Anterior Transfer of Tibialis Posterior through the Interosseous Membranes in Post Injection Drop Foot: The Expirence at CORU

Post injection foot drop constitutes 7.6% of paediatric orthopaedic pathology seen in our unit. It commonly results from intragluteal injection with quinine in the treatment of malaria. The patients present with equinus or equinovarus foot deformity. Because of abnormal weight bearing, the deformity usually worsened with age. Anterior transfer of the tibialis posterior to the dorsum of the foot through the interosseous membrane has been described before and results reported. The tendon is either transfixed by tenodesis to the cuneiform or cuboids. In our series the latter method was used. This is a follow up of 30 patients who had surgeries at least 18 months after the injection and muscles power of the tendon transferred ranged from 3 to 5. We used three incisions of approximately 4cm each instead of four. Postoperative plaster of Paris cast for 6 weeks and ankle foot orthosis were used. We evaluated for correction and ability of the transferred tendon to actively dorsiflex at the ankle joint. Nineteen patients had good results 8 fair and 3 poor there was no neurovascular deficit. The purpose of this paper is to outline our outcome and technique of anterior transfer of the tibialis posterior through the interosseous membrane

Nowcasting COVID-19 incidence indicators during the Italian first outbreak

A novel parametric regression model is proposed to fit incidence data typically collected during epidemics. The proposal is motivated by real-time monitoring and short-term forecasting of the main epidemiological indicators within the first outbreak of COVID-19 in Italy. Accurate short-term predictions, including the potential effect of exogenous or external variables are provided. This ensures to accurately predict important characteristics of the epidemic (e.g., peak time and height), allowing for a better allocation of health resources over time. Parameter estimation is carried out in a maximum likelihood framework. All computational details required to reproduce the approach and replicate the results are provided

New Insights into the Lactate Shuttle: Role of MCT4 in the Modulation of the Exercise Capacity.

Lactate produced by muscle during high-intensity activity is an important end product of glycolysis that supports whole body metabolism. The lactate shuttle model suggested that lactate produced by glycolytic muscle fibers is utilized by oxidative fibers. MCT4 is a proton coupled monocarboxylate transporter preferentially expressed in glycolytic muscle fibers and facilitates the lactate efflux. Here we investigated the exercise capacity of mice with disrupted lactate shuttle due to global deletion of MCT4 (MCT4−/−) or muscle-specific deletion of the accessory protein Basigin (iMSBsg−/−). Although MCT4−/− and iMSBsg−/− mice have normal muscle morphology and contractility, only MCT4−/− mice exhibit an exercise intolerant phenotype. In vivo measurements of compound muscle action potentials showed a decrement in the evoked response in the MCT4−/− mice. This was accompanied by a significant structural degeneration of the neuromuscular junctions (NMJs). We propose that disruption of the lactate shuttle impacts motor function and destabilizes the motor unit

Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK-LKB1 Signaling Axis.

Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 may couple cell proliferation to energy homeostasis

Kinase-independent role of cyclin D1 in chromosomal instability and mammary tumorigenesis

Cyclin D1 is an important molecular driver of human breast cancer but better understanding of its oncogenic mechanisms is needed, especially to enhance efforts in targeted therapeutics. Currently, pharmaceutical initiatives to inhibit cyclin D1 are focused on the catalytic component since the transforming capacity is thought to reside in the cyclin D1/CDK activity. We initiated the following study to directly test the oncogenic potential of catalytically inactive cyclin D1 in an in vivo mouse model that is relevant to breast cancer. Herein, transduction of cyclin D1(-/-) mouse embryonic fibroblasts (MEFs) with the kinase dead KE mutant of cyclin D1 led to aneuploidy, abnormalities in mitotic spindle formation, autosome amplification, and chromosomal instability (CIN) by gene expression profiling. Acute transgenic expression of either cyclin D1(WT) or cyclin D1(KE) in the mammary gland was sufficient to induce a high CIN score within 7 days. Sustained expression of cyclin D1(KE) induced mammary adenocarcinoma with similar kinetics to that of the wild-type cyclin D1. ChIP-Seq studies demonstrated recruitment of cyclin D1(WT) and cyclin D1(KE) to the genes governing CIN. We conclude that the CDK-activating function of cyclin D1 is not necessary to induce either chromosomal instability or mammary tumorigenesis

Aberrant splicing and expression of the non muscle myosin heavy-chain gene MYH14 in DM1 muscle tissues

Myotonic dystrophy type 1 (DM1) is a complex multisystemic disorder caused by an expansion of a CTG repeat located at the 3' untranslated region (UTR) of DMPK on chromosome 19q13.3. Aberrant messenger RNA (mRNA) splicing of several genes has been reported to explain some of the symptoms of DM1 including insulin resistance, muscle wasting and myotonia. In this paper we analyzed the expression of the MYH14 mRNA and protein in the muscle of DM1 patients (n=12) with different expansion lengths and normal subjects (n=7). The MYH14 gene is located on chromosome 19q13.3 and encodes for one of the heavy chains of the so called class II "nonmuscle" myosins (NMHCII). MYH14 has two alternative spliced isoforms: the inserted isoform (NMHCII-C1) which includes 8 amino acids located in the globular head of the protein, not encoded by the non inserted isoform (NMHCII-C0). Results showed a splicing unbalance of the MYH14 gene in DM1 muscle, with a prevalent expression of the NMHCII-C0 isoform more marked in DM1 patients harboring large CTG expansions. Minigene assay indicated that levels of the MBNL1 protein positively regulates the inclusion of the MYH14 exon 6. Quantitative analysis of the MYH14 expression revealed a significant reduction in the DM1 muscle samples, both at mRNA and protein level. No differences were found between DM1 and controls in the skeletal muscle localization of MYH14, obtained through immunofluorescence analysis. In line with the thesis of an "RNA gain of function" hypothesis described for the CTG mutation, we conclude that the alterations of the MYH14 gene may contribute to the DM1 molecular pathogenesis

Local environment of optically active Nd3 + ions in the ultratransparent BaMgF 4 ferroelectric crystal

A comprehensive study of the site location of Nd3 + ions in the BaMgF 4 ultratransparent ferroelectric crystal is presented. By combining different low-temperature optical spectroscopies and electron paramagnetic resonance, the crystal field energy levels of Nd3 + ions and the gyromagnetic factors are experimentally determined. These results are employed to perform the crystal field analysis of Nd3 + ions considering a Cs point symmetry. The crystal field calculation yields a small root-mean-square deviation of 18 cm -1 and reveals a large crystal field strength (621 cm -1), verifying the assignment of the Ba2 + cationic site as the location for Nd3 + ions in this fluoride host. The results suggest a slight displacement of Nd3 + from the barium regular site with a rearrangement of the fluorine ions around it. The work gives a deep insight into the properties of the Nd3 +-doped BaMgF 4 crystal, a ferroelectric widely ultra-transparent material with potential applications as optical device operating in the Vacuum Ultraviolet-Ultraviolet and midinfrared spectral regionsThis work has been supported by the Spanish Ministry of Science under projects MAT2010-17443, MAT2010-21270-C04-02, Consolider-Ingenio MALTA CSD 2007-0045, and Comunidad Autonoma de Madrid under Grant 2009/MAT-175

Spinal cord from body donors is suitable for multicolor immunofluorescence

Immunohistochemistry is a powerful tool for studying neuronal tissue from humans at the molecular level. Obtaining fresh neuronal tissue from human organ donors is difficult and sometimes impossible. In anatomical body donations, neuronal tissue is dedicated to research purposes and because of its easier availability, it may be an alternative source for research. In this study, we harvested spinal cord from a single organ donor 2 h (h) postmortem and spinal cord from body donors 24, 48, and 72 h postmortem and tested how long after death, valid multi-color immunofluorescence or horseradish peroxidase (HRP) immunohistochemistry is possible. We used general and specific neuronal markers and glial markers for immunolabeling experiments. Here we showed that it is possible to visualize molecularly different neuronal elements with high precision in the body donor spinal cord 24 h postmortem and the quality of the image data was comparable to those from the fresh organ donor spinal cord. High-contrast multicolor images of the 24-h spinal cords allowed accurate automated quantification of different neuronal elements in the same sample. Although there was antibody-specific signal reduction over postmortem intervals, the signal quality for most antibodies was acceptable at 48 h but no longer at 72 h postmortem. In conclusion, our study has defined a postmortem time window of more than 24 h during which valid immunohistochemical information can be obtained from the body donor spinal cord. Due to the easier availability, neuronal tissue from body donors is an alternative source for basic and clinical research

OBJETIVOS DE PRÁCTICAS ASISTENCIALES EN LA UNIDAD DE URGENCIAS HOSPITALARIA. PERCEPCIÓN DEL ALUMNADO SOBRE SU CUMPLIMIENTO.

El objetivo de este trabajo se centra en medir el aprendizaje de determinadas técnicas, la aportación de los seminarios impartidos, las preferencias del alumno en cuanto a su ubicación y el grado de satisfacción dentro de la unidad en las prácticas asistenciales de un grupo de 25 estudiantes de enfermería de tercer curso, correspondiente al curso 2002-2003, que realizaron sus prácticas asistenciales (médico quirúrgica II) en una unidad de urgencias hospitalarias