Experimental Study of White Light Interferometry in Mach-Zehnder Interferometers Based on Standard Single Mode Fiber.

In this work, we experimentally analyzed and demonstrated the performance of an in-line Mach-Zehnder interferometer in the visible region, with an LED light source. The different waist diameter taper and asymmetric core-offset interferometers proposed used a single-mode fiber (SMF). The visibility achieved was V = 0.14 with an FSR of 23 nm for the taper MZI structure and visibilities of V = 0.3, V = 0.27, and V = 0.34 with FSRs of 23 nm, 17 nm, and 8 nm and separation lengths L of 2.5 cm, 4.0 cm, and 5.0 cm between the core-offset structure, respectively. The experimental investigation of the response to the temperature sensor yielded values from 50 °C to 300 °C; the sensitivity obtained was 3.53 a.u./°C, with R2 of 0.99769 and 1% every 1 °C in the transmission. For a range of 50 °C to 150 °C, 20.3 pm/°C with a R2 of 0.96604 was obtained.

The S-REAL study: Spanish real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy.

OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.

The Role of Specialized Pro-Resolving Lipid Mediators in Inflammation-Induced Carcinogenesis.

Cancer is a process involving cell mutation, increased proliferation, invasion, and metastasis. Over the years, this condition has represented one of the most concerning health problems worldwide due to its significant morbidity and mortality. At present, the incidence of cancer continues to grow exponentially. Thus, it is imperative to open new avenues in cancer research to understand the molecular changes driving DNA transformation, cell-to-cell interaction derangements, and immune system surveillance decay. In this regard, evidence supports the relationship between chronic inflammation and cancer. In light of this, a group of bioactive lipids derived from polyunsaturated fatty acids (PUFAs) may have a position as novel anti-inflammatory molecules known as the specialized pro-resolving mediators (SPMs), a group of pro-resolutive inflammation agents that could improve the anti-tumor immunity. These molecules have the potential role of chemopreventive and therapeutic agents for various cancer types, and their effects have been documented in the scientific literature. Thus, this review objective centers around understanding the effect of SPMs on carcinogenesis and their potential therapeutic effect.

Silencing of the Laccase (lacc2) Gene from Pleurotus ostreatus Causes Important Effects on the Formation of Toxocyst-like Structures and Fruiting Body.

A wide variety of biological functions, including those involved in the morphogenesis process of basidiomycete fungi, have been attributed to laccase enzymes. In this work, RNA interference (RNAi) was used to evaluate the role of the laccase (lacc2) gene of Pleurotus ostreatus PoB. Previously, transformant strains of P. ostreatus were obtained and according to their level of silencing they were classified as light (T7), medium (T21) or severe (T26 and T27). The attenuation of the lacc2 gene in these transformants was determined by RT-PCR. Silencing of lacc2 resulted in a decrease in laccase activity between 30 and 55%, which depended on the level of laccase expression achieved. The silenced strains (T21, T26, and T27) displayed a delay in the development of mycelium on potato dextrose agar (PDA) medium, whereas in the cultures grown on wheat straw, we found that these strains were incapable of producing aerial mycelium, primordia, and fruiting bodies. Scanning electron microscopy (SEM) showed the presence of toxocyst-like structures. The highest abundance of these structures was observed in the wild-type (PoB) and T7 strains. However, the abundance of toxocysts decreased in the T21 and T26 strains, and in T27 they were not detected. These results suggest that the presence and abundance of toxocyst-like structures are directly related to the development of fruiting bodies. Furthermore, our data confirm that lacc2 is involved in the morphogenesis process of P. ostreatus.

Laccase Production from Agrocybe pediades: Purification and Functional Characterization of a Consistent Laccase Isoenzyme in Liquid Culture.

Laccases are valuable enzymes as an excellent ecological alternative for bioremediation issues because they can oxidize persistent xenobiotic compounds. The production and characterization of extracellular laccases from saprotrophic fungi from disturbed environments have been scarcely explored, even though this could diversify their functional characteristics and expand the conditions in which they carry out their catalysis. Agrocybe pediades, isolated from a disturbed forest, produces an extracellular laccase in liquid culture. The enzyme was purified, identified and characterized. Copper and hexachlorobenzene do not function as inducers for the laccase produced. Partial amino acid sequences were obtained by LC-MS/MS that share similarity with laccases from other fungi. Purified laccase is a monomer with a molecular mass between 55-60 kDa and had an optimum activity at pH 5.0 and the optimum temperature at 45 °C using 2,6-dimethoxyphenol (2,6-DMP) as substrate. The Km and Vmax also determined with 2,6-DMP were 100 µM and 285 µmol∙min-1∙mg-1, respectively, showing that the laccase of A. pediades has a higher affinity for this substrate than that of other Agaricales. These features could provide a potential catalyst for different toxic substrates and in the future laccase could be used in environmental recovery processes.

A new host-targeted antiviral cyclolignan (SAU-22.107) for Dengue Virus infection in cell cultures. Potential action mechanisms based on cell imaging.

Dengue virus (DENV) infection is the most arbovirosis in the world. However, medications have not been approved for its treatment. Drug discovery based on the host-targeted antiviral (HTA) constitutes a new promising strategy, considering their high genetic barrier to resistance and the low probability of selecting drug resistance strains. In this study, we have tested fifty-seven podophyllotoxin-related cyclolignans on DENV-2 infected cells and found the most promising compound was S.71. Using cellular and molecular biology experiments, we have discovered that the new lignan altered the distribution of microtubules, induced changes in cell morphology, and caused retraction of the rough endoplasmic reticulum. In addition, the compound alters the viral envelope protein and the double-stranded RNA, while there is a decrease in negative-strand RNA synthesis; especially when the compound was added between 6- and 12-hours post-infection. Altogether, S.71 decreases the viral yield through an HTA-related mechanism of action, possibly altering the DENV genome replication and/or polyprotein translation, through the alteration of microtubule distribution and endoplasmic reticulum deterioration. Finally, pharmacokinetic predictors show that S.71 falls within the standard ranges established for drugs.

Electroconvulsive Therapy in Psychiatric Disorders: A Narrative Review Exploring Neuroendocrine-Immune Therapeutic Mechanisms and Clinical Implications.

Electroconvulsive therapy (ECT) is based on conducting an electrical current through the brain to stimulate it and trigger generalized convulsion activity with therapeutic ends. Due to the efficient use of ECT during the last years, interest in the molecular bases involved in its mechanism of action has increased. Therefore, different hypotheses have emerged. In this context, the goal of this review is to describe the neurobiological, endocrine, and immune mechanisms involved in ECT and to detail its clinical efficacy in different psychiatric pathologies. This is a narrative review in which an extensive literature search was performed on the Scopus, Embase, PubMed, ISI Web of Science, and Google Scholar databases from inception to February 2022. The terms "electroconvulsive therapy", "neurobiological effects of electroconvulsive therapy", "molecular mechanisms in electroconvulsive therapy", and "psychiatric disorders" were among the keywords used in the search. The mechanisms of action of ECT include neurobiological function modifications and endocrine and immune changes that take place after ECT. Among these, the decrease in neural network hyperconnectivity, neuroinflammation reduction, neurogenesis promotion, modulation of different monoaminergic systems, and hypothalamus-hypophysis-adrenal and hypothalamus-hypophysis-thyroid axes normalization have been described. The majority of these elements are physiopathological components and therapeutic targets in different mental illnesses. Likewise, the use of ECT has recently expanded, with evidence of its use for other pathologies, such as Parkinson's disease psychosis, malignant neuroleptic syndrome, post-traumatic stress disorder, and obsessive-compulsive disorder. In conclusion, there is sufficient evidence to support the efficacy of ECT in the treatment of different psychiatric disorders, potentially through immune, endocrine, and neurobiological systems.

Fiber Optic Sensors for Vital Signs Monitoring. A Review of Its Practicality in the Health Field.

Vital signs not only reflect essential functions of the human body but also symptoms of a more serious problem within the anatomy; they are well used for physical monitoring, caloric expenditure, and performance before a possible symptom of a massive failure-a great variety of possibilities that together form a first line of basic diagnosis and follow-up on the health and general condition of a person. This review includes a brief theory about fiber optic sensors' operation and summarizes many research works carried out with them in which their operation and effectiveness are promoted to register some vital sign(s) as a possibility for their use in the medical, health care, and life support fields. The review presents methods and techniques to improve sensitivity in monitoring vital signs, such as the use of doping agents or coatings for optical fiber (OF) that provide stability and resistance to the external factors from which they must be protected in in vivo situations. It has been observed that most of these sensors work with single-mode optical fibers (SMF) in a spectral range of 1550 nm, while only some work in the visible spectrum (Vis); the vast majority, operate through fiber Bragg gratings (FBG), long-period fiber gratings (LPFG), and interferometers. These sensors have brought great advances to the measurement of vital signs, especially with regard to respiratory rate; however, many express the possibility of monitoring other vital signs through mathematical calculations, algorithms, or auxiliary devices. Their advantages due to miniaturization, immunity to electromagnetic interference, and the absence of a power source makes them truly desirable for everyday use at all times.

Fiber Optic Sensors: A Review for Glucose Measurement.

Diabetes mellitus is a chronic metabolic disorder, being globally one of the most deadly diseases. This disease requires continually monitoring of the body's glucose levels. There are different types of sensors for measuring glucose, most of them invasive to the patient. Fiber optic sensors have been proven to have advantages compared to conventional sensors and they have great potential for various applications, especially in the biomedical area. Compared to other sensors, they are smaller, easy to handle, mostly non-invasive, thus leading to a lower risk of infection, high precision, well correlated and inexpensive. The objective of this review article is to compare different types of fiber optic sensors made with different experimental techniques applied to biomedicine, especially for glucose sensing. Observations are made on the way of elaboration, as well as the advantages and disadvantages that each one could have in real applications.

Internal oblique line implants in severe mandibular atrophies.

BACKGROUND: Maxillary atrophy may be related to mechanical, inflammatory or systemic factors, being a consequence of a reduction in the amount and quality of available bone. Several surgical techniques have been developed for the restoration of bone volume needed for placing dental implants; guided bone regeneration or three-dimensional reconstructions with autologous bone, inter alia, are techniques described in the literature which demonstrate this, all of which preceded by a proper prosthetic surgical assessment. Even when the majority of authors recommend the use of these techniques prior to placing implants, it has been shown that implants with a smaller diameter and length may be placed in severely atrophied jaws without the need for performing any surgery, offering excellent results. MATERIAL AND METHODS: Twenty-four (24) implants were placed in six patients with severe mandibular atrophy. The implants were placed in the anterior sector and on an internal oblique line. Patients were rehabilitated with a total implant-supported prosthesis, with monitoring over a 10-year period. RESULTS: After a 12-month monitoring period, all the patients presented successful rehabilitation. Marginal bone loss in general (n=24 implants) was +0.11 mm ± 0.53. In the implants in zones 1 and 4 (posterior) it was +0.06 mm ± 0.48 and in implants in zones 2 and 3 (anterior), +0.14 mm ± 0.57. CONCLUSIONS: Implants can be placed in the anterior zone and on an internal oblique line in patients with severe mandibular atrophy, using a diameter and length adapted to bone availability, for later prosthetic rehabilitation, offering satisfactory results since phonetic and masticatory function can be restored, as well as facial and buccal aesthetics, in a single surgical operation, with minimum morbidity. Key words:Severe atrophy, implants, bone grafts, ridge atrophy, internal oblique line.

Assessment of the antinociceptive and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea.

Context: Since there is still a great need to search for plant species with antinociceptive and anti-inflammatory activities, Diploptropis purpurea (Rich.) Amshoff (Fabaceae) is studied for the first time. Objective: This evaluates the analgesic and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea (MEDP). Material and methods: The anti-inflammatory and analgesic effects of MEDP of D. purpurea were evaluated in vivo. The antinociceptive activity was assessed in CD1 male mice were treated by oral gavage with 500 mg/kg of MEDP 30 min before submitting to acetic acid-induced abdominal writhing, hot-plate, and formalin tests. Paws oedema induced by carrageenan, histamine or serotonin were performed in male Sprague-Dawley rats to determinate the anti-inflammatory activity. Results: Oral administration of MEDP produced significant antinociceptive effects on the inflammatory phase in the formalin test [12.0 s versus 72.5 s in carboxymethyl cellulose (CMC) control group]. MEDP produced an analgesic effect in the hot-plate model, although the effect was modest compared to tramadol (40 and 60%, respectively). The oral administration of MEDP in a dose of 500 mg/kg showed maximum inhibition (75.1%) after 0.5 h in carrageenan-induced oedema, but it did not modify histamine or serotonin-induced oedemas. Discussion and conclusion: In the peripheral nociception model, acetic acid-induced abdominal writhing, the MEDP did not show a protective effect, but its analgesic effects were evident in the inflammatory phase of the formalin test and in the hot-plate model. These results show that the anti-inflammatory effect was accompanied by a reduction in the perception of painful stimuli.

Offset femoral en los resultados clínicos y funcionales de los pacientes / Femoral offset in the clinical and functional results of patients; Le déport fémoral dans les résultats cliniques et fonctionnels des patients

Introducción: La restauración de las fuerzas biomecánicas a través del ajuste del offset y la longitud de miembros se ha convertido en un objetivo importante cuando el cirujano busca un buen resultado funcional postoperatorio. Sin embargo, las ventajas clínicas de la restauración del offset femoral y las complicaciones del fallo en la restauración no han sido claramente establecidas. Objetivo: Evaluar el efecto del offset o voladizo femoral en los resultados clínicos y funcionales de los pacientes. Adquisición de la evidencia: Se realizó una exploración en la base de datos Pubmed, con las palabras clave: artroplastia de cadera, prótesis de cadera, resultado clínico y resultado funcional.Se buscaron artículos publicados entre 2008 y 2018, basados en humanos y escritos en inglés, español o francés. Se seleccionaron seis artículos que incluían la presencia de una medición radiológica del offset femoral claramente explicada, escalas validadas y análisis comparativo. Resultados: La literatura consultada reflejó resultados heterogéneos. En el grupo de pacientes con offset disminuido, un artículo mostró menos función. En otro estudio se observó mejor puntuación en el grupo de enfermos con offset aumentado. A su vez, en una investigación se comprobó menos dolor en el grupo de offset disminuido. Conclusiones: Debido a la inconsistencia en los resultados y en las metodologías empleadas, no ha sido posible reconocer el beneficio clínico y funcional de la restauración del offset. Algunos autores incluidos en esta revisión, después de no encontrar diferencias estadísticamente significativas, afirmaron que la restauración o el aumento del offset femoral aportó buenos resultados, sin efectos negativos(AU)

Introduction: The restoration of biomechanical forces through offset adjustment and limb length has become an important objective when the surgeon seeks a good postoperative functional result. However, the clinical advantages of femoral offset restoration and complications of restoration failure have not been clearly established. Objective: To evaluate the effect of offset or femoral cantilever on the clinical and functional results of the patients. Acquisition of evidence: An exploration was carried out in the Pubmed database, with the keywords: hip arthroplasty, hip prosthesis, clinical result and functional result. We searched for articles published from 2008 to 2018, based on humans and written in English, Spanish or French. Six articles were selected because they clearly explained the presence of a radiological measurement of the femoral offset, including validated scales and comparative analysis. Results: The literature consulted reflected heterogeneous results. In the group of patients with decreased offset, one article showed less function. In another study, a better score was observed in the group of patients with increased offset. In turn, one investigation reported less pain was found in the reduced offset group. Conclusions: Due to the inconsistency in the results and the methodologies used, it has not been possible to recognize the clinical and functional benefit of offset restoration. Some authors included in this review, after not finding statistically significant differences, stated that the restoration or increase of the femoral offset provided good results, without negative effects(AU)

Leptospirosis humana: un abordaje epidemiológico desde los factores ambientales / Human leptospirosis: an epidemiologic approach from environmental factors

Introducción: la leptospirosis es una enfermedad infecciosa zoonótica. La vía por la que el hombre puede enfermar está relacionada con el medio natural y su calidad. Objetivo: describir aspectos epidemiológicos de la leptospirosis y la influencia de los factores ambientales en la incidencia de la enfermedad. Métodos: se realizó una revisión bibliográfica relacionada con las formas clínicas de la enfermedad, diagnóstico y tratamiento preventivo, así como la influencia de los factores ambientales en la incidencia de la enfermedad. Conclusiones: la leptospirosis es una enfermedad en la que el médico de la atención primaria ejerce un papel fundamental al tener un pensamiento epidemiológico y poder realizar un diagnóstico oportuno ante la sospecha de un paciente con síntomas clínicos; y la identificación de grupos riesgo; para orientar las medidas de prevención relacionadas con la enfermedad, debido a que el agente causal utiliza el medio ambiente natural o creado por el hombre con condiciones favorables para sobrevivir y pasar al huésped susceptible(AU)

Introduction: Leptospirosis is an infectious zoonotic disease. The way the human being can become sick is related to the natural environment and its quality. Objective: To describe epidemiological aspects of leptospirosis and the influence of environmental factors on the disease incidence. Methods: A bibliographic review was carried out considering the disease's clinical forms, diagnosis and preventive treatment, as well as the influence of environmental factors on the disease incidence. Conclusions: Leptospirosis is a disease in which the primary care physician plays a fundamental role in having an epidemiological approach and being able to make a timely diagnosis when a patient is suspected with clinical symptoms, and the identification of risk groups, to guide the prevention measures related to the disease, because the causal agent uses the natural or man-made environment with favorable conditions to survive and pass to the susceptible host(AU)

Mycobacterium smegmatis proteoliposome induce protection in a murine progressive pulmonary tuberculosis model.

Tuberculosis (TB) remains an important cause of mortality and morbidity. The TB vaccine, BCG, is not fully protective against the adult form of the disease and is unable to prevent its transmission although it is still useful against severe childhood TB. Hence, the search for new vaccines is of great interest. In a previous study, we have shown that proteoliposomes obtained from Mycobacterium smegmatis (PLMs) induced cross reactive humoral and cellular response against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLMs, a murine model of progressive pulmonary TB was used. Animals immunized with PLMs with and without alum (PLMs/PLMsAL respectively) showed protection compared to non-immunized animals. Mice immunized with PLMsAL induced similar protection as that of BCG. Animals immunized with BCG, PLMs and PLMsAL showed a significant decrease in tissue damage (percentage of pneumonic area/lung) compared to non-immunized animals, with a more prominent effect in BCG vaccinated mice. The protective effect of the administration of PLMs in mice supports its future evaluation as experimental vaccine candidate against Mtb.

Uprolides N, O and P from the Panamanian Octocoral Eunicea succinea.

Three new diterpenes, uprolide N (1), uprolide O (2), uprolide P (3) and a known one, dolabellane (4), were isolated from the CH2Cl2-MeOH extract of the gorgonian octocoral Eunicea succinea, collected from Bocas del Toro, on the Caribbean coast of Panama. Their structures were determined using spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HRMS) together with molecular modeling studies. Compounds 1-3 displayed anti-inflammatory properties by inhibiting production of Tumor Necrosis Factor (TNF) and Interleukin (IL)-6 induced by lipopolysaccharide (LPS) in murine macrophages.

Data set of the protein expression profiles of Luminal A, Claudin-low and overexpressing HER2(+) breast cancer cell lines by iTRAQ labelling and tandem mass spectrometry.

Breast cancer is the most common and the leading cause of mortality in women worldwide. There is a dire necessity of the identification of novel molecules useful in diagnosis and prognosis. In this work we determined the differentially expression profiles of four breast cancer cell lines compared to a control cell line. We identified 1020 polypeptides labelled with iTRAQ with more than 95% in confidence. We analysed the common proteins in all breast cancer cell lines through IPA software (IPA core and Biomarkers). In addition, we selected the specific overexpressed and subexpressed proteins of the different molecular classes of breast cancer cell lines, and classified them according to protein class and biological process. Data in this article is related to the research article "Determination of the protein expression profiles of breast cancer cell lines by Quantitative Proteomics using iTRAQ Labelling and Tandem Mass Spectrometry" (Calderón-González et al. [1] in press).

Sepsis severa y shock séptico en la Unidad de Cuidados IntensivosPediátrico de Sancti Spíritus / Severe sepsis and septic shock in the Intensive Care Unit of José Martí Pediatric Hospital of Sancti Spíritus

Fundamento: La sepsis severa y el shock séptico constituyen una de las causas de morbilidad y mortalidad en la población pediátrica mundialmente. Se ha observado en los últimos años un incremento de los pacientes que ingresan en estos estadios de la sepsis en la Unidad de Cuidados Intensivos Pediátricos de Sancti Spíritus. Objetivo: Describir las características clínico epidemiológicas de la sepsis severa y el shock séptico en la Unidad de Cuidados Intensivos Pediátricos de Sancti Spíritus del 2005 al 2008. Metodología: Se realizó un estudio descriptivo retrospectivo de pacientes ingresados en la Unidad de Cuidados Intensivos Pediátricos de Sancti Spíritus con sepsis severa y shock séptico en el periodo estudiado, con las variables edad, sexo, factores de riesgo por sepsis, lugar de referencia a la Unidad de Cuidados Intensivos, estadio de la sepsis, focalización, disfunción multiorgánica, tratamiento empleado, estado al egreso. Resultados: Ingresaron en estadio de sepsis severa y shock séptico 32 pacientes (43,9 %); fueron más afectados los menores de un año (62,5 %), menores de tres meses (37,5 %) y con enfermedad crónica subyacente (37,5 %). El 90.6 % fue referido del cuerpo de guardia. Predominó la focalización de la infección en el aparato respiratorio, digestivo y la infección no focalizada. La mayoría de los pacientes recibió fluidoterapia entre 20 y 40 ml/kg en la primera hora, el uso de antibióticos y drogas vasoactivas fue oportuno. El 75 % evolucionó a la disfunción multiorgánica y el 46,88 % falleció, este representó el 27,8 % de la mortalidad hospitalaria. Conclusiones: la mortalidad por sepsis severa y shock séptico es elevada, muere uno de cada 2,1 pacientes.

Background: severe sepsis and septic shock are one of the causes of morbidity and mortality in the pediatric population worldwide. There has been an increase in patients admitted with these stages of sepsis in recent years in the Pediatric Intensive Care Unit of Sancti Spíritus. Objective: to describe the clinical and epidemiological characteristics of severe sepsis and septic shock in the Pediatric Intensive Care Unit of Sancti Spíritus from 2005 to 2008. Methodology: a retrospective study of patients admitted to the Pediatric Intensive Care Unit of Sancti Spíritus with severe sepsis and septic shock in the studied period with the variables age, sex, risk factors for sepsis, place of reference to the Intensive Care Unit, stage of sepsis, targeting, multiple organ dysfunction, used treatment and discharge status. Results: 32 patients were admitted with severe sepsis stadium and septic shock (43.9 %); most affected were children under one year (62.5 %), less than 3 months (37.5 %) and underlying chronic illness (37.5 %). 90.6 % were referred from the emergency rooms. The focus of infection in the respiratory, gastrointestinal apparatus and unfocused infection prevailed. Most of the patients received fluid between 20 and 40 ml/kg in the first hour, the use of antibiotics and vasoactive drugs was appropriate. 75 % progressed to multiorgan dysfunction and 46.88 % died, this accounted for 27.8 % of hospital mortality. Conclusions: the mortality from severe sepsis and septic shock is high, die 1 for each 2.1 patients.

Protective capacity of proteoliposomes from Mycobacterium bovis BCG in a mouse model of tuberculosis.

Tuberculosis (TB) is one of the most important causes of mortality and morbidity due to infectious diseases. BCG, the vaccine in use, is not fully protective against TB. In a previous study, we have shown that proteoliposomes (outer membrane extracts), obtained from BCG (PLBCG) were able to induce humoral immune responses against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLBCG alone or as a booster with BCG, a murine model of progressive pulmonary TB was used. Animals immunized with PLBCG adjuvanted with alum (PLBCG-Al) showed similar protection to that conferred by BCG. The group immunized with PLBCG-Al as a booster to BCG gave superior protection than BCG as evidenced by a reduction of bacterial load in lungs 2 months after infection with Mtb. Animals immunized with BCG, PLBCG-Al and this formulation as a booster of BCG, showed a significant decrease of tissue damage (percentage of pneumonic area/lung) compared with non-immunized animals. These results demonstrate that immunization with PLBCG-Al alone or as a booster to BCG induce appropriate protection against challenge with Mtb in mice and support the future evaluation of PLBCG as a promising vaccine candidate against Mtb.

Bacterial outer membrane vesicles and vaccine applications.

Vaccines based on outer membrane vesicles (OMV) were developed more than 20 years ago against Neisseria meningitidis serogroup B. These nano-sized structures exhibit remarkable potential for immunomodulation of immune responses and delivery of meningococcal antigens or unrelated antigens incorporated into the vesicle structure. This paper reviews different applications in OMV Research and Development (R&D) and provides examples of OMV developed and evaluated at the Finlay Institute in Cuba. A Good Manufacturing Practice (GMP) process was developed at the Finlay Institute to produce OMV from N. meningitidis serogroup B (dOMVB) using detergent extraction. Subsequently, OMV from N. meningitidis, serogroup A (dOMVA), serogroup W (dOMVW), and serogroup X (dOMVX) were obtained using this process. More recently, the extraction process has also been applied effectively for obtaining OMV on a research scale from Vibrio cholerae (dOMVC), Bordetella pertussis (dOMVBP), Mycobacterium smegmatis (dOMVSM), and BCG (dOMVBCG). The immunogenicity of the OMV has been evaluated for specific antibody induction, and together with functional bactericidal and challenge assays in mice has shown their protective potential. dOMVB has been evaluated with non-neisserial antigens, including with a herpes virus type 2 glycoprotein, ovalbumin, and allergens. In conclusion, OMV are proving to be more versatile than first conceived and remain an important technology for development of vaccine candidates.