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Background: Strength and mobility are essential for activities of daily living. With aging, weaker handgrip strength, mobility, and asymmetry predict poorer cognition. We therefore sought to quantify the relationship between handgrip metrics and volumes quantified on brain magnetic resonance imaging (MRI). Objective: To model the relationships between handgrip strength, mobility, and MRI volumetry. Methods: We selected 38 participants with Alzheimer’s disease dementia: biomarker evidence of amyloidosis and impaired cognition. Handgrip strength on dominant and non-dominant hands was measured with a hand dynamometer. Handgrip asymmetry was calculated. Two-minute walk test (2MWT) mobility evaluation was combined with handgrip strength to identify non-frail versus frail persons. Brain MRI volumes were quantified with Neuroreader. Multiple regression adjusting for age, sex, education, handedness, body mass index, and head size modeled handgrip strength, asymmetry and 2MWT with brain volumes. We modeled non-frail versus frail status relationships with brain structures by analysis of covariance. Results: Higher non-dominant handgrip strength was associated with larger volumes in the hippocampus (p = 0.02). Dominant handgrip strength was related to higher frontal lobe volumes (p = 0.02). Higher 2MWT scores were associated with larger hippocampal (p = 0.04), frontal (p = 0.01), temporal (p = 0.03), parietal (p = 0.009), and occipital lobe (p = 0.005) volumes. Frailty was associated with reduced frontal, temporal, and parietal lobe volumes. Conclusion: Greater handgrip strength and mobility were related to larger hippocampal and lobar brain volumes. Interventions focused on improving handgrip strength and mobility may seek to include quantified brain volumes on MR imaging as endpoints.

Background: Distinguishing between subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia in a scalable, accessible way is important to promote earlier detection and intervention. Objective: We investigated diagnostic categorization using an FDA-cleared quantitative electroencephalographic/event-related potential (qEEG/ERP)-based cognitive testing system (eVox® by Evoke Neuroscience) combined with an automated volumetric magnetic resonance imaging (vMRI) tool (Neuroreader® by Brainreader). Methods: Patients who self-presented with memory complaints were assigned to a diagnostic category by dementia specialists based on clinical history, neurologic exam, neuropsychological testing, and laboratory results. In addition, qEEG/ERP (n = 161) and quantitative vMRI (n = 111) data were obtained. A multinomial logistic regression model was used to determine significant predictors of cognitive diagnostic category (SCD, MCI, or dementia) using all available qEEG/ERP features and MRI volumes as the independent variables and controlling for demographic variables. Area under the Receiver Operating Characteristic curve (AUC) was used to evaluate the diagnostic accuracy of the prediction models. Results: The qEEG/ERP measures of Reaction Time, Commission Errors, and P300b Amplitude were significant predictors (AUC = 0.79) of cognitive category. Diagnostic accuracy increased when volumetric MRI measures, specifically left temporal lobe volume, were added to the model (AUC = 0.87). Conclusion: This study demonstrates the potential of a primarily physiological diagnostic model for differentiating SCD, MCI, and dementia using qEEG/ERP-based cognitive testing, especially when combined with volumetric brain MRI. The accessibility of qEEG/ERP and vMRI means that these tools can be used as adjuncts to clinical assessments to help increase the diagnostic certainty of SCD, MCI, and dementia.

Supplemental Material, sj-pdf-1-aja-10.1177_15333175211055325 for Quantitative MRI Differences Between Early versus Late Onset Alzheimer���s Disease by Somayeh Meysami, Cyrus A. Raji, David A. Merrill, Verna R. Porter and Mario F. Mendez in American Journal of Alzheimer's Disease & Other Dementias

Background: Patients with diabetic and idiopathic gastroparesis with delayed gastric emptying and moderate to severe nausea were enrolled into a phase II multicenter, randomized, double-blind, placebo-controlled trial. Subjects were randomized to receive oral 85mg tradipitant bid or placebo (1:1) for 4 weeks. Of the 152 patients, 60% of patients had idiopathic and 40% had diabetic gastroparesis. Methods: The primary outcome was change in average nausea from baseline, measured using the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Overall gastroparesis symptoms were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). Results: A statistically significant and clinically meaningful improvement in nausea and overall gastroparesis symptoms was observed in patients on tradipitant. Subjects receiving tradipitant had a significant decrease in their average nausea score compared to placebo with LS mean difference (95% CI) of -0.53 (-0.92, -0.13, p=0.0099) as well as a significant increase in nausea free days (28.8% increase on tradipitant compared to 15.0% increase on placebo, p=0.0160). A clinically meaningful response of 1-point or more improvement on the GCSI total score was observed in 46.0% of patients on tradipitant compared to 24.2% of patients on placebo (p=0.0086). Conclusions: Tradipitant treatment resulted in statistically and clinically meaningful improvements in nausea and overall gastroparesis symptoms. Tradipitant was well tolerated with comparable rates of adverse events between tradipitant and placebo groups. These robust efficacy results suggest tradipitant has the potential to become a first line treatment for idiopathic and diabetic gastroparesis. Disclosure J.L. Carlin: Employee; Self; Vanda Pharmaceuticals, Inc. V.R. Lieberman: Employee; Self; Vanda Pharmaceuticals, Inc. Stock/Shareholder; Self; Vanda Pharmaceuticals, Inc. A. Dahal: Employee; Self; Vanda Pharmaceuticals, Inc. Stock/Shareholder; Self; Vanda Pharmaceuticals, Inc. M.S. Keefe: Employee; Self; Vanda Pharmaceuticals. Stock/Shareholder; Self; Vanda Pharmaceuticals. C. Xiao: Employee; Self; Vanda pharmaceutical inc. G. Birznieks: Employee; Self; Vanda Pharmaceuticals. M.H. Polymeropoulos: Employee; Self; Vanda Pharmaceuticals Inc.

Background The impact of low-fat diets on the plasma lipoprotein profile is incompletely understood. Methods We conducted two 16-week dietary studies to compare the effects of a moderate-fat (mod-FAT) baseline diet with isocaloric and ad libitum low-fat diets rich in either carbohydrates (high-CHO, n = 16) or protein (high-PRO, n = 19) on plasma lipids, post-heparin lipase activities, cholesteryl ester transfer protein, and phospholipid transfer protein. Results Switching from the mod-FAT to the isocaloric high-CHO diet lowered plasma high-density lipoprotein cholesterol concentrations ( P < 0.001) and tended to increase triglyceride levels ( P = 0.087). Cholesterol content in the larger, buoyant low-density lipoprotein (LDL) fractions decreased, whereas those of the very-low-density lipoprotein, intermediate-density lipoprotein, and smaller, denser LDL fractions tended to increase. These changes were largely reversed when subjects lost weight by consuming this high-CHO diet ad libitum. Switching from the mod-FAT diet to the isocaloric high-PRO diet did not increase cholesterol content in the small-dense LDL fraction and led to decreases in both LDL and high-density lipoprotein cholesterol in plasma ( P < 0.001 for both). Consumption of the high-protein ad libitum diet accompanied by weight loss did not change plasma lipids further, except for a shift of cholesterol from dense low-density lipoprotein fractions to more buoyant low-density lipoprotein fractions. Cholesteryl ester transfer protein concentrations decreased with high-cholesterol feeding, whereas cholesteryl ester transfer protein concentrations and hepatic lipase and phospholipid transfer protein activities all decreased during high-protein feeding. Conclusions Both high-CHO and high-PRO diets improve plasma lipid-related risk of cardiovascular disease when consumed ad libitum.

Objective: Serotonin mediates satiety in the central nervous system. Brain serotonin content depends on the plasma ratio of tryptophan (Trp) to large neutral amino acids (LNAA) and may be affected by diet composition. We examined whether high-carbohydrate or high-protein diets induce satiety and weight loss by altering plasma concentrations of these amino acids. Methods: In study 1 (n = 16, BMI = 27.0 ± 2.3), we compared plasma Trp and LNAA concentrations averaged over 24 h after 2 weeks of consuming isocaloric diets containing either 45 or 65% of total energy as carbohydrate. In study 2 (n = 19, BMI = 26.2 ± 2.1), we made the same measurements following diets containing either 15 or 30% of total energy as protein. To assess satiety in both studies, we recorded caloric intake and weight changes during a subsequent 12-week period of ad libitum consumption of the experimental diets. Results: Ad libitum caloric intake fell by 222 ± 81 kcal/day with a 3.7 ± 0.6 kg weight loss at 12 weeks in study 1. Ad libitum caloric intake fell by 441 ± 63 kcal/ day with a 4.9 ± 0.5 kg weight loss at 12 weeks in study 2. The 24-hour averaged plasma concentration of Trp and the Trp:LNAA ratio were unaffected by the isocaloric increase in carbohydrate or protein consumption that preceded the ad libitum administration of the 2 diets. Conclusion: An increase in either carbohydrate or protein intake increases satiety and leads to significant weight loss, however, these effects are not mediated by an increase in plasma concentration of Trp or the Trp:LNAA ratio.

Background Ad libitum, low-carbohydrate diets decrease caloric intake and cause weight loss. It is unclear whether these effects are due to the reduced carbohydrate content of such diets or to their associated increase in protein intake. Objective We tested the hypothesis that increasing the protein content while maintaining the carbohydrate content of the diet lowers body weight by decreasing appetite and spontaneous caloric intake. Design Appetite, caloric intake, body weight, and fat mass were measured in 19 subjects placed sequentially on the following diets: a weight-maintaining diet (15% protein, 35% fat, and 50% carbohydrate) for 2 wk, an isocaloric diet (30% protein, 20% fat, and 50% carbohydrate) for 2 wk, and an ad libitum diet (30% protein, 20% fat, and 50% carbohydrate) for 12 wk. Blood was sampled frequently at the end of each diet phase to measure the area under the plasma concentration versus time curve (AUC) for insulin, leptin, and ghrelin. Results Satiety was markedly increased with the isocaloric high-protein diet despite an unchanged leptin AUC. Mean (+/-SE) spontaneous energy intake decreased by 441 +/- 63 kcal/d, body weight decreased by 4.9 +/- 0.5 kg, and fat mass decreased by 3.7 +/- 0.4 kg with the ad libitum, high-protein diet, despite a significantly decreased leptin AUC and increased ghrelin AUC. Conclusions An increase in dietary protein from 15% to 30% of energy at a constant carbohydrate intake produces a sustained decrease in ad libitum caloric intake that may be mediated by increased central nervous system leptin sensitivity and results in significant weight loss. This anorexic effect of protein may contribute to the weight loss produced by low-carbohydrate diets.

Background: It is well known that exercise has beneficial effects on health. Although intense exercise is experienced by the body as a condition of stress, a well designed training has long term beneficial effects on the organism of an athlete. Less is known about the effects that the genetic background might have on training adaptation and on the consequent modification of laboratory parameters. Methods: In our study we evaluated the blood chemistry parameters of a group of 41 athletes compared with a group of 45 amateur athletes, to assess whether the training has effects on their variation. In addition we typed our subjects for polymorphisms 308 A/G of the tumor necrosis factor-α (TNF-α) and 1082 A/G of Interleukin-10 (IL10). Results: After statistical analysis, performed with Mann-Whitney Test, we observed a statistically significant (p value< 0,05) increase of basophils, eosinophils, monocytes, and total bilirubin and decreased levels of neutrophils, glucose, electrolytes and AST in professionals compared to amateurs. These parameters were not modified by the genetic background. Actually the training modification observed were independent of the presence of pro-inflammatory (carrier allele A of 1082 A/G of IL10) or anti-inflammatory alleles (subjects A negative for 308 A/G of TNFα). Conclusions: The genetic polymorphisms analyzed do not influence changes in laboratory parameters values induced by professional training.

Objective: Retrospectively analyze several histopathologic variables that may predict neck recurrence after neck dissection. Design: From 1970 through 1980, 284 patients with pathologically confirmed metastatic squamous cell carcinoma underwent neck dissection and received no adjuvant therapy. Kaplan-Meier evaluation estimated a 74% 2-year neck recurrence–free rate. After adjusting for the standard covariates of age, gender, neck stage, and tumor grade, we also controlled for the time-dependent co-variates of primary recurrence, occurrence in the side of the neck not operated on, or development of new head and neck primary disease. Setting: A large referral-based practice. Results: The number of lymph nodes involved, invasion of vascular/lymphatic space, invasion of soft tissue, and desmoplastic lymph node pattern adversely affect neck recurrence. A desmoplastic stromal pattern was associated with almost a sevenfold increased risk of neck recurrence. To our knowledge, this finding has not been reported previously. Conclusion: Histopathologic evaluation of metastatically involved cervical nodes can identify patients with head and neck cancer who are at high risk for recurrence. (Arch Otolaryngol Head Neck Surg. 1994;120:1370-1374)

The impact of low-fat diets on the plasma lipoprotein profile is incompletely understood.We conducted two 16-week dietary studies to compare the effects of a moderate-fat (mod-FAT) baseline diet with isocaloric and ad libitum low-fat diets rich in either carbohydrates (high-CHO, n = 16) or protein (high-PRO, n = 19) on plasma lipids, post-heparin lipase activities, cholesteryl ester transfer protein, and phospholipid transfer protein.Switching from the mod-FAT to the isocaloric high-CHO diet lowered plasma high-density lipoprotein cholesterol concentrations (P0.001) and tended to increase triglyceride levels (P = 0.087). Cholesterol content in the larger, buoyant low-density lipoprotein (LDL) fractions decreased, whereas those of the very-low-density lipoprotein, intermediate-density lipoprotein, and smaller, denser LDL fractions tended to increase. These changes were largely reversed when subjects lost weight by consuming this high-CHO diet ad libitum. Switching from the mod-FAT diet to the isocaloric high-PRO diet did not increase cholesterol content in the small-dense LDL fraction and led to decreases in both LDL and high-density lipoprotein cholesterol in plasma (P0.001 for both).Consumption of the high-protein ad libitum diet accompanied by weight loss did not change plasma lipids further, except for a shift of cholesterol from dense low-density lipoprotein fractions to more buoyant low-density lipoprotein fractions. Cholesteryl ester transfer protein concentrations decreased with high-cholesterol feeding, whereas cholesteryl ester transfer protein concentrations and hepatic lipase and phospholipid transfer protein activities all decreased during high-protein feeding.Both high-CHO and high-PRO diets improve plasma lipid-related risk of cardiovascular disease when consumed ad libitum.

Objective. This study was designed to compare the initial efficacy of Motivational Interviewing (MI), Online Transtheoretical Model (TTM)-tailored communications and a brief Health Risk Intervention (HRI) on four health risk factors (inactivity, BMI, stress and smoking) in a worksite sample. Method. A randomized clinical trial assigned employees to one of three recruitment strategies and one of the three treatments. The treatment protocol included an HRI session for everyone and in addition either a recommended three TTM online sessions or three MI in person or telephone sessions over 6 months. At the initial post-treatment assessment at 6 months, groups were compared on the percentage who had progressed from at risk to taking effective action on each of the four risks. Results. Compared to the HRI only group, the MI and TTM groups had significantly more participants in the Action stage for exercise and effective stress management and significantly fewer risk behaviors at 6 months. MI and TTM group outcomes were not different. Conclusion. This was the first study to demonstrate that MI and online TTM could produce significant multiple behavior changes. Future research will examine the long-term impacts of each treatment, their cost effectiveness, effects on productivity and quality of life and process variables mediating outcomes.

In recent years, the improvement in results in terms of survival in the treatment of laryngeal and hypopharyngeal cancer at the same stage has been rather poor. Therefore, oncologists have tried to improve the quality of life through a decrease in morbidity while not decreasing the treatment efficacy. In particular, the objective was to preserve with noninvasive procedures the anatomy and function of the larynx and hypopharynx while not affecting the possible cure. The refinement on diagnostic, surgical and anesthetic procedures, the potential of modern radiotherapy, the acquisition of new knowledge in medical oncology have allowed the planning of combined modality therapy protocols aimed at organ preservation in many patients. Concurrent radiation and chemotherapy in patients with locally advanced disease is a clinical problem still under study. Results of some phase I and III studies have shown the efficacy of radiochemotherapy, at times with a non negligible toxicity involving healthy tissues, but with a real effective improvement in survival and organ preservation in laryngeal and hypopharyngeal cancer.