Can MRI predict olfactory loss and improvement in posttraumatic olfactory dysfunction?

BACKGROUND: Although most patients with post-traumatic olfactory dysfunction (PTOD) undergo MRI, there is no consensus about its diagnostic or prognostic value. The aims were: 1) to classify the extent of post-traumatic neurodegeneration; 2) to determine its relationship with chemosensory dysfunction (smell, taste, trigeminal); and 3) to establish whether MRI can predict olfactory improvement. METHODOLOGY: We conducted a retrospective cohort study based on a series of 56 patients with PTOD. All patients underwent validated psychophysical tests of their smell, taste, and trigeminal functions, otorhinolaryngologic evaluation, and MRI. An experienced radiologist blinded to patient data evaluated 40 chemosensory-relevant brain regions according to a four-point scale (0=no lesion to 3=large lesion). Follow up data after 4 years (on average) were available in 46 patients. RESULTS: The cluster analysis showed 4 brain lesion patterns that differed in lesion localization and severity. They are associated with diagnostic categories: anosmia, hyposmia and normosmia. Two clusters were highly specific for anosmia (100% specificity)and could accurately predict this condition (100% positive predictive value). No clusters were associated with trigeminal or taste dysfunction. Regarding improvement, 72.7% of patients in the cluster with mild lesions experienced subjective and measurable olfactory improvement whereas this was only the case in 21.7-37.5% of patients with larger lesions. The odds of subjective smell improvement were 5.9 times higher in patients within the milder cluster compared to larger ones. CONCLUSIONS: The analysis of brain lesions in PTOD allows corroboration of smell test results and prediction of subjective and measurable improvement.

In-situ X-ray monitoring of solidification and related processes of metal alloys.

X-ray radioscopy enables the in-situ monitoring of metal alloy processes and then gives access to crucial information on the dynamics of the underlying phenomena. In the last decade, the utilisation of this powerful imaging technique has been adapted to microgravity platforms such as sounding rockets and parabolic flights. The combination of microgravity experimentation with X-ray radioscopy has resulted in a leap in the understanding of fundamental science and has opened new paths in the fields of materials science. The present review focuses on the short history of this research, which includes facility developments, microgravity experiments and results obtained by partners of the XRMON (In-situ X-Ray MONitoring of advanced metallurgical processes under microgravity and terrestrial conditions) research project in the framework of the MAP (Microgravity Application Promotion) programme of the European Space Agency. Three illustrative research topics that were advanced significantly through the use of X-ray radioscopy will be detailed: solidification of metal alloys, metallic foam formation and diffusion in melts.

[Skin manifestations of the external male genitals]. / Hauterscheinungen des männlichen Genitals.

The urological examination includes the inspection of the external male genitals. Harmless normal variants, such as heterotopic sebaceous glands and pearly penile papules must be differentiated from malignant and infectious manifestations. Lichen sclerosus et atrophicus is a frequent connective tissue disease that can lead to functional impairments and an associated high level of suffering for those affected. Both conservative and invasive treatment options are available. Sexually transmitted diseases, such as syphilis, are gaining increasing importance in routine clinical and daily practice due to the increasing incidence in recent years. An early diagnosis and treatment of malignant neoplasms, such as Queyrat's erythroplasia can be carried out by routine inspection of the genital skin.

Platelet-Rich stroma from Crohn's disease patients for treatment of perianal fistula shows a higher myeloid cell profile compared to non-IBD controls.

BACKGROUND: New cell-based therapies are under investigation to improve perianal fistulizing Crohn's disease (pCD) healing. Autologous stromal vascular fraction combined with platelet-rich plasma (referred to as platelet-rich stroma [PRS]) is a new adipose-derived stromal therapy. The effect of Crohn's disease (CD) on adipose tissue, and adipose-derived therapies, is largely unknown. We characterized the cellular composition of subcutaneous lipoaspirate and PRS of pCD patients and non-Inflammatory Bowel Disease (IBD) controls. METHODS: Consecutive pCD patients (≥18 years) and non-IBD controls, who underwent liposuction for the purpose of autologous PRS therapy, were included (October 2020 and March 2021). Mechanically fractionated lipoaspirate and the combined PRS product were analyzed for cell surface marker expression using fluorescence-activated cell sorting analysis. RESULTS: Twenty-three patients (37.8 [IQR 30.7-45.0] years; 9 [39.1 %] male; 11CD patients) were included. Similar total number of cells were found in CD and non-IBD lipoaspirate (CD 8.23 ± 1.62*105 cells/mL versus non-IBD 12.20 ± 3.39*105). Presence of stromal cells, endothelial like cells, immune cells, T-cells, myeloid cells and M2/M1 macrophage ratio were similar in CD and non-IBD lipoaspirate. In PRS samples, more cells/mL were seen in CD patients (P = 0.030). Myeloid cells were more abundant in CD PRS samples (P = 0.007), and appeared to have a higher regulatory M2/M1 ratio. Interdonor variation was observed between lipoaspirate and PRS samples. CONCLUSIONS: The composition of CD and non-IBD lipoaspirate were found to be similar and interdonor variation was observed. However, PRS from CD patients showed more myeloid cells with a regulatory phenotype. Crohn's disease does not appear to alter the immunological composition of adipose-derived products.

Trends in the incidence and mortality of infective endocarditis in high-income countries between 1990 and 2019.

BACKGROUND: Infective endocarditis (IE) remains a life-threatening disease with high morbidity and mortality. OBJECTIVES: To describe temporal trends in IE incidence, mortality and survival over the last 30 years. METHODS: Nineteen high-income countries (the 'EU 15+') were included. Age-standardised and sex-stratified incidence rates (ASIRs) and mortality rates (ASMRs) for IE were extracted from the Global Burden of Disease (GBD) database between 1990 and 2019, and mortality to incidence ratios (ASMIRs) were calculated. Trends were analysed using Joinpoint regression analysis. RESULTS: ASIRs were higher in males than females and increased in both sexes in all countries between 1990 and 2019. A recent steep rise in ASIRs was noted in several countries including the UK, the USA and Germany. ASMRs increased for both sexes in all countries except Finland and Austria. The largest increase in ASMR was observed in females in Italy (+246%). ASMIRs were generally higher in females compared to males, with large increases in ASMIRs (indicating worsening survival) at the end of the 20th century, but more recent stabilisation or decline across the study cohort. CONCLUSIONS: While the incidence and mortality of IE have increased over the last 30 years, recent data suggest that these trends have plateaued or reversed in most countries studied. However, a recent surge in incidence in several countries (including the USA and UK) is of concern, while unfavourable outcomes in females also merit attention. More encouragingly, this analysis provides the first indication of improving IE survival at population level, supporting recent advances in diagnosis and treatment.

Temporal trend analysis of rheumatic heart disease burden in high-income countries between 1990 and 2019.

AIMS: To assesses trends in rheumatic heart disease (RHD) burden in high-income, European Union 15+ (EU15+) countries between 1990 and 2019. METHODS AND RESULTS: Cross-sectional analysis of the incidence and mortality of RHD was conducted using data from the Global Burden of Disease Study (GBD) database. Age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were extracted for EU15 + countries per sex for each of the years from 1990-2019, inclusive, and mortality-to-incidence indices (MII) were computed. Joinpoint regression analysis was used for the description of trends. Over 29 years, an overall declining trend in RHD incidence and mortality across EU 15 + nations were observed. There was significant variability in RHD incidence and mortality rates across high-income countries. However, both RHD incidence and mortality were higher among females compared to males across EU15 + countries over the observed period. The most recent incidence trend, starting predominantly after 2014, demonstrated a rise in RHD incidence in most countries for both sexes. The timing of this RHD resurgence corresponds temporally with an influx of migrants and refugees into Europe. The recent increasing RHD incidence rates ranged from + 0.4% to + 24.7% for males, and + 0.6% to + 11.4% for females. CONCLUSIONS: More than half of EU15 + nations display a recent increase in RHD incidence rate across both sexes. Possible factors associated with this rise are discussed and include increase in global migration from nations with higher RHD prevalence, host nation factors such as migrants' housing conditions, healthcare access and migrant health status on arrival.

Effects of COVID-19 on the Human Central Olfactory System: A Natural Pre-Post Experiment.

BACKGROUND AND PURPOSE: Reduced olfactory function is the symptom with the highest prevalence in coronavirus disease 2019 (COVID-19) with nearly 70% of infected individuals experiencing partial or total loss of their sense of smell at some point during the disease. The exact cause is not known, but beyond peripheral damage, studies have demonstrated insults to both the olfactory bulb and central olfactory brain areas. However, these studies often lack both baseline pre-COVID-19 assessments and control groups, and the effects could, therefore, simply reflect pre-existing risk factors. MATERIALS AND METHODS: Shortly before the COVID-19 outbreak, we completed an olfactory-focused study, which included structural MR brain images and a full clinical olfactory test. Opportunistically, we invited participants back 1 year later, including 9 participants who had experienced mild-to-moderate COVID-19 (C19+) and 12 who had not (C19-), creating a natural pre-post experiment with a control group. RESULTS: Despite C19+ participants reporting subjective olfactory dysfunction, few showed signs of objectively altered function. Critically, all except 1 individual in the C19+ group had reduced olfactory bulb volume (average reduction, 14.3%), but this did not amount to a significant statistical difference compared with the control group (2.3%) using inference statistics. We found no morphologic differences in olfactory brain areas but stronger functional connectivity between olfactory brain areas in the C19+ group at the postmeasure. CONCLUSIONS: Our data suggest that COVID-19 might cause long-term reduction in olfactory bulb volume and altered functional connectivity but with no discernible morphologic differences in cerebral olfactory regions.

Diffusion-Weighted Imaging to Assess HPV-Positive versus HPV-Negative Oropharyngeal Squamous Cell Carcinoma: The Importance of b-Values.

BACKGROUND AND PURPOSE: Controversy exists as to whether ADC histograms are capable to distinguish human papillomavirus-positive (HPV+) from human papillomavirus-negative (HPV-) oropharyngeal squamous cell carcinoma. We investigated how the choice of b-values influences the capability of ADC histograms to distinguish between the two tumor types. MATERIALS AND METHODS: Thirty-four consecutive patients with histologically proved primary oropharyngeal squamous cell carcinoma (11 HPV+ and 23 HPV-) underwent 3T MR imaging with a single-shot EPI DWI sequence with 6 b-values (0, 50, 100, 500, 750, 1000 s/mm2). Monoexponentially calculated perfusion-sensitive (including b=0 s/mm2) and perfusion-insensitive/true diffusion ADC maps (with b ≥ 100 s/mm2 as the lowest b-value) were generated using Matlab. The choice of b-values included 2 b-values (ADCb0-1000, ADCb100-1000, ADCb500-1000, ADCb750-1000) and 3-6 b-values (ADCb0-750-1000, ADCb0-500-750-1000, ADCb0-50-100-1000, ADCb0-50-100-750-1000, ADCb0-50-100-500-750-1000). Readers blinded to the HPV- status contoured all tumors. ROIs were then copied onto ADC maps, and their histograms were compared. RESULTS: ADC histogram metrics in HPV+ and HPV- oropharyngeal squamous cell carcinoma changed significantly depending on the b-values. The mean ADC was lower, and skewness was higher in HPV+ than in HPV- oropharyngeal squamous cell carcinoma only for ADCb0-1000, ADCb0-750-1000, and ADCb0-500-750-1000 (P < .05), allowing distinction between the 2 tumor types. Kurtosis was significantly higher in HPV+ versus HPV- oropharyngeal squamous cell carcinoma for all b-value combinations except 2 perfusion-insensitive maps (ADCb500-1000 and ADCb750-1000). Among all b-value combinations, kurtosis on ADCb0-1000 had the highest diagnostic performance to distinguish HPV+ from HPV- oropharyngeal squamous cell carcinoma (area under the curve = 0.893; sensitivity = 100%, specificity = 82.6%). Acquiring multiple b-values for ADC calculation did not improve the distinction between HPV+ and HPV- oropharyngeal squamous cell carcinoma. CONCLUSIONS: The choice of b-values significantly affects ADC histogram metrics in oropharyngeal squamous cell carcinoma. Distinguishing HPV+ from HPV- oropharyngeal squamous cell carcinoma is best possible on the ADCb0-1000 map.

Measurement of the Nuclear Modification Factor and Prompt Charged Particle Production in p-Pb and pp Collisions at sqrt[s_{NN}]=5 TeV.

The production of prompt charged particles in proton-lead collisions and in proton-proton collisions at the nucleon-nucleon center-of-mass energy sqrt[s_{NN}]=5 TeV is studied at LHCb as a function of pseudorapidity (η) and transverse momentum (p_{T}) with respect to the proton beam direction. The nuclear modification factor for charged particles is determined as a function of η between -4.8<η<-2.5 (backward region) and 2.0<η<4.8 (forward region), and p_{T} between 0.2

Analysis of Neutral B-Meson Decays into Two Muons.

Branching fraction and effective lifetime measurements of the rare decay B_{s}^{0}→µ^{+}µ^{-} and searches for the decays B^{0}→µ^{+}µ^{-} and B_{s}^{0}→µ^{+}µ^{-}γ are reported using proton-proton collision data collected with the LHCb detector at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a luminosity of 9 fb^{-1}. The branching fraction B(B_{s}^{0}→µ^{+}µ^{-})=(3.09_{-0.43-0.11}^{+0.46+0.15})×10^{-9} and the effective lifetime τ(B_{s}^{0}→µ^{+}µ^{-})=2.07±0.29±0.03 ps are measured, where the first uncertainty is statistical and the second systematic. No significant signal for B^{0}→µ^{+}µ^{-} and B_{s}^{0}→µ^{+}µ^{-}γ decays is found and upper limits B(B^{0}→µ^{+}µ^{-})<2.6×10^{-10} and B(B_{s}^{0}→µ^{+}µ^{-}γ)<2.0×10^{-9} at the 95% C.L. are determined, where the latter is limited to the range m_{µµ}>4.9 GeV/c^{2}. The results are in agreement with the standard model expectations.

Cross-Reactivity to Mutated Viral Immune Targets Can Influence CD8+ T Cell Functionality: An Alternative Viral Adaptation Strategy.

Loss of T cell immunogenicity due to mutations in virally encoded epitopes is a well-described adaptation strategy to limit host anti-viral immunity. Another described, but less understood, adaptation strategy involves the selection of mutations within epitopes that retain immune recognition, suggesting a benefit for the virus despite continued immune pressure (termed non-classical adaptation). To understand this adaptation strategy, we utilized a single cell transcriptomic approach to identify features of the HIV-specific CD8+ T cell responses targeting non-adapted (NAE) and adapted (AE) forms of epitopes containing a non-classical adaptation. T cell receptor (TCR) repertoire and transcriptome were obtained from antigen-specific CD8+ T cells of chronic (n=7) and acute (n=4) HIV-infected subjects identified by either HLA class I tetramers or upregulation of activation markers following peptide stimulation. CD8+ T cells were predominantly dual tetramer+, confirming a large proportion of cross-reactive TCR clonotypes capable of recognizing the NAE and AE form. However, single-reactive CD8+ T cells were identified in acute HIV-infected subjects only, providing the potential for the selection of T cell clones over time. The transcriptomic profile of CD8+ T cells was dependent on the autologous virus: subjects whose virus encoded the NAE form of the epitope (and who transitioned to the AE form at a later timepoint) exhibited an 'effective' immune response, as indicated by expression of transcripts associated with polyfunctionality, cytotoxicity and apoptosis (largely driven by the genes GZMB, IFNÉ£, CCL3, CCL4 and CCL5). These data suggest that viral adaptation at a single amino acid residue can provide an alternative strategy for viral survival by modulating the transcriptome of CD8+ T cells and potentially selecting for less effective T cell clones from the acute to chronic phase.

Branching Fraction Measurements of the Rare B_{s}

The branching fraction of the rare B_{s}^{0}→ϕµ^{+}µ^{-} decay is measured using data collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to integrated luminosities of 1, 2, and 6 fb^{-1}, respectively. The branching fraction is reported in intervals of q^{2}, the square of the dimuon invariant mass. In the q^{2} region between 1.1 and 6.0 GeV^{2}/c^{4}, the measurement is found to lie 3.6 standard deviations below a standard model prediction based on a combination of light cone sum rule and lattice QCD calculations. In addition, the first observation of the rare B_{s}^{0}→f_{2}^{'}(1525)µ^{+}µ^{-} decay is reported with a statistical significance of 9 standard deviations and its branching fraction is determined.

CD127+ CD94+ innate lymphoid cells expressing granulysin and perforin are expanded in patients with Crohn's disease.

Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn's disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules. Population B expresses granulysin, a cytotoxic molecule linked to bacterial lysis and/or chemotaxis of monocytes. Granulysin protein is secreted by population B cells upon stimulation with IL-15. Activation of population B in the presence of TGF-ß strongly reduces the expression of cytotoxic effector molecules of population B. Strikingly, samples from individuals that suffer from active Crohn's disease display enhanced frequencies of granulysin-expressing effector CD127+CD94+ ILCs in comparison to controls. Thus this study identifies group 1 ILC populations which accumulate in inflamed intestinal tissue of Crohn's disease patients and may play a role in the pathology of the disease.

Observation of the Mass Difference between Neutral Charm-Meson Eigenstates.

A measurement of mixing and CP violation in neutral charm mesons is performed using data reconstructed in proton-proton collisions collected by the LHCb experiment from 2016 to 2018, corresponding to an integrated luminosity of 5.4 fb^{-1}. A total of 30.6 million D^{0}→K_{S}^{0}π^{+}π^{-} decays are analyzed using a method optimized for the measurement of the mass difference between neutral charm-meson eigenstates. Allowing for CP violation in mixing and in the interference between mixing and decay, the mass and decay-width differences are measured to be x_{CP}=[3.97±0.46(stat)±0.29(syst)]×10^{-3} and y_{CP}=[4.59±1.20(stat)±0.85(syst)]×10^{-3}, respectively. The CP-violating parameters are measured as Δx=[-0.27±0.18(stat)±0.01(syst)]×10^{-3} and Δy=[0.20±0.36(stat)±0.13(syst)]×10^{-3}. This is the first observation of a nonzero mass difference in the D^{0} meson system, with a significance exceeding seven standard deviations. The data are consistent with CP symmetry and improve existing constraints on the associated parameters.

Observation of New Resonances Decaying to J/ψK

The first observation of exotic states with a new quark content cc[over ¯]us[over ¯] decaying to the J/ψK^{+} final state is reported with high significance from an amplitude analysis of the B^{+}→J/ψϕK^{+} decay. The analysis is carried out using proton-proton collision data corresponding to a total integrated luminosity of 9 fb^{-1} collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. The most significant state, Z_{cs}(4000)^{+}, has a mass of 4003±6_{-14}^{+4} MeV, a width of 131±15±26 MeV, and spin parity J^{P}=1^{+}, where the quoted uncertainties are statistical and systematic, respectively. A new 1^{+} X(4685) state decaying to the J/ψϕ final state is also observed with high significance. In addition, the four previously reported J/ψϕ states are confirmed and two more exotic states, Z_{cs}(4220)^{+} and X(4630), are observed with significance exceeding 5 standard deviations.

Centromedial amygdala is more relevant for phobic confrontation relative to the bed nucleus of stria terminalis in patients with spider phobia.

Recent studies indicate differential involvement of the centromedial amygdala (CM) and the bed nucleus of the stria terminalis (BNST) during processing (anticipation and confrontation) of threat stimuli. Here, temporal predictability was shown to be a relevant factor. In this study, we want to investigate the relevance of these effects, which were found in healthy subjects, for anxiety disorders. Therefore, we investigated the differential involvement of CM and BNST in the anticipation and confrontation of phobic stimuli under variation of temporal predictability in spider phobia. 21 patients with spider phobia and 21 healthy controls underwent a temporally predictable/unpredictable phobic and neutral anticipation and confrontation paradigm using functional magnetic resonance imaging (fMRI) and ROI analyses. During the anticipation phase, healthy controls showed higher CM and BNST activity during the predictable compared with the unpredictable condition compared with the anxiety patients. During a confrontation phase that followed the anticipation phase, CM was more activated than BNST during the phobic compared with the neutral confrontation. While this effect was independent of threat predictability in patients, healthy controls showed higher activation in the CM compared with the BNST only during the predictable spider confrontation compared with the predictable bird confrontation. The results contribute to a better understanding of the separate roles of the CM and BNST during phobic processes. The CM was found to be more relevant to phobic confrontation in patients with spider phobia compared with the BNST.

Influence Of Pre-Existing Neurological Illnesses On The Outcome Of Severe Burn Injuries.

It is known that patients suffering from neurological illnesses have an increased risk of burn injuries. These burns are often very severe and lead to poor outcomes. To date, only a few studies have evaluated the impact of pre-existing neurological illnesses on the outcome of burn injuries. None of them performed a regression analysis regarding specific influence on mortality. Between 1996 and 2016, 1475 patients were admitted to the BICU of a specialized German burn center: 26 had less than 1% TBSA burned and were excluded; 177 had pre-existing neurological disorders (group N). 87 patients with psychological disorders were excluded. 1185 patients without neurological or psychological disorders formed the control group. Length of hospital stay, TBSA and number of operations were analyzed using the chi-squared test and Mann-Whitney U-test. Additionally, mortality was evaluated using the logistic regression analysis adjusted for known outcome predictors. Mean age of the patients in the control group was 41.53 years with a BICU stay of 18 days, TBSA of 18.25% and mortality rate of 12.4%; 23.7% had inhalation injuries. Patients in group N had a mean age of 54.63 years, a BICU stay of 27 days, mean TBSA of 20.97%; 31.1% had inhalation injuries and mortality was 20.3%. Patients with neurological disorders were older and showed higher affected TBSA, higher rates of inhalation injury, mortality and affected TBSA, and a longer stay in the BICU compared to the control group. Nevertheless, pre-existing neurological disorders alone had no significant influence on mortality.

Il est avéré que les patients souffrant de pathologie neurologique ont un risque plus élevé de brûlure. Elles sont souvent particulièrement graves et d'évolution défavorable mais la littérature à ce sujet reste pauvre et aucune étude n'a utilisé de régression logistique pour évaluer la corrélation pathologie neurologique- évolution d'une brûlure. Entre 1996 et 2016, 1 475 patients ont été hospitalisés en réanimation spécifique dans un CTB allemand. Vingt- six d'entre eux, brûlés sur moins de 1% SCT, n'ont pas été inclus dans l'étude, pas plus 87 patients psychiatriques si bien que 177 patients souffrant de pathologie neurologique (N) ont été comparés à 1 185 n'en souffrant pas (C). Les durées d'hospitalisation, la surface brûlée et le nombre d'interventions chirurgicales ont été analysée en utilisant C² ou Mann-Whitney. En outre, nous avons effectué une régression logistique étudiant la mortalité, en utilisant les facteurs connus de mortalité. Le groupe C avait 41,53 ans, souffrait de brûlures sur 18,25% SCT, avait inhalé des fumées dans 23,7% des cas, avait un taux de mortalité de 12,4% et restait 18 j en réanimation. Dans le groupe N, ces chiffres étaient respectivement de 54,63 ans, 20,97% SCT, 31,1% de fumées, 20,3% de mortalité et 27 jours en réa. Tous les chiffres étudiés étaient plus élevés dans N que dans C. Toutefois, l'existence de comorbidité neurologique n'apparaissait pas un critère indépendant de mortalité.

Angular Analysis of the B

We present an angular analysis of the B^{+}→K^{*+}(→K_{S}^{0}π^{+})µ^{+}µ^{-} decay using 9 fb^{-1} of pp collision data collected with the LHCb experiment. For the first time, the full set of CP-averaged angular observables is measured in intervals of the dimuon invariant mass squared. Local deviations from standard model predictions are observed, similar to those in previous LHCb analyses of the isospin-partner B^{0}→K^{*0}µ^{+}µ^{-} decay. The global tension is dependent on which effective couplings are considered and on the choice of theory nuisance parameters.