Genome-wide study of familial juvenile hyperuricaemic (gouty) nephropathy (FJHN) indicates a new locus, FJHN3, linked to chromosome 2p22.1-p21

Familial juvenile hyperuricaemic (gouty) nephropathy (FJHN), is an autosomal dominant disease associated with a reduced fractional excretion of urate, and progressive renal failure. FJHN is genetically heterogeneous and due to mutations of three genes: uromodulin (UMOD), renin (REN) and hepatocyte nuclear factor-1beta (HNF-1β) on chromosomes 16p12, 1q32.1, and 17q12, respectively. However, UMOD, REN or HNF-1β mutations are found in only ~45% of FJHN probands, indicating the involvement of other genetic loci in ~55% of probands. To identify other FJHN loci, we performed a single nucleotide polymorphism (SNP)-based genome-wide linkage analysis, in six FJHN families in whom UMOD, HNF-1β and REN mutations had been excluded. Parametric linkage analysis using a 'rare dominant' model established linkage in five of the six FJHN families, with a LOD score >+3, at 0% recombination, between FJHN and SNPs at chromosome 2p22.1-p21. Analysis of individual recombinants in two unrelated affected individuals defined a ~5.5 Mbp interval, flanked telomerically by SNP RS372139 and centromerically by RS896986 that contained the locus, designated FJHN3. The interval contains 28 genes, and DNA sequence analysis of the most likely candidate, solute carrier family 8 member 1 (SLC8A1), did not identify any abnormalities in the FJHN3 probands. FJHN3 is likely located within a ~5.5 Mbp interval on chromosome 2p22.1-p21, and identifying the genetic abnormality will help to further elucidate mechanisms predisposing to gout and renal failure.

Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32

PURPOSE The restricted genetic diversity and homogeneous molecular basis of Mendelian disorders in isolated founder populations have rarely been explored in epilepsy research. Our long-term goal is to explore the genetic basis of epilepsies in one such population, the Gypsies. The aim of this report is the clinical and genetic characterization of a Gypsy family with a partial epilepsy syndrome. METHODS Clinical information was collected using semistructured interviews with affected subjects and informants. At least one interictal electroencephalography (EEG) recording was performed for each patient and previous data obtained from records. Neuroimaging included structural magnetic resonance imaging (MRI). Linkage and haplotype analysis was performed using the Illumina IVb Linkage Panel, supplemented with highly informative microsatellites in linked regions and Affymetrix SNP 5.0 array data. RESULTS We observed an early-onset partial epilepsy syndrome with seizure semiology strongly suggestive of temporal lobe epilepsy (TLE), with mild intellectual deficit co-occurring in a large proportion of the patients. Psychiatric morbidity was common in the extended pedigree but did not cosegregate with epilepsy. Linkage analysis definitively excluded previously reported loci, and identified a novel locus on 5q31.3-q32 with an logarithm of the odds (LOD) score of 3 corresponding to the expected maximum in this family. DISCUSSION The syndrome can be classified as familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild intellectual deficit. The linked 5q region does not contain any ion channel-encoding genes and is thus likely to contribute new knowledge about epilepsy pathogenesis. Identification of the mutation in this family and in additional patients will define the full phenotypic spectrum.

Concordance of disease severity among family members with ankylosing spondylitis?

Objective. The heritability of disease activity and function in ankylosing spondylitis (AS) have been estimated at 0.51 and 0.63 (i.e., 51% and 63%), respectively. We examined the concordance of disease severity among family members in terms of disease activity, function, radiological change, prevalence of iritis, and juvenile onset. Methods. Disease activity and functional impairment due to AS were studied using the Bath AS Disease Activity Index (BASDAI) and Functional Index (BASFI) self-administered questionnaires; radiographic involvement was measured using the Bath AS Radiology Index (BASRI) scale. Familial correlation of BASDAI and BASFI was assessed in 406 families with 2 or more cases, using the program PAP. Parent-child and sibling-sibling concordance for iritis and juvenile AS were also studied in these families. Heritability of radiological disease severity based on the BASRI was assessed in 29 families containing 60 affected individuals using the program SOLAR. Results. Correlations between parent-child pairs for disease activity and function were 0.07 for both. Correlations between sibling pairs for disease activity and function were 0.27 and 0.36, respectively. The children of AS parents with iritis were more likely to develop iritis [27/71 (38%)] than children of non-iritis AS parents [13/70 (19%)] (p = 0.01). Parents with JAS were more likely to have children with JAS [17/30 (57%) compared to non-JAS parents 34/111 (30%)] (p = 0.002). The heritability of radiological disease severity based on the BASRI was 0.62. Conclusion. While correlation in severity between parent and child is poor, siblings do resemble each other in terms of severity, supporting the findings of segregation studies indicating significant genetic dominance in the heritable component of disease activity. Significant parent-child concordance for iritis and juvenile disease onset suggest that there are genetic risk factors for these traits independent of those determining the risk of AS itself. The finding of significant heritability of radiological change (BASRI) provides support using an objective measure for the observed heritability of the questionnaire-assessed disease severity scores, ASDAI and BASFI.

The treatment of recurrent abdominal pain in children : a controlled comparison of cognitive-behavioral family intervention and standard pediatric care

This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were randomly allocated to either cognitive-behavioral family intervention (CBFI) or standard pediatric care (SPC). Both treatment conditions resulted in significant improvements on measures of pain intensity and pain behavior. However, the children receiving CBFI had a higher rate of complete elimination of pain, lower levels of relapse at 6- and 12-month follow-up, and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC. After controlling for pretreatment levels of pain, children's active self-coping and mothers' caregiving strategies were significant independent predictors of pain behavior at posttreatment.

Expression of the extracellular domain of the human heat-stable enterotoxin receptor in Escherichia coli and generation of neutralizing antibodies

The entire extracellular domain of the human heat-stable enterotoxin (ST) receptor as well as a truncated N-terminal domain were cloned as glutathione S-transferase fusion proteins and expressed in Escherichia coli. The recombinant fusion proteins were purified from both the cytosol and the inclusion body fractions by selective detergent extraction followed by glutathione-agarose affinity chromatography. The purified protein, corresponding to the entire extracellular domain, bound the stable toxin peptide with an affinity comparable to that of the native receptor characterized from the human colonic T84 cell line. No binding was observed with the N-terminal truncated fragment of the receptor under similar conditions, Polyclonal antibodies were raised to the entire extracellular domain fusion protein as well as the truncated extracellular domain fusion protein, and the antibodies were purified by affinity chromatography. Addition of the purified antibodies to T84 cells inhibited ST binding and abolished ST-mediated cGMP production, indicating that critical epitopes involved in ligand interaction are present in the N-terminal fragment of the receptor, Purified antibodies recognized a single protein of M(r) 160,000 Da on Western blotting with T84 membranes, corresponding to a size of the native glycosylated receptor in T84 cells. These studies are the first report of the expression, purification, and characterization of any member of the guanylyl cyclase family of receptors in E. coli and show that binding of the toxin to the extracellular domain of the receptor is possible in the absence of any posttranslational modifications such as glycosylation. The recombinant fusion proteins as well as the antibodies that we have generated could serve as useful tools in the identification of critical residues of the extracellular domain involved in ligand interaction.

Guanylyl Cyclase C Receptor: Regulation of Catalytic Activity by ATP

Guanylyl cyclase C (GCC), a member of the family of membrane bound guanylyl cyclases is the receptor for the heat-stable enterotoxin (ST) peptides and the guanylin family of endogenous peptides. GCC is activated upon ligand binding to increase intracellular cGMP levels, which in turn activates other downstream signalling events in the cell. GCC is also activated in vitro by nonionic detergents. We have used the T84 cell line as a model system to investigate the regulation of GCC activity by ATP. Ligand-stimulated GCC activity is potentiated in the presence of ATP, whereas detergent-stimulated activity is inhibited. The potentiation of GCC activity by ATP is dependent on the presence of Mg2+ ions, and is probably brought about by a direct binding of Mg-ATP to GCC. The protein kinase-like domain of GCC, which has earlier been shown to play a critical role in the regulation of GCC activity, may be a possible site for the binding of Mg-ATP to GCC.

Influence of lanthanum doping on the dielectric, ferroelectric and relaxor behaviour of barium bismuth titanate ceramics

Barium lanthanum bismuth titanate (Ba1−(3/2)xLaxBi4Ti4O15, x = 0–0.4) ceramics were fabricated using the powders synthesized via the solid-state reaction route. X-ray powder diffraction analysis confirmed the above compositions to be monophasic and belonged to the m = 4 member of the Aurivillius family of oxides. The effect of the partial presence of La3+ on Ba2+ sites on the microstructure, dielectric and relaxor behaviour of BaBi4Ti4O15 (BBT) ceramics was investigated. For the compositions pertaining to x ≤ 0.1, the dielectric constant at both room temperature and in the vicinity of the temperature of the dielectric maximum (Tm) of the parent phase (BBT) increased significantly with an increase in x while Tm remained almost constant. Tm shifted towards lower temperatures accompanied by a decrease in the magnitude of the dielectric maximum (εm) with an increase in the lanthanum content (0.1 < x ≤ 0.4). The dielectric relaxation was modelled using the Vogel–Fulcher relation and a decrease in the activation energy for frequency dispersion with increasing x was observed. The frequency dispersion of Tm was found to decrease with an increase in lanthanum doping, and for compositions corresponding to x ≥ 0.3, Tm was frequency independent. Well-developed P(polarization)–E(electric field) hysteresis loops were observed at 150 °C for all the samples and the remanent polarization (2Pr) was improved from 6.3 µC cm−2 for pure BBT to 13.4 µC cm−2 for Ba0.7La0.2Bi4Ti4O15 ceramics. Dc conductivities and associated activation energies were evaluated using impedance spectroscopy.

Fostering collaboration in the management of family finances

Managing finances is a practice carried out daily in homes across the world. Despite this, the practice is not yet a strong focus for HCI work in the home. This paper looks specifically at the ways that families organise and manage their finances. Based on a process of in-situ qualitative interviews, we find that money management is often a collaborative process in the family and occurs in a similar way to other household tasks; as part of existing divisions of domestic labour. Participating families reflected upon the creative and often low-tech systems they used to manage their finances and ideas they had for “ideal” technologies that would better help them organise their money. This paper presents ideas for fostering collaboration around family finances. Design propositions are made towards a Family Holiday Expense Tracker and family-situated bill payment reminder, both of which aim to encourage whole-of-family collaboration around money management and better including children in what is, at-present, an activity they are largely excluded from.

Family violence in culturally and linguistically diverse communities: An evaluation of a family relationship centre

Federal legislative changes in Australia have sought to improve how family relationship centres (FRCs) can be more responsive to culturally and linguistically diverse (CALD) communities when addressing family disputes and family violence. Research on the prevalence of family violence against women from CALD backgrounds is sparse. This article seeks to contribute to the understanding of this issue by describing findings of an evaluation of the FRC at Broadmeadows conducted by the authors. The findings focus on family violence and the appropriateness of the services offered to three CALD community groups, namely Iraqi, Lebanese and Turkish. The final section provides reflections on these findings and offers suggestions about how FRC services might better cater to the family violence needs of CALD communities by developing more extensive partnerships with community groups and by expanding the range of processes they offer beyond mediation.

Interactions of natural products with β-lactoglobulins, members of the lipocalin family

Natural products constitute an important source of new drugs. The bioavailability of the drugs depends on their absorption, distribution, metabolism and elimination. To achieve good bioavailability, the drug must be soluble in water, stable in the gastrointestinal tract and palatable. Binding proteins may improve the solubility of drug compounds, masking unwanted properties, such as bad taste, bitterness or toxicity, transporting or protecting these compounds during processing and storage. The focus of this thesis was to study the interactions, including ligand binding and the effect of pH and temperature, of bovine and reindeer β-lactoglobulin (βLG) with such compounds as retinoids, phenolic compounds as well as with compounds from plant extracts, and to investigate the transport properties of the βLG-ligand complex. To examine the binding interactions of different ligands to βLG, new methods were developed. The fluorescence binding method for the evaluation of ligand binding to βLG was miniaturized from a quartz cell to a 96-well plate. A method of ultrafiltration sampling combined with high-performance liquid chromatography was developed to assess the binding of compounds from extracts. The interactions of phenolic compounds or retinoids and βLG were investigated using the 96-well plate method. The majority of flavones, flavonols, flavanones and isoflavones and all of the retinoids included were shown to bind to bovine and reindeer βLG. Phenolic compounds, contrary to retinol, were not released at acidic pH. Those results suggest that βLG may have more binding sites, probably also on the surface of βLG. An extract from Camellia sinensis (L.) O. Kunze (black tea), Urtica dioica L. (nettle) and Piper nigrum (black pepper) were used to evaluate whether βLG could bind compounds from plant extracts. Piperine from P. nigrum was found to bind tightly and rutin from U. dioica weakly to βLG. No components from C. sinensis bound to βLG in our experiment. The uptake and membrane permeation of bovine and reindeer βLG, free and bound with retinol, palmitic acid and cholesterol, were investigated using Caco-2 cell monolayers. Both bovine and reindeer βLG were able to cross the Caco-2 cell membrane. Free and βLG-bound retinol and palmitic acid were transported equally, whereas cholesterol could not cross the Caco-2 cell monolayer free or bound to βLG. Our results showed that βLG can bind different natural product compounds, but cannot enhance transport of retinol, palmitic acid or cholesterol through Caco-2 cells. Despite this, βLG, as a water-soluble binding protein, may improve the solubility of natural compounds, possibly protecting them from early degradation and transporting some of them through the stomach. Furthermore, it may decrease their bad or bitter taste during oral administration of drugs or in food preparations. βLG can also enhance or decrease the health benefits of herbal teas and food preparations by binding compounds from extracts.

Murtuva säätyvalta, kestävä eliitti : Senaattori Lennart Gripenbergin sukupiiri ja sääty-yhteiskunnan muodonmuutos

This study examines the transformation of the society of estates in the Finnish Grand Duchy through the case study of Senator Lennart Gripenberg and his family circle. While national borders and state structures changed, the connections between old ruling elite families remained intact as invisible family networks, ownership relations, economic collaboration and power of military families. These were the cornerstones of trust, which helped to strengthen positions gained in society. Also, these connections often had a central if unperceivable impact on social development and modernization. Broadly speaking, the intergenerational social reproduction made it possible for this network of connections to remain in power and, as an imperceptible factor, also influenced short-term developments in the long run. Decisions which in the short term appeared unproductive, would in the long run produce cumulative immaterial and material capital across generations as long-term investments. Social mobility, then, is a process which clearly takes several generations to become manifest. The study explores long-term strategies of reproducing and transferring the capital accumulated in multinational elite networks. Also, what was the relationship of these strategies to social change? For the representatives of the military estate the nobility and for those men of the highest estates who had benefited from military training, this very education of a technical-military nature was the key to steering, controlling and dealing with the challenges following the industrial breakthrough. The disintegration of the society of estates and the rising educational standards also increased the influence of those professionals previously excluded, which served to intensify competition for positions of power. The family connections highlighted in this study overlapped in many ways, working side by side and in tandem to manage the economic and political life in Finland, Russia and Sweden. The analysis of these ties has opened up a new angle to economic co-operation, for example, as seen in the position of such family networks not only in Finnish, but also Swedish and Russian corporations and in the long historical background of the collaboration. This also highlights in a new way the role of women in transferring the cumulative social capital and as silent business partners. The marriage strategies evident in business life clearly had an impact on the economic life. The collaborative networks which transcended generations, national boundaries and structures also uncover, as far as the elites are concerned, serious problems in comparative studies conducted from purely national premises. As the same influential families and persons in effect held several leading positions in society, the line would blur between public and invisible uses of power. The power networks thus aimed to build monopolies to secure their key positions at the helm. This study therefore examines the roles of Lennart Gripenberg senator, business executive, superintendent of the Department of Industry, factory inspector, and founding member of industrial interest groups as part of the reproduction strategies of the elite. The family and other networks of the powerful leaders of society, distinguished by social, economic and cultural capital, provided a solid backdrop for the so-called old elites in their quest for strategies to reproducing power in a changing world. Crucially, it was easier for the elites to gain expertise to steer the modernization process and thereby secure for the next generation a leading position in society, something that they traditionally, too, had had the greatest interest in.

Aggressive surgical interventions for severe stroke: Impact on quality of life, caregiver burden and family outcomes

Introduction: Decompressive hemicraniectomy, clot evacuation, and aneurysmal interventions are considered aggressive surgical therapeutic options for treatment of massive cerebral artery infarction (MCA), intracerebral hemorrhage (ICH), and severe subarachnoid hemorrhage (SAH) respectively. Although these procedures are saving lives, little is actually known about the impact on outcomes other than short-term survival and functional status. The purpose of this study was to gain a better understanding of personal and social consequences of surviving these aggressive surgical interventions in order to aid acute care clinicians in helping family members make difficult decisions about undertaking such interventions. Methods: An exploratory mixed method study using a convergent parallel design was conducted to examine functional recovery (NIHSS, mRS & BI), cognitive status (Montreal Cognitive Assessment Scale, MoCA), quality of life (Euroqol 5-D), and caregiver outcomes (Bakas Caregiver Outcome Scale, BCOS) in a cohort of patients and families who had undergone aggressive surgical intervention for severe stroke between the years 2000–2007. Data were analyzed using descriptive statistics, univariate and multivariate analysis of variance, and multivariate logistic regression. Content analysis was used to analyze the qualitative interviews conducted with stroke survivors and family members. Results: Twenty-seven patients and 13 spouses participated in this study. Based on patient MOCA scores, overall cognitive status was 25.18 (range 23.4-26.9); current functional outcomes scores: NIHSS 2.22, mRS 1.74, and BI 88.5. EQ-5D scores revealed no significant differences between patients and caregivers (p=0.585) and caregiver outcomes revealed no significant differences between male/female caregivers or patient diagnostic group (MCA, SAH, ICH; p=""0.103).<"/span><"/span> Discussion: Overall, patients and families were satisfied with quality of life and decisions made at the time of the initial stroke. There was consensus among study participants that formal community-based support (e.g., handibus, caregiving relief, rehabilitation assessments) should be continued for extended periods (e.g., years) post-stroke. Ongoing contact with health care professionals is valuable to help them navigate in the community as needs change over time.

Inconsistencies in and the inadequacies of the family counselling and FDR confidentiality and admissibility provisions: The need for reform

In this article the author discusses issues arising from counselling and family dispute resolution (FDR) in relation to confidentiality and admissibility, such as whether an admission of abuse to a child, or a threat to harm the other parent, can be disclosed by the counsellor or family dispute resolution practitioner (FDRP) and used in court proceedings. It is found that the admissibility provisions in the Family Law Act 1975 (Cth) are far more narrowly defined than the confidentiality requirements and have been interpreted strictly by the courts. There are competing policy considerations: the strict “traditionalist” approach, that people can have absolute faith in the integrity of counsellors and mediators and in the confidential nature of the process, must be balanced against a more “protectionist” stance, being the individual rights of victims to have all relevant information placed before the court and to be protected from violence and abuse. It is suggested that legislative reform is required to ensure that courts balance these considerations appropriately and don’t compromise the safety of victims of abuse and family violence.

Family type and depression in pregnancy: Factors mediating risk in a community sample

The rate of severe depression among women in single-parent and biological families and in a variety of stepfamilies was examined in a large community sample of 13,088 pregnant women in the United Kingdom. Compared with women in biological families and published population rates, women in single-parent families and step-families reported significantly elevated rates of depression. Family-type differences in several risk factors were examined, including cohabiting (vs. married) status, relationship history, and socioeconomic and psychosocial risks, such as crowding, social support, and stressful life events. Family-type differences in depression were mediated partly by differences in social support, stressful life events, and crowding, but a main effect of family type in predicting depression remained after statistically controlling for these risks.