Discovery and Development of an Advanced Lead for the Treatment of African Trypanosomiasis.

African trypanosomiasis is a widespread disease of human and veterinary importance caused by various with a globally devastating impact and a need for novel treatment options. We here provide a comprehensive preclinical evaluation of nucleoside analogues, 6-thioether-modified tubercidins, with curative activity against African trypanosomiasis. Promising hits were identified following screening against the most relevant trypanosome species.

Mortality and functional outcomes 18 months after hospitalization for COVID-19 in geriatric patients: a multicentric cohort study.

Background: Few data are available on the long-term mortality and functional status of geriatric patients surviving after hospitalization for COVID-19. We compared the mortality and functional status 18 months after hospitalization for geriatric patients who were hospitalized for COVID-19 or another diagnosis.

Methods: This was a multicentric cohort study in Paris from January to June 2021.

A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death.

In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is compromised by a quick decline in the expression of hepatic PPARα, a transcription factor essential in intracellular catabolism of free fatty acids. The mechanism upstream of this PPARα downregulation is unknown. We found that sepsis causes a progressive hepatic loss-of-function of HNF4α, which has a strong impact on the expression of several important nuclear receptors, including PPARα.

A deep phenotyping study in mouse and iPSC models to understand the role of oligodendroglia in optic neuropathy in Wolfram syndrome.

Wolfram syndrome (WS) is a rare childhood disease characterized by diabetes mellitus, diabetes insipidus, blindness, deafness, neurodegeneration and eventually early death, due to autosomal recessive mutations in the WFS1 (and WFS2) gene. While it is categorized as a neurodegenerative disease, it is increasingly becoming clear that other cell types besides neurons may be affected and contribute to the pathogenesis. MRI studies in patients and phenotyping studies in WS rodent models indicate white matter/myelin loss, implicating a role for oligodendroglia in WS-associated neurodegeneration.

Effect of Leishmania infantum infection on B cell lymphopoiesis and memory in the bone marrow and spleen.

Visceral leishmaniasis (VL) is characterized by an uncontrolled infection of internal organs such as the spleen, liver and bone marrow (BM) and can be lethal when left untreated. No effective vaccination is currently available for humans. The importance of B cells in infection and VL protective immunity has been controversial, with both detrimental and protective effects described.

Q586B2 is a crucial virulence factor during the early stages of Trypanosoma brucei infection that is conserved amongst trypanosomatids.

Human African trypanosomiasis or sleeping sickness, caused by the protozoan parasite Trypanosoma brucei, is characterized by the manipulation of the host's immune response to ensure parasite invasion and persistence. Uncovering key molecules that support parasite establishment is a prerequisite to interfere with this process. We identified Q586B2 as a T.

Cancer therapy-related vaginal toxicity: its prevalence and assessment methods-a systematic review.

Purpose: In 2020, almost 9 million women were diagnosed with cancer worldwide. Despite advancements in cancer treatment strategies, patients still suffer from acute and long-term side effects. This systematic review aims to evaluate the most frequently reported adverse effects in the genitourinary system and compare them across cancer types, treatment modalities, and evaluation methods.

A novel, multi-active emollient for the prevention of acute radiation dermatitis in breast cancer patients: a randomized clinical trial.

Purpose: To investigate the efficacy of a novel, multi-active emollient in preventing and managing acute radiation dermatitis (ARD) in breast cancer patients undergoing moderate hypofractionated (HF) radiotherapy (RT) compared to standard of care.

Methodsa: A monocentric, open-label, randomized clinical trial (RCT) with breast cancer patients receiving moderate HF (dose: 40.05-55.

Patient-Centred Outcomes after Totally Endoscopic Cardiac Surgery: One-Year Follow-Up.

Patient-centred outcomes have grown in popularity over recent years in surgical care research. These patient-centred outcomes can be measured through the health-related quality of life (HRQL) without professional interpretations. In May 2022, a study regarding patient-centred outcomes up to 90 days postoperatively was published.

Immune stimulation recruits a subset of pro-regenerative macrophages to the retina that promotes axonal regrowth of injured neurons.

The multifaceted nature of neuroinflammation is highlighted by its ability to both aggravate and promote neuronal health. While in mammals retinal ganglion cells (RGCs) are unable to regenerate following injury, acute inflammation can induce axonal regrowth. However, the nature of the cells, cellular states and signalling pathways that drive this inflammation-induced regeneration have remained elusive.

The use of photobiomodulation therapy for the management of chemotherapy-induced alopecia: a randomized, controlled trial (HAIRLASER trial).

Purpose: The purpose of this trial was to evaluate if photobiomodulation (PBM) can accelerate hair regrowth after chemotherapy in breast cancer patients and if this is correlated with a better quality of life (QoL).

Methods: A randomized controlled trial with breast cancer patients that underwent an anthracycline and taxane-containing chemotherapy regimen was set up at the Jessa Hospital (Hasselt, Belgium). Patients were randomized into the control group (no intervention) or the PBM group (three PBM sessions each week for 12 weeks, starting the last day of their chemotherapy).

Baseline CT-Based Risk Factors for Atrioventricular Block after Surgical AVR.

Background:  We aimed to evaluate the impact of membranous interventricular septum (MIS) length and calcifications of the native aortic valve (AV), via preoperative multidetector computed tomography (MDCT) scan, on postoperative atrioventricular block III (AVB/AVB III) and permanent pacemaker implantation in surgical aortic valve replacement (SAVR).

Methods:  We retrospectively analyzed preoperative contrast-enhanced MDCT scans and procedural outcomes of patients affected by AV stenosis who underwent SAVR at our center (June 2016-December 2019). The study population was divided into two groups (AVB and non-AVB), and variables were compared with a Mann-Whitney's -test or chi-square test.

Evaluation of a novel skin care product for the management of chemotherapy-related dermatologic toxicities: A quasi-experimental study.

Purpose: Evaluate the efficacy of a novel skincare product for the management of chemotherapy-related dermatological toxicities.

Methods: A monocentric, prospective, interventional, open-label, pretest-posttest, single-group study with cancer patients receiving chemotherapy (n = 100) was set up. All enrolled patients applied the emollient daily to their face and body for three weeks.

Comparison of Bioluminescent Substrates in Natural Infection Models of Neglected Parasitic Diseases.

The application of in vivo bioluminescent imaging in infectious disease research has significantly increased over the past years. The detection of transgenic parasites expressing wildtype firefly luciferase is however hampered by a relatively low and heterogeneous tissue penetrating capacity of emitted light. Solutions are sought by using codon-optimized red-shifted luciferases that yield higher expression levels and produce relatively more red or near-infrared light, or by using modified bioluminescent substrates with enhanced cell permeability and improved luminogenic or pharmacokinetic properties.

A long-term follow-up of early breast cancer patients treated with photobiomodulation during conventional fractionation radiotherapy in the prevention of acute radiation dermatitis.

Objectives: The evidence demonstrating the efficacy of photobiomodulation (PBM) therapy for preventing and managing acute radiation dermatitis (ARD) is growing steadily. The question that arises from many clinicians is, if PBM is safe for oncologic patients. This study aimed to evaluate the disease-free survival (DFS), cancer-free survival (CFS), and overall survival (OS) of breast cancer patients treated with PBM for ARD.

Retinal Ganglion Cells: Global Number, Density and Vulnerability to Glaucomatous Injury in Common Laboratory Mice.

How many RBPMS retinal ganglion cells (RGCs) does a standard C57BL/6 laboratory mouse have on average and is this number substrain- or sex-dependent? Do RGCs of (European) C57BL/6J and -N mice show a different intrinsic vulnerability upon glaucomatous injury? Global RGC numbers and densities of common laboratory mice were previously determined via axon counts, retrograde tracing or BRN3A immunohistochemistry. Here, we report the global RGC number and density by exploiting the freely available tool RGCode to automatically count RGC numbers and densities on entire retinal wholemounts immunostained for the pan-RGC marker RBPMS. The intrinsic vulnerability of RGCs from different substrains to glaucomatous injury was evaluated upon introduction of the microbead occlusion model, followed by RBPMS counts, retrograde tracing and electroretinography five weeks post-injury.

Chronic Chemogenetic Activation of the Superior Colliculus in Glaucomatous Mice: Local and Retrograde Molecular Signature.

One important facet of glaucoma pathophysiology is axonal damage, which ultimately disrupts the connection between the retina and its postsynaptic brain targets. The concurrent loss of retrograde support interferes with the functionality and survival of the retinal ganglion cells (RGCs). Previous research has shown that stimulation of neuronal activity in a primary retinal target area-i.

90-Day Patient-Centered Outcomes after Totally Endoscopic Cardiac Surgery: A Prospective Cohort Study.

Over the past years, minimally invasive procedures have been developed to reduce surgical trauma after cardiac surgery. The value of patient-centered outcomes, including the quality of recovery after hospital discharge, is increasingly recognized. Identifying meaningful changes in postoperative function that might have a negative impact on patients without noticeable complications can provide a more comprehensive understanding of the impact on the patient's life.

Risk of conduction disturbances following different transcatheter aortic valve prostheses: the role of aortic valve calcifications.

Objectives: To assess the impact of prosthesis choice and aortic valve calcifications on the occurrence of conduction disturbances after transcatheter aortic valve implantation (TAVI).

Methods: We retrospectively analyzed the preoperative clinical characteristics, electrocardiograms, contrast-enhanced multidetector computed tomography scans and procedural strategies of patients who underwent TAVI in our center between January 2012 and June 2017. Quantification of calcium volume was performed for each aortic cusp above (aortic valve) and below (left ventricular outflow tract, LVOT) the basal plane.

The DREADDful Hurdles and Opportunities of the Chronic Chemogenetic Toolbox.

The chronic character of chemogenetics has been put forward as one of the assets of the technique, particularly in comparison to optogenetics. Yet, the vast majority of chemogenetic studies have focused on acute applications, while repeated, long-term neuromodulation has only been booming in the past few years. Unfortunately, together with the rising number of studies, various hurdles have also been uncovered, especially in relation to its chronic application.

MMP2 Modulates Inflammatory Response during Axonal Regeneration in the Murine Visual System.

Neuroinflammation has been put forward as a mechanism triggering axonal regrowth in the mammalian central nervous system (CNS), yet little is known about the underlying cellular and molecular players connecting these two processes. In this study, we provide evidence that MMP2 is an essential factor linking inflammation to axonal regeneration by using an in vivo mouse model of inflammation-induced axonal regeneration in the optic nerve. We show that infiltrating myeloid cells abundantly express MMP2 and that MMP2 deficiency results in reduced long-distance axonal regeneration.

A Fair Assessment of Evaluation Tools for the Murine Microbead Occlusion Model of Glaucoma.

Despite being one of the most studied eye diseases, clinical translation of glaucoma research is hampered, at least in part, by the lack of validated preclinical models and readouts. The most popular experimental glaucoma model is the murine microbead occlusion model, yet the observed mild phenotype, mixed success rate, and weak reproducibility urge for an expansion of available readout tools. For this purpose, we evaluated various measures that reflect early onset glaucomatous changes in the murine microbead occlusion model.

Impact of COVID-19 on Multiple Sclerosis Topic Discussion on Twitter.

Introduction: Multiple sclerosis (MS) is one of the world's most common neurologic disorders. Social media have been proposed as a way to maintain and even increase social interaction for people with MS. The objective of this work is to identify and compare the topics on Twitter during the first wave of COVID-19 pandemic.

ERG transcription factors have a splicing regulatory function involving RBFOX2 that is altered in the EWS-FLI1 oncogenic fusion.

ERG family proteins (ERG, FLI1 and FEV) are a subfamily of ETS transcription factors with key roles in physiology and development. In Ewing sarcoma, the oncogenic fusion protein EWS-FLI1 regulates both transcription and alternative splicing of pre-messenger RNAs. However, whether wild-type ERG family proteins might regulate splicing is unknown.

4E Interacting Protein as a Potential Novel Drug Target for Nucleoside Analogues in .

Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets.