The Xenorhabdus nematophila LrhA transcriptional regulator modulates production of γ-keto-N-acyl amides with inhibitory activity against mutualistic host nematode egg hatching.

Xenorhabdus nematophila is a symbiotic Gammaproteobacterium that produces diverse natural products that facilitate mutualistic and pathogenic interactions in their nematode and insect hosts, respectively. The interplay between X. nematophila secondary metabolism and symbiosis stage is tuned by various global regulators. An example of such a regulator is the LysR-type protein transcription factor LrhA, which regulates amino acid metabolism and is necessary for virulence in insects and normal nematode progeny production. Here, we utilized comparative metabolomics and molecular networking to identify small molecule factors regulated by LrhA and characterized a rare γ-ketoacid (GKA) and two new N-acyl amides, GKA-Arg (1) and GKA-Pro (2) which harbor a γ-keto acyl appendage. A lrhA null mutant produced elevated levels of compound 1 and reduced levels of compound 2 relative to wild type. N-acyl amides 1 and 2 were shown to be selective agonists for the human G-protein-coupled receptors (GPCRs) C3AR1 and CHRM2, respectively. The CHRM2 agonist 2 deleteriously affected the hatch rate and length of Steinernema nematodes. This work further highlights the utility of exploiting regulators of host-bacteria interactions for the identification of the bioactive small molecule signals that they control. IMPORTANCE: Xenorhabdus bacteria are of interest due to their symbiotic relationship with Steinernema nematodes and their ability to produce a variety of natural bioactive compounds. Despite their importance, the regulatory hierarchy connecting specific natural products and their regulators is poorly understood. In this study, comparative metabolomic profiling was utilized to identify the secondary metabolites modulated by the X. nematophila global regulator LrhA. This analysis led to the discovery of three metabolites, including an N-acyl amide that inhibited the egg hatching rate and length of Steinernema carpocapsae nematodes. These findings support the notion that X. nematophila LrhA influences the symbiosis between X. nematophila and S. carpocapsae through N-acyl amide signaling. A deeper understanding of the regulatory hierarchy of these natural products could contribute to a better comprehension of the symbiotic relationship between X. nematophila and S. carpocapsae.

Bilateral Inferior Rectus Schwannoma and Strabismus: A Case Report.

Schwannomas, also known as neurilemomas, are peripheral nerve sheath neoplasms. They can be sporadic or associated with genetic syndromes including neurofibromatosis type 2 (NF2). Schwannomas may lead to symptoms by exerting pressure on nearby structures, such as nerve and muscle fibers. In this study, we present the case of a 22-year-old female with a history of NF2 who, upon examination, presented with a visibly enlarged salmon-colored mass involving the left inferior rectus that she had since the age of 12 years. Ocular examinations revealed a small left hypertropia and exotropia in all gazes. Magnetic resonance imaging confirmed bilateral involvement of the inferior rectus muscles. She had a partial excisional biopsy of the mass involving the left inferior rectus muscle that confirmed the presence of schwannoma. This case highlights the importance of comprehensive evaluation of sensory and motor functions as well as considering orbital schwannomas in cases of strabismus, especially within the context of neurofibromatosis.

Síndrome metabólico y su relación con la microbiota intestinal / Metabolic syndrome and its relationship with gut microbiota

Introducción: el síndrome metabólico es uno de los problemas de salud pública más importantes en la actualidad, considerado como una epidemia mundial. Es producto de la interacción entre los procesos de inflamación y la resistencia a la insulina. Objetivo: actualizar los conocimientos concernientes al papel de la microbiota en el desarrollo del síndrome metabólico Método: se realizó una búsqueda bibliográfica no sistemática en las bases de datos PubMed, SciELO, Science Direct, EMBASE, LILACS y Redalyc. Los criterios de inclusión fueron publicaciones en inglés, portugués y español, en las que el título y palabras clave, incluyeran información pertinente con el objetivo planteado, con una periodicidad de 10 años, obteniendo 50 artículos de los cuales fueron seleccionados 30. Resultados: los 30 artículos presentaban correspondencia continua con el tema planteado en esta revisión, entre ellos 1 consenso de expertos, 25 revisiones narrativas y documentales, 1 investigación original, 2 libros uno de ellos actualizado y 1 estudio prospectivo. Discusión: la microbiota intestinal tiene un rol importante en la conservación de la homeostasis intestinal, proporcionando energía y nutrientes, así como protección contra la colonización de patógenos. La alteración de la composición y la actividad de la microbiota intestinal. La alteración de la composición y actividad de la microbiota intestinal se conoce como disbiosis y está implicada en la etiopatogenia de múltiples enfermedades crónicas, incrementando el riesgo cardiovascular en el contexto del síndrome metabólico. Conclusiones: entre las estrategias para la prevención y tratamiento del síndrome metabólico, sobresale la modificación de los patrones de alimentación de manera individualizada, se recomienda además una dieta rica en vegetales, fibra, granos integrales y baja en grasas. El uso de los prebióticos y probióticos ejercen un efecto beneficioso sobre la salud del hospedador, mediante la modulación de la microbiota intestinal.

Traversing the Cell Wall: The Chitinolytic Activity of Histoplasma capsulatum Extracellular Vesicles Facilitates Their Release.

Histoplasma capsulatum is the causative agent of histoplasmosis. Treating this fungal infection conventionally has significant limitations, prompting the search for alternative therapies. In this context, fungal extracellular vesicles (EVs) hold relevant potential as both therapeutic agents and targets for the treatment of fungal infections. To explore this further, we conducted a study using pharmacological inhibitors of chitinase (methylxanthines) to investigate their potential to reduce EV release and its subsequent impact on fungal virulence in an in vivo invertebrate model. Our findings revealed that a subinhibitory concentration of the methylxanthine, caffeine, effectively reduces EV release, leading to a modulation of H. capsulatum virulence. To the best of our knowledge, this is the first reported instance of a pharmacological inhibitor that reduces fungal EV release without any observed fungicidal effects.

The bitter taste receptor (TAS2R) agonist denatonium promotes a strong relaxation of rat corpus cavernosum.

Bitter taste receptors (TAS2R) are found in numerous extra-oral tissues, including smooth muscle (SM) cells in both vascular and visceral tissues. Upon activation, TAS2R stimulate the relaxation of the SM. Nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway is involved in penile erection, and type 5 phosphodiesterase (PDE5) inhibitors, a cGMP-specific hydrolase are used as first-line treatments for erectile dysfunction (ED). Nevertheless, PDE5 inhibitors are ineffective in a considerable number of patients, prompting research into alternative pharmacological targets for ED. Since TAS2R agonists regulate SM contractility, this study investigates the role of TAS2Rs in rat corpus cavernosum (CC). We performed immunohistochemistry to detect TAS2R10, isometric force recordings for TAS2R agonists denatonium and chloroquine, the slow-release H2S donor GYY 4137, the NO donor SNAP, the ß-adrenoceptor agonist isoproterenol and electrical field stimulation (EFS), as well as measurement of endogenous hydrogen sulfide (H2S) production. The immunofluorescence staining indicated that TAS2R10 was broadly expressed in the CC SM and to some extent in the nerve fibers. Denatonium, chloroquine, SNAP, and isoproterenol cause potent dose-dependent SM relaxations. H2S production was decreased by NO and H2S synthase inhibitors, while it was enhanced by denatonium. In addition, denatonium increased the relaxations induced by GYY 4137 and SNAP but failed to modify EFS- and isoproterenol-induced responses. These results suggest neuronal and SM TAS2R10 expression in the rat CC, where denatonium induces a strong SM relaxation per se and promotes the H2S- and NO-mediated inhibitory gaseous neurotransmission. Thus, TAS2R10 might represent a valuable therapeutic target in ED.

Characteristics and clinical outcome in 312 patients with moderate to severe pneumonia due to SARS-COV-2 and hyperinflammation treated with anakinra and corticosteroids: A retrospective cohort study.

OBJECTIVE: To assess the clinical outcome (death and/or Intensive Care Unit (ICU) admission) based on the time from hospital admission to the administration of anakinra and the possible usefulness of a "simplified" SCOPE score to stratify the risk of worse prognosis in our cohort of patients with moderate/severe SARS-CoV-2 pneumonia, both vaccinated and unvaccinated, that received anakinra and corticosteroids. In addition, the clinical, analytical, and imaging characteristics of patients at admission are described. METHODS: Retrospective cohort study of 312 patients admitted to Hospital Clínico San Cecilio in Granada for moderate/severe pneumonia caused by SARS-CoV-2 that received anakinra and corticosteroids between March 2020 and January 2022. Clinical and analytical data were collected as well as the patient outcome at 30 and 60 days after admission. Three treatment groups were established according to the time from hospital admission to administration of anakinra: early (1st-2nd day), intermediate (3rd-5th day), and late (after the 5th day). RESULTS: The median age was 67.4 years (IQR 22-97 years) and 204 (65.4%) were male. The most common comorbidity was hypertension (58%). The median time from the start of symptoms to anakinra administration was 6 days (IQR 5-10) and the SaFi (SaO2/FiO2) was 228 (IQR 71-471). The cure rate was higher in the early-onset anakinra group versus the late-onset group (73% vs 56.6%). The latter had a higher percentage of deaths (27.4%) and a greater number of patients remained hospitalized for a month (16%). On admission, the patients had elevated C-reactive protein (CRP), ferritin, and D-dimer values and decreased total lymphocytes. Analytical improvement was observed at both 72 hours and one month after treatment. 42 (13.5%) required ICU admission, and 23 (7.3%) orotracheal intubation. At 60 days, 221 (70.8%) were discharged, 87 (27.8%) had died and 4 (1.4%) remained hospitalized. The mean dose of anakinra was 1000 mg (100-2600 mg) with differences found between the dose administered and the clinical outcome. There were no differences in the primary outcome based on vaccination. A simplified SCOPE score at the start of anakinra administration was lower in patients with better clinical evolution. CONCLUSIONS: Early treatment with anakinra and corticosteroids was associated with a better outcome regardless of vaccination status. A simplified SCOPE was found to be a good prognostic tool.

Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation.

Neurulation is a crucial process in the formation of the central nervous system (CNS), which begins with the folding and fusion of the neural plate, leading to the generation of the neural tube and subsequent development of the brain and spinal cord. Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD+; regulating processes such as cell migration and synaptic transmission. Changes in the state of phosphorylation and/or the intracellular redox potential activate the opening of HCs in different cell types. Cxs such as Cx43 and Cx32 have been associated with proliferation and migration at different stages of CNS development. Here, using molecular and cellular biology techniques (permeability), we demonstrate the expression and functionality of HCs-Cxs, including Cx46 and Cx32, which are associated with the release of ATP during the neurulation process in Xenopus laevis. Furthermore, applications of FGF2 and/or changes in intracellular redox potentials (DTT), well known HCs-Cxs modulators, transiently regulated the ATP release in our model. Importantly, the blockade of HCs-Cxs by carbenoxolone (CBX) and enoxolone (ENX) reduced ATP release with a concomitant formation of NTDs. We propose two possible and highly conserved binding sites (N and E) in Cx46 that may mediate the pharmacological effect of CBX and ENX on the formation of NTDs. In summary, our results highlight the importance of ATP release mediated by HCs-Cxs during neurulation.

Ultralarge Flakes of Ti3C2Tx MXene via Soft Delamination.

Two-dimensional (2D) titanium carbide MXene (Ti3C2Tx) has attracted significant attention due to its combination of properties and great promise for various applications. The size of the 2D sheets is a critical parameter affecting multiple properties of assembled films, fibers and 3D structures. The increased lateral size of MXene flakes can benefit not only their assemblies by improving the interflake contacts and alignment but also fundamental studies at the individual flake level, allowing for facile patterning and investigation of intrinsic physical properties of MXenes. Increasing the average size of the parent MAX phase is one of the strategies previously used to increase the flake size of the resultant MXene. Here, we show that the protocol used for the next step of the synthesis procedure, delamination of multilayer MXene into individual nanosheets, significantly affects the lateral size of the resultant flakes. We developed a soft delamination approach, which prevents fracture of flakes and preserves their size. Combining this approach with the large-grain Ti3AlC2 MAX phase precursor, we achieved individual flakes of up to 40 µm in lateral size. These flakes can be used for patterning multiple contacts and fabrication of field-effect transistors for multiprobe electrical characterization and other measurements. These findings indicate the importance of controlling the delamination process in order to achieve large MXene flakes and improve properties of MXene-based materials and devices.

In vitro inhibition of phosphodiesterase type 4 enhances rat corpus cavernosum nerve-mediated relaxation induced by gasotransmitters.

AIMS: Nitric oxide (NO) and hydrogen sulfide (H2S) are involved in nerve-mediated corpus cavernosum (CC) relaxation. Expression of phosphodiesterase type 5 (PDE5) and type 4 (PDE4), cyclic guanosine monophosphate (cGMP)- and cyclic adenosine monophosphate (cAMP)-specific, respectively, has been described and PDE5- and PDE4-inhibitors induce cavernous smooth muscle relaxation. Whereas the NO/cGMP signaling pathway is well established in penile erection, the cAMP-mediated mechanism is not fully elucidated. The aim of this study is to investigate the localization and the functional significance of PDE4 in rat CC tone regulation. MAIN METHODS: We performed immunohistochemistry for the detection of the PDE4A isoenzyme. Isometric tension recordings for roflumilast and tadalafil, PDE4 and PDE5 inhibitors, respectively, electrical field stimulation (EFS) and ß-adrenoceptor agonist isoproterenol and endogenous H2S production measurement. KEY FINDINGS: A marked PDE4A expression was detected mainly localized in the nerve cells of the cavernous smooth muscle. Furthermore, roflumilast and tadalafil exhibited strong corpus cavernous relaxations. Endogenous H2S production was decreased by NO and H2S synthase inhibitors and increased by roflumilast. Isoproterenol- and EFS-induced relaxations were increased by roflumilast. SIGNIFICANCE: These results indicate that PDE4A is mainly expressed within the nerves cells of the rat CC, where roflumilast induces a potent corpus cavernous relaxation per se and potentiates the response induced by ß-adrenoceptor activation. The fact that roflumilast enhances H2S production, as well as EFS-elicited responses suggests that PDE4 inhibitors modulate, in a positive feedback fashion, nerve-mediated relaxation induced by gasotransmitters, thus indicating a key role for neuronal PDE4 in penile erection.

Distinct innate immune responses between sublethal and lethal models of disseminated candidiasis in newborn BALB/c mice.

Invasive candidiasis is associated with a high incidence and mortality rates in infants, especially in preterm newborns. The immunopathogenesis of the mycosis during the neonatal period is poorly understood. Although several in vivo models exist to study invasive candidiasis, the majority of studies employ distinct routes of infection and use 2 to 6 day-old mice that could be less comparable in studying candidiasis in preterm infants. In this study, by using 0-days-old mice we developed a new neonatal murine model of intravenous Candida albicans infection. Using different inoculums of Candida albicans we evaluated survival, dissemination of the fungus, frequency of CD45+ cells, and cytokine production in the liver, brain, and kidneys of newborn and adult BALB/c mice. Unexpectedly, the newborn mice infected with a low inoculum (1×105 cfu per mouse) of Candida albicans survive to the infection. Compared to adult mice, the liver and brain of newborn animals had the greatest fungal burden, fungal invasion and leukocyte infiltrate. A moderate production of TNFα, IL-1ß, IL-6 and IFNγ was detected in tissues of newborn mice infected with a non-lethal inoculum of Candida albicans. In contrast, overproduction of TNFα, IL-1ß, IL-6 and IL-10 was determined when injecting with a lethal inoculum. In agreement, flow cytometry of brain and liver showed an inoculum-dependent CD45+ leukocyte infiltration in newborn mice infected with Candida albicans. Overall, our data shows that Candida albicans infection in newborn mice affects mainly the brain and liver and a 2-fold increase of the inoculum rapidly becomes lethal probably due to massive fungal invasion and exacerbated CD45+ leukocyte infiltrate and cytokine production. This study is the first analysis of innate immune responses in different tissues during early neonatal disseminated candidiasis.

Rac inhibition as a novel therapeutic strategy for EGFR/HER2 targeted therapy resistant breast cancer.

BACKGROUND: Even though targeted therapies are available for cancers expressing oncogenic epidermal growth receptor (EGFR) and (or) human EGFR2 (HER2), acquired or intrinsic resistance often confounds therapy success. Common mechanisms of therapy resistance involve activating receptor point mutations and (or) upregulation of signaling downstream of EGFR/HER2 to Akt and (or) mitogen activated protein kinase (MAPK) pathways. However, additional pathways of resistance may exist thus, confounding successful therapy. METHODS: To determine novel mechanisms of EGFR/HER2 therapy resistance in breast cancer, gefitinib or lapatinib resistant variants were created from SKBR3 breast cancer cells. Syngenic therapy sensitive and resistant SKBR3 variants were characterized for mechanisms of resistance by mammosphere assays, viability assays, and western blotting for total and phospho proteins. RESULTS: Gefitinib and lapatinib treatments reduced mammosphere formation in the sensitive cells, but not in the therapy resistant variants, indicating enhanced mesenchymal and cancer stem cell-like characteristics in therapy resistant cells. The therapy resistant variants did not show significant changes in known therapy resistant pathways of AKT and MAPK activities downstream of EGFR/HER2. However, these cells exhibited elevated expression and activation of the small GTPase Rac, which is a pivotal intermediate of GFR signaling in EMT and metastasis. Therefore, the potential of the Rac inhibitors EHop-016 and MBQ-167 to overcome therapy resistance was tested, and found to inhibit viability and induce apoptosis of therapy resistant cells. CONCLUSIONS: Rac inhibition may represent a viable strategy for treatment of EGFR/HER2 targeted therapy resistant breast cancer.

Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammation. A retrospective cohort study.

INTRODUCTION: Little evidence appears to exist for the use of anakinra, a recombinant interleukin-1 receptor antagonist, after non-response to treatment with corticosteroids alone or combined with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammatory state. PATIENTS AND METHODS: A retrospective observational cohort study was carried out involving 143 patients with severe COVID-19 pneumonia and moderate hyperinflammation. They received standard therapy along with pulses of methylprednisolone (group 1) or methylprednisolone plus tocilizumab (group 2), with the possibility of receiving anakinra (group 3) according to protocol. The aim of this study was to assess the role of anakinra in the clinical course (death, admission to the intensive care ward) during the first 60 days after the first corticosteroid pulse. Clinical, laboratory, and imaging characteristics as well as infectious complications were also analyzed. RESULTS: 74 patients (51.7%) in group 1, 59 (41.3%) patients in group 2, and 10 patients (7%) in group 3 were included. 8 patients (10.8%) in group 1 died, 6 (10.2%) in group 2, and 0 (0%) in group 3. After adjustment for age and clinical severity indices, treatment with anakinra was associated with a reduced risk of mortality (adjusted hazard ratio 0.518, 95% CI 0.265-0.910; p = 0.0437). Patients in group 3 had a lower mean CD4 count after 3 days of treatment. No patients in this group presented infectious complications. CONCLUSIONS: In patients with moderate hyperinflammatory state associated with severe COVID-19 pneumonia, treatment with anakinra after non-response to corticosteroids or corticosteroids plus tocilizumab therapy may be an option for the management of these patients and may improve their prognosis.

Analogues of cannabinoids as multitarget drugs in the treatment of Alzheimer's disease.

Given that neuronal degeneration in Alzheimer's disease (AD) is caused by the combination of multiple neurotoxic insults, current directions in the research of novel therapies to treat this disease attempts to design multitarget strategies that could be more effective than the simply use of acetylcholinesterase inhibitors; currently, the most used therapy for AD. One option, explored recently, is the synthesis of new analogues of cannabinoids that could competitively inhibit the acetylcholinesterase (AChE) enzyme and showing the classic neuroprotective profile of cannabinoid compounds. In this work, molecular docking has been used to design some cannabinoid analogues with such multitarget properties, based on the similarities of donepezil and Δ9-tetrahydrocannabinol. The analogues synthesized, compounds 1 and 2, demonstrated to have two interesting characteristics in different in vitro assays: competitive inhibition of AChE and competitive antagonism at the CB1/CB2 receptors. They are highly lipophilic, highlighting that they could easily reach the CNS, and apparently presented a low toxicity. These results open the door to the synthesis of new compounds for a more effective treatment of AD.

Tratamiento y evolución del síndrome de tormenta de citoquinas asociados a infección por SARS-CoV-2 en pacientes octogenarios / Evolution and treatment of storm cytoquine syndrome associated to SARS-CoV-2 infection among octogenarians

INTRODUCCIÓN: El síndrome de tormenta de citoquinas (STC) es una complicación muy grave de los pacientes con infección por SARS-CoV-2. El tratamiento y la evolución no están bien definidos. Nuestro objetivo es describir sus características clínicas, los tratamientos empleados y su evolución clínica. PACIENTES Y MÉTODO: Estudio retrospectivo observacional de pacientes consecutivos ingresados en el período comprendido entre el 23 de marzo y el 12 de abril de 2020 con infección por SARS-CoV-2 confirmada, con neumonía por estudio radiológico o tomografía de tórax, que cumplían criterios de STC y que recibieron tratamiento. Clasificamos a los pacientes en los que recibieron solo pulsos de glucocorticoides (GC), o pulsos de GC y tocilizumab. Determinamos niveles séricos de ferritina, PCR y dímeros-D. La variable final fue la supervivencia. RESULTADOS: Veintiún pacientes con una edad de 83 años (80-88 años). La ferritina media fue de 1.056 microg/L (317-3.553), la PCR de 115,8mg/dL (22-306) y los dímeros-D de 2,9mg/L (0,45-17,5). Todos los pacientes recibieron pulsos de GC y en 2 casos simultáneamente tocilizumab. El tiempo medio de seguimiento fue de 13,7 días (8-21). La mortalidad global fue del 38,1% (8/21pacientes). Los 2 pacientes que recibieron tocilizumab fallecieron. Los fallecidos presentaron niveles significativamente más elevados de ferritina (1.254 vs. 925microg/L; p = 0,045) y PCR (197,6 vs. 76mg/dL; p = 0,007). Al final del seguimiento se observó una disminución en los parámetros bioquímicos con ferritina de 727microg/L, PCR de 27mg/dl y dímeros-D de 1,18mg/L. En 13/21 pacientes (61,9%) el STC se controló sin necesidad de añadir otros tratamientos. CONCLUSIONES: La mortalidad del STC por SARS-CoV-2 es alta a pesar del tratamiento. Una mayor respuesta inflamatoria se asoció con una mayor mortalidad. Aunque parece que el uso precoz de pulsos de GC puede controlarlo, pudiendo disminuir la necesidad de uso de otros tratamientos, con el diseño del estudio y sus limitaciones, no se puede establecer esta conclusión

INTRODUCTION: Cytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defiREVned. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution. PATIENTS AND METHOD: Retrospective observational study of consecutive patients admitted in the period between March 23 and April 12, 2020 with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whith STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival. RESULTS: 21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3,553), CRP 115.8mg/dL (22-306) and D-dimers 2.9m/L (0.45-17.5). All patients received GC pulses and in 2 cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1,254 vs. 925microg/L; P=.045) and CRP (197.6 vs. 76mg / dL; P=.007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727microg/L, CRP of 27mg/dl and D-dimers of 1.18mg/L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments. CONCLUSIONS: STC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished

Facile Production of Large-Area Cell Arrays Using Surface-Assembled Microdroplets.

Techniques that enable the spatial arrangement of living cells into defined patterns are broadly applicable to tissue engineering, drug screening, and cell-cell investigations. Achieving large-scale patterning with single-cell resolution while minimizing cell stress/damage is, however, technically challenging using existing methods. Here, a facile and highly scalable technique for the rational design of reconfigurable arrays of cells is reported. Specifically, microdroplets of cell suspensions are assembled using stretchable surface-chemical patterns which, following incubation, yield ordered arrays of cells. The microdroplets are generated using a microfluidic-based aerosol spray nozzle that enables control of the volume/size of the droplets delivered to the surface. Assembly of the cell-loaded microdroplets is achieved via mechanically induced coalescence using substrates with engineered surface-wettability patterns based on extracellular matrices. Robust cell proliferation inside the patterned areas is demonstrated using standard culture techniques. By combining the scalability of aerosol-based delivery and microdroplet surface assembly with user-defined chemical patterns of controlled functionality, the technique reported here provides an innovative methodology for the scalable generation of large-area cell arrays with flexible geometries and tunable resolution.

[Evolution and treatment of storm cytoquine syndrome associated to SARS-CoV-2 infection among octogenarians]. / Tratamiento y evolución del síndrome de tormenta de citoquinas asociados a infección por SARS-CoV-2 en pacientes octogenarios.

INTRODUCTION: Cytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defined. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution. PATIENTS AND METHOD: Retrospective observational study of consecutive patients admitted in the period between March 23 and April 12, 2020 with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whith STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival. RESULTS: 21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3,553), CRP 115.8mg/dL (22-306) and D-dimers 2.9m/L (0.45-17.5). All patients received GC pulses and in 2 cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1,254 vs. 925microg/L; P=.045) and CRP (197.6 vs. 76mg / dL; P=.007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727microg/L, CRP of 27mg/dl and D-dimers of 1.18mg/L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments. CONCLUSIONS: STC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished.

Beneficios de la actividad física para niños y adolescentes en el contexto escolar / Physical activity benefits for children and adolescents in the school

Introducción: La actividad física que se desarrolla en las clases de educación física son un espacio ideal para promover buenas prácticas que conduzcan a mejorar la salud física y emocional de niños y adolescentes, entre otros beneficios. El estudio del rol de la escuela, los profesores, su interacción con los niños y adolescentes, entre otros actores como padres, familias y medio social, es fundamental para optimizar el proceso docente educativo. Por ello, se plantea como objetivo analizar los beneficios de la actividad física sobre la salud de niños y adolescentes, y especialmente los retos que esto implica para la escuela y los profesores. Métodos: Se desarrolló una investigación bibliográfica, con la revisión de obras recientes sobre la temática, con el fin de determinar aspectos clave en la temática abordada. Se determinaron aspectos clave en relación a los beneficios que representa la actividad física para los niños y adolescentes en el ámbito escolar; así como las premisas y funciones de la asignatura de educación física, los profesores y la escuela. Conclusiones: La actividad física constituye un eje fundamental para el desarrollo de los niños y adolescentes tanto en la escuela como en su vida social, por lo que deberá considerarse en investigaciones futuras, especialmente dirigido a evaluar el impacto de este tipo de actividades en el rendimiento escolar, las relaciones sociales y otros aspectos que se consideren de interés(AU)

Introduction: The physical activity that takes place in physical education classes is an ideal space to promote good practices that lead to improve the physical and emotional health of children and adolescents, among other benefits. The study of the role of the school, teachers, their interaction with children and adolescents, among other actors such as parents, families and social environment, is essential to optimize the educational teaching process. Therefore, it is intended as an objective to analyze the benefits of physical activity on the health of children and adolescents, and especially the challenges that this implies for school and teachers. Methods: A bibliographic investigation was developed, with the review of recent works on the subject, in order to determine key aspects in the subject addressed. Key aspects were determined in relation to the benefits that physical activity represents for children and adolescents in the school environment; as well as the premises and functions of the physical education subject, the teachers and the school. Conclusions: Physical activity constitutes a fundamental axis for the development of children and adolescents both in school and in their social life, so it should be considered in future research, especially aimed at assessing the impact of these types of activities on performance. school, social relations and other aspects that are considered of interest(AU)

Extremely low frequency non-uniform magnetic fields induce changes in water relations, photosynthesis and tomato plant growth.

Purpose: To elucidate the effects during the vegetative growth of pre-sowing magnetic treatments on water relations, photosynthesis and plant growth in tomato (Vyta) plants under greenhouse conditions.Materials and methods: Tomato seeds were exposed to full-wave rectified sinusoidal non-uniform magnetic fields (MFs) induced by an electromagnet at 120 mT (rms) for 10 min and at 80 mT (rms) for 5 min. Non-treated seeds were used as controls. Plants were grown in polystyrene trays and water relations, photosynthesis and plant growth were measured.Results: Plants from magnetically treated seeds maintained better leaf water status in terms of increases in leaf water potential, leaf osmotic potential, leaf turgor potential and relative water content, and decreases in stomatal conductance and transpiration rate. Net photosynthesis rate, chlorophyll a, chlorophyll b, carotenoids and total chlorophyll contents increase in plants from magnetically exposed seeds compared to controls. The MF treatments lead to a notable increase in root length, plant height, root and shoot dry mass, leaf area per plant, and root and shoot relative growth rates.Conclusions: Application of full-wave rectified sinusoidal non-uniform MF as a pre-sowing treatment has the potential to improve tomato plant vegetative growth through the enhancement of water relations and photosynthesis.

Highly Selective Gas Sensors Based on Graphene Nanoribbons Grown by Chemical Vapor Deposition.

Despite the recent advances in bottom-up synthesis of different kinds of atomically precise graphene nanoribbons (GNRs) with very diverse physical properties, the translation of these GNRs into electronic devices remains challenging. Among other factors, the electronic characterization of GNRs is hampered by their complex synthesis that often requires custom-made organic precursors and the need for their transfer to dielectric substrates compatible with the conventional device fabrication procedures. In this paper, we demonstrate that uniform electrically conductive GNR films can be grown on arbitrary high-temperature-resistant substrates, such as metals, Si/SiO2, or silica glasses, by a simple chemical vapor deposition (CVD) approach based on thermal decomposition of commercially available perylenetetracarboxylic dianhydride molecules. The results of spectroscopic and microscopic characterization of the CVD-grown films were consistent with the formation of oxygen-terminated N = 5 armchair GNRs. The CVD-grown nanoribbon films exhibited an ambipolar electric field effect and low on-off ratios, which were in agreement with the predicted metallic properties of N = 5 armchair GNRs, and remarkable gas sensing properties to a variety of volatile organic compounds (VOCs). We fabricated a GNR-based electronic nose system that could reliably recognize VOCs from different chemical classes including alcohols (methanol, ethanol, and isopropanol) and amines (n-butylamine, diethylamine, and triethylamine). The simplicity of the described CVD approach and its compatibility with the conventional device fabrication procedures, as well as the demonstrated sensitivity of the GNR devices to a variety of VOCs, warrant further investigation of CVD-grown nanoribbons for sensing applications.

Diverticulosis diagnosticada por colon por enema en pacientes adultos / Frequency of diagnosed diverticulosis byenema colon in adult patients

Introducción. Los divertículos del colon son herniaciones de la mucosa que se proyectan a través de aberturas creadas por los vasos rectos al penetrar en la pared. La diverticulosis colónica constituye una afección común en los países occidentales, comprometiendo entre el 5 y 10% de la población mayor de 45 años, y al 80% de los mayores de 85 años aproximadamente. Objetivo. Determinar la frecuencia de divertículos diagnosticados por colon por enema en pacientes adultos que acudieron al Servicio de Radiología del Hospital Central del IPS entre julio a diciembre del 2014. Metodología. Se realizó un estudio observacional descriptivo, retrospectivo, de corte transversal en el que se evaluaron 105 pacientes entre 20 a 88 años de edad, el 82,86% era del sexo femenino. Resultados. Se observó diverticulosis en el 22,86% de los casos, de los cuales el 83,33% correspondió al sexo femenino, la franja etaria más afectada fue la de 64 a 80 años. Las localizaciones más frecuentes fueron el colon sigmoides y descendente en el 58,33% de los casos, el compromiso de todo el marco colónico fue el de menor porcentaje con 8,33%. Conclusiones. Es posible reafirmar que el colon por enema con bario es el método ideal para la demostración de la diverticulosis y la extensión del compromiso en el marco colónico a pesar del advenimiento de nuevas técnicas.

Introduction. The diverticula of the colon are hernias of the mucosa that project through openings created by the straight vessels when penetrating in the wall. Colonic diverticulosis is a common condition in Western countries, compromising between 5-10% of the population over 45 years and approximately 80% of those over 85 years. Objective. to identify the frequency of diverticula diagnosed by colon by enema in adult patients who attended the Radiology Service of the Central Hospital of the IPS from July to December 2014. Methodology. An observational, retrospective, descriptive study was carried out, that included 105 patients between 20 and 88 years old, 82.86% was female. Results. Diverticulosis was observed in 22.86%, female was 83.33%, the most affected age group was 64 to 80 years. The most frequent locations were the sigmoid and descending colon with 58.33% and the commitment of the entire colonic frame was the lowest percentage with 8.33%. Conclusions. It is possible to reaffirm that the colon by barium enema is the ideal method for the demonstration of diverticulosis and the extension of the compromise in the colonic framework despite the advent of new techniques.