Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections

It\u27s Time to Listen: There is Much to be Learned from the Sounds of Tropical Ecosystems

Knowledge that can be gained from acoustic data collection in tropical ecosystems is low‐hanging fruit. There is every reason to record and with every day, there are fewer excuses not to do it. In recent years, the cost of acoustic recorders has decreased substantially (some can be purchased for under US$50, e.g., Hill et al. 2018) and the technology needed to store and analyze acoustic data is continuously improving (e.g., Corrada Bravo et al. 2017, Xie et al. 2017). Soundscape recordings provide a permanent record of a site at a given time and contain a wealth of invaluable and irreplaceable information. Although challenges remain, failure to collect acoustic data now in tropical ecosystems would represent a failure to future generations of tropical researchers and the citizens that benefit from ecological research. In this commentary, we (1) argue for the need to increase acoustic monitoring in tropical systems; (2) describe the types of research questions and conservation issues that can be addressed with passive acoustic monitoring (PAM) using both short‐ and long‐term data in terrestrial and freshwater habitats; and (3) present an initial plan for establishing a global repository of tropical recordings

Highly precise community science annotations of video camera‐trapped fauna in challenging environments

As camera trapping grows in popularity and application, some analytical limitations persist including processing time and accuracy of data annotation. Typically images are recorded by camera traps although videos are becoming increasingly collected even though they require much more time for annotation. To overcome limitations with image annotation, camera trap studies are increasingly linked to community science (CS) platforms. Here, we extend previous work on CS image annotations to camera trap videos from a challenging environment; a dense tropical forest with low visibility and high occlusion due to thick canopy cover and bushy undergrowth at the camera level. Using the CS platform Chimp&See, established for classification of 599 956 video clips from tropical Africa, we assess annotation precision and accuracy by comparing classification of 13 531 1-min video clips by a professional ecologist (PE) with output from 1744 registered, as well as unregistered, Chimp&See community scientists. We considered 29 classification categories, including 17 species and 12 higher-level categories, in which phenotypically similar species were grouped. Overall, annotation precision was 95.4%, which increased to 98.2% when aggregating similar species groups together. Our findings demonstrate the competence of community scientists working with camera trap videos from even challenging environments and hold great promise for future studies on animal behaviour, species interaction dynamics and population monitoring. © 2024 The Author(s). Remote Sensing in Ecology and Conservation published by John Wiley & Sons Ltd on behalf of Zoological Society of London

Modified Alvarado Scoring System as a diagnostic tool for Acute Appendicitis at Bugando Medical Centre, Mwanza, Tanzania

<p>Abstract</p> <p>Background</p> <p>Decision-making in patients with acute appendicitis poses a diagnostic challenge worldwide, despite much advancement in abdominal surgery. The Modified Alvarado Scoring System (MASS) has been reported to be a cheap and quick diagnostic tool in patients with acute appendicitis. However, differences in diagnostic accuracy have been observed if the scores were applied to various populations and clinical settings. The purpose of this study was to evaluate the diagnostic value of Modified Alvarado Scoring System in patients with acute appendicitis in our setting.</p> <p>Methods</p> <p>A cross-sectional study involving all patients suspected to have acute appendicitis at Bugando Medical Centre over a six-month period between November 2008 and April 2009 was conducted. All patients who met the inclusion criteria were consecutively enrolled in the study. They were evaluated on admission using the MASS to determine whether they had acute appendicitis or not. All patients underwent appendicectomy according to the hospital protocol. The decision to operate was the prerogative of the surgeon or surgical resident based on overall clinical judgment and not the MASS. The diagnosis was confirmed by histopathological examination. Data was collected using a pre-tested coded questionnaire and analyzed using SPSS statistical computer software.</p> <p>Results</p> <p>A total number of 127 patients were studied. Their ages ranged from eight to 76 years (mean 29.64 ± 12.97). There were 37 (29.1%) males and 90 (70.9%) females (M: F = 1:2.4). All patients in this study underwent appendicectomy. The perforation rate was 9.4%. Histopathological examination confirmed appendicitis in 85 patients (66.9%) and the remaining 42 patients had normal appendix giving a negative appendicectomy rate of 33.1% (26.8% for males and 38.3% for females). The sensitivity and specificity of MASS in this study were 94.1% (males 95.8% and females 88.3%) and 90.4% (males 92.9% and females 89.7%) respectively. The Positive Predictive Value and Negative Predictive Value were 95.2% (males 95.5% and females 90.6%) and 88.4% (males 89.3% and females 80.1%) respectively. The accuracy of MASS was 92.9% (males 91.5% and females 87.6%).</p> <p>Conclusion</p> <p>The study shows that use of MASS in patients suspected to have acute appendicitis provides a high degree of diagnostic accuracy and can be employed at Bugando Medical Centre to improve the diagnostic accuracy of acute appendicitis and subsequently reduces negative appendicectomy and complication rates. However, additional investigations may be required to confirm the diagnosis in case of atypical presentation.</p

Chimpanzees (Pan troglodytes) indicate mammalian abundance across broad spatial scales

Ongoing ecosystem change and biodiversity decline across the Afrotropics call for tools to monitor the state of biodiversity or ecosystem elements across extensive spatial and temporal scales. We assessed relationships in the co-occurrence patterns between great apes and other medium to large-bodied mammals to evaluate whether ape abundance serves as a proxy for mammal diversity across broad spatial scales. We used camera trap footage recorded at 22 research sites, each known to harbor a population of chimpanzees, and some additionally a population of gorillas, across 12 sub-Saharan African countries. From ~350,000 1-min camera trap videos recorded between 2010 and 2016, we estimated mammalian community metrics, including species richness, Shannon diversity, and mean animal mass. We then fitted Bayesian Regression Models to assess potential relationships between ape detection rates (as proxy for ape abundance) and these metrics. We included site-level protection status, human footprint, and precipitation variance as control variables. We found that relationships between detection rates of great apes and other mammal species, as well as animal mass were largely positive. In contrast, relationships between ape detection rate and mammal species richness were less clear and differed according to site protection and human impact context. We found no clear association between ape detection rate and mammal diversity. Our findings suggest that chimpanzees hold potential as indicators of specific elements of mammalian communities, especially population-level and composition-related characteristics. Declines in chimpanzee populations may indicate associated declines of sympatric medium to large-bodied mammal species and highlight the need for improved conservation interventions.Changes in chimpanzee abundance likely precede extirpation of sympatric mammals

Complex variation in Afrotropical mammal communities with human impact

The diversity and composition of mammal communities are strongly influenced by human activities, though these relationships may vary across broad scales. Understanding this variation is key to conservation, as it provides a baseline for planning and evaluating management interventions. We assessed variation in the structure and composition of Afrotropical medium and large mammal communities within and outside protected areas, and under varying human impact. We collected data at 512 locations from 22 study sites in 12 Afrotropical countries over 7 years and 3 months (2011–2018) with 164,474 camera trap days in total. Half of these sites are located inside protected areas and half in unprotected areas. The sites are comparable in that they all harbor at least one great ape species, indicating a minimum level of habitat similarity, though they experience varying degrees of human impact. We applied Bayesian Regression models to relate site protection status and the degree of human impact to mammal communities. Protected area status was positively associated with the proportion of all threatened species, independent of the degree of human impact. Similarly, species richness was associated with area protection but was more sensitive to human impact. For all other attributes of the mammal communities, the pattern was more complex. The influence of human impact partially overrides the positive effects of protected area status, resulting in comparable mammal communities being observed both within protected areas and in similarly remote locations outside these areas. We observed a common pattern for large carnivores, whose probability of occurrence declined significantly with increasing human impact, independent of site protection status. Mammal communities benefit from sustainability measures of socio-economic context that minimize human impact. Our results support the notion that conservation of mammalian species can be achieved by reducing human impact through targeted conservation measures, adopting landscape-level management strategies, fostering community engagement, and safeguarding remote habitats with high mammal diversity

Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics

Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections.This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50-200 µg/mL, which were well below the concentrations required to limit bacterial growth (530-1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects.These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections

Feasibility, acceptability, and effectiveness of non-pharmaceutical interventions against infectious diseases among crisis-affected populations: a scoping review

BACKGROUND: Colonization of large part of Europe by the Asian tiger mosquito Aedes albopictus is causing autochthonous transmission of chikungunya and dengue exotic arboviruses. While pyrethroids are recommended only to reduce/limit transmission, they are widely implemented to reduce biting nuisance and to control agricultural pests, increasing the risk of insurgence of resistance mechanisms. Worryingly, pyrethroid resistance (with mortality < 70%) was recently reported in Ae. albopictus populations from Italy and Spain and associated with the V1016G point mutation in the voltage-sensitive sodium channel gene conferring knockdown resistance (kdr). Genotyping pyrethroid resistance-associated kdr mutations in field mosquito samples represents a powerful approach to detect early signs of resistance without the need for carrying out phenotypic bioassays which require availability of live mosquitoes, dedicated facilities and appropriate expertise. METHODS: Here we report results on the PCR-genotyping of the V1016G mutation in 2530 Ae. albopictus specimens from 69 sampling sites in 19 European countries. RESULTS: The mutation was identified in 12 sites from nine countries (with allele frequencies ranging from 1 to 8%), mostly distributed in two geographical clusters. The western cluster includes Mediterranean coastal sites from Italy, France and Malta as well as single sites from both Spain and Switzerland. The eastern cluster includes sites on both sides of the Black Sea in Bulgaria, Turkey and Georgia as well as one site from Romania. These results are consistent with genomic data showing high connectivity and close genetic relationship among West European populations and a major barrier to gene flow between West European and Balkan populations. CONCLUSIONS: The results of this first effort to map kdr mutations in Ae. albopictus on a continental scale show a widespread presence of the V1016G allele in Europe, although at lower frequencies than those previously reported from Italy. This represents a wake-up call for mosquito surveillance programs in Europe to include PCR-genotyping of pyrethroid resistance alleles, as well as phenotypic resistance assessments, in their routine activities