COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses.

An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein1. Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 18-55 years of age. Two doses of 1-50 µg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-µg dose) to 3.5-fold (50-µg dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon-γ was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms.

p53 and TAp63 promote keratinocyte proliferation and differentiation in breeding tubercles of the zebrafish.

p63 is a multi-isoform member of the p53 family of transcription factors. There is compelling genetic evidence that ΔNp63 isoforms are needed for keratinocyte proliferation and stemness in the developing vertebrate epidermis. However, the role of TAp63 isoforms is not fully understood, and TAp63 knockout mice display normal epidermal development. Here, we show that zebrafish mutants specifically lacking TAp63 isoforms, or p53, display compromised development of breeding tubercles, epidermal appendages which according to our analyses display more advanced stratification and keratinization than regular epidermis, including continuous desquamation and renewal of superficial cells by derivatives of basal keratinocytes. Defects are further enhanced in TAp63/p53 double mutants, pointing to partially redundant roles of the two related factors. Molecular analyses, treatments with chemical inhibitors and epistasis studies further reveal the existence of a linear TAp63/p53->Notch->caspase 3 pathway required both for enhanced proliferation of keratinocytes at the base of the tubercles and their subsequent differentiation in upper layers. Together, these studies identify the zebrafish breeding tubercles as specific epidermal structures sharing crucial features with the cornified mammalian epidermis. In addition, they unravel essential roles of TAp63 and p53 to promote both keratinocyte proliferation and their terminal differentiation by promoting Notch signalling and caspase 3 activity, ensuring formation and proper homeostasis of this self-renewing stratified epithelium.

Efectos de ejercicios especializados en la rehabilitación del esguince de tobillo grado 1 en futbolistas / Effects of specialized exercises in the rehabilitation of grade 1 ankle sprain in soccer players

Introducción: Las lesiones en los futbolistas provocan limitaciones en la movilidad osteomuscular, provocando un descanso pasivo, y por ende el no cumplimiento del principio de sistematicidad del entrenamiento; por lo cual, puede provocar abandono deportivo en casos extremos, y normalmente disminución del rendimiento. La recuperación mediante terapia requiere una valoración de su eficiencia, siendo necesario estudiar las acciones más efectivas desde el punto de vista terapéutico. Objetivo: Valorar los efectos de un proceso de intervención con ejercicios terapéuticos para la rehabilitación del esguince de tobillo grado 1 en futbolistas. Métodos: Investigación descriptiva/explicativa de orden cuasiexperimental y enfoque longitudinal (4 años de estudio), investigando a 43 futbolistas con una lesión previa en el tobillo por esguince grado 1 (Grupo 1: Experimental, Grupo 2: Control), interviniendo al grupo experimental con tres fases de tratamiento, que incluye un grupo de ejercicios físicos especializados para fortalecer y mantener las condiciones óptimas del musculo. Resultados: El grupo experimental requiere menos tiempo para recuperarse de una lesión por esguince (p ( 0,001), mientras que la reincidencia de la lesión fue menor que en el grupo control (p ( 0,019) en un periodo de cuatro años. Conclusiones: El proceso de intervención ha sido efectivo al lograse una mejor rehabilitación en la muestra experimental, en términos de prontitud en el proceso de recuperación, y en términos de disminución de las recaídas en un periodo de cuatro años. Una vez recuperado el deportista, se recomienda proseguir sistemáticamente con el proceso de fortalecimiento y prevención en las sesiones de entrenamiento, y en el hogar(AU)

Introduction: Injuries in soccer players cause limitations in musculoskeletal mobility, causing a passive rest, and therefore non-compliance with the principle of systematic training; Therefore, it can cause sports abandonment in extreme cases, and usually a decrease in performance. Recovery through therapy requires an assessment of its efficiency, and it is necessary to study the most effective actions from the therapeutic point of view. Objective: To assess the effects of an intervention process with therapeutic exercises for the rehabilitation of grade 1 ankle sprain in soccer players. Methods: Descriptive/explanatory research of quasi-experimental order and longitudinal approach (4 years of study), researching 43 soccer players with a previous ankle injury due to grade 1 sprain (Group 1: Experimental, Group 2: Control), intervening in the experimental group. with three phases of treatment, which includes a group of specialized physical exercises to strengthen and maintain optimal muscle conditions. Results: The experimental group required less time to recover from a sprain injury (p ( 0.001), while the recurrence of the injury was less than in the control group (p ( 0.019) in a period of four years. Conclusions: The intervention process has been effective in achieving better rehabilitation in the experimental sample, in terms of speed in the recovery process, and in terms of reducing relapses in a four years period. Once the athlete has recovered, it is recommended to systematically continue with the strengthening and prevention process in training sessions and at home(AU)

Kindlin-1 mutant zebrafish as an in vivo model system to study adhesion mechanisms in the epidermis.

From a forward genetic screen for epidermal defects in zebrafish, we identified a loss-of-function mutation in Kindlin-1, an essential regulator of integrin function. The mutation generates a premature stop codon, deleting the integrin-binding site. The mutant zebrafish develops cell-matrix and cell-cell adhesion defects in the basal epidermis leading to progressive fin rupturing, and was therefore designated rupturing-of-fins (rof). Similar defects were observed in the epidermis of Kindler syndrome patients, carrying a loss-of-function mutation in kindlin-1. Mutational analysis and rescue experiments in zebrafish revealed that residues K610, W612, and I647 in the F3 domain are essential for Kindlin-1 function in vivo, and that Kindlin-2 can functionally compensate for the loss of Kindlin-1. The fin phenotype of rof/kindlin-1 mutants resembles that of badfin mutants, carrying a mutation in integrin α3. We show here that this mutation impairs the biosynthesis of integrin α3ß1 and causes cell-matrix and cell-cell defects in vivo. Whereas both Integrin-linked kinase (Ilk) and Kindlin-1 cooperate with Integrin α3ß1 to resist trauma-induced epidermal defects, Kindlin-1 and Ilk, surprisingly, do not act synergistically but in parallel. Thus, the rof/kindlin-1 mutant zebrafish provides a unique model system to study epidermal adhesion mechanisms in vivo.

Pure bipolar plasma vaporization of the prostate: the Zürich experience.

INTRODUCTION AND OBJECTIVES: Bipolar plasma vaporization (BPV) has been introduced as an alternative to transurethral resection of the prostate (TURP). Promising short-term results, but inferior mid-term results compared to TURP have been reported following first-generation bipolar electrovaporization. Outcome data following second-generation BPV are still scarce. The aim of this investigation was to evaluate the intra- and postoperative outcomes of contemporary BPV in a center with long-standing expertise on laser vaporization of the prostate. METHODS: A consecutive series of 83 patients undergoing BPV in a tertiary referral center was prospectively evaluated. The investigated outcome parameters included the maximum flow rate (Qmax), postvoid residual volume, International Prostate Symptom Score (IPSS)/quality of life (Qol), and prostate-specific antigen (PSA) tests. Follow-up investigations took place after 6 weeks, 6 months, and 12 months. The Wilcoxon signed-rank test was used to compare pre- and post-treatment parameters. RESULTS: The median (range) preoperative prostate volume was 41 mL (17-111 mL). The preoperative IPSS, Qol, Qmax, and residual volume were 16 (2-35), 4 (0-6), 10.1 mL/s (3-29.3 mL/s), and 87 mL (0-1000 mL), respectively. One third of the patients were undergoing platelet aggregation inhibition (PAI). No intraoperative complications occurred. Postoperatively, 13 patients (15.7%) had to be recatheterized. Three patients (3.6%) had clot retention and 28 patients (34%) reported any grade of dysuria. After 6 weeks, all outcome parameters improved significantly and remained improved over the 12-month observation period [IPSS: 3 (0-2); Qol: 1 (0-4); Qmax: 17.2 mL/s (3.2-56 mL/s); residual volume 11 mL (0-190 mL)]. The PSA reduction was 60% at study conclusion. Three patients (3.6%) developed a urethral stricture and four patients (4.8%) bladder neck sclerosis. Re-resections were not necessary. CONCLUSIONS: Contemporary BPV is a safe and efficacious treatment option even for patients undergoing PAI. Early urinary retention and temporary dysuria seem to be specific side effects of the treatment. Bleeding complications are rare. Long-term follow-up is needed to confirm these promising short-term results.

Preperitoneal robotic prostate adenomectomy.

OBJECTIVES: To describe the surgical technique and evaluate the feasibility of robotic-assisted preperitoneal prostate adenomectomy for large benign adenomas in a pilot series. METHODS: A total of 13 consecutive patients with a median age 70 years and body mass index of 26 kg/m(2) in whom open adenomectomy was planned were included in this pilot study. The extraperitoneal robotic approach was standardized in all cases. The demographic, operative, and outcome measurements were analyzed. The conversion rate, total operative time, and blood loss served as the feasibility parameters. RESULTS: The total operative time was 210 minutes (range 150-330). No open conversion was necessary. The blood loss was 500 mL (range 100-1100), with a 0% transfusion rate. Single-finger assistance improved the total operative time to 140 minutes (range 110-180; P = .007) and blood loss to 250 mL (range 200-350; P = .02). The specimen weight was 82 g (range 50-150). The indwelling catheters were removed after 6 days (range 3-15), and the patients returned to work after 13 days (range 8-17). After a median follow-up of 13 months (range 2-18), the patients had a median flow rate of 23 mL/s without any postvoid residual urine. CONCLUSIONS: The results of our study have shown that preperitoneal robotic transvesical prostate adenomectomy is a feasible and reproducible procedure. Additional series with larger patient cohorts and prostate adenomas are needed.

Complications of robotic assisted radical prostatectomy.

OBJECTIVES: Robotic radical prostatectomy claims optimal oncologic results, minimal morbidity and best outcomes of urinary continence and erection function. Potential benefits concerning side effects and complications compared to open radical prostatectomy are analysed. METHODS: Out of 450 robotic radical prostatectomies performed, the last 210 patients aged 64 (41-78), PSA of 7.2 ng/ml (0.6-75) and body mass index of 27 (20-37) were assessed in detail using the Clavien's classification of surgical complications. In addition, a retrospective Medline based meta-analysis of 4,928 patients from eight centres involved was performed and compared to published data of open retropubic radical prostatectomy. RESULTS: In total 55/210 (26%) of the patients had complications, whereof 48/55 (87%) were minor (Clavien's grade I-IIIa). Complications (IIIb and IVa) with open reoperations occurred in 7/210 (3%) of the patients including three bleedings, two incarcerated small bowels, one perforation of a sigmoid diverticle and one trocar hernia. No IVb or V complication occurred. Overall robotic complication rate is very low and appears to be even less than in open series. Minor and major complications seem to decrease after 200 individual console surgeries. CONCLUSIONS: Robotic radical prostatectomy has proven to be a safe and reproducible surgical treatment with low morbidity. We encourage further trials using the same classification of complications to evaluate the morbidity of robotic prostatectomy conclusively in the near future.