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Sports Medicine - Open Jun 2023The quantity and quality of skeletal muscle are important determinants of daily function and metabolic health. Various forms of physical exercise can improve muscle...
BACKGROUND
The quantity and quality of skeletal muscle are important determinants of daily function and metabolic health. Various forms of physical exercise can improve muscle function, but this effect can be inconsistent and has not been systematically examined across the health-neurological disease continuum. The purpose of this systematic scoping review with meta-analyses was to determine the effects and potential moderators of exercise training on morphological and neuromuscular muscle quality (MMQ, NMQ) in healthy older individuals. In addition and in the form of a scoping review, we examined the effects of exercise training on NMQ and MMQ in individuals with neurological conditions.
METHODS
A systematic literature search was performed in the electronic databases Medline, Embase, and Web of Science. Randomized controlled trials were included that examined the effects of exercise training on muscle quality (MQ) in older individuals with and without neurological conditions. Risk of bias and study quality were assessed (Cochrane Risk of Bias Tool 2.0). We performed random-effects models using robust variance estimation and tested moderators using the approximate Hotelling-Zhang test.
RESULTS
Thirty studies (n = 1494, 34% females) in healthy older individuals and no studies in individuals with neurological conditions were eligible for inclusion. Exercise training had small effects on MMQ (g = 0.21, 95% confidence interval [CI]: 0.03-0.40, p = 0.029). Heterogeneity was low (median I = 16%). Training and demographic variables did not moderate the effects of exercise on MMQ. There was no association between changes in MMQ and changes in functional outcomes. Exercise training improved NMQ (g = 0.68, 95% CI 0.35-1.01, p < 0.000) across all studies, in particular in higher-functioning older individuals (g = 0.72, 95% CI 0.38-1.06, p < 0.001), in lower extremity muscles (g = 0.74, 95% CI 0.35-1.13, p = 0.001), and after resistance training (g = 0.91; 95% CI 0.42-1.41, p = 0.001). Heterogeneity was very high (median I = 79%). Of the training and demographic variables, only resistance training moderated the exercise-effects on NMQ. High- versus low-intensity exercise moderated the exercise-effects on NMQ, but these effects were considered unreliable due to a low number of studies at high intensity. There was no association between changes in NMQ and changes in functional outcomes.
CONCLUSION
Exercise training has small effects on MMQ and medium-large effects on NMQ in healthy older individuals. There was no association between improvements in MQ and increases in muscle strength, mobility, and balance. Information on dose-response relations following training is currently lacking. There is a critical gap in muscle quality data for older individuals with lower function and neurological conditions after exercise training. Health practitioners should use resistance training to improve muscle function in older individuals. Well-designed studies are needed to examine the relevance of exercise training-induced changes in MQ in daily function in older individuals, especially to those with lower function and neurological conditions.
PubMed: 37278947
DOI: 10.1186/s40798-023-00585-5 -
The Lancet. Haematology May 2023Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus... (Review)
Review
Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus process involving key experts in this area. We aimed to assess consensus within a panel of experts on issues related to patient eligibility, imaging techniques, staging and response assessment, follow-up, and treatment decision-making, and to provide interim guidance by our expert consensus. We used a three-stage consensus process. First, we systematically reviewed and appraised the quality of existing evidence. Second, we generated a list of 153 statements based on the literature review to be agreed or disagreed with, with an additional statement added after the first round. Third, the 154 statements were scored by a panel of 26 experts purposively sampled from authors of published research on haematological tumours on a 1 (strongly disagree) to 9 (strongly agree) Likert scale in a two-round electronic Delphi review. The RAND and University of California Los Angeles appropriateness method was used for analysis. Between one and 14 systematic reviews were identified on each topic. All were rated as low to moderate quality. After two rounds of voting, there was consensus on 139 (90%) of 154 of the statements. There was consensus on most statements concerning the use of PET in non-Hodgkin and Hodgkin lymphoma. In multiple myeloma, more studies are required to define the optimal sequence for treatment assessment. Furthermore, nuclear medicine physicians and haematologists are awaiting consistent literature to introduce volumetric parameters, artificial intelligence, machine learning, and radiomics into routine practice.
Topics: Humans; Consensus; Nuclear Medicine; Artificial Intelligence; Hematologic Neoplasms; Molecular Imaging
PubMed: 37142345
DOI: 10.1016/S2352-3026(23)00030-3 -
International Journal of Molecular... Mar 2023Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor...
Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome. The aim of this systematic, narrative review was to assess the level of knowledge on TME implicated in the biology, behavior, and prognosis of sporadic VSs. A search (updated to November 2022) was run in Scopus, PubMed, and Web of Science electronic databases according to the PRISMA guidelines, retrieving 624 titles. After full-text evaluation and application of inclusion/exclusion criteria, 37 articles were included. VS microenvironment is determined by the interplay of a dynamic ecosystem of stromal and immune cells which produce and remodel extracellular matrix, vascular networks, and promote tumor growth. However, evidence is still conflicting. Further studies will enhance our understanding of VS biology by investigating TME-related biomarkers able to predict tumor growth and recognize immunological and molecular factors that could be potential therapeutic targets for medical treatment.
Topics: Humans; Ecosystem; Neuroma, Acoustic; Treatment Outcome; Tumor Burden; Tumor Microenvironment
PubMed: 37047498
DOI: 10.3390/ijms24076522 -
Journal of Neuroinflammation Mar 2023Diabetes mellitus is a heterogeneous chronic metabolic disorder characterized by the presence of hyperglycemia, commonly preceded by a prediabetic state. The excess of... (Review)
Review
Diabetes mellitus is a heterogeneous chronic metabolic disorder characterized by the presence of hyperglycemia, commonly preceded by a prediabetic state. The excess of blood glucose can damage multiple organs, including the brain. In fact, cognitive decline and dementia are increasingly being recognized as important comorbidities of diabetes. Despite the largely consistent link between diabetes and dementia, the underlying causes of neurodegeneration in diabetic patients remain to be elucidated. A common factor for almost all neurological disorders is neuroinflammation, a complex inflammatory process in the central nervous system for the most part orchestrated by microglial cells, the main representatives of the immune system in the brain. In this context, our research question aimed to understand how diabetes affects brain and/or retinal microglia physiology. We conducted a systematic search in PubMed and Web of Science to identify research items addressing the effects of diabetes on microglial phenotypic modulation, including critical neuroinflammatory mediators and their pathways. The literature search yielded 1327 records, including 18 patents. Based on the title and abstracts, 830 papers were screened from which 250 primary research papers met the eligibility criteria (original research articles with patients or with a strict diabetes model without comorbidities, that included direct data about microglia in the brain or retina), and 17 additional research papers were included through forward and backward citations, resulting in a total of 267 primary research articles included in the scoping systematic review. We reviewed all primary publications investigating the effects of diabetes and/or its main pathophysiological traits on microglia, including in vitro studies, preclinical models of diabetes and clinical studies on diabetic patients. Although a strict classification of microglia remains elusive given their capacity to adapt to the environment and their morphological, ultrastructural and molecular dynamism, diabetes modulates microglial phenotypic states, triggering specific responses that include upregulation of activity markers (such as Iba1, CD11b, CD68, MHC-II and F4/80), morphological shift to amoeboid shape, secretion of a wide variety of cytokines and chemokines, metabolic reprogramming and generalized increase of oxidative stress. Pathways commonly activated by diabetes-related conditions include NF-κB, NLRP3 inflammasome, fractalkine/CX3CR1, MAPKs, AGEs/RAGE and Akt/mTOR. Altogether, the detailed portrait of complex interactions between diabetes and microglia physiology presented here can be regarded as an important starting point for future research focused on the microglia-metabolism interface.
Topics: Humans; Microglia; Diabetes Mellitus; Hyperglycemia; Central Nervous System; Dementia
PubMed: 36869375
DOI: 10.1186/s12974-023-02740-x -
Frontiers in Plant Science 2023The C4 grass pearl millet is one of the most drought tolerant cereals and is primarily grown in marginal areas where annual rainfall is low and intermittent. It was...
The C4 grass pearl millet is one of the most drought tolerant cereals and is primarily grown in marginal areas where annual rainfall is low and intermittent. It was domesticated in sub-Saharan Africa, and several studies have found that it uses a combination of morphological and physiological traits to successfully resist drought. This review explores the short term and long-term responses of pearl millet that enables it to either tolerate, avoid, escape, or recover from drought stress. The response to short term drought reveals fine tuning of osmotic adjustment, stomatal conductance, and ROS scavenging ability, along with ABA and ethylene transduction. Equally important are longer term developmental plasticity in tillering, root development, leaf adaptations and flowering time that can both help avoid the worst water stress and recover some of the yield losses asynchronous tiller production. We examine genes related to drought resistance that were identified through individual transcriptomic studies and through our combined analysis of previous studies. From the combined analysis, we found 94 genes that were differentially expressed in both vegetative and reproductive stages under drought stress. Among them is a tight cluster of genes that are directly related to biotic and abiotic stress, as well as carbon metabolism, and hormonal pathways. We suggest that knowledge of gene expression patterns in tiller buds, inflorescences and rooting tips will be important for understanding the growth responses of pearl millet and the trade-offs at play in the response of this crop to drought. Much remains to be learnt about how pearl millet's unique combination of genetic and physiological mechanisms allow it to achieve such high drought tolerance, and the answers to be found may well be useful for crops other than just pearl millet.
PubMed: 36844091
DOI: 10.3389/fpls.2023.1059574 -
International Journal of Environmental... Feb 2023This study aimed to investigate the effects of eccentric cycling (ECC) training on performance, physiological, and morphological parameters in comparison to concentric... (Meta-Analysis)
Meta-Analysis Review
This study aimed to investigate the effects of eccentric cycling (ECC) training on performance, physiological, and morphological parameters in comparison to concentric cycling (CON) training. Searches were conducted using PubMed, Embase, and ScienceDirect. Studies comparing the effect of ECC and CON training regimens on performance, physiological, and/or morphological parameters were included. Bayesian multilevel meta-analysis models were used to estimate the population's mean difference between chronic responses from ECC and CON training protocols. Group levels and meta-regression were used to evaluate the specific effects of subjects and study characteristics. Fourteen studies were included in this review. The meta-analyses showed that ECC training was more effective in increasing knee extensor strength, vastus lateralis fiber cross-sectional area, and six-minute walking distance compared to CON. Moreover, ECC was as effective as CON in decreasing body fat percentage. CON was more effective in increasing V˙O2max and peak power output attained during concentric incremental tests. However, group-level analyses revealed that ECC was more effective than CON in improving V˙O2max in patients with cardiopulmonary diseases. ECC is a viable modality for exercise interventions aiming to improve parameters of muscle strength, hypertrophy, functional capacity, aerobic power, and body composition, with more advantages than CON training in improving neuromuscular variables.
Topics: Humans; Bayes Theorem; Muscle Strength; Quadriceps Muscle; Knee; Knee Joint; Adaptation, Physiological; Muscle, Skeletal; Resistance Training
PubMed: 36833557
DOI: 10.3390/ijerph20042861 -
Frontiers in Systems Neuroscience 2022Although neural plasticity is now widely studied, there was a time when the idea of adult plasticity was antithetical to the mainstream. The essential stumbling block...
Although neural plasticity is now widely studied, there was a time when the idea of adult plasticity was antithetical to the mainstream. The essential stumbling block arose from the seminal experiments of Hubel and Wiesel who presented convincing evidence that there existed a critical period for plasticity during development after which the brain lost its ability to change in accordance to shifts in sensory input. Despite the zeitgeist that mature brain is relatively immutable to change, there were a number of examples of adult neural plasticity emerging in the scientific literature. Interestingly, some of the earliest of these studies involved visual plasticity in the adult cat. Even earlier, there were reports of what appeared to be functional reorganization in adult rat somatosensory thalamus after dorsal column lesions, a finding that was confirmed and extended with additional experimentation. To demonstrate that these findings reflected more than a response to central injury, and to gain greater control of the extent of the sensory loss, peripheral nerve injuries were used that eliminated ascending sensory information while leaving central pathways intact. Merzenich, Kaas, and colleagues used peripheral nerve transections to reveal unambiguous reorganization in primate somatosensory cortex. Moreover, these same researchers showed that this plasticity proceeded in no less than two stages, one immediate, and one more protracted. These findings were confirmed and extended to more expansive cortical deprivations, and further extended to the thalamus and brainstem. There then began a series of experiments to reveal the physiological, morphological and neurochemical mechanisms that permitted this plasticity. Ultimately, Mowery and colleagues conducted a series of experiments that carefully tracked the levels of expression of several subunits of glutamate (AMPA and NMDA) and GABA (GABAA and GABAB) receptor complexes in primate somatosensory cortex at several time points after peripheral nerve injury. These receptor subunit mapping experiments revealed that membrane expression levels came to reflect those seen in early phases of critical period development. This suggested that under conditions of prolonged sensory deprivation the adult cells were returning to critical period like plastic states, i.e., developmental recapitulation. Here we outline the heuristics that drive this phenomenon.
PubMed: 36762289
DOI: 10.3389/fnsys.2022.1086680 -
Cancer Gene Therapy Jun 2023Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL).... (Meta-Analysis)
Meta-Analysis
Long-term response to autologous anti-CD19 chimeric antigen receptor T cells in relapsed or refractory B cell acute lymphoblastic leukemia: a systematic review and meta-analysis.
Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL). However, identifying the factors that influence long-term response to this therapy is necessary to optimize patient selection and treatment allocation. We conducted a literature review and meta-analysis to investigate the use of autologous anti-CD19 CAR T cell therapy in both pediatric and adult patients with R/R B-ALL, using several databases including MEDLINE, Cochrane Central, ScienceDirect, Web of Science, Journals@Ovid, Embase, and clinicaltrial.gov. A total of 38 reports were analyzed, which enrolled 2134 patients. Time-to-event endpoints were estimated using reconstructed patient survival data. The study explored key modulators of response, including costimulatory domains, disease status, age, and lymphodepletion. The median overall survival and event-free survival were 36.2 months [95% CI 28.9, NR] and 13.3 months [95% CI 12.2, 17], respectively. The overall response rate was 76% [95% CI 71, 81]. The use of 4-1BB costimulatory domain in the CAR construct, administration of low-dose cyclophosphamide lymphodepletion, and pretreatment morphologic remission were associated with better overall survival, with hazard ratios of 0.72, 0.56, and 0.66, respectively. Morphologic remission and 4-1BB domain were associated with better event-free survival, with hazard ratios of 0.66 and 0.72, respectively. These findings suggest that CAR T cell therapy may offer long-term benefits to patients with R/R B-ALL. However, further research is needed to optimize patient selection and better understand the impact of various factors on the outcome of CAR T cell therapy.
Topics: Adult; Humans; Child; Receptors, Chimeric Antigen; Receptors, Antigen, T-Cell; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; T-Lymphocytes
PubMed: 36750666
DOI: 10.1038/s41417-023-00593-3 -
Frontiers in Plant Science 2022Plant root traits play a crucial role in resource acquisition and crop performance when soil nutrient availability is low. However, the respective trait responses are...
Plant root traits play a crucial role in resource acquisition and crop performance when soil nutrient availability is low. However, the respective trait responses are complex, particularly at the field scale, and poorly understood due to difficulties in root phenotyping monitoring, inaccurate sampling, and environmental conditions. Here, we conducted a systematic review and meta-analysis of 50 field studies to identify the effects of nitrogen (N), phosphorous (P), or potassium (K) deficiencies on the root systems of common crops. Root length and biomass were generally reduced, while root length per shoot biomass was enhanced under N and P deficiency. Root length decreased by 9% under N deficiency and by 14% under P deficiency, while root biomass was reduced by 7% in N-deficient and by 25% in P-deficient soils. Root length per shoot biomass increased by 33% in N deficient and 51% in P deficient soils. The root-to-shoot ratio was often enhanced (44%) under N-poor conditions, but no consistent response of the root-to-shoot ratio to P-deficiency was found. Only a few K-deficiency studies suited our approach and, in those cases, no differences in morphological traits were reported. We encountered the following drawbacks when performing this analysis: limited number of root traits investigated at field scale, differences in the timing and severity of nutrient deficiencies, missing data (e.g., soil nutrient status and time of stress), and the impact of other conditions in the field. Nevertheless, our analysis indicates that, in general, nutrient deficiencies increased the root-length-to-shoot-biomass ratios of crops, with impacts decreasing in the order deficient P > deficient N > deficient K. Our review resolved inconsistencies that were often found in the individual field experiments, and led to a better understanding of the physiological mechanisms underlying root plasticity in fields with low nutrient availability.
PubMed: 36684760
DOI: 10.3389/fpls.2022.1067498 -
Biomedicines Jan 2023Neutrophil extracellular traps (NETs) recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA, extruded by activated... (Review)
Review
Neutrophil extracellular traps (NETs) recently emerged as a newly recognized contributor to venous and arterial thrombosis. These strands of DNA, extruded by activated or dying neutrophils, decorated with various protein mediators, become solid-state reactors that can localize at the critical interface of blood with the intimal surface of diseased arteries alongside propagating and amplifying the regional injury. NETs thus furnish a previously unsuspected link between inflammation, innate immunity, thrombosis, oxidative stress, and cardiovascular diseases. In response to disease-relevant stimuli, neutrophils undergo a specialized series of reactions that culminate in NET formation. DNA derived from either nuclei or mitochondria can contribute to NET formation. The DNA liberated from neutrophils forms a reticular mesh that resembles morphologically a net, rendering the acronym NETs particularly appropriate. The DNA backbone of NETs not only presents intrinsic neutrophil proteins (e.g., MPO (myeloperoxidase) and various proteinases) but can congregate other proteins found in blood (e.g., tissue factor procoagulant). This systematic review discusses the current hypothesis of neutrophil biology, focusing on the triggers and mechanisms of NET formation. Furthermore, the contribution of NETs to atherosclerosis and thrombosis is extensively addressed. Again, the use of NET markers in clinical trials was considered. Ultimately, given the vast body of the published literature, we aim to integrate the experimental evidence with the growing body of clinical information relating to NET critically.
PubMed: 36672621
DOI: 10.3390/biomedicines11010113