Cognitive Impairment Related to Chronic Kidney Disease Is Associated with a Decreased Abundance of Membrane-Bound Klotho in the Cerebral Cortex.

Cognitive impairment (CI) is a complication of chronic kidney disease (CKD) that is frequently observed among patients. The aim of this study was to evaluate the potential crosstalk between changes in cognitive function and the levels of Klotho in the brain cortex in an experimental model of CKD. To induce renal damage, Wistar rats received a diet containing 0.25% adenine for six weeks, while the control group was fed a standard diet. The animals underwent different tests for the assessment of cognitive function. At sacrifice, changes in the parameters of mineral metabolism and the expression of Klotho in the kidney and frontal cortex were evaluated. The animals with CKD exhibited impaired behavior in the cognitive tests in comparison with the rats with normal renal function. At sacrifice, CKD-associated mineral disorder was confirmed by the presence of the expected disturbances in the plasma phosphorus, PTH, and both intact and c-terminal FGF23, along with a reduced abundance of renal Klotho. Interestingly, a marked and significant decrease in Klotho was observed in the cerebral cortex of the animals with renal dysfunction. In sum, the loss in cerebral Klotho observed in experimental CKD may contribute to the cognitive dysfunction frequently observed among patients. Although further studies are required, Klotho might have a relevant role in the development of CKD-associated CI and represent a potential target in the management of this complication.

Neonatal SARS-CoV-2 immunoglobulin G antibodies at delivery and their impact on COVID-19.

OBJECTIVE: To assess neonatal SARS-CoV-2 anti-spike IgG antibody levels after maternal mRNA COVID-19 vaccination and/or infection during pregnancy and evaluate their protective effect. METHODS: Prospective observational study, conducted from January 2021 to December 2022. Infants were tested for anti-spike IgG antibodies at birth and then every 3 months until disappearance of titer. A follow-up was done for SARS-CoV-2 infection up to 12 months. RESULTS: In total, 147 newborns were enrolled with a median (IQR) gestational age of 39.60 weeks (38.3-40.4). Median (IQR) titers in UA/ml at 2 days were higher (P < .001) in newborns of vaccinated 7063.7 (2841.4-14,448.1), than of infected mothers 372.7 (158.00-884.90). Titers dropped significantly during the follow-up but 50% still had a detectable titer at 6 months. A high antibody titer at 2 days led to a longer persistence (HR 0.89, IC 95% 0.83-0.96, P = .004). In total, 36 infants were infected during the first months of life coinciding with the Omicron variant. Fifty percent had detectable antibodies during the infection period. Relationship between high IgG titers and month of infection was inverse (RHO - 0.52, P = .009). CONCLUSION: Though a high antibody titer at birth led to longer persistence, no protective effect against infection was found. As newborns are a high risk group for COVID-19, avoiding transmission during the first year of life is important.

New Functions of Intracellular LOXL2: Modulation of RNA-Binding Proteins.

Lysyl oxidase-like 2 (LOXL2) was initially described as an extracellular enzyme involved in extracellular matrix remodeling. Nevertheless, numerous recent reports have implicated intracellular LOXL2 in a wide variety of processes that impact on gene transcription, development, differentiation, proliferation, migration, cell adhesion, and angiogenesis, suggesting multiple different functions for this protein. In addition, increasing knowledge about LOXL2 points to a role in several types of human cancer. Moreover, LOXL2 is able to induce the epithelial-to-mesenchymal transition (EMT) process-the first step in the metastatic cascade. To uncover the underlying mechanisms of the great variety of functions of intracellular LOXL2, we carried out an analysis of LOXL2's nuclear interactome. This study reveals the interaction of LOXL2 with numerous RNA-binding proteins (RBPs) involved in several aspects of RNA metabolism. Gene expression profile analysis of cells silenced for LOXL2, combined with in silico identification of RBPs' targets, points to six RBPs as candidates to be substrates of LOXL2's action, and that deserve a more mechanistic analysis in the future. The results presented here allow us to hypothesize novel LOXL2 functions that might help to comprehend its multifaceted role in the tumorigenic process.

Hallux Partial Necrosis Associated with Antiphospholipid Syndrome: The Importance of Early Accurate Diagnosis.

This study highlights the importance of having a high clinical suspicion of hypercoagulopathy such as antiphospholipid syndrome (APS) in podiatric patients with normal foot pulses and normal standard coagulation tests. APS is an autoimmune disease that is characterized by inflammatory thrombosis in the arteries and veins and obstetric complications such as pregnancy loss. APS usually affects vessels of the lower extremities. We report herein the case of a 46-year-old woman with previous episodes of pre-eclampsia who suffered from partial ischemic necrosis of the hallux of the left foot. After several ischemic episodes of the hallux, with increased risk of toe amputation, the patient was finally diagnosed with APS and treated with specific anticoagulant medication. The patient's symptoms subsided, and toe amputation was prevented. Early accurate diagnosis and appropriate clinical management are critical to providing optimal outcomes and reducing the risk of amputation.

First Trimester Evaluation of Maternal Visceral Fat and Its Relationship with Adverse Pregnancy Outcomes.

Obese women are more likely to experience pregnancy complications. The distribution of fat, and more particularly the rise in visceral fat, is well established to be more closely linked to the onset of cardiovascular disease and metabolic syndrome than obesity itself. We aim to examine the relationship between maternal visceral fat assessment in the first trimester and the appearance of adverse pregnancy outcomes. A prospective cohort study including 416 pregnant women was conducted. During the first trimester scan (11-13 + 6 weeks), all individuals had their visceral fat and subcutaneous thicknesses measured by ultrasonography. Blood samples were obtained, and maternal demographics and clinical information were documented. After delivery, the obstetric outcomes were evaluated. We contrasted two groups: one with healthy pregnancies and the other with adverse pregnancy outcomes (APO), defined as the development of at least one of the following complications: gestational diabetes mellitus, hypertensive disorders of pregnancy, abnormal fetal growth, preterm delivery or preterm premature rupture of membranes. Median maternal age was 33 and 34 years old for the uncomplicated and adverse pregnancy outcomes groups, respectively. We found that women with adverse pregnancy outcomes had higher VFT (median 30 vs. 26.5 mm, p = 0.001) and SFT (median 18.9 vs. 17.1 mm, p = 0.03). However, the visceral/subcutaneous fat ratio was not statistically different between groups. Finally, we performed a subanalysis for metabolic and placental vascular dysfunction complications. After performing a multivariate logistic regression analysis adjusted for maternal age, smoking, and mean arterial pressure, both the VFT (aOR 1.03, p < 0.001) and the ratio of visceral/subcutaneous fat (aOR 1.37, p = 0.04) were significantly associated with the development of adverse pregnancy outcomes; however, the associations of VFT and the VFT-to-SFT ratio were higher for the occurrence of gestational diabetes (aOR 1.07, p < 0.001; aOR 2.09, p = 0.001; respectively) and showed no relationships with placental complications. When conducting a first-trimester ultrasound assessment, sonographers may measure VFT without additional time or cost involved. Identification of pregnant women with increased VFT (>37 mm) may benefit from a close follow-up, especially for the development of gestational diabetes, independent of BMI.

Hyponatremia after craniotomy in children: a single-institution review.

PURPOSE: Hyponatremia after craniotomy can be associated with increased morbidity. However, the incidence of and factors associated with post-craniotomy hyponatremia in children are not known. METHODS: We performed a retrospective cohort study of patients aged 0-21 years who underwent craniotomy in 2017-2019 at a single center to determine the incidence of and to identify risk factors for hyponatremia after craniotomy. Indications for craniotomy included tumors (excluding craniopharyngioma), epilepsy, intracranial infection, trauma, craniofacial, suboccipital decompression for the treatment of Chiari malformation, and cerebrovascular disease. Hyponatremia was defined as a serum sodium level ≤ 135 mEq/L any time during the postoperative hospital stay. Statistical significance was defined a priori at p < 0.05. RESULTS: Postoperative hyponatremia occurred in 61 (25%) of 240 children. On univariate analysis, hyponatremia was associated with younger age (8.5 vs 6.3 years, p = 0.01), use of preoperative anti-epileptic drugs (p = 0.02), need for blood transfusion (p = 0.02), government/private insurance (p = 0.04), and pre-existing hydrocephalus, defined as the requirement for permanent cerebrospinal fluid (CSF) diversion (p = 0.04). On multivariate analysis, only hydrocephalus (OR 2.95, 95% CI 1.03-8.40) remained statistically significant. Hyponatremia most occurred on the first postoperative day, with normonatremia achieved in a median of 14 (IQR 9.8-24.3) h. Hyponatremia was significantly associated with longer length of stay (median 8 vs 3 days, p < 0.01). CONCLUSION: Hyponatremia was present in 25% of children after craniotomy. Preoperative hydrocephalus as an independent risk factor for hyponatremia after craniotomy.

Emulsion Polymerization Using an Amphiphilic Oligoether Ionic Liquid as a Surfactant.

We investigate the use of an ionic liquid (IL) as a surfactant in emulsion polymerization (EP) reactions. ILs have been proposed as surfactants for micellar dispersions, emulsions, micro-emulsions and suspensions. Thus, it is important to acquire knowledge of the application of ILs in heterogeneous polymerizations. We selected the amphiphile cationic oligoether IoLiLyte C1EG™ as an IL for this purpose and compared its performance to that of the conventional surfactant dodecyl trimethyl ammonium bromide (DTAB) in the EP of methyl methacrylate and styrene. After we found the proper concentration range of the IL, this amphiphile showed similar polymerization rates to those observed with DTAB for both monomers. The evolution of monomer conversion and the final average diameter of formed polymeric particles were similar for both evaluated surfactants, demonstrating their capability to stabilize the EPs of the investigated monomers. We simulated the evolution of monomer conversion and particle size using a conventional model for emulsion polymerization, which showed good agreement with the experimental data, suggesting that the EP with this IL follows Smith-Ewart kinetics.

Large Lobular Capillary Hemangioma Associated with Ingrown Toenail: Histopathological Features and Case Report.

Lobular capillary hemangioma (LCH-PG) is a type of pyogenic granuloma characterized by proliferating blood vessels that resemble conventional granulation tissue. Granulation tissue is very often seen in association with ingrown toenails. Despite the close relationship between both entities, LCH-PG shows clinically different behaviors, such as rapid growth and frequent recurrence. Currently, it is unknown exactly how the different etiological factors contribute to the formation of differences between entities. We present a case of a large LCH-PG associated with chronic onychocryptosis in a 26-year-old man. Histopathological features included extensive signs of ulceration, hyperkeratosis, and patchy epidermal acanthosis with the presence of fibrous septa with lobular areas beneath the ulcerative area. The presence of stroma with a marked proliferation of blood vessels with wall thickening and mixed-type inflammatory changes was also characteristic. In advanced stages of onychocryptosis, as presented here, conventional granulation tissue or pyogenic granuloma can be clinically difficult to distinguish from other benign or malignant neoplasms. Histological examination is mandatory, and excisional biopsy can provide a definitive diagnosis.

The PANDORA Study: Prevalence and Outcome of Acute Hypoxemic Respiratory Failure in the Pre-COVID-19 Era.

OBJECTIVES: To establish the epidemiological characteristics, ventilator management, and outcomes in patients with acute hypoxemic respiratory failure (AHRF), with or without acute respiratory distress syndrome (ARDS), in the era of lung-protective mechanical ventilation (MV). DESIGN: A 6-month prospective, epidemiological, observational study. SETTING: A network of 22 multidisciplinary ICUs in Spain. PATIENTS: Consecutive mechanically ventilated patients with AHRF (defined as Pao2/Fio2 ≤ 300 mm Hg on positive end-expiratory pressure [PEEP] ≥ 5 cm H2O and Fio2 ≥ 0.3) and followed-up until hospital discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were prevalence of AHRF and ICU mortality. Secondary outcomes included prevalence of ARDS, ventilatory management, and use of adjunctive therapies. During the study period, 9,803 patients were admitted: 4,456 (45.5%) received MV, 1,271 (13%) met AHRF criteria (1,241 were included into the study: 333 [26.8%] met Berlin ARDS criteria and 908 [73.2%] did not). At baseline, tidal volume was 6.9 ± 1.1 mL/kg predicted body weight, PEEP 8.4 ± 3.1 cm H2O, Fio2 0.63 ± 0.22, and plateau pressure 21.5 ± 5.4 cm H2O. ARDS patients received higher Fio2 and PEEP than non-ARDS (0.75 ± 0.22 vs 0.59 ± 0.20 cm H2O and 10.3 ± 3.4 vs 7.7 ± 2.6 cm H2O, respectively [p < 0.0001]). Adjunctive therapies were rarely used in non-ARDS patients. Patients without ARDS had higher ventilator-free days than ARDS (12.2 ± 11.6 vs 9.3 ± 9.7 d; p < 0.001). All-cause ICU mortality was similar in AHRF with or without ARDS (34.8% [95% CI, 29.7-40.2] vs 35.5% [95% CI, 32.3-38.7]; p = 0.837). CONCLUSIONS: AHRF without ARDS is a very common syndrome in the ICU with a high mortality that requires specific studies into its epidemiology and ventilatory management. We found that the prevalence of ARDS was much lower than reported in recent observational studies.

Review of mobile applications for the detection and management of atrial fibrillation.

BACKGROUND: Free mobile applications (apps) that use photoplethysmography (PPG) waveforms may extend atrial fibrillation (AF) detection to underserved populations, but they have not been rigorously evaluated. OBJECTIVE: The purpose of this study was to systematically review and evaluate the quality, functionality, and adherence to self-management behaviors of existing mobile apps for AF. METHODS: We systematically searched 3 app stores for apps that were free, available in English, and intended for use by patients to detect and manage AF. A minimum of 2 reviewers evaluated (1) app quality, using the Mobile Application Rating Scale (MARS); (2) functionality using published criteria; and (3) features that support 4 self-management behaviors (including PPG waveform monitoring) identified using evidence-based guidelines. Interrater reliability between the reviewers was calculated. RESULTS: Of 12 included apps, 5 (42%) scored above average for quality (MARS score ≥3.0). App quality was highest for their ease of use, navigation, layout, and visual appeal (eg, functionality and aesthetics) and lowest for their behavioral change support and subjective impressions of quality. The most common app functionalities were capturing and graphically displaying user-entered data (n = 9 [75%]). Nearly all apps (n = 11 [92%]) supported PPG waveform monitoring, but only 2 (17%) supported all 4 self-management behaviors. Interrater reliability was high (0.75-0.83). CONCLUSION: The reviewed apps had wide variability in quality, functionality, and adherence to self-management behaviors. Given the accessibility of these apps to underserved populations and the tremendous potential they hold for improving AF detection and management, high priority should be given to improving app quality and functionality.

Giant Plantar Epidermoid Cyst with Invasion of the Interosseous Muscles.

Epidermoid cysts of the sole of the foot are rare lesions that must be differentiated from other, more common subcutaneous pathologic abnormalities located on the sole. Cases of epidermoid cysts that extend to the interosseous musculature are rarer still. We report the case of a giant epidermal cyst in a 64-year-old individual that extended to the intrinsic musculature of the third space of the right foot and that was diagnosed after fine-needle aspiration biopsy and subsequent cytologic study. Differential diagnosis of these lesions should be made with the support of additional imaging tests, and diagnostic confirmation should always be obtained after surgical removal and subsequent histopathologic study.

Survival analysis of surgically evacuated supratentorial spontaneous intracerebral hemorrhage with intraventricular extension.

OBJECTIVE: To conduct a survival study and evaluation of surgical treatment in a cohort of patients with diagnosis of supratentorial spontaneous intracerebral hemorrhage (ICH). MATERIALS AND METHODS: The study included all consecutive patients with supratentorial ICH admitted to the Intensive Care Units of three Spanish hospitals with Neurosurgery Department between 2009 and 2012. DATA COLLECTED: age, APACHE-II, Glasgow Coma Score (GCS), and pupillary anomalies on admission, intracerebral hemorrhage (ICH) score, location/volume of hematoma, intraventricular hemorrhage (IVH), surgical evacuation alone or with additional external ventricular drain, and 30-days survival and at hospital discharge RESULTS: A total of 263 patients were included. Mean age: 59.74±14.14 years. GCS: 8±4 points, APACHE II: 20.7±7.68 points. ICH Score: 2.32+1.04 points. Pupillary anomalies were observed in 30%. The 30-day mortality: 51.3% (45.3% predicted by ICH-score), and 53.2% at hospital discharge. A significant difference (p=0.004) was observed in hospital mortality rates between surgically treated patients (39.7%, n=78) versus those conservatively managed (58.9%, n=185); specifically in those with IVH surgically treated (34.2%, n=38) versus non-operated IVH (67.2%, n=125), p<0.001. No significant difference was found between mortality rates in patients without IVH. Multiple logistic regression analysis showed an OR for surgery of 1.04 (95% CI; 0.33-3.22) in patients without IVH versus 0.19 (95% CI; 0.07-0.53) in patients with IVH (decreased mortality with surgical treatment). The propensity score analysis for IVH patients showed improved survival of operated group (OR 0.23, 95% CI; 0.07-0.75), p=0.01. CONCLUSIONS: Hospital mortality was lower in patients who underwent surgery compared to patients conservatively managed, specifically for the subgroup of patients with intraventricular hemorrhage.

Virological and immunological characterization of novel NYVAC-based HIV/AIDS vaccine candidates expressing clade C trimeric soluble gp140(ZM96) and Gag(ZM96)-Pol-Nef(CN54) as virus-like particles.

UNLABELLED: The generation of vaccines against HIV/AIDS able to induce long-lasting protective immunity remains a major goal in the HIV field. The modest efficacy (31.2%) against HIV infection observed in the RV144 phase III clinical trial highlighted the need for further improvement of HIV vaccine candidates, formulation, and vaccine regimen. In this study, we have generated two novel NYVAC vectors, expressing HIV-1 clade C gp140(ZM96) (NYVAC-gp140) or Gag(ZM96)-Pol-Nef(CN54) (NYVAC-Gag-Pol-Nef), and defined their virological and immunological characteristics in cultured cells and in mice. The insertion of HIV genes does not affect the replication capacity of NYVAC recombinants in primary chicken embryo fibroblast cells, HIV sequences remain stable after multiple passages, and HIV antigens are correctly expressed and released from cells, with Env as a trimer (NYVAC-gp140), while in NYVAC-Gag-Pol-Nef-infected cells Gag-induced virus-like particles (VLPs) are abundant. Electron microscopy revealed that VLPs accumulated with time at the cell surface, with no interference with NYVAC morphogenesis. Both vectors trigger specific innate responses in human cells and show an attenuation profile in immunocompromised adult BALB/c and newborn CD1 mice after intracranial inoculation. Analysis of the immune responses elicited in mice after homologous NYVAC prime/NYVAC boost immunization shows that recombinant viruses induced polyfunctional Env-specific CD4 or Gag-specific CD8 T cell responses. Antibody responses against gp140 and p17/p24 were elicited. Our findings showed important insights into virus-host cell interactions of NYVAC vectors expressing HIV antigens, with the activation of specific immune parameters which will help to unravel potential correlates of protection against HIV in human clinical trials with these vectors. IMPORTANCE: We have generated two novel NYVAC-based HIV vaccine candidates expressing HIV-1 clade C trimeric soluble gp140 (ZM96) and Gag(ZM96)-Pol-Nef(CN54) as VLPs. These vectors are stable and express high levels of both HIV-1 antigens. Gag-induced VLPs do not interfere with NYVAC morphogenesis, are highly attenuated in immunocompromised and newborn mice after intracranial inoculation, trigger specific innate immune responses in human cells, and activate T (Env-specific CD4 and Gag-specific CD8) and B cell immune responses to the HIV antigens, leading to high antibody titers against gp140. For these reasons, these vectors can be considered vaccine candidates against HIV/AIDS and currently are being tested in macaques and humans.

Evaluation of prognostic scale Thrombolysis In Myocardial Infarction and Killip. An ST-elevation myocardial infarction new scale.

BACKGROUND: Prognostic systems are complex. So it is necessary to find tools, which are easy to use and have good calibration and discrimination. OBJECTIVES: The objective of this study is to evaluate the usefulness of Killip, Thrombolysis In Myocardial Infarction (TIMI), and age to develop a new prognostic scale for patients with ST-elevation myocardial infarction (STEMI). METHODS: The study population included all patients with STEMI consecutively admitted to the Intensive Care Unit of Carlos Haya Hospital, Malaga, Spain. Top variables included are Killip and TIMI, hospital mortality, intensive care unit stay, treatment received, and care times intervals. RESULTS: The results are 806 patients; 75.6% men; age 63.11 ± 12.83 years old; TIMI, 3.57 ± 2.38; Killip I, 81.4%; and hospital mortality, 11.3%. Mortality increased in relation to age, TIMI, and Killip (P < .001). Receiver operating characteristic (ROC) area for TIMI is 0.832 (0.786-0.878) and Killip, 0.757 (0.698-0.822). Thrombolysis In Myocardial Infarction classification was associated with Killip and age by multiple linear regression. Patients were stratified into 5 groups according to Killip and age: Killip I and younger than 65 years (n = 369; mortality, 1.4%; odds ratio [OR], 1), Killip I and 65 to 75 years old (n = 173; mortality, 6.9%; OR, 5.43 [1.88-15.66]), Killip I and older than 75 years (n = 112; mortality, 18.9%; OR, 13.03 [4.69-36.21]), Killip II to III (n = 129; mortality, 31%; OR, 22.72 [12.55-85.29]), Killip IV (n = 20; mortality, 80%; OR, 291.2 [71.32-1189]). ROC area is 0.84 (0.798-0.883). We created a scale with scores based on the ß coefficient of logistical regression. CONCLUSIONS: The TIMI scale discriminated hospital mortality correctly for STEMI. It performed better than Killip alone and similar to a simple model that included age and Killip. The 2-variable model consists of a simple scale with 5 categories.

Información sobre anticoncepción y métodos anticonceptivos en adolecentes del municipio "La Lisa" / Information about contraception and contraceptive methods in adolescents in \"La Lisa\" Municipality

Introducción: el control de la natalidad en la adolescencia y la prevención de las Infecciones de Transmisión Sexual (ITS), han sido una preocupación de nuestro Sistema Nacional de Salud, que ha realizado numerosos esfuerzos en aras de lograrlo.Objetivo: caracterizar la información que tienen sobre anticoncepción y métodos anticonceptivos un grupo de adolescentes.Métodos: se realizó un estudio descriptivo de corte transversal. El universo fue de 87 alumnos matriculados en la escuela y se trabajó con 78 de ellos, a los cuales se les aplicó una encuesta de manera anónima, con preguntas cerradas y validadas por criterios de expertos.Resultados: en ambos sexos se identificaron correctamente los métodos anticonceptivos. Los padres fueron la fuente de información más frecuente y predominaron aquellos que no reconocen la posibilidad de un embarazo con la práctica de algunos juegos sexuales.Conclusiones: el conocimiento por parte de los y las adolescentes de la importancia de la anticoncepción y los métodos anticonceptivos resulta aún insuficiente. Los programas de educación sexual para adolescentes deben reforzar estos aspectos. El protagonismo de loseducadores debe ser mayor pues en estas edades se necesita que los transmisores de la información tengan una adecuada preparación que en ocasiones falta en los padres

Background: birth control in adolescence and the prevention of Sexually Transmitted Infections (STI) have been a great concern for our National Health System, which has made many efforts in the interest of achieving it.Objective: to characterize the information that a group of adolescents have about contraception and contraceptive methods.Methods: a cross-sectional descriptive study was performed. The sample was composed of 87 students enrolled at school. To 78 of them, an anonymous inquiry was applied which included closed questions and was also validated by experts´ criteria.Results: in both sexes, the contraceptive methods were identified correctly. Their parents constituted the most frequent source of information and the group that predominated was the one that does not recognize the possibility of pregnancy after practicing some sexual games.Conclusions: the knowledge by adolescents about the importance of contraception and contraceptive methods is still insufficient. The programs about sexual education for adolescents should reinforce these aspects. The prominent role of educators should be bigger because these ages need that the transmitters of information have the adequate preparation that, in some occasions, their parents lack interest in

Deletion of the viral anti-apoptotic gene F1L in the HIV/AIDS vaccine candidate MVA-C enhances immune responses against HIV-1 antigens.

Vaccinia virus (VACV) encodes an anti-apoptotic Bcl-2-like protein F1 that acts as an inhibitor of caspase-9 and of the Bak/Bax checkpoint but the role of this gene in immune responses is not known. Because dendritic cells that have phagocytosed apoptotic infected cells cross-present viral antigens to cytotoxic T cells inducing an antigen-specific immunity, we hypothesized that deletion of the viral anti-apoptotic F1L gene might have a profound effect on the capacity of poxvirus vectors to activate specific immune responses to virus-expressed recombinant antigens. This has been tested in a mouse model with an F1L deletion mutant of the HIV/AIDS vaccine candidate MVA-C that expresses Env and Gag-Pol-Nef antigens (MVA-C-ΔF1L). The viral gene F1L is not required for virus replication in cultured cells and its deletion in MVA-C induces extensive apoptosis and expression of immunomodulatory genes in infected cells. Analysis of the immune responses induced in BALB/c mice after DNA prime/MVA boost revealed that, in comparison with parental MVA-C, the mutant MVA-C-ΔF1L improves the magnitude of the HIV-1-specific CD8 T cell adaptive immune responses and impacts on the CD8 T cell memory phase by enhancing the magnitude of the response, reducing the contraction phase and changing the memory differentiation pattern. These findings reveal the immunomodulatory role of F1L and that the loss of this gene is a valid strategy for the optimization of MVA as vaccine vector.

Factores de riesgo que influyeron en el bajo peso al nacer en el policlínico Aleida Fernández / Risk factors influencing low birth weight at Aleida Fernandez clinic

Introducción: el nacimiento de un niño bajo peso ha constituido una incógnita para los profesionales de la salud en todos los tiempos. Objetivo: determinar los factores de riesgo que influyeron en el bajo peso al nacer, en el policlínico Aleida Fernández en los años 2007-2009. Métodos: se realizó un estudio retrospectivo descriptivo de corte transversal en los años 2007-2009. El universo lo constituyeron las 31 embarazadas cuyos bebés presentaron pesos por debajo de 2 500 g, y la muestra quedó formada por las 22 que recibieron atención prenatal en nuestra área de salud. Se utilizó porcentaje, media y desviación estándar como estadística descriptiva. Resultados: de los recién nacidos, 16 (72,7 porciento) presentaron retardo del crecimiento intrauterino y 10 (45,4 porciento) fueron pretérminos. El 100 porciento de las estudiadas, presentó sepsis vaginal y 18 (81,8 porciento), anemia. Conclusiones: el bajo peso al nacer continúa siendo un problema de salud y durante el embarazo existen numerosos factores de riesgos favorecedores y/o causales de este, tales como: el antecedente de abortos provocados y la nuliparidad, la desnutrición materna con insuficiente ganancia ponderal, la presencia de anemia y la sepsis vaginal. El trabajo continuo y sistemático, consciente y orientado hacia la población de mayor riesgo, constituye un elemento crucial, para la reducción de este evento negativo

Introduction: the birth of an underweight child has been a mystery to health professionals at all times. Objective: to determine risk factors influencing low birth weight, at Aleida Fernández clinic from 2007 to 2009. Methods: a retrospective cross sectional study was carried out from 2007 to 2009. The universe was 31 pregnant women whose babies had weights below 2 500 g, and the sample 22 pregnant women, who received prenatal care in our health area. We used percentage, mean and standard deviation as descriptive statistics. Results: 16 (72.7 percent) out of the newborns had intrauterine growth retardation and 10 (45.4 percent) were preterm. 100 percent of the patients studied developed vaginal sepsis, and 18 (81.8 percent) developed anemia. Conclusions: low birth weight remains a health problem and during pregnancy, there are numerous predisposing risk factors and / or causes such as: a history of abortions and nulliparity, malnutrition, poor maternal weight gain, the presence of anemia, and vaginal sepsis. The continuous and systematic, conscious work aimed towards high-risk population is crucial for reducing this negative event

Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C.

Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world.

Removal of vaccinia virus genes that block interferon type I and II pathways improves adaptive and memory responses of the HIV/AIDS vaccine candidate NYVAC-C in mice.

Poxviruses encode multiple inhibitors of the interferon (IFN) system, acting at different levels and blocking the induction of host defense mechanisms. Two viral gene products, B19 and B8, have been shown to act as decoy receptors of type I and type II IFNs, blocking the binding of IFN to its receptor. Since IFN plays a major role in innate immune responses, in this investigation we asked to what extent the viral inhibitors of the IFN system impact the capacity of poxvirus vectors to activate immune responses. This was tested in a mouse model with single and double deletion mutants of the vaccine candidate NYVAC-C, which expresses the HIV-1 Env, Gag, Pol, and Nef antigens. When deleted individually or in double, the type I (B19) and type II (B8) IFN binding proteins were not required for virus replication in cultured cells. Studies of immune responses in mice after DNA prime/NYVAC boost revealed that deletion of B8R and/or B19R genes improved the magnitude and quality of HIV-1-specific CD8(+) T cell adaptive immune responses and impacted their memory phase, changing the contraction, the memory differentiation, the effect magnitude, and the functionality profile. For B cell responses, deletion of the viral gene B8R and/or B19R had no effect on antibody levels to HIV-1 Env. These findings revealed that single or double deletion of viral factors (B8 and B19) targeting the IFN pathway is a useful approach in the design of improved poxvirus-based vaccines.