Is telomerase reactivation associated with the down-regulatoin of TGFβ receptor-II expression in human breast cancer?

Background Telomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in chromosomal stability and cellular immortalisation. Telomerase activity is detectable in most human cancers but not in normal somatic cells. TGF beta (transforming growth factor beta) is a member of a family of cytokines that are essential for cell survival and seems to be down-regulated in human cancer. Recent in vitro work using human breast cancer cell lines has suggested that TGF beta down-regulates the expression of hTERT (human telomerase reverse transcriptase) : the catalytic subunit of telomerase. We have therefore hypothesised that telomerase reactivation is associated with reduced immunohisto-chemical expression of TGF beta type II receptor (RII) in human breast cancer. Methods TGF beta RII immunohistochemical expression was determined in 24 infiltrating breast carcinomas with known telomerase activity (17 telomerase-positive and 7 telomerase-negative). Immunohistochemical expression of TGF beta RII was determined by a breast pathologist who was blinded to telomerase data. Results TGF beta RII was detected in all lesions. The percentage of stained cells ranged from 1–100%. The difference in TGF beta RII expression between telomerase positive and negative tumours was not statistically significant (p = 1.0). Conclusion The results of this pilot study suggest that there is no significant association between telomerase reactivation and TGF-beta RII down-regulation in human breast cancer

Spinor-Vector Duality in Heterotic String Orbifolds

The three generation heterotic-string models in the free fermionic formulation are among the most realistic string vacua constructed to date, which motivated their detailed investigation. The classification of free fermion heterotic string vacua has revealed a duality under the exchange of spinor and vector representations of the SO(10) GUT symmetry over the space of models. We demonstrate the existence of the spinor-vector duality using orbifold techniques, and elaborate on the relation of these vacua to free fermionic models.Comment: 20 pages. v2 minor corrections. Version to appear on JHEP. v3 misprints correcte

Podiatry services for patients with arthritis: an unmet need

Foot problems are extremely common in patients with rheumatoid arthritis (RA). There is ample evidence that foot pain, either alone or as a comorbidity, contributes significantly to disability. Despite the high prevalence of foot disease in RA, this problem is often trivialised or underappreciated. The inequity in foot health provision for patients with rheumatic disorders in New Zealand has recently been highlighted. Expertise in dealing with foot problems is often limited among healthcare professionals, and it has been argued that better integration of podiatric services into rheumatology services would be beneficial. The aim of this paper is to highlight the major issues related to foot care for patients with arthritis and provide key recommendations that should implemented to improve access to podiatric services in New Zealand

Plio-Quaternary exhumation history of the central Nepalese Himalaya: 1. Apatite and zircon fission track and apatite [U-Th]/He analyses

New apatite and zircon fission track and (U-Th)/He analyses serve to document the bedrock cooling history of the central Nepalese Himalaya near the Annapurna Range. We have obtained 82 apatite fission track (AFT), 7 zircon fission track (ZFT), and 7 apatite (U-Th)/He (AHe) ages from samples collected along the Marsyandi drainage, including eight vertical relief profiles from ridges on either side of the river averaging more than 2 km in elevation range. In addition, three profiles were sampled along ridge crests that also lie ∼2 km above the adjacent valleys, and a transect of >20 valley bottom samples spans from the Lesser Himalaya across the Greater Himalaya and into the Tethyan strata. As a consequence, these data provide one of the more comprehensive low-temperature thermochronologic studies within the Himalaya. Conversely, the youthfulness of this orogen is pushing the limits of these dating techniques. AFT ages range from >3.8 to 0 Ma, ZFT ages from 1.9 to 0.8 Ma, and AHe ages from 0.9 to 0.3 Ma. Most ridges have maximum ages of 1.3–0.8 Ma at 2 km above the valley bottom. Only one ridge crest (in the south central zone of the field area) yielded significantly older ZFT and AFT ages of ∼2 Ma; we infer that a splay of the Main Central Thrust separates this ridge from the rest of the Greater Himalaya. ZFT and AFT ages from a vertical transect along this ridge indicate exhumation rates of ∼1.5 km Myr−1 (r2 > 0.7) from ∼2 to 0.6–0.8 Ma, whereas AHe ages indicate a faster exhumation rate of ∼2.6 km Myr−1 (r2 = 0.9) over the last 0.8 Myr. Exhumation rates calculated for six of the remaining seven vertical profiles ranged from 1.5 to 12 km Myr−1 (all with low r2 values of <0.6) for the time period from ∼1.2 to 0.3 Ma, with no discernible patterns in south to north exhumation rates evident. The absence of a trend in exhumation rates, despite a strong spatial gradient in rainfall, argues against a correlation of long-term exhumation rates with modern patterns of rainfall. AFT ages in the Tethyan strata are, on average, older than in the Greater Himalaya and may be a response to a drier climate, slip on the South Tibetan Detachment, or a gentler dip of the underlying thrust ramp. These data are further evaluated with thermokinematic modeling in the companion paper by Whipp et al

The association of maternal prenatal psychosocial stress with vascular function in the child at age 10-11 years: findings from the Avon longitudinal study of parents and children

Objective To investigate whether (1) maternal psychosocial stress (depression/anxiety) during pregnancy is associated with offspring vascular function and (2) whether any association differs depending on the gestational timing of exposure to stress. We also investigated whether any association is likely to be due to intrauterine mechanisms by (3) comparing with the association of paternal stress with offspring vascular function and (4) examining whether any prenatal association is explained by maternal postnatal stress. Methods and results Associations were examined in a UK birth cohort, with offspring outcomes (systolic and diastolic blood pressure, SBP and DBP, endothelial function assessed by brachial artery flow-mediated dilatation (FMD); arterial stiffness assessed by carotid to radial pulse wave velocity (PWV), brachial artery distensibility (DC), and brachial artery diameter (BD) assessed at age 10–11 years (n = 4318). Maternal depressive symptoms and anxiety were assessed at 18 and 32 weeks gestation and 8 months postnatally. Paternal symptoms were assessed at week 19. With the exception of DBP and BD, there were no associations of maternal depressive symptoms with any of the vascular outcomes. Maternal depressive and anxiety symptoms were associated with lower offspring DBP and wider BD, though the latter attenuated to the null with adjustment for confounding factors. Paternal symptoms were not associated with offspring outcomes. Maternal postnatal depressive symptoms were associated with lower offspring SBP. Conclusions We found no evidence to support the hypothesis that maternal stress during pregnancy adversely affects offspring vascular function at age 10–12 years via intrauterine mechanisms

An evaluation of seasonal variations in footwear worn by adults with inflammatory arthritis: a cross-sectional observational study using a web-based survey

Background: Foot problems are common in adults with inflammatory arthritis and therapeutic footwear can be effective in managing arthritic foot problems. Accessing appropriate footwear has been identified as a major barrier, resulting in poor adherence to treatment plans involving footwear. Indeed, previous New Zealand based studies found that many people with rheumatoid arthritis and gout wore inappropriate footwear. However, these studies were conducted in a single teaching hospital during the New Zealand summer therefore the findings may not be representative of footwear styles worn elsewhere in New Zealand, or reflect the potential influence of seasonal climate changes. The aim of the study was to evaluate seasonal variations in footwear habits of people with inflammatory arthritic conditions in New Zealand. Methods: A cross-sectional study design using a web-based survey. The survey questions were designed to elicit demographic and clinical information, features of importance when choosing footwear and seasonal footwear habits, including questions related to the provision of therapeutic footwear/orthoses and footwear experiences. Results: One-hundred and ninety-seven participants responded who were predominantly women of European descent, aged between 46–65 years old, from the North Island of New Zealand. The majority of participants identified with having either rheumatoid arthritis (35%) and/or osteoarthritis (57%) and 68% reported established disease (>5 years duration). 18% of participants had been issued with therapeutic footwear. Walking and athletic shoes were the most frequently reported footwear type worn regardless of the time of year. In the summer, 42% reported wearing sandals most often. Comfort, fit and support were reported most frequently as the footwear features of greatest importance. Many participants reported difficulties with footwear (63%), getting hot feet in the summer (63%) and the need for a sandal which could accommodate a supportive insole (73%). Conclusions: Athletic and walking shoes were the most popular style of footwear reported regardless of seasonal variation. During the summer season people with inflammatory arthritis may wear sandals more frequently in order to accommodate disease-related foot deformity. Healthcare professionals and researchers should consider seasonal variation when recommending appropriate footwear, or conducting footwear studies in people with inflammatory arthritis, to reduce non-adherence to prescribed footwear

Guidelines for the management of the foot health problems associated with rheumatoid arthritis

Background. Rheumatoid arthritis (RA) as a chronic systemic disease, commonly affects the feet, impacting negatively on patients' quality of life. Specialist podiatrists have a prime role to play in the assessment and management of foot and ankle problems within this patient group. However, it has been identified that in many areas there is no specialist podiatry service, with many patients being managed by non‐specialist podiatrists. Therefore, the North West Clinical Effectiveness Group for the Foot in Rheumatic Diseases (NWCEG) identified the need to develop ‘practitioner facing’ guidelines for the management of specific foot health problems associated with RA. Methods. Members of a guideline development group from the NWCEG each reviewed the evidence for specific aspects of the assessment and management of foot problems. Where evidence was lacking, ‘expert opinion’ was obtained from the members of the NWCEG and added as a consensus on current and best practice. An iterative approach was employed, with the results being reviewed and revised by all members of the group and external reviewers before the final guideline document was produced. Results. The management of specific foot problems (callus, nail pathology, ulceration) and the use of specific interventions (foot orthoses, footwear, patient education, steroid injection therapy) are detailed and standards in relation to each are provided. A diagrammatic screening pathway is presented, with the aim of guiding nonspecialist podiatrists through the complexity of assessing and managing those patients with problems requiring input from a specialist podiatrist and other members of the rheumatology multidisciplinary team. Conclusion. This pragmatic approach ensured that the guidelines were relevant and applicable to current practice as ‘best practice’, based on the available evidence from the literature and consensus expert opinion. These guidelines provide both specialist and non‐specialist podiatrists with the essential and ‘gold standard’ aspects of managing people with RA‐related foot problems

Abdominal wall desmoid tumour: revisited

No Abstract