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Introduction: Lesbian, gay, bisexual, and questioning (LGBQ) adolescents are particularly at risk for suicidal ideation; however, little clinical research is focused on treating this population. Attachment‐based family therapy (ABFT) is among the few empirically supported youth suicide treatments adapted for LGBQ adolescents. The purpose of this exploratory study is to determine the differential treatment effects and rates of change for LGBQ and heterosexual adolescents with depression and suicidal ideation receiving either ABFT or family enhanced nondirective supportive therapy (FE‐NST). Method: The sample included 129 adolescents (31% LGBQ), ages 12–18 randomized to the two treatment groups. Multilevel modeling was used to examine individual changes in depression and suicidal ideation over the 16‐week treatment. Results: Results revealed that LGBQ adolescents in the ABFT condition showed a greater rate of reduction in depressive symptoms over treatment, slope = −0.94, p < 0.001, than did LGBQ adolescents in the NST condition, slope = −0.41, p = 0.12. Heterosexual adolescents showed symptom reduction in both treatment conditions (ABFT slope = −0.47, p < 0.001; NST slope = −0.79, t (113) = −7.48, p < 0.001). Changes in suicidal ideation were found across time, but not across conditions. Conclusion: LGBQ adolescents in the ABFT condition had a sharper decrease in depressive symptoms and better outcomes at week 16. [ABSTRACT FROM AUTHOR]

Objective: The present study tested the validity and clinical utility of adolescents' reports of two distinct modes of processing during the recall of a suicidal episode in the Suicide Narrative Interview (SNI). Recall Intensity (RI) items were designed to capture a tendency to become immersed in thoughts and feelings during the interview, while Meaning Making (MM) items were designed to assess more distant and reflective processing. Method: The construct and predictive validity of pretreatment MM and RI was tested in a 16-week randomized clinical trial (RCT) for depressed and suicidal adolescents (N = 113, Mage = 14.95, 84.1% female, 51.8% Black/African American). Adolescents rated MM and RI immediately following the SNI during a baseline assessment. Results: Baseline MM was associated with protective factors related to reduced suicidality, and RI was associated with several risk factors for suicidal symptoms. Adolescents who reported high MM and low RI reported greater reductions in both suicidal ideation and depressive symptoms during the RCT. Conclusions: The results support MM and RI as two distinct modes of how adolescents process memories of suicidal episodes and highlight the potential clinical utility of RI and MM in assessing and treating suicidal adolescents. What is the public health significance of this article?: Identifying both risk and protective factors for adolescent suicidality is imperative for effective assessment and treatment. The present study extends prior research by testing the validity of Meaning Making (MM) and Recall Intensity (RI) as two modes of processing while recalling a past suicidal episode. Results support MM as a protective factor and RI as a risk factor and demonstrate that attachment-based family therapy and family-enhanced nondirective supportive therapy were particularly effective in reducing suicidal ideation and depression in teens reporting high MM and low RI at the start of treatment. [ABSTRACT FROM AUTHOR]

Objective: Despite considerable evidence that supports perceived burdensomeness (PB) and thwarted belongingness (TB) as risk factors for suicidal ideation (SI), far less is known about the direction of effects between these constructs in treatments for suicidal adolescents. The present study examined bidirectional relations between PB, TB, and adolescents' suicidal ideation (SI) during a 16-week randomized clinical trial. Method: 129 depressed and suicidal adolescents completed PB, TB, and SI measures at three time points: baseline (T1), mid-treatment (T2), and treatment completion (T3). Random-intercept cross-lagged panel models (RI-CLPM) examined within-subject direction of effects between interpersonal variables (PB & TB) and suicidal ideation (SI) in the first and second halves of treatment. Results: Within-subjects, autoregressive paths indicated significant carryover in PB and SI. In the first half of treatment, a significant cross-lagged path indicated that T1 PB predicted change in T2 SI, and in the last half of treatment change in T2 SI predicted change in T3 PB. There were no significant auto-regressive or cross-lagged effects for TB. Conclusions: In the first half of treatment, baseline PB predicted fewer reductions in SI suggesting that PB initially moderated adolescents' response to treatment. However, in the last half of treatment, initial reductions in SI predicted subsequent reductions in PB suggesting that adolescents' initial response to treatment decreased their perceptions of burdening others. The clinical and treatment implications of these bidirectional findings are discussed. What is the public health significance of this article?: Identifying factors that predict response to treatment can help practitioners identify targets for intervening with suicidal and depressed adolescents. This study identifies perceived burdensomeness as a predictor of worse treatment response in suicidal adolescents, while also noting that reductions in suicidal ideation early in treatment predict subsequent reductions in perceived burdensomeness. [ABSTRACT FROM AUTHOR]

Objective: Although there are currently several efficacious treatments for depressed and suicidal adolescents, less is known about predictors and moderators of adolescents' treatment response. A growing literature has identified family functioning as a prognostic indicator of adolescents' likelihood of benefiting from treatment. The current study tested both observational and perceived measures of family functioning as indicators of adolescents' response to 2 treatment conditions. Method: The sample consisted of 129 depressed and suicidal adolescents (Mage = 14.96, 82.9% female, 56% Black/African American) who were randomized to attachment-based family therapy or family-enhanced nondirective supportive therapy (Diamond et al., 2019). Baseline assessments of family functioning included ratings of parent–adolescent communication coded with the Goal-Corrected Partnership in Adolescence Coding System (Lyons-Ruth, Hennighausen, & Holmes, 2005) and adolescent and parent reports of Family Conflict and Cohesion from the Self-Report of Family Functioning (Bloom, 1985). Results: Adolescents who engaged in more uncooperative communication with their parents during a 10-min conflict discussion showed greater reductions in depressive symptoms in both treatments. Adolescents from traditionally underserved (non-White or lower income) families showed greater reductions in suicidal ideation in both treatments. Conclusions: Attachment-based family therapy and family-enhanced nondirective supportive therapy were most effective for adolescents from traditionally underserved families and adolescents who engaged in less cooperative communication with their caregivers. Observational ratings of parent–adolescent communication were better prognostic indicators of treatment response than were self-reported indicators of global family functioning. Implications for generalizing these results to other treatments for depressed and suicidal adolescents are discussed. Identification of factors that predict treatment response for depressed and suicidal adolescents holds important implications for treatment planning. The current study extends prior literature by testing multiple measures of family functioning as well as demographic factors as predictors and moderators of depressed and suicidal adolescents' response to attachment-based family therapy (ABFT) and family-enhanced nondirective supportive therapy (FE-NST). ABFT and FE-NST were particularly effective in reducing depressive symptoms in adolescents who engaged in less cooperative communication with their parent at the start of treatment and in reducing suicidal ideation in non-White adolescents and adolescents from lower income families. [ABSTRACT FROM AUTHOR]

Objective: Although several treatments have been shown to be effective in treatment of youth suicidal thoughts and behaviors (STBs), there is a pressing need to account for the substantial variation in adolescents' response to and outcomes from these treatments.Method: Secondary analyses of data from a 16-week randomized trial of Attachment-Based Family Therapy (ABFT) and Family-Enhanced NonDirective Supportive Therapy (FE-NST) identified distinct classes of adolescents' treatment response. Established risk factors for STBs, along with treatment condition and sociodemographic variables, were then tested as predictors of class membership.Results: Three patterns of adolescents' treatment response and outcome were identified: a) nonresponders (15.8%), b) good responders (57.5%), and c) partial responders (26.7%). After controlling for initial symptom severity, nonresponders were more likely to have higher levels of nonsuicidal self-injury and pessimism and were more likely to meet diagnostic criteria for major depressive disorder (MDD) than good or partial responders. Partial responders were more likely than good responders to meet criteria for MDD and to have higher perceived burdensomeness.Conclusion: Although most adolescents showed significant symptom reductions with both treatments, adolescents with higher pretreatment levels of pessimism, MDD, nonsuicidal self-injury, and perceived burdensomeness were less likely to show an optimal pattern of treatment benefit. The findings point to heterogeneity in treatment response that may require adapting treatments for adolescents with these pretreatment profiles.Clinical Trial Registration Information: Attachment-Based Family Therapy for Suicidal Adolescents; http://clinicaltrials.gov; NCT01537419. [ABSTRACT FROM AUTHOR]

Objectives: Although research has identified interpersonal difficulties as risk factors for adolescent suicidality, parent and peer relationships are often assessed as discrete risk domains.Methods: The current study uses a social network approach to assess individual differences in the degree to which a clinical sample of 129 adolescents being treated for suicidal ideation rely on parents or peers for their attachment needs.Results: Youth who affiliated with deviant peers were more likely to: (a) report greater intensity (increased frequency and duration and decreased controllability) of their suicide ideation, and (b) identify peers rather than adults as attachment figures.Conclusions: Adolescents' peer relationships are associated with suicide ideation intensity in a clinical sample of suicidal and depressed adolescents. [ABSTRACT FROM AUTHOR]

Objective: Little is known about the extent to which previous weeks' stressful events spill over and influence adolescents' abilities to derive insight from treatment sessions. Even less is known about factors that moderate clients' vulnerabilities to these spillover effects. The current study examined the spillover of negative interpersonal events to postsession insight and the role of difficulties in emotion regulation in this spillover effect. Method: Participants were 129 adolescents with moderate to severe depressive symptoms and suicidal ideation (Mage = 14.96, 83% female, 56% African American/Black) participating in a comparative efficacy trial of Attachment-Based Family Therapy (ABFT) and Family- Enhanced Nondirective Supportive Therapy (FE-NST). A within-subject mediation model tested presession negative affect as a mediator of spillover of past week's events on postsession insight. We then examined baseline difficulties in emotion regulation (DERS) as a between-subjects moderator of the mediation model. Results: Negative affect partially mediated (44%) the spillover of the past week's negative events on adolescents' ratings of postsession insight (p = .03, 95% confidence interval, Cl [-.09., -.002]). Baseline DERS increased adolescents' vulnerabilities to spillover effects (p = .01,95% Cl [-.28, -.03]). Negative interpersonal events from the past week influence presession negative affect and spill over to adolescents' abilities to gain insight from their treatment sessions. Adolescents who began treatment with greater DERS were particularly vulnerable to these spillover effects. Findings indicate the need for therapists to adapt sessions to individual differences in depressed and suicidal adolescents' exposure to negative interpersonal events preceding treatment and in their vulnerabilities to spillover and emotion dysregulation. [ABSTRACT FROM AUTHOR]

Insecure attachment styles have consistently been identified as risk factors for adolescent psychopathology and, more specifically, suicidal ideation. However, much less is known about the mechanisms that account for the relationship between attachment styles and severity of suicidal ideation within clinical samples. In the current study, adolescents’ expectancies for caregiver availability and responsiveness were coded from transcripts of the Suicide Narrative Interview in a clinical sample of 129 depressed and suicidal adolescents. Results indicated that negative expectancies for caregiver availability in the Suicide Narrative Interview were associated both with attachment insecurity and with the intensity of adolescents’ suicidal ideation. The implications of adolescents’ expectancies for caregiver availability as targets for clinical intervention are discussed. [ABSTRACT FROM AUTHOR]

Eighty-five young adults exposed to a cluster of peer suicides as adolescents completed measures of attitudes toward suicide, grief, and social support. Closeness to the peers lost to suicide was positively correlated with grief and the belief that suicide is not preventable, with grief further elevated in close individuals with high social support from friends. Overall, social support was related to healthy attitudes about suicide including preventability, yet it was also related to some stigmatizing beliefs. Compared with 67 young adults who had not been exposed to a suicide cluster, the exposed sample was more likely to think that suicide is normal but more likely to think of it as incomprehensible. [ABSTRACT FROM AUTHOR]

Context: Recent studies have shown that patients' quality of life at the end of life (QOL@EOL) affects the psychosocial adjustment of bereaved family caregivers.Objectives: To examine the relationship between patients' QOL@EOL and the suicidal ideation of their surviving bereaved caregivers.Methods: Data were derived from the Coping with Cancer (CwC1) Study, a U.S. National Cancer Institute-funded multicenter prospective cohort investigation of patients with advanced cancer and their caregivers, in which patients were enrolled September 2002 to February 2008. CwC1 data were used to examine changes in suicidal ideation in family caregivers before and after the patient's death (N = 127). Caregiver baseline suicidal ideation was assessed using the Yale Evaluation of Suicidality (YES) Scale a median of 4.1 months pre-loss; caregivers' perception of patients' QOL@EOL was assessed a median of 1.9 months postloss; and caregiver suicidal ideation in bereavement was assessed using the YES a median of 6.5 months postloss. Suicidal ideation was defined as a positive screen on the YES. We used multiple logistic regression analysis to examine the effect of caregivers' perceptions of patients' QOL@EOL on the suicidal ideation of bereaved caregiver's, adjusting for the caregiver's baseline suicidal ideation and confounding influences.Results: Caregivers' perception of patients' QOL@EOL was significantly inversely related to caregivers' suicidal ideation postloss (adjusted odds ratio = 0.79, P = 0.023), after we adjusted for caregivers' baseline suicidal ideation, relationship to patient, and years of education.Conclusion: The more caregivers perceive their loved ones' QOL@EOL to be poor, the greater their risk for suicidal ideation in bereavement over and above prior levels of suicidal ideation. Caregivers of patients who have poor QOL@EOL appear to be a group of caregivers to target for reduction of suicidal risk. [ABSTRACT FROM AUTHOR]

Context Recent studies have shown that patients' quality of life at the end of life (QOL@EOL) affects the psychosocial adjustment of bereaved family caregivers. Objectives To examine the relationship between patients' QOL@EOL and the suicidal ideation of their surviving bereaved caregivers. Methods Data were derived from the Coping with Cancer (CwC1) Study, a U.S. National Cancer Institute-funded multicenter prospective cohort investigation of patients with advanced cancer and their caregivers, in which patients were enrolled September 2002 to February 2008. CwC1 data were used to examine changes in suicidal ideation in family caregivers before and after the patient's death ( N = 127). Caregiver baseline suicidal ideation was assessed using the Yale Evaluation of Suicidality (YES) Scale a median of 4.1 months pre-loss; caregivers' perception of patients' QOL@EOL was assessed a median of 1.9 months postloss; and caregiver suicidal ideation in bereavement was assessed using the YES a median of 6.5 months postloss. Suicidal ideation was defined as a positive screen on the YES. We used multiple logistic regression analysis to examine the effect of caregivers' perceptions of patients' QOL@EOL on the suicidal ideation of bereaved caregiver's, adjusting for the caregiver's baseline suicidal ideation and confounding influences. Results Caregivers' perception of patients' QOL@EOL was significantly inversely related to caregivers' suicidal ideation postloss (adjusted odds ratio = 0.79, P = 0.023), after we adjusted for caregivers' baseline suicidal ideation, relationship to patient, and years of education. Conclusion The more caregivers perceive their loved ones' QOL@EOL to be poor, the greater their risk for suicidal ideation in bereavement over and above prior levels of suicidal ideation. Caregivers of patients who have poor QOL@EOL appear to be a group of caregivers to target for reduction of suicidal risk. [ABSTRACT FROM AUTHOR]

BACKGROUND Young adults with cancer are at an increased risk of suicidal ideation. To the authors' knowledge, the impact of the patient-oncologist alliance on suicidal ideation has not been examined to date. The current study examined the relationship between the patient-oncologist therapeutic alliance and suicidal ideation in young adults with advanced cancer. METHODS A total of 93 young adult patients (aged 20 years-40 years) with incurable, recurrent, or metastatic cancer were evaluated by trained interviewers. Suicidal ideation was assessed with the Yale Evaluation of Suicidality scale, dichotomized into a positive and negative score. Predictors included diagnoses of major depressive disorder and posttraumatic stress disorder, physical quality of life, social support, and use of mental health and supportive care services. The Human Connection Scale, dichotomized into a strong (upper third) and weak (lower two-thirds) therapeutic alliance, assessed the strength of the patients' perceived oncologist alliance. RESULTS Approximately 22.6% of patients screened positive for suicidal ideation. Patients with a strong therapeutic alliance were found to be at reduced risk of suicidal ideation after controlling for confounding influences of cancer diagnosis, Karnofsky performance status, number of physical symptoms, physical quality of life, major depressive disorder, posttraumatic stress disorder, and social support. A strong therapeutic alliance was also associated with a reduced risk of suicidal ideation after controlling for mental health discussions with health care providers and use of mental health interventions. CONCLUSIONS The patient-oncologist alliance was found to be a robust predictor of suicidal ideation and provided better protection against suicidal ideation than mental health interventions, including psychotropic medications. Oncologists may significantly influence patients' mental health and may benefit from training and guidance in building strong alliances with their young adult patients. Cancer 2014;120:2272-2281. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Aims: High plantar pressure is a major risk factor in the development of diabetic foot ulcers (DFUs) and recent evidence shows plantar pressure feedback reduces DFU recurrence. This study investigated whether continued use of an intelligent insole system by patients at high-risk of DFUs causes a reduction in plantar pressures.Methods: Forty-six patients with diabetic peripheral neuropathy and previous DFU were randomised to intervention (IG) or control groups (CG). Patients received an intelligent insole system, consisting of pressure-sensing insoles and digital watch. Patients wore the device during all daily activity for 18-months or until ulceration, and integrated pressure was recorded continuously. The device provided high-pressure feedback to IG only via audio-visual-vibrational alerts. High-pressure parameters at the whole foot, forefoot and rearfoot were compared between groups, with multilevel binary logistic regression analysis.Results: CG experienced more high-pressure bouts over time than IG across all areas of the foot (P < 0.05). Differences between groups became apparent >16 weeks of wearing the device.Conclusions: Continuous plantar pressure feedback via an intelligent insole system reduces number of bouts of high-pressure in patients at high-risk of DFU. These findings suggest that patients were learning which activities generated high-pressure, and pre-emptively offloading to avoid further alerts. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To assess, in the general diabetic population, 1) the prevalence of painful neuropathic symptoms; 2) the relationship between symptoms and clinical severity of neuropathy; and 3) the role of diabetes type, sex, and ethnicity in painful neuropathy. RESEARCH DESIGN AND METHODS--Observational study of a large cohort of diabetic patients receiving community-based health care in northwest England (n = 15,692). Painful diabetic neuropathy (PDN) was assessed using neuropathy symptom score (NSS) and neuropathy disability score (NDS). RESULTS--Prevalence of painful symptoms (NSS ≥5) and PDN (NSS ≥5 and NDS ≥3) was 34 and 21%, respectively. Painful symptoms occurred in 26% of patients without neuropathy (NDS ≤2) and 60% of patients with severe neuropathy (NDS >8). Adjusted risk of painful neuropathic symptoms in type 2 diabetes was double that of type 1 diabetes (odds ratio [OR] = 2.1 [95% CI 1.7-2.4], P < 0.001) and not affected by severity of neuropathy, insulin use, foot deformities, smoking, or alcohol. Women had 50% increased adjusted risk of painful symptoms compared with men (OR= 1.5 [1.4-1.6], P < 0.0001). Despite less neuropathy in South Asians (14%) than Europeans (22%) and African Caribbeans (21%) (P < 0.0001), painful symptoms were greater in South Asians (38 vs. 34 vs. 32%, P < 0.0001). South Asians without neuropathy maintained a 50% increased risk of painful neuropathy symptoms compared with other ethnic groups (P < 0.0001). CONCLUSIONS--One-third of all community-based diabetic patients have painful neuropathy symptoms, regardless of their neuropathic deficit. PDN was more prevalent in patients with type 2 diabetes, women, and people of South Asian origin. This highlights a significant morbidity due to painful neuropathy and identifies key groups who warrant screening for PDN. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Risks of diabetes and cardiovascular disease are elevated worldwide in Indian Asians. However, risks of other diabetes-related complications, i.e., foot ulceration and amputation, also with a vascular basis, are substantially lower in Asians than in white Europeans in the U.K., possibly due to less neuropathy. We therefore compared signs, symptoms, and objective quantitative measures of diabetic neuropathy and their risk factors in Indian Asians and Europeans. RESEARCH DESIGN AND METHODS-- This was a cross-sectional study of a population-based sample of age- and sex-matched adults with type 2 diabetes of European (95 male and 85 female) and Asian (96 male and 84 female) descent in the U.K. Patients were assessed for neuropathic symptoms, signs, nerve conduction, autonomic function, and quantitative sensory testing. Peripheral vascular function and other potential risk factors for neuropathy were measured. RESULTS-- Mean nerve conduction velocity Z scores were better in Asians (mean ± SD 0.07 ± 0.62) than in Europeans (-0.11 ± 0.60; P = 0.007) and were explained by the shorter height, fewer pack-years smoked, and higher transcutaneous oxygen levels (TCpO[sub 2]) in Indian Asians (P value for ethnic comparison attenuated to 0.2). Small fiber neuropathy was less prevalent in Indian Asians compared with Europeans (odds ratio 0.58 [95% CI 0.37-0.93]; P = 0.02) and was primarily accounted for by better TCpO[sub 2] (0.70 [0.40-1.21]; P = 0.2). CONCLUSIONS -- Asians with diabetes have substantially less large and small fiber neuropathy than Europeans, despite comparable traditional risk factors. Independent from smoking, the lower risk of neuropathy in Asians is due to better skin microvascularization and may help explain the substantially reduced Asian foot ulcer risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To determine 1) foot ulcer rates for European, South-Asian, and African-Caribbean diabetic patients in the U.K. and 2) the contribution of neuropathy and peripheral arterial disease (PAD) differences to altered ulcer risk between the groups. RESEARCH DESIGN AND METHODS -- In this U.K. population-based study, we screened 15,692 type 1 and type 2 diabetic patients in the community health care setting for foot ulcers, foot deformities, neuropathy, and PAD plus other characteristics. In total, 13,409 were European (85.5%), 1,866 were South Asian (11.9%), and 371 were African Caribbean (2.4%). RESULTS -- The age-adjusted prevalence of diabetic foot ulcers (past or present) for Europeans, South Asians, and African Caribbeans was 5.5, 1.8, and 2.7%, respectively (P < 0.0001). Asians and African Caribbeans had less neuropathy, PAD, and foot deformities than Europeans (P = 0.003). The unadjusted risk of ulcer (odds ratio [OR]) for Asians versus Europeans was 0.29 (95% CI 0.20-0.41) (P < 0.0001). PAD, neuropathy, foot deformities, and insulin use attenuated the age-adjusted OR from 0.32 to 0.52 (0.35-0.76) (P < 0.0001). African-Caribbean versus European ulcer risk in males was attenuated from 0.60 to 0.71 by vibration sensation. CONCLUSIONS -- South Asians with diabetes in the U.K. have about one-third the risk of foot ulcers of Europeans. The lower levels of PAD, neuropathy, insulin usage, and foot deformities of the Asians account for approximately half of this reduced foot ulcer risk. Lower neuropathy is the main contributor to the reduced African-Caribbean ulcer rate, particularly in men. The reasons for these ethnic differences warrant further investigation. [ABSTRACT FROM AUTHOR]

Abstract: The vagus nerve forms a neuro-anatomical link between the gastrointestinal tract and the brain. A number of gastrointestinal hormones, including cholecystokinin and ghrelin, require an intact vagal–brainstem–hypothalamic pathway to affect CNS feeding circuits. We have shown that the effects of peripheral administration of both peptide YY3–36 (PYY3–36) and glucagon-like peptide-1 (GLP-1) on food intake and activation of hypothalamic arcuate feeding neurones are abolished following either bilateral sub-diaphragmatic total truncal vagotomy or brainstem–hypothalamic pathway transectioning in rodents. These findings suggest that the vagal–brainstem–hypothalamic pathway may also play a role in the effects of circulating PYY3–36 and GLP-1 on food intake. [Copyright &y& Elsevier]

Abstract: The gastrointestinal-derived hormone peptide YY (PYY) is released from intestinal L-cells post-prandially in proportion to calorie intake, and modulates food intake. Peripheral administration of PYY(3–36) reduces food intake and body weight in rodents and suppresses appetite and food intake in humans. PYY(3–36) is hypothesised to inhibit food intake via activation of the auto-inhibitory pre-synaptic neuropeptide Y (NPY) Y2 receptor (Y2R) present on arcuate (ARC) NPY neurons. We aimed to investigate the feeding effect of PYY(3–36) following blockade of ARC Y2R, using the specific receptor antagonist BIIE0246, in the rat. We found that pre-treatment with BIIE0246 (1 nmol) into the ARC attenuated the reduction in feeding observed following intraperitoneal injection of PYY(3–36) (7.5 nmol/kg) (0–1 h food intake: BIIE0246/PYY(3–36): 3.8 ± 0.4 g; vs. Vehicle/PYY(3–36): 2.7 ± 0.2 g; P &#60; 0.05). We found plasma PYY levels to be maximal at 120 min post-initiation of feeding. On investigation of the endogenous role of the Y2R, we found that ARC administration of BIIE0246 alone significantly increased feeding in satiated rats compared to vehicle-injected controls (0–1 h food intake: BIIE0246: 4.1 ± 0.7 g; vs. vehicle: 1.7 ± 0.7 g; P &#60; 0.05), suggesting that Y2R antagonism disinhibits the NPY neuron thus stimulating feeding in otherwise satiated rats. These studies suggest that the Y2R plays an important role in post-prandial satiety and provide further insight into the mechanisms of action of PYY(3–36). [Copyright &y& Elsevier]

Presents a study which assessed the efficacy of a specialist foot care program for diabetic unilateral lower-limb amputees in the United States. Etiology of a lower-limb amputation; Research design and methodology; Results and conclusions.

OBJECTIVE -- The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. RESEARCH DESIGN AND METHODS -- A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). RESULTS -- Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = - 0.475, P < 0.0001; NBD r = - 0.511, P < 0.0001; and NFL r = -0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm² with a sensitivity of 0.82 (95% CI 0.68-0.92) and specificity of 0.52 (0.40-0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm² with a sensitivity of 0.71 (0.42-0.92) and specificity of 0.64 (0.54-0.74). CONCLUSIONS -- CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. [ABSTRACT FROM AUTHOR]

AMP-activated protein kinase (AMPK) is the down- stream component of a protein kinase cascade that acts as an intracellular energy sensor maintaining the energy balance within the cell. The finding that leptin and adiponectin activate AMPK to alter metabolic pathways in muscle and liver provides direct evidence for this role in peripheral tissues. The hypothalamus is a key regulator of food intake and energy balance, coordinating body adiposity and nutritional state in response to peripheral hormones, such as leptin, peptide YY-(3-36), and ghrelin. To date the hormonal regulation of AMPK in the hypothalamus, or its potential role in the control of food intake, have not been reported. Here we demonstrate that counter-regulatory hormones involved in appetite control regulate AMPK activity and that pharmacological activation of AMPK in the hypothalamus increases food intake. In vivo administration of leptin, which leads to a reduction in food intake, decreases hypothalamic AMPK activity. By contrast, injection of ghrelin in vivo, which increases food intake, stimulates AMPK activity in the hypothalamus. Consistent with the effect of ghrelin, injection of 5-amino-4-imidazole carboxamide riboside, a pharmacological activator of AMPK, into either the third cerebral ventricle or directly into the paraventricular nucleus of the hypothalamus significantly increased food intake. These results suggest that AMPK is regulated in the hypothalamus by hormones which regulate food intake. Furthermore, direct pharmacological activation of AMPK in the hypothalamus is sufficient to increase food intake. These findings demonstrate that AMPK plays a role in the regulation of feeding and identify AMPK as a novel target for anti-obesity drugs. [ABSTRACT FROM AUTHOR]

Intracerebroventricular (ICV) injection of Agouti related protein (AgRP), an endogenous melanocortin 3 and 4 receptor (MC3/4-R) antagonist, produces a prolonged increase in food intake. To clarify the roles of the MC3-R and MC4-R in AgRP-induced hyperphagia, the feeding effect of AgRP (83–132) was compared with that of the selective MC4-R antagonist, JKC-363 (cyclic [Mpr11, D-Nal14, Cys18, Asp22-NH2]-beta-MSH11-22). Single ICV administration of AgRP (83–132) increased food intake for 48 h whilst ICV JKC-363 increased food intake for 8 h. An increase in body weight at 24 and 48 h was observed following AgRP (83–132) but not JKC-363 treatment. These data suggest that the sustained orexigenic action of AgRP (83–132) may not be through MC4-R antagonism. [Copyright &y& Elsevier]

Ghrelin, a circulating growth hormone-releasing peptide derived from the stomach, stimulates food intake. The lowest systemically effective orexigenic dose of ghrelin was investigated and the resulting plasma ghrelin concentration was compared with that during fasting. The lowest dose of ghrelin that produced a significant stimulation of feeding after intraperitoneal injection was 1 nmol. The plasma ghrelin concentration after intraperitoneal injection of 1 nmol of ghrelin (2.83 +/- 0.13 pmol/ml at 60 min postinjection) was not significantly different from that occurring after a 24-h fast (2.79 +/- 0.32 pmol/ml). After microinjection into defined hypothalamic sites, ghrelin (30 pmol) stimulated food intake most markedly in the arcuate nucleus (Arc) (0-1 h food intake, 427 +/- 43% of control; P < 0.001 vs. control, P < 0.01 vs. all other nuclei), which is potentially accessible to the circulation. After chronic systemic or intracerebroventricular (ICV) administration of ghrelin for 7 days, cumulative food intake was increased (intraperitoneal ghrelin 13.6 +/- 3.4 g greater than saline-treated, P < 0.01; ICV ghrelin 19.6 +/- 5.5 g greater than saline-treated, P < 0.05). This was associated with excess weight gain (intraperitoneal ghrelin 21.7 +/- 1.4 g vs. saline 10.6 +/- 1.9 g, P < 0.001; ICV ghrelin 15.3 +/- 4.3 g vs. saline 2.2 +/- 3.8 g, P < 0.05) and adiposity. These data provide evidence that ghrelin is important in long-term control of food intake and body weight and that circulating ghrelin at fasting concentrations may stimulate food intake. [ABSTRACT FROM AUTHOR]

Investigates the effect of angiotensin-converting enzyme (ACE) inhibition on diabetic neuropathy. Data on peroneal motor nerve conduction velocity, vibration-perception threshold, and autonomic function; The ability of ACE inhibitor trandolapril to improve peripheral neuropathy in normotensive patients.

Objective: This study examined proposed sequential pathways through which suicidal adolescents are thought to shift from secondary global distress and rejecting anger to primary adaptive hurt, grief and assertive anger in the context of attachment-based family therapy (ABFT). Method: Participants were 39 suicidal adolescents who had received 16 weeks of ABFT as part of a randomized clinical trial, and who had been assigned to one of three outcome groups (i.e., good responders, slow responders and non-responders). Adolescents' in-session emotions were observationally coded using the Classification of Affective-Meaning States. Results: Across outcome groups, adolescents evidenced shifts from global distress to maladaptive shame, from maladaptive rejecting anger to adaptive assertive anger, and from adaptive assertive anger to adaptive grief/hurt. Adolescents who did not respond to treatment evidenced higher rates of maladaptive global distress. Conclusions: Findings are discussed in the context of ABFT and sequential emotional processing theories. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic utility of corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for corneal nerve loss.Research Design and Methods: A total of 490 participants, including 72 healthy control subjects, 149 with type 1 diabetes, and 269 with type 2 diabetes, underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors.Results: Corneal nerve fiber density (CNFD) (P < 0.0001 and P < 0.0001), corneal nerve fiber branch density (CNBD) (P < 0.0001 and P < 0.0001), and corneal nerve fiber length (CNFL) (P < 0.0001 and P = 0.02) were significantly lower in patients with type 1 and type 2 diabetes compared with control subjects. CNFD (P < 0.0001), CNBD (P < 0.0001), and CNFL (P < 0.0001) were lower in type 1 diabetes compared with type 2 diabetes. Receiver operating characteristic curve analysis for the diagnosis of DPN demonstrated a good area under the curve for CNFD of 0.81, CNBD of 0.74, and CNFL of 0.73. Multivariable regression analysis showed a significant association among reduced CNFL with age (β = -0.27, P = 0.007), HbA1c (β = -1.1; P = 0.01), and weight (β = -0.14; P = 0.03) in patients with type 2 diabetes and with duration of diabetes (β = -0.13; P = 0.02), LDL cholesterol (β = 1.8, P = 0.04), and triglycerides (β = -2.87; P = 0.009) in patients with type 1 diabetes.Conclusions: CCM identifies more severe corneal nerve loss in patients with type 1 diabetes compared with type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in corneal nerve fiber length differ between type 1 and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: Diabetes guidelines recommend screening for the risk of foot ulceration but vary substantially in the underlying evidence base. Our purpose was to derive and validate a prognostic model of independent risk factors for foot ulceration in diabetes using all available individual patient data from cohort studies conducted worldwide. Methods: We conducted a systematic review and meta‐analysis of individual patient data from 10 cohort studies of risk factors in the prediction of foot ulceration in diabetes. Predictors were selected for plausibility, availability and low heterogeneity. Logistic regression produced adjusted odds ratios (ORs) for foot ulceration by ulceration history, monofilament insensitivity, any absent pedal pulse, age, sex and diabetes duration. Results: The 10 studies contained data from 16 385 participants. A history of foot ulceration produced the largest OR [6.59 (95% CI 2.49 to 17.45)], insensitivity to a 10 g monofilament [3.18 (95% CI 2.65 to 3.82)] and any absent pedal pulse [1.97 (95% CI 1.62 to 2.39)] were consistently, independently predictive. Combining three predictors produced sensitivities between 90.0% (95% CI 69.9% to 97.2%) and 95.3% (95% CI 84.5% to 98.7%); the corresponding specificities were between 12.1% (95% CI 8.2% to 17.3%) and 63.9% (95% CI 61.1% to 66.6%). Conclusions: This prognostic model of only three risk factors, a history of foot ulceration, an inability to feel a 10 g monofilament and the absence of any pedal pulse, compares favourably with more complex approaches to foot risk assessment recommended in clinical diabetes guidelines. What's new?: Cohort studies to identify risk factors for foot ulceration in people with diabetes have been published in the biomedical literature since the early 1990s.We assembled an international data set of risk factors collected from 16 385 individuals with diabetes who took part in cohort studies to derive and validate a prognostic model of three risk factors: a history of foot ulceration, an inability to feel a 10 g monofilament and at least one absent pedal pulse.The use of only these three risk factors in foot risk assessments during annual diabetes foot checks could reduce the amount of time spent assessing risk and thereby increase the number of people with diabetes who have checks performed.The frequency of risk assessment should be considered in future research. [ABSTRACT FROM AUTHOR]

Objective: Patients often anticipate cure from palliative chemotherapy. Better resources are needed to convey its risks and benefits. We describe the stakeholder-driven development and acceptability testing of a prototype video and companion booklet supporting informed consent (IC) for a common palliative chemotherapy regimen.Methods: Our multidisciplinary team (researchers, advocates, clinicians) employed a multistep process of content development, production, critical evaluation, and iterative revisions. Patient/clinician stakeholders were engaged throughout using stakeholder advisory panels, featuring their voices within the intervention, conducting surveys and qualitative interviews. A national panel of 57 patient advocates, and 25 oncologists from nine US practices critiqued the intervention and rated its clarity, accuracy, balance, tone, and utility. Participants also reported satisfaction with existing chemotherapy IC materials.Results: Few oncologists (5/25, 20%) or advocates (10/22, 45%) were satisfied with existing IC materials. In contrast, most rated our intervention highly, with 89-96% agreeing it would be useful and promote informed decisions. Patient voices were considered a key strength. Every oncologist indicated they would use the intervention regularly.Conclusion: Our intervention was acceptable to advocates and oncologists. A randomized trial is evaluating its impact on the chemotherapy IC process.Practice Implications: Stakeholder-driven methods can be valuable for developing patient educational interventions. [ABSTRACT FROM AUTHOR]

The Goal-Corrected Partnership Adolescent Coding System (GPACS) has shown promise in assessing a secure as well as three atypical patterns of parent–adolescent interaction during a conflict discussion. The current study of 186 economically disadvantaged families examines the degree to which four GPACS patterns: secure/collaborative, hostile/punitive, role confused, and disoriented, prospectively predict adolescents’ social competence and maladaptive behavior (internalizing, externalizing, and risk behaviors) at age 15 years after controlling for these social behaviors at age 13 years and contemporaneous GPACS scores. Adolescents from secure/collaborative dyads at age 13 were more likely to have a secure state of mind in the Adult Attachment Interview at age 15 and showed higher levels of teachers’ ratings of empathy and lower levels of teachers’ ratings of externalizing behaviors at age 15 years. Adolescents in disoriented dyads showed higher levels of teacher-rated internalizing problems, while male adolescents in role confused dyads reported higher levels of involvement in risk behaviors, including unprotected sexual activity and substance use problems. [ABSTRACT FROM PUBLISHER]

Abstract: There is a tendency worldwide for the automation of farms; this has included the introduction of automatic milking systems (AMS) in the dairy industry. Lameness in dairy cows is highly prevalent and painful. These impacts potentially affect not only animal welfare, but also farm economies. Three independent observational studies were carried out to assess the impact of lameness on the behaviour of zero grazed high yielding Holstein cows managed in an AMS. The aim of the first study was to examine the impact of lameness on rumination time, the second study investigated differences between lame and sound dairy cows in total eating time and the third study assessed the impact of lameness on milking behaviour (frequency and time of visits to the AMS). In the first study data from 150 cows were used to analyse rumination (collected using rumination collars) for the 48h following locomotion scoring. A multilevel linear regression demonstrated that lameness had a small but significant negative association (coefficient: −7.88 (SE: 3.93)) with rumination. In the second study the behaviour of eleven matched lame and sound pairs of cows at the feed face was analysed for 24h after locomotion scoring. Each feeding behaviour variable (total duration time, frequency of feeding bouts and length of bouts) was analysed using individual single level regression models. There was a significant negative association between total feeding time and lameness (coefficient: −73.65 (SE: 25.47)) and the frequency of feeding bouts and lameness (−9.93 (2.49)). Finally, the third observational study used 38 matched pairs of lame and sound cows. Data on the number and timings of visits to the AMS were collected for 24h after each locomotion score and analysed using a binomial logistic regression model. There was a significant difference in AMS visits between groups; lame animals visiting the robot less frequently than sound cows (median difference 0.50 milking visits; T =256.0; N =25; p =0.01) and lame cows were 0.33 times less likely to visit the AMS between 24:01 and 06:00. Results from these studies reveal that lameness in an AMS affected feeding behaviour, rumination and AMS visits. All of these impacts are likely to have negative consequences for farm profitability, but also implications for the health and welfare of the animals. [Copyright &y& Elsevier]

Background: Diabetes-related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a metaanalysis based on individual patient data (IPD). There are however many challenges and fundamental methodological omissions are common; protocols are rare and the assessment of the risk of bias arising from the conduct of individual studies is frequently not performed, largely because of the absence of widely agreed criteria for assessing the risk of bias in this type of review. In this protocol we propose key methodological approaches to underpin our IPD systematic review of prognostic factors of foot ulceration in diabetes. Review questions; 1.What are the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes? 2.Can the data from each study be adjusted for a consistent set of adjustment factors? 3.Does the model accuracy change when patient populations are stratified according to demographic and/or clinical characteristics? Methods: MEDLINE and EMBASE databases from their inception until early 2012 were searched and the corresponding authors of all eligible primary studies invited to contribute their raw data. We developed relevant quality assurance items likely to identify occasions when study validity may have been compromised from several sources. A confidentiality agreement, arrangements for communication and reporting as well as ethical and governance considerations are explained. We have agreement from the corresponding authors of all studies which meet the eligibility criteria and they collectively possess data from more than 17000 patients. We propose, as a provisional analysis plan, to use a multilevel mixed model, using "study" as one of the levels. Such a model can also allow for the within-patient clustering that occurs if a patient contributes data from both feet, although to aid interpretation, we prefer to use patients rather than feet as the unit of analysis. We intend to only attempt this analysis if the results of the investigation of heterogeneity do not rule it out and the model diagnostics are acceptable. Discussion: This review is central to the development of a global evidence-based strategy for the risk assessment of the foot in patients with diabetes, ensuring future recommendations are valid and can reliably inform international clinical guidelines. [ABSTRACT FROM AUTHOR]

Objective: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies.Research Design and Methods: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM).Results: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = -0.475, P < 0.0001; NBD r = -0.511, P < 0.0001; and NFL r = -0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm(2) with a sensitivity of 0.82 (95% CI 0.68-0.92) and specificity of 0.52 (0.40-0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm(2) with a sensitivity of 0.71 (0.42-0.92) and specificity of 0.64 (0.54-0.74).Conclusions: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. [ABSTRACT FROM AUTHOR]

Objective: To determine 1) foot ulcer rates for European, South-Asian, and African-Caribbean diabetic patients in the U.K and 2) the contribution of neuropathy and peripheral arterial disease (PAD) differences to altered ulcer risk between the groups.Research Design and Methods: In this U.K. population-based study, we screened 15,692 type 1 and type 2 diabetic patients in the community health care setting for foot ulcers, foot deformities, neuropathy, and PAD plus other characteristics. In total, 13,409 were European (85.5%), 1,866 were South Asian (11.9%), and 371 were African Caribbean (2.4%).Results: The age-adjusted prevalence of diabetic foot ulcers (past or present) for Europeans, South Asians, and African Caribbeans was 5.5, 1.8, and 2.7%, respectively (P < 0.0001). Asians and African Caribbeans had less neuropathy, PAD, and foot deformities than Europeans (P = 0.003). The unadjusted risk of ulcer (odds ratio [OR]) for Asians versus Europeans was 0.29 (95% CI 0.20-0.41) (P < 0.0001). PAD, neuropathy, foot deformities, and insulin use attenuated the age-adjusted OR from 0.32 to 0.52 (0.35-0.76) (P < 0.0001). African-Caribbean versus European ulcer risk in males was attenuated from 0.60 to 0.71 by vibration sensation.Conclusions: South Asians with diabetes in the U.K. have about one-third the risk of foot ulcers of Europeans. The lower levels of PAD, neuropathy, insulin usage, and foot deformities of the Asians account for approximately half of this reduced foot ulcer risk. Lower neuropathy is the main contributor to the reduced African-Caribbean ulcer rate, particularly in men. The reasons for these ethnic differences warrant further investigation. [ABSTRACT FROM AUTHOR]

Intracerebroventricular (ICV) administration of Neuromedin U (NMU), a hypothalamic neuropeptide, or leptin, an adipostat hormone released from adipose tissue, reduces food intake and increases energy expenditure. Leptin stimulates the release of NMU in vitro, and NMU expression is reduced in models of low or absent leptin. We investigated the role of NMU in mediating leptin-induced satiety. ICV administration of anti-NMU immunoglobulin G (IgG) (5 nmol) to satiated rats significantly increased food intake 4 h after injection, an effect seen for ≤8 h after injection. ICV administration of NMU (1 nmol) to fasted rats reduced food intake 1 h after injection compared with control, an effect attenuated by pretreatment with anti-NMU IgG. ICV administration of leptin (0.625 nmol) reduced 24-h food intake. This was partially attenuated by the administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 22.5 ± 2.0 g; leptin, 13.7 ± 2.3 g (P < 0.005 vs. vehicle), leptin/NMU IgG, 19.4 ± 1.3 g (P < 0.05 vs. leptin)]. Intraperitoneal administration of leptin (1.1 mg/kg body wt) reduced 24-h food intake. This was partially attenuated by ICV administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 31.4 ± 4.9 g; leptin, 20.8 ± 2.6 g (P < 0.01 vs. vehicle); leptin/NMU IgG, 28.7 ± 1.1 g (P < 0.01 vs. leptin)]. These results suggest that NMU plays a physiological role in the regulation of appetite and partially mediates the leptin-induced satiety. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have demonstrated that AMP-activated protein kinase (AMPK) in the hypothalamus is involved in the regulation of food intake. Because exercise is known to influence appetite and cause substrate depletion, it may also influence AMPK in the hypothalamus. Male rats that either rested or ran for 30 or 60min on a treadmill (22m/min, 10% slope) were sacrificed immediately after exercise or after 60min recovery either in the fasted state or after oral gavage with glucose (3g/kg body weight). Exercise decreased muscle and liver glycogen substantially. Hypothalamic total or α2-associated AMPK activity and phosphorylation state of the AMPK substrate acetyl-CoA carboxylase were not changed significantly immediately following treadmill running or during fed or fasted recovery. Plasma ghrelin increased (P<0.05) by 40% during exercise whereas the concentration of PYY was unchanged. In recovery, glucose feeding increased plasma glucose and insulin concentrations whereas ghrelin and PYY decreased to (ghrelin) or below (PPY) resting levels. It is concluded that 1h of strenuous exercise in rats does not elicit significant changes in hypothalamic AMPK activity despite an increase in plasma ghrelin. Thus, changes in energy metabolism during or after exercise are likely not coordinated by changes in hypothalamic AMPK activity. [Copyright &y& Elsevier]

Objective: This study examined motor nerve conduction velocity (MNCV) and other peripheral nerve and vascular tests as predictors for foot ulceration, amputation, and mortality in diabetes over a 6-year follow-up period.Research Design and Methods: We recruited 169 diabetic subjects (without significant peripheral vascular disease with an ankle brachial pressure index [ABPI] >/=0.75) for the study and separated them into groups (to ensure diversity of nerve function). The control group consisted of 22 nondiabetic people. At baseline, all subjects underwent assessment of MNCV; vibration, pressure, and temperature perception thresholds; peripheral vascular function; and other diabetes assessments.Results: Over the 6-year outcome period, 37.3% of the diabetic subjects developed at least one new ulcer, 11.2% had a lower-limb amputation (LLA) (minor or major), and 18.3% died. Using multivariate Cox's regression analysis (RR [95% CI] and removing previous ulcers as a confounding variable, MNCV was found to be the best predictor of new ulceration (0.90 [0.84-0.96], P = 0.001) and the best predictors of amputation were pressure perception threshold (PPT) (5.18 [1.96-13.68], P = 0.001) and medial arterial calcification (2.88 [1.13-7.35], P = 0.027). Creatinine (1.01 [1.00-1.01], P < 0.001), MNCV (0.84 [0.73-0.97], P = 0.016), and skin oxygen levels (14.32 [3.04-67.52], P = 0.001) were the best predictors of mortality.Conclusions: This study shows that MNCV, which is often assessed in clinical trials of neuropathy, can predict foot ulceration and death in diabetes. In addition, tests of PPT and medial arterial calcification can be used in the clinic to predict LLA in diabetic subjects. [ABSTRACT FROM AUTHOR]

Provides information on the characterization of the role of arcuate nucleus (ARC) cocaine and amphetamine-regulated transcript (CART) in the long-term regulation of food intake and brown adipose tissue. Way in which the role played by ARC CART was characterized; Result that occurred from repeated intra-arcuate CART peptide injections; Use of targeted gene transfer.

Background: Diabetes-related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a meta-analysis based on individual patient data (IPD).There are however many challenges and fundamental methodological omissions are common; protocols are rare and the assessment of the risk of bias arising from the conduct of individual studies is frequently not performed, largely because of the absence of widely agreed criteria for assessing the risk of bias in this type of review. In this protocol we propose key methodological approaches to underpin our IPD systematic review of prognostic factors of foot ulceration in diabetes.Review questions;1. What are the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes?2. Can the data from each study be adjusted for a consistent set of adjustment factors?3. Does the model accuracy change when patient populations are stratified according to demographic and/or clinical characteristics?Methods: MEDLINE and EMBASE databases from their inception until early 2012 were searched and the corresponding authors of all eligible primary studies invited to contribute their raw data. We developed relevant quality assurance items likely to identify occasions when study validity may have been compromised from several sources. A confidentiality agreement, arrangements for communication and reporting as well as ethical and governance considerations are explained.We have agreement from the corresponding authors of all studies which meet the eligibility criteria and they collectively possess data from more than 17000 patients. We propose, as a provisional analysis plan, to use a multi-level mixed model, using "study" as one of the levels. Such a model can also allow for the within-patient clustering that occurs if a patient contributes data from both feet, although to aid interpretation, we prefer to use patients rather than feet as the unit of analysis. We intend to only attempt this analysis if the results of the investigation of heterogeneity do not rule it out and the model diagnostics are acceptable.Discussion: This review is central to the development of a global evidence-based strategy for the risk assessment of the foot in patients with diabetes, ensuring future recommendations are valid and can reliably inform international clinical guidelines. [ABSTRACT FROM AUTHOR]