Dimethylene-Cyclopropanide Units as Building Blocks for Fluorescence Dyes.

Many organic dyes are fluorescent in solution. In the solid state, however, quenching processes often dominate, hampering material science applications such as light filters, light-emitting devices, or coding tags. We show that the dimethylene-cyclopropanide scaffold can be used to form two structurally different types of chromophores, which feature fluorescence quantum yields up to 0.65 in dimethyl sulfoxide and 0.53 in solids. The increased fluorescence in the solid state for compounds bearing malonate substituents instead of dicyanomethid ones is rationalized by the induced twist between the planes of the cyclopropanide core and a pyridine ligand.

Familial Recurrence of Autism: Updates From the Baby Siblings Research Consortium.

OBJECTIVES: Autism spectrum disorder (ASD) is estimated to be ∼10 times higher in children with versus without an autistic sibling in population-based studies. Prospective studies of infant siblings have revealed even higher familial recurrence rates. In the current prospective longitudinal study, we provide updated estimates of familial ASD recurrence using a multinational database of infants with older autistic siblings. METHODS: Data were collated across 18 sites of the Baby Siblings Research Consortium, an international network studying the earliest manifestations of ASD. A total of 1605 infants with an older autistic sibling were followed from early in life to 3 years, when they were classified as ASD or non-ASD. Hierarchical generalized linear modeling, with site as a random effect, was used to examine predictors of recurrence in families and calculate likelihood ratios. RESULTS: A total of 20.2% of siblings developed ASD, which is not significantly higher than the previously reported rate of 18.7%. Male infant sex and >1 older affected sibling were significant predictors of familial recurrence. Proband sex also influenced recurrence rates, with siblings of female probands significantly more likely to develop ASD than siblings of male probands. Race and maternal education were also associated with recurrence in families. CONCLUSIONS: The familial recurrence rate of ASD, as measured in infant sibling studies, has not changed appreciably since previous estimates were made in 2011. Younger siblings of autistic children, particularly those who are male, have an affected female sibling, multiple affected siblings, or are impacted by social inequities, should be closely monitored and promptly referred for diagnostic evaluation.

Microglia Morphological Response to Mesenchymal Stromal Cell Extracellular Vesicles Demonstrates EV Therapeutic Potential for Modulating Neuroinflammation.

Background: Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of the brain, to exert their immunomodulatory effects. In response to inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative of their function e.g. morphology and secretion. However, these changes in response to MSC-EVs are not well understood. Additionally, no disease-relevant screening tools to assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed a quantitative, high throughput morphological profiling approach to assess the response of microglia to neuroinflammation-relevant signals and whether this morphological response can be used to indicate the bioactivity of MSC-EVs. Results: Using an immortalized human microglia cell-line, we observed increased size (perimeter, major axis length) and complexity (form factor) upon stimulation with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Upon treatment with MSC-EVs, the overall morphological score (determined using principal component analysis) shifted towards the unstimulated morphology, indicating that MSC-EVs are bioactive and modulate microglia. The morphological effects of MSC-EVs in TNF-γ/IFN-α stimulated cells were concomitant with reduced secretion of 14 chemokines/cytokines (e.g. CXCL6, CXCL9) and increased secretion of 12 chemokines/cytokines (e.g. CXCL8, CXCL10). Proteomic analysis of cell lysates revealed significant increases in 192 proteins (e.g. HIBADH, MEAK7, LAMC1) and decreases in 257 proteins (e.g. PTEN, TOM1, MFF) with MSC-EV treatment. Of note, many of these proteins are involved in regulation of cell morphology and migration. Gene Set Variation Analysis revealed upregulation of pathways associated with immune response, such as regulation of cytokine production, immune cell infiltration (e.g. T cells, NK cells) and morphological changes (e.g. Semaphorin, RHO/Rac signaling). Additionally, changes in microglia mitochondrial morphology were measured suggesting that MSC-EV modulate mitochondrial metabolism. Conclusion: This study comprehensively demonstrates the effects of MSC-EVs on human microglial morphology, cytokine secretion, cellular proteome, and mitochondrial content. Our high-throughput, rapid, low-cost morphological approach enables screening of MSC-EV batches and manufacturing conditions to enhance EV function and mitigate EV functional heterogeneity in a disease relevant manner. This approach is highly generalizable and can be further adapted and refined based on selection of the disease-relevant signal, target cell, and therapeutic product.

Psychological sequelae following second-trimester termination of pregnancy: A longitudinal study.

INTRODUCTION: The decision to terminate a pregnancy due to fetal anomalies can have a significant emotional impact, especially in second-trimester terminations. Previous studies on the psychological consequences of pregnancy termination have had limitations, and little is known about the outcomes for partners and the impact of fetal donation. Therefore, we aimed to investigate the psychological effects of second-trimester pregnancy termination and identify factors associated with outcomes in both women and men, including donation of fetal remains to science. MATERIAL AND METHODS: A longitudinal cohort study was conducted at the Amsterdam UMC in the Netherlands, involving women and partners who underwent termination at or before 23 weeks and 6 days of gestation. Questionnaires were administered at termination, 6 weeks, and 4 months after. We utilized validated questionnaires to assess psychological morbidity (grief, post-traumatic stress and postnatal depression and quality of life [QoL]), and factors that could potentially influence outcomes. RESULTS: Of 241 participants, women displayed more pronounced psychological distress than men, though both groups improved over time. Four months after termination, 27.4% of women and 9.1% of men showed signs of pathological grief. Scores indicative for postnatal depression occurred in 19.8% women and 4.1% of men. A prior psychiatric history was a consistent predictor of poorer outcomes. Fetal donation to the Dutch Fetal Biobank was associated with reduced likelihood of symptoms of complicated grief four months after termination. CONCLUSIONS: Second-trimester termination of pregnancy for fetal anomalies can lead to psychological morbidity, particularly in women. However, there is a notable improvement over time for both groups. Individuals with prior psychiatric history appear more vulnerable post-termination. Also, fetal donation to science did not have a negative impact on psychological well-being.

Reaching While Learning to Sit: Capturing the Kinematics of Co-Developing Skills at Home.

This study examined the co-development of infant reaching and postural control across the transition to arms-free sitting at home. We observed infants with typical likelihood (TL; n = 24) and elevated likelihood (EL; n = 20) for autism at four biweekly sessions spanning the transition to arms-free sitting (infant age = 4.5-8 months at first session). At each session, infants sat on a pressure-sensitive mat with external support or independently, wore magneto-inertial sensors on both wrists, and reached for toys presented at midline. Analyses focused on characterizing and comparing control of sitting during reaching actions and standard kinematic metrics of reaching during Supported versus Independent Sitting. Although EL infants achieved arms-free sitting later than TL peers, there were no group differences on any measures. Across sessions, infants' control of the sitting posture during concurrent reaching movements improved in both contexts, though they were less stable as they reached when sitting independently compared to when sitting with support. A similar effect was apparent in the kinematics of reaches, with overall improvement over time, but evidence of poorer control in Independent relative to Supported Sitting. Taken together, these findings underscore the mutually influential and dynamic relations between emerging skills and well-established behaviors.

Natural mycobacterium tuberculosis complex infection in a brown howler monkey (Alouatta guariba clamitans) in Brazil.

Neotropical primates rarely exhibit active tuberculosis. A brown howler monkey was found injured in an urban area. Histopathology revealed granulomatous inflammation in the lungs, lymph nodes, and liver. Immunohistochemistry and molecular analysis confirmed the presence of Mycobacterium tuberculosis complex. The findings highlight the importance of TB surveillance in nonhuman primates.

DETECTION OF SARS-COV-2 IN A SQUIRREL MONKEY (SAIMIRI SCIUREUS): A ONE HEALTH INVESTIGATION AND RESPONSE.

Through collaborative efforts, One Health partners have responded to outbreaks of COVID-19 among animals, including those in human care at zoos. Zoos have been faced with numerous challenges, including the susceptibility of many mammalian species, and therefore the need to heighten biosecurity measures rapidly. Robust One Health collaborations already exist in Arizona to address endemic and emerging zoonoses, but these have rarely included zoos. The pandemic shed light on this, and Arizona subsequently expanded its SARS-CoV-2 surveillance efforts to include zoo animals. Testing and epidemiologic support was provided to expedite the detection of and response to zoonotic SARS-CoV-2 infection in zoo animals, as well as to understand possible transmission events. Resulting from this program, SARS-CoV-2 was detected from a rectal swab collected from an 8-yr-old squirrel monkey (Saimiri sciureus) from a zoo in Southern Arizona. The animal had rapidly become ill with nonrespiratory symptoms and died in July 2022. Genomic sequencing from the swab revealed mutations consistent with the Omicron (BA.2) lineage. An epidemiologic investigation identified an animal caretaker in close proximity to the affected squirrel monkey who tested positive for COVID-19 the same day the squirrel monkey died. Critical One Health partners provided support to the zoo through engagement of local, state, and federal agencies. Necropsy and pathologic evaluation showed significant necrotizing colitis; the overall clinical and histopathological findings did not implicate SARS-CoV-2 infection alone as a causal or contributing factor in the squirrel monkey's illness and death. This report documents the first identification of SARS-CoV-2 in a squirrel monkey and highlights a successful and timely One Health investigation conducted through multisectoral collaboration.

A Diagnostic Algorithm for Detection of Leishmania spp. in Human Fresh and Fixed Tissue Samples.

Leishmaniasis is an important travel-related parasitic infection in the United States. Treatment regimens vary by Leishmania species and require an accurate diagnosis. The sensitivity and specificity of diagnostic methods depend on the type and condition of specimen analyzed. To identify the best algorithm for detection of parasites in fresh and fixed tissue samples, we evaluated parasite cultures, two PCR methods, and Leishmania immunohistochemistry (IHC) in samples received by the CDC from 2012 through 2019. The sensitivity and specificity of IHC assays were evaluated in fresh specimens tested. Diagnostic accuracy for formalin-fixed tissue was evaluated by using PCR-based methods and IHC. Of 100 suspected cases with fresh tissue available, Leishmania spp. infection was identified by PCR in 56% (56/100) of specimens; from these, 80% (45/56) were positive by parasite culture and 59% (33/56) by IHC. Of 420 possible cases where only fixed specimens were available, 58% (244/420) were positive by IHC and/or PCR. Of these, 96% (235/420) were positive by IHC and 84% (204/420) by PCR-based methods. Overall parasite detection using all methodologies was similar for fresh and formalin-fixed tissue specimens (56% versus 58%, respectively). Although PCR-based methods were superior for diagnosis of leishmaniasis and species identification in fresh samples, IHC in combination with PCR increased the accuracy for Leishmania spp. detection in fixed samples. In conclusion, PCR is the most effective method for detecting Leishmania infection in fresh tissue samples, whereas for formalin-fixed samples, IHC and PCR-based methods should be used in combination.

Dermatologic Fungal Neglected Tropical Diseases-Part I. Epidemiology and Clinical Features.

In this part 1 of a 2-part continuing medical education series, the epidemiology, clinical features, and diagnostic methods for fungal skin neglected tropical diseases (NTDs), which include eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis, are reviewed. These infections, several of which are officially designated as NTDs by the World Health Organization (WHO), cause substantial morbidity and stigma worldwide and are receiving increased attention due to the potential for climate change-related geographic expansion. Domestic incidence may be increasing in the setting of global travel and immunosuppression. United States dermatologists may play a central role in early detection and initiation of appropriate treatment, leading to decreased morbidity and mortality.

Dermatologic Fungal Neglected Tropical Diseases-Part II. Management and Morbidity.

In this part 2 of a 2-part continuing medical education series, the management, outcomes, and morbidities for fungal skin neglected tropical diseases (NTDs), including eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis are reviewed. While fungal skin NTDs are associated with poverty in resource-limited settings, they are more often associated with immunosuppression and global migration in the United States. These infections have a high morbidity burden, including disfigurement, physical disability, coinfection, malignant transformation, mental health issues, and financial impact. For most fungal skin NTDs, management is difficult and associated with low cure rates. Dermatologists play a central role in initiating appropriate treatment early in disease course in order to improve patient outcomes.

Adaptations of interpersonal psychotherapy in psycho-oncology and its effects on distress, depression, and anxiety in patients with cancer: a systematic review.

Objective: Patients with cancer experience significant psychosocial distress. Stressors include interpersonal difficulties like loneliness, isolation, thwarted belongingness, communication impediments, and conflicts. Interventions are required that address their specific psychosocial needs. Interpersonal Psychotherapy (IPT) is a promising concept for the treatment of psychosocial distress associated with cancer because it addresses patients' interactions and role transformations. This review aims to provide an overview of the current evidence regarding interventions for patients with cancer based on IPT. Methods: A systematic review following PRISM guidelines was conducted, including randomized controlled trials of IPT-based interventions in patients with cancer, assessing effects on distress, depression, and anxiety. Results: Eight studies were included, sampling 390 patients in total. Seven out of eight studies assessed exclusively women with breast cancer. Two studies described IPT interventions and showed stronger improvement in depression and anxiety compared to TAU and equal improvement in depression compared to other psychotherapy interventions. Six studies described remote Interpersonal Counselling (IPC). One found remote IPC to be superior to control conditions regarding depression, and one found remote IPC to be superior to attention control, but not active control conditions. No study found remote IPC to be superior to control conditions regarding distress. Discussion: There are few randomized controlled trials of IPT for patients with cancer. Results regarding depression and anxiety are promising for in-person IPT, but mixed for remote IPC. Conclusion: The review suggests in-person IPT, but not remote IPC, may yield benefits for patients with cancer. Research on the subject is scarce, and to inform implementation of IPT interventions, research with diverse groups of patients with cancer is required. Systematic trial registration: PROSPERO, Identifier CRD42023410687.

Single-nucleus sequencing reveals enriched expression of genetic risk factors in extratelencephalic neurons sensitive to degeneration in ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive loss of motor function linked to degenerating extratelencephalic neurons/Betz cells (ETNs). The reasons why these neurons are selectively affected remain unclear. Here, to understand the unique molecular properties that may sensitize ETNs to ALS, we performed RNA sequencing of 79,169 single nuclei from cortices of patients and controls. In both patients and unaffected individuals, we found significantly higher expression of ALS risk genes in THY1+ ETNs, regardless of diagnosis. In patients, this was accompanied by the induction of genes involved in protein homeostasis and stress responses that were significantly induced in a wide collection of ETNs. Examination of oligodendroglial and microglial nuclei revealed patient-specific downregulation of myelinating genes in oligodendrocytes and upregulation of an endolysosomal reactive state in microglia. Our findings suggest that selective vulnerability of extratelencephalic neurons is partly connected to their intrinsic molecular properties sensitizing them to genetics and mechanisms of degeneration.

A Prototype Software Framework for Transferable Computational Health Economic Models and Its Early Application in Youth Mental Health.

We are developing an economic model to explore multiple topics in Australian youth mental health policy. To help make that model more readily transferable to other jurisdictions, we developed a software framework for authoring modular computational health economic models (CHEMs) (the software files that implement health economic models). We specified framework user requirements for: a simple programming syntax; a template CHEM module; tools for authoring new CHEM modules; search tools for finding existing CHEM modules; tools for supplying CHEM modules with data; reproducible analysis and reporting tools; and tools to help maintain a CHEM project website. We implemented the framework as six development version code libraries in the programming language R that integrate with online services for software development and research data archiving. We used the framework to author five development version R libraries of CHEM modules focussed on utility mapping in youth mental health. These modules provide tools for variable validation, dataset description, multi-attribute instrument scoring, construction of mapping models, reporting of mapping studies and making out of sample predictions. We assessed these CHEM module libraries as mostly meeting transparency, reusability and updatability criteria that we have previously developed, but requiring more detailed documentation and unit testing of individual modules. Our software framework has potential value as a prototype for future tools to support the development of transferable CHEMs.Code: Visit https://www.ready4-dev.com for more information about how to find, install and apply the prototype software framework.

A Systematic Review and Meta-analysis: Paternal Anxiety and the Emotional and Behavioral Outcomes in Their Offspring.

OBJECTIVE: Anxiety disorders are highly prevalent worldwide; however, the literature lacks a meta-analytic quantification of the risk posed by fathers' anxiety for offspring development. This systematic review and meta-analysis aimed to provide a comprehensive estimate of the magnitude of the association between paternal anxiety and emotional and behavioral problems of offspring. METHOD: In February 2022, Web of Science, Ovid (Embase, MEDLINE, PsycINFO), Trip Database, and ProQuest were searched to identify all quantitative studies that measured anxiety in fathers and emotional and/or behavioral outcomes in offspring. No limits were set for offspring age, publication language, or publication year. Summary estimates were extracted from the primary studies. Meta-analytic random-effects 3-level models were used to calculate correlation coefficients. Quality was assessed using the Newcastle-Ottawa Scale. The study protocol was preregistered with PROSPERO (CRD42022311501) and adhered to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) reporting guidelines. RESULTS: Of 11,746 records identified, 98 were included in the meta-analysis. Small but significant associations were found between paternal anxiety and offspring emotional and behavioral problems overall (r = 0.16, 95% CI [0.13, 0.19]) and behavioral (r = 0.19, 95% CI [0.13, 0.24]), emotional (r = 0.15, 95% CI [0.12, 0.18]), anxiety (r = 0.13, 95% CI [0.11, 0.16]), and depression (r = 0.13, 95% CI [0.03, 0.23]) problems. Some significant moderators were identified. CONCLUSION: Paternal mental health is associated with offspring development, and the offspring of fathers with anxiety symptoms or disorders are at increased risk of negative emotional and behavioral outcomes, in line with the principles of multifinality and pleiotropy. The substantial heterogeneity among studies and the overrepresentation of White European American groups in this literature highlight the need for further research. DIVERSITY & INCLUSION STATEMENT: While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list.

Replicon particle vaccination induces non-neutralizing anti-nucleoprotein antibody-mediated control of Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe human disease and is considered a WHO priority pathogen due to the lack of efficacious vaccines and antivirals. A CCHF virus replicon particle (VRP) has previously shown protective efficacy in a lethal Ifnar-/- mouse model when administered as a single dose at least 3 days prior to challenge. Here, we determine that non-specific immune responses are not sufficient to confer short-term protection, since Lassa virus VRP vaccination 3 days prior to CCHFV challenge was not protective. We also investigate how CCHF VRP vaccination confers protective efficacy by examining viral kinetics, histopathology, clinical analytes and immunity early after challenge (3 and 6 days post infection) and compare to unvaccinated controls. We characterize how these effects differ based on vaccination period and correspond to previously reported CCHF VRP-mediated protection. Vaccinating Ifnar-/- mice with CCHF VRP 28, 14, 7, or 3 days prior to challenge, all known to confer complete protection, significantly reduced CCHFV viral load, mucosal shedding, and markers of clinical disease, with greater reductions associated with longer vaccination periods. Interestingly, there were no significant differences in innate immune responses, T cell activation, or antibody titers after challenge between groups of mice vaccinated a week or more before challenge, but higher anti-NP antibody avidity and effector function (ADCD) were positively associated with longer vaccination periods. These findings support the importance of antibody-mediated responses in VRP vaccine-mediated protection against CCHFV infection.

Attention and sensory integration for gait in young adults with autism spectrum disorder.

INTRODUCTION: Altered sensorimotor function is a common feature of autism spectrum disorder (ASD). As a result, spatiotemporal walking patterns are typically affected. Attentional processes relevant for locomotion may be altered in people with ASD. This study assessed the extent to which gait alterations observed under sensory challenging conditions are due to reduced attention-related processes in young adults with ASD. METHODS: Twenty-one adults with ASD and 21 age- and sex-matched neurotypical participants walked at a self-selected pace on a 10-m walkway under 12 sensory/attention conditions: hard or carpet flooring; well-lit or dim lighting; no attention task, an auditory choice-reaction time information-processing task, or a simple reaction time information-processing task. Gait data were collected with a 12-marker motion capture set and a trunk accelerometer. Spatiotemporal characteristics of gait were derived and compared between the two groups across gait conditions. RESULTS: Floor/light conditions impacted gait speed, average step length, average stance time, average step width, and step width variability similarly in both groups (p<0.05). The information processing tasks impacted average step length, gait speed, and step length variability (p<0.05). Group differences were found in step length metrics: the ASD group had decreased average step length during the simple reaction time information-processing task and neurotypical participants did not (p=0.039); the ASD group had increased variability on carpet compared to hard floor and the neurotypical group had no change in variability due to floor (p=0.015). SIGNIFICANCE: These results suggest that attentional set-shifting and somatosensory inputs may play an important role in ASD-related gait alterations. Step length metrics appear to be sensitive to group differences between ASD and neurotypical adults during sensory challenging conditions.

Adding to the Conversation: Language Delays and Parent-Child Interactions in the Younger Siblings of Children With Autism.

In their first three years, children begin to maintain topics and add new information in conversation. In turn, caregivers create opportunities for language learning. Compared to children with no family history of autism (typical likelihood, TL), the younger siblings of children with autism spectrum disorder (ASD) are at elevated likelihood (EL) for both ASD and language delays. This study asked: (1) Do profiles of spoken language and conversational skills differ across groups? (2) Does spoken language relate to conversational skills? and (3) How does parent speech relate to child spoken language and conversational skills? Child spoken language, conversational skills, and parent speech were examined during toy play at home with three-year-old TL (n = 16) and EL children with ASD (EL-ASD, n = 10), non-ASD language delay (EL-LD, n = 21), and no delays or diagnoses (EL-ND, n = 37). EL-ASD children produced fewer intelligible utterances, and EL-LD and EL-ASD children produced shorter utterances than TL and EL-ND children. When utterances were intelligible, all groups were highly contingent to the topic. EL-ASD children were less likely than all other groups to add new information, and adding new information was positively associated with utterance length. Parents of EL-ASD children had fewer opportunities to respond contingently. However, all parents were highly topic-contingent when child speech was intelligible, and parent speech complexity varied with child language and conversational skills. Findings highlight strengths in conversational skills for EL-ASD children during toy play with parents and show that children and caregivers together shape opportunities for developing language and conversation.

Movement as a Gateway to Participation for Individuals With Neuromotor Conditions: A Scoping Review.

PURPOSE: The purpose of this scoping review was to examine and analyze the developmental and rehabilitation literature related to movement and participation at key points of transition for individuals with neuromotor conditions. METHODS: Arksey and O'Malley's scoping review protocol was applied, and 37 articles were included. Extracted data included population, developmental transition points, movement opportunity, type of participation, and outcome measures. RESULTS: Most studies covered developmental transition points; none examined transitions as a variable for participation outcomes. Physical activity/exercise was the most common movement opportunity. Most publications used formal outcome measures of participation; others used observation or interviews. CONCLUSION: No publications adequately addressed the effect of movement opportunities on participation during developmental transition points.

ORF virus causes tumor-promoting inflammation in sheep and goats.

ORF virus (ORFV) causes contagious ecthyma ("ORF"), a disease of sheep and goats characterized by lesions ranging from vesicles and pustules to atypical papilloma-like and angiomatous lesions in the skin and mucosae. The authors investigated the molecular factors leading to the ORF-associated atypical tumor-like changes. Fifteen lambs, 15 kids, and an adult ram clinically affected by natural ORFV infection were enrolled in the study and examined by several methods. ORFV was detected by viral culture or real-time polymerase chain reaction (RT-PCR) in the lesioned tissues and in the blood of the clinically affected sheep and goats. Surprisingly, ORFV was also detected in the blood of healthy goats from an affected herd. Microscopically, they found a pseudo-papillomatous proliferation of the epithelium, while the dermis and lamina propria were expanded by a proliferating neovascular component that highly expressed the viral vascular endothelial growth factor (vVEGF) and its host receptor vascular endothelial growth factor receptor 2 (VEGFR2). Immunohistochemistry, immunofluorescence, and in situ hybridization for mRNA showed that epidermal growth factor receptor (EGFR) was expressed in the fibrovascular component, in the infiltrating CD163+ macrophages, and in the basal stratum of the epidermis. Confocal immunofluorescence microscopy demonstrated that CD163+ macrophages were associated with VEGF and VEGFR2. Finally, they found by quantitative RT-PCR the overexpression of the interleukin-6 and VEGFR2 genes in the lesioned tissues. These findings suggest that ORFV activates an inflammatory reaction characterized by CD163+ macrophages expressing EGFR and VEGFR2, which might play an oncogenic role through synergistic action with vVEGF signaling.

Burkholderia gladioli deep pyoderma in a dog secondary to immunosuppressive ciclosporin and prednisone therapy.

A dog presented with deep pyoderma on the paw, following treatment with ciclosporin and prednisone for immune-mediated haemolytic anaemia. Cytological evaluation, skin biopsy, aerobic culture, next-generation DNA sequencing and PCR were used to detect the first reported case of Burkholderia gladioli in a dog.