Creation of forest edges has a global impact on forest vertebrates.

Forest edges influence more than half of the world's forests and contribute to worldwide declines in biodiversity and ecosystem functions. However, predicting these declines is challenging in heterogeneous fragmented landscapes. Here we assembled a global dataset on species responses to fragmentation and developed a statistical approach for quantifying edge impacts in heterogeneous landscapes to quantify edge-determined changes in abundance of 1,673 vertebrate species. We show that the abundances of 85% of species are affected, either positively or negatively, by forest edges. Species that live in the centre of the forest (forest core), that were more likely to be listed as threatened by the International Union for Conservation of Nature (IUCN), reached peak abundances only at sites farther than 200-400 m from sharp high-contrast forest edges. Smaller-bodied amphibians, larger reptiles and medium-sized non-volant mammals experienced a larger reduction in suitable habitat than other forest-core species. Our results highlight the pervasive ability of forest edges to restructure ecological communities on a global scale.

The attitude of healthcare professionals plays an important role in the uptake of diabetes self-management education: analysis of the Barriers to Uptake of Type 1 Diabetes Education (BUD1E) study survey.

AIM: To explore reasons for the poor uptake of accredited diabetes self-management education (DSME) in adults with Type 1 diabetes. METHODS: The study was set in an urban population in South London, UK. A cross sectional survey gathered demographic, diabetes service-use data, psychological scores and reasons for non-attendance at locally-available DSME. In addition, 56 healthcare professionals were surveyed. RESULTS: Responses to surveys were returned by 496 adults with Type 1 diabetes (33% response rate), of whom 263 had attended DSME (53%). Multivariable analysis adjusted for significant variables identified four key variables influencing attendance. Non-attendance was associated with men (OR 0.55 CI 0.37-0.84, p = 0.005), lower educational attainment (OR 0.45 CI 0.28-0.73, p = 0.001), higher glycated haemoglobin (OR 1.74 CI 1.03-2.94, p = 0.04) and healthcare professional encouragement to attend (OR 1.7 CI 1.28-2.3, p = 0.001). The most frequently reported barriers to attendance were work (37%) and time (14%) commitments. Only 49% of healthcare professionals (HCPs) correctly identified the most likely barriers. Those HCPs who had observed courses believed more in their efficacy, with higher uptake within their clinic population. CONCLUSIONS: Social determinants of health, particularly educational attainment and gender, increase health inequalities by influencing decisions to attend evidence-based education courses. Healthcare professional communication is paramount to encourage attendance, and observation of a course may facilitate this.

Factors influencing attendance at structured education for Type 1 diabetes in south London.

AIM: To investigate the factors influencing uptake of structured education for people with Type 1 diabetes in our local population in order to understand why such uptake is low. METHODS: We conducted a cross-sectional database study of adults with Type 1 diabetes in two south London boroughs, analysed according to Dose Adjustment For Normal Eating (DAFNE) attendance or non-attendance. Demographics, glycaemic control and service use, with subset analysis by ethnicity, were compared using univariate analysis. An exploratory regression model was used to identify influencing factors. RESULTS: The analysis showed that 73% of adults had not attended the DAFNE programme. For non-attenders vs attenders, male gender (59 vs 48%; P = 0.002), older age (39 vs 35 years; P < 0.001), non-white ethnicity (30 vs 20%; P = 0.001) and coming from an area of social deprivation (index of multiple deprivation score 31 vs 28; P < 0.001) were associated with non-attendance. The difference in gender (88% men vs 70% women; P < 0.001) and age (43 vs 34 years) persisted in the non-white group. Regression analysis showed that higher baseline HbA1c level (odds ratio 1.96; P = 0.004), younger age (odds ratio 0.98; P = 0.001) and lower social deprivation (odds ratio 0.52; P = 0.001) was associated with attendance. CONCLUSION: Socio-economic status and factors perceived as indicating greater severity of disease (HbA1c ) influence attendance at DAFNE. More work is necessary to understand the demography of non-attenders to aid future service design and alternative engagement strategies for these groups.

Synapsin I (Protein I), a nerve terminal-specific phosphoprotein. II. Its specific association with synaptic vesicles demonstrated by immunocytochemistry in agarose-embedded synaptosomes.

Synapsin I (protein I) is a major neuron-specific endogenous substrate for cAMP-dependent and Ca/calmodulin-dependent protein kinases that is widely distributed in synapses of the central and peripheral nervous system (De Camilli, P., R. Cameron, and P. Greengard, 1983, J. Cell Biol. 96:1337-1354). We have now carried out a detailed analysis of the ultrastructural localization of synapsin I in the synapse. For this purpose we have developed a novel immunocytochemical technique that involves the labeling of isolated synaptosomes immobilized in a thin agarose gel. Special fixation conditions were designed to maximize accessibility of synapsin I to marker molecules. Immunoferritin and immunoperoxidase studies of this preparation indicated that synapsin I is localized in the presynaptic compartment and that it is present in close to 100% of all nerve endings. Immunoferritin labeling also indicated that, inside the nerve ending, synapsin I is specifically associated with the cytoplasmic surface of synaptic vesicles. In agreement with these immunoferritin results, the labeling produced by immunoperoxidase was compatible with a specific association of synapsin I with synaptic vesicle membranes. However, at variance with the very specific distribution of immunoferritin, immunoperoxidase reaction product was also found on other membranes of the terminals, presumably as a result of its diffusion over a short distance from the synaptic vesicles. Anti-synapsin I immunoperoxidase staining of tissue sections for electron microscopy produced an uneven labeling of terminals of the neuropile, in agreement with results of a previous study (Bloom, F. E., T. Ueda, E. Battenberg, and P. Greengard, 1979, Proc. Natl. Acad. Sci. USA. 76:5982-5986). A comparison with results obtained in isolated synapses indicates that the limited labeling of nerve endings in tissue sections results from limited and uneven penetration by marker molecules. The specific association of synapsin 1 with synaptic vesicle membranes in the great majority of nerve terminals suggests a prominent role for this phosphoprotein in the regulation of synaptic vesicle function.

Achieving selectivity for copper over zinc with luminescent terbium probes bearing phenanthridine antennas.

A family of terbium probes was synthesized and evaluated for the luminescence detection of copper and zinc in water at neutral pH. Each probe incorporates a terbium ion chelated by a macrocyclic polyaminocarboxylate and conjugated to either one, two, or three phenanthridine antennas via a diamine linker. All three probes, Tb-1Phen, Tb-2Phen, and Tb-3Phen, exhibit similar responses toward copper and zinc. In each case, the terbium-centered time-gated phosphorescence decreases upon binding either CuI or CuII but not upon addition of ZnII. The phosphorescence of Tb-2Phen is also not significantly affected by other metal ions including MgII, CaII, MnII, FeII, NiII, CdII, and HgII. Tb-1Phen, on the other hand, responds weakly to MnII, FeII and NiII. The lack of affinity of each probe for ZnII was further confirmed by competition experiments with CuI and CuII. Notably, whereas the terbium-centered emission of each probe is quenched upon copper coordination, the phenanthridine-centered luminescence emission is not. As such, each probe functions as a ratiometric probe for the selective detection of copper over zinc. Theoretical calculations further demonstrate that the turn off response of the probe is due to an increase in the distance separating the lanthanide ion from its phenanthridine antennas upon coordination of copper, which in turn decreases the efficiency of terbium sensitization by the phenanthridines.

Complete on/off responsive ParaCEST MRI contrast agents for copper and zinc.

Two thulium-based ParaCEST responsive contrast agents, Tm-DOTAm-py and Tm-DOTAm-ßAla-py, have been synthesized and evaluated for imaging copper and zinc. Unusual for responsive MRI contrast agents, both agents display a complete on/off response in the presence of transition metals. Both complexes function as paraCEST agents in the absence of copper and zinc, with the positively charged Tm-DOTAm-py being more sensitive than the neutrally charged Tm-DOTAm-ßAla-py. In each case, the CEST signal arises from amide protons rather than from a water molecule coordinated to Tm3+ ions. Upon binding to Cu+, Cu2+, or Zn2+, the exchange rate of the amide protons increases substantially, resulting in a complete loss of the CEST signal. This efficient mode of action along with the lack of inner-sphere water molecules both in the presence and absence of transition metals was confirmed by 1/T1 NMRD profiles, 17O NMR measurements, and molecular modelling simulations. Neither complex is selective for copper over zinc. Both form either a 1 : 1 TmL : Cu+ or a 2 : 1 TmL : Cu2+ and TmL : Zn2+ complexes with binding affinities comparable to that of other responsive MRI contrast agents and sensitivity comparable to that of other CEST contrast agents.

Thyrotropin releasing hormone, cholecystokinin and endogenous opioids in the modulation of spinal reflexes in the rabbit.

Electrical stimulation of the sural nerve of the rabbit evokes reflexes in the ipsilateral ankle extensor gastrocnemius medialis and in the knee flexor semitendinosus which are differentially modulated by endogenous opioids. Intravenous injection of the putative functional opioid antagonist, thyrotropin releasing hormone (TRH) or its analogue RX77368, caused the extensor response to double in size and the flexor reflex to increase to 1.5-1.7 times pre-drug controls. The opioid RX77368 had no effect on the naloxone-reversible inhibition of the gastrocnemius reflex which followed tetanic stimulation of the fine afferent fibres of the common peroneal or sural nerves. The cholecystokinin antagonist proglumide, which has been shown to enhance the actions of endogenous opioids in some species, had no effects on either reflex. It is possible that TRH acts as an excitatory neurotransmitter or modulator in the spinal cord of the rabbit opposing, but not blocking, the actions of endogenous opioids.

Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators.

The comparative antihypertensive efficacy and tolerability of the angiotensin II receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine were evaluated in an 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study in 251 adult patients (45% women, 16% black) with mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period, patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily. After 4 weeks of double-blind treatment, patients were uptitrated to candesartan cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant differences between the candesartan cilexetil and amlodipine regimens for reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients on candesartan cilexetil and 87% of those on amlodipine were controlled (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil discontinued treatment, compared with 9.4% of patients on amlodipine, including 2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema, respectively. Peripheral edema, the prespecified primary tolerability end point, occurred with significantly greater frequency in patients on amlodipine (22.1%; mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and amlodipine are both highly effective in controlling BP in patients with mild hypertension. Candesartan cilexetil offers a significant tolerability advantage with respect to less risk of developing peripheral edema.

Attenuation of AMPA-induced neurotoxicity by a calpain inhibitor.

The effects of a membrane-permeable inhibitor of calpain, Cbz-Val-Phe-H, were examined in an in vitro model of neurotoxicity. Cerebellar slices from young rats were treated with the glutamate receptor agonist, amino-3-hydroxy-5-methyl-4-isoazole propionic acid (AMPA), and cytotoxicity was quantified using conventional histological techniques. Slices treated with AMPA exhibited damage to 83.0% of cerebellar Purkinje cells. In contrast, only 23.6% of Purkinje cells were damaged in slices treated with Cbz-Val-Phe-H and AMPA. These findings indicate that calcium-activated proteolysis is a critical event in AMPA-induced toxicity, and provide evidence that calpain inhibitors are capable of attenuating this form of excitotoxic damage in the central nervous system.

Therapist physical attractiveness: an unexplored influence on client disclosure.

Existing research indicates that clients perceive facially attractive therapists as more competent, trustworthy, genuine, and effective than less attractive therapists. No studies exist to help explain how the therapist's attractiveness influences a client's self-disclosure. Participants (n = 241) were randomly assigned to one of eight experimental groups to test the interaction of the therapist's attractiveness, client's gender, the nature of presenting problem, and the client's comfort with disclosing in a hypothetical couple therapy scenario. Analysis of variance procedures established that most participants reported feeling more comfortable disclosing a benign (communication) problem than a potentially embarrassing (sexual) problem, and more comfortable disclosing problems to an attractive than to a less attractive female therapist. Therapists are encouraged to understand the power attractiveness may have in their own and their clients' lives.

Antisocial personality, substance abuse, and exposure to parental violence in males referred for domestic violence.

This study investigated whether childhood disruptive behavior (hyperactivity, oppositional-defiance, conduct problems) plus adult psychopathic adjustment are associated with domestic violence. Adult males (n = 66) in diversion programs completed the Wender Utah Rating Scale (WURS), MMPI Psychopathic Deviate scale (PD), Conflict Tactics Scales representing themselves and their parents, and substance use measures. Substance use and lifespan antisocial personality (measured by high WURS and PD scores) were robust predictors of verbal and moderate physical domestic abuse. Violence in the family of origin was associated with abuse when tested alone, but failed to exhibit unique association with abuse when other predictors were taken into account. The possibility that antisocial batterers respond to contingencies by moderating physical harm, while persisting at psychological harm, is discussed.

Retrospective report on the effectiveness of a polyurethane football helmet cover on the repeated occurrence of cerebral concussions.

This report reviews the literature and unpublished data and presents survey results related to the use of a polyurethane football helmet cover. Two hundred forty-five individuals, identified by the helmet manufacturer as having purchased at least one device, were sent a survey after the 1992, 1993, and 1994 football seasons; 155 (63.3%) of the surveys were returned. The questionnaire, designed to be completed by the athlete, required a detailed history of concussions occurring both prior to and during the period the device was used. Individuals used the device as a result of having incurred at least one concussion. Rates of concussion reoccurrence while the device was worn were grouped by the number of previous concussions (1, 2, 3, or 4+) that occurred over a 4year period prior to use of the device. The rate of concussion reoccurrence was 2.4%, 7.3%, 15.8%, and 33.3%, respectively, over a 4-year period. The range appeared to reflect a parallel relationship between pre- and post-device concussion experiences: the more concussions experienced prior to adopting the device, the higher the rate of concussion reoccurrence while using the device. The natural history of repeated occurrences of concussive events may not be affected by the use of a polyurethane football helmet cover. We suggest that such a device not be routinely used prophylactically, but instead be reserved for individuals with 1 to 2 prior concussion injuries. However, at this time, we neither recommend nor discommend the device.

Stress and illness in adolescence: issues of race and gender.

There is an abundance of information on the association between stressful life events and illness within the adult population. In contrast, research on this relationship among adolescents is limited. This study evaluated the role of individual differences (gender and race) on the stress-illness relationship within the adolescent population. Participants were 119 adolescents (54 females and 65 males), recruited from two public high schools located in the southeast, who were administered four questionnaires designed to measure levels of stress, anxiety, and illness. Overall, correlational analysis revealed that stress and anxiety were positively correlated with reported illness. However, racial and gender differences did emerge. Although no gender differences were found with regard to the experience of stress, African-American athletes reported a higher frequency of stressful life events than did their Euro-American counterparts. Further, African-American adolescents reported a lower frequency of illness than did the Euro-Americans. Females reported more illnesses than did males. Possible explanations for individual differences in reported stress and illness are discussed.

Concomitant myasthenia gravis and macroprolactinoma: the immunomodulatory role of prolactin and its potential therapeutic use.

Considerable evidence attests to the role of the hypothalamic-pituitary endocrine axis (HPA) in the maintenance of normal immunocompetence. The immune and neuroendocrine systems are integrally linked and coordinated with bidirectional communication maintaining immune balance. Any disturbance of the normal function of the HPA may significantly alter native immunocompetence and therefore be associated with the development of disorders which have a clearly established autoimmune basis. Molecular and functional evidence shows prolactin, produced by the anterior pituitary, to be a cytokine, exerting its effect via both paracrine and endocrine mechanisms [1]. Its involvement in the activation of multiple immune responses may adversely upregulate certain autoimmune diseases. Myasthenia gravis (MG) has long been recognized as an autoimmune disorder. In this mini review, we present the coterminous presentation of MG and prolactin-secreting macroadenoma. We review published cases in the world literature, discuss pathological mechanism, and consider future targeted therapies.

Enhancement of adipogenesis and fibrogenesis in skeletal muscle of Wagyu compared with Angus cattle.

Intramuscular fat and collagen content are major factors affecting beef quality, but mechanisms regulating intramuscular adipose and connective tissue deposition are far from clear. Japanese Wagyu cattle are well known for their extremely high marbling. The objective of this study was to evaluate intramuscular fat (IMF) and collagen deposition in the muscle of Wagyu compared with Angus cattle. Animals were managed under the same condition and slaughtered at an averaging 585 ± 12.1 kg of BW. Samples of sternomandibularis muscle were collected from Wagyu (n = 3) and Angus (n = 3) for molecular and histological investigations of adipogenesis and fibrogenesis. With exception of C/EBPß (P = 0.2864), the expression of the adipogenic markers C/EBPα (P = 0.008), PPARγ (P = 0.028), and zip finger protein 423 (Zfp423; P = 0.047) in Wagyu were greater than in Angus muscle, which was consistent with greater IMF deposition in Wagyu (P < 0.05). In addition, more adipocytes and preadipocytes were detected intramuscularly in Wagyu cattle. Similarly, fibrogenesis was also enhanced in Wagyu, with a greater expression of fibroblast growth factor (FGF)-2 (P = 0.028), FGF receptor 1 (P = 0.030), transforming growth factor (TGF)-ß (P = 0.028), collagen I (P = 0.012), and collagen III (P = 0.025). Similarly, Wagyu muscle had greater collagen content (P = 0.002) and decreased collagen solubility (P = 0.005). In addition, muscle fiber diameter was larger (P < 0.0001) in Wagyu than in Angus cattle. These results clearly show that both IMF and collagen contents are enhanced in Wagyu cattle and more adipogenic cells are detected in Wagyu muscle, indicating intramuscular adipogenesis is enhanced in Wagyu compared with Angus muscle.

Antitumour activity of XR5944 in vitro and in vivo in combination with 5-fluorouracil and irinotecan in colon cancer cell lines.

XR5944 (MLN944), a novel bis-phenazine, has demonstrated potent cytotoxic activity against a variety of murine and human tumour models. In the present study, the antitumour activity of XR5944 was investigated in combination with 5-fluorouracil (5-FU) or irinotecan in human colon carcinoma cell lines and xenografts. In vitro cytotoxicity of the combinations following exposure to the drugs sequentially or simultaneously was evaluated by the sulphorhodamine-B assay and interactions were determined using median-effect analysis. Antagonism was observed (CI >1) following exposure of HT29 cells simultaneously to XR5944 and 5-FU or SN38 (active metabolite of irinotecan). In contrast, sequential exposure of either combination in either order demonstrated at least an additive response (CI< or =1). At least an additive response was also observed with these combinations in HCT116 cells regardless of schedule. Antitumour activity in HT29 xenografts in nude mice was enhanced by sequential administration of 5-FU (65 mg kg(-1)) or irinotecan (CPT-11) (35 mg kg(-1)) 48 h before XR5944 (5, 10, or 15 mg kg(-1)) compared to single agent treatment at the same or higher doses. Administration of irinotecan (35 mg kg(-1)) and XR5944 (15 mg kg(-1)) just 30 min apart yielded similar efficacy to sequential administration 48 h apart. All combinations were well tolerated. These data suggest that combinations of XR5944 with irinotecan or 5-FU are of significant interest in the treatment of colon cancer.

Racial differences in predictors of college women's body image attitudes.

African-American and Euro-American women from three predominantly Euro-American colleges in the southeast U.S. between 17 and 23 years of age completed instruments assessing body image attitudes, social competence, sex-role attitudes, racial identity, and a measure of family and personal characteristics. Analyses revealed race differences on all body image measures with the exception of appearance evaluation which was influenced by family income and race. Specifically, African-American women reported more satisfaction with and positive feelings towards their bodies and less dissatisfaction than Euro-American women. Unlike Euro-Americans, African-American women attached importance to fitness and health. The relationship between personal/physical factors and body image was stronger for African-American than Euro-American women. Additionally, personal/physical characteristics were the best model of appearance evaluation for African-American women, whereas personal/physical and sociodemographic factors best predicted this measure for Euro-American women. The results are discussed in relation to body image norms and standards of the African-American subculture and middle-class, Euro-American mainstream culture.

Save the young--the elderly have lived their lives: ageism in marriage and family therapy.

The paucity of literature addressing mental health issues concerning geriatric populations represents the perpetuation of ageist practices and beliefs in the field of marriage and family therapy. The purpose of this study was to assess whether client age and clinical training relate to the evaluation of couples who present for conjoint therapy. Written vignettes describing two couples, one older and one younger, who report issues involving the absence of sexual intimacy, increased frequency of arguments, and increased use of alcohol were evaluated by practicing marriage and family therapists, therapists-in-training, and individuals with no clinical background. It was hypothesized that respondents' views would vary in connection with the age of the couple and with the three levels of participant training. Results indicate that client age and participant training are associated with perceptions of individual and couple functioning. Our findings suggest that the relational and mental health concerns experienced by elder couples are not perceived as seriously as are identical concerns experienced by younger couples. Contrary to our expectations the observed differences between views of the two age conditions did not significantly differ between levels of participant training. Training and experience in marriage and family therapy may not significantly mitigate vulnerability to age-discrepant views.