Efficiency and sensitivity optimization of a protocol to quantify indoor airborne SARS-CoV-2 levels.

BACKGROUND: Development of methodologies to quantify airborne micro-organisms is needed for the prevention and control of infections. It is difficult to conclude which is the most efficient and sensitive strategy to assess airborne SARS-CoV-2 RNA levels due to the disparity of results reported in clinical settings. AIM: To improve our previously reported protocol of measuring SARS-CoV-2 RNA levels, which was based on bioaerosol collection with a liquid impinger and RNA quantification with droplet digital polymerase chain reaction (ddPCR). METHODS: Air samples were collected in COVID-19 patient rooms to assess efficiency and/or sensitivity of different air samplers, liquid collection media, and reverse transcriptases (RT). FINDINGS: Mineral oil retains airborne RNA better than does hydrophilic media without impairing integrity. SARS-CoV-2 ORF1ab target was detected in 80% of the air samples using BioSampler with mineral oil. No significant differences in effectiveness were obtained with MD8 sampler equipped with gelatine membrane filters, but the SARS-CoV-2 copies/m3 air obtained with the latter were lower (28.4 ± 6.1 vs 9 ± 1.7). SuperScript II RT allows the detection of a single SARS-CoV-2 genome RNA molecule by ddPCR with high efficiency. This was the only RT that allowed the detection of SARS-CoV-2 N1 target in air samples. CONCLUSION: The collection efficiency and detection sensivity of a protocol to quantify SARS-CoV-2 RNA levels in indoor air has been improved in the present study. Such optimization is important to improve our understanding of the microbiological safety of indoor air.

[Moyamoya disease: revision and description of a number of pedriatic cases]. / Enfermedad de moyamoya: descripción de una serie de casos pediátricos.

INTRODUCTION: Moyamoya disease is caused because of progressive occlusion of the arterial circle of Willis, leading to a compensatory net-like abnormal vessels development. The objective is to describe the number of cases in our center (tertiary hospital). PATIENTS AND METHODS: Retrospective study. Revision of pediatric medical histories diagnosed of moyamoya disease or moyamoya syndrome (in case of predisposing disease) between 2005 and 2018. Demographic variables were collected, related to diagnosis, risk factors, treatment, and follow-up. RESULTS: Seven cases were collected with a median age of 6 years and an equitable distribution by sex. Five associated predisposing pathologies (Down syndrome, neurofibromatosis, sickle cell disease, Behcet). The main clinical diagnosis was neurological focus (five cases), followed by epileptic seizures (four), and headache (two). One was asymptomatic at diagnosis. Six strokes were documented, five of them were isquemic. The arteriography (goldstardard) was made in five patients. Five presented bilateral involvement of the vessels, the internal carotid arteries and the middle cerebral arteries were the most affected. Six received acetylsalicylic acid treatment and five of them required antiepileptic drugs. Revascularization surgery (encephaloduroarteriomyosinangiosis) was performed in four patients, and in one, strokes persisted. The most prevalent sequelae were hemiparesis and psychomotor retardation. CONCLUSIONS: The risk factors presented in our patients match to those described in the literature. The symptoms at the onset can be diverse and ischemic strokes predominate in our series. Revascularization surgery was effective in more than half of the cases. Subsequent follow-up is necessary to assess complications and sequelae.

TITLE: Enfermedad de moyamoya: descripción de una serie de casos pediátricos.Introducción. La enfermedad de moyamoya se produce por la oclusión de las arterias alrededor del polígono de Willis y genera una amplia red de vasos colaterales. El objetivo es describir la serie histórica de nuestro centro (hospital terciario). Pacientes y métodos. Es un estudio retrospectivo. Se hizo una revisión de historias clínicas de pacientes pediátricos diagnosticados de enfermedad o síndrome de moyamoya (si patología predisponente) entre 2005 y 2018. Se recogieron variables demográficas, relacionadas con el diagnóstico, factores de riesgo, tratamiento y seguimiento. Resultados. Se obtuvieron siete casos, con una mediana de edad de seis años y distribución por sexos equitativa. Cinco asociaban patologías predisponentes (síndrome de Down, neurofibromatosis, drepanocitosis y Behçet). La clínica predominante en el diagnóstico fue focalidad neurológica (cinco casos), seguida de crisis epilépticas (cuatro) y cefalea (dos). Un paciente era asintomático en el momento del diagnóstico. Se documentaron seis ictus, cinco de los cuales fueron isquémicos. La arteriografía (técnica de referencia) constaba en cinco pacientes. Cinco presentaban afectación bilateral y estaban mayormente afectadas las arterias carótidas internas y las cerebrales medias. Seis recibieron tratamiento con ácido acetilsalicílico y cinco necesitaron fármacos antiepilépticos. La cirugía de revascularización (encefaloduroarteriomiosinangiosis) se realizó en cuatro pacientes y en uno persistieron los ictus. Las secuelas más prevalentes fueron hemiparesia y retraso psicomotor. Conclusiones. Los factores de riesgo presentados en nuestros pacientes se ajustan a los descritos en la bibliografía. La clínica en el inicio puede ser diversa y predominan los ictus isquémicos en nuestra serie. La cirugía de revascularización fue efectiva en más de la mitad de los casos. Es necesario un seguimiento posterior para evaluar complicaciones y secuelas.

Synthesis of aminopyrazoles from sydnones and ynamides.

Aminopyrazoles are prepared from readily accessible sydnones and sulfonyl ynamides using either a copper-mediated sydnone alkyne cycloaddition (CuSAC) or in situ generated strained cyclic ynamides.

Endogenous jasmonic and salicylic acids levels in the Cd-hyperaccumulator Noccaea (Thlaspi) praecox exposed to fungal infection and/or mechanical stress.

KEY MESSAGE: Sensitivity to Erysiphe in Noccaea praecox with low metal supply is related to the failure in enhancing SA. Cadmium protects against fungal-infection by direct toxicity and/or enhanced fungal-induced JA signaling. Metal-based defense against biotic stress is an attractive hypothesis on evolutionary advantages of plant metal hyperaccumulation. Metals may compensate for a defect in biotic stress signaling in hyperaccumulators (metal-therapy) by either or both direct toxicity to pathogens and by metal-induced alternative signaling pathways. Jasmonic acid (JA) and salicylic acid (SA) are well-established components of stress signaling pathways. However, few studies evaluate the influence of metals on endogenous concentrations of these defense-related hormones. Even less data are available for metal hyperaccumulators. To further test the metal-therapy hypothesis we analyzed endogenous SA and JA concentrations in Noccaea praecox, a cadmium (Cd) hyperaccumulator. Plants treated or not with Cd, were exposed to mechanical wounding, expected to enhance JA signaling, and/or to infection by biotrophic fungus Erysiphe cruciferarum for triggering SA. JA and SA were analyzed in leaf extracts using LC-ESI(-)-MS/MS. Plants without Cd were more susceptible to fungal attack than plants receiving Cd. Cadmium alone tended to increase leaf SA but not JA. Either or both fungal attack and mechanical wounding decreased SA levels and enhanced JA in the Cd-rich leaves of plants exposed to Cd. High leaf Cd in N. praecox seems to hamper biotic-stress-induced SA, while triggering JA signaling in response to fungal attack and wounding. To the best of our knowledge, this is the first report on the endogenous JA and SA levels in a Cd-hyperaccumulator exposed to different biotic and abiotic stresses. Our results support the view of a defect in SA stress signaling in Cd hyperaccumulating N. praecox.

[Applications of diffusion techniques in magnetic resonance imaging of musculoskeletal tumors]. / Aplicaciones de la técnica de difusión por resonancia magnética en el manejo de la patología tumoral osteomuscular.

Magnetic resonance imaging (MRI) is the technique of choice in the diagnosis, staging, and follow-up of musculoskeletal tumors. Diffusion imaging is a new functional MRI technique that provides information that is complementary to that obtained in conventional MRI sequences. Diffusion imaging has proven useful in different clinical situations like the characterization of disease involving the bone marrow (bone metastases, benign fractures, or hematological disease), the evaluation of tumors of the bones and soft tissues, and the monitoring of the response to treatment in patients with tumors. The aim of this article is to review the diffusion technique in MRI and its current clinical applications in the management of musculoskeletal tumors.

Docetaxel combined with irinotecan or 5-fluorouracil in patients with advanced oesophago-gastric cancer: a randomised phase II study.

BACKGROUND: Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesophago-gastric cancer. This randomised phase II study evaluated the efficacy and toxicity profile of two non-platinum docetaxel-based doublet regimens in advanced oesophago-gastric cancer. METHODS: Chemotherapy-naïve patients with advanced oesophago-gastric cancer were randomised to receive either 3-weekly DI (docetaxel 60 mg m(-2) plus irinotecan 250 mg m(-2) (Day 1)) or 3-weekly DF (docetaxel 85 mg m(-2) (Day 1) followed by 5-fluorouracil 750 mg m(-2) per day as a continuous infusion (Days 1-5)). RESULTS: A total of 85 patients received DI (n=42) or DF (n=43). The primary endpoint was overall response rate (ORR). The ORR and time to progression (TTP) in the evaluable population (n=65) were 37.5% (DI) vs 33.3% (DF), and 4.2 months vs 4.4 months, respectively. In the intent-to-treat population, the observed ORR, TTP and median overall survival were similar between the two groups. Grade 3-4 neutropenia, febrile neutropenia and diarrhoea were more frequent in the DI arm as compared with the DF arm (83.3% vs 69.8%, 40.5% vs 18.6%, and 42.9% vs 16.3%, respectively). CONCLUSION: Both docetaxel-based doublet regimens show comparable efficacy; however, the DF regimen was associated with a better toxicity profile and is an alternative treatment option for patients in whom platinum-based regimens are unsuitable.

[Usefulness of magnetic resonance imaging in prostate cancer]. / Utilidad de la resonancia magnética en el cáncer de próstata.

In the last decade, technical advances in magnetic resonance imaging (MRI) have made it the technique of choice in the overall management of patients with suspected or confirmed prostate cancer. MR makes it possible to acquire information about morphology and function in the same examination by using techniques like spectroscopy, diffusion, and dynamic sequences with intravenous contrast material administration. Moreover, MRI enables both focused study of the prostate gland and of regional and/or whole-body involvement, depending on the clinical indications, in less than an hour. The main clinical indications for MRI of the prostate are a) staging local, regional, and/or remote disease; b) detecting prostate cancer or guiding prostate biopsy in cases of clinical suspicion or negative findings in previous biopsy specimens; and c) monitoring the response to treatment. It is important to know the different protocols with specific MRI sequences for the prostate, depending on the different clinical indications, to ensure that they are performed and interpreted correctly. This article provides up-to-date information about the use of MRI for the study of the prostate to show how the morphological and functional information can be used in clinical practice.

Mutational characterization of steroid 21-hydroxylase gene in Portuguese patients with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is a common inherited disorder of adrenal hormone biosynthesis due to mutations in the 21-hydroxylase gene, CYP21A2. Genotyping for ten of the most frequent mutations was performed in 84 Portuguese CAH patients: 10 salt-wasters, 6 simple-virilizers and 68 non-classical patients. The patients were diagnosed by a level of 17-hydroxyprogesterone above 10 ng/ml either in basal conditions or after an ACTH 0,25 mg IV Test. A variety of genotyping techniques were used to detect these ten mutations. CYP21A2 mutations were detected in 91.7% (77/84) of the patients. The frequency of alleles carrying two or more CYP21A2 mutations (9.5% - 16/168) is higher than in other populations. The most frequent mutations identified in our population were V281L (41.7%) and deletions/conversions involving the promoter region of the CYP21A2 gene (28.3%). A decreased frequency of IVS2-12C/A>G mutation (5.6%) was the most characteristic feature of our population. This study allow the characterization of the mutational spectrum of CAH patients, mainly non-classical CAH, with 21-hydroxylase deficiency from Portugal showing specific genetic features of this population which reveals differences with worldwide countries.

[Breast MRI: the usefulness of diffusion-weighted sequences for differentiating between benign and malignant lesions]. / Resonancia magnética de mama: utilidad de la difusión para diferenciar entre lesiones benignas y malignas.

OBJECTIVE: To evaluate the usefulness of diffusion-weighted MRI sequences and of the apparent diffusion coefficient (ADC) to differentiate between benign and malignant breast lesions. MATERIAL AND METHODS: We prospectively studied 88 patients (aged 31 to 79 years) with 94 lesions (80 malignant and 14 benign) who were referred for preoperative local staging. All patients underwent dynamic MRI examination after intravenous contrast administration and a diffusion-weighted sequence with ADC calculation. The results obtained at diffusion-weighted imaging were correlated with those obtained at histological examination. RESULTS: The mean value of the ADC for malignant lesions (1.12+/-0.25x10(-3)mm(2)/s) was significantly lower (p<0.001) than for benign lesions (1.61+/-0.52x10(-3)mm(2)/s). No significant differences in ADC values were found between the different subtypes of invasive carcinomas or between intraductal carcinoma and invasive carcinoma (p>0.05). Using an ADC lower than 0.95x10(-3)mm(2)/s as a threshold for malignancy, the sensitivity is 52% and the specificity is 100%. CONCLUSION: Diffusion-weighted sequences provide additional information in breast MRI that is useful for differentiating between benign and malignant lesions, thus improving the specificity of the technique.

[Glucose metabolism alterations and follow-up study of a non-diabetic adult population]. / Alteraciones del metabolismo de la glucosa y estudio de seguimiento de una población adulta no diabética.

OBJECTIVE: To determine the appearance of type 2 diabetes mellitus (DM2) and impaired fasting glucose (IFG) at five years of follow-up in a known non-diabetic population. DESIGN: nested case control studies (case s-control into a cohort) developed in two stages: 1) identification and characterization of the cohort and 2) follow-up. STUDY POPULATION: representative sample of a non-diabetic population between 40 and 75 years old attended in a Primary Health Center. IDENTIFICATION: 326 persons, 2.1% of whom were diagnosed of previously unknown DM2 and 7.3% of IFG. Insulin resistance (IR) was higher in patients with IFG and pancreatic function of beta cells (PFBC) was higher in the population without glucose metabolism alteration. FOLLOW-UP: 121 persons, 9.7 % of whom evolved to DM2 (all with IFG). IFG proportion at the end of the follow-up was 23.96%. CONCLUSIONS: At 5 years of follow-up, more than 1/3 of the population studied developed DM2 or IFG. These diagnoses were related with IR and PFBC.

Transfer of selected mineral nutrients and trace elements in the host-hemiparasite association, Cistus-Odontites lutea, growing on and off metal-polluted sites.

The role of a hemiparasitic life-style in plant resistance to toxic trace elements in polluted soils is unclear. Restriction of metal uptake by the host, restriction of metal transfer from host to parasite, or transformation of metals into a less toxic form may play a role. This study analysed the transfer of selected mineral elements from soil to host (Cistus spp.) and from host to hemiparasite (Odontites lutea) at locations with different metal burdens: a Cu-rich serpentine site, Pb-Ba mine spoil and an unpolluted soil. Highest soil-to-host transfer factors for K, Mg, Ca, Zn, Cu and Pb were observed on the unpolluted soil. Statistically significant differences among locations of host-to-parasite transfer factors were only found for Ca and Pb. Restriction of transfer of unfavourable Ca/Mg ratios, characteristic at the serpentine site, and of high Pb and Zn concentrations at the Pb-Ba mine occurred mainly at the soil-host, and not at the host-parasite, level. Odontites lutea was able to withstand enhanced Zn and Pb concentrations and low Fe/Cu ratios in shoot tissue without developing toxicity symptoms. This could be caused by specific metal resistance mechanisms in this hemiparasite and/or the transformation and transfer of these metals into a less toxic form by the metal-tolerant host.

Diagnostic value of apparent diffusion coefficients to differentiate benign from malignant vertebral bone marrow lesions.

AIM: The aim of this study is to evaluate the value of the apparent diffusion coefficient (ADC) obtained in diffusion-weighted (DW) MR sequences for the differentiation between malignant and benign bone marrow lesions. METHOD: Forty-five patients with altered signal intensity vertebral bodies on conventional MR sequences were included. The cause of altered signal intensity was benign osteoporotic collapse in 16, acute neoplastic infiltration in 15, and infectious processes in 14; based on plain-film, CT, bone scintigraphy, conventional MR studies, biopsy or follow-up. All patients underwent isotropic DW MR images (multi-shot EPI, b values of 0 and 500 s/mm(2)). Signal intensity at DW MR images was evaluated and ADC values were calculated and compared between malignancy, benign edema and infectious spondylitis. RESULTS: Acute malignant fractures were hyperintense compared to normal vertebral bodies on the diffusion-weighted sequence, except in one patient with sclerotic metastases. Mean ADC value from benign edema (1.9+/-0.39 x 10(-3) mm(2)/s) was significantly (p<0.0001) higher than untreated metastasic lesions (0.9+/-1.3 x 10(-3)mm (2)/s). Mean ADC value of infectious spondilytis (0.96+/-0.49 x 10(-3) mm(2)/s) was not statistically (p>0.05) different from untreated metastasic lesions. ADC value was low (0.75 x 10(-3) mm(2)/s) in one case of subacute benign fracture. CONCLUSIONS: ADC values are a useful complementary tool to characterize bone marrow lesions, in order to distinguish acute benign fractures from malignant or infectious bone lesions. However, ADC values are not valuable in order to differentiate malignancy from infection.

Effect of single-nucleotide polymorphisms of the 5' untranslated region of the human α-galactosidase gene on enzyme activity, and their frequencies in Portuguese caucasians.

BACKGROUND: The α-galactosidase gene (GLA) has three single-nucleotide polymorphisms in the 5' untranslated region of exon 1, respectively g.1150G>A, g.1168G>A, g.1170C>T. The g.1150A allele is associated with increased plasma α-galactosidase (α-Gal) activity in hemizygotes, while the others are regarded as biologically neutral. The primary goal of this investigation was to test the hypothesis, raised by a clinical observation and results of a family study, that the g.1170T allele polymorphism is associated with lower α-Gal expression. SUBJECTS AND METHODS: Plasma and leukocyte α-Gal activities were assayed in unrelated healthy young adults of both sexes, who had been genotyped for GLA exon 1, and enzyme activity values in carriers of any of the polymorphisms were compared to those of individuals with the standard genotype; GLA exon 1 was genotyped in males who had α-Gal activity in dried blood spots lower than 2 SD below the cohort average. RESULTS AND CONCLUSIONS: Mean α-Gal leukocyte activity was ∼ 25% higher in subjects with the g.1170C or CC genotype than in those with the alternative genotypes (p < 0.05). The frequency of the g.1170T allele in subjects with low α-Gal activity in dried blood spots was 4-fold higher (p < 0.05) than in the general population. As in hemizygotes, the g.1150A heterozygote identified in this study had plasma α-Gal activity more than 2-fold above the normal mean. The g.1168A allele did not affect enzyme activity. Surprisingly, females with the standard GLA exon 1 genotype had significantly higher plasma α-Gal activity than genetically comparable males.

Optimally discriminant moments for speckle detection in real B-scan images.

The paper presents and evaluates a speckle detection method for B-scan images. This is a fully automatic method and does not require information about the sensor parameters, which is often missing in retrospective studies. The characterization and posterior detection of speckle noise in ultrasound (US) has been regarded as an important research topic in US imaging, for improving signal-to-noise ratio by removing speckle noise and for exploiting speckle correlation information. Most of the existing methods require either manual intervention, the need to know sensor parameters or are based on statistical models which often do not generalize well to B-scans of different imaging areas. The proposed method aims to overcome those limitations. The main novelty of this work is to show that speckle detection can be improved based on finding optimally discriminant low order speckle statistics. In addition, and in contrast with other approaches the presented method is fully automatic and can be efficiently implemented to B-scan images. The method detects speckle patches using an ellipsoid discriminant function which classifies patches based on features extracted from optimally discriminant low order moments of the uncompressed intensity B-scan information. In addition, if the uncompressed signal is not available, we propose and evaluate a method for the estimation of this factor. The computation of low order moments using an optimality criteria, the decompression factor estimation and other key aspects of the method are quantitatively evaluated using both simulated and real (phantom and in vivo) data. Speckle detection results are obtained using again phantom and in vivo studies which show the validity of our approach. In addition, speckle probability images (SPI) are presented which provide valuable information about the distribution of speckle and non-speckle areas in an image. The presented evaluation and results show the effectiveness of our approach. In particular, the need for using discriminant analysis to determine the optimal discriminant power of the statistical moments and that this optimal value strongly depends on the characteristics and imaged tissues in the B-scan data.

[Stent thrombosis]. / Trombosis del stent.

Stent thrombosis (ST) is an uncommon but potentially lethal complication of coronary endoprothesis. Clinical trials have not shown differences in the incidence of early and late thrombosis among bare-metal stents and drug-eluting stents. Very late stent thrombosis occurs more than a year after stent implantation and is more specific of drug-eluting stents. Factors related to the patient, the stent, the coronary lesion and the technique are involved in the pathogenesis of ST. The main risk factor ST is the premature discontinuation of antiplatelet therapy. Currently, patients must receive aspirin and a thienopyridine for at least one month after the implantation of a bare-metal stent and 12 months after the implantation of a drug-eluting stent, then maintaining one antiplatelet agent indefinitely.

The effect of silicon on the symptoms of manganese toxicity in maize plants.

The effect of exogenously applied silicon (Si) on plant growth, lipid peroxidation, total phenolic compounds and non-protein thiols was studied in two maize varieties (Zea mays L. vars. Kneja 605, 434) differing in sensitivity to excess manganese (Mn). Based on the density of brown spots per leaf area and relative shoot weight (RSW) used to define Mn tolerance var. Kneja 434 was found to be more Mn-tolerant than Kneja 605. The lipid peroxidation level and total phenolic compounds were enhanced with increasing Mn concentration in the nutrient solution. In addition, the Mn-sensitive var. Kneja 605 with markedly expressed first visible Mn toxicity symptoms had higher levels of total phenolic acids than var. Kneja 434 thus supporting the hypothesis that a stimulating effect of Mn on phenol content reflected rather a stress response to Mn excess than a tolerance mechanism. In contrast, non-protein SH content increased to a higher extent in the Mn-tolerant var. Kneja 434. The increased amount of non-protein SH compounds was accompanied by a much stronger oxidative stress in the Mn-sensitive plants when compared with the Mn-tolerant variety, thus suggesting that non-protein SH compounds may play a role in Mn tolerance in maize. The addition of silicon (Si) reduced the density of brown spots per leaf area as well as lipid peroxidation level and improved plant growth in Mn-treated plants.

[Diffusion-weighted whole-body MRI (virtual PET) in screening for osseous metastases]. / Resonancia magnética de todo el cuerpo con técnica de difusión (PET virtual) para el cribado de las metástasis óseas.

OBJECTIVE: To present our preliminary experience in whole-body MRI with an added diffusion-weighted sequence in screening for osseous metastases. MATERIAL AND METHODS: 24 patients with malignant neoplasms underwent bone scintigraphy and whole-body MRI with the addition of a diffusion-weighted sequence. Whole-body MRI was performed on a 1.5 T unit using a three-station protocol; coronal T1-weighted FSE and STIR sequences and sagittal T1-weighted FSE of the spine were acquired. A diffusion-weighted sequence (b: 600 s/mm2) was added in the axial plane at five different stations and iconographic presentation in coronal-plane reconstructions with contrast inversion was used to obtain an image similar to that provided by PET (virtual PET). The findings at bone scintigraphy (BS) and MRI were compared for the presence of osseous metastases, evaluating the results for each patient both globally and for different osseous regions. Metastatic lesions were confirmed by biopsy or by six to eight months' follow-up. RESULTS: Globally, whole-body MRI with diffusion-weighted sequences was superior to bone scintigraphy, with a sensitivity of 100% (BS 71%), specificity 90% (BS 80%), and reliability 96% (BS 75%). In the evaluation by osseous region, the results of MRI were also better than those of bone scintigraphy: sensitivity 96% (BS 52%). In the diffusion-weighted sequence, lytic metastases were hyperintense in all cases, with an apparent diffusion coefficient (ADC) value higher than normal bone but lower than lesions with acute edema of benign etiology. Whole-body MRI also revealed unknown extraosseous findings related to the tumors and extraosseous metastases in 42% of the patients. CONCLUSIONS: Whole-body MRI with an added diffusion-weighted sequence is an efficacious method of detecting osseous metastases and is more reliable than bone scintigraphy. Moreover, whole-body MRI provides information about extraosseous lesions. Lytic metastases are hyperintense in diffusion-weighted sequences and have a lower ADC than benign edema.

Role of FK778 alone or in combination with tacrolimus or mTOR inhibitors as an immunomodulator of immunofunctions: in vitro evaluation of T cell proliferation and the expression of lymphocyte surface antigens.

We evaluated the in vitro capacity of FK778, alone or in combination with other immunosuppressive drugs: Tacrolimus (TRL); Sirolimus (SRL), Everolimus (EVL), to inhibit clonal expansion of T-lymphocytes and expression of lymphocyte-activation surface antigens; secondly, we compared the immunosuppressive potential of FK778 combined with TRL, SRL and EVL with the same combinations using Mycophenolic acid (MPA) as antimetabolite. Lymphocyte proliferation was assessed by 3H-Thymidine incorporation, in whole blood cultures stimulated with ConA. The effect of FK778 on alloresponse was evaluated by MLC and the expression of lymphocyte surface antigens by cytometry. FK778, TRL, SRL and EVL showed a high in vitro capacity to inhibit lymphocyte proliferation in a concentration-dependent way. Combinations of FK778 with TRL, SRL, or EVL presented an additive effect, especially FK778+TRL. Similar inhibition capacity of the clonal expansion was observed, when FK778 was combined with TRL, SRL or EVL, respecting the same combinations but using MPA instead of FK778. In addition, FK778 inhibited the expression of lymphocyte surface antigens involved in activation, co-stimulatory and apoptosis signals. In conclusion, FK778 inhibits the proliferative response induced by mitogeneic and allogeneic stimuli and the expression of surface antigens. Combinations of FK778 with TRL or mTOR inhibitors presented an additive effect and their action on T cell proliferation was similar to that of combinations with MPA. Since FK778, TRL and mTOR inhibitors present different action mechanisms and involve different cellular targets, these combinations may help prevent episodes of allorejection in organ transplants. FK778 and mTOR inhibitors may represent an alternative treatment for patients with renal failure.

Clinical profiles in fibromyalgia patients of the community mental health center: a predictive index of psychopathological severity.

INTRODUCTION: In recent years we have seen an increasing demand for mental health care in patients with fibromyalgia and psychiatric symptoms, although it is not clear if the symptoms are primary or secondary to the presence of the syndrome. This fact has led mental health providers to think that there would be some psychological factors influencing the vulnerability of suffering this painful syndrome, because its etiology is quite non-specific. Bradley et al. (1978) identified different psychopathological profiles within chronic pain syndromes with the MMPI, which were subsequently adapted by Yunus et al. (1991) for fibromyalgia. This present work studied the clinical profile in patients with fibromyalgia. SAMPLE: 75 patients with fibromyalgia from the community mental health center and 55 healthy subjects. Tools: STAI-E/R, BDI, MMPI-2, MMPI-2 personality disorders, MMPI-2 PSY-5. STATISTICAL ANALYSIS: descriptive statistics and mean comparison (Student's t test). Confirmatory cluster analysis. Discriminative analysis of subgroups. RESULTS: Two different patterns were obtained: group A (32 %) with a typical chronic pain profile (CP) and group B (68 %) with a psychological maladjustment profile (PM). With the discriminative analysis, we obtained the coefficients of the discriminative canonical functions that maximize the differences between both groups. CONCLUSIONS: We confirmed Bradley's classification, obtaining two different psychopathological patterns in the fibromyalgia syndrome sample we studied. We obtained an index of psychopathological profile in fibromyalgia, which would form a new scale, from MMPI-2 for discriminating psychopathological severity in fibromyalgia.