A comprehensive overview of the cystic fibrosis on the island of São Miguel (Azores, Portugal).

BACKGROUND: Early diagnosis and treatment are improving significantly the quality of life of patients with cystic fibrosis (CF). This recessive disease is caused by a great variability of mutations in the CF transmembrane conductance (CFTR) gene, whose spectrum and frequency can be different across populations. METHODS: We performed a retrospective cross-sectional study of CF patients from the island of São Miguel (Azores, Portugal) through a clinical, genealogical, genetic and epidemiological investigation. The clinical course of patients was analyzed as a whole and according to their genotype. RESULTS: We identified 14 CF patients within a 23-year period, corresponding to a cumulative incidence of 1:3012 births, being three of them born from consanguineous unions. Genetic analysis revealed three CFTR genotypes: p.[Ser4Ter];[Gln1100Pro] was present in one patient with a less severe phenotype (1/14); c.[120del23];p.[Phe508del], a very rare one (2/14); and p.[Phe508del];[Phe508del] in the remaining patients (11/14). Clinically, respiratory infections (8/14) and growth failure (6/14) were the most common initial manifestations. All patients presented pancreatic dysfunction, with 21.4 and 100% of them showing endocrine and exocrine insufficiency, respectively. As expected, patients with severe phenotype were homozygous for p.Phe508del and had the lowest value of body mass index. CONCLUSIONS: The present study demonstrated that São Miguel Island has an increased incidence of CF when compared to recent Portuguese data (1:7500 live births). It also allowed a comprehensive overview of CF in São Miguel, improving medical practice along with genetic counselling and creating opportunities for genotype-targeted therapies.

The use of ultrasound to assist epidural injection in obese dogs.

OBJECTIVE: To evaluate the use of ultrasound for identifying the site for needle puncture and to determine the depth to the epidural space in obese dogs. STUDY DESIGN: Prospective study in dogs undergoing elective orthopedic surgery. ANIMALS: A group of seven obese Labrador male dogs aged 6.93 ± 2.56 years and weighing 46.5 ± 4.1 kg (mean ± standard deviation). METHODS: The anesthetic protocol for these dogs included epidural anesthesia. With the dogs anesthetized and positioned in sternal recumbency with the pelvic limbs flexed forward, ultrasound imaging was used to locate the lumbosacral intervertebral space. Intersection of dorsal and transverse lines about the probe identified the point of needle insertion. A 17 gauge, 8.9 cm Tuohy needle was inserted perpendicularly through the skin and advanced to the lumbosacral intervertebral space. The number of puncture attempts was recorded and needle depth was compared with skin to ligamentum flavum distance. RESULTS: Epidural injection was performed in all dogs at the first attempt of needle insertion. The distance from skin to epidural space was 5.95 ± 0.62 cm measured by ultrasound and 5.89 ± 0.64 cm measured with the Tuohy needle. These measurements were not different (p = 0.26). A highly significant correlation coefficient of 0.966 between measurement techniques was obtained (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasound imaging identified the point of needle insertion for lumbosacral epidural injection in seven obese dogs. The results indicate that ultrasound can be used to locate the lumbosacral intervertebral space and identify an appropriate point for needle insertion to perform epidural injection.

Right hemisphere dominance for language in a woman with schizophrenia and a porencephalic cyst of the left hemisphere.

A large left hemisphere porencephalic cyst was incidentally found in a 48-year-old woman (MS) with a Diagnostic and Statistical Manual (DSM)-5 diagnosis of schizophrenia. The encephaloclastic characteristics of the cyst indicated that it was acquired between the 22nd and 24th gestational weeks, after the major waves of neuronal migration had tapered off. The cyst destroyed the left temporal and occipital lobes, and the inferior parietal lobule. Surprisingly, MS had no evidence of aphasia, alexia, agraphia, or ideational apraxia; in contrast, cognitive functions dependent on the integrity of the right hemisphere were severely impaired. To test the hypothesis that the development of language in MS took place at the expense of functions that are normally carried out by the right hemisphere, we investigated MS's correlates of oral comprehension with fMRI as a proxy for auditory comprehension and other cognitive functions strongly lateralized to the posterior left hemisphere, such as ideational praxis and reading. Comprehension of spoken language engaged the homologous of Wernicke's area in the right planum temporale. Porencephaly may represent a natural model of neuroplasticity supervening at predictable epochs of prenatal development.

Climate change and water resources in arid mountains: an example from the Bolivian Andes.

Climate change is projected to have a strongly negative effect on water supplies in the arid mountains of South America, significantly impacting millions of people. As one of the poorest countries in the region, Bolivia is particularly vulnerable to such changes due to its limited capacity to adapt. Water security is threatened further by glacial recession with Bolivian glaciers losing nearly half their ice mass over the past 50 years raising serious water management concerns. This review examines current trends in water availability and glacier melt in the Bolivian Andes, assesses the driving factors of reduced water availability and identifies key gaps in our knowledge of the Andean cryosphere. The lack of research regarding permafrost water sources in the Bolivian Andes is addressed, with focus on the potential contribution to mountain water supplies provided by rock glaciers.

Use of a Bipolar Device (LigaSure) to Seal the Appendiceal Stump in Pediatric Laparoscopic Appendectomy: 10-year Latin-American Experience.

BACKGROUND: Closure of the appendiceal stump is a critical step during an appendectomy. There is a lack of knowledge about the feasibility of using electrosurgical devices for the occlusion of the appendix. This study aims to determine the safety of this technique in pediatric patients. METHODS: We performed a cross-sectional analytical study in patients less than 18 years of age treated at Hospital Militar Central Colombia between 2012 and 2021. Our institution's ethics committee approved the study. We analyzed the data using SPSS 22 statistical program. We present frequencies for qualitative variables and measures of central tendency or dispersion for quantitative variables depending on the distribution measured by the Kolmogorov-Smirnov test. In addition, we measured the association of nominal variables with the Chi-square test or Fisher's exact test. For numerical variables, the difference of means with the Student's t-test or the difference of medians with the Mann-Whitney U test. RESULTS: We treated 209 patients. One hundred sixteen (55.5%) were boys, and the mean age was 9.7 years (SD 3.2). The median intraoperative time was 60 min, and the hospital stay was 2.8 days on average. There were no cases of stump leakage, and only two patients (1%) had an organ-space surgical site infection, which was unrelated to the closure technique. We found no association between procedural complications and appendicular status (p = 0.450). CONCLUSIONS: Our research suggests that using a bipolar sealing device (Ligasure, Medtronic, USA) for appendiceal stump closure in pediatric patients undergoing laparoscopic appendectomy is feasible and should be further studied. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.

Thrombotic genetic risk factors and warfarin pharmacogenetic variants in São Miguel's healthy population (Azores).

BACKGROUND: The Azorean population presents the highest standardized mortality rate for cardiovascular diseases (CVD) when compared to mainland Portugal and other populations. Since thrombosis is a common cause of CVD, we assessed four polymorphisms in three thrombotic risk genes - F5 (G1691A), F2 (G20210A) and MTHFR (C677T, A1298C), in 469 healthy blood donors from São Miguel Island (Azores). We also analysed the CYP2C9 (C430T, A1075C) and VKORC1 (G1639A) variants in fifty-eight individuals with predisposition to thrombosis (possessing at least one variation in F5 or F2 genes and one in MTHFR) to evaluate their warfarin drug response genetic profiles. RESULTS: Among the 469 individuals, the data showed that thrombotic risk allele frequencies - 1691A (4.9%), 20210A (1.8%), 677T (41.7%) and 1298C (24.8%) - were similar to other Caucasians, but significantly different from mainland Portuguese (chi2, p < 0.001). The combined analysis of these variants identified twenty-two different genetic profiles (genotype order: F5, F2, MTHFR C677T and A1298C). Complete homozygosity for all wild-type alleles (GG GG CC AA) was present in 11.7%, being GG GG CT AA (22.4%) the most frequent profile. The results also demonstrated that 12.4% (58 out of 469) of São Miguel islanders have increased genetic predisposition to thrombosis. Subsequently, we evaluated these individuals for their warfarin response genetic profiles. The data showed that seven out of fifty-eight individuals are poor metabolizers (two with CYP2C9*2/*2 and five with CYP2C9*2/*3 genotypes). VKORC1 polymorphism analysis identified twelve individuals (20.7%) with AA genotype, who probably will require lower doses of warfarin. The joint analysis of CYP2C9 and VKORC1 revealed that 79.3% (46 out of 58) of the individuals carry at least one polymorphism in these genes. Within these, twenty-five individuals (43.1%) need intermediate and/or low doses of warfarin, if treatment is started. CONCLUSION: The present study demonstrated, for the first time, that São Miguel, and possibly the Azores population, shows significant differences on allele frequencies of thrombotic risk factors when compared to mainland Portugal. This research constitutes a primary approach for future studies on CVD, as well as for the implementation of warfarin dosing protocols using the patient's genotypic information.

Linkage disequilibrium and diversity for three genomic regions in Azoreans and mainland Portuguese.

Studies on linkage disequilibrium (LD) across the genome and populations have been used in recent years with the main objective of improving gene mapping of complex traits. Here, we characterize the patterns of genetic diversity of HLA loci and evaluate LD (D') extent in three genomic regions: Xq13.3, NRY and HLA. In addition, we examine the distribution of DXS1225-DXS8082 haplotype diversity in Azoreans and mainland Portuguese. Allele distribution has demonstrated that the São Miguel population is genetically very diverse; haplotype analysis revealed 100% discriminatory power for X- and Y-markers and 94.3% for HLA markers. Standardized multiallelic D' in these three genomic regions shows values lower than 0.33, thereby suggesting there is no extensive LD in the São Miguel population. Data regarding the distribution of DXS1225-DXS8082 haplotypes indicate that there are no significant differences among all the populations studied, (Azorean geographical groups, the Azores archipelago and mainland Portugal). Moreover, in these as well as in other European populations, the most frequent DXS1225-DXS8082 haplotype is 210-219. Even though São Miguel islanders and Azoreans do not constitute isolated populations and show LD for only very short physical distances, certain characteristics, such as the absence of genetic structure, the same environment and the possibility of constructing extensive pedigrees through church and civil records, offer an opportunity for dissecting the genetic background of complex diseases in these populations.

Literature review on the implications of decriminalization for the care of drug users in Portugal and Brazil. / Revisão da literatura sobre implicações para assistência de usuários de drogas da descriminalização em Portugal e Brasil.

INTRODUCTION: Substance use problems remain at the core of public concern in countries sharing a common culture and a distinct history like Brazil and Portugal. OBJECTIVE: To describe findings of scientific literature about the implications of drug legislation change for the care of drug users in Brazil and Portugal. METHODS: This is an integrative review of literature that considers inclusion and exclusion criteria, sample selection, analyses and categorization of 21 articles selected that were published in databases PubMed, SciELO and Biblioteca do Conhecimento on-line (B-ON) and included ordinances and laws related to the subject. RESULTS: We observed that production on the repercussions of changes of legislation on care is scarce. Alcohol and tobacco are still a matter of concern in both countries. In Portugal, concerns about heroin-related issues have declined in recent years, but opioids use prevalence rates remain well above those of Brazil. Crack-related problems are a Brazilian reality without parallel in Portugal. In both cases, some actions are in place to change the policy in favor of a reduced repressive approach, with differentiation between users and drug dealers, increased punishment of dealers and reduced punishment of drug users.

Os problemas relacionados ao uso de drogas se mantêm como foco de preocupação em países que têm uma história em comum e trajetórias distintas como Brasil e Portugal. Objetivo: descrever os achados na literatura científica sobre os impactos das mudanças na legislação sobre drogas na assistência a estas pessoas nos dois países. Método: revisão integrativa da literatura, por meio de critérios de inclusão e exclusão, seleção da amostra, análise e categorização dos estudos com a escolha de 21 artigos publicados nas bases PubMed, SciELO e Biblioteca do Conhecimento on-line, mais portarias e leis referentes ao tema. Resultados: Observa-se que é escassa a produção sobre as repercussões das mudanças da legislação para a assistência. Nos dois países, o álcool e o tabaco se mantêm como foco de preocupação. Em Portugal, a preocupação com os problemas relacionados ao uso de heroína diminuiu nos últimos anos, mas as taxas de prevalência do uso de opióides se mantêm muito acima das do Brasil. Os problemas com o crack configuram uma realidade brasileira sem paralelo em Portugal. Em ambos os casos, há iniciativas para a mudança da política em direção à diminuição da abordagem repressiva, com a diferenciação entre usuários e traficantes, o aumento da punição dos traficantes e abrandamento da punição dos usuários.

Advances in Triazole Synthesis from Copper-catalyzed Azide-alkyne Cycloadditions (CuAAC) Based on Eco-friendly Procedures.

BACKGROUND: 1,2,3-triazoles are an important class of organic compounds and because of their aromatic stability, they are not easily reduced, oxidized or hydrolyzed in acidic and basic environments. Moreover, 1,2,3-triazole derivatives are known by their important biological activities and have drawn considerable attention due to their variety of properties. The synthesis of this nucleus, based on the click chemistry concept, through the 1,3-dipolar addition reaction between azides and alkynes is a well-known procedure. This reaction has a wide range of applications, especially on the development of new drugs. METHODS: The most prominent eco-friendly methods for the synthesis of triazoles under microwave irradiation published in articles from 2012-2018 were reviewed. RESULTS: In this review, we cover some of the recent eco-friendly CuAAC procedures for the click synthesis of 1,2,3-triazoles with remarks to new and easily recoverable catalysts, such as rhizobial cyclic ß-1,2 glucan; WEB (water extract of banana); biosourced cyclosophoraose (CyS); egg shell powder (ESP); cyclodextrin (ß- CD); fish bone powder; nanoparticle-based catalyst, among others. CONCLUSION: These eco-friendly procedures are a useful tool for the synthesis of 1,2,3-triazoles, providing many advantages on the synthesis of this class, such as shorter reaction times, easier work-up and higher yields when compared to classical procedures. Moreover, these methodologies can be applied to the industrial synthesis of drugs and to other areas.

Auditory, visual, tactile, olfactory, and bodily hallucinations in patients with obsessive-compulsive disorder.

Although much attention has been paid to patients who lack insight into their obsessional beliefs, less importance has been given to individuals with obsessive-compulsive disorder (OCD) who display perceptual disturbances typically found in psychotic disorders, including schizophrenia, schizoaffective disorders, or mood disorders with psychotic features. We would like to call the attention to a phenomenon that has been neglected in the psychiatric literature: the occurrence of hallucinations and related phenomena in patients with OCD. In this case report, we describe five clinical vignettes of patients with OCD with hallucinations in several different sensory modalities, including the auditory, the visual, the tactile, the olfactory, and the cenesthetic ones. Further psychopathological research should clarify the clinical significance of hallucinations among patients with OCD.

Evaluation of linkage disequilibrium on the Xq13.3 region: comparison between the Azores islands and mainland Portugal.

The design of genetic studies of complex diseases is dependent on the extent and distribution of linkage disequilibrium (LD) across the genome in different populations. Here, we characterize the extent of LD in the Azores (Western, Central, and Eastern island groups) and mainland Portugal populations. LD was evaluated in the Xq13.3 region by genotyping eight STR markers spanning 20.9 Mb. Standardized multiallelic disequilibrium coefficient (D') analysis indicates that the Western group presents higher values when compared with the Central and Eastern groups. However, all island groups show values of D' lower than 0.5 and 0.33, suggesting no extensive LD in these populations. Taken together, the data show that the Azorean population presents a lower D' (0.142) than mainland Portugal (0.226). Although, both populations do not show extensive LD, the easy reconstruction of large pedigrees in the Azorean population is a valuable resource for the fine mapping of disease genes.

Sleep Spindle Refractoriness Segregates Periods of Memory Reactivation.

The stability of long-term memories is enhanced by reactivation during sleep. Correlative evidence has linked memory reactivation with thalamocortical sleep spindles, although their functional role is not fully understood. Our initial study replicated this correlation and also demonstrated a novel rhythmicity to spindles, such that a spindle is more likely to occur approximately 3-6 s following a prior spindle. We leveraged this rhythmicity to test the role of spindles in memory by using real-time spindle tracking to present cues within versus just after the presumptive refractory period; as predicted, cues presented just after the refractory period led to better memory. Our findings demonstrate a precise temporal link between sleep spindles and memory reactivation. Moreover, they reveal a previously undescribed neural mechanism whereby spindles may segment sleep into two distinct substates: prime opportunities for reactivation and gaps that segregate reactivation events.

Revisão da literatura sobre implicações para assistência de usuários de drogas da descriminalização em Portugal e Brasil / Literature review on the implications of decriminalization for the care of drug users in Portugal and Brazil

Resumo Os problemas relacionados ao uso de drogas se mantêm como foco de preocupação em países que têm uma história em comum e trajetórias distintas como Brasil e Portugal. Objetivo: descrever os achados na literatura científica sobre os impactos das mudanças na legislação sobre drogas na assistência a estas pessoas nos dois países. Método: revisão integrativa da literatura, por meio de critérios de inclusão e exclusão, seleção da amostra, análise e categorização dos estudos com a escolha de 21 artigos publicados nas bases PubMed, SciELO e Biblioteca do Conhecimento on-line, mais portarias e leis referentes ao tema. Resultados: Observa-se que é escassa a produção sobre as repercussões das mudanças da legislação para a assistência. Nos dois países, o álcool e o tabaco se mantêm como foco de preocupação. Em Portugal, a preocupação com os problemas relacionados ao uso de heroína diminuiu nos últimos anos, mas as taxas de prevalência do uso de opióides se mantêm muito acima das do Brasil. Os problemas com o crack configuram uma realidade brasileira sem paralelo em Portugal. Em ambos os casos, há iniciativas para a mudança da política em direção à diminuição da abordagem repressiva, com a diferenciação entre usuários e traficantes, o aumento da punição dos traficantes e abrandamento da punição dos usuários.

Abstract Introduction: Substance use problems remain at the core of public concern in countries sharing a common culture and a distinct history like Brazil and Portugal. Objective: To describe findings of scientific literature about the implications of drug legislation change for the care of drug users in Brazil and Portugal. Methods: This is an integrative review of literature that considers inclusion and exclusion criteria, sample selection, analyses and categorization of 21 articles selected that were published in databases PubMed, SciELO and Biblioteca do Conhecimento on-line (B-ON) and included ordinances and laws related to the subject. Results: We observed that production on the repercussions of changes of legislation on care is scarce. Alcohol and tobacco are still a matter of concern in both countries. In Portugal, concerns about heroin-related issues have declined in recent years, but opioids use prevalence rates remain well above those of Brazil. Crack-related problems are a Brazilian reality without parallel in Portugal. In both cases, some actions are in place to change the policy in favor of a reduced repressive approach, with differentiation between users and drug dealers, increased punishment of dealers and reduced punishment of drug users.

Anesthetic complications in diabetic dogs subjected to phacoemulsification / Complicações anestésicas em cães diabéticos submetidos a facoemulsificação

The aim of this paper was to compare the incidence of anesthetic complications in diabetic and nondiabetic dogs subjected to phacoemulsification. In total, 30 male and female dogs of different breeds were used. The dogs were distributed into two groups: diabetic (DG) (n=15) and control (CG) (n=15). The animals were premedicated with acepromazine (0.03mg/kg) and meperidine (4mg/kg), intramuscularly. After 20 minutes, anesthesia was induced with propofol (2 to 5mg/kg) and maintained with isoflurane. The animals were monitored and the heart rate, respiratory rate, peripheral oxyhemoglobin saturation, end tidal carbon dioxide tension, inspired and expired isoflurane fraction, and invasive arterial pressure were recorded at 10 minute intervals during the surgical procedure. Arterial hemogasometry was performed after anesthetic induction (T0) and at the end of the surgical procedure. Diabetic patients (DG 10±2 years) were older than non-diabetic group (CG 6±2 years). The expired isoflurane fraction after induction was 30% higher in the control group (CG 1.3±0.3%, DG 1.0±0.2%) (p<0.01). The most common anesthetic complication was hypotension. In total, 80% of the diabetic animals (n=12) exhibited mean arterial pressure (MAP) lower than 60mmHg (54±9.6mmHg) after anesthetic induction, and 83% of the hypotensive dogs (n=10) required vasoactive drugs to treat hypotension. Regarding hemodynamic changes, diabetic patients subjected to general anesthesia were more likely to exhibit hypotension which may be due to the response of older animals to the drugs used; however, this change deserves further investigation.(AU)

O objetivo do presente estudo foi comparar a incidência de complicações anestésicas em cães diabéticos e não diabéticos submetidos a cirurgia de facoemulsificação. Foram utilizados 30 cães, machos ou fêmeas de diversas raças. Os cães foram distribuídos em dois grupos: diabético (GD) (n=15) e controle (GC) (n=15). Os animais foram pré-tratados com acepromazina (0,03mg/kg) e meperidina (4mg/kg), pela via intramuscular. Após 20 minutos, a indução foi realizada com propofol (2 a 5mg/kg) e a manutenção da anestesia com isofluorano. Os animais foram monitorados e as variáveis de frequência cardíaca, frequência respiratória, saturação oxihemoglobina periférica, concentração dióxido de carbono no final da expiração, fração inspirada e expirada de isofluorano e pressão arterial invasiva, foram registradas em intervalos de 10 minutos durante o procedimento cirúrgico. A hemogasometria arterial foi realizada após a indução (T0) e ao final do procedimento cirúrgico (T40). A idade dos animais do grupo diabético (10±2 anos) foi superior em relação aos animais do grupo controle (6±2 anos) (p<0,0001). A concentração expirada de isofluorano após a indução foi 30% superior nos animais do grupo controle (GC 1,3±0,3%, GD 1,0±0,2%) (p<0,01). A complicação anestésica mais comum foi a hipotensão arterial, 80% dos animais diabéticos (n=12) apresentaram pressão arterial média inferior a 60mmHg (54±9.6 mmHg) após indução anestésica; 83% dos cães hipotensos (n=10) necessitaram de fármacos vasoativos para tratamento da hipotensão. Com relação às alterações hemodinâmicas, os pacientes diabéticos submetidos à anestesia geral foram mais propensos à hipotensão arterial que pode ser decorrente da resposta dos animais mais velhos aos fármacos empregados; entretanto essa alteração merece maior investigação.(AU)

Serum proteomics signature of cystic fibrosis patients: a complementary 2-DE and LC-MS/MS approach.

Complementary 2D-PAGE and 'shotgun' LC-MS/MS approaches were combined to identify medium and low-abundant proteins in sera of Cystic Fibrosis (CF) patients (mild or severe pulmonary disease) in comparison with healthy CF-carrier and non-CF carrier individuals aiming to gain deeper insights into the pathogenesis of this multifactorial genetic disease. 78 differentially expressed spots were identified from 2D-PAGE proteome profiling yielding 28 identifications and postulating the existence of post-translation modifications (PTM). The 'shotgun' approach highlighted altered levels of proteins actively involved in CF: abnormal tissue/airway remodeling, protease/antiprotease imbalance, innate immune dysfunction, chronic inflammation, nutritional imbalance and Pseudomonas aeruginosa colonization. Members of the apolipoproteins family (VDBP, ApoA-I, and ApoB) presented gradually lower expression from non-CF to CF-carrier individuals and from those to CF patients, results validated by an independent assay. The multifunctional enzyme NDKB was identified only in the CF group and independently validated by WB. Its functions account for ion sensor in epithelial cells, pancreatic secretion, neutrophil-mediated inflammation and energy production, highlighting its physiological significance in the context of CF. Complementary proteomics-based approaches are reliable tools to reveal pathways and circulating proteins actively involved in a heterogeneous disease such as CF.

Obsessive-compulsive symptoms among patients with blepharospasm and hemifacial spasm.

OBJECTIVE: The aim of this study was to compare the prevalence and the severity of different obsessive-compulsive disorder (OCD) symptoms reported by patients with blepharospasm (BSP) with those reported by patients with hemifacial spasm (HFS). We hypothesized that, since patients with BSP present a dysfunctional striato-thalamo-cortical circuitry, they would exhibit higher prevalence and/or greater severity of OCD symptoms than patients with HFS, a condition that results from peripheral irritation of the facial nerve. METHODS: Twenty-two patients with BSP and 31 patients with HFS were systematically evaluated by means of a sociodemographic and clinical questionnaire, the Mini International Neuropsychiatric Interview, the Obsessive-Compulsive Inventory-Revised, the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI) and the Mini Mental State Examination (MMSE). Diagnostic groups were compared using the Mann-Whitney U test for continuous variables and the Pearson's goodness-of-fit χ(2) test for categorical ones; Fisher's Exact Test was employed when indicated. Correlations between continuous variables were evaluated by means of Spearman coefficients. RESULTS: Patients with BSP and HFS were not significantly different in terms of sociodemographic characteristics and most neuropsychiatric features. Nevertheless, while checking was associated with shorter duration of BSP (Spearman's rho=-0.54; P=.01), hoarding correlated with a longer duration of HFS (Spearman's rho=0.40; P=.04). Length of abnormal movements did not correlate with the BDI, BAI and MMSE scores. CONCLUSIONS: The finding that the severity of different OCD symptoms did not differ between the BSP and HFS groups suggests that BSP may not interfere significantly with behavioral components of the striato-thalamo-cortical circuitry. However, the fact that OCD symptoms were found to follow different courses in distinct diagnostic groups deserves further study.

HLA Class I and II profiles in São Miguel Island (Azores): genetic diversity and linkage disequilibrium.

BACKGROUND: Human leukocyte antigen (HLA) genes are characterized by high levels of polymorphism and linkage disequilibrium (LD), important characteristics to study the genetic background of human populations and their genetic structure. Here, we analyse the allele distribution and LD extent of HLA class I and II in São Miguel Island population (Azores archipelago, Portugal). FINDINGS: The sample set was composed of 106 healthy blood donors living in São Miguel Island obtained from the anonymized Azorean DNA bank. HLA class I (-A, -B and -Cw) and class II (-DRB1, -DQB1, -DPA1 and -DPB1) genotyping was performed by PCR-SSP Olerup SSP (GenoVision Inc.), according to the manufacturer's instructions.Genetic diversity values, based on the 7 loci, ranged from 0.821 both for HLA-DPA1 and -DQB1 to 0.934 for HLA-B, with a mean value of 0.846. Analysis of 5 HLA-A-Cw-B-DRB1-DQB1 haplotypes revealed that A*01-Cw*07-B*08-DRB1*03-DQB1*02 is the most frequent in São Miguel (7.9%) followed by A*24-B*08-Cw*07-DRB1*03-DQB1*02 (3.8%). In addition, even though the reports of high LD for HLA markers in worldwide populations, São Miguel islanders do not have extensive LD (average D' = 0.285). CONCLUSIONS: In summary, the results demonstrate high variability of HLA in São Miguel Island population as well as absence of genetic structure and extensive LD. The data here presented suggest that in São Miguel islanders autoimmune diseases studies will necessarily encompass a more focused analysis of HLA extended haplotypes as well as the evaluation of other non-HLA candidate genes.

SELDI-TOF biomarker signatures for cystic fibrosis, asthma and chronic obstructive pulmonary disease.

OBJECTIVES: The aim of this work was to establish protein profiles in serum and nasal epithelial cells of cystic fibrosis individuals in comparison with controls, asthma and chronic obstructive pulmonary disease patients for specific biomarker signatures identification. DESIGN AND METHODS: Protein extracts were analyzed by Surface Enhanced Laser Desorption/Ionization Time-Of-Flight Mass-Spectrometry (SELDI-TOF-MS). RESULTS: The mass spectra revealed a set of peaks with differential expression in serum and nasal cells among the different groups studied, resulting into peak signatures representative/specific of each pathology. Logistic regressions were applied to those peaks; sensitivity, specificity, Youden's indexes and area under the curve (AUC) of the respective receiver operating characteristic (ROC) curves were compared. DISCUSSION: Multivariate analysis demonstrated that combination of peaks has a better predictive value than the individual ones. These protein signatures may serve as diagnostic/prognostic markers for the studied diseases with common clinical features, or as follow-up assessment markers of therapeutic interventions.

Diagnostic value of CSF protein profile in a Portuguese population of sCJD patients.

The clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is difficult, and reliable markers are highly desired. In this work we assess the value of several cerebrospinal fluid (CSF) markers for sCJD diagnosis. Within the framework of the Portuguese Epidemiological Surveillance Program for Human Prion Diseases, CSF samples from 71 patients with clinically suspected sCJD, 30 definite sCJD and 41 non-CJD patients, were analysed for the presence of 14-3-3 protein. CSF levels of tau (t-tau), and phosphorylated tau (p-tau181), S-100b and beta amyloid (Abeta42) proteins were determined. The influence of clinical and genetic characteristics on CSF markers sensitivity was also evaluated. Protein 14-3-3 was detected in 29/30 sCJD patients and 9/41 non-CJD patients. Extremely elevated t-tau and S-100b protein levels were found in sCJD patients, while p-tau181 levels were only slightly elevated and Abeta42 showed no differences compared to controls. 14-3-3 was the most sensitive parameter (97%), but its specificity was low (78%); sensitivity/specificity for other proteins were: S-100b-93/93%, t-tau-93/95%, with maximum accuracy being obtained by a combination of tests (14-3-3 combined with either t-tau or S-100b, or combining S-100b with t-tau/Abeta42 or p-tau/t-tau ratios). The sensitivity of 14-3-3, as well as of p-tau181/t-tau ratio, was decreased in younger patients with long disease duration, with the PrP-2 isotype and MV genotype. Both 14-3-3, t-tau and S-100b are sensitive markers for sCJD, but 14-3-3 specificity seems to be lower in this special clinical setting of rapidly progressing dementias. We propose that in cases with a 14-3-3 weak positive result, or in young patients with long disease duration, a second CSF marker would be valuable for the diagnosis of sCJD.

UGT1A1, UGT1A6 and UGT1A7 genetic analysis: repercussion for irinotecan pharmacogenetics in the São Miguel Island Population (Azores, Portugal).

BACKGROUND: Glucuronidation reactions, catalyzed by uridine-diphosphate glucuronosyltransferase (UGT) enzymes, constitute a detoxification process that adds glucuronic acid to endogenous and exogenous compounds, aiding their excretion. UGT1A proteins have been implicated as risk factors for both the development of cancer and adverse drug effects. METHODS: Here, we assess the genome of 469 individuals from São Miguel Island (Azores, Portugal) in order to determine the frequencies of polymorphisms and haplotypes in UGT1A1, UGT1A6, and UGT1A7, the co-occurrence of reduced enzyme activity UGT1A variants related to irinotecan toxicity, and to calculate the extent of linkage disequilibrium (LD) in the genomic region encompassing these genes. RESULTS: Allelic analysis disclosed the presence of rare alleles - UGT1A1*36 and UGT1A1*37--only found in individuals of African descent, and UGT1A7*4. These alleles confirm our previous results on the São Miguel Island genetic background. We identified five different genotypes in UGT1A1 and UGT1A6 and nine in UGT1A7. Haplotype analysis showed that three haplotypes constituted approximately 80% of the allelic variants. Interestingly, haplotype 3 (UGT1A1*28-UGT1A6*2-UGT1A7*3), with a frequency of 0.235, gathers the three alleles encoding the low-function UGT isoforms. Additionally, LD indicates a strong interaction between functional polymorphisms related to the alteration of the UGT enzyme activity. CONCLUSIONS: In summary, the results demonstrate a high variability of alleles and haplotypes, which have important roles in modifying expression and activity of UGTs. The data presented here could improve the understanding of the predisposition to cancers and susceptibility to the adverse effects of irinotecan in the São Miguel Island population.