Equine infection with Leishmania spp. in Costa Rica: Study of five cases

Background: Cutaneous forms of leishmaniosis due to Leishmania braziliensis have been reported in horses in the New World. Domestic animals play a role in the transmission of the disease. In Costa Rica, human cases of L. braziliensis, L. panamensis and L. infantum have been reported. Objectives: The present report describes five cases of equine cutaneous leishmaniosis in Costa Rica. The aetiological diagnosis was based on the presence of the parasite within the lesions. Methods: Skin biopsies were used to perform histopathological analyses of the lesions. Immunohistochemistry was used to detect the presence of the Leishmania spp. antigens in tissue sections. Laser-capture micro-dissection and quantitative real-time PCR techniques were carried out to detect the pathogen nucleic acid within the microscopic lesions. Results: Histopathological analyses showed a granulomatous inflammation within the dermis, with multi-nucleated giant cells, macrophages, lymphocytes and few neutrophils and eosinophils. We detected the parasite by immunohistochemistry, using a rabbit polyclonal antibody raised against Leishmania spp. However, we could not identify Leishmania spp. by quantitative real-time PCR in formalin-fixed paraffin-embedded tissues, using specific primers for the conserved region in the minicircle of the Leishmania DNA kinetoplast. Conclusions: Our results emphasise the importance of Leishmania spp. not only as a causative agent of equine cutaneous disease in the New World, but also as a possible emerging pathogen. Leishmaniosis is one of the most prevalent parasitic public health problems worldwide, and equines may have a role in the epidemiology of the disease.This study was supported by the Ayuntamiento de Madrid of the Comunidad de Madrid S2013/ABI-2747 (TAVS-CM) and by the Structural Funds of the European Union.S

Evaluation of P22 ELISA for the Detection of Mycobacterium bovis-Specific Antibody in the Oral Fluid of Goats

The ante-mortem diagnosis of tuberculosis (TB) in ruminants is based mainly on the intradermal tuberculin test and the IFN-γ assay. Antibody (Ab)-based tests have emerged as potential tools for the detection of TB infected animals using serum, plasma, or even milk samples. Oral fluids have also been evaluated as alternative samples with which to detect specific Abs against Mycobacterium bovis in pigs or wild boars, but not in ruminants. The objective of this study was, therefore, to evaluate the performance of an in house-ELISA for TB diagnosis (P22 ELISA) in goats as an experimental model for the diagnosis of TB using oral fluid samples. Oral fluid samples from 64 goats from a TB-infected herd (n = 197) and all the animals from a TB-free herd (n = 113) were analyzed using the P22 ELISA. The estimated sensitivity (Se) and specificity (Sp) were 34.4% (95% CI: 22.4-45.6) and 100% (95% CI: 97.4-100), respectively. The optimal cut-off point was set at 100% according to the ROC analysis. Those animals with a higher level of Abs in their oral fluid attained a higher lesion score (p = 0.018). In fact, when taking into account only the setting of the animals with severe lesions (n = 16), the ELISA showed a Se of 75% (95% CI: 53.7-96.2). Results of the present study suggest that the P22 ELISA is highly specific but has a limited value detecting infected animals in oral fluid samples. Nevertheless, its performance is significantly higher in the presence of severe lesions.This study was funded by the Herramientas para alcanzar la erradicación de la tuberculosis caprina (GoaTBfree) project (PID2019-105155RB-C31) and the Spanish Government's Ministerio de Agricultura, Pesca y Alimentación. JO was supported by an FPU (Formación de Profesorado Universitario) contract-fellowship provided by the Spanish Ministerio de Ciencia, Innovación y Universidades (FPU18/05197).S

Neuroimagen estructural y funcional en las enfermedades priónicas humanas

INTRODUCTION: Prion diseases are neurodegenerative disorders resulting from the accumulation of a misfolded isoform of the cellular prion protein (PrPc). They can occur as acquired, sporadic or hereditary forms. Although prion diseases show a wide range of phenotypic variations, pathological features and clinical evolution, they are all characterised by a common unfavourable course and a fatal outcome. REVIEW SUMMARY: Some variants, such as kuru, have practically disappeared, while others, for example the variant Creutzfeldt-Jakob (vCJD) or those attributable to iatrogenic causes, are still in force and pose a challenge to current medicine. There are no definitive pre-mortem diagnostic tests, except for vCJD, where a tonsil biopsy detects 100% of the cases. For this reason, diagnostic criteria dependent on statistical probability have had to be created. These require complementary examinations, such as an electroencephalogram (EEG) or the detection of 14-3-3 protein in cerebrospinal fluid (CSF). Only the "pulvinar sign" in magnetic resonance imaging (MRI) has been included as a vCJD diagnostic criterion. The present review discusses neuroimaging findings for each type of prion disease in patients with a definitive histopathological diagnosis. CONCLUSIONS: The aim is to define the usefulness of these complementary examinations as a tool for the diagnosis of this family of neurodegenerative diseases

Genetically Confirmed Familial Hypercholesterolemia in Patients With Acute Coronary Syndrome

BACKGROUND: Genetic screening programs in unselected individuals with increased levels of low-density lipoprotein cholesterol (LDL-C) have shown modest results in identifying individuals with familial hypercholesterolemia (FH). OBJECTIVES: This study assessed the prevalence of genetically confirmed FH in patients with acute coronary syndrome (ACS) and compared the diagnostic performance of FH clinical criteria versus FH genetic testing. METHODS: Genetic study of 7 genes (LDLR, APOB, PCSK9, APOE, STAP1, LDLRAP1, and LIPA) associated with FH and 12 common alleles associated with polygenic hypercholesterolemia was performed in 103 patients with ACS, age ≤65 years, and LDL-C levels ≥160 mg/dl. Dutch Lipid Clinic (DLC) and Simon Broome (SB) FH clinical criteria were also applied. RESULTS: The prevalence of genetically confirmed FH was 8.7% (95% confidence interval [CI]: 4.3% to 16.4%; n = 9); 29% (95% CI: 18.5% to 42.1%; n = 18) of patients without FH variants had a score highly suggestive of polygenic hypercholesterolemia. The prevalence of probable to definite FH according to DLC criteria was 27.2% (95% CI: 19.1% to 37.0%; n = 28), whereas SB criteria identified 27.2% of patients (95% CI: 19.1% to 37.0%; n = 28) with possible to definite FH. DLC and SB algorithms failed to diagnose 4 (44%) and 3 (33%) patients with genetically confirmed FH, respectively. Cascade genetic testing in first-degree relatives identified 6 additional individuals with FH. CONCLUSIONS: The prevalence of genetically confirmed FH in patients with ACS age ≤65 years and with LDL-C levels ≥160 mg/dl is high (approximately 9%). FH clinical algorithms do not accurately classify patients with FH. Genetic testing should be advocated in young patients with ACS and high LDL-C levels to allow prompt identification of patients with FH and relatives at risk.This research was supported in part by the Instituto de Salud Carlos III (grants RD012/0042/0066 and CB16/11/00432), Spanish Ministry of Economy and Competitiveness (grant SAF2015-71863-REDT), and Alexion through an Investigator Initiated Research Grant. Grants from the Instituto de Salud Carlos III and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de I+D+I 2013-2016 European Regional Development Fund (FEDER), "A way of making Europe." The sponsors played no role in the design, collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Drs. Castillo, Lluis-Ganella, and Quintana are employees of Gendiag.exe/Ferrer inCode.S

Laparoscopic surgery in 3D improves results and surgeon convenience in sleeve gastrectomy for morbid obesity

Purpose Advanced laparoscopic procedures are still challenging. One critical issue is the lack of stereoscopic vision. The aim of this surgical study is to evaluate whether 3D vision offers any advantages for surgical performance over 2D vision during sleeve gastrectomy for morbid obesity using a laparoscopic system that allows changing between 2D and 3D optics. Methods A total of 78 patients were analyzed, with 37 in the 2D group and 41 in the 3D group. Performance time, hospital stay, complications, and early outcomes were collected. To assess the quality of the 2D and 3D techniques, visual analog scales from 0 to 10 were designed, and image quality, depth of field, precision in performing tasks, and general ergonomics were measured. Results According to the vision system used, the mean duration of surgery was 85 ± 16.8 min for patients operated on with the 2D system and 69 ± 16.9 min for those operated on with the 3D system. There were no significant differences between the overall percentages of complications according to the type of vision used. However, postoperative complications were more severe in the 2D laparoscopy group. The average length of stay was shorter for patients in the 3D group. Regarding the differences perceived by the surgeon, the depth of field and the precision of tasks were better in the 3D vision group. Conclusion The 3D system provided greater depth perception and precision in more complex tasks, enabling safer surgery. This led to a reduction in the operative time and hospital stay. Moreover, the severity of complications was less

Guía docente común de las titulaciones de Ingeniero en Electrónica en las universidades andaluzas

El presente documento constituye el resultado del trabajo elaborado de acuerdo con la Convocatoria de Elaboración de Guías Docentes de Titulaciones Andaluzas conforme al Sistema de Créditos Europeos (años 2005/2006) de la Dirección General de Universidades, dependiente de la Secretaría General de Universidades, Investigación y Tecnología de la Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía

Myc and cell cycle control

Soon after the discovery of the Myc gene (c-Myc), it became clear thatMyc expression levels tightly correlate to cell proliferation. The entry in cell cycle of quiescent cells upon Myc enforced expression has been described in manymodels. Also, the downregulation or inactivation ofMyc results in the impairment of cell cycle progression. Given the frequent deregulation of Myc oncogene in human cancer it is important to dissect out the mechanisms underlying the role ofMyc on cell cycle control. Several parallel mechanisms account forMyc-mediated stimulation of the cell cycle. First,most of the critical positive cell cycle regulators are encoded by genes induced byMyc. These Myc target genes include Cdks, cyclins and E2F transcription factors. Apart from its direct effects on the transcription, Myc is able to hyperactivate cyclin/Cdk complexes through the induction of Cdk activating kinase (CAK) and Cdc25 phosphatases. Moreover, Myc antagonizes the activity of cell cycle inhibitors as p21 and p27 through different mechanisms. Thus, Myc is able to block p21 transcription or to induce Skp2, a protein involved in p27 degradation. Finally, Myc induces DNA replication by binding to replication origins and by upregulating genes encoding proteins required for replication initiation. Myc also regulates genes involved in the mitotic control. A promising approach to treat tumors with deregulated Myc is the synthetic lethality based on the inhibition of Cdks. Thus, the knowledge of the Myc-dependent cell cycle regulatory mechanisms will help to discover new therapeutic approaches directed against malignancies with deregulated Myc. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.The work in the laboratory of the authors is funded by grants SAF11-23796 from Spanish Ministry of Industry and Innovation, and ISCIII-RETIC RD12/0036/0033 from Spanish Ministry of Health to JL, and FIS 11/00397 to MDD. GB is recipient of a fellowship form the FPI Program. We apologize to colleagues whose work has not been cited in the form of their original papers but in reviews and whose work has not been discussed due to space limitations or unintentional omission

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old