Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy.

Background: The alternative complement pathway plays a key role in the pathogenesis of IgA nephropathy. Iptacopan specifically binds to factor B and inhibits the alternative pathway.

Methods: In this phase 3, double-blind, randomized, placebo-controlled trial, we enrolled adults with biopsy-confirmed IgA nephropathy and proteinuria (defined as a 24-hour urinary protein-to-creatinine ratio of ≥1 [with protein and creatinine both measured in grams]) despite optimized supportive therapy.

A whole-cell pertussis vaccine engineered to elicit reduced reactogenicity protects baboons against pertussis challenge.

Whole-cell pertussis (wP) vaccines introduced in the 1940s led to a dramatic reduction of pertussis incidence and are still widely used in low- and middle-income countries (LMICs) worldwide. The reactogenicity of wP vaccines resulted in reduced public acceptance, which drove the development and introduction of acellular pertussis (aP) vaccines in high-income countries in the 1990s. Increased incidence of pertussis disease has been observed in high-income countries following the introduction of aP vaccines despite near universal rates of pediatric vaccination.

The periscope sign as a new dermatoscopy finding to facilitate the diagnosis of furuncular myiasis.

In this text, we introduce the ‘periscope sign’ as a novel dermatoscopic finding in furuncular myiasis. This clinical sign may aid in diagnosing this rare condition, particularly in patients with a history of travel to endemic areas.

The contribution of BvgR, RisA, and RisS to global gene regulation, intracellular cyclic-di-GMP levels, motility, and biofilm formation in .

is a highly contagious respiratory bacterial veterinary pathogen. In this study the contribution of the transcriptional regulators BvgR, RisA, RisS, and the phosphorylation of RisA to global gene regulation, intracellular cyclic-di-GMP levels, motility, and biofilm formation were evaluated. Next Generation Sequencing (RNASeq) was used to differentiate the global gene regulation of both virulence-activated and virulence-repressed genes by each of these factors.

The impact of phototherapy on itch intensity and itch-related quality of life amongst different skin diseases, skin phototypes and genders - A prospective study with 102 patients.

Background: Phototherapy is a mainstay to treat itchy conditions. However, only little is known about differences in the antipruritic effect of phototherapy amongst different skin conditions, phototypes and genders.

Methods: In this prospective, single-center study, we analyzed the effect of phototherapy on itch intensity and itch-related quality of life amongst these subgroups after a treatment duration of 4 weeks, while on-demand treatment with topical corticosteroids, topical calcineurin inhibitors and/or antihistamines was allowed.

Repeated Bordetella pertussis Infections Are Required to Reprogram Acellular Pertussis Vaccine-Primed Host Responses in the Baboon Model.

Background: The United States has experienced a resurgence of pertussis following the introduction of acellular pertussis (aP) vaccines. This is likely due to the failure of aP vaccines to induce durable immunity and prevent infection, carriage, and transmission.

Methods: To evaluate the impact of aP vaccination on the immune response to infection and test the ability of infection to reprogram aP-imprinted immune responses, we challenged unvaccinated and aP-vaccinated baboons with Bordetella pertussis multiple times and accessed the immune responses and outcomes of infections after each exposure.

T cell reactivity to Bordetella pertussis is highly diverse regardless of childhood vaccination.

The incidence of whooping cough due to Bordetella pertussis (BP) infections has increased recently. It is believed that the shift from whole-cell pertussis (wP) vaccines to acellular pertussis (aP) vaccines may be contributing to this rise. While T cells are key in controlling and preventing disease, nearly all knowledge relates to antigens in aP vaccines.

Increased TIM-3 and galectin-9 serum levels in patients with advanced systemic mastocytosis.

Background: Systemic mastocytosis is characterized by expansion of clonal mast cells in various tissues. Several biomarkers with diagnostic and therapeutic potential have recently been characterized in mastocytosis, such as the serum marker tryptase and the immune checkpoint molecule PD-L1.

Objective: We aimed to investigate whether serum levels of other checkpoint molecules are altered in systemic mastocytosis and whether these proteins are expressed in mastocytosis infiltrates in the bone marrow.

Genome-wide characterization of T cell responses to reveals broad reactivity and similar polarization irrespective of childhood vaccination profiles.

The incidence of whooping cough (pertussis), the respiratory disease caused by (BP) has increased in recent years, and it is suspected that the switch from whole-cell pertussis (wP) to acellular pertussis (aP) vaccines may be a contributing factor to the rise in morbidity. While a growing body of evidence indicates that T cells play a role in the control and prevention of symptomatic disease, nearly all data on human BP-specific T cells is related to the four antigens contained in the aP vaccines, and data detailing T cell responses to additional non-aP antigens, are lacking. Here, we derived a full-genome map of human BP-specific CD4+ T cell responses using a high-throughput Activation Induced Marker (AIM) assay, to screen a peptide library spanning over 3000 different BP ORFs.

Indirect epigenetic testing identifies a diagnostic signature of cardiomyocyte DNA methylation in heart failure.

Precision-based molecular phenotyping of heart failure must overcome limited access to cardiac tissue. Although epigenetic alterations have been found to underlie pathological cardiac gene dysregulation, the clinical utility of myocardial epigenomics remains narrow owing to limited clinical access to tissue. Therefore, the current study determined whether patient plasma confers indirect phenotypic, transcriptional, and/or epigenetic alterations to ex vivo cardiomyocytes to mirror the failing human myocardium.

Antigen Discovery for Next-Generation Pertussis Vaccines Using Immunoproteomics and Transposon-Directed Insertion Sequencing.

Background: Despite high vaccination rates, the United States has experienced a resurgence in reported cases of pertussis after switching to the acellular pertussis vaccine, indicating a need for improved vaccines that enhance infection control.

Methods: Bordetella pertussis antigens recognized by convalescent-baboon serum and nasopharyngeal wash were identified by immunoproteomics and their subcellular localization predicted. Genes essential or important for persistence in the baboon airway were identified by transposon-directed insertion-site sequencing (TraDIS) analysis.

Differences in phototherapy among skin diseases and genders in real-life conditions-A retrospective analysis of the cumulative doses, numbers of sessions, side effects and costs in 561 patients.

Background: Phototherapy has been a mainstay therapy for dermatological diseases since more than a century. Although phototherapy is still extensively used and some recommendations exist, only scarce data are available addressing disease-specific differences in cumulative doses, treatment durations and costs. Knowledge of such differences could help to avoid over-/undertreatment, predict treatment duration and costs.

Perfluorodioxolane Polymers for Gas Separation Membrane Applications.

Since the discovery of polytetrafluoroethylene (PTFE) in 1938, fluorinated polymers have drawn attention in the chemical and pharmaceutical field, as well as in optical and microelectronics applications. The reasons for this attention are their high thermal and oxidative stability, excellent chemical resistance, superior electrical insulating ability, and optical transmission properties. Despite their unprecedented combination of desirable attributes, PTFE and copolymers of tetrafluoroethylene (TFE) with hexafluoropropylene and perfluoropropylvinylether are crystalline and exhibit poor solubility in solvents, which makes their processability very challenging.

Tracheal colonization factor A (TcfA) is a biomarker for rapid and specific detection of Bordetella pertussis.

Pertussis is a highly contagious disease for which prompt, point-of-care diagnosis remains an unmet clinical need. Results from conventional test modalities (nucleic acid detection, serology, and culture) take hours to days. To overcome this challenge, we identified a new biomarker (tracheal colonization factor A, TcfA) for detection of Bordetella pertussis infection by lateral flow immunoassay (LFIA).

Development and Validation of a Whole-Genome Screening Strategy.

The immune response elicited by the protective whole-cell pertussis (wP) versus the less-protective acellular pertussis (aP) vaccine has been well characterized; however, important clinical problems remain unsolved, as the inability of the currently administered aP vaccine is resulting in the reemergence of clinical disease (i.e., whooping cough).

Pertussis Toxin: A Key Component in Pertussis Vaccines?

is a human-specific pathogen and the causative agent of whooping cough. The ongoing resurgence in pertussis incidence in high income countries is likely due to faster waning of immunity and increased asymptomatic colonization in individuals vaccinated with acellular pertussis (aP) vaccine relative whole-cell pertussis (wP)-vaccinated individuals. This has renewed interest in developing more effective vaccines and treatments and, in support of these efforts, defining pertussis vaccine correlates of protection and the role of vaccine antigens and toxins in disease.

Asymptomatic Infection and Transmission of Pertussis in Households: A Systematic Review.

We conducted a systematic review to describe the frequency of mild, atypical, and asymptomatic infection among household contacts of pertussis cases and to explore the published literature for evidence of asymptomatic transmission. We included studies that obtained and tested laboratory specimens from household contacts regardless of symptom presentation and reported the proportion of cases with typical, mild/atypical, or asymptomatic infection. After screening 6789 articles, we included 26 studies.

Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1.

An aged circulatory environment can activate microglia, reduce neural precursor cell activity and impair cognition in mice. We hypothesized that brain endothelial cells (BECs) mediate at least some of these effects. We observe that BECs in the aged mouse hippocampus express an inflammatory transcriptional profile with focal upregulation of vascular cell adhesion molecule 1 (VCAM1), a protein that facilitates vascular-immune cell interactions.

Pertussis vaccines and protective immunity.

Despite high vaccine coverage, reported cases of pertussis have increased steadily over the last twenty years. This resurgence has stimulated interest in host responses to pertussis infection and vaccination with the goal of developing more effective next-generation vaccines and vaccination strategies. Optimal protection against Bordetella pertussis appears to be multifactorial requiring both humoral and cellular responses.

Flocculant Screening Method at Lab Scale for Application in Disc Stack Centrifuges with Hermetic Design.

Chemicals produced using biotechnological methods like fermentation processes are obtained as complex diluted aqueous mixture, which still contains the production organism. Centrifugation is a commonly used technology for biomass separation. By flocculation, the settling velocity of microorganisms can be increased.

Myocardial metabolism in heart failure: Purinergic signalling and other metabolic concepts.

Despite significant therapeutic advances in heart failure (HF) therapy, the morbidity and mortality associated with this disease remains unacceptably high. The concept of metabolic dysfunction as an important underlying mechanism in HF is well established. Cardiac function is inextricably linked to metabolism, with dysregulation of cardiac metabolism pathways implicated in a range of cardiac complications, including HF.