Risk factors, management, and outcomes in isolated parafalcine or tentorial subdural hematomas.

INTRODUCTION: Indications for hospitalization in patients with parafalcine or tentorial subdural hematomas (SDH) remain unclear. This study derived and validated a clinical decision rule to identify patients at low risk for complications such that hospitalization can be avoided. METHODS: A multicenter retrospective medical record review of adult patients with parafalcine or tentorial SDHs was completed. The primary outcome was significant injury, defined as injury that led to neurosurgery, discharge to another facility, or death. A multivariable logistic regression was performed to identify variables independently associated with the outcome in the derivation cohort. These variables were then validated on a separate cohort from a different institution abstracted without knowledge of the identified variables. RESULTS: In the derivation cohort, 134 patients with parafalcine/tentorial SDHs were identified. The mean age was 63 ± 19 years with 82 (61%) male. Seventy-one (53%) had significant injuries. Variables independently associated with significant injury included: age over 60, adjusted odds ratio (aOR) 3.46 (95% CI 1.24, 9.62), initial Glasgow Coma Scale score below 15, aOR =7.92 (95% CI 2.78, 22.5), and additional traumatic brain injuries (TBIs) on computerized tomography (CT), aOR =5.97 (95% CI 2.48, 14.4). These three variables had a sensitivity of 71/71 (100%, 95% CI 96, 100%) and specificity of 12/63 (19%, 95% CI 10, 31%). The validation cohort (n = 83) had a mean age of 62 ± 22 years with 50 (60%) male. The three variables had a sensitivity of 36/36 (100%, 95% CI 92, 100%) and specificity of 7/47 (15%, 95% CI 6.2, 28%). All 39 (100%, 95% CI 93, 100%) patients from both cohorts who underwent neurosurgery had additional TBI findings on their CT scan. CONCLUSIONS: Patients with parafalcine/tentorial SDHs who are under 60 years with initial GCS scores of 15 and no addition TBIs on CT are at low risk and may not need hospitalization. Furthermore, patients with isolated parafalcine/tentorial SDHs are unlikely to undergo neurosurgery. Prospective, external validation with a larger sample size is now recommended. STUDY TYPE: Retrospective Cohort Study.

[MIA 2021, Comprehensive Asthma Management. Guidelines for Mexico]. / MIA 2021, Manejo Integral del Asma. Lineamientos para México.

BACKGROUND: Asthma continues to be one of the most frequent chronic respiratory diseases in our country. New methods for diagnosis and treatment have been described; accordingly, the international guidelines were renewed. OBJECTIVE: To create a national platform for the development of updated guidelines, solidly based on evidence: Comprehensive Asthma Management (Spanish acronym: MIA). METHODS: MIA uses the ADAPTE method. The MIA development group consists of experts in pulmonology-allergology-methodology and representatives of 13 institutions and societies of specialties that manage asthma. The international reference guidelines (selected with AGREE-II): GINA 2020, GEMA 5.0, BTS/SIGN 2019 and ATS/ERS consensus document 2014-2019 on severe asthma. MIA covers suspected asthma, diagnosis, treatment, and special groups. Key clinical questions were formulated on treatment steps 1-3, biomarkers and severe asthma. RESULTS: Based on evidence, safety, cost and local reality, the core group developed responses. Through a Delphi process the broad MIA development group suggested adjustments until consensus was reached. CONCLUSION: A document was generated with multiple figures and algorithms, solidly based on evidence about asthma management, adjusted for Mexico with a broad base among different societies that participated in its development. It does not include guidelines for acute asthma.

Antecedentes: El asma sigue siendo una patología respiratoria crónica frecuente en México. Se han descrito nuevos métodos para el diagnóstico y tratamiento conforme se renuevan las guías internacionales. Objetivo: Crear la plataforma nacional Manejo Integral del Asma (MIA), para el desarrollo de lineamientos actualizados con base en evidencia. Métodos: Se utilizó el método ADAPTE. El grupo de desarrollo de MIA estuvo integrado por expertos en neumología, alergología y metodología y representantes de 13 instituciones y sociedades de especialidades que manejan asma. Las guías internacionales de referencia (seleccionadas con AGREE-II) fueron GINA 2020, GEMA 5.0, BTS/SIGN 2019 y consenso ATS/ERS 2014-2019. En MIA se aborda sospecha de asma, diagnóstico, tratamiento y grupos especiales. Se formularon preguntas clínicas clave sobre tratamiento en los pasos 1 a 3, biomarcadores y asma grave. Resultados: Con base en evidencia, seguridad, costo y realidad local, el grupo nuclear desarrolló respuestas. Mediante proceso Delphi, el grupo amplio de desarrollo sugirió ajustes hasta que se logró el consenso. Conclusión: El documento generado contiene múltiples figuras y algoritmos, está sólidamente basado en evidencia acerca del manejo del asma y fue ajustado para México con participación de diferentes sociedades para su desarrollo; no se incluyeron lineamientos para la crisis asmática.

Diagnostic value of the stand-alone synthetic image in digital breast tomosynthesis examinations.

OBJECTIVE: To demonstrate the non-inferiority of synthetic image (SI) mammography versus full-field digital mammography (FFDM) in breast tomosynthesis (DBT) examinations. METHODS: An observational, retrospective, single-centre, multireader blinded study was performed, using 2384 images to directly compare SI and FFDM based on Breast Imaging Reporting and Data System (BIRADS) categorisation and visibility of radiological findings. Readers had no access to digital breast tomosynthesis slices. Multiple reader, multiple case (MRMC) receiver operating characteristic (ROC) methodology was used to compare the diagnostic performance of SI and FFDM images. The kappa statistic was used to estimate the inter-reader and intra-reader reliability. RESULTS: The area under the ROC curves (AUC) reveals the non-inferiority of SI versus FFDM based on BIRADS categorisation [difference between AUC (ΔAUC), -0.014] and lesion visibility (ΔAUC, -0.001) but the differences were not statistically significant (p=0.282 for BIRADS; p=0.961 for lesion visibility). On average, 77.4% of malignant lesions were detected with SI versus 76.5% with FFDM. Sensitivity and specificity of SI are superior to FFDM for malignant lesions scored as BIRADS 5 and breasts categorised as BIRADS 1. CONCLUSIONS: SI is not inferior to FFDM when DBT slices are not available during image reading. SI can replace FFDM, reducing the dose by 45%. KEY POINTS: • Stand-alone SI demonstrated performance not inferior for lesion visibility as compared to FFDM. • Stand-alone SI demonstrated performance not inferior for lesion BIRADS categorisation as compared to FFDM. • Synthetic images provide important dose savings in breast tomosynthesis examinations.

Enhanced Oxidative Stress and Other Potential Biomarkers for Retinopathy in Type 2 Diabetics: Beneficial Effects of the Nutraceutic Supplements.

We have studied the global risk of retinopathy in a Mediterranean population of type 2 diabetes mellitus (T2DM) patients, according to clinical, biochemical, and lifestyle biomarkers. The effects of the oral supplementation containing antioxidants/omega 3 fatty acids (A/ω3) were also evaluated. Suitable participants were distributed into two main groups: (1) T2DMG (with retinopathy (+DR) or without retinopathy (-DR)) and (2) controls (CG). Participants were randomly assigned (+A/ω3) or not (-A/ω3) to the oral supplementation with a daily pill of Nutrof Omega (R) for 18 months. Data collected including demographics, anthropometrics, characteristics/lifestyle, ophthalmic examination (best corrected visual acuity, ocular fundus photographs, and retinal thickness as assessed by optical coherence tomography), and blood parameters (glucose, glycosylated hemoglobin, triglycerides, malondialdehyde, and total antioxidant capacity) were registered, integrated, and statistically processed by the SPSS 15.0 program. Finally, 208 participants (130 diabetics (68 +DR/62 -DR) and 78 controls) completed the follow-up. Blood analyses confirmed that the T2DMG+DR patients had significantly higher oxidative stress (p < 0.05), inflammatory (p < 0.05), and vascular (p < 0.001) risk markers than the T2DMG-DR and the CG. Furthermore, the A/ω3 oral supplementation positively changed the baseline parameters, presumptively by inducing metabolic activation and ameliorating the ocular health after 18 months of supplementation.

Ocular Surface and Tear Film Changes in Older Women Working with Computers.

The aim of this work is to investigate changes in the ocular surface (OS) and tear film (TF) by means of questionnaire-based subjective symptoms, TF break-up time, Schirmer test, and TF analysis in women working with computers and to analyze the effects of the oral supplementation with antioxidants/omega 3 fatty acids (A/ω3) in the OS outcomes. Women aged 40-65 years (n = 148) were recruited at the Administrative Offices of Valencia (Spain) and distributed into two age groups, 40-52 years (AGE1; n = 87) and 53-65 years (AGE2; n = 61), and then subdivided according to being (or not) computer users (CUG; NCUG) during the workday. Homogeneous subgroups were randomly assigned (or not) to the daily intake of three pills of A/ω3 for three months. At baseline and at the end of follow-up, personalized interviews and ocular examination were done. Reflex tear samples were collected from the inferior meniscus and processed for a multiplexed particle-based flow cytometry assay to measure proinflammatory molecules. Statistics were performed using the SPSS 15.0 program. The OS pathology was clinically evident in the AGE1-CUG (33%) versus the AGE2-CUG (64%) of women. Significantly higher interleukins-1ß and -6 tear levels were found in the AGE1 versus the AGE2 women employees (P = 0.006 and P = 0.001, resp.), as well as in the CUG versus the NCUG (P = 0.001 and P = 0.000, resp.). Supplementation with A/ω3 positively influenced the OS pathology as manifested by the amelioration of the clinical signs/symptoms related to computer uses. Strategies involving a safe environment and oral micronutrient supplements may be managed within eye-care standards in older women.

A metabolomic approach to dry eye disorders. The role of oral supplements with antioxidants and omega 3 fatty acids.

PURPOSE: We used nuclear magnetic resonance spectroscopy of hydrogen-1 nuclei ((1)H NMR S) to analyze the metabolic profile of reflex tears from patients with dry eye disorders. METHODS: We performed a prospective case-control study involving 90 participants: 55 patients diagnosed with dry eye syndrome (DESG) and 35 healthy subjects (control group, CG). From the DESG, two subgroups were formed: mild DES (n=22) and moderate DES (n=33). Participants were prescribed an oral nutraceutic supplementation containing antioxidants and essential polyunsaturated fatty acids to be taken as three capsules per day for 3 months. Reflex tears (20-30 µl) were collected from the tear meniscus of both eyes of each subject with a microglass pipette. Nuclear magnetic resonance (NMR) spectra were acquired with a standard one-dimensional pulse sequence with water suppression; 256 free induction decays were collected into 64,000 data points with 14 ppm spectral width. RESULTS: Basal tears showed a differential metabolomic profile between groups. Almost 50 metabolites were identified by H cholesterol, N-acetylglucosamine, glutamate, amino-n-butyrate, choline, glucose, and formate were detected before supplementation and choline/acetylcholine after supplementation. The metabolic profile of the tears was statistically different between groups, as well as before and after supplementation. CONCLUSIONS: Our data indicate that DES induces changes in the tear metabolic profile that can be modified with appropriate oral supplementation with antioxidants and essential polyunsaturated fatty acids.

Differential effects of dry eye disorders on metabolomic profile by 1H nuclear magnetic resonance spectroscopy.

We used (1)H NMR spectroscopy to analyze the metabolomic profile of reflex tears from patients with dry eye disorders (DEDs). 90 subjects were divided into 2 groups: (1) patients with DEDs (DEDG; n = 55) and (2) healthy subjects (CG; n = 35). Additionally, the DEDG was subdivided into 2 subgroups based on DED severity: mild-to-moderate and moderate (n = 22 and n = 33, resp.). Personal interviews and systematized ophthalmologic examinations were carried out. Reflex tears (20-30 µL) were collected by gently rubbing in the inferior meniscus of both eyelids with a microglass pipette and stored at -80°C until analysis. NMR spectra were acquired using a standard one-dimensional pulse sequence with water suppression. Data were processed and transferred to MATLAB for further chemometric analysis. Main differences in tear composition between DEDG and CG were found in cholesterol, N-acetylglucosamine, glutamate, creatine, amino-n-butyrate, choline, acetylcholine, arginine, phosphoethanolamine, glucose, and phenylalanine levels. This metabolic fingerprint helped also to discriminate between the three additional subgroups of DEDG. Our results suggest that tear metabolic differences between DEDG and CG identified by NMR could be useful in understanding ocular surface pathogenesis and improving biotherapy.

Oxidative stress and its downstream signaling in aging eyes.

BACKGROUND: Oxidative stress (OS) and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS) production and the ability of the antioxidant (AOX) biological systems to fight against oxidative injury. OBJECTIVE: We reviewed the role of OS and its downstream signaling in aging eyes. METHODS: A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy. RESULTS: Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed. CONCLUSION: OS, nutritional status, and nutraceutic supplements have to be considered within the standards of care of older ophthalmologic patients. OS biomarkers and surrogate end points may help in managing the aging population with ocular diseases.

Patients undergoing long-term treatment with antihypertensive eye drops responded positively with respect to their ocular surface disorder to oral supplementation with antioxidants and essential fatty acids.

BACKGROUND: Glaucoma and dry eye disorders (DEDs) are frequent comorbidities. The antioxidant and anti-inflammatory properties of essential polyunsaturated fatty acids have been extensively studied in relation to eye diseases. OBJECTIVE: Our objective was to determine the effects of oral supplementation with a combined formulation of antioxidants and essential polyunsaturated fatty acids on expression of cytokines and chemokines in tears from patients with DEDs or primary open-angle glaucoma (POAG). METHODS: Participants (n = 97) were distributed into three groups: (1) individuals with nonsevere DEDs (DEDG), (2) individuals with nonadvanced POAG (POAGG), and (3) healthy controls. These groups were randomized into two subgroups: one received a daily antioxidant and essential polyunsaturated fatty acid supplement (two pills) for 3 months (+S), and the other did not (-NS). Participants were interviewed and ophthalmologically examined. Concentrations of specific cytokines and chemokines in reflex tears were determined by multiplexed particle-based flow cytometry. The data were analyzed statistically (SPSS version 15.0). RESULTS: Comparison of the results from the DEDG and POAGG patients showed significant differences in tear expression of granulocyte-macrophage colony-stimulating factor (P = 0.008), tumor necrosis factor α (P = 0.005), vascular endothelial growth factor (P = 0.038), interleukin-4 (P = 0.030), and interleukin-6 (P = 0.044). The main signs and symptoms of dry eyes such as dryness, burning, photophobia, eye heaviness, and blurred vision, as well as positive changes in eyelashes, hair, nails and skin, were significantly improved in DEDG +S and POAGG +S patients relative to unsupplemented patients. CONCLUSION: Inflammation biomarkers were differentially expressed in glaucomatous tears, but the differences changed upon antioxidant/essential polyunsaturated fatty acid supplementation. Chronic instillation of antihypertensive eye drops must be considered for integrating protocols to glaucoma standards of care.

Effects of a nutraceutical formulation based on the combination of antioxidants and ω-3 essential fatty acids in the expression of inflammation and immune response mediators in tears from patients with dry eye disorders.

BACKGROUND: Women, and those older than 65 years of age, are particularly susceptible to dry eye disorders (DEDs). Inflammation is clearly involved in the pathogenesis of DEDs, and there is mounting evidence on the antioxidant and antiinflammatory properties of essential polyunsaturated fatty acids (EPUFAs). OBJECTIVE: To analyze whether a combined formulation of antioxidants and long-chain EPUFAs may improve the evolution of DEDs. METHODS: We used a prospective study to address the relationship between risk factors, clinical outcomes, and expression levels of inflammation and immune response (IIR) mediators in human reflex tear samples. Participants included: (1) patients diagnosed with nonsevere DEDs (DED group [DEDG]); and (2) healthy controls (control group [CG]). Participants were randomly assigned to homogeneous subgroups according to daily oral intake (+S) or not (-NS) of antioxidants and long-chain EPUFAs for 3 months. After an interview and a systematized ophthalmic examination, reflex tears were collected simultaneously from both eyes; samples were later subjected to a multiplexed particle-based flow cytometry assay. A specific set of IIR mediators was analyzed. All data were statistically processed through the SPSS 15.0 software program. RESULTS: Significantly higher expressions of interleukin (IL)-1ß, IL6, and IL10 and significantly lower vascular endothelial growth factor expressions were found in the DEDG as compared to the CG. In the DEDG, significant negative correlations were detected between the Schirmer test and IL-1ß, IL6, IL8, and vascular endothelial growth factor levels, and between the fluorescein breakup time with IL6 and IL8 levels. However, levels of IL-1ß, IL6, and IL10 in tears were significantly lower in the DEDG+S versus the DEDG-NS and in the CG+S versus the CG-NS. Subjective symptoms of dry eye significantly improved in the DEDG+S versus the DEDG-NS. CONCLUSION: IIR mediators showed different expression patterns in DED patients, and these patterns changed in response to a combined formulation of antioxidant and EPUFAs supplementation. Our findings may be considered for future protocols integrating clinical/biochemical data to help manage DED patients.

ADAM-17/tumor necrosis factor-α-converting enzyme inhibits neurogenesis and promotes gliogenesis from neural stem cells.

Neural precursor cells (NPCs) are activated in central nervous system injury. However, despite being multipotential, their progeny differentiates into astrocytes rather than neurons in situ. We have investigated the role of epidermal growth factor receptor (EGFR) in the generation of non-neurogenic conditions. Cultured mouse subventricular zone NPCs exposed to differentiating conditions for 4 days generated approximately 50% astrocytes and 30% neuroblasts. Inhibition of EGFR with 4-(3-chloroanilino)-6,7-dimethoxyquinazoline significantly increased the number of neuroblasts and decreased that of astrocytes. The same effects were observed upon treatment with the metalloprotease inhibitor galardin, N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide (GM 6001), which prevented endogenous transforming growth factor-α (TGF-α) release. These results suggested that metalloprotease-dependent EGFR-ligand shedding maintained EGFR activation and favored gliogenesis over neurogenesis. Using a disintegrin and metalloprotease 17 (ADAM-17) small interference RNAs transfection of NPCs, ADAM-17 was identified as the metalloprotease involved in cell differentiation in these cultures. In vivo experiments revealed a significant upregulation of ADAM-17 mRNA and de novo expression of ADAM-17 protein in areas of cortical injury in adult mice. Local NPCs, identified by nestin staining, expressed high levels of ADAM-17, as well as TGF-α and EGFR, the three molecules necessary to prevent neurogenesis and promote glial differentiation in vitro. Chronic local infusions of GM6001 resulted in a notable increase in the number of neuroblasts around the lesion. These results indicate that, in vivo, the activation of a metalloprotease, most probably ADAM-17, initiates EGFR-ligand shedding and EGFR activation in an autocrine manner, preventing the generation of new neurons from NPCs. Inhibition of ADAM-17, the limiting step in this sequence, may contribute to the generation of neurogenic niches in areas of brain damage.

Validación de la escala Kessler 10 (K-10) en la detección de depresión y ansiedad en el primer nivel de atención. Propiedades psicométricas / Validity of the kessler 10 (k-10) scale in detecting depression and anxiety disorders in the primary care services. Psychometric properties

According to studies conducted in different countries, it is estimated that approximately 30% to 50% of people with mental health problems are not recognized by the general practitioner. Given this situation, it has been proposed that the practitioner at the primary care services must play a decisive role in the early detection of cases by establishing a definitive diagnostic and a timely treatment. Several organizations have pointed out that one of the first actions that need to be implemented to fulfill the aims in the care of people with mental disorders is to prepare the first-contact doctors and to have a brief, low cost, self-applied, valid and reliable scale. The studies mention that using screening tests at the primary care level is crucial for the success of the programs. The detection and recognition of psychiatric symptomatology rates vary depending on the type of scale applied. The tools that have been widely used are the Goldberg's General Health Questionnaire (GHQ), Zung Self-Rating Depression Scale, Beck Depression Inventory, the Depression Symptom Checklist (DS 20), the Hopkins Symptom Checklist (SCL), the Hamilton Depression Scale, the Center for Epidemiologic Studies Depression Scale (CES-D), the Montgomery-Asberg Depression Rating Scale, the Geriatric Depression Scale (GDS), the self-administered computerized assessment (PROQSY), the criteria of the 3rd revised edition of the Diagnostical and Statistical Manual of Mental Disorders (DSM-III-R), the Structured Clinical Interview for DSM-IV (SCID), and the criteria of the Symptom Driven Diagnostic System for Primary Care (SDDS-PC), among others. The preliminary results confirm the existence of a high percentage of possible psychiatric cases (46.9%), but only 4% of cases are referral. The low capability of the general practitioner at the primary care level in detecting these pathologies has been confirmed as well. These scales have been applied in different scenarios and to different types of population. Although the dominating criteria for choosing the tool are sensitivity and specificity, some authors mention that strategies for adequately handling cases, such as the confirmation of the diagnosis and follow-up of the patients, are required once the treatment has started. In this paper, we present the psychometric characteristics of the Kessler (K-10) scale in detecting depression and anxiety disorders in the primary care. Material and methods The study is a methodological process that aims to validate the Kessler Psychological Distress scale (K-10). It was conducted in two health care centers of primary care level in Mexico City. The subjects were 280 individuals who requested attention at the mentioned centers and to whom the K-10 test was applied after giving their informed consent. Later on, the computerized version of the International Neuropsychiatric Interview (MINI), which uses the diagnostic criteria of the DSM-IV, was applied to the subjects in order to confirm the diagnostics for depression and anxiety. The MINI is a version adapted to Latin American Spanish by the National Institute of Psychiatry Ramon de la Fuente Muñiz. The diagnostic accuracy was processed following the MINI diagnoses for depression and anxiety closely, and the scores on the scale K-10 as a predictor. The sensitivity and specificity were calculated for all possible cut points in order to establish the optimal cut off point. The efficiency and maximum likelihood ratios were also calculated. The area under the ROC curve as well as the probability quotients, positive and negative (LR+ and LR-), were also calculated. The K-10 is a brief screening tool that can be easily applied by the primary care personnel which measures the psychological distress of a person during the four weeks prior to the application. It consists of ten questions with Likert-like answers that range from 1 to 5 and are categorized in a five level ordinal scale: Always, Very Often, Sometimes, Rarely, Never; where «Never¼ has an assigned value of 1, and «Always¼ has assigned value of 5. It has a minimum score of 10 and a maximum of 50. The ranges of the instrument are four levels: low (10-15), moderate (16-21), high (22-29) and very high (30-50). The instrument showed an internal consistency of 0.90 and it has been used in various population studies promoted by the World Health Organization as well as government organizations in Australia, Spain, Colombia and Peru. Results Out of 280 individuals to whom the tool was applied, 78.9% (221) were female and 21.1% (59) male. These values represent the proportion of patients attending the primary care services (95% confidence interval=±5.4%). The mean age of women was 39 years, and the mean age of men was 41. The 70.6% of the women manifested more psychological distress than men (52.5%)[χ2(1)=6.05,p=0.014. No other socio-demographic variable showed significant differences. The instrument is highly precise, it can detect up to 87% of depression cases, and 82.4% of anxiety cases. The scale was compared with the MINI and it presented a prevalence of 26.8% and 10.6%, respectively. Of the total of depression cases, 26.4% also presented anxiety; these represent a co-morbidity of 5.4%. The construct validity presented one factor alone that explains the 53.4% of the total variance, this is why the scale is considered as one-dimensional. In other words, the scale only measures the construct of the psychological distress. The internal consistency was α=0.901. Once the sensitivity and specificity for all cut off points had been determined using the MINI as a golden rule, it was observed that the cut off point for maximum sensitivity and specificity corresponded to 21 for the diagnosis of depression, and 22 for anxiety. Conclusions The K-10 is a good instrument for the detection of depression and anxiety cases at the primary care level which meets the criteria of validity and reliability. However, given that only one diagnosis was considered for all the range of anxiety disorders, the scale must be chosen carefully for all the other disorders that are not included in this paper. The use of the instrument is recommended for the general practitioners at the primary care level, mainly for diagnosing depression. Various studies in which other screening instruments have been used for the detection of depressive disorder at primary care point out that any screening method are useful in making the diagnosis. By using these instruments, the depression diagnosis at primary care level increases from 10% to 47%. The latter supports the fact that the selection of a good instrument turns out to be effective in detection, treatment and clinical outcomes of the entity. Since this recommendation is only one of the activities required in primary care level for good handling of detected cases, it is noteworthy to mention that a comprehensive care model that encompasses both the detection as well as the pharmacological and psychosocial treatments is required.

De acuerdo con estudios realizados en diferentes países se estima que aproximadamente hay entre 30% a 50% de personas que presentan algún problema de salud mental que no es reconocido por el médico general. En virtud de esta situación se ha propuesto como estrategia a la atención primaria como base del sistema de salud, lo que permitiría la detección temprana de pacientes con algún trastorno psiquiátrico. Diferentes organismos señalan que una de las primeras acciones para cumplir con los objetivos en la atención de personas con algún trastorno mental, consiste en contar con una escala breve, autoaplicable, válida y confiable y de bajo costo. En este trabajo se presentan las características psicométricas de la escala Kessler (K-10) para detectar trastornos depresivos y ansiosos. La K-10 es un instrumento de tamizaje breve y de fácil aplicación por el personal del primer nivel de atención y ha sido utilizada en diferentes estudios a nivel poblacional. En Australia, en 1997, se aplicó la K-10 en una encuesta de salud, por medio del Consejo Nacional de Encuestas de Salud Mental. Material y métodos Se trata de un estudio de proceso metodológico, cuyo objetivo fue la validación de la escala de malestar psicológico K-10 de Kessler. El estudio se llevó a cabo en dos Centros de Salud del primer nivel de atención en la Ciudad de México. Los participantes fueron 280 personas que acudieron a la consulta externa de dichos centros. Se utilizaron los criterios del DSM-IV para la confirmación del diagnóstico de depresión y de ansiedad, por medio de la Mini International Neuropsychiatric Interview (MINI), en su versión computarizada, adaptada al español latinoamericano en el Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. La validez diagnóstica se procesó utilizando los diagnósticos de la MINI para depresión y ansiedad como regla de oro y las puntuaciones obtenidas en la escala K-10 como predictor. Se calculó la sensibilidad y especificidad para todos los posibles puntos de corte con el fin de establecer el óptimo. Se calculó adicionalmente la eficiencia y las razones de máxima verosimilitud, así como el área bajo la curva ROC y los cocientes de probabilidad, positivo y negativo (LR+ y LR-). Resultados Del total de personas a quiénes se les aplicó la escala, el 78.9% (221) fueron mujeres y 21.1% (59) hombres. Estos valores representan la proporción en que los pacientes acuden a los servicios de primer nivel (IC 95%=±5.4%). El 70.6% de las mujeres presentaron mayor malestar psicológico en comparación con los hombres que representaron el 52.5% [χ²(1)=6.05,p=0.014]. En ninguna otra variable socio-demográfica se presentaron diferencias significativas. El instrumento tiene una alta precisión, ya que puede detectar hasta el 87% de los casos de depresión y un 82.4% de los casos de ansiedad. La escala se comparó con el MINI en español y presentó una prevalencia de 26.8% y 26.4%, respectivamente. Conclusiones El instrumento cumple con los criterios de validez y confiabilidad, por lo que se recomienda su uso por los médicos generales en el primer nivel de atención. Dado que esta recomendación sólo es una de las actividades que se requieren en la atención primaria para un buen manejo de los casos que se detecten, es necesario señalar que se requiere de un modelo de atención integral que incorpore tanto la detección como el tratamiento farmacológico y psicosocial.

Combined pre- and postnatal ethanol exposure in rats disturbs the myelination of optic axons.

AIMS: To analyse myelination and outgrowth of the optic axons in relation to the neuro-ophthalmological manifestations of ethanol (EtOH) abuse during pregnancy. METHODS: An experimental model of chronic EtOH exposure was developed in rats and their offspring by subjecting the dams to a liquid diet (35% of the daily total calories as either EtOH or maltose-dextrose nutritional controls (Con). Eyeballs and optic nerves were obtained at key developmental stages and processed for morphologic, immunocytochemical and immunoblotting procedures, using alternatively antibodies against myelin basic protein (MBP) or neurofilament (NF) protein, and image analysing. RESULTS: A significant delay in onset of optic axons myelination, as well as a significant reduction in optic nerve size (P < 0.001), optic axons number (P < 0.001), myelinated axons density (P < 0.001), number of myelin lamellae linked to axon diameter (P < 0.001) and optic axon cross-sectional area (P < 0.001) were detected in the global morphometric assessment of the EtOH nerves with respect to the Con. Expression of MBP and NF was noticeably reduced in the EtOH optic nerves when compared with the Con. CONCLUSION: Disturbed myelination of optic axons, caused by EtOH abuse, strongly disrupts the optic nerve development and the establishment of definitive retinal and optic nerve targets, and subsequently the visual patterns.

Thyroid hormone deficiency disrupts rat eye neurodevelopment.

Clinical and experimental studies have highlighted the role played by thyroid hormones (TH) in neural and neuro-sensorial development. However, knowledge on TH mechanisms on the developing visual system is still incomplete. To uncover TH actions on the eyes and vision we carried out a microscopical study on the role of TH in the developing retina and optic nerve, in a rat model of controlled TH deficiency (THD). Morphometric and stereological analyses of the retina and optic nerve showed a reduction in the volume of the eye (p<0.001) and optic nerve cross-sectional area (p<0.001), and thinning of the retinal layers (p<0.001). Glial development and myelination was significantly delayed in the THD optic nerves (p<0.001), as compared to controls. The data indicate that TH play an essential role in neuro-retinogenesis. Substitutive TH therapy in critical periods, should be considered in hypothyroidism-related eye disorders as well as neurodegenerative retinal processes.

S-Nitrosylation of the epidermal growth factor receptor: a regulatory mechanism of receptor tyrosine kinase activity.

Nitric oxide (NO) donors inhibit the epidermal growth factor (EGF)-dependent auto(trans)phosphorylation of the EGF receptor (EGFR) in several cell types in which NO exerts antiproliferative effects. We demonstrate in this report that NO inhibits, whereas NO synthase inhibition potentiates, the EGFR tyrosine kinase activity in NO-producing cells, indicating that physiological concentrations of NO were able to regulate the receptor activity. Depletion of intracellular glutathione enhanced the inhibitory effect of the NO donor 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (DEA/NO) on EGFR tyrosine kinase activity, supporting the notion that such inhibition was a consequence of an S-nitrosylation reaction. Addition of DEA/NO to cell lysates resulted in the S-nitrosylation of a large number of proteins including the EGFR, as confirmed by the chemical detection of nitrosothiol groups in the immunoprecipitated receptor. We prepared a set of seven EGFR(C --> S) substitution mutants and demonstrated in transfected cells that the tyrosine kinase activity of the EGFR(C166S) mutant was completely resistant to NO, whereas the EGFR(C305S) mutant was partially resistant. In the presence of EGF, DEA/NO significantly inhibited Akt phosphorylation in cells transfected with wild-type EGFR, but not in those transfected with C166S or C305S mutants. We conclude that the EGFR can be posttranslationally regulated by reversible S-nitrosylation of C166 and C305 in living cells.

Homocysteine inhibits proliferation of neuronal precursors in the mouse adult brain by impairing the basic fibroblast growth factor signaling cascade and reducing extracellular regulated kinase 1/2-dependent cyclin E expression.

Hyperhomocysteinemia (HHcy)-abnormally elevated plasma levels of homocysteine (Hcy)-has been associated with the development of neurodegenerative dementia and mild cognitive impairment. This association suggests that HHcy might facilitate memory loss in the elderly. As memory loss can occur through a deteriorated neurogenic capacity, we have studied the effects of Hcy on neural progenitor cells (NPCs) both in vitro and in vivo. We show that Hcy exerts an antiproliferative effect on basic fibroblast growth factor (bFGF) -stimulated NPCs isolated from the postnatal subventricular zone (SVZ), accompanied by inactivation of the extracellular signal-regulated kinase (Erk1/2) and inhibition of Erk1/2-dependent expression of cyclin E. Using a mice model we show that, under normal folate conditions, HHcy exerts an inhibitory effect on adult brain neurogenesis. This inhibition occurs in the caudal areas of the dentate gyrus (DG) of the hippocampus, a neurogenic area mainly involved in learning and memory performance, and in the SVZ, recently implicated in olfactory learning performance. In both areas reduced number of proliferative neuroblasts were found. Since neuroblasts are primarily bFGF-responsive progenitors already committed to a neuronal phenotype, our results strongly suggest that excess Hcy inhibits neurogenesis in the DG and SVZ by inhibiting the bFGF-dependent activation of Erk1/2 in these cells.

Age-dependent effect of nitric oxide on subventricular zone and olfactory bulb neural precursor proliferation.

Nitric oxide (NO) synthase (NOS) is developmentally regulated in the embryonic brain, where NO participates in cell proliferation, survival, and differentiation. In adults, NO inhibits neurogenesis under physiological conditions. This work investigates whether the NO action is preserved all along development up to adulthood or whether its effects in adults are a new feature acquired during brain maturation. The relationship between nitrergic neurons and precursors, as well as the functional consequences of pharmacological NOS inhibition, were comparatively analyzed in the subventricular zone (SVZ) and olfactory bulb (OB) of postnatal (P7) and adult (>P60) mouse brains. The SVZ was markedly reduced between P7 and adults, and, at both ages, neurons expressing neuronal NOS (nNOS) were found in its striatal limits. In postnatal mice, these nitrergic neurons contained PSA-NCAM, and their projections were scarce, whereas, in adults, mature nitrergic neurons, devoid of PSA-NCAM, presented abundant neuropil. In the OB, local proliferation almost disappeared in the transition to adulthood, and periglomerular nitrergic neurons, some of which were PSA-NCAM positive, were found in postnatal and adult mice. Administration of the NOS inhibitor L-NAME did not affect cell proliferation in the SVZ or in the OB of postnatal mice, whereas it significantly enhanced the number of mitotic cells in both regions in adults. Thus, the NO action on SVZ neurogenesis is a phenomenon that appears after the postnatal age, which is probably due to the germinal layer size reduction, allowing exposure of the NO-sensitive neural precursors to the NO produced in the SVZ-striatum limits.

Impact of the "Tobacco control law" on exposure to environmental tobacco smoke in Spain.

BACKGROUND: The initial evaluations of the introduction of legislation that regulates smoking in enclosed public places in European countries, describe an important effect in the control of exposure to environmental tobacco smoke. However, the evidence is still limited. The objective of this study is to estimate the short-term effects of the comprehensive "Tobacco control law" introduced in Spain on January 2006, which includes a total ban of smoking in workplaces and a partial limitation of smoking in bars and restaurants. METHODS: Cross-sectional, population-based study. The self-reported exposure to environmental tobacco smoke at home, at work, in bars and restaurants of the population aged 18 to 64 years in the Madrid Region during a period prior to the law (October and November 2005; n = 1750) was compared to that of the period immediately after the law came into force (January-July 2006; n = 1252). Adjusted odds ratios (OR) were calculated using logistic regression models. RESULTS: Passive exposure to tobacco smoke at home has hardly changed. However, at indoor workplaces there has been a considerable reduction: after the law came into force the OR for daily exposure > 0-3 hours versus non-exposure was 0.11 (95% CI: 0.07 to 0.17) and for more than 3 hours, 0.12 (95% CI: 0.09 to 0.18). For fairly high exposure in bars and restaurants versus non-exposure, the OR in the former was 0.30 (95% CI: 0.20 to 0.44) and in the latter was 0.24 (95% CI: 0.18 to 0.32); for very high exposure versus non-exposure they were 0.16 (95% CI: 0.10 to 0.24) and 0.11 (95% CI: 0.07 to 0.19), respectively. These results were similar for the smoking and non-smoking populations. CONCLUSION: A considerable reduction in exposure to environmental tobacco smoke in the workplace and, to a lesser extent, in bars and restaurants, is related to the implementation of the "Tobacco control law". Although only initial figures, these results already demonstrate the effectiveness of strategies that establish control measures to guarantee smoke-free places.

Nitric oxide decreases subventricular zone stem cell proliferation by inhibition of epidermal growth factor receptor and phosphoinositide-3-kinase/Akt pathway.

Nitric oxide (NO) inhibits proliferation of subventricular zone (SVZ) neural precursor cells in adult mice in vivo under physiological conditions. The mechanisms underlying this NO effect have now been investigated using SVZ-derived neural stem cells, which generate neurospheres in vitro when stimulated by epidermal growth factor (EGF). In these cultures, NO donors decreased the number of newly formed neurospheres as well as their size, which indicates that NO was acting on the neurosphere-forming neural stem cells and the daughter neural progenitors. The effect of NO was cytostatic, not proapoptotic, and did not involve cGMP synthesis. Neurosphere cells expressed the neuronal and endothelial isoforms of NO synthase (NOS) and produced NO in culture. Inhibition of NOS activity by N(omega)-nitro-L-arginine methylester (L-NAME) promoted neurosphere formation and growth, thus revealing an autocrine/paracrine action of NO on the neural precursor cells. Both exogenous and endogenous NO impaired the EGF-induced activation of the EGF receptor (EGFR) tyrosine kinase and prevented the EGF-induced Akt phosphorylation in neurosphere cells. Inhibition of the phosphoinositide-3-kinase (PI3-K)/Akt pathway by LY294002 significantly reduced the number of newly formed neurospheres, which indicates that this is an essential pathway for neural stem cell self-renewal. Chronic administration of l-NAME to adult mice enhanced phospho-Akt staining in the SVZ and reduced nuclear p27(Kip1) in the SVZ and olfactory bulb. The inhibition of EGFR and PI3-K pathway by NO explains, at least in part, its antimitotic effect on neurosphere cells and may be a mechanism involved in the physiological role of NO as a negative regulator of SVZ neurogenesis in adult mice.

Chronic inhibition of nitric oxide synthesis enhances both subventricular zone neurogenesis and olfactory learning in adult mice.

The ability to generate new neurons during the course of adult life is preserved in the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus in the mammalian brain. These two regions constitute specifically regulated neurogenic niches, and provide newborn neurons involved in olfactory and spatial learning, respectively. Nitric oxide (NO) is a negative regulator of neurogenesis in the subventricular zone, whereas its role in the dentate gyrus remains controversial. Using systemic administration of NO synthase (NOS) inhibitors to chronically inhibit NO production, we increased neural precursor proliferation in the subventricular zone as well as neurogenesis in the olfactory bulb, without modifying the number of mitotic cells or the granular cell layer thickness in the dentate gyrus. The same treatment specifically improved olfactory learning performance, whereas spatial learning and memory was unchanged, thus demonstrating that olfactory memory is closely associated with the level of ongoing neurogenesis in the subventricular zone-olfactory bulb. The anatomical specificity of the NOS inhibitor actions was not due to differences in the availability of NO, as demonstrated by immunohistochemical detection of neuronal NOS and S-nitrosylated proteins in both regions. Remarkably, the distinct NO sensitivity might result from a differential expression of epidermal growth factor receptor in precursor cells in both regions, as the proliferative effect of NOS inhibitors in the subventricular zone was restricted to the cells that expressed this receptor.