Chronic Central Serous Chorioretinopathy with Pigment Epithelium Detachment Treated with Sildenafil: A Case Report

Central serous chorioretinopathy (CSCR) is a retinal disease that may be complicated by the development of serous retinal pigment epithelial detachment (PED). The exact molecular mechanisms of CSCR have remained uncertain as well as there is no effective medical therapy. Herein, we describe a case of a 43-year-old male suffering from chronic CSCR with PED and visual acuity reduction (20/40) that showed improvement in visual acuity (20/25) and metamorphopsia 2 weeks after daily intake of 20 mg sildenafil tablets. Optical coherence tomography (OCT) scan showed resolution of PED with residual degeneration of the photoreceptor inner and outer segment layer and retinal pigmented epithelium. The patient continued treatment with sildenafil 20 mg for 2 months. Six months after the discontinuation of therapy, visual acuity was maintained, with absence of PED at OCT. Our case supports the hypothesis that phosphodiesterase type 5 (PDE-5) inhibitors may be an alternative in the treatment of patients with CSCR, alone or combined with other medications

Design and advancement status of the Beam Expander Testing X-ray facility (BEaTriX)

The BEaTriX (Beam Expander Testing X-ray facility) project is an X-ray apparatus under construction at INAF/OAB to generate a broad (200 x 60 mm2), uniform and low-divergent X-ray beam within a small lab (6 x 15 m2). BEaTriX will consist of an X-ray source in the focus a grazing incidence paraboloidal mirror to obtain a parallel beam, followed by a crystal monochromation system and by an asymmetrically-cut diffracting crystal to perform the beam expansion to the desired size. Once completed, BEaTriX will be used to directly perform the quality control of focusing modules of large X-ray optics such as those for the ATHENA X-ray observatory, based on either Silicon Pore Optics (baseline) or Slumped Glass Optics (alternative), and will thereby enable a direct quality control of angular resolution and effective area on a number of mirror modules in a short time, in full X-ray illumination and without being affected by the finite distance of the X-ray source. However, since the individual mirror modules for ATHENA will have an optical quality of 3-4 arcsec HEW or better, BEaTriX is required to produce a broad beam with divergence below 1-2 arcsec, and sufficient flux to quickly characterize the PSF of the module without being significantly affected by statistical uncertainties. Therefore, the optical components of BEaTriX have to be selected and/or manufactured with excellent optical properties in order to guarantee the final performance of the system. In this paper we report the final design of the facility and a detailed performance simulation.Comment: Accepted paper, pre-print version. The finally published manuscript can be downloaded from http://dx.doi.org/10.1117/12.223895

The hypoxia sensitive metal transcription factor MTF-1 activates NCX1 brain promoter and participates in remote postconditioning neuroprotection in stroke

Remote limb ischemic postconditioning (RLIP) is an experimental strategy in which short femoral artery ischemia reduces brain damage induced by a previous harmful ischemic insult. Ionic homeostasis maintenance in the CNS seems to play a relevant role in mediating RLIP neuroprotection and among the effectors, the sodium-calcium exchanger 1 (NCX1) may give an important contribution, being expressed in all CNS cells involved in brain ischemic pathophysiology. The aim of this work was to investigate whether the metal responsive transcription factor 1 (MTF-1), an important hypoxia sensitive transcription factor, may (i) interact and regulate NCX1, and (ii) play a role in the neuroprotective effect mediated by RLIP through NCX1 activation. Here we demonstrated that in brain ischemia induced by transient middle cerebral occlusion (tMCAO), MTF-1 is triggered by a subsequent temporary femoral artery occlusion (FAO) and represents a mediator of endogenous neuroprotection. More importantly, we showed that MTF-1 translocates to the nucleus where it binds the metal responsive element (MRE) located at −23/−17 bp of Ncx1 brain promoter thus activating its transcription and inducing an upregulation of NCX1 that has been demonstrated to be neuroprotective. Furthermore, RLIP restored MTF-1 and NCX1 protein levels in the ischemic rat brain cortex and the silencing of MTF-1 prevented the increase of NCX1 observed in RLIP protected rats, thus demonstrating a direct regulation of NCX1 by MTF-1 in the ischemic cortex of rat exposed to tMCAO followed by FAO. Moreover, silencing of MTF-1 significantly reduced the neuroprotective effect elicited by RLIP as demonstrated by the enlargement of brain infarct volume observed in rats subjected to RLIP and treated with MTF-1 silencing. Overall, MTF-dependent activation of NCX1 and their upregulation elicited by RLIP, besides unraveling a new molecular pathway of neuroprotection during brain ischemia, might represent an additional mechanism to intervene in stroke pathophysiology

Volumetric Absorptive Microsampling (VAMS) for Targeted LC-MS/MS Determination of Tryptophan-Related Biomarkers

L-Tryptophan (TRP) metabolites and related biomarkers play crucial roles in physiological functions, and their imbalances are implicated in central nervous system pathologies and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, schizophrenia and depression. The measurement of TRP metabolites and related biomarkers possesses great potential to elucidate the disease mechanisms, aid preclinical drug development, highlight potential therapeutic targets and evaluate the outcomes of therapeutic interventions. An effective, straightforward, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of 24 TRP-related compounds in miniaturised murine whole blood samples. Sampling and sample pretreatment miniaturisation were achieved thanks to the development of a volumetric dried blood microsampling approach. Volumetric absorptive microsampling (VAMS) allows the accurate sampling of microvolumes of blood with advantages including, but not limited to, minimal sampling invasiveness, logistical improvements, method sustainability in terms of solvents and energy consumption, and improvement of animal studies in the framework of the 3Rs (Replacement, Reduction and Refinement) principles on animal welfare. The VAMS-LC-MS/MS method exhibited good selectivity, and correlation coefficient values for the calibration curves of each analyte were >0.9987. The limits of quantitation ranged from 0.1 to 25 ng/mL. The intra- and inter-day precisions in terms of RSD were <9.6%. All analytes were stable in whole blood VAMS samples stored at room temperature for at least 30 days with analyte losses < 14%. The developed method was successfully applied to the analysis of biological samples from mice, leading to the unambiguous determination of all the considered target analytes. This method can therefore be applied to analyse TRP metabolites and related biomarkers levels to monitor disease states, perform mechanistic studies and investigate the outcomes of therapeutic interventions

Design and Motion Planning for a Reconfigurable Robotic Base

A robotic platform for mobile manipulation needs to satisfy two contradicting requirements for many real-world applications: A compact base is required to navigate through cluttered indoor environments, while the support needs to be large enough to prevent tumbling or tip over, especially during fast manipulation operations with heavy payloads or forceful interaction with the environment. This paper proposes a novel robot design that fulfills both requirements through a versatile footprint. It can reconfigure its footprint to a narrow configuration when navigating through tight spaces and to a wide stance when manipulating heavy objects. Furthermore, its triangular configuration allows for high-precision tasks on uneven ground by preventing support switches. A model predictive control strategy is presented that unifies planning and control for simultaneous navigation, reconfiguration, and manipulation. It converts task-space goals into whole-body motion plans for the new robot. The proposed design has been tested extensively with a hardware prototype. The footprint reconfiguration allows to almost completely remove manipulation-induced vibrations. The control strategy proves effective in both lab experiment and during a real-world construction task.Comment: 8 pages, accepted for RA-L and IROS 202

Carbon monoxide poisoning in the home as an indicator of social integration of immigrant population

Verona is a town in Veneto Region (Italy) characterised by a high socio-economic status, but we register some health problems related to low income or social deprivation, such as unintentional carbon monoxide poisoning in private houses. Recently, indeed, there has been a rise in the number of accidents concerning immigrant populations. Since early 1990s, epidemiological informations in the matter weren?t complete and the number of cases was therefore probably underestimated. Presently no centralised system exists in Italy or in Veneto Region for recording the incidence of household CO poisoning. An ?Observatory on CO poisonings? was therefore activated in Verona Municipality in 1994 to overcome the problem of lacking data. The Observatory systematically collects data on cases of acute household CO poisoning occurring in the whole Verona area. These informations are used to assess public health interventions. During 13 years? activity 671 cases of CO poisoning and 22 deaths were recorded. The accidents were caused by the malfunctioning of home heating appliances. Statistics show a progressive increase in the number of not Italian involved in these episodes. Inspections revealed that immigrants often live in poor houses with unsafe systems or with extremely precarious heating systems. Data from this surveillance system on CO poisoning have shown that this is a public health problem involving immigrants much more often than local population. This system in real time supplies epidemiological and environmental data for improving public health intervention strategies. Such data collection systems could be useful to study other relevant problems of health disparities in lower socio-economical classes

Playing “hide and seek” with the Mediterranean monk seal: a citizen science dataset reveals its distribution from molecular traces (eDNA)

Animal conservation relies on assessing the distribution and habitat use of species, but for endangered/elusive animals this can prove difficult. The Monk Seal, Monachus monachus, is one of the world's most endangered species of pinniped, and the only one endemic to the Mediterranean Sea. During recent decades, direct observations have been few and scattered, making it difficult to determine its distribution away from the Aegean Sea (core distribution area of the post-decline relict population). This study relies on environmental DNA (eDNA) analysis to detect the presence of the Monk Seal in 135 samples collected in 120 locations of the central/western Mediterranean Sea, spanning about 1500 km longitudinally and 1000 km latitudinally. A recently described species-specific qPCR assay was used on marine-water samples, mostly collected during 2021 by a Citizen Science (CS) project. Positive detections occurred throughout the longitudinal range, including the westernmost surveyed area (Balearic archipelago). The distribution of the positive detections indicated six “hotspots”, mostly overlapping with historical Monk Seal sites, suggesting that habitat-specific characteristics play a fundamental role. We applied single-season occupancy models to correct for detection probability and to assess the importance of site-specific characteristics. The distance from small islets and protected (or access-restricted) areas was correlated negatively with the detection probability. This novel molecular approach, applied here for the first time in an extensive CS study, proved its potential as a tool for monitoring the distribution of this endangered/elusive species