A decade of research has sought to identify circulating endothelial progenitor cells (EPC) in order to harness their potential for cardiovascular regeneration. Endothelial outgrowth cells (EOC) most closely fulfil the criteria for an EPC, but their origin remains obscure. Our aim was to identify the source and precursor of EOC and to assess their regenerative potential compared to mature endothelial cells. EOC are readily isolated from umbilical cord blood (6/6 donors) and peripheral blood mononuclear cells (4/6 donors) but not from bone marrow (0/6) or peripheral blood following mobilization with granulocyte-colony stimulating factor (0/6 donors). Enrichment and depletion of blood mononuclear cells demonstrated that EOC are confined to the CD341 cell fraction. EOC derived from blood mononuclear cells are indistinguishable from mature human umbilical vein endothelial cells (HUVEC) by morphology, surface antigen expression, immunohistochemistry, real-time polymerase chain reaction, proliferation, and functional assessments. In a subcutaneous sponge model of angiogenesis, both EOC and HUVEC contribute to de novo blood vessel formation giving rise to a similar number of vessels (7.0 6 2.7 vs. 6.6 6 3.7 vessels, respectively, n 5 9). Bone marrow-derived outgrowth cells isolated under the same conditions expressed mesenchymal markers rather than endothelial cell markers and did not contribute to blood vessels in vivo. In this article, we confirm that EOC arise from CD34 CD1461 mononuclear cells and are similar, if not identical, to mature endothelial cells. Our findings suggest that EOC do not arise from bone marrow and challenge the concept of a bone marrowderived circulating precursor for endothelial cells. STEM

Vaginal birth may result in damage to the levator ani muscle (LAM) with subsequent pelvic floor dysfunction and there may be accompanying psychological problems. This study examines associations between these somatic injuries and psychological symptoms. A qualitative study using semi-structured interviews to examine the experiences of primiparous women (n = 40) with known LAM trauma was undertaken. Participants were identified from a population of 504 women retrospectively assessed by a perinatal imaging study at two obstetric units in Sydney, Australia. LAM avulsion was diagnosed by 3D/4D translabial ultrasound 3-6 months postpartum. The template consisted of open-ended questions. Main outcome measures were quality of information provided antenatally; intrapartum events; postpartum symptoms; and coping mechanisms. Thematic analysis of maternal experiences was employed to evaluate prevalence of themes. Ten statement categories were identified: (1) limited antenatal education (29/40); (2) no information provided on potential morbidities (36/40); (3) conflicting advice (35/40); (4) traumatized partners (21/40); (5) long-term sexual dysfunction/relationship issues (27/40); (6) no postnatal assessment of injuries (36/40); (7) multiple symptoms of pelvic floor dysfunction (35/40); (8) "putting up" with injuries (36/40); (9) symptoms of post-traumatic stress disorder (PTSD) (27/40); (10) dismissive staff responses (26/40). Women who sustain LAM damage after vaginal birth have reduced quality of life due to psychological and somatic morbidities. PTSD symptoms are common. Clinicians may be unaware of the severity of this damage. Women report they feel traumatized and abandoned because such morbidities were not discussed prior to birth or postpartum.

BackgroundThe corticotropin-releasing factor type 2 receptor (CRFR2) is suggested to play an important role in aiding recovery from acute stress, but any chronic effects of CRFR2 activation are unknown. CRFR2 in the midbrain raphé nuclei modulate serotonergic activity of this key source of serotonin (5-HT) forebrain innervation.MethodsTransgenic mice overexpressing the highly specific CRFR2 ligand urocortin 3 (UCN3OE) were analyzed for stress-related behaviors and hypothalamic-pituitary-adrenal axis responses. Responses to 5-HT receptor agonist challenge were assessed by local cerebral glucose utilization, while 5-HT and 5-hydroxyindoleacetic acid content were quantified in limbic brain regions.ResultsMice overexpressing urocortin 3 exhibited increased stress-related behaviors under basal conditions and impaired retention of spatial memory compared with control mice. Following acute stress, unlike control mice, they exhibited no further increase in these stress-related behaviors and showed an attenuated adrenocorticotropic hormone response. 5-HT and 5-hydroxyindoleacetic acid content of limbic nuclei were differentially regulated by stress in UCN3OE mice as compared with control mice. Responses to 5-HT type 1A receptor challenge were significantly and specifically reduced in UCN3OE mice. The distribution pattern of local cerebral glucose utilization and 5-HT type 1A receptor messenger RNA expression levels suggested this effect was mediated in the raphé nuclei.ConclusionsChronic activation of CRFR2 promotes an anxiety-like state, yet with attenuated behavioral and hypothalamic-pituitary-adrenal axis responses to stress. This is reminiscent of stress-related atypical psychiatric syndromes such as posttraumatic stress disorder, chronic fatigue, and chronic pain states. This new understanding indicates CRFR2 antagonism as a potential novel therapeutic target for such disorders.

This literature review seeks to examine current knowledge of birth trauma associated with major pelvic floor dysfunction by interpreting and critically appraising existing published material. A search of the literature for peer reviewed journal articles was conducted between September and December 2013 of the following databases: PubMed; Wiley Online; MEDLINE; OvidSP; ScienceDirect; MD Consult Australia; Biomed Central; Sage; Cochrane Database of Systematic Reviews. Unpublished interviews from mothers who attended two tertiary teaching hospitals in Sydney, Australia and international Internet blogs/websites were also utilised. Maternal birth trauma seems to be a common cause of pelvic floor dysfunction. Women who have sustained birth trauma to the levator ani muscle or the anal sphincters are often injured more seriously than generally believed. There often is a substantial latency between trauma and the manifestation of symptoms. Urinary and faecal incontinence, prolapse and sexual dysfunction are commonly seen as too embarrassing to discuss with clinicians, and frequently, new mothers have inaccurate recollections of obstetric procedures that occurred without much explanation or explicit consent. Moreover, somatic trauma may contribute to psychological trauma and post-traumatic stress disorder. The link between somatic and psychological trauma is poorly understood.