Characterization of Recombinant Human PRG4 as an Ocular Surface Boundary Lubricant

Introduction: Dry-eye disease involves tear film instability that can result in surface-to-surface contact between the cornea and eyelid or contact lens, where boundary lubrication can be dominant1. Motivated by the recent discovery that proteoglycan 4 (PRG4, a mucin-like glycoprotein originally discovered in synovial fluid as a boundary lubricant2), functions as an ocular surface boundary lubricant3, advances in recombinant protein expression technology4, and PRG4’s potential use as a friction-reducing contact lens coating, the objectives of this study were to: 1) biochemically characterize recombinant human PRG4 (rh- PRG4); and 2) assess the boundary lubricating properties of rh-PRG4, both before and after autoclave sterilization, at a cornea-contact lens material (PDMS) biointerface. Methods: SDS-PAGE western blot analysis using a variety of anti-PRG4 antibodies and lectins was performed on native PRG4 (nPRG4) and rh-PRG4 samples, both nonreduced and reduced, with and without enzymatic removal of O-linked glycosylations. Human corneas and PDMS were articulated against each other, subject to physiological loads of 8-25 kPa, at effective sliding velocities of 0.3-30 mm/s. Test lubricant sequences were A) saline, rh-PRG4 @300μg/mL, nPRG4 @300μg/mL, and saline; and B) saline, autoclaved rh-PRG4 @300μg/mL, rh-PRG4 @300μg/mL, and saline. Static and kinetic coefficients of friction were calculated. Results: rh-PRG4 demonstrated similar immunoreactivity to nPRG4, and effectively lowered friction at the cornea-PDMS biointerface. Western blotting indicated immunoreactive rh-PRG4 bands had a similar apparent molecular weight (MW) to nPRG4, and decreased appropriately upon reduction as well as enzymatic removal of glycosylations. Kinetic friction coefficients, which were highest in saline (0.31±0.06 to 0.40±0.06, mean±SEM), were similar in rh-PRG4 (0.12±0.01 to 0.25±0.03) and nPRG4 (0.19±0.02 to 0.28±0.03) across all velocities. Autoclaved rh-PRG4 had similar values to rh-PRG4 as well (0.19±0.02 to 0.26±0.04, 0.16±0.02 to 0.26±0.02, respectively). Conclusions: rh-PRG4 demonstrates similar biochemical and ocular surface lubricating properties to nPRG4, and may function as an effective friction-reducing contact lens coating

Alterations of gustatory sensitivity and taste liking in individuals with blindness or deafness

Food ingestion is crucial for an organism, and eating and drinking are multisensory, complex experiences affected by all functioning modalities. Still, little is known about gustatory perception in blindness and deafness. Empirical studies with this regard have been very scarce and the aim of the current study was to explore whether gustatory compensation may occur like the adjustments observed in other aspects of sensory processing, or if liking of various tastes is affected by blindness or deafness. We hypothesized a decreased gustatory sensitivity and lower liking of all tastes in subjects with hearing disabilities; expected outcomes in the group with blindness were less well justified by the mixed results reported to date. To address the relationship of gustatory sensitivity and taste liking with sensory impairments, we compared the gustatory acuity and liking of bitter, salty, sour and sweet tastes of 100 individuals with blindness and 74 people with deafness with matched control groups without sensory impairments. We found that deafness was associated with lower gustatory sensitivity toward the basic tastes and their decreased likeability, and that blindness predicted an increased sensitivity only towards the salty taste, and just among individuals with an early visual loss. Our results suggest that auditory and visual deficits may undermine food experience and may lead to altered taste liking. Reasons of these outcomes discussed in the current article vary from anatomy to social and economic decisions driving gustatory experience

Dietary determinants of changes in waist circumference adjusted for body mass index - a proxy measure of visceral adiposity

Background Given the recognized health effects of visceral fat, the understanding of how diet can modulate changes in the phenotype “waist circumference for a given body mass index (WCBMI)”, a proxy measure of visceral adiposity, is deemed necessary. Hence, the objective of the present study was to assess the association between dietary factors and prospective changes in visceral adiposity as measured by changes in the phenotype WCBMI. Methods and Findings We analyzed data from 48,631 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years. WCBMI was defined as the residuals of waist circumference regressed on body mass index, and annual change in WCBMI (¿WCBMI, cm/y) was defined as the difference between residuals at follow-up and baseline, divided by follow-up time. The association between energy, energy density (ED), macronutrients, alcohol, glycemic index (GI), glycemic load (GL), fibre and ¿WCBMI was modelled using centre-specific adjusted linear regression, and random-effects meta-analyses to obtain pooled estimates. Men and women with higher ED and GI diets showed significant increases in their WCBMI, compared to those with lower ED and GI [1 kcal/g greater ED predicted a ¿WCBMI of 0.09 cm (95% CI 0.05 to 0.13) in men and 0.15 cm (95% CI 0.09 to 0.21) in women; 10 units greater GI predicted a ¿WCBMI of 0.07 cm (95% CI 0.03 to 0.12) in men and 0.06 cm (95% CI 0.03 to 0.10) in women]. Among women, lower fibre intake, higher GL, and higher alcohol consumption also predicted a higher ¿WCBMI. Conclusions Results of this study suggest that a diet with low GI and ED may prevent visceral adiposity, defined as the prospective changes in WCBMI. Additional effects may be obtained among women of low alcohol, low GL, and high fibre intake

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis

Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation

A7. SITUAZIONE NAZIONALE: CORPI IDRICI INTERESSATI DA CIANOBATTERI TOSSICI

I cianobatteri sono diffusi in moltissimi ambienti acquatici, dove possono produrre cianotossine con diversi profili tossicologici. Il presente rapporto riporta le linee guida per la gestione delle fioriture di cianobatteri nelle acque di balneazione, elaborate da un gruppo di esperti. La prima parte sintetizza le attuali conoscenze scientifiche su vari aspetti, fra cui la loro presenza nei laghi italiani, le caratteristiche chimiche e tossicologiche delle varie cianotossine, gli effetti osservati sulla salute dell\u2019uomo e la valutazione del rischio. La seconda parte definisce le linee guida per prevenire effetti dannosi per la salute dei bagnanti e gestire il rischio associato alle fioriture. Vengono fornite indicazioni per pianificare attivit\ue0 di monitoraggio ambientale e sorveglianza sanitaria nelle aree a maggiore criticit\ue0. Viene inoltre presentato un sistema di reportistica, ambientale e sanitario, anche allo scopo di uniformare le informazioni a livello nazionale. Il rapporto \ue8 completato dalle indicazioni tecniche rivolte alle strutture territoriali preposte.Cyanobacteria thrive in many aquatic environments, where they can produce cyanotoxins with different toxicological profiles. This report provides the guidelines for the management of cyanobacterial blooms in bathing water, put together by a group of experts. The first part summarizes the current scientific knowledge on various aspects, including their presence in the Italian lakes, chemical and toxicological characteristics of different cyanotoxins, the observed effects on human health and the risk assessment. The second part defines the guidelines to prevent harmful effects on the health of bathers and manage the risk associated with blooms. It provides recommendations for planning environmental monitoring activities and a health surveillance system in most critical areas. It also introduces an environmental and health reporting system, with the purpose to standardize the information at national level too. The report is supplemented by technical information aimed at territorial authorities in charge

Trigonometry of 'complex Hermitian' type homogeneous symmetric spaces

This paper contains a thorough study of the trigonometry of the homogeneous symmetric spaces in the Cayley-Klein-Dickson family of spaces of 'complex Hermitian' type and rank-one. The complex Hermitian elliptic CP^N and hyperbolic CH^N spaces, their analogues with indefinite Hermitian metric and some non-compact symmetric spaces associated to SL(N+1,R) are the generic members in this family. The method encapsulates trigonometry for this whole family of spaces into a single "basic trigonometric group equation", and has 'universality' and '(self)-duality' as its distinctive traits. All previously known results on the trigonometry of CP^N and CH^N follow as particular cases of our general equations. The physical Quantum Space of States of any quantum system belongs, as the complex Hermitian space member, to this parametrised family; hence its trigonometry appears as a rather particular case of the equations we obtain.Comment: 46 pages, LaTe

Balloon kyphoplasty in the treatment of metastatic disease of the spine: a 2-year prospective evaluation

There is currently little data on the longer term efficacy and safety of balloon kyphoplasty (BKP) in patients with metastatic vertebral compression fractures (VCFs). To prospectively assess the long-term efficacy and safety of BKP in treating thoracic and lumbar spinal metastatic fractures that result in pain or instability. Sixty-five patients (37 men, mean age: 66 years) underwent 99 BKP procedures. Patient-related outcomes of pain visual analogue scale (VAS) and Oswestry Disability Index were assessed pre- and post-operatively and after 3, 6, 12 and 24 months. Correction of vertebral height and kyphotic deformity were assessed by radiographic measurements. Mean pain VAS and Oswestry Disability Index significantly improved from pre- to post-treatment (P < 0.0001), this improvement being sustained up to 24-month follow up. A gain in height restoration and a reduction of the post-operative kyphotic angle were seen post-operatively and at 3 months although these radiographic outcomes returned to pre-operative levels at 12 months. BKP was associated with a rate of cement leakage and incidence vertebral fracture of 12 and 8%, respectively. No symptomatic cement leaks or serious adverse events were seen during the 24 months of follow up. BKP is a minimally invasive procedure that provides immediate and long-term pain relief and improvement in functional ability in selected patients with metastatic VCFs. The procedure appears to have good long-term safety