Systemic Anti-Inflammatory Agents in the Prevention of Chemoradiation-Induced Mucositis: A Review of Randomised Controlled Trials.

Mucositis is a pathological condition characterised by inflammation and ulceration of the mucous membranes lining the alimentary canal, particularly in the mouth (oral mucositis) and the gastrointestinal tract. It is a common side effect of cancer treatments, including chemotherapy and radiotherapy, and it is sometimes responsible for treatment interruptions. Preventing mucositis throughout the alimentary tract is therefore crucial. However, current interventions mainly target either oral or gastrointestinal side effects. This review aimed to investigate the use of systemically administered anti-inflammatory agents to prevent mucositis in cancer patients undergoing cancer treatment. PubMed, Ovid, Scopus, Web of Science, WHO ICTRP and ClinicalTrials.gov were screened to identify eligible randomised controlled trials (RCTs). The published literature on anti-inflammatory agents provides mixed evidence regarding the degree of efficacy in preventing/reducing the severity of mucositis in most anticancer treatments; however, sample size continued to be a significant limitation, alongside others discussed. Our review yielded a list of several anti-inflammatory agents that exhibit potential mucositis-preventive effects in cancer patients undergoing cancer treatment, which can be used to inform clinical practice.

Distribution and trends of mercury in aquatic and terrestrial biota of New York, USA: a synthesis of 50 years of research and monitoring.

Mercury (Hg) inputs have particularly impacted the northeastern United States due to its proximity to anthropogenic emissions sources and abundant habitats that efficiently convert inorganic Hg into methylmercury. Intensive research and monitoring efforts over the past 50 years in New York State, USA, have informed the assessment of the extent and impacts of Hg exposure on fishes and wildlife. By synthesizing Hg data statewide, this study quantified temporal trends of Hg exposure, spatiotemporal patterns of risk, the role that habitat and Hg deposition play in producing spatial patterns of Hg exposure in fish and other wildlife, and the effectiveness of current monitoring approaches in describing Hg trends. Most temporal trends were stable, but we found significant declines in Hg exposure over time in some long-sampled fish. The Adirondack Mountains and Long Island showed the greatest number of aquatic and terrestrial species with elevated Hg concentrations, reflecting an unequal distribution of exposure risk to fauna across the state. Persistent hotspots were detected for aquatic species in central New York and the Adirondack Mountains. Elevated Hg concentrations were associated with open water, forests, and rural, developed habitats for aquatic species, and open water and forested habitats for terrestrial species. Areas of consistently elevated Hg were found in areas driven by atmospheric and local Hg inputs, and habitat played a significant role in translating those inputs into biotic exposure. Continued long-term monitoring will be important in evaluating how these patterns continue to change in the face of changing land cover, climate, and Hg emissions.

Associations between total mercury, trace minerals, and blood health markers in Northwest Atlantic white sharks (Carcharodon carcharias).

The ecology and life-histories of white sharks make this species susceptible to mercury bioaccumulation; however, the health consequences of mercury exposure are understudied. We measured muscle and plasma total mercury (THg), health markers, and trace minerals in Northwest Atlantic white sharks. THg in muscle tissue averaged 10.0 mg/kg dry weight, while THg in blood plasma averaged 533 µg/L. THg levels in plasma and muscle were positively correlated with shark precaudal length (153-419 cm), and THg was bioaccumulated proportionally in muscle and plasma. Nine sharks had selenium:mercury molar ratios in blood plasma >1.0, indicating that for certain individuals the potential protective effects of the trace mineral were diminished, whereas excess selenium may have protected other individuals. No relationships between plasma THg and any trace minerals or health markers were identified. Thus, we found no evidence of negative effects of Hg bioaccumulation, even in sharks with very high THg.

Identification of 2-Aryl-Quinolone Inhibitors of Cytochrome bd and Chemical Validation of Combination Strategies for Respiratory Inhibitors against Mycobacterium tuberculosis.

Mycobacterium tuberculosis cytochrome bd quinol oxidase (cyt bd), the alternative terminal oxidase of the respiratory chain, has been identified as playing a key role during chronic infection and presents a putative target for the development of novel antitubercular agents. Here, we report confirmation of successful heterologous expression of M. tuberculosis cytochrome bd. The heterologous M. tuberculosis cytochrome bd expression system was used to identify a chemical series of inhibitors based on the 2-aryl-quinolone pharmacophore. Cytochrome bd inhibitors displayed modest efficacy in M. tuberculosis growth suppression assays together with a bacteriostatic phenotype in time-kill curve assays. Significantly, however, inhibitor combinations containing our front-runner cyt bd inhibitor CK-2-63 with either cyt bcc-aa3 inhibitors (e.g., Q203) and/or adenosine triphosphate (ATP) synthase inhibitors (e.g., bedaquiline) displayed enhanced efficacy with respect to the reduction of mycobacterium oxygen consumption, growth suppression, and in vitro sterilization kinetics. In vivo combinations of Q203 and CK-2-63 resulted in a modest lowering of lung burden compared to treatment with Q203 alone. The reduced efficacy in the in vivo experiments compared to in vitro experiments was shown to be a result of high plasma protein binding and a low unbound drug exposure at the target site. While further development is required to improve the tractability of cyt bd inhibitors for clinical evaluation, these data support the approach of using small-molecule inhibitors to target multiple components of the branched respiratory chain of M. tuberculosis as a combination strategy to improve therapeutic and pharmacokinetic/pharmacodynamic (PK/PD) indices related to efficacy.

Recognition of visual kinship signals in chimpanzees (Pan troglodytes) by humans (Homo sapiens).

Associating with kin provides individual benefits but requires that these relationships be detectable. In humans, facial phenotype matching might help assess paternity; however, evidence for it is mixed. In chimpanzees, concealing visual cues of paternity may be beneficial due to their promiscuous mating system and the considerable risk of infanticide by males. On the other hand, detecting kin can also aid chimpanzees in avoiding inbreeding and in forming alliances that improve kin-mediated fitness. Although previous studies assessing relatedness based on facial resemblance in chimpanzees exist, they used images of captive populations in whom selection pressures and reproductive opportunities are controlled and only assessed maternity or paternity of adult offspring. In natural populations, the chances of infanticide are highest during early infancy, suggesting that young infants would benefit most from paternity concealment, whereas adults and subadults would benefit from the detection of all types of kin, including half-siblings. In our experiment, we conducted an online study with human participants, in which they had to assess the relatedness of chimpanzees based on facial similarity. To address previous methodological constraints, we used chimpanzee images across all ages, as well as maternal and paternal half-siblings. We found that kin status was detected above chance across all relatedness categories, with easier kin detection of father-offspring pairs, females, and older chimpanzees. Together, these findings support the existence of paternity confusion in infant chimpanzees and provide a possible mechanism for incest avoidance and kin-based social alliances in older individuals. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Systematic analysis of Kaposi's sarcoma (KS)-associated herpesvirus genomes from a KS case-control study in Cameroon: Evidence of dual infections but no association between viral sequence variation and KS risk.

In sub-Saharan Africa, Kaposi's sarcoma-associated herpesvirus (KSHV) is endemic, and Kaposi's sarcoma (KS) is a significant public health problem. Until recently, KSHV genotype analysis was performed using variable gene regions, representing a small fraction of the genome, and thus the contribution of sequence variation to viral transmission or pathogenesis are understudied. We performed near full-length KSHV genome sequence analysis on samples from 43 individuals selected from a large Cameroonian KS case-control study. KSHV genomes were obtained from 21 KS patients and 22 control participants. Phylogenetic analysis of the K1 region indicated the majority of sequences were A5 or B1 subtypes and all three K15 alleles were represented. Unique polymorphisms in the KSHV genome were observed including large gene deletions. We found evidence of multiple distinct KSHV genotypes in three individuals. Additionally, our analyses indicate that recombination is prevalent suggesting that multiple KSHV infections may not be uncommon overall. Most importantly, a detailed analysis of KSHV genomes from KS patients and control participants did not find a correlation between viral sequence variations and disease. Our study is the first to systematically compare near full-length KSHV genome sequences between KS cases and controls in the same endemic region to identify possible sequence variations associated with disease risk.

Dominance style and intersexual hierarchy in wild bonobos from Wamba.

Dominance hierarchies vary between species and possess particular characteristics depending on the distribution and abundance of food resources that affect the competitive regime. Bonobos have been described as having female intersexual dominance, based mainly on female coalitionary support against males, and more egalitarian hierarchies than chimpanzees. In this study, we tested whether female intersexual dominance is dependent on female coalitions or whether it still arises when only dyadic interactions are considered. We also examined the role of food abundance in shaping dominance style in a wild population of bonobos in Wamba, Democratic Republic of Congo. We found partial support concerning our first prediction in which we expected a male dominance over females when only dyadic agonistic interactions were considered because females were not systematically dominant over males, finding instead an intersexual codominance pattern. We failed to find support for our second prediction that hierarchies become more despotic under low fruit abundance, in fact, we found the opposite pattern. We discuss that codominance based on dyadic interactions in this group may arise as a consequence of male deference rather than females winning conflicts against males and that more despotic hierarchies during high fruit season may arise as a consequence of competition for high-quality resources or variation in party size.

Risk assessment for seafood consumers exposed to mercury and other trace elements in fish from Long Island, New York, USA.

We determined concentrations of Hg, Pb, Cd, Cr, As, Ni, Ag, Se, Cu, and Zn in muscle tissue of six commonly consumed Long Island fish species (black seabass, bluefish, striped bass, summer flounder, tautog, and weakfish, total sample size = 1211) caught off Long Island, New York in 2018 and 2019. Long-term consumption of these coastal fish could pose health risks largely due to Hg exposure; concentrations of the other trace elements were well below levels considered toxic for humans. By combining the measured Hg concentrations in the fish (means ranging from 0.11 to 0.27 mg/kg among the fish species), the average seafood consumption rate, and the current US EPA Hg reference dose (0.0001 mg/kg/d), it was concluded that seafood consumption should be limited to four fish meals per month for adults for some fish (bluefish, tautog) and half that for young children. Molar ratios of Hg:Se exceeded 1 for some black seabass, bluefish, tautog, and weakfish.

Effects of methylmercury on the early life stages of an estuarine forage fish using two different dietary sources.

Marine fish accumulate methylmercury (MeHg) to elevated concentrations, often higher than in freshwater systems. As a neurotoxic compound, high MeHg tissue concentrations could affect fish behavior which in turn could affect their populations. We examined the sublethal effects of MeHg on larvae of the Sheepshead minnow (Cyprinodon variegatus), an estuarine fish, using artificial or natural diets with varying MeHg concentrations (0-4.8 ppm). Larvae were fed control and MeHg-contaminated diets at low or normal (10% of their body mass) daily food rations from 7 to 29 days when they reached juvenile stage. Growth, respiration, swimming activity and prey capture ability were assessed. Food ration affected Hg toxicity in our study. Natural diets containing 3.2 ppm MeHg had no impacts on growth and swimming in fish that were fed normal food rations but depressed growth and swimming at low food rations. MeHg toxicity did not differ between artificial and natural foods, however fish accumulated more MeHg from the former. Artificial food containing 4.8 ppm MeHg only affected prey capture after 21 days of exposure. Sheepshead minnows, a forage fish species occupying a low trophic level in coastal waters, can be MeHg tolerant, especially when food is abundant, and can serve as an enriched Hg source for higher trophic level predators.

Metal concentrations in coastal sharks from The Bahamas with a focus on the Caribbean Reef shark.

Over the last century anthropogenic activities have rapidly increased the influx of metals and metalloids entering the marine environment, which can bioaccumulate and biomagnify in marine top consumers. This may elicit sublethal effects on target organisms, having broad implications for human seafood consumers. We provide the first assessment of metal (Cd, Pb, Cr, Mn, Co, Cu, Zn, As, Ag, and THg) and metalloid (As) concentrations in the muscle tissue of coastal sharks from The Bahamas. A total of 36 individual sharks from six species were evaluated, spanning two regions/study areas, with a focus on the Caribbean reef shark (Carcharhinus perezi), and to a lesser extent the tiger shark (Galeocerdo cuvier). This is due their high relative abundance and ecological significance throughout coastal Bahamian and regional ecosystems. Caribbean reef sharks exhibited some of the highest metal concentrations compared to five other species, and peaks in the concentrations of Pb, Cr, Cu were observed as individuals reached sexual maturity. Observations were attributed to foraging on larger, more piscivorous prey, high longevity, as well a potential slowing rate of growth. We observed correlations between some metals, which are challenging to interpret but may be attributed to trophic level and ambient metal conditions. Our results provide the first account of metal concentrations in Bahamian sharks, suggesting individuals exhibit high concentrations which may potentially cause sublethal effects. Finally, these findings underscore the potential toxicity of shark meat and have significant implications for human consumers.

Separating Thermal and Viscous Effects of Temperature on Copepod Respiration and Energy Budget.

AbstractChanges in temperature alter the viscosity of fluids, which impacts the force needed to move and the diffusion rates of gases. This is particularly salient for organisms that operate at mid to low Reynolds numbers. In this study, we investigated the independent effects of changes in temperature and viscosity on oxygen consumption rates of two coastal copepods (Acartia tonsa and Parvocalanus crassirostris) and used bioenergetic models to predict how these patterns could influence copepods in the natural environment. We found that only temperature influenced copepod oxygen consumption rates, indicating that copepods were not impacted by reduced oxygen diffusivity or increased energetics of movement resulting from higher seawater viscosity. We developed energy budgets based on novel respiration experiments in conjunction with data from the literature and found that cold temperatures do not result in higher scope for growth, because decreased metabolic costs are offset by reduced feeding capability. Our energy budgets imply that observed copepod temperature ranges in natural waters match theoretical ranges of optimal net carbon assimilation. At cold temperatures, feeding on motile prey yielded higher net carbon assimilation compared to feeding on non-motile prey, implying that motile prey are more favorable and may be actively selected for at cold temperatures. Finally, our models predicted that A. tonsa had a higher maximum net carbon assimilation as a percentage of body mass, indicating that copepods that use a similar sink-and-wait feeding strategy may be better able to exploit ephemeral food sources compared to continuous-swimming copepods such as P. crassirostris.

Minor effects of dietary methylmercury on growth and reproduction of the sheepshead minnow Cyprinodon variegatus and toxicity to their offspring.

Methylmercury (MeHg) is a neurotoxic compound that is found in virtually all fish and biomagnifies in aquatic food webs. Although MeHg concentrations in marine and estuarine fish are often elevated, the impacts of MeHg on marine and estuarine fish have largely been understudied. To evaluate the impact of dietary MeHg on marine fish reproduction and effects on their offspring, female juvenile sheepshead minnows (Cyprinodon variegatus) at three months of age were experimentally exposed to MeHg-contaminated diets for two months and then paired with Hg-free males for spawning. Egg production, hatching success of embryos, time to hatching, survival of larvae, growth of larvae and swimming behavior of larvae were determined. Selenium (Se) was also measured and Se/Hg molar ratios were calculated to assess whether Se reduced MeHg toxicity. MeHg had no significant impact on fish reproduction or on survival and growth of larvae. Larvae produced by MeHg-exposed mothers had concentrations of Hg about 1 ppm (dry wt), or about 12% of that in the muscle of their mothers and consistently displayed 6-15% increased swimming speed relative to controls; the ecological significance of this moderate effect on swimming speed requires further study. The Se/Hg molar ratios in these fish, which were >1 in controls (adults and larvae) and MeHg-exposed larvae but <1 in Hg-exposed adults, did not correlate with MeHg effects. The sheepshead minnow, at a low trophic level, appears to have a high tolerance of MeHg; however, it can pass MeHg to higher trophic levels in marine ecosystems where upper level predators have MeHg concentrations sometimes exceeding US FDA safety limits of 1 ppm wet wt.

Copepod feeding strategy determines response to seawater viscosity: videography study of two calanoid copepod species.

Calanoid copepods, depending on feeding strategy, have different behavioral and biological controls on their movements, thereby responding differently to environmental conditions such as changes in seawater viscosity. To understand how copepod responses to environmental conditions are mediated through physical, physiological and/or behavioral pathways, we used high-speed microvideography to compare two copepod species, Acartia hudsonica and Parvocalanus crassirostris, under different temperature, viscosity and dietary conditions. Acartia hudsonica exhibited 'sink and wait' feeding behavior and typically responded to changes in seawater viscosity; increased seawater viscosity reduced particle-capture behavior and decreased the size of the feeding current. In contrast, P. crassirostris continuously swam and did not show any behavioral or physical responses to changes in viscosity. Both species showed a physiological response to temperature, with reduced appendage beating frequency at cold temperatures, but this did not generally translate into effects on swimming speed, feeding flux or active time. Both copepod species swam slower when feeding on diatom rather than dinoflagellate prey, showing that prey type mediates copepod behavior. These results differentiate species-specific behaviors and responses to environmental conditions, which may lead to better understanding of niche separation and latitudinal patterns in copepod feeding and movement strategies.

The cytochrome bc1 complex as an antipathogenic target.

The cytochrome bc1 complex is a key component of the mitochondrial respiratory chains of many eukaryotic microorganisms that are pathogenic for plants or humans, such as fungi responsible for crop diseases and Plasmodium falciparum, which causes human malaria. Cytochrome bc1 is an enzyme that contains two (ubi)quinone/quinol-binding sites, which can be exploited for the development of fungicidal and chemotherapeutic agents. Here, we review recent progress in determination of the structure and mechanism of action of cytochrome bc1 , and the associated development of antimicrobial agents (and associated resistance mechanisms) targeting its activity.

Flexibility in the Energy Balancing Network of Photosynthesis Enables Safe Operation under Changing Environmental Conditions.

Given their ability to harness chemical energy from the sun and generate the organic compounds necessary for life, photosynthetic organisms have the unique capacity to act simultaneously as their own power and manufacturing plant. This dual capacity presents many unique challenges, chiefly that energy supply must be perfectly balanced with energy demand to prevent photodamage and allow for optimal growth. From this perspective, we discuss the energy balancing network using recent studies and a quantitative framework for calculating metabolic ATP and NAD(P)H demand using measured leaf gas exchange and assumptions of metabolic demand. We focus on exploring how the energy balancing network itself is structured to allow safe and flexible energy supply. We discuss when the energy balancing network appears to operate optimally and when it favors high capacity instead. We also present the hypothesis that the energy balancing network itself can adapt over longer time scales to a given metabolic demand and how metabolism itself may participate in this energy balancing.

Mutational analysis of the Qi-site proton pathway in yeast cytochrome bc1 complex.

The respiratory cytochrome bc1 complex functions as a protonmotive ubiquinol:cytochrome c oxidoreductase. Lysine 228 (K228) located within the quinol reduction (Qi) site of the bc1 complex, has been reported as a key residue for proton transfer during the redox chemistry cycle to substrate quinone at Qi. In yeast, while single mutations had no effect, the combination of K228L and F225L resulted in a severe respiratory growth defect and inhibition of O2 consumption in intact cells. The inhibition was overcome by uncoupling the mitochondrial membrane or by suppressor mutations in the region of K228L-F225L. We propose that the K228L mutation introduces energetic (and kinetic) barriers into normal electron- and proton transfer chemistry at Qi, which are relieved by dissipation of the opposing protonmotive force or through the restoration of favourable intraprotein proton transfer networks via suppressor mutation.

Dual infection and recombination of Kaposi sarcoma herpesvirus revealed by whole-genome sequence analysis of effusion samples.

Kaposi sarcoma herpesvirus (KSHV) is the etiological agent of three malignancies, Kaposi sarcoma (KS), primary effusion lymphoma (PEL) and KSHV-associated multicentric Castelman disease. KSHV infected patients may also have an interleukin six-related KSHV-associated inflammatory cytokine syndrome. KSHV-associated diseases occur in only a minority of chronically KSHV-infected individuals and often in the setting of immunosuppression. Mechanisms by which KSHV genomic variations and systemic co-infections may affect the pathogenic pathways potentially leading to these diseases have not been well characterized in vivo. To date, the majority of comparative genetic analyses of KSHV have been focused on a few regions scattered across the viral genome. We used next-generation sequencing techniques to investigate the taxonomic groupings of viruses from malignant effusion samples from fourteen participants with advanced KSHV-related malignancies, including twelve with PEL and two with KS and elevated KSHV viral load in effusions. The genomic diversity and evolutionary characteristics of nine isolated, near full-length KSHV genomes revealed extensive evidence of mosaic patterns across all these genomes. Further, our comprehensive NGS analysis allowed the identification of two distinct KSHV genome sequences in one individual, consistent with a dual infection. Overall, our results provide significant evidence for the contribution of KSHV phylogenomics to the origin of KSHV subtypes. This report points to a wider scope of studies to establish genome-wide patterns of sequence diversity and define the possible pathogenic role of sequence variations in KSHV-infected individuals.

Intra-community infanticide in wild, eastern chimpanzees: a 24-year review.

Infanticide is well documented in chimpanzees and various hypotheses have been proposed to explain this behavior. However, since infanticide by chimpanzees is relatively rare, it has thus far not been possible to thoroughly test these hypotheses. Here we present an analysis of the largest dataset of infanticides from a single community of chimpanzees, a full record of all intra-community infanticides and failed attempts at infanticide over a 24-year period for the Sonso community of chimpanzees in the Budongo Forest, Uganda. We use these data to test four hypotheses for this behavior: the sexual selection hypothesis, male mating competition, resource competition, and meat acquisition. Our dataset consisted of 33 attacks on 30 victims, 11 of which were 'definite' infanticides, four of which 'almost certain', and nine were 'suspected', while nine were 'attempted' infanticides. The majority of attacks where the perpetrators were known (23) had only male attackers and victims were disproportionately young (two-thirds of victims with known ages were under 1 week old). Our data best support the sexual selection hypothesis for infanticide. Cannibalism was infrequent and partial, suggesting meat acquisition was a by-product of infanticide, and there was no evidence to suggest that infanticide was part of a male strategy to eliminate future competitors. Infanticide by females was rare, but we suggest sexual selection, operating through intra-sexual competition, may also be responsible for infanticide by females.

An assessment of temporal trends in mercury concentrations in fish.

The importance of fish consumption as the primary pathway of human exposure to mercury and the establishment of fish consumption advisories to protect human health have led to large fish tissue monitoring programs worldwide. Data on fish tissue mercury concentrations collected by state, tribal, and provincial governments via contaminant monitoring programs have been compiled into large data bases by the U.S. Environmental Protection Agency's Great Lakes National Monitoring Program Office (GLNPO), the Ontario Ministry of the Environment's Fish Contaminants Monitoring and Surveillance Program (FMSP), and many others. These data have been used by a wide range of governmental and academic investigators worldwide to examine long-term and recent trends in fish tissue mercury concentrations. The largest component of the trend literature is for North American freshwater species important in recreational fisheries. This review of temporal trends in fish tissue mercury concentrations focused on published results from freshwater fisheries of North America as well as marine fisheries worldwide. Trends in fish tissue mercury concentrations in North American lakes with marked overall decreases were reported over the period 1972-2016. These trends are consistent with reported mercury emission declines as well as trends in wet deposition across the U.S. and Canada. More recently, a leveling-off in the rate of decreases or increases in fish tissue mercury concentrations has been reported. Increased emissions of mercury from global sources beginning between 1990 and 1995, despite a decrease in North American emissions, have been advanced as an explanation for the observed changes in fish tissue trends. In addition to increased atmospheric deposition, the other factors identified to explain the observed mercury increases in the affected fish species include a systematic shift in the food-web structure with the introduction of non-native species, creating a new or expanding role for sediments as a net source for mercury. The influences of climate change have also been identified as contributing factors, including considerations such as increases in temperature (resulting in metabolic changes and higher uptake rates of methylmercury), increased rainfall intensity and runoff (hydrologic export of organic matter carrying HgII from watersheds to surface water), and water level fluctuations that alter either the methylation of mercury or the mobilization of monomethylmercury. The primary source of mercury exposure in the human diet in North America is from the commercial fish and seafood market which is dominated (>90%) by marine species. However, very little information is available on mercury trends in marine fisheries. Most of the data used in the published marine trend studies are assembled from earlier reports. The data collection efforts are generally intermittent, and the spatial and fish-size distribution of the target species vary widely. As a result, convincing evidence for the existence of fish tissue mercury trends in marine fish is generally lacking. However, there is some evidence from sampling of large, long-lived commercially-important fish showing both lower mercury concentrations in the North Atlantic in response to reduced anthropogenic mercury emission rates in North America and increases in fish tissue mercury concentrations over time in the North Pacific in response to increased mercury loading.