Iatrogenic tracheal rupture in a patient with acute respiratory distress syndrome due to SARS-CoV-2 pneumonia.

Iatrogenic tracheal rupture (ITR) is a serious complication secondary to procedures such as emergent orotracheal intubation or tracheostomy, among others. The management of ITR depends on the size, extension and location of the injury, along with the patient's respiratory status and comorbidities. The priority of treatment is to keep the airway permeable to ensure adequate ventilation. We present the case of a tracheal rupture after performing a percutaneous tracheostomy, in a patient diagnosed with severe acute respiratory distress syndrome secondary to bilateral interstitial pneumonia due to SARS-Cov-2. The issues are discussed, such as the management (conservative vs. surgical) depending on the features of the injury and the patient, in the extraordinary context that the COVID-19 pandemic has entailed.

Not all that glitters is COVID-19: a case series demonstrating the need for histopathology when skin findings accompany SARS-CoV-2 infection.

BACKGROUND: Descriptions of cutaneous findings associated with COVID-19 have not been consistently accompanied by histopathology or confirmatory testing for SARS-CoV-2. OBJECTIVE: To describe and classify the cutaneous findings with supporting histopathology of confirmed COVID-19 inpatients. METHODS: We included consecutive inpatients with a confirmed diagnosis of COVID-19 for whom a dermatology consult was requested. A skin biopsy was performed in all cases. Skin findings were classified as being compatible with a cutaneous manifestation of COVID-19 or as representing a distinct clinical entity. RESULTS: Twenty-eight patients were studied in whom thirty-one dermatologic diagnoses were made. Twenty-two of the dermatoses were compatible with a cutaneous manifestation of COVID-19; nine entities were not associated with infection by SARS-CoV-2. The most common COVID-19-associated pattern was an exanthematous presentation. In four patients, a new pattern was observed, characterized by discrete papules with varied histopathological findings including a case of neutrophilic eccrine hidradenitis. No cases of pernio-like lesions were identified. Skin findings not associated with COVID-19 represented 29% of diagnoses and included Malassezia folliculitis, tinea, miliaria and contact dermatitis. LIMITATIONS: There is no gold-standard test to distinguish between viral exanthems and drug reactions. CONCLUSION: A histopathological study is critical before attributing skin findings to a manifestation of COVID-19.

Eimeria ninakohlyakimovae casts NOX-independent NETosis and induces enhanced IL-12, TNF-α, IL-6, CCL2 and iNOS gene transcription in caprine PMN.

Eimeria ninakohlyakimovae represents a highly pathogenic coccidian parasite causing severe haemorrhagic typhlocolitis in goat kids worldwide. NETosis was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites in vitro and in vivo. In vitro interactions of caprine PMN with parasitic stages of E. ninakohlyakimovae (i. e. oocysts and sporozoites) as well as soluble oocyst antigens (SOA) were analyzed at different ratios, concentrations and time spans. Extracellular DNA staining was used to illustrate classical molecules induced during caprine NETosis [i. e. histones (H3) and neutrophil elastase (NE)] via antibody-based immunofluorescence analyses. Functional inhibitor treatments with DPI and DNase I were applied to unveil role of NADPH oxidase (NOX) and characterize DNA-backbone composition of E. ninakohlyakimovae-triggered caprine NETosis. Scanning electron microscopy (SEM)- and immunofluorescence-analyses demonstrated that caprine PMN underwent NETosis upon contact with sporozoites and oocysts of E. ninakohlyakimovae, ensnaring filaments which firmly entrapped parasites. Detailed co-localization studies of E. ninakohlyakimovae-induced caprine NETosis revealed presence of PMN-derived DNA being adorned with nuclear H3 and NE corroborating molecular characteristics of NETosis. E. ninakohlyakoimovae-induced caprine NETosis was found to be NOX-independent since DPI inhibition led to a slight decrease of NETosis. Exposure of caprine PMN to vital E. ninakohlyakimovae sporozoites as well as SOA resulted in up-regulation of IL-12, TNF-α, IL-6, CCL2 and iNOS gene transcription in stimulated PMN. Since vital E. ninakohlyakimovae-sporozoites induced caprine NETosis, this effective entrapment mechanism might reduce initial sporozoite epithelial host cell invasion during goat coccidiosis ultimately resulting in less macromeront formation and reduced merozoites I production.

Iatrogenic tracheal rupture in a patient with acute respiratory distress syndrome due to SARS-CoV-2 pneumonia. / Rotura traqueal iatrogénica en paciente con síndrome de distrés respiratorio agudo por neumonía SARS-CoV-2.

Iatrogenic tracheal rupture is a serious complication secondary to procedures such as emergent orotracheal intubation or tracheostomy, among others. The management of iatrogenic tracheal rupture depends on the size, extension and location of the injury, along with the patient's respiratory status and comorbidities. The priority of treatment is to keep the airway permeable to ensure adequate ventilation. We present the case of a tracheal rupture after performing a percutaneous tracheostomy, in a patient diagnosed with severe acute respiratory distress syndrome secondary to bilateral interstitial pneumonia due to SARS-CoV-2. The issues are discussed, such as the management (conservative vs. surgical) depending on the features of the injury and the patient, in the extraordinary context that the COVID-19 pandemic has entailed.

Controlled Sign Reversal of Electroresistance in Oxide Tunnel Junctions by Electrochemical-Ferroelectric Coupling.

The persistence of ferroelectricity in ultrathin layers relies critically on screening or compensation of polarization charges which otherwise destabilize the ferroelectric state. At surfaces, charged defects play a crucial role in the screening mechanism triggering novel mixed electrochemical-ferroelectric states. At interfaces, however, the coupling between ferroelectric and electrochemical states has remained unexplored. Here, we make use of the dynamic formation of the oxygen vacancy profile in the nanometer-thick barrier of a ferroelectric tunnel junction to demonstrate the interplay between electrochemical and ferroelectric degrees of freedom at an oxide interface. We fabricate ferroelectric tunnel junctions with a La_{0.7}Sr_{0.3}MnO_{3} bottom electrode and BaTiO_{3} ferroelectric barrier. We use poling strategies to promote the generation and transport of oxygen vacancies at the metallic top electrode. Generated oxygen vacancies control the stability of the ferroelectric polarization and modify its coercive fields. The ferroelectric polarization, in turn, controls the ionization of oxygen vacancies well above the limits of thermodynamic equilibrium, triggering the build up of a Schottky barrier at the interface which can be turned on and off with ferroelectric switching. This interplay between electronic and electrochemical degrees of freedom yields very large values of the electroresistance (more than 10^{6}% at low temperatures) and enables a controlled switching between clockwise and counterclockwise switching modes in the same junction (and consequently, a change of the sign of the electroresistance). The strong coupling found between electrochemical and electronic degrees of freedom sheds light on the growing debate between resistive and ferroelectric switching in ferroelectric tunnel junctions, and moreover, can be the source of novel concepts in memory devices and neuromorphic computing.

Potential value of tedera (B. bituminosa) as high protein resource for poultry feed.

Bituminaria bituminosa (C.H. Stirt.) is a drought tolerant legume that grows spontaneously in subtropical areas: Canary Islands (Spain) and in North African and Mediterranean regions, traditionally used as forage for ruminants. The aim of this research was to investigate the potential of B. bituminosa as a high protein resource for poultry feed by means of feed intake, growth, feed conversion rate (FCR), protein efficiency ratio (PER), and the influence of B. bituminosa feed form (fresh green and dried) on the preference by chicks. B. bituminosa showed higher crude protein content (CP), neutral detergent fiber (NDF), and gross energy than commercial feed. Average daily feed intake (ADFI) for the commercial feed group (control group) was higher than ADFI of the B. bituminosa group (experimental group). However, both groups had no significant differences in total crude protein intake, total NDF intake, average daily gain (ADG), FCR, and PER. The poultry's preference for fresh green B. bituminosa was higher than for dry B. bituminosa. Our results suggest that B. bituminosa (tedera) could be an alternative feedstuff in tropical countries or where protein sources are scarce and costly.

Age-related immune response to experimental infection with Eimeria ninakohlyakimovae in goat kids.

Both the immune response developed in ruminants against Eimeria spp. and the ability to bear patent infections seems to be dependent on the age of the host. In the present study we have evaluated the influence of the age in the development of protective immune responses against Eimeria ninakohlyakimovae. For this purpose, 3, 4 and 5-week-old goat kids were infected with sporulated oocysts and subjected to a homologous challenge 3 weeks later. Goat kids primary infected at 6, 7 and 8 weeks of age served as challenge controls, and uninfected animals were used as negative controls. The protective immunity was assessed by clinical, haematological, parasitological, immunological and pathological parameters. Altogether, the results demonstrate that goat kids of either 3, 4 or 5 weeks of age are able to develop patent infections and immunoprotective responses against E. ninakohlyakimovae, as all age groups: (i) released significantly less oocysts after challenge, which was associated to milder clinical signs; (ii) displayed a local immune response, with significant increase of numerous cellular populations; and (iii) had increased levels of IgG and IgM, and mainly of local IgA. Nevertheless, detailed analysis of the data showed some differences between the three age groups, related both to the Eimeria infection outcome and the resulting immune response, suggesting that youngest goat kids are not fully immunocompetent. This finding may be of interest for the design of immunoprophylactic approaches and/or prophylactic/methaphylactic treatments against goat coccidiosis.

Protective immune responses during prepatency in goat kids experimentally infected with Eimeria ninakohlyakimovae.

During the first schizogony, the goat coccidia Eimeria ninakohlyakimovae develops macroschizonts in lacteal duct endothelial cells, whose rupture leads to severe ileal damage and clinical signs during the prepatent period. The immune response elicited against early stages of the parasite development still requires to be investigated. In the present study we have evaluated immune reactions in goat kids primary- and challenged-infected with Eimeria ninakohlyakimovae, and sacrificed during prepatency (7days after challenge). The oocyst output during the primary infection, body weight and clinical condition of all the animals were examined and, at the end of the experiment, all the goat kids were euthanized and subjected to necropsy. Samples were taken from different sections of the ileum, colon and mesenteric lymph nodes (MLN) of primary- and challenged E. ninakohlyakimovae-infected animals. Intestinal leukocyte subpopulations were characterized in E. ninakohlyakimovae-infected mucosa and counts of lymphocytes, eosinophils, polymorphonuclear neutrophils (PMN), globular leukocytes and mast cells were recorded. Additionally, gene expression of caprine IL-2, IL-4, IL-10 and INFγ of ileal, colonic and MLN tissues were performed, as well as the immunohistochemical characterization of immune cells. The E. ninakohlyakimovae primary infection resulted in moderate to severe enteritis with different degrees of diarrhoea and was accompanied by high OPG counts and an increase of most immune cells analyzed when compared to uninfected control animals. Furthermore, eosinophil-, lymphocyte-, globular leukocyte- and mast cell-counts were significantly higher in the challenge group compared to the primary infected animals, whilst the opposite was true for PMN counts. The challenge infection was also associated with moderate increased levels of local mucosal IgA. Interestingly, the number of immature schizonts found at the ileal mucosa was statistically higher in the challenge infected group compared to the challenged control animals. Furthermore, in the challenged E. ninakohlyakimovae-infected animals a significantly higher number of mucosal CD4+ and CD8+ lymphocytes were observed, indicating that these T cell subpopulations might be involved in protective host immune response elicited against early stages of parasite development. The immune response was however very complex, as antigen presenting cells and other effector cell populations of the innate immune system, as well as certain cytokines, were involved. In summary, the results of this study contribute to the better understanding of local cellular and humoral immune responses against caprine E. ninakohlyakimovae, particularly during the prepatency.

Unprecedented simultaneous enhancement in damage tolerance and fatigue resistance of zirconia/Ta composites.

Dense (>98 th%) and homogeneous ceramic/metal composites were obtained by spark plasma sintering (SPS) using ZrO2 and lamellar metallic powders of tantalum or niobium (20 vol.%) as starting materials. The present study has demonstrated the unique and unpredicted simultaneous enhancement in toughness and strength with very high flaw tolerance of zirconia/Ta composites. In addition to their excellent static mechanical properties, these composites also have exceptional resistance to fatigue loading. It has been shown that the major contributions to toughening are the resulting crack bridging and plastic deformation of the metallic particles, together with crack deflection and interfacial debonding, which is compatible with the coexistence in the composite of both, strong and weak ceramic/metal interfaces, in agreement with predictions of ab-initio calculations. Therefore, these materials are promising candidates for designing damage tolerance components for aerospace industry, cutting and drilling tools, biomedical implants, among many others.

Chronic blockade of the AT2 receptor with PD123319 impairs insulin signaling in C57BL/6 mice.

The renin-angiotensin system modulates insulin action. Angiotensin type 1 receptor exerts a deleterious effects while the angiotensin type 2 receptor (AT2R) appears to have beneficial effects providing protection against insulin resistance and type 2 diabetes. Although recent reports indicate that agonism of AT2R ameliorates diabetes and insulin resistance, the phenotype of AT2R-knockout mice seems to be controversial relating this aspect. Thus, in this study we have explored the role of AT2R in the control of insulin action. To that end, C57Bl/6 mice were administered the synthetic AT2R antagonist PD123319 for 21days (10mg/kg/day ip); vehicle treated animals were used as control. Glucose tolerance, metabolic parameters, in vivo insulin signaling in main insulin-target tissues as well as levels of adiponectin, TNF-α, MCP-1 and IL-6 in adipose tissue were assessed. AT2R blockade with PD123319 induced a marginal effect on glucose homeostasis but an important reduction in the insulin-induced phosphorylation of the insulin receptor and Akt in both liver and adipose tissue. Insulin signaling in skeletal muscle remained unaltered after treatment with PD123319, which could explain the minimal effect on glucose homeostasis induced by PD123319. Our current results reinforce the notion that the AT2R has a physiological role in the conservation of insulin action.

Eimeria ninakohlyakimovae induces NADPH oxidase-dependent monocyte extracellular trap formation and upregulates IL-12 and TNF-α, IL-6 and CCL2 gene transcription.

Extracellular trap (ET) formation has been demonstrated as novel effector mechanism against diverse pathogens in polymorphonuclear neutrophils (PMN), eosinophils, mast cells, macrophages and recently also in monocytes. In the current study, we show that E. ninakohlyakimovae triggers the deliverance of monocyte-derived ETs in vitro. Fluorescence illustrations as well as scanning electron microscopy (SEM) analyses showed that monocyte-derived ET formation was rapidly induced upon exposure to viable sporozoites, sporocysts and oocysts of E. ninakohlyakimovae. Classical features of monocyte-released ETs were confirmed by the co-localization of extracellular DNA adorned with myeloperoxidase (MPO) and histones (H3) in parasite-entrapping structures. The treatment of caprine monocyte ET structures with NADPH oxidase inhibitor diphenylene iodondium (DPI) significantly reduced ETosis confirming the essential role of reactive oxygen species (ROS) in monocyte mediated ETs formation. Additionally, co-culture of monocytes with viable sporozoites and soluble oocyst antigen (SOA) induced distinct levels of cytokine and chemokine gene transcription. Thus, the transcription of genes encoding for IL-12 and TNF-α was significantly upregulated after sporozoite encounter. In contrast IL-6 and CCL2 gene transcripts were rather weakly induced by parasites. Conversely, SOA only induced the up-regulation of IL-6 and CCL2 gene transcription, and failed to enhance transcripts of IL-12 and TNF-α in vitro. We here report on monocyte-triggered ETs as novel effector mechanism against E. ninakohlyakimovae. Our results strongly suggest that monocyte-mediated innate immune reactions might play an important role in early host immune reactions against E. ninakohlyakimovae in goats.

Targeting essential Eimeria ninakohlyakimovae sporozoite ligands for caprine host endothelial cell invasion with a phage display peptide library.

Eimeria ninakohlyakimovae is an important coccidian parasite of goats which causes severe diarrhoea in young animals. Specific molecules that mediate E. ninakohlyakimovae host interactions and molecular mechanisms involved in the pathogenesis are still unknown. Although strong circumstantial evidence indicates that E. ninakohlyakimovae sporozoite interactions with caprine endothelial host cells (ECs) are specific, hardly any information is available about the interacting molecules that confer host cell specificity. In this study, we describe a novel method to identify surface proteins of caprine umbilical vein endothelial cells (CUVEC) using a phage display library. After several panning rounds, we identified a number of peptides that specifically bind to the surface of CUVEC. Importantly, caprine endothelial cell peptide 2 (PCEC2) and PCEC5 selectively reduced the infection rate by E. ninakohlyakimovae sporozoites. These preliminary data give new insight for the molecular identification of ligands involved in the interaction between E. ninakohlyakimovae sporozoites and host ECs. Further studies using this phage approach might be useful to identify new potential target molecules for the development of anti-coccidial drugs or even new vaccine strategies.

Modulation of the pro-inflammatory molecules E-selectin and TNF-α gene transcription in Eimeria ninakohlyakimovae-infected primary caprine host endothelial cells.

Eimeria ninakohlyakimovae is an important coccidian parasite of goats which causes severe hemorrhagic typhlocolitis in young animals, thereby leading to high economic losses in goat industry worldwide. The first merogony of E. ninakohlyakimovae occurs within host endothelial cells (ECs) of the lacteal capillaries of the villi of the distal ileum resulting in the formation of macromeronts (up to 170 µm) within 10-12 days post-infection (p.i.) and releasing >120,000 merozoites I. The E. ninakohlyakimovae-macromeront formation within highly immunoreactive host endothelial cells (ECs) should rely on several regulatory processes to fulfill this massive replication. Here host EC-parasite interactions were investigated to determine the extent of modulation carried out by E. ninakohlyakimovae in primary caprine umbilical vein endothelial cells (CUVEC) during the first merogony. Gene transcription of the adhesion molecule E-selectin and the cytokine TNF-α were significantly enhanced in the first hours and days p.i. in E. ninakohlyakimovae-infected CUVEC. The activation of CUVEC was also demonstrated by enhanced chemokine CCL2 and cytokine GM-CSF gene transcription, whereas no differences of the eNOS gene transcription were observed in E. ninakohlyakimovae-infected CUVEC when compared to un-infected controls. The data presented here suggest that infection of caprine host ECs by E. ninakohlyakimovae results in EC activation associated with enhanced gene transcription encoding for pro-inflammatory as well as immunomodulatory molecules, which might be important for the defense against this intracellular parasite.

Formation of titanium monoxide (001) single-crystalline thin film induced by ion bombardment of titanium dioxide (110).

A plethora of technological applications justify why titanium dioxide is probably the most studied oxide, and an optimal exploitation of its properties quite frequently requires a controlled modification of the surface. Low-energy ion bombardment is one of the most extended techniques for this purpose and has been recently used in titanium oxides, among other applications, to favour resistive switching mechanisms or to form transparent conductive layers. Surfaces modified in this way are frequently described as reduced and defective, with a high density of oxygen vacancies. Here we show, at variance with this view, that high ion doses on rutile titanium dioxide (110) induce its transformation into a nanometric and single-crystalline titanium monoxide (001) thin film with rocksalt structure. The discovery of this ability may pave the way to new technical applications of ion bombardment not previously reported, which can be used to fabricate heterostructures and interfaces.

Histologic study of the effects of chemoembolization with preloaded doxorubicin beads in patients with hepatocellular carcinoma.

OBJECTIVE: To determine the degree of tumor necrosis in surgical specimens of hepatocellular carcinomas treated with microspheres preloaded with doxorubicin and to analyze the relationship between the degree of necrosis and a) morphologic factors and b) imaging biomarkers. MATERIAL AND METHODS: We studied the livers of 21 patients who had undergone selective arterial chemoembolization with DC beads (Biocompatibles, UK) before receiving liver transplants. RESULTS: Imaging techniques detected 43 nodules (mean size, 25 mm). Angiography showed 25 hypervascularized nodules, 12 slightly vascularized nodules, and 6 avascular nodules. A total of 81 hepatocellular carcinomas (mean size, 15 mm) were detected in the specimens: two were capsular and two had vascular infiltration. The mean degree of necrosis after chemoembolization was 39%; necrosis was greater than 60% in 28 hepatocellular carcinomas and less than 60% in 52. The degree of necrosis correlated significantly with the time elapsed between the last chemoembolization treatment and liver transplantation (the degree of necrosis decreased as time increased), with the number of nodules in the specimen, and with capsular infiltration. When imaging techniques detected 1 or 2 nodules, there was a greater probability of achieving greater than 90% necrosis. No relation with the degree of necrosis achieved was found for the size of the nodules detected at imaging, the enhancement pattern, or the number of chemoembolization treatments. CONCLUSION: The degree of necrosis achieved depends on the time spent on the waiting list, on the number of nodules in the specimen, and on whether capsular infiltration is present.

[Stroke mimics: a challenge for the emergency physician]. / Imitadores del ictus: un reto para el médico de urgencias.

BACKGROUND: To study the number of patients diagnosed with a stroke in the emergency service of a first level hospital and the proportion of these patients who were finally stroke mimics, as well as to describe and analyze the variables that can help in differential diagnosis in hospital emergency services. METHOD: Nine month prospective study. All patients evaluated in emergency services and admitted with a diagnosis of stroke were included. Different clinical variables were analyzed that included prior history, history of the current event, general physical and neurological examination, NIHSS classification and Oxfordshire Community Stroke Project Classification. The final diagnosis was made by a panel of experts with access to clinical characteristics, image studies and other tests. The univariate and multivariate analysis determined the characteristics that help in distinguishing strokes from stroke mimics. RESULTS: One hundred and forty-four cases of stroke were registered; the final sample was made up of 140 patients. The final diagnosis was stroke in 103 out of 140 (73.6%) and stroke mimic in the rest. Eleven variables predicted the diagnosis in patients with a suspected stroke: age over 70 years (p=0.012), NIHSS classification > 5, reaching a clinical classification (p=0.019) capable of determining the exact start (p=0.000), abnormal vascular findings (p=0.014), gaze deviation (p=0.042), sight loss (p=0.052) and extensor plantar response (p=0.025) favored diagnosis of stroke, while epileptic seizures (p=0.029), neurological symptoms not congruent with the vascular territory (p=0.022) and abnormal findings in other systems (p=0.14) favored diagnosis of stroke mimic. CONCLUSION: Stroke mimics constitute one-third of the patients admitted from emergency services as strokes, with a highly varied etiology. Achieving a suitable clinical history and a precise physical examination is of great importance and can help less experienced doctors.