Immunohistochemical expression of p16(INK4a) is predictive of HR-HPV infection in cervical low-grade lesions.

The p16(INK4a) is a cyclin-dependent kinase inhibitor that decelerates the cell cycle by inactivating the cyclin-dependent kinases involved in the phosphorylation of the retinoblastoma protein (RB). Expression of E6 and E7 oncogenes of high-risk (HR) human papillomavirus (HPV), affecting the RB-p16 pathway, leads to p16 upregulation. Although it is widely reported that p16 is overexpressed in a high percentage of preneoplastic lesions and in almost all carcinomas of the uterine cervix, protein upregulation and its correlation with HPV infection in low-grade lesions is still being debated. In this study, we investigated in parallel, p16 expression and HPV infection in 100 cervical biopsies (17 normal tissues, 54 CIN1, 10 CIN2, 11 CIN3, eight invasive squamous cancers). Results obtained demonstrated that none of the 17 normal cervical tissues, evaluated by immunohistochemistry, presented p16 positivity whereas, starting from CIN1 (31%) to CIN2 (90%), CIN3 (100%) and carcinomas (100%), a constant and significant increase of protein overexpression (P<0.0001) was observed. In addition, p16 overexpression consistently showed elevated sensitivity (84%) and specificity (98%) in detecting HR-HPV infection with a high positive predictive value (97%) and negative predictive value (86%). Of interest, 93% of the p16-positive CIN1 were also HR-HPV infected. Our findings confirmed that p16 overexpression is associated to high-grade precancerous lesions and cervical carcinomas, and further demonstrated that immunohistochemical evaluation of p16 may be a useful biomarker in identifying HR-HPV-infected low-grade lesions.     

Different variables predict anomia in different subjects: a longitudinal study of two Alzheimer's patients

Two Alzheimer's patients participated in a longitudinal study of picture naming aimed at analysing the effect of lexical frequency, age of acquisition, stimulus familiarity, word length, name imageability, visual complexity and semantic category membership on naming success. The results were analysed with a new method [Capitani, E., & Laiacona, M. (2004). A method for studying the evolution of naming error types in the recovery of acute aphasia: A single-patient and single-stimulus approach. Neuropsychologia, 42, 613-623] that allows us to consider the consistency of responses to stimuli over repeated testing within clinical stages. The experiment was carried out as a longitudinal study of single cases, and the effect of each variable was estimated after removing the overlap with the other predictors. The semantic category of stimuli was not an influential factor for either patient. Other findings sharply distinguished between the two patients. In one case, disease-related decline consistently affected mainly late acquired names, whereas in the other case the decline affected names corresponding to low-familiarity items. To interpret this contrast, we further analysed the quality of the errors produced by each patient. This study shows that the psycholinguistic characteristics of a stimulus may exert varying influence in different patients, warranting further development of this line of inquiry.     

Prospective memory and working memory: Asymmetrical effects during frontal lobe TMS stimulation

The role of working memory (WM) for the realization of an intended action (prospective memory, PM) has been debated in recent neuropsychological literature. The present study aimed to assess whether WM and PM share resources or are, alternatively, two distinct mechanisms. A verbal task was used, which manipulated the cognitive demand of both WM and PM dimensions on an event-based prospective task. Transcranial magnetic stimulation (TMS) was also employed to clarify the causal contribution of frontal areas previously related to WM, to the PM process. The prospective task required the participant to respond whenever a word appeared which had been presented before the beginning of the task. Two ongoing tasks were administered: an updating WM task (in two conditions of medium and high WM demands) and a lexical decision task (representing a low WM demand). In the first two experiments, higher PM demand affected WM only at higher loads, but the PM load effect was independent of WM, showing asymmetrical behavioural effects. In the third experiment, single pulse TMS was applied to left and right dorsolateral prefrontal cortices. When applied to the experimental sites, stimulation increased error rates of the PM task, while the effect was only marginal in the WM task. The effect was bilateral, since there was no difference between left and right stimulation sites. These findings demonstrated, from both behavioural and neurofunctional perspectives, that WM and PM processes are not based on the same memory system, but PM may require WM resources at high demand.     

The Recognition of Facial Emotions in Spinocerebellar Ataxia Patients

Patients with cerebellar lesions present some affective and cognitive disorders, defining a peculiar pattern of cognitive impairment, so-called cerebellar cognitive affective syndrome. This pattern has been confirmed in many genotypes of spinocerebellar ataxias (SCA), a group of genetically defined pathologies characterized by the degeneration of the cerebellum and its connections. Recently, in SCA patients, some authors focused the interest on social cognition evidencing an impairment of theory of mind and basic emotion recognition by verbal material. The recognition of emotions in faces is an essential component of social cognition; therefore, we assessed this ability in SCA patients, expanding the study from the basic verbal emotions to the basic and social visual emotion recognition. We assessed facial emotion recognition using two basic and social emotion tasks in a group of SCA patients together with a complete clinical and neuropsychological evaluation. We compared results with the performance of a control group. We demonstrated a significant difference between patients and controls both in basic and social emotion recognition, although we found a specific impairment only for social emotions. The deficit was not correlated to clinical and demographic features. The cognitive and psychological profile did not explain the impairment in emotion recognition. This result supports the hypothesis that the impairment in social emotion recognition could be specifically related to a defect in the corticocerebellar network.     

Frovatriptan versus zolmitriptan for the acute treatment of migraine with aura: a subgroup analysis of a double-blind,randomized, multicenter,Italian study

Migraine with aura affects ~20–30 % of migraineurs and it is much less common than migraine without aura. The aim of this study was to compare the efficacy of frovatriptan 2.5 mg and zolmitriptan 2.5 mg in the treatment of migraine with aura. Analysis was carried out in a subset of 18 subjects with migraine with aura (HIS criteria) out of the 107 enrolled in a multicenter, randomized, double-blind, cross-over study. According to the study design, each patient had to treat three episodes of migraine in no more than 3 months with one drug, before switching to the other treatment. The rate of pain-free episodes at 2 h was significantly (p < 0.05) larger under frovatriptan (45.8 %) than under zolmitriptan (16.7 %). Pain free at 4 h, pain relief at 2 and 4 h and recurrent episodes were similar between the two treatments, while sustained pain-free episode was significantly (p < 0.05) more frequent during frovatriptan treatment (33.3 vs. 8.3 % zolmitriptan). Our study suggests that frovatriptan is superior to zolmitriptan in the immediate treatment of patients with migraine with aura, and it is capable of maintaining its acute analgesic effect over 48 h.     

Pure topographical disorientation in a patient with right occipito-temporal lesion

We describe a patient who presented with a pure topographical disorientation after a stroke involving the right mesial occipito-temporal cortex. He could not point to external unseen landmarks or draw a map of his city, while he could recognize landmarks, and judge the distance, and describe the route between pairs of landmarks of the same city. He underwent standardized cognitive tests, and 6 tasks were used to assess a topographical orientation route-survey. This study provides evidence that topographical disorientation can be subdivided into very specific components. The results suggest that one of these components might refer to the processing of an allocentric map separable from the representation of route knowledge.