Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Insight upon Chitosan Solution and Chitosan Nanoparticles Application on the Phenolic Content, Antioxidant and Antimicrobial Activities of Individual Grape Components of Sousão Variety

Chitosan, a natural polysaccharide, has been previously proposed as an elicitor in plants to prevent pathogen infections. The present study aimed to analyze the effect of chitosan solution and chitosan nanoparticles treatment applied on the grapevine variety Sousão with respect to the phenolic composition, antioxidant potential and antibacterial activity of its individual grape components. Grapevine plants of selected lines were sprayed with chitosan solution and chitosan nanoparticles, and ethanolic extracts of stems, seeds and skins were prepared from grapevines treated and not treated with chitosan. Total phenolic, anthocyanin and tannin contents were studied, and the identification of the individual phenolic compounds was performed by HPLC-DAD. The antimicrobial susceptibility method was performed using the Kirby-Bauer disc diffusion method against multidrug-resistant bacteria. Overall, there was small increase in the concentration of phenolic compounds, antioxidant and antimicrobial activities in grape components treated with chitosan solution. Seed extracts showed the highest antioxidant and antimicrobial activities. The studied individual components obtained from chitosan-treated grapevines could represent an added value due to the increased antioxidant and antibacterial potentials. The phenolic compounds found in components may be used in food and pharmaceutical industries as natural food preservers and antibiotic adjuvants.
Risk factors for progression of age‐related macular degeneration

Age‐related macular degeneration (AMD) is a degenerative disease of the macula, often leading to progressive vision loss. The rate of disease progression can vary among individuals and has been associated with multiple risk factors. In this review, we provide an overview of the current literature investigating phenotypic, demographic, environmental, genetic, and molecular risk factors, and propose the most consistently identified risk factors for disease progression in AMD based on these studies. Finally, we describe the potential use of these risk factors for personalised healthcare.
Lipids and Alzheimer’s Disease

Lipids, as the basic component of cell membranes, play an important role in human health as well as brain function. The brain is highly enriched in lipids, and disruption of lipid homeostasis is related to neurologic disorders as well as neurodegenerative diseases such as Alzheimer’s disease (AD). Aging is associated with changes in lipid composition. Alterations of fatty acids at the level of lipid rafts and cerebral lipid peroxidation were found in the early stage of AD. Genetic and environmental factors such as apolipoprotein and lipid transporter carrying status and dietary lipid content are associated with AD. Insight into the connection between lipids and AD is crucial to unraveling the metabolic aspects of this puzzling disease. Recent advances in lipid analytical methodology have led us to gain an in-depth understanding on lipids. As a result, lipidomics have becoming a hot topic of investigation in AD, in order to find biomarkers for disease prediction, diagnosis, and prevention, with the ultimate goal of discovering novel therapeutics.
Outpatient Reduction Mammaplasty Offers Significantly Lower Costs with Comparable Outcomes: A Propensity Score–Matched Analysis of 18,780 Cases

Supplemental Digital Content is available in the text. Background: Breast reduction mammaplasty is a common plastic surgery operation. Although many contemporary surgeons provide breast reduction mammaplasty as an outpatient procedure, roughly 15 percent of patients are still observed postoperatively. The authors hypothesize that observation confers no safety benefit but engenders significant cost. Methods: The authors reviewed cases of breast reduction mammaplasty in a commercial database and formulated three propensity score–matched cohorts: inpatient, 23-hour observation, and outpatient. Comparisons were made between inpatients and outpatients and between 23-hour observation patients and outpatients. The primary outcome variable was 14-day re-presentation rate to the emergency department or readmission. Financial data were also collected. Results: Comparison of inpatients and outpatients included 1237 patients each (n = 2474 total patients). The 23-hour observation–outpatient comparison included 8153 patients each (n = 16,306 total patients). For inpatients versus outpatients, the 14-day re-presentation rate was 1.4 percent for inpatients and 0.3 percent for outpatients (p < 0.01). The overall surgical complication rate was higher for inpatients (7.8 percent) than for outpatients (4.9 percent) (p < 0.01). Comparing outpatients to 23-hour observation patients, the 14-day re-presentation rate was similar (0.5 percent observation versus 0.3 percent outpatient; p = 0.10). The complication rate was higher for 23-hour observation patients (4.8 percent) than for outpatients (3.2 percent) (p < 0.01). When compared with outpatients (median, $9077), inpatients (median, $19,975) generated $10,898 more in costs. Similarly, 23-hour observation patients (median, $12,451) generated $4050 more in costs than outpatients (median, $8401) (p < 0.01). Conclusions: Outpatient breast reduction mammaplasty is equally safe when compared to observation or admission. Non–outpatient breast reduction mammaplasty had median costs of 148 to 220 percent that of outpatient breast reduction mammaplasty. In an era of cost consciousness, ambulatory reduction mammaplasty may offer a relatively simple method of decreasing expenditures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
A biophysical model of striatal microcircuits suggests gamma and beta oscillations interleaved at delta/theta frequencies mediate periodicity in motor control

Striatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. Local field potential recordings in rodent striatum show dopamine- and reward-dependent transitions between two states: a “spontaneous” state involving β (∼15-30 Hz) and low γ (∼40-60 Hz), and a state involving θ (∼4-8 Hz) and high γ (∼60-100 Hz) in response to dopaminergic agonism and reward. The mechanisms underlying these rhythmic dynamics, their interactions, and their functional consequences are not well understood. In this paper, we propose a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of these rhythms, as well as their modulation by dopamine. Building on previous modeling and experimental work suggesting that striatal projection neurons (SPNs) are capable of generating β oscillations, we show that networks of striatal fast-spiking interneurons (FSIs) are capable of generating δ/θ (ie, 2 to 6 Hz) and γ rhythms. Under simulated low dopaminergic tone our model FSI network produces low γ band oscillations, while under high dopaminergic tone the FSI network produces high γ band activity nested within a δ/θ oscillation. SPN networks produce β rhythms in both conditions, but under high dopaminergic tone, this β oscillation is interrupted by δ/θ-periodic bursts of γ-frequency FSI inhibition. Thus, in the high dopamine state, packets of FSI γ and SPN β alternate at a δ/θ timescale. In addition to a mechanistic explanation for previously observed rhythmic interactions and transitions, our model suggests a hypothesis as to how the relationship between dopamine and rhythmicity impacts motor function. We hypothesize that high dopamine-induced periodic FSI γ-rhythmic inhibition enables switching between β-rhythmic SPN cell assemblies representing the currently active motor program, and thus that dopamine facilitates movement in part by allowing for rapid, periodic shifts in motor program execution.
Encapsulation of β-Carotene by Emulsion Electrospraying Using Deep Eutectic Solvents

The encapsulation β-carotene in whey protein concentrate (WPC) capsules through the emulsion electrospraying technique was studied, using deep eutectic solvents (DES) as solvents. These novel solvents are characterized by negligible volatility, a liquid state far below 0 °C, a broad range of polarity, high solubilization power strength for a wide range of compounds, especially poorly water-soluble compounds, high extraction ability, and high stabilization ability for some natural products. Four DES formulations were used, based on mixtures of choline chloride with water, propanediol, glucose, glycerol, or butanediol. β-Carotene was successfully encapsulated in a solubilized form within WPC capsules; as a DES formulation with choline chloride and butanediol, the formulation produced capsules with the highest carotenoid loading capacity. SEM micrographs demonstrated that round and smooth capsules with sizes around 2 µm were obtained. ATR-FTIR results showed the presence of DES in the WPC capsules, which indirectly anticipated the presence of β-carotene in the WPC capsules. Stability against photo-oxidation studies confirmed the expected presence of the bioactive and revealed that solubilized β-carotene loaded WPC capsules presented excellent photo-oxidation stability compared with free β-carotene. The capsules developed here clearly show the significant potential of the combination of DES and electrospraying for the encapsulation and stabilization of highly insoluble bioactive compounds.
The Global Macroeconomic Burden of Breast Cancer

Supplemental Digital Content is available in the text Objective: In this study, we quantified the global macroeconomic burden of breast cancer to underscore the critical importance of improving access to oncologic surgical care internationally. Summary Background Data: Breast cancer mortality in many low and middle-income countries (LMICs) is dramatically higher than in high-income countries. Prior to identifying solutions, however, it is important to first define the burden of disease. Methods: Data from the Institute of Health Metrics and Evaluation (2005–2015) were used to assess epidemiologic trends for 194, middle, and low-income countries. Economic burden defined by Welfare Loss (WL) was calculated by measuring disability-adjusted-life-years lost to breast cancer alongside the dollar equivalent of a value of statistical life year and as a function of each country's gross domestic product (GDP). Results: Annual mortality rates among breast cancer patients were significantly greater in LMICs in South Asia (3.06 per 100 women) and Sub-Saharan Africa (2.76 per 100 women), compared with high-income countries like the United States (1.69 per 100 women). From 2005–2015, mortality in South Asia increased by 8.20% and decreased by 6.45% in Sub-Saharan Africa; mortality rates in 2015 were observed as 27.9 per 100,000 in South Asia and 18.61 per 100,000 in Sub-Saharan Africa. Countries in South Asia demonstrated the greatest rise in WL due to breast cancer, from 0.05% to 0.08% of GDP. Conclusions: The burden of disease and economic impact of breast cancer is intensifying in LMICs. Global efforts to improve access to surgical care for women with breast cancer could reduce mortality and mitigate the social and financial impact of this disease in LMICs.
Physical activity habit formation through a technology-based program.

BACKGROUND Only about half of adults in the United States meet the minimum federal guidelines for physical activity (PA), with less than one quarter getting an optimal amount of weekly activity. Programs to increase PA can improve health and increase worker productivity. LOCAL PROBLEM Clinic patients of a nurse practitioner-run employee health clinic in a self-insured health care system experienced health conditions associated with insufficient PA and wanted to form habits of adequate PA for health promotion. METHODS A quantitative design was used to assess pre- and postintervention measures in this quality improve project. INTERVENTIONS Patients of the clinic enrolled in a technology-based 3-month PA habit development program that included wearable technology, tracked step counts, daily text messaging, and weekly electronic newsletters. Biometric and habit measures were taken at baseline and at the conclusion of the 3-month program to determine effectiveness. RESULTS Participants who completed the program developed strong habits of PA, on average. Small improvements in blood pressure, weight, and body mass index occurred but were not clinically significant. Two thirds of participants dropped out, which was fewer than anticipated based on prior reports. CONCLUSIONS Habits make an activity less difficult to continue than to stop. Thus, PA habits developed through this innovative intervention should persist and lead to decreased risk of conditions such as diabetes, heart disease, cancers, and dementia. The self-insured employer should reap the benefits of employee's PA through increased productivity, decreased absenteeism, and lower health care costs.
The Timing and Extent of Motor Neuron Vulnerability in ALS Correlates with Accumulation of Misfolded SOD1 Protein in the Cortex and in the Spinal Cord

Understanding the cellular and molecular basis of selective vulnerability has been challenging, especially for motor neuron diseases. Developing drugs that improve the health of neurons that display selective vulnerability relies on in vivo cell-based models and quantitative readout measures that translate to patient outcome. We initially developed and characterized UCHL1-eGFP mice, in which motor neurons are labeled with eGFP that is stable and long-lasting. By crossing UCHL1-eGFP to amyotrophic lateral sclerosis (ALS) disease models, we generated ALS mouse models with fluorescently labeled motor neurons. Their examination over time began to reveal the cellular basis of selective vulnerability even within the related motor neuron pools. Accumulation of misfolded SOD1 protein both in the corticospinal and spinal motor neurons over time correlated with the timing and extent of degeneration. This further proved simultaneous degeneration of both upper and lower motor neurons, and the requirement to consider both upper and lower motor neuron populations in drug discovery efforts. Demonstration of the direct correlation between misfolded SOD1 accumulation and motor neuron degeneration in both cortex and spinal cord is important for building cell-based assays in vivo. Our report sets the stage for shifting focus from mice to diseased neurons for drug discovery efforts, especially for motor neuron diseases.
Virological suppression and clinical management in response to viremia in South African HIV treatment program: A multicenter cohort study

Background Uptake of antiretroviral treatment (ART) is expanding rapidly in low- and middle-income countries (LMIC). Monitoring of virological suppression is recommended at 6 months of treatment and annually thereafter. In case of confirmed virological failure, a switch to second-line ART is indicated. There is a paucity of data on virological suppression and clinical management of patients experiencing viremia in clinical practice in LMIC. We report a large-scale multicenter assessment of virological suppression over time and management of viremia under programmatic conditions. Methods and findings Linked medical record and laboratory source data from adult patients on first-line ART at 52 South African centers between 1 January 2007 and 1 May 2018 were studied. Virological suppression, switch to second-line ART, death, and loss to follow-up were analyzed. Multistate models and Cox proportional hazard models were used to assess suppression over time and predictors of treatment outcomes. A total of 104,719 patients were included. Patients were predominantly female (67.6%). Median age was 35.7 years (interquartile range [IQR]: 29.9–43.0). In on-treatment analysis, suppression below 1,000 copies/mL was 89.0% at month 12 and 90.4% at month 72. Suppression below 50 copies/mL was 73.1% at month 12 and 77.5% at month 72. Intention-to-treat suppression was 75.0% and 64.3% below 1,000 and 50 copies/mL at month 72, respectively. Viremia occurred in 19.8% (20,766/104,719) of patients during a median follow-up of 152 (IQR: 61–265) weeks. Being male and below 35 years of age and having a CD4 count below 200 cells/μL prior to start of ART were risk factors for viremia. After detection of viremia, confirmatory testing took 29 weeks (IQR: 16–54). Viral resuppression to below 1,000 copies/mL without switch of ART occurred frequently (45.6%; 6,030/13,210) but was associated with renewed viral rebound and switch. Of patients with confirmed failure who remained in care, only 41.5% (1,872/4,510) were switched. The median time to switch was 68 weeks (IQR: 35–127), resulting in 12,325 person-years spent with a viral load above 1,000 copies/mL. Limitations of this study include potential missing data, which is in part addressed by the use of cross-matched laboratory source data, and the possibility of unmeasured confounding. Conclusions In this study, 90% virological suppression below the threshold of 1,000 copies/mL was observed in on-treatment analysis. However, this target was not met at the 50-copies/mL threshold or in intention-to-treat analysis. Clinical management in response to viremia was profoundly delayed, prolonging the duration of viremia and potential for transmission. Diagnostic tools to establish the cause of viremia are urgently needed to accelerate clinical decision-making.
Extracellular Vesicles from Human Papilloma Virus-Infected Cervical Cancer Cells Enhance HIV-1 Replication in Differentiated U1 Cell Line

In the current study, we hypothesized that extracellular vesicles (EVs) secreted from human papilloma virus (HPV)-infected cervical cancer cells exacerbate human immunodeficiency virus (HIV)-1 replication in differentiated U1 cell line through an oxidative stress pathway. To test the hypothesis, we treated an HIV-1-infected macrophage cell line (U1) with HPV-infected Caski cell culture supernatant (CCS). We observed a significant increase in HIV-1 replication, which was associated with an increase in the expression of cytochrome P450 (CYPs 1A1 and 2A6) in the CCS-treated U1 cells. Furthermore, we isolated EVs from CCS (CCS-EVs), which showed the presence of CYPs (1A1, 2A6), superoxide dismutase 1 (SOD1), and HPV oncoproteins HPV16 E6. CCS-EVs when exposed to the U1 cells also significantly increased HIV-1 replication. Treatment of antioxidant, CYP1A1 and CYP2A6 inhibitors, and chemodietary agents with antioxidant properties significantly reduced the CCS and CCS-EVs mediated HIV-1 replication in U1 cells. Altogether, we demonstrate that cervical cancer cells exacerbate HIV-1 replication in differentiated U1 cell line via transferring CYPs and HPV oncoproteins through EVs. We also show that the viral replication occurs via CYP and oxidative stress pathways, and the viral replication is also reduced by chemodietary agents. This study provides important information regarding biological interactions between HPV and HIV-1 via EVs leading to enhanced HIV-1 replication.
Histone variant dictates fate biasing of neural crest cells to melanocyte lineage

ABSTRACT In the neural crest lineage, progressive fate restriction and stem cell assignment are crucial for both development and regeneration. Whereas fate commitment events have distinct transcriptional footprints, fate biasing is often transitory and metastable, and is thought to be moulded by epigenetic programmes. Therefore, the molecular basis of specification is difficult to define. In this study, we established a role for a histone variant, H2a.z. 2, in specification of the melanocyte lineage from multipotent neural crest cells. H2a.z. 2 silencing reduces the number of melanocyte precursors in developing zebrafish embryos and from mouse embryonic stem cells in vitro. We demonstrate that this histone variant occupies nucleosomes in the promoter of the key melanocyte determinant mitf, and enhances its induction. CRISPR/Cas9-based targeted mutagenesis of this gene in zebrafish drastically reduces adult melanocytes, as well as their regeneration. Thereby, our study establishes the role of a histone variant upstream of the core gene regulatory network in the neural crest lineage. This epigenetic mark is a key determinant of cell fate and facilitates gene activation by external instructive signals, thereby establishing melanocyte fate identity. Summary: This study reports a mechanism underpinning the crucial role of histone variant H2A.Z. 2 in fate allocation and subsequent commitment of melanocyte identity, from a multipotent state.
Antioxidant and Antimicrobial Properties of Semi-Processed Frozen Prickly Pear Juice as Affected by Cultivar and Harvest Time

Consumer interest toward natural ingredients is creating a growing trend in the food industry and research for the development of natural products such as colorants, antimicrobials and antioxidants. Semi-processed frozen prickly pear (Opuntia ficus-indica (L.) Mill. ) juices (PPJs), obtained from three cultivars with white, red and yellow pulp, with different harvest times (“Agostani” and “Bastardoni”), were characterized for betalains, total phenolics, flavonoids, carotenoids, antioxidant capacity (by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH)) and antimicrobial potential against foodborne pathogenic bacteria. Through chemical assays, PPJs showed high contents of total polyphenols, flavonoids and betalains and marked antioxidant capacity. PPJs from the first harvest (“Agostani”) revealed the significantly highest amount of polyphenols in white cultivar and of betacyanin and betaxanthin in yellow and red cultivars; antioxidant capacity was significantly higher in “Agostani” PPJs than in “Bastardoni” ones. Regarding antimicrobial potential, all PPJs revealed good antibacterial activity, particularly against Salmonella enterica as evidenced by the widest inhibition haloes. These results encourage the suitability of the first flowering prickly pear fruits, with low market value as fresh fruit but with high nutritional features, to be processed as semi-finished product. In particular, its use as ingredient in foods with high risk of Salmonella contamination may act as a natural preservative.