Vascular endothelial growth factor reduces tamoxifen efficacy and promotes metastatic colonization and desmoplasia in breast tumors

Clinical studies have shown that decreased tamoxifen effectiveness correlates with elevated levels of vascular endothelial growth factor (VEGF)-A(165) in biopsy samples of breast cancers. To investigate the mechanisms underlying tamoxifen resistance and metastasis, we engineered the estrogen receptor (ER)-positive MCF-7 human breast cancer cell line to express VEGF to clinically relevant levels in a doxycycline-regulated manner. Induction of VEGF expression in orthotopically implanted xenografts that were initially tamoxifen responsive and noninvasive resulted in tamoxifen-resistant tumor growth and metastasis to the lungs. Lung metastases were also observed in a VEGF-dependent manner following tail vein injection of tumor cells. At both primary and metastatic sites, VEGF-overexpressing tumors exhibited extensive fibroblastic stromal content, a clinical feature called desmoplasia. VEGF-induced metastatic colonies were surrounded by densely packed stromal cells before detectable angiogenesis, suggesting that VEGF is involved in the initiation of desmoplasia. Because expression of VEGF receptors R1 and R2 was undetectable in these tumor cells, the observed VEGF effects on reduction of tamoxifen efficacy and metastatic colonization are most likely mediated by paracrine signaling that enhances tumor/stromal cell interactions and increases the level of desmoplasia. This study reveals new roles for VEGF in breast cancer progression and suggests that combination of antiestrogens and VEGF inhibitors may prolong tamoxifen sensitivity and prevent metastasis in patients with ER-positive tumors.     

The role of the avian hippocampus in orientation in space and time

We examined the effects of hippocampus (Hp) and area parahippocampalis (APH) lesions in pigeons on their ability to perform a battery of tasks including autoshaping, time discrimination, spatial memory, and pattern discrimination. Pigeons with Hp-APH lesions were impaired in the acquisition of an autoshaped response, emitting fewer pecks to the stimulus than control animals. Hp-APH pigeons were also impaired in the acquisition of a radial-arm maze analogue task, and those birds that did learn the task seemed to do so by adopting a stereotypic response strategy. In contrast, Hp-APH lesions had no effect on the ability of the birds to discriminate on the basis of either temporal or visual information. Overall, these studies complement our earlier studies and suggest that the avian hippocampus is important for the processing and retention of spatial rather than non-spatial information.     

Quantitative ultrasound and bone mineral density are equally strongly associated with risk factors for osteoporosis.

Because resources do not allow all women to be screened for osteoporosis, clinical risk factors are often used to identify those individuals at increased risk of fracture who are then assessed by bone densitometry. The aim of this study was to compare calcaneal quantitative ultrasound (QUS) and axial bone mineral density (BMD) T and Z scores in a large group of women, some with no clinical risk factors and others with one or more risk factors for osteoporosis. The study population consisted of 1115 pre- and postmenopausal women. A subgroup of 530 women was used to construct reference data for calculating T and Z scores. A total of 786 women was found to have one or more of the following risk factors: (i) atraumatic fracture since the age of 25 years, (ii) report of X-ray osteopenia, (iii) predisposing medical condition or use of therapy known to affect bone metabolism, (iv) premature menopause before the age of 45 years or a history of amenorrhea of longer than 6 months duration, (v) family history of osteoporosis, (vi) body mass index (BMI) <20 kg/m2, and (vii) current smoking habit. Calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements were performed on a Hologic Sahara and a DTUone and BMD was measured at the spine and hip using dual-energy X-ray absorptiometry (DXA). The Z score decrements associated with the seven risk factors calculated using multivariate regression analysis were similar for QUS and BMD measurements. Z score decrements (mean of BMD and QUS measurements combined) associated with a history of atraumatic fracture (-0.67), X-ray osteopenia (-0.36), a family history of osteoporosis (-0.23), and a low BMI (-0.53) were all statistically significant compared with women with no risk factors. Z score decrements associated with a medical condition or use of therapy known to affect bone metabolism, a premature menopause or prolonged amenorrhea, or those who were current smokers were not significantly different from zero. As the number of risk factors present in each individual increased, the mean Z score decrements became more negative, increasing from -0.28 for women with one risk factor to -1.19 for those with four or more risk factors. QUS and BMD measurements yielded similar mean Z scores for women with one, two, three, or more than four risk factors. Using the World Health Organization (WHO) criteria to diagnose osteoporosis for BMD measurements and revised diagnostic criteria for QUS, approximately one-third of postmenopausal women aged 50+ years with clinical risk factors were classified as osteoporotic compared with only 12% of women without clinical risk factors. Over two-thirds of postmenopausal women with risk factors were classified as osteopenic or osteoporotic and approximately 28% were classified as normal. The proportion of women classified into each diagnostic category was similar for BMD and QUS. In conclusion, clinical risk factors for osteoporosis affected calcaneal BUA and SOS Z score measurements to the same extent as axial BMD Z score measurements. Provided revised diagnostic criteria are adopted for QUS, similar proportions of postmenopausal women are identified as osteopenic or osteoporotic as with BMD.     

Neonatal urinary ascites complicated by ileal perforation in a recipient of twin-to-twin transfusion syndrome

We present a case of iatrogenic neonatal urinary ascites following antenatal amnioreduction in one of the monochorionic diamniotic recipient twin 2 of twin-to-twin transfusion syndrome (TTTS). He had ileal perforation following postnatal abdominal paracentesis. The patient had an uneventful recovery following exploratory laparotomy, resection of perforated segment of ileum with end-to-end anastomosis and open vesicostomy with subsequent closure of the vesicostomy.     

The Ububele Baby Mat Service – A primary preventative mental health intervention in a culturally diverse setting

The Ububele Baby Mat Service is a community-based, parent–infant mental health intervention offered at five primary health care clinics in Alexandra Township, in Johannesburg. The aim of the intervention is to promote healthy caregiver-infant attachments. There has been a steady increase in the number of mother-baby dyads making use of the service. This paper aims to explore how the Baby Mat Service and Baby Mat practitioners position and locate themselves in a culturally diverse community setting where multiple meaning systems are drawn on for making sense of health concerns. Two key components of the Baby Mat Service are discussed: i) the presence of an inter-racial therapeutic couple on the mat; and ii) the stance adopted by the Baby Mat practitioners in relation to culturally diverse understandings of a presenting problem. The therapeutic couple engages with culturally-informed frames of reference in an attitude of wondering and tentative thinking (“mhlawumbe” in isiZulu). When a respectfully curious stance was taken by practitioners, it was found to help those accessing the mat to find symbolic meaning in the presenting problem and integrate this with cultural understandings.     

The Evidence for Present‐Centered Therapy as a Treatment for Posttraumatic Stress Disorder

To examine the evidence for present‐centered therapy (PCT) as a treatment for posttraumatic stress disorder (PTSD), 5 randomized clinical trials that compared PCT to an existing evidence‐based treatment for PTSD were reviewed. A meta‐analysis was used to estimate between‐treatment differences on targeted measures, secondary measures, and dropout. PCT was found to be as efficacious as the comparison evidence‐based treatment in 3 of the 5 trials, and in the 2 cases where a no‐treatment condition was included, PCT was superior, with large effect sizes for targeted variables (d = 0.88, 0.74, and 1.27). When results were aggregated using meta‐analysis, effects for PCT versus an evidence‐based treatment for both targeted and secondary measures were small and nonsignificant (d = 0.13 and d = 0.09, respectively). As well, the dropout rate for PCT was significantly less than for the comparison evidence‐based treatments (14.3% and 31.3%, respectively). It appears that PCT is an efficacious and acceptable treatment for PTSD.