Leuzzi V, Carducci Ca, Carducci Cl, Pozzessere S, Burlina A, Cerone R, Concolino D, Donati MA, Fiori L, Meli C, Ponzone A, Porta F, Strisciuglio P, Antonozzi I, Blau N. Phenotypic variability, ...neurological outcome and genetics background of 6‐pyruvoyl‐tetrahydropterin synthase deficiency.
This study aimed to investigate the clinical variability and factors implied in the outcome of 6‐pyruvoyl‐tetrahydropterin synthase deficiency (PTPSd). Biochemical and clinical phenotype, treatment variables, and 6‐pyruvoyl‐tetrahydropterin synthase (PTS) genotype, were explored retrospectively in 19 Italian patients (12 males and 7 females, aged 4 months to 33 years).
According to the level of biogenic amines in cerebrospinal fluid (CSF) at the diagnosis, the patients were classified as mild (6) (normal level) or severe (13) (abnormal low level) form (MF and SF, respectively). Blood Phe ranged from 151 to 1053 µmol/l in MF (mean ± SD: 698 ± 403) and 342–2120 µmol/l in SF (mean ± SD: 1175 ± 517) (p = 0.063). Patients with MF showed a normal neurological development (a transient dystonia was detected in one), while all SF patients except one presented with severe neurological impairment and only four had a normal neurological development. The outcome of the SF was influenced by the precocity of the treatment. Serial CSF examinations revealed a decline of 5‐hydroxyindolacetic acid in MFs and an incomplete restoration of neurotransmitters in SFs: neither obviously affected the prognosis. PTS gene analysis detected 17 different mutations (seven so far unreported) (only one affected allele was identified in three subjects). A good correlation was found between genotype and clinical and biochemical phenotype.
The occurrence of brain neurotransmitter deficiency and its early correction (by the therapy) are the main prognostic factors in PTPSd.
•Uncertainty of the Unified Method for TEMs characterization is carried out.•The uncertainty is Evaluated by means of a Monte Carlo Simulation.•A sensitivity analysis, gives a comprehensive insight ...into the most critical issues.•Experimental results show that two proposed stimuli provide compatible estimates.
In this paper the uncertainty evaluation of the recently proposed Unified Method for Thermo-Electric Module characterization is carried out. The measurement model is detailed and individual uncertainty contributions are highlighted, with close reference to the instrumentation and measurement setup. The uncertainty evaluation is performed by means of a Monte Carlo Simulation. The same algorithm is used to perform a sensitivity analysis, giving a comprehensive insight into the most critical issues of the proposed method and assessing the performance of the two adopted electrical stimuli. The experimental results thereby obtained are discussed and improvements to the measurement setup and technique are finally proposed.
Abstract
Introduction
The Post-traumatic Stress Disorder (PTSD) is a group of persistent psychological and physiological symptoms due to a traumatic, severe, event. Only few studies focused on the ...effects of Covid-19 on psychosocial outcomes in children with Type 1 Diabetes (T1D) and their parents.
Aim of the study
The aim of this study was to evaluate the presence PTSD in parents of children with T1D during COVID-19 pandemic lockdown.
Patients and methods
In the period between March and May 2020 we submitted the “Impact of Event Scale – Revised” (IES-R) questionnaire to the parents of 34 children with Type 1 Diabetes, asking them to express their emotions about the ongoing Covid-19 pandemic.
Results
A total of thirty mothers (mean age 43.0 ± 4.2 years) and 25 fathers (mean age 45.6 ± 5.9 years) participated in the survey and completed the questionnaires. 29.1% of parents had a score that allows to define a clinically relevant level of PTSD; ten mothers and 6 fathers had a PTSD clinically relevant score, corresponding, respectively, to 28.4 and 24% of total mothers and fathers. Finally, mothers and fathers, both express PTSD symptoms mainly in the form of intrusion and hyperarousal.
Conclusions
The present study confirms a high prevalence symptoms related to PTSD in mothers and fathers of children with Type 1 Diabetes. We believe that psychosocial outcomes of the COVID-19 pandemic should be taken into account in the planning of the next future assistance for children with T1D.
Objective
The Advanced Hybrid Closed Loop (AHCL) systems have provided the potential to ameliorate glucose control in children with Type 1 Diabetes. The aim of the present work was to compare ...metabolic control obtained with 2 AHCL systems (Medtronic 780G system and Tandem Control IQ system) in a pediatric real-life clinical context.
Research design and methods
It is an observational, real-life, monocentric study; thirty one children and adolescents (M:F = 15:16, age range 7.6–18 years, mean age 13.05 ± 2.4 years, Diabetes duration > 1 year) with T1D, previously treated with Predictive Low Glucose Suspend (PLGS) systems and then upgraded to AHCL have been enrolled. CGM data of the last four weeks of “PLGS system” (PRE period) with the first four weeks of AHCL system (POST period) have been compared.
Results
For both AHCL systems, Medtronic 780G and Tandem Control IQ, respectively TIR at 4 weeks significantly increased, from 65.7 to 70.5% (
p
< 0.01) and from 64.8 to 70.1% (
p
< 0.01). (
p
< 0.01). The comparison between CGM metrics of the 2 evaluated systems doesn’t show difference at baseline (last four weeks of PLGS system) and after four weeks of AHCL use.
Conclusions
To our knowledge, this study is the first real-life one comparing 2 AHCL systems in a pediatric population with T1D. It shows an improvement in glucose control when upgrading to AHCL. The comparison between the two AHCL systems did not show significant differences in the analyzed CGM metrics, meaning that the algorithms currently available are equally effective in promoting glucose control.
PNKP gene encodes for a kinase/phosphatase involved in DNA damage response, controlled and stabilized by ATM phosphorylation. PNKP deficiency, thus far described in 40 subjects, has been associated ...with a complex neurological phenotype encompassing microcephaly, seizures, developmental delay, ataxia, oculomotor apraxia and polyneuropathy. We report a new case expanding the clinical phenotype of this rare disorder. This 25 years old girl presented with chorea at the age of 2 years and remained stable up to the adult age when the emergence of fatigability and asthenia of lower limbs prompted a new examination disclosing a sensory-motor axonal demyelinating neuropathy. Clinical exome sequencing revealed two previously described variants in PNKP gene. This case highlights the phenotypic variability of PNKP associated disorders, showing that an early onset apparently non progressive chorea can be the presenting symptoms of this rare condition.
Summary
CD4+CD25+ T regulatory cells may play a role in the different clinical presentations of chronic hepatitis C virus (HCV) infection by suppressing CD4+ T cell responses. Peripheral CD4+CD25+ T ...cells from chronic HCV carriers with normal and abnormal alanine aminotransferase (ALT) were analysed for specificity and effect on HCV‐specific CD4+ T cell reactivity by flow cytometry for intracellular cytokine production and proliferation assay. HCV‐specific CD4+CD25+high T cells consistently produced transforming growth factor (TGF)‐β but only limited amounts of interleukin (IL)‐10 and no IL‐2 and interferon (IFN)‐γ. The HCV‐specific TGF‐β response by CD4+CD25+high T cells was significantly greater in patients with normal ALT compared to patients with elevated ALT. In addition, a significant inverse correlation was found between the HCV‐specific TGF‐β response by CD4+CD25+high T cells and liver inflammation. In peripheral blood mononuclear cells (PBMC), both HCV antigen‐induced IFN‐γ production and proliferation of CD4+ T cells were greater in patients with elevated ALT compared with patients with normal ALT. Depletion of CD4+CD25+ cells from PBMC resulted in an increase of both IFN‐γ production and proliferation of HCV‐specific CD4+ T cells that was significantly greater in patients with normal ALT levels compared with patients with elevated ALT. In addition, CD4+CD25+ T cells from patients with normal ALT levels proved to be significantly more potent to suppress CD4+ T cell reactivity with respect to those from patients with elevated ALT. In conclusion, these data support the hypothesis that CD4+CD25+ cells may play a role in controlling chronic inflammatory response and hepatic damage in chronic HCV carriers.
Telemedicine in diabetes includes telemonitoring and transmission of important data (self monitoring of blood glucose data, insulin therapy, pump setting, etc.) from the patient s home to the ...diabetic unit, with a real-time health feedback. Moreover, an eHealth approach is thought to facilitate diabetes management and to improve compliance to CSII/SAP treatment in adolescents, but to date, limited literature related to this topic is available and long-term studies are still lacking. The main aim of this study was to compare the long-term effect on glycometabolic control of eHealth intervention and traditional care in T1DM SAP-treated adolescents. In our study we demonstrated a favorable impact of monthly teleassistance on treatment compliance. Adolescents receiving frequent feedback provided by the medicalmultidisciplinary team, due to the telemonitoring, resulted more compliant in self-management of diabetes. In particular, the medical team feedback resulted in interventions on behavioral errors and insulin therapy adjustments, leading to an improved glycometabolic control.
Purpose
The Quality of Life in Short Stature Youth (QoLISSY) questionnaire is a disease-specific instrument developed to assess health-related quality of life (HrQoL) in children with short stature. ...While the original instrument was simultaneously developed in five European countries, this study describes the results of the Italian QoLISSY translation, cultural adaptation, and validation.
Methods
Focus group discussions and a cognitive debriefing process with children (
N
= 12) diagnosed with growth hormone deficiency or idiopathic short stature and one parent each, as well as parents of younger children (
N
= 20) were conducted to examine the linguistic and content validity of the Italian version. Psychometric testing was performed using data from the subsequent field- and re-test (
N
= 32).
Results
The results of the qualitative testing of the Italian sample revealed comparability of content to data of the original five European countries. The following field- and re-test results were psychometrically satisfactory including good item and scale operating characteristics, sufficient evidence of reliability, and acceptable evidence of construct validity.
Conclusion
In conclusion, the Italian QoLISSY HrQoL-dimensions are comparable to other European countries. The psychometric quality of the Italian QoLISSY version is satisfactory and the instrument is ready for use in Italian patients and their parents.
Objective: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. Methods: Thirty‐two patients with phenylalanine hydroxylase deficiency (21 with early and 11 ...with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion‐weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. Results: All patients had white matter abnormalities on T2‐weighted (T2W) and fluid‐attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1‐weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues λmin, λmiddle, λmax obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient's age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). Conclusions: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.
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