An in vitro model to evaluate the accuracy of guided surgery systems

Purpose: An in vitro model was developed and tested to evaluate the precision of guided implant systems. The accuracy of dental implants placed with a flapless technique was analyzed using a stereolithographic template in vitro. Differences between the virtual and actual positions of the implants were measured. Materials and Methods: Six polyurethane mandibles with artificial silicone gums were fabricated, and each was fitted with an individual computed tomography (CT) guide. Stereolithographic guides were created using computer-aided design/computer-assisted manufacturing technology and virtual planning software. All stereolithographic guides had four holes for stabilization pins and three holes for cylindric implants. After implant placement, the mandibles were subjected to another CT scan to compare the actual implant positions with the planned positions. The pre- and postimplantation CT images were superimposed using digital processing image software to evaluate the linear and angular deviations between the virtual planning data and the surgical results. Results: The mean angular discrepancy between the virtual and actual positions of the 18 placed implants was 2.16 ± 0.92 degrees. Among the placed implants, 66.7% were situated a mean of 0.38 ± 0.03 mm apical to the planned vertical position, and 33.3% were situated 0.39 ± 0.03 mm coronal to the planned position. Conclusions: Within the limitations of the present study, this tool showed promising accuracy in virtual implant placement.     

Estimation of COVID-19 vaccine effectiveness against hospitalisation in individuals aged ≥ 65 years using electronic health registries; a pilot study in four EU/EEA countries,October 2021 to March 2022

By employing a common protocol and data from electronic health registries in Denmark, Navarre (Spain), Norway and Portugal, we estimated vaccine effectiveness (VE) against hospitalisation due to COVID-19 in individuals aged ≥ 65 years old, without previous documented infection, between October 2021 and March 2022. VE was higher in 65–79-year-olds compared with ≥ 80-year-olds and in those who received a booster compared with those who were primary vaccinated. VE remained high (ca 80%) between ≥ 12 and < 24 weeks after the first booster administration, and after Omicron became dominant.     

A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy

Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia‐inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors. © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Role of heat-shock factor 2 in cerebral cortex formation and as a regulator of p35 expression

Heat-shock factors (HSFs) are associated with multiple developmental processes, but their mechanisms of action in these processes remain largely enigmatic. Hsf2-null mice display gametogenesis defects and brain abnormalities characterized by enlarged ventricles. Here, we show that Hsf2-/- cerebral cortex displays mispositioning of neurons of superficial layers. HSF2 deficiency resulted in a reduced number of radial glia fibers, the architectural guides for migrating neurons, and of Cajal-Retzius cells, which secrete the positioning signal Reelin. Therefore, we focused on the radial migration signaling pathways. The levels of Reelin and Dab1 tyrosine phosphorylation were reduced, suggesting that the Reelin cascade is affected in Hsf2-/- cortices. The expression of p35, an activator of cyclin-dependent kinase 5 (Cdk5), essential for radial migration, was dependent on the amount of HSF2 in gain- and loss-of-function systems. p39, another Cdk5 activator, displayed reduced mRNA levels in Hsf2-/- cortices, which, together with the lowered p35 levels, decreased Cdk5 activity. We demonstrate in vivo binding of HSF2 to the p35 promoter and thereby identify p35 as the first target gene for HSF2 in cortical development. In conclusion, HSF2 affects cellular populations that assist in radial migration and directly regulates the expression of p35, a crucial actor of radial neuronal migration.     

A new dominant branchiogenic-deafness syndrome with internal auditory canal hypoplasia and abnormal extremities

Two sibs from one Lebanese family presented with congenital hearing loss, meatal atresia, preauricular tags and pits, branchial cysts or fistulae, strabismus, difficulty in opening the mouth wide enough, abnormal fifth fingers, somewhat short stature, and learning disability and patchy skin depigmentation in one. Temporal bone abnormalities identified on computed tomography included atresia of the external auditory canal with reduction in size of the middle ear, malformed ossicles, and unilateral internal auditory canal hypoplasia. Hand radiographs showed pointed phalanges of the 5th fingers with osseous erosions. Their father, his sister, and his half-brother had unilateral auricular pits and/or branchial cysts. Results of all laboratory investigations including sequencing of the EYA1 gene were normal. Differential diagnosis is discussed and the possibility of the report of a new autosomal dominant type of branchiogenic-deafness syndrome with variable expressivity is raised.     

Sexual Rehabilitation and Penile Pain Associated with Intracavernous Alprostadil after Radical Prostatectomy

IntroductionIntracavernous alprostadil injection (IAI) is widely used for sexual rehabilitation (SR) after radical prostatectomy (RP). However, the rate of spontaneous erection recovery with IAI remains unclear, and IAI causes pain that may hinder SR.AimsTo assess SR in IAI users after RP and to evaluate the course and impact on SR of postinjection penile pain.MethodsWe prospectively studied 87 patients who underwent nerve‐sparing laparoscopic RP, reported normal preoperative erectile function, and used IAI for 12 months. Patients started with 2.5 µg alprostadil and were advised to increase the dose gradually until erection hardness allowed vaginal penetration.Main Outcome MeasuresAt 6 and 12 months, the International Index of Erectile Function (IIEF‐15) and Erection Hardness Score (EHS) were determined with and without IAI, and injection‐related penile pain was assessed using a numeric rating scale. Correlations linking penile pain, IIEF‐15, and EHS scores were evaluated.ResultsThe mean alprostadil dose was 8.1 µg after 6 months and 9.9 µg after 12 months. With/without IAI, mean IIEF‐15 scores for erectile and orgasmic function and mean EHS score were 14.6/4.6, 4.1/2.1, and 2.5/0.4, respectively, after 6 months; and 17.2/5.4, 4.9/2.6, and 2.7/0.9 after 12 months. Pain scores were 3.2 ± 2.5/10 and 2.5 ± 2.5/10 after 6 and 12 months, respectively. Pain intensity correlated with erectile function (r = ?0.23), intercourse satisfaction (r = ?0.23), and overall satisfaction (r = ?0.24) after 6 months but not after 12 months. Follow‐up was short and only patients who used IAI for 12 months were included.ConclusionsIn patients who were willing and able to use IAI, erectile function improved after 1 year but remained below preoperative levels. The adverse impact of pain on SR was significant during the first 6 months and diminished over time. These data may help to counsel IAI users with painful erections. Yiou R, Cunin P, de la Taille A, Salomon L, Binhas M, Lingombet O, Paul M, and Abbou C. Sexual rehabilitation and penile pain associated with intracavernous alprostadil after radical prostatectomy.     

The effect of RGD density on osteoblast and endothelial cell behavior on RGD-grafted polyethylene terephthalate surfaces

Hybrid materials combining polyethylene terephthalate and different types of cells (endothelial and osteoblastic cells) have been developed thanks to the covalent grafting of different densities of RGD containing peptides onto the polymer surface. Biomimetic modifications were performed by means of a three-step reaction procedure: creation of COOH functions, coupling agent grafting and the immobilization of the RGDC peptides. High resolution μ-imager was used to evaluate RGD densities (varying between 0.6 and 2.4 pmol/mm²) and has exhibited the stability of the surface grafted peptides when treated in harsh conditions. The efficiency of this route for biomimetic modification of a PET surface was demonstrated by measuring the adhesion of MC3T3 and HSVEC cells and by focal adhesion observation. Results obtained prove that a minimal RGDC density of 1 pmol/mm² is required to improve MC3T3 and HSVEC cells responses. Indeed, cells seeded onto a RGDC-modified PET with a density higher than 1 pmol/mm² were able to establish focal adhesion as visualized by fluorescence microscope compared to cells immobilized onto unmodified PET and RGDC-modified PET with densities lower than 1 pmol/mm². Moreover, the number of focal contacts was enhanced by the increase of RGDC peptide densities grafted onto the material surface. With this study we proved that the density of peptides immobilized on the surface is a very important parameter influencing osteoblast or endothelial cell adhesion and focal contact formation.     

Diagnosis of growth hormone (GH) deficiency: comparison of pituitary stalk interruption syndrome and transient GH deficiency

Background  

Most patients with childhood non-organic growth hormone (GH) deficiency (GHD) produce a normal GH peak as young adults. Our objectives were to better define this transient GHD and evaluate the factors influencing the growth response of patients with pituitary stalk interruption syndrome (PSIS).     

The change of the scFv into the Fab format improves the stability and in vivo toxin neutralization capacity of recombinant antibodies

The antigen-binding fragment (Fab) has been considered a more functionally stable version of recombinant antibodies than single chain antibody fragments (scFvs), however this intuitive consideration has not been sufficiently proven in vivo. This communication shows that three out of four specific scFvs against a scorpion toxin, with different affinities and stabilities, become neutralizing in vivo when expressed as Fabs, despite the fact that they are not neutralizing in the scFv format. A scFv fragment previously obtained from a neutralizing mouse antibody (BCF2) was used to produce three derived scFvs by directed evolution. Only one of them was neutralizing, however when expressed as Fab, all of them became neutralizing fragments in vivo. The initial scFvBCF2 (earlier used for directed evolution) was not neutralizing in the scFv format. After expressing it as Fab did not become a neutralizing fragment, but did reduce the intoxication symptoms of experimental mice. The stability of the four Fabs derived from their respective scFvs was improved when tested in the presence of guanidinium chloride. The in vitro stability of the Fab format has been shown earlier, but the physiological consequences of this stability are shown in this communication. The present results indicate that improved functional stability conferred by the Fab format can replace additional maturation steps, when the affinity and stability are close to the minimum necessary to be neutralizing.