IL-22 Is Deleterious along with IL-17 in Allergic Asthma but Is Not Detrimental in the Comorbidity Asthma and Acute Pneumonia.

There is evidence that IL-22 and IL-17 participate in the pathogenesis of allergic asthma. To investigate the role of IL-22, we used IL-22 deficient mice (IL-22 KO) sensitized and challenged with ovalbumin (OVA) and compared with wild type (WT) animals exposed to OVA. IL-22 KO animals exposed to OVA showed a decreased number and frequency of eosinophils, IL-5 and IL-13 in the airways, reduced mucus production and pulmonary inflammation. In addition, IL-22 KO animals exhibited a decreased percentage and number of lung CD11c+CD11b+ cells and increased apoptosis of eosinophils. Th17 cell transfer generated from IL-22 KO to animals previously sensitized and challenged with OVA caused a reduction in eosinophil frequency and number in the airways compared to animals transferred with Th17 cells generated from WT mice. Therefore, IL-22 is deleterious with concomitant secretion of IL-17. Our findings show a pro-inflammatory role for IL-22, confirmed in a model of allergen-free and allergen-specific immunotherapy. Moreover, during the comorbidity asthma and pneumonia that induces neutrophil inflammation, IL-22 was not detrimental. Our results show that targeting IL-22 would negatively affect the survival of eosinophils, reduce the expansion or migration of CD11c+CD11b+ cells, and negatively regulate allergic asthma.

Effect of a Single Platinum Atom within a Small Metal Oxide Cluster: Reaction of DMMP with Size-Selected Pt1Zr2O7 Supported on HOPG.

Chemical warfare agents (CWAs) are a persistent threat facing civilians and military personnel across the modern geopolitical landscape. The development of the next generation of protective and sensing materials stands to benefit from an improved fundamental understanding of the interaction of CWA molecules with the active components of such candidate materials. The use of model systems in well-controlled environments offers a route to glean such information and has been applied here to investigate the fundamental interaction of a nerve agent simulant molecule, dimethyl methylphosphonate (DMMP), with a small cluster model of a single atom catalyst (SAC) active site. The cluster models, Pt1Zr2O7, were prepared by depositing mass-selected cluster anions synthesized in the gas phase onto a 100 K highly oriented pyrolytic graphite (HOPG) substrate surface prepared in ultra-high vacuum (UHV) at sub-monolayer coverage. Upon deposition, the cluster anions lost their charge to the electrically conductive surface to yield free-standing neutral clusters. The HOPG-supported clusters were characterized by X-ray photoelectron spectroscopy (XPS) to determine the oxidation states and chemical environment of the metal atoms present within the clusters. The reactivity of the clusters with DMMP was investigated via temperature-programmed desorption/reaction (TPD/R) and XPS experiments in which the clusters were exposed to DMMP and incrementally heated to higher temperatures. In contrast to two other HOPG-supported clusters, (ZrO2)3 and Pt1Ti2O7, recently investigated in our laboratory, Pt1Zr2O7 decomposed DMMP to primarily evolve a methane species, which was completely absent for the other clusters.

Cell death induced by NLRP3-palmitate axis impairs pulmonary damage tolerance and aggravates immunopathology during obesity-tuberculosis comorbidity.

A low-grade and persistent inflammation, which is the hallmark of obesity, requires the participation of NLRP3 and cell death. During Mycobacterium tuberculosis infection, NLRP3 signaling is important for bacterial killing by macrophages in vitro but was shown to be dispensable for host protection in vivo. We hypothesized that during obesity-tuberculosis (TB) comorbidity, NLRP3 signaling might play a detrimental role by inducing excessive inflammation. We employed a model of high-fat-diet-induced obesity, followed by M. tuberculosis infection in C57BL/6 mice. Obese mice presented increased susceptibility to infection and pulmonary immunopathology compared to lean mice. Using treatment with NLRP3 antagonist and Nlrp3-/- mice, we showed that NLRP3 signaling promoted cell death, with no effect in bacterial loads. The levels of palmitate were higher in the lungs of obese infected mice compared to lean counterparts, and we observed that this lipid increased M. tuberculosis-induced macrophage death in vitro, which was dependent on NLRP3 and caspase-1. At the chronic phase, although lungs of obese Nlrp3-/- mice showed an indication of granuloma formation compared to obese wild-type mice, there was no difference in the bacterial load. Our findings indicate that NLRP3 may be a potential target for host-directed therapy to reduce initial and severe inflammation-mediated disease and to treat comorbidity-associated TB. © 2022 The Pathological Society of Great Britain and Ireland.

Ultrasmall Cluster Model for Investigating Single Atom Catalysis: Dehydrogenation of 1-Propanamine by Size-Selected Pt1Zr2O7 Clusters Supported on HOPG.

The selective dehydrogenation of hydrocarbons and their functionalized derivatives is a promising pathway in the realization of endothermic fuel systems for powering important technologies such as hypersonic aircraft. The recent surge in interest in single atom catalysts (SACs) over the past decade offers the opportunity to achieve the ultimate levels of selectivity through the subnanoscale design tailoring of novel catalysts. Experimental techniques capable of investigating the fundamental nature of the active sites of novel SACs in well-controlled model studies offer the chance to reveal promising insights. We report here an approach to accomplish this through the soft landing of mass-selected, ultrasmall metal oxide cluster ions, in which a single noble metal atom bound to a metal oxide moiety serves as a model SAC active site. This method allows the preparation of model catalysts in which monodispersed neutral SAC model active sites are decorated across an inert electrically conductive support at submonolayer surface coverage, in this case, Pt1Zr2O7 clusters supported on highly oriented pyrolytic graphite (HOPG). The results contained herein show the characterization of the Pt1Zr2O7/HOPG model catalyst by X-ray photoelectron spectroscopy (XPS), along with an investigation of its reactivity toward the functionalized hydrocarbon molecule, 1-propanamine. Through temperature-programmed desorption/reaction (TPD/R) experiments it was shown that Pt1Zr2O7/HOPG decomposes 1-propanamine exclusively into propionitrile and H2, which desorb at 425 and 550 K, respectively. Conversely, clusters without the single platinum atom, that is, Zr2O7/HOPG, exhibited no reactivity toward 1-propanamine. Hence, the single platinum atom in Pt1Zr2O7/HOPG was found to play a critical role in the observed reactivity.

Obesity-Induced Dysbiosis Exacerbates IFN-γ Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection.

The microbiota of the gut-lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4+IFN-γ+IL-17- cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut-lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.

Distrofia Retiniana Familiar. Reporte de dos casos / Retinal Dystrophy Family. Report of two cases

La distrofia de conos es un grupo de enfermedades retinianas hereditarias en forma monogenética que siguen los patrones de herencia mendeliana, se caracterizan por baja de agudeza visual por afectación macular, con poca o ninguna repercución en retina periférica y deben diferenciarse de otras patologías como las degenerativas o las tóxicas. Es muy poco frecuente encontrar esta afectación en la consulta, sobre todo en dos miembros de una familia de edades 11 y 13 años de edad respectivamente, que se presentan con baja de agudeza visual con largo tiempo de evolución, sin antecedentes personales ni patológicos de importancia, es por eso que vemos por conveniente la presentación de estos casos clínicos. Se realizó una revisión oftalmológica completa con los exámenes disponibles en Cochabamba entre los cuales no se incluyo Electroretinograma. De acuerdo a las características del cuadro clínico baja de visión, heme-ralopía y fotofobia, y los exámenes realizados, retinografía, campo visual, test de color de FM 100, los cuales se encontraron alterados y, se llega presunción diagnóstica de una presencia de distrofia de conos dominante,con mal pronóstico visual, al no existir actualmente un tratamiento efectivo para evitar la progresión de la enfermedad, y en éstos casos se recomienda ayudas visuales con anteojos y lupas.

The cone dystrophy is a group of hereditary retinal diseases in a single gene that follow Mendelian inheritance patterns are characterized by low visual acuity macula, with little or no repercussion in the peripheral retina and should be distinguished from other pathologies such as degenerative or toxic. It is very rare to find this involvement in the consultation, especially two family members ages 11 and 13 years respectively, presented with low visual acuity with long evolution, no personal or important pathological , that is why we see presenting appropriate clinical cases. We performed a complete ophthalmologic examination with in Cochabamba, including Elec-troretinogram was not included. According to the characteristics of clinical low vision, night blindness and photophobia, and previous tests, fundus, visual field, color test FM 100, which were found altered and will reach a presumptive diagnosis of Duchenne presence of dominant cones, with poor visual prognosis, as there currently an effective treatment to prevent disease progression, and in these cases it is recommended visual aids and magnifying glasses.

Cierre de ductus arterioso persistente en neonatos pretérmino. Uso de diclofenaco sódico endovenoso, Hospital de San José, Bogotá DC / Closure of persistent arterial duct in preterm newborns. Use of iv diclofenac sodium - Hospital de San José Bogotá DC

El ductus arterioso persistente (DAP) aumenta el riesgo de hemorragia intraventricular, enterocolitis necrosante, displasia broncopulmonar y muerte. La indometacina se ha considerado el medicamento de elección para su cierre farmacológico, pero la imposibilidad de importarla al país motivó el uso de diclofenaco sódico como alternativa. Objetivo: uso de diclofenaco endovenoso para el cierre del DAP en neonatos pretérmino en el Hospital de San de José de Bogotá, de febrero de 2007 a junio de 2010. Diseño y metodología: estudio descriptivo retrospectivo de 38 recién nacidos pretérmino de 0 a 20 días de edad posnatal con diagnóstico de DAP, repercusión hemodinámica y/o diámetro mayor o igual a 2 mm y que recibieron diclofenaco para el cierre farmacológico. Resultados: con un solo ciclo del medicamento hubo cierre en el 81,5%. El 65,8% requirieron menos de siete días de soporte ventilatorio. Las principales complicaciones fueron renales y neurológicas, con escasas reacciones adversas. Conclusiones: el diclofenaco mostró un buen porcentaje de cierre de DAP con bajos efectos adversos, por lo cual podría considerarse como alternativa para el manejo de esta patología cuando la terapia estándar no está disponible, pero consideramos necesarios nuevos estudios comparativos para obtener conclusiones relevantes.

Persistent arterial duct (PAD) increases the risk of intraventricular hemorrhage, necrotizing enteropathy, bronchial/pulmonary dysplasia and death. Indomethacin is considered the preferred drug for pharmacological closure of PAD. Diclofenac sodium is used as an alternative due to import-related restrictions for indomethacin in our country. Objective: use of IV diclofenac for PAD closure in preterm newborns at Hospital de San de José, Bogotá, from February 2007 to June 2010. Design and Methodology: this is a descriptive retrospective study conducted in 38 preterm newborns 0 to 20 days after birth who have been diagnosed with PAD, hemodynamic repercussion, and/or major diameter greater than 2 mm, who received diclofenac for pharmacologic closure. Results: closure was achieved with only one cycle in 81.5%. 65.8% required less than seven days of ventilatory support. Major complications were renal and neurological, with few adverse reactions. Conclusions: diclofenac showed a good rate of PAD closure with few adverse effects, thus it can be considered an alternative to handle this condition when standard therapy is not available. Nonetheless, we consider new comparative studies are necessary in order to obtain relevant conclusions...