Effects of bisphenol F, bisphenol S, and bisphenol AF on cultured human osteoblasts.

Bisphenol A (BPA) analogs, like BPA, could have adverse effects on human health including bone health. The aim was to determine the effect of BPF, BPS and BPAF on the growth and differentiation of cultured human osteoblasts. Osteoblasts primary culture from bone chips harvested during routine dental work and treated with BPF, BPS, or BPAF for 24 h at doses of 10-5, 10-6, and 10-7 M. Next, cell proliferation was studied, apoptosis induction, and alkaline phosphatase (ALP) activity. In addition, mineralization was evaluated at 7, 14, and 21 days of cell culture in an osteogenic medium supplemented with BP analog at the studied doses. BPS treatment inhibited proliferation in a dose-dependent manner at all three doses by inducing apoptosis; BPF exerted a significant inhibitory effect on cell proliferation at the highest dose alone by an increase of apoptosis; while BPAF had no effect on proliferation or cell viability. Cell differentiation was adversely affected by treatment with BPA analogs in a dose-dependent, observing a reduction in calcium nodule formation at 21 days. According to the results obtained, these BPA analogs could potentially pose a threat to bone health, depending on their concentration in the organism.

Es útil el cannabis medicinal para el tratamiento de la fibromialgia? / Is medical cannabis useful for the treatment of fibromyalgia?

La fibromialgia es una enfermedad crónica de etiología desconocida hasta la fecha, que asocia una sintomatología muy variada, condicionando severamente la calidad de vida de las personas que la padecen. Clínicamente se caracteriza por presentar dolor musculoesquelético generalizado, cansancio desmesurado para la actividad física realizada, mala higiene del sueño o alteraciones emocionales. Se trata de una patología prevalente, pudiendo llegar a afectar hasta un 2-3 % de la población, en su mayoría mujeres de edad media. El diagnóstico es clínico y habitualmente tardío. Según la literatura, existe una demora de aproximadamente dos años desde el diagnóstico hasta el inicio de un tratamiento adecuado. Durante este tiempo, el consumo de recursos derivados por pruebas innecesarias o pérdida de jornadas laborales la convierte en un problema de salud de primera índole. Condicionado por esa etiología desconocida, el tratamiento disponible para la fibromialgia no es curativo. Existen diversos tratamientos que han demostrado un efecto beneficioso en la evolución de la enfermedad como una educación del paciente, psicoterapia, ejercicio físico y tratamiento farmacológico. A pesar de su variedad, ninguno de estos tratamientos consigue de manera efectiva una mejoría permanente y duradera, lo que va a dar lugar a una búsqueda constante por parte de estos pacientes de tratamientos alternativos que les aporten nuevos resultados. En la actualidad, el cannabis medicinal es uno de esos posibles nuevos tratamientos que goza de una ilusión o esperanza como alternativa del tratamiento analgésico en estos pacientes. Se va a proceder a analizar la situación actual de la enfermedad de la fibromialgia, así como una revisión sistemática sobre la evidencia existente hasta la fecha, entre la fibromialgia y los cannabinoides.(AU)

Fibromyalgia is a chronic disease of unknown etiology that severely conditions the quality of life of people who suffer from it. It is characterized by general musculoskeletal pain, excessive fatigue for the physical activity performed, poor sleep hygiene or emotional disturbances. It is a very prevalent pathology and can affect up to 2-3 % of the population, mostly middle-aged women. Diagnosis is clinical, based on physical examination and usually it is usually carried out late. According to the literature, there is a delay of approximately two years from diagnosis to the initiation of appropriate treatment. During this time, the consumption of resources derived by unnecessary testing or loss of working hours derivate from the fibromyalgia makes it a major health problem. Conditioned by that unknown etiology, the available treatment for fibromyalgia is not curative. There are several treatments that have shown a beneficial effect on the evolution of the disease, such as patient education or psychotherapy, physical exercise and pharmacological treatment. Despite their variety, none of these treatments achieves a permanent and lasting improvement. This will lead to a constant search by these patients for alternative treatments that bring them new results. Currently, medical cannabis is one of those possible new treatments that has a certain illusion or hope as an alternative to these patients. We will proceed to analyze the current situation of fibromyalgia disease, as well as a systematic review of the evidence existing to date between fibromyalgia and cannabinoids.(AU)

Análisis de una encuesta sobre conocimientos en contenciones mecánicas de las enfermeras de unidades de críticos / Analysis of a nurses' knowledge survey on the use of physical restraint in intensive care units

Objetivos: Determinar el grado de conocimientos de las enfermeras sobre el uso de contenciones mecánicas en las unidades de críticos y los factores relacionados. Método: Estudio multicéntrico, observacional, en 12 unidades de críticos de 8 hospitales en España (n = 354 enfermeras). Se elaboró una encuesta ad-hoc de conocimientos cuyo contenido fue validado por expertos. La encuesta obtuvo una estabilidad test-retest de CCI = 0,71 (IC 95%: 0,57-0,81) en un estudio piloto previo. El instrumento final quedó conformado por 8 ítems. Se recogieron datos sociodemográficos y profesionales de los participantes, así como variables estructurales y clínicas de las unidades a estudio. Se llevó a cabo un análisis descriptivo y de asociación entre variables. Se consideró estadísticamente significativo un valor de p < 0,05. Resultados: Respondieron 250 enfermeras (70,62%), con una edad media de 36,8 (DE 9,54) años y una media de 10,75 (DE 8,38) años de experiencia profesional en unidades de críticos. El 73,6% no había recibido formación previa sobre contenciones mecánicas. La media de conocimientos fue de 4,21 (DE 1,39) (rango 0-8). El grado de conocimientos se asoció al hospital de referencia (p < 0,001). Las enfermeras con mayor grado de conocimientos es más probable que trabajen en unidades con consentimiento informado para el uso de contenciones mecánicas (p < 0,001); visita familiar flexible (p < 0,001); y que dispongan de protocolo de analgosedación (p = 0,011), o que la enfermera tenga autonomía en el manejo de la analgosedación (p < 0,001). Ningún dato sociodemográfico ni profesional individual se asoció al grado de conocimientos. Conclusiones: Es necesaria una mayor formación de las enfermeras sobre el uso de contenciones mecánicas. El entorno de trabajo donde se desarrollan los cuidados tiene una gran influencia en el grado de conocimientos de las enfermeras sobre esta intervención

Objectives: To determine nurses' knowledge level regarding physical restraint use in intensive care units and its associated factors. Method: A cross-sectional multicentre study was carried out in 12 critical care units of 8 hospitals in Spain (n = 354 nurses). An 'ad-hoc' knowledge survey was developed, and their content was validated by experts. The survey obtained a test-retest stability of ICC=.71 (95% CI: .57-.81) in a previous pilot study. A final 8-item tool was designed. Sociodemographic and professional variables from the participants were collected; as well as structural and clinical variables from the units analyzed. A descriptive and association analysis between variables was performed. A p-value <.05 was deemed statistically significant. Results: Two hundred and fifty nurses answered the survey (70.62%). Mean age of the participants was 36.80 (SD 9.54) with 10.75 (SD 8.38) years of professional experience in critical care. Seventy-three point six percent had never received previous training about physical restraints. Knowledge mean value was 4.21 (SD 1.39) (range 0-8). Knowledge level was associated with the referral hospital (p < .001). Nurses with a higher knowledge level are more likely to work in units with informed consent sheets for physical restraint use (p < .001); flexible family visiting (p < .001); analgo-sedation protocol (p = .011), and units in which nurses had autonomy to manage analgo-sedation (p < .001). Individual sociodemographic and professional data was not associated with knowledge level. Conclusions: Further training regarding physical restraint use is needed for critical care nurses. The work environment where nursing care is given has a great influence on nurses' knowledge level about this intervention

Analysis of a nurses' knowledge survey on the use of physical restraint in intensive care units. / Análisis de una encuesta sobre conocimientos en contenciones mecánicas de las enfermeras de unidades de críticos.

OBJECTIVES: To determine nurses' knowledge level regarding physical restraint use in intensive care units and its associated factors. METHOD: A cross-sectional multicentre study was carried out in 12 critical care units of 8 hospitals in Spain (n=354 nurses). An 'ad-hoc' knowledge survey was developed, and their content was validated by experts. The survey obtained a test-retest stability of ICC=.71 (95% CI: .57-.81) in a previous pilot study. A final 8-item tool was designed. Sociodemographic and professional variables from the participants were collected; as well as structural and clinical variables from the units analyzed. A descriptive and association analysis between variables was performed. A p-value <.05 was deemed statistically significant. RESULTS: Two hundred and fifty nurses answered the survey (70.62%). Mean age of the participants was 36.80 (SD 9.54) with 10.75 (SD 8.38) years of professional experience in critical care. Seventy-three point six percent had never received previous training about physical restraints. Knowledge mean value was 4.21 (SD 1.39) (range 0-8). Knowledge level was associated with the referral hospital (p<.001). Nurses with a higher knowledge level are more likely to work in units with informed consent sheets for physical restraint use (p<.001); flexible family visiting (p<.001); analgo-sedation protocol (p=.011), and units in which nurses had autonomy to manage analgo-sedation (p<.001). Individual sociodemographic and professional data was not associated with knowledge level. CONCLUSIONS: Further training regarding physical restraint use is needed for critical care nurses. The work environment where nursing care is given has a great influence on nurses' knowledge level about this intervention.

Longitudinal evaluation of hepatitis C viral persistence in HIV-infected patients with spontaneous hepatitis C clearance.

Hepatitis C virus (HCV) viral persistence in patients with spontaneous viral clearance is controversial. Several studies have shown HCV-RNA in peripheral blood mononuclear cells (PBMCs) and/or liver tissue among patients who have cleared the virus spontaneously, suggesting that viral persistence is a common situation that could involve the entire population studied. Thus, our aim was to evaluate HCV-RNA persistence in PBMCs and hepatocytes in subjects infected with the human immunodeficiency virus (HIV). A total of 1508 patients were prospectively followed and tested for anti-HCV antibodies and HCV-RNA to identify the patients who achieved spontaneous viral clearance. In all of the patients, the persistence of HCV-RNA in PBMCs was evaluated longitudinally during 2 years of follow-up. Fifty-nine patients fulfilled the inclusion/exclusion criteria and were included in the study. HCV-RNA was not detected in the PBMCs at baseline [59 PBMCs samples tested; 0 %; 95 % confidence interval (CI): 0-3.3 %] or during the follow-up (147 PBMCs samples tested; 0 %; 95 % CI: 0-2.02 %). Our study shows that HCV viral persistence is not a frequent occurrence in HIV-infected patients who have spontaneously resolved an HCV infection. Thus, the lack of serum HCV-RNA should continue to be addressed as the standard of healing.

Efficacy and safety of once-daily maraviroc plus ritonavir-boosted darunavir in pretreated HIV-infected patients in a real-life setting.

OBJECTIVES: Nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens may be needed in patients with NRTI toxicity. Maraviroc (MVC) plus ritonavir-boosted darunavir (DRV-r) or atazanavir is associated with slightly lower response rates than triple therapy in drug-naïve patients. No information is available on these combinations in pretreated patients. The aim of this study was to assess the efficacy and safety of MVC plus DRV/r once-daily (qd) in HIV-infected pretreated patients. METHODS: A retrospective cohort study including patients starting MVC 150 mg plus DRV/r 800/100 mg qd, with CCR5 tropism and no resistance mutations for DRV/r, was performed. The primary efficacy endpoint was the achievement of plasma HIV RNA < 50 HIV-1 RNA copies/mL after 48 weeks. The frequency of serious adverse effects was investigated. RESULTS: Sixty patients were recruited to the study, of whom 48 (80%) had HIV RNA < 50 copies/mL at baseline. Reasons for starting MVC plus DRV/r were: adverse effects in 38 individuals (63%), simplification in 15 (25%) and virological failure in seven (12%). The main analysis (intention to treat, noncompleter = failure) showed that 47 patients (78%) achieved HIV RNA < 50 copies/mL at 48 weeks (paired comparison with baseline, P = 1.0). On-treatment analysis showed that 42 (86%) of 49 patients presented HIV RNA < 50 copies/mL at 48 weeks (paired comparison with baseline, P = 1.0). Median (interquartile range) CD4 cell counts increased from 491 (301-729) to 561 (367-793) cells/µL at 48 weeks (P = 0.013). Only one patient discontinued therapy because of adverse effects. CONCLUSIONS: Most individuals starting MVC plus DRV/r qd because of simplification or adverse effects maintained HIV suppression after 48 weeks of follow-up.

Eczema generalizado secundarioal tratamiento con interferón alfa pegiladoy ribavirina en dos pacientes / Generalized eczema secondary to treatment with peginterferon alpha an ribavirin in two patients

Los efectos adversos cutáneos del tratamiento con interferón alfa o la combinación de interferón alfa y ribavirina en pacientes con hepatitis crónica C son relativamente frecuentes, pero son principalmente locales y relacionados con el lugar de inyección del interferón. Sin embargo, las reacciones eczematosas a distancia o generalizadas son raras. La introducción de los interferones alfa pegilados podría aumentar la frecuencia de estas lesiones cutáneas (AU)

Treatment with interferon alpha or interferon alpha plus ribavirin in patients with chronic hepatitis C frequenty cause cutaneous local side effects limited to the injection sites. Distant or generalized eczematous reactions are rare. However, distant lesions may increase with the use of pegylated interferons alpha (AU)

[Extracorporeal photopheresis in dermatology]. / Fotoféresis extracorpórea en Dermatología.

Extracorporeal photochemotherapy or photopheresis is an immunomodulatory therapy that combines leukapheresis with phototherapy. Blood from the patient is processed to give a leukocyte-rich plasma, which is then treated ex vivo with a photosensitizer and ultraviolet A radiation before reinfusion back into the patient. The exact mechanism of action of photopheresis has not been fully elucidated although it is thought that induction of leukocyte apoptosis and formation of dendritic cells is essential for the development of an immune response to pathogenic cells. Extracorporeal photophoresis was initially used for treating cutaneous T-cell lymphoma. Since then, in view of its efficacy and safety, it has been used in a number of cutaneous and noncutaneous diseases with uneven results, which can in part be explained by the different patient selection criteria, therapy regimens, and follow-up protocols used in different hospitals.

Fotoféresis extracorpórea en Dermatología / Extracorporeal Photopheresis in Dermatology

La fotoquimioterapia extracorpórea o fotoféresis es una terapia inmunomoduladora que combina la leucoféresis con la fototerapia. Después de la separación de un plasma rico en leucocitos, se administra ex vivo un fotosensibilizante junto con radiación ultravioleta A y posteriormente se reinfunde en el paciente. El mecanismo de acción exacto de la fotoféresis no se conoce completamente, aunque se piensa que la inducción de apoptosis de linfocitos y la formación de células dendríticas desempeña un papel fundamental en el desarrollo de una respuesta inmunológica contra las células patógenas. Esta terapia se utilizó inicialmente para el tratamiento del linfoma cutáneo de células T. Desde entonces, basándose en su eficacia y seguridad, se ha empleado en múltiples patologías tanto cutáneas como no cutáneas, con resultados variables. Los distintos centros han utilizado diferentes criterios de selección de pacientes, pautas de tratamiento y protocolos de monitorización, lo que podría contribuir a la diferencia de resultados (AU)

Extracorporeal photochemotherapy or photopheresis is an immunomodulatory therapy that combines leukapheresis with phototherapy. Blood from the patient is processed to give a leukocyte-rich plasma, which is then treated ex vivo with a photosensitizer and ultraviolet A radiation before reinfusion back into the patient. The exact mechanism of action of photopheresis has not been fully elucidated although it is thought that induction of leukocyte apoptosis and formation of dendritic cells is essential for the development of an immune response to pathogenic cells. Extracorporeal photophoresis was initially used for treating cutaneous T-cell lymphoma. Since then, in view of its efficacy and safety, it has been used in a number of cutaneous and noncutaneous diseases with uneven results, which can in part be explained by the different patient selection criteria, therapy regimens, and follow-up protocols used in different hospitals (AU)

Metástasis cutáneas de presentación atípicade adenocarcinoma de probable origenendometrial / Cutaneous metastases of atypical presentation from adenocarcinoma

Las metástasis cutáneas son poco frecuentes y en ocasiones representa la primera manifestación de una neoplasia desconocida. Aunque la clínica esvariable, generalmente se confunde con un proceso infeccioso o inflamatorio. Las metástasis de localización acral son particularmente raras y el pronósticoes muy malo. Presentamos el caso de un paciente con metástasis en las manos y los pies como signo inicial de una neoplasia no conocida previamente (AU)

Cutaneous metastases are infrequent and in some cases represent the first sign of cancer from an unknown primary site. Although the clinical presentationvaries, they are generally confused with an infectious or inflammatory process. Acral metastases are particularly rare and the prognosis is verypoor. A patient with metastases on the hands and feet as an initial sign of a previously unknown tumour is reported (AU)

Lesiones cutáneas múltiples pormycobacterium chelonae en huésped inmunocompetente / Multiple cutaneous lesions by mycobacterium chelonae in an immunocompetent host

Mycobacterium chelonae es una micobacteria no tuberculosa (MNTB) de rápido crecimiento, que en el huésped inmunocompetente puede producirlesiones cutáneas localizadas relacionadas con traumatismos.Presentamos dos casos de infección cutánea en hermanas inmunocompetentes quienes desarrollaron lesiones múltiples en muslos y piernas relacionadascon el uso de cera depilatoria. Del cultivo de la lesión se aisló M. chelonae sensible a eritromicina. Se trataron con claritromicina durante 3 mesescon respuesta clínica favorable (AU)

Mycobacterium chelonae is a rapidly growing mycobacterium. In inmunocompetent host cutaneous infection is ussualy isolated, localized and associated with trauma.Two inmunocompetent sisters who consulted because of multiple skin lesion localized in legs and thigs associated to depilation are reported. The cultureof skin lesion showed M. chelonae (AU)

Fibroxantoma atípico. Estudio clínicopatológico e inmunohistoquímico de diez casos / Atypical fibroxanthoma. A clinicopathological and immunohistochemical

El fibroxantoma atípico es un tumor infrecuente, de histogénesis incierta. La mayoría de los autores lo consideran una variante superficial del histiocitomafibroso maligno. Generalmente se manifiesta como un nódulo solitario en personas de edad avanzada y zonas expuestas al sol. El diagnósticodel fiborxantoma atípico es siempre de exclusión, y debe diferenciarse mediante inmunohistoquímica de otros tumores fusocelulares como los carcinomas escamosos y melanomas. Describimos las características clínicopatológicas e inmunohistoquímicas de diez casos de fibroxantoma atípico (AU)

Atypical fibroxanthoma is a rare tumor of unknown histogenesis, considered by most authors to represent a superficial or minimally invasive variant ofmalignant fibrous histiocytoma that most often presents as a solitary nodule on sun-exposed skin of the elderly. The diagnosis of atypical fibroxanthomais always one of exclusion. Other spindle-cell tumor such as squamous cell carcinoma and melanoma must be ruled out by immunohistochemical techniques. We report the clinicopathological and immunohistochemical features of ten cases of atypical fibroxanthoma (AU)

Eczema generalizado secundarioal tratamiento con interferón alfa pegilado y ribavirina en dos pacientes con hepatitis C / Generalized eczema secondary to treatment with peginterferon alpha and ribavirin in two patients with hepatitis C

Los efectos adversos cutáneos del tratamiento con interferón alfa o la combinación de interferón alfa y ribavirina en pacientes con hepatitis crónica C son relativamente frecuentes, pero son principalmente locales y relacionados con el lugar de inyección del interferón. Sin embargo, las reacciones eczematosas a distancia o generalizadas son raras. La introducción de los interferones alfa pegilados podría aumentar la frecuencia de estas lesionescutáneas (AU)

Treatment with interferon alpha or interferon alpha plus ribavirin in patientes with chronic hepatitis C frequently cause cutaneous local side effects limited to the injection sites. Generalized eczematous reactions are rare. However, distant lesions may increase with the use of pegylated inteferons alpha (AU)

Polyene macrolide antibiotic biosynthesis.

Polyenes constitute a large class of natural metabolites produced by giant multifunctional enzymes in a process resembling fatty acid biosynthesis. Like fatty acids, polyene macrolides and other polyketides are assembled by decarboxylative condensations of simple carboxylic acids. But while fatty acid intermediates are fully reduced, polyene macrolide intermediates suffer the suppression of reduction or dehydration reactions at given biosynthetic steps. In the last years, much progress has been made in our understanding of the linear and modular organization of the gene clusters, and the enzymes encoded by them, responsible for the biosynthesis of these macrocyclic metabolites. This know-how about the rules that govern polyene chain growth has provided the basis for the first rational manipulations of these fascinating systems for the production of engineered derivatives and promises a new era of novel polyene development, which will hopefully yield new molecules with improved pharmacological properties.

Endometriosis sobre cicatriz de episiotomía y cesárea previa: 2 casos clínicos / Endometriosis in a surgical scar after prior episiotomy and cesarean section. Two case reports

La endometriosis localizada en tejido cicatrizal tras cirugía pélvica del aparato genital, se presenta como una lesión nodular acompañada de dolor cíclico catamenial en el área cicatrizal, y no se asocia de forma habitual a endometriosis genital. Presentamos 2 casos de endometriosis localizada en tejido cicatrizal tras intervenciones obstétricas (episiotomía y cesárea, respectivamente) diagnosticados en nuestro hospital. El diagnóstico, basado en la sospecha clínica, fue histológico tras biopsia-exéresis de la lesión que resultó terapéutica, y las mujeres presentaron remisión completa de la sintomatología. En ambos casos, se asoció tratamiento hormonal postoperatorio, aunque su eficacia está discutida (AU)

Characterization of the ask-asd operon in aminoethoxyvinylglycine-producing Streptomyces sp. NRRL 5331.

The first two genes of the threonine pathway, ask and asd, were cloned and sequenced from the aminoethoxyvinylglycine-producing Streptomyces sp. NRRL 5331. The two genes are organized in a bicistronic operon. ask, encoding the apartokinase (ASK), is located upstream from asd. The presence of a ribosome-binding site within the ask sequence suggests that this open reading frame encodes two overlapping proteins. The formation of both subunits of the aspartokinase from a single gene was studied using antibodies raised against the C-terminal end of the aspartokinase subunits. Disruption of asd results in a significant decrease of aminoethoxyvinylglycine production, thus supporting the involvement of the ask-asd operon in the biosynthesis of this metabolite. This is the first report in which a gene cluster for the first two steps of aminoethoxyvinylglycine biosynthesis is characterized.

Pustulosis exantemática aguda generalizada. Presentación de dos casos

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Engineered biosynthesis of novel polyenes: a pimaricin derivative produced by targeted gene disruption in Streptomyces natalensis.

BACKGROUND: The post-polyketide synthase biosynthetic tailoring of polyene macrolides usually involves oxidations catalysed by cytochrome P450 monooxygenases (P450s). Although members from this class of enzymes are common in macrolide biosynthetic gene clusters, their specificities vary considerably toward the substrates utilised and the positions of the hydroxyl functions introduced. In addition, some of them may yield epoxide groups. Therefore, the identification of novel macrolide monooxygenases with activities toward alternative substrates, particularly epoxidases, is a fundamental aspect of the growing field of combinatorial biosynthesis. The specific alteration of these activities should constitute a further source of novel analogues. We investigated this possibility by directed inactivation of one of the P450s belonging to the biosynthetic gene cluster of an archetype polyene, pimaricin. RESULTS: A recombinant mutant of the pimaricin-producing actinomycete Streptomyces natalensis produced a novel pimaricin derivative, 4,5-deepoxypimaricin, as a major product. This biologically active product resulted from the phage-mediated targeted disruption of the gene pimD, which encodes the cytochrome P450 epoxidase that converts deepoxypimaricin into pimaricin. The 4,5-deepoxypimaricin has been identified by mass spectrometry and nuclear magnetic resonance following high-performance liquid chromatography purification. CONCLUSIONS: We have demonstrated that PimD is the epoxidase responsible for the conversion of 4,5-deepoxypimaricin to pimaricin in S. natalensis. The metabolite accumulated by the recombinant mutant, in which the epoxidase has been knocked out, constitutes the first designer polyene obtained by targeted manipulation of a polyene biosynthetic gene cluster. This novel epoxidase could prove to be valuable for the introduction of epoxy substituents into designer macrolides.