Diagnostic value of cutaneous manifestation of SARS-CoV-2 infection.

BACKGROUND: One of the challenging aspects of SARS-CoV-2 infection is its diverse multisystemic disease presentation. OBJECTIVES: To evaluate the diagnostic value of cutaneous manifestations of SARS-CoV-2 infection and investigate their duration and timing in relation to other COVID-19 symptoms. METHODS: We used data from 336 847 UK users of the COVID Symptom Study app to assess the diagnostic value of body rash or an acral rash in SARS-CoV-2 infection, and data from an independent online survey of 11 544 respondents to investigate skin-specific symptoms and collect their photographs. RESULTS: Using data from the app, we show significant association between skin rashes and a positive swab test result (odds ratio 1·67, 95% confidence interval 1·42-1·97). Strikingly, among the respondents of the independent online survey, we found that 17% of SARS-CoV-2-positive cases reported skin rashes as the first presentation, and 21% as the only clinical sign of COVID-19. Together with the British Association of Dermatologists, we have compiled a catalogue of images of the most common skin manifestations of COVID-19 from 400 individuals (https://covidskinsigns.com), which we have made publicly available to assist clinicians in recognition of this early clinical feature of COVID-19. CONCLUSIONS: Skin rashes cluster with other COVID-19 symptoms, are predictive of a positive swab test, and occur in a significant number of cases, either alone or before other classical symptoms. Recognizing rashes is important in identifying new and earlier cases of COVID-19.

A multicenter, observational, prospective study of self- and parent-reported quality of life in adolescent multiple sclerosis patients self-administering interferon-ß1a using RebiSmart™-the FUTURE study.

Besides the impact of disease per se, the use of immunomodulatory therapies in adolescents with relapsing-remitting multiple sclerosis (RRMS) may have an effect on quality of life (QL). The FUTURE (Quality of liFe in adolescent sUbjecTs affected by mUltiple sclerosis treated with immunomodulatoRy agEnt using self-injecting device) study was designed to evaluate the changes in QL of Italian adolescents with RRMS receiving treatment with IFN-ß1a (Rebif; 22 µg), administered subcutaneously three times weekly using the RebiSmart™ electronic autoinjection device over a 52-week period. Fifty adolescents with RRMS were enrolled and 40 completed the study. Changes from baseline to end of treatment (EoT) in adolescent self-reported and parent-reported QL were assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL), which has been validated for use in pediatric MS and for which an Italian version is available. The adolescent self-reported total PedsQL4.0 score and all of its subscales tended to increase from baseline to EoT, the only exception being "Emotional functioning." In parent-reported measures, the total PedsQL4.0 score increased significantly from baseline to EoT (+ 5.27 points, p = 0.041). Significant increases were also evident for parent-reported "Psychosocial health summary score" (+ 5.90 points; p = 0.015) and "School functioning" (+ 7.84 points; p = 0.029). Our results indicate that adolescents with RRMS using the electronic injection device RebiSmart™ for self-administration of Rebif® can experience long-term improvements in QL.

Oxidative stress and viral Infections: rationale, experiences, and perspectives on N-acetylcysteine.

This article explores current evidence on the role of oxidative stress in viral infections, and on the use of antioxidant drugs as adjunctive treatment. MEDLINE/PubMed was searched for appropriate keywords, and preclinical and clinical studies with reviews were retrieved and examined by authors. Old and current evidence shows that GSH content reduction is the main mechanism of redox imbalance in viral-infected cells. Clinical studies found that GSH levels are depleted in patients with viral infections such as HIV and SARS-CoV. Viral infections activate inflammation through different pathways, and several of these mechanisms are related to oxidative stress. NAC is a precursor of GSH, and many of its intracellular effects are mediated by GSH replenishment, but it also activates some anti-inflammatory mechanisms. NAC has an excellent safety profile and better oral and topical bioavailability than GSH. These characteristics make NAC a suitable option as a repurposed drug. Adjunctive antioxidant treatment may improve the outcomes of antiviral therapies. Current evidence supports the rationale for this practice and some clinical experience showed encouraging results.

HLA-class I markers and multiple sclerosis susceptibility in the Italian population.

Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A*02, HLA-Cw*05 and MOG-142L. In this work, we tested the association with MS of A*02 and Cw*05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A*02 conferred a statistically robust MS protection (odds ratio, OR=0.61; 95% confidence intervals, CI=0.51-0.72, P<10(-9)), which was independent of DRB1*15 and of any other DRB1* allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for MOG-142L was secondary to its linkage disequilibrium with A*02. Cw*05 was not associated considering the whole sample, but its presence significantly enhanced the protection in the HLA-A*02-positive group, independently of DRB1: the OR conferred by A*02 in Cw*05-positive individuals (0.22, 95% CI=0.13-0.38) was significantly lower than in Cw*05-negative individuals (0.69, 95% CI=0.58-0.83) with a significant (P=4.94 x 10(-5)) multiplicative interaction between the two markers. In the absence of A*02, Cw*05 behaved as a risk factor, particularly in combination with DRB1*03 (OR=3.89, P=0.0006), indicating that Cw*05 might be a marker of protective or risk haplotypes, respectively.

Influence of Lobesia botrana field control on black aspergilli rot and ochratoxin A contamination in grapes.

The grape berry moth Lobesia botrana is a key pest in vineyards in southern Europe. Damage caused by L. botrana larvae may encourage growth of black aspergilli, leading to ochratoxin A (OTA) accumulation in grapes. Field trials were conducted during three grape growing seasons (2005 through 2007) in Apulia, Italy, to evaluate an insecticide control strategy for L. botrana in the vineyard as an indirect method of reducing OTA contamination by reducing black aspergilli on the grapes. In the 2005 field trials, the insecticide treatment controlled attacks by L. botrana larvae and reduced OTA concentrations by up to 66% in the must samples of Negroamaro and Primitivo grape varieties. Significant differences (P < or = 0.05) also were observed in the incidence of black aspergilli. Environmental conditions in 2006 and 2007 resulted in a natural low level of infestation by L. botrana, low levels of OTA in both treated and untreated samples, and no significant differences between treated and nontreated samples. The results of our field study confirm previous reports that L. botrana is an important risk factor for OTA accumulation and are consistent with the hypothesis that controlling L. botrana in vineyards reduces OTA concentrations in grapes.

Influence of in vitro exposure to mycotoxin zearalenone and its derivatives on swine sperm quality.

Zearalenone (ZEA) is a fusariotoxin naturally occurring in crops with known estrogenic activity in swine, the most sensitive known species. The metabolism by swine of ZEA, principally into alpha-zearalenol (alpha-ZOL), is considered as a bio-activation because of its high affinity with estrogenic receptors. Discordant data on male reproductive failures induced by ZEA in vivo are described. In this study, we evaluated the effects to boar spermatozoa when they are exposed in vitro to ZEA and its derivatives (alpha-ZOL, beta-ZOL). We analyzed viability, apoptosis (terminal deoxynucleotidyltransferase dUTP nick end-labelling (TUNEL)), sperm chromatin stability (sperm chromatin structure assay (SCSA)) and motility (using computer-aided sperm analysis (CASA)). Each mycotoxin influenced a specific function of spermatic cells. alpha-Zearalenol and ZEA, at picomolar levels, negatively influenced chromatin structure stability and viability, respectively, whereas beta-ZOL negatively influenced the sperm motility at micromolar levels. This study is the first using these direct measures of sperm integrity to show the potential for an adverse effect of ZEA exposure on boar fertility.

Strains of Aureobasidium pullulans can lower ochratoxin A contamination in wine grapes.

Wine contamination with ochratoxin A (OTA) is due to the attack of wine grapes by ochratoxigenic Aspergillus carbonarius and Aspergillus spp. section Nigri. Four A. pullulans strains, AU14-3-1, AU18-3B, AU34-2, and LS30, are resistant to and actively degrade ochratoxin A in vitro. The less toxic ochratoxin alpha and the aminoacid L-beta-phenylalanine were the major degradation products, deriving from the cleavage of the amide bond linking these two moieties of OTA. The same strains were studied further as biocontrol agents of A. carbonarius on wine grapes in laboratory experiments. Three of the four strains significantly prevented infections by A. carbonarius. Berries pretreated with the biocontrol agents and infected with A. carbonarius contained lower amounts of OTA as compared to the untreated infected control berries. Two of these strains were shown to degrade OTA to ochratoxin alpha in fresh grape must, but the mechanisms of the decrease of OTA accumulation in infected berries pretreated with the biocontrol agents remain to be elucidated. Assessment of one strain carried out in the vineyard during the growing season of 2006 showed that the tested strain was an effective biocontrol agent, reducing both severity of Aspergillus rots and OTA accumulation in wine grapes. To our knowledge this is the first report describing the positive influence of biocontrol agents on OTA accumulation in this crop species.

To d , or not to d : recent developments and comparisons of regularization schemes.

We give an introduction to several regularization schemes that deal with ultraviolet and infrared singularities appearing in higher-order computations in quantum field theories. Comparing the computation of simple quantities in the various schemes, we point out similarities and differences between them.

Development of a quantitative real-time PCR assay for the detection of Aspergillus carbonarius in grapes.

Aspergillus carbonarius is the main species responsible for the production of ochratoxin A (OTA) in wine grapes. To monitor and quantify A. carbonarious in grapes, a quantitative real-time PCR assay was developed as a possible tool for predicting the potential ochratoxigenic risk. DNA extraction from grape berries was performed by using conventional extraction and clean up through EZNA Hi-bond spin columns. A TaqMan probe was used to quantify A. carbonarius genomic DNA in grape berries samples. An exogenous internal positive control was used to overcome DNA recovery losses due to matrix inhibition. The quantification of fungal genomic DNA in naturally contaminated grape was performed using the TaqMan signal versus spectrophotometrically measured DNA quantities (Log10) calibration curve with a linearity range from 50 to 5 x 10(-4) ng of DNA. A positive correlation (R2=0.92) was found between A. carbonarious DNA content and OTA concentration in naturally contaminated grape samples. This is the first application of TaqMan real-time PCR for identifying and quantifying A. carbonarius genomic DNA occurring in grapes. The rapid DNA extraction method for grapes, together with the commercial availability of reagents and instrumentation, allows to perform a remarkable number of reproducible assays (96-well format) in less than 4 h.

Effect of Lobesia botrana damages on black aspergilli rot and ochratoxin A content in grapes.

Sixty-nine wine grape samples of two varieties (Bombino Nero and Uva di Troia) were collected from four vineyards in a high ochratoxin A (OTA) incidence grape-growing area in Apulia, southern Italy, during the 2001 and 2002 crop harvests. The levels of toxin, measured in the two year harvests, ranged from 0.02 to 681 ng/g of fresh berries. In both surveys, higher levels of contamination by black aspergilli and OTA were found in both intact and rotten berries originating from bunches damaged by Lobesia botrana larvae as compared to bunches without L. botrana attacks. All berry samples with an OTA level >1 ng/g were contaminated by black aspergilli with a CFU>10(6), and all but one of these samples belonged to the Lobesia damaged berries group. This is the first evidence of an interaction between L. botrana damaged berries and OTA contamination, in field.

An electrochemical bioassay for dichlorvos analysis in durum wheat samples.

The use of an acetylcholinesterase inhibition assay for the detection of dichlorvos in durum wheat samples by a simplified extraction procedure is reported. After an incubation step, the residual activity was determined with an amperometric biosensor using a portable potentiostat. The use of electric eel and recombinant acetylcholinesterase was compared. The effect of the matrix extract was evaluated by using various sample:solvent ratios, 1:2.5, 1:5, 1:10, and 1:20. The optimal extraction ratio, considering the electrochemical interferences and the effect on enzyme activity and bioavailability of the pesticide, was 1:10. Calibrations were performed in buffer and durum wheat extract. The calculated detection limits in buffer solution were 10 ng/ ml and 0.045 ng/ml for electric eel and recombinant acetylcholinesterase, respectively, whereas operating in the matrix extract they increased up to 45 ng/ml and 0.07 ng/ml, corresponding to 0.45 mg/kg (extraction ratio 1:10) and 0.07 mg/kg in samples. These characteristics allowed the detection of contaminated samples at the maximum residue limit, which is 2 mg/kg and well below. Fortified samples of durum wheat were obtained with both dichlorvos and the commercial product Didivane, which contains dichlorvos as an active molecule. At all the tested levels, the occurrence of contaminant was detected with an average recovery of 75%. The total assay time, including the extraction step, was 30 min. Because several extractions as well as most of the assay steps can be run simultaneously, the throughput for one operator is 12 determinations per hour.

Single-ion dosemeter based on floating gate memories.

Floating Gate (FG) nonvolatile memories are based on a tiny polysilicon layer (the FG) which can be permanently charged with electrons or holes, thus changing the threshold voltage of a MOSFET. Every time a FG is hit by a high energy ion, it experiences a charge loss, depending on the ion linear energy transfer (LET) and on the transistor geometrical and electrical characteristics. This paper discusses the opportunities to use this devices as single an ion dosemeter with sub-micrometer spatial resolution and capable of distinguish the impinging ion LET.

Sensitivity and dynamic range of FGMOS dosemeters.

UVPROM memory devices employing FGMOS transistors as memory cells make excellent dosemeters for applications involving ionising radiation. With proper preparation and programming, these devices can be used in remote-sensing applications in high-radiation environments with no power required during exposure.

[Congenital cystic adenomatoid malformation: a case report]. / Malformazione adenomatosa cistica del polmone: un caso singolare.

Cystic adenomatoid malformation is a rare pulmonary hamartomatous lesion, of an unknown etiology. Report a singular case of CAM of one newborn, with marked respiratory distress. Using different method (chest X-ray, Multidetector row CT associated at multiplanar and three-dimensional reconstructions), we obtained an accurate diagnosis of site and nature, critical for a correct therapeutic approach.

Effect of alkaline cooking of maize on the content of fumonisins B1 and B2 and their hydrolysed forms.

The effect of nixtamalization on the content of fumonisins (FBs), hydrolysed (HFBs) and partially hydrolysed (PHFBs) fumonisins in maize was investigated at laboratory-scale. Maize naturally contaminated with FBs and PHFBs was cooked with lime. Starting raw maize, steeping and washing waters and final masa fractions were analysed for toxin content. Control-cooking experiments without lime were also carried out. The nixtamalization reduced the amount of FBs and PHFBs in masa and converted them to HFBs. However, the three forms of fumonisins collected in all fractions amounted to 183%, indicating that nixtamalization made available forms of matrix-associated fumonisins that were then converted to their hydrolysed forms. Control-cooking enhanced FBs and PHFBs reduction, due to the solubility of fumonisins in water during the steeping process, but did not form HFBs. These findings indicate that benefits associated with enhancing the nutritional value of nixtamalized maize are also associated with a safer product in terms of fumonisin contamination.

Identification of a beta-lactoglobulin lactosylation site.

Thermal treatment of milk leads to non-enzymatic glycosylation of proteins through Maillard reaction. Free NH2 groups of basic amino acids react with the reducing carbonyl group of lactose forming the so-called Amadori products. Electrospray mass spectrometry analysis shows that beta-lactoglobulin (beta-LG), the major whey protein, undergoes lactosylation under industrial thermal treatment. In order to investigate the specificity of reactive sites for lactose binding the analysis of trypsin hydrolysates of beta-LG isolated from different industrial milks was performed. Results demonstrate that Lys-100 is a preferential lactosylation site of beta-LG during industrial milk treatment. These results were confirmed by an analysis of the three-dimensional model of the protein which showed that Lys-100 had the highest solvent accessibility and proximity to another amino group making Lys-100 the best candidate to lactosylation. Lys-47, previously identified by other authors, showed a good proximity to another Lys residue, but an intermediate level of exposition to solvent.

Dose-dependent lipid peroxidation induction on ex vivo intestine tracts exposed to chyme samples from fumonisins contaminated corn samples.

Fumonisins (FBs), Fusarium mycotoxins common food contaminant, are a potent inducer of oxidative stress and lipid peroxidation in intestinal cells. In order to verify this toxic effect in intestine tract, the aim was to assess lipid peroxidation (as malondialdehyde MDA increased levels) on intestine rat samples exposed to chyme samples from in vitro digestion of FBs contaminated corn samples. Naturally (9.61±3.2 µg/gr), artificially (726±94 µg/gr) and spiked corn samples at EU permitted FBs levels were digested and added to luminal side of Ussing chamber for 120 min. Fumonisins-free corn sample was used as control. The MDA increase was observed just in 83% of intestine samples exposed at EU FBs levels and the digestion process seems to reduce this incidence (50% of samples). Malondialdehyde levels were FBs dose- and subject-related and ranged from 0.07±0.01 to 3.59±0.6 nmol/mg. Highest incidence and MDA % increment (I) were found when intestine tracts were exposed to chymes from artificially corn sample. The induction of lipid peroxidation induced by FBs could be due to interactions between FBs and intestinal membranes, with consequent modifications in membrane permeability and oxygen diffusion-concentration, as suggested by other authors.

Development of loop-mediated isothermal amplification (LAMP) assay for the rapid detection of Penicillium nordicum in dry-cured meat products.

The need of powerful diagnostic tools for rapid, simple, and cost-effective detection of food-borne fungi has become very important in the area of food safety. Currently, several isothermal nucleic acid amplification methods have been developed as an alternative to PCR-based analyses. Loop-mediated isothermal amplification (LAMP) is one of these innovative methods; it requires neither gel electrophoresis to separate and visualize the products nor expensive laboratory equipment and it has been applied already for detection of pathogenic organisms. In the current study, we developed a LAMP assay for the specific detection of Penicillium nordicum, the major causative agent of ochratoxin A contamination in protein-rich food, especially dry-cured meat products. The assay was based on targeting otapksPN gene, a key gene in the biosynthesis of ochratoxin A (OTA) in P. nordicum. Amplification of DNA during the reaction was detected directly in-tube by color transition of hydroxynaphthol blue from violet to sky blue, visible to the naked eye, avoiding further post amplification analyses. Only DNAs isolated from several P. nordicum strains led to positive results and no amplification was observed from non-target OTA and non OTA-producing strains. The assay was able to detect down to 100 fg of purified targeted genomic DNA or 10(2) conidia/reaction within 60 min. The LAMP assay for detection and identification of P. nordicum was combined with a rapid DNA extraction method set up on serially diluted conidia, providing an alternative rapid, specific and sensitive DNA-based method suitable for application directly "on-site", notably in key steps of dry-cured meat production.

HTLV-II/HIV-1 coinfection and risk for progression to AIDS among intravenous drug users.

To determine whether coinfection with HTLV-II influences the course of HIV-1 infection, we evaluated the progression from asymptomatic HIV infection (CDC group II) to persistent generalized lymphadenopathy (CDC group III) to AIDS-related complex (CDC group IVA) to full-blown AIDS (CDC group IVC) to death from AIDS in two groups of HIV-seropositive intravenous drug users (IVDUs). The first group consisted of 123 patients infected with HIV-1 only, and the second comprised 22 patients with serological and molecular evidence of HTLV-II/HIV-1 coinfection. Results of the immunological and clinical follow-up indicated a greater likelihood of developing persistent generalized lymphadenopathy among individuals infected with HIV-1 alone than among those coinfected with HTLV-II. However, no statistical difference was detected between the two groups in the depletion of CD4+ cells, the temporal decrease of the CD4/CD8 ratio, or the progression to ARC or AIDS or to death from AIDS. These findings suggest that HTLV-II may have no effect on the clinical evolution of HIV infection in IVDUs, which may be explained by the lack of pathogenicity of the HTLV-II coinfecting strain(s) and/or other still unclear biological or immunological cofactors or mechanisms.

Validation of morning dip of peak expiratory flow as an indicator of the severity of nocturnal asthma.

Overnight falls in peak expiratory flow (PEF) (with the morning dip of the index) may be considered the hallmark of nocturnal asthma. To validate the morning dip a quantitative marker of the degree of nocturnal bronchoconstriction, the dip was measured in 11 subjects (six with a history consistent with nocturnal asthma) undergoing all-night monitoring of lower respiratory resistance by a double-catheter method. In six subjects, marked and recurrent increases in resistance were recorded, along with morning dips higher than 20 percent; however, on the following morning, only two of them reported having suffered significant breathlessness and wheeze. Peak and average values for resistance, as well as the duration for which resistance was increased, were closely correlated with the magnitude of morning dips. Therefore, unlike the subjective report, PEF may be considered a reliable quantitative indicator of nocturnal bronchoconstriction.