Communication of Information about Genetic Risks: Putting Families at the Center.

Genetic information is a family affair. With the expansion of genomic technologies, many new causal genes and variants have been established and the potential for molecular diagnoses increased, with implications not only for patients but also their relatives. The need for genetic counseling and intrafamilial circulation of information on genetic risks grew accordingly.

Muscle development in the shark : implications for the evolution of the gnathostome head and paired appendage musculature.

Background: The origin of jawed vertebrates was marked by profound reconfigurations of the skeleton and muscles of the head and by the acquisition of two sets of paired appendages. Extant cartilaginous fish retained numerous plesiomorphic characters of jawed vertebrates, which include several aspects of their musculature. Therefore, myogenic studies on sharks are essential in yielding clues on the developmental processes involved in the origin of the muscular anatomy.

Differential expression of Cathepsin E in transthyretin amyloidosis: from neuropathology to the immune system.

Background: Increasing evidence supports a key role for inflammation in the neurodegenerative process of familial amyloidotic polyneuropathy (FAP). While there seems to be an overactivation of the neuronal interleukin-1 signaling pathway, the immune response is apparently compromised in FAP. Accordingly, little immune cell infiltration is observed around pre-fibrillar or fibrillar amyloid deposits, with the underlying mechanism for this phenomenon remaining poorly understood.

A Trans-acting Factor May Modify Age at Onset in Familial Amyloid Polyneuropathy ATTRV30M in Portugal.

Although all familial amyloid polyneuropathy (FAP) ATTRV30M patients carry the same causative mutation, early (<40) and late-onset forms (≥50 years) of FAP may coexist in the same family. However, this variability in age at onset is still unexplained. To identify modifiers closely linked to the TTR locus that may in part be associated with age at onset of FAP ATTRV30M, in particular in a group of very early-onset patients (≤30 years) when compared with late-onset individuals.

The perceived impact of the European registration system for genetic counsellors and nurses.

The aim of the European Board of Medical Genetics has been to develop and promote academic and professional standards necessary in order to provide competent genetic counselling services. The aim of this study was to explore the impact of the European registration system for genetic nurses and counsellors from the perspectives of those professionals who have registered. Registration system was launched in 2013.

Complementarity between medical geneticists and genetic counsellors: its added value in genetic services in Europe.

Clinical genetic services have progressed significantly the last few decades. This has led to the need for non-medical health-care professionals working as genetic counsellors in Europe and worldwide. However, there is no unified approach to genetic counsellors' role in health-care services in Europe, as in most countries the profession is still emerging and the educational backgrounds diverge noticeably, within and between countries.

Discredited legacy: Stigma and familial amyloid polyneuropathy in Northwestern Portugal.

Rationale: Genetic inherited conditions may result in feelings of stigmatisation, mainly because of visible physical appearance and its transmissibility to offspring.

Objective: This article reports accounts of stigmatisation from Portuguese patients affected by the inherited neurodegenerative disease, familial amyloid polyneuropathy (FAP), living in the largest cluster of patients worldwide.

Method: We draw on semi-structured interviews conducted with individuals at-risk or affected by FAP, recruited through the national patients' association, about their experiences of stigmatisation related to the illness.

A proteomic and ultrastructural characterization of Aspergillus fumigatus' conidia adaptation at different culture ages.

Unlabelled: The airborne fungus Aspergillus fumigatus is one of the most common agents of human fungal infections with a remarkable impact on public health. However, A. fumigatus conidia atmospheric resistance and longevity mechanisms are still unknown.

VDAC regulates AAC-mediated apoptosis and cytochrome release in yeast.

Mitochondrial outer membrane permeabilization is a key event in apoptosis processes leading to the release of lethal factors. We have previously shown that absence of the ADP/ATP carrier (AAC) proteins (yeast orthologues of mammalian ANT proteins) increased the resistance of yeast cells to acetic acid, preventing MOMP and the release of cytochrome from mitochondria during acetic acid - induced apoptosis. On the other hand, deletion of (yeast voltage-dependent anion channel - VDAC) increased the sensitivity of yeast cells to acetic acid.

From older to younger: intergenerational promotion of health behaviours in Portuguese families affected by familial amyloid polyneuropathy.

The role of older generations in families with hereditary diseases has been recognised and associated to their function as guardians of the family's medical history. However, research is scarce in examining the roles that older generations play in terms of health promotion and risk management towards younger generations, which is particularly evident with incurable genetically inherited disorders such as familial amyloid polyneuropathy (FAP) ATTR Val30Met. This qualitative exploratory study examines the roles that older generations play towards younger generations, in terms of health promotion and risk management, in families with FAP.

Reliability and validity of the Bowel Function Index for evaluating opioid-induced constipation: translation, cultural adaptation and validation of the Portuguese version (BFI-P).

Objective: The Bowel Function Index (BFI) is a simple and sound bowel function and opioid-induced constipation (OIC) screening tool. We aimed to develop the translation and cultural adaptation of this measure (BFI-P) and to assess its reliability and validity for the Portuguese language and a chronic pain population.

Methods: The BFI-P was created after a process including translation, back translation and cultural adaptation.

Portuguese Version of the Pain Beliefs and Perceptions Inventory: A Multicenter Validation Study.

Background: We aimed to perform the translation, cultural adaptation, and validation of the Pain Beliefs and Perceptions Inventory (PBPI) for the European Portuguese language and chronic pain population.

Methods: This is a longitudinal multicenter validation study. A Portuguese version of the PBPI (PBPI-P) was created through a process of translation, back translation, and expert panel evaluation.

Transthyretin provides trophic support via megalin by promoting neurite outgrowth and neuroprotection in cerebral ischemia.

Transthyretin (TTR) is a protein whose function has been associated to binding and distribution of thyroid hormones in the body and brain. However, little is known regarding the downstream signaling pathways triggered by wild-type TTR in the CNS either in neuroprotection of cerebral ischemia or in physiological conditions. In this study, we investigated how TTR affects hippocampal neurons in physiologic/pathologic conditions.

Urinary Neurotrophin Levels Increase in Women With Stress Urinary Incontinence After a Midurethral Sling Procedure.

Objective: To investigate the association between urinary neurotrophin levels, maximum flow rate (Qmax) variation, and the appearance of urgency in women with stress urinary incontinence (SUI) after a midurethral sling (MUS) procedure.

Materials And Methods: Thirty-one women with SUI were treated with a MUS. One year later, the outcome of surgery and the onset of urgency were assessed.

A systematic review of interventions to provide genetics education for primary care.

Background: At least 10 % of patients seen in primary care are said to have a condition in which genetics has an influence. However, patients at risk of genetic disease may not be recognised, while those who seek advice may not be referred or managed appropriately. Primary care practitioners lack knowledge of genetics and genetic testing relevant for daily practice and feel inadequate to deliver genetic services.

Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum.

Visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, is one of the most important zoonotic diseases affecting dogs and humans in the Mediterranean area. The presence of infected dogs as the main reservoir host of L. infantum is regarded as the most significant risk for potential human infection.

Activity of Bisnaphthalimidopropyl Derivatives against Trypanosoma brucei.

Current treatments for African trypanosomiasis are either toxic, costly, difficult to administer, or prone to elicit resistance. This study evaluated the activity of bisnaphthalimidopropyl (BNIP) derivatives againstTrypanosoma brucei BNIPDiaminobutane (BNIPDabut), the most active of these compounds, showedin vitroinhibition in the single-unit nanomolar range, similar to the activity in the reference drug pentamidine, and presented low toxicity and adequate metabolic stability. Additionally, using a murine model of acute infection and live imaging, a significant decrease in parasite load in BNIPDabut-treated mice was observed.

Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities.

In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2 Gy/fraction/day).

Biophysical characterization of laforin-carbohydrate interaction.

Laforin is a human dual-specificity phosphatase (DSP) involved in glycogen metabolism regulation containing a carbohydrate-binding module (CBM). Mutations in the gene coding for laforin are responsible for the development of Lafora disease, a progressive fatal myoclonus epilepsy with early onset, characterized by the intracellular deposition of abnormally branched, hyperphosphorylated insoluble glycogen-like polymers, called Lafora bodies. Despite the known importance of the CBM domain of laforin in the regulation of glycogen metabolism, the molecular mechanism of laforin-glycogen interaction is still poorly understood.

Cellular uptake and transcytosis of lipid-based nanoparticles across the intestinal barrier: Relevance for oral drug delivery.

Oral administration is the preferred route for drug delivery and nanosystems represent a promising tool for protection and transport of hardly soluble, chemically unstable and poorly permeable drugs through the intestinal barrier. In the present work, we have studied lipid nanoparticles cellular uptake, internalization pathways and transcytosis routes through Caco-2 cell monolayers. Both lipid nanosystems presented similar size (∼180nm) and surface charge (-30mV).

Redescription and life cycle of the monorchiid Postmonorcheides maclovini Szidat, 1950 (Digenea) from the Southwestern Atlantic Ocean: Morphological and molecular data.

The adult monorchiid, Postmonorcheides maclovini Szidat, 1950, digenean parasite of the Patagonian blennie Eleginops maclovinus (Cuvier) (Eleginopidae) from Puerto Deseado (47° 45' S, 65° 55' W), Argentina, was characterized and its life cycle elucidated. P. maclovinus is the only species of the genus Postmonorcheides, proposed by Szidat (1950) from Tierra del Fuego province (~54° S), Argentina.