A new airway spiral stent designed to maintain airway architecture with an atraumatic removal after full epithelization - Research of feasibility and viability in canine patients with tracheomalacia

Objective: Surgical management of tracheomalacia is a challenge, with current treatments still presenting numerous complications. In the field of veterinary medicine, this same pathology is present in a significant number of dogs. For this reason, we present an experimental clinical trial performed on canines with tracheobronchomalacia, using a new atraumatic removable tracheal spiral stent (SS). Both implantation procedure and clinical improvement have been analyzed in this study.Methods: In this study, four small dogs, a mean weight of 4.89 kg and body condition scores IV‐V, were included. SS was implanted by two different surgical approaches. Image and clinical follow‐up have been performed during 90 days. Symptoms were evaluated from 1 to 10 every week. Results: This study achieved 100% technical and clinical success. Median tracheal diameters were as follows: cervical 10.85 (3.3), inlet 7.75 (2.1), and carina 7.75 (1.9) mm, and length was 77.5 (26) mm. A 12 × 10 × 100‐mm SS was implanted in all cases. Goose honk cough punctuation improved from 8 to 1; also, there were important changes in exercise intolerance, a mean weight loss of 8.76%. The values of modified Karnofsky scale varied from 50 (20) before surgery to 90 (10) after 30 days of surgery. Neither granuloma tissue nor fractures of the prosthesis was observed.Conclusion: The results in dogs are promising, and a new therapeutic alternative seems to be available for veterinarian field. The similarity of this disease between dogs and newborns suggests that this SS design can also be useful for human trials

Altered protein expression and protein nitration pattern during d-galactosamine-induced cell death in human hepatocytes: a proteomic analysis

BACKGROUND/AIMS: Hepatic injury by d-galactosamine (d-GalN) is a suitable experimental model of hepatocellular injury. The induction of oxidative and nitrosative stress participates during d-GalN-induced cell death in cultured rat hepatocytes. This study aimed to identify protein expression changes during the induction of apoptosis and necrosis by d-GalN in cultured human hepatocytes. METHODS: A proteomic approach was used to identify the proteins involved and those altered by tyrosine nitration. A high dose of d-GalN (40 mM) was used to induce apoptosis and necrosis in primary culture of human hepatocytes. Cellular lysates prepared at different times after addition of d-GalN were separated by two-dimensional electrophoresis. Gel spots with an altered expression and those matching nitrotyrosine-immunopositive proteins were excised and analyzed by mass spectrometry. RESULTS: d-GalN treatment upregulated microsomal cytochrome b5, fatty acid binding protein and manganese superoxide dismutase, and enhanced annexin degradation. d-GalN increased tyrosine nitration of four cytosolic (Hsc70, Hsp70, annexin A4 and carbonyl reductase) and three mitochondrial (glycine amidinotransferase, ATP synthase beta chain, and thiosulfate sulfurtransferase) proteins in human hepatocytes. CONCLUSIONS: The results provide evidences that oxidative stress and nitric oxide-derived reactive oxygen intermediates induce specific alterations in protein expression that may be critical for the induction of apoptosis and necrosis by d-GalN in cultured human hepatocytes

Prototyping of petalets for the Phase-II Upgrade of the silicon strip tracking detector of the ATLAS Experiment

In the high luminosity era of the Large Hadron Collider, the HL-LHC, the instantaneous luminosity is expected to reach unprecedented values, resulting in about 200 proton-proton interactions in a typical bunch crossing. To cope with the resultant increase in occupancy, bandwidth and radiation damage, the ATLAS Inner Detector will be replaced by an all-silicon system, the Inner Tracker (ITk). The ITk consists of a silicon pixel and a strip detector and exploits the concept of modularity. Prototyping and testing of various strip detector components has been carried out. This paper presents the developments and results obtained with reduced-size structures equivalent to those foreseen to be used in the forward region of the silicon strip detector. Referred to as petalets, these structures are built around a composite sandwich with embedded cooling pipes and electrical tapes for routing the signals and power. Detector modules built using electronic flex boards and silicon strip sensors are glued on both the front and back side surfaces of the carbon structure. Details are given on the assembly, testing and evaluation of several petalets. Measurement results of both mechanical and electrical quantities are shown. Moreover, an outlook is given for improved prototyping plans for large structures.Comment: 22 pages for submission for Journal of Instrumentatio

Characteristics of prosthetic joint infections due to Enterococcus sp. and predictors of failure: a multi-national study

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Plasma?-III tubulin, neurofilament light chain and glial fibrillary acidic protein are associated with neurodegeneration and progression in schizophrenia

Schizophrenia is a progressive disorder characterized by multiple psychotic relapses. After every relapse, patients may not fully recover, and this may lead to a progressive loss of functionality. Pharmacological treatment represents a key factor to minimize the biological, psychological and psychosocial impact of the disorder. The number of relapses and the duration of psychotic episodes induce a potential neuronal damage and subsequently, neurodegenerative processes. Thus, a comparative study was performed, including forty healthy controls and forty-two SZ patients divided into first-episode psychosis (FEP) and chronic SZ (CSZ) subgroups, where the CSZ sub group was subdivided by antipsychotic treatment. In order to measure the potential neuronal damage, plasma levels of beta-III tubulin, neurofilament light chain (Nf-L), and glial fibrillary acidic protein (GFAP) were performed. The results revealed that the levels of these proteins were increased in the SZ group compared to the control group (P < 0.05). Moreover, multiple comparison analysis showed highly significant levels of beta-III tubulin (P = 0.0002), Nf-L (P = 0.0403) and GFAP (P < 0.015) in the subgroup of CSZ clozapine-treated. In conclusion, beta-III tubulin, Nf-L and GFAP proteins may be potential biomarkers of neurodegeneration and progression in SZ

Systematic Review and Meta-Analysis of Randomized Clinical Trials in the Treatment of Human Brucellosis

BACKGROUND: Brucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance. METHODS AND FINDINGS: A search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified. Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05-4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81-4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63-2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future. CONCLUSIONS: Although the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current treatment of choice

The Tumor Suppressive Role of eIF3f and Its Function in Translation Inhibition and rRNA Degradation

Deregulated translation plays an important role in human cancer. We previously reported decreased eukaryotic initiation factor 3 subunit f (eIF3f) expression in pancreatic cancer. Whether decreased eIF3f expression can transform normal epithelial cells is not known. In our current study, we found evidence that stable knockdown of eIF3f in normal human pancreatic ductal epithelial cells increased cell size, nuclear pleomorphism, cytokinesis defects, cell proliferation, clonogenicity, apoptotic resistance, migration, and formation of 3-dimensional irregular masses. Our findings support the tumor suppressive role of eIF3f in pancreatic cancer. Mechanistically, we found that eIF3f inhibited both cap-dependent and cap-independent translation. An increase in the ribosomal RNA (rRNA) level was suggested to promote the generation of cancer. The regulatory mechanism of rRNA degradation in mammals is not well understood. We demonstrated here that eIF3f promotes rRNA degradation through direct interaction with heterogeneous nuclear ribonucleoprotein (hnRNP) K. We showed that hnRNP K is required for maintaining rRNA stability: under stress conditions, eIF3f dissociates hnRNP K from rRNA, thereby preventing it from protecting rRNA from degradation. We also demonstrated that rRNA degradation occurred in non-P body, non-stress granule cytoplasmic foci that contain eIF3f. Our findings established a new mechanism of rRNA decay regulation mediated by hnRNP K/eIF3f and suggest that the tumor suppressive function of eIF3f may link to impaired rRNA degradation and translation