Guillain-Barré syndrome associated with SARS-CoV-2 infection. A systematic review.

Guillain-Barré syndrome (GBS) incidence can increase during outbreaks of infectious illnesses. A few cases of GBS associated with coronavirus disease 2019 (COVID-19) infection have been reported. The aim was to identify specific clinical features of GBS associated with COVID-19. PubMed, Embase and Cochrane were searched from 1 November 2019 to 17 May 2020 and included all papers with full text in English, Spanish, French or Italian, reporting original data of patients with GBS and COVID-19. Data were extracted according to a predefined protocol. A total of 18 patients reported in 14 papers were included in this review. All the patients were symptomatic for COVID-19, with cough and fever as the most frequently reported symptoms. The interval between the onset of symptoms of COVID-19 and the first symptoms of GBS ranged from -8 to 24 days (mean 9 days; median 10 days). Most of the patients had a typical GBS clinical form predominantly with a demyelinating electrophysiological subtype. Mechanical ventilation was necessary in eight (44%) patients. Two (11%) patients died. Published cases of GBS associated with COVID-19 report a sensorimotor, predominantly demyelinating GBS with a typical clinical presentation. Clinical features and disease course seem similar to those observed in GBS related to other etiologies. These results should be interpreted with caution since only 18 cases have been heterogeneously reported so far.

CDH1 POLYMORPHISMS AND LOW EXPRESSION OF E-CADHERIN AND ß-CATENIN IN COLORECTAL CANCER PATIENTS.

Epithelial-mesenchymal transition (EMT) process has a central role in tumor progression and metastases. Loss of cell-to-cell adhesiveness is a key step in EMT. In particular, E-cadherin and ß-catenin, components of the adherens junctions, play a strategic role. Accumulation of ß-catenin at cytoplasmic level following adherens junctions disruption, induces its translocation into the nucleus, where it binds to members of the TCF/LEF family of transcription factors. In particular, Lymphoid Enhancer-Binding factor 1 (LEF1) product can target genes involved in EMT. The aim of the present study was to evaluate the influence of CDH1 and CTNNB1 genes, coding for E-cadherin and ß-catenin respectively and LEF1 in a sample study of 140 Italian patients affected by colorectal cancer. An association study between four single nucleotide polymorphisms (rs11865026, rs11642413, rs13689, and rs10431923) of CDH1 and the disease did not provide statistically significant results. The gene expression analysis carried out for CDH1, CTNNB1 and LEF1 in 54 paired specimens from 27 patients provided evidence of a reduced expression of the first two in cancer tissues. We believe there may be a sort of cross regulation between the products of these two genes which closely interact in EMT activation and that such hypothesis should be further investigated in a greater number of cases.

Reward contingencies and the recalibration of task monitoring and reward systems: a high-density electrical mapping study.

Task execution almost always occurs in the context of reward-seeking or punishment-avoiding behavior. As such, ongoing task-monitoring systems are influenced by reward anticipation systems. In turn, when a task has been executed either successfully or unsuccessfully, future iterations of that task will be re-titrated on the basis of the task outcome. Here, we examined the neural underpinnings of the task-monitoring and reward-evaluation systems to better understand how they govern reward-seeking behavior. Twenty-three healthy adult participants performed a task where they accrued points that equated to real world value (gift cards) by responding as rapidly as possible within an allotted timeframe, while success rate was titrated online by changing the duration of the timeframe dependent on participant performance. Informative cues initiated each trial, indicating the probability of potential reward or loss (four levels from very low to very high). We manipulated feedback by first informing participants of task success/failure, after which a second feedback signal indicated actual magnitude of reward/loss. High-density electroencephalography (EEG) recordings allowed for examination of event-related potentials (ERPs) to the informative cues and in turn, to both feedback signals. Distinct ERP components associated with reward cues, task-preparatory and task-monitoring processes, and reward feedback processes were identified. Unsurprisingly, participants displayed increased ERP amplitudes associated with task-preparatory processes following cues that predicted higher chances of reward. They also rapidly updated reward and loss prediction information dependent on task performance after the first feedback signal. Finally, upon reward receipt, initial reward probability was no longer taken into account. Rather, ERP measures suggested that only the magnitude of actual reward or loss was now processed. Reward and task-monitoring processes are clearly dissociable, but interact across very fast timescales to update reward predictions as information about task success or failure is accrued. Careful delineation of these processes will be useful in future investigations in clinical groups where such processes are suspected of having gone awry.

CD99 suppresses osteosarcoma cell migration through inhibition of ROCK2 activity.

CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions. In osteosarcoma, CD99 is expressed at low levels and functions as a tumour suppressor. The full-length protein (CD99wt) and the short-form harbouring a deletion in the intracytoplasmic domain (CD99sh) have been associated with distinct functional outcomes with respect to tumour malignancy. In this study, we especially evaluated modulation of cell-cell contacts, reorganisation of the actin cytoskeleton and modulation of signalling pathways by comparing osteosarcoma cells characterised by different metastasis capabilities and CD99 expression, to identify molecular mechanisms responsible for metastasis. Our data indicate that forced expression of CD99wt induces recruitment of N-cadherin and ß-catenin to adherens junctions. In addition, transfection of CD99wt inhibits the expression of several molecules crucial to the remodelling of the actin cytoskeleton, such as ACTR2, ARPC1A, Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) as well as ezrin, an ezrin/radixin/moesin family member that has been clearly associated with tumour progression and metastatic spread in osteosarcoma. Functional studies point to ROCK2 as a crucial intracellular mediator regulating osteosarcoma migration. By maintaining c-Src in an inactive conformation, CD99wt inhibits ROCK2 signalling and this leads to ezrin decrease at cell membrane while N-cadherin and ß-catenin translocate to the plasma membrane and function as main molecular bridges for actin cytoskeleton. Taken together, we propose that the re-expression of CD99wt, which is generally present in osteoblasts but lost in osteosarcoma, through inhibition of c-Src and ROCK2 activity, manages to increase contact strength and reactivate stop-migration signals that counteract the otherwise dominant promigratory action of ezrin in osteosarcoma cells.

Incidence of major coronary heart disease events: the experience of the Project "Community Control of Chronic Diseases".

Data on incidence of first major coronary heart disease (CHD) event have been collected in a population sample studied in the control area, the municipality of Priverno in Central Italy, 100 km South-East of Rome as part of a Community Control Project of Chronic Diseases run in nearby communities. Men and women aged 40-69 years, examined in population screenings, were followed-up for variable periods of time ranging from 1 month to 11 years, after exclusion of those already carrier of a previous major CHD event. A total of 1427 men and 1675 women corresponding to a maximum of 9590 and 11499 person/years respectively were followed-up. Diagnostic criteria were based on a number of different items including history and ECG data, from screening examinations; discharge records from local hospitals; causes of death from death certificates; and information from mail questionnaires. Four hundred and forty-six men and 501 women were considered partially non respondent since they were examined only once, they did not answer the postal questionnaire, although they were surely alive at the end of the observation period. Incidence estimates were based on different denominators, including or excluding these non respondents. The age adjusted lower incidence estimate was of 40.7 per 10000 person/years among men and 19.7 among women; the higher estimate was of 51.3 and 24.4 per 10000 person/years respectively. Rates were higher among men than among women and were increasing with aging. These incidence rates were slightly lower than those reported from other population studies conducted in Italy in the 1970's and the 1980's, but were in line with the hypothesis of a declining incidence paralleling the decline in CHD mortality. These data, including also estimates in women, represent a reference point for the early 1990's of the frequency and distribution of major CHD events.

Change in cardiovascular risk factors during a 10-year community intervention program.

The study describes changes in cardiovascular risk factors during 10 years of a community intervention program conducted in a rural area in Central Italy. Two areas were involved, one for treatment and one for reference. In 1983-84, 739 men and 859 women in the treatment area and 942 men and 1045 women in the control area, aged 20-69 years, were screened; total and HDL cholesterol, systolic and diastolic blood pressure, fasting blood glucose, smoking habit, weight and height were measured. Between 1983 and 1993 several intervention activities based on community medicine were carried out in the treatment area. They were based on interaction with the local socio-sanitary institutions and school system in order to influence individual persons, small groups and entire community. Major effort was addressed to mass health education, nutrition education, antismoking-propaganda and detection and treatment of hypertension, diabetes and hyperlipidemia.

Quantitative morphometry measurements of transitional cell bladder cancer nuclei as indicator of tumor aggression.

Superficial transitional cell carcinomas of the urinary bladder in 30 patients were studied by quantitative morphometry of the initial and subsequent tumor occurrences. Nuclear histograms were constructed and demonstrated narrow base and single modal peak in 9 of 10 patients not exhibiting tumor recurrence or invasion. In contrast, broad-based multimodal nuclear histograms were present in 15 of 20 patients in whom tumor invasion of carcinoma in situ subsequently developed. Nuclear histograms may provide an accurate means of determining invasive/recurrence potential of transitional cell carcinoma.