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•Pro-inflammatory factors play a central role in COVID-19 severity and mortality.•Down Syndrome is characterised by immune dysregulation and respiratory infections.•Down Syndrome ...patients with COVID-19 are at high risk of an unfavourable outcome.
We report two cases of Corona Virus Disease-19 (COVID-19) in patients with Down Syndrome (DS) and describe the identification, diagnosis, clinical course and management of the infection. Down Syndrome, which is caused by trisomy 21, is characterized by immune dysregulation, anatomical differences in the upper respiratory tract and higher rate of comorbidities. All these risk factors can contribute to more severe clinical presentations of COVID-19 in this population. It is essential to raise awareness of the clinical relevance of SARS-COV-2 infection in DS patients, as well as in other most vulnerable patients, in order to improve their management and treatment and to encourage vaccinating these individuals early, once a vaccination is available.
Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with increased gene dosage for PMP22. Therapeutic approaches are currently aiming at correcting PMP22 over-expression. It is unknown whether ...PMP22 can be used as a biological marker of disease progression and therapy efficacy. We performed quantitative real-time polymerase chain reaction on skin biopsies of 45 patients with CMT1A, obtained at study entry and after 24-months of treatment either with ascorbic acid or placebo. Data of a subgroup of patients were also compared with matched healthy subjects. Finally, we analysed PMP22 messenger RNA levels in sural nerve biopsies. We did not find significant differences in the levels of any known PMP22 transcripts in treated or untreated patients with CMT1A, thus confirming that ascorbic acid does not impact on the molecular features of CMT1A. Most importantly, we did not observe any correlation between PMP22 messenger RNA levels and the different clinical and electrophysiological outcome measures, underscoring the weakness of PMP22 to mirror the phenotypic variability of patients with CMT1A. We did not find increased PMP22 messenger RNA levels in skin and sural nerve biopsies of patients with CMT1A compared with relative controls. In conclusion, this study shows that ascorbic acid does not impact on PMP22 transcriptional regulation and PMP22 is not a suitable biomarker for CMT1A.
Objective: To describe a new FHM kindred, and to analyse the functional consequences of the disease-associated ATP1A2 p.G301R mutation in human cellular models grown at 37°C.
Patients and methods: ...Seven patients were clinically evaluated and gave informed consent for molecular analysis. Extra-pyramidal rigidity of the limbs was present in four subjects and in three of them tongue apraxia was also observed. ATP1A2 and CACNA1A were analysed by direct sequencing. Functional consequences of the mutation were investigated by cell viability assays, Western blots, and immunocytochemistry. Three-dimensional models of the human Na+/K+-ATPase α2 subunit were generated by homology modelling using SWISS-MODEL.
Findings: Analysis of ATP1A2 showed a heterozygous mutation, c.901G>A predicting the replacement of arginine for glycine at residue 301 (p.G301R). Functional analysis suggested that the mutation completely abolished Na+/K+-ATPase function.
Conclusions: The phenotypic spectrum of our FHM2 family includes some peculiar features. Functional data confirm that Na+/K+-ATPase haploinsufficiency caused by the ATP1A2 p.G301R mutation is responsible for FHM in the described family.
Introduction
An ongoing national multicenter survey Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS) is evaluating the characteristics of breakthrough cancer pain (BTP) in different ...clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here.
Methods
Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity.
Results
Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids.
Conclusions
These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients’ satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients.
Funding
Molteni Farmaceutici, Italy.
Abstract This study evaluates primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease ...severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy controls. Using hierarchical clustering, we identified four significant clusters of patients according to clinical severity. We then tested the impact of each of the CMTNS components and of the secondary clinical parameters with regard to their power to differentiate these four clusters. The CMTNS components ulnar sensory nerve action potential (SNAP), pin sensibility, vibration and strength of arms did not increase the discriminant value of the remaining five CMTNS components (Ulnar compound motor action potential CMAP, leg motor symptoms, arm motor symptoms, leg strength and sensory symptoms). However, three of the six additional clinical outcome measures – the 10 m-timed walking test (T10MW), 9 hole-peg test (9HPT), and foot dorsal flexion dynamometry – further improved discrimination between severely and mildly affected patients. From these findings, we identified three different composite measures as score hypotheses and compared their discriminant power with that of the CMTNS. A composite of eight components CMAP, Motor symptoms legs, Motor symptoms arms, Strength of Legs, Sensory symptoms), displayed the strongest power to discriminate between the clusters. As a conclusion, five items from the CMTNS and three secondary clinical outcome measures improve the clinical assessment of patients with CMT1A significantly and are beneficial for upcoming clinical and therapeutic trials.
In this paper, we report, for the first time, experimental evidence of multiphoton photolysis of a caged proton compound, 2-nitrobenzaldehyde (o-NBA), using a new sensor system that utilizes ...fluorescent-labeled nanocapsules, i.e., a fluorescent nanostructured shell of micrometric size and nanometric thickness. The photolabile compound undergoes one-photon absorption in the UV range (200−380 nm), and the mechanism that leads to proton release is based on the well-known 2-nitrobenzyl photochemistry, which has been used for many photoactivatable-caged compounds. Because the use of UV excitation can cause biological damage, we changed our focus to multiphoton absorption−uncaging processes. The induced pH decrease was monitored by imaging changes in the pH-dependent emission of fluorescein isothiocyanate that was embedded in a nanostructured system (so-called “nanocapsules”). The nanocapsules with covalently bound dyes allow improved stability in fluorescence monitoring. Moreover, an original image processing method is introduced to quantify the uncaging. Using a femtosecond Ti:sapphire laser that was operating at 720 nm, with a pulse width of ∼200 fs at the sample, delivered through an adapted confocal laser scanning head and a 1-min exposure time with high power (45−50 mW), we obtained appreciable photolysis of 2-nitrobenzaldehyde. So far, we demonstrated that fluorescent-labeled nanocapsules are a suitable system as fluorescence sensors.
One of the genetic features of the Sardinian population is the high prevalence of hemoglobin disorders. It has been estimated that 13% to 33% of Sardinians carry a mutant allele of the alpha-globin ...gene (alpha-thalassemia trait) and that 6% to 17% are beta-thalassemia carriers. In this population, a single mutation of beta-globin gene (Q39X, beta(0) 39) accounts for >95% of beta-thalassemia cases. Because previous studies have shown that Sardinian beta-thalassemia carriers have lower total and low density lipoprotein (LDL) cholesterol than noncarriers, we wondered whether this LDL-lowering effect of the beta-thalassemia trait was also present in subjects with familial hypercholesterolemia (FH). In a group of 63 Sardinian patients with the clinical diagnosis of FH, we identified 21 unrelated probands carrying 7 different mutations of the LDL receptor gene, 2 already known (313+1 g>a and C95R) and 5 not previously reported (D118N, C255W, A378T, T413R, and Fs572). The 313+1 g>a and Fs572 mutations were found in several families. In cluster Fs572, the plasma LDL cholesterol level was 5.76+/-1.08 mmol/L in subjects with beta(0)-thalassemia trait and 8.25+/-1.66 mmol/L in subjects without this trait (P<0.001). This LDL-lowering effect was confirmed in an FH heterozygote of the same cluster who had beta(0)-thalassemia major and whose LDL cholesterol level was below the 50th percentile of the distribution in the normal Sardinian population. The hypocholesterolemic effect of beta(0)-thalassemia trait emerged also when we pooled the data from all FH subjects with and without beta(0)-thalassemia trait, regardless of the type of mutation in the LDL receptor gene. The LDL-lowering effect of beta(0)-thalassemia may be related to (1) the mild erythroid hyperplasia, which would increase the LDL removal by the bone marrow, and (2) the chronic activation of the monocyte-macrophage system, causing an increased secretion of some cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) known to affect the hepatic secretion and the receptor-mediated removal of apolipoprotein B-containing lipoproteins. The observation that our FH subjects with beta(0)-thalassemia trait (compared with noncarriers) have an increase of blood reticulocytes (40%) and plasma levels of interleukin-6 (+60%) supports these hypotheses. The lifelong LDL-lowering effect of beta(0)-thalassemia trait might slow the development and progression of coronary atherosclerosis in FH.
Objective. –
This study was made to determine the incidence of nosocomial viral gastroenteritis in all children aged 0–4 years, admitted in the Pediatric Hospital over a 3-year period.
Methods. –
...Astrovirus was detected by reverse transcriptase-PCR; routine diagnostic tests for Rotavirus, Adenovirus, and common bacterial pathogens were carried out on all samples.
Results. –
Of the 460 children with nosocomial diarrhea, 23 harbored Astrovirus (5%). Most cases occurred during the coldest months of the year. Children under 1 year of age were the most susceptible population.
Conclusion. –
The collected data confirms the importance of viral etiology in nosocomial gastroenteritis. The reported rate of detection stresses the importance of Astrovirus in pediatric diarrhea. The authors recommend screening for this virus on a routine basis.
Objectif. –
Nous avons développé une étude pour déterminer l'incidence d'infection d'Astrovirus auprès des enfants ages de zero à quatre ans hospitalisés à l'hôpital pédiatrique durant trois ans.
Méthodes. –
L'Astrovirus a été détecté grâce au RT-PCR, et des tests diagnostiques de routine ont été effectués pour Rotavirus, Adenovirus et autres bactéries pathogènes communes sur tous les échantillons.
Résultats. –
Sur 460 enfants affectés de diarrhée nosocomiale, 23 (5 %) présentaient une infection à Astrovirus. La majorité des cas se manifestait pendant les mois les plus froids de l'année. Les enfants âgés de moins d'un an étaient les plus touchés.
Conclusion. –
Ces données confirment l'importance de l'étiologie virale dans les gastroentérites. Les taux de détection rapportés par les auteurs montrent l'importance de l'Astrovirus dans la diarrhée infantile. Ils conseillent son dépistage avec des contrôles de routine.
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