Targeted re-sequencing in pediatric and perinatal stroke Grossi, Alice; Severino, Mariasavina; Rusmini, Marta ...
European journal of medical genetics,
November 2020, 2020-Nov, 2020-11-00, 20201101, Letnik:
63, Številka:
11
Journal Article
Recenzirano
Pediatric and perinatal stroke can present as an early symptom in undiagnosed syndromes characterized by simple Mendelian inheritance. In order to diagnose those patients affected with a monogenic ...disorder in which an arterial cerebrovascular event or arteriopathy may have preceded any other specific symptom, we aimed to establish and validate a targeted gene panel, and to determine its diagnostic yield and clinical utility. To this end, thirty-eight patients were selected with heterogeneous cryptogenic stroke phenotypes, mostly including multiple and recurrent ischemic or hemorrhagic arterial strokes and porencephalies, variably associated with calcifications, intracranial or systemic steno-occlusive arteriopathies, positive family history, and syndromic conditions. Clinical and neuroradiological data were collected for every patient enrolled in the study, and DNA samples were tested by means of a customized gene panel including 15 genes associated with known genetic diseases related to pediatric stroke. In four patients (10.5%) the analyses unraveled pathogenetic variants in ABCC6 and COL4A1 genes, leading to a definite genetic diagnosis with a great beneficial impact on patients management, while results were null in the remaining patients. These findings suggest a high complexity and variability of the included stroke phenotypes, that could not be fully accounted for by the genes tested in the present study. A wider gene panel or an unbiased genomic approach may be better suited and advisable to explain a greater proportion of pediatric and perinatal stroke events.
•Stroke and cerebrovascular disorders cause morbidity and mortality also in children.•A targeted gene panel has been developed for simple disorders with arterial stroke.•Diagnosis and clinical management has been improved for specific stroke-associated genetic diseases.•Genes tested do not fully account for complex stroke associated clinical phenotypes.
Purpose
Vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2) are thought to mediate MIBG uptake in adult neuroendocrine tumors. In neuroblastoma, the norepinephrine transporter (NET) has been ...investigated as the principal MIBG uptake protein, though some tumors without NET expression concentrate MIBG. We investigated VMAT expression in neuroblastoma and correlated expression with MIBG uptake and clinical features.
Methods
We evaluated VMAT1 and VMAT2 expression by immunohistochemistry (IHC) in neuroblastoma tumors from 76 patients with high-risk metastatic disease treated in a uniform cooperative group trial (COG A3973). All patients had baseline MIBG diagnostic scans centrally reviewed. IHC results were scored as the product of intensity grading (0 – 3+) and percent of tumor cells expressing the protein of interest. The association between VMAT1 and VMAT2 scores and clinical and biological features was tested using Wilcoxon rank-sum tests.
Results
Patient characteristics were typical of high-risk neuroblastoma, though the cohort was intentionally enriched in patients with MIBG-nonavid tumors (
n
= 20). VMAT1 and VMAT2 were expressed in 62 % and 75 % of neuroblastoma tumors, respectively. VMAT1 and VMAT2 scores were both significantly lower in
MYCN
amplified tumors and in tumors with high mitotic karyorrhectic index. MIBG-avid tumors had significantly higher VMAT2 scores than MIBG-nonavid tumors (median 216 vs. 45;
p
= 0.04). VMAT1 expression did not correlate with MIBG avidity.
Conclusion
VMAT1 and VMAT2 are expressed in the majority of neuroblastomas. Expression correlates with other biological features. The expression level of VMAT2 but not that of VMAT1 correlates with avidity for MIBG.
Previous studies on the photosensitization of bacterial cells with different neutral or negatively charged porphyrins and phthalocyanines have demonstrated that, although Gram-positive bacteria are ...efficiently photoinactivated, Gram-negatrive bacteria become photosensitive only after modification of the permeability of their outer membrane.
The results described in this paper show that two meso-substituted cationic porphyrins, namely tetra(4
N-methyl-pyridyl) porphine tetraiodide and the tetra(4
N,
N,
N,-trimethyl-anilinium) porphine, efficiently photosensitive the inactivation of Gram-negative bacteria, such as
Vibrio anguillarum and
Escherichia coli. A negatively charged meso-substituted porphyrin, tetra(4-sulphonatophenyl)porphine, has no appreciable photosensitizing activity towards Gram-negative bacteria, although all three porphyrins exhibit a similar subcellular distribution pattern, being mainly localized in the protoplasts or spheroplasts. Moreover, the three porphyrins show similar efficiency in the photoinactivation of the Gram-positive bacterium
Entorecoccus seriolicida.
This is the first record of protoporphyrinogen oxidase (PPO) inhibitor resistance in eastern Canada, and the second record of a glyphosate-resistant weed in Quebec. In 2016 and 2017, waterhemp seed ...was collected from 25 locations across Ontario and Quebec. All populations tested positive for imazethapyr resistance. Three-way resistance to imazethapyr, atrazine, and glyphosate was confirmed in 80% of the samples. Additionally, between 2015 and 2017, waterhemp seed was collected from 74 locations in Ontario or Quebec and resistance to lactofen was confirmed in 28% of the seed lots screened.
Accidents are the main cause of injury in children, more than half events happen at home. Aims of this study were to assess if SARS-CoV-2 lockdown influence emergency department (ED) visits due to ...children domestic accident (DAs) and to identify factors associated with hospitalization. This was a multicentre, observational, and retrospective cohort study involving 16 EDs in Italy and enrolling children (3–13 years) receiving a visit in ED during March–June 2019 and March–June 2020. Risk factors for hospitalization were identified by logistic regression models. In total, 8860 ED visits due to domestic accidents in children occurred before (4380) and during (4480) lockdown, with a mean incidence of DA of 5.6% in 2019 and 17.9% in 2020 (
p
< 0.001) (
IRR
: 3.16;
p
< 0.001). The risk of hospitalization was influenced by the type of occurred accident, with fourfold higher for poisoning and twofold lower risk for stab-wound ones. In addition, a higher risk was reported for lockdown period vs 2019 (
OR
: 1.9;
p
< 0.001), males (
OR
: 1.4;
p
< 0.001), and it increased with age (
OR
: 1.1;
p
< 0.001).
Conclusions
: The main limitation of this study is the retrospective collection of data, available only for patients who presented at the hospital. This does highlight possible differences in the total number of incidents that truly occurred. In any case, the COVID-19 lockdown had a high impact on the frequency of DAs and on hospitalization. A public health campaign aimed at caregivers would be necessary to minimize possible risks at home.
What is Known:
•
In Italy, domestic accidents are the second leading cause of paediatric mortality after cancer.
• During the first SARS-CoV-2 lockdown in 2020, a sharp decrease in the total number of Emergency Departments visits for all causes was observed, both in children and in adults.
What is New:
• During the first SARS-CoV-2 lockdown in 2020, domestic accidents involving children increased threefold from the previous year.
• Higher risk of hospitalization was showed in minors accessing during 2020 vs 2019, in males than in females and it increased with advancing age. Considering the type of injury, a significant higher risk of hospitalization for poisoning was observed.
Healthcare-associated infections (HAIs) surveillance is an essential part of any infection prevention and control programme. Repeated point prevalence surveys (PPSs) according to European Centre for ...Disease Prevention and Control (ECDC) protocol have been implemented in all Friuli Venezia Giulia (FVG) region (Italy) acute hospitals to reduce and control HAIs.
Using the repeated PPSs within a regional-healthcare system (RHS) to promote and evaluate infection prevention and control (IPC) programmes.
The standard versions of the ECDC PPS protocols were used in all four surveys (2011, 2013, 2015, 2017). All RHS public and private accredited hospitals were involved within the ‘safe care network’ programme.
The numbers of surveyed patients in the four PPSs were 3172, 3253, 2969 and 3036, respectively. Prevalence of HAIs and antimicrobial use (AU) decreased significantly from 2011: HAIs (P<0.05) 7.1%, 6.3%, 5.5%, 5.8% and AU (P<0.01) 40.4%, 39.2%, 36.0%, 37.2%, respectively. The appropriateness of duration of surgical prophylaxis increased significantly (<24 h increased through surveys related to one in 2011: odds ratio (OR), 95% confidence interval (CI) 1.29, 0.92–1.81; 1.95, 1.31–2.91; 1.78, 1.20–2.64, respectively). The most frequently detected HAIs were: bloodstream, urinary tract, pneumonia and surgical site (more than the 70% of HAIs in each PPS).
The FVG regional approach to HAIs and AU surveillance was able to contribute to reduce prevalence over a 7-year period. Furthermore, it was able to keep hospital attention on HAIs and AU through the years and to guarantee a standardized and comparable evaluation of HAIs and AU burden in all RHS hospitals, as well as impacting on HAIs and AU regional programmes.
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