Prospective Comparison of Longer Needle Lengths to Assess the Risk of OnabotulinumtoxinA-Associated Neck Pain in Patients with Chronic Migraine.

BACKGROUND: We aimed to prospectively assess the role of needle length in improving the tolerability/safety profile of OnabotulinumtoxinA (BoNTA) for chronic migraine (CM) prophylaxis, with a specific focus on neck pain, based on patients' body habitus and other variables. METHODS: BoNTA was administered quarterly for two consecutive cycles, using the standard 0.5-inch 27 G needle at all pre-defined PREEMPT injection sites, except the left-hand side trapezius and paraspinal muscles, which were injected using longer needles of 1-inch 23 G at first and 1-inch 27 G at second infusion. Participants were interviewed at day 14 following each session for evidence of neck pain. The predictive significance of Body Mass Index (BMI) and other variables with neck pain was also examined. RESULTS: A total of 100 consecutive CM patients were evaluated, and each patient served as her/his self-control. The incidence, duration and intensity of neck pain did not significantly differ using either 1-inch needle compared with standard 0.5-inch 27 G needle, although the incidence and characteristics of neck pain with the use of longer needles appeared slightly higher and more intense. The BMI index and other tested variables remained unrelated to neck pain. CONCLUSIONS: We were not able to identify significant differences or correlations in the incidence, characteristics and location of neck pain with the use of different needle length to inject BoNTA, although the use of the longer 1-inch needles likely increased the risk of this adverse event.

Assessing the Significance of the Circadian Time of Administration on the Effectiveness and Tolerability of OnabotulinumtoxinA for Chronic Migraine Prophylaxis.

We aimed to provide insights on the role of the circadian time of administration in influencing the efficacy and tolerability/safety profile of OnabotulinumtoxinA (BoNTA) for chronic migraine (CM) prophylaxis. Methods: We retrospectively reviewed the medical files of BoNTA-naïve patients with CM who completed three consecutive cycles of treatment, according to the standard PREEMPT paradigm. Participants were classified to those scheduled to be treated in the morning hours from 8:00 to 12:00 (AM) or afternoon hours from 13:00 to 18:00 (PM). We then assessed and compared between groups the changes from baseline (T0­trimester before BoNTA's first administration) to the period after its third administration (T3) in the following efficacy outcomes: (i) mean number of headache days/month, (ii) mean number of days/month with peak headache intensity of >4/10, (iii) mean number of days/month with consumption of any abortive treatment. Safety−tolerability was also compared between groups. Results: A total of 50 AM and 50 PM-treated patients were evaluated. The within-group analysis in both groups showed a significant decrease in all efficacy variables between T0 and T3. However, the between-group comparisons of all BoNTA-related efficacy outcomes at T3 vs. T0 documented comparable improvements between AM vs. PM-treated patients. Safety/tolerability was also similar between groups. Conclusions: We were not able to identify significant differences between patients treated in the AM vs. PM, so as to demonstrate that the circadian time of administration should be considered before initiating BoNTA in CM patients.

Long-term adherence, safety, and efficacy of repeated onabotulinumtoxinA over five years in chronic migraine prophylaxis.

BACKGROUND: OnabotulinumtoxinA (BoNTA) demonstrated a positive benefit-risk in chronic migraine (CM) patients in PREEMPT I and II phase III trials and many subsequent real-world studies. We herein aimed at evaluating the adherence to repeated BoNTA over a period of five years, while secondary objectives included the assessment of its long-term safety/efficacy and patients' satisfaction to treatment. METHODS: We studied 56 CM patients who had successfully received consequent cycles of BoNTA over five years. Adherence was calculated as the percentage of patients actively choosing to follow with repeated BoNTA treatment, as instructed. Safety and efficacy data were collected throughout the study period. The overall patients' belief in and satisfaction by the efficacy of treatment was assessed at last follow-up, using the self-report 7-point measure patient global impression of change (PGIC). RESULTS: A total of 36 (64.3%) out of 56 patients remained adherent to BoNTA over five years. Long-term BoNTA exposure was safe and well-tolerated, without severe side-effects justifying treatment discontinuation. The mean monthly headache days and associated clinical efficacy outcomes remained consistent and quite low at last follow-up with evidence of continuous improvements in headache monthly frequency between year three and over five years of therapy. All patients who were able to maintain treatment over five years (n = 36), remained very satisfied and scored at least 5 in PGIC. CONCLUSION: Considerably high adherence, considerable satisfaction and sustained safety/efficacy were observed in patients followed up for five years, supporting a favorable benefit/risk profile for consistently delivering long-term BoNTA in CM.

Mosquito population structure, pathogen surveillance and insecticide resistance monitoring in urban regions of Crete, Greece.

BACKGROUND: In Greece vector borne diseases (VBD) and foremost West Nile virus (WNV) pose an important threat to public health and the tourist industry, the primary sector of contribution to the national economy. The island of Crete, is one of Greece's major tourist destinations receiving annually over 5 million tourists making regional VBD control both a public health and economic priority. METHODOLOGY: Under the auspices of the Region of Crete, a systematic integrative surveillance network targeting mosquitoes and associated pathogens was established in Crete for the years 2018-2020. Using conventional and molecular diagnostic tools we investigated the mosquito species composition and population dynamics, pathogen infection occurrences in vector populations and in sentinel chickens, and the insecticide resistance status of the major vector species. PRINCIPAL FINDINGS: Important disease vectors were recorded across the island including Culex pipiens, Aedes albopictus, and Anopheles superpictus. Over 75% of the sampled specimens were collected in the western prefectures potentially attributed to the local precipitation patterns, with Cx. pipiens being the most dominant species. Although no pathogens (flaviviruses) were detected in the analysed mosquito specimens, chicken blood serum analyses recorded a 1.7% WNV antibody detection rate in the 2018 samples. Notably detection of the first WNV positive chicken preceded human WNV occurrence in the same region by approximately two weeks. The chitin synthase mutation I1043F (associated with high diflubenzuron resistance) was recorded at an 8% allelic frequency in Lasithi prefecture Cx. pipiens mosquitoes (sampled in 2020) for the first time in Greece. Markedly, Cx. pipiens populations in all four prefectures were found harboring the kdr mutations L1014F/C/S (associated with pyrethroid resistance) at a close to fixation rate, with mutation L1014C being the most commonly found allele (≥74% representation). Voltage gated sodium channel analyses in Ae. albopictus revealed the presence of the kdr mutations F1534C and I1532T (associated with putative mild pyrethroid resistance phenotypes) yet absence of V1016G. Allele F1534C was recorded in all prefectures (at an allelic frequency range of 25-46.6%) while I1532T was detected in populations from Chania, Rethymnon and Heraklion (at frequencies below 7.1%). Finally, no kdr mutations were detected in the Anopheles specimens included in the analyses. CONCLUSIONS/SIGNIFICANCE: The findings of our study are of major concern for VBD control in Crete, highlighting (i) the necessity for establishing seasonal integrated entomological/pathogen surveillance programs, supporting the design of targeted vector control responses and; ii) the need for establishing appropriate insecticide resistance management programs ensuring the efficacy and sustainable use of DFB and pyrethroid based products in vector control.

The role of Mediterranean diet in the course of subjective cognitive decline in the elderly population of Greece: results from a prospective cohort study.

Very few data are available regarding the association of adherence to the Mediterranean Diet (MeDi) with Subjective Cognitive Decline (SCD) evolution over time. A cohort of 939 cognitively normal individuals reporting self-experienced, persistent cognitive decline not attributed to neurological, psychiatric or medical disorders from the Hellenic Epidemiological Longitudinal Investigation of Aging and Diet (HELIAD study) was followed-up for a mean period of 3·10 years. We defined our SCD score as the number of reported SCD domains (memory, language, visuoperceptual and executive), ranging from 0 to 4. Dietary intake at baseline was assessed through a food frequency questionnaire; adherence to the MeDi pattern was evaluated through the Mediterranean Diet Score (MDS) that ranged from 0 to 55, with higher values indicating greater adherence to the MeDi. The mean SCD score in our cohort increased by 0·20 cognitive domains during follow-up. After adjustment for multiple potential confounders, we showed that an MDS higher by 10 points was associated with a 7% reduction in the progression of SCD within one year. In terms of food groups, every additional vegetable serving consumption per day was associated with a 2·2% reduction in SCD progression per year. Our results provide support to the notion that MeDi may have a protective role against the whole continuum of cognitive decline, starting at the first subjective complaints. This finding may strengthen the role of the MeDi as a population-wide, cost-effective preventive strategy targeting the modifiable risk factors for cognitive decline.

Incidence of mild cognitive impairment in the elderly population in Greece: results from the HELIAD study.

BACKGROUND: There are no published data on Mild Cognitive Impairment (MCI) incidence in people over 65 years of age in Greece, relevant literature is scarce for Southern Europe, and reported rates worldwide show great variability. AIMS: To investigate the incidence and risk factors of MCI and its subtypes in the elderly population in Greece. METHODS: The incidence cohort of the HELIAD study (Hellenic Epidemiological Longitudinal Investigation of Aging and Diet) comprised 955 individuals who received full neurological and neuropsychological evaluation on two separate occasions about three years apart. RESULTS: The MCI incidence rate in our cohort is 54.07 new cases per 1000 person-years, standardized by age and sex to 59.99. Each additional year of age over 65 raises the probability of novel MCI by 6.2%, while lower educational attainment more than doubles the risk for incident MCI. Apolipoprotein E-ε4 (APOE-ε4) carriage results in increased risk for MCI by more than 1.7 times. Incidence rates for amnestic MCI are slightly higher than for the non-amnestic subtype, and AD is the most common potential underlying etiology. DISCUSSION: The MCI incidence rate in the Greek population over 65 years of age is 54/1000 person-years. Advanced age and APOE-ε4 carriage are predisposing factors, while higher educational attainment was found to exert a protective effect. CONCLUSIONS: MCI incidence in people over 65 years-old in Greece is consistent with reported rates around the world. Larger studies encompassing neuroimaging and cerebrospinal fluid biomarkers will hopefully shed more light on MCI epidemiology in Greece in the future.

Dementia Incidence in the Elderly Population of Greece: Results From the HELIAD Study.

OBJECTIVES: Recently a declining trend in dementia incidence rates has been reported in high-income countries. We investigated dementia incidence in a representative sample of the Greek population in the age group of 65 years and above. METHODS: This research is part of the Hellenic Epidemiological Longitudinal Investigation of Aging and Diet (HELIAD). The incidence cohort consisted of 1072 participants who were reevaluated after a mean period of 3.09 years. RESULTS: The incidence rate of dementia was 19.0 cases per 1000 person-years (age-standardized and sex-standardized incidence: 25.4/1000 person-years), of which 16.3 per 1000 person-years were attributable to Alzheimer disease. Each additional year of age increased dementia risk by 19.3% and each additional year of education decreased dementia risk by 12.1%. Apolipoprotein E (APOE)-ε4 homozygous participants were 18 times more likely to be diagnosed with dementia. A baseline diagnosis of mild cognitive decline (MCI) resulted in a risk for dementia increased by 3.7 times compared with the cognitively normal; in participants with MCI at baseline, APOE-ε4 carriage increased dementia risk by 4.5 times. CONCLUSIONS: The incidence rate of dementia in people 65 years and above in Greece is generally consistent with recently published rates in Europe and North America. Advancing age, baseline MCI, and APOE-ε4 homozygosity are risk factors, while higher educational attainment seems protective.

Open Label Prospective Experience of Supplementation with a Fixed Combination of Magnesium, Vitamin B2, Feverfew, Andrographis Paniculata and Coenzyme Q10 for Episodic Migraine Prophylaxis.

BACKGROUND: To investigate the efficacy and safety of supplementation with a fixed combination of magnesium, vitamin B2, feverfew, andrographis paniculata and coenzyme Q10 in episodic migraine (EM) prevention. METHODS: A pilot, single-arm, open-label study was conducted. After a one-month baseline period, the above-described supplementation was introduced in 113 EM Greek patients, who were prospectively followed-up for three months. The primary endpoint was the change in monthly migraine days between baseline period (BSL) and the third month of supplementation (T3). Secondary endpoints included changes in mean intensity of migraine and in days with use of acute migraine medications. Changes in scores of Migraine Disability Assessment questionnaire (MIDAS), Headache Impact Test-6 (HIT-6), Migraine Therapy Assessment questionnaire (MTAQ), Migraine-Specific Quality-of-life questionnaire (MSQ-QOL), Hospital Anxiety and Depression Scale (HADS) were also evaluated. Those with ≥50% reduction in monthly migraine days at T3, compared to BSL were considered supplementation-responders. RESULTS: The mean number of migraine days was significantly decreased between BSL and T3 (9.4 ± 3.7 vs. 6.1 ± 3.5; p < 0.001). Likewise, days with peak headache intensity of >4/10 (5.7 ± 3.4 vs. 4.9 ± 3.1; p < 0.001) as well as days using acute headache medications per month (8.9 ± 3.6 vs. 5.7 ± 3.4; p < 0.001) were significantly reduced. At T3, 64 patients (56.6%) were classified as responders. The beneficial effect of supplementation was also associated with significant changes in HIT-6, MIDAS, MTAQ and MSQ-QOL scores. There were no safety concerns. CONCLUSIONS: The supplementation we have tested appears to be an effective and well-tolerated preventive approach against EM. A randomized, placebo-controlled study is needed to confirm our results.

Prevalence of Mild Cognitive Impairment in the Elderly Population in Greece: Results From the HELIAD Study.

INTRODUCTION: Timely recognition of mild cognitive impairment (MCI) is essential in optimizing prevention and treatment for Alzheimer disease. Because of the paucity of data on MCI epidemiology in Greece and the variability of worldwide published results, we investigated the prevalence and determinants of MCI in the elderly population in Greece. METHODS: As part of the Hellenic Epidemiological Longitudinal Investigation of Aging and Diet (HELIAD), we randomly selected 1960 individuals 65 years and older to undergo full neurological and neuropsychological assessment by a multidisciplinary team. MCI was diagnosed according to the Petersen criteria. RESULTS: The age-standardized and gender-standardized prevalence of MCI in people aged 65 years and older in Greece is 13.11%. The amnestic and multidomain MCI subtypes are more common than their nonamnestic and single-domain counterparts, respectively. Almost two thirds of cases are because of suspected Alzheimer disease. Every additional year of age increases the odds of prevalent MCI by 7.4%, every additional year of education decreases the odds of MCI by 6.3%, and apolipoprotein E (APOE-ε4) carriage increases the odds of MCI by 57.9%. CONCLUSIONS: MCI prevalence in the elderly population in Greece is on par with previously reported rates. Prospective studies with robust methodology will enhance our understanding of the dementia continuum.

Exploring the association between subjective cognitive decline and frailty: the Hellenic Longitudinal Investigation of Aging and Diet Study (HELIAD).

Background: Subjective cognitive decline (SCD) refers to self-evaluations of impairment in cognitive functions in the absence of objective deficits. Frailty is a multidimensional syndrome that results in increased vulnerability. Both terms are associated with cognitive decline and increased incidence of dementia. The aim of this study was to explore potential associations between SCD and frailty in elderly individuals.Methods: In this cross-sectional study, we included 1454 participants aged 65 and older from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study. Individuals with a diagnosis of dementia, mild cognitive impairment, severe anxiety or depression were excluded. SCD were assessed with eighteen questions categorized into cognitive domains. Frailty was assessed according to the Fried definition, the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI). Logistic regression analysis was used to investigate the association.Results: Lower educational level, female sex and low socioeconomic status were found to be associated with frailty and more SCD complaints. Having two or more types of SCD complaints was significantly associated with frailty according to all frailty definitions. All types of SCD complaints were significantly associated with the FI and the TFI. In addition, SCD complaints concerning problems requiring mathematical reasoning had the strongest association with frailty.Conclusion: We found that SCD complaints may be a valid indicator of frailty in cognitively unimpaired older people. We believe that SCD may provide a crucial proactive assessment to detect frailty and to implement programs that will help maintain good health and quality of life during aging.

Dietary interventions in mild cognitive impairment and dementia.

Dietary intervention is an enticing approach in the fight against cognitive impairment. Nutritional supplements and dietetic counseling are relatively easy and benign interventions, but research has not yet yielded irrefutable evidence as to their clinical utility. Heterogeneity in the results of available clinical studies, as well as methodological and practical issues, does not allow replication and generalization of findings. The paper at hand reviews only randomized clinical trials of single nutrients, multi-nutrient formulations and dietary counseling in mild cognitive impairment and dementia of the Alzheimer's type focusing on both cognitive and functional outcomes. Thus far, folate, vitamin E, Ω-3 fatty acids, and certain multi-nutrient formulations have shown some preliminary promising results; larger, well-designed trials are needed to confirm these findings before nutritional elements can be incorporated in recommended clinical guidelines.

Prevalence and determinants of subjective cognitive decline in a representative Greek elderly population.

OBJECTIVES: We studied the prevalence of subjective cognitive decline (SCD) and its determinants in a sample of 1456 cognitively normal Greek adults ≥65 years old. METHODS/DESIGN: Subjects were evaluated by a multidisciplinary team on their neurological, medical, neuropsychological, and lifestyle profile to reach consensus diagnoses. We investigated various types of SCD, including single-question, general memory decline, specific subjective memory decline based on a list of questions and three types of subjective naming, orientation, and calculation decline. RESULTS: In a single general question about memory decline, 28.0% responded positively. The percentage of our sample that reported at least one complaint related to subjective memory decline was 76.6%. Naming difficulties were also fairly common (26.0%), while specific deficits in orientation (5.4%) and calculations/currency handling (2.6%) were rare. The majority (84.2%) of the population reported subjective deficits in at least one cognitive domain. Genetic predisposition to dementia increased the odds for general memory decline by more than 1.7 times. For each one-unit reduction in the neuropsychological composite score (a mean of memory, executive, language, visuospatial, and attention-speed composite scores), the odds for decline in orientation increased by 40.3%. Depression/anxiety and increased cerebrovascular risk were risk factors for almost all SCD types. CONCLUSIONS: SCD regarding memory is more frequent than non-memory decline in the cognitively normal Greek elderly population. Genetic predisposition to dementia, lower cognitive performance, affective symptoms, and increased cerebrovascular risk are associated with prevalent SCD. Further prospective research is needed to improve understanding of the evolution of SCD over time.

Dementia Prevalence in Greece: The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD).

INTRODUCTION: Study of the epidemiology of dementia to gain insight into putative predisposing and prophylactic factors is the first step toward establishing effective preventive and therapeutic strategies for this ever-growing public health problem. Relevant data in Greece are scattered and outdated. METHODS: We investigated dementia prevalence as part of a population-representative epidemiological study [Hellenic Longitudinal Investigation of Aging and Diet (HELIAD)] in 2 Greek regions. RESULTS: Our sample comprised 1792 adults 65 years of age or older, who received a full neurological and neuropsychological evaluation that led to a consensus diagnosis. The overall prevalence of dementia was 5.0%, with 75.3% of the cases attributed to Alzheimer disease. Dementia odds were 15.8% higher for every year of advancing age and 9.4% lower for every additional year of education. Carrying at least 1 APOE-ε4 allele doubled the risk of dementia, whereas sex did not exert a statistically significant effect. CONCLUSIONS: Our results are consistent with previous research in Southern European countries; dementia prevalence in Greece is in the lower range of what has been reported globally.

Subserosal uterine injection of blue dye for the identification of the sentinel node in patients with endometrial cancer: a feasibility study.

OBJECTIVE: To define the detection rate, sensitivity, and negative predictive value (NPV) of the sentinel node technique in patients with endometrial cancer. METHODS: Patients with endometrial cancer after informed consent underwent subserosal injection of blue dye during hysterectomy in a tertiary gynae/oncology department between 2010 and 2014. The procedure was performed in all cases by the same team including two gynae/oncologist consultants and one trainee. All relevant perioperative clinicopathological characteristics of the population were recorded prospectively. The identified sentinel nodes were removed separately and a completion bilateral pelvic lymphadenectomy followed in all cases. Simple statistics were used to calculate the sensitivity and NPV of the method on per patient basis. RESULTS: Fifty-four patients were included in this study. At least one sentinel node was mapped in 46 patients yielding a detection rate of 85.2%. Bilateral detection of sentinel nodes was accomplished in only 31 patients (57.4%). The mean number of sentinel nodes was 2.6 per patient and the commonest site of identification was the external iliac artery and vein area (66%). Six patients (11%) had a positive lymph node, and in five of them, this was the sentinel one yielding a sensitivity of 83.3% and an NPV of 97.5%. The overall detection rate improved significantly after the first 15 cases; however, this was not the case for the bilateral detection rate. CONCLUSION: Our study is in accordance with previous studies of sentinel node in endometrial cancer and further demonstrates and enhances the confidence in the technique. In the current era of an ongoing debate on whether a systematic lymphadenectomy in patients with endometrial cancer is still necessary, we believe that the sentinel node is an acceptable alternative and should be applied routinely in tertiary centres following a strict algorithm.

Clinical experience with transcutaneous supraorbital nerve stimulation in patients with refractory migraine or with migraine and intolerance to topiramate: a prospective exploratory clinical study.

BACKGROUND: Migraine is included in the top-ten disabling diseases and conditions among the Western populations. Non-invasive neurostimulation, including the Cefaly® device, for the treatment of various types of pain is a relatively new field of interest. The aim of the present study was to explore the clinical experience with Cefaly® in a cohort of migraine patients previously refractory or intolerant to topiramate prophylaxis. METHODS: A prospective, multi-center clinical study was performed in patients diagnosed with episodic or chronic migraine with a previous failure to topiramate treatment requiring prevention with Cefaly® according to the treating physician's suggestion. A 1-month period of baseline observation was followed by a 3-month period of observation during the use of transcutaneous supraorbital nerve stimulation (t-SNS) with Cefaly® as the only preventive treatment. RESULTS: A small but statistically significant decline was shown over time in the number of days with headache (HA), the number of days with HA with intensity ≥5/10, and the number of days with use of acute medication after 3 months (p < 0.001 for all of the three changes). Twenty-three patients (65.7%) expressed their satisfaction and intent to continue treatment with Cefaly®. Compliance was higher among satisfied subjects compared to non-satisfied subjects. None of the explored factors were significantly associated with the reason for the failure of topiramate. CONCLUSION: Three-months of preventive treatment for episodic or chronic migraine with t-SNS proved to be an effective, safe and well tolerated option for the treatment of patients with migraine who were intolerant or did not respond to topiramate. TRIAL REGISTRATION: ClinicalTrials NCT03125525 . Registered 21 April 2017.

Differential Expression of miR-4520a Associated With Pyrin Mutations in Familial Mediterranean Fever (FMF).

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent, acute, and self-limiting attacks of fever. Mutations in MEFV gene encoding pyrin account for FMF, but the high number of heterozygote patients with typical symptoms of the disease has driven a number of alternative aetiopathogenic hypotheses. The MEFV gene was knocked down in human myelomonocytic cells that express endogenous pyrin to identify deregulated microRNAs (miRNAs). Microarray analyses revealed 29 significantly differentially expressed miRNAs implicated in pathways associated with cellular integrity and survival. Implementation of in silico gene network prediction algorithms and bioinformatics analyses showed that miR-4520a is predicted to target genes implicated in autophagy through regulation of RHEB/mTOR signaling. Differential expression levels of RHEB were confirmed by luciferase reporter gene assays providing further evidence that is directly targeted by miR-4520a. Although the relative expression levels of miR-4520a were variable among FMF patients, the statistical expression of miR-4520a was different between FMF mutation carriers and controls (P = 0.0061), indicating an association between miR-4520a expression and MEFV mutations. Comparison between FMF patients bearing the M694V mutation, associated with severe disease, and healthy controls showed a significant increase in miR-4520a expression levels (P = 0.00545). These data suggest that RHEB, the main activator of mTOR signaling, is a valid target of miR-4520a with the relative expression levels of the latter being significantly deregulated in FMF patients and highly dependent on the presence of pyrin mutations, especially of the M694V type. These results suggest a role of deregulated autophagy in the pathogenesis of FMF. J. Cell. Physiol. 232: 1326-1336, 2017. © 2016 Wiley Periodicals, Inc.

Profiling of Discrete Gynecological Cancers Reveals Novel Transcriptional Modules and Common Features Shared by Other Cancer Types and Embryonic Stem Cells.

Studies on individual types of gynecological cancers (GCs), utilizing novel expression technologies, have revealed specific pathogenetic patterns and gene markers for cervical (CC), endometrial (EC) and vulvar cancer (VC). Although the clinical phenotypes of the three types of gynecological cancers are discrete, the fact they originate from a common embryological origin, has led to the hypothesis that they might share common features reflecting regression to early embryogenesis. To address this question, we performed a comprehensive comparative analysis of their profiles. Our data identified both common features (pathways and networks) and novel distinct modules controlling the same deregulated biological processes in all three types. Specifically, four novel transcriptional modules were discovered regulating cell cycle and apoptosis. Integration and comparison of our data with other databases, led to the identification of common features among cancer types, embryonic stem (ES) cells and the newly discovered cell population of squamocolumnar (SC) junction of the cervix, considered to host the early cancer events. Conclusively, these data lead us to propose the presence of common features among gynecological cancers, other types of cancers, ES cells and the pre-malignant SC junction cells, where the novel E2F/NFY and MAX/CEBP modules play an important role for the pathogenesis of gynecological carcinomas.

Low mutational burden of eight genes involved in the MAPK/ERK, PI3K/AKT, and GNAQ/11 pathways in female genital tract primary melanomas.

Mucosal melanomas exhibit discrete genetic features compared to cutaneous melanoma. Limited studies on gynecological melanomas revealed significant heterogeneity and low mutational burden. To gain further insight into their genetics and DNA repair efficiency, we systematically investigated the status of eight genes whose products are critically involved in the MAPK/ERK, PI3K/AKT, and GNAQ/11 pathways, including BRAF, NRAS, HRAS, KRAS, c-KIT, PI3K, GNAQ, and GNA11, in a series of 16 primary gynecological melanomas, covering all anatomical locations, ranging from stages I to III. Analysis either by real-time PCR coupled with fluorescence melting curve analysis or by PCR followed by direct sequencing, along with studies for DNA mismatch repair status using immunohistochemistry, disclosed that 15 out of the 16 cases displayed wild-type genotypes, with a single case of vulvar primary melanoma, harboring the activating mutation BRAF(V600E). Investigations on whether this could reflect partly an efficient mismatch repair (MMR) mechanism were confirmed by normal expression of hMLH1 and hMSH2, suggesting that the lack of mutations could be explained by the operation of alternative pathogenetic mechanisms modulating downstream effectors of the signaling pathways. Our data suggest the presence of additional genetic components and provide the impetus for systematic approaches to reveal these yet unidentified genetic parameters.

Hypoglycemia-induced hemichorea in a patient with Fahr's syndrome.

Non-ketotic hyperglycemia may be a cause of hemiballism-hemichorea. We present an elderly female type II diabetic patient with right-sided hemiballism-hemichorea of acute onset during hypoglycemia following insulin overtreatment of non-ketotic hyperglycemia. Brain computerized tomography and magnetic resonance imaging scans revealed characteristic hyperdensity and T1 hyperintensity, respectively, in the left basal ganglia, in addition to pallido-dentate calcifications, suggestive of Fahr's syndrome. Although extremely rare, hypoglycemia may be a cause of hemiballism-hemichorea especially in the presence of predisposing factors such as previous hyperglycemic episodes and Fahr's syndrome.