Leg length discrepancies (LLD): An etiology to be considered in its proper measure. A critical and historical review.

Introduction: Studies of leg-length discrepancies (LLD) have been the subject of debate for almost 200 years. A large number of studies have emerged, most frequently using assessment criteria based on painful symptoms or joint damage.

Development: While many authors argue for a threshold of 10-20 mm to establish a link between pain and LLD, most publications based on radiography show lesion stigmata on lumbar, hip and knee joints as early as 6 mm.

Ethical and coordinative challenges in setting up a national cohort study during the COVID-19 pandemic in Germany.

With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites.

Impact of Clinical Study Implementation on Data Quality Assessments - Using Contradictions within Interdependent Health Data Items as a Pilot Indicator.

Introduction: Contradiction is a relevant data quality indicator to evaluate the plausibility of interdependent health data items. However, while contradiction assessment is achieved using domain-established contradictory dependencies, recent studies have shown the necessity for additional requirements to reach conclusive contradiction findings. For example, the oral or rectal methods used in measuring the body temperature will influence the thresholds of fever definition.

Analysis of acute COVID-19 including chronic morbidity: protocol for the deep phenotyping National Pandemic Cohort Network in Germany (NAPKON-HAP).

Background: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19).

The Importance of Being FAIR and FAST - The Clinical Epidemiology and Study Platform of the German Network University Medicine (NUKLEUS).

The COVID-19 pandemic has urged the need to set up, conduct and analyze high-quality epidemiological studies within a very short time-scale to provide timely evidence on influential factors on the pandemic, e.g. COVID-19 severity and disease course.

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics.

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany.

Neutralizing Anti-IL-17A Antibody Demonstrates Preclinical Activity Enhanced by Vinblastine in Langerhans Cell Histiocytosis.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterised by the accumulation into granulomas of apoptosis-resistant pathological dendritic cells (LCH-DCs). LCH outcome ranges from self-resolving to fatal. Having previously shown that, () monocyte-derived DCs (Mo-DCs) from LCH patients differentiate into abnormal and pro-inflammatory IL-17A-producing DCs, and () recombinant IL-17A induces survival and chemoresistance of healthy Mo-DCs, we investigated the link between IL-17A and resistance to apoptosis of LCH-DCs.

Comparison of three different ELISAs for the detection of recombinant, native and plasma IL-17A.

Plasma IL-17A detection in Langerhans Cell Histiocytosis (LCH) is currently a source of debate. Indeed, 500-P07G (PeproTech) and 41802 (R&D Systems) anti-IL-17A antibodies have been suspected to recognize nonspecific proteins. To resolve this discrepancy, we set up two new ELISAs by using 41802 or neutralizing eBio64CAP17 (eBioscience) capture monoclonal antibodies that we compared to the commercial PeproTech ELISA kit.

High levels of plasma interleukin-17A are associated with severe neurological sequelae in Langerhans cell histiocytosis.

Objective: Langerhans cell histiocytosis (LCH) is a granulomatous inflammatory myeloid neoplasia associated with a cytokine storm in both serum and lesions. Increased levels of plasma interleukin-17A (IL-17A) in LCH patients have been reported, but this finding was not confirmed in all studies. Neurodegeneration is a devastating complication of LCH (ND-LCH).

Factors Associated to Medication Consumption Among the Immigrant Population Residing in Spain.

We aimed to determine the prevalence of medication use by the immigrant population residing in Spain, and to identify the factors associated with this consumption. Descriptive cross-sectional study was performed using secondary data retrieved from the 2012 Spanish National Health Survey (SNHS). Using logistic multivariate regression analysis, three models were generated: one for immigrants from high income countries (HIC), another for immigrants from low income countries (LIC), and a third one for the native population.

Targeting BCL2 family in human myeloid dendritic cells: a challenge to cure diseases with chronic inflammations associated with bone loss.

Rheumatoid arthritis (RA) and Langerhans cell histiocytosis (LCH) are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC), and, especially, regulating their half-life and fusion, is a challenge.

Tax protein-induced expression of antiapoptotic Bfl-1 protein contributes to survival of human T-cell leukemia virus type 1 (HTLV-1)-infected T-cells.

Human T lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL). ATLL is a severe malignancy with no effective treatment. HTLV-1 regulatory proteins Tax and HTLV-1 basic leucine zipper factor (HBZ) play a major role in ATLL development, by interfering with cellular functions such as CD4(+) T-cell survival.

Cellular receptors, differentiation and endocytosis requirements are key factors for type I IFN response by human epithelial, conventional and plasmacytoid dendritic infected cells by measles virus.

While the antiviral response during measles virus (MeV) infection is documented, the contribution of the hosting cell type to the type I interferon (IFN-alpha/beta) response is still not clearly established. Here, we report that a signature heterogeneity of the IFN-alpha/beta response according to the cell type. The MeV tropism dictated by the expression of appropriate cellular receptor appeared to be crucial for epithelial cells.

Identification of plant sphingolipid desaturases using chromatography and mass spectrometry.

This manuscript describes an efficient analytical assay combining high-performance liquid chromatography with UV detection (HPLC-UV), liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS), and gas chromatography with mass spectrometry (GC-MS) for the characterization and C=C bond localization on the long chain base of sphingolipids in yeast extracts in order to identify the plant sphingolipid desaturases activity. Samples of wild type control and transgenic yeast expressing putative sphingolipid desaturases were hydrolyzed into long chain bases. Mono-unsaturated long chain base, dehydrophytosphingosine (t18:1), in transgenic yeast as a result of the function of plant sphingolipid desaturase was detected with cis, trans-isomers resolution by reverse phase HPLC-UV as DNP (2,4-dinitrophenyl) derivatives along with saturated phytosphingosine (t18:0).

Measles virus interaction with host cells and impact on innate immunity.

Because viruses are obligate parasites, numerous partnerships between measles virus and cellular molecules can be expected. At the entry level, measles virus uses at least two cellular receptors, CD150 and a yet to be identified epithelial receptor to which the virus H protein binds. This dual receptor strategy illuminates the natural infection and inter-human propagation of this lymphotropic virus.

Cell-cell fusion induced by measles virus amplifies the type I interferon response.

Measles virus (MeV) infection is characterized by the formation of multinuclear giant cells (MGC). We report that beta interferon (IFN-beta) production is amplified in vitro by the formation of virus-induced MGC derived from human epithelial cells or mature conventional dendritic cells. Both fusion and IFN-beta response amplification were inhibited in a dose-dependent way by a fusion-inhibitory peptide after MeV infection of epithelial cells.

Cytosolic 5'-triphosphate ended viral leader transcript of measles virus as activator of the RIG I-mediated interferon response.

Background: Double stranded RNA (dsRNA) is widely accepted as an RNA motif recognized as a danger signal by the cellular sentries. However, the biology of non-segmented negative strand RNA viruses, or Mononegavirales, is hardly compatible with the production of such dsRNA.

Methodology And Principal Findings: During measles virus infection, the IFN-beta gene transcription was found to be paralleled by the virus transcription, but not by the virus replication.

Identification and characterization of an Arabidopsis homogentisate phytyltransferase paralog.

Tocochromanols (tocopherols and tocotrienols) are micronutrients with antioxidant properties synthesized by photosynthetic bacteria and plants that play important roles in animal and human nutrition. There is considerable interest in identifying the genes involved in tocochromanol biosynthesis to allow transgenic modification of both tocochromanol levels and tocochromanol composition in agricultural crops. The first committed reaction in tocopherol biosynthesis is the condensation of homogentisic acid (HGA) with phytyldiphosphate or geranylgeranyldiphosphate, catalyzed by the homogentisate phytyltransferase (VTE2) or by the homogentisate geranylgeranyl transferase (HGGT).

The Arabidopsis vitamin E pathway gene5-1 mutant reveals a critical role for phytol kinase in seed tocopherol biosynthesis.

We report the identification and characterization of a low tocopherol Arabidopsis thaliana mutant, vitamin E pathway gene5-1 (vte5-1), with seed tocopherol levels reduced to 20% of the wild type. Map-based identification of the responsible mutation identified a G-->A transition, resulting in the introduction of a stop codon in At5g04490, a previously unannotated gene, which we named VTE5. Complementation of the mutation with the wild-type transgene largely restored the wild-type tocopherol phenotype.

Application of the Synechococcus nirA promoter to establish an inducible expression system for engineering the Synechocystis tocopherol pathway.

Tocopherols are important antioxidants in lipophilic environments. They are synthesized by plants and some photosynthetic bacteria. Recent efforts to analyze and engineer tocopherol biosynthesis led to the identification of Synechocystis sp.

Metabolically engineered oilseed crops with enhanced seed tocopherol.

Tocochromanols (tocopherols and tocotrienols) are important lipid soluble antioxidants and are an essential part of the mammalian diet. Oilseeds are particularly rich in tocochromanols with an average concentration 10-fold higher than other plant tissues. Here we describe a systematic approach to identify rate-limiting reactions in the tocochromanol biosynthetic pathway, and the application of this knowledge to engineer tocochromanol biosynthesis in oilseed crops.

Biotechnological production and application of vitamin E: current state and prospects.

Tocochromanols (tocopherols and tocotrienols) are important lipophilic antioxidants for animals and humans. Their biological activity is expressed as vitamin E activity. This article describes the current need for vitamin E production, and compares different strategies to engineer the vitamin E content in photosynthetic bacteria and plants, with a focus on oilseed as target tissues.

Measles virus nucleoprotein induces cell-proliferation arrest and apoptosis through NTAIL-NR and NCORE-FcgammaRIIB1 interactions, respectively.

Measles virus (MV) nucleoprotein (N) is a cytosolic protein that is released into the extracellular compartment after apoptosis and/or secondary necrosis of MV-infected cells in vitro. Thus, MV-N becomes accessible to inhibitory cell-surface receptors: FcgammaRIIB and an uncharacterized nucleoprotein receptor (NR). MV-N is composed of two domains: NCORE (aa 1-400) and NTAIL (aa 401-525).

Engineering vitamin E content: from Arabidopsis mutant to soy oil.

We report the identification and biotechnological utility of a plant gene encoding the tocopherol (vitamin E) biosynthetic enzyme 2-methyl-6-phytylbenzoquinol methyltransferase. This gene was identified by map-based cloning of the Arabidopsis mutation vitamin E pathway gene3-1 (vte3-1), which causes increased accumulation of delta-tocopherol and decreased gamma-tocopherol in the seed. Enzyme assays of recombinant protein supported the hypothesis that At-VTE3 encodes a 2-methyl-6-phytylbenzoquinol methyltransferase.