Management of patients with suspected or confirmed COVID-19, in the radiology department.

OBJECTIVES: From December 2019, a novel coronavirus disease named COVID-19 was reported in China. Within 3 months, the World Health Organization defined COVID-19 as a pandemic, with more than 370,000 cases and 16,000 deaths worldwide. In consideration of the crucial role of diagnostic testing during COVID-19, the aim of this technical note was to provide a complete synthesis of approaches implemented for the management of suspected or confirmed COVID-19 patients. KEY FINDINGS: The planning of a robust plan to prevent the transmission of the virus to patients and department staff members should be fundamental in each radiology service. Moreover, the speed of spread and the incidence of the pandemic make it necessary to optimize the use of personal protective devices and dedicated COVID-19 equipment, given the limited availability of supplies. CONCLUSION: In the management of radiographic and CT imaging, staff should take special precautions to limit contamination between patients and other patients or professionals. IMPLICATIONS FOR PRACTICE: An isolated imaging room should be dedicated to suspected or confirmed COVID-19 cases, including radiography and CT scanners. This paper will provide guidance concerning disposable protective gear to be utilized, as well as on the cleaning and sanitation of radiology room and equipment.

Italian guidelines for the surgical management of enteral stomas in adults.

BACKGROUND: Worldwide, stomas represent a medical and social problem. Data from the literature on stoma management are extensive but not homogeneous. In Italy, no guidelines exist for this topic. Thus, clear and comprehensive clinical guidelines based on evidence-based data and best practice are need. In 2018, the Multidisciplinary Italian Study group for STOmas, called MISSTO, was founded. The aim was to elaborate guidelines for practice management of enteral and urinary stomas in adults. METHODS: A systematic review of the literature was performed using PubMed, National Guideline Clearinghouse, and other databases. The research included guidelines, systematic reviews, meta-analyses, randomized clinical trials, cohort studies, and case reports. Five main topics were identified: "stoma preparation", "stoma creation", "stoma complications", "stoma care", and "stoma reversal". The systematic review was performed for each topic, and studies were evaluated according to the GRADE system, AGREE II tool. RESULTS: Recommendations were elaborated in the form of statements with an established grade of recommendation for each statement. For low levels of scientific evidence statements, a consensus conference composed of expert members of the major Italian scientific societies in the field of stoma management and care was held. After discussing, correcting, validating, or eliminating the statements by the experts, the final version of the guidelines was elaborated and prepared for publication. This manuscript is focused on statements on the surgical management of enteral stomas. CONCLUSIONS: These guidelines are the first Italian guidelines on multidisciplinary management of enteral stomas with the aim of assisting surgeons during stoma management and care.

Laboratory evidence of dynamo amplification of magnetic fields in a turbulent plasma.

Magnetic fields are ubiquitous in the Universe. The energy density of these fields is typically comparable to the energy density of the fluid motions of the plasma in which they are embedded, making magnetic fields essential players in the dynamics of the luminous matter. The standard theoretical model for the origin of these strong magnetic fields is through the amplification of tiny seed fields via turbulent dynamo to the level consistent with current observations. However, experimental demonstration of the turbulent dynamo mechanism has remained elusive, since it requires plasma conditions that are extremely hard to re-create in terrestrial laboratories. Here we demonstrate, using laser-produced colliding plasma flows, that turbulence is indeed capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. These results support the notion that turbulent dynamo is a viable mechanism responsible for the observed present-day magnetization.

Flour from Prosopis alba cotyledons: A natural source of nutrient and bioactive phytochemicals.

The Prosopis alba seed is a waste material in the process to produce pod flour. To suggest a potential use of these seeds it is necessary to determine the nutritional, phytochemical and functional quality of cotyledon flour from Prosopis alba. This flour showed high level of proteins (62%), low content of total carbohydrate and fat. Free polyphenol (1150±20mg GAE/100g flour) and carotenoids (10.55±0.05mg ß-CE/100g flour) compounds were the dominant compounds. The main identified constituents in the polyphenolic extracts were C- glycosyl flavones, including schaftoside, isoschaftoside, vicenin II, vitexin and isovitexin. The extract enriched in polyphenolic compounds exhibited ABTS(+) reducing capacity and scavenging activity of H2O2; and was able to inhibit phospholipase, lipoxygenase and cyclooxygenase, three pro-inflammatory enzymes. According to our results, the P. alba cotyledon flour could be considered as a new alternative in the formulation of functional foods or food supplements.

PROBIOTICS AND INFLAMMATORY BOWEL DISEASES.

Intestinal microbiota is composed by symbiotic innocuous bacteria and potential pathogens also called pathobionts. Even if the mechanism of action of intestinal bacteria remain still unknown, specific microbial species seem to have important role in the maintenance of immunological equilibrium in the gut through the direct interaction with immune cells. Some studies have found a dysregulated interaction between the intestinal bacteria, the gut barrier, and the intestinal associated immune system in Inflammatory Bowel Disease (IBD) patients and in the pathogenesis of these pathologies. In IBD patients some Butyrate producing bacteria, as Faecalibacterium Prausnitzii, are under represented and this could be related with their chronic inflammatory state.

Laser capture microdissection is a valuable tool in the preoperative molecular screening of follicular lesions of the thyroid: an institutional experience.

OBJECTIVES: The application of molecular tests to thyroid fine needle aspiration (FNA) has been shown to be a valuable tool to better refine the pre-operative malignant risk of patients with indeterminate cytology results. In this study, we investigated the feasibility of using the laser capture microdissection (LCM) technique to obtain DNA and RNA for molecular tests in routine thyroid FNA smears. METHODS: Nine coupled FNA and histological retrospective cases and 31 prospective FNA cases with a follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) diagnosis were included in this study. Both cytological and histological specimens were investigated by direct sequencing and reverse transcription-polymerase chain reaction (RT-PCR) for BRAF and RAS mutations and for PAX8/PPARG and RET/PTC rearrangements, respectively. RESULTS: LCM yielded good DNA and RNA quality in all cases (100%) in both series, irrespective of the staining used (Giemsa, Papanicolaou, immunostain for thyroglobulin) and the cytology technique (conventional or liquid-based preparations). Total mutations found in the FNA and in the corresponding histological specimen in both series were: one PAX8/PPARG rearrangement in a follicular carcinoma (FC), four NRAS mutations [in two FCs, one papillary carcinoma and one follicular adenoma (FA)] and one HRAS mutation in one FA. The sensitivity was 67% and the specificity was 91%. CONCLUSIONS: LCM is a valuable tool to obtain good quality DNA and RNA for molecular tests in cytological material from thyroid FNA, and can be a useful option in the management of patients with an FN/SFN FNA diagnosis.

Shear-driven dynamo waves at high magnetic Reynolds number.

Astrophysical magnetic fields often display remarkable organization, despite being generated by dynamo action driven by turbulent flows at high conductivity. An example is the eleven-year solar cycle, which shows spatial coherence over the entire solar surface. The difficulty in understanding the emergence of this large-scale organization is that whereas at low conductivity (measured by the magnetic Reynolds number, Rm) dynamo fields are well organized, at high Rm their structure is dominated by rapidly varying small-scale fluctuations. This arises because the smallest scales have the highest rate of strain, and can amplify magnetic field most efficiently. Therefore most of the effort to find flows whose large-scale dynamo properties persist at high Rm has been frustrated. Here we report high-resolution simulations of a dynamo that can generate organized fields at high Rm; indeed, the generation mechanism, which involves the interaction between helical flows and shear, only becomes effective at large Rm. The shear does not enhance generation at large scales, as is commonly thought; instead it reduces generation at small scales. The solution consists of propagating dynamo waves, whose existence was postulated more than 60 years ago and which have since been used to model the solar cycle.

Multiple BM harvests in pediatric donors for thalassemic siblings: safety, efficacy and ethical issues.

Allogeneic BMT represents the only chance of cure for beta-thalassemia. Occasionally, two affected individuals from the same family share a matched healthy sibling. Moreover, a high incidence of transplant rejection is still observed in Pesaro class III patients, requiring a second BMT procedure. In these settings, one option is to perform a second BM harvest from the same donor. Although BM harvest is a safe procedure in children, ethical issues concerning this invasive practice still arise. Here, we describe our series of seven pediatric, healthy donors, who donated BM more than once in favor of their beta-thalassemic HLA-identical siblings between June 2005 and January 2008. Three donors donated BM twice to two affected siblings and four donors donated twice for the same sibling following graft rejection of the first BMT. All donors tolerated the procedures well and no relevant side effects occurred. There was no significant difference between the two harvests concerning cell yield and time to engraftment. Our experience shows that for pediatric donors, a second BM donation is safe and feasible and good cellularity can be obtained. We suggest that a second harvest of a pediatric donor can be performed when a strong indication for BMT exists.

Progress and prospects: gene therapy clinical trials (part 2).

This is the second part of a review summarizing progress and prospects in gene therapy clinical research. Twenty key diseases/strategies are succinctly described and commented on by leaders in the field. This part includes clinical trials for skin diseases, neurological disorders, HIV/AIDS, ornithine transcarbamylase deficiency, alpha(1)-antitrypsin deficiency, haemophilia and cancer.

Lentiviral vectors targeting WASp expression to hematopoietic cells, efficiently transduce and correct cells from WAS patients.

Gene therapy has been proposed as a potential treatment for Wiskott-Aldrich syndrome (WAS), a severe primary immune deficiency characterized by multiple hematopoietic-specific cellular defects. In order to develop an optimal lentiviral gene transfer cassette for this application, we compared the performance of several internal promoters in a variety of cell lineages from human WAS patients. Vectors using endogenous promoters derived from short (0.5 kb) or long (1.6 kb) 5' flanking sequences of the WAS gene, expressed the transgene in T, B, dendritic cells as well as CD34(+) progenitor cells, but functioned poorly in non-hematopoietic cells. Defects of T-cell proliferation and interleukin-2 production, and the cytoskeletal anomalies in WAS dendritic cells were also corrected. The levels of reconstitution were comparable to those obtained following transduction with similar lentiviral vectors incorporating constitutive PGK-1, EF1-alpha promoters or the spleen focus forming virus gammaretroviral LTR. Thus, native regulatory sequences target the expression of the therapeutic WAS transgene to the hematopoietic system, as is naturally the case for WAS, and are effective for correction of multiple cellular defects. These vectors may have significant advantages for clinical application in terms of natural gene regulation, and reduction in the potential for adverse mutagenic events.

Identification and expression analysis of Drosophila melanogaster genes encoding beta-hexosaminidases of the sperm plasma membrane.

Sperm surface beta-N-acetylhexosaminidases are among the molecules mediating early gamete interactions in invertebrates and vertebrates, including man. The plasma membrane of Drosophila spermatozoa contains two beta-N-acetylhexosaminidases, DmHEXA and DmHEXB, which are required for egg fertilization. Here, we demonstrate that three putative Drosophila melanogaster genes predicted to code for beta-N-acetylhexosaminidases, Hexo1, Hexo2, and fdl, are all expressed in the male germ line. fdl codes for a homolog of the alpha-subunit of the mammalian lysosomal beta-N-acetylhexosaminidase Hex A. Hexo1 and Hexo2 encode two homologs of the beta-subunit of all known beta-N-acetylhexosaminidases, which we have named beta(1) and beta(2), respectively. Immunoblot analysis of sperm proteins indicated that the gene products associate in different heterodimeric combinations forming DmHEXA, with an alphabeta(2) structure, and DmHEXB, with a beta(1)beta(2) structure. Immunofluorescence demonstrated that all the gene products localized to the sperm plasma membrane. Although none of the genes was testis-specific, fdl was highly and preferentially expressed in the testis, whereas Hexo1 and Hexo2 showed broader tissue expression. Enzyme assays carried out on testis and on a variety of somatic tissues corroborated the results of gene expression analysis. These findings for the first time show the in vivo expression in insects of genes encoding beta-N-acetylhexosaminidases, the only molecules so far identified as involved in sperm/egg recognition in this class, whereas in mammals, the organisms where these enzymes have been best studied, only two types of polypeptide chains forming dimeric functional beta-N-acetylhexosaminidases are present in Drosophila three different gene products are available that might generate numerous dimeric isoforms.

Slow light and chromatic temporal dispersion in photonic crystal waveguides using femtosecond time of flight.

We report time-of-flight experiments on photonic-crystal waveguide structures using optical Kerr gating of a femtosecond white-light supercontinuum. These photonic-crystal structures, based on engineered silicon-nitride slab waveguides, possess broadband low-loss guiding properties, allowing the group velocity dispersion of optical pulses to be directly tracked as a function of wavelength. This dispersion is shown to be radically disrupted by the spectral band gaps associated with the photonic-crystal periodicity. Increased time-of-flight effects, or "slowed light," are clearly observed at the edges of band gaps in agreement with two-dimensional plane-wave theoretical models of group velocity dispersion. A universal model for slow light in such photonic crystals is proposed, which shows that slow light is controlled predominantly by the detuning from, and the size of, the photonic band gaps. Slowed light observed up to time delays of approximately 1 ps, corresponds to anomalous dispersion of approximately 3.5 ps/nm per mm of the photonic crystal structure. From the decreasing intensity of time-gated slow light as a function of time delay, we estimate the characteristic losses of modes which are guided in the spectral proximity of the photonic band gaps.

Thyrotoxicosis and the cardiovascular system.

Thyrotoxicosis is associated with increased cardiovascular morbidity and mortality, primarily due to heart failure and thromboembolism. Palpitations, caused by sinus tachycardia and occasionally by atrial fibrillation, are the most frequent cardiovascular symptom. As atrial fibrillation may be the only manifestation of thyrotoxicosis, thyroid hormone excess should routinely be excluded in patients with this rhythm disturbance. Heart failure occurs mostly in the presence of underlying heart disease or tachycardia-induced cardiomyopathy in patients with long-standing atrial fibrillation. On occasion, long-standing hyperthyroidism may lead to heart failure even in the absence of concomitant cardiac conditions. Beta-blockers offer symptomatic relief and at the same time slow the ventricular response in patients with atrial fibrillation. Amiodarone, and occasionally iodinated contrast agents, may cause iodine-induced thyrotoxicosis. Clinical suspicion is essential in the diagnosis of amiodarone-induced thyrotoxicosis (AIT), because the antiadrenergic effect of the drug may conceal symptoms. AIT should be considered in any patient on amiodarone in the presence of new-onset or recurrent atrial arrhythmias or unexplained weight loss. Beyond discontinuation of amiodarone, treatment options include propylthiouracil or methimazole, potassium perchlorate, steroids, lithium and, if pharmacological treatment fails, surgery. Amiodarone may potentially be used less frequently in the future since recent studies have shown that this drug is inferior to implantable cardioverter defibrillators in prevention of sudden cardiac death in patients with severe heart failure. In addition, non-iodinated amiodarone analogues are currently in advanced phase of clinical testing.

Cytokine gene polymorphisms in gastric cancer patients from two Italian areas at high and low cancer prevalence.

Polymorphisms of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL1-RN), and tumor necrosis factor-alpha (TNF-alpha) genes are supposed to be key determinants of gastric cancer risk. Our aim was to study the association between these polymorphisms and gastric cancer in two areas characterized by high (Pavia/Bologna, North Italy) and low (San Giovanni Rotondo, South Italy) gastric cancer prevalence. Genomic DNA was obtained from 216 healthy donors and 98 gastric cancer patients from Pavia and Bologna, and 146 healthy donors and 86 gastric cancer patients from San Giovanni Rotondo. Two SNP in IL-1beta (-511 C/T) and TNF-alpha (-308 G/A) as well as the VNTR polymorphism of IL-1RN locus were studied. A significant linkage disequilibrium was found between IL-1beta -511 and IL-1RN. Genotype and allele frequencies at the IL-1beta, IL-1RN, and TNF-alpha loci in gastric cancer cases were not significantly different from controls. An epistatic effect between IL-1beta -511 and IL-1RN was found with the IL-1beta -511C/IL-1RN*2 haplotype conferring a significant protection against the intestinal-type of gastric cancer in the Southern population. In conclusion, IL-1beta, IL1-RN, and TNF-alpha genotypes are not associated with gastric cancer in Italian patients. An epistatic interrelationship between IL-1beta -511 and IL-1RN confers protection against gastric cancer in low-risk Italian population.

Determination of nonlinear refractive index in a Ta2O5 rib waveguide using self-phase modulation.

Self-phase modulation has been observed for ultrashort pulses of wavelength 800nm propagating through a 1 cm-long Ta2O5 rib waveguide. The associated nonlinear refractive index n2 was estimated to be 7.23x10-19 m2/W, which is higher than silica glass by more than one order of magnitude. Femtosecond time of flight measurements based on a Kerr shutter configuration show that the group velocity dispersion is small at a wavelength of 800 nm, confirming that dispersion may be neglected in the estimation of n2 so that a simplified theory can be used with good accuracy.

Purification and characterization of the plasma membrane glycosidases of Drosophila melanogaster spermatozoa.

Previous studies from our laboratory have demonstrated the presence of two integral proteins with glycosidase activity in the plasma membrane of Drosophila melanogaster spermatozoa and we have suggested that these enzymes might have a role in sperm-egg binding. In this study the glycosidases have been purified and characterized. We have evidenced the presence of three distinct enzymes, two beta-N-acetylhexosaminidase isoforms, named HEX 1 and HEX 2, and an alpha-mannosidase. The molecular size of the native enzymes estimated by gel filtration was 158 kDa for beta-hexosaminidases and 317 kDa for alpha-mannosidase. SDS-PAGE showed that HEX 1 and HEX 2 are dimers formed by subunits with different molecular sizes, whereas alpha-mannosidase consists of three subunits with different molecular weights. All the enzymes are terminally glycosylated. Characterization of the purified enzymes included their 4-methylumbelliferyl-substrate preferences, kinetic properties, inhibitor constants and thermal stability. On the basis of substrate specificity, kinetics and the results of inhibition studies, beta-hexosaminidases appear to differ from each other. HEX 1 and HEX 2 are similar to mammalian isoenzyme A and isoenzyme B, respectively. These findings represent the first report on the characterization of sperm proteins that are potentially involved in interactions with the egg in Insects.

Male sterile mutant casanova gives clues to mechanisms of sperm-egg interactions in Drosophila melanogaster.

The plasma membrane of the spermatozoa of Drosophila melanogaster contains two integral proteins with glycosidase activity, beta-N-acetylglucosaminidase and alpha-D-mannosidase. Biochemical analysis and ultrastructural cytochemistry of spermatozoa of the autosomal male sterile mutant casanova reveal that at least one of these enzymes, beta-N-acetylglucosaminidase, is crucial for sperm-egg interactions. casanova sperm are motile, morphologically normal, are transferred to the female at mating, but are unable to fertilize the eggs. The mutation was localised by deficiency mapping to the chromosomal region 95E8-F7. Fluorimetric assays showed that the mutant's sperm have the same level of alpha-D-mannosidase activity as wild-type sperm, whereas beta-N-acetylglucosaminidase activity reaches only 51% of the wild-type level. The biochemical characteristics of alpha-D-mannosidase and of the residual beta-N-acetylglucosaminidase are the same as in wild-type males. Ultrastructural localization of the enzymes indicated that casanova spermatozoa lacks beta-N-acetylglucosaminidase on the plasma membrane covering the acrosome, whereas the location of this glycosidase at the terminal part of the sperm tail is indistinguishable from the wild-type situation. The results strongly suggest that in Drosophila the beta-N-acetylglucosaminidase of the plasma membrane covering the acrosome functions as a receptor for the glycoconjugates on the egg surface. We named the putative egg receptor EROS. This is the first evidence for an egg/sperm recognition system in insects. The mechanism is similar to those known from higher animals.

Macroprolactinaemia, the major unknown in the differential diagnosis of hyperprolactinaemia.

We report on 10 cases of macroprolactinaemia and discuss recent evidence that many patients with hyperprolactinaemia (8-26%, depending on the population studied) have in fact normal amounts of circulating prolactin but false-high values in commercial assays. This is caused by macromolecular prolactin (also named big-big prolactin or macroprolactin), a complex of prolactin with IgG antibodies leading to apparent hyperprolactinaemia. In spite of the expanding literature on this topic, it remains an underrecognised problem, typically causing unnecessary procedures such as laboratory controls, MRI of the pituitary, treatment with dopamine agonists or even pituitary surgery. Physicians involved with diagnosis and treatment of hyperprolactinaemia (general practitioners, gynaecologists, neurosurgeons, endocrinologists and biochemists) should suspect the presence of apparent hyperprolactinaemia in any patient with a high prolactin value but no related symptoms. Medical laboratories should be aware that their prolactin assay can interfere with macroprolactin and should implement the use of the PEG precipitation test in the work-up of hyperprolactinaemia, a simple and effective means of correctly diagnosing apparent hyperprolactinaemia.

Antithrombin activity of an algal polysaccharide.

In an effort to reduce the risks of a possible iatrogenic transmission of bovine spongiform encephalitis (BSE) through the use of bovine-derived medicinal products, we patented in the USA in 1999 a polysaccharide from brown algae, endowed with interesting pharmacological activities: (a) concentration-dependent inhibition of thromboplastin or cephalin-kaolin-induced thrombin generation from platelets, (b) concentration-dependent inhibition of thrombin-induced platelet aggregation, (c) thrombin has hypotensive effect, which was blunted and zeroed by our fucansulfate in a dose-dependent way, (d) when aortae are stimulated with thrombin, they become stickier for polymorphonucleated leukocytes (PMNs); our fucansulfate decreased concentration-dependently, PMNs sticking to autologous rabbit aortae, (e) dose-dependent inhibition of thrombin-induced thrombosis. All the above data suggest that our fucansulfate could be a heparin substitute endowed with antithrombotic and anti-inflammatory activities, devoid or the problems caused to heparin by its animal origin, i.e., possible prion protein contamination.

Concomitant occurrence of macroprolactin, exercise-induced amenorrhea, and a pituitary lesion: a diagnostic pitfall. Case report.

The authors report the case of a 37-year-old woman who presented with amenorrhea and an increased level of serum prolactin. Magnetic resonance images of the pituitary revealed a lesion with characteristics consistent with those of a microadenoma. Transsphenoidal exploration was performed, but a prolactinoma was not found. After endocrinological review, the patient's hyperprolactinemia was found to be caused by the presence of macroprolactin and her amenorrhea was due to intense exercise and low body weight. Macroprolactin is an isoform of prolactin that is variably reactive in assays for prolactin, but displays minimum bioactivity in vivo. Patients with macroprolactin are mostly asymptomatic. This phenomenon may cause elevated prolactin values, which the authors view as apparent hyperprolactinemia. The presence of macroprolactin is an underrecognized problem, occurring in as many as 15 to 20% of patients with elevated prolactin values and often leading to unnecessary, expensive diagnostic procedures and inappropriate treatment. The presence of macroprolactin should always be suspected when the patient's clinical history or clinical or radiological data are incompatible with the prolactin value. Physicians dealing with diagnosis and treatment of hyperprolactinemia (general practitioners, gynecologists, neurosurgeons, endocrinologists, and biochemists) should be aware of the potentially misleading nature of macroprolactin.