Neurological phenotype of Potocki–Lupski syndrome

Potocki–Lupski syndrome is a condition mainly characterized by infantile hypotonia, developmental delay/intellectual disability (DD/ID), and congenital anomalies, caused by duplications of the 17p11.2 region, encompassing RAI1 gene. Its clinical presentation is extremely variable, especially for what concerns the cognitive level and the behavioral phenotype. Such aspects, as well as the dysmorphic/malformative ones, have been covered by previous studies; otherwise neurological features have never been systematically described. In order to delineate the neurological phenotype of Potocki–Lupski Syndrome, we collect an 8‐patients cohort. Developmental milestones are delayed and a mild to moderate cognitive impairment is present in all patients, variably associated with features of autism spectrum disorder, behavioral disturb, and sleep disturb. Hypotonia appears a less frequent finding than what previously reported, while motor clumsiness/coordination impairment is frequent. EGG registration demonstrated a common pattern with excess of diffuse rhythmic activity in sleep phases or while the patient is falling asleep. Brain MRI did not reveal common anomalies, although unspecific white matter changes may be present. We discuss such findings and compare them to literature data, offering an overview on the neurological and cognitive‐behavioral presentation of the syndrome.     

Update on Pneumocystis carinii f. sp. hominis Typing Based on Nucleotide Sequence Variations in Internal Transcribed Spacer Regions of rRNA Genes

Pneumocystis carinii f. sp. hominis isolates from 207 clinical specimens from nine countries were typed based on nucleotide sequence variations in the internal transcribed spacer regions I and II (ITS1 and ITS2, respectively) of rRNA genes. The number of ITS1 nucleotides has been revised from the previously reported 157 bp to 161 bp. Likewise, the number of ITS2 nucleotides has been changed from 177 to 192 bp. The number of ITS1 sequence types has increased from 2 to 15, and that of ITS2 has increased from 3 to 14. The 15 ITS1 sequence types are designated types A through O, and the 14 ITS2 types are named types a through n. A total of 59 types of P. carinii f. sp. hominis were found in this study.     

The small subset of CD56brightCD16- natural killer cells is selectively responsible for both cell proliferation and interferon-gamma production upon interaction with dendritic cells

The encounter of NK cells with dendritic cells (DC) undergoing maturation may result in the induction of NK cell proliferation. Whether such proliferation involves most NK cells or just a subset has yet to be determined. In the present study we analyzed the nature of such proliferating NK cells by combining carboxyfluorescein succinimidyl ester staining and double-fluorescence cytofluorimetric analysis. Freshly isolated peripheral blood NK cells cultured with LPS and immature DC underwent proliferation; however, proliferating cells were confined to a minor NK cell subset. This subset is characterized by the CD56(bright)CD16(-)NKG2A(+)KIR(-) surface phenotype (KIR, killer Ig-like receptor). This was further confirmed by the fact that, after cell sorting, only the CD56(bright) NK cells were able to proliferate in response to the DC stimulus, whereas the CD56(dull) were not. We also provide evidence that the CD56(bright) subset is the main source of IFN-gamma-producing NK cells, upon interaction with DC. The CD56(bright)CD16(-) NK cells express a panel of surface molecules including CD62L, CCR7 and CXCR3 that may allow their homing either to secondary lymphoid compartments or to inflamed tissues. This implies that, in vivo, the interactions between DC undergoing maturation and CD56(bright) NK cells may occur in different tissues and have different functional implications.     

Administration of tibolone decreases 24 h heart rate but not blood pressure of post-menopausal women

OBJECTIVE: Elevation of blood pressure and heart rate increase the risk of cardiovascular disease. Administration of estrogens does not affect heart rate but may decrease 24 h blood pressure. In this study, we tested the effect of the estro-progestogenic compound tibolone. METHODS: Thirty healthy, post-menopausal women were randomized to receive placebo (n = 15) or tibolone, at the commonly prescribed dose of 2.5 mg per day (n = 15). Before and after 6 months of treatment, in each woman blood pressure and heart rate were monitored every 30 min for 41 h by an ambulatory device. Valuable readings were those collected from 8:00 a.m. of the second day to 8:00 a.m. of third day. Analyses were performed of 24 h, day-time (7:00 a.m.-11:00 p.m.) and night-time (11:00 p.m.-7:00 a.m.) values. Day to night difference was also calculated. Results: Placebo did not modify 24h, day-time, and night-time blood pressure or heart rate values. Day-night differences were also not affected by placebo. Similarly to placebo, tibolone administration did not modify any of the blood pressure parameters taken into consideration. By contrast, a significant decline of 24 h heart rate (73.2 +/- 2.3 beats/min versus 69.3 +/- 1.7 beats/min; P < 0.0008) was observed. The effect was significant both at day (76.6 +/- 2.4 beats/min versus 72.1 +/- 1.9 beats/min; P < 0.0001) and night (65.8 +/ 2.6 beats/min versus 62.4 +/- 1.9 beats/min; P < 0.05). Day-night blood pressure and heart rate differences were not affected by tibolone. CONCLUSIONS: In post-menopausal women, administration of tibolone does not influence 24 h blood pressure but reduces heart rate.     

Time course of EEG background activity level before spontaneous awakening in infants

This research aimed to investigate the time course of the cortical activity level preceding spontaneous awakening as a function of age and state. Two groups of infants (1-4 and 9-14 weeks of age) were continuously monitored by polygraphic recording and behavioural observation during the night. The electroencephalographic (EEG) activity recorded by the C3-O1 lead was analysed through an automatic analysis method which provides, for each 30-s epoch, a single measure, time domain based, of the EEG synchronization. The EEG parameter values were computed in the 6 min preceding each awakening out of non-rapid eye movement (NREM) sleep and out of rapid eye movement (REM) sleep. The EEG background activity level did not change in the minutes preceding awakening out of REM sleep. Awakening out of NREM sleep was preceded by a change of EEG activity level in the direction of higher activation with different time course according to the age. Both REM and NREM sleep results suggest that a high level of EEG activity is a prerequisite for the occurrence of a spontaneous awakening.     

Mediastinal large-cell lymphoma with sclerosis

Summary The Southern blot hybridization technique has been applied to study the configuration of immunoglobulin and T-cell receptor genes in 6 cases of the so called mediastinal large cell lymphoma with sclerosis. This lymphoma has been recently recognized as a separate entity among non-Hodgkin lymphomas mainly affecting young adult patients. The B-cell origin of this neoplasm was suggested by means of immunohistochemical analysis. However, the immunophenotypical B-cell related markers used do not always exhibit lineage fidelity. The Southern blot analysis demonstrated the presence of unique heavy and k-light chain immunoglobulin gene rearrangements, establishing genotypically their B-cell origin.This work was supported by the Associazione Italiana per la Ricerca sul Cancro, Milano, Italy, and Progetto finalizzato Oncologia (contratto n^o 86.00461.44), CNR, Rome, Italy. Aldo Scarpa and Maurizio Lestani are supported by a Scholarship from the Associazione Italiana per la Ricerca sul Cancro, Milano, Italy     

Neural control of fast-regular saccades and antisaccades: an investigation using positron emission tomography

 Regional cerebral blood flow changes related to the performance of two oculomotor tasks and a central fixation task were compared in ten healthy human subjects. The tasks were: (a) performance of fast-regular saccades; (b) performance of voluntary antisaccades away from a peripheral cue; (c) passive maintenance of central visual fixation in the presence of irrelevant peripheral stimulation. The saccadic task was associated with a relative increase in activity in a number of occipitotemporal areas. Compared with both the fixation and the saccadic task, the performance of antisaccades activated a set of areas including: the superior and inferior parietal lobules, the precentral and prefrontal cortex, the cingulate cortex, and the supplementary motor area. The results of the present study suggest that: (a) compared with self-determined saccadic responses the performance of fast regular, reflexive saccades produces a limited activation of the frontal eye fields; (b) in the antisaccadic task the inferior parietal lobes subserve operations of sensory-motor integration dealing with attentional disengagement from the initial peripheral cue (appearing at an invalid spatial location) and with the recomputation of the antisaccadic vector on the basis of the wrong (e.g., spatially opposite) information provided by the same cue. Received: 20 May 1996 / Accepted: 28 January 1997     

Employing a systematic approach to biobanking and analyzing clinical and genetic data for advancing COVID-19 research

Within the GEN-COVID Multicenter Study, biospecimens from more than 1000 SARS-CoV-2 positive individuals have thus far been collected in the GEN-COVID Biobank (GCB). Sample types include whole blood, plasma, serum, leukocytes, and DNA. The GCB links samples to detailed clinical data available in the GEN-COVID Patient Registry (GCPR). It includes hospitalized patients (74.25%), broken down into intubated, treated by CPAP-biPAP, treated with O₂ supplementation, and without respiratory support (9.5%, 18.4%, 31.55% and 14.8, respectively); and non-hospitalized subjects (25.75%), either pauci- or asymptomatic. More than 150 clinical patient-level data fields have been collected and binarized for further statistics according to the organs/systems primarily affected by COVID-19: heart, liver, pancreas, kidney, chemosensors, innate or adaptive immunity, and clotting system. Hierarchical clustering analysis identified five main clinical categories: (1) severe multisystemic failure with either thromboembolic or pancreatic variant; (2) cytokine storm type, either severe with liver involvement or moderate; (3) moderate heart type, either with or without liver damage; (4) moderate multisystemic involvement, either with or without liver damage; (5) mild, either with or without hyposmia. GCB and GCPR are further linked to the GCGDR, which includes data from whole-exome sequencing and high-density SNP genotyping. The data are available for sharing through the Network for Italian Genomes, found within the COVID-19 dedicated section. The study objective is to systematize this comprehensive data collection and begin identifying multi-organ involvement in COVID-19, defining genetic parameters for infection susceptibility within the population, and mapping genetically COVID-19 severity and clinical complexity among patients.Subject terms: Genetics research, Viral infection     

Well-being therapy of generalized anxiety disorder

BACKGROUND: There is increasing awareness that the goal of treatment in generalized anxiety disorder (GAD) should not simply be a response, but restoration of normal function. The aim of this study was to apply a novel psychotherapeutic approach for increasing the level of remission in GAD. METHODS: Twenty patients with DSM-IV GAD devoid of comorbid conditions were randomly assigned to 8 sessions of cognitive behavioral therapy (CBT) or the sequential administration of 4 sessions of CBT followed by other 4 sessions of well-being therapy (WBT). Assessment methods included the Anxiety and Depression Scales of Paykel's Clinical Interview for Depression, Ryff's Psychological Well-being Scales and Kellner's Symptom Questionnaire. A one-year follow-up was undertaken. RESULTS: Significant advantages of the CBT-WBT sequential combination over CBT only were observed with both observer and self-rated methods after treatment. Such gains were maintained at follow-up. CONCLUSIONS: These preliminary results suggest the feasibility and clinical advantages of adding WBT to the treatment of GAD. They lend support to a sequential use of treatment components for achieving a more sustained recovery.