Childhood abuse predicts affective symptoms via HPA reactivity during mother-infant stress.

Despite extensive literature positing the hypothalamic-pituitary-adrenal (HPA) axis as a mechanism in the association between early childhood maltreatment and later adult psychopathology, empirical support for this full pathway is lacking. We tested indirect effects of childhood maltreatment on women's later affective symptomatology via HPA axis responding to a stressor involving their own infant. Women (n = 47) in a larger longitudinal study were assessed following the birth of their infant from 3 to 18 months postnatal. They reported childhood maltreatment history at 3 months and participated in a dyadic stress task with their infant at 12 months, at which time four salivary cortisol samples were collected to assess HPA response. Depression and anxiety symptoms at 18 months (controlling for symptom levels reported at 12 months) served as the primary outcome. Multilevel modeling was used to estimate both levels and dynamics of women's cortisol response trajectories. Tests of indirect effects revealed a significant effect of total Childhood Trauma Questionnaire (CTQ) scores on anxiety symptoms and a marginally significant effect on depression symptoms. Follow-up analyses with CTQ subscales revealed significant indirect effects of emotional and physical abuse on women's ongoing anxiety symptoms via more pronounced cortisol reactivity curves during the mother-infant stressor. We discuss methodological choices that may have allowed these effects to be detected in the present study and implications for stress-related risk and intervention.

Up-regulation of alpha-smooth muscle actin in cardiomyocytes from non-hypertrophic and non-failing transgenic mouse hearts expressing N-terminal truncated cardiac troponin I.

We previously reported that a restrictive N-terminal truncation of cardiac troponin I (cTnI-ND) is up-regulated in the heart in adaptation to hemodynamic stresses. Over-expression of cTnI-ND in the hearts of transgenic mice revealed functional benefits such as increased relaxation and myocardial compliance. In the present study, we investigated the subsequent effect on myocardial remodeling. The alpha-smooth muscle actin (α-SMA) isoform is normally expressed in differentiating cardiomyocytes and is a marker for myocardial hypertrophy in adult hearts. Our results show that in cTnI-ND transgenic mice of between 2 and 3 months of age (young adults), a significant level of α-SMA is expressed in the heart as compared with wild-type animals. Although blood vessel density was increased in the cTnI-ND heart, the mass of smooth muscle tissue did not correlate with the increased level of α-SMA. Instead, immunocytochemical staining and Western blotting of protein extracts from isolated cardiomyocytes identified cardiomyocytes as the source of increased α-SMA in cTnI-ND hearts. We further found that while a portion of the up-regulated α-SMA protein was incorporated into the sarcomeric thin filaments, the majority of SMA protein was found outside of myofibrils. This distribution pattern suggests dual functions for the up-regulated α-SMA as both a contractile component to affect contractility and as possible effector of early remodeling in non-hypertrophic, non-failing cTnI-ND hearts.

Altered calsequestrin glycan processing is common to diverse models of canine heart failure.

Calsequestrin-2 (CSQ2) is a resident glycoprotein of junctional sarcoplasmic reticulum that functions in the regulation of SR Ca(2+) release. CSQ2 is biosynthesized in rough ER around cardiomyocyte nuclei and then traffics transversely across SR subcompartments. During biosynthesis, CSQ2 undergoes N-linked glycosylation and phosphorylation by protein kinase CK2. In mammalian heart, CSQ2 molecules subsequently undergo extensive mannose trimming by ER mannosidase(s), a posttranslational process that often regulates protein breakdown. We analyzed the intact purified CSQ2 from mongrel canine heart tissue by electrospray mass spectrometry. The average molecular mass of CSQ2 in normal mongrel dogs was 46,306 ± 41 Da, corresponding to glycan trimming of 3-5 mannoses, depending upon the phosphate content. We tested whether CSQ2 glycan structures would be altered in heart tissue from mongrel dogs induced into heart failure (HF) by two very different experimental treatments, rapid ventricular pacing or repeated coronary microembolizations. Similarly dramatic changes in mannose trimming were found in both types of induced HF, despite the different cardiomyopathies producing the failure. Unique to all samples analyzed from HF dog hearts, 20-40 % of all CSQ2 contained glycans that had minimal mannose trimming (Man9,8). Analyses of tissue samples showed decreases in CSQ2 protein levels per unit levels of mRNA for tachypaced heart tissue, also indicative of altered turnover. Quantitative immunofluorescence microscopy of frozen tissue sections suggested that no changes in CSQ2 levels occurred across the width of the cell. We conclude that altered processing of CSQ2 may be an adaptive response to the myocardium under stresses that are capable of inducing heart failure.

The treatment of patients with medically unexplained physical symptoms in China: a study comparing expectations and treatment satisfaction in psychosomatic medicine, biomedicine, and traditional Chinese medicine.

OBJECTIVE: Little is known about treatment for patients with medically unexplained symptoms (MUS) in China. This study investigates the treatment expectations and treatment satisfaction of patients with MUS in psychosomatic medicine, biomedicine, and Traditional Chinese Medicine (TCM). METHOD: In a cross-sectional survey, n = 96 (10.3%) out of 931 participating patients were screened positive for multiple somatoform symptoms. These patients answered questionnaires concerning symptom duration, number of doctor visits, functional impairment, emotional distress, treatment expectations, treatment satisfaction, and empathy in the consultation. The physicians filled in a questionnaire about applied or recommended treatment. RESULTS: Most of the patients from psychosomatic medicine wanted psychotherapy. In TCM, 55% of the patients had already received TCM treatment and most of them wanted to continue TCM treatment. Patients in biomedicine did not express clear expectations; most of them had had no previous treatment. A combination of treatment methods was most prevalent in biomedicine in comparison to psychosomatic medicine and TCM. The outcome from the patients' point of view was significantly better in TCM than in psychosomatic medicine and biomedicine. Psychosomatic medicine's strength was the empathetic physician-patient interaction. CONCLUSIONS: From a biopsychosocial perspective, these results suggest that various treatment approaches with various emphases can be effective depending on the patient's complaints, his illness beliefs, and what the physician offers. The results will be verified in a larger multicenter longitudinal study.

Adaptation of Clostridium difficile toxin A for use as a protein translocation system.

A cellular delivery system is a useful biotechnology tool, with many possible applications. Two derivatives of Clostridium difficile toxin A (TcdA) have been constructed (GFP-TcdA and Luc-TcdA), by fusing reporter genes to functional domains of TcdA, and evaluated for their ability to translocate their cargo into mammalian cells. The cysteine protease and receptor binding domains of TcdA have been examined and found to be functional when expressed in the chimeric construct. Whereas GFP failed to internalize in the context of the TcdA fusion, significant cellular luciferase activity was detected in vero cell lysates after treatment with Luc-TcdA. Treatment with bafilomycin A1, which inhibits endosomal acidification, traps the luciferase activity within endosomes. To further understand these results, clarified lysates were subjected to molecular weight sieving, demonstrating that active luciferase was released from Luc-TcdA after translocation and internal processing.

Problems with medical devices may be severely under-reported.

The purposes of this study were to determine whether registered nurses are familiar with the Health Canada Medical Device Problem Report Form, and if so, how often they use it to report problems and concerns compared to how often they experience problems and concerns with medical devices. A survey was mailed to a random sample of 1,000 Ontario nurses to collect demographic information and to determine their familiarity with the aforementioned form, as well as the frequency with which they encounter problems/concerns with medical devices. Seventy-two and a half percent of the nurses reportedly have problems/concerns with medical devices at least yearly, yet 94.2% of them did not know that the Health Canada Medical Device Problem Report Form existed. Therefore, problems/concerns with medical devices encountered by registered nurses may be severely under-reported to Health Canada, contributing to an underestimate of the actual threat that devices pose to patient safety.