Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia

Journal of Neurology - STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1...     

Properties of Cryptic Epitopes and Their Corresponding Antibodies as Indicated by the Study of Human and Ovine Growth Hormones

Antibodies (Ab) directed to hidden antigenic determinants (cryptotopes) are undesirable because they are not neutralizing. Additionally, we have previously demonstrated a close association between the extent of Ab to cryptic determinants and the expression of autoantibodies (autoAb) under some experimental conditions. Thus, the first objective of this work was to establish the physicochemical characteristics of Ab to cryptotopes and the second one was to examine the structural features of cryptic epitopes themselves. Using human and ovine growth hormones (hGH and oGH) as antigenic models and competition ELISA under different conditions of temperature, pH or ionic strength, we did not find any difference between the binding properties of anti-cryptic epitope antibodies (Ab) and anti-native epitope Ab. Then, using synthetic peptides and tryptic digests and direct and competition ELISAs we studied the structures of cryptic hGH and oGH epitopes. Isolated peptides either in solution or adsorbed on microplates failed to react. Partially digested hGH was recognized only when insolubilized on microplates, and anti-oGH Ab only reacted with a large fragment of the hormone either in solution or insolubilized. These results indicate that, at least in the case of hGH and oGH, cryptic epitopes are not simple linear sequences, as commonly referred without any evidence, but new exposed conformational structures different from those found in the native antigen.     

COVID-19 or not COVID-19? Compared characteristics of patients hospitalized for suspected COVID-19

European Journal of Clinical Microbiology & Infectious Diseases - During an epidemic period, we compared patients hospitalized for initial suspicion of COVID-19 but for whom an alternative...     

Positive selection of protective variants for type 2 diabetes from the Neolithic onward: a case study in Central Asia

The high prevalence of type 2 diabetes and its uneven distribution among human populations is both a major public health concern and a puzzle in evolutionary biology. Why is this deleterious disease so common, while the associated genetic variants should be removed by natural selection? The ‘thrifty genotype'' hypothesis proposed that the causal genetic variants were advantageous and selected for during the majority of human evolution. It remains, however, unclear whether genetic data support this scenario. In this study, we characterized patterns of selection at 10 variants associated with type 2 diabetes, contrasting one herder and one farmer population from Central Asia. We aimed at identifying which alleles (risk or protective) are under selection, dating the timing of selective events, and investigating the effect of lifestyle on selective patterns. We did not find any evidence of selection on risk variants, as predicted by the thrifty genotype hypothesis. Instead, we identified clear signatures of selection on protective variants, in both populations, dating from the beginning of the Neolithic, which suggests that this major transition was accompanied by a selective advantage for non-thrifty variants. Combining our results with worldwide data further suggests that East Asia was particularly prone to such recent selection of protective haplotypes. As much effort has been devoted so far to searching for thrifty variants, we argue that more attention should be paid to the evolution of non-thrifty variants.     

Reverse Iodine Transfer Polymerization (RITP) of 1,1,2,2‐Tetrahydroperfluorodecyl Acrylate in Supercritical Carbon Dioxide

Reverse iodine transfer polymerization (RITP) of 1,1,2,2‐tetrahydroperfluorodecyl acrylate (FDA) is successfully performed in supercritical carbon dioxide (scCO₂) at 70 °C under a CO₂ pressure of 300 bar. PolyFDA (PFDA) of increasing molecular weights (from 10 000 to 100 000 g mol^?1) is synthesized with good agreement between theoretical, ¹H NMR spectroscopy and and size exclusion chromatography/refractive index/right‐angle laser‐light scattering/differential viscometer (SEC/RI/RALLS/DV)‐estimated molecular weights (). Furthermore, the increase of goes with a decrease of the dispersity of the polymers (? from 2.06 to 1.33), which is consistent with a controlled radical polymerization (CRP). Lastly, the structure of final PFDA and therefore the RITP process are confirmed by matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) analyses.

     

Surgical pathology of native valve endocarditis in 310 specimens from 287 patients (1985–2004)

BackgroundFew large studies have documented the clinical and pathologic features of native valve endocarditis (NVE) independently from prosthetic valve endocarditis (PVE).MethodsA retrospective study of medical records of all patients undergoing operation for NVE at Mayo Clinic in Rochester, MN (1985–2004), was performed. Medical records were reviewed from 287 patients for demographics, infecting organism, and comorbidities. Microscopic slides from 310 valves were reviewed for features of infection.ResultsThe study cohort included 287 patients, with age ranging from 9 to 87 years (mean, 54), yielding 310 valves. Most (73%) were from men, and 84% were regurgitant. Risk factors included bicuspid aortic valve (23%), dental manipulation (20%), mitral valve prolapse (18%), diabetes mellitus (16%), and others (< 5% each); in 15%, no risk factor was identified. The four most commonly identified organisms were viridans group streptococci (28%), Staphylococcus aureus (18%), enterococci (9%), and coagulase-negative staphylococci (8%). NVE was histologically active in 58% and healed in 42%, and affected left-sided valves in 94%. It was associated with embolization in 29%, acute heart failure in 29%, and annular abscess in 18%. Men accounted for a higher percentage of aortic NVE than mitral NVE (82% versus 63%, respectively; P=.001). Among 126 valves with active endocarditis, 25% had no microorganisms identified histologically.ConclusionNVE affected men nearly three times as frequently as women. Diabetes mellitus emerged as a prevalent (and previously underrecognized) risk factor for NVE. The most common infecting organisms were streptococci and staphylococci. Microorganisms were identified histologically in the majority of active endocarditis cases.     

Variation of the impact duration during the in vitro insertion of acetabular cup implants

The acetabular cup (AC) is an implant impacted into a bone cavity and used for hip prosthesis surgery. Initial stability of the AC is an important factor for long term surgical success. The aim of this study is to determine the variations of the impact duration during AC implant insertion.Twenty-two bone samples taken from bovine femurs were prepared ex vivo for the insertion of an acetabular cup implant, following the surgical procedure used in the clinic. For each bone sample, ten impacts were applied using reproducible mass falls (3.5 kg) in order to insert the AC implant. Each impact duration was recorded using a wide bandwidth force sensor.For all bone samples, the impact duration was shown to first decrease as a function of the impact number, then reaching a stationary value equal in average to 4.2 ± 0.7 ms after an average number of 4.1 ± 1.7 impacts. The impact duration may be related to variations of the bone–implant interface contact rigidity because of an increase the amount of bone tissue in contact with the AC implant.Measurements of impact duration have a good potentiality for clinical application to assist the surgeon during the insertion of the AC implant, providing valuable information on the bone–implant interface contact properties.