemia-reperfusion injury, myocardial chronic intermittent hypoxia injury, pulmonary hypertension, hypertension, valvular heart diseases, vascular diseases, and lipid metabolism. As an inexpensive and well tolerated drug, melatonin may be a new therapeutic option for cardiovascular disease.