ZeroExpander® effectiveness assessment in PEEK or PA12 in a group of paediatric patients with transverse maxillary deficiency.

AIM: The aim of this article is to compare the performance of ZeroExpander® realised using PEEK or PA12 for the expansion of the maxilla in paediatric patients, exploring a new concept for approaching maxillary expansion with a metal-free fixed automatic appliance, based on pre-programmed set-up and anchored on deciduous teeth. MATERIALS: It is a retrospective comparative study with a sample of 40 children in early or mixed deciduous dentition and transversal maxillary deficit, 20 treated with ZeroExpander® in PEEK and 20 treated with ZeroExpander® in PA12 with a mean age of 7.3 years old. The intraoral scans at T0 and at the end of the expansion were all performed by the same operator to obtain digital models on which were performed measurements by two other different operators. A descriptive analysis was conducted using frequencies and percentages for nominal variables and means and standard deviations for continuous variables. CONCLUSION: In cases of allergy or hypersensitivity to metals or to specific chronic or acute pathological conditions, which may require periodic magnetic resonance imaging (MRI), it may not be possible to use traditional and metal fixed expansion devices. Moreover the concept of autonomous driving in paediatric orthodontics is not only possible, but it is and will be more real and very useful in the future. The "ortho-paediatric dentistry concept" will increase the range of benefits for children and their families which, in addition to care and thanks to technology, demand well-being, safety, comfort and quality of life beyond clinics.

Epileptic encephalopathies and progressive neurodegeneration.

Developmental encephalopathies (DE), epileptic encephalopathies (EE) and developmental and epileptic encephalopathies (DEE) are overlapping neurodevelopmental disorders characterized by early-onset, often severe epileptic seizures, developmental delay, or regression and have multiple etiologies. Classical nosology in child neurology distinguished progressive and nonprogressive conditions. A progressive course with global cognitive worsening in DEE is usually attributed to severe seizures and electroencephalographic abnormalities whose deleterious effects interfere with developmental processes both in an apparently healthy brain and in an anatomically compromised one. Next generation sequencing and functional studies have helped identifying and characterizing clinical conditions, each with a broad spectrum of clinical and anatomic severity corresponding to a variable level of neurodegeneration, such that both a rapidly progressive course and considerably milder phenotypes with no obvious deterioration can be configured with mutations in the same gene. In this mini review, we present examples of genetic DEE that draw connections between neurodevelopmental and neurodegenerative disorders.

New olive-pomace fertilizer tested with a 2-tiers approach: Biomarkers on Eisenia fetida, physiochemical effects on Solanum lycopersicum and Olea europaea.

Every year, the olive oil industry generates a substantial amount of pomace, a semi-solid residue made up of skin, pulp, pit, and kernel fragments. Rather than being disposed of, the pomace can be dried and transported to an extraction facility where pomace oil can be extracted. Utilizing its high thermal capacity, the extracted pomace can be used as a supplementary fuel in the drying process, resulting in the production of ashes. In this study, the effect of pomace waste applied to the soil was investigated by testing two mixtures with different proportions of de-oiled pomace flour and kernel ash (50:50 and 70:30, respectively) in powder and pellet form. We used a dual approach, evaluating the effects of the mixtures on both soil communities and plant physiology and productivity, to assess the actual usability of the fertilizer in agriculture. The biomarker approach was valuable in assessing the sublethal effects of the two mixtures in powder form in soil. After 30 days of exposure, the bioindicator organism Eisena fetida showed lipid peroxidation, glutathione S-transferase and lactate dehydrogenase levels similar to the control, while lysozyme activity was reduced in all treatments. The powder mixture was lethal to the tomato plants, while there was no evidence of any damage to the olive trees. During 60 days of monitoring, both mixtures in pellet form showed a slight increase in physiological parameters, suggesting a benefit to the photosynthetic system. The improved carbon assimilation in tomato plants treated with the mixtures results in increased plant productivity, both in terms of number and weight of fruits, while maintaining the antioxidant content. This study paves the way for the use of the pomace mixture as a soil improver, thus increasing the value of this waste product.

Myxoid glioneuronal tumor: Histopathologic, neuroradiologic, and molecular features in a single center series.

BACKGROUND: Myxoid glioneuronal tumor (MGT) is a benign glioneuronal neoplasm recently introduced in the World Health Organization (WHO) classification of the central nervous system (CNS) tumors. MGTs are typically located in the septum pellucidum, foramen of Monro or periventricular white matter of the lateral ventricle. They were previously diagnosed as dysembryoplastic neuroepithelial tumors (DNT), showing histological features almost indistinguishable from classical cortical DNT. Despite that, MGTs have been associated with a specific dinucleotide substitution at codon 385 in the platelet-derived growth factor receptor alpha (PDGFRA) gene, replacing a lysine residue with either leucine or isoleucine (p. LysK385Leu/Iso). This genetic variation has never been described in any other CNS tumor. MATERIALS AND METHODS: Thirty-one consecutive tumors, previously diagnosed as DNTs at the Meyer Children's Hospital IRCCS between January 2010 and June 2021 were collected for a comprehensive study of their clinical, imaging, pathological features, and molecular profile. RESULTS: In six out of the thirty-one tumors we had previously diagnosed as DNTs, we identified the recurrent dinucleotide mutation in the PDGFRA. All six tumors were typically located within the periventricular white matter of the lateral ventricle and in the septum pellucidum. We then renamed these lesions as MGT, according to the latest WHO CNS classification. In all patients we observed an indolent clinical course, without recurrence. CONCLUSION: MGT represent a rare but distinct group of neoplasm with a typical molecular profiling, a characteristic localization, and a relative indolent clinical course.

Burden of compensated and decompensated cirrhosis: real world data from an Italian population-based cohort study.

OBJECTIVE: To quantify the annual healthcare resource utilization, costs and mortality rate for a large cohort of Italian patients with compensated (CC) and decompensated cirrhosis (DC). PATIENTS AND METHODS: A population-based cohort study was conducted through the data-linkage of mortality for all-cause, hospitalizations and outpatient drugs and service databases of the Campania Region. All adults hospitalized with cirrhosis diagnosis (2007-2015) were grouped in CC and DC (prevalent patients) on January 1, 2016 and followed for 1-year. Incident patients with DC (2015) were also retrieved and followed from discharge date up to 1-year. Negative binomial regression was used to estimate Incidence Rate Ratios (IRRs) for predictors of all-cause hospitalizations. Costs were evaluated from the Italian National Health Service perspective and expressed in euro patient/year. RESULTS: A total of 21,433 prevalent cirrhotic patients (57.1% CC and 42.9% DC) and 1,371 incident patients with DC were identified. During a 1-year, 21.5% of prevalent patients with CC were admitted for acute events, 26.8% of those with DC and 55.4% of incident patients with DC. Ascites (IRR=1.71;95% CI: 1.37-2.14) and hepatic encephalopathy (IRR=1.35; 95% CI: 1.04-1.77) at index admission were strong predictors of hospitalizations in incident DC patients. The 1-year mortality rate was respectively 5.8% and 10.1% for prevalent patients with CC and DC and 35.6% for incident patients with DC. Direct costs amounted to 3,194€ patient/year for the prevalent CC group and 4,001€ patient/year for the DC group and 13,806 € patient/year for incident individuals with DC. CONCLUSIONS: The burden of cirrhosis dramatically differs between CC and DC patients, especially after the first decompensation episode. Ascites and hepatic encephalopathy at index admission were strong predictors of hospitalizations in incident DC patients.

Characteristics of viral pneumonia in the COVID-19 era: an update.

Influenza virus, rhinovirus, and adenovirus frequently cause viral pneumonia, an important cause of morbidity and mortality especially in the extreme ages of life. During the last two decades, three outbreaks of coronavirus-associated pneumonia, namely Severe Acute Respiratory Syndrome, Middle-East Respiratory Syndrome, and the ongoing Coronavirus Infectious Disease-2019 (COVID-19) were reported. The rate of diagnosis of viral pneumonia is increasingly approaching 60% among children identified as having community-acquired pneumonia (CAP). Clinical presentation ranges from mild to severe pneumonitis complicated by respiratory failure in severe cases. The most vulnerable patients, the elderly and those living with cancer, report a relevant mortality rate. No clinical characteristics can be useful to conclusively distinguish the different etiology of viral pneumonia. However, accessory symptoms, such as anosmia or ageusia together with respiratory symptoms suggest COVID-19. An etiologic-based treatment of viral pneumonia is possible in a small percentage of cases only. Neuraminidase inhibitors have been proven to reduce the need for ventilatory support and mortality rate while only a few data support the large-scale use of other antivirals. A low-middle dose of dexamethasone and heparin seems to be effective in COVID-19 patients, but data regarding their possible efficacy in viral pneumonia caused by other viruses are conflicting. In conclusion, viral pneumonia is a relevant cause of CAP, whose interest is increasing due to the current COVID-19 outbreak. To set up a therapeutic approach is difficult because of the low number of active molecules and the conflicting data bearing supportive treatments such as steroids.

Phenolic Plant Extracts Induce Sirt1 Activity and Increase Antioxidant Levels in the Rabbit's Heart and Liver.

BACKGROUND: Several dietary phytochemicals potentially regulate the equilibrium between oxidant and antioxidant species. The aim of this study was to evaluate the effects of Lippia citriodora, Raphanus sativus, and Solanum lycopersicum on blood parameters, oxidative/antioxidant status, and SIRT1 activity in the rabbit's heart and liver. METHODS: Twenty rabbits were divided into 4 groups of 5 animals each. The control group (CN) received a feed without any additives. One intervention group received a supplement containing verbascoside (VB), another Raphanus sativus extract (RAP), and lastly lycopene (LYC). Oxidant-antioxidant parameters and SIRT1 activity were measured in plasma and in the heart and liver, respectively. RESULTS: The treatment with VB, RAP, and LYC resulted in a marked improvement in the blood lipid and glycaemic profile in respect to CN. VB was the most effective, but all three plant extracts induced a significant reduction in oxidant parameters as well as an increase in antioxidant tissue activity and vitamin A and E levels. SIRT1 activity was significantly increased in both VB and LYC compared to CN, but the increased levels in the VB group were far the highest. The multivariate analysis suggests that the benefits of VB, particularly the antiglycaemic and antioxidant effects, might be mediated by increasing SIRT1 activity.

[Sulphurous vaginal douching and vulvovaginal atrophy].

OBJECTIVE: During climacteric the reduction or interruption of estrogenic stimulus determines a gradual atrophy of the tissues of the urogenital tract.Vulvovaginal atrophy can be cause of dryness, itch, burning, and dyspareunia. Vulvovaginal atrophy is associated also with depression. Hence the importance of an appropriate treatment of the vulvovaginal atrophy. Between therapeutic options we can add, particularly for women who suffer only from vaginal symptoms, the spa therapy that uses mineral waters with benefic effects on vaginal tissue wellness and health. On the basis of considerations described above and on the insufficient literature data, the objective of our single-arm pilot study has been to evaluate, in women suffering from vulvovaginal atrophy, the effects and safety of a vaginal douching cycle with sulphurous mineral water and impact on depression disorder frequently observed. PATIENTS AND METHODS: The study was conducted on 24 women affected by vulvovaginal atrophy; mean age:57±11 years; age range:42-81 years. The subjects were treated, for 2 weeks, with sulphurous vaginal douching from Terme of Telese S.p.A. (Benevento-Italy). At the beginning and at the end of the SPA treatment the following symptoms were evaluated: dryness, burning, itch, dyspareunia and leucorrhoea (using VAS scale); the impact on psychological distress (using S.D.S. Zung-test). RESULT: At the end of the spa treatment, the mean values±SD, compared to baseline, have showed a significant (p<0.05) reduction in leucorrhoea (-88%), in vulvar itch (-79%), in vaginal burning (-71%), in vaginal dryness (-65%) with an improvement of psichological distress as demonstrated by S.D.S. Zung-test. CONCLUSION: The data of this single-arm pilot clinical trial show that the sulphurous vaginal douching cycle can be considered very useful in women suffering from vulvovaginal atrophy with improving of the quality of life and social relationship.

Isolation, proliferation and characterization of endometrial canine stem cells.

In the last decade, progenitor cells isolated from dissociated endometrial tissue have been the subject of many studies in several animal species. Recently, endometrial cells showing characteristics of mesenchymal stem cells (MSC) have been demonstrated in human, pig and cow uterine tissue samples. The aim of this study was the isolation and characterization of stromal cells from the endometrium of healthy bitches, a tissue that after elective surgery is routinely discarded. Multipotent stromal cells could be isolated from all bitches enrolled in the study (n = 7). The multipotency of cells was demonstrated by their capacity to differentiate into adipocytic, osteocytic and chondrocytic lineages. Clonogenicity and cell proliferation ability were also tested. Furthermore, gene expression analysis by RT-PCR was used to compare the expression of a set of genes (CD44, CD29, CD34, CD45, CD90, CD13, CD133, CD73, CD31 CD105, Oct4) with adipose tissue-derived MSC. Stromal cells isolated from uterine endometrium showed similar morphology, ability of subculture and plasticity, and also expressed a panel of genes comparable with adipose tissue-derived MSC. These data suggest that endometrial stromal cells fulfil the basic criteria proposed by the "Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy" for the identification of mesenchymal stem cells. Although endometrial mesenchymal stem cells (EnMSC) showed a lower replicative ability in comparison with adipose tissue-derived MSC, they could be considered a cell therapeutic agent alternative to adipose tissue or bone marrow-derived MSC in dog.

Blood and sputum biomarkers in COPD and asthma: a review.

Chronic obstructive pulmonary disease (COPD) and asthma are lung inflammatory diseases that represent major public health problems. The primary, and often unique, method to evaluate lung function is spirometry, which reflects disease severity rather than disease activity. Moreover, its measurements strictly depend on patient's compliance, physician's expertise and data interpretation. The limitations of clinical history and pulmonary function tests have encouraged focusing on new possible tracers of diseases. The increase of the inflammatory response in the lungs represents an early pathological event, so biological markers related to inflammation may play key roles in earlier diagnosis, evaluation of functional impairment and prognosis. Biomarkers are measurable indicators associated with the presence and/or severity of a biological or pathogenic process, which may predict functional impairment, prognosis and response to therapy. The traditional approach based on invasive techniques (bronchoalveolar lavage and biopsies) may be replaced, at least in part, by using less invasive methods to collect specimens (sputum and blood), in which biomarkers could be measured. Proteomics, by the association between different protein profiles and pathogenic processes, is gaining an important role in pulmonary medicine allowing a more precise discrimination between patients with different outcomes and response to therapy. The aim of this review was to evaluate the use of biomarkers of airway inflammation in the context of both research and clinical practice.

Predictors of outcome for patients with severe respiratory failure requiring non invasive mechanical ventilation.

OBJECTIVE: Failure to identify patients in whom non-invasive ventilation (NIV) would be unsuccessful may cause inappropriate delay in intubation. Aim of this study was to determine predictors of NIV failure. PATIENTS AND METHODS: We retrospectively evaluated COPD patients, undergoing NIV for at least 12h because of hypercapnic acute respiratory failure. Univariable and multivariable analyses were performed on: age, gender, APACHE II and GCS, gas exchange at admission, during NIV and at discharge/death, length of stay. ROC analysis for pH START and APACHE II were performed. RESULTS: Among 201 individuals enrolled, NIV failed in 50. In the logistic regression model only APACHE II was found to have an independent effect on the outcome (p < 0.0001, OR 1.179, 95% CI 1.101-1.263 as quantitative variable; p < 0.0001, OR 3.753, 95% CI 1.798-7.835, as qualitative variable, > 20.5). CONCLUSIONS: APACHE II may be a crucial parameter in predicting NIV failure; further multicentric studies are needed to better define NIV indications.

A new method to evaluate the residual activity in patients undergoing (131)I thyroid therapy.

The radioiodine administration is a standard therapeutic approach to both benign thyroid diseases, such as hyperthyroidism, and carcinomas. The high administered (131)I activities are of radiation protection concern, due to relevant patient residual contamination. The aim of this work was to develop a new procedure based on external radiometric surveys and on a mathematical model in order to estimate the (131)I activity in patients undergoing hyperthyroidism radioiodine therapy. In the first stage of this study, a suitable detector was chosen and its response vs. activity was characterized. The experimental verification was performed measuring the ambient dose equivalent rate from patients receiving radioiodine administration. The results confirm the reliability of the proposed method, as shown by the slight differences between the administered activities and the ones calculated from external measurements. Furthermore, the same procedure was applied to detect the percentage residual activity in patients at two preset time intervals: 4 hours and 4 days after the radioiodine administration. The obtained results clearly highlight that the method can ensure a level of reliability compatible with the radiation protection purposes.

[Sulphureous mud-bath therapy and changes in blood pressure: observational investigation]. / Fangobalneoterapia sulfurea e variazioni della pressione arteriosa: studio osservazionale.

BACKGROUND AND OBJECTIVE: The chronic arthropathies currently appear to be a major cause of disability with a negative impact on quality of life and health care spending. The mud-bath therapy is a spa treatment that induces benefic effects in chronic rheumatic diseases. It has long been debated on the assumption that the mud-bath spa therapy could have adverse cardiovascular effects which often induce caution and even a contraindication to the use of this treatment in chronic arthropathies associated with cardiovascular alterations such as hypertension. The aim of this observational study was to investigate, in arthrorheumatic subjects, the effects of sulphureous mud-bath cycle on blood pressure and the possible appearance of adverse drug reaction. PATIENTS AND METHODS: 169 patients, with age range 42-86 years, suffering by chronic arthropathies were treated with sulphureous mud-bath therapy for 2 weeks. According to the arterial pressure values, measured before the spa treatment, the patients considered were divided in three groups: with normal blood pressure (NOR group); with high blood pressure, after, the latter group was divided in IPET (patients in treatment with antihypertensive drugs) and IPENT (patients not in antihypertensive therapy). The arterial pressure values, maximum and minimum, expressed in mmHg, were detected in the first (T1) - sixth (T6) and twelfth (T12) day of spa treatment. The media arterial pressure values collected before and after T1, before and after T6, before and after T12 , before T1 and after T12 were compared. The data, presented as mean±SD, were compared with the paired Student t test. A p value ≤0.05 was considered significant. RESULTS: The comparison between the mean values detected in pre and post T1, pre and post T6, pre and post T12 have showed that sulphureous mud-bath therapy induced a significant (p<0.05) reduction of arterial blood pressure values in patients suffering of chronic arthropathies with high blood pressure in antihypertensive therapy or not (IPET and IPENT groups); while in patients with normal blood pressure (NOR group) were observed modest reduction at the limit of statistical significance. Similarly, the comparison between the data detected at the end of sulphureous mud-bath therapy (post-T12) vs baseline (pre-T1) have demonstrated: in IPET and IPENT groups a significant (p<0,01) decrease of arterial blood pressure values; in NOR group very small decrease, this reduction is significant (p<0.05) only for maximum arterial pressure value. Were not observed adverse drug reaction. CONCLUSIONS: The results of our study, in according with the few data in the literature, evidenced that is possible include the sulphureous mud-bath therapy in interdisciplinary therapeutic p rotocol of patients suffering of chronic arthropathies and arterial hypertension.

Sirtuin 1 and aging theory for chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population. Drug therapies are symptomatic and inadequate to contrast disease progression and mortality. Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets. Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD. Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD. The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes. Recent evidence corroborating the statement of the "aging theory for COPD" was also discussed.

High prevalence of gluten sensitivity in a cohort of patients with undifferentiated connective tissue disease.

OBJECTIVES: The aim of this study was to investigate if co-morbid conditions as hepatitis C virus infection and celiac disease may be associated to undifferentiated connective tissue disease. METHODS: We studied retrospectively and prospectively 52 patients with diagnosis of undifferentiated connective tissue disease, subdivided, according to Vaz criteria, in systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome-like subgroups. Serological markers of celiac disease as anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies were investigated. An esophagogastroduodenoscopy with duodenal biopsy and histological examination was proposed to patients with positive celiac disease serology. In addition antibodies directed to hepatitis C virus and total IgA-antibodies were investigated. RESULTS: Six patients (11,5%) were positive for celiac disease serological tests although two of them were asymptomatic. Four patients underwent an esophagogastroduodenoscopy, showing total or subtotal villous atrophy at duodenal biopsies. Hepatitis C virus serology was negative in all patients and none had IgA deficiency. 83% of celiac patients showed a scleroderma-like phenotype. We observed a statistically higher incidence of autoimmune symptoms in patients with gluten sensitivity. Fatigue and myalgia regressed early after the beginning of gluten-free diet. CONCLUSIONS: In our cohort of patients the prevalence of celiac disease was higher than that reported in the general population. We believe that all patients with diagnosis of undifferentiated connective tissue disease, especially those with a systemic sclerosis-like presentation, should be investigated for celiac disease, even in absence of gastrointestinal symptoms. Gluten-free diet should be early recommended to all patients having undifferentiated connective tissue disease and gluten sensitivity.

A Prospective Screening of HLA-B*57.01 Allelic Variant for Preventing the Hypersensivity Reaction to Abacavir: Experience from the Laboratory of Molecular Biology of the Infectious Diseases Division at the University Hospital of Salerno.

Abacavir is a nucleoside reverse transcriptase inhibitor largely used as part of the antiretroviral therapy in Human Immunodeficiency Virus (HIV)-infected patients. Some individuals (2-9%) who start an abacavir treatment show an immunologic reaction indicated as hypersensitivity reaction syndrome (HSR) that is often responsible for therapy discontinuation and could represent a life-threatening event. Some studies demonstrated a correlation between this adverse reaction and the class I of the major histocompatibility complex (MHC) allele, HLA-B*57.01, in several populations, including Caucasians. Nowadays, International HIV treatment guidelines recommend the HLA-B*57.01 genotyping before abacavir administration to reduce the incidence of HSR. Both male and female HIV-infected patients were enrolled at the Infectious Diseases Division at the University Hospital of Salerno, and admitted to a prospective HLAB*57.01 screening. Genetic analysis was carried out through two sequential Real-Time PCR reactions in which Sybr-Green was used. Out of 248 patients, 215 were Italians from Southern Italy and 33 were coming from several non-EU members countries. All were genotyped: 6 Italians (2.8%) and 1 of the non-EU group (3%) were identified as HLAB*57.01 carriers. In this paper we present our experience in the field of abacavir pharmacogenetic and confirm the importance of Real Time PCR as a valid and cost-effective HLA-B*57.01 typing methodology.

The Role Of Physical Activity On The Prevention Of Cognitive Impairment.

Physical exercise is associated with reduced risk of heart disease, type II diabetes mellitus, and overall mortality. However, growing evidence shows that physical activity can also improve cognitive function and may lower the risk of developing dementia, but Randomized Clinical Trials gave mixed results. Aim of this article was to review the knowledge available in literature on the effects of physical activity on cognition and the suggested possible mechanisms involved in these effects. Our group have planned a trial aiming to evaluate the effectiveness of physical activity in preventing or delaying the cognitive decline in individuals at risk of developing dementia. Beside the effects of exercise on cognition are not fully defined, also the mechanisms underlying the benefits of physical activity on cognitive sphere are not completely known. Recently the SIRT1 loss is both closely associated with accumulation of beta amyloid and tau protein in AD patients. Although there is no specific exercise that can be recommended, the available evidence suggests that practicing more types of physical activity is particularly advantageous. It is important to explore further mechanisms involved in the pathogenesis of the AD in order to be able to identify new and effective target treatment, including physical activity.

Focal dysplasia of the cerebral cortex and infantile spasms associated with somatic 1q21.1-q44 duplication including the AKT3 gene.

Somatic and germline duplications or activating mutations of AKT3 have been reported in patients with hemimegalencephaly and megalencephaly. We performed array comparative genomic hybridization on brain tissue and blood in 16 consecutive patients with symptomatic epilepsy due to focal or multilobar malformations of cortical development who underwent surgical treatment of epilepsy. One patient with infantile spasms and a dysplastic left frontal lobe harboured a somatic trisomy of the 1q21.1-q44 chromosomal region, encompassing the AKT3 gene, in the dysplastic brain tissue but not in blood and saliva. Histopathology revealed severe cortical dyslamination, a thin cortex in the premotor area with microgyri and microsulci, immature neurons with disoriented dendrites and areas of cortical heterotopia in the sub-cortical white matter. These cytoarchitectural changes are close to those defining type Ib focal cortical dysplasia. Immunohistochemistry in brain specimens showed hyperactivation of the PI3K/AKT/mTOR pathway. These findings indicate that AKT3 upregulation may cause focal malformations of cortical development. There appears to be an etiologic continuum between hemimegalencephaly and focal cortical dysplastic lesions. The extent of brain malformations due to AKT3 upregulation may be related to the embryonic stage when the post-zygotic gene alteration occurs.

Adverse cardiovascular events associated with triptans and ergotamines for treatment of migraine: systematic review of observational studies.

BACKGROUND: Apart from the underlying cardiovascular (CV) risk associated with migraine, both triptans and ergotamines can induce vasoconstriction and potentially increase the risk of serious ischemic events. Because of the low frequency of such events in eligible patients, randomized controlled trials are not exhaustive to assess the drug-related CV risk. Observational studies are, therefore, an essential source of information to clarify this matter of concern. AIM: The aim of this study was to systematically review the available published observational studies investigating the risk of serious CV events in triptan or ergotamine users, as compared to unexposed migraineur controls. METHODS: We systematically searched MEDLINE and EMBASE electronic databases for cohort or case-control studies up to December 1, 2013. Studies retrieved from CDSR, DARE and HTA databases of the Cochrane Library were used for snowballing. Studies investigating the risk of any CV outcome in patients with a migraine diagnosis and exposed to triptans or ergotamines were considered for inclusion. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were computed using a random-effects model for studies and outcomes judged eligible for quantitative data synthesis. RESULTS: From a total of 3370 citations retrieved, after duplicate removal and screening, only four studies met the inclusion criteria (three nested case-control analyses and one retrospective cohort study). These studies investigated the risk of different CV outcomes associated with either the recency or the intensity of exposure to the studied drugs. As for the intensity of use, the pooled OR of serious ischemic events was 2.28 (95% CI 1.18-4.41; I (2 )= 0%) for ergotamine use (two studies), whereas for triptans (three studies) it was 0.86 (95% CI 0.52-1.43; I (2 )= 24.5%). Recent use of ergotamines was not significantly associated with any CV outcome (only one available study). Two studies investigated the risk of stroke related to recent triptan use: the first study reported an OR of 0.90 (0.64-1.26), and the second one suggested an increased risk of 2.51 (1.10-5.71). In this case, because of the high degree of heterogeneity, results were not pooled. CONCLUSIONS: To date, few comparative observational studies have investigated the CV safety of migraine-specific drugs in clinical practice. Evidence gathered here suggests that intense consumption of ergotamines may be associated with an increased risk of serious ischemic complications. As for triptans, available studies do not suggest strong CV safety issues, although no firm conclusions can be drawn. In particular, evidence on stroke risk is conflicting. However, if an increase of the absolute stroke risk in recently exposed patients does actually exist, it must be small. Overall, residual uncontrolled confounding factors reduce the confidence in the risk estimates collected from the included studies. Further investigations are needed to better define the risk for rare but serious CV events related to triptan and ergotamine use for treatment of migraine.

Adherence to generic v. brand antidepressant treatment and the key role of health system factors.

One of the major challenges with antidepressant (AD) use is poor adherence and early treatment discontinuation. In addition to socio-demographic and clinical variables, treatment discontinuation may also be related to the capacity of the health system to assure and maintain continuity and intensity of care. Among health system factors that may interfere with adherence to pharmacological treatment, use of generic drugs may play a key role. It has been argued that, although the lower cost of generics may favour persistence on treatment, a widespread a priori scepticism about their effectiveness and safety by doctors and patients may have an opposite effect. This compelling research question has recently been addressed by an observational cohort study that involved 16 778 Medicare fee-for-service beneficiaries who received a new depression diagnosis and initiated generic v. brand AD therapy. The study found that generic initiation was associated with improved adherence. The benefits resulted from the lower out-of-pocket cost associated with generic ADs. In this commentary, we discuss the main findings of this study in view of its methodological strengths and limitations, and we suggest implications for policy.