Evaluación del estado nutricional en la enfermedad de Alzheimer y su influencia en la progresión tras el diagnóstico / Nutritional status assessment in Alzheimer disease and its influence on disease progression

Introducción: Las deficiencias nutricionales son frecuentes en la enfermedad de Alzheimer (EA), incluso en fases iniciales. El deterioro nutricional (DN) puede asociarse con una progresión más rápida de la enfermedad. El objetivo fue describir la frecuencia y los factores de riesgo asociados a DN en el momento del diagnóstico y analizar su influencia en la evolución posterior.MétodosEstudio observacional, multicéntrico, prospectivo. Se incluyeron sujetos recién diagnosticados de EA prodrómica (EAp) o demencia por EA (EAd). Se realizaron dos evaluaciones en un periodo de 18 meses. Para estimar el estado nutricional se empleó el Mini Nutritional Assessment Test (MNA, rango 0-30; DN: MNA < 24). El criterio de progresión fue un incremento en la Clinical Dementia Rating-sum of boxes ≥ 3.ResultadosSe incluyeron 50 sujetos con EAp (edad 76,1 ± 5,3 años; 68% mujeres) y 127 con EAd (edad 80 ± 5,9 años; 72,4% mujeres); 141 (79,7%) completaron las dos evaluaciones. La prevalencia de DN fue del 28,2% (EAp 24%, EAd 29,9%; p = 0,43), la mayoría (92%) en riesgo de desnutrición. El DN se asoció con el sexo femenino (OR: 4,2; IC 95%: 1,7-10,5; p < 0,001) y mayor afectación conductual (OR: 5,8; IC 95%: 2,6-12,7; p < 0,001). Se observó mayor proporción de sujetos con progresión entre los que tenían un DN respecto a estado nutricional normal (50% vs 28,7%, p < 0,05; EAd 53,6% vs 31,8%, p < 0,05; EAp 41,7% vs 22,9%; p = 0,21). Una mayor afectación cognitiva (OR: 2,1; IC 95%: 1,03-4,4; p < 0,05) y un DN (OR: 2,4; IC 95%: 1,1-5,1; p < 0,05) fueron factores de riesgo independientes de progresión.ConclusionesLa prevalencia de DN en la EA es elevada. La evaluación del estado nutricional en el momento del diagnóstico puede permitir identificar pacientes con mayor riesgo de progresión de la enfermedad. (AU)

Introduction: Nutritional deficiencies are frequent in Alzheimer disease (AD), even in early stages. Nutritional impairment (NI) may be associated with faster disease progression. The objective of this study was to describe the frequency of NI and the associated risk factors at the time of diagnosis and to analyse its influence on subsequent progression.MethodsWe performed a prospective, multicentre, observational study of patients recently diagnosed with prodromal AD (pAD) or dementia due to AD (ADd). Two clinical assessments were conducted over a period of 18 months. The Mini Nutritional Assessment test (MNA; score range, 0-30; cut-off point for NI, < 24) was used to estimate nutritional status. Progression was defined as an increase of ≥ 3 points on the Clinical Dementia Rating-sum of boxes test.ResultsThe sample included 50 patients with pAD (mean [standard deviation] age, 76.1 [5.3] years; 68% women), and 127 with ADd (80 [5.9] years; 72.4% women). A total of 141 (79.7%) completed both evaluations. The prevalence of NI was 28.2% (24% for pAD, 29.9% for ADd; P = .43), with the majority (92%) at risk of malnutrition. NI was associated with female sex (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 1.7-10.5; P < .001) and greater behavioural involvement (OR: 5.8; 95% CI: 2.6-12.7; P < .001). A larger proportion of patients with progression was observed among those with NI than among those with normal nutritional status (50% vs 28.7%, P < .05; ADd: 53.6% vs 31.8%, P < .05; pAD: 41.7% vs 22.9%, P = .21). Greater cognitive impairment (OR: 2.1; 95% CI: 1.03-4.4; P < .05) and NI (OR: 2.4; 95% CI: 1.1-5.1; P < .05) were independent risk factors for disease progression.ConclusionsNI is highly prevalent in patients with AD. Assessing nutritional status at the time of diagnosis may enable identification of patients at greater risk of disease progression. (AU)

Nutritional status assessment in Alzheimer disease and its influence on disease progression.

INTRODUCTION: Nutritional deficiencies are frequent in Alzheimer disease (AD), even in early stages. Nutritional impairment (NI) may be associated with faster disease progression. The objective of this study was to describe the frequency of NI and the associated risk factors at the time of diagnosis and to analyse its influence on subsequent progression. METHODS: We performed a prospective, multicentre, observational study of patients recently diagnosed with prodromal AD (pAD) or dementia due to AD (ADd). Two clinical assessments were conducted over a period of 18 months. The Mini Nutritional Assessment test (MNA; score range, 0-30; cut-off point for NI, < 24) was used to estimate nutritional status. Progression was defined as an increase of ≥ 3 points on the Clinical Dementia Rating-sum of boxes test. RESULTS: The sample included 50 patients with pAD (mean [standard deviation] age, 76.1 [5.3] years; 68% women), and 127 with ADd (80 [5.9] years; 72.4% women). A total of 141 (79.7%) completed both evaluations. The prevalence of NI was 28.2% (24% for pAD, 29.9% for ADd; P = .43), with the majority (92%) at risk of malnutrition. NI was associated with female sex (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 1.7-10.5; P < .001) and greater behavioural involvement (OR: 5.8; 95% CI: 2.6-12.7; P < .001). A larger proportion of patients with progression was observed among those with NI than among those with normal nutritional status (50% vs 28.7%, P < .05; ADd: 53.6% vs 31.8%, P < .05; pAD: 41.7% vs 22.9%, P = .21). Greater cognitive impairment (OR: 2.1; 95% CI: 1.03-4.4; P < .05) and NI (OR: 2.4; 95% CI: 1.1-5.1; P < .05) were independent risk factors for disease progression. CONCLUSIONS: NI is highly prevalent in patients with AD. Assessing nutritional status at the time of diagnosis may enable identification of patients at greater risk of disease progression.

Nutritional status assessment in Alzheimer disease and its influence on disease progression. / Evaluación del estado nutricional en la enfermedad de Alzheimer y su influencia en la progresión tras el diagnóstico.

INTRODUCTION: Nutritional deficiencies are frequent in Alzheimer disease (AD), even in early stages. Nutritional impairment (NI) may be associated with faster disease progression. The objective of this study was to describe the frequency of NI and the associated risk factors at the time of diagnosis and to analyse its influence on subsequent progression. METHODS: We performed a prospective, multicentre, observational study of patients recently diagnosed with prodromal AD (pAD) or dementia due to AD (ADd). Two clinical assessments were conducted over a period of 18months. The Mini Nutritional Assessment test (MNA; score range, 0-30; cut-off point for NI, <24) was used to estimate nutritional status. Progression was defined as an increase of ≥3points on the Clinical Dementia Rating-sum of boxes test. RESULTS: The sample included 50 patients with pAD (mean [standard deviation] age, 76.1 [5.3] years; 68% women), and 127 with ADd (80 [5.9] years; 72.4% women). A total of 141 (79.7%) completed both evaluations. The prevalence of NI was 28.2% (24% for pAD, 29.9% for ADd; P=.43), with the majority (92%) at risk of malnutrition. NI was associated with female sex (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 1.7-10.5; P<.001) and greater behavioural involvement (OR: 5.8; 95%CI: 2.6-12.7; P<.001). A larger proportion of patients with progression was observed among those with NI than among those with normal nutritional status (50% vs 28.7%, P<.05; ADd: 53.6% vs 31.8%, P<.05; pAD: 41.7% vs 22.9%, P=.21). Greater cognitive impairment (OR: 2.1; 95%CI: 1.03-4.4; P<.05) and NI (OR: 2.4; 95%CI: 1.1-5.1; P<.05) were independent risk factors for disease progression. CONCLUSIONS: NI is highly prevalent in patients with AD. Assessing nutritional status at the time of diagnosis may enable identification of patients at greater risk of disease progression.

Anosognosia en la enfermedad de Alzheimer: prevalencia, factores asociados e influencia en la evolución de la enfermedad / Anosognosia in Alzheimer disease: Prevalence, associated factors, and influence on disease progression

Introducción: La anosognosia es frecuente en la enfermedad de Alzheimer (EA). El objetivo fue describir su prevalencia en el momento del diagnóstico y analizar los factores predisponentes y su influencia en la evolución posterior de la EA. Métodos: Estudio observacional, multicéntrico, prospectivo, analítico, realizado en consultas de neurología general. Se incluyó a pacientes recién diagnosticados de EA (criterios NINCDS-ADRDA). Se realizaron 2 evaluaciones -cognitivas, funcionales y neuropsiquiátricas-, con un intervalo de 18 meses. Se empleó la Clinical Insight Rating scale como medida de anosognosia (CIR, rango 0-8). El criterio de progresión fue un incremento en la Clinical Dementia Rating-sum of boxes mayor a 2,5 puntos. Las variables predictoras se analizaron mediante regresión logística. Resultados: Se incluyó a 127 pacientes, 94 completaron las 2 evaluaciones. El 31,5% mostraba anosognosia grave (CIR 7-8), el 39,4% conciencia alterada (CIR 3-6) y el 29,1% conciencia normal (CIR 0-2). La mediana del CIR basal en la cohorte fue 4 (Q1-Q3: 1-7) y a los 18 meses 6 (Q1-Q3: 3-8); p < 0,001. La edad avanzada (odds ratio [OR] 2,43; IC del 95%, 1,14-5,19), menor escolaridad (OR 2,15; IC del 95%, 1,01-4,58) y mayor afectación neuropsiquiátrica (OR 2,66; IC del 95%, 1,23-5,74) fueron variables predictoras de anosognosia. El CIR basal fue similar en los grupos con y sin progresión clínica significativa. Conclusiones: La gran mayoría de los pacientes con EA en el momento del diagnóstico muestran un grado significativo de anosognosia que se asocia a mayor edad, menor escolaridad y mayor afectación conductual. No se demostró influencia de la anosognosia sobre la evolución inicial de la EA tras el diagnóstico

Introduction: Anosognosia is a frequent symptom in Alzheimer disease (AD). The objective of this article is to describe prevalence of this condition at time of diagnosis and analyse any predisposing factors and their influence on disease progression. Methods: Observational, prospective, and analytical multi-centre study in an outpatient setting. Patients recently diagnosed with AD (NINCDS-ADRDA criteria) were included. Each patient underwent two cognitive, functional, and neuropsychiatric assessments separated by an interval of 18 months. The Clinical Insight Rating Scale was employed as a measure of anosognosia (CIR, scored 0-8). Progression was defined as an increase in the Clinical Dementia Rating Scale-sum of boxes of more than 2.5 points. The predictor variables were analysed using binary logistic regression. Results: The study included 127 patients, and 94 completed both assessments. Of the total, 31.5% displayed severe anosognosia (CIR 7-8); 39.4%, altered level of consciousness (CIR 3-6); and 29.1%, normal awareness (CIR 0-2). The median baseline CIR in this cohort was 4 (Q1-Q3: 1-7), and at 18 months, 6 (Q1-Q3: 3-8), P<.001. Advanced age (odds ratio (OR) 2.43; CI 95%:1.14-5.19), lower educational level (OR 2.15; CI 95%:1.01-4.58), and more marked neuropsychiatric symptoms (OR 2.66; CI 95%:1.23-5.74) were predictor variables of anosognosia. Baseline CIR was similar in the groups with and without significant clinical progression. Conclusions: The large majority of patients with AD at the time of diagnosis showed significant anosognosia, and this condition was associated with advanced age, lower educational level, and more marked behavioural symptoms. Our results did not show that anosognosia had an effect on the initial clinical progression of AD after diagnosis

Anosognosia in Alzheimer disease: Prevalence, associated factors, and influence on disease progression. / Anosognosia en la enfermedad de Alzheimer: prevalencia, factores asociados e influencia en la evolución de la enfermedad.

INTRODUCTION: Anosognosia is a frequent symptom in Alzheimer disease (AD). The objective of this article is to describe prevalence of this condition at time of diagnosis and analyse any predisposing factors and their influence on disease progression. METHODS: Observational, prospective, and analytical multi-centre study in an outpatient setting. Patients recently diagnosed with AD (NINCDS-ADRDA criteria) were included. Each patient underwent two cognitive, functional, and neuropsychiatric assessments separated by an interval of 18 months. The Clinical Insight Rating Scale was employed as a measure of anosognosia (CIR, scored 0-8). Progression was defined as an increase in the Clinical Dementia Rating Scale-sum of boxes of more than 2.5 points. The predictor variables were analysed using binary logistic regression. RESULTS: The study included 127 patients, and 94 completed both assessments. Of the total, 31.5% displayed severe anosognosia (CIR 7-8); 39.4%, altered level of consciousness (CIR 3-6); and 29.1%, normal awareness (CIR 0-2). The median baseline CIR in this cohort was 4 (Q1-Q3: 1-7), and at 18 months, 6 (Q1-Q3: 3-8), P<.001. Advanced age (odds ratio (OR) 2.43; CI 95%:1.14-5.19), lower educational level (OR 2.15; CI 95%:1.01-4.58), and more marked neuropsychiatric symptoms (OR 2.66; CI 95%:1.23-5.74) were predictor variables of anosognosia. Baseline CIR was similar in the groups with and without significant clinical progression. CONCLUSIONS: The large majority of patients with AD at the time of diagnosis showed significant anosognosia, and this condition was associated with advanced age, lower educational level, and more marked behavioural symptoms. Our results did not show that anosognosia had an effect on the initial clinical progression of AD after diagnosis.

Síndrome de Collet-Sicard / Collet-Sicard syndrome

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The Salmonella enterica serovar Typhi ltrR-ompR-ompC-ompF genes are involved in resistance to the bile salt sodium deoxycholate and in bacterial transformation.

A characterization of the LtrR regulator, an S. Typhi protein belonging to the LysR family is presented. Proteomics, outer membrane protein profiles and transcriptional analyses demonstrated that LtrR is required for the synthesis of OmpR, OmpC and OmpF. DNA-protein interaction analysis showed that LtrR binds to the regulatory region of ompR and then OmpR interacts with the ompC and ompF promoters inducing porin synthesis. LtrR-dependent and independent ompR promoters were identified, and both promoters are involved in the synthesis of OmpR for OmpC and OmpF production. To define the functional role of the ltrR-ompR-ompC-ompF genetic network, mutants in each gene were obtained. We found that ltrR, ompR, ompC and ompF were involved in the control of bacterial transformation, while the two regulators and ompC are necessary for the optimal growth of S. Typhi in the presence of one of the major bile salts found in the gut, sodium deoxycholate. The data presented establish the pivotal role of LtrR in the regulatory network of porin synthesis and reveal new genetic strategies of survival and cellular adaptation to the environment used by Salmonella.

Hemicorea de Sydenham como manifestación de fiebre reumática / Sydenham's hemichorea as a manifestation of rheumatic fever

No disponible

Síndrome de Opalski: una variante del síndrome medular lateral / Opalski syndrome: a variant of lateral-medullary syndrome

No disponible

Blefarospasmo y espasmo hemifacial: tratamiento a largo plazo con toxina botulínica / Blepharospasm and hemifacial spasm: long-term treatment with botulinum toxin

Introducción: Nuestro objetivo es describir las características clínico epidemiológicas y terapéuticas de los pacientes con blefarospasmo (BS) y espasmo hemifacial (EH) en tratamiento con toxina botulínica tipo A (TBA). Pacientes y métodos: Se estudió retrospectivamente a los pacientes diagnosticados de BS y EH en tratamiento con TBA en la consulta de neurología del Complejo Asistencial de Segovia, desde marzo del 1991 hasta diciembre del 2009. Resultados: Se recogieron distintas variables de 34 pacientes con BS y 55 pacientes con EH, de los cuales el 44,1 y el 32,7%, respectivamente, llevaban más de 10 años en tratamiento con TBA. Desde el inicio de los síntomas hasta la consulta la mediana de tiempo fue de 24 meses en el grupo de BS, y de 59,7 meses en el grupo de EH, diagnosticándose en la primera visita el 76,5 y el 90,7%, respectivamente. El 34,6% de los pacientes con BS y el 77,6% de los pacientes con EH fueron derivados desde atención primaria. En ambos grupos, el preparado farmacológico de TBA más utilizado fue BOTOX®, sin hallarse resistencias primarias ni secundarias. La mediana de la dosis se incrementó progresivamente en ambas entidades, de forma significativa en los primeros años de tratamiento. La ptosis fue el efecto secundario más frecuente (el 47,1% en el BS, el 32,5% en el EH). Conclusiones: El BS y el ES constituyen los trastornos del movimiento faciales más comunes, recogiendo en esta serie diferentes parámetros epidemiológicos, clínicos y terapéuticos, confirmándose el beneficio y la seguridad del tratamiento con TBA a largo plazo (AU)

Introduction: Our purpose is to describe the demographic, clinical and therapeutic characteristics of patients with blepharospasm (BS) and hemifacial spasm (HFS) in treatment with botulinum toxin type A (BtA). Patients and methods: Retrospective analysis of patients diagnosed with BS or HFS and treated with BtA in the Neurology Department at Complejo Asistencial de Segovia between March 1991 and December 2009. Results: Different variables were collected from 34 patients with BS and 55 with HFS, of whom44.1% and 32.7% respectively had been undergoing treatment with BtA for more than 10 years. Elapsed time from symptom onset to the first visit was 24 months in the BS group and 59.7 months in the HFS group. Diagnosis was given on the first visit for 76.5% of the BS patients and90.7% of the HFS patients. Patients were referred by their primary care centres in 34.6% of the cases with BS and in 77.6% of the cases with HFS. The most commonly used BtA preparation was BOTOX® in both groups, and there were no cases of primary or secondary resistance. The median dose of BtA was raised gradually in both groups, and the increase was statistically significant during the early years of treatment. The most common side effect was ptosis (47.1% in BS, 32.5% in HFS). Conclusions: BS and HFS are the most common facial movement disorders. The demographic and clinical characteristics and therapeutic findings from this study show that treatment with BtA is both effective and safe over the long term (AU)

Blepharospasm and hemifacial spasm: long-term treatment with botulinum toxin.

INTRODUCTION: Our purpose is to describe the demographic, clinical and therapeutic characteristics of patients with blepharospasm (BS) and hemifacial spasm (HFS) in treatment with botulinum toxin type A (BtA). PATIENTS AND METHODS: Retrospective analysis of patients diagnosed with BS or HFS and treated with BtA in the Neurology Department at Complejo Asistencial de Segovia between March 1991 and December 2009. RESULTS: Different variables were collected from 34 patients with BS and 55 with HFS, of whom 44.1% and 32.7% respectively had been undergoing treatment with BtA for more than 10 years. Elapsed time from symptom onset to the first visit was 24 months in the BS group and 59.7 months in the HFS group. Diagnosis was given on the first visit for 76.5% of the BS patients and 90.7% of the HFS patients. Patients were referred by their primary care centres in 34.6% of the cases with BS and in 77.6% of the cases with HFS. The most commonly used BtA preparation was BOTOX(®) in both groups, and there were no cases of primary or secondary resistance. The median dose of BtA was raised gradually in both groups, and the increase was statistically significant during the early years of treatment. The most common side effect was ptosis (47.1% in BS, 32.5% in HFS). CONCLUSIONS: BS and HFS are the most common facial movement disorders. The demographic and clinical characteristics and therapeutic findings from this study show that treatment with BtA is both effective and safe over the long term.

Trastornos del movimiento en el ictus / Movement disorders in stroke

Introduccion. Los trastornos del movimiento son síntomas poco frecuentes tras un ictus, pudiendo ser hipercinéticos o hipocinéticos. Objetivo. Se han revisado los principales artículos publicados de trastornos del movimiento tras el ictus, describiendo la epidemiología, etiología, fisiopatología, relación temporal entre el ictus y la aparición del movimiento anormal, características clínicas, tratamiento y pronóstico. Desarrollo. El corea y el balismo son los trastornos del movimiento más frecuentes, y que más precozmente aparecen, siendo el parkinsonismo el que se presenta con un mayor intervalo de tiempo tras el ictus. No existe una localización específica para cada trastorno del movimiento, afectándose generalmente los ganglios basales. Habitualmente son autolimitados, pero pueden requerir tratamiento sintomático. Conclusiones. Los trastornos del movimiento tras el ictus son infrecuentes, de diferentes tipos y relación temporal, con afectación habitual de los ganglios basales y buen pronóstico (AU)

Introduction. Movement disorders are infrequent symptoms following a stroke and may be hyperkinetic or hypokinetic. Aims. A review was conducted of the most important articles published on movement disorders after a stroke, which covered the following areas: epidemiology, aetiology, pathophysiology, relationship in the time elapsed between the stroke and the appearance of abnormal movements, clinical features, treatment and prognosis. Development. Chorea and ballismus are the most frequent movement disorders and the ones that appear the earliest, parkinsonism being the one that appears after the greatest interval of time following the stroke. There is no specific location for each movement disorder, although the basal ganglia are generally involved. They are usually self-limiting but may require symptomatic treatment. Conclusions. Movement disorders following a stroke are rare, of different types with different time relationships, usually with involvement of the basal ganglia and a good prognosis (AU)

Neuroimagen en los parkinsonismos: resonancia magnética y sonografía transcraneal / Neuroimaging in parkinsonisms: magnetic resonance imaging and transcranial sonography

Introducción. El diagnóstico diferencial de los síndromes parkinsonianos puede ser difícil, especialmente en las fases iniciales. Diversas pruebas neurorradiológicas podrían ser de ayuda. Objetivo. Describir los hallazgos típicos de la resonancia magnética (RM) craneal y sonografía transcraneal en la parálisis supranuclear progresiva (PSP), degeneración corticobasal (DCB) y atrofia multisistémica (AMS). Desarrollo. El hallazgo más típico de la PSP en los estudios de RM craneal es la atrofia del mesencéfalo. A nivel cerebral se puede observar atrofia talámica, dilatación del tercer ventrículo, y atrofia simétrica del lóbulo frontal, cuerpo estriado y cuerpo calloso. En la DCB es característica la atrofia cortical asimétrica de predominio frontoparietal. Y en la AMS se puede observar atrofia de putamen, cerebelo y tronco encefálico, así como alteraciones en la intensidad de señal en T2 como hipointensidad putaminal, hiperintensidad en el margen posterolateral del putamen, e hiperintensidad en cruz protuberancial. En la sonografía transcraneal la hiperecogenicidad de sustancia negra orientará hacia una enfermedad de Parkinson (EP) o DCB. En la PSP es característica la dilatación del III ventrículo. En la PSP, DCB, y AMS puede haber hiperecogenicidad en los núcleos lenticular y caudado, hallazgos infrecuentes en EP. Conclusión. El conocimiento de estos hallazgos en los estudios de neuroimagen puede aumentar la precisión diagnóstica de los síndromes parkinsonianos atípicos (AU)

Introduction. The differential diagnosis of parkinsonian syndromes can be difficult, especially in the early stages, but there are several different neuroimaging tests that could be a valuable aid. Aims. The purpose of this study is to describe the typical findings in magnetic resonance imaging (MRI) of the head and transcranial sonography in progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA). Development. The most typical finding of PSP in MRI studies of the head is atrophy of the mesencephalon. In the brain, thalamic atrophy, dilatation of the third ventricle and symmetrical atrophy of the frontal lobe, striatum and corpus callosum can all be seen. CBD is characterised by asymmetrical cortical atrophy with frontoparietal predominance. And in MSA it is possible to observe atrophy of the putamen, cerebellum and brain stem, as well as alterations in the T2 signal intensity, such as putaminal hypointensity, hyperintensity in the posterolateral margin of the putamen, and cruciform hyperintensity in the pons. In the transcranial sonography scan the hyperechogenicity of the substantia nigra is suggestive of Parkinson's disease (PD) or CBD. PSP is characterised by dilatation of the 3rd ventricle. In PSP, CBD and MSA there may be hyperechogenicity in the lenticular and caudate nuclei, which are infrequent findings in PD. Conclusions. Knowledge of these findings in neuroimaging studies can increase the accuracy of the diagnoses in the atypical parkinsonian síndromes (AU)

The CRISPR/Cas immune system is an operon regulated by LeuO, H-NS, and leucine-responsive regulatory protein in Salmonella enterica serovar Typhi.

Prokaryotes have developed multiple strategies to survive phage attack and invasive DNA. Recently, a novel genetic program denominated the CRISPR/Cas system was demonstrated to have a role in these biological processes providing genetic immunity. This defense mechanism is widespread in the Archaea and Bacteria, suggesting an ancient origin. In the last few years, progress has been made regarding the functionality of the CRISPR/Cas system; however, many basic aspects of the system remain unknown. For instance, there are few studies about the conditions and regulators involved in its transcriptional control. In this work, we analyzed the transcriptional organization of the CRISPR/Cas system as well as the positive and negative regulators involved in its genetic expression in Salmonella enterica serovar Typhi. The results obtained show that in S. Typhi the CRISPR/Cas system is a LeuO-dependent operon silenced by the global regulator LRP, in addition to the previously known nucleoid-associated protein H-NS; both LRP and H-NS bind upstream and downstream of the transcriptional start site of casA. In this study, relevant nucleotides of the casA regulatory region that mediate its LeuO transcriptional activation were identified. Interestingly, specific growth conditions (N-minimal medium) were found for the LeuO-independent expression of the CRISPR/Cas system in S. Typhi. Thus, our work provides evidence that there are multiple modulators involved in the genetic expression of this immune system in S. Typhi IMSS-1.

Networks of transcriptional regulation encoded in a grammatical model.

The work here presented enriches a previous grammatical model of the transcriptional regulation of gene expression. The previous model is centered on the representation of the regulatory regions upstream of genes, and their internal organization in the DNA. This paper is centered in discussing some alternatives related to the representation of the organization of operons and their alternative states of transcription, as active or inactive units of transcription. Transformational rules can be used to describe the binding and unbinding of regulatory proteins, and the associated representations of (ON/OFF) gene expression. The initial representation of a regulated promoter is linked to that of the operon encoding its regulatory protein. In this way the representation of a regulated operon depends on that of all others regulating its transcription, enabling in principle the encoding of regulatory networks within an expanded grammatical model of gene regulation.