Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.     

Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model

Males and females exhibit several differences in brain structure and function. To examine the basis for these sex differences, we investigated the influences of sex hormones and sex chromosomes on brain structure and function in mice. We used the Four Core Genotype (4CG) mice, which can generate both male and female mice with XX or XY sex chromosome complement, allowing the decoupling of sex chromosomes from hormonal milieu. To examine whole brain structure, high-resolution ex vivo MRI was performed, and to assess differences in cognitive function, mice were trained on a radial arm maze. Voxel-wise and volumetric analyses of MRI data uncovered a striking independence of hormonal versus chromosomal influences in 30 sexually dimorphic brain regions. For example, the bed nucleus of the stria terminalis and the parieto-temporal lobe of the cerebral cortex displayed steroid-dependence while the cerebellar cortex, corpus callosum, and olfactory bulbs were influenced by sex chromosomes. Spatial learning and memory demonstrated strict hormone-dependency with no apparent influence of sex chromosomes. Understanding the influences of chromosomes and hormones on brain structure and function is important for understanding sex differences in brain structure and function, an endeavor that has eventual implications for understanding sex biases observed in the prevalence of psychiatric disorders.     

Tectal control of locomotion, steering, and eye movements in lamprey

The intrinsic function of the brain stem-spinal cord networks eliciting the locomotor synergy is well described in the lamprey-a vertebrate model system. This study addresses the role of tectum in integrating eye, body orientation, and locomotor movements as in steering and goal-directed behavior. Electrical stimuli were applied to different areas within the optic tectum in head-restrained semi-intact lampreys (n = 40). Motions of the eyes and body were recorded simultaneously (videotaped). Brief pulse trains (<0.5 s) elicited only eye movements, but with longer stimuli (>0.5 s) lateral bending movements of the body (orientation movements) were added, and with even longer stimuli locomotor movements were initiated. Depending on the tectal area stimulated, four characteristic response patterns were observed. In a lateral area conjugate horizontal eye movements combined with lateral bending movements of the body and locomotor movements were elicited, depending on stimulus duration. The amplitude of the eye movement and bending movements was site specific within this region. In a rostromedial area, bilateral downward vertical eye movements occurred. In a caudomedial tectal area, large-amplitude undulatory body movements akin to struggling behavior were elicited, combined with large-amplitude eye movements that were antiphasic to the body movements. The alternating eye movements were not dependent on vestibuloocular reflexes. Finally, in a caudolateral area locomotor movements without eye or bending movements could be elicited. These results show that tectum can provide integrated motor responses of eye, body orientation, and locomotion of the type that would be required in goal-directed locomotion.     

Challenges of adopting the role of care manager when implementing the collaborative care model for people with common mental illnesses: A scoping review

This review aimed to identify the main factors influencing the adoption of the role of care manager (CM) by nurses when implementing the collaborative care model (CCM) for common mental illnesses in primary care settings. A total of 19 studies met the inclusion criteria, reporting on 14 distinct interventions implemented between 2000 and 2017 in five countries. Two categories of factors were identified and described as follows: (i) strategies for the CCM implementation (e.g. initial care management training and supervision by a mental health specialist) and (ii) context‐specific factors (e.g. organizational factors, collaboration with team members, nurses’ care management competency). Identified implementation strategies were mainly aimed towards improving the nurse's care management competency, but their efficacy in developing the set of competencies needed to fulfil a CM role was not well demonstrated. There is a need to better understand the relationship between the nurses’ competencies, the care management activities, the strategies used to implement the CCM and the context‐specific factors. Strategies to optimize the adoption of the CM role should not be solely oriented towards the individual's competency in care management, but also consider other context‐specific factors. The CM also needs a favourable context in order to perform his or her activities with competency.     

Introducing Diaphragms into the Mix: What Happens to Male Condom Use Patterns?

The objective of this analysis was to assess the effect of introducing the diaphragm on condom use patterns. Participants included One hundred eighty nine women attending family planning clinics in Harare, Zimbabwe who reported less than 100% condom use. The proportion of acts where at least one method was used significantly increased over using follow-up; male condom use remained stable. A diaphragm was used with 50% to 54% of acts; male condoms were also used about 50% of the time. The proportion of acts where a female condom was used decreased. Women who used both male and female condoms were more likely to use diaphragms than those who reported not using female condoms. Introducing the diaphragm increased the overall proportion of protected acts. The proportion of acts where a male condom was used did not change. Female condoms use declined because concurrent use with the diaphragm is not possible.     

Barrier Method Preferences and Perceptions Among Zimbabwean Women and their Partners

In Zimbabwe, adult HIV prevalence is over 25% and acceptable prevention methods are urgently needed. Sixty-eight Zimbabwean women who had completed a barrier-methods study and 34 of their male partners participated in focus group discussions and in-depth interviews to qualitatively explore acceptability of male condoms, female condoms and diaphragms. Most men and about half of women preferred diaphragms because they are female-controlled and do not detract from sexual pleasure or carry stigma. Unknown efficacy and reuse were concerns and some women reported feeling unclean when leaving the diaphragm in for six hours following sex. Nearly half of women and some men preferred male condoms because they are effective and limit women's exposure to semen, although they reportedly detract from sexual pleasure and carry social stigma. Female condoms were least preferred because of obviousness and partial coverage of outer-genitalia that interfered with sexual pleasure.     

Raynaud’s phenomenon

Opinion statement Treatment of Raynaud’s phenomenon in any one individual depends on the severity of symptoms and whether or not there is an underlying disease process requiring specific intervention. Many patients with primary (idiopathic) Raynaud’s phenomenon respond well to treatment with general measures, perhaps with the addition of a calcium channel blocker. Conversely, others with underlying structural vascular abnormality (as occurs in connective tissue diseases such as systemic sclerosis [SSc]) are often refractory to treatment and may progress to irreversible tissue injury, sometimes with gangrene. Because these patients are the most challenging and because a large proportion of the research into Raynaud’s phenomenon has been conducted in patients with SSc-spectrum disorders, much of this review is weighted toward them. The key principles of management are removal/treatment of any triggering factor/underlying cause, general (nondrug) measures, drug treatment, and surgery, although the last is rarely indicated. New insights into pathogenesis have led, and continue to lead, to new approaches to treatment, including endothelin-1 receptor antagonism and nitric oxide supplementation.     

Cardiac medication during pregnancy,data from the ROPAC

Background

Data on pharmacological management during pregnancy are scarce. The aim of this study was to describe the type and frequency of cardiac medication used in pregnancy in patients with cardiovascular disease and to assess the relationship between medication use and fetal outcome.

Methods and results

Between 2007 and 2011 sixty hospitals in 28 countries enrolled 1321 pregnant women. All patients had structural heart disease (congenital 66%, valvular 25% or cardiomyopathy 7% or ischemic 2%). Medication was used by 424 patients (32%) at some time during pregnancy: 22% used beta-blockers, 8% antiplatelet agents, 7% diuretics, 2.8% ACE inhibitors and 0.5% statins. Compared to those who did not take medication, patients taking medication were older, more likely to be parous, have valvular heart disease and were less often in sinus rhythm. The odds ratio of fetal adverse events in users versus non-users of medication was 2.6 (95% CI 2.0–3.4) and after adjustment for cardiac and obstetric parameter was 2.0 (95% CI 1.4–2.7). Babies of patients treated with beta-blockers had a significantly lower adjusted birth weight (3140 versus 3240 g, p = 0.002). The highest rate of fetal malformation was found in patients taking ACE inhibitors (8%).

Conclusion

One third of pregnant women with heart disease used cardiac medication during their pregnancy, which was associated with an increased rate of adverse fetal events. Birth weight was significantly lower in children of patients taking beta-blockers. A randomized trial is needed to distinguish the effects of the medication from the effects of the underlying maternal cardiac condition.     

Consensus opinion of a North American Working Group regarding the classification of digital ulcers in systemic sclerosis

The objectives of this study were to develop a standard classification of digital ulcers (DUs) in systemic sclerosis (SSc) for use in observational or therapeutic studies and to assess the reliability of these definitions as well as of the measurement of ulcer area. Ten North American rheumatologists with expertise in SSc reviewed multiple photos of DUs, examined four SSc subjects with DUs, and came to a consensus on the definitions for digital, active, healed, and indeterminate ulcers. These ten raters then examined the right hand of ten SSc subjects twice and the left hand once to classify ulcers and to measure ulcer area. Weighted and Fleiss kappa were used to calculate intra- and interrater agreement on classification of ulcers, and intraclass correlation coefficient (ICC) was used to assess agreement on ulcer area. Because the traditional ICC calculations relied on a small number of ulcers, ICCs were recalculated using the results of linear mixed models to evaluate the variance components of observations on all the data. Intrarater kappa for classifying DU as not an ulcer/healed ulcer versus active/indeterminate ulcer was substantial (0.76), and interrater kappa was moderate (0.53). The ICC for ulcer area using the linear mixed models was moderate both for intrarater (0.57) and interrater (0.48) measurements. A consensus for the classification of DUs in SSc was developed, and after a training session, rheumatologists with expertise in SSc are able to reliably classify DUs and to measure ulcer area.     

Validity and reliability of a pediatric patient classification instrument

OBJECTIVES:

to assess the construct validity and reliability of the Pediatric Patient Classification Instrument.

METHODS:

correlation study developed at a teaching hospital. The classification involved 227 patients, using the pediatric patient classification instrument. The construct validity was assessed through the factor analysis approach and reliability through internal consistency.

RESULTS:

the Exploratory Factor Analysis identified three constructs with 67.5% of variance explanation and, in the reliability assessment, the following Cronbach''s alpha coefficients were found: 0.92 for the instrument as a whole; 0.88 for the Patient domain; 0.81 for the Family domain; 0.44 for the Therapeutic procedures domain.

CONCLUSIONS:

the instrument evidenced its construct validity and reliability, and these analyses indicate the feasibility of the instrument. The validation of the Pediatric Patient Classification Instrument still represents a challenge, due to its relevance for a closer look at pediatric nursing care and management. Further research should be considered to explore its dimensionality and content validity.