Multisession anodal epidural direct current stimulation of the auditory cortex delays the progression of presbycusis in the Wistar rat.

Presbycusis or age-related hearing loss (ARHL) is one of the most prevalent chronic health problems facing aging populations. Along the auditory pathway, the stations involved in transmission and processing, function as a system of interconnected feedback loops. Regulating hierarchically auditory processing, auditory cortex (AC) neuromodulation can, accordingly, activate both peripheral and central plasticity after hearing loss. However, previous ARHL-prevention interventions have mainly focused on preserving the structural and functional integrity of the inner ear, overlooking the central auditory system. In this study, using an animal model of spontaneous ARHL, we aim at assessing the effects of multisession epidural direct current stimulation of the AC through stereotaxic implantation of a 1-mm silver ball anode in Wistar rats. Consisting of 7 sessions (0.1 mA/10 min), on alternate days, in awake animals, our stimulation protocol was applied at the onset of hearing loss (threshold shift detection at 16 months). Click- and pure-tone auditory brainstem responses (ABRs) were analyzed in two animal groups, namely electrically stimulated (ES) and non-stimulated (NES) sham controls, comparing recordings at 18 months of age. At 18 months, NES animals showed significantly increased threshold shifts, decreased wave amplitudes, and increased wave latencies after click and tonal ABRs, reflecting a significant, spontaneous ARHL evolution. Conversely, in ES animals, no significant differences were detected in any of these parameters when comparing 16 and 18 months ABRs, indicating a delay in ARHL progression. Electrode placement in the auditory cortex was accurate, and the stimulation did not cause significant damage, as shown by the limited presence of superficial reactive microglial cells after IBA1 immunostaining. In conclusion, multisession DC stimulation of the AC has a protective effect on auditory function, delaying the progression of presbycusis.

Comparing the effects of transcranial alternating current and temporal interference (tTIS) electric stimulation through whole-brain mapping of c-Fos immunoreactivity.

The analysis of the topography of brain neuromodulation following transcranial alternating current (AC) stimulation is relevant for defining strategies directed to specific nuclei stimulation in patients. Among the different procedures of AC stimulation, temporal interference (tTIS) is a novel method for non-invasive neuromodulation of specific deep brain targets. However, little information is currently available about its tissue effects and its activation topography in in vivo animal models. After a single session (30 min, 0.12 mA) of transcranial alternate current (2,000 Hz; ES/AC group) or tTIS (2,000/2,010 Hz; Es/tTIS group) stimulation, rat brains were explored by whole-brain mapping analysis of c-Fos immunostained serial sections. For this analysis, we used two mapping methods, namely density-to-color processed channels (independent component analysis (ICA) and graphical representation (MATLAB) of morphometrical and densitometrical values obtained by density threshold segmentation. In addition, to assess tissue effects, alternate serial sections were stained for glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba1), and Nissl. AC stimulation induced a mild superficial increase in c-Fos immunoreactivity. However, tTIS stimulation globally decreased the number of c-Fos-positive neurons and increased blood brain barrier cell immunoreactivity. tTIS also had a stronger effect around the electrode placement area and preserved neuronal activation better in restricted areas of the deep brain (directional stimulation). The enhanced activation of intramural blood vessels' cells and perivascular astrocytes suggests that low-frequency interference (10 Hz) may also have a trophic effect.

Effects of Multisession Anodal Electrical Stimulation of the Auditory Cortex on Temporary Noise-Induced Hearing Loss in the Rat.

The protective effect of the efferent system against acoustic trauma (AT) has been shown by several experimental approaches, including damage to one ear, sectioning of the olivocochlear bundle (OCB) in the floor of the IV ventricle, and knock-in mice overexpressing outer hair cell (OHC) cholinergic receptors, among others. Such effects have been related to changes in the regulation of the cholinergic efferent system and in cochlear amplification, which ultimately reverse upon protective hearing suppression. In addition to well-known circuits of the brainstem, the descending corticofugal pathway also regulates efferent neurons of the olivary complex. In this study, we applied our recently developed experimental paradigm of multiple sessions of electrical stimulation (ES) to activate the efferent system in combination with noise overstimulation. ABR thresholds increased 1 and 2 days after AT (8-16 kHz bandpass noise at 107 dB for 90 min) recovering at AT + 14 days. However, after multiple sessions of epidural anodal stimulation, no changes in thresholds were observed following AT. Although an inflammatory response was also observed 1 day after AT in both groups, the counts of reactive macrophages in both experimental conditions suggest decreased inflammation in the epidural stimulation group. Quantitative immunocytochemistry for choline acetyltransferase (ChAT) showed a significant decrease in the size and optical density of the efferent terminals 1 day after AT and a rebound at 14 days, suggesting depletion of the terminals followed by a long-term compensatory response. Such a synthesis recovery was significantly higher upon cortical stimulation. No significant correlation was found between ChAT optical density and size of the buttons in sham controls (SC) and ES/AT + 1day animals; however, significant negative correlations were shown in all other experimental conditions. Therefore, our comparative analysis suggests that cochleotopic cholinergic neurotransmission is also better preserved after multisession epidural stimulation.

Analysis of patients attitude to undergo urgent endoscopic procedures during COVID-19 outbreak in Italy.

We conducted a survey to investigate to what extent the fear of COVID-19 has influenced the patients decision to undergo or to cancel endoscopic procedures. We collected data from 847 patients from 13 centres. The main indication for endoscopy was anemia, followed by pain and unexplained weight loss. The percentage of not presenters progressively increased throughout the three weeks of study, from 15.1% at the beginning to 48.2% at the end. 37 (34.2%) upper GI endoscopies and 112 (56.3 %) colonoscopies showed an organic cause explaining the symptoms presented by the patients, respectively; 5 cases of gastric cancer (4.6%) and 16 cases of colorectal cancer (CRC) (6.0%), respectively, were detected; during the second week the percentage of organic diseases found at upper endoscopy was 19 (33.3%) with 5 cancer (8.7%), and 61 (49.1% ) at colonoscopy, with 2 CRC (1.6%); finally, during the third week the corresponding figures were 19 (48.7%) for upper GI examinations, with 3 gastric cancers (7.7%), and 43 (60.5%) with 4 (6.5%) CRC cases found.We conclude that patients weighted the fear of having a clinically relevant disease with the fear of becoming infected by coronavirus, and a relevant percentage of them (29.4%) decided not to attend the endoscopy suites at the scheduled date.

The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C.

AIMS: To assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti-viral therapy on insulin resistance and serum levels of adipocytokines. METHODS: Clinical and biochemical features, anthropometrical characteristics, and levels of fasting insulin, leptin, adiponectin and resistin were measured in 'naïve' patients with chronic hepatitis C, before, during and after therapy with Peg-Interferon-alpha 2a plus Ribavirin. RESULTS: Forty-eight patients were included (M/F 28/20; mean age 50.0 +/- 12.6 years; 62.5% genotype-1). Body mass index was 26.4 +/- 4.0 kg/m(2), and visceral obesity was present in 24 patients. At multivariate analysis (RR; 95% CI), steatosis was associated to older age (1.08; 1-1.18), necroinflammatory activity (17.67; 1.6-194.46), and raised insulin levels (1.39; 1.1-1.77). Fibrosis was related to necroinflammatory activity (25.73; 2.54-261.11), and steatosis (6.47; 1.09-38.29). Sustained viral response was achieved by 62.5% of patients and was associated with younger age (0.92; 0.85-0.99), genotype non-1 (10.61; 1.52-73.76) and absence of visceral obesity (13.78; 2.36-80.29). At the end of follow-up, insulin and the homeostasis model assessment for insulin resistance were reduced and adiponectin increased when compared with baseline, all unrelated to the outcome of treatment. CONCLUSIONS: Visceral obesity correlates with the degree of steatosis and fibrosis, and it negatively affects treatment response. Significant changes of insulin resistance and adipocytokines occur under treatment, irrespective of virological outcome.

Acute polymyositis during treatment of acute hepatitis C with pegylated interferon alpha-2b.

Hepatitis C virus is not cleared after primary infection in 50-85% of subjects exposed to hepatitis C virus. Anti-viral treatment during the early phase of infection significantly enhances the likelihood of a sustained clearance of hepatitis C virus. Although, a variety of autoimmune-related side effects have been observed during interferon therapy for chronic hepatitis, immuno-mediated adverse reactions have not been reported during treatment of acute hepatitis C. We describe the case of a patient who developed acute hepatitis C virus infection and, while receiving pegylated interferon alpha-2b monotherapy, developed a severe polymyositis. This case illustrates the potential risk of autoimmunity by interferon, also for acute hepatitis, and underlines the importance of a prompt diagnosis and a rapid discontinuation of interferon treatment for an improvement of clinical outcomes.

Prolonged prothrombin time, Factor VII and activated FVII levels in chronic liver disease are partly dependent on Factor VII gene polymorphisms.

BACKGROUND: Prothrombin time is a benchmark for functional assessment in cirrhosis and Factor VII levels (FVII), crucial in determining the prothrombin time, are genetically determined. METHODS: We have evaluated the prothrombin time, a number of haemostatic variables synthesised by the liver (FII, FV, FVII and activated FVII, AT and fibrinogen) and two polymorphisms of the FVII gene (5'F7 and 353R/Q) in: (a) patients with liver cirrhosis (n=118), (b) patients with chronic hepatitis (n=102) and (c) controls (n=100). RESULTS: By one-way analyses of variance, the prothrombin time and the mean levels of the FII, FV, FVIIc, FVIIa, and AT were statistically different between cirrhotics, chronic hepatitis patients and controls. The allele frequency of the FVII polymorphisms did not differ between the three groups. Those rare patients (4.6%) who were homozygous for the type 2 alleles had markedly reduced FVIIc and FVIIa levels. The analysis carried out taking into account Child class versus FVII genotype showed that the mean FVIIc levels were comparable for different genotypes within each Child's class, with the exception of the patients homozygous for the type 1 allele. CONCLUSION: Our findings help to explain the not infrequent finding of a severely prolonged prothrombin time in patients who are otherwise in a good functional class.

Does an 'autoimmune' profile affect the clinical profile of chronic hepatitis C? An Italian multicentre survey.

Nonorgan-specific autoantibodies (NOSA) are common in patients with chronic hepatitis C virus infection. It is unclear whether serological markers of autoimmunity segregate in a cohort of cases with more severe liver damage. We assessed the relationship between NOSA and demographic, biochemical and histological features in 502 subjects with anti-HCV positive, HCV-RNA positive, HBsAg negative chronic hepatitis consecutively referred to four Italian liver units. Percutaneous liver biopsy was performed in all subjects. A single pathologist scored the biopsies using histology activity index classification. The overall prevalence of positivity for any NOSA was 36.9%. Antinuclear antibodies, anti-smooth muscle antibodies, and anti-liver/kidney microsomal antibodies were found in 15.7, 27.3 and 2.2% of cases. Multivariate analysis showed that gamma-globulin >2 g/dL was the only independent predictor of the likelihood of NOSA positivity (OR, 2.1; 95% CI, 1.3-3.4). No other clinical (age, gender, ALT, HCV genotype) or histological features (grading and staging score, bile ductular damage) were linked to NOSA. Antiviral therapy in 155 subjects with NOSA did not cause any adverse events related to autoimmunity during and after treatment. The presence of NOSA in patients with chronic HCV hepatitis is not related to specific demographic features and has no impact on the biochemical and histological profile of the liver disease at presentation and the response to antiviral treatment.

The impact of antiviral therapy on the course of chronic HCV infection. A systematic review.

AIM: Chronic hepatitis C is a progressive disease that leads to liver cirrhosis and hepatocellular carcinoma in a period ranging from 10 to 30 y. Many factors have been related to disease progression and, among them, persistent HCV replication has been advocated as one of the major determinant of hepatic deterioration. With this respect any treatment of chronic hepatitis C is mainly aimed to reduce necro-inflammation by suppressing viral activity in the long-term. We evaluated the persistence of HCV clearance after interferon therapy during follow-up in patients considered as long-term responders. Secondly, we analyzed the rate of progression from hepatitis to cirrhosis and hepatocellular carcinoma in patients with persistent viral elimination as compared to those who did not respond to treatment. METHODS: We performed a systematic review of published data as full papers on treatment of chronic hepatitis that reported data on long-term follow-up of patients with persistent HCV suppression and the rate of cirrhosis and hepatocellular carcinoma in long-term responders as compared to non-responders. Data were pooled to obtain a combined estimate of the reduced relative risk using the random effect model. RESULTS: In patients achieving a sustained virological response a relapse was observed in about 13% (range 0-86%). In subjects with a sustained viral response progression to cirrhosis is uncommon. When compared to relapsers or non-responders the calculated risk reduction in this group was -0.22 (95% C.I. - 0.36/-0.08). The calculated estimates of risk reduction of developing hepatocellular carcinoma in patients achieved sustained response were -0.097 (95% C.I. -0.13/-0.07). CONCLUSION: There is a high chance that patients in remission during the first 6 mo after antiviral treatment will remain so for the rest of their life. Cumulative data from literature showed a significant reduction in the rate of progression to cirrhosis and development of hepatocellular carcinoma in sustained viral responders as compared to non-responders or relapsers. However, since factors predictive of sustained response to interferon are independently associated with less frequent and/or later development of decompensation or HCC, the beneficial effects of antiviral therapy may be probably overestimated.

[Role of ultrasonic diagnosis in patients with clinically suspected acute intestinal invagination]. / Ruolo dell'esame ecografico nei pazienti con sospetto clinico di invaginazione intestinale acuta.

Acute intestinal intussusception is one of the commonest causes of abdominal emergency in infants. It strikes mainly infants 3 to 30 months old. Ileo-colic intussusception is the commonest form (75-95%), whereas ileo-ileo-colic, colono-colic and ileo-ileal intussusceptions are rather uncommon. Intussusception is primitive in 95% of cases and secondary in the extant 5%. Over the last 3 years we examined 25 infants with clinical suspicion of acute intestinal intussusception by means of plain abdominal radiographs and US. In 11 cases US diagnosed acute intestinal intussusception. US signs useful for diagnosis were: intussusception "pudding" on both transverse and longitudinal scans, and communicating intussusception "pudding" and bowel. US allowed intestinal intussusception to be diagnosed in 11 cases and ruled out in 14, with 100% reliability. In agreement with literature data, our results confirm US as the method of choice--versus conventional radiology--in the diagnosis of acute intestinal intussusception and stress the value of US studies in helping avoid surgery.

[Ultrasonic diagnosis of 22 gastric tumors]. / Diagnostica sonografica di ventidue tumori gastrici.

A report is presented on 22 patients with advanced stomach cancer in whom echography revealed the characteristic signs ("pseudokidney", "cockade", "target", "doughnut", etc.). Though not considered wholly specific indicators of gastric neoplasm (they may be artefacts or errors of interpretation) they are helpful in the diagnosis of the stomach. Ultrasound has made it possible to identify the site (antrum and body) and spread of the cancer both locally and at a distance and only a few forms (not encountered in the present series) have presented characteristic images. Endoscopic ultrasonography and the high resolution intraoperative type offer the chance for significant progress in this diagnostic field.