Incidence and Risk Factors Epilepsy in Patients with Dementia: A Population-Based Study Using Regional Healthcare Databases in Umbria.

Background: Dementia is prevalent among the elderly, also representing a risk for seizures/epilepsy. Estimations of epilepsy risk in dementia patients are not widely available. Objective: Our research aims to ascertain the incidence of epilepsy and its associated risk factors in subjects with dementia in the Umbria region, based on data from healthcare databases. Methods: In this retrospective study based on the healthcare administrative database of Umbria, we identified all patients diagnosed with dementia from 2013 to 2017, based on ICD-9-CM codes. For epilepsy ascertainment, we used a validated algorithm that required an EEG and the prescription of one or more anti-seizure medications post-dementia diagnosis. A case-control analysis was conducted, matching five non-dementia subjects by gender and age to each dementia patient. Cox proportional hazards models were then utilized in the analysis. Results: We identified 7,314 dementia cases, also including 35,280 age- and sex-matched control subjects. Out of patients with dementia, 148 individuals (2.02%) were diagnosed with epilepsy. We observed a progressive increase in the cumulative incidence of seizures over time, registering 1.45% in the first year following the diagnosis, and rising to 1.96% after three years. Analysis using Cox regression revealed a significant association between the development of epilepsy and dementia (HR = 4.58, 95% CI = 3.67-5.72). Additional risk factors were male gender (HR = 1.35, 95% CI = 1.07-1.69) and a younger age at dementia onset (HR = 1.03, 95% CI=1.02-1.04). Conclusions: Dementia increases epilepsy risk, especially with early onset and male gender. Clinicians should have a low threshold to suspect seizures in dementia cases.

Barriers to Accessing Primary Care and Appropriateness of Healthcare Among Immigrants in Italy.

INTRODUCTION: The health status and health care needs of immigrant populations must be assessed. The aim of this study was to evaluate barriers to accessing primary care and the appropriateness of health care among resident immigrants in Italy, using indicators regarding maternal health, avoidable hospitalization, and emergency care. METHODS: Cross-sectional study using some indicators of the National Monitoring System of Health Status and Healthcare of the Immigrant Population (MSHIP), coordinated by the National Institute for Health, Migration and Poverty (INMP), calculated on perinatal care, hospital discharge, and emergency department databases for the years 2016-2017 in nine Italian regions (Piedmont, Trento, Bolzano, Emilia-Romagna, Tuscany, Umbria, Latium, Basilicata, Sicily). The analyses were conducted comparing immigrant and Italian residents. RESULTS: Compared to Italian women, immigrant women had fewer than five gynecological examinations (8.5 vs. 16.3%), fewer first examinations after the 12th week of gestational age (3.8 vs. 12.5%), and fewer than two ultrasounds (1.0 vs. 3.8%). Compared to Italians, immigrants had higher standardized rates (× 1,000 residents) of avoidable hospitalizations (males: 2.1 vs. 1.4; females: 0.9 vs. 0.7) and of access to emergency departments for non-urgent conditions (males: 62.0 vs. 32.7; females: 52.9 vs. 31.4). CONCLUSIONS: In Italy, there appear to be major issues regarding accessing services and care for the immigrant population. Policies aimed at improving socioeconomic conditions and promoting integration can promote healthy lifestyles and appropriate access to health care, counteracting the emergence of health inequities in the immigrant population.

Incidence and Antiseizure Medications of Post-stroke Epilepsy in Umbria: A Population-Based Study Using Healthcare Administrative Databases.

Introduction: Post-stroke epilepsy (PSE) requires long-term treatment with antiseizure medications (ASMs). However, epidemiology of PSE and long-term compliance with ASM in this population are still unclear. Here we report, through population-level healthcare administrative data, incidence, risk factors, ASM choice, and ASM switch over long-term follow-up. Materials and Methods: This is a population-based retrospective study using Umbria healthcare administrative database. Population consisted of all patients with acute stroke, either ischaemic or hemorrhagic, between 2013 and 2018. ICD-9-CM codes were implemented to identify people with stroke, while PSE was adjudicated according to previously validated algorithm, such as EEG and ≥1 ASM 7 days after stroke. Results: Overall, among 11,093 incident cases of acute stroke (75.9% ischemic), 275 subjects presented PSE, for a cumulative incidence of 2.5%. Patients with PSE were younger (64 vs. 76 years), more frequently presented with hemorrhagic stroke, and had longer hospital stay (15.5 vs. 11.2 days) compared with patients without PSE. Multivariable Cox proportional hazards models confirmed that PSE associated with hemorrhagic stroke, younger age, and longer duration of hospital stay. Levetiracetam was the most prescribed ASM (55.3%), followed by valproate and oxcarbazepine. Almost 30% of patients prescribed with these ASMs switched treatment during follow-up, mostly toward non-enzyme-inducing ASMs. About 12% of patients was prescribed ASM polytherapy over follow-up. Conclusions: Post-stroke epilepsy is associated with hemorrhagic stroke, younger age, and longer hospital stay. First ASM is switched every one in three patients, suggesting the need for treatment tailoring in line with secondary prevention.

Accuracy of ICD-9 codes in identifying patients with peptic ulcer and gastrointestinal hemorrhage in the regional healthcare administrative database of Umbria.

BACKGROUND: Peptic ulcer is a widespread disease, frequently complicated by perforation and bleeding. Administrative databases are useful tool to perform epidemiological and drug utilization studies, but they need a validation process based on a comparison with the original data contained in the medical charts. Our aim was to evaluate the accuracy of the ICD-9 codes in identifying patients with peptic ulcer and gastrointestinal hemorrhage in the regional administrative database of Umbria. METHODS: The index test of our study was the hospital discharge abstract database of the Umbria region (Italy), while the reference standard was the clinical information collected in the medical charts. The study population were adult patients with a hospital discharge for peptic ulcer or gastrointestinal hemorrhage in the period 2012-2014. A random sample of cases and non-cases was selected and the corresponding medical charts were reviewed. Cases of peptic ulcer were confirmed based on endoscopy, radiology, and surgery, while adjudication of gastrointestinal hemorrhage was based on presence of hematemesis, melena, and rectal bleeding. RESULTS: Overall, we reviewed 445 clinical charts of cases and 80 clinical charts of non-cases. The diagnostic accuracy results were: code 531 (gastric ulcer), sensitivity and NPV 98%, specificity 88%, and PPV 91%; code 532 (duodenal ulcer), sensitivity and NPV 100%, specificity and PPV 98%; code 534 (gastrojejunal ulcer), sensitivity and NPV 100%, specificity 70%, and PPV 45%; code 578 (gastrointestinal hemorrhage), sensitivity 96%, specificity 90%, PPV and NPV 94%. CONCLUSIONS: Our results showed a high level of diagnostic accuracy for most of the codes considered. The ICD-9 code 534 of gastrojejunal ulcer had a lower level of specificity and PPV due to false positives, being mainly misclassifications for coding errors. These validated codes can be used for future epidemiological studies and for health services research.

Validity of cerebrovascular ICD-9-CM codes in healthcare administrative databases. The Umbria Data-Value Project.

BACKGROUND: Validation of administrative databases for cerebrovascular diseases is crucial for epidemiological, outcome, and health services research. The aim of this study was to validate ICD-9 codes for hemorrhagic or ischemic stroke in administrative databases, to use them for a comprehensive assessment of the burden of disease in terms of major outcomes, such as mortality, hospital readmissions, and use of healthcare resources. METHODS: We considered the hospital discharge abstract database of the Umbria Region (890,000 residents). Source population was represented by patients aged >18 discharged from hospital with a diagnosis of hemorrhagic or ischemic stroke between 2012 and 2014 using ICD-9-CM codes in primary position. We randomly selected and reviewed medical charts of cases and non-cases from hospitals. For case ascertainment we considered symptoms and instrumental tests reported in the medical charts. Diagnostic accuracy measures were computed using 2x2 tables. RESULTS: We reviewed 767 medical charts for cases and 78 charts for non-cases. Diagnostic accuracy measures were: subarachnoid hemorrhage: sensitivity (SE) 100% (95% CI: 97%-100%), specificity (SP) 96% (90-99), positive predictive value (PPV) 98% (93-100), negative predictive value (NPV) 100% (95-100); intracerebral hemorrhage: SE 100% (97-100), SP 98% (91-100), PPV 98% (94-100), NPV 100% (95-100); other and unspecified intracranial hemorrhage: SE 100% (97-100), SP 96% (90-99), PPV 98% (93-100), NPV 100% (95-100); ischemic stroke due to occlusion and stenosis of precerebral arteries: SE 99% (94-100), SP 66 (57-75), PPV 70% (61-77), NPV 99% (93-100); occlusion of cerebral arteries: SE 100% (97-100), SP 87% (78-93), PPV 91% (84-95), NPV 100% (95-100); acute, but ill-defined, cerebrovascular disease: SE 100% (97-100), SP 78% (69-86), PPV % 83 (75-89), NPV 100% (95-100). CONCLUSIONS: Case ascertainment for both ischemic and hemorrhagic stroke showed good or high levels of accuracy within the regional healthcare databases in Umbria. This database can confidently be employed for epidemiological, outcome, and health services research related to any type of stroke.

[Evaluating health care of the immigrant population in Italy through indicators of a national monitoring system]. / Valutazione dell'assistenza sanitaria della popolazione immigrata in Italia attraverso alcuni indicatori di un sistema nazionale di monitoraggio.

OBJECTIVES: to evaluate maternal and child healthcare, avoidable hospitalisation, access to emergency services among immigrants in Italy. DESIGN: cross sectional study of some health and health care indicators among Italian and foreign population residing in Italy in 2016-2017. SETTING AND PARTICIPANTS: indicators based on the national monitoring system coordinated by the Italian National Institute for Health, Migration and Poverty (INMP) of Rome, calculated on perinatal care (CedAP), hospital discharge (SDO), emergency services (EMUR) archives for the years 2016-2017, by of the following regions: Piedmont, Trento, Bolzano, Emilia-Romagna, Tuscany, Umbria, Lazio, Basilicata, Sicily. MAIN OUTCOME MEASURES: number and timeliness of pregnancy visits, number of ultrasounds, invasive prenatal investigations; perinatal mortality rates, birth weight, Apgar score at 5 minutes, need for neonatal resuscitation; standardized rates of avoidable hospitalisation and access to emergency services by triage code. RESULTS: more often than Italians, immigrant women have during pregnancy: less than 5 gynaecological examination (16.3% vs 8.5%), first examination after the 12th week of gestational age (12.5% vs 3.8%), less than 2 ultrasounds (3.8% vs 1.0%). Higher perinatal mortality rates among immigrants compared to Italians (3.6 vs 2.3 x1,000). Higher standardized rates (x1,000) among immigrants compared to Italians of avoidable hospitalisation (men: 2.1 vs 1.4; women: 0.9 vs 0.7) and of white triage codes in emergency (men: 62.0 vs 32.7; women: 52.9 vs 31.4). CONCLUSIONS: study findings show differences in access and outcomes of healthcare between Italians and immigrants. National monitoring system of indicators, coordinated by INMP, represents a useful tool for healthcare intervention policies aimed to health equity.

[Epidemiology of postpartum hemorrhages in the Umbrian population in the years 2006-2017.] / Epidemiologia delle emorragie post partum nella popolazione umbra nel periodo 2006-2017.

INTRODUCTION: Postpartum haemorrhage (PPH) is one of the main causes of mortality and severe maternal morbidity and its incidence is increasing also in Western countries. Aim of this study is to estimate the incidence and the trend of PPH in the Umbrian population using the validated Umbrian health database and to identify possible determinants for the development of PPH. METHODS: The source of the data was the regional Healthcare Database of the Umbria Region. The population of interest was represented by women who gave birth in Umbria between 2006 and 2017. The PPH was identified from the hospital data using the ICD-9-CM 666.x codes. Demographic data, principal and secondary diagnoses and data on maternal morbidity and blood component transfusion were collected. The incidence of PPH was calculated taking into account cases of PPH over the total number of births. The determinants of PPH, the associated morbidity and the variation in the severity of the PPH over time have been identified by logistic regression models. RESULTS: In Umbria, between 2006 and 2017, 93,403 births were registered (69% by vaginal delivery and 31% by caesarean section) and the rate of caesarean sections decreased by about 4%. The incidence of PPH increased three-fold during this period with an increase (p<0.001) of women with PPH who received transfusions. Regarding the caesarean sections, the PPH trend increased by 53% (p=0.3), while in the vaginal deliveries the PPHs increased by 233% (p<0.001). Logistic regression analysis showed that possible risk factors for the occurrence of PPH are maternal morbidity (OR 22.8, 95% CI 18.5-30.0), twin birth (OR 2.0, 95% CI 1.3-3.2) and antepartum haemorrhage (OR 5.7, 95% CI 3.1-10.4). CONCLUSIONS: The incidence of PPH has increased in recent years, while the morbidity associated with PPH has remained substantially unchanged. The study identified several risk factors responsible for PPH that can be used in the monitoring of pregnant women and for planning prevention strategies such as Patient Blood Management.

[Postpartum haemorrhage in Umbria: accuracy of the regional health information system for the code ICD-9-CM 666.x.] / Emorragia post partum in Umbria: accuratezza del sistema informativo sanitario regionale per il codice ICD-9-CM 666.x.

INTRODUCTION: Postpartum haemorrhage (PPH) is the main cause of morbidity and mortality for pregnant women. Administrative databases are useful sources of information for the assessment of PPH and related outcomes, once the corresponding ICD-9-CM code is validated. The objective of the present study is to evaluate the accuracy of the ICD-9-CM code related to PPH. MATERIAL AND METHODS: Source of the data was the Regional Healthcare Database of the Umbria Region. The population of interest were women with at least 20 weeks of gestation that delivered in any hospital in the Umbria Region during 2012-2016. Cases of interest were identified using the ICD-9-CM 666.x code. For validation purposes, both cases (women who delivered and developed PPH) and non-cases (women who delivered without occurrence of PPH) were considered and algorithms proposed. The basic criterion used for the validity of ICD-9-CM codes was the presence of bleeding ≥500 ml. Additional criteria based on values of haemoglobin or transfusion of red blood cells were considered. Sensitivity, specificity and predictive values were calculated. RESULTS: Medical charts of 422 cases and 200 non-cases were examined. Accuracy results for code 666.x related to the presence of bleeding ≥500 ml were: sensitivity 97% (95% CI, 96-99%), specificity 70% (65-76%), positive predictive value (PPV) 79% (76-82%) and negative predictive value (NPV) 95% (91-97%). The best algorithm was the one that, in addition to the basic criterion, considered both the haemoglobin values and red blood cell transfusion: sensitivity 93% (90-95%), specificity 85% (80-90%), PPV 92% (89-94%) and NPV 86% (81-90%). ICD-9 subcodes showed a higher specificity and PPV for immediate bleeding (666.0, 666.1) than delayed or secondary haemorrhage (666.2). CONCLUSIONS: The accuracy data from the present study confirm that the Regional Healthcare Database of the Umbria Region can be used as a reliable source for the evaluation of epidemiological studies relating to PPHs, in order to improve the quality of maternity care.

Incidence and prevalence of Parkinson's disease in the Italian region of Umbria: a population-based study using healthcare administrative databases.

Parkinson's disease is known to pose a significant burden on society in industrialized countries. However, few studies have been conducted in Italy using administrative healthcare databases for epidemiological purposes. We wanted to estimate the incidence and prevalence rates of Parkinson's disease in the Italian region of Umbria by means of linkage between several sources of administrative healthcare data: hospitalization episodes, exemptions from medical charges, drug prescriptions from general practitioners and physicians working in the public sector. Using a pre-defined algorithm, we estimated incident and prevalent cases of Parkinson's disease for the year 2016. The regional incidence rate, adjusted with Italian standard population data, was 0.40 new cases/1000 person-years (0.41 in females, 0.39 in males). We estimated that 5550 subjects were affected by Parkinson's disease, leading to an age-adjusted prevalence rate of 5.42/1000 inhabitants. Prevalence and incidence increased with age and male gender. However, due to the longer life expectancy of females, the absolute number of prevalent cases was greater among females. The heterogeneity of spatial distribution of disease was high. A considerable proportion of prevalent cases was hospitalized in 2016. The most recurrent reasons for hospitalization episodes were disorders related to the nervous system, respiratory system, cardiovascular system, and musculoskeletal and connective tissue apparatus. The study findings support the feasibility of future epidemiological studies of Parkinson's disease with administrative data as well as the need for an integrative care pathway for the patients with Parkinson's disease.

Accuracy of colorectal cancer ICD-9-CM codes in Italian administrative healthcare databases: a cross-sectional diagnostic study.

Objectives To assess the accuracy of International Classification of Diseases, Ninth Revision - Clinical Modification (ICD-9-CM) codes in identifying subjects with colorectal cancer. DESIGN: A diagnostic accuracy study comparing ICD-9-CM codes (index test) for colorectal cancers with medical chart (as a reference standard). Case ascertainment based on neoplastic lesion(s) within the colon/rectum and histological documentation from a primary or metastatic site positive for colorectal cancer. SETTING: Administrative databases from the Umbria region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) region and Friuli Venezia Giulia (FVG) region. PARTICIPANTS: We randomly selected 130 incident patients from each hospital discharge database, admitted between 2012 and 2014, having colorectal cancer ICD-9 codes located in primary position, and 94 non-cases, that is, patients having a diagnosis of cancer (ICD-9 140-239) other than colorectal cancer in primary position. OUTCOME MEASURES: Sensitivity, specificity and predictive values for 153.x code (colon cancer) and for 154.x code (rectal cancer). RESULTS: The positive predictive value (PPV) for colon cancer diagnoses was 80% for Umbria (95% CI 73% to 87%), 81% for NA (95% CI 73% to 88%) and 80% for FVG (95% CI 72% to 87%).The sensitivity ranged from 98% to 99%, while the specificity ranged from 78% to 80% in the three units.For rectal cancer, the PPV was 84% for Umbria (95% CI 77% to 90%), 80% for NA (95% CI 72% to 87%) and 81% for FVG (95% CI 73% to 87%). The sensitivities ranged from 98% to 100%, while the specificity estimates from 79% to 82%. CONCLUSIONS: Administrative databases in Italy can be a valuable tool for cancer surveillance as well as monitoring geographical and temporal variation of cancer practice.

Sensitivity and specificity of breast cancer ICD-9-CM codes in three Italian administrative healthcare databases: a diagnostic accuracy study.

OBJECTIVES: To assess the accuracy of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in identifying patients diagnosed with incident carcinoma in situ and invasive breast cancer in three Italian administrative databases. DESIGN: A diagnostic accuracy study comparing ICD-9-CM codes for carcinoma in situ (233.0) and for invasive breast cancer (174.x) with medical chart (as a reference standard). Case definition: (1) presence of a primary nodular lesion in the breast and (2) cytological or histological documentation of cancer from a primary or metastatic site. SETTING: Administrative databases from Umbria Region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) and Friuli VeneziaGiulia (FVG) Region. PARTICIPANTS: Women with breast carcinoma in situ (n=246) or invasive breast cancer (n=384) diagnosed (in primary position) between 2012 and 2014. OUTCOME MEASURES: Sensitivity and specificity for codes 233.0 and 174.x. RESULTS: For invasive breast cancer the sensitivities were 98% (95% CI 93% to 99%) for Umbria, 96% (95% CI 91% to 99%) for NA and 100% (95% CI 97% to 100%) for FVG. Specificities were 90% (95% CI 82% to 95%) for Umbria, 91% (95% CI 83% to 96%) for NA and 91% (95% CI 84% to 96%) for FVG.For carcinoma in situ the sensitivities were 100% (95% CI 93% to 100%) for Umbria, 100% (95% CI 95% to 100%) for NA and 100% (95% CI 96% to 100%) for FVG. Specificities were 98% (95% CI 93% to 100%) for Umbria, 86% (95% CI 78% to 92%) for NA and 90% (95% CI 82% to 95%) for FVG. CONCLUSIONS: Administrative healthcare databases from Umbria, NA and FVG are accurate in identifying hospitalised news cases of carcinoma of the breast. The proposed case definition is a powerful tool to perform research on large populations of newly diagnosed patients with breast cancer.

Is the Robson's classification system burdened by obstetric pathologies, maternal characteristics and assistential levels in comparing hospitals cesarean rates? A regional analysis of class 1 and 3.

OBJECTIVE: To assess if maternal risk profile and Hospital assistential levels were able to influence the inter-Hospitals comparison in the class 1 and 3 of the "The Ten Group Classification System" (TGCS). METHODS: A population-based analysis using data from Institutional data-base of an Italian Region was carried out. The 11 maternity wards were divided into two categories: second-level hospitals (SLH), and first-level hospitals (FLH). The recorded deliveries were classified according to the TGCS. To analyze if different maternal characteristics and the hospitals assistential level could influence the cesarean section (CS) risk, a multivariate analysis was done considering separately women in the TGCS class 1 and 3. RESULTS: From January 2011 to December 2013 were recorded 19,987 deliveries. Of those 7,693 were in the TGCS class 1 and 4,919 in the class 3. The CS rates were 20.8% and 14.7% in class 1 (p < 0.0001) and 6.9% and 5.3% (p < 0.0230) in class 3, respectively in the FLH and SLH. The multivariate logistic regression showed that the FLH, older maternal age and gestational diabetes were independent risk factors for CS in groups 1 and 3. Obesity and gestational hypertension were also independent risk factors for group 1. CONCLUSIONS: TGCS is a useful tool to analyze the incidence of CS in a single center but in comparing different Hospitals, maternal characteristics and different assistential levels should be considered as potential bias.

Validity of ICD-9-CM codes for breast, lung and colorectal cancers in three Italian administrative healthcare databases: a diagnostic accuracy study protocol.

INTRODUCTION: Administrative healthcare databases are useful tools to study healthcare outcomes and to monitor the health status of a population. Patients with cancer can be identified through disease-specific codes, prescriptions and physician claims, but prior validation is required to achieve an accurate case definition. The objective of this protocol is to assess the accuracy of International Classification of Diseases Ninth Revision-Clinical Modification (ICD-9-CM) codes for breast, lung and colorectal cancers in identifying patients diagnosed with the relative disease in three Italian administrative databases. METHODS AND ANALYSIS: Data from the administrative databases of Umbria Region (910,000 residents), Local Health Unit 3 of Napoli (1,170,000 residents) and Friuli--Venezia Giulia Region (1,227,000 residents) will be considered. In each administrative database, patients with the first occurrence of diagnosis of breast, lung or colorectal cancer between 2012 and 2014 will be identified using the following groups of ICD-9-CM codes in primary position: (1) 233.0 and (2) 174.x for breast cancer; (3) 162.x for lung cancer; (4) 153.x for colon cancer and (5) 154.0-154.1 and 154.8 for rectal cancer. Only incident cases will be considered, that is, excluding cases that have the same diagnosis in the 5 years (2007-2011) before the period of interest. A random sample of cases and non-cases will be selected from each administrative database and the corresponding medical charts will be assessed for validation by pairs of trained, independent reviewers. Case ascertainment within the medical charts will be based on (1) the presence of a primary nodular lesion in the breast, lung or colon-rectum, documented with imaging or endoscopy and (2) a cytological or histological documentation of cancer from a primary or metastatic site. Sensitivity and specificity with 95% CIs will be calculated. DISSEMINATION: Study results will be disseminated widely through peer-reviewed publications and presentations at national and international conferences.

α-Synuclein expression is modulated at the translational level by iron.

Several studies have suggested an interaction between α-synuclein protein and iron in Parkinson's disease. The presence of iron together with α-synuclein in Lewy bodies, the increase of iron in the substantia nigra and the correlation between polymorphism of the several genes implicated in iron metabolism and Parkinson's disease, support a role for iron in the neurodegeneration. Analysis of post mortem brains revealed increased amount of insoluble α-synuclein protein despite unchanged/reduced levels of α-synuclein mRNA in Parkinson's disease. Interestingly, on the basis of the presence of a putative iron responsive element in the 5'-UTR, it has been suggested that there is a possible iron-dependent translational control of human α-synuclein mRNA. Considering the similarity between the sequences present in human α-synuclein mRNA and the ferritin iron responsive element, we postulated that iron deficiency would decrease the translation of α-synuclein mRNA. Here we used HEK293 cells treated with iron chelator deferoxamine or ferric ammonium citrate to verify the possible iron-dependent translational control of human α-synuclein biosynthesis. We show that the amount of polysome-associated endogenous human α-synuclein mRNA decreases in presence of deferoxamine. Our data demonstrate that human α-synuclein expression is regulated by iron mainly at the translational level. This result not only supports a role for iron in the translational control of α-synuclein expression, but also suggests that iron chelation may be a valid approach to control α-synuclein levels in the brain.

The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses.

The Fragile X syndrome, which results from the absence of functional FMRP protein, is the most common heritable form of mental retardation. Here, we show that FMRP acts as a translational repressor of specific mRNAs at synapses. Interestingly, FMRP associates not only with these target mRNAs, but also with the dendritic, non-translatable RNA BC1. Blocking of BC1 inhibits the interaction of FMRP with its target mRNAs. Furthermore, BC1 binds directly to FMRP and can also associate, in the absence of any protein, with the mRNAs regulated by FMRP. This suggests a mechanism where BC1 could determine the specificity of FMRP function by linking the regulated mRNAs and FMRP. Thus, when FMRP is not present, loss of translational repression of specific mRNAs at synapses could result in synaptic dysfunction phenotype of Fragile X patients.

Comparative structure analysis of vertebrate U17 small nucleolar RNA (snoRNA).

Intron-encoded U17 RNA is a member of the H/ACA box class of small nucleolar RNAs (snoRNAs) involved in ribosomal RNA (rRNA) maturation. U17 snoRNA shows typical characteristics of guide RNAs, which specify sites of pseudouridylation on the precursor rRNA (pre-rRNA). However, in spite of the presence of H and ACA boxes and short regions complementary to the pre-rRNA, its secondary structure does not show any evident pseudouridylation pocket. Moreover, its length is larger than the typical one of snoRNAs and it shows a more complex secondary structure compared to the canonical hairpin-hinge-hairpin-tail architecture. Greater knowledge of eukaryotic U17 snoRNA structure is needed to understand its precise function. Comparative molecular studies of this snoRNA with different vertebrates is still limited to a few cases. With the aim of increasing our understanding of the U17 snoRNA secondary structure, we cloned the U17 snoRNA coding sequence from 10 additional vertebrate taxa. On the basis of structure homology derived from sequence comparison and thermodynamic prediction, we propose a vertebrate consensus secondary structure and novel conserved sequence boxes for U17 snoRNA. Host gene localization of U17 coding sequence and its ability to serve as a guide sequence for RNA/RNA interaction has been evolutionarily traced from fish to mammals. It is interesting to note that turtle U17 snoRNAs show a noncanonical ACA box, mainly consisting in the GCA box. Microinjections in X. laevis oocytes of in vitro synthesized turtle transcripts containing the U17 RNA sequence which have canonical ACA, wild-type GCA, and mutated CCA and UCA boxes resulted in efficient production of mature U17 snoRNA.