Process and Outcome Evaluation of a Mindfulness-Based Cognitive Therapy Intervention for Cisgender and Transgender African American Women Living with HIV/AIDS.

There is a need for evidence-based contextualized mental health interventions for persons living with HIV/AIDS. In the current study, the primary researcher conducted open trials with African American women living with HIV/AIDS (AAWLWHA) to examine the acceptability and feasibility of Project UPLIFT, a mindfulness-based cognitive therapy intervention that has demonstrated effectiveness in persons living with epilepsy. Women were recruited for a tele-delivered phone intervention group separated by gender identity, as well as participated in pre- and post-test assessments. Additionally, data on acceptability was collected. Both cis- and transgender women were highly satisfied with the intervention and demonstrated improvement in depressive and stress symptoms. The intervention seemed to be particularly feasible for cisgender women, though more qualitative mental health research may be warranted with transgender women. The current research has implications for the utility of mindfulness-based interventions such as UPLIFT, with AAWLWHA.

Clinical course and prognostic factors across different musculoskeletal pain sites: A secondary analysis of individual patient data from randomised clinical trials.

BACKGROUND: Previous research has identified similar prognostic factors in patients with musculoskeletal (MSK) conditions regardless of pain presentation, generating opportunities for management based on prognosis rather than specific pain presentation. METHODS: Data from seven RCTs (2483 participants) evaluating a range of primary care interventions for different MSK pain conditions were used to investigate the course of symptoms and explore similarities and differences in predictors of outcome. The value of pain site for predicting changes in pain and function was investigated and compared with that of age, gender, social class, pain duration, widespread pain and level of anxiety/depression. RESULTS: Over the initial three months of follow-up, changes in mean pain intensity reflected an improvement, with little change occurring after this period. Participants with knee pain due to osteoarthritis (OA) showed poorer long-term outcome (mean difference in pain reduction at 12 months -1.85, 95% CI -2.12 to -1.57, compared to low back pain). Increasing age, manual work, longer pain duration, widespread pain and increasing anxiety/depression scores were significantly associated with poorer outcome regardless of pain site. Testing of interactions showed some variation between pain sites, particularly for knee OA, where age, manual work and pain duration were most strongly associated with outcome. CONCLUSIONS: Despite some differences in prognostic factors for trial participants with knee OA who were older and had more chronic conditions, similarity of outcome predictors across regional MSK pain sites provides evidence to support targeting of treatment based on prognostic factors rather than site of pain. SIGNIFICANCE: Individual patient data analysis of trials across different regional musculoskeletal pain sites was used to evaluate course and prognostic factors associated with pain and disability. Overall, similarity of outcome predictors across these different pain sites supports targeting of treatment based on prognostic factors rather than pain site alone.

Well-differentiated liposarcoma of the epiglottis.

OBJECTIVE: Liposarcomas of the larynx and its sub-sites are rare. Within this group of tumours, well-differentiated liposarcomas of the epiglottis have been only sporadically reported. In view of its infrequent presentation, difficulty still exists over the diagnosis of this pathological entity, together with uncertainty over its exact accepted management. METHOD: We present the case of a well-differentiated liposarcoma of the epiglottis, and we review the associated English-language literature. RESULTS: The reported patient underwent multiple attempts at surgical treatment prior to establishment of a firm diagnosis. In light of the diagnosis and other mitigating factors, a conservative approach was adopted. CONCLUSION: A high index of clinical suspicion and detailed histological analysis are required when encountering a recurrent soft tissue lesion of the larynx. In the presented case, a multidisciplinary approach and conservative management plan were adopted, based on a holistic management approach and a review of the published literature.

New oral anticoagulants and regional anaesthesia.

The new oral anticoagulants are approved for a variety of clinical syndromes, including the prevention of stroke in atrial fibrillation, acute coronary syndromes, treatment of venous thromboembolism (VTE), and prevention of venous thrombosis after total joint surgery or hip fracture. Published guidelines have differing recommendations on the safe interval between discontinuation of the anticoagulant and performance of neuraxial procedures and between the interventional procedure and redosing of the drug. While two to three half-life intervals might be acceptable in patients who are at high risk for VTE or stroke, an interval of four to six half-lives between discontinuation of the drug and neuraxial injections is probably safer in most patients at low risk of thrombosis. In those with renal disease, the interval should be based on creatinine clearance. After a neuraxial procedure or removal of an epidural catheter, anticoagulants can be resumed within 24-48 h in most patients, but they can be taken sooner in patients who are at higher risk for VTE or stroke, that is, 24 h minus the time to peak effect of the drug. The new antiplatelet drugs prasugrel and ticagrelor should be stopped 7 or 5 days, respectively, before a neuraxial injection and can be restarted 24 h later. In selected situations, laboratory monitoring of the anticoagulant effect is appropriate, and reversal agents are suggested when there is a need to rapidly restore haemostatic function.

Meal provision in a UK National Spinal Injury Centre: a qualitative audit of service users and stakeholders.

STUDY DESIGN: A single centre survey. OBJECTIVES: The objective of this study is to (1) assess patients' food intake and (2) measure satisfaction with current food provision, as judged by patients and by stakeholders (medical and nursing staff, managers and catering staff). METHODS: Standardised questionnaires were used to record food intake over a 24-h period, and to evaluate the quality, ordering, delivery and overall acceptability of food provided. RESULTS: The food intake of 67 patients with spinal cord injury (SCI) was recorded (64% response rate) and 166 evaluations (50% response rate) were returned. Twenty-nine patients (48%) consumed three full meals a day, 17 (26%) received oral nutritional supplements, 22 (34%) received vitamin/mineral supplements, and 23 (35%) required assistance to eat. Some patients and stakeholders expressed satisfaction with the current food provision: taste good: 25 versus 17% (for patients and stakeholders, respectively); appropriate texture: 22 versus 21%; appropriate temperature: 55 versus 72% (P = 0.002); well presented: 43 versus 28%; good choice: 49 versus 59%; received meal ordered: 65 versus 37% (P < 0.001); meal served on time: 71 versus 58%; and no interruption during mealtimes: 62 versus 46%. Principal component analyses of item scores identified three main factors (food quality, food presentation and food delivery (logistics). CONCLUSION: The present study identified some areas where there appeared to have been improvement in SCI hospital catering, but with much still to be achieved. Hospital-catering systems should be tailored to meet the demands of the different patient groups to optimise nutritional intake. Periodic quality control is essential to meet recommendations and patients' expectations.

The role of cerebral oximetry in combination with awake testing in patients undergoing carotid endarterectomy under local anaesthesia.

INTRODUCTION: The aim of this study is to analyse the role of cerebral oximetry in combination with awake testing in detecting cerebral ischaemia in patients undergoing carotid endarterectomy (CEA) under local anaesthesia (LA). METHODS: One hundred consecutive patients scheduled for CEA under LA were investigated. Regional oxygen saturation (rSO(2)) was measured with a cerebral oximeter. Cerebral ischaemia was assessed by awake testing in conjunction with rSO(2). Shunting was based solely on deterioration in conscious state assessed by awake testing. The correlation between awake testing and percentage fall in rSO(2) levels was statistically analysed. RESULTS: Patients requiring general anaesthesia were excluded from analysis (n = 17). Seven patients developed deterioration in conscious state and an immediate drop in rSO(2) ≥20% following carotid cross-clamping. Two patients requiring shunting for non-neurological reasons were excluded from analysis. Two patients had a drop in rSO(2) ≥20%, but remained conscious and were not shunted. There were no permanent neurological deficits postoperatively. Statistical analysis showed a sensitivity of 100% with a specificity of 96% yielding a positive predictive value of 81% and negative predictive value of 100% for a ≥19% drop in rSO(2). CONCLUSION: Cerebral oximetry using a cut off ≥19% drop in rSO(2) has a high sensitivity and specificity when compared with awake testing.

Use of biogenic and abiotic elemental selenium nanospheres to sequester elemental mercury released from mercury contaminated museum specimens.

Mercuric chloride solutions have historically been used as pesticides to prevent bacterial, fungal and insect degradation of herbarium specimens. The University of Manchester museum herbarium contains over a million specimens from numerous collections, many preserved using HgCl(2) and its transformation to Hg(v)(0) represents a health risk to herbarium staff. Elevated mercury concentrations in work areas (∼ 1.7 µg m(-3)) are below advised safe levels (<25 µg m(-3)) but up to 90 µg m(-3) mercury vapour was measured in specimen boxes, representing a risk when accessing the samples. Mercury vapour release correlated strongly with temperature. Mercury salts were observed on botanical specimens at concentrations up to 2.85 wt% (bulk); XPS, SEM-EDS and XANES suggest the presence of residual HgCl(2) as well as cubic HgS and HgO. Bacterially derived, amorphous nanospheres of elemental selenium effectively sequestered the mercury vapour in the specimen boxes (up to 19 wt%), and analysis demonstrated that the Hg(v)(0) was oxidised by the selenium to form stable HgSe on the surface of the nanospheres. Biogenic Se(0) can be used to reduce Hg(v)(0) in long term, slow release environments.

Glycoprotein emulsifiers from two marine Halomonas species: chemical and physical characterization.

AIMS: To partially purify and characterize bioemulsifiers produced by two new marine Halomonas species, TG39 and TG67, and to compare their emulsifying activities with those of commercial emulsifiers. METHODS AND RESULTS: The production of emulsifiers HE39 and HE67 was achieved from glucose-supplemented marine broth, and recovered by cell removal, concentration by ultrafiltration, precipitation with salt and ethanol, and lyophilization. Purification and chemical analysis revealed both emulsifiers to be glycoproteins of high molecular weight with a notably high content of protein and uronic acids. Physical characterization showed both glycoproteins to effectively emulsify a wide range of food oils under both neutral and acidic pH conditions and withstand acid and high temperature treatment. CONCLUSIONS: The emulsifying activities of these two new glycoprotein emulsifiers were comparable and, under certain conditions, superior to those produced by commercial emulsifiers tested (xanthan gum, gum arabic and lecithin). They show the highest reported emulsifying activities derived from a Halomonas species. SIGNIFICANCE AND IMPACT OF THE STUDY: These strains, and the emulsifiers produced, appear to be promising candidates for further development in applications requiring emulsifiers that are natural and compatible to the existing commercial emulsifiers.

Short-term carnitine deficiency does not alter aerobic rat heart function but depresses reperfusion recovery after ischemia.

Clinical and experimental studies have shown that long-term carnitine deficiency is often associated with cardiomyopathy and ischemic failure. The present study was designed to determine whether cardiac dysfunction is seen in an experimental model of short-terrm carnitine deficiency. Carnitine deficiency was induced in Sprague-Dawley rats by supplementing the drinking water with sodium pivalate for a period of 2 weeks. This resulted in a 25% depletion of total myocardial carnitine content. When isolated working hearts from these animals were paced and subjected to increments in left atrial filling pressure, there were no differences in mechanical function compared with control hearts. Following no-flow ischemia, however, recovery of cardiac output and relaxation parameters was depressed in hearts from pivalate-treated animals. Under these conditions, L-carnitine prevented the depressions of function from occurring. Our results show that short-term carnitine deficiency is not associated with cardiac dysfunction under normoxic conditions. However, hearts from pivalate-treated animals are more susceptible to ischemic injury and thus may prove to be useful for the study of metabolic and functional aspects of carnitine deficiency.

Discovery of a new inhibitor lead of adenovirus proteinase: steps toward selective, irreversible inhibitors of cysteine proteinases.

Using the computer docking program EUDOC, in silico screening of a chemical database for inhibitors of human adenovirus cysteine proteinase (hAVCP) identified 2,4,5,7-tetranitro-9-fluorenone that selectively and irreversibly inhibits hAVCP in a two-step reaction: reversible binding (Ki = 3.09 microM) followed by irreversible inhibition (ki = 0.006 s(-1)). The reversible binding is due to molecular complementarity between the inhibitor and the active site of hAVCP, which confers the selectivity of the inhibitor. The irreversible inhibition is due to substitution of a nitro group of the inhibitor by the nearby Cys122 in the active site of hAVCP. These findings suggest a new approach to selective, irreversible inhibitors of cysteine proteinases involved in normal and abnormal physiological processes ranging from embryogenesis to apoptosis and pathogen invasions.

Prediction of biological activity for high-throughput screening using binary kernel discrimination.

High-throughput screening has made a significant impact on drug discovery, but there is an acknowledged need for quantitative methods to analyze screening results and predict the activity of further compounds. In this paper we introduce one such method, binary kernel discrimination, and investigate its performance on two datasets; the first is a set of 1650 monoamine oxidase inhibitors, and the second a set of 101 437 compounds from an in-house enzyme assay. We compare the performance of binary kernel discrimination with a simple procedure which we call "merged similarity search", and also with a feedforward neural network. Binary kernel discrimination is shown to perform robustly with varying quantities of training data and also in the presence of noisy data. We conclude by highlighting the importance of the judicious use of general pattern recognition techniques for compound selection.

Inhibition of human alpha-thrombin by a phosphonate tripeptide proceeds via a metastable pentacoordinated phosphorus intermediate.

X-ray crystallographic studies of human alpha-thrombin with a novel synthetic inhibitor, an acyl (alpha-aminoalkyl)phosphonate, reveal the existence of a pentacovalent phosphorus intermediate state. Crystal structures of the complex of alpha-thrombin with the phosphonate compound were determined independently using crystals of different ages. The first structure, solved from a crystal less than seven days old, showed a pentacoordinated phosphorus moiety. The second structure, determined from a crystal that was 12 weeks old, showed a tetracoordinated phosphorus moiety. In the first structure, a water molecule, made nucleophilic by coordination to His57 of alpha-thrombin, is bonded to the pentacoordinated phosphorus atom. Its position is approximately equivalent to that occupied by the water molecule responsible for hydrolytic deacylation during normal hydrolysis. The pentacoordinated phosphorus adduct collapses to give the expected pseudo tetrahedral complex, where the phosphorus atom is covalently bonded to Ser195 O(gamma). The crystallographic data presented here therefore suggest that the covalent bond formed between the inhibitor's phosphorus atom and O(gamma) of Ser195 proceeds via an addition-elimination mechanism, which involves the formation of a pentacoordinate intermediate.

Dihydroagarofuran sesquiterpene alkaloids from Maytenus putterlickoides.

Two new dihydroagarofuran sesquiterpene alkaloids, putterines A (2) and B (3), and a known alkaloid, mayteine (1), were isolated from the root of Maytenus putterlickoides. The structures of these compounds were elucidated by various spectroscopic techniques, including 1H and 13C NMR, COSY, ROESY, HMBC, and high-resolution FABMS.

Synthesis of thiophene-2-carboxamidines containing 2-aminothiazoles and their biological evaluation as urokinase inhibitors.

The serine protease urokinase (uPa) has been implicated in the progression of both breast and prostate cancer. Utilizing structure based design, the synthesis of a series of substituted 4-[2-amino-1,3-thiazolyl]-thiophene-2-carboxamidines is described. Further optimization of this series by substitution of the terminal amine yielded urokinase inhibitors with excellent activities.

Limited brain access for leptin in obesity.

Obesity is a major health problem that contributes to the development of type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease. The current pharmacological therapies for obesity are limited and may have significant side effects. Leptin therapy was shown to effectively cause weight loss in obese rats, however its effectiveness in humans is still under investigation. Obese humans have significantly elevated plasma leptin concentrations compared with lean individuals. Plasma leptin concentrations strongly correlated with percentage of body fat. Leptin concentration in the cerebrospinal fluid (CSF) is correlated, in a nonlinear manner, with plasma leptin levels and body mass index (BMI). The ratio of CSF leptin levels to serum leptin levels was 4 times greater in lean individuals than in obese individuals. One interpretation of this finding is that human obesity could be secondary to a central resistance to leptin action, causing a relative leptin deficiency in the CNS. Six years after the discovery of leptin we still do not have a clear understanding of how leptin accesses its targets in the brain, or whether there is defect in this process in the brain of obese individuals. In this manuscript we will review the different leptin gateways to the brain and the potential sites where a defect in leptin action may be present, as well as some potential clinical implications of leptin. A better understanding of how leptin reaches the brain and how it modulates the release of hypothalamic neuropeptides will be important in understanding the role that leptin plays in the pathophysiology of obesity.

Efficacy of preoperative autologous blood donation: analysis of blood loss and transfusion practice in total hip replacement.

STUDY OBJECTIVE: To determine the frequency of allogeneic transfusion for total hip replacement (THR) surgery and to examine the efficacy of preoperative autologous blood donation (PABD) under specified, standardized blood transfusion guidelines. DESIGN: Prospective, nonrandomized study. SETTING: University medical center. PATIENTS: All ASA physical status I, II, III, and IV patients undergoing single, primary, THR surgery from April 1998 to March 1999. INTERVENTIONS: All patients received standardized transfusion and anticoagulation therapy. Demographic, blood loss, and transfusion data were collected and compared between all patients participating in PABD (donors) and patients not participating in PABD (nondonors). Overall allogeneic blood exposure was established. Since most anemic patients could not participate in PABD, allogeneic transfusion frequency was also examined in a subset of nonanemic patients (hemoglobin > or =12 g/dL) who were potentially able to participate in PABD. MEASUREMENTS AND MAIN RESULTS: n = 231 patients, 142 donors and 89 nondonors. Mean estimated blood volume (EBV) of donors was 4991 +/- 1042 mL versus nondonors 4631 +/- 1108 mL (p < 0. 01). ASA physical status I-II/III-IV among donors was 118/24 versus nondonors 61/28 (p < 0.01). Overall allogeneic blood exposure was 22% (51/231). Allogeneic transfusion frequency for all donors was 15% (22/142) versus nondonors 33% (29/89) (p < 0.05). Among nonanemic patients, donor versus nondonor EBV and ASA physical status I-II/III-IV were 5074 +/- 1019 mL versus 4743 +/- 1172 mL and 107/20 versus 48/15 (p = NS); allogeneic transfusion frequency reduced to 13% (16/127) versus 17% (11/63) (p = NS), respectively. CONCLUSIONS: Allogeneic blood exposure was >10% despite the use of PABD. The efficacy of PABD has been obscured by the fact that donors of autologous blood tend to be larger and healthier than nondonors. After exclusion of anemic patients, autologous donors and nondonors were clinically comparable and the difference in allogeneic blood exposure was not statistically significant. PABD offers only a modest, if any, benefit for THR surgery.

Effects of chelation with EDTA and vitamin B therapy on nitric oxide-related endothelial vasodilator function.

1. 'Chelation therapy' with EDTA is being frequently used in patients with cardiovascular disease, despite limited objective evidence of effectiveness. Depressed nitric oxide (.NO)-related endothelial function accompanies atherosclerosis, and even the vascular risk factors alone, and is improved by numerous interventions that also improve prognosis in vascular disease. 2. The aim of the present study was to determine the influence of chelation therapy with EDTA alone and EDTA in combination with B vitamins on endothelial function. 3. After a control series of saline infusions, we examined the effects of a series of EDTA infusions (1.5 g, 10 times over 6 weeks) in eight subjects with coronary artery disease. In addition, because EDTA is commonly supplemented by other components, particularly B group vitamins, we subsequently examined the effect of a similar series of vitamin-supplemented EDTA infusions. 4. Forearm blood flow (FBF) was assessed by plethysmography and graded intrabrachial infusions of the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent dilator sodium nitroprusside (SNP). 5. There was no difference in vasodilation to either drug after EDTA alone compared with the control periods, but the response to ACh was augmented after combined therapy (P < 0.03, ANOVA). The latter was accompanied by a small but consistent mean (+/- SEM) fall in plasma homocysteine of 1.6 +/- 0.5 mumol/L (P < 0.05). 6. The selective increase in the vasodilator response to ACh after therapy with EDTA and several B group vitamins indicates that NO-related endothelial function was improved. The absence of response to EDTA alone suggests that the supplementary vitamins were necessary for this benefit, which may have been related to the accompanying decrease in plasma homocysteine. These results, along with the current interest in the possible cardioprotective effects of vitamins and the increasing administration of 'chelation therapy', call for more definitive studies on these aspects of 'alternative medicine'.

Risk factors for reduced bone density in haemodialysis patients.

BACKGROUND: Renal osteodystrophy may result in considerable morbidity for patients with end-stage renal disease. Secondary hyperparathyroidism, adynamic bone disease and osteomalacia, the main bony problems in chronic renal failure, may all be responsible for a reduction in bone mineral density (BMD). This can result in an increased fracture risk. By virtue of their age, post-menopausal status (in women), sedentary life-style and treatment (including previous corticosteroids), haemodialysis patients may be expected also to be at risk for developing osteoporosis, but little is known about the relative importance of these factors. METHODS: We report a prospective study examining the prevalence of reduced bone mineral density (BMD) and its association with a wide range of factors, in a heterogenous group of 88 chronic haemodialysis patients. Femoral neck and lumbar BMD were measured by dual-energy X-ray absorptiometry (DXA). Stepwise multiple linear regression analysis was used to identify risk factors associated with low bone mass. RESULTS: Forty three patients (48.9%) had reduced BMD, and in 17 (19.3%) BMD was below the fracture threshold as defined on DXA measurements by the World Health Organization (WHO). The BMD had significant negative associations with age, serum parathyroid hormone (PTH) levels, current gastric acid suppression therapy, female gender, age at menarche and history of previous fracture. Positive associations were found with weight, haemoglobin concentration, average serum phosphate, weekly heparin dose, oral calcium supplementation and history of parathyroidectomy. CONCLUSIONS: We have confirmed the importance of PTH-related bone disease in affecting BMD in haemodialysis patients, but have found that some other factors, which are known to be risk factors for osteoporosis, are also important.

Association of dietary fish and n-3 fatty acid intake with hemostatic factors in the coronary artery risk development in young adults (CARDIA) study.

Hemostatic factors play an important role in the complications of ischemic heart and vessel disease. Dietary fats such as n-3 fatty acids have been shown to possibly influence hemostatic factors. However, most studies reporting an inverse association between cardiovascular disease and fish and n-3 fatty acid consumption used supplemental doses of fish oil or intakes exceeding the typical amount consumed by the US population. This report examined the associations of usual intakes of fish, linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid with fibrinogen, factor VII, factor VIII, and von Willebrand factor in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The analyses reported here included 1672 black and white men and women aged 24 to 42 years in 1992 to 1993. After adjustment for age, body mass index, diabetes, number of cigarettes smoked per day, race, and energy and alcohol consumption, no significant associations were observed between those who consumed no fish versus those who consumed the highest level of dietary fish with respect to fibrinogen, factor VIII, or von Willebrand factor for any race-sex group. Comparisons of tertile 1 versus tertile 3 for dietary linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid were also not significantly associated with fibrinogen, factor VII, factor VIII, or von Willebrand factor for any race-sex group. These data suggest that customary intakes of fish and n-3 fatty acids in populations that generally do not consume large amounts of these food items are not associated with these hemostatic factors.