There are reports of the familial occurrence of Kawasaki disease but only a few reports described Kawasaki disease in siblings. However, the familial cases were not simultaneous. In these patients ...the idea of infective agents as trigger must be considered.
We describe two siblings with atypical presentations of Kawasaki disease; the sister was first diagnosed as having parvovirus infection with anemia and the brother was diagnosed as having myocarditis. The first patient was a 9-month-old Caucasian girl with fever, conjunctivitis, rash, and pharyngitis, and later she had cervical adenopathy, diarrhea and vomiting, leukocytosis, and anemia, which were explained by positive immunoglobulin M against parvovirus. However, coronary artery lesions with aneurysms were documented at day 26 after fever onset. An infusion of intravenous immunoglobulin and high doses of steroids were not efficacious to resolve the coronary lesions. She was treated with anakinra, despite a laboratory test not showing inflammation, with prompt and progressive improvement of coronary lesions. Her 7-year-old Caucasian brother presented vomiting and fever at the same time as she was unwell, which spontaneously resolved after 4 days. Four days later, he again presented with fever with abdominal pain, associated with tachypnea, stasis at the pulmonary bases, tachycardia, gallop rhythm, hypotension, secondary anuria, and hepatomegaly. An echocardiogram revealed a severe hypokinesia, with a severe reduction of the ejection fraction (20%). He had an increase of immunoglobulin M anti-parvovirus, tested for the index case of his sister, confirming the suspicion of viral myocarditis. He received dopamine, dobutamine, furosemide plus steroids, with a progressive increase of the ejection fraction to 50%. However, evaluating his sister's history, the brother showed a myocardial dysfunction secondary to Kawasaki shock syndrome.
We report on familial Kawasaki disease in two siblings which had the same infectious trigger (a documented parvovirus infection). The brother was diagnosed as having post-viral myocarditis. However, in view of the two different and simultaneous evolutions, the girl showed Kawasaki disease with late coronary artery lesions and aneurysms, whereas the brother showed Kawasaki shock syndrome with myocardial dysfunction. We stress the effectiveness of anakinra in non-responder Kawasaki disease and the efficacy on coronary aneurysms.
Introduction
Triple Network Model (TNM), which considers the dynamic interaction between Default Mode (DMN), Salience (SN), and Central Executive (CEN) networks, explains clinical features in mental ...disorders from a neurophysiological perspective. Some studies highlight the increased connectivity in TNM in adults with Borderline Personality Disorder (BPD), but little is known about adolescents.
Objectives
The aim of our preliminary study was to investigate TN functional connectivity (FC) in BPD adolescents with a history of traumatic experiences, and its correlation with dissociative symptoms.
Methods
15 BPD adolescents (DSM-5 criteria) with early traumatic experiences were compared to 15 healthy controls, matched for sex and age. Dissociation Questionnaire (DIS-Q) was administered. Eyes-closed resting-state (RS) EEG recordings were performed (19 electrodes; 10- 20 system) and analyzed using Exact Low-Resolution Electromagnetic Tomography software (eLORETA). FC was computed for all frequency bands and 9 Regions of Interest for TNM.
Results
BPD adolescents showed a hyper-connection between CEN and DMN dorso-lateral prefrontal cortex (dlPFC) and posterior cingulate cortex (PCC); PCC and left posterior parietal cortex (PPC) and within the CEN (left and right PPC). The strength of PCC-dlPFC and left-right PPC connections was correlated with dissociative symptoms severity.
Conclusions
FC alterations can already be identified in BPD adolescents, supporting the need for early diagnosis. Normally DMN and CEN show opposite functioning. In our BPD adolescents, the absence of this “anti-correlation” reflects the typical confusion between internal and external mental states, which clarify their difficulties in metacognition or mentalization. Moreover, in dissociative symptoms, two CEN nodes are also involved, not only DMN as previously described.
Disclosure
No significant relationships.
Introduction
Literature on childhood Functional Neurological Disorders (FNDs) is spare. Clinical presentations are vaguely characterized and often misdiagnosed in younger ages. Their main ...neurological features enrol: Psychogenic non-epileptic seizures (PNES), Functional movement disorders (FMDs), sensory alterations, cephalgia and feeding problems.
Objectives
The study was aimed to better characterize the childhood population of FND, because of they represent an emerging challenge for clinicians, giving its higher presentation in the younger age and the difficulties of an early and differential diagnosis as well as an effective management.
Methods
Our study retrospectively examined the characteristics of 82 FNDs children and adolescents (8 to 16 y.o.; 13 males; 29 females) referred as neurological inpatients of an urban academic neuropsychiatric department, from 2014 to 2019. Three main clinical aspects were analysed: type and pattern of symptoms manifestations (DSM-5 criteria); Life Events; family functioning.
Results
FND accounted for 2% of 5-years consultations of neurological inpatients (M: F=1:2). The clinical presentation was characterized in 70% by pattern of co-expressed neurological symptoms: FMDs (9.5%); PNES (12%); dizziness/lipothymia (12%); paraesthesia/anaesthesia (16%). Generalized pain was associated in 38% of the reported patterns while cephalgia in 44%. Sleep disorders were reported in 40%. Previous psychiatric diagnoses were uncommon (2 out 82). Antecedent stressors were identified in 97% of patients for personal illness history and in the 93% for chronic illness in the family anamnesis. Family problems were in 25% of cases.
Conclusions
Our data contributes to better characterize the childhood population of FND, describing clinical patterns of presentation, highlighting putative antecedent stressors and risk factors
In situ electric field (E) measurements and inferred lightning initiation locations of three cloud‐to‐ground flashes are used to identify a thunderstorm region in which the preflash E exceeded the ...threshold for runaway breakdown. The maximum measured E in the region was 186 kV m−1 at 5.77 km altitude, which for runaway electrons is equivalent to 370 kV m−1 at sea level; this E value is ∼130% of the estimated threshold for an avalanche of runaway electrons. In addition, the volume where E exceeded the runaway threshold was estimated to be 1–4 km3, with a vertical depth of about 1000 m. At least within part of this volume the characteristic scale height for exponential growth of runaway electrons was 100 m or less. Thus for these three flashes the electric field conditions necessary for runaway breakdown existed, and runaway breakdown could have initiated the flashes.
The role of reactive oxygen species (ROS) production on DNA damage and potentiation of fludarabine lethality by the histone deacetylase inhibitor (HDACI) LAQ-824 was investigated in human leukemia ...cells. Preexposure (24 h) of U937, HL-60, Jurkat, or K562 cells to LAQ-824 (40 nmol/L) followed by fludarabine (0.4 micromol/L) dramatically potentiated apoptosis (>or=75%). LAQ-824 triggered an early ROS peak (30 min-3 h), which declined by 6 h, following LAQ-824-induced manganese superoxide dismutase 2 (Mn-SOD2) upregulation. LAQ-824/fludarabine lethality was significantly diminished by either ROS scavengers N-acetylcysteine or manganese (III) tetrakis (4-benzoic acid) porphyrin or ectopic Mn-SOD2 expression and conversely increased by Mn-SOD2 antisense knockdown. During this interval, LAQ-824 induced early (4-8 h) increases in gamma-H2AX, which persisted (48 h) secondary to LAQ-824-mediated inhibition of DNA repair (e.g., down-regulation of Ku86 and Rad50, increased Ku70 acetylation, diminished Ku70 and Ku86 DNA-binding activity, and down-regulated DNA repair genes BRCA1, CHEK1, and RAD51). Addition of fludarabine further potentiated DNA damage, which was incompatible with cell survival, and triggered multiple proapoptotic signals including activation of nuclear caspase-2 and release of histone H1.2 into the cytoplasm. The latter event induced activation of Bak and culminated in pronounced mitochondrial injury and apoptosis. These findings provide a mechanistic basis for understanding the role of early HDACI-induced ROS generation and modulation of DNA repair processes in potentiation of nucleoside analogue-mediated DNA damage and lethality in leukemia. Moreover, they show for the first time the link between HDACI-mediated ROS generation and the recently reported DNA damage observed in cells exposed to these agents.
L’objectif de cette recherche était d’explorer les variations liées à l’âge dans le déploiement de stratégies de contrôle, puis d’étudier dans quelle mesure ces stratégies de contrôle sont associées ...à des indicateurs de bien-être et d’efficience cognitive. Pour cela, nous avons évalué les stratégies de contrôle, le niveau d’anxiété-état et différentes ressources cognitives chez 85 participants âgés de 18 à 93 ans. Les résultats indiquent que (1) les individus d’âge moyen sont les plus aptes à utiliser des stratégies de contrôle centrées sur les émotions et de désengagement de but, (2) les individus qui déploient davantage de stratégies de contrôle portées sur des processus méta-motivationnels ressentent moins d’anxiété et (3) les ressources cognitives modèrent les relations entre l’âge et le déploiement des stratégies de contrôle. En effet, bien que les stratégies de contrôle tendent en moyenne à être moins déployées au fil de l’âge adulte, les individus qui manifestent de plus grandes ressources cognitives montrent de moins grands effets de l’âge sur le déploiement de ces stratégies. En d’autres termes, ils les utilisent davantage pour s’adapter tout au long de la vie adulte.
The current study investigated the age-related differences in control strategies deployment, and examined the relations of control strategies with indicators of well-being and cognitive efficiency. Eighty-five participants aged from 18 to 93 years old completed measures of control strategies and anxiety, and were administered several cognitive tests designed to assess processing speed, reasoning and episodic memory. Results showed that (1) middle-aged individuals use more control strategies based on emotional regulation and goal disengagement than younger and older individuals, (2) individuals who deploy more control strategies focused on emotions report lower levels of anxiety, and (3) cognitive resources moderate the relation between age and control strategies deployment. That is, although increased age is associated with lower deployment of control strategies, the current project showed that age effects in control strategies were weaker for people with higher levels of cognitive resources than for people with lower levels of cognitive resources.
Determinants of differentiation and apoptosis induction by the novel histone deacetylase inhibitor (HDACI) LAQ824 were examined in human leukemia cells (U937 and Jurkat). Exposure of U937 cells to a ...low concentration of LAQ824 (30 nM) resulted in a delayed (2 h) increase in reactive oxygen species (ROS), induction of p21(WAF1/CIP1), pRb dephosphorylation, growth arrest of cells in G(0)/G(1) phase, and differentiation. On the other hand, exposure of cells to a higher concentration of LAQ824 (75 nM) resulted in the early (30 min) generation of ROS, arrest of cells in G(2)/M phase, down-regulation of XIAP (at the transcriptional level) and Mcl-1 (through a caspase-mediated process), the acid sphingomyelinase-dependent generation of ceramide, and profound mitochondrial injury, caspase activation, and apoptosis. LAQ824-induced lethality in U937 cells did not involve the extrinsic apoptotic pathway, nor was it associated with death receptor up-regulation; instead, it was markedly inhibited by ectopic expression of Bcl-2, Bcl-x(L), XIAP, and Mcl-1. The free radical scavenger N-acetyl cysteine blocked LAQ824-mediated ROS generation, mitochondrial injury, Mcl-1 down-regulation, ceramide generation, and apoptosis, suggesting a primary role for oxidative injury in LAQ824 lethality. Together, these findings indicate that LAQ824-induced lethality represents a multifactorial process in which LAQ824-mediated ROS generation is necessary but not sufficient to induce apoptosis, and that the degree of XIAP and Mcl-1 down-regulation and ceramide generation determines whether this agent engages a maturation rather than an apoptotic program.
Interactions between the novel benzamide histone deacetylase (HDAC) inhibitor MS-275 and fludarabine were examined in lymphoid and myeloid human leukemia cells in relation to mitochondrial injury, ...signal transduction events, and apoptosis. Prior exposure of Jurkat lymphoblastic leukemia cells to a marginally toxic concentration of MS-275 (e.g., 500 nM) for 24 h sharply increased mitochondrial injury, caspase activation, and apoptosis in response to a minimally toxic concentration of fludarabine (500 nM), resulting in highly synergistic antileukemic interactions and loss of clonogenic survival. Simultaneous exposure to MS-275 and fludarabine also led to synergistic effects, but these were not as pronounced as observed with sequential treatment. Similar interactions were noted in the case of (a) other human leukemia cell lines (e.g., U937, CCRF-CEM); (b) other HDAC inhibitors (e.g., sodium butyrate); and (c) other nucleoside analogues (e.g., 1-beta-D-arabinofuranosylcytosine, gemcitabine). Potentiation of fludarabine lethality by MS-275 was associated with acetylation of histones H3 and H4, down-regulation of the antiapoptotic proteins XIAP and Mcl-1, enhanced cytosolic release of proapoptotic mitochondrial proteins (e.g., cytochrome c, Smac/DIABLO, and apoptosis-inducing factor), and caspase activation. It was also accompanied by the caspase-dependent down-regulation of p27(KIP1), cyclins A, E, and D(1), and cleavage and diminished phosphorylation of retinoblastoma protein. However, increased lethality of the combination was not associated with enhanced fludarabine triphosphate formation or DNA incorporation and occurred despite a slight reduction in the S-phase fraction. Prior exposure to MS-275 attenuated fludarabine-mediated activation of MEK1/2, extracellular signal-regulated kinase, and Akt, and enhanced c-Jun NH(2)-terminal kinase phosphorylation; furthermore, inducible expression of constitutively active MEK1/2 or Akt significantly diminished MS-275/fludarabine-induced lethality. Combined exposure of cells to MS-275 and fludarabine was associated with a significant increase in generation of reactive oxygen species; moreover, both the increase in reactive oxygen species and apoptosis were largely attenuated by coadministration of the free radical scavenger L-N-acetylcysteine. Finally, prior administration of MS-275 markedly potentiated fludarabine-mediated generation of the proapoptotic lipid second messenger ceramide. Taken together, these findings indicate that the HDAC inhibitor MS-275 induces multiple perturbations in signal transduction, survival, and cell cycle regulatory pathways that lower the threshold for fludarabine-mediated mitochondrial injury and apoptosis in human leukemia cells. They also provide insights into possible mechanisms by which novel, clinically relevant HDAC inhibitors might be used to enhance the antileukemic activity of established nucleoside analogues such as fludarabine.
Puberty is a critical age for patients with Turner syndrome (TS): infertility is reported to be linked to karyotype and spontaneous puberty and menarche occur in approximately 30% of patients, ...especially in mosaicism. However, it is not always predictable considering hormonal pattern and pelvic transabdominal ultrasound scan (US).The aim of the study is to compare the accuracy of Magnetic Resonance Imaging (MRI) and US to evaluate uterine and gonads volume, to visualize the presence of follicles and to predict spontaneous puberty and menarche in girls with TS. In a retrospective study, we evaluated 19 TS patients (age: 9-16 years), who underwent transabdominal pelvic US and pelvic MRI as required by parents. We correlated pelvic imaging with karyotype, hormonal data and pubertal outcome, and we compared US resolution to MRI.MRI revealed a higher accuracy in the study of uterus and ovaries, and permitted to measure ovaries not visualized by US. Ovarian volume, the presence of follicles and the occurrence of spontaneous puberty were not related to the karyotype; spontaneous puberty started in one patient with a karyotype 45,X and in two patients with mosaicism (45,X/46,XX; 47,XXX/45, X). Ovarian follicles were relieved by MRI in patients with a spontaneous menarche and the persistence of menstrual cycles correlated with an ovarian volume corresponding to Tanner stage 3-4. We stress the role of MRI in the follow-up of TS adolescents, guide in the choice of the timing of treatment.
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