PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency

OBJECTIVE: Mutations of the PROP1 gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD. DESIGN, PATIENTS AND MEASUREMENTS: A multicentric study involving 46 cases of CPHD (17 familial cases belonging to seven kindreds and 29 sporadic cases) selected on the basis of clinical and hormonal evidence of GH deficiency, central hypothyroidism and hypogonadotrophic hypogonadism, in the absence of an identified cause of hypopituitarism. Mutations of PROP1 were investigated by DNA sequencing. Clinical, hormonal and neuroradiological data were collected at each centre. RESULTS: PROP1 mutations were identified in all familial cases: five kindreds presented a c. 301-302delAG mutation, one kindred presented a c. 358C --> T (R120C) mutation and one presented a previously unreported initiation codon mutation, c. 2T --> C. Of the 29 sporadic cases, only two (6.9%) presented PROP1 germline mutations (c. 301-302delAG, in both). Phenotypic variability was observed among patients with the same mutations, particularly the presence and age of onset of hypocortisolism, the levels of PRL and the results of pituitary imaging. One patient presented a sellar mass that persisted into adulthood. CONCLUSIONS: This is the first report of a mutation in the initiation codon of the PROP1 gene and this further expands the spectrum of known mutations responsible for CPHD. The low mutation frequency observed in sporadic cases may be due to the involvement of other unidentified acquired or genetic cause

Prevalence of antimicrobial resistance in enteric Escherichia coli from domestic pets and assessment of associated risk markers using a generalized linear mixed model

Antimicrobial resistance (AMR) is a growing global public health problem, which is caused by the use of antimicrobials in both human and animal medical practice. The objectives of the present cross-sectional study were as follows: (1) to determine the prevalence of resistance in Escherichia coli isolated from the feces of pets from the Porto region of Portugal against 19 antimicrobial agents and (2) to assess the individual, clinical and environmental characteristics associated with each pet as risk markers for the AMR of the E. coli isolates. From September 2009 to May 2012, rectal swabs were collected from pets selected using a systematic random procedure from the ordinary population of animals attending the Veterinary Hospital of Porto University. A total of 78 dogs and 22 cats were sampled with the objective of isolating E. coli. The animals’ owners, who allowed the collection of fecal samples from their pets, answered a questionnaire to collect information about the markers that could influence the AMR of the enteric E. coli. Chromocult tryptone bile X-glucuronide agar was used for E. coli isolation, and the disk diffusion method was used to determine the antimicrobial susceptibility. The data were analyzed using a multilevel, univariable and multivariable generalized linear mixed model (GLMM). Several (49.7%) of the 396 isolates obtained in this study were multidrug-resistant. The E. coli isolates exhibited resistance to the antimicrobial agent's ampicillin (51.3%), cephalothin (46.7%), tetracycline (45.2%) and streptomycin (43.4%). Previous quinolone treatment was the main risk marker for the presence of AMR for 12 (ampicillin, cephalothin, ceftazidime, cefotaxime, nalidixic acid, ciprofloxacin, gentamicin, tetracycline, streptomycin, chloramphenicol, trimethoprim–sulfamethoxazole and aztreonam) of the 15 antimicrobials assessed. Coprophagic habits were also positively associated with an increased risk of AMR for six drugs, ampicillin, amoxicillin–clavulanic acid, cephamycin, ciprofloxacin, streptomycin, and trimethoprim–sulfamethoxazole. In summary, pets with a record of one or more previous quinolone treatments and exhibiting coprophagic habits were at an increased risk of harboring multidrug-resistant E. coli strains in their feces compared to pets without these characteristics. AMR is a serious global problem, and assessing the risk markers for the presence of drug-resistant bacteria in pets, a very close source of resistance determinants to humans, is essential for the implementation of safe handling procedures for companion animals and for the prudent selection of antimicrobial compounds in veterinary practice

Crystal structures and binding dynamics of Odorant-Binding Protein 3 from two aphid species Megoura viciae and Nasonovia ribisnigri

Aphids use chemical cues to locate hosts and find mates. The vetch aphid Megoura viciae feeds exclusively on the Fabaceae, whereas the currant-lettuce aphid Nasonovia ribisnigri alternates hosts between the Grossulariaceae and Asteraceae. Both species use alarm pheromones to warn of dangers. For N. ribisnigri this pheromone is a single component (E)-β-farnesene but M. viciae uses a mixture of (E)-β-farnesene, (-)-α- pinene, β-pinene, and limonene. Odorant-binding proteins (OBP) are believed to capture and transport such semiochemicals to their receptors. Here, we report the first aphid OBP crystal structures and examine their molecular interactions with the alarm pheromone components. Our study reveals some unique structural features: 1) the lack of internal ligand binding site; 2) a striking groove in the surface of the proteins as a putative binding site; 3) the N-terminus rather than the C-terminus occupies the site closing off the conventional OBP pocket. The results from fluorescent binding assays, molecular docking and dynamics demonstrate that OBP3 from M. viciae can bind to all four alarm pheromone components and the differential ligand binding between these very similar OBP3s from the two aphid species is determined mainly by the direct π-π interactions between ligands and the aromatic residues of OBP3s in the binding pocket

The emotional movie database (EMDB): a self-report and psychophysiological study

Film clips are an important tool for evoking emotional responses in the laboratory. When compared with other emotionally potent visual stimuli (e.g., pictures), film clips seem to be more effective in eliciting emotions for longer periods of time at both the subjective and physiological levels. The main objective of the present study was to develop a new database of affective film clips without auditory content, based on a dimensional approach to emotional stimuli (valence, arousal and dominance). The study had three different phases: (1) the pre-selection and editing of 52 film clips (2) the self-report rating of these film clips by a sample of 113 participants and (3) psychophysiological assessment [skin conductance level (SCL) and the heart rate (HR)] on 32 volunteers. Film clips from different categories were selected to elicit emotional states from different quadrants of affective space. The results also showed that sustained exposure to the affective film clips resulted in a pattern of a SCL increase and HR deceleration in high arousal conditions (i.e., horror and erotic conditions). The resulting emotional movie database can reliably be used in research requiring the presentation of non-auditory film clips with different ratings of valence, arousal and dominance.Portuguese Foundation for Science and Technology with individual grants (SFRH/BD/41484/2007 and SFRH/BD/64355/2009

Regulatory considerations for the clinical and research use of transcranial Direct Current Stimulation (tDCS): Review and recommendations from an expert panel

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. Therefore, a group of research and clinician experts on tDCS were convened to review the research and clinical use of tDCS. This report reviews the regulatory status of tDCS and summarizes the results according to research, off-label, and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan, and the US. Research use, off label treatment, and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials.F.F. is supported by a grant from National Institutes of Health (NIH) (Grant number 1R44NS08063201). A.R.B. is supported by the following grants: 2013 NARSAD Young Investigator from the Brain & Behavior Research Foundation (Grant Number 20493), 2013 FAPESP Young Researcher from the São Paulo State Foundation (Grant Number 20911-5) and National Council for Scientific and Technological Development (CNPq, Grant Number 470904). J.B. is supported by the 2013 NARSAD Young Investigator from the Brain & Behavior Research Foundation (Grant Number 20988). H.E. is supported by grants from Tehran University of Medical Sciences. J.L. (SFRH/BPD/86027/2012) and S.C. (SFRH/BPD/86041/2012) are supported by grants from the Portuguese Foundation for Science and Technology (FCT). C.H.J. is supported by MOST (101-2811-H-008-014). G.V. is supported by as the Department of Science and Technology (Government of India) Research Grant (SR/CSI/158/2012) as well as Wellcome Trust / DBT India Alliance Senior Fellowship Research Award (500236/Z/11/Z). N.B. is supported by a F.A.R. grant from the University of Milano-Bicocca. M.B. is supported by NIH (NINDS, NIMH, NCI), Wallace H Coulter Foundation, Grove Foundation, DoD. W.C. is supported by National Council for Scientific and Technological Development-CNPq WC-301256/2013-6. The group is also grateful to the support from the Conselho Brasileiro de Neuromodulacao Clinica – Instituto Scala

Burden and modifications in life from the perspective of caregivers for patients after stroke

OBJECTIVE: to analyze the impact that caring has on a member of the family caring for a patient after a cerebrovascular accident, correlating life modifications and mental suffering with the perceived burden. METHOD: a cross-sectional, quantitative study, undertaken in January-April 2010 in Fortaleza, Ceará, Brazil. RESULT: 61 individuals were investigated, monitored by three hospitals' Home Care Program. Data collection was through interviews for identifying life changes, and through the application of three scales for investigating perceived burden, mental state and mental suffering. Respectively these were the Caregiver Burden Scale (CBS), the Mini-Mental State Examination (MMSE) and the Self Reported Questionnaire (SRQ). The majority of the carers were female, married, and the children of the stroke patients. The average age was 48.2 years (±12.4). The most-cited life modifications referred to the daily routine, to leisure activities, and to exhaustion or tiredness. Regarding burden, the dimensions of General tension, Isolation and Disappointment stood out. It was ascertained that overload was more severe when the carer presented more symptoms of psychological distress, in the absence of a secondary carer, and when the principal carers reported perceiving changes in their bodies and health. CONCLUSION: an association between burden and the carer's mental state was not observed. Understanding the care, through analysis of the burden and of the knowledge of the biopsychosocial situation will provide support for the nurse's work in reducing the overload for family caregivers.OBJETIVO: analizar el impacto del cuidar para el cuidador familiar de paciente después de accidente vascular cerebral, correlacionando modificaciones de vida y sufrimiento psíquico con la sobrecarga percibida. MÉTODO: estudio transversal, cuantitativo, realizado de enero a abril de 2010, en Fortaleza, Ceará, Brasil. RESULTADO: se investigaron 61 individuos, acompañados por el Programa de Servicio Domiciliar de tres hospitales. La colecta de los datos ocurrió mediante entrevista para identificar modificaciones de vida, y con la aplicación de tres escalas para investigar la sobrecarga percibida, estado mental y sufrimiento psíquico. Son ellas, respectivamente: Caregiver Burden Scale (CBS), Mini Examen del Estado Mental (MEEM) y Self Reported Questionnaire (SRQ). Los cuidadores, en su mayoría, eran del sexo femenino, casados (as) e hijo (as) de los pacientes después del AVC. Edad Media de 48,2 años (±12,4). Las modificaciones de vida más citadas fueron referentes a la rutina diaria, a las actividades de ocio y agotamiento o cansancio. En cuanto a la sobrecarga, se destacaron las dimensiones Tensión general, Aislamiento y Decepción. Se verificó mayor sobrecarga cuanto más síntomas de sufrimiento psíquico el cuidador presentase, en la ausencia de cuidador secundario y cuando los cuidadores principales relataron percibir modificación en el cuerpo y en la salud. CONCLUSIÓN: no fue observada asociación de la sobrecarga con el estado mental del cuidador. Entender la coyuntura del cuidado, mediante análisis del recargo de trabajo, y del conocimiento de la situación biopsicosocial, suministrará subsidios para la actuación del enfermero para reducir la carga generada para los cuidadores familiares.OBJETIVO: analisar o impacto do cuidar para o cuidador familiar de paciente após acidente vascular cerebral (AVC), correlacionando modificações de vida e sofrimento psíquico com a sobrecarga percebida. MÉTODO: estudo transversal, quantitativo, realizado de janeiro a abril de 2010, em Fortaleza, Ceará, Brasil. RESULTADO: investigaram-se 61 indivíduos, acompanhados pelo Programa de Atendimento Domiciliar (PAD), de três hospitais. A coleta dos dados ocorreu mediante entrevista para identificar modificações de vida, e com a aplicação de três escalas para investigar sobrecarga percebida, estado mental e sofrimento psíquico. São elas, respectivamente: Caregiver Burden Scale (CBS), Miniexame do Estado Mental (MEEM) e Self Reported Questionnaire (SRQ). Os cuidadores, na sua maioria, eram do sexo feminino, casados(as) e filho(as) dos pacientes após AVC. A média de idade era de 48,2 anos (±12,4). As modificações de vida mais citadas foram referentes à rotina diária, às atividades de lazer e esgotamento ou cansaço. Quanto à sobrecarga, destacaram-se as dimensões tensão geral, isolamento e decepção. Verificou-se maior sobrecarga quanto mais sintomas de sofrimento psíquico o cuidador apresentasse, na ausência de cuidador secundário e quando os cuidadores principais relataram perceber modificação no corpo e na saúde. CONCLUSÃO: não foi observada associação da sobrecarga com o estado mental do cuidador. Entender a conjuntura do cuidado, mediante análise da sobrecarga de trabalho, e do conhecimento da situação biopsicossocial fornecerá subsídios para a atuação do enfermeiro para reduzir a carga gerada para os cuidadores familiares