Progressive Decrement Research Articles

An intermittent recovery test for soccer players: a validation study.

Soccer is an intermittent team sport that demands high aerobic capacity. On field, soccer players' aerobic capacity, assessed through the maximal oxygen uptake (VO<inf>2</inf>max), is usually determined by an intermittent recovery test. The aim of this study was to obtain a construct validity of a new intermittent recovery test (IRT) with a fixed speed and a progressive decrement of rest period. Twenty-five male soccer players were recruited to perform an incremental continuous test (ICT) and the new IRT, to compare their physiological data. Fifteen male soccer players were involved to perform a test-retest of IRT to assess its reliability. VE<inf>peak</inf>, absolute VO<inf>2</inf>max, relative VO<inf>2</inf>max and VCO<inf>2</inf>peak registered during ICT and IRT correlated strongly (Pearson's correlation coefficient ranges from 0.75 to 0.80, with very large as magnitude of effects and with P<0.001). IRT showed reliability from good to excellent regarding VE<inf>peak</inf>, absolute VO<inf>2</inf>max, relative VO<inf>2</inf>max, VCO<inf>2</inf>peak and covered distance (ICC values ranged from 0.82 to 0.95). These findings and its underlying physiological and muscular demands, suggest that IRT can be considered as a valid and reliable test to assess aerobic capacity in soccer players during the competitive period.

Circular walking is useful for assessing the risk of falls in early progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is characterized by early onset postural instability and frequent falls. Circular walking necessitates dynamic postural control, which is impaired in patients with PSP. We aimed to explore gait parameters associated with the risk of falls in patients with PSP, focusing on circular walking. Sixteen drug-naïve patients with PSP, 22 drug-naïve patients with Parkinson's disease (PD), and 23 healthy controls were enrolled. Stride lengths/velocities and their coefficients of variation (CV) during straight and circular walking (walking around a circle of 1-m diameter) were measured under single-task and cognitive dual-task conditions. Correlation analysis was performed between gait parameters and postural instability and gait difficulty (PIGD) motor subscores, representing the risk of falls. Patients with PSP had significantly higher CVs of stride lengths/velocities during circular walking than those during straight walking, and the extent of exacerbation of CVs in patients with PSP was larger than that in patients with PD under single-task conditions. Stride lengths/velocities and their CVs were significantly correlated with PIGD motor subscores in patients with PSP only during single-task circular walking. In addition, patients with PSP showed progressive decrements of stride lengths/velocities over steps only during single-task circular walking. Worse gait parameters during circular walking are associated with an increased risk of falls in patients with PSP. Circular walking is a challenging task to demand the compromised motor functions of patients with PSP, unmasking impaired postural control and manifesting sequence effect. Assessing circular walking is useful for evaluating the risk of falls in patients with early PSP.

Investigating the impact of oral probiotic supplementation for acne management: A randomized controlled trial

Background: Acne vulgaris (AV) is a common skin disorder that affects up 10% of the worldwide population. Its pathogenesis involves a complex interplay of factors, leading to the development of cutaneous lesions (papules, pustules, and comedones). This clinical trial aimed to evaluate the efficacy of a specific probiotic formulation composed by Lactiplantibacillus plantarum PBS067, Lacticaseibacillus rhamnosus LRH020, and Limosilactobacillus reuteri PBS072 in improving AV symptoms in adult subject from the APAC region. Materials and methods: A double-blind randomized placebo-controlled clinical study was carried out on 64 women supplemented for 56 days plus a follow-up period. Instrumental evaluations of different skin parameters and clinical assessments of lesions were performed at 28 and 56 days after supplementation (T28 and T56, respectively) and during follow-up (T70). Results: A significant increase in skin hydration was achieved by probiotic group compared to the placebo (p &lt; 0.05). An improved trend in sebum content and pH resulted in a statistically significant difference with respect to placebo (p &lt; 0.05 for the former parameter at T28 and T70; p &lt; 0.05 for the latter at T70). A progressive decrement of lesions was demonstrated at each endpoint considered by probiotic supplementation, reaching significant values for non-inflammatory ones at T56 and T70 (p &lt; 0.05 and p &lt; s0.01, respectively). Conclusions: This specific probiotic formulation may help improving acne symptoms, offering a possible adjuvant therapy to the conventional one and thus overall ameliorating the patient’s quality of life. Key words: Acne vulgaris, Food supplements, Skin disease, Dermatology, Probiotics, Clinical trial

A pediatric case of tubulointerstitial nephritis and uveitis syndrome

Tubulointerstitial Nephritis and Uveitis Syndrome (TINU Syndrome) is a rare entity of unknown origin. Most cases described affect adolescents and women. It often implies a renal biopsy and is established upon the presence of uveitis and tubulointerstitial nephritis in the same patient, after all possible causes are excluded. The authors report the case of a 12-year-old teenage boy with nausea, vomiting, and weight loss lasting two weeks, taken to his local hospital with acute kidney injury, oliguria, and high blood pressure. After transfer to a specialized centre and exclusion of infectious, toxic, and autoimmune causes, intravenous and oral corticosteroid therapy was started. Renal biopsy confirmed interstitial nephritis of undetermined aetiology and the patient was discharged after favourable restauration of renal function, with a course of 4 weeks of steroids and progressive decrements over 10 weeks. Four months after the onset of the condition, the teenager was taken to the hospital with eye redness and tenderness. Bilateral anterior uveitis was described, which established the diagnosis of TINU Syndrome. After two years of joint follow-up by Paediatric Nephrology and Ophthalmology, the patient remains stable, without relapses, or ocular or renal sequelae.

Long-term levodopa ameliorates sequence effect in simple, but not complex walking in early Parkinson's disease patients

BackgroundThe sequence effect (SE) is characterized by the progressive decrement of movements and is often observed in Parkinson's disease (PD) patients. While acute effect of levodopa does not ameliorate the SE, the effect of long-term levodopa treatment for the SE remains unknown. ObjectiveWe aimed to elucidate the SEs during various gait conditions and their response to long-term levodopa treatment in drug-naïve PD patients. MethodsNineteen drug-naïve PD patients and 21 healthy controls were enrolled. Gait parameters were measured via wearable inertial sensors in the following conditions:1) straight walking, 2) circular walking: walking a circle of 1 m diameter in a clock-wise direction for 3 laps, 3) straight or circular walking under cognitive-motor dual-task (serial 7s subtractions). PD patients were evaluated at baseline, within 1 h after intravenous administration of levodopa, and after one, three, and six months treatment with levodopa. The SE was measured by a linear regression slope by plotting consecutive stride lengths over steps. Patients were also separately analyzed depending on laterality of symptoms. ResultsLong-term levodopa treatment ameliorated the SE only during single-task straight walking. The SE during circular walking was exacerbated after long-term levodopa treatment for right-side dominant patients. During dual-task straight walking, the SE at baseline was greater in right-side dominant PD patients. ConclusionsThe SE only during single-task straight walking can be ameliorated by long-term levodopa treatment. However, the SE may be exaggerated by cognitive motor interference or by asymmetrical stride length with/without long-term levodopa treatment, depending on the laterality of symptoms.

WS3.7. Repetitive Nerve Stimulation Testing

Repetitive nerve stimulation (RNS) is the most frequently used electrodiagnostic test to diagnose neuromuscular junction disorders. Although seemingly simple, attention to technique is essential to avoid technical errors. Stimulation at low rates (2–5 Hz) (LF-RNS) depletes acetylcholine stores at diseased motor endplates, causing failure of neuromuscular transmission. A decrement of at least 10% to trains of 2-3 Hz stimulation at rest or immediately after a period of maximal muscle contraction (“activation”) is the usual criterion of abnormality; 5% can be used if technical artifacts can be excluded. Take care to deliver adequate stimulation and prevent movement of the tested muscle throughout nerve stimulation; peripheral muscles should be kept warm during testing. RNS is reportedly abnormal in up to 90% of generalized myasthenia gravis (MG) patients and in up to 60% of ocular myasthenia – sensitivity is strongly dependent on the muscles selected for testing. RNS is more often abnormal in proximal, facial and clinically weak muscles; even so, RNS is frequently normal in mild or purely ocular disease. For maximal diagnostic yield, test several muscles, including those that are weak. The characteristic findings in Lambert-Eaton myasthenia (LEM) are: small CMAPs at rest, a decrement to LF-RNS, and marked facilitation. In MG, activation for 30–60 seconds is used to unmask a mild decrement. In LEM, activation is used to demonstrate facilitation; the simplest procedure is to elicit a single CMAP from the rested muscle, have the patient contract the muscle for 10 seconds, then immediately elicit a single CMAP. Facilitation of at least 60% is evidence of a pre-synaptic disorder, but may not be seen in all muscles. A decrement in at least one hand muscle is the most frequent RNS abnormality in LEM and may be seen even when CMAPs are not small and diagnostic facilitation cannot be demonstrated. In MG the decrement is usually greatest in the 4th or 5th response and is less during subsequent responses, producing a so-called ‘‘U-shaped” pattern. A continually progressive decrement is usually seen in LEM. The pattern in MuSK MG resembles that in LEM.

Determinants of Cognitive Trajectories in Normal Aging: A Longitudinal PET-MRI Study in a Community-based Cohort.

The determinants of the progressive decrement of cognition in normal aging are still a matter of debate. Alzheimer disease (AD)-signature markers and vascular lesions, but also psychological variables such as personality factors, are thought to have an impact on the longitudinal trajectories of neuropsychological performances in healthy elderly individuals. The current research aimed to identify the main determinants associated with cognitive trajectories in normal aging. We performed a 4.5-year longitudinal study in 90 older community-dwellers coupling two neuropsychological assessments, medial temporal atrophy (MTA), number of cerebral microbleeds (CMB), and white matter hyperintensities (WMH) at inclusion, visual rating of amyloid and FDG PET at follow-up, and APOE genotyping. Personality factors were assessed at baseline using the NEO-PIR. Univariate and backward stepwise regression models were built to explore the association between the continuous cognitive score (CCS) and both imaging and personality variables. The number of strictly lobar CMB at baseline (4 or more) was related to a significant increase in the risk of cognitive decrement. In multivariable models, amyloid positivity was associated with a 1.73 unit decrease of the CCS at follow-up. MTA, WMH and abnormal FDG PET were not related to the cognitive outcome. Among personality factors, only higher agreeableness was related to better preservation of neuropsychological performances. CMB and amyloid positivity are the only imaging determinants of cognitive trajectories in this highly selected series of healthy controls. Among personality factors, higher agreeableness confers a modest but significant protection against the decline of cognitive performances.

Assessing the integrity of auditory processing and sensory memory in adults with cystinosis (CTNS gene mutations)

BackgroundCystinosis, a rare lysosomal storage disease, is characterized by cystine crystallization and accumulation within tissues and organs, including the kidneys and brain. Its impact on neural function appears mild relative to its effects on other organs, but therapeutic advances have led to substantially increased life expectancy, necessitating deeper understanding of its impact on neurocognitive function in adulthood. We previously demonstrated intact auditory sensory processing, accompanied by mild sensory memory difficulties, in children and adolescents with cystinosis.MethodsWe investigated whether further progressive decrements in these processes would be observed in adults with cystinosis, comparing high-density auditory-evoked potential (AEP) recordings from adults with cystinosis (N = 15; ages: 19–38 years) to those of age-matched controls (N = 17). We employed a duration oddball paradigm with different stimulation rates, in which participants passively listened to regularly occurring standard tones interspersed with infrequently occurring deviant tones. Analyses focused on AEP components reflecting auditory sensory-perceptual processing (N1 and P2), sensory memory (mismatch negativity, MMN), and attentional orienting (P3a).ResultsOverall, adults with cystinosis produced highly similar sensory-perceptual AEP responses to those observed in controls suggesting intact early auditory cortical processing. However, significantly increased P2 and P3a amplitudes and reduced MMN at slower stimulation rates were observed, suggesting mild-to-moderate changes in auditory sensory memory and attentional processing. While cognitive testing revealed lower scores on verbal IQ and perceptual reasoning in cystinosis, these did not correlate with the AEP measures.ConclusionsThese neurophysiological data point to the emergence of subtle auditory processing deficits in early adulthood in cystinosis, warranting further investigation of memory and attentional processes in this population, and of their consequences for perceptual and cognitive function.

Experimental and numerical investigation on the thermal performance of triple tube heat exchanger equipped with different inserts with WO3/water nanofluid under turbulent condition

A novel curve tube design called Triple Tube Heat Exchanger was investigated to identify the thermofluidic characteristics in the current paper. This research analysis comprises of both computational fluid dynamics and experimental results. A three-dimensional computational fluid dynamics model was developed using Ansys R19.1 (fluent) research package, and the k-epsilon model is used to realize the thermofluidic characteristics. In this new design, an additional tube is introduced between a double concentric tube heat exchanger. The complete analysis is done under consideration of turbulent fluid to fluid heat transfer conditions. The influence of different thermal parameters such as overall heat transfer and effectiveness were the main points of research interest by using WO3/water nanofluid with different novel inserts like twisted tape, rib, and porous plate. The thermodynamic effect of nanofluid was considered under the concentration range of 0.5%–3.0%. The computational fluid dynamics method is used to simulate the process, and experimental data is used to validate it. The result shows that the maximum overall heat transfer rate and effectiveness were 1767.91 W/m2K, 1702.71 W/m2K, and 1.86, 1.79, respectively, at 1% optimized volume concentration with WO3/water nanofluid by using rib type insert during experimental and computational fluid dynamics methods, respectively. The maximum thermal performance factor by using nanofluid in the rib type insert was observed at 0.75. The study shows an enhancement of 11.84%, 12.38%, and 14.56%, 14.30% in overall heat transfer and effectiveness by using a rib-type insert for both experimental and computational fluid dynamics methods, respectively, in comparison to without using inserts. There was also a progressive decrement in friction factor during the increment in mass flow rates.

Compensatory control between the legs in automatic postural responses to stance perturbations under single-leg fatigue.

In response to sudden perturbations of stance stability, muscles of both legs are activated for balance recovery. In conditions that one of the legs has a reduced capacity to respond, the opposite leg is predicted to compensate by responding more powerfully to restore stable upright stance. In this investigation, we aimed to evaluate between-leg compensatory control in automatic postural responses to sudden perturbations in a situation in which plantar flexor muscles of a single leg were fatigued. Young participants were evaluated in response to a series of perturbations inducing forward body sway, with a focus on activation of plantar flexor muscles: lateral and medial gastrocnemii and soleus. Muscular responses were analyzed through activation magnitude and latency of muscular activation onset. For evaluation of balance and postural stability, we also analyzed the center of pressure and upper trunk displacement and weight-bearing asymmetry between the legs. Responses were assessed in three conditions: pre-fatigue, under single-leg fatigue, and following the recovery of muscular function. Results showed (a) compensation of the non-fatigued leg through the increased magnitude of muscular activation in the first perturbation under fatigue; (b) adaptation in the non-fatigued leg over repetitive perturbations, with a progressive decrement of muscular activation over trials; and (c) maintenance of increased muscular activation of the non-fatigued leg following fatigue dissipation. These findings suggest that the central nervous system is able to modulate the descending motor drive individually for each leg's muscles apparently based on their potential contribution for the achievement of the behavioral aim of recovering stable body balance following stance perturbations.

Impact of acute fonofos exposure on skeletal muscle of zebrafish: Histopathological and biometric analyses

It is widely known that pesticides generally do not show target specificity, and off-target species are strikingly affected by these chemicals. In the current work, histological changes in skeletal muscles of zebrafish (Danio rerio) caused by fonofos, an acetylcholinesterase (AChE) inhibitor organophosphate insecticide, were examined. Zebrafish were treated with 1 mg/L, 2 mg/L and 4 mg/L of fonofos for 96 hours. Skeletal muscle samples were removed from the pectoral region and embedded in paraffin. Sections were stained with Mayer's Hematoxylin and Eosin, Gomori's Trichrome and Periodic Acid Schiff techniques. Histopathological alterations were investigated by light microscopy. Fibrosis, intramyofibrillar vacuoles, disintegrated myofibrils, splitting of myofibers, atrophic and disappeared fibers, histoarchitectural loss, necrosis and progressive decrement in glycogen content were noted. Muscle fiber diameter measurements were also performed. Statistical analysis showed that measured fiber diameters of all fonofos exposed groups were significantly different from the control group, and they decreased in a concentration-dependent manner. These results suggested that fonofos caused significant myoarchitectural impairments in non-target freshwater zebrafish.

Nutrient-dense protein as a primary dietary strategy in healthy ageing: please sir, may we have more?

A progressive decrement in muscle mass and muscle function, sarcopoenia, accompanies ageing. The loss of skeletal muscle mass and function is the main feature of sarcopoenia. Preventing the loss of muscle mass is relevant since sarcopoenia can have a significant impact on mobility and the quality of life of older people. Dietary protein and physical activity have an essential role in slowing muscle mass loss and helping to maintain muscle function. However, the current recommendations for daily protein ingestion for older persons appear to be too low and are in need of adjustment. In this review, we discuss the skeletal muscle response to protein ingestion, and review the data examining current dietary protein recommendations in the older subjects. Furthermore, we review the concept of protein quality and the important role that nutrient-dense protein (NDP) sources play in meeting overall nutrient requirements and improving dietary quality. Overall, the current evidence endorses an increase in the daily ingestion of protein with emphasis on the ingestion of NDP choices by older adults.

Combined therapy with Endoret-Gel and plasma rich in growth factors vs Endoret-Gel alone in the management of facial rejuvenation: A comparative study.

Skin suffers progressive decrement. An endogenous regenerative technology has been developed that has the versatility to provide an autologous injectable gel (Endoret-Gel) or a liquid plasma rich in growth factors (PRGF) based on the patient´s own platelet-rich plasma. To compare the efficacy of the combined therapy with Endoret-Gel and PRGF versus Endoret-Gel alone in the management of facial rejuvenation. Twenty clinically diagnosed patients with aged skin received either Endoret-Gel monotherapy or Endoret-Gel+PRGF combined therapy. Patients underwent three sessions at one-month intervals and were clinically assessed for six months. Corneometry, sebumetry, and high-resolution topographic analysis were carried out. Patient self-assessment questionnaires and clinical improvement scores were also performed. The combined therapy showed to promote a higher hydration index. These results were also significant for spot improvement at three months, while conversely, monotherapy with Endoret-Gel demonstrated higher UV spot improvement. A significant decrease of sebum production and wrinkle development was observed for both treatment groups. Red areas also improved in a similar way at the end of the follow-up period. After Endoret-Gel or Endoret-Gel+PRGF therapy, 30% and 70% of patients referred to be very satisfied, respectively. Accordingly, 40% and 80% showed a "very improved" esthetic performance. None of the patients reported a negative change and no adverse events were recorded. Both Endoret-Gel monotherapy and the combined treatment with PRGF were shown to promote facial rejuvenation and to palliate the age-related cutaneous atrophy. The combined therapy may exert a synergistic effect that addresses both skin quality improvement and soft tissue restoration in a shorter period.

Impact of Physical Activity on Cognitive Functions: A New Field for Research and Management of Cystic Fibrosis.

Cystic Fibrosis (CF) is a genetic disease inherited by an autosomal recessive mechanism and characterized by a progressive and severe multi-organ failure. Mutations in Cystic Fibrosis Conductance Regulator (CFTR) protein cause duct obstructions from dense mucus secretions and chronic inflammation related to organ damage. The progression of the disease is characterized by a decline of lung function associated with metabolic disorders and malnutrition, musculoskeletal disorders and thoracic deformities, leading to a progressive decrement of the individual’s quality of life. The World Health Organization (WHO) qualifies Physical Activity (PA) as a structured activity produced by skeletal muscles’ movements that requires energy consumption. In the last decade, the number of studies on PA increased considerably, including those investigating the effects of exercise on cognitive and brain health and mental performance. PA is recommended in CF management guidelines, since it improves clinic outcomes, such as peripheral neuropathy, oxygen uptake peak, bone health, glycemic control and respiratory functions. Several studies regarding the positive effects of exercise in patients with Cystic Fibrosis were carried out, but the link between the effects of exercise and cognitive and brain health in CF remains unclear. Animal models showed that exercise might improve learning and memory through structural changes of brain architecture, and such a causal relationship can also be described in humans. Indeed, both morphological and environmental factors seem to be involved in exercise-induced neural plasticity. An increase of gray matter volume in specific areas is detectable as a consequence of regular training in humans. Neurobiological processes associated with brain function improvements include biochemical modifications, such as neuromodulator or neurohormone release, brain-derived neurotrophic factor (BDNF) production and synaptic activity changes. From a functional point of view, PA also seems to be an environmental factor enhancing cognitive abilities, such as executive functions, memory and processing speed. This review describes the current state of research regarding the impacts of physical activity and exercise on cognitive functions, introducing a possible novel field of research for optimizing the management of Cystic Fibrosis.

EVALUATION OF REPETITIVE NERVE STIMULATION WITH DIFFERENT STIMULATION FREQUENCIES IN PATIENTS WITH MYASTHENIA GRAVIS

Objective: To investigate the effect of voluntary contraction at low frequency repetitive nerve stimulation (RNS) as a sign of presynaptic compensation in patients with Myasthenia Gravis (MG). Material and Method: Thirty-five patients with MG were included. RNS at 3 Hz, recorded from the abductor digiti minimi, trapezius, nasalis, and orbicularis oculi muscles were performed. In muscles with more than 10% decrement, RNS at 1 Hz with 20-90 stimuli was applied after 10-second maximal isometric voluntary muscle contraction (MIVMC). Progressive decremental pattern was considered when decrement values were increasing until the last response. Facilitation after MIVMC was determined by dividing the amplitude of motor response in resting state by the amplitude of the motor response recorded just after contraction. Results: Among 15 patients having RNS at 1 Hz, nine had facilitation after MIVMC. In the muscle with facilitation, there was a significant positive correlation between the increment ratio and the progressive decrement difference between responses 1-4 and 1-9 (correlation coefficient 0.730, p=0.026). Although not statistically significant, muscles showing facilitation following decrement tended to have a progressive decremental pattern. Conclusion: During RNS, facilitation after MIVMC followed by progressive decremental pattern may be related to presynaptic compensation of neuromuscular transmission failure in MG.&nbsp;

Lung Function Abnormalities among Tannery Workers in Vellore District

Vellore and its allied areas have a high concentration of tanneries. There is a very large population engagedin the different sections of the tanneries. They are constantly exposed to leather tanning chemicals likechromium, HCL, H2SO4, alum etc. The constant exposure to these chemicals makes the workers susceptibleto many lung function abnormalities. More over the contact with these chemicals can cause skin diseases,nasal cancer, ocular abnormalities and respiratory diseases. Duration of exposure is a major criterion for thereduction in lung function. It is a cross sectional study involving 39 male subjects aged between 18-60 yearsworking in different sections of the tanneries in Vellore district as study group and 25 male subjects of thesame age group and socio economic status and who do not have any previous exposure to leather tanningchemicals as control group . Lung function testing was done using Eagles’s global spirometer. Our studyshows moderate restriction and mild obstruction in study group when compared to normal subjects and alsoshows progressive decrement in FVC and FEFmax with their age and duration of occupation.

Effect of pyrolysis carbon black from waste tires on the properties of styrene–butadiene rubber compounds

Only a few works focus on the use of commercial pyrolysis carbon black (PCB) to replace with commodity carbon black in terms of increasing environmental awareness. In this work, a commercial PCB (ET (Enrestec) black) from waste tires was compared with N660 carbon black in styrene–butadiene rubber (SBR) compounds using standard American Society for Testing and Materials recipes. Particle aggregate size, composition, and surface functionality of ET black and N660 were analyzed through light scattering, energy-dispersive X-ray spectroscopy (EDS), and Fourier transform infrared spectroscopy, respectively. Higher compound viscosity and aggregation power for ET black filler in the rubber matrix was observed. A progressive decrement of approximately 20% in M300 from 15.2 MPa for N660-filled SBR to 12.4 MPa for ET black-filled SBR with increasing ET black ratio in the fillers was clearly observed. ET black could potentially replace 20% in N660 without much influence for SBR compounds in terms of tensile strength. The effect of ET black content on the tear strength was less marginal than the tensile strength. However, with increasing the ET black content, the abrasion resistance index progressively decreased. Thus, it was quite beneficial to consider the merit of PCB in terms of the applications required for tearing resistance. This paves the way for the opportunities to expand further commercial application of PCB from waste tires in the light of environmental awareness.

Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects

Background: Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions. Methods: We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL. Results: There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele. Conclusion: The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.

Amyloid Load, Hippocampal Volume Loss, and Diffusion Tensor Imaging Changes in Early Phases of Brain Aging.

Background and PurposeAmyloid imaging, gray matter (GM) morphometry and diffusion tensor imaging (DTI) have all been used as predictive biomarkers in dementia. Our objective was to define the imaging profile of healthy elderly controls as a function of their cognitive trajectories and explore whether amyloid burden and white matter (WM) microstructure changes are associated with subtle decrement of neuropsychological performances in old age.Materials and MethodsWe performed a 4.5-year longitudinal study in 133 elderly individuals who underwent cognitive testing at inclusion and follow-up, amyloid PET, MRI including DTI sequences at inclusion, and APOE epsilon 4 genotyping. All cases were assessed using a continuous cognitive score (CCS) taking into account the global evolution of neuropsychological performances. Data processing included region of interest analysis of amyloid PET analysis, GM densities and tract-based spatial statistics (TBSS)-DTI. Regression models were built to explore the association between the CCS and imaging parameters controlling for significant demographic and clinical covariates.ResultsAmyloid uptake was not related to the cognitive outcome. In contrast, GM densities in bilateral hippocampus were associated with worst CCS at follow-up. In addition, radial and axial diffusivities in left hippocampus were negatively associated with CCS. Amyloid load was associated with decreased VBM and increased radial and axial diffusivity in the same area. These associations persisted when adjusting for gender and APOE4 genotype. Importantly, they were absent in amygdala and neocortical areas studied.ConclusionThe progressive decrement of neuropsychological performances in normal aging is associated with volume loss and WM microstructure changes in hippocampus long before the emergence of clinically overt symptoms. Higher amyloid load in hippocampus is compatible with cognitive preservation in cases with better preservation of GM densities and WM microstructure in this area.

Anabolic Signaling Phosphorylation Does Not Explain Differential Muscle Protein Synthesis with Intra-Set Rest Manipulation

Power development is imperative for dynamic sport athletes. Cluster sets (CLU) are an effective method to allay the progressive decrement in power output normally observed in a traditional (TRD) resistance exercise strategy. CLU configurations incorporate a brief intra-set rest period to preserve velocity and power. Despite favorable performance, we previously established that TRD configurations elicit higher myofibrillar protein synthesis (MPS) rates when compared to CLU. However, it remains unclear if hallmark readouts related to mTORC1-signaling underlie this observation. PURPOSE: To elucidate anabolic signaling mechanisms driving differential MPS rates observed between CLU and TRD paradigms of the barbell back squat in trained men and women. METHODS: In randomized crossover design, 8 resistance-trained adults (7M, 1F; 23 ± 4 y; LBM, 63 ± 9 kg; back squat 1RM, 150 ± 26 kg) performed an acute bout of either CLU (4 sets × (2 × 5) repetitions, 30s intra-set rest, 90s inter-set rest) or TRD (4 sets × 10 repetitions, 120s inter-set rest) barbell back squats at ~70% 1RM. Volume load and total rest were matched between bouts. Participants ingested 20g of whey protein immediately before and after exercise. Muscle biopsies were collected at rest and at 0, 2, and 5 h post-exercise during primed-continuous L-[ring-13C6]phenylalanine infusions. Total and phosphorylated states of targeted proteins were assessed through immunoblotting. Data was normalized to an internal loading control. RESULTS: The phosphorylation of focal adhesion kinase (FAK) was doubled with TRD, but not significantly different, from CLU (TRD 2.1 ± 0.9-fold increase from baseline; CLU 1.3 ± 0.9-fold; p>0.05). Downstream targets of mTORC1 also showed no differences in phosphorylation between paradigms (4E-BP1: TRD 1.6 ± 0.3-fold, CLU 0.4 ± 0.2-fold; p706SK: TRD 1.5 ± 0.4-fold, CLU 0.9 ± 0.4-fold). Similarly, there was no difference in AMPK phosphorylation between conditions (TRD 1.3 ± 0.9-fold; CLU 0.9 ± 0.7-fold). CONCLUSION: Our data demonstrated that changes in protein phosphorylation as noted by various readouts within the mTORC1 pathway do not underpin the greater post-exercise muscle protein synthetic response with TRD versus CLU-style in resistance trained men and women.