The long-term survival of Acinetobacter baumannii ATCC 19606(T) under nutrient-deprived conditions does not require the entry into the viable but non-culturable state.

Acinetobacter baumannii possesses a tremendous potential to thrive under hostile conditions. To learn more about its survival strategy and capacity to persist in the environment, we studied the effect of temperature, nutrient deprivation and dryness on the long-term survival of two A. baumannii strains (ATCC 19606(T) and a clinical isolate). Our results revealed that both strains show a great persistence under stress that appears to involve a bust-and-boom strategy. Bacterial survival was differentially affected by temperature and physical environment: Desiccation favored cell resistance to stress at 20 and 37 °C, while survival in aqueous environments was temperature dependent and led to changes in several cellular characteristics. In addition, we tested the ability of the A. baumannii ATCC 19606(T) strain to form biofilms by monitoring the expression of adhesion-/biofilm-related genes (ompA, bfmR and csuAB). The observed downregulation of these genes suggests that the potential difficulties to adhere to solid surfaces and form biofilms likely limit the capacity of starved cells to spread and colonize abiotic surfaces.

Prevalence of Trypanosoma cruzi infection in pregnant Latin American women and congenital transmission rate in a non-endemic area: the experience of the Valencian Health Programme (Spain).

This study describes the results of the health programme implemented in the Valencian Community (Spain) to achieve an early diagnosis of Chagas disease in pregnant Latin American women and their newborns. During 2009 and 2010, 1975 women living in the health districts of three university hospitals were enrolled via midwives or at the time of delivery. Diagnosis of disease was performed using two serological tests with different antigens. Congenital infection was diagnosed by parasitological, molecular or serological methods from blood samples obtained at birth or in subsequent controls. The overall seroprevalence of Chagas infection in pregnant women from 16 different endemic countries was 11·4%. Infection was higher in those from countries in the Gran Chaco Region (Bolivia, 34·1%; Paraguay, 7·4%; Argentina, 5·3%). Eight newborn infants from Bolivian mothers had congenital Chagas which represents a vertical transmission rate of 3·7%. In conclusion, this work supports the benefits of offering an early diagnosis to pregnant women and newborns during routine prenatal healthcare.

The mechanism of TGF-ß signaling during palate development.

Cleft palate, a malformation of the secondary palate development, is one of the most common human congenital birth defects. Palate formation is a complex process resulting in the separation of the oral and nasal cavities that involves multiple events, including palatal growth, elevation, and fusion. Recent findings show that transforming growth factor beta (TGF-ß) signaling plays crucial roles in regulating palate development in both the palatal epithelium and mesenchyme. Here, we highlight recent advances in our understanding of TGF-ß signaling during palate development.

Ophthalmology examination during well-child visits in primary care health centres: Knowledge and difficulties experienced by health workers. / Examen oftalmológico durante el control del niño sano en atención primaria: conocimiento y dificultades de los miembros del equipo de salud.

INTRODUCTION: The red reflex examination (RRE) and visual acuity testing (VA) is a mandatory part of the examination during the well-child visits (WCV) in primary health care centres of the public system of health in Chile. The eye examination is aimed at the early detection of severe eye diseases in children, such as retinoblastoma, congenital cataracts, and amblyopia. The knowledge and difficulties experienced by health workers in primary care health centres for evaluating the red reflex during WCV in Chile is unknown. MATERIAL AND METHODS: A survey was performed in primary community health centres of XXX Santiago de Chile. RESULTS: The WCV were mainly performed by physicians (45.2%) and nurses (35.8%). Only 34% of health workers performed the red reflex test, and 42.3% checked VA during the WCV. The main reasons for not doing it include the lack of direct ophthalmoscopes and VA charts (55.2% and 43.9%, respectively) at their centres, and not having the knowledge or skills (29.3% and 22%, respectively) to properly perform these clinical tests. CONCLUSION: In this series, the eye examination of children attending WCV was unfrequently performed. A better implementation of the health centres and training of the health workers are needed in order to improve the access and quality of the paediatric eye examination in primary health care institutions in Chile.

Therapeutic and Preventive Effect of Voluntary Running Wheel Exercise on Social Defeat Stress (SDS)-induced Depressive-like Behavior and Chronic Pain in Mice.

Major depressive disorders (MDD) and chronic pain (CP) affect significant portion of the world's population and have high comorbidity rate. Social defeat stress (SDS) model was standardized in mice and can trigger depressive-like behavior and chronic pain. Based especially on clinical trials showing an effective preventive and therapeutic effect of physical exercise on CP and symptoms associated with MDD, this study aimed to investigate if the voluntary running wheel exercise can exert these effects in mice submitted to the 10-day SDS protocol, using fluoxetine as positive control. For this, we ran two set of experiments: in the first set mice started performing voluntary running wheel exercise after submitted to SDS and, in the second set, mice performed voluntary running wheel exercise before and during SDS. Mechanical and chemical hyperalgesia was analyzed through electronic von Frey and capsaicin test, respectively. Depressive-like behavior was assessed through social interaction test. Our results showed that the voluntary running wheel exercise was more effective than fluoxetine reversing the SDS-induced persistent hyperalgesia and both, fluoxetine and voluntary running wheel exercise, was effective reversing SDS-induced social avoidance. Also, voluntary running wheel exercise is an effective tool preventing both hyperalgesia and social avoidance induced by SDS. To the best of our knowledge, this was the first study using physical exercise as a therapeutic and preventive tool for chronic pain and depressive-like behavior simultaneously induced by social stress.

Social stress as a trigger for depressive-like behavior and persistent hyperalgesia in mice: study of the comorbidity between depression and chronic pain.

BACKGROUND: There is great comorbidity and similarity between chronic pain and major depressive disorders. We have recently shown that 10 days of social defeat stress (SDS) induces hyperalgesia regardless depressive-like behavior in mice. Here we aimed to investigate whether social stress predisposes to chronic pain and, inversely, whether chronic pain predisposes to stress-induced depression. METHODS: Firstly, we used the 10 days SDS paradigm in mice followed by a mild protocol of repetitive inflammatory stimulus to evaluate if SDS would predispose to persistent hyperalgesia development. Secondly, we used the intense protocol of repetitive inflammatory stimulus followed by a subthreshold SDS to evaluate if persistent hyperalgesia would predispose to depressive-like behavior of social avoidance. RESULTS: Our results showed that SDS predispose to chronic pain, since stressed mice injected with PGE2 for 7 days (mild protocol), stimuli normally not sufficient to trigger chronic pain, showed persistent hyperalgesia. Also, we showed that persistent hyperalgesia induced by repetitive inflammatory stimuli predispose to long-lasting depressive-like behavior of social avoidance induced by subthreshold SDS. LIMITATIONS: We did not analyze molecular mechanism associated with chronic pain and depressive-like behavior induced by SDS. However, we hypothesized that SDS and 14 days of PGE2 would generate neuroplasticity on brain areas shared by chronic pain and depression, predisposing to pain chronification and depressive-like behavior, respectively. CONCLUSIONS: We can conclude social stress as a key and a common factor for chronic pain and depression. We can also conclude that SDS predisposes to chronic pain and, inversely, chronic pain predisposes to depressive-like behavior.

Moderate protection is induced by a chimeric protein composed of leucine aminopeptidase and cathepsin L1 against Fasciola hepatica challenge in sheep.

Leucine aminopeptidase (FhLAP) and cathepsin L1 (FhCL1) of Fasciola hepatica play a critical role in parasite feeding, migration through host tissue, and immune evasion. These antigens have been tested for immune protection as single components with variable degrees of success. The chimeric-protein approach could improve protection levels against fasciolosis. Previously, we reported the design and construction of a chimeric protein composed of antigenic sequences of FhLAP and FhCL1 of F. hepatica. The goal of the present study was to express and evaluate the immune-protective capacity of this chimeric protein (rFhLAP-CL1) in sheep. Animals were randomly allocated into five groups with five animals in each group. Groups 1, 2 and 3 were immunized twice with 100 µg, 200 µg and 400 µg of rFhLAP-CL1 emulsified with Quil A adjuvant, whereas groups 4 and 5 were the adjuvant control and infection control groups, respectively. The animals were then challenged with 200 metacercariae two weeks after the rFhLAP-CL1 booster. The fluke burden was reduced by 25.5%, 30.7% (p < 0.05) and 46.5% (p < 0.01) in sheep immunized with 100 µg, 200 µg and 400 µg of chimeric protein, respectively, in comparison to the infection control group. There was a reduction of 22.7% (p < 0.05) and 24.4% (p < 0.01) in fecal egg count in groups 2 and 3, respectively, compared to the infection control group. Sheep immunized with chimeric protein produced F. hepatica excretion-secretion product-specific total IgG antibody, which were increased after challenge. Moreover, the levels of rFhLAP-CL1-specific IgG1 and IgG2 isotypes in immunized sheep increased rapidly two weeks after the first immunization and were significantly more elevated than those of the control groups, indicating a mixed Th1/Th2 response. This is a preliminary evaluation of the chimeric protein rFhLAP-CL1 as a possible immunogen against F. hepatica infection in sheep.

Anti-inflammatory effects of propranolol in the temporomandibular joint of female rats and its contribution to antinociceptive action.

BACKGROUND: ß-Blockers reduce temporomandibular joint (TMJ) pain. We asked whether they also reduce TMJ inflammation and, if so, whether this anti-inflammatory effect contributes to its analgesic action. METHODS: We measured many parameters of the inflammatory response after co-administration of the ß-blocker propranolol with the inflammatory agent carrageenan in the TMJ of female rats. We also hypothesized that the activation of ß-adrenoceptors in the TMJ induces nociception mediated, at least in part, by the inflammatory response. To test this hypothesis, we examined the nociceptive response induced by the activation of the ß-adrenoceptors in the TMJ in female rats pretreated with thalidomide and fucoidan. RESULTS: We found that the co-administration of propranolol with carrageenan in the TMJ of female rats significantly reduced several parameters of the inflammatory response induced by carrageenan such as plasma extravasation, neutrophil migration and the release of the pro-inflammatory cytokines TNF-α, IL-1ß and CINC-1. Furthermore, the injection of the ß-adrenergic receptor agonist isoproterenol in the TMJ induced nociception that was significantly reduced by thalidomide, fucoidan and by the co-administration of propranolol but not of the α-adrenergic receptor antagonist phentolamine. CONCLUSIONS: Propranolol has anti-inflammatory effects that contribute to its antinociceptive action in the TMJ of females. SIGNIFICANCE: ß-Blockers have an anti-inflammatory effect on temporomandibular joint (TMJ) that contributes to its analgesic effect. The results of this work suggest that ß-blockers can be used to treat the painful conditions of TMJ, especially when they are associated with an inflammatory process.

18F-choline PET/MRI in suspected recurrence of prostate carcinoma. / PET/RM con 18F-colina en la sospecha de recurrencia del carcinoma de próstata.

OBJECTIVE: To evaluate the usefulness of simultaneous 18F-choline PET/MRI in the suspicion of prostate cancer recurrence and to relate 18F-choline PET/MRI detection rate with analytical and pathological variables. MATERIAL AND METHODS: 27 patients with prostate cancer who received local therapy as primary treatment underwent a 18F-choline PET/MRI due to suspicion of recurrence (persistently rising serum PSA level). 18F-choline PET/MRI findings were validated by anatomopathological analysis, other imaging tests or by biochemical response to oncological treatment. RESULTS: 18F-choline PET/MRI detected disease in 15 of 27 patients (detection rate 55.56%). 4 (15%) presented exclusively local recurrence, 5 (18%) lymph node metastases and 7 (26%) bone metastases. Mean PSA (PSAmed) at study time was 2.94ng/mL (range 0.18-10ng/mL). PSAmed in patients with positive PET/MRI was 3.70ng/mL (range 0.24-10ng/mL), higher than in patients with negative PET/MRI, PSAmed 1.97ng/mL (range 0.18-4.38ng/mL), although without statistically significant differences. Gleason score at diagnosis in patients with a positive study was 7.33 (range 6-9) and in patients with a negative study was 7 (range 6-9), without statistically significant differences. CONCLUSION: 18F-choline PET/MRI detection rate was considerable despite the relatively low PSA values in our sample. The influence of Gleason score and PSA level on 18F-choline PET/MRI detection rate was not statistically significant.

5-HT acts on nociceptive primary afferents through an indirect mechanism to induce hyperalgesia in the subcutaneous tissue.

We have recently demonstrated that s.c.-injected 5-hydroxytryptamine (5-HT) induces nociception by an indirect action on the primary afferent nociceptor in addition to its previously described direct action. Although the mechanisms mediating hyperalgesia can be quite separate and distinct from those mediating nociception, the aim of this study was to test the hypothesis that 5-HT induces mechanical hyperalgesia by mechanisms similar to those mediating nociception. s.c. injection of 5-HT induced a dose-dependent mechanical hyperalgesia measured by the mechanical paw withdrawal nociceptive threshold test in the rat. 5-HT-induced hyperalgesia was significantly reduced by local blockade of the 5-HT(3) receptor by tropisetron, by the nonspecific selectin inhibitor fucoidan, by the cyclooxygenase inhibitor indomethacin, by guanethidine depletion of norepinephrine in the sympathetic terminals, and by local blockade of the beta(1)- or beta(2)-adrenergic receptor by atenolol or ICI 118,551, respectively. Taken together, these findings indicate that like nociception, hyperalgesia induced by the injection of 5-HT in the s.c. tissue is also mediated by an indirect action of 5-HT on the primary afferent nociceptor. This indirect hyperalgesic action of 5-HT is mediated by a combination of mechanisms involved in inflammation such as neutrophil migration and the local release of prostaglandin and norepinephrine. However, in contrast to nociception, hyperalgesia induced by 5-HT in the s.c. tissue is mediated by a norepinephrine-dependent mechanism that involves the activation of peripheral beta(2) adrenoceptors.

A novel technique to perform direct intraganglionar injections in rats.

The present work describes a simple method for direct drug administration into the dorsal root ganglion (DRG) in anesthetized rats. This technique does not involve surgery, is easy to learn and allows behavioral testing within minutes after the injection. Based on landmarks that target the L5 DRG, an orifice was created with a guide needle through which a specially designed needle was inserted for solution injection. Its introduction into the ganglia was ensured by the triggering of an ipsilateral hindpaw reflex. The precision of the technique was checked by injections of the biological dye Pontamine Sky Blue (PSB) or C14-labeled arginine. There was no leakage of the dye to the surrounding tissues after a single 4 microl or three successive 2.5 microl injections (at 30-min intervals). Moreover, identical effects were observed with prostaglandin E2 (PGE2), morphine or glibenclamide injected intraplantarly or in the DRG, thus confirming the precision of the method and suggesting that the ganglion cells and peripheral nociceptors may display similar receptor population.

A novel mechanism involved in 5-hydroxytryptamine-induced nociception: the indirect activation of primary afferents.

The aim of this study was to test the hypothesis that 5-hydroxytryptamine induces nociception by an indirect action on the primary afferent nociceptor in addition to its previously described direct action. Injection of 5-hydroxytryptamine into the s.c. tissue of the hind paw of rats produced nociceptive flinch behavior and inflammatory cell migration, that were significantly reduced by the nonspecific selectin inhibitor fucoidan. 5-Hydroxytryptamine-induced nociception was also significantly reduced by local blockade of the 5-HT3 receptor by tropisetron, by the cyclooxygenase inhibitor indomethacin and by local blockade of the beta1-adrenergic receptor or of the D1 receptor by atenolol or SCH 23390, respectively. Neither guanethidine depletion of norepinephrine in the sympathetic terminals nor local blockade of the beta2-adrenergic receptor by ICI-118,551 significantly reduced 5-hydroxytryptamine-induced nociception. Taken together, these findings indicate that 5-hydroxytryptamine induces nociception by a novel, indirect and norepinephrine-independent mechanism mediated by neutrophil migration and local release of prostaglandin and dopamine. Furthermore, to test whether dopamine acts on beta1-adrenergic and/or D1 receptor to contribute to 5-hydroxytryptamine-induced nociception, dopamine was s.c. injected either alone or combined with atenolol or with SCH 23390. S.c.-injected dopamine also produced a dose-dependent nociceptive behavior that was significantly reduced by both SCH 23390 and atenolol. Based on that it is proposed that dopamine, once released, activates D1 and beta1-adrenergic receptors to contribute to 5-hydroxytryptamine-induced nociception.

Atorvastatin inhibits inflammatory hypernociception.

BACKGROUND AND PURPOSE: Atorvastatin is an inhibitor of the enzyme 3-hydroxyl-3-methylglutaryl coenzyme A reductase used to prevent coronary heart disease. We have studied the analgesic effect of atorvastatin in inflammatory models in which a sequential release of mediators (bradykinin, (BK), tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and the chemokine, KC/CXCL) links the stimulus with release of directly acting hypernociceptive mediators such as prostaglandin E(2) (PGE(2)). EXPERIMENTAL APPROACH: The effects of orally administered atorvastatin on inflammatory mechanical hypernociception in mouse paws were evaluated with an electronic pressure-meter. Cytokines and PGE(2) were measured by ELISA and RIA. KEY RESULTS: Treatment with atorvastatin for 3 days dose-dependently reduced hypernociception induced by lipopolysaccharide (LPS) or that following antigen challenge in sensitized animals. Atorvastatin pre-treatment reduced hypernociception induced by bradykinin and cytokines (TNF-alpha, IL-1beta and KC), and the release of IL-1beta and PGE(2) in paw skin, induced by lipopolysaccharide. The antinociceptive effect of atorvastatin on LPS-induced hypernociception was prevented by mevalonate co-treatment without affecting serum cholesterol levels. Hypernociception induced by PGE(2) was inhibited by atorvastatin, suggesting intracellular antinociceptive mechanisms for atorvastatin. The antinociceptive effect of atorvastatin upon LPS- or PGE(2)-induced hypernociception was prevented by non-selective inhibitors of nitric oxide synthase (NOS) but not by selective inhibition of inducible NOS or in mice lacking this enzyme. CONCLUSIONS AND IMPLICATIONS: Antinociceptive effects of atorvastatin depend on inhibition of cytokines and prostanoid production and on stimulation of NO production by constitutive NOS. Our study suggests that statins may constitute a novel class of analgesic drugs.

PET/MRI: A luxury or a necessity? / PET/RM: ¿un lujo o una necesidad?

PET/MRI is a new multimodality technique with a promising future in diagnostic imaging. Technical limitations are being overcome. Interference between the two systems (PET and MRI) seems to have been resolved. MRI-based PET attenuation correction can be performed safely. Scan time is acceptable and the study is tolerable, with claustrophobia prevalence similar to that of MRI. Quantification with common parameters, such as Standardized Uptake Value (SUV), shows a fairly good correlation between both systems. However, PET/CT currently provides better results in scan time, scan costs, and patient comfort. Less patient radiation exposure is a big advantage of PET/MRI over PET/CT, which makes it particularly recommended in paediatric and adolescent patients requiring one or more studies. PET/MRI indications are the same as those of PET/CT, given that in cases where MRI is superior to CT, PET/MRI is superior to PET/CT. This superiority is clear in many soft tissue tumours. Moreover, it is common to perform both PET/CT and MRI in neurological diseases, as well as in some tumours, such as breast cancer. A single PET/MRI study replaces both with obvious benefit. MRI also allows other MRI-based PET corrections, such as motion or partial volume effect corrections. The better spatial resolution of MRI allows the transfer of well-defined MRI areas or small volumes of interest to PET image, in order to measure PET biomarkers in these areas. The richness of information of both techniques opens up immense possibilities of synergistic correlation between them.

Simultaneous PET/MRI vs PET/CT in oncology. A systematic review. / PET/RM simultánea vs. PET/TC en oncología. Una revisión sistemática.

OBJECTIVE: The aim of this review was to evaluate the diagnostic performance of simultaneous PET/MRI in oncology compared with that of PET/CT, based upon the available evidence. MATERIAL AND METHODS: A systematic search was performed in the Medline and Embase databases to identify original clinical articles published up to 21 January 2016, in order to compare simultaneous PET/MRI and PET/CT in oncology patients. RESULTS: A total of 57 articles were obtained that included various diseases: head and neck cancer (5), lung cancer and lung nodules (13), colorectal cancer (1), liver lesions (2), abdominal incidentalomas (1), neuroendocrine tumours (2), thyroid carcinoma (2), breast cancer (3), gynaecological cancer (2), prostate cancer (4), lymphoma (2), multiple myeloma (1), bone metastases (3), intracranial tumours (2), paediatric oncology (1) and various tumours (13). Diagnostic performance of simultaneous PET/MRI was similar or even better to that of PET/CT in most oncological diseases. However, PET/CT was superior for small lung nodule detection. CONCLUSION: Simultaneous PET/MRI in oncology is feasible, performing at least equally as well as PET/CT, with lower radiation exposure. However, available evidence is still limited. Studies including more patients and tumours are needed to establish PET/MRI indications and to identify appropriate protocols for each disease.

Experiencia en trasplante pulmonar pediátrico en Chile / Experience with pediatric lung transplantation in Chile

El trasplante de pulmón (TP) es una opción para pacientes pediátricos con enfermedades pulmonares terminales. OBJETIVO: Evaluar resultados y sobrevida de pacientes pediátricos trasplantados de pulmón. MÉTODOS: Análisis retrospectivo de registros clínicos de pacientes TP ≤ 15 años de Clínica Las Condes. Se analizaron datos demográficos, tipo de trasplante, función pulmonar basal y post trasplante, complicaciones precoces y tardías y sobrevida. RESULTADOS: Nueve pacientes < 15 años de edad se han trasplantado. La edad promedio fue 12,7 años. La principal indicación fue fibrosis quística (7 pacientes). El IMC promedio fue de 17,6 y todos estaban con oxígeno domiciliario. El 77% utilizó soporte extracorpóreo intraoperatorio. Las principales complicaciones precoces fueron hemorragia y la disfunción primaria de injerto mientras que las tardías fueron principalmente las infecciones y la disfunción crónica de injerto. Cuatro pacientes han fallecido y la sobrevida a dos años fue de 85%. El trasplante les permitió una reinserción escolar y 3 lograron completar estudios universitarios. CONCLUSIÓN: El trasplante pulmonar es una alternativa para niños con enfermedades pulmonares avanzadas mejorando su sobrevida y calidad de vida.

Lung transplantation (TP) is a treatment option in children with terminal lung diseases. OBJECTIVE: To evaluate the results and survival of pediatrics lung transplant patients. METHODS: Retrospective analysis of clinical records of lung transplantation of patients ≤ 15 years from Clínica Las Condes, Santiago, Chile. Demographic data, type of transplant, baseline and post transplant lung function, early and late complications and survival rate were analyzed. RESULTS: Nine patients ≤ 15 years-old were transplanted. The average age at transplant was 12.7 years. The main indication was cystic fibrosis (7 patients). The average BMI was 17.6 and all the patients were with home oxygen therapy. 77% used extracorporeal intraoperative support. Average baseline FEV1 was 25.2% with progressive improvement in FEV1 of 77% in the first year. The main early complications were hemorrhage and primary graft dysfunction, while late complications were infections and chronic graft dysfunction. Four patients have died and the estimated 2 years survival was 85%. They achieved school reinsertion and three managed to complete university studies. CONCLUSION: Lung transplantation is an alternative for children with advanced lung diseases improving their survival and quality of life.

Caracterización clínica y tomográfica de pacientes hospitalizados con COVID-19 / Clinical and tomographic characterization of patients hospitalized with COVID-19

OBJETIVO: Realizar una caracterización clínica y por imágenes a pacientes hospitalizados por COVID-19 y analizar si existen predictores de riesgo asociados con una mayor gravedad. MÉTODO: Estudio observacional, retrospectivo. Se incluyeron pacientes hospitalizados con COVID-19, entre abril y julio de 2020. Se registraron datos demográficos, comorbilidades, exámenes de laboratorio, tipo de compromiso en tomografía computada (TC) de tórax, terapias recibidas y tipo de soporte respiratorio. En el análisis estadístico para identificar factores de riesgo se utilizó test χ2 de Pearson o test de Fisher para comparar variables categóricas y test de Mann-Whitney para comparar variables continuas. RESULTADOS: Se analizaron 164 pacientes. La mediana de edad fue de 57 años (rango 21 a 89). 111 pacientes (68%) de género masculino y mediana de 7 días de síntomas previo al ingreso (rango 1 a 23). 68 pacientes (41%) tienen obesidad (significativamente mayor en pacientes < 60 años, p = 0,026), 56 (34%) hipertensión arterial (HTA) y 43 (26%) diabetes. El patrón predominante en la TC de ingreso fue de vidrio esmerilado (VE) con "crazy paving" (35%) y luego VE puro (28%). Como indicador de gravedad se tomó en cuenta el tipo de soporte ventilatorio requerido: 51 pacientes (31%) requieren soporte ventilatorio no invasivo (cánula nasal de alto flujo o VMNI) y 19 (11%) ventilación invasiva (VMI). Las variables predictoras de gravedad, estadísticamente significativas, fueron: HTA (p = 0,001), Diabetes Mellitus (p = 0,001) y Obesidad. (p = 0,002). CONCLUSIONES: Los pacientes hospitalizados por COVID 19 con mayor riesgo de evolución tórpida, del punto de vista respiratorio, fueron los pacientes obesos, hipertensos y diabéticos.

OBJECTIVE: To perform a clinical and imaging characterization in patients hospitalized for COVID-19 and to analyze whether there are risk predictors associated with greater severity of the condition. METHOD: Observational, retrospective study. Patients hospitalized with COVID-19 were included between April and July 2020. Demographic data, comorbidities, laboratory tests, tomographic pattern in thorax tomography (TC), therapies received, and type of respiratory support were recorded. In the statistical analysis to identify risk factors, we used Pearson's χ2 test or Fisher's test to compare categorical variables and Mann-Whitney test to compare continuous variables. RESULTS: 164 patients were analyzed. Median age was 57 years (21 to 89). 111 patients (68%) were male and a median of 7 days of symptoms prior to admission (1 to 23). 68 patients (41%) have obesity (significantly higher in patients < 60 years, p = 0.026), 56 (34%) arterial hypertension (HT) and 43 (26%) with diabetes mellitus. The predominant pattern in the admission CT scan was ground glass opacity (GGO) with "crazy paving" (35%) and then pure GGO (28%). Type of ventilatory support required was considered as an indicator of severity. 51 patients (31%) require non-invasive ventilatory support (high-flow nasal cannula or NIMV) and 19 (11%) invasive ventilation (IMV). The statistically significant predictor variables of severity were HT (p = 0.001), Diabetes Mellitus (p = 0.001) and Obesity. (p = 0.002). CONCLUSIONS: Patients hospitalized for COVID 19 with the highest risk of respiratory torpid evolution were obese, hypertensive and diabetic patients

Chronic hyperalgesic priming in the rat involves a novel interaction between cAMP and PKCepsilon second messenger pathways.

Toward the goal of defining new pharmacological targets for the treatment of chronic pain conditions, in previous studies we established a model, termed 'hyperalgesic priming,' in which an acute inflammatory stimulus causes a long-lasting latent susceptibility to hyperalgesia induced by subsequent exposures to the inflammatory mediator, prostaglandin E2 (PGE2). Those investigations suggested the hypothesis that priming induces a novel linkage between the PGE2-activated second messenger cascade and the epsilon isoform of protein kinase C (PKCepsilon). In the present study, comparison of dose-response relations for hyperalgesia produced by PGE2, forskolin, 8-Br-cAMP, or the protein kinase A (PKA) catalytic subunit, in primed versus normal animals, demonstrated that priming-induced enhancement of the PGE2-activated second messenger cascade occurs downstream to adenylate cyclase and upstream to PKA. Therefore, PGE2-induced hyperalgesia in the primed animal is enhanced by the recruitment of a novel cAMP/PKCepsilon signaling pathway in addition to the usual cAMP/PKA pathway. These observations suggest that pharmacological disruption of the novel interaction between cAMP and PKCepsilon might provide a route toward the development of highly specific methods to reverse cellular processes that underlie chronic pain states.