Pregnancy-associated plasma protein-A2 (PAPP-A2): tissue expression and biological consequences of gene knockout in mice

Pregnancy-associated plasma protein-A2 (PAPP-A2) is a novel homolog of PAPP-A in the metzincin superfamily. However, compared with the accumulating data on PAPP-A, very little is known about PAPP-A2. In this study, we determined the tissue expression pattern of PAPP-A2 mRNA in wild-type (WT) mice and characterized the phenotype of mice with global PAPP-A2 deficiency. Tissues expressing PAPP-A2 in WT mice were more limited than those expressing PAPP-A. The highest PAPP-A2 mRNA expression was found in the placenta, with abundant expression in fetal, skeletal, and reproductive tissues. Heterozygous breeding produced the expected Mendelian distribution for the pappa2 gene and viable homozygous PAPP-A2 knockout (KO) mice that were normal size at birth. The most striking phenotype of the PAPP-A2 KO mouse was postnatal growth retardation. Male and female PAPP-A2 KO mice had 10 and 25-30% lower body weight, respectively, than WT littermates. Adult femur and body length were also reduced in PAPP-A2 KO mice, but without significant effects on bone mineral density. PAPP-A2 KO mice were fertile, but with compromised fecundity. PAPP-A expression was not altered to compensate for the loss of PAPP-A2 expression, and proteolysis of PAPP-A2's primary substrate, IGF-binding protein-5, was not altered in fibroblasts from PAPP-A2 KO embryos. In conclusion, tissue expression patterns and biological consequences of gene KO indicate distinct physiological roles for PAPP-A2 and PAPP-A in mice.     

Surrogates of Large Artery versus Small Artery Stiffness and Ankle-Brachial Index

Peripheral artery tonometry (PAT) is a novel method for assessing arterial stiffness of small digital arteries. Pulse pressure can be regarded as a surrogate of large artery stiffness. When ankle-brachial index (ABI) is calculated using the higher of the two ankle systolic pressures as denominator (ABI-higher), leg perfusion can be reliably estimated. However, using the lower of the ankle pressures to calculate ABI (ABI-lower) identifies more patients with isolated peripheral arterial disease (PAD) in ankle arteries. We aimed to compare the ability of PAT, pulse pressure, and different calculations of ABI to detect atherosclerotic disease in lower extremities. We examined PAT, pulse pressure, and ABI in 66 cardiovascular risk subjects in whom borderline PAD (ABI 0.91 to 1.00) was diagnosed 4 years earlier. Using ABI-lower to diagnose PAD yielded 2-fold higher prevalence of PAD than using ABI-higher. Endothelial dysfunction was diagnosed in 15/66 subjects (23%). In a bivariate correlation analysis, pulse pressure was negatively correlated with ABI-higher (r = −0.347, p = 0.004) and with ABI-lower (r = −0.424, p < 0.001). PAT hyperemic response was not significantly correlated with either ABI-higher (r = −0.148, p = 0.24) or with ABI-lower (r = −0.208, p = 0.095). Measurement of ABI using the lower of the two ankle pressures is an efficient method to identify patients with clinical or subclinical atherosclerosis and worth performing on subjects with pulse pressure above 65 mm Hg. The usefulness of PAT measurement in detecting PAD is vague.     

Addressing schemes of self-monitoring of blood glucose in type 2 diabetes: a European perspective and expert recommendation

Self-monitoring of blood glucose (SMBG) in type 2 diabetes has increasingly been shown to display beneficial effects on glycemic control. SMBG is not only associated with a reduction of hemoglobin A1c but has also been demonstrated to increase patients' awareness of the disease. SMBG has also the potential to visualize and predict hypoglycemic episodes. International guidelines by the International Diabetes Federation, the European Society of Cardiology, and the European Association for the Study of Diabetes and also the International Society for Pediatric and Adolescent Diabetes emphasize that SMBG is an integral part of self-management. More recently, two European consensus documents have been published to give recommendations for frequency and timing of SMBG also for various clinical scenarios. Recently, a European expert panel was held to further facilitate and enhance standardized approaches to SMBG. The aim was to present simple, clinically meaningful, and standardized SMBG strategies for type 2 diabetes. The panel recommended a less intensive and an intensive scheme for SMBG across the type 2 diabetes continuum. The length and frequency of SMBG performance depend on the clinical circumstances and the quality of glycemic control. The expert panel also recommended further evaluation of various schemes for SMBG in type 2 diabetes in clinical studies.     

Enhancing the population impact of collaborative care interventions: mixed method development and implementation of stepped care targeting posttraumatic stress disorder and related comorbidities after acute trauma

Objective

The objective of the study was to develop and implement a stepped collaborative care intervention targeting posttraumatic stress disorder (PTSD) and related comorbidities to enhance the population impact of early trauma-focused interventions.

Method

We describe the design and implementation of the Trauma Survivors Outcomes and Support study. An interdisciplinary treatment development team was composed of trauma surgical, clinical psychiatric and mental health services “change agents” who spanned the boundaries between frontline trauma center clinical care and acute care policy. Mixed method clinical epidemiologic and clinical ethnographic studies informed the development of PTSD screening and intervention procedures.

Results

Two hundred seven acutely injured trauma survivors with high early PTSD symptom levels were randomized into the study. The stepped collaborative care model integrated care management (i.e., posttraumatic concern elicitation and amelioration, motivational interviewing and behavioral activation) with cognitive behavioral therapy and pharmacotherapy targeting PTSD. The model was feasibly implemented by frontline acute care masters in social work and nurse practioner providers.

Conclusions

Stepped care protocols targeting PTSD may enhance the population impact of early interventions developed for survivors of individual and mass trauma by extending the reach of collaborative care interventions to acute care medical settings and other nonspecialty posttraumatic contexts.     

Psychiatric comorbidity in couples: a longitudinal study of 202,959 married and cohabiting individuals

Purpose  

To examine whether partner’s psychiatric and somatic disorders are risk factors for incidence of psychiatric disorders among non-psychiatric individuals at baseline.     

Cognitive functioning in severe psychiatric disorders: a general population study

In clinical samples, patients with severe psychiatric disorders are found to have cognitive impairments. Less is known whether this applies to samples derived from the general population. We aimed to study cognitive functioning in a population-based sample comprising individuals with schizophrenia, other non-affective psychoses, bipolar disorders, major depressive disorder, and controls derived from the same population. The current analysis was based on 148 persons with severe mental disorders and 66 control subjects, derived from the Psychoses in Finland study. All subjects were interviewed with SCID, and a neuropsychological test battery was administered. Subjects with schizophrenia had a generalized cognitive impairment (d = 0.43–1.07), while those with other non-affective psychoses were impaired in verbal memory and processing speed (d = 0.43–0.59). Subjects with bipolar disorders were not impaired. Unipolar major depressive disorder associated with slowed processing speed (d = 0.64). Our findings on cognitive impairments in subjects with schizophrenia and other non-affective psychoses derived from the general population support previous findings of a generalized cognitive dysfunction in these subjects. However, our results suggest that subjects with bipolar disorders from non-clinical populations may not have significant cognitive impairments. Our results emphasize the importance of using control samples derived from the same population and studied similarly as those with disorders in evaluating cognitive functioning of subjects with severe mental disorders.