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Body size has a long history of study in paleobiology and underlies many important phenomena in macroevolution. Body-size patterns in the fossil record are often examined by utilizing size data alone, which hinders our ability to describe the biological meaning behind size change on macroevolutionary timescales. Without data reflecting the biological and geologic factors that drive size change, we cannot assess its mechanistic underpinnings. Existing frameworks for studying ontogeny and phylogeny can remedy this problem, particularly the classic age–size–"shape" space originally developed for studies of heterochrony. When evaluated based on metrics for age, size, and phenotype in populations, proposed mechanisms for size change can be outlined theoretically and tested empirically in the record. Using this framework, we can compare ontogenetic trajectories within and between species and determine how changes in size emerge. Here, we outline ontogenetic mechanisms for evolutionary size change, such as heterochrony, as well as how geologic factors can drive apparent, non-biological size change (e.g., taphonomic size sorting). To demonstrate the utility of this framework in actual paleobiological problems, we apply it to the Lilliput effect, a compelling and widely documented pattern of size decrease during extinction events. However, little is known about the mechanisms underlying this pattern. We provide a brief history of the Lilliput effect and refine its definition in a framework that can be mechanistically tested. Processes that likely produce Lilliput effects include allometric and sequence repatterning (including heterochrony) and evolutionary size-selective sorting. We describe these mechanisms and highlight relevant examples of the Lilliput effect for which feasible empirical tests are possible. [ABSTRACT FROM AUTHOR]

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: 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]

The predominant risk factor of diabetic foot ulcers (DFU), peripheral neuropathy, results in loss of protective sensation and is associated with abnormally high plantar pressures. DFU prevention strategies strive to reduce these high plantar pressures. Nevertheless, several constraints should be acknowledged regarding the research supporting the link between plantar pressure and DFUs, which may explain the low prediction ability reported in prospective studies. The majority of studies assess vertical, rather than shear, barefoot plantar pressure in laboratory-based environments, rather than during daily activity. Few studies investigated previous DFU location-specific pressure. Previous studies focus predominantly on walking, although studies monitoring activity suggest that more time is spent on other weight-bearing activities, where a lower "peak" plantar pressure might be applied over a longer duration. Although further research is needed, this may indicate that an expression of cumulative pressure applied over time could be a more relevant parameter than peak pressure. Studies indicated that providing pressure feedback might reduce plantar pressures, with an emerging potential use of smart technology, however, further research is required. Further pressure analyses, across all weight-bearing activities, referring to location-specific pressures are required to improve our understanding of pressures resulting in DFUs and improve effectiveness of interventions. [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]

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]

Background: Low foot ulcer risk in South Asian, compared with European, people with type 2 diabetes in the UK has been attributed to their lower levels of neuropathy. We have undertaken a detailed study of corneal nerve morphology and neuropathy risk factors, to establish the basis of preserved small nerve fibre function in South Asians versus Europeans.Methods: In a cross-sectional, population-based study, age- and sex-matched South Asians (n = 77) and Europeans (n = 78) with type 2 diabetes underwent neuropathy assessment using corneal confocal microscopy, symptoms, signs, quantitative sensory testing, electrophysiology and autonomic function testing. Multivariable linear regression analyses determined factors accounting for ethnic differences in small fibre damage.Results: Corneal nerve fibre length (22.0 ± 7.9 vs. 19.3 ± 6.3 mm/mm2 ; P = 0.037), corneal nerve branch density (geometric mean (range): 60.0 (4.7-246.2) vs. 46.0 (3.1-129.2) no./mm2 ; P = 0.021) and heart rate variability (geometric mean (range): 7.9 (1.4-27.7) vs. 6.5 (1.5-22.0); P = 0.044), were significantly higher in South Asians vs. Europeans. All other neuropathy measures did not differ, except for better sural nerve amplitude in South Asians (geometric mean (range): 10.0 (1.3-43.0) vs. 7.2 (1.0-30.0); P = 0.006). Variables with the greatest impact on attenuating the P value for age- and HbA1C -adjusted ethnic difference in corneal nerve fibre length (P = 0.032) were pack-years smoked (P = 0.13), BMI (P = 0.062) and triglyceride levels (P = 0.062).Conclusions: South Asians have better preserved small nerve fibre integrity than equivalent Europeans; furthermore, classic, modifiable risk factors for coronary heart disease are the main contributors to these ethnic differences. We suggest that improved autonomic neurogenic control of cutaneous blood flow in Asians may contribute to their protection against foot ulcers. [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]

High plantar pressure as a result of diabetic peripheral neuropathy is often reported as a major risk factor for ulceration. However, previous studies are confined to laboratories with equipment limited by cables, reducing the validity of measurements to daily life. The participant concerned in this case report was wearing an innovative plantar pressure feedback system as part of a wider study. The system allows for continuous plantar pressure monitoring and provides feedback throughout all activities of daily living. The participant concerned was a 59-year-old male with type 2 diabetes who presented with severe peripheral neuropathy. In addition, the right ankle had previously undergone fusion. Between monthly study appointments, the participant unknowingly had a screw embedded in his right shoe, while pressure was being recorded. Although no significant differences in pressure were present for the right foot with the embedded screw, the contralateral foot showed significantly higher pressure when the screw was embedded, compared with pre and post time periods. The increase in pressure on the contralateral foot is expected to result from the protrusion of the screw in the right shoe, causing a perturbation to balance and a shift in the center of pressure toward the contralateral side. This compensatory effect is likely to have been magnified by the limited mobility of the fused right ankle. These findings highlight the importance of checking both feet for ulcer risk, in the event of receiving high-pressure feedback. This innovative technology may improve our understanding of diabetic plantar foot ulcer development. [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]

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]

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: 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/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]

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: 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]

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]

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]

Background and Objectives: Barefoot peak plantar pressures (PPPs) are elevated in diabetes patients with neuropathic foot ulcer (DFU) history; however, there is limited reported evidence for a causative link between high barefoot PPP and DFU risk. We aimed to determine, using a simple mat-based methodology, the site-specific, barefoot PPP critical threshold that will identify a plantar site with a previous DFU. Materials and Methods: In a cross-sectional study, barefoot, site-specific PPPs were measured with normal gait for patients with DFU history (n = 21) and healthy controls (n = 12), using a validated carbon footprint system. For each participant, PPP was recorded at twelve distinct plantar sites (1st–5th toes, 1st–5th metatarsal heads (MTHs), midfoot and heel), per right and left foot, resulting in the analysis of n = 504 distinct plantar sites in the diabetes group, and n = 288 sites in the control group. Receiver operator characteristic curve analysis determined the optimal critical threshold for sites with DFU history. Results: Median PPPs for the groups were: diabetes sites with DFU history (n = 32) = 5.0 (3.25–7.5) kg/cm2, diabetes sites without DFU history (n = 472) = 3.25 (2.0–5.0) kg/cm2, control sites (n = 288) = 2.0 (2.0–3.25) kg/cm2; (p < 0.0001). Diabetes sites with elevated PPP (>6 kg/cm2) were six times more likely to have had DFU than diabetes sites with PPP ≤ 6 kg/cm2 (OR = 6.4 (2.8–14.6, 95% CI), p < 0.0001). PPP > 4.1 kg/cm2 was determined as the optimal critical threshold for identifying DFU at a specific plantar site, with sensitivity/specificity = 100%/79% at midfoot; 80%/65% at 5th metatarsal head; 73%/62% at combined midfoot/metatarsal head areas. Conclusions: We have demonstrated, for the first time, a strong, site-specific relationship between elevated barefoot PPP and previous DFU. We have determined a critical, highly-sensitive, barefoot PPP threshold value of >4.1 kg/cm2, which may be easily used to identify sites of previous DFU occurrence and, therefore, increased risk of re-ulceration. This site-specific approach may have implications for how high PPPs should be investigated in future trials. [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.