Miracle-dz/UniFAR-FTUs huggingface dataset:
UV Irradiation Affects Melanocyte Stimulatory Activity and Protein Binding of Piperine

Abstract Piperine, the major alkaloid of black pepper (Piper nigrum L.; Piperaceae), stimulates melanocyte proliferation and dendrite formation in vitro. This property renders it a potential treatment for the skin depigmentation disorder vitiligo. However, piperine does not stimulate melanin synthesis in vitro, and treatments based on this compound may therefore be more effective with concomitant exposure of the skin to ultraviolet (UV) radiation or sunlight. The present study investigated the effect of UVA and simulated solar radiation (SSR) on the chemical stability of piperine, its melanocyte stimulatory effects and its ability to bind protein and DNA. Chromatographic and spectroscopic analysis confirmed the anticipated photoisomerization of irradiated piperine and showed the absence of any hydrolysis to piperinic acid. Isomerization resulted in the loss of ability to stimulate proliferation of a mouse melanocyte cell line, and to bind to human serum albumin. There was no evidence of DNA binding by piperine either before or after irradiation, showing the absence of photoadduct formation by either piperine or its geometric isomers. This is unlike the situation with psoralens, which form DNA adducts when administered with UVA in treating skin diseases. The present study suggests that exposure to bright sunlight should be avoided both during active application of piperine to the skin and in the storage of piperine products. If UVA radiation is used with piperine in the treatment of vitiligo, application of the compound and irradiation should be staggered to minimize photoisomerization. This approach is shown to effectively induce pigmentation in a sparsely pigmented mouse strain.
The association between trajectories of endocrine therapy adherence and mortality among women with breast cancer

Studies examining adherence to endocrine therapy (ET) and breast cancer‐related outcomes have traditionally used the proportion of days covered (PDC) by medication to define adherence which may mask true treatment–outcome associations for patients with different medication use behaviors. We use group‐based trajectory models to examine the association between ET adherence patterns and mortality compared to a standard PDC adherence measure.
Effects of 17α-Methyltestosterone and Aromatase Inhibitor Letrozole on Sex Reversal, Gonadal Structure, and Growth in Yellow Catfish Pelteobagrus fulvidraco

Monosex populations are in demand in many fish species with sexual dimorphism, e.g., better growth performance, higher gonad value, superior ornamental value. From the point of view of research, a monosex population is one of the best materials for investigating sex-determining mechanisms, sex differentiation, and sex-linked markers. Sex reversal of females (phenotypic reversal from XX female to XX male) is the first step in all-female production in species with an XX/XY system for sex determination. In the present study, masculinization of yellow catfish, a species with XX/XY sex determination, was investigated by oral administration of various doses of 17α-methyltestosterone (MT) or an aromatase inhibitor (AI) letrozole (LZ); effects on survival, growth performance, sex ratio, and changes in gonadal structure were evaluated. Three doses (20, 50, and 100 mg kg−1 diet) of oral MT or LZ were administered to fry from 10 days post-hatching (DPH) to 59 DPH. Oral administration of MT at all doses did not significantly change the ratio of males (45.8%, 33.3%, and 50.0% respectively) compared to the control group (37.5%), while yielding intersex fish at all doses (4.2% to 8.3%). Oral administration of LZ produced a significantly higher proportion of males in all doses (75.5%, 83.3%, and 75.0%, respectively). Additionally, the lowest dose of LZ improved the growth of treated fish compared to the control, and all doses of LZ enhanced spermatogenesis in treated males.
Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood

Marijuana and hashish are the illicit drugs most frequently used by human adolescents. Given the continued neurodevelopment throughout adolescence, adolescents may be more vulnerable than adults to certain neural consequences of heavy marijuana use. This study aimed to assess whether an experimental model of adolescent chronic exposure to Δ9‐tetrahydrocannabinol (THC), may induce lasting effects on learning and memory. Adolescent rats have been treated with THC or its vehicle from 35 to 45 postnatal days (PND) and left undisturbed until their adulthood (75 PND) when aversive and spatial memory was assessed using the passive avoidance and radial maze tasks. No alteration was found in aversive memory, but in the radial maze THC pretreated animals exhibited a worse performance than vehicles, suggesting a deficit in spatial working memory. To correlate memory impairment to altered neuroplasticity, level of marker proteins was investigated in the hippocampus, the most relevant area mediating spatial memory. A significant decrease in the astroglial marker glial fibrillar acid protein was found as well as in pre‐ and postsynaptic protein expression (VAMP2, PSD95) and NMDA receptor levels in pretreated rats. To parallel these changes to alteration in dendritic morphology, Golgi‐Cox staining was performed in the hippocampal dentate gyrus. Pretreated rats had a significantly lower total dendritic length and number than vehicles, as well as reduced spine density. Our data suggest that THC pretreated rats may establish less synaptic contacts and/or less efficient synaptic connections throughout the hippocampus and this could represent the molecular underpinning of the cognitive deficit induced by adolescent THC treatment. © 2009 Wiley‐Liss, Inc.
Early Medical History of Children with Autism Spectrum Disorders

ABSTRACT. Previous studies have suggested that children with autism spectrum disorders (ASD) may have different medical histories than nonspectrum children in several areas: their reactions to vaccinations, number of ear infections, chronic gastrointestinal problems, and use of antibiotics. Furthermore, some studies have found associations between regressive autism and gastrointestinal (GI) symptoms. The present study analyzes the medical records from birth to the age of 2 years of 99 children (24 typically developing; 75 with ASD, of whom 29 had parent-reported regression). Data were coded in the following areas: frequency and purpose of pediatrician visits, frequency and type of illnesses and medications, type and chronicity of GI complaints, date of vaccinations, growth data, and whether the pediatrician noted behaviors indicative of an ASD before the age of 2 years. Children with ASD were found to have significantly more ear infections than the typically developing children as well as to use significantly more antibiotics. Typically developing children had significantly more illness-related fevers. There was a nonsignificant trend toward the ASD group having more chronic gastrointestinal problems. There were no significant differences between the groups for the age of vaccination or for number of pediatrician visits. Finally, pediatricians noted symptoms of onset of possible autism, including language delay, for 44 of the 75 children with ASD and 2 of the 24 typical children. Results are discussed in terms of needs for future research.
A RESTUDY OF THE SURGICAL ANATOMY OF THE POSTERIOR ASPECT OF THE GLOBE: An Essential Topography For Exact Macular Buckling

Purpose: To study the anatomy of the posterior aspect of the globe comparing it with previous textbook descriptions, to find constant anatomical landmarks for macular buckling surgery. Design: This is an anatomical study on cadaver eyes with additional in vivo measurements during the macular buckling procedure. Methods: Twelve cadaver eyes were carefully dissected identifying important structures on the posterior aspect of the globe and measuring their cross-diameters and relative distances. The distance of the medial end of inferior oblique insertion from the foveal position projected on the scleral surface and the border of the optic nerve sheath were measured. The intrascleral course of temporal long posterior ciliary artery was identified and measured, and its distance from the optic nerve sheath was also measured. Results: The macula consistently lies on the horizontal meridian (foveal horizontal meridian) defined by the course of the long posterior ciliary arteries, which cross the optic nerve somewhere between its center and its lower border. Conclusion: The horizontal meridian (foveal horizontal meridian), defined by the entry site and course of the long posterior ciliary arteries, serves as an important surgical landmark if precise external scleral buckling of the fovea is the objective. For practical purposes, foveal horizontal meridian, geometrical horizontal meridian, and optic nerve horizontal meridian need to be distinguished.
Anesthetic Depth Defined Using Multiple Noxious Stimuli during Isoflurane/Oxygen Anesthesia I. Motor Reactions

BackgroundPotency of inhaled anesthetics usually is defined by determining the minimal alveolar concentration (MAC) that prevents movement in 50% of patients in response to skin incision. Skin incision, however, is usually only a single event and, thus, determination of potency cannot be repeated in one patient. Traditional MACskin incision cannot be used to predict response to other noxious stimuli. The aim of this study was to investigate the effects of other noxious stimulation patterns and then compare these to MACskin incision measuring the end-tidal isoflurane concentrations with the corresponding arterial concentrations. MethodsIn 26 patients, the end-tidal and corresponding arterial isoflurane concentrations needed to suppress eye opening to verbal command and motor response after trapezius squeeze, 50 Hz electric tetanic stimulation, laryngoscopy, skin incision, and tracheal intubation in 50% of all patients were determined. ResultsThe end-tidal (equivalent arterial) isoflurane concentrations (mean ± SE, adjusted to sea level) expressed in vol% (to allow comparison) increased in the following order (mean ± SE): vocal command 0.37 ± 0.09 (0.36 ± 0.09); trapezius squeeze 0.84 ± 0.07 (0.65 ± 0.07); laryngoscopy 1.00 ± 0.12 (0.78 ± 0.09); tetanic stimulation 1.03 ± 0.09 (0.80 ± 0.06); skin incision 1.16 ± 0.10 (0.97 ± 0.17); and intubation 1.76 ± 0.13 (1.32 ± 0.11). ConclusionsDifferent stimuli require different isoflurane concentrations to suppress motor responses. Tetanic stimulation and, to some extent, trapezius squeeze are reproducible and noninvasive stimulation patterns that can be used as an alternative to skin incision when evaluating potency of an anesthetic agent. In contrast to skin incision, they can be repeated.
Rejuvenation of Photoaged Skin: 5 Years Results with Intense Pulsed Light of the Face, Neck, and Chest

BACKGROUND Photorejuvenation involves the use of lasers or light sources to reverse signs of photoaging. Multiple devices have been shown to be effective over the short-term. OBJECTIVE To investigate the long-term clinical results on the face, neck and chest at 4 years using filtered flashlamp intense pulsed light (IPL) for treatment of photoaging changes of telangiectasias, dyspigmentation, and rough skin texture. METHODS A chart review of 80 randomly selected patients with skin types I-IV who were treated by IPL during 1996 and 1997 was performed. Photos and patient self-assessment were graded for features of textural smoothness, telangiectasia severity, and blotchy pigmentation into four categories of worse, no change, slightly better (less than 50% improvement) and much better (greater than 50% improvement). RESULTS At 4 years following initial treatment, skin textural improvement was noted in 83% of the subjects. Telangiectasias were improved in 82% of subjects, while pigmentation remained improved in 79%. The median number of treatments was 3. The face responded slightly better than the chest or neck. Most common side-effects included temporary mild crusting (19%), erythema (15%) and purpura (6%). CONCLUSION Signs of photoaging including telangiectasias and mottled pigmentation of the face, neck, and chest, can be improved by IPL with a long-lasting result. Minimal or no downtime with minimal adverse effects can be achieved with the settings reported. Skin textural smoothing, although not easily quantified, is an additional benefit observed long-term.
Perampanel in Parkinson Disease Fluctuations: A Double-Blind Randomized Trial With Placebo and Entacapone

ObjectivesPerampanel is a selective and noncompetitive &agr;-amino-3-hydroxy-5-methylisoxazole propionic acid–type glutamate receptor antagonist that improves motor symptoms in animal models of Parkinson disease (PD). The aim of this study was to assess the efficacy and tolerability of perampanel in L-dopa–treated patients with moderately severe PD and motor fluctuations using an active comparator study design. MethodsThis was a prospective, randomized, double-blind, 3-arm, parallel-group, controlled study assessing the effects of perampanel (4 mg/d), placebo, or entacapone (200 mg with each dose of L-dopa) in 723 L-dopa–treated patients with PD with “OFF” problems. The primary outcome measure was the change from baseline in mean total daily OFF time based on diaries. Secondary end points included change from baseline in Unified Parkinson’s Disease Rating Scale part II while OFF, Unified Parkinson’s Disease Rating Scale part III while “ON,” and mean total daily ON time without dyskinesias or with nontroublesome dyskinesias. ResultsIn total, 480 patients (66.4%) completed the study, which was terminated early after negative results of 2 other large placebo-controlled studies became available. Perampanel was not superior to placebo on any efficacy end point, whereas entacapone was superior to placebo on the primary end point (P = 0.034) and most secondary outcomes. Perampanel was generally well tolerated. ConclusionsPerampanel (4 mg/d) was well tolerated but did not have a clinically significant effect in improving motor symptoms of L-dopa–treated patients with moderately advanced PD and motor fluctuations. These patients did respond to the active comparator, entacapone, confirming the validity of the findings despite the early termination of the study.
Steroid-induced Deficiency of Mucosal-associated Invariant T Cells in the Chronic Obstructive Pulmonary Disease Lung. Implications for Nontypeable Haemophilus influenzae Infection.

RATIONALE Mucosal-associated invariant T (MAIT) cells are a recently described abundant, proinflammatory T-cell subset with unknown roles in pulmonary immunity. Nontypeable Haemophilus influenzae (NTHi) is the leading bacterial pathogen during chronic obstructive pulmonary disease (COPD) exacerbations and is a plausible target for MAIT cells. OBJECTIVES To investigate whether MAIT cells respond to NTHi and the effects of inhaled corticosteroids (ICS) on their frequency and function in COPD. METHODS Eleven subjects with COPD receiving ICS, 8 steroid-naive subjects with COPD, and 21 healthy control subjects underwent phlebotomy, sputum induction, bronchoalveolar lavage, and endobronchial biopsy. Pulmonary and monocyte-derived macrophages were cultured in vitro with NTHi. MEASUREMENTS AND MAIN RESULTS Frequencies of Vα7. 2+CD161+ MAIT cells, surface expression of the major histocompatibility complex-related protein 1 (MR1), and intracellular IFN-γ expression were measured by flow cytometry. MAIT-cell frequencies were reduced in peripheral blood of ICS-treated subjects with COPD (median 0.38%; interquartile range [IQR], 0.25-0.96) compared with healthy control subjects (1.8%; IQR, 1.4-2.5; P = 0.001) or steroid-naive patients with COPD (1.8%; IQR, 1.2-2.3; P = 0.04). MAIT cells were reduced in bronchial biopsies from subjects with COPD treated with steroids (0.73%; IQR, 0.46-1.3) compared with healthy control subjects (4.0%; IQR, 1.6-5.0; P = 0.02). Coculture of live NTHi increased macrophage surface expression of MR1 and induced IFN-γ from CD4 cells and CD8 cells, but most potently from MAIT cells (median IFN-γ-positive frequencies, 2.9, 8.6, and 27.6%, respectively). In vitro fluticasone and budesonide reduced MR1 surface expression twofold and decreased NTHi-induced IFN-γ secretion eightfold. CONCLUSIONS MAIT cells are deficient in blood and bronchial tissue in steroid-treated, but not steroid-naive, COPD. NTHi constitutes a target for pulmonary MAIT-cell immune responses, which are significantly impaired by corticosteroids.
An Orthotopic Nude Mouse Model for Evaluating Pathophysiology and Therapy of Pancreatic Cancer

Introduction Orthotopic, clinically relevant animal models are necessary for the study of pathophysiology and therapy for pancreatic cancer. Aims To develop a minimally traumatic technique of orthotopic tumor induction, to develop a scoring system to quantify local and systemic tumor spread, and to provide a model with a broad range of well-differentiated to undifferentiated pancreatic cancers. Methodology Orthotopic tumors were induced in nude mice by atraumatic pancreatic implantation of two fragments from subcutaneous donor tumors or intrapancreatic injection of human tumor cells (MIAPaCa-2, AsPC-1, HPAF-2, Capan-1). Animals were monitored for 14 weeks or until death. Primary tumor volume, local infiltration, and systemic metastasis were assessed and analyzed at autopsy. Macroscopic findings were confirmed by histologic evaluation. Results Tumor take rate in the implantation group was 100% for all four cell lines. Marked differences with regard to tumor size, metastatic spread, and survival were found depending on the grade of differentiation. Less differentiated cells (MIAPaCa-2, AsPC-1) caused higher dissemination scores and mortality than better-differentiated cells (HPAF-2, Capan-1). Clinical features included cachexia, jaundice, and malignant ascites. Orthotopic tumor cell injection resulted in an incomplete tumor take rate. Moreover, early artificial abdominal tumor spread was found in injected animals due to microscopic cell loss during the injection procedure. Conclusions Orthotopic implantation of donor tumor fragments into nude mice is technically feasible and is superior to the cell injection technique. It results in reproducible local and systemic development of pancreatic cancer that mimics the human disease. A dissemination score may help to better quantify therapeutic effects in future studies.
COMBINED TREATMENT WITH SAXAGLIPTIN PLUS DAPAGLIFLOZIN REDUCES INSULIN LEVELS BY INCREASED INSULIN CLEARANCE AND IMPROVES β-CELL FUNCTION.

OBJECTIVE To determine if reduction in serum insulin with dapagliflozin plus saxagliptin or dapagliflozin add-on to metformin contributed to increased insulin clearance and to assess the effects of these treatments on β-cell function. METHODS Patients (glycated hemoglobin, 8 to 12%; 64 to 108 mmol/mol) were randomized to 24-week, double-blind treatment with saxagliptin 5 mg/day plus dapagliflozin 10 mg/day (n = 179), saxagliptin 5 mg/day plus placebo (n = 176), or dapagliflozin 10 mg/day plus placebo (n = 179) added to metformin. C-peptide to insulin ratio was used as an index of insulin clearance during a meal tolerance test, and β-cell function was evaluated by Homeostasis Model Assessment 2. RESULTS At 24 weeks, compared with baseline, saxagliptin + dapagliflozin and saxagliptin + placebo increased mean (95% confidence interval [CI]) C-peptide area under the curve (AUC0-180 min) (40.2 [9.2 to 71.3] ng/mL and 95.4 [63.4 to 127.4] ng/mL, respectively); no change was noted with dapagliflozin + placebo (14.5 [-17.6 to 46.8] ng/mL). Insulin AUC was reduced from baseline with saxagliptin + dapagliflozin (-1,120.4 [-1,633.9 to -606.9] μU/mL) and dapagliflozin + placebo (-1,018.6 [-1550.5 to -486.8] μU/mL) but increased with saxagliptin + placebo (661.2 [131.1 to 1,191.3] μU/mL). C-peptide to insulin ratio did not change versus baseline with saxagliptin + placebo but increased after saxagliptin + dapagliflozin and dapagliflozin + placebo, largely due to decreased insulin AUC with dapagliflozin. All treatments improved β-cell function (mean change [95% CI] from baseline, saxagliptin+dapagliflozin: 20.6% [16.5% to 24.8%]; dapagliflozin + placebo: 17.0% [12.7% to 21.4%]; saxagliptin + placebo: 11.0% [6.6% to 15.5%]). CONCLUSION Increased C-peptide to insulin ratio with saxagliptin + dapagliflozin and dapagliflozin + placebo add-on to metformin compared with saxagliptin + placebo add-on to metformin suggests that dapagliflozin increases insulin clearance and may contribute to lower circulating insulin. All treatments improved β-cell function, with the greatest improvements with saxagliptin + dapagliflozin and dapagliflozin + placebo. ABBREVIATIONS A1c = glycated hemoglobin AUC0-180 min = area under the curve from 0 to 180 minutes HOMA-2β = homeostasis model assessment-2 β-cell function SGLT-2 = sodium-glucose cotransporter-2 T2D = type 2 diabetes.
Response Bias and the Personality Inventory for DSM–5: Contrasting Self- and Informant-Report

Previous research has raised concerns that scores derived from the Personality Inventory for DSM–5 (PID-5; American Psychiatric Association, 2013; Krueger, Derringer, Markon, Watson, & Skodol, 2012) may be compromised by response styles such as underreporting or overreporting. The informant-report form of the PID-5 (PID-5-IRF; Markon, Quilty, Bagby, & Krueger, 2013) has been recommended for use when response bias is an assessment concern. The purpose of the current investigation was to evaluate PID-5 and PID-5-IRF scale score elevations across participants exhibiting signs of overreporting or underreporting. A total of 245 adults completed the PID-5 and the Revised NEO Personality Inventory (NEO PI-R; Costa & McCrae, 1992). A family member or friend of at least 1 year’s acquaintance completed the PID-5-IRF for 216 of these. A total of 211 target-informant pairs were available for analysis. Participants were categorized as overreporting and underreporting according to NEO PI-R validity scale cutoffs. The majority of PID-5 scale scores were elevated in those identified as overreporting; more than half of the PID-5-IRF scale scores were similarly elevated. The majority of PID-5 scale scores were lower in those scoring above underreporting cut-offs; however, PID-5-IRF scales were not as consistently or strongly impacted. PID-5 scales were strongly impacted by response bias, whereas PID-5-IRF scores were less strongly impacted overall, and more so by overreporting bias. Caution when using these instruments in the assessment of personality disorders prone to over- or underreporting may be warranted.