A longitudinal prospective study of active tuberculosis in a Western Europe setting: insights and findings.

PURPOSE: This study investigates the potential of inflammatory parameters (IP), symptoms, and patient-related outcome measurements as biomarkers of severity and their ability to predict tuberculosis (TB) evolution. METHODS: People with TB were included prospectively in the Stage-TB study conducted at five clinical sites in Barcelona (Spain) between April 2018 and December 2021. Data on demographics, epidemiology, clinical features, microbiology, and Sanit George Respiratory Questionnaire (SGRQ) and Kessler-10 as Health-Related Quality of Life (HRQoL) were collected at three time points during treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte, and monocyte/lymphocyte ratios (NLR and MLR), complement factors C3, C4, and cH50, clinical and microbiological data, and HRQoL questionnaires were assessed at baseline, 2 months, and 6 months. Their ability to predict sputum culture conversion (SCC) and symptom presence after 2 months of treatment was also analysed. RESULTS: The study included 81 adults and 13 children with TB. The CRP, ESR, NLR, and MLR values, as well as the presence of symptoms, decreased significantly over time in both groups. Higher IP levels at baseline were associated with greater bacillary load and persistent symptoms. Clinical severity at baseline predicted a delayed SCC. Kessler-10 improved during follow-up, but self-reported lung impairment (SGRQ) persisted in all individuals after 6 months. CONCLUSIONS: IP levels may indicate disease severity, and sustained high levels are linked to lower treatment efficacy. Baseline clinical severity is the best predictor of SCC. Implementing health strategies to evaluate lung function and mental health throughout the disease process may be crucial for individuals with TB.

Factors affecting the non-urgent consultations in the emergency department of a tertiary hospital in the Philippines: A cross-sectional study.

OBJECTIVES: The non-standard emergency medicine services and the limited utilisation of primary care providers in the Philippines may contribute towards the ED being a preferred area for patients with non-urgent conditions. Our study aims to determine the factors associated with non-urgent consultations in the ED of a tertiary hospital in the Philippines. METHODS: From 7 January to 15 February 2020, we surveyed non-urgent ED patients (n = 757) presenting to a tertiary hospital in the Philippines. We evaluated the data using descriptive statistics, while chi-squared and multivariate analyses versus urgent ED patients (n = 281) were used to show the association of factors. RESULTS: Our recruited non-urgent patients were mostly 21-40 years old (n = 576 [76%]), single (n = 437 [58%]), with full-time employment (n = 654 [86%]), have Health Maintenance Organization coverage (n = 684 [90%]), self-referred (n = 498 [66%]), and have private means of getting to ED (n = 414 [55%]). They had moderate scores of social support-seeking behaviours (mean 3.92/5; 95% confidence interval [CI] 3.88-3.96), health literacy (mean 3.58/5; 95% CI 3.56-3.61), self-efficacy (mean 3.09/5; 95% CI 3.56-3.61), whereas their ED access score (mean 4.10/5; 95% CI 4.06-4.14) was high. They had moderate self-assessed severity (mean 3.75/6; 95% CI 3.70-3.80), urgency (mean 3.83/6; 95% CI 3.78-3.88), and anxiety (mean 3.88/6; 95% CI 3.83-3.93) scores and high ED satisfaction rating (mean 4.73/6; 95% CI 4.69-4.77). They mostly had digestive (n = 203 [26.8%]) and infection-related (n = 172 [22.7%]) chief complaints and final diagnoses (n = 198 [26.2%] and n = 145 [19.2%], respectively), without previous consultations (n = 577 [76%]), and eventually discharged (n = 755 [99%]). Our urgent patients had similar characteristics, but with higher assessed patient severity, urgency, anxiety and satisfaction with ED services (P < 0.001). CONCLUSION: Non-urgent consultations in ED are attributed to multiple factors encompassing socio-demographic, socio-economic and psychosocial dimensions. These factors must be considered in improving the current healthcare management system for the appropriate utilisation of ED in the Philippines.

Revisión de las últimas novedades en el manejo del paciente con urticaria crónica: Consenso multidisciplinar de la comunidad autónoma de Andalucía / A Review of the Latest Recommendations on the Management of Chronic Urticaria: A Multidisciplinary Consensus Statement from Andalusia, Spain

La urticaria crónica es una enfermedad de la piel difícil de tratar que presenta un alto impacto negativo en la calidad de vida de los pacientes. La última actualización de la guía europea para el manejo del paciente con urticaria se publicó en 2018. Con el actual contexto, presentamos un enfoque multidisciplinar para la aplicación del nuevo algoritmo de tratamiento propuesto por la guía en el territorio español, más concretamente, en la comunidad autónoma de Andalucía

Chronic urticaria is a difficult-to-treat skin disorder that has a major impact on patient quality of life. The latest update of the European guideline on the management of urticaria was published in 2018. In this consensus statement, produced in the autonomous community of Andalusia, Spain, we describe a multidisciplinary approach for applying the new treatment algorithm proposed by the European guideline in our región

Corea secundaria a hiperglucemia no cetósica: a propósito de un caso / Chorea secondary to non-ketotic hyperglycaemia: presentation of a case

No disponible

Gastric duplication cyst in the adult. A case report.

Gastric duplication cyst is a very rare congenital anomaly accounting up to 4-9% of all gastrointestinal tract duplications. It is a quite rare anomaly in adults, the majority of cases are diagnosed in the neonatal period. Gastric duplication cysts are usually asymptomatic in the adult. They are usually discovered incidentally in TAC or RMN, although the best specificity diagnostic test is the echoendoscopy. The best election treatment is the surgical complete extirpation. We describe a case of an adult patient who is diagnosed of the incidentally gastric cyst duplication.

El quiste de duplicación gástrico es una anomalía congénita muy rara que representa entre 4 y 9% de todas las duplicaciones del aparato digestivo. Es una alteración bastante rara en el adulto y la mayoría de los casos se diagnostica en el periodo neonatal. En el adulto suele cursar de forma asintomática y la TC o RMN la descubren de forma incidental, aunque la prueba que la diagnóstica con mayor eficacia es la ecoendoscopia. La extirpación quirúrgica completa de la lesión se considera el tratamiento de elección. Se presenta el caso clínico de una paciente con un quiste de duplicación gástrico diagnosticado de forma incidental.

Voluntary Exercise-Induced Activation of Thyroid Axis and Reduction of White Fat Depots Is Attenuated by Chronic Stress in a Sex Dimorphic Pattern in Adult Rats.

The activity of the hypothalamus-pituitary-thyroid (HPT) axis is inhibited by energy deficit, by acute or chronic stress, but activated by cold exposure or exercise. Because stress curtails acute cold induced activation of HPT, we evaluated the effect of chronic stress on HPT axis response to voluntary exercise, a persistent energy-demanding situation. Adult male and female Wistar rats were exposed to restraint stress, 30 min/day for 2 weeks, or to isolation (Iso) [post-natal day [PND] 30-63]. Exercise was performed (7 p.m.-7 a.m.) in a running wheel, sedentary controls stayed in individual cages (Sed); at 7 a.m. they were housed with their cage mate or individually (Iso); food intake by the exercised group was measured day and night to pair-fed Sed. At sacrifice, hormones, mRNA levels and tissue weights were quantified. Control or restrained adult rats had access to running wheel daily for 2 weeks. Compared to C, exercise decreased white adipose tissue (WAT) mass in females and males, increased hypothalamic paraventricular nucleus (PVN)-Trh expression in males proportionally to exercise performed, and increased TSH and T4 serum concentration in females. These changes were not detected in restrained groups. Starting at PND 63 control (2/cage) and isolated (1/cage) rats either exercised on 10 alternated nights or were sedentary. In control male animals, compared to Sed rats, exercise did not decrease WAT mass, nor changed HPT axis activity, but increased Pomc and deiodinase 2 (Dio2) expression in mediobasal hypothalamus (MBH), adrenergic receptor ß3 and uncoupling protein-1 in brown adipose tissue. In control female animals, exercise decreased WAT mass, increased Pomc, Dio2, and Trhde expression in MBH, and TSH serum concentration. Iso females had lower TSH and T4 serum concentration, Dio2 and Trhde expression in MBH than controls. The stress response was higher in isolated males than females, but in males it did not alter the effects of exercise, in contrast to isolated females that had a blunted response to exercise compared to controls. In conclusion, chronic stress interferes with metabolic effects produced by exercise, such as loss of WAT mass, coincident with dampening of HPT activity.

Assessment of the bacterial community structure in shallow and deep sediments of the Perdido Fold Belt region in the Gulf of Mexico.

The Mexican region of the Perdido Fold Belt (PFB), in northwestern Gulf of Mexico (GoM), is a geological province with important oil reservoirs that will be subjected to forthcoming oil exploration and extraction activities. To date, little is known about the native microbial communities of this region, and how these change relative to water depth. In this study we assessed the bacterial community structure of surficial sediments by high-throughput sequencing of the 16S rRNA gene at 11 sites in the PFB, along a water column depth gradient from 20 to 3,700 m, including five shallow (20-600 m) and six deep (2,800-3,700 m) samples. The results indicated that OTUs richness and diversity were higher for shallow sites (OTUs = 2,888.2 ± 567.88; H' = 9.6 ± 0.85) than for deep sites (OTUs = 1,884.7 ± 464.2; H' = 7.74 ± 1.02). Nonmetric multidimensional scaling (NMDS) ordination revealed that shallow microbial communities grouped separately from deep samples. Additionally, the shallow sites plotted further from each other on the NMDS whereas samples from the deeper sites (abyssal plains) plotted much more closely to each other. These differences were related to depth, redox potential, sulfur concentration, and grain size (lime and clay), based on the environmental variables fitted with the axis of the NMDS ordination. In addition, differential abundance analysis identified 147 OTUs with significant fold changes among the zones (107 from shallow and 40 from deep sites), which constituted 10 to 40% of the total relative abundances of the microbial communities. The most abundant OTUs with significant fold changes in shallow samples corresponded to Kordiimonadales, Rhodospirillales, Desulfobacterales (Desulfococcus), Syntrophobacterales and Nitrospirales (GOUTA 19, BD2-6, LCP-6), whilst Chromatiales, Oceanospirillales (Amphritea, Alcanivorax), Methylococcales, Flavobacteriales, Alteromonadales (Shewanella, ZD0117) and Rhodobacterales were the better represented taxa in deep samples. Several of the OTUs detected in both deep and shallow sites have been previously related to hydrocarbons consumption. Thus, this metabolism seems to be well represented in the studied sites, and it could abate future hydrocarbon contamination in this ecosystem. The results presented herein, along with biological and physicochemical data, constitute an available reference for further monitoring of the bacterial communities in this economically important region in the GoM.

Ectima gangrenoso por Pseudomona aeuginosa / Ecthyma gangrenosum due to Pseudomonas aeruginosa

El ectima gangrenoso es una manifestación dermatológica característica de una infección severa causada casi siempre por Pseudomonas aeruginosa (P. aeruginosa), con o sin bacteriemia. Las infecciones severas por P. aeruginosa se presentan habitualmente en pacientes con inmunodepresión u hospitalizados, en los pacientes sanos existe el antecedente de foliculitis y forunculosis. El diagnóstico es evidentemente clínico con confirmación en cultivos. El ectima es una manifestación cutánea de una infección severa que lleva a confusión diagnóstica y causa retraso en el inicio del tratamiento. El tratamiento quirúrgico precoz asociado a una cobertura antibiótica amplia y a un soporte metabólico y nutricional adecuados son la primera elección terapéutica. Se presenta el caso de una paciente joven inmunocompetente que presentó un shock séptico asociado a neutropenia, ectima gangrenoso e infección de vías urinarias causado por P. aeruginosa

Ecthyma gangrenosum is a dermatological manifestation characteristic of a severe infection almost always caused by P. aeruginosa, with or without bacteraemia. Severe infections by P. aeruginosa usually present in immunocompromised or hospitalised patients, or in healthy patients with a history of folliculitis and furunculosis. The diagnosis is clinical with culture confirmation. Ecthyma is a cutaneous manifestation of a severe infection that leads to misdiagnosis and delayed treatment. Early surgical treatment associated with a broad antibiotic coverage and adequate metabolic and nutritional support are the first therapeutic choice. We describe the case of a young immunocompetent patient who presented septic shock associated with neutropenia, ecthyma gangrenosum and urinary tract infection caused by P. aeruginosa

Structural insight into the XTACC3/XMAP215 interaction from CD and NMR studies on model peptides.

TACC3 is a centrosomal adaptor protein that plays important roles during mitotic spindle assembly. It interacts with chTOG/XMAP215, which catalyzes the addition of tubulin dimers during microtubule growth. A 3D coiled-coil model for this interaction is available but the structural details are not well described. To characterize this interaction at atomic resolution, we have designed a simplified version of the system based on small peptides. Four different peptides have been studied by circular dichroism and nuclear magnetic resonance both singly and in all possible combinations; namely, five peptide pairs and two trios. In cosolvents, all single peptides tend to adopt helical conformations resembling those of the full-length protein. However, neither the single peptides nor pairs of peptides form coiled coils. We show that the simultaneous presence of all preformed helices is a prerequisite for binding. The simplest 3D model for the interaction, based on the NMR results, is proposed. Interestingly, the peptide's structure remains unaffected by mutations at essential positions for TACC3 activity. This suggests that the lack of interaction of this TACC3 mutant with XMAP does not correlate with changes in the protein structure and that specific interactions are likely responsible for the interaction and stability of the complex.

Análisis de costes del tratamiento del prolapso de órganos pélvicos mediante colposacropexia laparoscópica o malla transvaginal / Cost analysis of surgical treatment for pelvic organ prolapse by laparoscopic sacrocolpopexy or transvaginal mesh

Objetivos. El objetivo del estudio es realizar un análisis comparativo de los costes directos de la reparación del prolapso de órganos pélvicos mediante colposacropexia laparoscópica (CL) o malla transvaginal (MTV). La hipótesis inicial es que la corrección del prolapso de órganos pélvicos mediante CL presentaría al menos un coste por procedimiento similar a la corrección mediante MTV. Material y métodos. Análisis retrospectivo comparativo del coste medio por procedimiento de los primeros 69 procedimientos consecutivos de CL frente a los primeros 69 procedimientos consecutivos de MTV. Para cada procedimiento, se determinaron los costes directos: gastos estructurales, personal, ocupación de quirófano, estancia hospitalaria, material fungible e inventariable y el material protésico implantado. Se determinó el coste medio por procedimiento para cada uno de los grupos, con el intervalo de confianza al 95%. Resultados. Mientras que el grupo de CL incurrió en un mayor gasto en relación con un mayor tiempo quirúrgico, ocupación de quirófano y anestesia, el grupo de MTV incurrió en un mayor gasto en relación con una mayor estancia hospitalaria y un coste mayor del material protésico implantado. De forma global, si bien el grupo de CL presentó un coste medio por procedimiento menor que el grupo de MTV (5.985,7 Euros ± 1.550,8 Euros vs. 6.534,3 Euros ± 1.015,5 Euros), esta diferencia no alcanzó la significación estadística. Conclusiones. En nuestro medio, la corrección del prolapso de órganos pélvicos mediante CL presenta al menos, un coste por procedimiento similar a la corrección del mismo mediante MTV (AU)

Objectives. The objective of this study is to compare direct costs of repairing pelvic organ prolapse by laparoscopic sacrocolpopexy (LS) against vaginal mesh (VM). Our hypothesis is the correction of pelvic organ prolapse by LS has a similar cost per procedure compared to VM. Material and methods. We made a retrospective comparative analysis of medium cost per procedure of first 69 consecutive LS versus first 69 consecutive VM surgeries. We calculate direct cost for each procedure: structural outlays, personal, operating room occupation, hospital stay, perishable or inventory material and prosthetic material. Medium cost per procedure were calculated for each group, with a 95% confidence interval. Results. LS group has a higher cost related to a longer length of surgery, higher operating room occupation and anesthesia; VM group has a higher cost due to longer hospital stay and more expensive prosthetic material. Globally, LS has a lower medium cost per procedure in comparison to VM (5,985.7 Euros ± 1,550.8 Euros vs. 6,534.3 Euros ± 1,015.5 Euros), although it did not achieve statistical signification. Conclusions. In our midst, pelvic organ prolapse surgical correction by LS has at least similar cost per procedure compared to VM (AU)

Utilización de fármacos en niños en cuidados intensivos: estudio de las prescripciones off-label / Drug utilization pattern in children and off-label use of medicines in a pediatric intensive care unit

OBJETIVO: Evaluar los usos off-label (fuera de ficha técnica [FT]) y unlicensed (medicamentos no autorizados específicamente para niños) en cuidados intensivos neonatales y pediátricos. METODOLOGÍA: Se realizó un estudio transversal en la UCINP (Unidad de Cuidados Intensivos Neonatales y Pediátricos) de un hospital público de tercer nivel de Granada, incluyéndose a todos los niños en los que se indicara al menos un tratamiento farmacológico, mediante reclutamiento consecutivo, y durante un periodo de 5 meses (N = 81). Las variables recogidas fueron sociodemográficas, clínicas, y medicación. Todas las prescripciones fueron clasificadas a partir de la información contenida en FT sobre uso en niños. RESULTADOS: Hubo un total de 601 prescripciones, con una media de 7,4 ± 6 medicamentos por niño. Los fármacos más empleados pertenecían a los grupos J (antiinfecciosos), N (sistema nervioso) y C (cardiovascular). Algo más de la mitad de las prescripciones fueron off-label (52%), fundamentalmente por emplear una dosificación distinta de la recomendada en FT (79%), seguida de diferente indicación (13,5%), edad (5%) y vía de administración (2,5%). El uso de medicamentos no específicamente autorizados en niños solo supuso el 5% de las prescripciones. CONCLUSIONES: El presente estudio aporta datos sobre este tipo de prescripciones en una UCINP española. Pone de manifiesto que el 89% de los niños tiene al menos una prescripción fuera de FT y un 22,3% al menos un uso de fármaco no autorizado para niños. Cifras elevadas, pero justificables dentro del ámbito de unos cuidados intensivos que, además, incluyen neonatos. Pero aunque muchos de los tratamientos estén protocolizados, sería deseable mejorar la evidencia disponible, así como actualizar las FT

OBJECTIVE: This study aims to assess the prescription profile and license status of drugs used in a neonatal and pediatric intensive care unit (NPICU). METHODS: A prospective observational study was conducted on a dynamic cohort of children admitted to an NPICU (N = 81) in a tertiary hospital (Granada, Spain). All prescriptions were classified asoff-label or unlicensed based on the summary of product characteristics (SPC). RESULTS: Of a total of 601 prescriptions, the patients received a mean of 7.4 ± 6 drugs each. The most commonly prescribed drugs corresponded to classes J (anti-infectious, systemic use) N (nervous system) and C (cardiovascular). A little over one-half of the prescriptions were off-label (52%), usually due to dosages differing from the SPC recommendations (79%), followed by different indications (13.5%), age (5%) and administration route (2.5%). In this NPICU, unlicensed usage represented only 5% of all prescriptions. CONCLUSIONS: This study contributes data on prescription of this kind in a Spanish NPICU, revealing at least one off-label prescription in 89% of the children and at least one unlicensed use in 22.3%. These are high figures, but are to be expected given the inclusion of newborn infants and the critical care setting. Even though such usage follows clinical protocols, we underscore the dual need to base treatment on the best available evidence, and to upgrade the SPC accordingly

Executive summary of the consensus document on post-exposure prophylaxis against HIV, HBV and HCV in adults and children.

Post-exposure prophylaxis (PEP) can be a secondary measure to prevent infection by human immunodeficiency virus (HIV) when primary prevention has failed. PEP is advised for people with sporadic and exceptional risk exposure to HIV. This consensus document about occupational and non-occupational PEP recommendations aims to be a technical document for healthcare professionals. Its main objective is to facilitate the appropriate use of PEP. To this end, some recommendations have been established to assess the risk of transmission in different types of exposure, situations where PEP should be recommended, special circumstances to take into account, antiretroviral (ARV) guidelines including start and end of the treatment, early monitoring of tolerance and adherence to the treatment, subsequent monitoring of people exposed, independently of having received PEP or not, and need of psychological support. This document is intended for all professionals who work in clinical practice in the field of HIV infection.

Information and communication technologies for approaching smokers: a descriptive study in primary healthcare.

BACKGROUND: Common interventions for smoking cessation are based on medical advice and pharmacological aid. Information and communication technologies may be helpful as interventions by themselves or as complementary tools to quit smoking. The objective of the study was to determine the use of information and communication technologies (ICTs) in the smoking population attended in primary care, and describe the major factors associated with its use. METHODS: Descriptive observational study in 84 health centres in Cataluña, Aragon and Salamanca. We included by simple random sampling 1725 primary healthcare smokers (any amount of tobacco) aged 18-85. Through personal interview professionals collected Socio-demographic data and variables related with tobacco consumption and ICTs use were collected through face to face interviews Factors associated with the use of ICTs were analyzed by logistic regression. RESULTS: Users of at least one ICT were predominantly male, young (18-45 years), from most favoured social classes and of higher education. Compared with non-ICTs users, users declared lower consumption of tobacco, younger onset age, and lower nicotine dependence. The percentages of use of email, text messages and web pages were 65.3%, 74.0% and 71.5%, respectively. Factors associated with the use of ICTs were age, social class, educational level and nicotine dependence level. The factor most closely associated with the use of all three ICTs was age; mainly individuals aged 18-24. CONCLUSIONS: The use of ICTs to quit smoking is promising, with the technology of mobile phones having a broader potential. Younger and more educated subjects are good targets for ICTs interventions on smoking cessation.

[Metabolic encephalopathy secondary to vitamin D intoxication]. / Encefalopatía metabólica secundaria a intoxicación por vitamina D.

The association between vitamin D deficiency and increased risk of, among others, cardiovascular and autoimmune diseases has lead in the last years to an enhanced interest in the usage of supplements to achieve the normalization of plasmatic values at 25(OH) D. Apparently this search for normalization is resulting in an higher incidence on vitamin D intoxication. We present the case of an 81 years old woman with metabolic encephalopathy and renal failure secondary to iatrogenic vitamin D intoxication. Calcium and vitamin D oral supplements were prescribed after an osteoporotic vertebral fracture. The patient improved clinically as well as analytically after receiving treatment with diuretics and hydration. We emphasize the importance of discarding hypercalcemia as a cause of metabolic encephalopathy; moreover we highly recommend keeping vitamin D intoxication in mind as an uncommon although always possible etiology of reversible hypercalcemia and renal failure.

La asociación entre la deficiencia de vitamina D y un mayor riesgo de diversas enfermedades, entre ellas cardiovasculares y autoinmunes, ha aumentado en los últimos años el uso de suplementos para la normalización de los valores plasmáticos de esta vitamina. Desde entonces se ha descrito un mayor número de casos de intoxicación iatrogénica por vitamina D. Presentamos una enferma de 81 años con encefalopatía metabólica e insuficiencia renal secundarias a una intoxicación por vitamina D. Los suplementos orales con calcio y vitamina D se le prescribieron después de sufrir una fractura vertebral osteoporótica. La enferma mejoró clínica y analíticamente tras hidratación y diuréticos. Es importante destacar la hipercalcemia como causa de encefalopatía metabólica y considerar la intoxicación por vitamina D como etiología poco frecuente pero posible de hipercalcemia e insuficiencia renal reversibles.

Análisis de marcadores de superficie celular de utilidad en el diagnóstico de la sepsis neonatal: Reporte preliminar / Utility of the cellular surface markers in the diagnosis of neonatal sepsis: Preliminary report

La cuantificación de poblaciones leucocitarias en sangre periférica puede realizarse con ayuda del análisis por citometría de flujo. Los valores de poblaciones leucocitarias en neonatos son frecuentemente contrastados con sangre periférica de adultos. El presente reporte preliminar muestra el análisis de tres muestras de sangre de cordón umbilical de pacientes sanos y tres muestras de sangre periférica de neonatos con diagnóstico de sepsis tardía. Los resultados obtenidos muestran que CD69, CD71 y CD45RO pueden ser de utilidad para diferenciar estados de sepsis en neonatos. En un estudio futuro, la propuesta es realizar un análisis multiparamétrico por citometría de flujo que permita un análisis integral de la sepsis neonatal.

Quantification of leukocyte populations in peripheral blood can be performed using flow cytometry. The leukocyte populations are often contrasted between neonate and adult peripheral blood. This preliminary report shows the analysis of three samples of umbilical cord blood of healthy subjects and three peripheral blood samples of newborns diagnosed with late sepsis. Our results show that CD69, CD71 and CD45RO could be useful to differentiate states of sepsis in neonates. We propose a subsequent study to generate a multiparametric flow cytometry analysis that will allow a comprehensive analysis of neonatal sepsis.

Structure of a simplified ß-hairpin and its ATP complex.

The capacity of three designed duodecamer peptides with the low diversity sequence: H1ϕ2I3K4I5D6G7K8ϕ9I10K11H12 where ϕ is His, Phe or Trp, to adopt a ß-hairpin conformation was studied using NMR spectroscopy. Whereas KIAßH, the variant with His at positions two and nine, is disordered, KIAßF, the peptide with Phe at these positions, adopts a small population of ß-hairpin. A high population of ß-hairpin structure was detected for KIAßW, the variant with Trp. Utilizing NMR data, the structure of KIAßW was solved and it reveals a ß-hairpin stabilized by hydrophobic interactions between Ile residues on one face and Trp-Trp and cation-π interactions on the opposite face. Upon adding ATP, these peptides show chemical shift changes indicative of ATP binding. The binding of ATP to KIAßW shows a KD ≈ 20 µM at pH 5, 5 °C and has a 1:1 stoichiometry. The KIAßW-ATP complex was determined using NMR spectroscopy and reveals the adenine ring sandwiched between the two Trp indole rings and that ATP binding induces important conformational changes in His1, Trp2, Lys4, Trp9 and Lys11 in the ß-hairpin. The implications of these results for the hypothetic presence of ß-hairpins and amyloids alongside RNAs on the prebiotic Earth are discussed.

Functional cGMP-gated channels in cerebellar granule cells.

Cyclic nucleotide-gated channels (CNGCs) are important transducers of external signals in sensory processes. These channels are ubiquitously expressed in a variety of neurons, and are necessary to transduce signals for growth cone guidance and plasticity. Here, we demonstrate that the CNGC subunits (CNGA1 and CNGB1, presumably the 1b isoform) are expressed in rat cerebellar granule cells and that they combine to form functional channels. The expression of the mRNAs that encode these proteins is maximal after 7 days in cell culture, when the channels are expressed at synapses and co-localize with the synaptic marker synapsin I. These ligand-gated channels are functional and can be blocked by Mg(2+) or L-cis-diltiazem. Moreover, channel opening in response to increases in intracellular cGMP results in Ca(2+) entry into the cell. Chronic blockade (96 h) of these channels with L-cis-diltiazem significantly decreases the number of functional boutons, as determined by their capacity to load and unload the styryl dye FM1-43 when stimulated. Moreover, the unloading kinetics is modified from a biphasic to a monophasic profile in a subset of synaptic boutons. These channels are also expressed in early developmental stages, both in the soma and in emerging processes, and CNGA1 can be detected in growth cones. Pharmacological blockade of these channels with L-cis-diltiazem causes an overall change in growth cone morphology, impairing the formation of lamellipodia between filopodia and increasing the number of filopodia. J

Naphthalene triplet excited state as a probe for the assessment of drug distribution in binary protein systems.

Three drugs containing the naphthalene (NP) chromophore, namely, naproxen (NPX), propranolol (PPN), and cinacalcet (CIN), but with different affinities toward serum albumins (SAs) and α-1-acid glycoproteins (AAGs) have been employed for the assessment of drug distribution in binary SA/AAG systems. These three drugs represent an appropriate choice for checking whether a methodology based on transient absorption spectroscopy of a given reporter can be employed for discrimination between different distribution patterns in multicompartmental biological media. Thus, upon laser flash photolysis (LFP) of NPX, PPN, and CIN in the presence or absence of proteins, the NP triplet excited state ((3)NP*) at ∼420 nm was always detected, although the kinetics of the decay traces was structure- and medium-dependent. In aerated PBS, only a very short triplet lifetime (τ(T)) was found (1-2 µs). By contrast, in the presence of SAs, two longer triplet lifetimes (5-76 µs) were observed, ascribed to (3)NP* within site I and site II. Upon binding to AAGs, only a long τ(T) (15-47 µs) was found. When the two proteins were present simultaneously in the same media, fitting of the decay traces was clearly consistent with a distribution of the drug between the different biological compartments and the bulk solution, which correlates well with the known protein affinities of every drug. Experiments were performed in both human (HSA/HAAG) and bovine protein media (BSA/BAAG). The results showed that SAs are the major carriers for NPX; by contrast, PPN binds preferentially to AAGs. An intermediate situation was found for CIN, which presents comparable affinity for both proteins. The results obtained for the two enantiomers of each drug were very similar, although a small stereodifferentiation was observed between the triplet lifetimes in the protein binding sites.

Control de síntomas por un equipo de soporte de cuidados paliativos. Resultados preliminares / No disponible

Objetivos: describir el grado de control sintomático de enfermos oncológicos terminales, basándonos en herramientas diagnósticas específicas (ESAS y HAD). Analizar si algunos síntomas se asocian con una menor supervivencia. Material y métodos: estudio longitudinal prospectivo de pacientes atendidos por el ESCP de Badajoz durante un mes. Se incluyen: índice de Karnofsky, fechas de primera visita, última visita y éxitus, ESAS inicial y final, HAD inicial y final y TQSS inicial. Para observar el grado de mejoría sintomática, desarrollamos el test apareado de comparación de medias (Stata9). Se utilizaron las tablas de Kaplan Meyer para el análisis de supervivencia. Resultados: se incluyeron 25 pacientes. El nivel de intensidad de los síntomas (ESAS) reveló Que inicialmente los síntomas peor controlados fueron la astenia: X = 5,3 (3,79-6,82), la tristeza: 7,35 (6,50-8,20) y el bienestar, 6,27 (4,90-7,64). Con la intervención del ESCP disminuyó la intensidad de los síntomas excepto la astenia. Cuando empleamos el cuestionario específico HAD para monitorizar la depresión y ansiedad, se comprobó: X = 23.21 (lC 95%,19,75.26,67), en la última visita 19,73 05,79-23,681. En relación a la existencia de disnea la mediana de supervivencia fue de 40 días, si no había disnea inicial, frente a 24, cuando estaba presente (p long. rank: 0,00071. Conclusiones: tras la intervención del ESCP se asistió a una mejoría sintomática, estadísticamente significativa en la depresión, ansiedad y bienestar. El ESAS y el HAD como herramientas diagnósticas fueron útiles para la monitorización de síntomas. La disnea y la depresión se asociaron con una supervivencia inferior (AU)

Objectives: to describe symptom control extent in terminally iII patients based on specific diagnostic tools such as the Edmonton Symptom Assessment System (ESAS) and Hospital Anxiety and Depression Scale (HADS). To analyze whether some symptoms are associated with poor survival. Material and methods: this was a longitudinal prospective study in terminally ilI patients fram Badajoz (Spain) who were included in the Regional Palliative Care Program. They were cared for by the Palliative Care Team for a month. Karnofsky Index, first inclusion visit, last visit and demise data, first and last ESAS control, first and last HADS score, and initial assessment with TQSS were collected. Also, to observe improvement in symptomatic control a matched mean comparison test was used. Finally, the Kaplan Meyer procedure was applied for a survival analysis. Results: twenty-five patients were included in the study. Initially, the worst controlled symptoms were asthenia X = 5.3 (3.79-6.82), sadness 7.35 (6.50-8.20) and well-being 6.27 (4.90-7.64). Alter care by a Palliative Care Team symptom severity decreased except for asthenia. We also used the HADS test for measuring clinical anxiety and depression, and obtained the following scores: first meeting X = 23.21 (95% CI: 19.75.26.67) and last visit 19.73 (15.79-23.68). Regarding how survival was affected by dypsnea, we observed that it was longer when dyspnea was not initially present (40 days and 24 days, respectively); log-rank p: 0.0007. Conclusions: there was a statistically significant improvement in symptoms such as depression, anxiety and well-being after a Palliative Care Team intervention. ESAS and HADS are two useful tools for monitoring symptoms. Short survival was associated with the presence of dyspnea and depression (AU)

[Diagnostic errors and temporal stability in bipolar disorder]. / Errores de diagnóstico y estabilidad temporal en el trastorno bipolar.

INTRODUCTION: The diagnosis of bipolar disorder is frequently modified during the course of the illness. MATERIAL AND METHODS: Diagnostic changes and associated errors are described for 1,153 patients diagnosed as bipolar disorder, aged over 18 years and with at least ten follow-up visits. Data was extracted from a clinical registry of out-patient care specialized in Psychiatry and psychiatric hospitalizations of 25,152 patients representative of an urban area of 240,000 inhabitants. Limit for diagnostic stability was established as the maintenance of the bipolar disorder diagnosis in at least 75% of the visits. RESULTS: A total of 158 (46.1 %) out of 342 patients diagnosed as having a bipolar disorders in the first visit kept this diagnostic constant in subsequent evaluations. Infradiagnostic initial error was committed with 108 stable patients who were not diagnosed in the first visit. 184 patients diagnosed in the first visit with bipolar disorder had less than 75 % concordant diagnosis along the follow-up and could be considered as initial overdiagnosis. Two hundred and nine out of the 443 patients who were diagnosed as bipolar disorder in their last visit did not keep stability criteria in their follow-up and could be considered therefore as final overdiagnosis. Thirty two stable patients not diagnosed in their last visit could be considered as infradiagnosis final error. Diagnosis from schizophrenia spectrum (F2) appears in one of every four psychiatric visits of the patients included in this study. Overlap was seen in three other categories: anxiety disorders (F4), personality disorders (F6) and substance abuse disorders. CONCLUSION: Initial course of bipolar disorder causes difficulties in the diagnosis.