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Filter by:Intracranial interstitial fluid (ISF) flow is crucial for adequate clearance of extracellular waste products from the brain parenchyma. Recent demonstrations have shown that a deficiency in flow leads to the accumulation of such waste products in neurodegenerative disorders. Unfortunately, no clinical investigation that gives a quantitative measure of ISF flow exists. Such a test could prove very useful in the clinical setting for multiple neurologic disorders by providing a measure of potential diagnostic importance, as well as yielding a means to monitor response to treatment. The investigators hypothesize that such an investigation can be developed using magnetic resonance spectroscopy to give a quantitative measure of ISF flow, using spectroscopy of ethanol as a dynamic marker of interstitial fluid. Beneficially, the approach is non-invasive. This pilot project aims to develop this technique with proof of concept in healthy volunteers (males in the age range of 20-75). This pilot project aims to develop the technique, demonstrating its ability to detect ISF flow and potential differences in rates among healthy volunteers. Success at this stage will give rise to this technique being extended to studies involving individuals with various forms of intracranial pathology for comparison with values seen in healthy individuals, with the ultimate goal of it providing a measure of diagnostic significance in multiple clinical scenarios.
Considering that lenalidomide and cyclophosphamide are found to have anti-tumor effects in MALT lymphoma, the investigators speculated that combined lenalidomide and low-dose cyclophosphamide can increase the overall response rate as well as dural time of tumor remission, and avoid alternative treatments, including radiotherapy or chemotherapy-related adverse effects in antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma. Therefore, in this proposal, the investigators will design a prospective phase II study to evaluate the treatment efficacies of combination of oral lenalidomide and low-dose cyclophosphamide (LC: lenalidomide [Leavdo®] 15 mg daily, day 1 to day 21; cyclophosphamide [Endoxan] 50 mg daily, day 1 to day 21; courses will be repeated every 28 days) in patients with antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma.
Type 2 diabetes mellitus (T2DM) impairs the brain, leading to cognitive dysfunction, which carries substantial lifetime consequences. This highlights an urgent need to find effective therapeutic strategies to improve cognitive function among those with T2DM. Aerobic exercise enhances cognitive function among healthy subjects through increased release of BDNF. BDNF supports survival of existing neurons and promotes growth of new neurons and synapses. Emerging evidence suggests that reduced BDNF levels may exacerbate cognitive dysfunction associated with T2DM. Compared to drug delivery of BDNF, aerobic exercise is a low-cost, safe, and easily accessible path to increasing endogenous BDNF levels. One critical genetic variant that affects BDNF secretion and cognition is the BDNF Val66Met variant, which is a common missense polymorphism that results in a valine (Val) to methionine (Met) substitution at codon 66 located in exon IX of the BDNF gene. The Met allele alters intracellular processing, trafficking, packaging of pro-BDNF, and consequently interferes with the activity-dependent secretion of mature BDNF among Met carriers. In addition, previous research reported an influence of the Val66Met variant on the methylation level of the surrounding region. Carrying a G nucleotide (i.e., Val allele) will have an additional CpG site, and Val/Val homozygotes demonstrated a significant increase in methylation levels of four nearby CpG sites compared to Val/Met heterozygotes and Met/Met homozygotes. Because high BDNF gene methylation is associated with reduced BDNF mRNA levels, this may result in lower BDNF levels among Val/Val carriers. However, the transcription of promoter IV can be initiated by exercise, suggesting that epigenetic modulation of BDNF gene expression may be achieved by exercise. It is plausible that exercise may partly reverse transcriptional repression through dynamic DNA demethylation, but the interaction between DNA demethylation and Val homozygosity may be different from that in Met/Met and in Val/Met carriers, which could explain interpersonal differences in cognitive outcomes among these carriers following exercise training. So far, the evidence on the interplay of the Val66Met polymorphism, DNA methylation, and exercise on cognition among individuals with T2DM is still lacking. A total of 42 participants with T2DM will be randomized 2:1 to receive aerobic exercise intervention (n=28) or attention control (n=14) for 3 months. Both groups will receive weekly phone calls during the intervention and standard printed education materials regarding diabetes self-management. In addition to these interventions, the aerobic exercise group (i.e., experimental group) will also perform home-based walking exercise, while the attention control group will perform home-based stretching exercise. Trained students will monitor the exercise sessions for both groups at the Connected Health Platform (hereafter referred to as "platform"). Blood samples will be collected at baseline and three months. Outcomes of interest include post-intervention changes in plasma BDNF levels, BDNF DNA methylation executive function, memory, and processing speed. The study will evaluate the feasibility of the home-based exercise intervention. The study will also evaluate preliminary effectiveness of the supervised exercise program on of the exercise program on BDNF DNA demethylation. An exploratory aim is to explore the association of DNA demethylation with plasma BDNF levels and cognition.
Introduction. Although ageing is a general phenomenon, a great inter individual variability on the quality of ageing can be observed. This substantial heterogeneity may be partly explained by extrinsic factors such as lifestyle, habits, physical activity, diet, which may play an important role in the age-associated declines. The concept of frailty was introduced to account for variability in the aging process. This clinical and biological syndrome reflects a decrease in the physiological reserve, and leads to an insidious, precarious equilibrium that can break down during a stressful life event. In older adults, frailty is known to be associated with an increased risk of adverse outcomes, such as falls, fractures, unplanned hospitalizations, and death. Several frailty domains may only be slightly altered, so that early-stage frailty is not necessarily clinically visible. The most commonly used operational definitions of frailty are based on two different conceptual frameworks. Fried's rules-based criteria correspond to a physical phenotype, whereas the "Rockwood accumulative model" defines frailty as the accumulation of multiple deficits. These tools were built for individuals aged 65 and over. However, frailty can also be found in younger adults. Although the early detection of frailty is potentially important (since the condition might be reversible in its early stages), frailty has not been extensively investigated among middle-aged individuals. Indeed, most of the literature studies have focused on older adults or on a small number of frailty parameters the investigators hypothesized that the factors determining the main ageing-related adverse events are already present in middle age. The main objectives of the SUCCEED cohort are therefore to 1/investigate the prevalence of frailty parameters in community-dwelling individuals aged 50 and over, 2/ assess the parameters' prognostic value for future adverse health events, 3/ investigate frailty classifications in this population and assess the evolution of profiles over time Method. The SUCCEED survey is a French retrospective and prospective cohort that includes community-dwelling individuals aged 50 years or over consecutively attending an outpatient clinic ("successful ageing") in a geriatric teaching hospital in the Paris area, France. Baseline parameters are collected using a self-administered questionnaire followed by an interview, physical measurements, and performance tests conducted by trained nurses, and then a standardized clinical evaluation by a geriatrician. This clinical assessment includes evaluation of autonomy, cognition, mood, balance, mobility, muscle strength, nutrition, comorbidities, continence, sensory functions, bone density, sleeping disorders. Patients who have attended the outpatient clinic from the 01/01/2010 to 14/01/2020 are retrospectively included in the cohort, the other ones are prospectively included.
Many surgical procedures such as brachial plexus reconstruction, nerve repair, and dorsal root rhizotomies rely on the spatial selectivity of their neural stimulation methods to identify specific nerve fascicles or rootlets. Due to the variable distribution of nerves between patients, many times it is not enough to rely on the historical topography of nerves to determine their location and identity.Currently, electrical stimulation (ES) methods are used to stimulate nerves in order to locate and map them intraoperatively. ES, however, is subject to current spread in which the electrical stimulus extends beyond the area proximal to the electrode into the surrounding tissue. This can result in the stimulation of multiple fascicles introducing ambiguity as to the location and/or identity of a specific nerve or fascicle. Our group has shown that infrared neural stimulation (INS), a novel optical and label-free means of exciting neural tissue, is capable of safely stimulating nerves with a higher degree of spatial specificity than traditional ES methods. Our clinical studies have even shown that INS can outperform ES, achieving isolated rootlet responses. The investigators hypothesize that the spatial selectivity of INS can be further utilized in upper extremity surgeries such as brachial plexus reconstruction and nerve transfers to improve intraoperative nerve identification and localization. While the initial clinical work was performed with a costly clinical laser system, our group has demonstrated the efficacy of cost-effective laser diode systems for INS in animal models in vivo.The safety of these lasers, however, has yet to be proven histologically in human patients. The objective of this proposal is two-fold: to demonstrate the efficacy of INS for spatially selective nerve stimulation in the upper extremity and to determine the histological safety of INS using diode laser systems in human patients. To do so, the investigators will recruit patients undergoing brachial plexus reconstruction (BPR) and nerve transfer surgeries wherein both the effectiveness and spatial selectivity of INS can be demonstrated and histological samples can be obtained without detriment to the patients' quality of care or recovery. To accomplish these objectives, the investigators propose the following aims: Aim 1: Design and fabricate a clinical fiberoptic probe for a diode-based INS system Aim 2: Demonstrate the efficacy of INS in nerve transfer cases Aim 3: Determine the histological safety of the diode-based INS system
LP002 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors. In this study, the efficacy and safety of LP002 for the treatment of relapsed or refractory primary mediastinal large B-cell lymphoma will be evaluated.
We propose to validate an interactive, immersive spatial memory test from the laboratory test. This VR-based working memory test (VRWMT) is a first-person, self-pacing game embedded within a virtual reality environment, the program is easily implemented with minimal instructions and no supervision that can be community-users friendly. It is specifically designed to assess rapid spatial working memory - a common deficit in all NCD subtypes. Its ability to detect pathological models of dementia, age-related deterioration, and hippocampal dysfunction are well established in literature
Tuberculosis (TB) is still the leading cause of death in HIV-infected patients. Early diagnosis of TB substantially improves the survival of HIV-infected patients. Urine based detection of lipoarabinomannan (LAM) provides promising methods for quick diagnosis of TB in HIV-infected patients. However, the sensitivity and specificity of TB-LAM is still not well established, especially in area where non-tuberculosis mycobacterium is also prevalence. Here we aimed to evaluate the clinical utility of TB-LAM in diagnosis of active TB in hospitalized HIV-infected patients.
Remote Prescribed and Monitored Exercise Program After Pulmonary Rehabilitation in Individuals with Chronic Lung Disease
The aim of the present study is to assess the clinical performance of multilayered translucent zirconia laminate veneers versus lithium disilicate laminate veneers in terms of modified USPHS criteria for assessment of dental restorations (retention, restoration integrity, color match and marginal adaptation)