Gender differences in obsessive-compulsive disorder traits among chronic migraine patients.

BACKGROUND: Psychiatric illnesses are often associated with severe forms of headache as chronic migraine (CM) with medication overuse headaches (MOH). Few data are available about obsessive-compulsive disorders (OCD) in migraineurs. This study aimed to investigate OCD traits in CM with MOH patients of both sexes and the impact on migraine treatment. METHODS: We enrolled all consecutive patients with CM and MOH treated with onabotulinumtoxin-A (OBT-A) in our Headache Center. Each subject was submitted to the Obsessive-Compulsive Inventory-Revised (OCI-R) test at the start (T0) and after four OBT-A sessions (T1). Statistical analysis compared OCI-R results at T0 and T1 according to sex with the chi-square test. RESULTS: We analyzed a sample of 60 subjects (40 females, 66.7%). At T0, 25% of males and 37.5% of females had a normal profile while 60% of males and 22.5% of females presented pathologic OCD traits. At T1, 30% of males and 60% of females were normal, while 40% of males and 15% of females resulted frankly pathologic. The difference in the OCI-R distribution was significant at T0 (p = 0.024) and at T1 (p = 0.047). Both males and females underwent a significant increase in normalization rates at T1 (p < 0.05). CONCLUSION: We observed a significant OCD traits rate at baseline, moreover among men. Females showed a more significant improvement in OCD traits at T1. OBT-A confirmed its high efficacy on CM, with a migraine severity improvement in both genders and all the OCI-R classes. Psychological attitude in the management of migraine should be better investigated in future studies.

The role of spatial store and executive strategy in spatial working memory: a comparison between patients with obsessive-compulsive disorder and controls.

INTRODUCTION: Patients with obsessive-compulsive disorder (OCD) showed impaired spatial working memory (SWM). We evaluated whether patients and healthy controls (HCs) differed in spatial store capacity, and whether they differed in the relative weight of spatial store capacity and/or executive strategy in SWM. METHODS: Thirty inpatients with OCD and 31 age- and education-matched HCs underwent the CANTAB SWM, SRM (a measure of spatial store). The severity of OC symptoms was assessed using the Y-BOCS. Statistical significance: α = 0.05. RESULTS: Patients showed poorer performance than HCs in all neuropsychological outcomes. Both poorer SRM and SWM strategy were significantly associated with poorer SWM in the entire sample. No significant interaction between SRM and Group was found, while a significant interaction between SWM strategy and Group emerged; in patients the magnitude of this association was approximately twofold larger than in HCs. OC symptom severity did not correlate with neuropsychological performance. CONCLUSIONS: Patients with OCD had poorer spatial store capacity than HCs. However, the weight of poorer executive strategy in SWM was greater in patients than HCs, whereas the weight of spatial store was similar. We provided a direct evidence that an impairment in the executive component might be the crucial factor influencing the poorer SWM of these patients.

Childhood adversities in patients with fibromyalgia: are they related to comorbid lifetime major depression?

OBJECTIVES: Fibromyalgia (FM) is a syndrome of unknown aetiology that is frequently associated with depressive disorders, and childhood adversities (including maltreatment and parental loss) are frequently described in subjects with FM and depression. The aim of this study was to investigate the extent to which the high percentage of childhood adversities reported by patients with FM is related to FM itself or to a comorbid lifetime depressive disorder. METHODS: Ninety-four consecutive FM patients were assessed for lifetime major depression using the DSM-IVSCID-CV interview. Childhood maltreatment was investigated using the Childhood Trauma Questionnaire, and information relating to parental death or separation before the age of 18 years was collected by means of a semi-structured interview. The Zung Self-Rating Depression Scale, used as a quantitative measure of depressive symptoms, and the childhood adversity assessment were recorded at the same time. RESULTS: Sixty of the 94 FM patients (63.8%) were diagnosed as having a lifetime major depressive disorder. There were no significant associations between childhood parental loss, the presence/level of maltreatment, the occurrence of a lifetime major depression episode, and the Zung Self-Rating Depression Scale scores. CONCLUSIONS: The results of this study suggest that there is no association between childhood adversities and comorbid lifetime major depression in patients with FM. As it would be helpful to prevent the development of FM because of the high cost and limited efficacy of therapeutic interventions, childhood adversities may offer targets for primary prevention.

Definition of MYC genetic heteroclonality in diffuse large B-cell lymphoma with 8q24 rearrangement and its impact on protein expression.

MYC rearrangement can be detected in a subgroup of diffuse large B-cell lymphoma characterized by unfavorable prognosis. In contrast to Burkitt lymphoma, the correlation between MYC rearrangement and MYC protein expression in diffuse large B-cell lymphoma is less clear, as approximately one-third of rearranged cases show negative or low expression by immunohistochemistry. To better understand whether specific characteristics of the MYC rearrangement may influence its protein expression, we investigated 43 de novo diffuse large B-cell lymphoma positive for 8q24 rearrangement by FISH, using 14 Burkitt lymphoma for comparison. Different cell populations (clones), breakpoints (classical vs non-classical FISH patterns), partner genes (IGH vs non-IGH) and immunostaining were detected and analyzed using computerized image systems. In a subgroup of diffuse large B-cell lymphoma, we observed different clones within the same tumor distinguishing the founder clone with MYC rearrangement alone from other subclones, carrying MYC rearrangement coupled with loss/extra copies of derivatives/normal alleles. This picture, which we defined MYC genetic heteroclonality, was found in 42% of cases and correlated to negative MYC expression (P=0.026). Non-classical FISH breakpoints were detected in 16% of diffuse large B-cell lymphoma without affecting expression (P=0.040). Non-IGH gene was the preferential partner of rearrangement in those diffuse large B-cell lymphoma showing MYC heteroclonality (P=0.016) and/or non-classical FISH breakpoints (P=0.058). MYC heteroclonality was not observed in Burkitt lymphoma and all cases had positive MYC expression. Non-classical FISH MYC breakpoint and non-IGH partner were found in 29 and 20% of Burkitt lymphoma, respectively. In conclusion, MYC genetic heteroclonality is a frequent event in diffuse large B-cell lymphoma and may have a relevant role in modulating MYC expression.

Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review.

Many aspects of long-term pharmacological treatments for anxiety disorders (AnxDs) are still debated. We undertook an updated systematic review of long-term pharmacological studies on panic disorder (PD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). Relevant studies dating from January 1, 2012 to August 31, 2015 were identified using the PubMed database and a review of bibliographies. Of 372 records identified in the search, five studies on PD and 15 on GAD were included in the review. No studies on SAD were found. Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy. Paroxetine, escitalopram, and clonazepam can be effective for long-term treatment of PD. However, further studies are needed to draw conclusions about the long-term benzodiazepine use in PD, particularly for the possible cognitive side-effects over time. Pregabalin and quetiapine can be effective for long-term treatment of GAD, while preliminary suggestions emerged for agomelatine and vortioxetine. We did not find any evidence for determining the optimal length and/or dosage of medications to minimize the relapse risk. Few investigations have attempted to identify potential predictors of long-term treatment response. Personalized treatments for AnxDs can be implemented using predictive tools to explore those factors affecting treatment response/tolerability heterogeneity, including neurobiological functions/clinical profiles, comorbidity, biomarkers, and genetic features, and to tailor medications according to each patient's unique features.

Cigarette smoking has no pro-cognitive effect in subjects with obsessive-compulsive disorder: A preliminary study.

BACKGROUND: The prevalence of cigarette smoking in patients with different psychiatric disorders is higher than that in the general population, which is partly explained by the pro-cognitive effect of smoking on cognitive functions. In subjects with obsessive-compulsive disorder (OCD), the prevalence of smokers is lower than that in other psychiatric disorders. We hypothesized that cigarette smoking does not provide benefits and even worsen cognitive performance in OCD. SUBJECTS AND METHODS: We compared different executive function subdomains in 20 smoking and 20 non-smoking inpatients with OCD. At the beginning of hospitalization, we assessed visuo-spatial working memory, planning and set-shifting abilities (Cambridge Neuropsychological Test Automated Battery), smoking habits (standardized personal interviews), and the severity of obsessive-compulsive symptoms (Dimensional Yale-Brown Obsessive-Compulsive Scale). RESULTS: The performance of smokers and non-smokers did not differ significantly in any cognitive subdomain. The smoking duration was significantly associated with poorer visuo-spatial working memory performance (P=0.001). CONCLUSIONS: Our results showed that cigarette smoking did not provide cognitive enhancement across various executive function subdomains in subjects with OCD. The lack of beneficial cognitive effects of smoking may make these subjects less prone to smoking and may partially explain the lower rate of smokers in OCD compared with other psychiatric conditions.

NEU3 activity enhances EGFR activation without affecting EGFR expression and acts on its sialylation levels.

Several studies performed over the last decade have focused on the role of sialylation in the progression of cancer and, in particular, on the association between deregulation of sialidases and tumorigenic transformation. The plasma membrane-associated sialidase NEU3 is often deregulated in colorectal cancer (CRC), and it was shown that this enzyme co-immunoprecipitates in HeLa cells with epidermal growth factor receptor (EGFR), the molecular target of most recent monoclonal antibody-based therapies against CRC. To investigate the role of NEU3 sialidase on EGFR deregulation in CRC, we first collected data on NEU3 gene expression levels from a library of commercial colon cell lines, demonstrating that NEU3 transcription is upregulated in these cell lines. We also found EGFR to be hyperphosphorylated in all cell lines, with the exception of SW620 cells and the CCD841 normal intestinal cell line. By comparing the effects induced by overexpression of either the wild-type or the inactive mutant form of NEU3 on EGFR, we demonstrated that the active form of NEU3 enhanced receptor activation without affecting EGFR mRNA or protein expression. Moreover, through western blots and mass spectrometry analysis, we found that EGFR immunoprecipitated from cells overexpressing active NEU3, unlike the receptor from mock cells and cells overexpressing inactive NEU3, is desialylated. On the whole, our data demonstrate that, besides the already reported indirect EGFR activation through GM3, sialidase NEU3 could also play a role on EGFR activation through its desialylation.

Are respiratory abnormalities specific for panic disorder? A meta-analysis.

OBJECTIVES: There is evidence of baseline respiratory abnormalities in panic disorder (PD), but whether they are specific to PD remains unclear. To investigate this issue, we meta-analyzed results from studies comparing baseline respiratory and hematic variables between subjects with PD and subjects with other anxiety disorders. METHODS: A literature search in bibliographic databases was performed. Fixed-effects models were applied. Several moderator analyses and publication bias diagnostics were performed. RESULTS: We found: (1) significantly lower mean end-tidal partial pressure of CO(2) (et-pCO(2)) in subjects with PD than in those with social phobia (SP) or generalized anxiety disorder (GAD), and (2) higher mean respiratory rate, lower venous et-pCO(2) and HCO(3)(-) concentration in subjects with PD than in those with SP. No publication bias was found. CONCLUSIONS: Subjects with PD show a condition of baseline hyperventilation when compared to subjects with SP or GAD. Hematic variables suggest that the hyperventilation may be chronic. These results support the idea that baseline respiratory abnormalities are specific to PD pathophysiology. Further studies are needed to clarify whether these abnormalities are related to a malfunction of the respiratory system or to specific cognitive/emotional/behavioral factors in this population.

Self-reported quality of life and clinician-rated functioning in mood and anxiety disorders: relationships and neuropsychological correlates.

This study aimed to investigate 1) the relationship between subjective perception of quality of life (QoL) and clinician-rated levels of psychosocial functioning and 2) the relationship of these indicators with neuropsychological performances, in a sample of 117 subjects with mood and anxiety disorders hospitalized for a 4-week psychiatric rehabilitation program. At the beginning of the hospitalization, QoL and clinician-rated functioning were respectively measured by the World Health Organization Quality of Life Assessment-Brief Form (WHOQOL-BREF) and the Global Assessment of Functioning (GAF) scale, and subjects were administered a neuropsychological battery evaluating verbal and visual memory, working memory, attention, visual-constructive ability, language fluency and comprehension. We did not find any association between WHOQOL-BREF and GAF scores and between cognitive impairment and lower QoL or clinician-rated functioning. Our results suggest that 1) the individuals' condition encompasses different dimensions that are not fully captured by using only clinician-rated or self-administered evaluations; 2) the GAF scale seems unable to indicate the cognitive impairments of our subjects and the WHOQOL-BREF does not appear to be influenced by these deficits. Overall, our findings suggest the need of simultaneously use of multiple assessment tools, including objective evaluations of functioning and different measures of QoL, in order to obtain a more complete clinical picture of the patients. This may allow to identify more specific targets of therapeutic interventions and more reliable measures of outcome.

Ipsilateral and contralateral carotid stenosis contribute to the outcome of reperfusion treatment for ischemic stroke.

Introduction: Ipsilateral and contralateral carotid stenosis (ICS, CCS) influence acute ischemic stroke (AIS) severity and prognosis. Few data are available about their impact on reperfusion therapies efficacy. Aim of this study was to evaluate the impact of ICS and CCS on the effect of intravenous thrombolysis (IT), mechanical thrombectomy (MT) or both and of antiplatelet therapy (AT). Methods: We enrolled all the consecutive patients admitted for AIS to our stroke unit and submitted to IT, MT, IT+MT, or AT. We established the presence of a significant ICS or CCS (≥70%) by ultrasound examination or brain angio-CT, or MRI. Clinical and instrumental information were collected; delta National Institutes of Health Stroke Scale (NIHSS) from pre-treatment to patients' discharge was employed as the main outcome measure. Results: In total, 460 subjects were enrolled, 86 with ICS and 38 with CCS. We observed a significant linear trend of delta (NIHSS) between carotid stenosis categories for patients undergoing IT (p = 0.011), MT (p = 0.046), and MT+IT (p = 0.040), but no significant trend among subjects receiving no reperfusion treatments was observed (p = 0.174). Discussion: According to our findings, ICS and CCS negatively influence AIS patients' outcome treated by interventional therapies. ICS might exert an unfavorable effect both by cerebral hypoperfusion and by continuous microembolization toward ischemic area, while CCS is probable involved in reducing the collateral circles effectiveness. The importance of early carotid stenosis detection and treatment should then be reevaluated not only to manage the prevention approaches but also to obtain insights about post-stroke treatment strategies efficacy.

Detection of BRAF mutations in malignant melanoma and colorectal cancer by SensiScreen® FFPE BRAF qPCR assay.

Mutations in BRAF exon 15 lead to conformational changes in its activation loops, resulting in constitutively active BRAF proteins which are implicated in the development of several human cancer types. Different BRAF inhibitors have been developed and introduced in clinical practice. Identification of BRAF mutations influences the clinical evaluation, treatment, progression and for that reason a sensitive and specific identification of BRAF mutations is on request from the clinic. Here we present the SensiScreen® FFPE BRAF qPCR Assay that uses a novel real-time PCR-based method for BRAF mutation detection based on PentaBases proprietary DNA analogue technology designed to work on standard real-time PCR instruments. The SensiScreen® FFPE BRAF qPCR Assay displays high sensitivity, specificity, fast and easy-to-use. The SensiScreen® FFPE BRAF qPCR Assay was validated on two different FFPE tumour biopsy cohorts, one cohort included malignant melanoma patients previously analyzed by the Cobas® 4800 BRAF V600 Mutation Test, and one cohort from colorectal cancer patients previously analyzed by mutant-enriched PCR and direct sequencing. All BRAF mutant malignant melanoma patients were confirmed with the SensiScreen® FFPE BRAF qPCR Assay and additional four new mutations in the malignant melanoma cohort were identified. All the previously identified BRAF mutations in the colorectal cancer patients were confirmed, and additional three new mutations not identified with direct sequencing were detected. Also, one new BRAF mutation not previously identified with ME-PCR was found. Furthermore, the SensiScreen® FFPE BRAF qPCR Assay identified the specific change in the amino acid. The SensiScreen® FFPE BRAF qPCR Assay will contribute to a more specific, time and cost saving approach to better identify and characterize mutations in patients affected by cancer, and consequently permits a better BRAF characterization that is fundamental for therapy decision.

Predictors of Carotid Atherosclerosis Progression: Evidence from an Ultrasonography Laboratory.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the role of risk factors in predicting the variation in carotid atherosclerosis at ultrasonographic follow-up and, therefore, its role in the progression of large-vessel disease. METHODS: This retrospective population study included all the outpatients that underwent at least two carotid ultrasonographies at our laboratory from 2001 to 2017. Demographic data, vascular risk factors, and the results at follow-up were analysed to determine if correlations exist between these risk factors and variation in carotid atherosclerosis. RESULTS: Data from 600 patients (327 males and 273 females with a mean age of 67 years) were collected. The mean follow-up period was 49 months (range: 1-195). We analysed each demographic variable and risk factor to assess its correlation with a worsening of carotid atherosclerosis; previous myocardial infarction (2.594), previous carotid surgical treatment (2.368), and hypertension (1.85) were found to have the highest odds ratios, respectively. Furthermore, the sample was divided into specific subpopulations (diabetes, hypertension, and smoking), and an association was found between age and worsening stenosis. DISCUSSION AND CONCLUSIONS: Our results confirm the importance of carotid ultrasonographic follow-up in the monitoring and managing of large-vessel disease. Myocardial infarction, previous stroke, and previous surgical treatment were the strongest predictors of a worsening of carotid atherosclerosis. These findings suggest a strict follow-up is needed, even in the absence of significant carotid atherosclerosis at baseline.

Variables related to maternal satisfaction with intrapartum care in Northern Italy.

BACKGROUND: The experience of labour and birth is complex, multidimensional and subjective and has the potential to affect the women and their families physically and emotionally. However, there is a lack of research around maternal satisfaction in Italy. AIM: To evaluate mothers' satisfaction with their childbirth experience in relation to socio-demographic characteristics, obstetric history and intrapartum care variables. METHODS: A cross-sectional study involving 277 women who had given birth in a low risk maternity unit in Northern Italy was undertaken. Satisfaction with birth was measured using the Italian version of the Birth Satisfaction Scale-Revised (I-BSS-R). The scale comprises three Sub-Scales: quality of care provided, personal attributes of women and stress experienced during childbirth. FINDINGS: No socio-demographic variables were related to maternal satisfaction. Multiparous women had a higher satisfaction score (p=0.020; CI:0.23;2.75). Antenatal class attendance was negatively associated with maternal satisfaction (p=0.038; CI:-2.58; -0.07). Intrapartum variables that significantly reduced maternal satisfaction were: epidural usage (p=0.000; CI:-4.66; -2.07), active phase >12h (p=0.000; CI:-6.01; -2.63), oxytocin administration (p=0.000; CI:-5.08; -2.29) and vacuum assisted birth (p=0.001; CI:-6.50; -1.58). Women with an intact perineum were more likely to be satisfied (p=0.008; CI:-4.60; -0.69). DISCUSSION: In accordance with other research, we showed that intrapartum interventions are negatively associated with maternal outcomes and therefore also with maternal satisfaction with birth. The sub-scale that measured Quality of Care provided scored higher than the other two Sub-Scales. CONCLUSION: Further studies on maternal satisfaction in Italy should be conducted, using the I-BSS-R with the aim to compare outcomes and understand what matters to women during childbirth.

A new sensitive and fast assay for the detection of EGFR mutations in liquid biopsies.

BACKGROUND: A major perspective for the use of circulating tumor DNA (ctDNA) in the clinical setting of non-small cell lung cancer (NSCLC) is expected as predictive factor for resistance and response to EGFR TKI therapy and, especially, as a non-invasive alternative to tissue biopsy. However, ctDNA is both highly fragmented and mostly low concentrated in plasma and serum. On this basis, it is important to use a platform characterized by high sensitivity and linear performance in the low concentration range. This motivated us to evaluate the newly developed and commercially available SensiScreen® EGFR Liquid assay platform (PentaBase) with regard to sensitivity, linearity, repeatability and accuracy and finally to compare it to our already implemented methods. The validation was made in three independent European laboratories using two cohorts on a total of 68 unique liquid biopsies. RESULTS: Using artificial samples containing 1600 copies of WT DNA spiked with 50% - 0.1% of mutant copies across a seven-log dilution scale, we assessed the sensitivity, linearity, repeatability and accuracy for the p.T790M, p.L858R and exon 19 deletion assays of the SensiScreen® EGFR Liquid assay platform. The lowest value detectable ranged from 0.5% to 0.1% with R2≥0,97 indicating good linearity. High PCR efficiency was shown for all three assays. In 102 single PCRs each containing theoretical one copy of the mutant at initiating, assays showed repeatable positivity in 75.5% - 80.4% of reactions. At low ctDNA levels, as in plasma, the SensiScreen® EGFR Liquid assay platform showed better sensitivity than the Therascreen® EGFR platform (Qiagen) and equal performance to the ctEGFR Mutation Detection Kit (EntroGen) and the IOT® Oncomine cell-free nucleic acids assay (Thermo Fisher Scientific) with 100% concordance at the sequence level. CONCLUSION: For profiling clinical plasma samples, characterized by low ctDNA abundance, the SensiScreen® EGFR Liquid assay is able to identify down to 1 copy of mutant alleles and with its high sensitivity, linearity and accuracy it may be a competitive platform of choice.

Heart rate variability: Can it serve as a marker of mental health resilience?: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD.

BACKGROUND: Stress resilience influences mental well-being and vulnerability to psychiatric disorders. Usually, measurement of resilience is based on subjective reports, susceptible to biases. It justifies the need for objective biological/physiological biomarkers of resilience. One promising candidate as biomarker of mental health resilience (MHR) is heart rate variability (HRV). The evidence for its use was reviewed in this study. METHODS: We focused on the relationship between HRV (as measured through decomposition of RR intervals from electrocardiogram) and responses to laboratory stressors in individuals without medical and psychiatric diseases. We conducted a bibliographic search of publications in the PubMed for January 2010-September 2018. RESULTS: Eight studies were included. High vagally mediated HRV before and/or during stressful laboratory tasks was associated with enhanced cognitive resilience to competitive/self-control challenges, appropriate emotional regulation during emotional tasks, and better modulation of cortisol, cardiovascular and inflammatory responses during psychosocial/mental tasks. LIMITATIONS: All studies were cross-sectional, restricting conclusions that can be made. Most studies included only young participants, with some samples of only males or females, and a limited array of HRV indexes. Ecological validity of stressful laboratory tasks remains unclear. CONCLUSIONS: Vagally mediated HRV may serve as a global index of an individual's flexibility and adaptability to stressors. This supports the idea of HRV as a plausible, noninvasive, and easily applicable biomarker of MHR. In future longitudinal studies, the implementation of wearable health devices, able to record HRV in naturalistic contexts of real-life, may be a valuable strategy to gain more reliable insight into this topic.

The neuropsychological and neuroradiological correlates of slowly progressive visual agnosia.

The case of a 64-year-old woman affected by slowly progressive visual agnosia is reported aiming to describe specific cognitive-brain relationships. Longitudinal clinical and neuropsychological assessment, combined with magnetic resonance imaging (MRI), spectroscopy, and positron emission tomography (PET) were used. Sequential neuropsychological evaluations performed during a period of 9 years since disease onset showed the appearance of apperceptive and associative visual agnosia, alexia without agraphia, agraphia, finger agnosia, and prosopoagnosia, but excluded dementia. MRI showed moderate diffuse cortical atrophy, with predominant atrophy in the left posterior cortical areas (temporal, parietal, and lateral occipital cortical gyri). 18FDG-PET showed marked bilateral posterior cortical hypometabolism; proton magnetic resonance spectroscopic imaging disclosed severe focal N-acetyl-aspartate depletion in the left temporoparietal and lateral occipital cortical areas. In conclusion, selective metabolic alterations and neuronal loss in the left temporoparietooccipital cortex may determine progressive visual agnosia in the absence of dementia.

Are there advances in pharmacotherapy for panic disorder? A systematic review of the past five years.

INTRODUCTION: Several effective medications are available for treating panic disorder (PD). However, outcomes are unsatisfactory in a number of patients, suggesting the usefulness of expanding the array of antipanic drugs and improving the quality of response to current recommended treatments. AREAS COVERED: The authors have performed an updated systematic review of pharmacological studies (phase III onwards) to examine whether advances have been made in the last five years. Only four studies were included. D-cycloserine no longer seemed promising as a cognitive-behavioral therapy (CBT) enhancer. Some preliminary findings concerning the optimization of recommended medications deserved consideration, including: the possibility that SSRIs are more effective than CBT alone in treating panic attacks, combined therapy is preferable when agoraphobia is present, and clonazepam is more potent than paroxetine in decreasing panic relapse. EXPERT OPINION: Given the lack of novel treatments, expanding a personalized approach to the existing medications seems to be the most feasible strategy to improve pharmacotherapy outcomes regarding PD. Recent technological progress, including wearable devices collecting real-time data, 'big data' platforms, and application of machine learning techniques might help make outcome prediction more reliable. Further research on previously promising novel treatments is also recommended.

Deregulation of sialidases in human normal and tumor tissues.

BACKGROUND: Aberrant sialylation is a characteristic feature associated with cancer. The four types of mammalian sialidases identified to date have been shown to behave in different manners during carcinogenesis. While NEU1, NEU2 and NEU4 have been observed to oppose malignant phenotypes, the membrane-bound sialidase NEU3 was revealed to promote cancer progression. OBJECTIVES: With the aim of improving the knowledge about sialidases deregulation in various cancer types, we investigated the amount of NEU1, NEU3 and NEU4 transcripts in paired normal and tumor tissues from 170 patients with 11 cancer types. METHODS: mRNA was extracted from patients' tissue specimens and retrotranscribed into cDNA, which was quantified by Real-Time PCR. RESULTS: We found NEU1 and NEU3 to be up regulated, while NEU4 was down regulated in most cancer types. In particular, colorectal cancer tissues showed the highest increase in NEU3 expression. Both NEU1 and NEU3 showed a strong up-regulation in ovarian cancer. CONCLUSIONS: Our data show that human sialidases are expressed at different levels in healthy tissues and are strongly deregulated in tumors. Moreover, sialidases expression in our European cohort showed significant differences from Asian populations. Some of these peculiar features open potential applications of sialidases in cancer diagnosis and therapy.

SensiScreen®KRAS exon 2-sensitive simplex and multiplex real-time PCR-based assays for detection of KRAS exon 2 mutations.

Activating mutations in codon 12 and codon 13 of the KRAS (Kirsten rat sarcoma viral oncogene homolog) gene are implicated in the development of several human cancer types and influence their clinical evaluation, treatment and prognosis. Numerous different methods for KRAS genotyping are currently available displaying a wide range of sensitivities, time to answer and requirements for laboratory equipment and user skills. Here we present SensiScreen® KRAS exon 2 simplex and multiplex CE IVD assays, that use a novel real-time PCR-based method for KRAS mutation detection based on PentaBase's proprietary DNA analogue technology and designed to work on standard real-time PCR instruments. By means of the included BaseBlocker™ technology, we show that SensiScreen® specifically amplifies the mutated alleles of interest with no or highly subdued amplification of the wild type allele. Furthermore, serial dilutions of mutant DNA in a wild type background demonstrate that all SensiScreen® assays display a limit of detection that falls within the range of 0.25-1%. Finally, in three different colorectal cancer patient populations, SensiScreen® assays confirmed the KRAS genotype previously determined by commonly used methods for KRAS mutation testing, and notably, in two of the populations, SensiScreen® identified additional mutant positive cases not detected by common methods.

ALK testing in lung adenocarcinoma: technical aspects to improve FISH evaluation in daily practice.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) gene rearrangement characterizes a subgroup of patients with lung adenocarcinoma who may benefit from ALK inhibitors. Fluorescence in situ hybridization (FISH) with a break-apart/split-signal strategy is the gold standard to investigate ALK. The cutoff to define ALK positivity has been settled at 15% or greater. A subset of patients has ALK borderline status, showing 15% ± 5% positive cells. Several aspects, both biological and technical, might influence signals evaluation, making FISH interpretation a challenging task. To improve ALK evaluation, we classified the different FISH patterns on the basis of the type of the split signals, namely short, long, far away, and deleted. METHODS: We investigated ALK gene status by FISH in 244 lung adenocarcinomas and in a series of ALK negative cell lines samples, collected in three Institutions. RESULTS: ALK positive profile was found in 12% of patients; long, deleted, and far-away splits were the primary patterns observed. ALK borderline profile characterized 10% of samples; long and deleted splits were significantly more frequent in those borderline finally classified as ALK positive, whereas short split were mostly detected in those borderline patients finally classified as ALK negative (p = 3.4 × 10). In the ALK negative control series, short split was the predominant pattern. Concordance was observed among different operators and probes for both samples and controls. CONCLUSIONS: Difficulties in ALK FISH signal interpretation might be bypassed using this detailed scoring system, which is highly reproducible, helps clarify borderline samples (according to split type), and provides experimental evidence that 15% is a reasonable cutoff to overcome the assay-dependent background noise.