71 research outputs found
Co-occurrence of orbital venous varix and cavernoma: first report of combined clipping and cryosurgery treatment
Intraorbital arteries studied in pediatric age by high resolution superselective angiography
Angiography is a powerful tool to identify intraorbital arteries. However, the
incidence by which these vessels can be identified is unknown. Our purpose was to
determine such incidence and which angiographic approach is best for the identification
of each artery. A retrospective study of 353 angiographic procedures (via ophthalmic
artery and/or external carotid artery) carried out on 79 children affected by
intraocular retinoblastoma was made to investigate the arterial anatomy in 87 orbits.
For each intraorbital artery two parameters were calculated: the angiographic incidence,
as the percentage of times a given artery was identified, and the visibility
index, as the ratio between the angiographic incidence and the true anatomic incidence.
All collaterals of the ophthalmic artery could be spotted. Most of them were
identified with a high angiographic incidence; some of them were less easily identified
because too thin or because frequently shielded. The visibility index paralleled
the angiographic incidence of most arteries. However, the lacrimal and meningolacrimal
arteries had a higher visibility index suggesting that their identification was
more frequent than the angiographic incidence alone could suggest. Statistical analysis
demonstrated that the lacrimal artery and some muscular branches had higher
chances to be identified if the angiography of the ophthalmic artery was accompanied
by the study of the external carotid system. This work provides an objective
measure of how powerful angiography is to identify intraorbital arteries as well as
useful references for professionals who need to operate in the orbit
Safety of Intravenous Thrombolysis and Mechanical Thrombectomy in Bilateral Posterior Cerebral Artery Territory Infarction
Background: Acute bilateral blindness is an uncommon phenomenon that requires immediate diagnosis and action. The emergent evaluation should concentrate on an early distinction between ocular, cortical, and psychogenic etiologies.Objective: To present a case of cortical blindness without anosognosia due to the embolic occlusion of both posterior cerebral arteries (PCAs) and treated by intravenous and mechanical thrombolysis.Case Report: A 67-year-old woman was admitted to the Stroke Unit due to cortical blindness without anosognosia. At the admission to the hospital, an emergent computed tomography scan of the brain ruled out intracranial acute hemorrhage and showed subtle changes consistent with hyperacute ischemia of the left occipital cortex, while a CT angiography demonstrated the occlusion of the P3 segment of both right and left posterior cerebral arteries. The patient was treated with combined thrombolysis (intravenous and mechanical thrombolysis), obtaining complete revascularization and a significant clinical improvement.Conclusion: Even if there is no randomized controlled trial to compare the effectiveness and safety of mechanical thrombectomy (MT) to intravenous thrombolysis in patients with posterior circulation occlusion, the good outcome of this case encourages combined stroke treatments in posterior circulation stroke, even in case of mild but disabling neurological deficits
Characterizing determinants of BK Polyomavirus-specific immune response
BK polyomavirus (BKPyV) is one of now 13 human polyomavirus (HPyV) species detected in humans. BKPyV is only known to infect humans and seroprevalence rates of more than 90% have been reported in adult populations around the world. Following primary infection, BKPyV persists in the renourinary tract without causing any disease as evidenced by urinary shedding in 5% - 10% of healthy immunocompetent blood donors.
In immunocompromised persons, however, BKPyV can cause significant diseases whereby uncontrolled high-level replication may lead to organ invasive pathologies in kidneys, bladder, lungs, vasculature, and the central nervous system. The most consistently found diseases are BKPyV-associated hemorrhagic cystitis (BKPyVHC) in 5%-20% allogeneic hematopoietic stem cells transplant patients, and BKPyV-associated nephropathy (BKPyVAN) in 1%-15% of kidney transplant patients. BKPyVHC is highly symptomatic with pain, anemic bleeding, and increased mortality. BKPyVAN is asymptomatic except for progressive renal failure and premature return to dialysis. Both entities are characterized by high-level viral replication i.e. with urine BKPyV loads of 8-10 log10 Geq/mL, plasma BKPyV loads often above 4 log10 Geq/mL, and an allogeneic constellation between the virus-infected host cell and the available T-cell effectors. Despite these similarities, the clinical manifestations are strikingly different suggesting relevant, but experimentally undefined differences in pathogenesis. Thus, BKPyVHC typically occurs within 4 weeks after allogeneic HSCT and is confined to the bladder, and typically without kidney involvement. By contrast, BKPyVAN is diagnosed around 3-6 months after kidney transplantation and confined to the kidney allograft without causing cystitis. Although high-level BKPyV replication should be formally amenable to antiviral drug treatment, no effective and BKPyV-specific antiviral therapy is currently available. Therefore, a better understanding of the immune alteration in both diseases has been deemed essential to identify patients at risk and to develop prophylactic, preemptive and therapeutic strategies.
The currently recommended strategy for BKPyVAN is to screen kidney transplant patients for BKPyV replication and to promptly reduce immunosuppressive therapy in those with significant replication to facilitate mounting of BKPyV-specific T cell responses and thereby preventing progression to disease. This manoeuver has been linked to expanding BKPyV-specific T cell responses in the peripheral blood of kidney transplant patients. However, this approach may place patients at risk for acute rejection episodes that predispose equally well to premature kidney transplant failure. Although the clinical feasibility of reducing immunosuppression and curtailing BKPyV replication has been shown to be effective in prospective cohort studies for many, but not all of kidney transplant patients, this approach has not been possible in allogeneic HSCT patients because of concurrent or imminent graft-versus host disease. Thus, there are significant gaps in the current understanding of the BKPyV– host interaction in the normal host and in the allogeneic setting, which need to be investigated for a more effective and safer management of these significant viral complications.
In this thesis, the interaction of BKPyV and the immune response has been approached from two different angles. In the first project, potential mechanisms of BKPyV immune evasion were studied. Here, we focused on a small accessory protein called agnoprotein encoded as a leader protein in the late viral early region (LVGR). Although HPyV genomes overall show a very similar genome organization, agnoproteins are only found in the genomes of BKPyV and JCPyV that have a kidney tropisms, but not in any of the other 11 presumably non-renotropic HPyVs. We hypothesized that agnoprotein could play a role in immune evasion by downregulating HLA expression. The effects of agnoprotein were studied on HLA class I and II expression in vitro by flow cytometry following transfection of primary human renal tubular epithelial cells, which are the viral target of BKPyV-associated nephropathy. In addition, transfected human UTA-6 cells were studied as well as UTA-6 cells bearing a tetracycline-regulated agnoprotein. As control, the effects were compared with the ICP47 protein of Herpes simplex virus-1, which has been previously reported to effectively down-regulate HLA class I. Although both viral proteins share some similarities at the protein level, our results showed that BKPyV agnoprotein did not down-regulate HLA class I or class II molecules. Also, there was not inhibitory effect on the increase of HLA-class I or class-II surface expression following exposure to interferon-. By contrast, ICP47 reduced HLA class I surface expression, but not class II. We also evaluated effects of agnoprotein on virus epitope-specific T-cell killing by 51Chromium release assay, however no interference could be observed. We concluded that agnoprotein did not contribute to these types of HLA-dependent immune evasion processes. However, further investigations are needed to understand if agnoprotein could contribute to viral immune escape by other mechanisms.
In the second project, we aimed at better characterizing BKPyV-specific CD8 T cell immunity targeting epitopes encoded in the early viral gene region (EVGR). Selected coding sequences of the BKPyV EVGR were submitted to two web-based computer algorithms (SYFPEITHI, IEDB) in order to predict immunodominant 9mer epitopes presented by 14 frequent HLA-class I molecules. For an experimental confirmation, 97 different 9mer epitopes were chemically synthesized and tested in 42 healthy individuals. A total of 39 epitopes could be confirmed by interferon- ELISpot assay in at least 30% of healthy individuals. Interestingly, most of the 9mer epitopes appeared to cluster in short amino acid stretches, and some 9mer could be presented by more than one HLA class I allele as expected for immunodominant domains. HLA-specific presentation was demonstrated by 9mer- MHC-I streptamers for 21/39 (54%) epitopes. The 9mer dependent T-cell killing by 51Chromium release assay and the CD107a surface detection indicated that the 9mer epitopes could be recognized by cytotoxic T-cells. Moving to a clinically relevant situation, 13 9mer epitopes could be validated in 19 kidney transplant patients protected from, or recovering from, BKPyV viremia. The results suggest that, pending further corroboration in larger patient populations, novel 9mer epitopes can be identified, which are associated with CD8 T cell control of BKPyV replication. Thus the identified immunodominant 9mer T-cell epitopes could be further developed for clinical assays to better predict the risk and the recovery of BKPyV diseases, help guiding immunosuppression reduction, and to develop specific adoptive T-cell therapy or vaccine responses to prevent or treat BKPyV-associated disease
Results of RELAP4/MOD6 code applications", Lectures L8, L9, L10, L13, L16 at Course on Thermal-hydraulic Phenomena in Nuclear Reactor Technology - Sofia (BG),
A Course in Nuclear thermal-hydraulics was organized by UNIPI in Sofia at the time of the cold war (Soviet Union collapsed in 1991). Contacts crossing the iron curtain were extremely complex. The entire Course consists of several hundred slides (all preserved in paper format by the corresponding author) and a couple dozen lectures (see copies below). Two pages from the Course are reported below. The current lecture deals with the selected topics relevant in nuclear thermal-hydraulics –more details can be found in the copied program below
Transorbital anastomotic pathways between the external and internal carotid systems in children affected by intraocular retinoblastoma
Purpose: It is well known that many anastomoses can join the external carotid system and the ophthalmic artery. However, their frequency has never been reported. Since they can be relevant for interventional radiologists operating in the orbit, we decided to illustrate and determine the frequency of the anastomoses that can be found in children.
Methods: A retrospective study of 443 angiographic procedures (via ophthalmic artery and/or external carotid artery) carried out on 97 children affected by intraocular retinoblastoma was made to investigate the arterial anatomy of 106 orbits.
Results: Anastomoses were observed in 44.33% of orbits. However, their true frequency is likely much higher as the rate of visualization increased up to 91.11% of orbits when the angiographic study was extended to the external carotid artery. In order of frequency we detected the following anastomoses: lacrimal artery - middle meningeal artery, lacrimal artery - anterior deep temporal artery, ophthalmic artery - middle meningeal artery, ophthalmic artery - facial artery, supraorbital artery - superficial temporal artery, supratrochlear artery - superficial temporal artery, supraorbital artery - middle meningeal artery, dorsal nasal artery - infraorbital artery, supraorbital artery - zygomaticoorbital artery, lacrimal artery - zygomaticoorbital artery.
Conclusion: When properly searched, anastomoses between the ophthalmic artery and the external carotid artery are almost constant in children. Depending on the clinical scenario they can represent dangers or valuable alternative routes for collateral circulations and intraarterial chemotherapy
Cerebral circulation time is prolonged and not correlated with EDSS in multiple sclerosis patients: a study using digital subtracted angiography
Literature has suggested that changes in brain flow circulation occur in patients with multiple sclerosis. In this study, digital subtraction angiography (DSA) was used to measure the absolute CCT value in MS patients and to correlate its value to age at disease onset and duration, and to expand disability status scale (EDSS). DSA assessment was performed on eighty MS patients and on a control group of forty-four age-matched patients. CCT in MS and control groups was calculated by analyzing the angiographic images. Lesion and brain volumes were calculated in a representative group of MS patients. Statistical correlations among CCT and disease duration, age at disease onset, lesion load, brain volumes and EDSS were considered. A significant difference between CCT in MS patients (mean = 4.9s; sd = 1.27 s) and control group (mean = 2.8s; sd = 0.51 s) was demonstrated. No significant statistical correlation was found between CCT and the other parameters in all MS patients. Significantly increased CCT value in MS patients suggests the presence of microvascular dysfunctions, which do not depend on clinical and MRI findings. Hemodynamic changes may not be exclusively the result of a late chronic inflammatory process
Are callous unemotional traits and emotional dysregulation a predictor of response to methylphenidate in children with ADHD?
Attention-deficit/hyperactivity disorder (ADHD) is a childhood onset neurodevelopmental condition, characterized by age-inappropriate and pervasive levels of inattention and /or hyperactivity-impulsiveness that cause significant impairment and often continue into adulthood.
Oppositional defiant disorder (ODD) and Conduct disorder (CD) coexist in 40-80% and in 20-56% of children and young people with ADHD, respectively. Callous unemotional (CU) traits and emotional dysregulation (ED) may be association with ODD and CD. CU traits are a pattern of callousness, uncaring behaviour, reduced guilt, and reduced empathy and are a defining feature of psychopathy and aggressive youth. CU traits influence the clinical evolution of ADHD and comorbid conduct problems. ED is an individual’s inability to modulate emotion regulation, to such a degree that the inability results in the individual functioning meaningfully below their baseline. The comorbidity of ADHD with ED represents a major source of impairment and predicts a poor clinical outcome. Whilst there is evidence that CU and ED predict poorer outcome in individuals with ADHD/ODD-CD, the extent to which they impact on response to ADHD pharmacological treatment is unclear.
The purpose of the present thesis was to assess if CU traits and ED are a predictor of response to methylphenidate in children with ADHD with and without ODD or CD.
Two samples, providing complementary information, were included: an Italian group of 36 children (aged 6-18) prospectively recruited at the IRCCS Stella Maris, Calambrone, Pisa and a UK group of 53 children (aged 5-18) from the South Hampshire ADHD Register (SHARE), Southampton University.
According to the Italian protocol, parents completed at baseline the ADHD-rating scale (ADHD-RS) to assess ADHD symptoms severity, the Child Behaviour Checklist Report Form school age version (CBCL 6-18) for the assessment of ODD, CD, and ED, the Inventory of Callous-Unemotional Traits (ICU) as well as the Antisocial Process Screening Device (APSD) to measure CU traits, and the Aggression Questionnaires (AQ) along with the Modified Overt Aggression Scale (MOAS) based on the parents’ interview to assess aggression. After one month of treatment with methylphenidate, parents completed again the ADHD-RS. The UK protocol included the Conners Comprehensive Behaviour Rating Scale (Conners CBRS), parent and teacher forms, for ADHD and ODD, the ICU, parent and teacher version, for CU traits and the Affective Reactivity Index (ARI) parent version for ED, all completed at baseline. Parents and teachers completed again the Conners CBRS after six months of therapy.
We first correlated the severity of baseline CU and ED to the changes in ADHD symptoms severity from baseline to follow-up (= “response to methylphenidate”). We then compared the response to methylphenidate in children with ADHD and CU traits and in those without CU traits.
We repeated the same comparison in the subgroups of children with ADHD and ODD/CD with and without CU traits and finally we compared the response to methylphenidate in children with ADHD and ED with the response in children without ED. We analysed data with the Statistical Package for Social Science (SPSS Inc.), version 24, using the Independent sample T Test and the Pearson correlation procedure. A probability level of P<0.05 was used to indicate statistical significance.
In the Italian group, we found a significant and positive correlation (Pearson coefficient of +0.442 and a P of 0.01) between the severity of baseline ED and the effectiveness of the treatment. Additionally, we found a significant and positive correlation between CU traits and response to methylphenidate (Pearson coefficient of +0.368 and a P of 0.05), even though this was not the case in the two subgroups of children with ODD and/or CD in comorbidity. On the contrary, scores of baseline aggressiveness did not correlate with the response to methylphenidate. Furthermore, the correlation between the ICU callousness and unemotional subscales scores and response to methylphenidate was not significant.
In the UK sample, we could analyse the response to the two ADHD domains (i.e., inattention and hyperactivity/impulsivity) separately. We did not find any significant correlation between the ARI-P scores and response to methylphenidate, even though T test showed higher decrease in ADHD scores in subjects with ARI=OPO scores ≥ 1.
As for CU traits, there was a significant and positive correlation between the scores on the ICU-P Callousness subscale and the response to methylphenidate, for the total ADHD scores as well as for the inattentive subscores. With regards to emotional traits, whilst there was no significant correlation between the scores on the ICU-P Unemotional subscale and response to treatment, we found significantly higher average post-pre score differences on the Conners CBRS-P ADHD scales.
In conclusion, this is the first study to assess ED and CU as predictors of response to methylphenidate. We found evidence showing that the severity of CU traits and ED have an impact on the response to methylphenidate in children with ADHD.
Our findings need to be replicated in further studies with a longer follow-up, larger samples and assessing several classes of ADHD medications. Overall, our findings highlight that ED and CU should be systematically assessed in the daily clinical practice with individuals with ADHD
The Role of Radiomics in Salivary Gland Imaging: A Systematic Review and Radiomics Quality Assessment
Background: Radiomics of salivary gland imaging can support clinical decisions in different clinical scenarios, such as tumors, radiation-induced xerostomia and sialadenitis. This review aims to evaluate the methodological quality of radiomics studies on salivary gland imaging. Material and Methods: A systematic search was performed, and the methodological quality was evaluated using the radiomics quality score (RQS). Subgroup analyses according to the first author’s professional role (medical or not medical), journal type (radiological journal or other) and the year of publication (2021 or before) were performed. The correlation of RQS with the number of patients was calculated. Results: Twenty-three articles were included (mean RQS 11.34 ± 3.68). Most studies well-documented the imaging protocol (87%), while neither prospective validations nor cost-effectiveness analyses were performed. None of the included studies provided open-source data. A statistically significant difference in RQS according to the year of publication was found (p = 0.009), with papers published in 2021 having slightly higher RQSs than older ones. No differences according to journal type or the first author’s professional role were demonstrated. A moderate relationship between the overall RQS and the number of patients was found. Conclusions: Radiomics application in salivary gland imaging is increasing. Although its current clinical applicability can be affected by the somewhat inadequate quality of the papers, a significant improvement in radiomics methodologies has been demonstrated in the last year
Magmas with slab fluid and decompression melting signatures coexisting in the Gulf of Fonseca: evidence from Isla El Tigre volcano (Honduras, Central America)
Isla El Tigre volcano is located in the Gulf of Fonseca (Honduras) along the Central America volcanic front, where a significant change in the strike of the volcanic chain is observed. The studied samples of this poorly investigated volcano are mainly subalkaline basic to intermediate lavas (basalts and basaltic andesites) and subordinate subalkaline/alkaline transitional basalts, both having the typical mineralogical and geochemical characteristics of arc volcanic rocks. On the basis of petrographic and geochemical features, two groups of rocks have been distinguished. Lavas from the main volcanic edifice are highly porphyritic and hy-qz normative, and have lower MgO contents (5 wt%), are ol-hy normative and show lower HFSE depletions relative to LILE and LREE, with lower Ba/La, Ba/Nb and Zr/Nb ratios. This suggests that mantle-derived magmas were not produced by the same process throughout the activity of the volcano.
The bulk rock geochemistry and 87Sr/86Sr (0.70373-0.70382), 143Nd/144Nd (0.51298-0.51301), 206Pb/204Pb (18.55-18.58), 207Pb/204Pb (15.54-15.56) and 208Pb/204Pb (38.23-38.26) isotopic data of Isla El Tigre compared with the other volcanoes of the Gulf of Fonseca and all available literature data for Central America suggests that this stratovolcano was mainly built by mantle-derived melts driven by slab-derived fluid-flux melting, while magmas erupted through its parasitic cones have a clear signature of decompression melting with minor slab contribution. The coexistence of these two different mantle melting generation processes is likely related to the complex geodynamic setting of the Gulf of Fonseca, where the volcanic front changes direction by ca. 30° and two fundamental tectonic structures of the Chortis continental block, mainly the N-S Honduras Depression and the NE-SW Guayape Fault Zone, cross each other
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