Outbreak of Highly Pathogenic Avian Influenza A(H5N1) Virus in Seals, St. Lawrence Estuary, Quebec, Canada1.

We describe an unusual mortality event caused by a highly pathogenic avian influenza (HPAI) A(H5N1) virus clade 2.3.4.4b involving harbor (Phoca vitulina) and gray (Halichoerus grypus) seals in the St. Lawrence Estuary, Quebec, Canada, in 2022. Fifteen (56%) of the seals submitted for necropsy were considered to be fatally infected by HPAI H5N1 containing fully Eurasian or Eurasian/North American genome constellations. Concurrently, presence of large numbers of bird carcasses infected with HPAI H5N1 at seal haul-out sites most likely contributed to the spillover of infection to the seals. Histologic changes included meningoencephalitis (100%), fibrinosuppurative alveolitis, and multiorgan acute necrotizing inflammation. This report of fatal HPAI H5N1 infection in pinnipeds in Canada raises concerns about the expanding host of this virus, the potential for the establishment of a marine mammal reservoir, and the public health risks associated with spillover to mammals.Nous décrivons un événement de mortalité inhabituelle causé par un virus de l'influenza aviaire hautement pathogène A(H5N1) clade 2.3.4.4b chez des phoques communs (Phoca vitulina) et gris (Halichoerus grypus) dans l'estuaire du Saint-Laurent au Québec, Canada, en 2022. Quinze (56%) des phoques soumis pour nécropsie ont été considérés comme étant fatalement infectés par le virus H5N1 de lignées eurasiennes ou de réassortiment eurasiennes/nord-américaines. Un grand nombre simultané de carcasses d'oiseaux infectés par le H5N1 sur les sites d'échouement a probablement contribué à la contamination de ces phoques. Les changements histologiques associés à cette infection incluaient : méningo-encéphalite (100%), alvéolite fibrinosuppurée et inflammation nécrosante aiguë multi-organique. Cette documentation soulève des préoccupations quant à l'émergence de virus mortels, à la possibilité d'établissement de réservoirs chez les mammifères marins, et aux risques pour la santé publique associés aux propagations du virus chez les mammifères.

The prelude to industrial whaling: identifying the targets of ancient European whaling using zooarchaeology and collagen mass-peptide fingerprinting.

Taxonomic identification of whale bones found during archaeological excavations is problematic due to their typically fragmented state. This difficulty limits understanding of both the past spatio-temporal distributions of whale populations and of possible early whaling activities. To overcome this challenge, we performed zooarchaeology by mass spectrometry on an unprecedented 719 archaeological and palaeontological specimens of probable whale bone from Atlantic European contexts, predominantly dating from ca 3500 BCE to the eighteenth century CE. The results show high numbers of Balaenidae (many probably North Atlantic right whale (Eubalaena glacialis)) and grey whale (Eschrichtius robustus) specimens, two taxa no longer present in the eastern North Atlantic. This discovery matches expectations regarding the past utilization of North Atlantic right whales, but was unanticipated for grey whales, which have hitherto rarely been identified in the European zooarchaeological record. Many of these specimens derive from contexts associated with mediaeval cultures frequently linked to whaling: the Basques, northern Spaniards, Normans, Flemish, Frisians, Anglo-Saxons and Scandinavians. This association raises the likelihood that early whaling impacted these taxa, contributing to their extirpation and extinction. Much lower numbers of other large cetacean taxa were identified, suggesting that what are now the most depleted whales were once those most frequently used.

Influenza A(H5N1) Virus Infections in 2 Free-Ranging Black Bears (Ursus americanus), Quebec, Canada.

Wholly Eurasian highly pathogenic avian influenza H5N1 clade 2.3.4.4b virus was isolated from 2 free-ranging black bears with meningoencephalitis in Quebec, Canada. We found that isolates from both animals had the D701N mutation in the polymerase basic 2 gene, previously known to promote adaptation of H5N1 viruses to mammal hosts.

Co-Constructing a Community-Based Telemedicine Program for People With Opioid Use Disorder During the COVID-19 Pandemic: Lessons Learned and Implications for Future Service Delivery.

The COVID-19 pandemic triggered unprecedented expansion of telemedicine, including in the delivery of opioid agonist treatment (OAT) for people with opioid use disorder (OUD). However, many people with OUD lack the technological resources necessary for remote care, have complex needs, and are underserved, with precarious access to mainstream services. To address the needs of these individuals, we devised a unique program to deliver OAT via telemedicine with the support of community outreach workers in Montreal (Quebec, Canada). The program was co-constructed by the service de médecine des toxicomanies of the Centre hospitalier de l'Université de Montréal (CHUM-SMT)-a hospital-based addiction medicine service-and CACTUS Montréal-a community-based harm reduction organization known and trusted by its clientele. All procedures were jointly developed to enable flexible and rapid appointment scheduling. CACTUS Montréal workers promoted the program, facilitated private on-site telemedicine connections to the CHUM-SMT, accompanied patients during web-based appointments if requested, and provided ongoing holistic support and follow-up. The CHUM-SMT offered individualized OAT regimens and other health services as needed. Overall, our experience as clinicians and community-based workers intimately involved in establishing and running this initiative suggests that participants found it to be convenient, nonjudgmental, and responsive to their needs, and that the implication of CACTUS Montréal was highly valued and integral to patient engagement and retention. Beyond the context of the COVID-19 pandemic, similar programs may present a flexible and accessible means to deliver alternative treatment options for people with OUD disengaged from traditional care, bridge gaps between communities and health providers, and improve access to care in rural or remote settings.

To What Extent Do Musculoskeletal Ultrasound Biomarkers Relate to Pain, Flexibility, Strength, and Function in Individuals With Chronic Symptomatic Achilles Tendinopathy?

Introduction: Achilles tendinopathy (AT) is a chronic musculoskeletal pathology best evaluated by ultrasound imaging. This cross-sectional study aimed at better understanding the relationship between musculoskeletal ultrasound biomarkers (MUBs) of Achilles tendon and localized pain, ankle flexibility, ankle strength, and functional abilities. Method: Forty-one participants with unilateral midportion chronic AT had their tendon images analyzed bilaterally in the longitudinal and transverse planes. The Victorian Institute of Sport Assessment-Achilles questionnaire (VISA-A) and Lower Extremity Functional Scale (LEFS) assessed pain and function, respectively, during standing and walking-related activities. Ankle flexibility was evaluated by weight-bearing lunge tests, while ankle isometric peak strength was measured using an instrumented dynamometer. Achilles tendon ultrasonographic images were analyzed using geometric (thickness), composition (echogenicity), and texture (homogeneity) MUBs. Discriminative validity was evaluated using paired Student's t-tests to compare MUBs between symptomatic and asymptomatic sides. Predictive validity was evaluated by computing the Pearson product-moment correlations coefficient between MUBs and pain, ankle flexibility, ankle strength, and function. Results: Significant differences were found in MUBs between the symptomatic and asymptomatic sides, confirming the discriminative validity of the selected MUBs. On the symptomatic side, thickness was found 29.9% higher (p < 0.001), echogenicity 9.6% lower (p < 0.001), and homogeneity 3.8% higher (p = 0.001) when compared with the asymptomatic side. However, predictive validity was scarcely confirmed, as most of the correlation coefficients were found negligible for the associations investigated between MUBs with localized pain, ankle flexibility, strength, and function. Only 14 statistically significant low to moderate associations were found, with negative and positive correlations ranging between -0.31 and -0.55 and between 0.34 and 0.54, respectively. Discussion: Musculoskeletal ultrasound biomarkers have a clinical utility in visualizing in vivo tendon integrity and diagnosing AT. MUBs should be valued as part of a comprehensive neuro-musculoskeletal assessment as they complement pain, flexibility, strength, and function measures. Altogether, they may inform the development and monitoring of a personalized rehabilitation treatment plan.

Education for students with neurodevelopmental disabilities-Resources and educational adjustments.

Children with neurodevelopmental disorders are more likely to face challenges of various kinds throughout their schooling due to their vulnerability factors. Although certain evidence-based practices have been recognized to be effective in supporting academic performance or social and personal adjustment, transferring these practices to school realities remains a challenge. Indeed, the educational trend favored for more than 20 years promotes the development of all students in the most natural context possible. The objective of this chapter is to shed light on how resources and EBPs can be organized in an inclusive education context. A tiered framework, commonly adopted as different models across the world, is presented and used to demonstrate how interventions can be prioritized for the difficulties and special needs of specific (e.g., ADHD, dyslexia, and developmental coordination disorder) and complex (e.g., autism spectrum disorder) neurodevelopmental disorders. The chapter ends with a discussion of the conditions and drivers of intervention fidelity and effectiveness in an inclusive context and, more specifically, support for teachers and parents.

Pro-Inflammatory Signaling Upregulates a Neurotoxic Conotoxin-Like Protein Encrypted Within Human Endogenous Retrovirus-K.

Motor neuron degeneration and spinal cord demyelination are hallmark pathological events in Amyotrophic Lateral Sclerosis (ALS). Endogenous retrovirus-K (ERVK) expression has an established association with ALS neuropathology, with murine modeling pointing to a role for the ERVK envelope (env) gene in disease processes. Here, we describe a novel viral protein cryptically encoded within the ERVK env transcript, which resembles two distinct cysteine-rich neurotoxic proteins: conotoxin proteins found in marine snails and the Human Immunodeficiency Virus (HIV) Tat protein. Consistent with Nuclear factor-kappa B (NF-κB)-induced retrotransposon expression, the ERVK conotoxin-like protein (CTXLP) is induced by inflammatory signaling. CTXLP is found in the nucleus, impacting innate immune gene expression and NF-κB p65 activity. Using human autopsy specimens from patients with ALS, we further showcase CTXLP expression in degenerating motor cortex and spinal cord tissues, concomitant with inflammation linked pathways, including enhancement of necroptosis marker mixed lineage kinase domain-like (MLKL) protein and oligodendrocyte maturation/myelination inhibitor Nogo-A. These findings identify CTXLP as a novel ERVK protein product, which may act as an effector in ALS neuropathology.

Proposing a Minimal Data Set of Musculoskeletal Ultrasound Imaging Biomarkers to Inform Clinical Practice: An Analysis Founded on the Achilles Tendon.

Tendon integrity can be described using a wide range of biomarkers via specialized analysis software for images recorded by musculoskeletal ultrasonography. This study proposes a minimal biomarker data set to characterize Achilles tendon ultrasound images and to differentiate between symptomatic and asymptomatic Achilles tendon images. Forty-one individuals with unilateral Achilles tendinopathy and 35 healthy controls had their Achilles tendon images recorded bilaterally by ultrasonography in the longitudinal and transverse planes. A set of 22 biomarkers, organized around three dimensions (geometric, composition and texture), were computed in each plane. A symmetry index, reflecting relative side differences, was compared between groups and analyzed through principal component analysis to isolate biomarkers that best explained data variance. A specific minimal data set was identified by linear regression in the longitudinal (mean thickness, echogenicity, variance and homogeneity at 90°) and transverse (mean thickness, echogenicity and mean homogeneity) planes to characterize and differentiate Achilles tendon integrity.

Expression of Human Endogenous Retrovirus-K in Spinal and Bulbar Muscular Atrophy.

Background: Spinal and Bulbar Muscular Atrophy (SBMA) is caused by the extension of the polyglutamine tract within the androgen receptor (AR) gene, and results in a multisystem presentation, including the degeneration of lower motor neurons. The androgen receptor (AR) is known to modulate the expression of endogenous retrovirus-K (ERVK), a pathogenic viral genomic symbiont. Since ERVK is associated with motor neuron disease, such as Amyotrophic Lateral Sclerosis (ALS), we sought to determine if patients with SBMA exhibit evidence of ERVK reactivation. Results: Data from a pilot study demonstrate that peripheral blood mononuclear cell (PBMC) samples from controls and patients with SBMA were examined ex vivo for the expression of ERVK viral transcripts and proteins. No differences in ERVK RNA expression was observed between the clinical groups. In contrast, enhancement of processed ERVK Gag and integrase proteins were observed in SBMA-derived PBMC as compared to healthy control specimens. Increased ERVK protein maturation co-occurred with elevation in the expression of the pro-inflammatory transcription factor IRF1 in SBMA. Conclusions: Our findings indicate that ERVK viral protein maturation in SBMA is an unrecognized biomarker and facet of the disease. We discuss how our current understanding of ERVK-driven pathology may tie into key aspects of multi-system dysfunction in SBMA, with a focus on inflammation, proteinopathy, as well as DNA damage and repair.

A comparison study of bioanalytical methods for characterization of anti-idursulfase antibodies.

AIM: Legacy methods with complex testing scheme for characterization of anti-idursulfase antibodies (ADA) were simplified and optimized in order to meet current regulatory guidance and provide more timely and cost-effective support for routine patient care. RESULTS: To compare the performance of the original and updated methods, patient samples receiving commercially prescribed Elaprase treatment were analyzed by both test methods. The ADA and neutralizing antibody results obtained by both methods were highly correlated and the updated method had an overall higher ADA and neutralizing antibody positive rates and higher ADA titers. CONCLUSION: The updated methods and test schemes are much simpler, more sensitive, but are also highly comparable with the original methods for the measurement of total and neutralizing ADA.

Determinants of virulence and of resistance to ceftiofur, gentamicin, and spectinomycin in clinical Escherichia coli from broiler chickens in Québec, Canada.

Antimicrobials are frequently used for the prevention of avian colibacillosis, with gentamicin used for this purpose in Québec until 2003. Ceftiofur was also used similarly, but voluntarily withdrawn in 2005 due to increasing resistance. Spectinomycin-lincomycin was employed as a replacement, but ceftiofur use was partially reinstated in 2007 until its definitive ban by the poultry industry in 2014. Gentamicin resistance frequency increased during the past decade in clinical Escherichia coli isolates from broiler chickens in Québec, despite this antimicrobial no longer being used. Since this increase coincided with the use of spectinomycin-lincomycin, co-selection of gentamicin resistance through spectinomycin was suspected. Therefore, relationships between spectinomycin, gentamicin, and ceftiofur resistance determinants were investigated here. The distribution of 13 avian pathogenic E. coli virulence-associated genes and their association with spectinomycin resistance were also assessed. A sample of 586 E. coli isolates from chickens with colibacillosis in Québec between 2009 and 2013 was used. The major genes identified for resistance to ceftiofur, gentamicin, and spectinomycin were blaCMY, aac(3)-VI, and aadA, respectively. The aadA and aac(3)-VI genes were strongly associated and shown to be located on a modified class 1 integron. The aadA and blaCMY genes were negatively associated, but when present together, were generally located on the same plasmids. No statistical positive association was observed between aadA and virulence genes, and virulence genes were only rarely detected on plasmids encoding spectinomycin resistance. Thus, the use of spectinomycin-lincomycin may likely select for gentamicin but not ceftiofur resistance, nor for any of the virulence-associated genes investigated.

Fish Oncology: Diseases, Diagnostics, and Therapeutics.

The scientific literature contains a wealth of information concerning spontaneous fish neoplasms, although ornamental fish oncology is still in its infancy. The occurrence of fish neoplasms has often been associated with oncogenic viruses and environmental insults, making them useful markers for environmental contaminants. The use of fish, including zebrafish, as models of human carcinogenesis has been developed and knowledge gained from these models may also be applied to ornamental fish, although more studies are required. This review summarizes information available about fish oncology pertaining to veterinary clinicians.

Quantitative ultrasound imaging of Achilles tendon integrity in symptomatic and asymptomatic individuals: reliability and minimal detectable change.

BACKGROUND: Quantifying the integrity of the Achilles tendon (AT) is a rehabilitation challenge. Adopting quantitative ultrasound measurements (QUS measurements) of the AT could fill this gap by 1) evaluating the test-retest reliability and accuracy of QUS measurements of the AT; 2) determining the best protocol for collecting QUS measurements in clinical practice. METHODS: A total of 23 ATs with symptoms of Achilles tendinopathy and 63 asymptomatic ATs were evaluated. Eight images were recorded for each AT (2 visits × 2 evaluators × 2 images). Multiple sets of QUS measurements were taken: geometric (thickness, width, area), first-order statistics (computed from a grayscale histogram distribution: echogenicity, variance, skewness, kurtosis, entropy) and texture features (computed from co-occurrence matrices: contrast, energy, homogeneity). A generalizability study quantified the reliability and standard error of measurement (accuracy) of each QUS measurement, and a decision study identified the best measurement taking protocols. RESULTS: Geometric QUS measurements demonstrated excellent accuracy and reliability. QUS measurements computed from the grayscale histogram distribution revealed poor accuracy and reliability. QUS measurements derived from co-occurrence matrices showed variable accuracy and moderate to excellent reliability. In clinical practice, using an average of the results of three images collected by a single evaluator during a single visit is recommended. CONCLUSIONS: The use of geometric QUS measurements enables quantification of AT integrity in clinical practice and research settings. More studies on QUS measurements derived from co-occurrence matrices are warranted.

Too early and too northerly: evidence of temperate trees in northern Central Europe during the Younger Dryas.

This paper presents highly unexpected paleobotanical data. Eight (14) C-accelerator mass spectrometry (AMS) dates of soil macrocharcoal pieces, identified taxonomically, indicate the presence of oak and beech in the Younger Dryas, and pine in the Allerød, in the northernmost low mountain range of Central Europe, the Harz Mountains, in Germany. If the presence of pine at such latitude and periods is not surprising, the presence of temperate-adapted trees is highly improbable, because they are assumed to have reached the area from a southern location several thousand years later. Two hypotheses are postulated to explain this record. Both are related to the warm periods of the Bølling and Allerød: the classically 'short' duration of this warm period makes the migration of the temperate trees from the identified refuge areas in the southern location implausible, and so the presence of intermediary microrefugia at a medium latitude in Central Europe is postulated; recent data reveal that the warm period of the Late Glacial phase was much longer than considered in the classical view and, thus, would be long enough for a northward migration of temperate-adapted trees. Although our dataset does not permit disentanglement of these hypotheses, it provides significant innovative insights for the biogeography of Central Europe.

Ultrasound-Guided Single-Injection Infraclavicular Block Versus Ultrasound-Guided Double-Injection Axillary Block: A Noninferiority Randomized Controlled Trial.

BACKGROUND: Single-injection ultrasound-guided infraclavicular block is a simple, reliable, and effective technique. A simplified double-injection ultrasound-guided axillary block technique with a high success rate recently has been described. It has the advantage of being performed in a superficial and compressible location, with a potentially improved safety profile. However, its effectiveness in comparison with single-injection infraclavicular block has not been established. We hypothesized that the double-injection ultrasound-guided axillary block would show rates of complete sensory block at 30 minutes noninferior to the single-injection ultrasound-guided infraclavicular block. METHODS: After approval by our research ethics committee and written informed consent, adults undergoing distal upper arm surgery were randomized to either group I, ultrasound-guided single-injection infraclavicular block, or group A, ultrasound-guided double-injection axillary block. In group I, 30 mL of 1.5% mepivacaine was injected posterior to the axillary artery. In group A, 25 mL of 1.5% mepivacaine was injected posteromedial to the axillary artery, after which 5 mL was injected around the musculocutaneous nerve. Primary outcome was the rate of complete sensory block at 30 minutes. Secondary outcomes were the onset of sensory and motor blocks, surgical success rates, performance times, and incidence of complications. All outcomes were assessed by a blinded investigator. The noninferiority of the double-injection ultrasound-guided axillary block was considered if the limits of the 90% confidence intervals (CIs) were within a 10% margin of the rate of complete sensory block of the infraclavicular block. RESULTS: At 30 minutes, the rate of complete sensory block was 79% in group A (90% CI, 71%-85%) compared with 91% in group I (90% CI, 85%-95%); the upper limit of CI of group A is thus included in the established noninferiority margin of 10%. The rate of complete sensory block was lower in group A (proportion difference of 12% [95% CI, 2-22]; P = 0.0091), as was surgical success rate (82% [95% CI, 74%-89%] vs 93% [95% CI, 86%-97%]; proportion difference of 11% [95% CI 1-20]; P = 0.0153). Sensory block onset also was slower in group A (log rank test P = 0.0020). Performance times were faster in group I (231 seconds [95% CI, 213-250]) than in group A (358 seconds [95% CI, 332-387]; P < 0.0001). No statistically significant difference was observed for vascular puncture, paresthesia during block performance, or procedure-related pain. No neurologic complication was noted at follow-up. CONCLUSIONS: We failed to demonstrate that the rate of complete sensory block of the double-injection axillary block is noninferior to the single-injection infraclavicular block. However, the rate of complete sensory block at 30 minutes is statistically significantly lower with the axillary block. The ultrasound-guided single-injection infraclavicular block thus seems to be the preferred technique over the axillary for upper arm anesthesia.

Inside the Envelope: Endogenous Retrovirus-K Env as a Biomarker and Therapeutic Target.

Due to multiple ancestral human retroviral germ cell infections, the modern human genome is strewn with relics of these infections, termed endogenous retroviruses (ERVs). ERV expression has been silenced due to negative selective pressures and genetic phenomena such as mutations and epigenetic silencing. Nonetheless, select ERVs have retained the capacity to be damaging to their host when reawakened. Much of the current research on the ERVK Env protein strongly suggests a causal or contributive role in the pathogenesis of various cancers, autoimmune and infectious diseases. Additionally, there is a small body of research suggesting that ERVK Env has been domesticated for use in placental development, akin to the ERVW syncytin. Though much is left to ascertain, the innate immune response to ERVK Env expression has been partially characterized and appears to be due to a region located in the transmembrane domain of the Env protein. In this review, we aim to highlight ERVK Env as a biomarker for inflammatory conditions and explore its use as a future therapeutic target for cancers, HIV infection and neurological disease.

Quantitative diet reconstruction of a Neolithic population using a Bayesian mixing model (FRUITS): The case study of Ostorf (Germany).

OBJECTIVES: The island cemetery site of Ostorf (Germany) consists of individual human graves containing Funnel Beaker ceramics dating to the Early or Middle Neolithic. However, previous isotope and radiocarbon analysis demonstrated that the Ostorf individuals had a diet rich in freshwater fish. The present study was undertaken to quantitatively reconstruct the diet of the Ostorf population and establish if dietary habits are consistent with the traditional characterization of a Neolithic diet. METHODS: Quantitative diet reconstruction was achieved through a novel approach consisting of the use of the Bayesian mixing model Food Reconstruction Using Isotopic Transferred Signals (FRUITS) to model isotope measurements from multiple dietary proxies (δ13 Ccollagen , δ15 Ncollagen , δ13 Cbioapatite , δ34 Smethione , 14 Ccollagen ). The accuracy of model estimates was verified by comparing the agreement between observed and estimated human dietary radiocarbon reservoir effects. RESULTS: Quantitative diet reconstruction estimates confirm that the Ostorf individuals had a high protein intake due to the consumption of fish and terrestrial animal products. However, FRUITS estimates also show that plant foods represented a significant source of calories. Observed and estimated human dietary radiocarbon reservoir effects are in good agreement provided that the aquatic reservoir effect at Lake Ostorf is taken as reference. CONCLUSIONS: The Ostorf population apparently adopted elements associated with a Neolithic culture but adapted to available local food resources and implemented a subsistence strategy that involved a large proportion of fish and terrestrial meat consumption. This case study exemplifies the diversity of subsistence strategies followed during the Neolithic. Am J Phys Anthropol 158:325-340, 2015. © 2015 Wiley Periodicals, Inc.