Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.

Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.

One health and social research in disease ecology: A social contextual study of vector-borne diseases in the Yucatan Peninsula, Mexico.

Although disease ecology recognizes the multiplicity of factors involved in the (re)emergence of vector-borne diseases (VBD), it is necessary to strengthen attention to the social context and the social determinants of health. It is essential to integrate a sociocultural approach to health into the biological analysis of VBD ecology. To implement a coherent One Health approach in the prevention and control of VBD, it is pivotal to first understand the social and ecological interactions of the local context.

New potent EV-A71 antivirals targeting capsid.

The enterovirus is a genus of single-stranded, highly diverse positive-sense RNA viruses, including Human Enterovirus A-D and Human Rhinovirus A-C species. They are responsible for numerous diseases and some infections can progress to life-threatening complications, particularly in children or immunocompromised patients. To date, there is no treatment against enteroviruses on the market, except for polioviruses (vaccine) and EV-A71 (vaccine in China).

Evidence of DISC1 as an arsenic binding protein and implications regarding its role as a translational activator.

Disrupted-in-schizophrenia-1 (DISC1) is a scaffolding protein that plays a pivotal role in orchestrating signaling pathways involved in neurodevelopment, neural migration, and synaptogenesis. Among those, it has recently been reported that the role of DISC1 in the Akt/mTOR pathway can shift from a global translational repressor to a translational activator in response to oxidative stress induced by arsenic. In this study we provide evidence that DISC1 can directly bind arsenic via a C-terminal cysteine motif (C-X-C-X-C).

Evidence of Disrupted-in Schizophrenia 1 (DISC1) as an arsenic binding protein and implications regarding its role as a translational activator.

Disrupted-in-schizophrenia-1 (DISC1) is a scaffold protein that plays a pivotal role in orchestrating signaling pathways involved in neurodevelopment, neural migration, and synaptogenesis. Among those, it has recently been reported that the role DISC1 in the Akt/mTOR pathway can shift from a global translational repressor to a translational activator in response to oxidative stress induced by arsenic. In this study we are providing evidence that DISC1 can directly bind arsenic via a C-terminal cysteine motif (C-X-C-X-C).

SORD-related peripheral neuropathy in a French and Swiss cohort: Clinical features, genetic analyses, and sorbitol dosages.

Background And Purpose: Biallelic variants in SORD have been reported as one of the main recessive causes for hereditary peripheral neuropathies such as Charcot-Marie-Tooth disease type 2 (CMT2) and distal hereditary motor neuropathy (dHMN) resulting in lower limb (LL) weakness and muscular atrophy. In this study, phenotype and genotype landscapes of SORD-related peripheral neuropathies were described in a French and Swiss cohort. Serum sorbitol dosages were used to classify SORD variants.

Peripheral Neuropathies Derived from COVID-19: New Perspectives for Treatment.

Peripheral neuropathies constitute a group of disorders affecting the peripheral nervous system. Neuropathies have multiple causes such as infections (i.e.

An analysis of police transport in an Eastern Association for the Surgery of Trauma multicenter trial examining prehospital procedures in penetrating trauma patients.

Background: Police transport (PT) of penetrating trauma patients in urban locations has become routine in certain metropolitan areas; however, whether it results in improved outcomes over prehospital Advanced life support (ALS) transport has not been determined in a multicenter study. We hypothesized that PT would not result in improved outcomes.

Methods: This was a multicenter, prospective, observational study of adults (18+ years) with penetrating trauma to the torso and/or proximal extremity presenting at 25 urban trauma centers.

Pembrolizumab induces HIV latency reversal in people living with HIV and cancer on antiretroviral therapy.

In people living with HIV (PLWH) on antiretroviral therapy (ART), virus persists in a latent form where there is minimal transcription or protein expression. Latently infected cells are a major barrier to curing HIV. Increasing HIV transcription and viral production in latently infected cells could facilitate immune recognition and reduce the pool of infected cells that persist on ART.

An Eastern Association for the Surgery of Trauma multicenter trial examining prehospital procedures in penetrating trauma patients.

Background: Prehospital procedures (PHP) by emergency medical services (EMS) are performed regularly in penetrating trauma patients despite previous studies demonstrating no benefit. We sought to examine the influence of PHPs on outcomes in penetrating trauma patients in urban locations where transport to trauma center is not prolonged. We hypothesized that patients without PHPs would have better outcomes than those undergoing PHP.

How to Quantitatively Balance a Total Knee? A Surgical Algorithm to Assure Balance and Control Alignment.

To achieve a balanced total knee, various surgical corrections can be performed, while intra-operative sensors and surgical navigation provide quantitative, patient-specific feedback. To understand the impact of these corrections, this paper evaluates the quantitative impact of both soft tissue releases and bone recuts on knee balance and overall limb alignment. This was achieved by statistically analyzing the alignment and load readings before and after each surgical correction performed on 479 consecutive primary total knees.

Dasatinib Treatment Increases Sensitivity to c-Met Inhibition in Triple-Negative Breast Cancer Cells.

In pre-clinical studies, triple-negative breast cancer (TNBC) cells have demonstrated sensitivity to the multi-targeted kinase inhibitor dasatinib; however, clinical trials with single-agent dasatinib showed limited efficacy in unselected populations of breast cancer, including TNBC. To study potential mechanisms of resistance to dasatinib in TNBC, we established a cell line model of acquired dasatinib resistance (231-DasB). Following an approximately three-month exposure to incrementally increasing concentrations of dasatinib (200 nM to 500 nM) dasatinib, 231-DasB cells were resistant to the agent with a dasatinib IC value greater than 5 μM compared to 0.

Rupture limit evaluation of human cerebral aneurysms wall: Experimental study.

Background And Purpose: Rupture risk of intracranial aneurysms is a major issue for public healthcare. A way to obtain an individual rupture risk assessment is a main objective of many research teams in the world. For many years, we have investigated the relationship between the mechanical properties of aneurysm wall tissues and the rupture risk.

Phosphorylation of human aquaporin 2 (AQP2) allosterically controls its interaction with the lysosomal trafficking protein LIP5.

The interaction between the renal water channel aquaporin-2 (AQP2) and the lysosomal trafficking regulator-interacting protein LIP5 targets AQP2 to multivesicular bodies and facilitates lysosomal degradation. This interaction is part of a process that controls AQP2 apical membrane abundance in a vasopressin-dependent manner, allowing for urine volume adjustment. Vasopressin regulates phosphorylation at four sites within the AQP2 C terminus (Ser, Ser, Ser, and Thr), of which Ser is crucial and sufficient for AQP2 translocation from storage vesicles to the apical membrane.

High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation.

We examined nutrient transport in the intestines of mice exposed to chronic low-LET 137Cs gamma rays. The mice were whole-body irradiated for 3 days at dose rates of 0, 0.13 and 0.

Increased glycolipid storage produced by the inheritance of a complex intronic haplotype in the α-galactosidase A (GLA) gene.

Background: Accumulation of galactosphingolipids is a general characteristic of Fabry disease, a lysosomal storage disorder caused by the deficient activity of α-galactosidase A encoded by the GLA gene. Although many polymorphic GLA haplotypes have been described, it is still unclear whether some of these variants are causative of disease symptoms. We report the study of an inheritance of a complex intronic haplotype (CIH) (c.

Insights into the Hendra virus NTAIL-XD complex: Evidence for a parallel organization of the helical MoRE at the XD surface stabilized by a combination of hydrophobic and polar interactions.

The Hendra virus is a member of the Henipavirus genus within the Paramyxoviridae family. The nucleoprotein, which consists of a structured core and of a C-terminal intrinsically disordered domain (N(TAIL)), encapsidates the viral genome within a helical nucleocapsid. N(TAIL) partly protrudes from the surface of the nucleocapsid being thus capable of interacting with the C-terminal X domain (XD) of the viral phosphoprotein.

Bone density and functional results after femoral revision with a cementless press-fit stem.

Introduction: The influence of radiographic bone density changes in the area surrounding a total hip arthroplasty (THA) revision with a cementless press-fit stem is unknown, notably in terms of functional results. We have therefore conducted a study aiming to (1) propose a radiographic method to assess bone density, (2) measure the functional effects of reduced bone density, and (3) determine the factors contributing to these modifications.

Hypothesis: A reduction in radiographic bone density has a negative influence on the functional result after revision using a cementless press-fit stem.

A clinical in-hospital prognostic score for acute exacerbations of COPD.

Background: The use of a severity score to help orientation decisions could improve the efficiency of care for acute exacerbations of COPD (AECOPD). We previously developed a score ('2008 score', based on age, dyspnea grade at steady state and number of clinical signs of severity) predicting in-hospital mortality in patients with AECOPD visiting emergency departments (EDs). External validity of this score remained to be assessed.

Synthesis, biological activity and structure-activity relationship of 4,5-dimethoxybenzene derivatives inhibitor of rhinovirus 14 infection.

Human rhinoviruses are a common cause of respiratory infections, and thus constitute an important target for medicinal chemistry. Still, no drug has been approved for clinical use. We report herein the discovery of dibenzenic derivatives with potent and specific in vitro anti-rhinoviral 14 activity.

Top single nucleotide polymorphisms affecting carbohydrate metabolism in metabolic syndrome: from the LIPGENE study.

Rationale: Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk.

Objectives: Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS.

Methods: A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study.

Intranasal vaccination in mice with an attenuated Salmonella enterica Serovar 908htr A expressing Cp15 of Cryptosporidium: impact of malnutrition with preservation of cytokine secretion.

Cryptosporidium is a protozoan parasite associated with acute and persistent diarrhea that, even in asymptomatic persons, can impair normal growth and potentially cognitive and physical development in young children. The recent availability of the complete gene sequence for Cryptosporidium hominis antigen Cp15 allows examination of innovative vaccine regimens involving intra-nasal antigen priming with live bacterial vectors applicable to human populations. We used a recently described weaned mouse model of cryptosporidiosis, where nourished and malnourished vaccinated mice receive the Cp15 antigen recombinant with cytolysinA on a Salmonella serovar Typhi CVD 908-htr A vector, followed by parenteral exposure to antigen with adjuvant.

Marked changes in endogenous antioxidant expression precede vitamin A-, C-, and E-protectable, radiation-induced reductions in small intestinal nutrient transport.

Rapidly proliferating epithelial crypt cells of the small intestine are susceptible to radiation-induced oxidative stress, yet there is a dearth of data linking this stress to expression of antioxidant enzymes and to alterations in intestinal nutrient absorption. We previously showed that 5-14 days after acute γ-irradiation, intestinal sugar absorption decreased without change in antioxidant enzyme expression. In the present study, we measured antioxidant mRNA and protein expression in mouse intestines taken at early times postirradiation.