NFAT transcription factors: from cell cycle to tumor development

The nuclear factor of activated T cells (NFAT) family of transcription factors has been primarily identified in immune cells; however, these proteins have been recently found to be functionally active in several other non-immune cell types. NFAT proteins are activated upon different stimuli that lead to increased intracellular calcium levels. Regardless of their widely known cytokine gene expression properties, NFATs have been shown to regulate other genes related to cell cycle progression, cell differentiation and apoptosis, revealing a broader role for these proteins in normal cell physiology. Several reports have addressed the participation of NFATs in many aspects of malignant cell transformation and tumorigenic processes. In this review, we will discuss the involvement of the different NFAT family members in the regulation of cell cycling, differentiation and tumor formation, and also its implications on oncogenesis. Better understanding the mechanisms by which NFATs regulate cell cycle and tumor-related events should be relevant for the development of rational anti-cancer therapies.

A prospective study of hepatitis B virus markers in patients with chronic HBV infection from Brazilian families of Western and Asian origin

The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and non-genetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8%) than in family members of Western origin (36.5%). HBsAg was also more frequent among brothers (79.6 vs 8.5%; P < 0.0001), children (37.9 vs 3.3%; P < 0.0001) and other family members (33.9 vs 16.7%; P < 0.0007) of Asian than Western origin, respectivelly. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7%) and 23/26 (88.5%) of the Asian and Western origin, respectively.

Bone morphogenetic proteins: from structure to clinical use

Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the transforming growth factor ß superfamily. Family members are expressed during limb development, endochondral ossification, early fracture, and cartilage repair. The activity of BMPs was first identified in the 1960s but the proteins responsible for bone induction were unknown until the purification and cloning of human BMPs in the 1980s. To date, about 15 BMP family members have been identified and characterized. The signal triggered by BMPs is transduced through serine/threonine kinase receptors, type I and II subtypes. Three type I receptors have been shown to bind BMP ligands, namely: type IA and IB BMP receptors and type IA activin receptors. BMPs seem to be involved in the regulation of cell proliferation, survival, differentiation and apoptosis, but their hallmark is their ability to induce bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites. This suggests that, in the future, they may play a major role in the treatment of bone diseases. Several animal studies have illustrated the potential of BMPs to enhance spinal fusion, repair critical-size defects, accelerate union, and heal articular cartilage lesions. Difficulties in producing and purifying BMPs from bone tissue have prompted the attempts made by several laboratories, including ours, to express these proteins in the recombinant form in heterologous systems. This review focuses on BMP structure, molecular mechanisms of action and significance and potential applications in medical, dental and veterinary practice for the treatment of cartilage and bone-related diseases.

Prevalence of serological markers of hepatitis B virus in pregnant women from Paraná State, Brazil

The prevalence of hepatitis B virus (HBV) in Brazil increases from South to North but moderate to elevated prevalence has been detected in the Southwest of Paraná State. The prevalence of serological markers of HBV was evaluated in 3188 pregnant women from different counties in Paraná State and relevant epidemiological features were described. The prevalence of HBV markers in pregnant women for the state as a whole was 18.5% (95% CI = 17.2-19.9), ranging from 7.2% in Curitiba to 38.5% in Francisco Beltrão. The endemicity of HBV marker prevalence in pregnant women was intermediate in Cascavel, Foz do Iguaçu, and Francisco Beltrão, and low in Curitiba, Londrina, Maringá, and Paranaguá. Multiple logistic regression showed that HBV marker prevalence increased with age, was higher among black women, among women of Italian and German descent, and among women who had family members in neighboring Rio Grande do Sul State. Univariate analysis showed that HBV marker prevalence was also higher among women with no education or only primary education, with a lower family income and whose families originated from the South Region of Brazil. Pregnant women not having positive HBV markers (anti-HBc, HBsAg or anti-HBs detected by ELISA) corresponded to 73.7% of the population studied, implying that HBV vaccination needs to be reinforced in Paraná State. The highest prevalence was found in three counties that received the largest number of families from Santa Catarina and Rio Grande do Sul, where most immigrants were of German or Italian ascendance. This finding probably indicates that immigrants that came to this area brought HBV infection to Southwestern Paraná State.

Physiological implications of the regulation of vacuolar H+-ATPase by chloride ions

Vacuolar H+-ATPase is a large multi-subunit protein that mediates ATP-driven vectorial H+ transport across the membranes. It is widely distributed and present in virtually all eukaryotic cells in intracellular membranes or in the plasma membrane of specialized cells. In subcellular organelles, ATPase is responsible for the acidification of the vesicular interior, which requires an intraorganellar acidic pH to maintain optimal enzyme activity. Control of vacuolar H+-ATPase depends on the potential difference across the membrane in which the proton ATPase is inserted. Since the transport performed by H+-ATPase is electrogenic, translocation of H+-ions across the membranes by the pump creates a lumen-positive voltage in the absence of a neutralizing current, generating an electrochemical potential gradient that limits the activity of H+-ATPase. In many intracellular organelles and cell plasma membranes, this potential difference established by the ATPase gradient is normally dissipated by a parallel and passive Cl- movement, which provides an electric shunt compensating for the positive charge transferred by the pump. The underlying mechanisms for the differences in the requirement for chloride by different tissues have not yet been adequately identified, and there is still some controversy as to the molecular identity of the associated Cl--conducting proteins. Several candidates have been identified: the ClC family members, which may or may not mediate nCl-/H+ exchange, and the cystic fibrosis transmembrane conductance regulator. In this review, we discuss some tissues where the association between H+-ATPase and chloride channels has been demonstrated and plays a relevant physiologic role.

Participation of the endoplasmic reticulum protein chaperone thio-oxidoreductase in gonadotropin-releasing hormone receptor expression at the plasma membrane

Chaperone members of the protein disulfide isomerase family can catalyze the thiol-disulfide exchange reaction with pairs of cysteines. There are 14 protein disulfide isomerase family members, but the ability to catalyze a thiol disulfide exchange reaction has not been demonstrated for all of them. Human endoplasmic reticulum protein chaperone thio-oxidoreductase (ERp18) shows partial oxidative activity as a protein disulfide isomerase. The aim of the present study was to evaluate the participation of ERp18 in gonadotropin-releasing hormone receptor (GnRHR) expression at the plasma membrane. Cos-7 cells were cultured, plated, and transfected with 25 ng (unless indicated) wild-type human GnRHR (hGnRHR) or mutant GnRHR (Cys14Ala and Cys200Ala) and pcDNA3.1 without insert (empty vector) or ERp18 cDNA (75 ng/well), pre-loaded for 18 h with 1 µCi myo-[2-3H(N)]-inositol in 0.25 mL DMEM and treated for 2 h with buserelin. We observed a decrease in maximal inositol phosphate (IP) production in response to buserelin in the cells co-transfected with hGnRHR, and a decrease from 20 to 75 ng of ERp18 compared with cells co-transfected with hGnRHR and empty vector. The decrease in maximal IP was proportional to the amount of ERp18 DNA over the range examined. Mutants (Cys14Ala and Cys200Ala) that could not form the Cys14-Cys200 bridge essential for plasma membrane routing of the hGnRHR did not modify maximal IP production when they were co-transfected with ERp18. These results suggest that ERp18 has a reduction role on disulfide bonds in wild-type hGnRHR folding.

Ethical research as the target of animal extremism: an international problem

Animal extremism has been increasing worldwide; frequently researchers are the targets of actions by groups with extreme animal rights agendas. Sometimes this targeting is violent and may involve assaults on family members or destruction of property. In this article, we summarize recent events and suggest steps that researchers can take to educate the public on the value of animal research both for people and animals

Five years results after intrafamilial kidney post-transplant in a case of familial hypomagnesemia due to a claudin-19 mutation

Introduction: Familial Hypomagnesaemia with hypercalciuria and nephrocalcinosis, with severe ocular impairment secondary to claudin-19 mutation, is a rare recessive autossomic disorder. Its spectrum includes renal Mg2+ wasting, medullary nephrocalcinosis and progressive chronic renal failure in young people. Objective: To report a case of kidney transplantation father to daughter in a familial occurrence of severe bilateral nephrocalcinosis associated with ocular impairment in a non-consanguineous Brazilian family, in which two daughters had nephrocalcinosis and severe retinopathy. Methods: The index case, a 19 years-old female, had long-lasting past medical history of recurrent urinary tract infections, and the abdominal X-ray revealed bilateral multiple renal calcifications as well as ureteral lithiasis, and she was under haemodialysis. She had the diagnosis of retinitis pigmentosa in the early neonatal period. The other daughter (13 years-old) had also nephrocalcinosis with preserved kidney function, retinopathy with severe visual impairment, and in addition, she exhibited hypomagnesaemia = 0.5 mg/dL and hypercalciuria. The other family members (mother, father and son) had no clinical disease manifestation. Mutation analysis at claudin-19 revealed two heterozygous missense mutations (P28L and G20D) in both affected daughters. The other family members exhibited mutant monoallelic status. In despite of that, the index case underwent intrafamilial living donor kidney transplantation (father). Conclusion: In conclusion, the disease was characterized by an autosomal recessive compound heterozygous status and, after five years of donation the renal graft function remained stable without recurrence of metabolic disturbances or nephrocalcinosis. Besides, donor single kidney Mg2+ and Ca2+ homeostasis associated to monoallelic status did not affect the safety and the usual living donor post-transplant clinical course.

Detection, Identification and Molecular Variation of Human Enteroviruses

Picornaviruses are the most common human viruses and the identification of the picornaviruses is nowadays based on molecular techniques, for example, reverse transcriptase polymerase chain reaction (RT-PCR). One aim of this thesis was to improve the identification of picornaviruses, especially rhino- and enteroviruses, with a real-time assay format and, also, to improve the differentiation of the viruses with genus-specific locked nucleic acid (LNA) probes. Another aim was to identify and study the causative agent of the enterovirus epidemics that appeared in Finland during seasons 2008-2010. In this thesis, the first version of picornavirus qRT-PCR with a melting curve analysis was used in a study of rhinovirus transmission within families with a rhinovirus positive index child where rhinovirus infection was monitored in all family members. In conclusion, rhinoviruses spread effectively within families causing mostly symptomatic infections in children and asymptomatic infections in adults. To improve the differentiation between rhino- and enterovirus the picornavirus qRT-PCR was modified with LNA-incorporated probes. The LNA probes were validated with picornavirus prototypes and different clinical specimen types. The LNA probe-based picornavirus qRT-PCR was able to differentiate all rhino- and enteroviruses correctly, which makes it suitable for diagnostic use. Moreover, in this thesis enterovirus outbreaks were studied with a well-observed method to create a strain-specific qRT-PCR from the typing region VP1 protein. In a hand-foot-and-mouth-disease (HFMD) outbreak in 2008, the causative agent was identified as CV-A6 and when the molecular evolution of the new HFMD CV-A6 strain was studied it was found that CV-A6 was the emerging agent for HFMD and onychomadesis. Furthermore, unusual E-30 meningitis epidemics that apeared during seasons 2009 and 2010 were studied with strain-specific qRT-PCR. The E-30 affected mostly adolescents and was probably spread in sports teams.

Tehohoitopotilaan siirtotiedote hoitotyön päätöksenteon tukena - retrospektiivinen asiakirja-analyysi vuosilta 2001-2013

Tuija Lehtikunnas: Intensive care patient handover document in support of decision-making in nursing work - Retrospective document analysis for the period 2001–2013 University of Turku, Faculty of Medicine, Nursing Science Annales Universitatis Turkuensis Turku 2016 ABSTRACT The continuity of care and flow of information must be ensured when transferring the responsibility of care, whether this is done within an organisation or from one organisation to another. The purpose of this study was to describe and compare the nursing handover documents of long-term intensive care patients and changes to these documents during the years 2001–2013. Research data comprehended long-term intensive care patient handover documents (N = 250). Data was gathered from one university hospital intensive care unit and subjected to a content analysis of technical implementation, structure and content at five different time points. In addition to this, the nursing handover documents were analysed from a nursing decision-making standpoint. Sub-data (n = 5 x 50) from the years 2001, 2002, 2004, 2006 and 2013 was gathered. The first sub-data was manual, written on paper with a pen. The rest of the sub-data obtained was entered in a dedicated intensive care information system. The study developed an intensive care patient nursing handover document analysis framework, which was used to deductively analyse the research data. The results indicated that the transitioning to electronic records reinforced structure and identification improving the reusability of data was increased. Although intensive care nursing was recorded on nursing handover documents more comprehensively in more recent sub-data, it was done selectively with regard to overall patient care, e.g. there are no entries concerning the psychological support and counselling of patients or family members. Nursing handover documents do not contain a systematic description of the patient's communication and functional capacity at the moment of transfer. The patient's condition at the moment of transfer is not clearly indicated on the handover documents. Plans for follow-up treatment are not recorded at all. Nursing decision-making is difficult to find on the nursing handover documents used as research data. The study developed a handover document model for intensive care nursing that supports nursing decision-making and the continuity of care. Developmental recommendations focus on the management of co-operation within organisations for ensuring the continuity of care and enhancing each area of nursing in recording nursing handover documents by planning nursing for the patient, taking follow-up treatment resources into consideration. Keywords: Intensive care nursing, nursing decision-making, nursing records, information flow, nursing handover document, continuity of care

Physiological reactivity and the perception of emotional stimuli as they relate to social adaptive functioning after traumatic brain injury / y Melonie Jane Hopkins.

Traumatic brain injury (TBI) often affects social adaptive functioning and these changes in social adaptability are usually associated with general damage to the frontal cortex. Recent evidence suggests that certain neurons within the orbitofrontal cortex appear to be specialized for the processing of faces and facial expressions. The orbitofrontal cortex also appears to be involved in self-initiated somatic activation to emotionally-charged stimuli. According to Somatic Marker Theory (Damasio, 1994), the reduced physiological activation fails to provide an individual with appropriate somatic cues to personally-relevant stimuli and this, in turn, may result in maladaptive behaviour. Given the susceptibility of the orbitofrontal cortex in TBI, it was hypothesized that impaired perception and reactivity to socially-relevant information might be responsible for some of the social difficulties encountered after TBL Fifteen persons who sustained a moderate to severe brain injury were compared to age and education matched Control participants. In the first study, both groups were presented with photographs of models displaying the major emotions and either asked to identify the emotions or simply view the faces passively. In a second study, participants were asked to select cards from decks that varied in terms of how much money could be won or lost. Those decks with higher losses were considered to be high-risk decks. Electrodermal activity was measured concurrently in both situations. Relative to Controls, TBI participants were found to have difficulty identifying expressions of surprise, sadness, anger, and fear. TBI persons were also found to be under-reactive, as measured by electrodermal activity, while passively viewing slides of negative expressions. No group difference,in reactivity to high-risk card decks was observed. The ability to identify emotions in the face and electrodermal reactivity to faces and to high-risk decks in the card game were examined in relationship to social monitoring and empathy as described by family members or friends on the Brock Adaptive Functioning Questionnaire (BAFQ). Difficulties identifying negative expressions (i.e., sadness, anger, fear, and disgust) predicted problems in monitoring social situations. As well, a modest relationship was observed between hypo-arousal to negative faces and problems with social monitoring. Finally, hypo-arousal in the anticipation of risk during the card game related to problems in empathy. In summary, these data are consistent with the view that alterations in the ability to perceive emotional expressions in the face and the disruption in arousal to personally-relevant information may be accounting for some of the difficulties in social adaptation often observed in persons who have sustained a TBI. Furthermore, these data provide modest support for Damasio's Somatic Marker Theory in that physiological reactivity to socially-relevant information has some value in predicting social function. Therefore, the assessment of TBI persons, particularly those with adaptive behavioural problems, should be expanded to determine whether alterations in perception and reactivity to socially-relevant stimuli have occurred. When this is the case, rehabilitative strategies aimed more specifically at these difficulties should be considered.

Exploring exploration : career identity development and temperment /

Career identity exploration is a central component of the lives of undergraduate university students. Although students are encouraged to explore, it is unclear whether different methods of exploration are better suited for certain individuals. In the present study, quantitative data were collected to examine the relationship between shyness and various methods of exploration. Two hundred fifty-seven university undergraduate students (29 male), ranging in age from 17-25 years completed a 60-minute self-report questionnaire. Shyness, identity, identity distress, subjective dimensions of exploration (satisfaction with exploration, reasons for not exploring, helpfulness of exploration methods), foci of exploration (non-social, social, self, and environmental), approaches to exploration (breadth, depth), and moderating variables (social support, sociability) were measured. Shyness was positively correlated with moratorium (high exploration, low commitment) and uncorrelated with the other identity statuses. Shyness was also positively correlated with identity distress, and a predicted interaction between shyness and identity diffusion predicting career identity distress was supported. Shyness was negatively correlated with satisfaction with amount of exploration engaged in to-date. In addition, shyness was correlated with the likelihood of selecting too stressful and too anxiety provoking as reasons for engaging in less exploration than one would like. Expected relationships between shyness and beliefs about, and engagement in, various methods of exploration were largely non-significant. Exceptions to this were the negative correlations between shyness and engagement in social exploration, and beliefs about the helpfulness of social self-exploration, both of which were significant at a trend level. A predicted interaction between shyness and social support predicting total social exploration was supported, showing that high social support buffers the negative relationship between shyness and exploration; such a moderating relationship did not exist, however, between sociability, shyness and social exploration. Results suggest that although shy university students are engaged in career exploration, they are experiencing feelings of distress and dissatisfaction with their career identity exploration and development. Thus, to help shy students become successfiil in their exploration, it is important for counsellors, family members, and peers to be aware of the feelings the individuals are experiencing and help them reduce the anxiety and stress associated with the exploration process. One promising method, supported by the results in this study, is by encouraging shy individuals to explore with social support.

Other-race faces : limitations of expert face recognition /

Adults' expert face recognition is limited to the kinds of faces they encounter on a daily basis (typically upright human faces of the same race). Adults process own-race faces holistically (Le., as a gestalt) and are exquisitely sensitive to small differences among faces in the spacing of features, the shape of individual features and the outline or contour of the face (Maurer, Le Grand, & Mondloch, 2002), however this expertise does not seem to extend to faces from other races. The goal of the current study was to investigate the extent to which the mechanisms that underlie expert face processing of own-race faces extend to other-race faces. Participants from rural Pennsylvania that had minimal exposure to other-race faces were tested on a battery of tasks. They were tested on a memory task, two measures of holistic processing (the composite task and the part/whole task), two measures of spatial and featural processing (the JanelLing task and the scrambledlblurred faces task) and a test of contour processing (JanelLing task) for both own-and other-race faces. No study to date has tested the same participants on all of these tasks. Participants had minimal experience with other-race faces; they had no Chinese family members, friends or had ever traveled to an Asian country. Results from the memory task did not reveal an other-race effect. In the present study, participants also demonstrated holistic processing of both own- and other-race faces on both the composite task and the part/whole task. These findings contradict previous findings that Caucasian adults process own-race faces more holistically than other-race faces. However participants did demonstrate an own-race advantage for processing the spacing among features, consistent with two recent studies that used different manipulations of spacing cues (Hayward et al. 2007; Rhodes et al. 2006). They also demonstrated an other-race effect for the processing of individual features for the Jane/Ling task (a direct measure of featural processing) consistent with previous findings (Rhodes, Hayward, & Winkler, 2006), but not for the scrambled faces task (an indirect measure offeatural processing). There was no own-race advantage for contour processing. Thus, these results lead to the conclusion that individuals may show less sensitivity to the appearance of individual features and the spacing among them in other-race faces, despite processing other-race faces holistically.

An analysis of the systemic aspects of rights training for people with intellectual disabilities

Individuals with intellectual disabilities (ID) as a group have been subject to abuse. Individuals with ID need to be made aware of their rights. The 3Rs: Rights, Respect and Responsibility Human Rights Project is promoting rights awareness in individuals with ID, their caregivers and family members. To be effeCtive, abuse prevention must include support from the whole organization and its processes. This research evaluated the impact of the 3Rs initiative on the organization. It focused particularly on descriptions of organizational change perceived by full-time staff and managers in response to the initiation of the 3Rs Project. Behavioural interviews were conducted and a thematic analysis was used to describe changes in the organizational culture and behavioural mechanisms maintaining these changes. Systemic barriers to change were also explored. The results indicate that the Association is effectively implementing and supporting the rights-based philosophy.

Florence P. Dolmage estate papers, 1878, 1945-1946

In 1852 Robert Dolmage (ca. 1821-1889) a merchant of Palermo, Halton County, Ontario married Frances Palmer of Toronto. Together they had four daughters: Carrie, Fanny, Laura and Florence. The family resided in Halton County until they moved to Grimsby, Ont. after 1871 and before 1881. Robert Dolmage died in 1889 and his wife, Frances died in 1904. After Robert’s death the family continued to reside in the family home on Main Street in Grimsby, Ont. and the business interests were looked after by Claude A. Boden. Mr. Boden became one of the prime beneficiaries of Florence Palmer Dolmage’s estate after her death in 1945. Florence Dolmage was buried in Queen’s Lawn Cemetery on July 7, 1945. As she was the last remaining member of this family her estate was dispersed to extended family members as well as charitable organizations. At this time, no information is known about the connection between the Dolmage and Sillett families.