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Handbook of Clinical Neurology 2021Antipsychotic drugs are efficacious first-line treatments for many individuals diagnosed with a psychiatric illness. However, their adverse metabolic side-effect... (Review)
Review
Antipsychotic drugs are efficacious first-line treatments for many individuals diagnosed with a psychiatric illness. However, their adverse metabolic side-effect profile, which resembles the metabolic syndrome, represents a significant clinical problem that increases morbidity and limits treatment adherence. Moreover, the mechanisms involved in antipsychotic-induced adverse metabolic effects (AMEs) are unknown and mitigating strategies and interventions are limited. However, recent clinical trials show that nightly administration of exogenous melatonin may mitigate or even prevent antipsychotic-induced AMEs. This clinical evidence in combination with recent preclinical data implicate the circadian system in antipsychotic-induced AMEs and their mitigation. In this chapter, we provide an overview on the circadian system and its involvement in antipsychotic-induced AMEs, as well as the potential beneficial effect of nightly melatonin administration to mitigate them.
Topics: Antipsychotic Agents; Humans; Melatonin; Mental Disorders; Metabolic Syndrome
PubMed: 34225976
DOI: 10.1016/B978-0-12-819975-6.00024-8 -
Environmental Science & Technology Apr 2022Vegetable production systems are hotspots of nitrous oxide (NO) emissions and antibiotic pollution. However, little is known about the interconnections among NO...
Vegetable production systems are hotspots of nitrous oxide (NO) emissions and antibiotic pollution. However, little is known about the interconnections among NO emissions, vegetable growth, and antibiotic contamination. To understand how plants regulate NO emissions from enrofloxacin (ENR)-contaminated soils, in situ NO emissions were measured in pot experiments with cherry radish and pakchoi. Gross NO production and consumption processes were discriminated based on an acetylene inhibition experiment. Results indicated that vegetable growth decreased the cumulative NO flux from 0.71 to -0.29 kg ha and mitigated the ENR-induced increase in NO emissions. Radish displayed better mitigation of NO emissions than pakchoi. By combining the analysis of NO flux with soil physicochemical and microbiological properties, we demonstrated that growing vegetables could either promote gross NO consumption or decrease gross NO production, primarily by interacting with soil nitrate, clade II ()-carrying bacteria, and . ENR inhibited NO consumption more than NO production, with the -carrying bacteria, represented by , as the main inhibition target. However, increasing -carrying bacteria by growing radish offsets the inhibitory effect of ENR. These findings provide new insights into NO emissions and antibiotic pollution in vegetable-soil ecosystems and broaden the options for mitigating NO emissions.
Topics: Agriculture; Anti-Bacterial Agents; Ecosystem; Nitrous Oxide; Soil; Soil Microbiology; Vegetables
PubMed: 35274945
DOI: 10.1021/acs.est.1c06508 -
Biological Reviews of the Cambridge... Feb 2018Forest ecosystems are critical to mitigating greenhouse gas emissions through carbon sequestration. However, climate change has affected forest ecosystem functioning in... (Review)
Review
Forest ecosystems are critical to mitigating greenhouse gas emissions through carbon sequestration. However, climate change has affected forest ecosystem functioning in both negative and positive ways, and has led to shifts in species/functional diversity and losses in plant species diversity which may impair the positive effects of diversity on ecosystem functioning. Biodiversity may mitigate climate change impacts on (I) biodiversity itself, as more-diverse systems could be more resilient to climate change impacts, and (II) ecosystem functioning through the positive relationship between diversity and ecosystem functioning. By surveying the literature, we examined how climate change has affected forest ecosystem functioning and plant diversity. Based on the biodiversity effects on ecosystem functioning (B→EF), we specifically address the potential for biodiversity to mitigate climate change impacts on forest ecosystem functioning. For this purpose, we formulate a concept whereby biodiversity may reduce the negative impacts or enhance the positive impacts of climate change on ecosystem functioning. Further B→EF studies on climate change in natural forests are encouraged to elucidate how biodiversity might influence ecosystem functioning. This may be achieved through the detailed scrutiny of large spatial/long temporal scale data sets, such as long-term forest inventories. Forest management strategies based on B→EF have strong potential for augmenting the effectiveness of the roles of forests in the mitigation of climate change impacts on ecosystem functioning.
Topics: Biodiversity; Climate Change; Forests; Models, Biological; Plants; Time Factors
PubMed: 28695682
DOI: 10.1111/brv.12351 -
International Journal of Occupational... Dec 2021As the construction industry continues to develop across the world, it is crucial that the industry begins to integrate digital technologies into all aspects of design,... (Review)
Review
As the construction industry continues to develop across the world, it is crucial that the industry begins to integrate digital technologies into all aspects of design, planning, construction, maintenance and even demolition of construction projects. This review explores the current use of this technology to help mitigate risks on site with a focus on proactive design rather than reactive mitigations, with the aim of directing further research on the topic to help improve the health and safety record in construction. A variety of literature was reviewed specifically relating to the integration of building information modelling into construction alongside an array of construction safety literature. Integrating these two strands of literature has allowed for the suggestion of new practical methods of recording and presenting health and safety information by facilitating a risk identification process that assigns assets with hazards and mitigations.
Topics: Construction Industry; Humans
PubMed: 31684834
DOI: 10.1080/10803548.2019.1689719 -
Applied Network Science 2022Progress has been made in how to suppress epidemic spreading on temporal networks via blocking all contacts of targeted nodes or node pairs. In this work, we develop...
Progress has been made in how to suppress epidemic spreading on temporal networks via blocking all contacts of targeted nodes or node pairs. In this work, we develop contact blocking strategies that remove a fraction of contacts from a temporal (time evolving) human contact network to mitigate the spread of a Susceptible-Infected-Recovered epidemic. We define the probability that a contact (, , ) is removed as a function of a given centrality metric of the corresponding link (, ) in the aggregated network and the time of the contact. The aggregated network captures the number of contacts between each node pair. A set of 12 link centrality metrics have been proposed and each centrality metric leads to a unique contact removal strategy. These strategies together with a baseline strategy (random removal) are evaluated in empirical contact networks via the average prevalence, the peak prevalence and the time to reach the peak prevalence. We find that the epidemic spreading can be mitigated the best when contacts between node pairs that have fewer contacts and early contacts are more likely to be removed. A strategy tends to perform better when the average number contacts removed from each node pair varies less. The aggregated pruned network resulted from the best contact removal strategy tends to have a large largest eigenvalue, a large modularity and probably a small largest connected component size.
PubMed: 35013715
DOI: 10.1007/s41109-021-00436-w -
Animal : An International Journal of... Feb 2017Livestock production is a major contributor to greenhouse gas (GHG) emissions, so will play a significant role in the mitigation effort. Recent literature highlights... (Review)
Review
Livestock production is a major contributor to greenhouse gas (GHG) emissions, so will play a significant role in the mitigation effort. Recent literature highlights different strategies to mitigate GHG emissions in the livestock sector. Animal welfare is a criterion of sustainability and any strategy designed to reduce the carbon footprint of livestock production should consider animal welfare amongst other sustainability metrics. We discuss and tabulate the likely relationships and trade-offs between the GHG mitigation potential of mitigation strategies and their welfare consequences, focusing on ruminant species and on cattle in particular. The major livestock GHG mitigation strategies were classified according to their mitigation approach as reducing total emissions (inhibiting methane production in the rumen), or reducing emissions intensity (Ei; reducing CH4 per output unit without directly targeting methanogenesis). Strategies classified as antimethanogenic included chemical inhibitors, electron acceptors (i.e. nitrates), ionophores (i.e. Monensin) and dietary lipids. Increasing diet digestibility, intensive housing, improving health and welfare, increasing reproductive efficiency and breeding for higher productivity were categorized as strategies that reduce Ei. Strategies that increase productivity are very promising ways to reduce the livestock carbon footprint, though in intensive systems this is likely to be achieved at the cost of welfare. Other strategies can effectively reduce GHG emissions whilst simultaneously improving animal welfare (e.g. feed supplementation or improving health). These win-win strategies should be strongly supported as they address both environmental and ethical sustainability. In order to identify the most cost-effective measures for improving environmental sustainability of livestock production, the consequences of current and future strategies for animal welfare must be scrutinized and contrasted against their effectiveness in mitigating climate change.
Topics: Animal Husbandry; Animal Welfare; Animals; Climate Change; Livestock; Methane; Ruminants
PubMed: 27406001
DOI: 10.1017/S1751731116001440 -
Frontiers in Pharmacology 2021We previously reported several vignettes on types and classes of drugs able to mitigate acute and, in at least one case, late radiation syndromes in mice. Most of these...
We previously reported several vignettes on types and classes of drugs able to mitigate acute and, in at least one case, late radiation syndromes in mice. Most of these had emerged from high throughput screening (HTS) of bioactive and chemical drug libraries using ionizing radiation-induced lymphocytic apoptosis as a readout. Here we report the full analysis of the HTS screen of libraries with 85,000 small molecule chemicals that identified 220 "hits." Most of these hits could be allocated by maximal common substructure analysis to one of 11 clusters each containing at least three active compounds. Further screening validated 23 compounds as being most active; 15 of these were cherry-picked based on drug availability and tested for their ability to mitigate acute hematopoietic radiation syndrome (H-ARS) in mice. Of these, five bore a 4-nitrophenylsulfonamide motif while 4 had a quinoline scaffold. All but two of the 15 significantly ( < 0.05) mitigated H-ARS in mice. We had previously reported that the lead 4-(nitrophenylsulfonyl)-4-phenylpiperazine compound (NPSP512), was active in mitigating multiple acute and late radiation syndromes in mice of more than one sex and strain. Unfortunately, the formulation of this drug had to be changed for regulatory reasons and we report here on the synthesis and testing of active analogs of NPSP512 (QS1 and 52A1) that have increased solubility in water and bioavailability while retaining mitigator activity against H-ARS ( < 0.0001) and other radiation syndromes. The lead quinoline 057 was also active in multiple murine models of radiation damage. Taken together, HTS of a total of 150,000 bioactive or chemical substances, combined with maximal common substructure analysis has resulted in the discovery of diverse groups of compounds that can mitigate H-ARS and at least some of which can mitigate multiple radiation syndromes when given starting 24 h after exposure. We discuss what is known about how these agents might work, and the importance of formulation and bioavailability.
PubMed: 34084139
DOI: 10.3389/fphar.2021.666776 -
Frontiers in Pharmacology 2021There is a need for countermeasures to mitigate lethal acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE). In WAG/RijCmcr rats, ARS...
There is a need for countermeasures to mitigate lethal acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE). In WAG/RijCmcr rats, ARS occurs by 30-days following total body irradiation (TBI), and manifests as potentially lethal gastrointestinal (GI) and hematopoietic (H-ARS) toxicities after >12.5 and >7 Gy, respectively. DEARE, which includes potentially lethal lung and kidney injuries, is observed after partial body irradiation >12.5 Gy, with one hind limb shielded (leg-out PBI). The goal of this study is to enhance survival from ARS and DEARE by polypharmacy, since no monotherapy has demonstrated efficacy to mitigate both sets of injuries. For mitigation of ARS following 7.5 Gy TBI, a combination of three hematopoietic growth factors (polyethylene glycol (PEG) human granulocyte colony-stimulating factor (hG-CSF), PEG murine granulocyte-macrophage-CSF (mGM-CSF), and PEG human Interleukin (hIL)-11), which have shown survival efficacy in murine models of H-ARS were tested. This triple combination (TC) enhanced survival by 30-days from ∼25% to >60%. The TC was then combined with proven medical countermeasures for GI-ARS and DEARE, namely enrofloxacin, saline and the angiotensin converting enzyme inhibitor, lisinopril. This combination of ARS and DEARE mitigators improved survival from GI-ARS, H-ARS, and DEARE after 7.5 Gy TBI or 13 Gy PBI. Circulating blood cell recovery as well as lung and kidney function were also improved by TC + lisinopril. Taken together these results demonstrate an efficacious polypharmacy to mitigate radiation-induced ARS and DEARE in rats.
PubMed: 34079456
DOI: 10.3389/fphar.2021.634477 -
Anti-cancer Agents in Medicinal... May 2011Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of... (Review)
Review
Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it is likely that the mechanisms of radiation mitigation by these compounds in vivo are complex and may differ in the various target tissues. Indicators of oxidative stress are increased in lung and skin radiation injury models, and suppressed by salen Mn complexes. The role of oxidative stress in the renal injury model is unclear, though EUK-207 does mitigate. In certain experimental models, salen Mn complexes have shown "mito-protective" properties, that is, attenuating mitochondrial injury. Consistent with this, EUK-134 suppresses effects of ionizing radiation on mitochondrial function in rat astrocyte cultures. In summary, salen Mn complexes could be useful to mitigate delayed radiation injury to normal tissues following radiation therapy, accidental exposure, or radiological terrorism. Optimization of their mode of delivery and other key pharmaceutical properties, and increasing understanding of their mechanism(s) of action as radiation mitigators, are key issues for future study.
Topics: Animals; Ethylenediamines; Humans; Organometallic Compounds; Oxidative Stress; Radiation Injuries; Radiation Injuries, Experimental; Superoxide Dismutase
PubMed: 21453241
DOI: 10.2174/187152011795677490 -
Frontiers in Plant Science 2016Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the... (Review)
Review
Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including "all" papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity.
PubMed: 27200030
DOI: 10.3389/fpls.2016.00556