Problematic anger among military personnel after combat deployment: prevalence and risk factors.

Background: Problematic anger, characterized by excessive frequency, intensity, and duration of anger which causes substantial emotional distress and functional interference, poses a marked challenge in military populations. Despite its importance, research on this topic is limited. This study contributes to the literature by exploring problematic anger in a large sample of Norwegian military personnel who served in NATO missions in Afghanistan.

Rituximab treatment in pediatric-onset multiple sclerosis.

Background And Purpose: Rituximab (RTX) is frequently used off-label in multiple sclerosis. However, studies on the risk-benefit profile of RTX in pediatric-onset multiple sclerosis are scarce.

Methods: In this multicenter retrospective cohort study, patients with pediatric-onset multiple sclerosis from Sweden, Austria and Germany, who received RTX treatment were identified by chart review.

Differences in resilience profiles between military veterans and the general population: An exploratory latent profile analysis using the HUNT-4 survey.

Using latent profile analyses, the current work investigated levels of adverse childhood experiences, symptoms of anxiety and depression and 3 dimensions of relational promotive factors) to identify resilience profiles in a large general population sample (N = 161,622, mean age = 53.02; SD = 17.80; 56.

Non-functional ubiquitin C-terminal hydrolase L1 drives podocyte injury through impairing proteasomes in autoimmune glomerulonephritis.

Little is known about the mechanistic significance of the ubiquitin proteasome system (UPS) in a kidney autoimmune environment. In membranous nephropathy (MN), autoantibodies target podocytes of the glomerular filter resulting in proteinuria. Converging biochemical, structural, mouse pathomechanistic, and clinical information we report that the deubiquitinase Ubiquitin C-terminal hydrolase L1 (UCH-L1) is induced by oxidative stress in podocytes and is directly involved in proteasome substrate accumulation.

A mechanism of uncompetitive inhibition of the serotonin transporter.

The serotonin transporter (SERT/SLC6A4) is arguably the most extensively studied solute carrier (SLC). During its eponymous action - that is, the retrieval of serotonin from the extracellular space - SERT undergoes a conformational cycle. Typical inhibitors (antidepressant drugs and cocaine), partial and full substrates (amphetamines and their derivatives), and atypical inhibitors (ibogaine analogues) bind preferentially to different states in this cycle.

editing homology-directed repair in junctional epidermolysis bullosa.

Background: Epidermolysis bullosa (EB), a severe genetic disorder characterized by blister formation in skin, is caused by mutations in genes encoding dermal-epidermal junction proteins that function to hold the skin layers together. CRISPR/Cas9-induced homology-directed repair (HDR) represents a promising tool for editing causal mutations in in the treatment of junctional epidermolysis bullosa (JEB).

Methods: In this study, we treated primary type XVII collagen (C17)-deficient JEB keratinocytes with either Cas9 nuclease or nickase (Cas9n) ribonucleoproteins (RNP) and a single-stranded oligonucleotide (ssODN) HDR template in order to correct a causal pathogenic frameshift mutation within the gene.

Paired nicking-mediated COL17A1 reframing for junctional epidermolysis bullosa.

Junctional epidermolysis bullosa (JEB) is a debilitating hereditary skin disorder caused by mutations in genes encoding laminin-332, type XVII collagen (C17), and integrin-α6β4, which maintain stability between the dermis and epidermis. We designed patient-specific Cas9-nuclease- and -nickase-based targeting strategies for reframing a common homozygous deletion in exon 52 of COL17A1 associated with a lack of full-length C17 expression. Subsequent characterization of protein restoration, indel composition, and divergence of DNA and mRNA outcomes after treatment revealed auspicious efficiency, safety, and precision profiles for paired nicking-based COL17A1 editing.

Impact of low-dose calcipotriol ointment on wound healing, pruritus and pain in patients with dystrophic epidermolysis bullosa: A randomized, double-blind, placebo-controlled trial.

Background: Wound management is a critical factor when treating patients with the inherited skin fragility disease dystrophic epidermolysis bullosa (DEB). Due to genetic defects in structural proteins, skin and mucous epithelia are prone to blistering and chronic wounding upon minor trauma. Furthermore, these wounds are commonly associated with excessive pruritus and predispose to the development of life-threatening squamous cell carcinomas, underscoring the unmet need for new therapeutic options to improve wound healing in this patient cohort.

Tripartite Separation of Glomerular Cell Types and Proteomes from Reporter-Free Mice.

Background: The glomerulus comprises podocytes, mesangial cells, and endothelial cells, which jointly determine glomerular filtration. Understanding this intricate functional unit beyond the transcriptome requires bulk isolation of these cell types for biochemical investigations. We developed a globally applicable tripartite isolation method for murine mesangial and endothelial cells and podocytes (timMEP).

From a first person perspective: Soldiers' experiences three decades after an avalanche - A qualitative interview study.

Study Objectives: The aim of this study was to explore indirectly exposed soldiers' subjective experiences following an avalanche. Three decades after the trauma, this study describes the perceived impact of the disaster by peers of those who survived or died in the avalanche.

Method: A qualitative, cross-sectional, study based on 17 individual interviews with persons indirectly exposed to an avalanche.

ADAM10-Mediated Ectodomain Shedding Is an Essential Driver of Podocyte Damage.

Background: Podocytes embrace the glomerular capillaries with foot processes, which are interconnected by a specialized adherens junction to ultimately form the filtration barrier. Altered adhesion and loss are common features of podocyte injury, which could be mediated by shedding of cell-adhesion molecules through the regulated activity of cell surface-expressed proteases. A Disintegrin and Metalloproteinase 10 (ADAM10) is such a protease known to mediate ectodomain shedding of adhesion molecules, among others.

Advancing novel therapies for ichthyoses.

 Valentin 2021; :1123–1131.

Caring for Coronavirus Healthcare Workers: Lessons Learned From Long-Term Monitoring of Military Peacekeepers.

Background: The current outbreak of the coronavirus disease (COVID-19) is of unprecedented proportions in several regards. Recent reports suggest that many frontline healthcare workers (HCWs) suffer from mental health problems, including posttraumatic stress symptoms (PTSS). Previous studies have identified several key factors associated with short-term PTSS in pandemic HCWs, yet limited data is available on factors associated with long-term PTSS.

Gene expression is stable in a complete CIB1 knockout keratinocyte model.

Epidermodysplasia verruciformis (EV) is a genodermatosis characterized by the inability of keratinocytes to control cutaneous β-HPV infection and a high risk for non-melanoma skin cancer (NMSC). Bi-allelic loss of function variants in TMC6, TMC8, and CIB1 predispose to EV. The correlation between these proteins and β-HPV infection is unclear.

Prevalence and Correlates of Mental Health Problems in Norwegian Peacekeepers 18-38 Years Postdeployment.

Peacekeeping missions involve experiences that may impact the mental health of participating soldiers. However, research on the long-term mental health consequences of peacekeeping is sparse. The present study aimed to find the prevalence of mental health problems (MHPs), possible MHP predictors, and associations between predictors and MHPs in Norwegian peacekeepers 18-38 years after deployment to a United Nations peacekeeping mission.

Veno-Venous Extracorporeal Lung Support as a Bridge to or Through Lung Volume Reduction Surgery in Patients with Severe Hypercapnia.

Extracorporeal lung support (ECLS) represents an essential support tool especially for critically ill patients undergoing thoracic surgical procedures. Lung volume reduction surgery (LVRS) is an important treatment option for end-stage lung emphysema in carefully selected patients. Here, we report the efficacy of veno-venous ECLS (VV ECLS) as a bridge to or through LVRS in patients with end-stage lung emphysema and severe hypercapnia.

A cancer stem cell-like phenotype is associated with miR-10b expression in aggressive squamous cell carcinomas.

Background: Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from the rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is in marked contrast to the rarely metastasizing nature of these carcinomas in the general population. This remarkable difference is attributed to the frequent development of chronic wounds caused by impaired skin integrity. However, the specific molecular and cellular changes to malignancy, and whether there are common players in different types of aggressive cSCCs, remain relatively undefined.

Combined Use of CytoSorb and ECMO in Patients with Severe Pneumogenic Sepsis.

Background: High morbidity and mortality are frequently reported in intensive care patients suffering from severe sepsis with systemic inflammation. With the development of severe respiratory failure, extracorporeal membrane oxygenation (ECMO) is often required. In this study, cytokine adsorption therapy in combination with ECMO is applied in patients with acute respiratory distress syndrome (ARDS) due to severe pneumogenic sepsis.

The experiences of dealing with consequences of an avalanche - surviving soldiers' perspectives.

: The aim of the study was to explore and describe experiences of daily life after having experienced an avalanche three decades ago.: This paper presents a qualitative study of 12 male survivors of an avalanche during their military service, interviewed 30 years post-disaster.: A comprehensive understanding of the categories led to the latent theme "Finding my own way of managing and dealing with life".

Improved Double-Nicking Strategies for COL7A1-Editing by Homologous Recombination.

Current gene-editing approaches for treatment of recessive dystrophic epidermolysis bullosa (RDEB), an inherited, severe form of blistering skin disease, suffer from low efficiencies and safety concerns that complicate implementation in clinical settings. We present a strategy for efficient and precise repair of RDEB-associated mutations in the COL7A1 gene. We compared the efficacy of double-strand breaks (induced by CRISPR/Cas9), single nicks, or double nicks (induced by Cas9n) in mediating repair of a COL7A1 splice-site mutation in exon 3 by homologous recombination (HR).

Arginine- but not alanine-rich carboxy-termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti.

Ichthyosis with confetti (IWC) is a genodermatosis associated with dominant-negative variants in keratin 10 (KRT10) or keratin 1 (KRT1). These frameshift variants result in extended aberrant proteins, localized to the nucleus rather than the cytoplasm. This mislocalization is thought to occur as a result of the altered carboxy (C)-terminus, from poly-glycine to either a poly-arginine or -alanine tail.

Deubiquitinating Enzyme UCH-L1 Promotes Dendritic Cell Antigen Cross-Presentation by Favoring Recycling of MHC Class I Molecules.

The deubiquitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCH-L1) is required for the maintenance of axonal integrity in neurons and is thought to regulate the intracellular pool of ubiquitin in the brain. In this study, we show that UCH-L1 has an immunological function in dendritic cell (DC) Ag cross-presentation. UCH-L1 is expressed in mouse kidney, spleen, and bone marrow-derived DCs, and its expression and activity are regulated by the immune stimuli LPS and IFN-γ.