Molecular cytogenetic characterization of an interstitial deletion of chromosome 21 (21q22.13q22.3) in a patient with dysmorphic features, intellectual disability and severe generalized epilepsy

We report on a de novo interstitial deletion of chromosome 21q in a patient presenting with characteristic facial features, intellectual disability, and epilepsy. The deletion extent was about 4.9 Mb from position 37713441 bp (21q22.13) to position 42665162 bp (21q22.3) (NCBI36/hg18 map).Patients with partial monosomy 21 are quite rare; this anomaly has been associated with a wide spectrum of clinical signs, ranging from very mild to quite severe phenotypes. This variability results from variability in the deleted regions, thus accurate molecular definition of the chromosomal breakpoints is necessary to make better genotype-phenotype correlations.We compared our patient's phenotype with the few other patients reported in the literature and found to have similar deletion when analyzed by array CGH. The minimal overlapping region contains only two genes, DYRK1A and KCNJ6, which may play a major role in these patients' phenotype.     

Personality traits in patients with Parkinson’s disease: assessment and clinical implications

This study reviews empirical evidence on the association between personality traits and Parkinson's disease (PD), with a twofold aim. First, to better identify non-motor symptoms, such as affective symptoms and personality changes, that could help to define the pre-motor phase of PD; second, to better understand the neurobiological bases of personality traits, a goal that is not fully accomplished by a purely anatomical approach. A literature review was performed on studies of personality traits in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in July 2011. We found evidence that the existence of a characteristic premorbid personality profile of PD patients is not actually sustained by robust empirical evidence, mainly due to the methodological bias of the retrospective assessment of personality; PD patients present a personality profile of low novelty seeking and high harm avoidance. We concluded that the definition of a pre-motor phase of PD, based on non-motor symptoms, should search for the presence of concomitant affective disorders and for a positive psychiatric history for affective disorders rather than for a typical personality profile or personality changes. The low novelty seeking profile is probably related to the dopaminergic deficit, while the high harm avoidance profile is probably associated with the presence of affective disorders. Clinical implications of these findings, in regard to personality assessment and pharmacological treatments in PD, are also discussed.     

Depressive symptoms in Parkinson's disease

ObjectiveWe aimed to investigate the relationship between the presence and severity of depression and the degree of motor and functional disability in Parkinson's disease (PD).MethodsOne hundred twenty-two outpatients with PD were enrolled in a neurology department: 65 satisfied the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria for major depression, and 57 did not (PD-C). Depressive symptoms were assessed by means of the Hamilton Rating Scale for Depression (HRSD), and the PD severity was assessed according to the Hoehn and Yahr System. Activities of daily living and motor symptoms were measured by the Unified PD Rating Scale (UPDRS), parts II and III.ResultsTwenty-nine patients had a mild depression (HRSD total score ranging between 8 and 17), 30 had a moderate depression (HRSD total score ranging between 18 and 24), and 6 had a severe depression (HRSD total score, ≥25). By comparing the 3 groups of patients, it emerged that those with a severe depression showed significantly higher scores at the UPDRS II, UPDRS III, and HY scales than did PD-C or patients with a mild depression. Moreover, patients with a moderate depression scored significantly higher on the UPDRS II, UPDRS III, and HY scales than did PD-C or those with a mild depression.ConclusionsOur findings suggest that depression and motor symptoms/well-being are highly intertwined in patients with PD.     

Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and neuroradiological reversibility

Pyruvate dehydrogenase complex (PDHC) deficiency causes encephalomyopathies, of which there are four major categories: (1) neonatal encephalopathy with lactic acidosis; (2) an early infantile form, which (3) at times resembles Leigh syndrome; and (4) a later‐onset form. Long‐term clinical and radiological follow‐up is still incompletely elucidated. We report a 12‐year‐old male with intermittent‐relapsing PDHC deficiency who presented with three typical acute episodes of metabolic decompensation over 7 years. Neuroimaging showed reversible signal abnormalities in the basal ganglia, inferior olivary nuclei, periaqueductal grey matter, and dentate nuclei, with evidence of lactate on magnetic resonance spectroscopy. Molecular analysis of PDH1A revealed a novel hemizygous c.1045G>A mutation, predicting a p.A349T missense mutation. He was treated with thiamine supplementation and, while on this regimen, he experienced several intercurrent febrile episodes without neurological compromise. This case report stresses the importance of performing neuroimaging during acute clinical episodes because brain lesions in PDHC deficiency may be transient and reversible, and false‐negative results may mislead the diagnosis and delay the treatment.     

Efficacia delle misure volte a contenere la diffusione del virus Sars-Cov-2 negli ambienti di lavoro: un’indagine in nove aziende con sede nella regione Veneto

«Effectiveness of the measures aimed at containing Sars-cov-2 virus spreading in work settings: a survey in companies based in the Veneto region of Italy».Introduction:During the Sars-Cov-2 pandemic, occupational health physicians worked to respond to different needs of workers, employers, and health authorities. In collaboration with the Prevention Department of the Veneto region of Italy, a survey was promoted in nine manufacturing companies in the province of Padua, to investigate the prevalence of asymptomatic SarsCov-2 virus and the immunological status of 1,267 workers.Scope:The study was aimed at verifying the effectiveness of measures to contain the virus spread among workers in the workplace as required by the agreement between the social partners signed on March 14, 2020.Methods:The survey was carried out at workplaces by trained health physicians and almost all company workers enrolled on a voluntary basis. Each worker was tested for viral RNA using nasopharyngeal swab and for IgM and IgG antibodies by drawing venous or capillary blood, according to the availability of tests at that difficult period.Results:Swab-positive workers were 0.3%, and subjects with positive serological tests were 1.6% of the total workers examined.Discussion:The diagnostic test is based on the search for viral RNA through nasopharyngeal swab. To evaluate the immunological status of workers the CLIA or Elisa quantitative serological test should be preferred. Measures to contain the virus spreading at the workplace seem to be effective, as working settings do not entail any additional risk of SarsCov-2 infection.Key words: COVID-19, epidemiology, prevention at workplace     

A deletion involving exons 2–4 in the iduronate-2-sulfatase gene of a patient with intermediate Hunter syndrome

A large deletion in the iduronate-2-sulfatase (IDS) gene has been found in a patient affected by an intermediate form of Hunter syndrome (mucopolysaccharidosis II). The deletion involves exons 2–4, the breakpoints lying respectively in intron 1, at position 376, and in intron 4, at position 5725. cDNA analysis revealed a direct exon 1-exon 5 junction due to the deletion resulting in a frameshift mutation.     

IL-8 correlates with nonresponse to neoadjuvant nivolumab in HPV positive HNSCC via a potential extracellular vesicle miR-146a mediated mechanism

Therapy using anti-PD-1 immune checkpoint inhibitors (ICI) has revolutionized the treatment of many cancers including head and neck squamous cell carcinomas (HNSCC), but only a fraction of patients respond. To better understand the molecular mechanisms driving resistance, we performed extensive analysis of plasma and tumor tissues before and after a 4-week neoadjuvant trial in which HNSCC patients were treated with the anti-PD-1 inhibitor, nivolumab. Luminex cytokine analysis of patient plasma demonstrated that HPV^pos nonresponders displayed high levels of the proinflammatory chemokine, interleukin-8 (IL-8), which decreased after ICI treatment, but remained higher than responders. miRNAseq analysis of tetraspanin-enriched small extracellular vesicles (sEV) purified from plasma of HPV^pos nonresponders demonstrated significantly lower levels of seven miRNAs that target IL-8 including miR-146a. Levels of the pro-survival oncoprotein Dsg2, which has been to down-regulate miR-146a, are elevated with HPV^pos tumors displaying higher levels than HPV^neg tumors. Dsg2 levels decrease significantly following ICI in responders but not in nonresponders. In cultured HPV^pos cells, restoration of miR-146a by forced expression or treatment with miR-146a-loaded sEV, reduced IL-8 level, blocked cell cycle progression, and promoted cell death. These findings identify Dsg2, miR-146a, and IL-8 as potential biomarkers for ICI response and suggest that the Dsg2/miR-146a/IL-8 signaling axis negatively impacts ICI treatment outcomes and could be targeted to improve ICI responsiveness in HPV^pos HNSCC patients.     

Presynaptic cannabinoid CB2 receptors modulate [3H]‐Glutamate release at subthalamo‐nigral terminals of the rat

Recent studies suggested the expression of CB2 receptors in neurons of the CNS, however, most of these studies have only explored one aspect of the receptors, i.e., expression of protein, messenger RNA, or functional response, and more complete studies appear to be needed to establish adequately their role in the neuronal function. Electron microscopy studies showed the presence of CB2r in asymmetric terminals of the substantia nigra pars reticulata (SNr), and its mRNA appeared is expressed in the subthalamic nucleus. Here, we explore the expression, source, and functional effects of such receptors by different experimental approaches. Through PCR and immunochemistry, we showed mRNA and protein for CB2rs in slices and primary neuronal cultures from subthalamus. GW833972A, GW405833, and JHW 133, three CB2r agonists dose‐dependent inhibited K⁺‐induced [³H]‐Glutamate release in slices of SNr, and the two antagonist/inverse agonists, JTE‐907 and AM630, but not AM281, a CB1r antagonist, prevented GW833972A effect. Subthalamus lesions with kainic acid prevented GW833972A inhibition on release and decreased CB2r protein in nigral synaptosomes, thus nigral CB2rs originate in subthalamus. Inhibition of [³H]‐Glutamate release was PTX‐ and gallein‐sensitive, suggesting a Gi_βγ‐mediated effect. P/Q Ca²⁺‐type channel blocker, ω‐Agatoxin‐TK, also inhibited the [³H]‐Glutamate release, this effect was occluded with GW833972A inhibition, indicating that the βγ subunit effect is exerted on Ca²⁺channel activity. Finally, microinjections of GW833972A in SNr induced contralateral turning. Our data showed that presynaptic CB2rs inhibit [³H]‐Glutamate release in subthalamo‐nigral terminals by P/Q‐channels modulation through the Gi_βγ subunit and suggested their participation in motor behavior.