Langerhans cells in hypospadias : an analysis of Langerin (CD207) and HLA-DR on epidermal sheets and full thickness skin sections

Background: Hypospadias are among the most common genital malformations. Langerhans Cells (LCs) play a pivotal role in HIV and HPV infection. The migration of LC precursors to skin coincides with the embryonic period of hypospadias development and genetic alterations leading to the formation of hypospadias impact the development of ectodermally derived tissues. We hypothesized that this might be associated with a difference in frequency or morphology of epidermal and dermal LCs in hypospadias patients. Methods: A total of 43 patients from two centers were prospectively included into this study after parental consent and ethics approval. Epidermal and dermal sheets were prepared from skin samples of 26 patients with hypospadias, 13 patients without penile malformations and 4 patients with penile malformations other than hypospadias. Immunofluorescence staining of sheets was performed with anti-HLA-DR-FITC and anti-CD207/Langerin-A594 antibodies. Skin sections from 11 patients without penile malformation and 11 patients with hypospadias were stained for Langerin. Frequencies as well as morphology and distribution of epidermal and dermal LCs on sheets and sections were microscopically evaluated. Cell counts were compared by unpaired t-tests. Results: There was no difference in frequency of epidermal LCs, Neither on sheets (87361 vs. 940 +/- 84LCs/mm(2), p=0.522) nor on sections (32 +/- 3 vs. 30 +/- 2LCs/mm(2), p=0.697). Likewise, the frequency of dermal LCs (5,9 +/- 0,9 vs. 7.5 +/- 1.3LCs/mm(2), p=0.329) was comparable between patients with hypospadias and without penile malformation. No differences became apparent in subgroup analyses, comparing distal to proximal hypospadias (p=0.949), younger and older boys (p=0.818) or considering topical dihydrotestosterone treatment prior to surgery (p=0.08). The morphology of the LCs was not different comparing hypospadias patients with boys without penile malformations. Conclusions: p id=Par Cs are present in similar frequencies and with a comparable morphology and distribution in patients with hypospadias as compared to children without penile malformations. This suggests that patients with hypospadias are not different from patients with normal penile development considering this particular compartment of their skin immunity

Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities. [Abstract copyright: © 2023. The Author(s).

Power Management for RF-Powered vs. Battery-Powered Devices

Abstract – The general goal of power management (PM) is to achieve optimal system performance while meeting power constraints. Minimizing the energy consumption is mostly not sufficient. Especially power management policies for battery-powered and RFpowered devices require a deep understanding of the supplies ’ electrical characteristics. Thus, battery-aware PM aims to efficiently utilize the battery by reducing average current and avoiding relatively long (ms-sec) intervals of high discharge. In turn, RF-powered devices are additionally sensitive to instantaneous power consumption. This paper gives an overview of battery-aware PM approaches and draws avenues how these algorithms can be adapted and/or extended for RF-powered devices. Simulation and experimental results are presented to show the effects of power management policies on system life time and performance. I

Potential Mechanisms Leading to Overuse Injuries of the Back in Alpine Ski Racing - A Descriptive Biomechanical Study

Background: Overuse injuries of the back are a common complaint among top athletes and of competitive alpine skiers in particular. However, there is limited understanding about the sport-specific causes of these injuries that is essential for their prevention. Purpose/Hypothesis: This study was undertaken to describe the sport-specific, overall trunk kinematics and skiers’ loading during giant slalom turns and to assess the plausibility of the hypothesis that a combination of frontal bending, lateral bending, and/or torsion in the loaded trunk might be a potential mechanism leading to overuse injuries of the back in alpine ski racing. Study Design: Descriptive laboratory study. Methods: Eight European Cup–level athletes performed giant slalom runs with 2 different pairs of skis (varying in length, width, and sidecut). They were analyzed with respect to selected kinematic variables related to spinal disc loading. The overall trunk movement components (frontal bending, lateral bending, and torsion) were measured using 2 inertial measurement units fixed on the sacrum and sternum. Total ground-reaction forces were measured by pressure insoles. Results: During the turn phase in which the total ground-reaction forces were the greatest (up to 2.89 times the body weight), the highest average values of frontal bending (38.7 deg), lateral bending (14.7 deg), and torsion (7.7 deg) in the trunk occurred. Similar magnitudes were observed when skiing on longer, giant slalom skis with less width and sidecut. Conclusion: The typical loading patterns of the back in alpine ski racing include a combined occurrence of frontal bending, lateral bending, and torsion in the loaded trunk. Because these factors are known to be related to high spinal disc loading, they may be considered important components of mechanisms leading to overuse injuries of the back in alpine ski racing. Clinical Relevance: Prevention measures should aim to control and/or reduce the magnitude of frontal bending, lateral bending, and torsion in the trunk, as well as the peak loads, while skiing

Ureteroureterostomy in patients with duplex malformations: does a large diameter of the donor ureter affect the outcome?

Introduction Ureteroureterostomy is a commonly adopted, minimally invasive approach in the management of duplex anomalies requiring diversion, e.g., ectopic upper pole ureters. Objective The authors hypothesized that a large diameter of the donor ureter could affect the outcome of this procedure. Study design Forty-two patients from two centers were retrospectively reviewed. To compare patients with small (group 1) vs large donor ureters (group 2), they were split at the median of the sonographically measured diameter at the level of the future anastomosis (n = 20 = 1.2 cm, mean 1.75 cm; P = 1.2 cm is not factoring adversely into the occurrence of postoperative complications. Conclusion A donor ureter diameter >= 1.2 cm in ureteroureterostomy was not associated with a higher complication rate or worse outcome considering further fUTIs or reoperations. The postoperative reduction in hydronephrosis grade was more pronounced in patients with large donor ureters with disappearance of the preoperative significant difference between the two groups