Selenium bioactive compounds produced by beneficial microbes.

Selenium (Se) is an essential trace element present as selenocysteine (SeCys) in selenoproteins, which have an important role in thyroid metabolism and the redox system in humans. Se deficiency affects between 500 and 1000 million people worldwide. Increasing Se intake can prevent from bacterial and viral infections. Se deficiency has been associated with cancer, Alzheimer, Parkinson, decreased thyroid function, and male infertility. Se intake depends on the food consumed which is directly related to the amount of Se in the soil as well as on its availability. Se is unevenly distributed on the earth's crust, being scarce in some regions and in excess in others. The easiest way to counteract the symptoms of Se deficiency is to enhance the Se status of the human diet. Se salts are the most toxic form of Se, while Se amino acids and Se-nanoparticles (SeNPs) are the least toxic and most bio-available forms. Some bacteria transform Se salts into these Se species. Generally accepted as safe selenized microorganisms can be directly used in the manufacture of selenized fermented and/or probiotic foods. On the other hand, plant growth-promoting bacteria and/or the SeNPs produced by them can be used to promote plant growth and produce crops enriched with Se. In this chapter we discuss bacterial Se metabolism, the effect of Se on human health, the applications of SeNPs and Se-enriched bacteria, as well as their effect on food fortification. Different strategies to counteract Se deficiency by enriching foods using sustainable strategies and their possible implications for improving human health are discussed.

Effect of immersive visualization technologies on cognitive load, motivation, usability, and embodiment.

Virtual reality (VR) is a promising tool to promote motor (re)learning in healthy users and brain-injured patients. However, in current VR-based motor training, movements of the users performed in a three-dimensional space are usually visualized on computer screens, televisions, or projection systems, which lack depth cues (2D screen), and thus, display information using only monocular depth cues. The reduced depth cues and the visuospatial transformation from the movements performed in a three-dimensional space to their two-dimensional indirect visualization on the 2D screen may add cognitive load, reducing VR usability, especially in users suffering from cognitive impairments. These 2D screens might further reduce the learning outcomes if they limit users' motivation and embodiment, factors previously associated with better motor performance. The goal of this study was to evaluate the potential benefits of more immersive technologies using head-mounted displays (HMDs). As a first step towards potential clinical implementation, we ran an experiment with 20 healthy participants who simultaneously performed a 3D motor reaching and a cognitive counting task using: (1) (immersive) VR (IVR) HMD, (2) augmented reality (AR) HMD, and (3) computer screen (2D screen). In a previous analysis, we reported improved movement quality when movements were visualized with IVR than with a 2D screen. Here, we present results from the analysis of questionnaires to evaluate whether the visualization technology impacted users' cognitive load, motivation, technology usability, and embodiment. Reports on cognitive load did not differ across visualization technologies. However, IVR was more motivating and usable than AR and the 2D screen. Both IVR and AR rea ched higher embodiment level than the 2D screen. Our results support our previous finding that IVR HMDs seem to be more suitable than the common 2D screens employed in VR-based therapy when training 3D movements. For AR, it is still unknown whether the absence of benefit over the 2D screen is due to the visualization technology per se or to technical limitations specific to the device.

Non-invasive clinical and microscopic evaluation of the response to treatment with clobetasol cream vs. calcipotriol/betamethasone dipropionate foam in mild to moderate plaque psoriasis: an investigator-initiated, phase IV, unicentric, open, randomized clinical trial.

BACKGROUND: Treatment response for psoriasis is typically evaluated using clinical scores. However, patients can relapse after clinical clearance, suggesting persistent inflammation. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) can non-invasively improve treatment response assessment. OBJECTIVES: To compare the clinical and non-invasive microscopic features in a psoriatic target lesion treated with clobetasol cream or calcipotriol/betamethasone dipropionate foam (Cal/BD foam). METHODS: Prospective, unicentric, open, randomized clinical trial comparing clinical data [total clinical score (TCS)] and microscopic data (dermoscopy, RCM and OCT) in psoriasis patients treated with clobetasol or Cal/BD foam. RESULTS: We included 36 adult patients (22 men). At week 4, more patients treated with Cal/BD foam achieved TCS ≤1 than with clobetasol (63.2% vs. 18.8%, P = 0.016). Treatment satisfaction was higher with Cal/BD foam (P < 0.03). Microscopically, Cal/BD foam induced more reduction in epidermal thickness at week 4 (P < 0.049). Dilated horizontal blood vessels were more common with clobetasol than with Cal/BD foam at week 8 (69.2% vs. 31.2%, P = 0.159). If epidermal hyperplasia was noted at baseline, the response was poorer with clobetasol (P = 0.029). LIMITATIONS: Small sample size, open study, imaging sampling bias. CONCLUSION: Cal/BD foam is more effective than clobetasol, has better patient satisfaction and induces greater reduction in the hyperkeratosis/acanthosis, regardless of baseline epidermal hyperplasia.

Guía práctica de manejo inicial del dolor abdominal recurrente en la infancia / Practical guide for initial management of recurrent abdominal pain in children

El dolor abdominal recurrente (DAR) en niños es uno de los motivos de consulta más frecuentes por enfermedad crónica. Se estima que afecta a un 10% de niños y dolescentes (4-25% según distintas series)(1) y con frecuencia puede tener una gran repercusión familiar, económica y en la calidad de vida del paciente, interferir con su actividad diaria, provocar absentismo escolar, pruebas complementarias, visitas a urgencias e incluso hospitalizaciones(1,2). Predomina en niñas hasta la pubertad (odds ratio para el sexo femenino 1,5), pero después la frecuencia es similar en ambos sexos(3). La mayoría de los casos no tendrán una causa orgánica subyacente ni entrañan gravedad, pero hay que recordar la incertidumbre del médico que debe enfrentarse a esa consulta reiterada, ante la posibilidad de no estar realizando todas las pruebas complementarias necesarias para llegar a un diagnóstico correcto, dada su escasa especificidad clínica habitual. El temor a que se descubra posteriormente en nuestro paciente una causa orgánica o infrecuente para el mismo que hayamos podido pasar por alto, hace que en muchos casos nos enfrentemos con inseguridad a esta situación. Trataremos de hacer comprender mejor este cuadro, simplificando el problema, quizás en exceso, pero en aras a intentar ayudar en su manejo en la práctica clínica

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BCG y Enfermedad de Hansen: estudio clínico epidemiológico / BCG and Hansen disease: clinical epidemiological study

Resumen La enfermedad de Hansen es una infección granulomatosa cuya presentación clínica y severidad depende del estado inmunológico del individuo. Dadas las similitudes en la composición antigénica entre M. tuberculosis y M. leprae, se ha estudiado la utilización de la vacuna BCG frente al Hansen. Objetivo: Determinar la relación del tamaño de la cicatriz de BCG y la severidad clínica de los pacientes con Hansen en el Instituto de Biomedicina. Métodos: Se realizó un estudio descriptivo con revisión de 150 historias clínicas de pacientes con antecedente de vacunación con BCG en la infancia y diagnóstico de Hansen entre 2008 y 2018. Se registraron las formas clínicas y severidad de la enfermedad, fenómenos reaccionales y tamaño de la cicatriz de BCG. Resultado y discusión: Existe una relación entre el tamaño de la cicatriz de BCG y la forma clínica de la enfermedad. Los pacientes con lepra lepromatosa (LL) tienden a tener ausencia de cicatriz, a diferencia de los pacientes borderline tubercoloide (BT) y lepra indeterminada (LI), que tienen un tamaño mayor de ella. Observamos mayor frecuencia de fenómenos reaccionales tipo II en pacientes sin cicatriz de BCG. Los pacientes con enfermedad más severa mostraron una tendencia a presentar tamaños menores de la cicatriz de BCG. Dichos hallazgos se corresponden con los reportados por Convit y reflejan la importancia de la respuesta inmunitaria frente a la micobacteria para controlar la enfermedad. Además, abre una opción terapéutica a seguir evaluando, que es el papel de la BCG como profilaxis y protector frente a formas severas del Hansen.

Summary Hansen's disease is a granulomatous infection whose clinical presentation and severity depend on the immunological state of the patient. Given similarities in the antigenic composition between M. tuberculosis and M. leprae, because of this the use of BCG vaccine against Hansen has been studied. Objective: Determinate the relationship between the size of the BCG scar and the clinical severity of patients with Hansen in the Biomedicine Institute. Methods: A descriptive study was carried out with a clinical history review of patients with BCG vaccination and Hansen's diagnosis between 2008 and 2018. Clinical forms and severity of the disease, reaction phenomena, and size of the BCG scar were registered. Outcome and discussion: There is a relationship between the size of BCG scar and the clinical form of the disease. Patients with LL tend to have an absence of scar in a different way of the patients with BT y LI patients who have a larger size of the scar. We observed a greater frequency of type II reaction phenomena in patients without BCG scar. Patients with more severe disease shown a tendency to present small sizes of BCG scar. These findings correspond to those reported by Convit and reflects the importance of the innate response to mycobacteria for control the disease. In addition, it has had open a therapeutic tool to continue evaluating, which is the role of BCG as prophylaxis and protector against severe forms of Hansen.

Protection of GnRH analogue by chitosan-dextran sulfate nanoparticles for intravaginal application in rabbit artificial insemination.

The present study was designed to prove new rabbit insemination extenders containing aminopeptidase inhibitors (AMIs) with or without chitosan (CS)-dextran sulfate (DS) nanoparticles entrapping the GnRH analogue. In addition, different hormone concentrations were tested in these extenders, evaluating their in vivo effect on rabbit reproductive performance after artificial insemination. A total of 911 females were inseminated with semen diluted with the four experimental extenders (C4 group: 4 µg buserelin/doe in control medium (Tris-citric acid-glucose supplemented with bestatin 10 µM and EDTA 20 mM), C5 group: 5 µg of buserelin/doe in control medium, Q4 group: 4 µg of buserelin/doe into CS-DS nanoparticles in control medium, Q5 group: 5 µg of busereline/doe into CS-DS nanoparticles in control medium). Results showed that fertility was significantly lower in C4 group compared to C5, Q5 and Q4 groups (0.7 versus 0.85, 0.85 and 0.82, respectively). On the contrary, prolificacy was similar in the four experimental groups studied (P > 0.05). We conclude that the CS-DS nanoparticles prepared by a coacervation process as carrier for buserelin acetate allows reducing the concentration of hormone used in extenders supplemented with bestatin and EDTA without affecting the fertility and prolificacy of rabbit females.

Insemination extender supplementation with bestatin and EDTA has no effect on rabbit reproductive performance.

The addition of aminopeptidase inhibitors (AMIs) to rabbit semen extenders could be a solution to decrease the hormone degradation (GnRH) by the aminopeptidases existing in the seminal plasma. Therefore, the quantity of GnRH needed to induce ovulation in doe would be comparable with the amount administered intramuscularly (i.m.). This study was conducted to evaluate the effects of two AMIs (bestatin and EDTA) on rabbit semen quality parameters, ß nerve growth factor (ß-NGF) degradation and reproductive performance after artificial insemination. Results showed that seminal quality was not affected by the incubation with AMIs; the values of motility, acrosome integrity and sperm viability were not significantly different between the AMIs and the control groups (positive i.m. and negative intravaginally without AMIs). In addition, the aminopeptidase activity of seminal plasma was inhibited in a 55.5% by the AMIs as well as ß-NGF degradation. On the other hand, regarding the effect of AMIs on reproductive performance, our results showed that the presence of bestatin and EDTA did neither affect fertility (85.3 vs. 88.6%), nor the prolificacy rate (10.12 vs. 10.51 kits per delivery), comparing AMIs group to positive control group, respectively. We conclude that the addition of specific AMIs in the rabbit semen extender has no effect on reproductive performance. Therefore, due to the fact that AMIs inhibit part of the aminopeptidase activity that degrades the GnRH analogue and ß-NGF, they could be used to develop new extenders with less hormone concentration.

Chitosan-dextran sulphate nanoparticles for GnRH release in rabbit insemination extenders.

This study was designed to develop chitosan (CS)-dextran sulphate (DS) nanoparticles containing a GnRH analogue and to study their effect on rabbit (Oryctolagus cuniculus) semen quality. Six experimental extenders were tested as follows: (control) Tris-citric acid-glucose (TCG), (1) 0.05% CS-0.05% DS (4:1), (2) 0.1% CS-0.05% DS (4:1), (3) 0.05% CS-0.05% DS (3:1), (4) 0.1% CS-0.05% DS (3:1), (5) 0.1% CS-0.05% DS (2:1). CS and DS were dissolved in TCG medium, and nanoparticles were obtained through magnetic stirring. Rabbit seminal samples were incubated up to 5 hr at 37°C in the extenders, and seminal quality was evaluated. The entrapment efficiency was 40%-50%. After 5 hr at 37°C, a 20% of the hormone was released. Results showed that the presence of CS-DS nanoparticles did not affect rabbit semen motility, viability and membrane functionality; however, acrosome integrity was significantly higher versus control (p < .001).

Can the Genetic Origin Affect Rabbit Seminal Plasma Protein Profile along the Year?

The study was designed to evaluate the influence of genetic origin on rabbit seminal plasma protein profile variation along the year. Seminal plasma of rabbits from line A (maternal line) and R (paternal line) collected during a natural year was subjected to polyacrylamide gel electrophoresis (SDS-PAGE). The electrophoretic profile of rabbit seminal plasma resulted in multiple protein bands of different intensity ranging from 9 to 240 kDa. Results showed that seven protein bands were significantly different between genetic lines, and among these, three protein bands were significantly different between seasons. The differentially expressed proteins were identified by MALDI-TOF/TOF or LC-MS/MS analysis and were the following ones: FAM115E-like (220, 113 and 59 kDa), ectonucleoside triphosphate diphosphohydrolase 3 isoform X2 (72 kDa), annexin A5 (32 kDa), lipocalin allergen Ory c 4 precursor (19 kDa), and haemoglobin subunit zetalike (13 kDa) between genetic lines and FAM115E-like (113 kDa), haemoglobin subunit zetalike (13 kDa) and ß-nerve growth factor (12 kDa) between seasons. These results indicate that proteins from rabbit seminal plasma are under both seasonal control and genetic control. Furthermore, the differential presence of these proteins could be one of the causes explaining the differences observed in fertility and seminal parameters between these two lines in earlier studies.

Does the inclusion of protease inhibitors in the insemination extender affect rabbit reproductive performance?

The bioavailability of buserelin acetate when added to the seminal dose appears to be determined by the activity of the existing aminopeptidases. Thus, the addition of aminopeptidase inhibitors to rabbit semen extenders could be a solution to decrease the hormone degradation. This study was conducted to evaluate the effect of the protease activity inhibition on rabbit semen quality parameters and reproductive performance after artificial insemination. Seminal quality was not affected by the incubation with protease inhibitors, being the values of motility, viability, and acrosome integrity not significantly different between the protease inhibitors and the control group. In addition, seminal plasma aminopeptidase activity was inhibited in a 55.1% by the protease inhibitors. On the other hand, regarding the effect of protease inhibitors on reproductive performance, our results showed that the presence of protease inhibitors affected the prolificacy rate (9.2 ± 0.26 and 9.3 ± 0.23 vs. 8.2 ± 0.22 total born per litter for negative control, positive control, and aminopeptidase inhibitors group, respectively; P < 0.05), having this group one kit less per delivery. We conclude that the addition of a wide variety of protease inhibitors in the rabbit semen extender negatively affects prolificacy rate. Therefore, the development of new extenders with specific aminopeptidase inhibitors would be one of the strategies to increase the bioavailability of GnRH analogues without affecting the litter size.

FERTILITY PATTERN AND FITNESS OF THE SPANISH-MEXICAN COLONISTS OF CALIFORNIA (1742-1876).

The analysis of fertility in colonizing populations is of great interest, since its individuals experience a major environmental change, and fertility rates can reflect the level of adaptation of the population to its new conditions. Using Northrop's genealogical compilations, this paper examines the fertility pattern of California's early Spanish-Mexican colonists between 1742 and 1876, their fitness levels and their trend across time throughout the colonizing period. A total of 197 women from 599 compiled families who had completed their reproductive period and had at least one child were analysed. The correlations among variables were also analysed in order to infer the relationship between longevity and fertility, and the influence of fertility determinants. The results show a natural fertility pattern, with a very young age at marriage and birth of first child (17.2 and 19.1 years respectively), and also a young age at last childbirth (38.8 years). The population's fitness showed greater values than for contemporary European populations, with 8 of 9.2 children surviving to adulthood, in comparison with 55% of newborns in Finland for the same period, suggesting a good adaptation of the population to their new environmental conditions. No relationship between fertility and lifespan was observed, as has been reported by other authors and in opposition to classical theories. A temporal trend in the number of children, consisting of three different phases, was observed, in accordance with the stability of living conditions in the region.

Automatic prediction of chronic obstructive pulmonary disease exacerbations through home telemonitoring of symptoms.

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease of the lung with a great prevalence and a remarkable socio-economic impact on patients and health systems. Early detection of exacerbations could diminish the adverse effects on patients' health and cut down costs burdened on patients with COPD. A group of 16 patients were telemonitored at home using a novel electronic daily symptoms questionnaire during a 6-months field trial. Recorded data were used to train and validate a Probabilistic Neural Network (PNN) classifier in order to enable the automatic prediction of exacerbations. The proposed system was able to predict COPD exacerbations early with a margin of 4.8 ± 1.8 days (average ± SD). Detection accuracy was 80.5% (33 out of 41 exacerbations were early detected); 78.8% (26 out of 33) of theses detected events were reported exacerbation and 87.5% (7 out of 8) were unreported episodes. The proposed questionnaire and the designed automatic classifier could support the early detection of COPD exacerbations of benefit to both physicians and patients.

Porcine oocyte vitrification in optimized low toxicity solution with open pulled straws.

One of the greatest challenges for reproductive cryobiologists today is to develop an efficient cryopreservation method for human and domestic animal oocytes. The objective of the present study was to optimize a low toxicity solution called VM3 to vitrify porcine oocytes using an open pulled straw (OPS) device and to evaluate the effects on viability, chromosomal organization and cortical granules distribution. Two experiments were conducted in this study. Firstly, we determined the minimum concentration of cryoprotectant present in the VM3 solution required (7.6 M) for vitrification using an OPS device. The appearance of opacity was observed when using a cooling solution at -196°C; no observable opacity was noted as vitrification. In addition, the ultrastructure of oocytes in VM3 or VM3 optimized solution was examined using cryo-scanning electron microscopy. The minimum total cryoprotectant concentration present in VM3 solution necessary for apparent vitrification was 5.6 M when combined with use of an OPS device. Use of both vitrification solutions showed a characteristic plasticized surface. In the second experiment, the relative cytotoxicity of vitrification solutions (VM3 and VM3 optimized) was studied. Oocyte viability, chromosomal organization and the cortical granules distribution were assessed by fluorescent stain. After warming, oocyte survival rate was similar to that of fresh oocytes. The vitrification process significantly reduced correct chromosomal organization and cortical granules distribution rates compared with the fresh oocytes group. However, correct chromosomal organization and cortical granules distribution rates did not differ among oocytes placed in different vitrification solutions. In conclusion, our data demonstrated that the VM3 solution can be optimized and that reduction in concentration to 5.6 M enabled vitrification of oocytes with an OPS device, however use of the VM3 optimised solution had no beneficial effect on vitrification of porcine oocytes.

Effect of cytochalasin B pre-treatment of in vitro matured porcine oocytes before vitrification.

The study tested the efficacy of pre-treating mature porcine oocytes with cytochalasin B before vitrification by the open pulled straw method (OPS) in a low toxicity solution containing ice blockers. The effects of pre-treating the oocytes with 7.5 micrograms per ml cytochalasin B before vitrification on membrane integrity, chromosome organisation and cortical granule distribution were evaluated. When oocytes pre-treated with cytochalasin B before vitrification were compared with control oocytes, similar membrane integrity was observed. In contrast, when both vitrified oocytes groups (treated and untreated with cytochalasin B) were compared with fresh oocytes, significantly lower proportions of oocytes with normal chromosomes aligned regularly on the metaphase plate and peripheral cortical granule distribution were observed. The percentages of oocytes with normal chromosomes aligned regularly on the metaphase plate were similar between those treated or untreated with cytochalasin B before vitrification. Similar results were found for normal cortical granules distribution. Irrespective of previous cytochalasin B exposure, vitrification gave rise to higher abnormal cortical granule distribution percentages. Cytochalasin B pretreatment of oocytes before vitrification does not help to reduce the damage induced by the cryopreservation process of porcine oocytes.

Holoprosencephaly at prenatal diagnosis: analysis of 28 cases regarding etiopathogenic diagnoses.

OBJECTIVE: To assess the likelihood of finding an etiopathogenic cause in an ultrasonographic prenatal diagnosis of holoprosencephaly. MATERIALS AND METHODS: From January 1996 to June 2010, 13 883 prenatal diagnoses through chorionic villus sampling or amniocentesis were made. Every fetus with holoprosencephaly at ultrasound was evaluated. Gestational age, additional ultrasound findings, and fetal karyotype were recorded. Molecular diagnosis and parental karyotype were studied, if relevant. RESULTS: Twenty-eight fetuses were diagnosed with holoprosencephaly (0.20%). All cases had additional ultrasound findings (100%). A definitive etiology was found in 23 cases (82.14%): karyotype was abnormal in 19 (67.9%) and normal in 8 (28.5%) cases. In the normal karyotype group, although molecular testing was performed in a few cases, one mutation of gene SIX 3 was diagnosed, one diagnosis of dysgnathia complex was made, and two fetuses presented Smith-Lemli-Opitz syndrome. No etiopathogenic diagnosis was made in five fetuses. CONCLUSIONS: Our results showed that a definitive etiology can be established in most cases of prenatal holoprosencephaly. Chromosomal anomalies were the most frequent finding. However, in euploid fetuses, molecular diagnosis is worthwhile, as different genes with different inheritance patterns may be responsible for this malformation. Thorough evaluation proved beneficial for assessing more accurate prognosis and recurrence risks.

Resiliencia, Personalidad Resistente y Crecimiento en Cuidadores de Personas con Demencia en el Entorno Familiar: Una Revisión / Resilience, Hardiness and Growth in Dementia Patients' Family Caregivers: A Review

La investigación en torno al cuidado no profesional de mayores con demencia ha proliferado a lo largo de los últimos años, constatando muchos autores que, del mismo modo en que el cuidado se asocia a un buen número de consecuencias negativas, diversos efectos positivos pueden derivarse de esta experiencia. Sin embargo, y a pesar del impacto de la corriente positiva en la actualidad, son muy escasos los estudios que valoran la personalidad resistente (hardiness), la resiliencia y el crecimiento personal en cuidadores. El presente artículo hace una revisión sistemática de las contribuciones más relevantes a este campo, a partir del análisis de nueve publicaciones. Todos estos trabajos evalúan, de un modo cuantitativo, la resiliencia, el hardiness o el crecimiento en familiares de personas con demencia. Las características y resultados de dichos trabajos serán valoradas, teniendo en consideración sus implicaciones para el estudio y la atención a los cuidadores (AU)

In the last few years, research into non professional caregiving for dementia patients has increased, and has shown that such caregiving carries both negative and positive effects. Nevertheless, in spite of the growing influence of positive psychology, studies focused on resilience, hardiness and personal growth in caregivers remain fairly scarce. The present article aimed to systematically review the existing studies on this topic, analyzing nine studies that assess resilience, hardiness or growth in dementia patients' family caregivers. The features and results of these studies will be discussed, considering their implications for the study of, and attention to, caregivers (AU)

Prescription of antibiotics in intensive care units in Latin America: an observational study.

A one-day point prevalence study to investigate the patterns of antibiotic use was undertaken in 43 latin American (LA) intensive care units. Of 510 patients admitted, 231 received antibiotic treatment on the day of the study (45%); in 125 cases (54%) due to nosocomial-acquired infections. The most frequent infection reported was nosocomial pneumonia (43%). Only in 122 patients (53%) were cultures performed before starting antibiotic treatment. 33% of the isolated microorganisms were enterobacteriaceae (40% extended-spectrum beta-lactamase-producing), 23% methicillin-resistant Staphylococcus aureus and 17% carbapenems-resistant non-fermentative Gram-negatives. The antibiotics most frequently prescribed were carbapenems (99/231, 43%); alone (60/99, 60%) or in combination with vancomycin (39/99, 40%). "Restricted" antibiotics (carbapenems, vancomycin, piperacillin-tazobactam, broad-spectrum cephalosporins, tigecycline, polymixins and linezolid) were most frequently indicated in severely ill patients (APACHE II score at admission >15, p=0.0007 and, SOFA score at the beginning of the antibiotic treatment >3, p=0.0000). Only 36% of antibiotic treatments were cultured-directed.Our findings help explain the high rates of multidrug-resistant pathogens in LA settings (i.e. ESBL-producing Gram-negatives) and the severity of the registered patients illnesses.

Lymphoma cell adhesion-induced expression of B cell-activating factor of the TNF family in bone marrow stromal cells protects non-Hodgkin's B lymphoma cells from apoptosis.

This study explores whether lymphoma cell adhesion-induced B cell-activating factor (BAFF) expression in bone marrow stromal cells (BMSCs) protects B lymphoma cells from apoptosis. We first showed protection of lymphoma cells from apoptosis by conditioned medium of a stromal cell-lymphoma cell coculture, either spontaneous or induced by mitoxantrone, implying a role for soluble factor(s) in lymphoma cell survival. Addition of BAFF counteracted mitoxantrone-induced apoptosis and elicited a reduction in spontaneous apoptosis in primary lymphomas, suggesting a role of BAFF in sustaining B-cell survival. Abundant BAFF was detected in the BMSC cell line (HS-5) and primary BMSCs by flow cytometry, RT-PCR and immunoblotting. BAFF levels were 20- to 200-fold higher in BMSCs than in lymphoma cells, and lymphoma cell adhesion to BMSCs augmented BAFF secretion twofold through upregulation of BAFF gene expression. Finally, neutralization of BAFF by TACI-Ig or depletion of BAFF by small hairpin RNA (shRNA) in BMSCs significantly enhanced lymphoma cell response to chemotherapy and overcame stroma-mediated drug resistance, suggesting that lymphoma cells use BMSC-derived BAFF as a survival factor. These findings support the hypothesis that lymphoma cells interact with BMSCs, resulting in stromal niches with high BAFF concentration, and identify BMSC-derived BAFF as a functional determinant for B lymphoma cell survival in the bone marrow environment.