Transient vitamin B5 starving improves mammalian cell homeostasis and protein production.

Maintaining a metabolic steady state is essential for an organism's fitness and survival when confronted with environmental stress, and metabolic imbalance can be reversed by exposing the organism to fasting. Here, we attempted to apply this physiological principle to mammalian cell cultures to improve cellular fitness and consequently their ability to express recombinant proteins. We showed that transient vitamin B5 deprivation, an essential cofactor of central cellular metabolism, can quickly and irreversibly affect mammalian cell growth and division. A selection method was designed that relies on mammalian cell dependence on vitamin B5 for energy production, using the co-expression of the B5 transporter SLC5A6 and a gene of interest. We demonstrated that vitamin B5 selection persistently activates peroxisome proliferator-activated receptors (PPAR), a family of transcription factors involved in energy homeostasis, thereby altering lipid metabolism, improving cell fitness and therapeutic protein production. Thus, stable PPAR activation may constitute a cellular memory of past deprivation state, providing increased resistance to further potential fasting events. In other words, our results imply that cultured cells, once exposed to metabolic starvation, may display an improved metabolic fitness as compared to non-exposed cells, allowing increased resistance to cellular stress.

Anatomical and hormonal description of rootlet primordium development along white lupin cluster root.

Cluster root (CR) is one of the most spectacular plant developmental adaptations to hostile environment. It can be found in a few species from a dozen botanical families, including white lupin (Lupinus albus) in the Fabaceae family. These amazing structures are produced in phosphate-deprived conditions and are made of hundreds of short roots also known as rootlets. White lupin is the only crop bearing CRs and is considered as the model species for CR studies. However, little information is available on CRs atypical development, including the molecular events that trigger their formation. To provide insights on CR formation, we performed an anatomical and cellular description of rootlet development in white lupin. Starting with a classic histological approach, we described rootlet primordium development and defined eight developmental stages from rootlet initiation to their emergence. Due to the major role of hormones in the developmental program of root system, we next focussed on auxin-related mechanisms. We observed the establishment of an auxin maximum through rootlet development in transgenic roots expressing the DR5:GUS auxin reporter. Expression analysis of the main auxin-related genes [TIR, Auxin Response Factor (ARF) and AUX/IAA] during a detailed time course revealed specific expression associated with the formation of the rootlet primordium. We showed that L. albus TRANSPORT INHIBITOR RESPONSE 1b is expressed during rootlet primordium formation and that L. albus AUXIN RESPONSE FACTOR 5 is expressed in the vasculature but absent in the primordium itself. Altogether, our results describe the very early cellular events leading to CR formation and reveal some of the auxin-related mechanisms.

Asthma and atopy prevalence are not reduced among former tuberculosis patients compared with controls in Lima, Peru.

BACKGROUND: Although there are theoretical reasons for believing that asthma and atopy may be negatively correlated with tuberculosis, epidemiological studies have had conflicting findings. OBJECTIVE: To determine if people with confirmed tuberculosis were less likely to be atopic and less likely to have atopic disease including asthma compared to those with no previous tuberculosis. METHODS: Patients in Lima, Peru with a prior history of tuberculosis were identified from clinic records in this cohort study. A representative sample of individuals without a prior tuberculosis diagnosis was recruited from the same community. Allergen skin prick testing was performed to classify atopic status. Allergic rhinitis was identified by history. Asthma was defined by symptoms and spirometry. Eosinophilic airway inflammation was measured using exhaled nitric oxide levels. RESULTS: We evaluated 177 patients with, and 161 individuals without, previous tuberculosis. There was a lower prevalence of atopy among people with prior tuberculosis on univariate analysis (odds ratio 0.57; 95% confidence interval 0.37-0.88) but, after adjustment for potential confounders, this was no longer statistically significant (aOR 0.64, 95% CI 0.41-1.01). The prevalence of allergic rhinitis (aOR 0.76, 95% CI 0.47 to 1.24 and asthma (aOR 1.18, 95% CI 0.69 to 2.00) did not differ significantly between the two groups. We also found no significant difference in the prevalence of elevated exhaled nitric oxide (aOR 1.30, 95% CI 0.78 to 2.17) or a combined index of atopic disease (aOR 0.86, 95% CI 0.54 to 1.36). CONCLUSION: In this urban environment in a middle-income country, prior tuberculosis may be associated with a reduced risk of atopy but does not protect against asthma and atopic disease.

Baseline Predictors of Treatment Outcomes in Children With Multidrug-Resistant Tuberculosis: A Retrospective Cohort Study.

BACKGROUND: Globally, >30 000 children fall sick with multidrug-resistant (MDR) tuberculosis every year. Without robust pediatric data, clinical management follows international guidelines that are based on studies in adults and expert opinion. We aimed to identify baseline predictors of death, treatment failure, and loss to follow-up among children with MDR tuberculosis disease treated with regimens tailored to their drug susceptibility test (DST) result or to the DST result of a source case. METHODS: This retrospective cohort study included all children ≤15 years old with confirmed and probable MDR tuberculosis disease who began tailored regimens in Lima, Peru, between 2005 and 2009. Using logistic regression, we examined associations between baseline patient and treatment characteristics and (1) death or treatment failure and (2) loss to follow-up. RESULTS: Two hundred eleven of 232 (90.9%) children had known treatment outcomes, of whom 163 (77.2%) achieved cure or probable cure, 29 (13.7%) were lost to follow-up, 10 (4.7%) experienced treatment failure, and 9 (4.3%) died. Independent baseline predictors of death or treatment failure were the presence of severe disease (adjusted odds ratio [aOR], 4.96; 95% confidence interval [CI], 1.61-15.26) and z score ≤-1 (aOR, 3.39; 95% CI, 1.20-9.54). We did not identify any independent predictors of loss to follow-up. CONCLUSIONS: High cure rates can be achieved in children with MDR tuberculosis using tailored regimens containing second-line drugs. However, children faced significantly higher risk of death or treatment failure if they had severe disease or were underweight. These findings highlight the need for early interventions that can improve treatment outcomes for children with MDR tuberculosis.

Chronic airflow obstruction after successful treatment of multidrug-resistant tuberculosis.

Cross-sectional studies reveal an association between tuberculosis (TB) and chronic airflow obstruction, but cannot adequately address confounding. We hypothesised that treated pulmonary TB is an independent risk factor for chronic airflow obstruction. The Pulmones Post TB cohort study enrolled participants from Lima, Peru, aged 10-70 years with a history of drug-susceptible (DS)- or multidrug-resistant (MDR)-TB who had completed treatment and were clinically cured. Unexposed participants without TB were randomly selected from the same districts. We assessed respiratory symptoms, relevant environmental exposures, and spirometric lung function pre- and post-bronchodilator. In total, 144 participants with DS-TB, 33 with MDR-TB and 161 unexposed participants were fully evaluated. Compared with unexposed participants, MDR-TB patients had lower lung volumes (adjusted mean difference in forced vital capacity -370 mL, 95% CI -644- -97) and post-bronchodilator airflow obstruction (adjusted OR 4.89, 95% CI 1.27-18.78). Participants who had recovered from DS-TB did not have lower lung volumes than unexposed participants, but were more likely to have a reduced forced expiratory volume in 1 s/forced vital capacity ratio <0.70 (adjusted OR 2.47, 95% CI 1.01-6.03). Individuals successfully treated for TB may experience long-lasting sequelae. Interventions facilitating earlier TB treatment and management of chronic respiratory disease should be explored.

Características de las investigaciones presentadas en el Congreso Peruano de Educación Médica / No disponible

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Calidad de atención y relaciones familiares en la asistencia a los controles del servicio de consulta externa / Quality of care and family relations in assisting controls outpatient service

Para recolectar la información se realizaron 100 visitas domiciliarias; se aplicaron 2 instrumentos para c/u, (calidad de atención y apgar familiar); para la tabulación, se utilizaron tablas de contingencia; la información se presento a razón de disparidad, determinando la fuerza de asociación entre los factores de riesgo estudiados, de acuerdo con las hipótesis planteadas. Se pudo determinar que la insatisfacción de los usuarios para la calidad de los servicios ofertados por el H.M.R.S. es un factor predisponente para inasistencia a los controles por consulta externa. Se identificó que no hay evidencia estadísticamente, que el presentar insatisfacción, representa un factor asociado para la inasistencia a tratamiento por consulta externa. Para la funcionalidad familiar, se demostró que el 96.7% de cada 100 casos presentan disfuncionalidad familiar, y un 89.7% de cada 100 controles también presentan disfunción familiar, demostrando que esta variable es una característica principal de los pacientes mentales en general. Para concluir, la calidad de atención como la funcionalidad familiar, representan un factor predisponente a presentar inasistencia, pero no son la principal causa por la cual los usuarios del Hospital Mental Rudesindo Soto ( HMRS) no acuden a los controles programados por consulta externa de acuerdo a lo investigado.

For the harvesting of the information 100 domiciliary visits were realised; 2 instruments for c/u were applied, (quality of attention and to apgar familiar); for the tabulation, contingency tables were used, and the information I appear at the rate of disparity, determining the force of association between the studied factors of risk, in agreement with the raised hypotheses. With the investigation it was possible to be determined that the dissatisfaction of the users for the quality of the services supplied by the H.M.R.S is a factor prearranger for inasistencia to the controls by external consultation. I identify myself that there is no evidence statistically, that presenting/displaying dissatisfaction, represents a factor associated for the inasistencia treatment by external consultation. For the familiar functionality, one demonstrated that the 96,7% of each 100 cases present/display familiar disfunctionality, and 89,7% of each 100 controls also present/display familiar dysfunction, demonstrating that this variable is a basic characteristics of the mental patients generally. In order to conclude, the quality of attention like the familiar functionality, represents a factor prearranger to present/display inasistencia, but they are not the main cause by which the users of the HMRS do not go to the controls.

Neumonia por mycoplasma pneumoniae en 107 niños de Medellín

Se revisaron las historias de 107 niños con infección respiratoria aguda (IRA) baja que tenían una IgM positiva para Mycoplasma pneumoniae. La edad más afectada fue la de 2 a 6 años (58 por ciento). El tiempo de evolución antes de la consulta fue de 1 a 180 días, con un promedio de 10.7 días. El motivo de consulta más frecuente fue tos (95.3 por ciento), tos prolongada en el 22.45 por ciento, seguida de fiebre (73.5 por ciento), expectoración y rinitis (32.7 por ciento) respectivamente. Al examen se encontró: Sibilancias (67.3 por ciento), estertores crepitantes (30.8 por ciento) fiebre (37 por ciento), faringitis (15.9 por ciento), otitis (13.1 por ciento) y sinusitis (12 por ciento). El hallazgo radiológico más frecuente fue atrapamiento de aire (21.8 por ciento) derrame pleural abacteriano. La proteína C reactiva fue de < 4 mg por ciento en el 70.8 por ciento. El tratamiento fue a base de macrólidos, principalmente claritromicina (72-6 por ciento), broncodilatadores (40 por ciento) y estos asociados a esteroides en el 25.8 por ciento de los casos