A series of fifty cases involving reconstruction of the maxilla to normal contour, comfort, health, function and esthetics is retrospectively analyzed using 25 years of follow-up data.
Midlife risk factors such as type 2 diabetes mellitus (T2DM) confer a significantly increased risk of cognitive impairment in later life with executive function, memory, and attention domains often ...affected first. Spatiotemporal gait characteristics are emerging as important integrative biomarkers of neurocognitive function and of later dementia risk. We examined 24 spatiotemporal gait parameters across five domains of gait previously linked to cognitive function on usual-pace, maximal-pace, and cognitive dual-task gait conditions in 102 middle-aged adults with (57.5 ± 8.0 years; 40% female) and without (57.0 ± 8.3 years; 62.1% female) T2DM. Neurocognitive function was measured using a neuropsychological assessment battery. T2DM was associated with significant changes in gait phases and rhythm domains at usual pace, and greater gait variability observed during maximal pace and dual tasks. In the overall cohort, both the gait pace and rhythm domains were associated with memory and executive function during usual pace. At maximal pace, gait pace parameters were associated with reaction time and delayed memory. During the cognitive dual task, associations between gait variability and both delayed memory/executive function were observed. Associations persisted following covariate adjustment and did not differ by T2DM status. Principal components analysis identified a consistent association of slower gait pace (step/stride length) and increased gait variability during maximal-pace walking with poorer memory and executive function performance. These data support the use of spatiotemporal gait as an integrative biomarker of neurocognitive function in otherwise healthy middle-aged individuals and reveal discrete associations between both differing gait tasks and gait domains with domain-specific neuropsychological performance. Employing both maximal-pace and dual-task paradigms may be important in cognitively unimpaired populations with risk factors for later cognitive decline—with the aim of identifying individuals who may benefit from potential preventative interventions.
Type 2 Diabetes Mellitus (T2DM) in midlife is associated with a greater risk of dementia in later life. Both gait speed and spatiotemporal gait characteristics have been associated with later ...cognitive decline in community-dwelling older adults. Thus, the assessment of gait characteristics in uncomplicated midlife T2DM may be important in selecting-out those with T2DM at greatest risk of later cognitive decline. We assessed the relationship between Inertial Motion Unit (IMUs)-derived gait characteristics and cognitive function assessed via Montreal Cognitive Assessment (MoCA)/detailed neuropsychological assessment battery (CANTAB) in middle-aged adults with and without uncomplicated T2DM using both multivariate linear regression and a neural network approach. Gait was assessed under (i) normal walking, (ii) fast (maximal) walking and (iii) cognitive dual-task walking (reciting alternate letters of the alphabet) conditions. Overall, 138 individuals were recruited (n = 94 with T2DM; 53% female, 52.8 ± 8.3 years; n = 44 healthy controls, 43% female, 51.9 ± 8.1 years). Midlife T2DM was associated with significantly slower gait velocity on both slow and fast walks (both p < 0.01) in addition to a longer stride time and greater gait complexity during normal walk (both p < 0.05). Findings persisted following covariate adjustment. In analyzing cognitive performance, the strongest association was observed between gait velocity and global cognitive function (MoCA). Significant associations were also observed between immediate/delayed memory performance and gait velocity. Analysis using a neural network approach did not outperform multivariate linear regression in predicting cognitive function (MoCA) from gait velocity. Our study demonstrates the impact of uncomplicated T2DM on gait speed and gait characteristics in midlife, in addition to the striking relationship between gait characteristics and global cognitive function/memory performance in midlife. Further studies are needed to evaluate the longitudinal relationship between midlife gait characteristics and later cognitive decline, which may aid in selecting-out those with T2DM at greatest-risk for preventative interventions.
Midlife Type 2 Diabetes Mellitus (T2DM) is associated with an increased risk of Alzheimer Disease (AD) in later life, with altered inflammatory responses postulated as key pathological drivers. ...Previous studies have demonstrated increased responsiveness to NLR family pyrin domain containing 3 (NLRP3) inflammasome agonists, both in individuals with untreated T2DM in addition to those with established AD. We hypothesised that peripheral NLRP3 inflammasome responses may be altered during the early stages of T2DM-related cognitive dysfunction. Here, we assessed the relationship between NLPR3 responses in peripheral blood mononuclear cells (including to Aβ-42, the putative pathogenic protein in AD) and neuropsychological performance in uncomplicated midlife T2DM to identify early signatures of immune dysregulation which may predispose to later cognitive decline. We recruited a cross-sectional cohort of middle-aged adults with uncomplicated T2DM and matched Healthy Controls (HCs) for comprehensive neuropsychological assessment and
in vitro
PBMC responses to a range of NLRP3 agonists were assessed. T2DM was associated with subtle decrements on neuropsychological tests of delayed memory and executive function (both p<0.05). Overall, there were no differences between T2DM and HCs in immune responses induced by NLRP3 agonists. Further, we observed no relationship between the subtle neuropsychological decrements observed in T2DM and PBMC responsiveness to NLRP3 agonists. Our data suggests that peripheral NLRP3 inflammasome response dysregulation may not play a role in the early stages of cognitive dysfunction in midlife T2DM. Further longitudinal studies are warranted to examine the contribution of peripheral NLRP3 responses towards disease pathology and as cognitive decline accelerates in T2DM.
Context: Declarative memory largely depends upon normal functioning temporal lobes (hippocampal complex) and prefrontal cortex. Animal studies suggest abnormal hippocampal function in hypothyroidism.
...Objective: The aim of the study was to assess declarative memory in overt and subclinical (SCH) hypothyroid patients before and after l-T4 (LT4) replacement and in matched normal subjects.
Design and Setting: A prospective, open-labeled interventional study was conducted at a teaching hospital.
Participants and Intervention: Hypothyroid (n = 21) and SCH (n = 17) patients underwent neuropsychological tests at baseline and 3 and 6 months after LT4 replacement. Normal subjects were studied at the same time-points.
Main Outcome: Tests of spatial, verbal, associative, and working memory; attention; and response inhibition and the Hospital Anxiety and Depression Scale were administered.
Results: Baseline deficits in spatial, associative, and verbal memory, which rely upon the integrity of the hippocampal and frontal areas, were identified in patients with overt hypothyroidism. Spatial and verbal memory were impaired in SCH patients (P < 0.05). TSH levels correlated negatively (P < 0.05) with these deficits. After LT4 replacement, verbal memory normalized. Spatial memory normalized in the SCH group but remained impaired in the hypothyroid group. Associative memory deficits persisted in the overt hypothyroid group. Hospital Anxiety and Depression Scale scores did not correlate with cognitive function. Measures of attention and response inhibition did not differ from control subjects.
Conclusion: Cognitive impairment occurs in SCH and more markedly in overt hypothyroidism. These impairments appear predominantly mnemonic in nature, suggesting that the etiology is not indicative of general cognitive slowing. We propose that these deficits may reflect an underlying disruption of normal hippocampal function and/or connectivity.
Memory deficits in subclinical and overt hypothyroidism are indicative of an underlying hippocampal deficit, although the exact underlying neuronal deficits will require further elucidation.
The syndrome of adult GH deficiency and the effects of GH replacement therapy provide a useful model with which to study the effects of the GH/IGF-I axis on exercise physiology. Measures of exercise ...performance including maximal oxygen uptake and ventilatory threshold are impaired in adult GH deficiency and improved by GH replacement, probably through some combination of increased oxygen delivery to exercising muscle, increased fatty acid availability with glycogen sparing, increased muscle strength, improved body composition, and improved thermoregulation. In normal subjects, in addition to the long-term effects of GH/IGF-I status, there is evidence that the acute GH response to exercise is important in regulating substrate metabolism after exercise. Administration of supraphysiological doses of GH to athletes increases fatty acid availability and reduces oxidative protein loss, particularly during exercise, and increases lean body mass. Despite a lack of evidence that these metabolic effects translate to improved performance, GH abuse by athletes is widespread. Tests to detect GH abuse have been developed based on measurement in serum of 1) indirect markers of GH action, and 2) the relative proportions of the two major naturally occurring isoforms (20 and 22kDa) of GH. There is evidence that exercise performance and strength are improved by administration of GH and testosterone in combination to elderly subjects. The potential benefits of GH in these situations must be weighed against potential adverse effects.
Midlife Type 2 Diabetes Mellitus (T2DM) is associated with a greater risk of dementia in later life. Peripheral inflammation and its impact on cognition is proposed as one of the pathological ...mechanisms mediating this link. However, studies have primarily focused on older individuals with established cognitive impairment and a long duration of T2DM. Importantly, knowledge of which individuals with midlife T2DM who are at greatest risk of later cognitive decline is lacking. We examined the cross-sectional relationship between serum levels of 8 pro-inflammatory markers (IL-1β, IL-6, TNF-α, IL-8, MCP-1, CXCL10, IL-12p70, CRP) and performance on a detailed neuropsychological assessment battery in middle-aged adults with uncomplicated T2DM (
= 89; 52 ± 8.1 years, 47% female) and matched healthy controls (
= 50; 52 ± 8.3 years, 59% female). Linear regression was used to analyze associations between serum markers and cognitive performance in the overall cohort, followed by a
interaction analysis to identify any T2DM-specific effects. We observed a significant T2DM-specific association between serum TNF-α levels and scores on the Paired Associates Learning (PAL) task (β: -3.16, SE: 1.32,
= 0.01, Std. Beta: -0.94), a task with significant working memory demands previously implicated in T2DM-related cognitive dysfunction. However, this did not persist on controlling for multiple testing. We provide exploratory evidence for a significant T2DM-specific relationship between serum TNF-α and memory performance. These findings require further replication and longitudinal analysis with the aim of selecting-out individuals with midlife T2DM at risk of future cognitive decline for potential preventative interventions.
In the management of thyroid nodules, although the potential for malignancy exists, there is also the potential for overtreatment of subclinical disease. Although the TI-RADS (Thyroid ...Imaging-Reporting and Data System) system outlines a risk stratification score based on suspicious ultrasound findings, it has not been universally accepted. Many TI-RADS 2 or 3 patients proceed to fine needle aspiration biopsy (FNAB), potentially unnecessarily. The aim of the study was to identify whether lesions within a multinodular goiter (MNG) without suspicious features can be followed with ultrasound rather than biopsied as is recommended for single nodules.
Pathology records were retrospectively analysed for proven MNGs over a 5-year period. A total of 293 cases were identified. FNAB, prebiopsy ultrasound images, and reports were identified for each case. Images were reviewed and assessed for sonographically suspicious criteria guided by TI-RADS. Logistic regression was applied to determine if any sonographic features were associated with neoplasia. Odds ratios with 95% confidence intervals were calculated.
Of 293 samples, 14 (4.7%) were neoplastic. Having no suspicious features conferred an average risk of 0.0339 (95% confidence interval: 0.02831-0.04087) of neoplasia. Risk of neoplasm significantly increased by having 1 and >1 suspicious feature (P < .001). Regarding cytological results, of 237 patients with Thy-2 cytology, 159 were followed up and 8 had a neoplasm.
Ultrasound can be used to estimate risk of neoplasia in MNG. In the absence of suspicious radiological findings, follow-up with ultrasound rather than FNAB may be appropriate in patients who have a low clinical suspicion for neoplasia.
Dans un contexte de prise en charge des nodules thyroïdiens, il peut y avoir malignité, mais également surtraitement d'une affection subclinique. Le système TI-RADS (Thyroid Imaging-Reporting and Data System) calcule un score de stratification du risque fondé sur l'observation de caractéristiques suspectes par échographie. Toutefois, il n'est pas universellement reconnu. Dans bien des cas, les patients qui obtiennent le score 2 ou 3 selon le système TI-RADS subissent ensuite une cytoponction, potentiellement inutile. La présente étude avait pour objectif de déterminer si les lésions d'un goitre multinodulaire ne présentant pas de caractéristiques suspectes peuvent faire l'objet d'un suivi par échographie, plutôt que d'une biopsie, comme il est recommandé de le faire pour un nodule unique.
Une analyse rétrospective sur une période de cinq ans a été réalisée afin de relever les cas avérés de goitre multinodulaire dans les dossiers de pathologie. Au total, 293 cas englobant une cytoponction, des images échographiques avant la biopsie et des rapports ont été isolés. Les images ont été examinées et évaluées en fonction des aspects échographiques suspects définis par le système TI-RADS. Une régression logistique a été réalisée afin de déterminer si les caractéristiques échographiques observées étaient associées à une néoplasie. Les rapports des cotes avec intervalles de confiance de 95 % ont été calculés.
Quatorze (4,7 %) des 293 échantillons étaient néoplasiques. L'absence de caractéristiques suspectes était associée à un risque moyen de 0,0339 (intervalle de confiance de 95 %: de 0,02831 à 0,04087) de néoplasie. Le risque de néoplasie augmentait notablement en présence d'une ou de plusieurs caractéristiques suspectes (P < 0,001). En ce qui concerne les résultats cytologiques, 159 des 237 patients affichant le score TI-RADS 2 ont fait l'objet d'un suivi et 8 ont présenté une néoplasie.
L’échographie peut servir à estimer le risque de néoplasie en présence d'un goitre multinodulaire. En l'absence d'aspects radiologiques suspects, il peut être approprié d'effectuer un suivi par échographie au lieu d'une cytoponction chez les patients pour lesquels le niveau de suspicion clinique est faible.
Persons with type 2 diabetes mellitus (T2DM) have an elevated risk of atherosclerosis. High-density lipoproteins (HDL) normally protect against cardiovascular disease (CVD), but this may be ...attenuated by serum amyloid A (SAA). In a case-control study of young females, blood samples were compared between subjects with T2DM (n=42) and individuals without T2DM (n=42). SAA and apolipoprotein AI (apoAI) concentrations, paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP), and lecithin-cholesterol acyltransferase (LCAT) activities were measured in the serum and/or HDL2 and HDL3 subfractions. SAA concentrations were higher in T2DM compared to controls: serum (30 mg/L (17, 68) versus 15 mg/L (7, 36); p=0.002), HDL2 (1.0 mg/L (0.6, 2.2) versus 0.4 mg/L (0.2, 0.7); p<0.001), and HDL3 (13 mg/L (8, 29) versus 6 mg/L (3, 13); p<0.001). Serum-PON-1 activity was lower in T2DM compared to that in controls (38,245 U/L (7025) versus 41,109 U/L (5690); p=0.043). CETP activity was higher in T2DM versus controls in HDL2 (232.6 μmol/L (14.1) versus 217.1 μmol/L (25.1); p=0.001) and HDL3 (279.5 μmol/L (17.7) versus 245.2 μmol/L (41.2); p<0.001). These results suggest that individuals with T2DM have increased SAA-related inflammation and dysfunctional HDL features. SAA may prove to be a useful biomarker in T2DM given its association with elevated CVD risk.
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