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Nowadays we witness numerous partnerships and projects of national and international scope around active training, using digital tools and based on co-creation processes between different partners, to obtain more creative and appropriate processes to respond to current and future scientific, academic and professional challenges. This article presents the participation of a group of professors from Instituto Politécnico de Setúbal (IPS) in the DEMOLA® approach to be trained as facilitators. We present the objectives, the formation of the teams and the established work methodology, and the application of this methodology adapted to the curricular unit of Process Optimization of the Master of Biological and Chemical Engineering. We briefly describe the main phases that constitute the development of the project within the scope of IPS and the obtained results from the analysis of all components (student training, professors, challenges with companies/organizations and perceptions of the whole team). We emphasize the development of instrumental skills (Canva, Miro, PESTLE, Portfolio); scientific/ pedagogical skills (Teamwork, Multiprofessional Approach, Co-creation Processes, Design Thinking, Research, Facilitation, Disruptive Thinking and Co-construction, among others); and “win-win” situations, or rather “learn-learn” between facilitators and students, innovation, intergenerational, sustainability and freedom of thought.

Funding Information: The authors are grateful to all study participants and would like to thank the Instituto de Investiga??o Cient?fica Bento da Rocha Cabral for financial support. Publisher Copyright: © 2021 Aguiar L et al. Background: Since the emergence of the genus Homo, hominids have occupied a wide variety of environments, facing different selective pressures. Objectives: The aim this study is to compare genotype frequencies between South-West Europe and Peri-equatorial Africa in genes potentially modulators of blood pressure. Methods: The analyzed sample consisted of 325 individuals from Portugal and 226 individuals from Africa (48 from Mozambique and 178 from São Tomé and Príncipe). The following genetic variants were analyzed: intron 4 VNTR in eNOS, rs1050829 in G6PD,-3.7kb α-thalassemic deletion in HBA, rs1800457 in CYB5R3, Hp 1/2 genotype/phenotype in Hp and intron 16 I/D in ACE. Results: Frequencies of genotypes with the 4a allele in eNOS (p

Funding Information: Acknowledgments: H.H. has received a PhD Grant from J Mello Saude. The present publication was funded by Fundação Ciência e Tecnologia, IP national support through CHRC (UIDP/04923/2020). D.J.H. are funded by the National Institute for Health Research (NIHR) Biomedical Research Centre Programme. The work by M.A. is supported by project UID/MAT/00006/2020. Publisher Copyright: © 2021 by the authors. Tinnitus is the perception of a sound without an external source, often associated with adverse psychological and emotional effects leading to impaired quality of life (QoL). The present study investigated QoL and psychological distress in tinnitus patients and analysed the effects of associated comorbidities. Tonal and speech audiometry, tinnitus assessment, and clinical interviews were obtained from 122 Portuguese individuals (aged from 55 to 75). Portuguese versions of the Brief Symptoms Inventory (BSI), the Medical Outcomes Study Short Form Health Survey (MOS SF-36) and Tinnitus Handicap Inventory (THI) were used to evaluate psychological distress, health-related QoL, social difficulties and tinnitus severity. The presence of tinnitus was significantly associated with hearing loss. The increases in tinnitus severity were associated with decreases in QoL, particularly regarding MOS SF-36 subscales “perception of health”, “social functioning”, and “mental health”. Regarding BSI, patients with greater tinnitus severity had more severe psychopathology symptoms, measured with scales “Obsessive-compulsive”, “Depression”, “Anxiety”, “Hostility” and “Phobic Anxiety”. Our study supports the notion of the negative impact of increased tinnitus severity on QoL and psychological distress in older adults. Presented data strengthen the importance of a multidisciplinary approach to tinnitus assessment and treatment. View Full-Text. publishersversion published

Objective: Tinnitus is associated with various conditions such as presbycusis, infectious, autoimmune and many other diseases. Our study aims to identify an association between inflammatory markers...

Objectives: Research on the genetic basis of tinnitus is still in its first steps. A group of scientists dedicated to tinnitus genetics within European Tinnitus Network (TINNET) network recognize that further progress requires multicenter collaborative efforts for defining contributing genes. The purpose of the present work is to provide instructions regarding collection, processing, storage, and shipment of samples intended for genetic studies in auditory research. Design: One part of the recommendations has a general character; another part is of particular importance for auditory healthcare practitioners such as otolaryngology physicians, audiologists, and general practitioners. Results: We provide a set of instructions and various options for obtaining samples. We give advice regarding sample processing, storage, and shipment and define the minimal and essential clinical information that should accompany the samples collected for genetic processing. Conclusions: These recommendations offer a basis to standardize and optimize collaborations between geneticists and healthcare practitioners specialized in tinnitus and hearing disorders. info:eu-repo/semantics/publishedVersion

Subjective tinnitus is a phantom sound heard only by the affected person and may be a symptom of various diseases. Tinnitus diagnosis and monitoring is based on subjective audiometric and psychometric methods. This review aimed to synthesize evidence for tinnitus presence or its severity. We searched several electronic databases, citation searches of the included primary studies through Web of Science, and further hand searches. At least two authors performed all systematic review steps. Sixty-two records were included and were categorized according the biological variable. Evidence for possible tinnitus biomarkers come from oxidative stress, interleukins, steroids and neurotransmitters categories. We found conflicting evidence for full blood count, vitamins, lipid profile, neurotrophic factors, or inorganic ions. There was no evidence for an association between tinnitus and the remaining categories. The current review evidences that larger studies, with stricter exclusion criteria and powerful harmonized methodological design are needed. Protocol published on PROSPERO (CRD42017070998).

Affective disorders are a group of neuropsychiatric disorders characterized by severe mood dysregulations accompanied by sleep, eating, cognitive, and attention disturbances, as well as recurring thoughts of suicide. Clinical studies consistently show that affective disorders are associated with reduced size of brain regions critical for mood and cognition, neuronal atrophy, and synaptic loss in these regions. However, the molecular mechanisms that mediate these changes and thereby increase the susceptibility to develop affective disorders remain poorly understood. MicroRNAs (miRNAs or miRs) are small regulatory RNAs that repress gene expression by binding to the 3ʹUTR of mRNAs. They have the ability to bind to hundreds of target mRNAs and to regulate entire gene networks and cellular pathways implicated in brain function and plasticity, many of them conserved in humans and other animals. In rodents, miRNAs regulate synaptic plasticity by controlling the morphology of dendrites and spines and the expression of neurotransmitter receptors. Furthermore, dysregulated miRNA expression is frequently observed in patients suffering from affective disorders. Together, multiple lines of evidence suggest a link between miRNA dysfunction and affective disorder pathology, providing a rationale to consider miRNAs as therapeutic tools or molecular biomarkers. This review aims to highlight the most recent and functionally relevant studies that contributed to a better understanding of miRNA function in the development and pathogenesis of affective disorders. We focused on in vivo functional studies, which demonstrate that miRNAs control higher brain functions, including mood and cognition, in rodents, and that their dysregulation causes disease-related behaviors.

Subjective tinnitus is a phantom sound heard only by the affected person and may be a symptom of various diseases. Tinnitus diagnosis and monitoring is based on subjective audiometric and psychometric methods. This review aimed to synthesize evidence for tinnitus presence or its severity. We searched several electronic databases, citation searches of the included primary studies through Web of Science, and further hand searches. At least two authors performed all systematic review steps. Sixty-two records were included and were categorized according the biological variable. Evidence for possible tinnitus biomarkers come from oxidative stress, interleukins, steroids and neurotransmitters categories. We found conflicting evidence for full blood count, vitamins, lipid profile, neurotrophic factors, or inorganic ions. There was no evidence for an association between tinnitus and the remaining categories. The current review evidences that larger studies, with stricter exclusion criteria and powerful harmonized methodological design are needed. Protocol published on PROSPERO (CRD42017070998).

Neuronal activity is the main contributor to the high‐energy demand of the human brain. ATP is needed for the maintenance of ionic gradients, neurotransmitter transport, and release, as well as the signaling pathways that follow activation of post‐synaptic receptors. The inability to maintain a high supply of ATP through tight regulatory mechanisms can, therefore, have severe consequences for brain function. In this issue of EMBO Reports, Cui et al [1] show that pharmacological inhibition or genetic inactivation of CD39, an ectonucleotide tri(di)phosphohydrolase responsible for converting ATP into AMP, has antidepressant‐like effects by maintaining high extracellular ATP levels in the presence of stress., EMBO Reports (4), ISSN:1469-221X, ISSN:1469-3178

La sindrome di Pendred è, in ordine di frequenza, la seconda causa di ipoacusia su base genetica autosomica recessiva. Si manifesta con un ipoacusia accompagnata dalla presenza di un gozzo tiroideo con eventuale ipotiroidismo. Tali caratteristiche si accompagnano a malformazioni dell’orecchio interno, quali l’acquedotto vestibolare largo. Nel 50% dei casi vi è una mutazione del gene SLC26A4. Riportiamo nel presente lavoro il caso di una paziente portoghese di 47 anni affetta da ipoacusia di grado severo/profondo e ipotiroidismo. La madre e la sorella della paziente, entrambe decedute, erano a loro volta affette da ipoacusia associata a gozzo tiroideo. La risonanza magnetica e la TC hanno entrambe evidenziato un allargamento dell’acquedotto vestibolare e del sacco endolinfatico. La paziente è stata sottoposta a uno studio di GJB2 e GJB6 seguiti da uno screening di tutti gli esoni di SLC26A4 e delle regioni introniche 8 e 14. È stata rilevata, per la prima volta in omozigosi, una mutazione c.918 + 2T>C nella regione intronica 7 del gene SLC26A4. Sequenziando i campioni di controllo è stata rilevata una nuova mutazione c.821C>G presente in eterozigosi nell’estone 7 del gene SLC26A4, per la quale si è ipotizzato un ruolo dannoso. Il presente studio ha condotto alla scoperta di due nuovi genotipi di SLC26A4, e alla miglior definizione degli aspetti fenotipici associati alla sindrome di Pendred.

Introduction Recent advances in molecular genetics have increased the identification of genes and mutations responsible for inherited forms of hearing loss (HL), enabling early detection of these cases. Approximately, 60% of early-onset HL cases are due to genetic causes, of which 70% are non-syndromic. Of these, 75–80% are inherited in an autosomal recessive pattern (DFNB). Mutations in GJB2 gene, coding for connexin 26 (Cx26), are the major cause of autosomal recessive hereditary HL, but some GJB2 mutations are yet of unclear or controversial significance. Objectives The aim of the present study was to identify the etiology of hearing loss, and correlate genotype–phenotype, in two Portuguese siblings with profound and moderate non-syndromic sensorineural bilateral HL. Material and Methods The affected subjects and their parents underwent audiological and genetic study. Molecular analysis of GJB2 gene was performed, searching for mutations in the coding region and receptor splicing site by automated sequencing. Results The onset and the degree of HL were different in the two affected subjects. However, the same GJB2 genotype [p.Met34Thr] + [p.Arg184Pro] was identified in both siblings. The c.551G > C (p.Arg184Pro) and c.101T > C (p.Met34Thr) missense variants were inherited from the father and mother, respectively, both heterozygous carriers of these variants. Conclusion The clinical and genetic data here presented suggest that the non-syndromic sensorineural HL of these two Portuguese siblings might be due to the presence of p.Met34Thr and p.Arg184Pro variants in compound heterozygosity. If so, p.Met34Thr variant could have function as a hypomorphic allele that may cause HL depending on the opposing GJB2 allele. The observed phenotypic variability may not, however, be solely explained by variable expression of this genotype. A putative modifier gene or mutations in another HL-associated gene could probably be contributing to the severe HL in one of the siblings.

Background - Rubella infection can affect several organs and cause birth defects that are responsible for congenital rubella syndrome (CRS). Congenital hearing loss is the most common symptom of this syndrome, occurring in approximately 60% of CRS cases. Worldwide, over 100 000 babies are born with CRS every year. There is no specific treatment for rubella, but the disease is preventable by vaccination. Since 1969, the rubella vaccine has been implemented in many countries, but in Africa, only a few countries routinely immunize against rubella. The aim of this study was to estimate the rate of infection from the wild-type rubella virus in São Tomé and Príncipe by determining rubella seroprevalence with a DBS method. The goal of this study was to reinforce the need for implementation of the rubella vaccine in this country. As secondary objectives, the validation of a DBS method was first attempted and an association between seroprevalence and hearing loss was assessed. Methods - We collected samples from individuals observed during humanitarian missions in São Tomé and Príncipe. All individuals underwent an audiometric evaluation, and a drop of blood was collected for the dried blood spot (DBS). We define two groups: the case group (individuals with unilateral or bilateral hearing loss (HL)) and the control group (individuals with two normal ears). Patients were excluded if they suffered from conductive HL, if they showed evidence of possible causes of HL, if they had developmental delay or if they refused to participate in the study. Results - Among the 315 subjects, we found 64.1% individuals with IgG for the rubella virus, 32.1% without immunity for the rubella virus and 3.8% who were borderline. In the control group, 62.6% were positive for the rubella IgG, whereas in the case group, 72% were positive. Analyzing both groups, with ages ranging from 2 to 14 years of age and from 15 to 35 years of age, we found a seroprevalence of 50.3% to rubella in the younger group and 82.1% in the older group, with a significant difference between cases and control group noted within the younger patients (p = 0.025). Conclusions - Rubella is a disease that can be prevented. Rubella infections are still very common in São Tomé and Príncipe, and women of child-bearing age are still at risk for rubella infection during pregnancy, justifying the urgency of vaccination against rubella. A statistically significant association between the group of children under 14 years of age with HL and immunity for rubella was observed in this country, although this study did not allow us to establish a cause-effect relationship between rubella infection and SNHL. info:eu-repo/semantics/publishedVersion

Low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of HL in which frequencies at 2,000 Hz and below are predominantly affected. Most of the families with LFSNHL carry missense mutations in WFS1 gene, coding for wolframin. A Portuguese patient aged 49, reporting HL since her third decade of life, and also referring tinnitus, was shown to display bilateral moderate LFSNHL after audiological evaluation. Molecular analysis led to the identification of a novel mutation, c.511G>A (p.Asp171Asn), found in heterozygosity in the exon 5 of the WFS1 gene, and changing the aspartic acid at position 171 to an asparagine, in the extracellular N-terminus domain of the wolframin protein. This novel mutation wasn't present either in 200 control chromosomes analyzed or in the hearing proband's half-brother, and it had not been reported in 1000 Genomes, Exome Variant Server, HGMD or dbSNP databases. No mutations were found in GJB2 and GJB6 genes. Multi-alignment of 27 wolframin sequences from mammalian species, against the human wolframin sequence in ConSurf, indicated a conservation score corresponding to 7 in a 1-9 color scale where 9 is conserved and 1 is variable. In addition, the mutation p.Asp171Asn was predicted to be damaging and possibly damaging by SIFT and Polyphen-2, respectively. The auditory phenotype of this patient could thus be due to the novel mutation p.Asp171Asn. Further functional characterization might enable to elucidate in which way the change in the residue 171, as other changes introduced by LFSNHL-associated mutations previously described, leads to this type of HL.

Hearing loss (HL) is a common condition with both genetic and environmental causes, and it greatly impacts global health. The prevalence of HL is reportedly higher in developing countries such as the Sub-Saharan African island of Sao Tome and Principe, where the deaf community is estimated to be less than 1% of the population. We investigated the role of the DFNB1 locus (GJB2 and GJB6 genes) in the etiology of nonsyndromic sensorineural hearing loss (NSSHL) in Sao Tome and Principe. A sample of 316 individuals, comprising 136 NSSHL patients (92 bilateral, 44 unilateral) and 180 controls, underwent a clinical and audiological examination. Sequencing of the GJB2 coding region and testing for the (GJB6-D13S1830) and del(GJB6-D13S1854) GJB6 deletions were performed. A total of 311 out of 316 individuals were successfully analyzed regarding the GJB2 and GJB6 genetic variations, respectively. The frequency of the GJB2 coding mutations in patients and controls was low. Some of those coding mutations are the most commonly found in Eurasian and Mediterranean populations and have also been identified in Portugal. None of the GJB6 deletions was present. The presence of certain coding variants in Sao Tome and Principe suggests a non-Sub-Saharan genetic influx and supports the previously reported genetic influx from European (mainly Portuguese) ancestors. In summary, DFNB1 locus does not appear to be a major contributor to NSSHL in Sao Tome and Principe. However, the presence of both pathogenic and likely pathogenic mutations in GJB2 suggests that GJB2-related NSSHL might still occur in this population, warranting further research on GJB2 testing in NSSHL cases.

Background: Hearing loss is a problem with higher incidence in South Asia, Asia Pacific and sub-Saharan Africa. In these countries there is also associated history of anemia and malaria. Objective: This study aims to identify a putative role of Beta globin mutation - sickle cell trait and HL in São Tomé and Príncipe population. Methods: A retrospective case-control study of a convenience sample was collected during Otolaryngologist Humanitarian Missions in São Tomé and Príncipe. Control group includes individuals with normal hearing in both ears, and the case group has participants presenting bilateral or unilateral HL. It was evaluated the potential risk factors and sickle cell trait with HL, as well self-report of malaria infection, consanguinity, familial history of HL. The HbS gene point mutation (Glu6Val) was determined by PCR-RFLP. Results: Our results showed a statistical significance between HL - oral language and self-report of HL. Taken altogether, our data did not reveal association between sickle cell trait and HL. However, a statistical association between HL and self-report of malaria was found. Conclusion: No association between sickle cell trait and the high prevalence of HL was found. Self-report of Malaria was found as a risk factor for the development of HL in São Tomé and Príncipe population. The multifactorial profile of HL shall not exclude the relevance of other etiologic factors than Malaria to justify the high prevalence of HL in São Tomé and Príncipe and further investigation must be applied. info:eu-repo/semantics/publishedVersion

Mutations in the GJB2 gene account for up to 50% of hereditary nonsyndromic hearing loss in several populations. Over 200 mutations are already described in this gene, and three of them, c.35delG, c.167delT, and c.235delC, are the most frequent in Caucasians, Ashkenazi Jews, and Asians, respectively. Most of GJB2 hearing loss-related mutations are recessive, but a few dominant alleles have also been described. Apart from the clearly pathogenic mutations, there are some other variants whose pathogenicity is still controversial, such as p.Met34Thr, p.Val37Ile, p.Arg127His, and p.Val153Ile. The p.Arg127His allele has been found in some mono- and biallelic hearing-impaired patients from several countries. In this article we report on some Portuguese patients harboring this mutation. Taking into consideration the analysis of these Portuguese cases as well as the genetic and functional data regarding p.Arg127His available in the literature, we conclude that this variant may be a cause of hearing loss depending on environmental factors and/or genetic background.

Hereditary hearing loss (HL) is a very heterogeneous trait, with 46 gene identifications for non-syndromic HL. Mutations in GJB2 cause up to half of all cases of severe-to-profound congenital autosomal recessive non-syndromic HL, with 35delG being the most frequent mutation in Caucasians. Although a genotype-phenotype correlation has been established for most GJB2 genotypes, the HL of 35delG homozygous patients is mild to profound. We hypothesise that this phenotypic variability is at least partly caused by the influence of modifier genes. By performing a whole-genome association (WGA) study on 35delG homozygotes, we sought to identify modifier genes. The association study was performed by comparing the genotypes of mild/moderate cases and profound cases. The first analysis included a pooling-based WGA study of a first set of 255 samples by using both the Illumina 550K and Affymetrix 500K chips. This analysis resulted in a ranking of all analysed single-nucleotide polymorphisms (SNPs) according to their P-values. The top 250 most significantly associated SNPs were genotyped individually in the same sample set. All 192 SNPs that still had significant P-values were genotyped in a second independent set of 297 samples for replication. The significant P-values were replicated in nine SNPs, with combined P-values between 3 x 10(-3) and 1 x 10(-4). This study suggests that the phenotypic variability in 35delG homozygous patients cannot be explained by the effect of one major modifier gene. Significantly associated SNPs may reflect a small modifying effect on the phenotype. Increasing the power of the study will be of greatest importance to confirm these results.

Mitochondrial DNA (mtDNA) A7445G point mutation has been shown to be responsible for familial nonepidermolytic palmoplantar keratoderma (NEPPK) associated with deafness without any additional features. To date, only a few cases have been described. We report a Portuguese pedigree presenting an inherited combination of NEPPK and sensorineural deafness compatible with maternal transmission. Clinical expression and age of onset of NEPPK and deafness were variable. Normal expression patterns of epidermal keratins and filaggrin, intercellular junction proteins including connexin 26, loricrin and cornified envelope proteins, were observed. Molecular analysis revealed that all the affected members, previously screened for Cx26 mutations with negative results, presented the mtDNA A7445G point mutation in the homoplasmic form. To our knowledge, this is the fifth family in whom inherited NEPPK and hearing loss are related to this mitochondrial mutation.

A possible predisposition to aneuploidy in trisomic 21 individuals, their parents, and a control group was evaluated. Peripheral blood lymphocytes from those three groups were used to study the induction of micronuclei (MN) by mitomycin C, cyclophosphamide, and quercetin. Induced MN were further analysed by C-banding and CREST antibody. Trisomic 21 individuals have spontaneous frequencies of MN significantly higher than their parents and the control group. Quercetin without metabolic activation induces MN in trisomic 21 and their parents at a significantly higher level than in control group. The group of the parents of trisomic 21 individuals exhibits higher frequencies of induced MN by mitomycin C and cyclophosphamide than controls. Mitomycin C significantly induced CREST-positive-MN in ten of the sixteen parents evaluated. The results obtained seem to suggest a unique behaviour for the parents of trisomic 21 patients consisting in an increased susceptibility to chromosome loss in the presence of clastogenic genotoxicants, suggesting a higher predisposition to aneuploidy. Teratogenesis Carcinog. Mutagen. 21:369-382, 2001. (C) 2001 Wiley-Liss, Inc.

Objectives:Nonsyndromic sensorineural hearing loss (HL) is predominantly inherited in an autosomal recessive pattern. The DFNB1 locus, at chromosome 13q11-q12, includes the GJB2 and GJB6 genes, which encode connexin-26 (Cx26) and connexin-30 (Cx30), respectively. The objective of this study was to assess the genetic etiology of HL in a Portuguese family, presenting two siblings with nonsyndromic sensorineural moderate and severe HL, respectively.Methods:The individuals from one Portuguese family were evaluated by pure tone audiometry and blood samples were collected for DNA extraction. Polymerase chain reaction (PCR) amplification of GJB2 coding region followed standard methodologies. PCR products were automatically sequenced in both directions. A random control sample of 480 Portuguese individuals was also screened for the GJB2 coding region.Results:A novel mutation, c.638T>A (p.Leu213X), was identified in the GJB2 gene. This nonsense mutation was found in both siblings, and was inherited from their hear...

Objective: To assess the spectrum and prevalence of mutations in the GJB2 gene in Portuguese nonsyndromic sensorineural hearing loss (NSSHL) patients. Design: Sequencing of the coding region, basal promoter, exon 1 and donor splice site of the GJB2 gene; screening for the presence of the two common GJB6 deletions. Study sample: A cohort of 264 Portuguese NSSHL patients. Results: At least one out of 21 different GJB2 variants was identified in 80 (30.2%) of the 264 patients analysed. Two mutant alleles were found in 53 (20%) of these probands, of which 83% (44/53) harboured at least one c.35delG allele. Twenty-seven (10.2%) of the probands harboured only one mutant allele. Subsequent analysis revealed that the GJB6 deletion del(GJB6-D13S1854) was present in at least 7.4% (2/27) of the patients carrying only one mutant GJB2 allele. Overall, one in five (55/264) of the patients were diagnosed as having DFNB1-related NSSHL, of which the vast majority (53/55) harboured only GJB2 mutations. Conclusions: This study provides clear demonstration that mutations in the GJB2 gene are an important cause of NSSHL in Portugal, thus representing a valuable indicator as regards therapeutical and rehabilitation options, as well as genetic counseling of these patients and their families. info:eu-repo/semantics/publishedVersion

Healthcare-associated infection is an issue with major socio-economic implications worldwide. Urinary Tract Infection is a Healthcare-Associated infection with a high influence on morbidity and personal impact for patients and their families, also has a great economic impact on institutions. The financial cost of each infection is difficult to estimate. Urinary catheterization is recognized as a main risk factor associated with urinary tract infection. However, their use is often essential in providing health care. The frequency with which catheters are placed and the duration of catheterization determines the magnitude of the risk of infection. If the presence of a urinary catheter is inappropriate, then that risk is an avoidable one. The purpose of this study was to quantify the presence of inappropriate urinary catheterization in a Medicine Department in a general hospital, which involved the analysis of all admitted patients to determine the presence of indwelling catheters, on two different days, and later by means of review of the medical records, to identify the cases that develop urinary tract infection. At the moment of the study there were 160 inpatients and a bladder catheter was present in 20%. The prescription for catheterization was mainly (84,4%) a clinician one. Reason for the permanence of the urinary catheter without appropriate indication, was maybe the absence of an order to remove the catheter. In our study, we found that 25% of patients with a urinary catheter had no clear medical order for it on that day. Another result of the study showed that 12 individuals developed urinary tract infection. In this 12 patients group, five cases had no proper order for a urinary catheter. It might be argued that five urinary tract infections were potentially preventable. These five potentially avoidable infections represent 41.7% of the urinary tract infections diagnosed. This is important data considering the need to improve the quality of care as well as all costs associated with the treatment of urinary tract infections.

Individual’s hearing performance after cochlear implant (CI) is variable and depends on different factors such as etiology of deafness, age at implantation, and social/family hearing environment. Here we report the case of dizygotic twins, boy and girl, presenting with neurosensorial profound deafness prior CI (age of implantation = 3.5 years old). Both parents have severe/profound deafness, since childhood, and use sign language as primary mode of communication. Clinical and genetic characterization was performed, as well as the assessment of the auditory and oral (re)habilitation after CI, applying a battery of audiological, speech, and language tests. The twin girl and the father were homozygous for the c.35delG mutation in the GJB2 gene, while the twin boy and the mother were compound heterozygotes, both monoallelic for c.35delG and for the deletion del(GJB6-D13S1830) in theGJB6gene. The remaining hearing impaired relatives were c.35delG homozygotes. The genetic cause of deafness was thus identified in this family. Some noteworthy differences were observed regarding twins’ auditory and oral performance after CI. Subsequent follow-up of these children allowed us to conclude that those differences were most likely due to the different environment in which the twins have been living than to their differentGJB2/GJB6genotypes.

Involvement of GJB2 noncoding regions in hearing loss (HL) has not been extensively investigated. However, three noncoding mutations, c.-259C>T, c.-23G>T, and c.-23+1G>A, were reported. Also, c.-684_-675del, of uncertain pathogenicity, was found upstream of the basal promoter. We performed a detailed analysis of GJB2 noncoding regions in Portuguese HL patients (previously screened for GJB2 coding mutations and the common GJB6 deletions) and in control subjects, by sequencing the basal promoter and flanking upstream region, exon 1, and 3'UTR. All individuals were genotyped for c.-684_-675del and 14 SNPs. Novel variants (c.-731C>T, c.-26G>T, c.*45G>A, and c.*985A>T) were found in controls. A hearing individual homozygous for c.-684_-675del was for the first time identified, supporting the nonpathogenicity of this deletion. Our data indicate linkage disequilibrium (LD) between SNPs rs55704559 (c.*168A>G) and rs5030700 (c.*931C>T) and suggest the association of c.[*168G;*931T] allele with HL. The c.*168A>G change, predicted to alter mRNA folding, might be involved in HL.

Mutations in GJB2 gene (encoding connexin 26) are the most common cause of hereditary non-syndromic sensorineural hearing loss (NSSHL) in different populations. The majority of GJB2 mutations are recessive, but a few dominant mutations have been associated with hearing loss either isolated or associated with skin disease. We describe a novel dominant pathogenic GJB2 mutation, identified in a Portuguese family affected with bilateral mild/moderate high-frequency NSSHL. In vitro functional studies demonstrate that the mutant protein (p.M163L) has defective trafficking to the plasma membrane and is associated with increased cell death.

Mutations in the GJB2 gene are a major cause of non-syndromic recessive hearing loss in many countries. In a significant fraction of patients, only monoallelic GJB2 mutations known to be either recessive or of unclear pathogenicity are identified. This paper reports a novel GJB2 mutation, -3438C-->T, found in the basal promoter of the gene, in trans with V84M, in a patient with profound hearing impairment. This novel mutation can abolish the basal promoter activity of GJB2. These results highlight the importance of extending the mutational screening to regions outside the coding region of GJB2.

Inhibitors of poly(ADP-ribose)polymerase (PARP; EC 2.4.2.30), such as 3-aminobenzamide (3-AB), can be used to assess the role of the enzyme in the induction of DNA lesions in euploid cells as compared to cells of genetic conditions known to exhibit increased susceptibility to chemical or physical mutagens, such as Down’s syndrome (DS) lymphocytes. We report in this work on the effect of PARP inhibition by 3-AB in the induction of sister chromatid exchanges (SCE) and micronuclei (MN) in DS lymphocytes as compared to iymphocytes from normal controls exposed in vitro to a gradient of mitomycin C (MMC). For both tvpes of cells, DS and normal lymphocytes. MMC induces a significant increase in frequencies of SCE and MN in the absence and in the presence of 3-AB. In the presence of 3-AB the yield of SCE and MN induced by MMC was significantly higher in normal lymphocytes as compared to lymphocytes from DS patients. The molecular mechanisms by which 3-AB affects the yield of SCE and MN remains to be fully elucidated: however, it seems clear that DS patients display a diftèrent behavior in what concerns poly(ADP-ribosyl)ation as compared to normal individuais., The authors are grateful to Prof. J. Mexia, Dr. Pedro Aguiar and Dr. Ricardo Rosa, for invaluable help with statistical analysis. Our appreciation is extended to APPACDM (Portuguese association of parents and friends of mentally deficient people). This work was supported by the CIENCIA Program and PRAXIS XXI.

In order to evaluate the predisposition to the aneuploidy-inducing agent colchicine (Col) on lymphocytes from trisomic 21 patients compared with their parents and with a control group of subjects without trisomic children, we performed the micronucleus (MN) assay associated with C-banding, CREST staining, and nucleolar organizing region (NOR)-banding. According to our results Col behaves as an aneugenic agent independently of the population studied for CREST and C-banding. The Col-induced MN exhibited a clear majority (> 80%) of positive NOR-MN, meaning that they contain a NOR region transcriptionally active or inactive. The same data were observed in trisomic 21 individuals, their parents, and the control group, without significant differences between them. These results seem to suggest a preferential effect of the aneugen Col on acrocentric chromosomes in all of the three groups studied.

Quercetin, a mutagenic flavonoid widely distributed in edible plants, was studied for the induction of micronuclei (MN). We have carried out the MN assay in bone marrow polychromatic erythrocytes in mice, in cytokinesis-blocked human lymphocytes and in cytokinesis-blocked V79 cells. MN assay in vitro was performed in the presence and in the absence of S9. To further extend the study, an antikinetochore antibody (CREST staining) was used to distinguish MN containing whole chromosomes (kinetochore positive) from those containing acentric fragments (kinetochore negative). When tested in vivo quercetin failed to induce micronuclei, a result which is in agreement with other published reports. When tested in vitro in V79 cells quercetin clearly induces micronuclei in the absence of S9 and also in the presence of S9 for the highest dose used. When tested in vitro in human lymphocytes quercetin shows a significant induction of micronuclei in the absence and in the presence of S9. The presence of S9 compared to its absence is not significant for any of the systems used. Both in the presence and absence of S9, quercetin appears to behave as a clastogenic agent in human lymphocytes inducing a significant majority of kinetochore-negative MN.