Impact of COVID-19 pandemic on psychophysical stress in patients with adrenal insufficiency: the CORTI-COVID study.

PURPOSE: COVID-19 is a novel threat to patients with adrenal insufficiency (AI), whose life expectancy and quality (QoL) are impaired by an increased risk of infections and stress-triggered adrenal crises (AC). If infected, AI patients require prompt replacement tailoring. We assessed, in a cohort of AI patients: prevalence and clinical presentation of COVID-19; prevalence of AC and association with intercurrent COVID-19 or pandemic-related psychophysical stress; lockdown-induced emotional burden, and health-related QoL. METHODS: In this monocentric (Ancona University Hospital, Italy), cross-sectional study covering February-April 2020, 121 (40 primary, 81 secondary) AI patients (59 males, 55 ± 17 years) completed telematically three questionnaires: the purpose-built "CORTI-COVID", assessing medical history and concern for COVID-19-related global health, AI-specific personal health, occupational, economic, and social consequences; the AddiQoL-30; the Short-Form-36 (SF-36) Health Survey. RESULTS: COVID-19 occurred in one (0·8% prevalence) 48-year-old woman with primary AI, who promptly tailored her replacement. Dyspnea lasted three days, without requiring hospitalization. Secondary AI patients were not involved. No AC were experienced, but pandemic-related stress accounted for 6/14 glucocorticoid up-titrations. Mean CORTI-COVID was similar between groups, mainly depending on "personal health" in primary AI (ρ = 0.888, p < 0.0001) and "economy" in secondary AI (ρ = 0.854, p < 0.0001). Working restrictions increased occupational concern. CORTI-COVID correlated inversely with QoL. AddiQoL-30 and SF-36 correlated strongly. Comorbidities worsened patients' QoL. CONCLUSION: If educational efforts are made in preventing acute events, AI patients seem not particularly susceptible to COVID-19. The novel "CORTI-COVID" questionnaire reliably assesses the pandemic-related emotional burden in AI. Even under unconventional stress, educated AI patients preserve a good QoL.

ReportFlow: an application for EEG visualization and reporting using cloud platform.

BACKGROUND: The cloud is a promising resource for data sharing and computing. It can optimize several legacy processes involving different units of a company or more companies. Recently, cloud technology applications are spreading out in the healthcare setting as well, allowing to cut down costs for physical infrastructures and staff movements. In a public environment the main challenge is to guarantee the patients' data protection. We describe a cloud-based system, named ReportFlow, developed with the aim to improve the process of reporting and delivering electroencephalograms. METHODS: We illustrate the functioning of this application through a use-case scenario occurring in an Italian hospital, and describe the corresponding key encryption and key management used for data security guarantee. We used the X2 test or the unpaired Student t test to perform pre-post comparisons of some indexes, in order to evaluate significant changes after the application of ReportFlow. RESULTS: The results obtained through the use of ReportFlow show a reduction of the time for exam reporting (t = 19.94; p < 0.001) and for its delivering (t = 14.95; p < 0.001), as well as an increase of the number of neurophysiologic examinations performed (about 20%), guaranteeing data integrity and security. Moreover, 68% of exam reports were delivered completely digitally. CONCLUSIONS: The application resulted to be an optimal solution to optimize the legacy process adopted in this scenario. The comparative pre-post analysis showed promising preliminary results of performance. Future directions will be the creation and release of certificates automatically.

Beyond waist circumference in an adult male population of Southern Italy: Is there any role for subscapular skinfold thickness in the relationship between insulin-like growth factor-I system and metabolic parameters?

BACKGROUND: Apart from waist circumference, other adiposity measures, such as subscapular skin fold (SST), arouse growing interest due to their relationship to metabolic complications and cardiovascular risk. The IGF-I system is deregulated in obese subjects in proportion to their degree of visceral adiposity. AIM: To examine the association among IGF-I, IGF-binding protein (BP)-1 and -3 levels and different measures of adiposity in a sample of adult male population in Southern Italy. MATERIALS AND METHODS: A complete database for this analysis was available for 229 (age range 50-82 yr) participating at 2002-2004 Olivetti Heart Study follow-up. RESULTS: After adjustment for age, IGF-I was inversely associated with body mass index (BMI) and waist circumference (p<0.05). IGFBP-1 was inversely associated with BMI, waist circumference, SST, homeostasis model assessment (HOMA) index, fat mass. HOMA index, age, and SST significantly predicted the IGFBP-1 plasma levels, with 24% of IGFBP-1 variability explained at a linear regression analysis. CONCLUSIONS: IGFBP-1 inversely correlated to adiposity and HOMA index. Among adiposity indexes, SST was the best predictor of IGFBP-1 levels. The evaluation of some components of the IGF system, and simple measures of body adiposity, such as SST, may represent a further tool to better evidence phenotype profiles associated to the pathogenetic mechanism of cardiovascular risk factor clustering in male adults.

Infants later diagnosed with autism have lower canonical babbling ratios in the first year of life.

BACKGROUND: Canonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed. METHODS: Vocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome. RESULTS: No diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression. LIMITATIONS: Small numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds. CONCLUSIONS: Lower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own.

Chemoarchitectonics and corticocortical terminations within the superior temporal sulcus of the rhesus monkey: evidence for subdivisions of superior temporal polysensory cortex.

Cortex of the upper bank of the superior temporal sulcus (STS) in macaque monkeys, termed the superior temporal polysensory (STP) region, corresponds largely to architectonic area TPO and is connectionally distinct from adjacent visual areas. To investigate whether or not the STP region contains separate subdivisions, immunostaining for parvalbumin and neurofilament protein (using the SMI-32 antibody) was compared with patterns of corticocortical terminations in the STS. Chemoarchitectonic results provided evidence for three caudal-to-rostral subdivisions: TPOc, TPOi, and TPOr. Area TPOc was characterized by patchy staining for parvalbumin and SMI-32 in cortical layers IV/III and III, respectively. Area TPOi had more uniform chemoarchitectonic staining, whereas area TPOr had a thicker layer IV than TPOi. The connectional results showed prefrontal cortex in the location of the frontal eye fields (area 8) and dorsal area 46 projected in a columnar pattern to all cortical layers of area TPOc, to layer IV of TPOi, and in a columnar fashion, with a moderate increase in density in layer IV, to TPOr. In TPOc, columns of frontal connections showed a periodicity similar to that of the SMI-32 staining. The caudal inferior parietal lobule (area 7a) and superior temporal gyrus projected to each subdivision of area TPO, displaying either panlaminar or fourth-layer terminations. In addition to STP cortex, parvalbumin and SMI-32 immunostaining allowed identification of caudal visual areas of the STS, including MT, MST, FST, and V4t. These areas received first- and sixth-layer projections from prefrontal cortex and area 7a.

Neurochemical and connectional organization of the dorsal pulvinar complex in monkeys.

To investigate the organization of the dorsal pulvinar complex, patterns of neurochemical staining were correlated with cortico-pulvinar connections in macaques (Macaca mulatta). Three major neurochemical subdivisions of the dorsal pulvinar were identified by acetylcholinesterase (AChE) histochemistry, as well as immunostaining for calbindin-D(28K) and parvalbumin. The dorsal lateral pulvinar nucleus (PLd) was defined on histochemical criteria as a distinct AChE- and parvalbumin-dense, calbindin-poor wedge that was found to continue caudally along the dorsolateral edge of the pulvinar to within 1 mm of its caudal pole. The ventromedial border of neurochemical PLd with the rest of the dorsal pulvinar, termed the medial pulvinar (PM), was sharply defined. Overall, PM was lighter than PLd for AChE and parvalbumin and displayed lateral (PMl) and medial (PMm) histochemical divisions. PMm contained a central "oval" (PMm-c) that stained darker for AChE and parvalbumin than the surrounding region. The neurochemically defined PLd was labeled by tracer injections in the inferior parietal lobule (IPL) and dorsolateral prefrontal cortex but not the superior temporal gyrus (STG). Label within PMl was found after prefrontal and IPL and, to a lesser extent, after STG injections. The PMm was labeled after injections of the IPL and STG, but only sparsely following prefrontal injections. The histochemically distinct subregion or module of PMm, PMm-c, was labeled only by STG injections. Overlapping labeling was found in dorsal pulvinar divisions PMl and PLd following paired IPL/prefrontal, but not IPL/STG or these particular STG/prefrontal, injections. Thus, PLd may be a visuospatially related region whereas PM appears to contain several types of territories, some related to visual or auditory inputs, and others that receive directly converging input from posterior parietal and prefrontal cortex and may participate in a distributed cortical network concerned with visuospatial functions.

Overlapping and nonoverlapping cortical projections to cortex of the superior temporal sulcus in the rhesus monkey: double anterograde tracer studies.

To examine how fibers from functionally distinct cortical zones interrelate within their target areas of the superior temporal sulcus (STS) in the rhesus monkey, separate anterograde tracers were injected in two different regions of the same hemisphere known to project to the STS. Paired injections were placed in dorsal prearcuate cortex and the caudal inferior parietal lobule (IPL), interconnected regions that are part of a hypothesized distributed network concerned with visuospatial analysis or directed attention; in a presumed auditory region of the superior temporal gyrus (STG) and in extrastriate visual cortex, the caudal IPL and lower rim of the intraparietal sulcus; and in dorsal prearcuate cortex and the STG. Overlapping and nonoverlapping projections were then examined in STS visual and polysensory areas. Prefrontal and parietal fibers directly overlapped extensively in area MST and all subdivisions of presumed polysensory cortex (areas TPOc, TPOi, and TPOr), although nonoverlapping connections were also found. Although STG and IPL fibers targeted all TPO subdivisions, connections were to nonoverlapping, but often adjacent, columns. Paired prefrontal and STG injections revealed largely nonoverlapping vertical columns of connections but substantial overlap within layers VI and I or areas TPOc and TPOi. The findings suggest that area TPO contains differently connected modules that may maintain at least initial segregation of visual versus auditory inputs. Other modules within area TPO receive directly converging input from the posterior parietal and the prefrontal cortices and may participate in a distributed cortical network concerned with visuospatial functions.

Nonrandom chromosome changes in multiple sclerosis.

In order to study the role of genetic factors in multiple sclerosis, cytogenetic analysis was performed on 48 patients with the clinically defined disease. We found a high incidence of subjects (50%) with abnormal chromosomes, showing premature centromere division of the X chromosome and structural aberrations, translocations, or deletions that could suggest preferential breakpoints. Correlation between clinical and cytogenetic data showed that cytogenetic abnormalities were more common in patients with high frequency of relapse or with a progressive form of the disease.

Human thalamus: neurochemical mapping of inferior pulvinar complex.

The primate pulvinar connects with the entire array of known visual areas and is postulated to play a role in selective visual attention. Recently, five separate neurochemical subdivisions of a region termed the inferior pulvinar (PI) complex were identified in monkeys. In the present study, similar histochemical procedures were applied to map the extent of the PI complex in humans. Acetylcholinesterase histochemistry and cytochrome oxidase staining demarcated four histochemical zones in human pulvinar, corresponding to the medial, central, lateral and lateral-shell (PI(M), PI(C), PI(L), and PI(L-S)) divisions of the PI complex in monkeys.

Correlation between oscillations in ventilation and frequency content of the electroencephalogram.

Periodicities of ventilation are common in elderly subjects during stage 1/2 sleep. The mechanism producing these periodicities is unknown. We hypothesized that the oscillations in ventilation might be related to oscillations in sleep state. To address this hypothesis, we examined, using cross correlation, the relationship between the oscillations in ventilation and parameters (alpha power, mean frequency) derived from spectral analysis of the electroencephalogram. In wakefulness, although ventilation and mean frequency, and ventilation and alpha power, were related, there were no consistent patterns to these relationships. Both positive and negative correlations were found. Clearer relationships were found in stage 1/2 sleep. Correlation between mean frequency and ventilation was the most consistent. All correlations were positive; i.e., ventilation fell as mean frequency fell. The maximum correlation occurred at zero lag between the time series. Thus these oscillations are synchronous within the time resolution of our methodology. These data are compatible with the hypothesis that the initiation of apnea in stage 1/2 sleep is related to a reduction in the state-dependent input to the ventilatory control system.

Cytogenetic findings in terminal large cell transformation in a case of Sézary syndrome.

A long-lasting case of Sézary syndrome, whose chromosomal pattern had been repeatedly investigated during a follow-up period of several years, was studied in the terminal transforming phase, which took place more than 5 years after the initial diagnosis. To the best of the authors' knowledge, this appears to be the first instance of cytogenetic studies carried out in a large cell transformation of cutaneous T-cell lymphoma. The results clearly indicate that the atypical large cells seen in the transforming phase were clonally derived from the pre-existing cerebriform cells. Newly detected relevant cytogenetic findings were: a) drop of tumor cell ploidy from hypotetraploid to hypotriploid, with striking chromosomal imbalance; b) additional structural aberrations of chromosomes 2 and 7, which had been already preferentially involved in the earlier phases, and involvement of the previously unaffected chromosomes 1, 3, and X; and c) presence in 100% of the abnormal metaphases of a large HSR on the long arm of chromosome 17.

Cytogenetic follow-up in a case of Sézary syndrome.

A cytogenetic follow-up study was performed for a 3-year period on a 70-year-old patient with Sézary syndrome (SS). The results showed formation of hypotetraploid cell clones with 60 to 89 chromosomes and 19 markers, some of which appeared during the period of study and stabilized thereafter. The incidence of these clonal cells increased from 29% to 85% during the follow-up study. The results confirm the presence of hypotetraploid cell clones, especially in the more advanced stages of SS. Moreover, some marker chromosomes in our patient (M2 and M3), derived from chromosome 2, were similar to those observed in SS by other investigators. According to our data and to those in the literature, SS appears to involve preferentially chromosomal regions 2p12-13, 2p21-22, 2q37, 17p13, 13q1, 9q11, 10p13, 14q11, 14q32, 7p1 and, to a lesser extent, 5q and 6q.

Inhibitor of PI3Kγ ameliorates TNBS-induced colitis in mice by affecting the functional activity of CD4+CD25+FoxP3+ regulatory T cells.

BACKGROUND AND PURPOSE: Phosphoinositide 3-kinase-γ (PI3Kγ) is implicated in many pathophysiological conditions, and recent evidence has suggested its involvement in colitis. In the present study, we investigated the effects of AS605240, a relatively selective PI3Kγ inhibitor, in experimental colitis and its underlying mechanisms. EXPERIMENTAL APPROACH: Acute colitis was induced in mice by treatment with trinitrobenzene sulphonic acid (TNBS), and the effect of AS605240 on colonic injury was assessed. Pro-inflammatory mediators and cytokines were measured by immunohistochemistry, elisa, real time-polymerase chain reaction and flow cytometry. KEY RESULTS: Oral administration of AS605240 significantly attenuated TNBS-induced acute colitis and diminished the expression of matrix metalloproteinase-9 and vascular endothelial growth factor. The colonic levels and expression of IL-1ß, CXCL-1/KC, MIP-2 and TNF-α were also reduced following therapeutic treatment with AS605240. Moreover, AS605240 reduced MIP-2 levels in a culture of neutrophils stimulated with lipopolysaccharide. The mechanisms underlying these actions of AS605240 are related to nuclear factor-κ (NF-κB) inhibition. Importantly, the PI3Kγ inhibitor also up-regulated IL-10, CD25 and FoxP3 expression. In addition, a significant increase in CD25 and FoxP3 expression was found in isolated lamina propria CD4+ T cells of AS605240-treated mice. The effect of AS605240 on Treg induction was further confirmed by showing that concomitant in vivo blockade of IL-10R significantly attenuated its therapeutic activity. CONCLUSIONS AND IMPLICATIONS: These results suggest that AS605240 protects mice against TNBS-induced colitis by inhibiting multiple inflammatory components through the NF-κB pathway while simultaneously inducing an increase in the functional activity of CD4+CD25+ Treg. Thus, AS605240 may offer a promising new therapeutic strategy for the treatment of inflammatory bowel diseases.

Three-dimensional Wigner-function description of the quantum free-electron laser.

A free-electron laser (FEL) operating in the quantum regime can provide a compact and monochromatic x-ray source. Here we present the complete quantum model for a FEL with a laser wiggler in three spatial dimensions, based on a discrete Wigner-function formalism taking into account the longitudinal momentum quantization. The model describes the complete spatial and temporal evolution of the electron and radiation beams, including diffraction, propagation, laser wiggler profile and emittance effects. The transverse motion is described in a suitable classical limit, since the typical beam emittance values are much larger than the Compton wavelength quantum limit. In this approximation we derive an equation for the Wigner function which reduces to the three-dimensional Vlasov equation in the complete classical limit. Preliminary numerical results are presented together with parameters for a possible experiment.

Possible genotoxicity of melanin synthesis intermediates: tyrosinase reaction products interact with DNA in vitro.

The actual cellular target of the cytotoxic intermediates of melanin synthesis is not yet known. In the present paper it is shown that eukaryotic DNA binds in vitro to soluble reaction products of tyrosinase (EC 1.14.18.1) and is physically modified, as ascertained by the following criteria: (a) buoyant density in cesium chloride density gradients; (b) polyacrylamide gel electrophoresis; (c) deoxyribonuclease (EC 3.1.4.5) test; (d) electron microscopy. The results reported here support the view that DNA itself may be a target for the cytotoxic intermediates of melanin synthesis.

Developmental aspects of hexose metabolism in Bufo bufo.

Due to the close correlation between glucose mobilization and utilization within animal tissues, in this paper, the stages of appearance of phosphorylase, glucose-6-phosphatase and hexokinase as well as the levels of some intermediates of glucose metabolism have been investigated during Bufo bufo development. Phosphorylase first appears at stage 13 and is dominant in the neural part of the embryo, but, after this stage, increases relatively more in the nonneural one. Hexokinase appears at stage 17 and glucose-6-phosphatase soon after. Phosphorylase appearance at stage 13 is correlated with an increase of lactate content in the embryo; this may indicate a metabolization of hexoses. On this basis, the subsequent appearance of hexokinase and glucose-6-phosphatase activities also seems coherent with hexose mobilization and utilization within embryo. No direct causative factor for the changes observed was evident.

A study on melanogenesis and catecholamine biosynthesis during Bufo bufo development.

Tyrosinase and L-DOPA decarboxylase activities have been investigated during Bufo bufo development since catecholamines and melanin are formed from common substrates in homologous cells. Catecholamines first appear at stage 13 (neural plate), but tyrosinase, at a very low level, and L-DOPA decarboxylase are present throughout all of prior development. Hence, L-DOPA decarboxylase activity is not likely to be correlated with the control of catecholamine synthesis, although at stage 17 it is mainly localized in the nonneural part of the embryo. The distribution of young melanosomes and L-DOPA decarboxylase suggest a separation between melanogenesis and catecholamine synthesis.

Some properties of Bufo bufo tyrosinase during development.

Tyrosinase expression during Bufo bufo development has been investigated. Until stage 19, only 1 electrophoretic band is detectable, but at a later stage (25) 3 bands appear. The Km for L-3,4-dihydroxyphenylalanine (L-dopa) was also determined.

Possible role for Ca(2+) calmodulin-dependent protein kinase II as an effector of the fertilization Ca(2+) signal in mouse oocyte activation.

The present study shows that Ca(2+) calmodulin-dependent protein kinase II (CaM kinase II) is physiologically activated in fertilized mouse oocytes and is involved in the Ca(2+) response pathways that link the fertilization Ca(2+) signal to meiosis resumption and cortical granule (CG) exocytosis. After 10 min of insemination, CaM kinase II activity increased transiently, then peaked at 1 h and remained elevated 30 min later when most of the oocytes had completed the emission of the second polar body. In contrast, in ethanol-activated oocytes the early transient activation of CaM kinase II in response to a monotonic Ca(2+) rise was not followed by any subsequent increase. Inhibition of CaM kinase II by 20 micromol/l myristoylated-AIP (autocamtide-2-related inhibitory peptide) negatively affected MPF (maturing promoting factor) inactivation, cell cycle resumption and CG exocytosis in both fertilized and ethanol-activated oocytes. These results indicate that the activation of CaM kinase II in mouse oocytes is differently modulated by a monotonic or repetitive Ca(2+) rise and that it is essential for triggering regular oocyte activation.

Paracentric inversion of chromosome 15(q15q24): description of three families.

Three unrelated families with paracentric inversion of chromosome 15(q15q24) are reported. An additional pericentric inversion of chromosome 9 with breakpoints in p11.2q13 was also observed in one of the three families. Reproductive problems, such as stillbirths, spontaneous abortions and two live-born children with multiple abnormalities, were present.