Academic literature on the topic 'Aquatic metabolism'

Aquatic insects are well-adapted to freshwater environments, but metabolic mechanisms of such adaptations, particularly to primary environmental factors (e.g., hypoxia, water pressure, dark light, and abundant microbes), are poorly known. Most firefly species (Coleoptera: Lampyridae) are terrestrial, but the larvae of a few species are aquatic. We generated 24 global metabolomic profiles of larvae and adults of Aquatica leii (freshwater) and Lychnuris praetexta (terrestrial) to identify freshwater adaptation-related metabolites (AARMs). We identified 110 differentially abundant metabolites (DAMs) in A. leii (adults vs. aquatic larvae) and 183 DAMs in L. praetexta (adults vs. terrestrial larvae). Furthermore, 100 DAMs specific to aquatic A. leii larvae were screened as AARMs via interspecific comparisons (A. leii vs. L. praetexta), which were primarily involved in antioxidant activity, immune response, energy production and metabolism, and chitin biosynthesis. They were assigned to six categories/superclasses (e.g., lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compound). Finally, ten metabolic pathways shared between KEGG terms specific to aquatic fireflies and enriched by AARMs were screened as aquatic adaptation-related pathways (AARPs). These AARPs were primarily involved in energy metabolism, xenobiotic biodegradation, protection of oxidative/immune damage, oxidative stress response, and sense function (e.g., glycine, serine and threonine metabolism, drug metabolism-cytochrome P450, and taste transduction), and certain aspects of morphology (e.g., steroid hormone biosynthesis). These results provide evidence suggesting that abundance changes in metabolomes contribute to freshwater adaptation of fireflies. The metabolites identified here may be vital targets for future work to determine the mechanism of freshwater adaptation in insects.

We tested the hypothesis that ecosystem metabolism follows a quarter power scaling relation, analogous to organisms. Logarithm of Biomass/Production (B/P) to Trophic Level (TL) relationship was estimated to 98 trophic models of aquatic ecosystems. A normal distribution of the slopes gives a modal value of 0.64, which was significantly different of the theoretical value of 0.75 (p0.05). We also tested for error in both variables, Log (B/P) and TL, through a Reduced Major Axis regression with similar results, with a modal value of 0.756 (p>0.05). We also explored a geographic distribution showing no significant relation (p>0.05) to latitude and between different regions of the world. We conclude that: a) ecosystem metabolism follows the quarter-power scaling rule; b) transfer efficiency between TL plays a relevant role characterizing local attributes to ecosystem metabolism; and c) there is neither latitudinal nor geographic differences. These findings confirm the existence of a metabolic scaling regularity in aquatic ecosystems. Regularidad del escalamiento metabólico en ecosistemas acuáticos Se contrastó la hipótesis de que el metabolismo de un ecosistema sigue una relación de escalamiento análoga a la existente en los organismos. La relación entre el logaritmo de la razón Producción/Biomasa (B/P) y el nivel trófico (TL) se estimó para 98 modelos tróficos de los ecosistemas acuáticos. Una distribución normal de las pendientes de esta relación produjo un valor modal de 0.64 que es significativamente diferente del valor teórico de 0.75 (p0.05) similar al teórico esperado. También se contrastó la hipótesis de existencia de error en ambas variables, logaritmo (B/P) y TL, a través de la técnica de regresión denominada “Reduced Major Axis”, con resultados similares según el valor modal de 0.756, sin diferencia estadísticamente significativa (p>0.05) del valor teórico. Se exploró la existencia de algún patrón en la distribución geográfica, sin obtenerse relación significativa (p>0.05) con la latitud, o con diferentes regiones del mundo. Las conclusiones son: a) el metabolismo del ecosistema sigue la regla de escalamiento metabólico de 3/4; b) la eficiencia de la transferencia entre TL desempeña un papel relevante, representando los atributos locales del metabolismo del ecosistema; c) no hay una diferencias latitudinal o geográfica. Estos resultados confirman la existencia de una regularidad en el escalamiento metabólico en ecosistemas acuáticos.

We tested the hypothesis that ecosystem metabolism follows a quarter power scaling relation, analogous to organisms. Logarithm of Biomass/Production (B/P) to Trophic Level (TL) relationship was estimated to 98 trophic models of aquatic ecosystems. A normal distribution of the slopes gives a modal value of 0.64, which was significantly different of the theoretical value of 0.75 (p0.05). We also tested for error in both variables, Log (B/P) and TL, through a Reduced Major Axis regression with similar results, with a modal value of 0.756 (p>0.05). We also explored a geographic distribution showing no significant relation (p>0.05) to latitude and between different regions of the world. We conclude that: a) ecosystem metabolism follows the quarter-power scaling rule; b) transfer efficiency between TL plays a relevant role characterizing local attributes to ecosystem metabolism; and c) there is neither latitudinal nor geographic differences. These findings confirm the existence of a metabolic scaling regularity in aquatic ecosystems. Regularidad del escalamiento metabólico en ecosistemas acuáticos Se contrastó la hipótesis de que el metabolismo de un ecosistema sigue una relación de escalamiento análoga a la existente en los organismos. La relación entre el logaritmo de la razón Producción/Biomasa (B/P) y el nivel trófico (TL) se estimó para 98 modelos tróficos de los ecosistemas acuáticos. Una distribución normal de las pendientes de esta relación produjo un valor modal de 0.64 que es significativamente diferente del valor teórico de 0.75 (p0.05) similar al teórico esperado. También se contrastó la hipótesis de existencia de error en ambas variables, logaritmo (B/P) y TL, a través de la técnica de regresión denominada “Reduced Major Axis”, con resultados similares según el valor modal de 0.756, sin diferencia estadísticamente significativa (p>0.05) del valor teórico. Se exploró la existencia de algún patrón en la distribución geográfica, sin obtenerse relación significativa (p>0.05) con la latitud, o con diferentes regiones del mundo. Las conclusiones son: a) el metabolismo del ecosistema sigue la regla de escalamiento metabólico de 3/4; b) la eficiencia de la transferencia entre TL desempeña un papel relevante, representando los atributos locales del metabolismo del ecosistema; c) no hay una diferencias latitudinal o geográfica. Estos resultados confirman la existencia de una regularidad en el escalamiento metabólico en ecosistemas acuáticos.

This thesis explored the uptake into the freshwater shrimp (Gammarus pulex) and the water boatman (Notonecta glauca) of key pharmaceuticals drawn from different therapeutic classes and covering a range of physico-chemical properties. For one compound, uptake was also assessed using the freshwater snail Planobarius corneus. In G. pulex, bioconcentration factors (BCFs) ranged from 4.6 – 185900 and increased in the order moclobemide < 5-fluoruracil < carbamazepine < diazepam < carvedilol < fluoxetine. In N. glauca BCFs ranged from 0.1 – 1.6 and increased in the order 5-fluorouracil < carbamazepine < moclobemide < diazepam < fluoxetine < carvedilol. For P. corneus, the BCF for carvedilol was 57.3. The metabolism of the study pharmaceuticals in the shrimp was investigated. Diazepam was found to be metabolized by G. pulex and a metabolite was detected and tentatively identified as nordiazepam. For the other five study compounds no metabolites were observed and it was inferred that metabolism in G. pulex may not influence the BCF. The influence of dietary uptake was explored in the test organisms with carvedilol and fluoxetine. It was found that uptake from water was the predominant route of exposure for G. pulex but the data for N. glauca was contrasting and the exposure from the food was predominant. In both organisms a combination of food and water exposure resulted in a higher uptake of the compounds. The differences in degree of uptake from water across the organisms may be due to differences in mode of respiration, behaviour and the pH of the test system. The differences in degree of uptake from food across the organisms may be due to differences in feeding strategies. The degree of uptake of pharmaceuticals within an organism was related to the hydrophobicity of the pharmaceuticals.

Pharmaceuticals which are used worldwide are designed to facilitate the life for the human society and have an important role in treatment and prevention of disease for both humans and animals. They are ubiquitous in the aquatic environment and are mainly derived from municipal wastewater treatment plants (WWTPs) due to their low removal rate. Therefore, their presence in the environment is directly linked to the human impact. Various biological and abiotic processes in the environment can transform them to transformation products (TPs). In many cases, transformation is already initiated in the human body by a variety of drug-metabolizing enzymes. The metabolites formed through human metabolism present some modifications in their chemical structures that can differ in physicochemical properties to their parent compound. Once they are excreted from the human body, both the unmetabolised parent drug and their metabolites enter WWTPs by means of the sewer system. Since the WWTPs are not designed to remove completely pharmaceutical residues, the fraction not removed after the treatment will eventually end up in the receiving water bodies. Consequently, due to pharmaceutical transformations in the human body, biotransformations in WWTPs and phototransformations in surface water, they can potentially produce a high number of TPs in real world samples which makes their identification a challenge. In this thesis, two different approaches (TPs profiling and suspect screening) based on high resolution mass spectrometry (HRMS) for the detection and identification of TPs of pharmaceuticals were investigated. TPs profiling approach was applied for the identification of phototransformation products of an antiviral zanamivir (ZAN) in batch reactors filled with surface water. On the other hand, suspect screening approach was applied for evaluation of transformation, prioritization and identification of photoTPs of six iodinated contrast media in surface water. Finally, a combination of suspect and TPs profiling approach was applied for the detection of TPs of an anticonvulsant lamotrigine and its main human metabolite lamotrigine N2-glucuronide which were formed as the result of their degradation in both activated sludge and pH dependent hydrolysis. The TPs profiling approach for evaluation of these transformations is illustrated in the example of photodegradation of an antiviral ZAN with identification of its TPs in surface water (Chapter 3.). Here a set of lab- scale experiments was performed in order to determine the susceptibility of ZAN towards photodegradation under simulated and natural sunlight. The identification of the TPs was performed using hydrophilic interaction liquid chromatography coupled to high resolution mass spectrometry (HILIC-HRMS) where four photoTPs were tentatively identified and their proposed structures were rationalized by photolysis mechanisms. Kinetic experiments showed that photodegradation kinetics of ZAN in surface waters would proceed with slow kinetics since upon exposure of aqueous solutions of surface water (20 μg L-1) to simulated sunlight, ZAN was degraded with t1/2 of 3.6 h. Under natural sunlight irradiating surface water, about 30 % of the initial concentration of the antiviral disappeared within 18 days. However, when ZAN and its TPs were retrospectively screened from surface water extracts, neither the parent nor the TPs were detected. The results of this TP profiling used for the identification of TPs of ZAN, although straightforward, suggests that it is not suitable when dealing with a considerably elevated number of TPs formed in batch experiments. However, time and effort needed to be optimised for the structure elucidation of 108 photoTPs of six iodinated contrast media (ICM) (Chapter 3.). Again, the photodegradation study was performed in surface water spiked with the ICMs using a sunlight lab-scale simulator. 108 TPs were generated and each photoTP was characterised by its unique exact mass of the molecular ion and retention time and added to a suspect list. Once the suspect list was generated, the photoTPs were searched in thirteen surface water samples which were extracted using a generic solid- phase extraction method (four cartridges of different chemistries in order to retain ample number of compounds with different chemical properties). Based on their detection frequency (those TPs with the frequency higher than 50 % were deemed important), eleven TPs were prioritized and their structures elucidated by HRMS and NMR (when possible). Out of the eleven prioritised TPs, ten were formed as the result of deiodination (either by deiodination, oxidative deiodination or intramolecular elimination). In the real surface water samples, median concentration of parent compounds was 110 ngL-1 reaching up to 6 µgL-1 for iomeprol while TPs were found at median concentration of 8 ngL-1, reaching up to 0.4 µgL-1 for iomeprol TP651-B. Here detection-based prioritization served as a crucial step to reduce the number of TPs to be identified and thereby reducing costs and time for the subsequent target analysis. This time-effective approach not only guaranties that the degradation products elucidated would be found, but also that they are environmentally relevant. In summary, the proposed screening approach facilitates the evaluation of the degradation of polar compounds at a real scale with a fast detection of TPs without prior availability of the standards. Approach used for detection and identification of TPs of ICM in Chapter 3 was an example of suspect screening where the suspect list of TPs was generated at lab-scale, In Chapter 4, the work started with a suspect screening of lamotrigine (LMG) and related compounds (its human metabolites, synthetic impurities and photoTPs) which were listed from the literature and searched in wastewater and surface water samples. As the result of suspect screening, LMG, three human metabolites and a LMG synthetic impurity (OXO-LMG) were detected in the screened samples. Preliminary results showed significantly higher concentrations of OXO-LMG in wastewater effluent, suggesting its formation in the WWTPs. However, biodegradation reactors amended with mixed liquor at neutral pH showed that LMG is resistant to biodegradation with only about 5 % elimination after 6 days. Since LMG is extensively and predominantly metabolised by phase II metabolism to its N2-glucuronide, this metabolite (LMG-N2-G) was degraded following the same experimental setup. Results showed that this metabolite was the actual source of the TP detected. Additionally, in batch experiments, LMG-N2-G was transformed, following pseudo-first kinetics, to three TPs as a result of i) deconjugation (to LMG), ii) oxidation of the glucuronic acid (to LMG-N2-G-TP430) and iii) amidine hydrolysis in combination with deconjugation (to OXO-LMG). In order to further rationalize the formation of the TP OXO-LMG, the stability of LMG-N2-G and related compounds was studied as a function of pH in the range of 4 – 9. Same as during biodegradation, LMG was stable across the entire pH range tested. However, LMG-N2-G was transformed to three TPs at neutral – basic pH. They were identified as TPs formed after hydrolysis of amidine and guanidine moieties. The third TP detected was an intermediated in the guanidine hydrolysis reaction. Kinetic experiments in wastewater samples at different concentration (20 and 200 nM) and pH (pH 6.5, 7, 8, 8.5 and 9) demonstrated that while the degradation constants were concentration independent, at higher pH, LMG-N2-G degraded at higher rate. The pH-dependent stability experiments of related compounds with different nitrogen N2-substituents on the 1,2,4-triazine ring showed that reaction of amidine and guanidine hydrolysis depends on imine tautomer equilibrium whose formation depends directly on the N2-supsitutent. LMG- N2-G major abiotic TP (amidine hydrolysis TP) was detected in hospital effluent and WWTP influent samples. Having in mind the concentrations of both biotic and abiotic TPs detected, a total mass balance at two- concentration levels batch reactors was closed at 86% and 102%, respectively. In three WWTPs total mass balance of LMG-N2-G ranged from 71-102%. Finally, LMG-N2-G and its TPs were detected in surface water samples with median concentration ranges of 23–186 ngL-1. The work presented in this chapter gives a new insight into the behaviour of glucuronides of pharmaceuticals, suggesting that they might also be sources of yet undiscovered, but environmentally relevant TPs.
Els productes farmacèutics, l'ús dels quals s'estén a nivell mundial, estan dissenyats per millorar la qualitat de vida de la societat i juguen un paper clau en el tractament i la prevenció de malalties, tant en homes com en animals. Aquests compostos químics es troben de forma ubíqua en el medi ambient. Això es deu principalment a les estacions depuradores d'aigua residual (EDARs), les quals no són capaces d'eliminar de manera eficient aquest tipus de compostos, ja que no estan dissenyades amb aquesta finalitat. Per tant, la presència de fàrmacs en el medi ambient està directament relacionada amb l'activitat humana. Un cop al medi ambient, l'estructura d'aquests compostos pot ser modificada per diferents processos biològics i abiòtics, generant-se així els que es coneixen com a productes de transformació (PTs). De fet, la transformació dels fàrmacs pot iniciar-se en alguns casos en el cos humà, després de la seva administració a causa de l'activitat metabòlica dels diferents enzims que posseeix l'home. Els metabòlits formats en aquests processos presenten algunes modificacions en les seves estructures químiques pel que fa al compost original, i, en conseqüència, unes propietats fisicoquímiques diferents. Un cop excretats, tant el fàrmac original no metabolitzat com els seus metabòlits arriben a les EDARs mitjançant la xarxa de sanejament municipal d'aigües residuals. La fracció d'aquests compostos que no s'elimina en els diferents tractaments realitzats en l'EDAR, es descarrega juntament amb l'efluent de la planta als aigües receptores. El gran nombre de transformacions que poden experimentar els fàrmacs en el seu cicle de vida a causa del seu metabolisme en el cos humà, la seva biotransformació per microorganismes i la seva fototransformació per llum solar, pot generar un nombre molt elevat de PTs en el medi ambient, i, per tant, la identificació dels mateixos, necessària per avaluar el destí dels fàrmacs en el medi ambient, és un desafiament. En el desenvolupament d'aquesta tesi es van aplicar dues aproximacions analítiques diferents: a)avaluació de perfils de PTs generats en experiments a escala de laboratori i b) anàlisi qualitativa dirigida suspect screening en mostres reals, tots dues basades en espectrometria de masses d'alta resolució (HRMS) per a la detecció i identificació de PTs de productes farmacèutics. L'aproximació d'avaluació de perfils de PTs en reactors a escala de laboratori es va aplicar per identificar productes de fototransformació (fotoPTs) de l'antiviral zanamivir (ZAN) en aigua superficial. L'aproximació de suspect screening es va aplicar per prioritzar i identificar fotoPTs de sis mitjans de contrast radiològics iodats (ICM) en aigua superficial. Finalment, una combinació de les dues aproximacions es va aplicar per detectar PTs de l’anticonvulsiu lamotrigina (LMG) i del seu principal metabòlit humà, el lamotrigina-N2-glucurònid (LMG- N2-G), resultants de la seva degradació tant en fangs activats com a reaccions d'hidròlisi a diferents valors de pH.

This research explored fate of organic contaminants in aquatic plant systems through (i) experimental development of relationships to describe sorption, uptake and enzymatic processing of contaminants by plants and inhibition of aquatic plants by contaminants and (ii) incorporation of experimental relationships into a conceptual model which describes contaminant fate in aquatic plant systems. This study focused on interactions of aquatic plants L. minor and M. aquaticum with halogenated phenols. 2,4,5-trichlorophenol (2,4,5-TCP) and 2,4-dichlorophenol (2,4-DCP) are precursors for the highly toxic and heavily applied herbicides 2,4,5-T and 2,4-D and were examined in detail. Chlorophenols are generally resistant to microbial degradation, a property which may limit microbial remediation options as effective alternatives for clean up of contaminated sites. Relationships for fundamental interactions between plants and contaminants that dictate uptake, enzymatic processing and sequestration of contaminants by aquatic plants were established. An assay which quantified production of oxygen by plants was developed to quantify plant metabolic activity and inhibition. Uptake of chlorinated phenols depended on plant activity and aqueous phase concentration of contaminant in the protonated form. Therefore, plant activity, contaminant pKa and media pH were established as critical parameters controlling rate of contaminant uptake. A conceptual model was developed which incorporated plant activity and inhibition into a mathematical description of uptake of organic contaminants by aquatic plants. The conceptual model was parameterized using experimental data delineating effect of plant activity, inhibition and speciation on contaminant uptake and the model was verified using independently gathered data. Experimentation with radio-labeled chlorinated phenols established that contaminants were sequestered internal to plants by plant enzymatic processing. 19F NMR was established as a technique to quantify transformation and conjugation products internal to plants and contaminant assimilation by plants and demonstrated that multiple metabolites containing the parent compound were present and quantifiable internal to plants. Finally, fate of plant-sequestered contaminants in an anaerobic bioassay was examined using Desulfitobacterium sp. strain Viet1. The results of this study address the role of aquatic plants in sequestration of contaminants in surface waters that indicate the potential and limitations of use of aquatic plants in natural and engineered treatment systems.

Dominant genera of bacteria were isolated from three river waters during anthracene and pentachlorophenol biotransformation studies. The genera Pseudomonas, Acinetobacter, Micrococcus, Chromobacterium, Alcaligenes, Azomonos, Bacillus, and Flavobacterium were capable of biotransforming one or both of these compounds. These isolates were subjected to further biotransformation tests, including river water and a basal salt medium with and without additional glucose. The results of these experiments were evaluated statistically. It was concluded that only a limited number of the bacteria identified were able to transform these chemicals in river water. The addition of glucose to the growth medium significantly affected the biotransformation of these chemicals. It was also determined that the size of the initial bacterial population is not a factor in determining whether biotransformation of anthracene or pentachlorophenol can occur.

Cancer is one of the most life threatening diseases, causing nearly 13% death in the worldwide. Leukemia, cancer of the hematopoetic cells is the main cause of cancer death in adults and children. Therapeutic agents used in treatment of cancer are known to have narrow therapeutic window and tendency to develop resistance against some cancer cell lines thus, proposing a need to discover some novel agents to treat cancer. In the present study we investigated the anticancer activity of Neosetophomone B(NSP-B), an aquatic fungal metabolite isolated from Neosetophoma sp against leukemic cells (K562 and U937). MTT results demonstrated a dose dependent inhibition of cell proliferation in K562 and U937 cell lines. Annexin staining using flow cytometry indicated that NSP-B treatment cause a dose dependent apoptosis in leukemic cells.Western blot analysis showed that NSP-B mediated apoptosis involves sequential activation of caspase 9, 3 and poly (ADP-ribose) polymerase (PARP) cleavage. Furthermore NSP-B treatment of leukemic cells resulted in upregulation of pro-apoptotic proteins (Bax) with downregulation of anti-apoptotic proteins ( Bcl-2 ).Thus, present study focuses on exploring the mechanism of anticancer activity of NSP-B on leukemic cells, raising the possibility of its use as a novel therapeutic agent for hematological malignancies. Results: We sought to determine whether NSP-B suppresses the growth of leukemic cell lines. We tested a panel of leukemic cell lines with different doses of NSP-B. Cell viability decreased in a concentration-dependent manner in K562 and U937 cell lines. NSP-B induced apoptosis in K562 and U937 cell lines via downregulation of anti-apoptotic proteins and enhancement of pro-apoptotic proteins. NSP-B induced the activation of caspase cascade signaling pathway. Altogether our results suggest that the NSP-B plays an important role in apoptosis in leukemic cell lines .Conclusions: Our data provides insight on anticancer activities of NSP-B in leukemic cell lines (K562 and U937). NSP-B inhibit cell viability via inducing apoptosis. The NSP-B mediated apoptosis occurs via downregulation of anti-apoptotic proteins and enhancement of pro-apototic proteins, thereby activating the caspase-cascade signaling. Further studies are required to elicit role of NSP-B in regulating molecular pathway involved in the progression of cancer. Taken together, above results suggest that NSP-B may have a future therapeutic role in leukemia and possibly other hematological malignancies.

Soil is an essential component of all terrestrial ecosystems and is under increasing threat from human activity. Techniques available for removing radioactive contamination from soil and aquatic substrates are limited and often costly to implement; particularly over large areas. Frequently, bulk soil removal, with its attendant consequences, is a significant component of the majority of contamination incidents. Alternative techniques capable of removing contamination or exposure pathways without damaging or removing the soil are therefore of significant interest. An increasing number of old nuclear facilities are entering ‘care and maintenance’, with significant ground contamination issues. Phytoremediation — the use of plants’ natural metabolic processes to remediate contaminated sites is one possible solution. Its key mechanisms include phytoextraction and phytostabilisation. These are analogues of existing remedial techniques. Further, phytoremediation can improve soil quality and stability and restore functionality. Information on the application of phytoremediation in the nuclear industry is widely distributed over an extended period of time and sources. It is therefore difficult to quickly and effectively identify which plants would be most suitable for phytoremediation on a site by site basis. In response, a phytoremediation tool has been developed to address this issue. Existing research and case studies were reviewed to understand the mechanisms of phytoremediation, its effectiveness and the benefits and limitations of implementation. The potential for cost recovery from a phytoremediation system is also briefly considered. An overview of this information is provided here. From this data, a set of matrices was developed to guide potential users through the plant selection process. The matrices take the user through a preliminary screening process to determine whether the contamination present at their site is amenable to phytoremediation, and to give a rough indication as to what plants might be suitable. The second two allow the user to target specific plant species that would be most likely to successfully establish based on prevailing site conditions. The outcome of this study is a phytoremediation tool that can facilitate the development of phytoremediation projects, avoiding the need for in-depth research to identify optimal plant species on a case-by-case basis.

Objectives. Although the health benefits of physical activity are well described for the general population, less is known about the benefits and harms of physical activity in people dependent upon, partially dependent upon, or at risk for needing a wheelchair. This systematic review summarizes the evidence for physical activity in people with multiple sclerosis, cerebral palsy, and spinal cord injury regardless of current use or nonuse of a wheelchair. Data sources. We searched MEDLINE®, CINAHL®, PsycINFO®, Cochrane CENTRAL, Embase®, and Rehabilitation and Sports Medicine Source from 2008 through November 2020, reference lists, and clinical trial registries. Review methods. Predefined criteria were used to select randomized controlled trials, quasiexperimental nonrandomized trials, and cohort studies that addressed the benefits and harms of observed physical activity (at least 10 sessions on 10 different days of movement using more energy than rest) in participants with multiple sclerosis, cerebral palsy, and spinal cord injury. Individual study quality (risk of bias) and the strength of bodies of evidence for key outcomes were assessed using prespecified methods. Dual review procedures were used. Effects were analyzed by etiology of impairment and physical activity modality, such as treadmill, aquatic exercises, and yoga, using qualitative, and when appropriate, quantitative synthesis using random effects meta-analyses. Results. We included 146 randomized controlled trials, 15 quasiexperimental nonrandomized trials, and 7 cohort studies (168 studies in 197 publications). More studies enrolled participants with multiple sclerosis (44%) than other conditions, followed by cerebral palsy (38%) and spinal cord injury (18%). Most studies were rated fair quality (moderate risk of bias). The majority of the evidence was rated low strength. • In participants with multiple sclerosis, walking ability may be improved with treadmill training and multimodal exercise regimens that include strength training; function may be improved with treadmill training, balance exercises, and motion gaming; balance is likely improved with postural control exercises (which may also reduce risk of falls) and may be improved with aquatic exercises, robot-assisted gait training, treadmill training, motion gaming, and multimodal exercises; activities of daily living may be improved with aquatic therapy; sleep may be improved with aerobic exercises; aerobic fitness may be improved with multimodal exercises; and female sexual function may be improved with aquatic exercise. • In participants with cerebral palsy, balance may be improved with hippotherapy and motion gaming, and function may be improved with cycling, treadmill training, and hippotherapy. • In participants with spinal cord injury, evidence suggested that activities of daily living may be improved with robot-assisted gait training. • When randomized controlled trials were pooled across types of exercise, physical activity interventions were found to improve walking in multiple sclerosis and likely improve balance and depression in multiple sclerosis. Physical activity may improve function and aerobic fitness in people with cerebral palsy or spinal cord injury. When studies of populations with multiple sclerosis and cerebral palsy were combined, evidence indicated dance may improve function. • Evidence on long-term health outcomes was not found for any analysis groups. For intermediate outcomes such as blood pressure, lipid profile, and blood glucose, there was insufficient evidence from which to draw conclusions. There was inadequate reporting of adverse events in many trials. Conclusions. Physical activity was associated with improvements in walking ability, general function, balance (including fall risk), depression, sleep, activities of daily living, female sexual function, and aerobic capacity, depending on population enrolled and type of exercise utilized. No studies reported long-term cardiovascular or metabolic disease health outcomes. Future trials could alter these findings; further research is needed to examine health outcomes, and to understand the magnitude and clinical importance of benefits seen in intermediate outcomes.