Dermoscopy of cutaneous smooth muscle neoplasms: a morphological study of 136 cases.

BACKGROUND: A variety of cutaneous smooth muscle neoplasms may arise in the skin and are frequently unrecognized by clinicians. There is sparse data relating to the dermoscopy of piloleiomyomas (PL), and nothing has been published about the dermoscopy of angioleiomyomas (AL) and leiomyosarcomas (LS). OBJECTIVES: To evaluate the morphological findings of a large series of cutaneous PL, AL and LS under dermoscopic observation, comparing these findings among them. METHODS: Digital dermoscopic images of 136 histopathologically confirmed cases of cutaneous smooth muscle neoplasms (114 PL, 13 AL and 9 LS) collected from 10 Hospitals in Spain, Austria and Italy were evaluated for the presence of dermoscopic structures and patterns. RESULTS: The pattern composed of a symmetric, total delicate pigment network with the variable presence of multiple hypopigmented areas in a painful lesion is the most common dermoscopic pattern associated with PL. This pattern was found in 69.3% of PL and in no cases of AL and LS. The most common and characteristic pattern associated with AL was the one composed of symmetric pink-reddish tumour with vessels, white structures and the absence of ulceration, which was found in 46.2% of AL, but also in 3.5% of PL, and in 22.2% of LS. Finally, the most common pattern associated with LS was the one composed of an asymmetric, multilobulated tumour with linear-irregular or polymorphic-atypical vessels and white structures, which was found in 44.4% of cases, but also in 0.9% of PL and in 15.4% of AL. CONCLUSION: Dermoscopy is helpful in improving the diagnostic accuracy of PL. The dermoscopic patterns associated with AL and LS were more variable and less specific.

Microarray study reveals a transforming growth factor-ß-dependent mechanism of fibrosis in discoid lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus (DLE) is characterized by scarring lesions that develop and perpetuate fibrotic lesions. These are not observed in subacute cutaneous lupus erythematosus (SCLE). The pathophysiological basis of this is currently unknown. OBJECTIVES: To identify contradistinctive signalling pathways and cellular signatures between the two type of lupus, with a focus on the molecular mechanisms leading to fibrosis. METHODS: We conducted a gene expression microarray analysis in lesional and nonlesional skin biopsy specimens of patients with DLE (n = 10) and SCLE (n = 10). Confirmatory reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed on selected transcripts in a new cohort of paraffin-embedded skin biopsies (n = 20). Changes over time of a group of selected inflammatory and fibrotic genes were also evaluated in a second biopsy taken 12 weeks later. In vitro functional studies were performed in primary isolated fibroblasts. RESULTS: Compared with nonlesional skin, DLE samples expressed a distinctive T-cell gene signature. DLE samples displayed a significant CD4 T-cell enrichment with an imbalance towards T helper 1 cytokine predominance and a relative increased forkhead box (FOX)P3 response. RT-qPCR and immunochemical analysis over time showed a progressive increment of fibrotic markers and persistent FOXP3 recruitment. Ex vivo upregulation of SERPINE1, MMP9, TGFBR1, phosphorylated SMAD3 and TGFB1 suggested a transforming growth factor (TGF)-ß-dependent mechanism of fibrosis in DLE, also confirmed by the results observed following in vitro stimulation with TGF-ß. CONCLUSIONS: These results highlight major pathogenic pathways in DLE and provide novel molecular targets for the development of new therapies. The data suggest the existence of a TGF-ß-dependent pathway inducing fibrosis in DLE.

Binding by calmodulin is coupled to transient unfolding of the third FF domain of Prp40A.

Human pre-mRNA processing protein 40 homolog A (hPrp40A) is a splicing factor that interacts with the Huntington's disease protein huntingtin (Htt). Evidence has accumulated that both Htt and hPrp40A are modulated by the intracellular Ca2+ sensor calmodulin (CaM). Here we report characterization of the interaction of human CM with the third FF domain (FF3 ) of hPrp40A using calorimetric, fluorescence and structural approaches. Homology modeling, differential scanning calorimetry and small angle X-ray scattering (SAXS) data show FF3 forms a folded globular domain. CaM was found to bind FF3 in a Ca2+ -dependent manner with a 1:1 stoichiometry and a dissociation constant (Kd ) of 25 ± 3 µM at 25°C. NMR studies showed that both domains of CaM are engaged in binding and SAXS analysis of the FF3 -CaM complex revealed CaM occupies an extended configuration. Analysis of the FF3 sequence showed that the anchors for CaM binding must be buried in its hydrophobic core, suggesting that binding to CaM requires unfolding of FF3 . Trp anchors were proposed based on sequence analysis and confirmed by intrinsic Trp fluorescence of FF3 upon binding of CaM and substantial reductions in affinity for Trp-Ala FF3 mutants. The consensus model of the complex showed that binding to CaM binding occurs to an extended, non-globular state of the FF3 , consistent with coupling to transient unfolding of the domain. The implications of these results are discussed in the context of the complex interplay of Ca2+ signaling and Ca2+ sensor proteins in modulating Prp40A-Htt function.

[Quality of life in patients with spinal cord injury for at least 10years: Importance of secondary health complications]. / Calidad de vida en personas con lesión medular de más de 10 años de evolución. La implicación de las complicaciones secundarias.

OBJECTIVE: To determine the quality of life of spinal cord injuries with more than 10 years of evolution. Assess the prevalence of secondary complications, and their relationship with quality of life and time since the injury. PATIENTS AND METHOD DESIGN: Cross-sectional epidemiological study. STUDY SUBJECTS: Patients with traumatic spinal cord injury, more than 10 years after the injury, and who met the inclusion criteria. METHOD: Quality of life was assessed using the International spinal cord injury quality of life basic data set. Variables included: individual factors, neurological deficit, level of injury and secondary complications. RESULTS: 131 subjects were included in the study with a mean age of 49 years, and a time since the injury of 21 years (11-53 years). The mean number of secondary complications was 2, the most frequent being urological, in 76 subjects (58%). There were no significant differences between the number of complications and the time elapsed since the spinal cord injury. The quality of life was significantly lower in those with a higher number of complications (P=.003). Urological complications (P=.04, 95% CI: -1.02 to 2), musculoskeletal pain (P=.01, 95% CI: 1-6), respiratory complications (P=.05, 95% CI: -3 to 0.1) and neuropathic pain that interfered with basic life activities (P=.01, 95% CI: 1-5) were significantly related to a lower quality of life. CONCLUSIONS: Secondary complications are common after spinal cord injury, although their number does not increase over time after injury. Quality of life is conditioned by the existence of different complications such as the existence of musculoskeletal pain.

The impact of hip fracture on health-related quality of life and activities of daily living: the SPARE-HIP prospective cohort study.

PURPOSE: The medical morbidity and mortality associated with neck of femur fractures is well-documented, whereas there is limited data for patient-reported outcomes. The aim of this study was to characterize the impact of neck of femur fractures on activities of daily living and patient-reported health-related quality of life. METHODS: Design and participants: Multicentric prospective cohort study. Consecutive sample patients with fragility hip fracture over 50 years old admitted in 48 hospitals in Spain. OUTCOMES: daily living activity function (Barthel Index) and health-related quality of life (EQ-5D) pre-fracture, admission to hospital and at 1- and 4-month follow-up post-fracture. STATISTICS: Barthel and EQ-5D over time are described as mean (SD) and median (interquartile range). RESULTS: A total of 997 patients were recruited at baseline with 4-month outcomes available for, and 856 patients (89.5%). Barthel Index fell from 78.77 (23.75) at baseline to 43.62 (19.86) on admission to hospital with the fracture. Scores partially recovered to 54.89 (25.40) and 64.09 (21.35) at 1- and 4-month post-fracture, respectively. EQ-5D fell from a median of 0.75 (0.47-0.91) to - 0.01 (- 0.03 to 0.51) on admission. Partial recovery was observed again to (0.51 (- 0.06 to 0.67)) and (0.60 (0.10 to 0.80)) at 1- and 4-month post-fracture, respectively. CONCLUSIONS: Hip fracture results in a large decline in the ability to perform activities of daily living and patient-reported health-related quality of life with only partial recovery amongst survivors 4-month post-fracture.

The First Year of the AEVD Primary Cutaneous Lymphoma Registry. / Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. PATIENTS AND METHODS: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. RESULTS: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). CONCLUSION: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group.

Calidad de vida en personas con lesión medular de más de 10 años de evolución. La implicación de las complicaciones secundarias / Quality of life in patients with spinal cord injury for at least 10years: Importance of secondary health complications

Objetivo: Determinar la calidad de vida que presentan los lesionados medulares con más de 10 años de evolución. Valorar la prevalencia de complicaciones secundarias y su relación con la calidad de vida y el tiempo desde la lesión. Pacientes y método Diseño: Estudio epidemiológico transversal. Sujetos del estudio Pacientes: con lesión medular traumática, de más 10 años desde la lesión, y que cumplían los criterios de inclusión.Método: calidad de vida se valoró mediante el International spinal cord injury quality of life basic data set. Como variables se incluyeron: factores individuales, déficit neurológico, nivel de lesión y complicaciones secundarias. Resultados: Ciento treinta y un sujetos fueron incluidos en el estudio con edad media de 49 años y un tiempo desde la lesión de 21 años (11-53 años). La media de complicaciones secundarias fue de 2, siendo la más frecuente las urológicas, en 76 sujetos (58%). No existieron diferencias significativas entre el número de complicaciones y el tiempo transcurrido desde la lesión medular. La calidad de vida fue significativamente menor en aquellos que presentaban un mayor número de complicaciones (p = 0,003). Las complicaciones urológicas (p=0,04, IC del 95%, –1,02-2), el dolor musculoesquelético (p=0,01, IC del 95% IC, 1-6), las complicaciones respiratorias (p=0,05, IC del, –3-0,1) y el dolor neuropático que interfería con actividades básicas de la vida (p=0,01, IC del 95%, 1-5) se relacionaban significativamente con una menor calidad de vida. Conclusiones : Las complicaciones secundarias son frecuentes tras la lesión medular, aunque su número no aumenta con el tiempo desde la lesión. La calidad de vida sí está condicionada por la existencia de distintas complicaciones, como la existencia de dolor musculoesquelético.(AU)

Objective: To determine the quality of life of spinal cord injuries with more than 10 years of evolution. Assess the prevalence of secondary complications, and their relationship with quality of life and time since the injury. Patients and method Design: Cross-sectional epidemiological study. Study subjects: Patients with traumatic spinal cord injury, more than 10 years after the injury, and who met the inclusion criteria. Method: Quality of life was assessed using the International spinal cord injury quality of life basic data set. Variables included: individual factors, neurological deficit, level of injury and secondary complications. Results: 131 subjects were included in the study with a mean age of 49 years, and a time since the injury of 21 years (11–53 years). The mean number of secondary complications was 2, the most frequent being urological, in 76 subjects (58%). There were no significant differences between the number of complications and the time elapsed since the spinal cord injury. The quality of life was significantly lower in those with a higher number of complications (P=.003). Urological complications (P=.04, 95% CI: −1.02 to 2), musculoskeletal pain (P=.01, 95% CI: 1–6), respiratory complications (P=.05, 95% CI: −3 to 0.1) and neuropathic pain that interfered with basic life activities (P=.01, 95% CI: 1–5) were significantly related to a lower quality of life. Conclusions: Secondary complications are common after spinal cord injury, although their number does not increase over time after injury. Quality of life is conditioned by the existence of different complications such as the existence of musculoskeletal pain.(AU)

ALDH1A3 is epigenetically regulated during melanocyte transformation and is a target for melanoma treatment.

Despite the promising targeted and immune-based interventions in melanoma treatment, long-lasting responses are limited. Melanoma cells present an aberrant redox state that leads to the production of toxic aldehydes that must be converted into less reactive molecules. Targeting the detoxification machinery constitutes a novel therapeutic avenue for melanoma. Here, using 56 cell lines representing nine different tumor types, we demonstrate that melanoma cells exhibit a strong correlation between reactive oxygen species amounts and aldehyde dehydrogenase 1 (ALDH1) activity. We found that ALDH1A3 is upregulated by epigenetic mechanisms in melanoma cells compared with normal melanocytes. Furthermore, it is highly expressed in a large percentage of human nevi and melanomas during melanocyte transformation, which is consistent with the data from the TCGA, CCLE and protein atlas databases. Melanoma treatment with the novel irreversible isoform-specific ALDH1 inhibitor [4-dimethylamino-4-methyl-pent-2-ynthioic acid-S methylester] di-methyl-ampal-thio-ester (DIMATE) or depletion of ALDH1A1 and/or ALDH1A3, promoted the accumulation of apoptogenic aldehydes leading to apoptosis and tumor growth inhibition in immunocompetent, immunosuppressed and patient-derived xenograft mouse models. Interestingly, DIMATE also targeted the slow cycling label-retaining tumor cell population containing the tumorigenic and chemoresistant cells. Our findings suggest that aldehyde detoxification is relevant metabolic mechanism in melanoma cells, which can be used as a novel approach for melanoma treatment.

Activation of nuclear factor-kappa B is linked to resistance to neoadjuvant chemotherapy in breast cancer patients.

The nuclear factor (NF)-kappaB system is a promising anticancer target due to its role in oncogenesis and chemoresistance in preclinical models. To provide evidence in a clinical setting on the role of NF-kappaB in breast cancer, we aimed to study the value of basal NF-kappaB/p65 in predicting resistance to neoadjuvant chemotherapy, and to characterise the pharmacodynamic changes in NF-kappaB/p65 expression following chemotherapy in patients with locally advanced breast cancer. Pre- and post-chemotherapy tumour specimens from 51 breast cancer patients treated with anthracycline- and/or taxane-containing neoadjuvant chemotherapy were assayed by immunohistochemistry for NF-kappaB/p65 subcellular expression. We studied NF-kappaB/p65, a well-characterised member of the NF-kappaB family that undergoes nuclear translocation when NF-kappaB is activated. Activation of NF-kappaB (i.e. nuclear NF-kappaB/p65 staining in pre-therapy specimens) was linked to chemoresistance. Patients with NF-kappaB/p65 nuclear staining in pre-treatment samples had a 20% clinical response rate, while patients with undetected nuclear staining had a 91% response rate to chemotherapy (P = 0.002). Notably, four patients achieved a complete histological response and none of them had pre-treatment NF-kappaB/p65 nuclear staining. Moreover, the number of patients with NF-kappaB/p65 activation increased after chemotherapy exposure. It is concluded that NF-kappaB/p65 activation assayed by immunohistochemistry is a predictive factor of resistance to neoadjuvant chemotherapy in breast cancer patients. Moreover, NF-kappaB activation was inducible following chemotherapy in a proportion of breast cancer patients. These novel clinical findings strengthen the rationale for the use of NF-kappaB inhibitors to prevent or overcome chemoresistance in breast cancer.

Encefalitis y abscesificación cerebral como complicación de una sinusitis frontal aguda en un niño

Resumen Las sinusitis son procesos infecciosos-inflamatorios de las cavidades neumáticas paranasales. Entre las complicaciones de las sinusitis agudas se encuentra la afectación intracraneal, con meningoencefalitis e incluso abscesos extra o subdurales. En este trabajo se describe un caso de meningoencefalitis y empiemas subdurales derivados de una sinusitis frontal aguda en un niño de 12 años, que acudió a urgencias presentando alteración del nivel de conciencia y hemiparesia derecha. Se realizan estudios de tomografía computada y resonancia magnética cerebral, evidenciándose ocupación de seno frontal izquierdo, acompañada de extensa afectación hipercaptante en cubiertas en hemisferio cerebral izquierdo, con formación de empiemas subdurales a nivel frontal izquierdo, parafalciano y en reborde tentorial. Ingresa para tratamiento antibiótico intravenoso y dado el nivel de afectación y la escasa respuesta a tratamiento médico, se decide realizar cirugía endoscópica DRAF IIa con drenaje del absceso frontal, etmoidectomía y meatotomía media izquierda, con sonda de drenaje a fosa nasal. Las complicaciones a nivel de sistema nervioso central son graves y han de tenerse siempre presentes, requiriendo en ocasiones drenaje quirúrgico con abordaje por vía endonasal o abierta.

Abstract Sinusitis are infectious-inflammatory processes of the pneumatic paranasal cavities. Among the complications of acute sinusitis, we can find intracranial involvement, with meningoencephalitis and even extra or subdural abscesses. In this article we describe a case of meningoencephalitis and subdural empyemas associated with acute frontal sinusitis in a 12-year-old child who presented to the emergency room referring altered level of consciousness and right hemiparesis. Computed tomography scan and brain magnetic resonance imaging studies were performed, evidencing left frontal sinus occupation, accompanied by extensive hypercaptant defects in the left cerebral hemisphere, with formation of subdural empyemas at the left frontal level, parafalcian and in the tentorial area. He was hospitalized for intravenous antibiotic treatment, and given the lack of response to medical treatment, a DRAF IIa sinus surgery and drainage of the frontal abscess, ethmoidectomy and left middle meatotomy with drainage tube to the nasal cavity were performed. Complications at the central nervous system are serious and must always be kept in mind, sometimes requiring surgical drainage with an endonasal or open approach.

Efficacy of silver diamine fluoride for caries reduction in primary teeth and first permanent molars of schoolchildren: 36-month clinical trial.

We hypothesized that the six-monthly application of silver diamine fluoride (SDF) can arrest the development of caries in the deciduous dentition of six-year-old schoolchildren and prevent caries in their first permanent molars. A prospective controlled clinical trial was conducted on the efficacy of a 38% SDF solution for caries reduction. Four hundred and twenty-five six-year-old children were divided into two groups: One group received SDF solution in primary canines and molars and first permanent molars every 6 mos for 36 mos. The second group served as controls. The 36-month follow-up was completed by 373 children. The mean number of new decayed surfaces appearing in primary teeth during the study was 0.29 in the SDF group vs. 1.43 in controls. The mean of new decayed surfaces in first permanent molars was 0.37 in the SDF group vs. 1.06 in controls. The SDF solution was found to be effective for caries reduction in primary teeth and first permanent molars in schoolchildren.

First molecular switch encapsulated within the cavities of a zeolite. A dramatic lifetime increase of the charge-separated state.

A [2]-catenane consisting of a bipyridinium cyclophane and a dioxybenzene macrocyclic polyether has been encapsulated within the supercages of zeolite Y by ship-in-a-bottle synthesis; laser flash photolysis reveals that the charge-separated species decays in hundreds of microseconds in contrast to the few picoseconds previously reported for the same transient in acetonitrile.

Optimizing ammonia processing conditions to enhance susceptibility of legumes to fiber hydrolysis: alfalfa.

An ammonia process was applied at several ammonia loadings, moisture contents, temperatures, and dwell times. A cellulase loading of 5 FPU/g dry matter and a 24 h incubation time were used to produce the sugars, which were measured as reducing sugars and by HPLC. Optimal processing conditions caused a 76% of theoretical yield (2.9-fold above untreated). Cellulose and hemicellulose conversions were 68 and 85% (vs 38 and 34% in untreated, respectively). The short hydrolysis time and relatively low enzyme loading suggests great potential to produce sugars from alfalfa.

Optimizing ammonia processing conditions to enhance susceptibility of legumes to fiber hydrolysis: Florigraze rhizoma peanut.

A warm-season legume, Florigraze rhizoma peanut (FRP), was used as the source of fiber to produce sugars. FRP was subjected to several ammonia-processing conditions using temperature, biomass moisture content, and ammonia loading as process variables during a 5-min treatment. A cellulase loading of 2 FPU/g DM and 24 h incubation were used to produce the sugars. Total sugar yield was 3.34-fold higher in the optimal treatment (1.5 g ammonia/g DM-60%-90 degrees C) compared to untreated and was 65.3% of theoretical. Cellulose and hemicellulose conversions increased from 30 and 15.5% in untreated FRP to 78 and 34% in treated FRP.

Optimizing ammonia pressurization/depressurization processing conditions to enhance enzymatic susceptibility of dwarf elephant grass.

An ammonia pressurization/depressurization process was investigated to evaluate the potential of producing reducing sugars from dwarf elephant grass, a warm-season forage. Moisture, temperature, and ammonia loading affected sugar yield (p < 0.0001). At optimal conditions, ammonia processing solubilized 50.9% of the hemicellulose and raised the sugar yield (percentage of theoretical) from 18 to 83%. Glucose and xylose production were increased 3.2- and 8.2-fold, respectively. The mild processing conditions of the ammonia treatment (90-100 degrees C, 5 min), the low enzyme loading (2 international filter paper units/g), and the short hydrolysis time (24 h), greatly enhance the potential of using forages to produce sugars valuable for several applications.

[Severe abdominal complications in patients treated with heart transplantation: the problem of clinical inexpressiveness]. / Complicaciones abdominales graves en los pacientes sometidos a trasplante cardíaco: el problema de la inexpresividad clínica.

INTRODUCTION: In transplanted patients, immunosuppressive drugs can mask habitual pathologies that impede their diagnoses and management. Abdominal pathology gives up to 2-20%, 50% of which is surgical, with a mortality of 10-40%. The most frequently detected pathologies are: acute pancreatitis, peptic ulceration and intestinal obstruction. OBJECTIVES: To determine the alarm parameters, more adequate diagnostic procedures and the most frequent causes of morbidity and mortality in order to attempt to avoid them. METHODS: In our center 225 heart transplantations were performed from May 1984 to October 1997. The severe abdominal complications, time of appearance, implication of immunosuppressive drugs and presence of rejection were studied in these patients. RESULTS: 35 severe abdominal complications were detected (incidence 12.9%), with the majority differing (> 1 year following transplant). The most frequently detected pathologies were digestive hemorrhages and perforations. Acute pancreatitis was 11%. The immunosuppressive drugs used were prednisona, cyclosporin and azathioprine. In 12 out of 29 patients the abdominal complication was in the context of acute rejection. CONCLUSIONS: Even with some non-specific abdominal symptoms in these group of patients it is important to rule out severe pathologies such as acute pancreatitis or empty viscera perforation. The detection of amylases and lypases in the blood and an echographic or tomographic abdominal study should be performed early with a digestive hemorrhage it is important to perform an endoscopy. If the surgical intervention seems imminent it's better to perform it without any delay, because it has been demonstrated that the delay is worse than the probable rejection.