Alcoholism: Clinical and Experimental Research, 1998
The mechanisms by which alcohol intake, particularly moderate al-coho1 intake, effects bone metab... more The mechanisms by which alcohol intake, particularly moderate al-coho1 intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAl were obtained from each subject. SRAl was reported as SRAl (p = -0.281,~ = 0.003), 250-hydroxyvitamin D (p = -0.309,~ = 0.002), and testosterone (p = -184, p = 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentraUons. Atcoholism; and the VA Cooperative Studies Program (VA cooperative Study siderable effects on osteoblastic activity.22 On the other hand, there are also studies suggesting moderate alcohol 996).
In this review there is evidence that amyloid-beta peptide is a memory enhancer at physiological ... more In this review there is evidence that amyloid-beta peptide is a memory enhancer at physiological (picomolar) concentrations. Pathological overproduction of amyloid-beta leads to impaired memory, oxidative damage, damage to the blood brain barrier, neurofibrillary tangles and amyloid plaque formation. Antisenses to amyloid precursor protein (APP) can reverse these effects in mice when they lower amyloid-beta protein to physiological levels. Data suggests that overproduction of APP leads to oxidative stress producing a vicious cycle of neuronal damage. For these reasons we have revised the "amyloid cascade hypothesis" removing emphasis from the plaque to amyloid-beta overproduction and suggest that an "amyloid-beta mitochondrial vicious cycle" hypothesis may be a better pathophysiological model for understanding Alzheimer's disease.
The middle temporal area MT is a cortical area integral to the "where" pathway of prima... more The middle temporal area MT is a cortical area integral to the "where" pathway of primate visual processing, signalling the movement and position of objects in the visual world. The receptive field of a single MT neuron is sensitive to the direction of object motion, but is too large to signal precise spatial position. Here, we asked if the activity of MT neurons could be combined to support the high spatial precision required in the "where" pathway. Using multi-electrode arrays we recorded simultaneously neural activity at 24 - 65 sites in area MT of anaesthetised marmoset monkeys. We found that although individual receptive fields span more than 5 degrees of the visual field, the combined population response can support fine spatial discriminations (less than 0.2°). This is because receptive fields at neighbouring sites overlapped substantially, and changes in spatial position are therefore projected onto neural activity in a large ensemble of neurons. This fin...
Discusses the incidence of sexual dysfunction (SDY) among the elderly and illustrates this with t... more Discusses the incidence of sexual dysfunction (SDY) among the elderly and illustrates this with the case report of a 63-yr-old man whose SDY was corrected by testosterone injections. The authors' discussion focuses on the effects of age on male reproductive physiology and the differential diagnosis, pharmacologic treatment, and management of impotence. The ability to maintain a high quality sexual relationship is considered a major quality-of-life issue for senior citizens. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Older people dietary protein exercise protein quality physical function abstract New evidence sho... more Older people dietary protein exercise protein quality physical function abstract New evidence shows that older adults need more dietary protein than do younger adults to support good health, promote recovery from illness, and maintain functionality. Older people need to make up for age-related changes in protein metabolism, such as high splanchnic extraction and declining anabolic responses to ingested protein. They also need more protein to offset inflammatory and catabolic conditions associated with chronic and acute diseases that occur commonly with aging. With the goal of developing updated, evidence-based recommendations for optimal protein intake by older people, the European Union Geriatric Medicine Society (EUGMS), in cooperation with other scientific organizations, appointed an international study group to review dietary protein needs with aging (PROT-AGE Study Group). To help older people (>65 years) maintain and regain lean body mass and function, the PROT-AGE study group recommends average daily intake at least in the range of 1.0 to 1.2 g protein per kilogram of body weight per day. Both endurance-and resistance-type exercises are recommended at individualized levels that are safe and tolerated, and higher protein intake (ie, !1.2 g/kg body weight/d) is advised for those who are exercising and otherwise active. Most older adults All authors attended the setup meeting, so they all were involved in conception of principal content. Working teams then drafted text, and all authors critically reviewed and edited both the draft manuscript and the final text.
Journal of Alzheimer's disease : JAD, Jan 13, 2015
Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor agonists, currently used in... more Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor agonists, currently used in the management of type 2 diabetes, exhibit neurotrophic and neuroprotective effects in amyloid-β (Aβ) toxicity models of Alzheimer's disease (AD). We investigated the potential pro-cognitive and neuroprotective effects of the once-daily GLP-1 receptor agonist liraglutide in senescence-accelerated mouse prone 8 (SAMP8) mice, a model of age-related sporadic AD not dominated by Aβ plaques. Six-month-old SAMP8 mice received liraglutide (100 or 500 μg/kg/day, s.c.) or vehicle once daily for 4 months. Vehicle-dosed age-matched 50% back-crossed as well as untreated young (4-month-old) SAMP8 mice were used as control groups for normal memory function. Vehicle-dosed 10-month-old SAMP8 mice showed significant learning and memory retention deficits in an active-avoidance T-maze, as compared to both control groups. Also, 10-month-old SAMP8 mice displayed no immunohistological signatures of Aβ p...
The senescence-accelerated mouse (SAMP8) strain exhibits an age-related decrease in memory accomp... more The senescence-accelerated mouse (SAMP8) strain exhibits an age-related decrease in memory accompanied by an increase in hippocampal amyloid-β protein precursor (AβPP) and amyloid-β peptide (Aβ). We have shown that administration of an antisense oligonucleotide against the Aβ region of AβPP (AβPP antisense) reverses the memory deficits. The purpose of this study was to determine the effect of peripheral (IV) administration of AβPP antisense on hippocampal gene expression. The AβPP antisense reversed the memory deficits and altered expression of 944 hippocampal genes. Pathway analysis showed significant gene expression changes in nine pathways. These include the MAPK signaling pathway (p = 0.0078) and the phosphatidylinositol signaling pathway (p = 0.043), which we have previously shown to be altered in SAMP8 mice. The changes in these pathways contributed to significant changes in the neurotropin (p = 0.0083) and insulin signaling (p = 0.015) pathways, which are known to be importan...
A common finding in the elderly population is a chronic subclinical inflammatory status that coex... more A common finding in the elderly population is a chronic subclinical inflammatory status that coexists with immune dysfunction. These interconnected processes are of sufficient magnitude to impact health and survival time. In this review we discuss the different signals that may stimulate the inflammatory process in the aging population as well as the molecular and cellular components that can participate in the initiation, the modulation or termination of the said process. A special interest has been devoted to the intestine as a source of signals that can amplify local and systemic inflammation. Sentinel cells in the splanchnic area are normally exposed to more than one stimulus at a given time. In the intestine of the elderly, endogenous molecules produced by the cellular aging process and stress as well as exogenous evolutionarily conserved molecules from bacteria, are integrated into a network of receptors and molecular signalling pathways that result in chronic inflammatory act...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1992
In binocular viewing of real targets, the accommodative demand in the two eyes is not in general ... more In binocular viewing of real targets, the accommodative demand in the two eyes is not in general identical, yet the accommodation response in the two eyes is equal. In order to investigate how the accommodative signals from the two eyes are combined, this study has examined the effects of several forms of dynamic anisometropic stimulation on the accommodation response in both man and the rhesus monkey (Macaca mulatta). All experiments were performed in a computer-controlled haploscopic apparatus to allow independent control of the accommodative stimuli to the two eyes and of the vergence stimulus. The vergence stimulus was held constant while the accommodation demand was modulated independently in each eye. Accommodation was monitored continuously with a dynamic infrared optometer. Four anisometropic conditions were used. In two of these conditions, accommodation demand was varied sinusoidally with time in both eyes, but with phases differing by 90 degrees or 180 degrees between the...
Recurrent hypoglycemia is common in older people with diabetes and is likely to be less recognize... more Recurrent hypoglycemia is common in older people with diabetes and is likely to be less recognized and under reported by patients and health care professionals. Hypoglycemia in this age group is associated with significant morbidities leading to both physical and cognitive dysfunction. Repeated hospital admissions due to frequent hypoglycemia are also associated with further deterioration in patients' general health. This negative impact of hypoglycemia is likely to eventually lead to frailty, disability and poor outcomes. It appears that the relationship between hypoglycemia and frailty is bidirectional and mediated through a series of influences including under nutrition. Therefore, attention should be paid to the management of under nutrition in the general elderly population by improving energy intake and maintaining muscle mass. Increasing physical activity and having a more conservative approach to glycemic targets in frail older people with diabetes may be worthwhile.
The vertebrate retina is a clearly organized signal-processing system. It contains more than 60 d... more The vertebrate retina is a clearly organized signal-processing system. It contains more than 60 different types of neurons, arranged in three distinct neural layers. Each cell type is believed to serve unique role(s) in encoding visual information. While we now have a relatively good understanding of the constituent cell types in the retina and some general ideas of their connectivity, with few exceptions, how the retinal circuitry performs computation remains poorly understood. Computational modeling has been commonly used to study the retina from the single cell to the network level. In this article, we begin by reviewing retinal modeling strategies and existing models. We then discuss in detail the significance and limitations of these models, and finally, we provide suggestions for the future development of retinal neural modeling.
Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no ... more Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid-β protein precursor (AβPP) that can decrease AβPP expression and amyloid-β protein (Aβ) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress, and restores brain-to-blood efflux of Aβ in SAMP8 mice. Here, we examined the effects of this AβPP antisense in the Tg2576 mouse model of AD. We administered the OL-1 antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with OL-1 antisense 3 times at 2-week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze, novel object recognition, and elevated plu...
An international task force of academic and industry leaders in sarcopenia research met on Decemb... more An international task force of academic and industry leaders in sarcopenia research met on December 5, 2012 in Orlando, Florida to develop guidelines for designing and executing randomized clinical trials of sarcopenia treatments. The Task Force reviewed results from previous trials in related disease areas to extract lessons relevant to future sarcopenia trials, including practical issues regarding the design and conduct of trials in elderly populations, the definition of appropriate target populations, and the selection of screening tools, outcome measures, and biomarkers. They discussed regulatory issues, the challenges posed by trials of different types of interventions, and the need for standardization and harmonization. The Task Force concluded with recommendations for advancing the field toward better clinical trials.
Recent efforts to provide a consensus definition propose that sarcopenia be considered a clinical... more Recent efforts to provide a consensus definition propose that sarcopenia be considered a clinical syndrome associated with the loss of both skeletal muscle mass and muscle function that occurs with aging. Validation of sarcopenia definitions that include both low muscle mass and poor muscle function is needed. In the population-based African American Health (AAH) study (N = 998 at baseline/wave 1), muscle mass and mobility were evaluated in a clinical testing center in a subsample of N = 319 persons (ages 52-68) at wave 4 (2004). Muscle mass was measured using dual energy x-ray absorptiometry and mobility by a 6-min walk test and 4-m gait walk test. Height corrected appendicular skeletal mass (ASM; 9.0 ± 1.5 in n = 124 males, 8.3 ± 2.2 in n = 195 females) was computed as total lean muscle mass in arms and legs (kilograms) divided by the square of height (meters). Cross-sectional and longitudinal (6-year) associations of low ASM (bottom 25 % AAH sample; <7.96 males and <7.06 fe...
To validate the FRAIL scale. Longitudinal study. Community. Representative sample of African Amer... more To validate the FRAIL scale. Longitudinal study. Community. Representative sample of African Americans age 49 to 65 years at onset of study. The 5-item FRAIL scale (fatigue, resistance, ambulation, illnesses, and loss of weight), at baseline and activities of daily living (ADLs), instrumental activities of daily living (IADLs), mortality, short physical performance battery (SPPB), gait speed, one-leg stand, grip strength and injurious falls at baseline and 9 years. Blood tests for CRP, SIL6R, STNFR1, STNFR2 and 25 (OH) vitamin D at baseline. Cross-sectionally the FRAIL scale correlated significantly with IADL difficulties, SPPB, grip strength and one-leg stand among participants with no baseline ADL difficulties (N=703) and those outcomes plus gait speed in those with no baseline ADL dependencies (N=883). TNFR1 was increased in pre-frail and frail subjects and CRP in some subgroups. Longitudinally (N=423 with no baseline ADL difficulties or N=528 with no baseline ADL dependencies), ...
Oxidative damage is associated with neurodegenerative disorders such as Alzheimer's disease (... more Oxidative damage is associated with neurodegenerative disorders such as Alzheimer's disease (AD). The antioxidant alpha-lipoic acid has been found to improve memory in mouse models of AD. Here, we administered alpha-lipoic acid daily to SAMP8 mice starting at 11 months of age and continuing until death. We found that treatment with alpha-lipoic acid decreased survival from 34 weeks in those receiving vehicle to 20 weeks. A subset of 18 month old mice given alpha-lipoic acid for two weeks and then tested in an object-place recognition paradigm had improved memory. A second subset of 18 month old mice given alpha-lipoic acid for two weeks and tested in the Barnes maze had improved learning. After testing, the mice were sacrificed and indices of oxidative damage were measured in the brain tissue. The mice that received alpha-lipoic acid had significantly increased glutathione and decreased glutathione peroxidase and malondialdehyde indicating reversal of oxidative stress. These res...
The principles of ethical authorship and publishing in the Journal of Cachexia, Sarcopenia and Mu... more The principles of ethical authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle (JCSM) are: all authors listed on the manuscript have approved its submission and publication as provided to JCSM;no person who has a right to be recognized as author has been omitted from the list of authors;each author has made an independent material contribution to the work submitted for publication;the submitted work is original and is neither under consideration elsewhere nor has it been published previously in whole or in part other than in abstract form;all original research work is approved by the relevant bodies such as institutional review boards or ethics committees;all conflicts of interest, financial or otherwise, that may affect the authors' ability to present data objectively have been duly declared in the manuscript;the manuscript in its published form will be maintained on the servers of JCSM as a valid publication only as long as all statements in the guidelin...
Cholesterol, omega-3 fatty acids, and triglycerides have been postulated to play roles in affecti... more Cholesterol, omega-3 fatty acids, and triglycerides have been postulated to play roles in affecting cognition in Alzheimer's disease (AD), the elderly, and obesity. Animal, human epidemiological, and in vitro studies each suggest an important role for cholesterol in the regulation of amyloid-beta (Abeta) protein and the pathogenesis of AD. In contrast, well controlled studies have failed to show an effect of cholesterol lowering with statins on cognition, indicating that the cholesterol effect is spurious or indirect, possibly mediated through other lipids. Administration of diedocosahexanoic acid (DHA), a dietary omega-3 fatty acid derived primarily from fish and plants, improves cognition and reduces lipid peroxidation in animals, including in mouse models of AD. DHA also blocks Abeta-mediated tau phosphorylation. In humans, fish consumption or administration of DHA has been associated with cognitive improvement in many, but not all, studies. Both human and animal studies show...
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2008
The key to successful, clinical application of therapeutic neurostimulators lies primarily with t... more The key to successful, clinical application of therapeutic neurostimulators lies primarily with the safety and efficacy of their electrode-tissue interfaces. The authors posit that for electrical stimulation of the visual system, supra-choroidal electrode placement provides a safe, stable and readily-accessible site for implantation and the provision of electrical stimulation. The present paper explores the efficacy of supra-choroidal electrical stimulation of retinal neurons. Based upon recordings made with surface electrodes placed on the primary visual cortex, areas of activation in the cortex were shown to change when different areas on the supra-choroidal space were stimulated. Finally, the threshold to elicit a response from neurons in the visual cortex, was found to be 77.55 +/- 29.85 nC.
Alcoholism: Clinical and Experimental Research, 1998
The mechanisms by which alcohol intake, particularly moderate al-coho1 intake, effects bone metab... more The mechanisms by which alcohol intake, particularly moderate al-coho1 intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAl were obtained from each subject. SRAl was reported as SRAl (p = -0.281,~ = 0.003), 250-hydroxyvitamin D (p = -0.309,~ = 0.002), and testosterone (p = -184, p = 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentraUons. Atcoholism; and the VA Cooperative Studies Program (VA cooperative Study siderable effects on osteoblastic activity.22 On the other hand, there are also studies suggesting moderate alcohol 996).
In this review there is evidence that amyloid-beta peptide is a memory enhancer at physiological ... more In this review there is evidence that amyloid-beta peptide is a memory enhancer at physiological (picomolar) concentrations. Pathological overproduction of amyloid-beta leads to impaired memory, oxidative damage, damage to the blood brain barrier, neurofibrillary tangles and amyloid plaque formation. Antisenses to amyloid precursor protein (APP) can reverse these effects in mice when they lower amyloid-beta protein to physiological levels. Data suggests that overproduction of APP leads to oxidative stress producing a vicious cycle of neuronal damage. For these reasons we have revised the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;amyloid cascade hypothesis&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; removing emphasis from the plaque to amyloid-beta overproduction and suggest that an &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;amyloid-beta mitochondrial vicious cycle&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; hypothesis may be a better pathophysiological model for understanding Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease.
The middle temporal area MT is a cortical area integral to the "where" pathway of prima... more The middle temporal area MT is a cortical area integral to the "where" pathway of primate visual processing, signalling the movement and position of objects in the visual world. The receptive field of a single MT neuron is sensitive to the direction of object motion, but is too large to signal precise spatial position. Here, we asked if the activity of MT neurons could be combined to support the high spatial precision required in the "where" pathway. Using multi-electrode arrays we recorded simultaneously neural activity at 24 - 65 sites in area MT of anaesthetised marmoset monkeys. We found that although individual receptive fields span more than 5 degrees of the visual field, the combined population response can support fine spatial discriminations (less than 0.2°). This is because receptive fields at neighbouring sites overlapped substantially, and changes in spatial position are therefore projected onto neural activity in a large ensemble of neurons. This fin...
Discusses the incidence of sexual dysfunction (SDY) among the elderly and illustrates this with t... more Discusses the incidence of sexual dysfunction (SDY) among the elderly and illustrates this with the case report of a 63-yr-old man whose SDY was corrected by testosterone injections. The authors' discussion focuses on the effects of age on male reproductive physiology and the differential diagnosis, pharmacologic treatment, and management of impotence. The ability to maintain a high quality sexual relationship is considered a major quality-of-life issue for senior citizens. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Older people dietary protein exercise protein quality physical function abstract New evidence sho... more Older people dietary protein exercise protein quality physical function abstract New evidence shows that older adults need more dietary protein than do younger adults to support good health, promote recovery from illness, and maintain functionality. Older people need to make up for age-related changes in protein metabolism, such as high splanchnic extraction and declining anabolic responses to ingested protein. They also need more protein to offset inflammatory and catabolic conditions associated with chronic and acute diseases that occur commonly with aging. With the goal of developing updated, evidence-based recommendations for optimal protein intake by older people, the European Union Geriatric Medicine Society (EUGMS), in cooperation with other scientific organizations, appointed an international study group to review dietary protein needs with aging (PROT-AGE Study Group). To help older people (>65 years) maintain and regain lean body mass and function, the PROT-AGE study group recommends average daily intake at least in the range of 1.0 to 1.2 g protein per kilogram of body weight per day. Both endurance-and resistance-type exercises are recommended at individualized levels that are safe and tolerated, and higher protein intake (ie, !1.2 g/kg body weight/d) is advised for those who are exercising and otherwise active. Most older adults All authors attended the setup meeting, so they all were involved in conception of principal content. Working teams then drafted text, and all authors critically reviewed and edited both the draft manuscript and the final text.
Journal of Alzheimer's disease : JAD, Jan 13, 2015
Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor agonists, currently used in... more Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor agonists, currently used in the management of type 2 diabetes, exhibit neurotrophic and neuroprotective effects in amyloid-β (Aβ) toxicity models of Alzheimer's disease (AD). We investigated the potential pro-cognitive and neuroprotective effects of the once-daily GLP-1 receptor agonist liraglutide in senescence-accelerated mouse prone 8 (SAMP8) mice, a model of age-related sporadic AD not dominated by Aβ plaques. Six-month-old SAMP8 mice received liraglutide (100 or 500 μg/kg/day, s.c.) or vehicle once daily for 4 months. Vehicle-dosed age-matched 50% back-crossed as well as untreated young (4-month-old) SAMP8 mice were used as control groups for normal memory function. Vehicle-dosed 10-month-old SAMP8 mice showed significant learning and memory retention deficits in an active-avoidance T-maze, as compared to both control groups. Also, 10-month-old SAMP8 mice displayed no immunohistological signatures of Aβ p...
The senescence-accelerated mouse (SAMP8) strain exhibits an age-related decrease in memory accomp... more The senescence-accelerated mouse (SAMP8) strain exhibits an age-related decrease in memory accompanied by an increase in hippocampal amyloid-β protein precursor (AβPP) and amyloid-β peptide (Aβ). We have shown that administration of an antisense oligonucleotide against the Aβ region of AβPP (AβPP antisense) reverses the memory deficits. The purpose of this study was to determine the effect of peripheral (IV) administration of AβPP antisense on hippocampal gene expression. The AβPP antisense reversed the memory deficits and altered expression of 944 hippocampal genes. Pathway analysis showed significant gene expression changes in nine pathways. These include the MAPK signaling pathway (p = 0.0078) and the phosphatidylinositol signaling pathway (p = 0.043), which we have previously shown to be altered in SAMP8 mice. The changes in these pathways contributed to significant changes in the neurotropin (p = 0.0083) and insulin signaling (p = 0.015) pathways, which are known to be importan...
A common finding in the elderly population is a chronic subclinical inflammatory status that coex... more A common finding in the elderly population is a chronic subclinical inflammatory status that coexists with immune dysfunction. These interconnected processes are of sufficient magnitude to impact health and survival time. In this review we discuss the different signals that may stimulate the inflammatory process in the aging population as well as the molecular and cellular components that can participate in the initiation, the modulation or termination of the said process. A special interest has been devoted to the intestine as a source of signals that can amplify local and systemic inflammation. Sentinel cells in the splanchnic area are normally exposed to more than one stimulus at a given time. In the intestine of the elderly, endogenous molecules produced by the cellular aging process and stress as well as exogenous evolutionarily conserved molecules from bacteria, are integrated into a network of receptors and molecular signalling pathways that result in chronic inflammatory act...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1992
In binocular viewing of real targets, the accommodative demand in the two eyes is not in general ... more In binocular viewing of real targets, the accommodative demand in the two eyes is not in general identical, yet the accommodation response in the two eyes is equal. In order to investigate how the accommodative signals from the two eyes are combined, this study has examined the effects of several forms of dynamic anisometropic stimulation on the accommodation response in both man and the rhesus monkey (Macaca mulatta). All experiments were performed in a computer-controlled haploscopic apparatus to allow independent control of the accommodative stimuli to the two eyes and of the vergence stimulus. The vergence stimulus was held constant while the accommodation demand was modulated independently in each eye. Accommodation was monitored continuously with a dynamic infrared optometer. Four anisometropic conditions were used. In two of these conditions, accommodation demand was varied sinusoidally with time in both eyes, but with phases differing by 90 degrees or 180 degrees between the...
Recurrent hypoglycemia is common in older people with diabetes and is likely to be less recognize... more Recurrent hypoglycemia is common in older people with diabetes and is likely to be less recognized and under reported by patients and health care professionals. Hypoglycemia in this age group is associated with significant morbidities leading to both physical and cognitive dysfunction. Repeated hospital admissions due to frequent hypoglycemia are also associated with further deterioration in patients' general health. This negative impact of hypoglycemia is likely to eventually lead to frailty, disability and poor outcomes. It appears that the relationship between hypoglycemia and frailty is bidirectional and mediated through a series of influences including under nutrition. Therefore, attention should be paid to the management of under nutrition in the general elderly population by improving energy intake and maintaining muscle mass. Increasing physical activity and having a more conservative approach to glycemic targets in frail older people with diabetes may be worthwhile.
The vertebrate retina is a clearly organized signal-processing system. It contains more than 60 d... more The vertebrate retina is a clearly organized signal-processing system. It contains more than 60 different types of neurons, arranged in three distinct neural layers. Each cell type is believed to serve unique role(s) in encoding visual information. While we now have a relatively good understanding of the constituent cell types in the retina and some general ideas of their connectivity, with few exceptions, how the retinal circuitry performs computation remains poorly understood. Computational modeling has been commonly used to study the retina from the single cell to the network level. In this article, we begin by reviewing retinal modeling strategies and existing models. We then discuss in detail the significance and limitations of these models, and finally, we provide suggestions for the future development of retinal neural modeling.
Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no ... more Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid-β protein precursor (AβPP) that can decrease AβPP expression and amyloid-β protein (Aβ) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress, and restores brain-to-blood efflux of Aβ in SAMP8 mice. Here, we examined the effects of this AβPP antisense in the Tg2576 mouse model of AD. We administered the OL-1 antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with OL-1 antisense 3 times at 2-week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze, novel object recognition, and elevated plu...
An international task force of academic and industry leaders in sarcopenia research met on Decemb... more An international task force of academic and industry leaders in sarcopenia research met on December 5, 2012 in Orlando, Florida to develop guidelines for designing and executing randomized clinical trials of sarcopenia treatments. The Task Force reviewed results from previous trials in related disease areas to extract lessons relevant to future sarcopenia trials, including practical issues regarding the design and conduct of trials in elderly populations, the definition of appropriate target populations, and the selection of screening tools, outcome measures, and biomarkers. They discussed regulatory issues, the challenges posed by trials of different types of interventions, and the need for standardization and harmonization. The Task Force concluded with recommendations for advancing the field toward better clinical trials.
Recent efforts to provide a consensus definition propose that sarcopenia be considered a clinical... more Recent efforts to provide a consensus definition propose that sarcopenia be considered a clinical syndrome associated with the loss of both skeletal muscle mass and muscle function that occurs with aging. Validation of sarcopenia definitions that include both low muscle mass and poor muscle function is needed. In the population-based African American Health (AAH) study (N = 998 at baseline/wave 1), muscle mass and mobility were evaluated in a clinical testing center in a subsample of N = 319 persons (ages 52-68) at wave 4 (2004). Muscle mass was measured using dual energy x-ray absorptiometry and mobility by a 6-min walk test and 4-m gait walk test. Height corrected appendicular skeletal mass (ASM; 9.0 ± 1.5 in n = 124 males, 8.3 ± 2.2 in n = 195 females) was computed as total lean muscle mass in arms and legs (kilograms) divided by the square of height (meters). Cross-sectional and longitudinal (6-year) associations of low ASM (bottom 25 % AAH sample; <7.96 males and <7.06 fe...
To validate the FRAIL scale. Longitudinal study. Community. Representative sample of African Amer... more To validate the FRAIL scale. Longitudinal study. Community. Representative sample of African Americans age 49 to 65 years at onset of study. The 5-item FRAIL scale (fatigue, resistance, ambulation, illnesses, and loss of weight), at baseline and activities of daily living (ADLs), instrumental activities of daily living (IADLs), mortality, short physical performance battery (SPPB), gait speed, one-leg stand, grip strength and injurious falls at baseline and 9 years. Blood tests for CRP, SIL6R, STNFR1, STNFR2 and 25 (OH) vitamin D at baseline. Cross-sectionally the FRAIL scale correlated significantly with IADL difficulties, SPPB, grip strength and one-leg stand among participants with no baseline ADL difficulties (N=703) and those outcomes plus gait speed in those with no baseline ADL dependencies (N=883). TNFR1 was increased in pre-frail and frail subjects and CRP in some subgroups. Longitudinally (N=423 with no baseline ADL difficulties or N=528 with no baseline ADL dependencies), ...
Oxidative damage is associated with neurodegenerative disorders such as Alzheimer's disease (... more Oxidative damage is associated with neurodegenerative disorders such as Alzheimer's disease (AD). The antioxidant alpha-lipoic acid has been found to improve memory in mouse models of AD. Here, we administered alpha-lipoic acid daily to SAMP8 mice starting at 11 months of age and continuing until death. We found that treatment with alpha-lipoic acid decreased survival from 34 weeks in those receiving vehicle to 20 weeks. A subset of 18 month old mice given alpha-lipoic acid for two weeks and then tested in an object-place recognition paradigm had improved memory. A second subset of 18 month old mice given alpha-lipoic acid for two weeks and tested in the Barnes maze had improved learning. After testing, the mice were sacrificed and indices of oxidative damage were measured in the brain tissue. The mice that received alpha-lipoic acid had significantly increased glutathione and decreased glutathione peroxidase and malondialdehyde indicating reversal of oxidative stress. These res...
The principles of ethical authorship and publishing in the Journal of Cachexia, Sarcopenia and Mu... more The principles of ethical authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle (JCSM) are: all authors listed on the manuscript have approved its submission and publication as provided to JCSM;no person who has a right to be recognized as author has been omitted from the list of authors;each author has made an independent material contribution to the work submitted for publication;the submitted work is original and is neither under consideration elsewhere nor has it been published previously in whole or in part other than in abstract form;all original research work is approved by the relevant bodies such as institutional review boards or ethics committees;all conflicts of interest, financial or otherwise, that may affect the authors' ability to present data objectively have been duly declared in the manuscript;the manuscript in its published form will be maintained on the servers of JCSM as a valid publication only as long as all statements in the guidelin...
Cholesterol, omega-3 fatty acids, and triglycerides have been postulated to play roles in affecti... more Cholesterol, omega-3 fatty acids, and triglycerides have been postulated to play roles in affecting cognition in Alzheimer's disease (AD), the elderly, and obesity. Animal, human epidemiological, and in vitro studies each suggest an important role for cholesterol in the regulation of amyloid-beta (Abeta) protein and the pathogenesis of AD. In contrast, well controlled studies have failed to show an effect of cholesterol lowering with statins on cognition, indicating that the cholesterol effect is spurious or indirect, possibly mediated through other lipids. Administration of diedocosahexanoic acid (DHA), a dietary omega-3 fatty acid derived primarily from fish and plants, improves cognition and reduces lipid peroxidation in animals, including in mouse models of AD. DHA also blocks Abeta-mediated tau phosphorylation. In humans, fish consumption or administration of DHA has been associated with cognitive improvement in many, but not all, studies. Both human and animal studies show...
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2008
The key to successful, clinical application of therapeutic neurostimulators lies primarily with t... more The key to successful, clinical application of therapeutic neurostimulators lies primarily with the safety and efficacy of their electrode-tissue interfaces. The authors posit that for electrical stimulation of the visual system, supra-choroidal electrode placement provides a safe, stable and readily-accessible site for implantation and the provision of electrical stimulation. The present paper explores the efficacy of supra-choroidal electrical stimulation of retinal neurons. Based upon recordings made with surface electrodes placed on the primary visual cortex, areas of activation in the cortex were shown to change when different areas on the supra-choroidal space were stimulated. Finally, the threshold to elicit a response from neurons in the visual cortex, was found to be 77.55 +/- 29.85 nC.
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Papers by John Morley