Predicting Alzheimer’s disease severity by means of TMS–EEG coregistration

Clinical manifestations of Alzheimer's disease (AD) are associated with a breakdown in large-scale communication, such that AD may be considered as a “disconnection syndrome.” An established method to test effective connectivity is the combination of transcranial magnetic stimulation with electroencephalography (TMS–EEG) because the TMS-induced cortical response propagates to distant anatomically connected regions. To investigate whether prefrontal connectivity alterations may predict disease severity, we explored the relationship of dorsolateral prefrontal cortex connectivity (derived from TMS–EEG) with cognitive decline (measured with Mini Mental State Examination and a face–name association memory task) in 26 patients with AD. The amplitude of TMS–EEG evoked component P30, which was found to be generated in the right superior parietal cortex, predicted Mini Mental State Examination and face–name memory scores: higher P30 amplitudes predicted poorer cognitive and memory performances. The present results indicate that advancing disease severity might be associated with effective connectivity increase involving long-distance frontoparietal connections, which might represent a maladaptive pathogenic mechanism reflecting a damaged excitatory–inhibitory balance between anterior and posterior regions

Clinical and psychological characteristics associated with negative beliefs and concerns about treatment necessity in rheumatic diseases

Identifying factors that influence problematic beliefs and behaviors related to pharmacotherapy may be useful for clinicians to improve the patients' adherence. The study aims to assess patients' beliefs about the necessity and concerns regarding pharmacotherapy in rheumatic diseases and attitude styles, and to investigate the association between clinical factors and negative beliefs about medication. A sample of 712 patients affected by Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis was enrolled. They were assessed using the Beliefs about Medicines Questionnaires-Specific (BMQ), the Simplified Disease Activity Index (SDAI), the Visual Analogue Scale for pain (VAS), the Chalder Fatigue Scale (CFQ) and the Health Assessment Questionnaire-Disability Index (HAQ-DI). The balance between benefits and costs in the BMQ-Specific was positive in the 79.4% of patients, negative in the 12.1% and equal in the 8.6%. SDAI, taking more than 5 medications, taking anti interleukin 6 (Anti-IL6) or biological disease-modifying antirheumatic drugs (bDMARDs), or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), pain, and fatigue were significantly associated to higher Concerns. Having a longer disease duration was significantly associated with a higher Necessity, together with the current pharmacological treatments and the disability. The multivariate regression models estimated that higher pain and fatigue were associated to higher Concerns (p < 0.001), while a longer disease duration (p < 0.001) and all pharmacological treatments for a rheumatologic disease (p = 0.001) were associated to higher Necessity levels. A high length of disease, a low level of remission, a high number of total medications, the prescription of an Anti-IL6/bDMARDs/tsDMARDs drug, a high level of pain, fatigue and disability identified patients potentially less adherent to pharmacotherapy to be carefully looked after by clinicians

Comparison and potential determinants of health-related quality of life among rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis: A cross-sectional study

Objectives: This study aimed to compare the health-related quality of life scores among rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis and to evaluate socio-demographic and clinical determinantes of quality of life across diseases. Methods: The sample comprised 490 patients with rheumatoid arthritis, 198 with psoriatic arthritis, and 119 with spondyloarthritis who completed a series of health examinations and self-reported questionnaires. Quality of life was evaluated using the Short-Form 36 Health Survey, disease activity by DAS28-CRP, DAPSA, and ASDAS-CRP (for rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis, respectively), depression and anxiety using the Hospital Anxiety and Depression Scale. ANOVA was used to compare the quality of life dimensions and their physical and mental summary measures among rheumatic diseases, and multivariate analysis was used to explore their potential determinants. Results: Rheumatoid arthritis had significantly worse scores than spondyloarthritis in the following dimensions: physical functioning, role limitation due to physical health, physical component score, and mental health. Psoriatic arthritis was not significantly different from the other two diseases. Multivariate analysis revealed that physical quality of life was mainly associated with disease activity across rheumatic diseases, rheumatological treatment and depression in rheumatoid arthritis and psoriatic arthritis. Mental quality of life is primarily associated with depression and anxiety across rheumatic diseases. Conclusion: There were differences in quality of life among patients with inflammatory rheumatic diseases, but overall, approximately uniform factors explained the variance in quality of life across diseases. Clinicians should develop general approaches and strategies for inflammatory rheumatic diseases to improve patients' quality of life

Depression is associated with increased disease activity and higher disability in a large Italian cohort of patients with rheumatoid arthritis

Depression is a quite common comorbidity in patients with rheumatoid arthritis (RA) and is thought to influence its severity. This study aims to estimate, in a large cohort of Italian patients with RA, the prevalence of depression and to investigate the clinical correlates of depression in terms of disease activity and disability

Safety of percutaneous ultrasound-guided fine-needle aspiration of adrenal lesions in dogs: Perception of the procedure by radiologists and presentation of 50 cases

Background Percutaneous ultrasound (US)-guided fine-needle aspiration (FNA) of adrenal gland lesions is controversial in veterinary medicine. Objective To evaluate the frequency and radiologists' perception of the risk of the procedure as well as determining the incidence of complications. Methods Retrospective study. A first survey was submitted by e-mail to all board-certified radiologists of the American College of Veterinary Radiology (ACVR) and European College of Veterinary Diagnostic Imaging (ECVDI). A second survey was sent to radiologists who declared having performed the procedure at least once in their career (observational cross-sectional case study). Results The first survey was sent to 977 diplomates and answered by 138. Of 138 diplomates, 40 currently performed the procedure and 98 did not; 44 of the 98 gave the hypertensive crisis risk in pheochromocytoma as a reason. To the second survey, 12 of 65 responded positively; 50 dogs with 58 lesions were recruited, including 23 pheochromocytomas. Complications were reported in 4 of 50 dogs; 3 hemorrhages (1 mild and 1 moderate) and 1 death from acute respiratory distress syndrome (possibly related to laryngeal paralysis). No hypertensive crisis was reported. There was no relationship between the method of FNA/type of needle used and occurrence of complications. Based on the recollection of these 65 radiologists, who performed approximately 200 FNA of adrenal lesions, a death rate of approximately 1% was estimated. Conclusions and Clinical Importance Percutaneous US-guided FNA of adrenal lesions can be considered a minimally risky procedure, despite the negative perception by radiologists

Renal adenocarcinoma-associated erythrocytosis in a cat: Clinicopathological features and immunohistochemical results

This report documents a case of secondary inappropriate erythrocytosis in a cat with renal cell adenocarcinoma, its stabilization through manual erythrocytapheresis, and the EPO-immunostaining on the affected kidney. An 11-year-old cat was presented with lethargy, weight loss and polyuria/polydipsia. An abdominal mass was detected upon physical examination. Clinicopathological work-up revealed marked erythrocytosis (HCT value 64.8%), renal azotemia and decreased urine specific gravity (USG). An abdominal ultrasound was performed, localizing the mass in the right kidney. Serum erythropoietin (EPO) was above the reference interval (RI), and the cytology of the mass was indicative of renal carcinoma. Manual erythrocytapheresis was performed in order to stabilize the patient before surgery, improving the cat’s clinical and clinicopathological condition. After nephrectomy, EPO and creatinine concentrations returned within the RI, while the USG markedly increased. Histopathology confirmed the diagnosis of renal adenocarcinoma. Immunohistochemistry with anti-EPO antibody revealed diffuse and strong cytoplasmatic positivity in tumor cells

Acute acalculous cholecystitis during the course of primary Epstein-Barr virus infection: a new case and a review of the literature

OBJECTIVE: The aim of this study was to describe a case of acute acalculous cholecystitis occurring in the course of primary Epstein-Barr virus (EBV) infection. METHODS: The clinical features of the case were analyzed and compared to those of three other similar cases reported in the international literature. RESULTS: All cases occurred in European females with cholestatic hepatitis, presented with gallbladder wall thickening, and recovered uneventfully without the need for surgical intervention. CONCLUSIONS: Acute acalculous cholecystitis may occur during the course of acute EBV infection, especially in patients with cholestatic hepatitis. Clinicians should be aware of the possible involvement of the gallbladder during EBV infection to avoid unnecessary invasive procedures or the overuse of antibiotics

Construction and Modelling of an Inducible Positive Feedback Loop Stably Integrated in a Mammalian Cell-Line

Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL) by generating a clonal population of mammalian cells (CHO) carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA), whose expression is regulated by a tTA responsive promoter (CMV-TET), thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP), thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL), by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off), and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the “switch off” times, as comparared to the nonautoregulatated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+