Hertel-exophthalmometry-like multi-detector-row-CT-exophthalmometry: inter-disciplinary inter-observer reproducibility of measurements

Objectives: To investigate the interdisciplinary interobserver reproducibility of Hertel-exophthalmometry-like protrusion measurements on multidetector-row-computed-tomography- (MDCT-) images of the orbit to facilitate structured evaluation of the orbit and mid-face. Methods: Respective reproducibility of base-length along the interfronto-zygomatic line, right and left ocular protrusion, and deriving interocular difference was measured in this retrospective (04/2009-03/2020) single-centre observational study. MDCT-series and slice-positions were selected independently, using picture-archiving-and-communication-system- (PACS-) tools on tilt-corrected axial MDCT-images (slice-thickness 0.6–3.0 mm, window/centre 350/50 HU) in 37 selected adult patients (24 female, age 57 ± 13 years, average±standard-deviation) with clinical indication for Hertel-exophthalmometry, by one radiology-attending, two ophthalmology-attendings, one critical-care-attending, and one ear-nose-throat-surgery resident, respectively. Bland-Altman plots and Wilcoxon-matched-pairs-signed-rank-tests compared interobserver results. Results: Mean and median interobserver and intraobserver (radiology-attending) deviations were within 1 mm of respective averages of base-length (98 ± 4 mm), right and left ocular protrusion (21 ± 4 mm) and interocular difference (2 ± 1 mm). Relative interobserver deviations were within 2.0% of average (all patients) for base-length, and 5.0% (>80% of patients) for ocular protrusion. Pairwise interobserver comparison showed no significant differences between interocular differences of protrusion. Conclusions: Respective measurements of base-length, ocular protrusion, and deriving interocular difference show high interdisciplinary interobserver reproducibility in tilt-corrected axial MDCT-images of the orbit or mid-face. Advances in knowledge: Hertel-exophthalmometry-like protrusion measurements did not depend on the years of experience or the medical subspecialty of the observer. Measurements are objective, well reproducible and important for multiple medical disciplines and should thus be included in pertinent radiology reports

Unguis incarnatus – konservative oder operative Therapie?

Unguis incarnatus, an ingrown toenail, is a common condition in primary care, which is encountered by various medical professions. Inconsistent conservative treatment and nonindicated surgical treatment often result in complications and recurrence of the disease. Patients must be thoroughly informed about the complexity of the nail organ. This is a prerequisite to prevent trivialization of the disease and to achieve appropriate patient compliance for treatment. In this article a practical diagnostic and treatment algorithm for unguis incarnatus is presented. In mild cases of acute unguis incarnatus a consistent conservative treatment is the first-line strategy showing promising results. In cases of moderate to severe forms of acute unguis incarnatus, surgical procedures that preserve the nail matrix should be applied. For cases of chronic unguis incarnatus without an acute infection, elective partial matrixectomy can be indicated. Prior to any surgical intervention, detailed informed consent must be obtained from the patients. ZUSAMMENFASSUNG Der Unguis incarnatus ist ein häufiges Krankheitsbild, mit dem sich Patienten in der Hausarztpraxis, der dermatologischen Klinik oder der chirurgischen Notaufnahme vorstellen. Häufig führt die inkonsequente konservative Therapie oder die falsch-indizierte operative Intervention zu langwierigen und komplikationsreichen Verläufen, inklusive Rezidiven. Die Patienten sollten über die Komplexität des Nagelorgans aufgeklärt werden, um der Banalisierung der Erkrankung vorzubeugen, und eine entsprechende Compliance in der Therapie zu erreichen. In diesem Manuskript wird die sachgerechte Versorgung des Unguis incarnatus im Sinne eines praktischen Behandlungsalgorithmus dargestellt. Die konsequente konservative Therapie ist bei akutem Unguis incarnatus mit milder Ausprägung die Therapie der ersten Wahl mit guten Behandlungsergebnissen. Nagelerhaltende operative Eingriffe kommen bei moderaten/schweren akuten Formen zum Einsatz. Der chronische Unguis incarnatus, ohne floride Infektion, stellt eine elektive Operationsindikation dar. Sowohl bei den nagelerhaltenden Eingriffen als auch bei erweiterten operativen Maßnahmen ist eine chirurgische Operationsaufklärung obligat

Impact of Selection and Demography on the Diffusion of Lactase Persistence

BACKGROUND: The lactase enzyme allows lactose digestion in fresh milk. Its activity strongly decreases after the weaning phase in most humans, but persists at a high frequency in Europe and some nomadic populations. Two hypotheses are usually proposed to explain the particular distribution of the lactase persistence phenotype. The gene-culture coevolution hypothesis supposes a nutritional advantage of lactose digestion in pastoral populations. The calcium assimilation hypothesis suggests that carriers of the lactase persistence allele(s) (LCT*P) are favoured in high-latitude regions, where sunshine is insufficient to allow accurate vitamin-D synthesis. In this work, we test the validity of these two hypotheses on a large worldwide dataset of lactase persistence frequencies by using several complementary approaches. METHODOLOGY: We first analyse the distribution of lactase persistence in various continents in relation to geographic variation, pastoralism levels, and the genetic patterns observed for other independent polymorphisms. Then we use computer simulations and a large database of archaeological dates for the introduction of domestication to explore the evolution of these frequencies in Europe according to different demographic scenarios and selection intensities. CONCLUSIONS: Our results show that gene-culture coevolution is a likely hypothesis in Africa as high LCT*P frequencies are preferentially found in pastoral populations. In Europe, we show that population history played an important role in the diffusion of lactase persistence over the continent. Moreover, selection pressure on lactase persistence has been very high in the North-western part of the continent, by contrast to the South-eastern part where genetic drift alone can explain the observed frequencies. This selection pressure increasing with latitude is highly compatible with the calcium assimilation hypothesis while the gene-culture coevolution hypothesis cannot be ruled out if a positively selected lactase gene was carried at the front of the expansion wave during the Neolithic transition in Europe

Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis

It has been 100 years since the first report of sickle haemoglobin (HbS). More than 50 years ago, it was suggested that the gene responsible for this disorder could reach high frequencies because of resistance conferred against malaria by the heterozygous carrier state. This traditional example of balancing selection is known as the 'malaria hypothesis'. However, the geographical relationship between the transmission intensity of malaria and associated HbS burden has never been formally investigated on a global scale. Here, we use a comprehensive data assembly of HbS allele frequencies to generate the first evidence-based map of the worldwide distribution of the gene in a Bayesian geostatistical framework. We compare this map with the pre-intervention distribution of malaria endemicity, using a novel geostatistical area-mean comparison. We find geographical support for the malaria hypothesis globally; the relationship is relatively strong in Africa but cannot be resolved in the Americas or in Asia

The Origins of Lactase Persistence in Europe

Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (−13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the −13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on −13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the −13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe

Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses

available in PMC 2011 September 1Vaccines based on recombinant proteins avoid the toxicity and antivector immunity associated with live vaccine (for example, viral) vectors, but their immunogenicity is poor, particularly for CD8+ T-cell responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8+ T-cell responses comparable to those for live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. Interbilayer-crosslinked vesicles stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying vesicles form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to those for the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for therapeutic protein delivery.Ragon Institute of MGH, MIT and HarvardBill & Melinda Gates FoundationUnited States. Dept. of Defense (contract W911NF-07-D-0004)National Institutes of Health (U.S.) (P41RR002250)National Institutes of Health (U.S.) (RC2GM092599

Single-Cell Transcriptional Analysis of Normal, Aberrant, and Malignant Hematopoiesis in Zebrafish

Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4+ cell type, representing a putative cytotoxic T/NK cell. Our platform also quantified hematopoietic defects in rag2E450fs mutant fish and showed that these fish have reduced T cells with a subsequent expansion of NK-lysin 4+ cells and myeloid cells. These data suggest compensatory regulation of the innate immune system in rag2E450fs mutant zebrafish. Finally, analysis of Myc-induced T cell acute lymphoblastic leukemia showed that cells are arrested at the CD4+/CD8+ cortical thymocyte stage and that a subset of leukemia cells inappropriately reexpress stem cell genes, including bmi1 and cmyb. In total, our experiments provide new tools and biological insights into single-cell heterogeneity found in zebrafish blood and leukemia