Bioactive triterpenoid compounds of Poria cocos (Schw.) Wolf in the treatment of diabetic ulcers via regulating the PI3K-AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic ulcers represent a chronic condition characterized by prolonged hyperglycemia and delayed wound healing, accompanied by endocrine disorders, inflammatory responses, and microvascular damage in the epidermal tissue, demanding effective clinical treatment approaches. For thousands of years, ancient Chinese ethnopharmacological studies have documented the use of Poria cocos (Schw.) Wolf in treating diabetic ulcers. Recent research has substantiated the diverse pharmacological effects of Poria cocos (Schw.) Wolf, including its potential to alleviate hyperglycemia and exhibit anti-inflammatory, antioxidant, and immune regulatory properties, which could effectively mitigate diabetic ulcer symptoms. Furthermore, being a natural medicine, Poria cocos (Schw.) Wolf has demonstrated promising therapeutic effects and safety in the management of diabetic ulcers, holding significant clinical value. Despite its potential clinical efficacy and applications in diabetic ulcer treatment, the primary active components and underlying pharmacological mechanisms of Poria cocos (Schw.) Wolf remains unclear. Further investigations are imperative to establish a solid foundation for drug development in this domain. AIM OF THE STUDY AND MATERIALS AND METHODS: In this study, we aimed to identify the active compounds and potential targets of Poria cocos (Schw.) Wolf using UHPLC-Q-TOF-MS and TCMSP databases. Additionally, we attempt to identify targets related to diabetic ulcers. Following enrichment analysis, a network of protein-protein interactions was constructed to identify hub genes based on the common elements between the two datasets. To gain insights into the binding activities of the hub genes and active ingredients, molecular docking analysis was employed. Furthermore, to further validate the therapeutic effect of Poria cocos (Schw.) Wolf, we exerted in vitro experiments using human umbilical vein vascular endothelial cells and human myeloid leukemia monocytes (THP-1). The active ingredient of Poria cocos (Schw.) Wolf was applied in these experiments. Our investigations included various assays, such as CCK-8, scratch test, immunofluorescence, western blotting, RT-PCR, and flow cytometry, to explore the potential of Poria cocos (Schw.) Wolf triterpenoid extract (PTE) in treating diabetic ulcers. RESULTS: The findings here highlighted PTE as the primary active ingredient in Poria cocos (Schw.) Wolf. Utilizing network pharmacology, we identified 74 potential targets associated with diabetic ulcer treatment for Poria cocos (Schw.) Wolf, with five hub genes (JUN, MAPK1, STAT3, AKT1, and CTNNB1). Enrichment analysis revealed the involvement of multiple pathways in the therapeutic process, with the PI3K-AKT signaling pathway showing significant enrichment. Through molecular docking, we discovered that relevant targets within this pathway exhibited strong binding with the active components of Poria cocos (Schw.) Wolf. In vitro experiments unveiled that PTE (10 mg/L) facilitated the migration of human umbilical vein vascular endothelial cells (P < 0.05). PTE also increased the expression of CD31 and VEGF mRNA (P < 0.05) while activating the expressions of p-PI3K and p-AKT (P < 0.05). Moreover, PTE demonstrated its potential by reducing the expression of IL-1ß, IL-6, TNF-α, and NF-κB mRNA in THP-1 (P < 0.05) and fostering M2 macrophage polarization. These results signify the potential therapeutic effects of PTE in treating diabetic ulcers, with its beneficial actions mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: PTE is the main active ingredient in Poria cocos (Schw.) Wolf that exerts therapeutic effects. Through PI3K-AKT signaling pathway activation and inflammatory response reduction, PTE promotes angiogenesis, thereby healing diabetic ulcers.

Epidemiological survey of infectious agents in free-ranging maned wolves (Chrysocyon brachyurus) in Northeastern Brazil.

Infectious diseases are one of the most concerning threats to maned wolves (Chrysocyon brachyurus) due to the potential impact on free-ranging populations. The species is currently classified as vulnerable according to the national list of threatened species and occurs mainly in open habitats, such as the Cerrado, a tropical savannah, which comprises its main distribution area in Brazil. In the northeastern region, it occurs in the Cerrado of Bahia, Piauí, Maranhão, and Tocantins states. Therefore, this study aimed to investigate the occurrence of infectious agents in Chrysocyon brachyurus through an epidemiological assessment of free-ranging individuals in western Bahia, specifically in the Barreiras microregion, a Cerrado area intensely fragmented and anthropized by agricultural activity. Eleven specimens were evaluated for serological titration, antigen research, and genetic material research for canine distemper virus (CDV), canine parvovirus (CPV), adenovirus-canine-type 1 (CAdV-1), canine coronavirus (CCoV), Leptospira interrogans and Toxoplasma gondii from 2020 to 2022. In addition to maned wolves, domestic dogs were also evaluated and tested. All maned wolves (100%) evaluated by the dot-ELISA technique exhibited immunoglobulin M (IgM) and seven (64%) exhibited immunoglobulin G (IgG) against CDV and CPV, while 100% exhibited IgG against CDV when using the immunochromatographic technique. Regarding CAdV-1, 90% were seropositive for IgG, while 64% exhibited IgG against T. gondii. Nine dogs from the region were also sampled, and all (100%) exhibited IgM and IgG against CDV and CPV. For IgG against T. gondii and against CAdV-1, 90% of the animals were seropositive. Molecular evaluation yielded negative results for all maned wolves and dogs assessed for CAdV-1, CDV, and T. gondii, as well as the CCoV antigen. These data indicate the occurrence of viral agents and Toxoplasma gondii in maned wolves and dogs, suggesting circulation in both populations.

A RETROSPECTIVE STUDY OF DISEASE PROCESSES IN MANED WOLVES (CHRYSOCYON BRACHYURUS) IN NORTH AMERICAN ZOOLOGICAL INSTITUTIONS WITH EMPHASIS ON UROLITHIASIS, INFLAMMATORY BOWEL DISEASE, AND NEOPLASIA.

The objective of this retrospective study is to summarize causes of disease and mortality in maned wolves (Chrysocyon brachyurus) in the North American Species Survival Plan Program (SSP) population. This information will inform and enhance animal health, husbandry, and conservation efforts. Pathology reports were requested from all zoological institutions housing maned wolves between 1930 and 2021. Data were reviewed and cause of death (COD) and reported diseases were summarized and compared by age group, organ system and disease process. One hundred and seventy-one wolves, 82 females and 89 males, met the inclusion criteria. The majority were geriatric (>11 yr; n = 96) or adult (2-11 yr; n = 67). Noninfectious diseases were the most common COD by process (n = 94; 54.9%). For COD by organ system, diseases of the digestive (n = 41) and urinary (n = 34) systems were most common. Neoplasia was the most common noninfectious COD and was the primary COD in 37 wolves (21.6% overall; 39.4% of noninfectious diseases). A total of 145 benign (n = 72) and malignant (n = 73) neoplasms were diagnosed in 44 individuals. Dysgerminoma was the most commonly reported tumor (n = 18), and was the most common neoplastic COD (n = 8). Cystinuria or urolithiasis (n = 71) and gastritis, enteritis, enterocolitis, or colitis (n = 50) (overall and grouped in each system due to presumed common underlying cause) were also common but were more often reported as comorbidities than as COD (n = 16 and n = 11, respectively). Infectious COD were reported in 17 wolves and included babesiosis (n = 4), acanthocephalans (n = 2), and one viral infection. Infections with a variety of bacteria in different organ systems were a COD in eight wolves.

Efficacy and safety of traditional plant-based medicines for preventing chronic oxaliplatin-induced peripheral neurotoxicity in patients with colorectal cancer: A systematic review and meta-analysis with core herb contribution.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional plant-based medicines (TMs) have been widely used to prevent chronic oxaliplatin-induced peripheral neurotoxicity (OIPN). However, the prevention and safety of TMs for chronic OIPN remain ambiguous. Furthermore, diverse TM prescriptions and complicated components limit in-depth research on the mechanisms of TMs. AIM OF THIS STUDY: To determine core TMs and potential pharmacological pathways on the basis of a thorough investigation into the preventive benefits and safety of oral TMs for chronic OIPN in colorectal cancer (CRC). METHODS: A search of the PubMed, Cochrane, Embase, CNKI, VIP, and Wanfang databases for RCTs reporting on TMs for chronic OIPN was conducted through December 1, 2022. Subgroup analysis, sensitivity analysis and meta-regression were applied to assess the impacts of influencing variables. The assessment of Risk of Bias was relied on Cochrane Risk of Bias tool. The funnel plot, Egger's test, and the Trim and Fill method were applied to identify potential publication bias. Trial sequential analyses (TSA) were carried out by the TSA tool to increase the robustness. The assessment of the quality of evidence was according to the GRADE system. System pharmacology analysis was employed to screen core herbal combinations to elucidate possible mechanisms for preventing chronic OIPN in CRC. RESULTS: The pooled effect estimate with robustness increased by TSA analysis demonstrated that oral TMs appeared to significantly decrease the incidence of chronic OIPN (RR = 0.66, 95% CI (0.56, 0.78); P＜0.00001), leukocytopenia (RR = 0.65, 95% CI (0.54,0.79); P＜0.00001), and nausea and vomiting (RR = 0.72, 95% CI (0.61,0.84); P＜0.0001) as well as improve the Objective Response Rate (ORR) (RR = 1.31, 95% CI (1.09,1.56); P = 0.003). The incidence of severe chronic OIPN was revealed a significant reduction, particularly when chemotherapy was administered for periods of time shorter than six months (RR = 0.33, 95% CI (0.15,0.71); P = 0.005; actuation duration＜3 months; RR = 0.33, 95% CI (0.17,0.62); P = 0.0007; actuation duration≥3 months, ＜6 months). The considerable heterogeneity among studies may be attributable to the severity of dysfunction categorized by grade and accumulated dosage. Using core TMs consisting of Astragalus membranaceus (Fisch.) Bunge, Atractylodes Macrocephala Koidz., Poria cocos (Schw.) Wolf, and Codonopsis pilosula (Franch.) Nannf. To regulate nuclear factor-kappa B against inflammation caused by activation of microglia might be an approach to preventing chronic OIPN. CONCLUSIONS: TMs appear to be effective and safe in the prevention of chronic OIPN, especially severe chronic OIPN. Additionally, core TMs consisting of Astragalus membranaceus (Fisch.) Bunge, Atractylodes Macrocephala Koidz., Poria cocos (Schw.) Wolf, and Codonopsis pilosula (Franch.) Nannf were presumably responsible for reducing the incidence of chronic OIPN, and the mechanism may be related to relieving inflammation. However, quality-assured trials with long-term follow-up for exploring inflammatory factors and preliminary research on core TMs and pharmacological pathways are needed.

The anti-hyperlipidemic effects of Poria cocos (Schw.) Wolf extract: Modulating cholesterol homeostasis in hepatocytes via PPARα pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos (Schw.) Wolf (Polyporaceae, P.cocos), which is born on the pine root, has a history of more than two thousand years of medicine in China. P.cocos was first recorded in the Shennong's Herbal Classic, studies have proved its lipid-lowering effect. AIM OF STUDY: The aim of study was to investigate the underlying mechanism of P.cocos extract on hyperlipidemia. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats aged 9-12 weeks were intraperitoneally (IP) injected with Triton-WR 1339 to establish an acute hyperlipidemia model. At 0 h and 20 h after the model was established, low and high doses of P.cocos extract or simvastatin were given twice. After 48 h, the rats were sacrificed, and liver and serum samples were collected for analysis. The cell model was constructed by treating L02 cells with 1% fat emulsion-10% FBS-RPMI 1640 medium for 48 h. At the same time, low and high doses of P.cocos extract and simvastatin were administered. Oil red O staining was used to evaluate the lipid accumulation in the cells, and H&E staining was used to evaluate the liver lesions of rats. Real-time quantitative PCR and western blotting were used to detect the expressions of lipid metabolism-related genes. RESULTS: P.cocos extract relieved lipid accumulation in vitro and alleviated hyperlipidemia in vivo. Both gene and protein expressions of peroxisome proliferator-activated receptor α (PPARα) were shown to be up-regulated by P.cocos extract. Additionally, P.cocos extract down-regulated the expressions of fatty acid synthesis-related genes sterol regulatory element-binding protein-1 (SREBP-1), Acetyl-CoA Carboxylase 1 (ACC1) and fatty acid synthase (FAS), while up-regulated the expressions of cholesterol metabolism-related genes liver X receptor-α (LXRα), ATP-binding cassette transporter A1 (ABCA1), cholesterol 7alpha-hydroxylase (CYP7A1) and low density lipoprotein receptor (LDLR), which were reversed by the treatment with the PPARα inhibitor GW6471. CONCLUSION: P.cocos extract ameliorates hyperlipidemia and lipid accumulation by regulating cholesterol homeostasis in hepatocytes through PPARα pathway. This study provides evidence that supplementation with P.cocos extract could be a potential strategy for the treatment of hyperlipidemia.

High genetic diversity of Echinococcus canadensis G10 in northeastern Asia: is it the region of origin?

Echinococcus canadensis consists of 4 genotypes: G6, G7, G8 and G10. While the first 2 predominantly infect domestic animals, the latter are sylvatic in nature involving mainly wolves and cervids as hosts and can be found in the northern temperate to Arctic latitudes. This circumstance makes the acquisition of sample material difficult, and little information is known about their genetic structure. The majority of specimens analysed to date have been from the European region, comparatively few from northeast Asia and Alaska. In the current study, Echinococcus spp. from wolves and intermediate hosts from the Republic of Sakha in eastern Russia were examined. Echinococcus canadensis G10 was identified in 15 wolves and 4 cervid intermediate hosts. Complete mitochondrial cytochrome c oxidase subunit 1 (cox1) sequences were obtained from 42 worm and cyst specimens from Sakha and, for comparison, from an additional 13 G10 cysts from Finland. For comparative analyses of the genetic diversity of G10 of European and Asian origin, all available cox1 sequences from GenBank were included, increasing the number of sequences to 99. The diversity found in northeast Asia was by far higher than in Europe, suggesting that the geographic origin of E. canadensis (at least of G10) might be northeast Asia.

[Prevalence of Echinococcus infections in wild carnivores based on copro - DNA tests in Serthar County of Sichuan Province].

OBJECTIVE: To investigate the prevalence of Echinococcus infections in wild carnivores in Serthar County, Sichuan Province, so as to provide insights into echinococcosis control in local areas. METHODS: Stool samples were collected from wild carnivores in Serthar County, Sichuan Province in May 2021, and the host sources of stool samples and Echinococcus infections were identified using PCR assays. The prevalence of E. multilocularis, E. granulosus and E. shiquicus infections was estimated in different hosts. RESULTS: A total of 583 stool samples were collected from wild carnivores, including 147 stool samples from fox, 154 from wolf, 227 from wild dogs and 11 from lynx. The overall prevalence of E. multilocularis, E. granulosus and E. shiquicus infections was 5.68%, 0.19% and 14.20% in canine stool samples, and no E. granulosus infection was detected in fox stool samples, while the prevalence of E. multilocularis and E. shiquicus infections was 0.68% and 47.62% in fox stool samples (χ2 = 88.41, P < 0.001). No E. granulosus or E. shiquicus infection was detected in wolf stool samples, and the prevalence of E. multilocularis infection was 10.39% in wolf stool samples. The prevalence of E. multilocularis, E. granulosus and E. shiquicus infections was 5.73%, 0.44% and 2.20% in canine stool samples (χ2 = 12.13, P < 0.01). In addition, the prevalence of E. multilocularis infections was significantly higher in wolf stool samples than in canine and fox stool samples (χ2 = 13.23, P < 0.01), and the prevalence of E. shiquicus infections was significantly higher in fox stool samples than in canine and wolf stool samples (χ2 = 187.01, P < 0.001). No Echinococcus infection was identified in 11 lynx stool samples. CONCLUSIONS: The prevalence of Echinococcus infections is high in wild canines in Serthar County, Sichuan Province. Wolf, wild dog and fox all participate in the wild life cycle of E. multilocularis in Serthar County, and wolf and wild dogs may play a more important role.

CanISO: a database of genomic and transcriptomic variations in domestic dog (Canis lupus familiaris).

BACKGROUND: The domestic dog, Canis lupus familiaris, is a companion animal for humans as well as an animal model in cancer research due to similar spontaneous occurrence of cancers as humans. Despite the social and biological importance of dogs, the catalogue of genomic variations and transcripts for dogs is relatively incomplete. RESULTS: We developed CanISO, a new database to hold a large collection of transcriptome profiles and genomic variations for domestic dogs. CanISO provides 87,692 novel transcript isoforms and 60,992 known isoforms from whole transcriptome sequencing of canine tumors (N = 157) and their matched normal tissues (N = 64). CanISO also provides genomic variation information for 210,444 unique germline single nucleotide polymorphisms (SNPs) from the whole exome sequencing of 183 dogs, with a query system that searches gene- and transcript-level information as well as covered SNPs. Transcriptome profiles can be compared with corresponding human transcript isoforms at a tissue level, or between sample groups to identify tumor-specific gene expression and alternative splicing patterns. CONCLUSIONS: CanISO is expected to increase understanding of the dog genome and transcriptome, as well as its functional associations with humans, such as shared/distinct mechanisms of cancer. CanISO is publicly available at https://www.kobic.re.kr/caniso/ .

Prevalence of intestinal parasites in street dogs (Canis lupus familiaris) with highlights on zoonosis in Lalitpur, Nepal.

BACKGROUND: The presence of intestinal parasites influences the growth and well-being of canids. Additionally, infected dogs and their faeces with considerably higher eggs/oocysts released per gram (epg/opg) of zoonotic parasites contribute to parasitic spillover to humans, domestic animals and sympatric wildlife. OBJECTIVES: The current study aimed to reveal the prevalence of intestinal parasites (protozoa and helminths) and to list the zoonotically significant parasites in free-roaming street dogs in Lalitpur Metropolitan City, Nepal. METHODS: Fresh faecal samples (n = 332) were collected from feral dogs of varying ages and sexes and transported to the research laboratory. The copro microscopic examination was carried out via direct wet mount, formalin ethyl acetate sedimentation, saturated salt flotation, acid-fast staining and sporulation techniques. RESULTS: Coproscopy revealed an overall 95.7% (318/332) prevalence rate with 23 diverse species of intestinal parasites (10 protozoa and 13 helminths). Among them, 5 protozoa and 11 helminths possessed zoonotic potential, and their overall prevalence was 92.5%. Helminth's overall prevalence was double that of the protozoa (87.7% vs. 43%). Polyparasitism was dominant over mono parasitism (79.5% vs. 16.3%), and co-infection of up to seven species of parasites at a time was recorded. CONCLUSIONS: Urban street dogs harboured a higher prevalence of intestinal parasites that varied with age and sex. Since most of the reported parasites are zoonotic, dog density and parasitic richness indicate a greater spillover risk to humans and domestic animals. Furthermore, this study also provides appropriate 'baseline' data for assessing effective control measures against parasitic infestations among street dogs and controlling their transmission to humans.

Unusual presentation of telangiectasia macularis eruptiva perstans at the site of healed herpes zoster; Wolf's isotopic response.

There are several reported cases of Wolf's isotopic response, including infections, cancers, inflammatory and immune-related disorders. It is interesting that the majority of these occurred after herpes zoster (HZ) had healed. In this article, we describe an unusual case of adult mastocytosis/telangiectasia macularis eruptiva perstans (TMEP) at the location of recovered HZ. Given that adult mastocytosis is thought to be caused by dysregulation of the mast cell growth factor receptor, the c-Kit proto-oncogene (CD117), and the fact that the varicella zoster virus-infected cutaneous lesions contain CD117-positive mast cells (CD117+MCs), we hypothesize that CD117+ MCs may be in charge of the local immunological response and cytokine release those results in TMEP after HZ.

Dog Life Spans and the Evolution of Aging.

AbstractThe basic tenets of the evolutionary theories of senescence are well supported. However, there has been little progress in determining the relative influences of mutation accumulation and life history optimization. The causes of the well-established inverse relationship between life span and body size across dog breeds are used here to test these two classes of theories. The life span-body size relationship is confirmed for the first time after controlling for breed phylogeny. The life span-body size relationship cannot be explained by evolutionary responses to differences in extrinsic mortality either of contemporary breeds or of breeds at their establishment. The development of breeds larger and smaller than ancestral gray wolves has occurred through changes in early growth rate. This may explain the increase in the minimum age-dependent mortality rate with breed body size and thus higher age-dependent mortality throughout adult life. The main cause of this mortality is cancer. These patterns are consistent with the optimization of life history as described by the disposable soma theory of the evolution of aging. The dog breed life span-body size relationship may be the result of the evolution of greater defense against cancer lagging behind the rapid increase in body size during recent breed establishment.

Echinococcus Species Infections among Wild Canids in Pennsylvania, USA.

Echinococcus species are zoonotic tapeworms that can impact the health of wildlife, domestic animals, livestock, and humans. Two species of interest in North America are Echinococcus multilocularis and Echinococcus canadensis (Echinococcus granulosus sensu lato). The primary wildlife definitive hosts for E. multilocularis and E. canadensis are similar, including red foxes (Vulpes vulpes), gray foxes (Urocyon cinereoargenteus), coyotes (Canis latrans), and wolves (Canis lupus). These two Echinococcus spp. use different intermediate hosts, including small mammals for E. multilocularis and artiodactylids for E. canadensis. Although historically absent from much of the eastern US, recent reports in new US states (e.g., Virginia, Vermont, Maine, Missouri) highlight the need for Echinococcus spp. surveillance in this region. During 2019-2020, 308 gastrointestinal tracts were collected from wild canids in Pennsylvania and microscopically screened for adult Echinococcus species. Two coyotes (2/155) were co-infected with both E. multilocularis and E. canadensis as determined by molecular confirmation. No red foxes (n=137) or gray foxes (n=16) were positive. These data indicate both Echinococcus species are present in Pennsylvanian coyotes, highlighting the need to better understand the ecological and epidemiological consequences for human and animal health.

Exploring the genetic diversity of genotypes G8 and G10 of the Echinococcus canadensis cluster in Europe based on complete mitochondrial genomes (13 550-13 552 bp).

Echinococcus granulosus sensu lato is a group of tapeworm species known to cause cystic echinococcosis. Within this group, the Echinococcus canadensis cluster includes genotypes G8 and G10 that have a predominantly sylvatic life cycle ­ transmission occurs between wild cervids and wolves. Relatively few studies have explored the genetic variation of the elusive G8 and G10, and their extent of genetic variation is yet to be investigated at the complete mitochondrial (mt) genome level. The aim was to explore the genetic variation of these 2 genotypes in Europe using complete mtDNA sequences and provide a high-quality reference dataset for future studies. Sequences of complete mt genomes were produced for 29 samples of genotype G8 and G10 from wolves, moose, reindeer and roe deer, originating from Finland, Sweden, Russia, Poland, Latvia and Estonia. Genetic variation was explored based on phylogenetic network analysis, revealing marked differences between G8 and G10 (over 400 mutations), and more detailed patterns of variability within the 2 genotypes than previously observed. Understanding the mt genetic composition of a species provides a baseline for future studies aiming to understand whether this mt distinctiveness is mirrored in the nuclear genome and whether it has any impact on any phenotypic traits or parasite transmission.

Indoor radon survey in Whitehorse, Canada, and dose assessment.

Radon-222 (222Rn) and its decay products are the primary sources of a population's exposure to background ionizing radiation. Radon decay products are the leading cause of lung cancer for non-smokers and the second leading cause of lung cancer after smoking for smokers. A community-driven long-term radon survey was completed in 232 residential homes in different subdivisions of Whitehorse, the capital of the Yukon, during the heating season from November to April in 2016-2017 and in 2017-2018. Radon concentrations were measured in living rooms and bedrooms on ground floors. The arithmetic and geometric means of indoor radon activity concentrations in different subdivisions of Whitehorse ranged from 52 ± 0.6 Bq m-3and 37 ± 2.3 Bq m-3in the Downtown area of Whitehorse to 993.0 ± 55.0 Bq m-3and 726.2 ± 2.4 Bq m-3in Wolf Creek. Underlying geology and glacial surfaces may partly explain these variations of indoor radon concentrations in subdivisions of Whitehorse. A total of 78 homes (34.0%) had radon concentrations higher than 100 Bq m-3, 47 homes (20.5%) had concentrations higher than 200 Bq m-3and 33 homes (14.4%) had concentrations higher than 300 Bq m-3. The indoor radon contribution to the annual effective inhalation dose to residents ranged from 3.0 mSv in the Downtown area to 51.0 mSv in Wolf Creek. The estimated annual average dose to adults in Whitehorse, Yukon, is higher than the world's average annual effective dose of 1.3 mSv due to the inhalation of indoor radon. The annual radon inhalation effective dose was assessed using radon measurements taken during winter; hence the assessed dose may be overestimated. Cost-efficient mitigation methods are available to reduce radon in existing buildings and to prevent radon entry into new buildings.

Investigating the free-roaming dog population and gastrointestinal parasite diversity in Tulúm, México.

Free-roaming domestic dogs (Canis lupus familiaris) pose major conservation and public health risks worldwide. To better understand the threat of domestic dogs to wildlife and people and add to the growing literature on free-roaming dog ecology, a study was conducted to estimate the dog population in Tulúm, México. A modified mark-recapture technique and program MARK were used to obtain dog population estimates along six different transects dividing the city. Population estimates ranged from 19.75 dogs in one transect to 101.841 dogs in another, with 150 total dogs identified throughout the study and an estimated minimum population density of 48.57 dogs/km2. Fecal samples were also opportunistically collected for parasite identification through fecal flotation analysis using the McMaster technique. Out of 25 samples collected, 19 tested positive for gastrointestinal parasites with the most common species found being Ancylostoma caninum, followed by Toxocara canis, Dipylidium caninum, and Cystoisospora spp. Parasite loads ranged from 50 to 10,700 ova per gram of feces. The large population of free-roaming dogs and the prevalence of three zoonotic parasites highlight the importance of understanding free-roaming dog ecology and educating the public on the health risks free-roaming dogs pose. Los perros callejeros (Canis lupus familiaris) representan un gran riesgo para la conservación de animales y la salud pública mundialmente. Para comprender mejor la amenaza que significan los perros domésticos para la fauna silvestre y los humanos y aportar a la creciente bibliografía sobre la ecología de los perros callejeros, se realizó una investigación para estimar la población de los perros en Tulúm, México. Se utilizó una técnica modificada de marcado y recaptura junto con el programa MARK para estimar la población canina en seis transectos de la ciudad. Los estimados varían desde 19.75 perros en un transecto hasta 101,841 en otro, con un total de 150 perros identificados en el transcurso de la investigación y una densidad mínima estimada de 48,57 perros/km2. Además, se hizo una recolección oportunista de muestras de heces para la identificación de parásitos por medio del análisis de flotacíon fecal, con el método McMaster. De las 25 muestras recolectadas, 19 resultaron positivas para parásitos gastrointestinales, de las cuales las especies más comunes fueron Ancylostomoa caninum, seguida por Toxocara canis, Dipylidium caninum, y Cystoisospora spp. Las cargas parasitarias variaron desde 50 hasta 10.700 óvulos por gramo de heces. La alta población de perros callejeros y la prevalencia de tres enfermedades zoonóticas resaltan la importancia de entender la ecología de los perros callejeros y educar al público sobre los riesgos que significan los perros callejeros para la salud.

Canine Idiopathic Arteriopathy, Appendicular Bone Infarcts, and Neoplastic Transformation of Bone Infarcts in 108 Dogs (Canis lupus familiaris).

Osteosarcoma (OSA) is the most common primary bone tumor in both dogs and humans. The dog is an important research model for OSA, yet dogs have much higher prevalence of bone tumors than do humans, a disparity that has yet to be explained. Neoplastic transformation of cells within or adjacent to bone infarcts into primary bone tumors has been described in humans but only sparsely characterized in the veterinary literature. In this study, 653 cases of canine bone infarcts were received through a referral veterinary osteopathology service over a 14-y period. We identified an idiopathic disorder affecting the nutrient artery, termed canine idiopathic arteriopathy (CIA), which to our knowledge has no direct counterpart in human medicine. This disorder was documented alongside ischemic necrosis of the medullary cavity in 114 bone infarcts in 108 dogs. We hypothesize that CIA precipitated an ischemic environment, resulting in development of a bone infarct down- stream of the abnormal artery. In 52% (59 of 114) of cases, bone infarcts demonstrated evidence of repair (termed reparative bone infarcts [RBI]), while in 48% (55 of 114) of infarcts, a bone tumor was also present, including pleomorphic sarcoma, OSA, fibrosarcoma, and chondrosarcoma. In some cases, a spectrum of tumors was present. We hypothesize that the ischemic infarct environment provoked bone marrow mesenchymal stem cells (MSCs) to attempt repair of the stroma, and in approximately half of cases, MSCs underwent neoplastic transformation (BINT) to produce tumors. The most common sites of bone infarcts were the distal femur, distal radius, proximal humerus, and distal tibia, coinciding with common sites of canine OSA. The authors propose that CIA leading to bone infarcts and infarct-derived tumors, in combination with possible underdiagnosis of canine bone infarcts and misdiagnosis of some RBI as neoplasia, may contribute to the higher reported proportion of bone tumors in dogs compared with humans.

Clear cell variant mucoepidermoid carcinoma of salivary gland in a grey wolf (Canis lupus).

A 14-year-old male grey wolf (Canis lupus) with a history of severe facial swelling was submitted for necropsy. Clinical and radiological examination demonstrated an expansile neoplastic mass in the nasal and frontal sinuses. On necropsy, an amorphous neoplastic mass and extensive necrosis were observed in the nasal turbinate. Microscopic examination revealed a tumour principally composed of obvious clear tumour cells characterised by small hyperchromatic nuclei and abundant clear cytoplasm. These clear cells were positive for mucin with PAS, PAS-D reaction, and alcian blue (pH 2.5) staining, but negative for PTAH staining. Immunohistochemically, some of tumour cells were strongly positive for mesenchymal cells (vimentin), whereas they were negative for myoepithelial antigen (alpha-SMA) and cytokeratin. Based on the histopathological and immunohistochemical features, the present case was diagnosed as high-grade clear cell variant mucoepidermoid carcinoma (MEC). This is the first description of clear cell variant MEC in a wolf.

Estimación poblacional y sanitaria de Canis lupus familiaris en zonas rurales y urbanas de Huancarama, Perú / Population and health estimate of Canis lupus familiaris in rural and urban areas of Huancarama, Peru

RESUMEN El objetivo de la investigación fue estimar la población de canes con propietario y evaluar algunos aspectos de su estado sanitario en el distrito de Huancarama. El estudio fue cuantitativo, observacional, descriptivo y transversal. Se efectuó en noviembre de 2020. Las viviendas se seleccionaron mediante un muestreo estratificado aleatorio proporcional que contemplaba a los centros poblados como estratos. Se realizó una encuesta a los jefes de familia en las viviendas utilizando como instrumento una guía de entrevista validada por expertos. La información recolectada se transfirió a una hoja de Excel® para ser procesada con el software Epidat 4.2. El 70% (IC95% = 65,8-74,2%) de las viviendas tuvo canes. Los centros poblados con mayor tenencia de canes fueron Tunyabamba y Mateclla (100%, respectivamente). La mayoría de viviendas tuvo un solo can (51,3%), con predominio del sexo macho (68,8%) y edades entre 2 y 8 años (77,6%). Pocas familias tuvieron en confinamiento a sus canes (19%) y los han esterilizado (2%). Sin embargo, aunque la mayoría de los canes fueron vacunados contra la rabia (81,9%), son pocos los que tuvieron control veterinario (16%). Todos los centros poblados, a excepción de California, tuvieron en promedio un can por vivienda. En el distrito existen 1.717 canes con propietario y una razón de tres personas por cada can. Los centros poblados de Llactabamba, Acco, Tunyabamba, Lambraspata, Los Ángeles, Sotapa Pararani y otros tuvieron una razón de dos personas por can. En conclusión, existe excesiva cantidad de canes en el distrito de Huancarama, constituyendo una proporción elevada en relación con la de personas.

ABSTRACT The objective of the research was to estimate the population of dogs with an owner and to evaluate some aspects of their sanitary status in the district of Huancarama. The study was quantitative, observational, descriptive and cross-sectional. It was carried out in November 2020. The dwellings were selected through a proportional random stratified sampling considering the populated centers as strata. A survey of household heads was conducted using an interview guide validated by experts as an instrument. The information collected was transferred to an Excel* sheet to be processed later with the Epidat 4.2 software. 70% (95% CI = 65, 8-74, 2%) of the dwellings had dogs. The populated centers with the highest proportion of dog ownership were Tunyabamba and Mateclla (100%, respectively). Most of the dwellings had only one dog (51, 3%), with a predominance of the male sex (68, 8%) and ages between 2-8 years (77, 6%). Few families have their dogs confined (19%) and have them sterilized (2%). However, although the majority of the dogs were vaccinated against rabies (81,9%), few had veterinary control (16%). All populated centers, with the exception of California, had an average of one can per dwelling. In the district there are 1.717 dogs with owners and a ratio of three people to each dog. The population centers of Llactabamba, Acco, Tunyabamba, Lambraspata, Los Angeles, Sotapa Pararani, and others had a ratio of two people per dog. In conclusion, there is an excessive number of dogs in the district of Huancarama, constituting a high proportion in relation to that of people.

Grey wolf genomic history reveals a dual ancestry of dogs.

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived1-8. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.

Co-circulation of five species of dog parvoviruses and canine adenovirus type 1 among gray wolves (Canis lupus) in northern Canada.

Several viruses can infect wild carnivores but their impact on wildlife health is poorly understood. We investigated the presence, diversity and distribution of various DNA viruses in 303 wolves inhabiting a vast area of the Northwest Territories, Canada, over a period of 13 years. We found evidence for the presence of canine bufavirus (CBuV, 42.6%), canine parvovirus 2 (CPV-2, 34.0%), canine bocavirus 2 (CBoV-2, 5.0%), cachavirus (CachaV-1, 2.6%), canine adenovirus 1 (CAdV-1, 1%) and minute virus of canines (MVC, 0.3%). To our knowledge, this is the first detection of CBoV-2, MVC and CachV-1 in wild animals. We also demonstrate that CBuV and CachaV-1 were already circulating among wild animals at least 11 and 10 years, respectively, before their discoveries. Although CBuV prevalence was higher, CPV-2 was the most prevalent virus among juveniles, while CBuV infection was associated with poor nutrition conditions. Even if its prevalence was low, CachaV-1 had the highest multiple infection rate (87.5%). CadV-1 and MVC sequences were highly identical to reference strains, but we observed a high diversity among the other viruses and detected three new variants. One CPV-2 variant and one CBuV variant were endemic since the beginning of the 2000s in the entire investigated region, whereas one CBuV variant and two CBoV-2 variants were found in a more restricted area over multiple years and CachaV-1 was found only in one region. Two CPV-2 variants and one CachaV-1 variant were observed only once, indicating sporadic introductions or limited circulation. Different patterns of endemicity might indicate that viruses were introduced in the wolf population at different timepoints and that mixing between wolf packs may not be constant. Different epidemiological behaviors depend on viral factors like infectivity, transmission routes, pathogenicity and tissue-tropism, and on host factors like proximity to densely populated areas, carnivory and pack density and mixing.