Analytic and Diagnostic Performances of Human Papillomavirus E6/E7 mRNA Test on up-to 11-Year-Old Liquid-Based Cervical Samples. A Biobank-Based Longitudinal Study.

Human Papillomavirus (HPV) E6/E7 mRNA test demonstrated high specificity in detecting HPV infections, but studies assessing its efficacy in terms of cancer risk stratification are lacking. Follow-up studies are arduous and expensive. Biobank would be the answer to the problem, although data investigating the effects of long-term storage on RNA preservation are still needed. We addressed these issues by retrieving 202 residual liquid-based cervical specimens, collected from 149 women attending cervical cancer screening during the years 2001-2012. Samples were stored in Adriatic Biobank at room temperature and without any handing. After calculation of RNA yield and purity, E6/E7 mRNA test was retrospectively performed on each samples, to assess analytic and diagnostic performances. Using automated extraction procedures, RNA of good quantity and quality was obtained. The mean value of RNA concentration was 27.5 ng/µL. The mean A260/A280 ratio was 2.1. An invalid mRNA test result was found in 11.9% of the specimens. Neither RNA integrity, nor analytic performances of mRNA test were influenced by the year of sample collection. In total, 62.4% of the specimens tested as mRNA positive; among these, 89.2% were CIN2+. E6/E7 mRNA was detected in all Squamous Cervical Cancer (SCC) cases. Percentage of positive samples increased with the severity of histological diagnosis. mRNA testing, showing specificity and predictive values of 75.6% and 84.4%, respectively, significantly improved the corresponding values for DNA testing. Thus, the reflex mRNA test was demonstrated to be suitable to triage women with persistent cervical lesions. A "one sample for all" approach is possible, with practical benefits for Biobank-based long-term longitudinal studies, diseases prevention, prediction, diagnosis and treatment.

Mild cognitive impairment in Parkinson's disease is improved by transcranial direct current stimulation combined with physical therapy.

BACKGROUND: Parkinson's disease (PD) is characterized by both motor and cognitive deficits. In PD, physical exercise has been found to improve physical functioning. Recent studies demonstrated that repeated sessions of transcranial direct current stimulation led to an increased performance in cognitive and motor tasks in patients with PD. OBJECTIVES: The present study investigated the effects of anodal transcranial direct current stimulation applied over the dorsolateral prefrontal cortex and combined with physical therapy in PD patients. METHODS: A total of 20 patients with PD were assigned to 1 of 2 study groups: group 1, anodal transcranial direct current stimulation plus physical therapy (n = 10) or group 2, placebo transcranial direct current stimulation plus physical therapy (n = 10). The 2 weeks of treatment consisted of daily direct current stimulation application for 25 minutes during physical therapy. Long-term effects of treatment were evaluated on clinical, neuropsychological, and motor task performance at 3-month follow-up. RESULTS: An improvement in motor abilities and a reduction of depressive symptoms were observed in both groups after the end of treatment and at 3-month follow-up. The Parkinson's Disease Cognitive Rating Scale and verbal fluency test performances increased only in the anodal direct current stimulation group with a stable effect at follow-up. CONCLUSIONS: The application of anodal transcranial direct current stimulation may be a relevant tool to improve cognitive abilities in PD and might be a novel therapeutic strategy for PD patients with mild cognitive impairment. © 2016 International Parkinson and Movement Disorder Society.

Efficacy of semantic-phonological treatment combined with tDCS for verb retrieval in a patient with aphasia.

Recent studies reported enhanced performance on language tasks induced by transcranial direct current stimulation (tDCS) in patients with aphasia. One chronic patient with non-fluent aphasia received 20 sessions of a verb anomia training combined with off-line bihemispheric tDCS applied to the dorsolateral prefrontal cortex (DLPFC) - anodal tDCS over left DLPFC plus cathodal tDCS over right DLPFC. A significant improvement in verb naming was observed at all testing times (4, 12, 24, and 48 weeks from post-entry/baseline testing) for treated and untreated verbs. Our findings show beneficial effects of verb anomia training in combination with tDCS in chronic aphasic patient, suggesting a long-lasting effect of this treatment.

Expression of PTEN in endometrial liquid-based cytology.

OBJECTIVES: Endometrial cytology offers a reliable alternative to biopsy in endometrial cancer detection and it may be useful in obtaining material to study prognostic and predictive markers. Over the years, new sampling devices have been developed. Molecular alterations in endometrial cancers were previously described using formalin-fixed paraffin-embedded tissues with particular attention, in endometrioid carcinomas, to the PTEN-PI3K pathway. PTEN evaluation could be useful in endometrial carcinomas for selecting patients for target therapies. STUDY DESIGN: We studied 51 endometrial samples collected using the Endogyn device and 71 obtained with the Endoflower dispositive device, and processed using liquid-based cytology. Most of the cases were matched with a corresponding histological biopsy. The overall accuracy of Endoflower was 100%. Immunohistochemistry (IHC) and immunocytochemistry (ICC) for PTEN were performed using monoclonal antibody 6H2.1 from DAKO. RESULTS: The IHC showed PTEN-null glands in 4 cases. The same cancers were negative in ICC. Among the 10 carcinomas on cytology, PTEN-null glands were found in 1 case. All the normal endometrium control cases were positive in cytology and histology. CONCLUSIONS: Our results suggest that endometrial devices provide useful material for the diagnosis and evaluation of PTEN expression.

Comparison of oncogenic HPV type-specific viral DNA load and E6/E7 mRNA detection in cervical samples: results from a multicenter study.

High-risk human papillomavirus (HR-HPV) genotype viral load and E6/E7 mRNA detection are proposed as surrogate markers of malignant cervical lesion progression. Currently, the use of commercially available DNA-based or mRNA-based tests is under investigation. In this study, the viral DNA load and E6/E7 mRNA detection of the five most common HR-HPV types detected in cervical cancer worldwide were compared in 308 cervical samples by using in-house type-specific quantitative real-time PCR assays and PreTect HPV-Proofer test, respectively. Sensitivity and negative predictive values were higher for the HPV-DNA assays combined (95.0% and 96.0%, respectively) than the RNA assays (77.0% and 88.0%, respectively); conversely, the mRNA test showed a higher specificity and higher positive predictive value (81.7% and 66.9%, respectively) than the DNA test (58.6% and 52.5%, respectively) for detecting histology-confirmed high-grade cervical intraepithelial neoplasia. A significantly higher association between viral DNA load and severity of disease was observed for HPV 16 and 31 (γ = 0.62 and γ = 0.40, respectively) than for the other HPV types screened. A good degree of association between the two assays was found for detection of HPV 16 (k = 0.83), HPV 18 (k = 0.72), HPV 33 (k = 0.66), and HPV 45 (k = 0.60) but not for HPV 31 (k = 0.24). Sequence analysis in L1 and E6-LCR regions of HPV 31 genotypes showed a high level of intra-type variation. HR-HPV viral DNA load was significantly higher in E6/E7 mRNA positive than negative samples (P < 0.001), except for HPV 31. These findings suggest that transcriptional and replicative activities can coexist within the same sample.

Implementing specificity of HPV-DNA primary screening in a successful organised cervical cancer prevention programme.

OBJECTIVE: This two-arm longitudinal study was performed within a regional organized cervical-cancer-prevention program in which HPV-DNA test is used in primary screening. The aim was to analyze the diagnostic performances of p16INK4a/Ki-67 dual-test and E6/E7-mRNA test in identifying CIN2+ lesion among HPV-DNA positive (HPV-DNAve) women triaged for LSIL-or-worse liquid based cytology (LBC). METHODS: Thirty-six thousand thirty-one women participated to HPV-DNA screening program pilot study. Three thousand six hundred forty-one resulted HPV-DNAve; among these, 43% were LSIL-or-worse (LSIL+). HPV-DNAve/LSIL+ patients were submitted to colposcopy and histological assessment of any visible lesions. Dual-test was performed on 794 residual LBC specimens. In 405 cases, dual-test result was related to histology, considering CIN2+ as endpoint. mRNA test has been carried out retrospectively, on a subset of 173 residual LBC specimens. RESULTS: Agreement between dual-test and histological diagnosis was 59%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cytology-plus-dual-test approach were 62.3%, 76.8%, 63.1% and 84.2%, respectively. Dual-test improved specificity, PPV and NPV of cytological triage Agreement between mRNA testing and histology was 65%. Cytology-plus mRNA testing showing sensitivity, specificity, PPV and NPV reaching 32.1%, 94.9%, 75% and 50%, respectively; implemented specificity and PPV of cytology alone in triaging DNA-ve/LSIL+ patients (p<0.01). CONCLUSIONS: We provided promising data indicating the important role that p16(INK4)/Ki-67 dual-test, and mostly E6/E7 mRNA test, might have in triaging HPV-DNAve. These approaches would exclude the occurrence of cervical cancer and would avoid overtreatment, at the same time. Further longitudinal analysis has to be considered.

Brain stimulation improves associative memory in an individual with amnestic mild cognitive impairment.

In patients with cognitive deficits, brain stimulation has been shown to restore cognition ( Miniussi et al., 2008 , Brain Stimulation, 1, 326). The aim of this study was to assess whether repetitive Transcranial Magnetic Stimulation (rTMS) could improve memory performance in an individual with amnestic Mild Cognitive Impairment (aMCI). Stimulation of the left parietal cortex increased accuracy in an association memory task, and this improvement was still significant 24 weeks after stimulation began. These findings indicate that rTMS to the left parietal cortex improved memory performance in aMCI.

Sensitivity, specificity, and clinical value of human papillomavirus (HPV) E6/E7 mRNA assay as a triage test for cervical cytology and HPV DNA test.

There is evidence that testing for human papillomavirus (HPV) E6/E7 mRNA is more specific than testing for HPV DNA. A retrospective study was carried out to evaluate the performance of the PreTect HPV-Proofer E6/E7 mRNA assay (Norchip) as a triage test for cytology and HPV DNA testing. This study analyzed 1,201 women, 688 of whom had a colposcopy follow-up and 195 of whom had histology-confirmed high-grade intraepithelial neoplasia or worse (CIN2+). The proportion of positive results and the sensitivity and specificity for CIN2+ were determined for HPV mRNA in comparison to HPV DNA and cytology. All data were adjusted for follow-up completeness. Stratified by cytological grades, the HPV mRNA sensitivity was 83% (95% confidence interval [CI] = 63 to 94%) in ASC-US (atypical squamous cells of undetermined significance), 62% (95% CI = 47 to 75%) in L-SIL (low-grade squamous intraepithelial lesion), and 67% (95% CI = 57 to 76%) in H-SIL (high-grade squamous intraepithelial lesion). The corresponding figures were 99, 91, and 96%, respectively, for HPV DNA. The specificities were 82, 76, and 45%, respectively, for HPV mRNA and 29, 13, and 4%, respectively, for HPV DNA. Used as a triage test for ASC-US and L-SIL, mRNA reduced colposcopies by 79% (95% CI = 74 to 83%) and 69% (95% CI = 65 to 74%), respectively, while HPV DNA reduced colposcopies by 38% (95% CI = 32 to 44%) and by 15% (95% CI = 12 to 19%), respectively. As a HPV DNA positivity triage test, mRNA reduced colposcopies by 63% (95% CI = 60 to 66%), having 68% sensitivity (95% CI = 61 to 75%), whereas cytology at the ASC-US+ threshold reduced colposcopies by 23% (95% CI = 20 to 26%), showing 92% sensitivity (95% CI = 87 to 95%). In conclusion, PreTect HPV-Proofer mRNA can serve as a better triage test than HPV DNA to reduce colposcopy referral in both ASC-US and L-SIL. It is also more efficient than cytology for the triage of HPV DNA-positive women. Nevertheless, its low sensitivity demands a strict follow-up of HPV DNA positive-mRNA negative cases.

Improved language performance in Alzheimer disease following brain stimulation.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible treatment for the cognitive deficits associated with Alzheimer disease (AD). The aim of this study was to assess the long-term effects, on cognitive performance, of rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) in AD patients. METHODS: Ten AD patients were randomly assigned to one of two study groups. Multiple-baseline design was used.The first group underwent a 4-week real rTMS stimulation protocol, while the second underwent a 2-week placebo treatment, followed by 2 weeks of real rTMS stimulation. Each session consisted of the application of rhythmic high-frequency rTMS over the DLPFC for 25 min. Sessions occurred once daily, 5 days/week. The main analysed outcome was the change in cognitive test performance at 2 and 4 weeks after rTMS treatment initiation, with a follow-up performed 8 weeks after the end of rTMS, in comparison with baseline performance. RESULTS: A significant difference was found between groups over sessions in terms of the percentage of correct responses of auditory sentence comprehension. Only real treatment induced an improvement in performance with respect to baseline or placebo. Moreover, both groups showed a lasting effect on the improved performance 8 weeks after the end of treatment. CONCLUSION: The findings provide initial evidence for the persistent beneficial effects of rTMS on sentence comprehension in AD patients. Rhythmic rTMS, in conjunction with other therapeutic interventions, may represent a novel approach to the treatment of language dysfunction in AD patients.

Anomia training and brain stimulation in chronic aphasia.

Recent studies have reported enhanced performance on language tasks induced by non-invasive brain stimulation, i.e., repetitive transcranial magnetic stimulation (rTMS), or transcranial direct current stimulation (tDCS), in patients with aphasia due to stroke or Alzheimer's disease (AD). The first part of this article reviews brain stimulation studies related to language recovery in aphasic patients. The second part reports results from a pilot study with three chronic stroke patients who had non-fluent aphasia, where real or placebo rTMS was immediately followed by 25 minutes of individualised speech therapy. Real rTMS consisted of high-frequency rTMS over the left dorsolateral prefrontal cortex (BA 8/9) for 25 minutes. Each patient underwent a total of four weeks of intervention. P1 underwent four weeks of real rTMS (5 days/week) where individualised speech therapy was provided for 25 minutes immediately following each rTMS session. P2 and P3 each underwent two weeks of placebo rTMS, followed immediately by individualised speech therapy; then two weeks of real rTMS, followed immediately by individualised speech therapy. Assessments took place at 2, 4, 12, 24 and 48 weeks post-entry/baseline testing. Relative to entry/baseline testing, a significant improvement in object naming was observed at all testing times, from two weeks post-intervention in real rTMS plus speech therapy, or placebo rTMS plus speech therapy. Our findings suggest beneficial effects of targeted behavioural training in combination with brain stimulation in chronic aphasic patients. However, further work is required in order to verify whether optimal combination parameters (rTMS alone or speech therapy alone) and length of rTMS treatment may be found.

The lack of epithelial interleukin-7 and BAFF/BLyS gene expression in prostate cancer as a possible mechanism of tumor escape from immunosurveillance.

PURPOSE: The human prostate is endowed with intraepithelial and stromal lymphocytes, which may develop lymphoid follicles (LF) and allow a local immune response. We sought to investigate whether interleukin (IL)-7 and BAFF/BLyS, two fundamental survival factors for T and B cells, are expressed in the normal and neoplastic prostate and affect intraprostatic lymphocyte homeostasis. EXPERIMENTAL DESIGN: We have used real-time reverse transcription-PCR of microdissected prostatic glands and confocal microscopy to detect cytokine production, combined with immunohistochemistry to characterize intraprostatic lymphocytes. RESULTS: Prostatic epithelia constitutively produce IL-7 and, to a lesser extent, BAFF/BLyS. Indeed, we show that IL-7 receptor alpha is expressed by intraepithelial T lymphocytes and parafollicular T cells, whereas BAFF-R is found on periglandular B lymphocytes and mantle zone B cells of LFs. Prostate-homing B and T lymphocytes are scarcely proliferating, whereas most of them express the antiapoptotic protein bcl-2 and reveal a low apoptotic index in the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The transition from normal to neoplastic glands in prostate cancer (PCa) is marked by a dramatic decline of IL-7 and BAFF/BLyS production. Accordingly, PCa is characterized by a significant reduction of intraepithelial lymphocytes and loss of LFs. B-cell and T-cell expression of bcl-2 decrease, whereas the apoptotic events increase. The remaining PCa-infiltrating lymphocytes are mostly CD8(+) T cells that lack terminal differentiation and barely penetrate neoplastic glands. CONCLUSIONS: These results suggest that epithelial IL-7 and BAFF/BLyS production support intraprostatic lymphocyte survival. Its loss in PCa is associated with a severe depletion of prostate-associated lymphocytes and points to a novel tumor escape mechanism.

Age at onset reveals different functional connectivity abnormalities in prodromal Alzheimer's disease.

Age at symptom onset (AAO) underlies different Alzheimer's disease (AD) clinical variants: late-onset AD (LOAD) is characterized by memory deficits, while early-onset AD (EOAD) presents predominantly with non-memory symptoms. The involvement of different neural networks may explain these distinct clinical phenotypes. In this study, we tested the hypothesis of an early and selective involvement of neural networks based on AAO in AD. Twenty memory clinic patients with prodromal AD (i.e., mild cognitive impairment with an AD-like cerebrospinal fluid profile) and 30 healthy controls underwent a cognitive evaluation and a resting state functional MRI exam. Independent component analysis was performed to assess functional connectivity (FC) in the following networks: default mode, frontoparietal, limbic, visual, and sensorimotor. Patients were stratified into late-onset (pLOAD) and early-onset (pEOAD) prodromal AD according to the AAO and controls were stratified into younger and older groups accordingly. Decreased FC within the default mode and the limbic networks was observed in pLOAD, while pEOAD showed lower FC in the frontoparietal and visual networks. The sensorimotor network did not show differences between groups. A significant association was found between memory and limbic network FC in pLOAD, and between executive functions and frontoparietal network FC in pEOAD, although the latter association did not survive multiple comparison correction. Our findings indicate that aberrant connectivity in memory networks is associated with pLOAD, while networks underlying executive and visuo-spatial functions are affected in pEOAD. These findings are in line with the hypothesis that the pathophysiological mechanisms underlying EOAD and LOAD are distinct.

Cerebrovascular disease and hippocampal atrophy are differently linked to functional coupling of brain areas: an EEG coherence study in MCI subjects.

The working hypothesis of paper is that the functional coupling of brain areas is combined with different neuroradiological substrates and has different clinical manifestations. 31 normal old subjects and 85 subjects with mild cognitive impairment (MCI) underwent EEG recordings and magnetic resonance imaging (MRI). Intrahemispheric and interhemispheric linear EEG coherences were computed. At first, all normal old and MCI subjects were compared. Subsequently, three subgroups of MCI were obtained based on neuroradiological substrate (subcortical cerebrovascular damage, MCI-CVD; cholinergic pathways vascular damage MCI-CHOL; and hippocampal atrophy, MCI-HIPP) and compared with a normal old sample matched for age, education and Mini-Mental State Examination score. The group of MCI subjects compared to normal old subjects shows: 1) decrease of intrahemispheric coherence in fronto-parietal regions (both right and left hemisphere); 2) increase of interhemispheric coherence on frontal regions in delta frequency; and 3) increase of interhemispheric coherence on temporal regions (from delta to alpha3 frequency bands). In the MCI subgroups, hippocampal atrophy is linked to an increase of interhemispheric coherence seen on frontal and temporal regions whereas subcortical CVD is linked to the largest decrease of coherence in fronto-parietal regions. MCI-CVD patients performed worst on Trail Making Test battery whereas MCI-HIPP patients were impaired on Rey word list delayed recall and Rey figure recall.

Cervical cancer screening: from molecular basis to diagnostic practice, going through new technologies.

In the era of Human Papillomavirus (HPV) vaccination, a lot of misunderstanding still exists among healthcare professionals and patients regarding HPV infection. The purpose of this review is to synthesize the clinical molecular mechanisms that contribute to HPV-mediated cervical carcinogenesis, as well as to appraise the current status of new biomarkers and technologies in terms of available data on clinical applications and future promises.

Int6 expression can predict survival in early-stage non-small cell lung cancer patients.

PURPOSE: The Int6 gene was originally identified as a common insertion site for the mouse mammary tumor virus in virally induced mouse mammary tumors. Recent studies indicate that Int6 is a multifaceted protein involved in the regulation of protein translation and degradation through binding with three complexes: the eukaryotic translation initiation factor 3, the proteasome regulatory lid, and the constitutive photomorphogenesis 9 signalosome. This study aimed to investigate the prognostic role of Int6 in a large series of stage I non-small cell lung cancers (NSCLC) patients with long-term follow-up. EXPERIMENTAL DESIGN: We determined the methylation status of Int6 DNA by methylation-specific PCR and the steady-state levels of Int6 RNA by quantitative real-time reverse transcription-PCR in 101 NSCLCs and matched normal lung tissues. RESULTS: In 27% of the tumors, Int6 RNA levels were reduced relative to normal tissue. In 85% of the tumors with reduced Int6 expression, the transcription promoter and first exon were hypermethylated, whereas only 4% of the tumors with elevated Int6 RNA levels were hypermethylated (P <0.000001). Low levels of Int6 RNA were found a significant predictor of overall and disease-free survival (P=0.0004 and P=0.0020, respectively). A multivariate analysis confirmed that low Int6 expression was the only independent factor to predict poor prognosis, for both overall (P=0.0006) and disease-free (P=0.024) survival. CONCLUSIONS: Our results suggest that Int6 expression, evaluated by quantitative real-time PCR, may represent a new prognostic factor in patients with stage I NSCLC.

Facial feedback and autonomic responsiveness reflect impaired emotional processing in Parkinson's Disease.

Emotional deficits are part of the non-motor features of Parkinson's disease but few attention has been paid to specific aspects such as subjective emotional experience and autonomic responses. This study aimed to investigate the mechanisms of emotional recognition in Parkinson's Disease (PD) using the following levels: explicit evaluation of emotions (Self-Assessment Manikin) and implicit reactivity (Skin Conductance Response; electromyographic measure of facial feedback of the zygomaticus and corrugator muscles). 20 PD Patients and 34 healthy controls were required to observe and evaluate affective pictures during physiological parameters recording. In PD, the appraisal process on both valence and arousal features of emotional cues were preserved, but we found significant impairment in autonomic responses. Specifically, in comparison to healthy controls, PD patients revealed lower Skin Conductance Response values to negative and high arousing emotional stimuli. In addition, the electromyographic measures showed defective responses exclusively limited to negative and high arousing emotional category: PD did not show increasing of corrugator activity in response to negative emotions as happened in heathy controls. PD subjects inadequately respond to the emotional categories which were considered more "salient": they had preserved appraisal process, but impaired automatic ability to distinguish between different emotional contexts.

Role of E6/E7 mRNA test in the diagnostic algorithm of HPV-positive patients showing ASCUS and LSIL: clinical and economic implications in a publicly financed healthcare system.

OBJECTIVE: Colposcopy is widely used to triage women with mild cervical abnormalities. However, this approach is associated with low specificity and predictive value. The efficacy of E6/E7 mRNA test for this purpose has been demonstrated, but studies estimating its cost-effectiveness are still lacking. Given the limited healthcare financial resources, such an evaluation is a priority. METHODS: We analyzed the clinical history of 432 women referred to colposcopy and colposcopy-directed biopsy for persisting ASCUS and LSIL, and compared three alternative triage protocols: immediate colposcopy; reflex HPV DNA testing and HPV DNA plus mRNA tests in sequence. RESULTS: Molecular tests in sequence significantly reduce colposcopy referral, cost for assessed women, and cost for CIN2 detected. On the other hand, incremental cost-effectiveness ratio of this protocol was the highest. CONCLUSION: Our preliminary data, providing an estimation of the economic burden deriving from the introduction of E6/E7 mRNA test in the triage algorithm of patients with mild cervical abnormalities, may be useful for future healthcare policy.

A very rare case of HPV-53-related cervical cancer, in a 79-year-old woman with a previous history of negative Pap cytology.

The introduction of organized cervical cancer (CC) screening programs has drastically reduced the prevalence of CC. However the incidence is still too high, especially among elderly women. All guidelines strongly recommend a regular Papanicolaou (Pap) testing for young and middle-aged patients. On the other hand, many international professional societies no longer advise screening in women who have undergone hysterectomy, and in women aged 65 years and above, who have a previous history of regular Pap smears. Here we report the case of poorly differentiated CC, involving the pelvic lymph nodes and urinary bladder, occurring in a 79-year-old woman who regularly underwent Pap tests, with no reported cytological abnormalities. In this very rare case, the CC cells, as well as cells from metastatic lymph nodes and cells from urinary specimens, molecularly showed human papilloma virus (HPV)-53. With the limitations of a single case, this report brings important information to prevent CC in elderly patients: the utility of molecular tests to increase sensitivity of Pap smears in postmenopausal women; the importance of HPV-53 as one of the four "emergent" genotypes having a possible role in oncogenesis; and the presence of HPV-53 in lymph node metastases from cervical carcinoma, which would support the role of this virus in the maintenance of malignant status.

Noninvasive stimulation of prefrontal cortex strengthens existing episodic memories and reduces forgetting in the elderly.

Memory consolidation is a dynamic process. Reactivation of consolidated memories by a reminder triggers reconsolidation, a time-limited period during which existing memories can be modified (i.e., weakened or strengthened). Episodic memory refers to our ability to recall specific past events about what happened, including where and when. Difficulties in this form of long-term memory commonly occur in healthy aging. Because episodic memory is critical for daily life functioning, the development of effective interventions to reduce memory loss in elderly individuals is of great importance. Previous studies in young adults showed that the dorsolateral prefrontal cortex (DLPFC) plays a causal role in strengthening of verbal episodic memories through reconsolidation. The aim of the present study was to explore the extent to which facilitatory transcranial direct current stimulation (anodal tDCS) over the left DLPFC would strengthen existing episodic memories through reconsolidation in elderly individuals. On Day 1, older adults learned a list of 20 words. On Day 2 (24 h later), they received a reminder or not, and after 10 min tDCS was applied over the left DLPFC. Memory recall was tested on Day 3 (48 h later) and Day 30 (1 month later). Surprisingly, anodal tDCS over the left DLPFC (i.e., with or without the reminder) strengthened existing verbal episodic memories and reduced forgetting compared to sham stimulation. These results provide a framework for testing the hypothesis that facilitatory tDCS of left DLPFC might strengthen existing episodic memories and reduce memory loss in older adults with amnestic mild cognitive impairment.

Anodal tDCS during face-name associations memory training in Alzheimer's patients.

OBJECTIVE: Given the limited effectiveness of pharmacological treatments, non-pharmacological interventions to treat Alzheimer's disease (AD) have gained attention in recent years. The aim of the present study is to investigate the effects of anodal tDCS (AtDCS) combined with memory training on face-name associations in an AD patient sample. METHODS: Thirty six AD patients were randomly assigned to one of three study groups: Group 1, AtDCS plus individualized computerized memory training; Group 2, placebo tDCS plus individualized computerized memory training; Group 3, AtDCS plus motor training. RESULTS: A general improvement in performance was observed after 2 weeks of memory training. Both the anodal tDCS plus individualized computerized memory training and the placebo tDCS plus individualized computerized memory training groups had significantly improved performances at 2 weeks compared with the AtDCS plus motor training group. CONCLUSION: Our findings suggest a beneficial effect of individualized memory rehabilitation in AD patients.