Characterising recovery following abdominal aortic aneurysm repair using cardiopulmonary exercise testing and patient reported outcome measures.

PURPOSE: Surgery is associated with a post-operative stress response, changes in cardiopulmonary reserve, and metabolic demand. Here recovery after abdominal aortic aneurysm repair is investigated using cardiopulmonary exercise testing and patient-reported questionnaires. MATERIALS AND METHODS: Patients undergoing open (n = 21) or endovascular (n = 21) repair undertook cardiopulmonary exercise tests, activity, and health score questionnaires pre-operatively and, 8 and 16 weeks, post-operatively. Oxygen uptake and ventilatory parameters were measured, and routine blood tests were undertaken. RESULTS: Recovery was characterised by falls in anaerobic threshold, peak oxygen uptake, and oxygen pulse at 8 weeks which appeared to be associated with operative severity; the fall in peak oxygen uptake was greater following open vs. endovascular repair (3.5 vs. 1.6 ml.kg-1.min-1) and anaerobic threshold showed a similar tendency (3.1 vs. 1.7 ml.kg-1.min-1). In the smaller number of patients re-tested these changes resolved by 16 weeks. Reported health and activity did not change. CONCLUSIONS: Aortic repair is associated with falls in the anaerobic threshold, peak oxygen uptake, and oxygen pulse of a magnitude that reflects operative severity and appears to resolve by 16 weeks. Thus, post-operatively patients may be at higher risk of further metabolic insult e.g. infection. This further characterises physiological recovery from aortic surgery and may assist in defining post-operative shielding time.IMPLICATIONS FOR REHABILITATIONAbdominal aortic aneurysm repair is a life-saving operation, the outcome from which is influenced by pre-operative cardiopulmonary reserve; individuals with poor reserve being at greater risk of peri-operative complications and death. However, for this operation, the physiological impact of surgery has not been studied.In a relatively small sample, this study suggests that AAA repair is associated with a significant decline in cardiopulmonary reserve when measured 8 weeks post-operatively and appears to recover by 16 weeks. Moreover, the impact may be greater in endovascular vs. open repair.

Population-based study of mortality and major amputation following lower limb revascularization.

BACKGROUND: The aim of this study was to estimate separate risks of major lower limb amputation and death following revascularization for peripheral artery disease (PAD) using competing risks analysis. METHODS: Routinely collected data from Hospital Episode Statistics (HES) were used to identify patients who underwent endovascular or open lower limb revascularization for PAD in England from 2005 to 2015. The primary outcomes were major lower limb amputation and death within 5 years of revascularization. Cox proportional hazards and Fine-Gray competing risks regression were used to examine the competing risks of these outcomes. RESULTS: Some 164 845 patients underwent their first lower limb revascularization for PAD during the study interval. Most were men (64·6 per cent) and the median age was 71 (i.q.r. 62-78) years. Following endovascular revascularization, the 5-year cumulative incidence of amputation was 4·2 per cent in patients with intermittent claudication and 18·0 per cent in those with a record of tissue loss. The corresponding rates were 10·8 and 25·3 per cent respectively after open revascularization, and 8·1 and 25·0 per cent after combined procedures. The 5-year cumulative incidence of death varied from 24·5 to 39·8 per cent, depending on procedure type. Competing risks methods consistently produced lower estimates than standard methods. CONCLUSION: The 5-year risk of major amputation following lower limb revascularization for PAD appears lower than estimated previously. Patients undergoing revascularization for tissue loss and those who require an open procedure are at highest risk of limb loss.

Progressive skeletal benefits of physical activity when young as assessed at the midshaft humerus in male baseball players.

Physical activity benefits the skeleton, but there is contrasting evidence regarding whether benefits differ at different stages of growth. The current study demonstrates that physical activity should be encouraged at the earliest age possible and be continued into early adulthood to gain most skeletal benefits. INTRODUCTION: The current study explored physical activity-induced bone adaptation at different stages of somatic maturity by comparing side-to-side differences in midshaft humerus properties between male throwing athletes and controls. Throwers present an internally controlled model, while inclusion of control subjects removes normal arm dominance influences. METHODS: Throwing athletes (n = 90) and controls (n = 51) were categorized into maturity groups (pre, peri, post-early, post-mid, and post-late) based on estimated years from peak height velocity (<-2, -2 to 2, 2 to 4, 4 to 10, and >10 years). Side-to-side percent differences in midshaft humerus cortical volumetric bone mineral density (Ct.vBMD) and bone mineral content (Ct.BMC); total (Tt.Ar), medullary (Me.Ar), and cortical (Ct.Ar) areas; average cortical thickness (Ct.Th); and polar Strength Strain Index (SSIP) were assessed. RESULTS: Significant interactions between physical activity and maturity on side-to-side differences in Ct.BMC, Tt.Ar, Ct.Ar, Me.Ar, Ct.Th, and SSIP resulted from the following: (1) greater throwing-to-nonthrowing arm differences than dominant-to-nondominant arm differences in controls (all p < 0.05) and (2) throwing-to-nonthrowing arm differences in throwers being progressively greater across maturity groups (all p < 0.05). Regional analyses revealed greatest adaptation in medial and lateral sectors, particularly in the three post-maturity groups. Years throwing predicted 59% of the variance of the variance in throwing-to-nonthrowing arm difference in SSIP (p < 0.001). CONCLUSION: These data suggest that physical activity has skeletal benefits beginning prior to and continuing beyond somatic maturation and that a longer duration of exposure to physical activity has cumulative skeletal benefits. Thus, physical activity should be encouraged at the earliest age possible and be continued into early adulthood to optimize skeletal benefits.

Delayed discharges at a major arterial centre: a 4-month cross-sectional study at a single specialist vascular surgery ward.

OBJECTIVES: Delayed discharges are a significant problem for the National Health Service. The objectives of this study were to determine the prevalence and impact of delayed discharge at a single specialist vascular surgery ward. DESIGN: A cross-sectional observational study. SETTING: A single specialist vascular unit in the UK during a 4-month study period (01/09/2014-31/12/2014). PARTICIPANTS: All patients admitted to the ward during the study period were included. Patients spending ≥1 night on the ward once declared medically fit for discharge (MFFD) were prospectively identified and data prospectively collected. All other patients were identified retrospectively with data collected retrospectively from electronic records. OUTCOME MEASURES: Primary outcome was number of patients experiencing delayed discharge. Secondary outcome measures were length of stay, length of delay and cost of delay. RESULTS: There were 268 admissions with a total length of stay (LoS) of 2776 days. 57 admissions (21.3%) experienced delayed discharges with a total 535 excess bed days (19.3% total LoS) once MFFD. Unplanned admission (relative risk 7.3 (95% CI 2.7 to 20.0; p<0.001)) and index amputation (relative risk 9.2 (95% CI 3.8 to 22.0; p<0.001)) were associated with increased risk of delayed discharge. There were significant differences in the length of delay by the reason for the delay (p=0.01). Delay due to the provision of social services and inpatient rehabilitation were associated with longer length of delay (post hoc analysis). Age was not independently associated with either increased risk of delayed discharge or length of delay.The total estimated cost of delayed discharges during the study period was £146 055. CONCLUSIONS: A significant number of vascular patients experience delayed discharge. MFFD vascular patients occupy a high proportion of vascular beds at considerable financial cost. Unplanned admissions, amputees and those delayed due to social services contributed most to delays. Closer integration with community health and social care providers may reduce delays.

The associations between diet quality, Body Mass Index (BMI) and Health and Activity Limitation Index (HALex) in the Geisinger Rural Aging Study (GRAS).

OBJECTIVES: To determine the associations between diet quality, body mass index (BMI), and health-related quality of life (HRQOL) as assessed by the health and activity limitation index (HALex) in older adults. DESIGN: Multivariate linear regression models were used to analyze associations between Dietary Screening Tool (DST) scores, BMI and HALex score, after controlling for gender, age, education, living situation, smoking, disease burden and self-vs. proxy reporting. SETTING: Geisinger Rural Aging Study, Pennsylvania. PARTICIPANTS: 5,993 GRAS participants were mailed HRQOL and DST questionnaires with 4,009 (1,722 male, 2,287 female; mean age 81.5 ± 4.4) providing complete data. RESULTS: HALex scores were significantly lower for participants with dietary intakes categorized as unhealthy (<60) (0.70, 95% CI 0.69, 0.72, p<0.05) or borderline (60-75) (0.71, 95% CI 0.70, 0.73, p<0.05) compared to those scoring in the healthy range (>75) (0.75, 95% CI 0.73, 0.77) based on DST scores. HALex scores were significantly lower for underweight (0.67, 95% CI 0.63, 0.72, p<0.05), obese class II (0.68, 95% CI 0.66, 0.71, p<0.05) and class III participants (0.62 95% CI 0.57, 0.67, p<0.05) compared to those with BMI 18.5-24.9. CONCLUSIONS: Poor diet quality, as assessed by the DST, is associated with lower HRQOL in adults ≥ 74 years of age.

Dietary patterns and relationship to obesity-related health outcomes and mortality in adults 75 years of age or greater.

BACKGROUND: The prevalence of obesity-related adverse health outcomes is increasing among older adults. Because it is thought that nutrition plays an important role in successful aging, there has been considerable interest in the association between dietary patterns of older adults and obesity-related health outcomes. OBJECTIVE: This study examined the association between dietary patterns and mortality and prevalence of obesity-related health outcomes, namely cardiovascular disease (CVD), type 2 diabetes mellitus, hypertension, and metabolic syndrome (MetSyn), over a 5-year follow-up period in adults aged 75 years or greater. DESIGN: A longitudinal observational study with cross-sectional dietary assessment. SETTING: Rural Central Pennsylvania. PARTICIPANTS: Community-dwelling older adults (N = 449; 76.5 years old; 57% female). MEASUREMENTS: Multiple, unannounced, 24-hour dietary recalls were used to collect dietary intake. Cluster analysis was used to derive dietary patterns. Prevalence of CVD, diabetes mellitus, hypertension, and MetSyn was extracted from outpatient electronic medical records. Logistic regression was used to examine the associations between dietary patterns and health outcomes and mortality. RESULTS: 'Sweets and Dairy', 'Health-Conscious' and 'Western' dietary patterns were identified. Compared to the 'Health-Conscious' pattern, those in the 'Sweets and Dairy' pattern had increased odds of hypertension over the follow-up period; adjusted odds ratio (95% CI) was 2.18 (1.11-4.30). No significant associations were found for CVD, diabetes mellitus, MetSyn or mortality with dietary patterns. CONCLUSIONS: These findings support the potential value of healthy dietary patterns in the management of hypertension in older adults. We did not observe any other strong associations between dietary patterns and health outcomes or mortality in persons ≥ 75 years of age; thus failing to support the use of overly restrictive diet prescriptions for older persons, especially where food intake may be inadequate.

Dietary patterns and diet quality among diverse older adults: the University of Alabama at Birmingham Study of Aging.

OBJECTIVES: To characterize dietary patterns among a diverse sample of older adults (≥ 65 years). DESIGN: Cross-sectional. SETTING: Five counties in west central Alabama. PARTICIPANTS: Community-dwelling Medicare beneficiaries (N=416; 76.8 ± 5.2 years, 56% female, 39% African American) in the University of Alabama at Birmingham (UAB) Study of Aging. MEASUREMENTS: Dietary data collected via three, unannounced 24-hour dietary recalls was used to identify dietary patterns. Foods were aggregated into 13 groups. Finite mixture modeling (FMM) was used to classify individuals into three dietary patterns. Differences across dietary patterns for nutrient intakes, sociodemographic, and anthropometric measurements were examined using chi-square and general linear models. RESULTS: Three dietary patterns were derived. A "more healthful" dietary pattern, with relatively higher intakes of fruit, vegetables, whole grains, eggs, nuts, legumes and dairy, was associated with lower energy density, higher quality diets as determined by healthy eating index (HEI)-2005 scores and higher intakes of fiber, folate, vitamins C and B6, calcium, iron, magnesium, and zinc. The "western-like" pattern was defined by an intake of starchy vegetables, refined grains, meats, fried poultry and fish, oils and fats and was associated with lower HEI-2005 scores. The "low produce, high sweets" pattern was characterized by high saturated fat, and low dietary fiber and vitamin C intakes. The strongest predictors of better diet quality were female gender and non-Hispanic white race. CONCLUSION: The dietary patterns identified may provide a useful basis on which to base dietary interventions targeted at older adults. Examination of nutrient intakes regardless of the dietary pattern suggests that older adults are not meeting nutrient recommendations and should continue to be encouraged to choose high quality diets.

National risk prediction model for elective abdominal aortic aneurysm repair.

BACKGROUND: Mortality results for elective abdominal aortic aneurysm (AAA) repair are published by the Vascular Society of Great Britain and Ireland. These mortality results are not currently risk-adjusted. The objective of this study was to develop a national risk prediction model for elective AAA repair. METHODS: Data for consecutive patients undergoing elective AAA repair from the National Vascular Database between April 2008 and March 2011 were analysed. Multiple logistic regression and backwards model selection were used for model development. The study outcome measure was in-hospital mortality. Model calibration and discrimination were assessed for all AAA repairs, and separately for open repair and endovascular aneurysm repair (EVAR) subgroups. RESULTS: There were 312 in-hospital deaths among 11,423 AAA repairs (2.7 (95 per cent confidence interval (c.i.) 2.4 to 3.0) per cent): 230 after 4940 open AAA repairs (4.7 (4.1 to 5.3) per cent) and 82 after 6483 EVARs (1.3 (1.0 to 1.6) per cent). Variables associated with in-hospital death included in the final model were: open repair, increasing age, female sex, serum creatinine level over 120 µmol/l, cardiac disease, abnormal electrocardiogram, previous aortic surgery or stent, abnormal white cell count, abnormal serum sodium level, AAA diameter and American Society of Anesthesiologists fitness grade. The area under the receiver operating characteristic (ROC) curve was 0.781 (95 per cent c.i. 0.756 to 0.806) with a bias-corrected value of 0.774. Model calibration was good (P = 0.963) based on the Hosmer-Lemeshow goodness-of-fit test, (bias-corrected) calibration curves, risk group assessment and recalibration regression. CONCLUSION: This multivariable model for elective AAA repair can be used to risk-adjust outcome analyses and provide patient-specific estimates of in-hospital mortality risk for open AAA repair or EVAR.

ROCK1 & 2 perform overlapping and unique roles in angiogenesis and angiosarcoma tumor progression.

The serine/threonine protein kinase paralogs ROCK1 & 2 have been implicated as essential modulators of angiogenesis; however their paralog-specific roles in endothelial function are unknown. shRNA knockdown of ROCK1 or 2 in endothelial cells resulted in a significant disruption of in vitro capillary network formation, cell polarization, and cell migration compared to cells harboring non-targeting control shRNA plasmids. Knockdowns led to alterations in cytoskeletal dynamics due to ROCK1 & 2-mediated reductions in actin isoform expression, and ROCK2-specific reduction in myosin phosphatase and cofilin phosphorylation. Knockdowns enhanced cell survival and led to ROCK1 & 2-mediated reduction in caspase 6 and 9 cleavage, and a ROCK2-specific reduction in caspase 3 cleavage. Microarray analysis of ROCK knockdown lines revealed overlapping and unique control of global transcription by the paralogs, and a reduction in the transcriptional regulation of just under 50% of VEGF responsive genes. Finally, paralog knockdown in xenograft angiosarcoma tumors resulted in a significant reduction in tumor formation. Our data reveals that ROCK1 & 2 exhibit overlapping and unique roles in normal and dysfunctional endothelial cells, that alterations in cytoskeletal dynamics are capable of overriding mitogen activated transcription, and that therapeutic targeting of ROCK signaling may have profound impacts for targeting angiogenesis.

Remodelling of vascular (surgical) services in the UK.

The last few years have seen major changes in the delivery of vascular services in the UK. An increasingly elderly population with greater expectations from their medical services has challenged established methods. It also became apparent that outcomes for low volume, high risk index vascular interventions such as abdominal aortic aneurysm repair were poor in the UK compared to the rest of Europe. Other ongoing challenges were the introduction of a national aortic aneurysm screening programme and the development of vascular surgery as a separate speciality. This article details the approach taken to modernise vascular services in the UK, using a quality framework agreed by vascular specialists, which drove the structural change to move vascular interventions into fewer, higher volume centres. The introduction of modern networks is designed to maintain services in surrounding hospitals without on site vascular inpatient services. The initial effects of this service remodelling are positive, with elective aortic aneurysm mortality rates falling nationally from 7.5 to 2.4 per cent.

Relative validity of the Geisinger Rural Aging Study food frequency questionnaire.

OBJECTIVE: To determine the relative validity of a population specific food frequency questionnaire (FFQ) and evaluate the effectiveness of the instrument for assessing nutritional risk in older adults. DESIGN: A cross-over design with participants completing two different dietary assessment instruments in random order. SETTING: The Geisinger Rural Aging Study (GRAS), a longitudinal study of over 20,000 adults living in the central, northern and eastern counties of Pennsylvania. PARTICIPANTS: A subset of GRAS consisting of 245 older adults (60% women) ranging in age from 70 to 95 years. MEASUREMENTS: Energy and nutrient intakes were assessed from two instruments: a population specific food frequency questionnaire (FFQ) and four 24-hour dietary recalls conducted over a two week period. RESULTS: Pearson correlation coefficients between the FFQ and dietary recalls for most nutrients were 0.5 or higher which suggests that the FFQ provided relatively valid estimates of macro and micronutrient intakes examined. Bland-Altman plots were generated to examine the agreement between instruments. Data are shown for energy, folate and zinc with close agreement at lower intakes indicative of risk for folate and zinc. Sensitivity results also showed that the FFQ was able to correctly classify individuals adequately at risk for most nutrients examined. CONCLUSION: This population specific FFQ appears to be a valid instrument for use in in evaluating risk for many nutrients that are of particular concern in older adults residing throughout many predominately rural counties in Pennsylvania.

Evaluation of five risk prediction models for elective abdominal aortic aneurysm repair using the UK National Vascular Database.

BACKGROUND: There is no consensus on the best risk prediction model for mortality following elective abdominal aortic aneurysm (AAA) repair. The objective was to evaluate the performance of five risk prediction models using the UK National Vascular Database (NVD). METHODS: Data on elective AAA repairs from the NVD between January 2008 and December 2010 were analysed. The models assessed were: Glasgow Aneurysm Score (GAS), Vascular Biochemical and Haematological Outcome Model (VBHOM), physiological component of the Vascular Physiological and Operative Severity Score for enUmeration of Mortality (V-POSSUM), Medicare and Vascular Governance North West (VGNW). Overall model discrimination and calibration in equally sized risk-group quintiles were assessed. RESULTS: The study cohort included 10,891 patients undergoing elective AAA repair (median age 74 years, 87.3 per cent men). The in-hospital mortality rates following endovascular and open repair were 1.3 and 4.7 per cent respectively (2.9 per cent overall). The Medicare and VGNW models both showed good discrimination (area under receiver operating characteristic (ROC) curve 0.71), whereas the GAS, VBHOM and V-POSSUM models showed poor discrimination (area under ROC curve 0.60, 0.61 and 0.62 respectively). The VGNW model was the only one to predict the overall mortality rate in the cohort (3.3 per cent predicted versus 2.9 per cent observed; P = 0.066). The VGNW model demonstrated good calibration, predicting risk accurately in four risk-group quintiles. The Medicare, V-POSSUM and VBHOM models accurately predicted risk in three, two and no risk-group quintiles respectively. CONCLUSION: The Medicare and VGNW models contain similar risk factors and showed good discrimination when applied to the NVD. Both models would be suitable for risk prediction after elective AAA repair in the UK.

GEFT, A Rho family guanine nucleotide exchange factor, regulates lens differentiation through a Rac1-mediated mechanism.

The Rho-family of small GTPase specific guanine nucleotide exchange factor, GEFT, is expressed at high levels in adult human excitable tissues including the brain, heart, and skeletal muscle. Previously, we demonstrated that GEFT is specifically expressed in the adult mouse hippocampus and cerebellum, and that overexpression of this protein can result in neurite and dendrite remodeling. This finding prompted us to explore the expression of GEFT in other tissues, which share common developmental ancestry to the nervous system, specifically the ocular system. Using immunohistochemical analysis specific for GEFT protein expression, we observed the highest ocular expression of GEFT occurring in the neuroblastic layer and differentiating lens fibers of the late-stage mouse embryo, and in the postnatal corneal epithelium, lens epithelium, and throughout the retina. Exogenous expression of GEFT in N/N1003A rabbit lens epithelial cells induced lens fiber differentiation as reflected by cell elongation and lentoid formation, as well as a strong increase in ß-crystallin and filensin expression. Moreover, transfection of lens epithelial cells with GEFT resulted in a Rac-1 mediated up-regulation of αA-, αB-, ßB-, γC-, or γF-crystallin promoter activities that is in part dependent on the nuclear localization of Rac1. Furthermore, pharmacological inhibition of Rac1 blocked GEFT-induced N/N1003A lens fiber differentiation and ßB-crystallin expression in ex vivo mouse lens explants. These results demonstrate for the first time a role for GEFT in lens cell differentiation and mouse eye development. Moreover, GEFT regulation of lens differentiation and eye development occurs through a Rac1-dependent mechanism.

Randomized clinical trial of mesh versus sutured wound closure after open abdominal aortic aneurysm surgery.

BACKGROUND: Incisional herniation is a common complication of abdominal aortic aneurysm (AAA) repair. This study investigated whether prophylactic mesh placement could reduce the rate of postoperative incisional hernia after open repair of AAA. METHODS: This randomized clinical trial was undertaken in three hospitals. Patients undergoing elective open AAA repair were randomized to routine abdominal mass closure after AAA repair or to prophylactic placement of polypropylene mesh in the preperitoneal plane. RESULTS: Eighty-five patients with a mean age of 73 (range 59-89) years were recruited, 77 (91 per cent) of whom were men. There were five perioperative deaths (6 per cent), two in the control group and three in the mesh group (P = 0.663), none related to the mesh. Sixteen patients in the control group and five in the mesh group developed a postoperative incisional hernia (hazard ratio 4.10, 95 per cent confidence interval 1.72 to 9.82; P = 0.002). Hernias developed between 170 and 585 days after surgery in the control group, and between 336 and 1122 days in the mesh group. Four patients in the control group and one in the mesh group underwent incisional hernia repair (P = 0.375). No mesh became infected, but one was subsequently removed owing to seroma formation during laparotomy for small bowel obstruction. CONCLUSION: Mesh placement significantly reduced the rate of postoperative incisional hernia after open AAA repair without increasing the rate of complications.

Management of varicose veins: a survey of current practice by members of the Vascular Society of Great Britain and Ireland.

INTRODUCTION: In 1999, a survey was published detailing the management of varicose veins by members of the then Vascular Surgical Society (VSS). Since then, newer methods for treating varicose veins have been developed and far more explicit rationing has been introduced in the NHS. SUBJECTS AND METHODS: In order to examine whether there had been a significant change in established practice in the UK, a questionnaire was sent to all Vascular Society of Great Britain and Ireland (VSGBI) members in the 2004 yearbook by E-mail or post. RESULTS: Of the 426 questionnaires distributed, a 69% response rate was achieved. Of respondents, 97% treated varicose veins in their NHS practice, whilst 88% did so in private practice. Some 73% used hand-held Doppler assessment in the clinic and 96% used duplex ultrasound assessment selectively. Despite UK National Institute for Health and Clinical Excellence (NICE) guidelines, only 68% said that their primary care trusts funded treatment of symptomatic varicose veins, while 93% did so for complications. In either NHS or private practice, respectively, 83% or 72% of responders offered surgery as preferred treatment for primary varicose veins, while 14% or 20% preferred endovascular treatments (endovascular laser treatment, radiofrequency ablation and foam sclerotherapy). Of responders, 17% did not follow-up patients after treatment. CONCLUSIONS: This survey suggests that there is rationing of access to care for symptomatic varicose veins. Despite publicity for endovenous techniques, surgery remains the preferred treatment for varicose veins in the UK.

Protection against breathing dust: behavior over time in Californian farmers.

The aim of this study was to determine whether Californian farmers changed respiratory protective behaviors over time and the personal characteristics associated with protective behaviors. We surveyed 588 farmers longitudinally from 1993 to 2004. Questions included frequency of protective mask or respirator use in dusty conditions and the percentage of time the farmers drove a tractor with a closed cab. To assess longitudinal associations between protective behaviors and potential covariates, general estimating equation modeling was used with adjustment for subject age, study date, and other covariates. Only 25% of the farmers were "very" concerned about respiratory risks. Over time, any use of a dust mask or respirator decreased significantly, from 54% in 1993 to 37% in 2004 (p-value < or = 0.0001), while consistent use of respiratory protection was maintained by 20% of the cohort. Use of a closed-cab tractor increased slightly from 14% in 1993 to 17% in 2004 (p-value = 0.04). Farmers who were ex-smokers and those concerned about respiratory risk were more likely to consistently use a dust mask or respirator. However, the more acreage or time spent in dust, the less likely farmers were to use protection. Closed-cab tractor use was associated with higher salary, more time driving tractors, and larger acreage farmed. Emission reduction remains a priority. Exposure reduction by closed-cab tractor use was not associated with perception of respiratory risk. As mask or respirator use was most positively associated with respiratory concern, more effort needs to be concentrated on educating farmers about long-term respiratory health risks, and providing more user-friendly personal protective equipment.

The predictive value of haemodynamic assessment in chronic venous leg ulceration.

OBJECTIVES: The aim of this study was to assess the value of PPG in predicting healing and recurrence in patients with chronic venous ulceration. METHODS: 500 patients with open or recently healed venous ulceration were treated with either multilayer compression or compression plus superficial venous surgery and followed up in specialist clinics as part of a clinical study. At initial assessment, VRT was measured using PPG with and without a below-knee tourniquet inflated to 80 mmHg to occlude superficial veins. Legs were stratified into groups with VRT <11s, 11-20s and >20s and comparison of healing and recurrence rates between these groups was performed. RESULTS: VRT measurements were not achieved in 117 patients, primarily due to ankle stiffness. Of the remaining 383 patients, VRT without tourniquet did not correlate with ulcer healing (p=0.26, 0.40) or recurrence (p=0.20, 0.79, Log rank test) for legs treated with compression or compression plus surgery respectively. However, VRT readings taken with a below-knee tourniquet were predictive of ulcer healing (p<0.01) and recurrence (p=0.05, Log-rank test). The correlation was greatest for healing in legs treated with compression alone, where 24 week healing rates were 62%, 73% and 92% for legs with VRTs with tourniquet <11s, 11-20s and >20s respectively (p<0.01, Log rank test). For legs treated with surgery, 1 year recurrence rates were 24%, 10% and 3% for groups with VRTs with tourniquet <11s, 11-20s and >20s respectively (p=0.03, Log rank test). CONCLUSIONS: Digital PPG assessment may predict ulcer healing and recurrence, but only by using a below-knee tourniquet. This information could aid the selection of patients with venous ulceration most likely to benefit from superficial venous surgery.

Transcriptional regulation of KiSS-1 gene expression in metastatic melanoma by specificity protein-1 and its coactivator DRIP-130.

Loss of the metastasis suppressor gene, KiSS-1 has been strongly correlated to the progression of metastases in numerous types of cancers. The mechanism through which KiSS-1 is lost during metastasis, however, is still not completely known. Previous studies have shown that genetic material on human chromosome 6q16.3-q23 is essential for KiSS-1 expression in normal tissues. Additionally, microcell-mediated transfer of this chromosome in cancerous tissue results in rescued expression of KiSS-1 and reduced metastatic phenotype. Here, we show that loss of Sp1-coactivator protein DRIP-130, which is encoded by human chromosome 6q16.3-q23, results in reduced KiSS-1 promoter activation in highly malignant melanoma cells. Co-expression of Sp1 and DRIP-130 not only rescues KiSS-1 expression, but also induces an inhibition of the invasive and migratory behavior in highly metastatic melanoma cells, similar to the overexpression of KiSS-1 metastasis suppressor gene in those cells. Furthermore, we demonstrate that KiSS-1 expression is regulated by Sp1 elements within the first 100-bp region of the KiSS-1 promoter and that targeted deletion of a single GC-rich region spanning -93 to -58 interrupts Sp1- and DRIP-130-modulated transcriptional control of KiSS-1 expression. Our results thus suggest that DRIP-130 is a key regulator in KiSS-1 transactivation in normal tissue, and that the loss of DRIP-130 expression, as a result of the gross loss of human chromosome 6q16.3-q23, provokes increased tumor metastasis.