Clinical and magnetic resonance imaging findings of presumed limber tail syndrome in a cat.

A 4-year-old neutered female domestic shorthair indoor cat was presented with sudden onset of abnormal and painful tail-carriage. The tail was held horizontally for the first centimeters from the base and a flaccid paralysis was evident more distally. Magnetic resonance imaging of the lumbosacral spine and tail revealed a lesion located in the right and muscles along the 1st coccygeal vertebrae.

Preclinical development of lyophilized self-replicating RNA vaccines for COVID-19 and malaria with improved long-term thermostability.

Messenger RNA (mRNA) vaccines against COVID-19 have demonstrated high efficacy and rapid deployment capability to target emerging infectious diseases. However, the need for ultra-low temperature storage made the distribution of LNP/mRNA vaccines to regions with limited resources impractical. This study explores the use of lyophilization to enhance the stability of self-replicating mRNA (repRNA) vaccines, allowing for their storage at non-freezing temperatures such as 2-8 °C or room temperature (25 °C).

Full maturation of in vitro Plasmodium falciparum oocysts using the AlgiMatrix 3D culture system.

Background: Plasmodium falciparum oocysts undergo growth and maturation in a unique setting within the mosquito midgut, firmly situated between the epithelium and the basal lamina. This location exposes them to specific nutrient exchange and metabolic processes while in direct contact with the mosquito haemolymph. The limited availability of in vitro culture systems for growth of the various P.

Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

Malaria, caused by Plasmodium parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts to lower morbidity and mortality. Both advanced candidate vaccines, RTS,S and R21, are subunit (SU) vaccines that target a single Plasmodium falciparum (Pf) pre-erythrocytic (PE) sporozoite (spz) surface protein known as circumsporozoite (CS). These vaccines induce humoral immunity but fail to elicit CD8 + T-cell responses sufficient for long-term protection.

Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

Malaria, caused parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts that have lowered morbidity and mortality. The only vaccine candidates to show field efficacy are those targeting the asymptomatic pre-erythrocytic (PE) stages of infection. The subunit (SU) RTS,S/AS01 vaccine, the only licensed malaria vaccine to date, is only modestly effective against clinical malaria.

Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

Malaria, caused by parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts that have lowered morbidity and mortality. The only vaccine candidates to show field efficacy are those targeting the asymptomatic pre-erythrocytic (PE) stages of infection. The subunit (SU) RTS,S/AS01 vaccine, the only licensed malaria vaccine to date, is only modestly effective against clinical malaria.

Genetic variations in human ATP2B4 gene alter Plasmodium falciparum in vitro growth in RBCs from Gambian adults.

Background: Polymorphisms in ATP2B4 coding for PMCA4b, the primary regulator of erythrocyte calcium concentration, have been shown by GWAS and cross-sectional studies to protect against severe malaria but the mechanism remains unknown.

Methods: Using a recall-by-genotype design, we investigated the impact of a common haplotype variant in ATP2B4 using in vitro assays that model erythrocyte stage malaria pathogenesis. Ninety-six donors representing homozygote (carriers of the minor allele, C/C), heterozygote (T/C) and wildtype (T/T) carriers of the tagging SNP rs1541252 were selected from a cohort of over 12,000 participants in the Keneba Biobank.

Parasite Lines Expressing DC8 and Group A PfEMP1 Bind to Brain, Intestinal, and Kidney Endothelial Cells.

Cytoadhesion of -infected red blood cells is a virulence determinant associated with microvascular obstruction and organ complications. The gastrointestinal tract is a major site of sequestration in fatal cerebral malaria cases and kidney complications are common in severe malaria, but parasite interactions with these microvascular sites are poorly characterized. To study parasite tropism for different microvascular sites, we investigated binding of parasite lines to primary human microvascular endothelial cells from intestine (HIMEC) and peritubular kidney (HKMEC) sites.

Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer.

Colorectal cancer is a major health concern worldwide. Growing evidence for the role of the gut microbiota in the initiation of CRC has sparked interest in approaches that target these microorganisms. However, little is known about the composition and role of the microbiota associated with precancerous polyps.

"Driver-passenger" bacteria and their metabolites in the pathogenesis of colorectal cancer.

Colorectal cancer (CRC) is a significant public health problem accounting for about 10% of all new cancer cases globally. Though genetic and epigenetic factors influence CRC, the gut microbiota acts as a significant component of the disease's etiology. Further research is still needed to clarify the specific roles and identify more bacteria related to CRC development.

The PI3K/mTOR Pathway Is Targeted by Rare Germline Variants in Patients with Both Melanoma and Renal Cell Carcinoma.

: Malignant melanoma and RCC have different embryonic origins, no common lifestyle risk factors but intriguingly share biological properties such as immune regulation and radioresistance. An excess risk of malignant melanoma is observed in RCC patients and vice versa. This bidirectional association is poorly understood, and hypothetic genetic co-susceptibility remains largely unexplored.

BRAF inhibitor resistance of melanoma cells triggers increased susceptibility to natural killer cell-mediated lysis.

Background: Targeted therapies and immunotherapies are first-line treatments for patients with advanced melanoma. Serine-threonine protein kinase B-RAF (BRAF) and mitogen-activated protein kinase (MEK) inhibition leads to a 70% response rate in patients with advanced melanoma with a mutation. However, acquired resistance occurs in the majority of patients, leading to relapse.

NK Cell and Fibroblast-Mediated Regulation of Skin Squamous Cell Carcinoma Invasion by CLEC2A Is Compromised in Xeroderma Pigmentosum.

The ability of cancer cells to invade and disseminate can be affected by components of the surrounding microenvironment. To identify dermal components that regulate the growth of epidermal carcinomas, we studied the genetic disease called xeroderma pigmentosum that bears mutations in genes involved in the nucleotide excision repair of DNA. Patients with xeroderma pigmentosum are more prone to develop cutaneous tumors than the general population and their dermal fibroblasts display the features of dermal cancer-associated fibroblasts, which promote the invasion of keratinocytes.

[Rieger-Marchac flaps: Complications and patient satisfaction].

Purpose: Like all surgical procedures, dorsal nasal flaps may be followed by both early and late complications. The aim of this study was to evaluate the surgical complications and cosmetic outcome of dorsal nasal flaps over a 7-year period in an academic dermatologic surgery unit.

Patients And Methods: Data were collected retrospectively for all patients undergoing dorsal nasal flap between 1 January 2006 and 31 December 2013.

VAR2CSA binding phenotype has ancient origin and arose before Plasmodium falciparum crossed to humans: implications in placental malaria vaccine design.

VAR2CSA is a leading candidate for developing a placental malaria (PM) vaccine that would protect pregnant women living in malaria endemic areas against placental infections and improve birth outcomes. Two VAR2CSA-based PM vaccines are currently under clinical trials, but it is still unclear if the use of a single VAR2CSA variant will be sufficient to induce a broad enough humoral response in humans to cross-react with genetically diverse parasite populations. Additional immuno-focusing vaccine strategies may therefore be required to identify functionally conserved antibody epitopes in VAR2CSA.

Interplay of Plasmodium falciparum and thrombin in brain endothelial barrier disruption.

Recent concepts suggest that both Plasmodium falciparum factors and coagulation contribute to endothelial activation and dysfunction in pediatric cerebral malaria (CM) pathology. However, there is still limited understanding of how these complex inflammatory stimuli are integrated by brain endothelial cells. In this study, we examined how mature-stage P.

Binding Heterogeneity of Plasmodium falciparum to Engineered 3D Brain Microvessels Is Mediated by EPCR and ICAM-1.

Cerebral malaria is a severe neurological complication associated with sequestration of -infected erythrocytes (IE) in the brain microvasculature, but the specific binding interactions remain under debate. Here, we have generated an engineered three-dimensional (3D) human brain endothelial microvessel model and studied binding under the large range of physiological flow velocities that occur in both health and disease. Perfusion assays on 3D microvessels reveal previously unappreciated phenotypic heterogeneity in parasite binding to tumor necrosis factor alpha (TNF-α)-activated brain endothelial cells.

NKG2D/NKG2-Ligand Pathway Offers New Opportunities in Cancer Treatment.

The antitumor functions of NK cells are regulated by the integration of positive and negative signals triggered by numerous membrane receptors present on the NK cells themselves. Among the main activating receptors, NKG2D binds several stress-induced molecules on tumor targets. Engagement of NKG2D by its ligands (NKG2D-Ls) induces NK cell activation leading to production of cytokines and target cell lysis.

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT.

Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved.

Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium.

Pembrolizumab for Unresectable or Metastatic Melanoma in Patients Older than 85 Years of Age.

Background: Programmed cell death protein-1 (PD-1) inhibitors (pembrolizumab and nivolumab) have been approved for the treatment of advanced melanoma. Over the past decades, patients older than 85 years represent an expanding group of patients in developed countries. In France, 25% of melanomas are diagnosed in patients older than 75 years.

Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma.

Background: The objective was to assess the response rate and survival of patients with metastatic mucosal melanoma (MM) and uveal melanoma (UM) treated with anti-CTLA-4 or anti-PD-1 monoclonal antibodies (mAbs).

Methods: A multicenter retrospective study was performed in 25 dermatology departments in France. All patients with stage III-C to IV MM or UM who were treated with anti-CTLA-4 or anti-PD-1 mAbs between 2008 and 2016 were included and compared after adjustment for main prognostic factors with a second cohort of patients treated with chemotherapy.