Fluorescent Calixarene-Schiff as a Nanovehicle with Biomedical Purposes

Gene therapy is a technique that is currently under expansion and development. Recent advances in genetic medicine have paved the way for a broader range of therapies and laid the groundwork for next-generation technologies. A terminally substituted difluorene-diester Schiff Base calix[4]arene has been studied in this work as possible nanovector to be used in gene therapy. Changes to luminescent behavior of the calixarene macrocycle are reported in the presence of ct-DNA. The calixarene macrocycle interacts with calf thymus DNA (ct-DNA), generating changes in its conformation. Partial double-strand denaturation is induced at low concentrations of the calixarene, resulting in compaction of the ct-DNA. However, interaction between calixarene molecules themselves takes place at high calixarene concentrations, favoring the decompaction of the polynucleotide. Based on cytotoxicity studies, the calixarene macrocycle investigated has the potential to be used as a nanovehicle and improve the therapeutic efficacy of pharmacological agents against tumors

Microangiopatía trombótica en el seno de una prostatitis aguda

We present the case of a 46-year-old man who was admitted to the hospital for an episode of acute prostatitis and who, during hospitalization, presented a progressive and severe deterioration of renal function accompanied by hemolytic anemia and severe thrombocytopenia. After an etiological study, a diagnosis of thrombotic microangiopathy was reached. Treatment with eculizumab and plasmapheresis was started with a good response.Presentamos el caso de un varón de 46 años que ingresó por un episodio de prostatitis aguda y durante la hospitalización presentó un deterioro progresivo y severo de la función renal acompañado de anemia hemolítica y trombocitopenia severa. Tras estudio etiológico se llegó al diagnóstico de una microangiopatía trombótica. Se inició tratamiento con eculizumab y plasmaféresis con buena respuesta

Interleukin-6 Gene Promoter Polymorphisms and Cardiovascular Risk Factors. A family study

Objective: To determine whether the advanced paternal age associated factor for bipolar disorder in patients attended at the Regional Teaching Hospital of Cajamarca. Material and Methods: An observational, retrospective, case-control study was conducted. The study population consisted of 136 adult patients with; Which were divided into 2 groups: with or without bipolar disorder; The odds ratio and chi-square test were calculated. Results: There were no significant differences regarding the variables age, gender or origin among patients with or without bipolar disorder. The frequency of advanced paternal age in patients with bipolar disorder was 20%. The frequency of advanced paternal age in patients without bipolar disorder was 9%. Advanced paternal age is a associated factor for bipolar disorder with an odds ratio of 2.67 which was significant (p <0.05). Conclusions: The advanced paternal age associated factor for bipolar disorder in patients attended at the Regional Teaching Hospital of Cajamarca.Objetivo: Determinar si la edad paterna avanzada es factor asociado para trastorno bipolar en pacientes atendidos en el Hospital Regional Docente de Cajamarca. Material y Métodos: Se llevó a cabo un estudio de tipo observacional, retrospectivo de casos y controles. La población de estudio estuvo constituida por 136 pacientes adultos con; las cuales fueron divididas en 2 grupos: con trastorno bipolar o sin él; se calculó el odds ratio y la prueba chi cuadrado. Resultados: No se apreciaron diferencias significativas respecto a las variables edad, genero ni procedencia entre los pacientes con trastorno bipolar o sin él. La frecuencia de edad paterna avanzada en los pacientes con trastorno bipolar fue de 20%. La frecuencia de edad paterna avanzada en los pacientes sin trastorno bipolar fue de 9%. La edad paterna avanzada es factor asociado para trastorno bipolar con un odds ratio de 2.67 el cual fue significativo (p<0.05). Conclusiones: La edad paterna avanzad es factor asociado para trastorno bipolar en pacientes atendidos en el Hospital Regional Docente de Cajamarca

Isogenic GAA-KO Murine Muscle Cell Lines Mimicking Severe Pompe Mutations as Preclinical Models for the Screening of Potential Gene Therapy Strategies

Pompe disease (PD) is a rare disorder caused by mutations in the acid alpha-glucosidase (GAA) gene. Most gene therapies (GT) partially rely on the cross-correction of unmodified cells through the uptake of the GAA enzyme secreted by corrected cells. In the present study, we generated isogenic murine GAA-KO cell lines resembling severe mutations from Pompe patients. All of the generated GAA-KO cells lacked GAA activity and presented an increased autophagy and increased glycogen content by means of myotube differentiation as well as the downregulation of mannose 6-phosphate receptors (CI-MPRs), validating them as models for PD. Additionally, different chimeric murine GAA proteins (IFG, IFLG and 2G) were designed with the aim to improve their therapeutic activity. Phenotypic rescue analyses using lentiviral vectors point to IFG chimera as the best candidate in restoring GAA activity, normalising the autophagic marker p62 and surface levels of CI-MPRs. Interestingly, in vivo administration of liver-directed AAVs expressing the chimeras further confirmed the good behaviour of IFG, achieving cross-correction in heart tissue. In summary, we generated different isogenic murine muscle cell lines mimicking the severe PD phenotype, as well as validating their applicability as preclinical models in order to reduce animal experimentation.Fundacion Poco Frecuente (Almeria)Asociacion Espanola de Enfermos de Glucogenosis (AEEG)Asociacion Espanola de Enfermos de Pompe (AEEP

Neumonía Adquirida en la Comunidad por Streptococcus Pneumoniae Asociada a Tuberculosis Pulmonar en Adulto Mayor. Reporte de Caso

Community-acquired pneumonia is an infectious process of acute onset in the lung parenchyma caused by microorganisms, which affects the distal portion of the respiratory tract and sometimes involves the alveolar interstitium. This process generates an inflammatory cellular infiltrate of the alveolar space called consolidation, which alters gas exchange. Among the bacterial etiologies, the main one is S. pneumoniae. Regarding the clinical manifestations of the disease, in older adults it presents several signs and symptoms, which leads to a delay in diagnosis. The characteristic symptoms such as fever, cough and chest pain may not appear, which in some cases leads to confusion about the condition, non-specific malaise or detriment of the general condition. Its management depends on the etiology, and antibiotic therapy is indicated. We report the case of a 66-year-old male patient with a history of significant arterial hypertension diagnosed 12 years ago under continuous treatment, who came for 1 month reporting dyspnea on great exertion that evolved to minor exertion, accompanied by unquantified temperature rise and productive cough.La neumonía adquirida en la comunidad es un proceso infeccioso de instauración aguda en el parénquima pulmonar causado por microrganismos, el cual afecta la porción distal de las vías respiratorias y, en ocasiones, involucra el intersticio alveolar. Este proceso genera un infiltrado celular inflamatorio del espacio alveolar denominado consolidación, que altera el intercambio gaseoso, dentro de las etiologías bacterianas la principal es S. pneumoniae. Con relación a las manifestaciones clínicas de la enfermedad, en los adultos mayores presenta varios signos y síntomas, lo que conlleva a una demora en el diagnóstico. Los síntomas característicos como fiebre, tos y dolor torácico pueden no presentarse, lo que provoca en algunos casos a confusiones sobre el cuadro, el malestar inespecífico o el detrimento del estado general. Su manejo depende de la etiología, y se indica antibioticoterapia. Se Reporta el caso de un paciente masculino de 66 años con antecedentes de importancia, Hipertensión arterial diagnosticada hace 12 años en tratamiento continuo, acude por referir desde hace 1 mes disnea de grandes esfuerzos que evoluciona a pequeños esfuerzos, acompañada de alza térmica no cuantificada y tos productiva

Reduced IgG anti-small nuclear ribonucleoprotein autoantibody production in systemic lupus erythematosus patients with positive IgM anti-cytomegalovirus antibodies

INTRODUCTION: Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA-protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein-Barr virus in the pathogenesis has been suggested. Similar to Epstein-Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1-70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus. METHODS: Sixty-one Mexican patients with systemic lupus erythematosus were tested for CMV and Epstein-Barr virus serology (viral capsid antigen, IgG, IgM) and autoantibodies by immunoprecipitation and ELISA (IgG and IgM class, U1RNP/Sm, U1-70 k, P peptide, rheumatoid factor, dsDNA, beta2-glycoprotein I). RESULTS: IgG anti-CMV and IgM anti-CMV were positive in 95% (58/61) and 33% (20/61), respectively, and two cases were negative for both. Clinical manifestation and autoantibodies in the IgM anti-CMV+ group (n = 20) versus the IgM anti-CMV(-)IgG+ (n = 39) group were compared. Most (19/20) of the IgM anti-CMV+ cases were IgG anti-CMV+, consistent with reactivation or reinfection. IgM anti-CMV was unrelated to rheumatoid factor or IgM class autoantibodies and none was positive for IgM anti-Epstein-Barr virus-viral capsid antigen, indicating that this is not simply due to false positive results caused by rheumatoid factor or nonspecific binding by certain IgM. The IgM anti-CMV+ group has significantly lower levels of IgG anti-U1RNP/Sm and IgG anti-U1-70 k (P = 0.0004 and P = 0.0046, respectively). This finding was also confirmed by immunoprecipitation. Among the IgM anti-CMV(-) subset, anti-Su was associated with anti-U1RNP and anti-Ro (P < 0.05). High levels of IgG anti-CMV were associated with production of lupus-related autoantibodies to RNA or DNA-protein complex (P = 0.0077). CONCLUSIONS : Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs and may provide a unique insight to understand the pathogenesis

Polarimetric imaging for the detection of synthetic models of SARS-CoV-2: A proof of concept

Objective: To conduct a proof-of-concept study of the detection of two synthetic models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using polarimetric imaging. Approach: Two SARS-CoV-2 models were prepared as engineered lentiviruses pseudotyped with the G protein of the vesicular stomatitis virus, and with the characteristic Spike protein of SARS-CoV-2. Samples were prepared in two biofluids (saline solution and artificial saliva), in four concentrations, and deposited as 5-µL droplets on a supporting plate. The angles of maximal degree of linear polarization (DLP) of light diffusely scattered from dry residues were determined using Mueller polarimetry from87 samples at 405 nm and 514 nm. A polarimetric camera was used for imaging several samples under 380–420 nm illumination at angles similar to those of maximal DLP. Per-pixel image analysis included quantification and combination of polarization feature descriptors in 475 samples. Main results: The angles (from sample surface) of maximal DLP were 3° for 405 nm and 6° for 514 nm. Similar viral particles that differed only in the characteristic spike protein of the SARS-CoV-2, their corresponding negative controls, fluids, and the sample holder were discerned at 10-degree and 15-degree configurations. Significance: Polarimetric imaging in the visible spectrum may help improve fast, non-contact detection and identification of viral particles, and/or other microbes such as tuberculosis, in multiple dry fluid samples simultaneously, particularly when combined with other imaging modalities. Further analysis including realistic concentrations of real SARS-CoV-2 viral particles in relevant human fluids is required. Polarimetric imaging under visible light may contribute to a fast, cost-effective screening of SARS-CoV-2 and other pathogens when combined with other imaging modalities.12 página

Hyperspectral image processing for the identification and quantification of lentiviral particles in fluid samples

Optical spectroscopic techniques have been commonly used to detect the presence of biofilm-forming pathogens (bacteria and fungi) in the agro-food industry. Recently, near-infrared (NIR) spectroscopy revealed that it is also possible to detect the presence of viruses in animal and vegetal tissues. Here we report a platform based on visible and NIR (VNIR) hyperspectral imaging for non-contact, reagent free detection and quantification of laboratory-engineered viral particles in fluid samples (liquid droplets and dry residue) using both partial least square-discriminant analysis and artificial feed-forward neural networks. The detection was successfully achieved in preparations of phosphate buffered solution and artificial saliva, with an equivalent pixel volume of 4 nL and lowest concentration of 800 TU.mu L-1. This method constitutes an innovative approach that could be potentially used at point of care for rapid mass screening of viral infectious diseases and monitoring of the SARS-CoV- 2 pandemic.This research was funded by grants number COV20-00080 and COV20-00173 of the 2020 Emergency Call for Research Projects about the SARS-CoV-2 virus and the COVID-19 disease of the Institute of Health 'Carlos III', Spanish Ministry of Science and Innovation, and by grant number EQC2019-006240-P of the 2019 Call for Acquisition of Scientific Equipment, FEDER Program, Spanish Ministry of Science and Innovation. This work has been supported by the European Commission through the JRC HUMAINT project. ABR was supported by grant number RTI2018-094465-J funded by the Spanish National Agency of Research. The authors would like to gratefully acknowledge the assistance of the members of the EOD-CBRN Group of the Spanish National Police, whose identities cannot be disclosed, and who are represented here by JMNG. Authors thank continuous support from their institutions

IgG Anti-ghrelin Immune Complexes Are Increased in Rheumatoid Arthritis Patients Under Biologic Therapy and Are Related to Clinical and Metabolic Markers

Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with increased risk of cardiovascular disease and metabolic alterations. The mechanisms underlying these alterations remain unclear. Ghrelin is a gastrointestinal hormone with potent effects on food intake, body weight, metabolism, and immune response. Recent studies reported the presence of anti-ghrelin autoantibodies in healthy subjects and the levels and affinity of these autoantibodies were altered in anorectic and obese individuals. In this cross-sectional study we analyzed anti-ghrelin autoantibodies in RA patients and evaluated its relationship with clinical, body-composition and metabolic parameters. Clinical measurements of RA patients included the disease activity score-28 (DAS-28), inflammatory biomarkers, autoantibodies (RF and anti-CCP), body composition, glucose and lipid profile. Serum ghrelin levels were measured by enzyme-linked immunosorbent assay (ELISA). Free and total anti-ghrelin autoantibodies quantification (IgG and IgA isotypes) was performed by in-house ELISA. RA patients had lower IgG anti-ghrelin autoantibodies levels and higher immune complexes percentage (IgG+ghrelin) compared to the control group, while the IgA anti-ghrelin autoantibodies showed no significant differences. In the bivariate analysis, the percentage of IgG anti-ghrelin immune complexes positively correlated with BMI and ghrelin whereas in the multivariate regression model, the variables associated were DAS-28, body weight, visceral fat, LDL-C and TG (R2 = 0.72). The percentage of IgA anti-ghrelin immune complexes positively correlated with RF and anti-CCP and the multivariate regression model showed an association with RF and body fat percentage (R2 = 0.22). Our study shows an increased percentage of IgG anti-ghrelin immune complexes in RA patients despite ghrelin levels were similar in both groups, suggesting an increase in the affinity of these autoantibodies toward ghrelin. The associations found in the multiple regression analysis for anti-ghrelin immune complexes support the previously reported functions of these natural autoantibodies as carriers and modulators of the stability and physiological effect of the hormone. However, in RA both the disease activity and the RF appear to influence the formation of these anti-ghrelin immune complexes