Sex in its daily relational context

IntroductionThe present study measured the daily correlates of sexual behavior in an ecologically valid context by relying on a daily diary approach. AimExamining the dyadic and multicomponent nature of sexual behavior is essential to create valid models of sexual responding that are better aligned with the day-to-day context of having sex in a relationship. Methods and Main Outcome MeasuresDuring 3 weeks, heterosexual couples completed, two times a day, an electronic diary to report on mood, own and perceived partner behavior, relational feelings (in the evening), sexual activity, physical intimacy, and masturbation (in the morning). This design allowed testing bidirectional temporal associations between daily context and different types of sexual behavior. ResultsPositive mood, displays of positive partner behavior, perceived positive partner behavior, and positive relational feelings predicted more sexual activity and intimacy in men, which then further increased their positive mood, perceived positive partner behavior, and positive feelings about the relationship on the following day. Women showed a similar pattern of predictors regarding sexual activity as men, though the effect of sexual behavior on next-day feelings and behavior was more relationship-oriented rather than affecting personal mood. Intimacy was related to almost all daily variables in women, but related only to own and perceived positive partner behavior and positive relational feelings the next day. Several partner effects also reached significance, and these were more influential in predicting male than female intimacy. Solitary sexual activity showed a different pattern of results than dyadic sexual activity, with men experiencing masturbation as negatively in the context of their relationship. ConclusionThese results confirm the regulatory function of sex and intimacy in maintaining a positive relational climate and indicate that the quality of the everyday relational context is important to get partners in the mood to act in a sexual way. Dewitte M, Van Lankveld J, Vandenberghe S, and Loeys T. Sex in its daily relational context. J Sex Med 2015;12:2436-2450

iPSC-cardiomyocyte models of Brugada syndrome : achievements, challenges and future perspectives

Brugada syndrome (BrS) is an inherited cardiac arrhythmia that predisposes to ventricular fibrillation and sudden cardiac death. It originates from oligogenic alterations that affect cardiac ion channels or their accessory proteins. The main hurdle for the study of the functional effects of those variants is the need for a specific model that mimics the complex environment of human cardiomyocytes. Traditionally, animal models or transient heterologous expression systems are applied for electrophysiological investigations, each of these models having their limitations. The ability to create induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), providing a source of human patient-specific cells, offers new opportunities in the field of cardiac disease modelling. Contemporary iPSC-CMs constitute the best possible in vitro model to study complex cardiac arrhythmia syndromes such as BrS. To date, thirteen reports on iPSC-CM models for BrS have been published and with this review we provide an overview of the current findings, with a focus on the electrophysiological parameters. We also discuss the methods that are used for cell derivation and data acquisition. In the end, we critically evaluate the knowledge gained by the use of these iPSC-CM models and discuss challenges and future perspectives for iPSC-CMs in the study of BrS and other arrhythmias

Factor score regression with social relations model components : a case study exploring antecedents and consequences of perceived support in families

The family social relations model (SRM) is applied to identify the sources of variance in interpersonal dispositions in families, but the antecedents or consequences of those sources are rarely investigated. Simultaneous modeling of the SRM with antecedents or consequences using structural equation modeling (SEM) allows to do so, but may become computationally prohibitive in small samples. We therefore consider two factor score regression (FSR) methods: regression and Bartlett FSR. Based on full information maximum likelihood (FIML), we derive closed-form expressions for the regression and Bartlett factor scores in the presence of missingness. A simulation study in both a complete- and incomplete-case setting compares the performance of these FSR methods with SEM and an ANOVA-based approach. In both settings, the regression FIML factor scores as explanatory variable produces unbiased estimators with precision comparable to the SEM-estimators. When SRM-effects are used as dependent variables, none of the FSR methods are a suitable alternative for SEM. The latter result deviates from previous studies on FSR in more simple settings. As an example, we explore whether gender and past victimhood of relational and physical aggression are antecedents for family dynamics of perceived support, and whether those dynamics predict physical and relational aggression

Forward Mortality Rates in Discrete Time II: Longevity Risk and Hedging Strategies

Longevity risk has emerged as an important risk in the early 21st century for the providers of pension benefits and annuities. Any changes in the assumptions for future mortality rates can have a major financial impact on the valuation of these liabilities and motivates many of the longevity-linked securities that have been proposed to hedge this risk. Using the framework developed in Hunt and Blake (2020c), we investigate how these assumptions can change over a one-year period and the potential for hedging longevity risk in an illustrative annuity portfolio and find that relatively simple hedging strategies can significantly mitigate longevity risk over a one-year period

The resting membrane potential of hSC-CM in a syncytium is more hyperpolarised than that of isolated cells

Human-induced pluripotent stem cell (hiPSC) and stem cell (hSC) derived cardiomyocytes (CM) are gaining popularity as in vitro model for cardiology and pharmacology studies. A remaining flaw of these cells, as shown by single-cell electrophysiological characterization, is a more depolarized resting membrane potential (RMP) compared to native CM. Most reports attribute this to a lower expression of the Kir2.1 potassium channel that generates the I-K1 current. However, most RMP recordings are obtained from isolated hSC/hiPSC-CMs whereas in a more native setting these cells are interconnected with neighboring cells by connexin-based gap junctions, forming a syncytium. Hereby, these cells are electrically connected and the total pool of I-K1 increases. Therefore, the input resistance (Ri) of interconnected cells is lower than that of isolated cells. During patch clamp experiments pipettes need to be well attached or sealed to the cell, which is reflected in the seal resistance (Rs), because a nonspecific ionic current can leak through this pipette-cell contact or seal and balance out small currents within the cell such as I-K1. By recording the action potential of isolated hSC-CMs and that of hSC-CMs cultured in small monolayers, we show that the RMP of hSC-CMs in monolayer is approximately -20 mV more hyperpolarized compared to isolated cells. Accordingly, adding carbenoxolone, a connexin channel blocker, isolates the cell that is patch clamped from its neighboring cells of the monolayer and depolarizes the RMP. The presented data show that the recorded RMP of hSC-CMs in a syncytium is more negative than that determined from isolated hSC/hiPSC-CMs, most likely because the active pool of Kir2.1 channels increased

This Other Eden: Exploring a Sense of Place in Twentieth-Century Reconstructions of Australian Childhoods

This thesis explores the sense of place formed during childhood, as remembered by adult Australians who reconstruct their youth through various forms of life writing. While Australian writers do utilize traditional tropes of Western autobiography, such as the mythology of Eden and the Wordsworthian image of the child communing with Nature, these themes are frequently transformed to meet a uniquely Australian context. Isolation and distance from Europe, and the apparent indifference of our landscape towards white settlement, have received much critical attention in Australian studies generally and, indeed, broadly influence the formation of children’s sense of place across the continent. However, writers are also concerned with the role of place on a more local level. Through a comparison of writing from Western Australia, Queensland and Victoria, this thesis explores regional landscape preoccupations that create an awareness of local identity, variously contributing to or frustrating the child’s sense of belonging. Western Australian writing is dominated by images of isolation, the fragility of white settlement in a dry land lacking fresh water, and a pervasive beach culture. A strong sense of the littoral pervades writing from this region. Queensland’s frontier mythology is of a different flavour: warm and tropical, nature here is exuberant, constantly threatening to overwhelm culture, already perceived as transient due to the flimsy aspect of the “Queenslander” house. Writing from Victoria, to some extent, tends to more closely follow English models, juxtaposing country and city environments, although there is a distinctly local flavour to many representations of urban Melbourne and its flat, grid-like organization. As Australian society becomes more concentrated on the coastal fringe, the beach is an increasingly significant environment. Though more prominent in writing from some regions than others, coastal imagery broadly reflects the modern Australian’s sense of inhabiting a liminal zone with negotiable boundaries

Severe aortic and arterial aneurysms associated with a TGFBR2 mutation.

BACKGROUND: A 24-year-old man presented with previously diagnosed Marfan\u27s syndrome. Since the age of 9 years, he had undergone eight cardiovascular procedures to treat rapidly progressive aneurysms, dissection and tortuous vascular disease involving the aortic root and arch, the thoracoabdominal aorta, and brachiocephalic, vertebral, internal thoracic and superior mesenteric arteries. Throughout this extensive series of cardiovascular surgical repairs, he recovered without stroke, paraplegia or renal impairment. INVESTIGATIONS: CT scans, arteriogram, genetic mutation screening of transforming growth factor beta receptors 1 and 2. DIAGNOSIS: Diffuse and rapidly progressing vascular disease in a patient who met the diagnostic criteria for Marfan\u27s syndrome, but was later rediagnosed with Loeys-Dietz syndrome. Genetic testing also revealed a de novo mutation in transforming growth factor beta receptor 2. MANAGEMENT: Regular cardiovascular surveillance for aneurysms and dissections, and aggressive surgical treatment of vascular disease

Atenolol versus losartan in children and young adults with Marfan's syndrome

BACKGROUND : Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS : We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS : From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [+/- SD] age, 11.5 +/- 6.5 years in the atenolol group and 11.0 +/- 6.2 years in the losartan group), who had an aorticroot z score greater than 3.0. The baseline-adjusted rate of change (+/- SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139 +/- 0.013 and -0.107 +/- 0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS : Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aorticroot dilatation between the two treatment groups over a 3-year period

Biological activity differences between TGF-β1 and TGF-β3 correlate with differences in the rigidity and arrangement of their component monomers

[Image: see text] TGF-β1, -β2, and -β3 are small, secreted signaling proteins. They share 71–80% sequence identity and signal through the same receptors, yet the isoform-specific null mice have distinctive phenotypes and are inviable. The replacement of the coding sequence of TGF-β1 with TGF-β3 and TGF-β3 with TGF-β1 led to only partial rescue of the mutant phenotypes, suggesting that intrinsic differences between them contribute to the requirement of each in vivo. Here, we investigated whether the previously reported differences in the flexibility of the interfacial helix and arrangement of monomers was responsible for the differences in activity by generating two chimeric proteins in which residues 54–75 in the homodimer interface were swapped. Structural analysis of these using NMR and functional analysis using a dermal fibroblast migration assay showed that swapping the interfacial region swapped both the conformational preferences and activity. Conformational and activity differences were also observed between TGF-β3 and a variant with four helix-stabilizing residues from TGF-β1, suggesting that the observed changes were due to increased helical stability and the altered conformation, as proposed. Surface plasmon resonance analysis showed that TGF-β1, TGF-β3, and variants bound the type II signaling receptor, TβRII, nearly identically, but had small differences in the dissociation rate constant for recruitment of the type I signaling receptor, TβRI. However, the latter did not correlate with conformational preference or activity. Hence, the difference in activity arises from differences in their conformations, not their manner of receptor binding, suggesting that a matrix protein that differentially binds them might determine their distinct activities

Compound heterozygous SCN5A mutations in severe sodium channelopathy with Brugada syndrome : a case report

Aims:Brugada syndrome (BrS) is an inherited cardiac arrhythmia with an increased risk for sudden cardiac death (SCD). About 20% of BrS cases are explained by mutations in theSCN5Agene, encoding the main cardiac sodium Na(v)1.5 channel. Here we present a severe case of cardiac sodium channelopathy with BrS caused bySCN5Acompound heterozygous mutations. We performed a genetic analysis ofSCN5Ain a male proband who collapsed during cycling at the age of 2 years. Because of atrial standstill, he received a pacemaker, and at the age of 3 years, he experienced a collapse anew with left-sided brain stroke. A later ECG taken during a fever unmasked a characteristic BrS type-1 pattern. The functional effect of the detected genetic variants was investigated. Methods and Results:Next-generation sequencing allowed the detection of twoSCN5Avariants intrans: c.4813+3_4813+6dupGGGT-a Belgian founder mutation-and c.4711 T>C, p.Phe1571Leu. A familial segregation analysis showed the presence of the founder mutation in the proband's affected father and paternal aunt and thede novooccurrence of the p.Phe1571Leu. The functional effect of the founder mutation was previously described as a loss-of-function. We performed a functional analysis of the p.Phe571Leu variant in HEK293 cells alone or co-expressed with the beta(1)-subunit. Compared to theSCN5Awild type, p.Phe1571Leu displayed a hyperpolarizing shift in the voltage dependence of inactivation (loss-of-function), while the activation parameters were unaffected. Using the peptide toxin nemertide alpha-1, the variant's loss-of-function effect could be restored due to a toxin-dependent reduction of channel inactivation. Conclusion:This is the first report providing support for the pathogenicity of the p.Phe1571LeuSCN5Avariant which, together with the c.4813+3_4813+6dupGGGT founder mutation, explains the severity of the phenotype of cardiac sodium channelopathy with BrS in the presented case