The lower nasal base: an anatomical study Daniel, Rollin K; Glasz, Tibor; Molnar, Gyongyver ...
Aesthetic surgery journal,
02/2013, Letnik:
33, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Currently, most rhinoplasty surgeons focus their analysis and operative techniques on the upper nasal base, with its alar cartilages. They tend to minimize the lower nasal base, composed of the ...columellar base, nostril sills, and alar lobules. The requisite operative techniques are often considered ancillary techniques. In this article, the authors describe anatomical composition of the columellar base, nostril sill, and alar lobule; discuss the presence of a distinct lower nasal base; and reevaluate the nasal musculature and the nasal superficial muscular aponeurotic system in an anatomical cadaver model. They also discuss the results of both a detailed literature review (for articles related to the levator labii superioris alaeque nasalis, orbicularis oris, depressor septi nasalis, myrtiformis, and dilator naris) and the results of their own dissection of 45 fresh cadavers.
Le frottis cervical reste le meilleur outil de dépistage des lésions précancéreuses du col. En revanche, la sensibilité n'est pas parfaite et la spécificité non plus dans les anomalies mineures. Le ...contrôle de qualité est un des moyens d'améliorer les performances du test. Le Centre de regroupement informatique et statistique des données en anatomie pathologique (CRISAP) Ile-de-France a mis au point un système de contrôle de qualité externe dont l'objectif était de tester la reproductibilité du diagnostic cytologique entre plusieurs observateurs. Treize anatomocytopathologistes ont participé volontairement à la relecture de 650 cas qui ont été choisis de manière randomisée et stratifiée. Chaque lecteur a relu 50 cas et a donné 50 cas à relire de manière anonyme. Le diagnostic a été fait d'après la classification de Bethesda. La variabilité a été évaluée par le pourcentage de concordance et le kappa. Le pourcentage de concordance a été de 65 % et le kappa de 0,66 pour l'ensemble du groupe. Quand les normaux et les ininterprétables ont été regroupés en négatif et les ASCUS, bas grade et haut grade en positif, le pourcentage de concordance a été de 83% et le kappa de 0,66. Quand les normaux et les ininterprétables ont été regroupés avec les ASCUS en négatif et les bas grade et les haut grade en positif, le pourcentage de concordance a été de 90 % et le kappa de 0,76. Cette étude montre qu'il est possible d'évaluer la reproductibilité du diagnostic entre plusieurs structures de manière fiable par un test simple et convivial. La corrélation entre les observateurs est substantielle pour le diagnostic cytologique dans son ensemble. Le diagnostic de frottis ininterprétables et ASCUS varie entre les observateurs. Ce type d'étude devrait permettre aux auteurs de reconsidérer les critères utilisés pour ces diagnostics.
The cervical Pap smear is the method of choice for early detection of precancerous cervical lesions. However, sensibility of the Pap smear is not perfect nor specificity, in particular for minor atypia ; quality control is the best method to improve the efficiency of the test. The “ Centre de regroupement informatique et statistique des données en anatomie pathologique ” (CRISAP) Ile-de-France initiated an external quality control with a protocol aimed at assessing diagnosis reproducibility among observers. Thirteen pathologists accepted to participate in a voluntary basis to this protocol which consisted of the rereading of 650 slides chosen at random. Each participant had reread 50 cases and had sent 50 cases to be reread anonymously. The diagnosis was given according to the Bethesda classification. The reproducibility was assessed using the percentage of agreement and kappa statistics. The percentage of agreement for all the group was 65 % and the weighted kappa 0.66. When normal and unsatisfactory cases were combined as negative and ASCUS, Low Grade Squamous Intraepithelial Lesion (LGSIL) and High Grade Squamous Intraepithelial Lesion (HGSIL) as positive , the percentage of agreement was 83 % and Kappa 0.66. When normal, unsatisfactory and ASCUS were combined as negative and LGSIL and HGSIL as positive, the percentage agreement raised to 90 % and Kappa to 0.77. This attempt at assessing the reproducibility of cytologic diagnosis using an informal method had led to good participation among participants. A fairly good agreement for overall cytologic diagnosis was found, though a variability remained concerning the diagnosis of unsatisfactory and those labelled as ASCUS. These results should lead the participants to reflect upon and eventually reassess their own criteria on these cases.
Congenital anomalies of the kidney and urinary tract (CAKUT) constitute a major cause of chronic kidney disease in children and 20% of prenatally detected anomalies. CAKUT encompass a spectrum of ...developmental kidney defects, including renal agenesis, hypoplasia, and cystic and non-cystic dysplasia. More than 50 genes have been reported as mutated in CAKUT-affected case subjects. However, the pathophysiological mechanisms leading to bilateral kidney agenesis (BKA) remain largely elusive. Whole-exome or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L (growth regulation by estrogen in breast cancer 1-like), a gene reported as a target of retinoic acid signaling. Four loss-of-function and 12 damaging missense variants, 14 being absent from GnomAD, were identified. Twelve of them were present in familial or simplex BKA-affected case subjects. Female BKA-affected fetuses also displayed uterus agenesis. We demonstrated a significant association between GREB1L variants and BKA. By in situ hybridization, we showed expression of Greb1l in the nephrogenic zone in developing mouse kidney. We generated a Greb1l knock-out mouse model by CRISPR-Cas9. Analysis at E13.5 revealed lack of kidneys and genital tract anomalies in male and female Greb1l−/− embryos and a slight decrease in ureteric bud branching in Greb1l+/− embryos. We showed that Greb1l invalidation in mIMCD3 cells affected tubulomorphogenesis in 3D-collagen culture, a phenotype rescued by expression of the wild-type human protein. This demonstrates that GREB1L plays a major role in early metanephros and genital development in mice and humans.
We review some recent results of quantitative long-time convergence for the law of a killed Markov process conditioned to survival toward a quasi-stationary distribution, and on the analogous ...question for the particle systems used in practice to sample these distributions. With respect to the existing literature, one of the novelties of these works is the degeneracy of the underlying process with respect to classical elliptic diffusion, namely it can be a non-elliptic hypoelliptic diffusion, a piecewise deterministic Markov process or an Euler numerical scheme.
Nous présentons quelques résultats récents d’estimées quantitatives de convergence en temps long pour la loi de processus de Markov tués, conditionnellement à leur survie, vers une mesure quasi-stationnaire, et sur la question analogue pour les systèmes de particules utilisés en pratique pour échantillonner ces mesures. Par rapport à la littérature antérieure, l’une des nouveautés de ces travaux est le caractère dégénéré du processus de Markov sous-jacent par rapport aux diffusions elliptiques classiques, au sens où ce peut être une diffusion hypoelliptique non-elliptique, un processus déterministe par morceaux, ou un schéma d’Euler.
Qu’en fut-il de l’architecture et de l’urbanisme sous l’Occupation ? Si les travaux sur la France de Vichy foisonnent, le champ architectural et urbain est longtemps resté ignoré. Les politiques ...conduites en la matière ne sauraient se mesurer à la quantité d’édifices réalisés, mais plutôt à l’ampleur des réorganisations administratives – telle la création de l’Ordre des architectes en décembre 1940 – ou à l’abondante production de textes et de plans. Les architectes furent-ils majoritairement collaborateurs et profiteurs de guerre, dans des contextes allant de la spoliation des biens des Juifs à la pressante reconstruction des villes détruites ? Quel rôle jouèrent des architectes comme Le Corbusier ou Auguste Perret ? Quelle place les langages architecturaux ont-ils réservé au moderne et à la tradition ? Quel enseignement dispensait-on dans les écoles ? Sans prétendre en dévoiler toutes les continuités et les ruptures, l’ouvrage pose de front la question des politiques architecturales et urbaines mises en oeuvre sous le régime de Vichy, de leurs origines et de leur héritage.
Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate, typically co-occurring with intellectual disability, facial dysmorphism, and congenital heart defects. The identification ...of patients with loss-of-function variants in MEIS2, a gene within this deletion, suggests that these features are attributed to haploinsufficiency of MEIS2. To further delineate the phenotypic spectrum of the MEIS2-related syndrome, we collected 23 previously unreported patients with either a de novo sequence variant in MEIS2 (9 patients), or a 15q14 microdeletion affecting MEIS2 (14 patients). All but one de novo MEIS2 variant were identified by whole-exome sequencing. One variant was found by targeted sequencing of MEIS2 in a girl with a clinical suspicion of this syndrome. In addition to the triad of palatal defects, heart defects, and developmental delay, heterozygous loss of MEIS2 results in recurrent facial features, including thin and arched eyebrows, short alae nasi, and thin vermillion. Genotype-phenotype comparison between patients with 15q14 deletions and patients with sequence variants or intragenic deletions within MEIS2, showed a higher prevalence of moderate-to-severe intellectual disability in the former group, advocating for an independent locus for psychomotor development neighboring MEIS2.
Context. Congenital neutropenia (CN) is a heterogeneous group of diseases characterized by low neutrophil count, severe bacterial infections, increased risk of leukemic transformation and various ...extra-hematopoietic organ dysfunctions. Even if 24 different genes have been linked to the etiology of CN, in many patients the genetic causes of CN remain unknown.
Methods. Whole-exome sequencing (WES) was performed on a trio-based approach in 8 sporadic cases and 6 multiplex families. Sanger sequencing was performed in a second phase on 66 additional patients from the French CN registry. Structural and functional studies were performed using primary cells from patients including fibroblasts and hematopoietic cells. In vitro granulocytic differentiation was conducted by culturing CD34+ in serum-free medium with SCF, IL-3 and G-CSF for 21 days.
Results. WES analysis identified a heterozygous mutation in the SRP54 gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and an autosomal dominant family. Considering these results we directly sequenced SRP54 in the French CN cohort and identified 13 additional sporadic cases and 2 multiplex families, thus reaching a total of 23 cases carrying a SRP54 mutation (19 families, Figure 1A). The Thr117del in-frame deletion was found in 12 probands. In all patients, neutropenia was profound (mean neutrophil absolute count 0.23x109/L), diagnosed in the neonate period or during childhood (mean age 4.2 months), and required long-term G-CSF therapy (mean dose 9 µg/kg/day). Bone marrow examination showed a maturation arrest at the promyelocytic stage. In contrast to CN associated with ELANE mutations, SRP54-mutated patients presented an important degree of dysgranulopoiesis (abnormal localization and number of mature granules) and enlarged endoplasmic reticulum (ER) in promyelocytes as well as dystrophic neutrophils (Figure 1B-1C). No evolution into acute myeloid leukemia was observed in this cohort after a median follow-up period of 14.8 years despite high doses of G-CSF. Six out of the 23 patients had extra-hematopoietic manifestations comprising severe neurodevelopmental delay (n=5) and/or exocrine pancreatic insufficiency (n=3), and/or bone abnormalities (n=2) (Figure 1A).
The SRP54 protein is a key component of the ribonucleoprotein complex SRP that mediates the co-translational targeting and the insertion of secretory and membrane proteins to the ER. We identified 7 distinct mutations that affect highly conserved residues within or interacting with G motifs involved in the GTPase activity of SRP54. Of note, 17 out of 18 patients with mutations located within the G1 element and predicted to affect the structure and/or stability of the NG domain presented only a severe neutropenia. In contrast, the other 5 patients with mutations affecting either the magnesium-binding or the guanine-binding site and/or implied in the heterodimeric association with the receptor of SRP54, were associated with Shwachman-Diamond-like syndrome features. During the in vitro granulocytic differentiation of both normal and mutated hematopoietic progenitors, we found a strong increase in SRP54 mRNA expression levels associated with a slight decrease in the protein level in patients compared to controls. Moreover, SRP54 mutations induced a major deleterious effect on proliferation (Figure 1D) and a delay in the differentiation associated with increased apoptosis. Using both in vitro-derived granulocytic cells and primary fibroblasts, we also observed that SRP54 mutations led to ER stress (increased eIF2a phosphorylation, XBP1 splicing, ATF4 and CHOP expression) and enhanced autophagy (higher levels of LC3-II and ULK1 expression).
Conclusions. This study thus identifies a novel pathological pathway implicating the co-translational process of protein targeting. This new genetic subtype which represents the second cause of CN in the French registry (prevalence 6.9%), is characterized by a promyelocytic maturation arrest with dysgranulopoiesis leading to a profound neutropenia, with a poor response to G-CSF, and in few patients, is associated with severe neurodevelopmental delay and exocrine pancreatic insufficiency.
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No relevant conflicts of interest to declare.
Phelan-McDermid syndrome (PMS) is characterized by a variety of clinical symptoms with heterogeneous degrees of severity, including intellectual disability (ID), absent or delayed speech, and autism ...spectrum disorders (ASD). It results from a deletion of the distal part of chromosome 22q13 that in most cases includes the
gene.
is considered a major gene for PMS, but the factors that modulate the severity of the syndrome remain largely unknown. In this study, we investigated 85 patients with different 22q13 rearrangements (78 deletions and 7 duplications). We first explored the clinical features associated with PMS, and provide evidence for frequent corpus callosum abnormalities in 28% of 35 patients with brain imaging data. We then mapped several candidate genomic regions at the 22q13 region associated with high risk of clinical features, and suggest a second locus at 22q13 associated with absence of speech. Finally, in some cases, we identified additional clinically relevant copy-number variants (CNVs) at loci associated with ASD, such as 16p11.2 and 15q11q13, which could modulate the severity of the syndrome. We also report an inherited
deletion transmitted to five affected daughters by a mother without ID nor ASD, suggesting that some individuals could compensate for such mutations. In summary, we shed light on the genotype-phenotype relationship of patients with PMS, a step towards the identification of compensatory mechanisms for a better prognosis and possibly treatments of patients with neurodevelopmental disorders.
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