Machine-guided design of synthetic cell type-specific cis-regulatory elements.

Cis-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing, and stimulus responses, which collectively define the thousands of unique cell types in the body. While there is great potential for strategically incorporating CREs in therapeutic or biotechnology applications that require tissue specificity, there is no guarantee that an optimal CRE for an intended purpose has arisen naturally through evolution. Here, we present a platform to engineer and validate synthetic CREs capable of driving gene expression with programmed cell type specificity. We leverage innovations in deep neural network modeling of CRE activity across three cell types, efficient in silico optimization, and massively parallel reporter assays (MPRAs) to design and empirically test thousands of CREs. Through in vitro and in vivo validation, we show that synthetic sequences outperform natural sequences from the human genome in driving cell type-specific expression. Synthetic sequences leverage unique sequence syntax to promote activity in the on-target cell type and simultaneously reduce activity in off-target cells. Together, we provide a generalizable framework to prospectively engineer CREs and demonstrate the required literacy to write regulatory code that is fit-for-purpose in vivo across vertebrates.

In silico prediction of B and T cell epitopes of infectious salmon anemia virus proteins and molecular modeling of T cell epitopes to salmon major histocompatibility complex (MHC) class I.

Infectious salmon anemia (ISA) can be devastating in farmed Atlantic salmon (Salmo salar). The disease can evolve into epidemics if it is not contained and controlled. ISA epidemics were seen in Norway in the early 1990s and Chile in 2007-2009. Consequently, there is an urgent need to develop a vaccine to prevent or treat the infection. In this study, an immunoinformatic approach was employed to predict 32 lineal B-cell epitopes based on antigenicity and surface accessibility prediction for ISAV fusion (F), hemagglutinin-esterase (HE), and matrix (M) proteins. On the other hand, twelve conformational B-cell epitopes were also predicted. We further identified six antigenic cytotoxic T lymphocyte (CTL) epitopes and investigated the binding interactions with five salmon MHC-I proteins after docking the peptides to the binding groove of the MHC-I proteins. Our results showed that all the predicted epitopes could bind to salmon MHC-I with high negative ΔG values with medium to high binding affinities. Hence, the predicted epitopes have a high potential of being recognized by Atlantic salmon MHC-I to elicit a CD8+ T cell response in salmon. The predicted and analyzed B and T cell antigenic epitopes in this work might present an initial set of peptides for future vaccine development against ISAV. The ability to model and predict these interactions will ultimately lead to the ability to predict potential binding for MHCs and epitopes that were not studied previously. As current knowledge of salmon MHC specificity is limited, studying and modeling interactions in the peptide/MHC complex is a key to resolving unknown epitope specificity.

Effect of PEG grafting density on surface properties of polyurethane substrata and the viability of osteoblast and fibroblast cells.

The surface of Tecoflex SG-80A Polyurethane (PU) films was modified by grafting polyethylene glycol (PEG) chains at three different molar amounts (0.05, 0.10, and 0.15 mmol). The resulting substrata were characterized by FTIR-ATR, TGA, AFM, SEM and contact angle to assess the surface modifications occurred during the grafting reactions. Osteoblasts and fibroblasts were cultured with PU extracts for 24 h, and their cell viability and morphology were evaluated by CellTiterBlue assay, Crystal Violet staining and Live/Dead assay. FTIR and TGA results indicated that PEG chains were successfully grafted onto PU surfaces, specifically in the hard segment of PU forming allophanate groups as the PEG grafting density increased. SEM and AFM images suggest that PU substrata were partially covered by PEG, increasing the dispersive and basic components of the PU surface energy. It was found that extracts from PEG-grafted polyurethanes increased the osteoblast viability, although fibroblasts viability remained constant regardless PEG grafting density; in spite of this both cells presented a more spread morphology at the lower PEG grafting density. Our results showed that surface energy of PU substrata can be tuned by PEG grafting density; also, the PEG leached tends to increase the pH of culture medium which leads to a higher viability of osteoblasts; nevertheless, PEG grafting density should be optimized to promote a healthy cell morphology as alterations in its morphology were detected at higher concentrations. Graphical abstract.

Restless legs syndrome in patients with multiple sclerosis: evaluation of risk factors and clinical impact.

INTRODUCTION: Restless legs syndrome (RLS) is a disorder characterised by an irresistible urge to move the legs, usually accompanied by unpleasant sensations. It is more frequent in patients with multiple sclerosis (MS) than in the general population. OBJECTIVES: To evaluate the prevalence of RLS, defined according to the 4 essential requirements included in the diagnostic criteria proposed by the International Restless Leg Syndrome Study Group, in a cohort of patients with MS; and to identify potential risk factors and the clinical impact of RLS. RESULTS: The sample included 120 patients with MS, with a mean age of symptom onset of 40 years and an average disease duration of 46 months. The prevalence rate of RLS was 23.3%. MS progression time was significantly shorter in patients with RLS (P=.001). A recent relapse, and symptoms of anxiety, depression, and neuropathic pain were significantly associated with risk of RLS (P=.001, P<.001, P<.001, and P=.001, respectively). In addition, patients with RLS had a greater risk of poor sleep quality, fatigue, daytime sleepiness, and poor quality of life than those without RLS (P=.002, P=.017, P=.013, and P=.009, respectively). CONCLUSIONS: RLS should be considered in the neurological evaluation of patients with MS; early diagnosis and treatment would improve the quality of life of patients with MS presenting RLS.

Síndrome de piernas inquietas en esclerosis múltiple: evaluación de factores de riesgo y repercusión clínica / Restless legs syndrome in patients with multiple sclerosis: evaluation of risk factors and clinical impact

Introducción: El síndrome de piernas inquietas (SPI) es un trastorno caracterizado por la necesidad imperiosa de mover las piernas, estando a menudo acompañado de sensaciones desagradables. Su frecuencia es superior en pacientes con esclerosis múltiple (EM) que en la población general. Objetivos: Evaluar la prevalencia del SPI, según el cumplimiento de los 4 requisitos esenciales incluidos en los criterios diagnósticos propuestos por la International Restless leg syndrome study group (IRLSSG, 2003), en una cohorte de pacientes con EM e identificar posibles factores de riesgo y repercusión clínica. Resultados: Se incluyeron 120 pacientes con EM, con una edad media de inicio de 40 años y un tiempo medio de evolución de 46 meses. La prevalencia de SPI, según el cumplimiento de criterios diagnósticos de la IRLSSG, fue del 23,3%. El tiempo de evolución de EM, desde la aparición de los primeros síntomas, fue significativamente menor en pacientes con SPI (p=0,001). La presencia de un brote reciente, así como de síntomas de ansiedad, depresión y dolor neuropático se asociaron de forma significativa con el riesgo de SPI (p=0,001, p<0,001, p<0,001 y p=0,001, respectivamente). Además, los pacientes con SPI y EM presentaron mayor riesgo de mala calidad de sueño, fatiga, somnolencia diurna y peor calidad de vida, que aquellos sin SPI (p=0,002, p=0,017, p=0,013 y p=0,009, respectivamente). Conclusiones: El SPI debe ser considerado en la evaluación neurológica de pacientes con EM, cuyo diagnóstico y tratamiento precoz mejoraría la calidad de vida de estos sujetos. (AU)

Introduction: Restless legs syndrome (RLS) is a disorder characterised by an irresistible urge to move the legs, usually accompanied by unpleasant sensations. It is more frequent in patients with multiple sclerosis (MS) than in the general population. Objectives: To evaluate the prevalence of RLS, defined according to the 4 essential requirements included in the diagnostic criteria proposed by the International Restless Leg Syndrome Study Group, in a cohort of patients with MS; and to identify potential risk factors and the clinical impact of RLS. Results: The sample included 120 patients with MS, with a mean age of symptom onset of 40 years and an average disease duration of 46 months. The prevalence rate of RLS was 23.3%. MS progression time was significantly shorter in patients with RLS (P = 0.001). A recent relapse, and symptoms of anxiety, depression, and neuropathic pain were significantly associated with risk of RLS (P = 0.001, P < 0.001, P < 0.001, and P = 0.001, respectively). In addition, patients with RLS had a greater risk of poor sleep quality, fatigue, daytime sleepiness, and poor quality of life than those without RLS (P = 0.002, P = 0.017, P = 0.013, and P = 0.009, respectively). Conclusions: RLS should be considered in the neurological evaluation of patients with MS; early diagnosis and treatment would improve the quality of life of patients with MS presenting RLS.

Analysis of rainbow trout TCRαß/CD3 complex: An in-silico modeling approach.

In mammals, the T lymphocyte receptor (TCR) is a multiprotein complex formed by the proteins TCRα, TCRß, CD3ε, CD3γ, CD3δ, and CD3ζ. It is responsible for recognizing antigens processed and presented by antigen-presenting cells (APC). The TCR is located at the cytoplasmic membrane of the T lymphocyte but is functional assembled in the rough endoplasmic reticulum (RER). Most of the available information on TCR constituents in salmonids comes from numerous nucleotide sequences available in different databases. In this work, by in silico homology modeling, we generated the TCRαß/CD3 complex of rainbow trout (Oncorhynchus mykiss) and characterized the structure of the different proteins and their potential interactions. The results show that the main structural features described in mammalian TCR/CD3 are present in the model predicted for trout. Furthermore, we highlighted several aminoacidic interactions between TCRα, TCRß, CD3γδ, and CD3ε. In silico structural analyses suggest that trout TCRαß complex would fit similarly to that described for mammals. Herein, we explore the implications of the modeled trout complex and the leukocyte phenotypes, mainly associated with different regulation mechanisms of trout TCRαß/CD3 subunits gene expression or may be due to differences in the assembly process of the complex in the RER. However, further studies will be needed to study deeper the mechanisms involved.

La Cruz Roja Británica al auxilio de refugiados húngaros en 1956 / The British Red Cross to the aid of Hungarian refugees in 1956

Tras la Segunda Guerra Mundial, Hungría cayó bajo la esfera de la influencia rusa. Durante la represión del levantamiento que tuvo lugar en Hungría en octubre de 1956, más de 200.000 húngaros huyeron como refugiados a otros países, entre ellos, Inglaterra. La Cruz Roja dispuso el bienestar de 7.500 refugiados húngaros en su llegada al país. Este trabajo dará a conocer algunos de los cuidados que realizó esta institución, concretamente, en la provincia de Hampshire. Para ello, se consultan fuentes documentales primarias de los Archivos Históricos de Winchester y la Universidad de Southampton (AU)

A multi-herd study shows that saliva is more than a reflection of serum biomarkers in pigs.

This study evaluates if biomarkers of porcine health status in saliva samples is a mere reflection of serum to detect disease in pigs under field conditions. Four farms from the same commercial company were included to obtain samples from animals with different pathological conditions. A total of 10 healthy animals and 10-15 animals from each farm with clinical symptoms of the disease were sampled for paired saliva and blood during a veterinary clinical visit. The biomarker panel included acute-phase proteins (APPs), C-reactive protein (CRP), haptoglobin (Hp), an inflammatory marker, adenosine deaminase (ADA), the total antioxidant capacity (TAC), the levels of essential trace elements, copper (Cu) and zinc (Zn), and the measurement of the total protein content (TP). After detailed statistical analysis, the results showed that saliva could replace serum for APP measurements since a good agreement has been observed between the concentrations of APPs in both body fluids. For any other biomarker, no agreement between the concentrations quantified in serum and saliva samples was observed visually. However, salivary ADA and TP concentrations were statistically significantly higher in the diseased, whereas the statistical tests with serum concentrations were inconclusive. Furthermore, greater differentiation between healthy and diseased animals could be observed when the distribution of biomarkers was analysed in saliva than in other serum samples. The diagnostic power to discriminate between healthy and diseased pigs is similar in saliva and in serum samples. Preliminary regression models may offer an optimal combination of biomarkers for disease detection in saliva (Hp, CRP, and TAC) and serum (Hp, CRP, and Cu), which demands less labour, sample, and financial cost for saliva determinations. The contradictory results observed for TAC, Cu, and Zn levels between body fluids indicate a need for further studies. To sum up, saliva-based biomarkers instead of serum-based biomarkers could contribute to more efficient detection of diseased animals.

Synthesis and characterization of pH sensitive hydrogel nanoparticles based on poly(N-isopropyl acrylamide-co-methacrylic acid).

In this work, pH-sensitive hydrogel nanoparticles based on N-isopropyl acrylamide (NIPAM) and methacrylic acid (MAA) at various molar ratios, were synthesized and characterized in terms of physicochemical and biological properties. FTIR and 1HNMR spectra confirmed the successful synthesis of the copolymer that formed nanoparticles. AFM images and FE-SEM micrographs showed that nanoparticles were spherical, but their round-shape was slightly compromised with MAA content; besides, the size of particles tends to decrease as MAA content increased. The hydrogels nanoparticles also exhibited an interesting pH-sensitivity, displaying changes in its particle size when changes in pH media occurred. Biological characterization results indicate that all the synthesized particles are non-cytotoxic to endothelial cells and hemocompatible, although an increase of MAA content leads to a slight increase in the hemolysis percentage. Therefore, the pH-sensitivity hydrogels may serve as a versatile platform as self-regulated drug delivery systems in response to environmental pH changes.

Development of Ureteral Stenosis/Obstruction in Kidney Transplant.

This retrospective study describes the incidence and prevalence of ureteral stenosis/obstruction (US/O) in a cohort of 334 renal transplants recipients in our center over the last 5 years and evaluates the risk factors that may influence the occurrence of US/O. The parameters studied included the following: history of prostate disease, smoking, urinary tract infection, renal lithiasis, ureterovesical reflux, presence and level of polar artery, type of ureterovesical anastomosis, delayed graft function, double J catheter, lymphocele, urinoma, acute rejection, prolonged catheterization, post-transplant infravesical obstruction and BK virus infection, age of the donor and recipient, and months on dialysis. Also evaluated were the nadir creatinine and instances of cold ischemia, asystole, reanastomosis, and double J catheter removal. The average incidence of US/O was 7.6% and was significantly correlated with factors of alteration of the uretero-bladder dynamics without finding a relation to vascular factors.

Síndrome compartimental posangioplastía coronaria transradial: a propósito de un caso / Post transradial coronary angioplasty compartimental syndrome

Resumen Introducción: El síndrome compartimental se genera por aumento de presión compartimental que sobrepasa a la de perfusión. Es una entidad rara en contexto posangioplastía coronaria. Requiere alta sospecha y medidas rápidas. Caso clínico: Hombre de 41 años con diagnóstico de infarto agudo de miocardio (IAM) con supradesnivel ST (SDST) que fue trombolizado y derivado para angioplastía, que sufre sangrado en antebrazo derecho posprocedimiento y evoluciona con síndrome compartimental que requiere de fasciotomía en volar y medial. Discusión: La entidad clínica es rara en este contexto, por ende, requiere alta sospecha basándose principalmente en dolor de inicio súbito con aumento de volumen. El tratamiento es fasciotomía de urgencias. De no pesquisarse a tiempo puede evolucionar con severas alteraciones neuromusculares llevando a trastornos de la anatomía de la mano.

Introduction: The compartment syndrome is caused by an increase on the compartment pressure that exceed the perfusion pressure. In coronary postangioplasty context it is a rare entity. Requires a high suspicion and to take fast steps. Clinical case: Forty-one years old man with a STEMI thrombolysed and derived to angioplasty suffered a post-procedure bleeding on his right forearm and evolved with a compartment syndrome that required a volar and medial fasciotomy. Discussion: The clinical entity is rare in this context, so require a high suspicion based basically on sudden pain with an increase of volume. The treatment is the urgent fasciotomy. To not diagnose it at time could evolve with severe neuromuscular disorders and hand anatomy disorders.

Restless legs syndrome in patients with multiple sclerosis: evaluation of risk factors and clinical impact. / Síndrome de piernas inquietas en esclerosis múltiple: evaluación de factores de riesgo y repercusión clínica.

INTRODUCTION: Restless legs syndrome (RLS) is a disorder characterised by an irresistible urge to move the legs, usually accompanied by unpleasant sensations. It is more frequent in patients with multiple sclerosis (MS) than in the general population. OBJECTIVES: To evaluate the prevalence of RLS, defined according to the 4 essential requirements included in the diagnostic criteria proposed by the International Restless Leg Syndrome Study Group, in a cohort of patients with MS; and to identify potential risk factors and the clinical impact of RLS. RESULTS: The sample included 120 patients with MS, with a mean age of symptom onset of 40 years and an average disease duration of 46 months. The prevalence rate of RLS was 23.3%. MS progression time was significantly shorter in patients with RLS (P = 0.001). A recent relapse, and symptoms of anxiety, depression, and neuropathic pain were significantly associated with risk of RLS (P = 0.001, P < 0.001, P < 0.001, and P = 0.001, respectively). In addition, patients with RLS had a greater risk of poor sleep quality, fatigue, daytime sleepiness, and poor quality of life than those without RLS (P = 0.002, P = 0.017, P = 0.013, and P = 0.009, respectively). CONCLUSIONS: RLS should be considered in the neurological evaluation of patients with MS; early diagnosis and treatment would improve the quality of life of patients with MS presenting RLS.

Integrating a newly developed BAC-based physical mapping resource for Lolium perenne with a genome-wide association study across a L. perenne European ecotype collection identifies genomic contexts associated with agriculturally important traits.

BACKGROUND AND AIMS: Lolium perenne (perennial ryegrass) is the most widely cultivated forage and amenity grass species in temperate areas worldwide and there is a need to understand the genetic architectures of key agricultural traits and crop characteristics that deliver wider environmental services. Our aim was to identify genomic regions associated with agriculturally important traits by integrating a bacterial artificial chromosome (BAC)-based physical map with a genome-wide association study (GWAS). METHODS: BAC-based physical maps for L. perenne were constructed from ~212 000 high-information-content fingerprints using Fingerprint Contig and Linear Topology Contig software. BAC clones were associated with both BAC-end sequences and a partial minimum tiling path sequence. A panel of 716 L. perenne diploid genotypes from 90 European accessions was assessed in the field over 2 years, and genotyped using a Lolium Infinium SNP array. The GWAS was carried out using a linear mixed model implemented in TASSEL, and extended genomic regions associated with significant markers were identified through integration with the physical map. KEY RESULTS: Between ~3600 and 7500 physical map contigs were derived, depending on the software and probability thresholds used, and integrated with ~35 k sequenced BAC clones to develop a resource predicted to span the majority of the L. perenne genome. From the GWAS, eight different loci were significantly associated with heading date, plant width, plant biomass and water-soluble carbohydrate accumulation, seven of which could be associated with physical map contigs. This allowed the identification of a number of candidate genes. CONCLUSIONS: Combining the physical mapping resource with the GWAS has allowed us to extend the search for candidate genes across larger regions of the L. perenne genome and identified a number of interesting gene model annotations. These physical maps will aid in validating future sequence-based assemblies of the L. perenne genome.

Impairment in exploratory behavior is associated with arc gene overexpression in the dorsolateral striatum of rats with nigral injection of l-buthionine sulfoximine.

The aims of the present work were to evaluate the exploratory activity in Sprague-Dawley rats, as well as to analyze the nigral and striatal mRNA expression of the plasticity-related genes bdnf and arc after L-buthionine sulfoximine (BSO) injection into substantia nigra compacta. Lesioned rats traveled less distance in open field but did not show a decline in the novel object recognition test. On the other hand, RT-PCR analysis showed overexpression of striatal arc 24 h post-lesion; no significant changes in bdnf expression were observed in nigral or striatal tissue. These results suggest that intranigral BSO injection causes impairment in exploratory behavior in these rats, by affecting locomotion, which is associated with changes in striatal synaptic plasticity.

Cytomegalovirus Infection Monitoring Based on Interferon Gamma Release Assay in Kidney Transplantation.

BACKGROUND: Cytomegalovirus (CMV) is the most common viral infection after kidney transplantation and is associated with significant morbidity and mortality. Recent studies showed that CMV-specific CD8+ T cells play the crucial role in protection against CMV. The Quantiferon-CMV (QF-CMV) is an interferon gamma (IFN-γ) release assay (IGRA test) that measures the IFN-γ response to a range of T-cell epitopes of CMV. In the present study, we analyzed the clinical utility of QF-CMV assay to predict CMV infection in kidney transplant recipients and evaluated if reactive result in QF-CMV test could be predictor of the duration of treatment. METHODS: We studied 75 renal transplant recipients who had IGRA testing just before transplantation. The donor and recipient variables were reported from the clinical history. The variables related to transplantation were collected from transplantation process data and included CMV infection or disease, CMV treatment, and immunosuppressive treatment. Laboratory variables were C3-C4 complement fractions and DNA quantification of CMV. RESULTS: Fifty percent of patients had CMV infection, and 35.9% had CMV disease. The time of negativization of CMV DNA was 56.61 ± 23.5 days. Univariate analysis related to CMV infection only showed a statistically significant relation with thymoglobulin treatment (P = .001). Statistically significant variables in relation with CMV infection incidence were donor serology (P = .044) and thymoglobulin treatment (P = .004). The probability of CMV infection was lower with positive IGRA assay (P = .025). CONCLUSION: We found that IFN-γ response measured by QF-MV is a protective factor against CMV infection in post-transplantation kidney recipients.

Rendimiento diagnóstico de la histerosalpingografía por resonancia magnética: resultados iniciales / Diagnostic performance of magnetic resonance hysterosalpingography: initial results Abstract

Objetivo: Determinar el rendimiento diagnóstico de la histerosalpingografía por resonancia magnética (HSG-RM), utilizando la laparoscopia como método de referencia. Materiales y métodos: Se incluyeron 22 pacientes. A todas se les realizó una HSG-RM con un resonador 1.5 Tesla y luego una laparoscopia con cromotubación. Dos radiólogos examinaron las RM, determinando la permeabilidad tubaria por consenso. Se realizaron análisis descriptivos y de rendimiento diagnóstico. Resultados: La HSG-RM tuvo una tasa de éxito del 91%. La duración del estudio fue 49ą15 minutos, el volumen inyectado 26 ą 16 cm³ y la escala de dolor 30ą 19 de 100. La sensibilidad y especificidad de la HSG-RM fueron del 100% para la prueba de Cotte global y a la izquierda, y del 25% y 93,3% para la prueba de Cotte a la derecha, respectivamente. Hubo 2 complicaciones menores y ninguna importante. Discusión: Nuestros resultados iniciales demostraron una alta sensibilidad y especificidad. Si bien otros estudios analizaron la capacidad de la HSG-RM para evaluar la permeabilidad tubaria con buenos resultados, el uso de un patrón de referencia defectuoso dejaba margen para una duda razonable, impidiendo una recomendación basada en pruebas sólidas. Sin embargo, al cotejar nuestros resultados con los publicados, observamos un alto grado de concordancia en tanto el derrame positivo se diagnostica correctamente con una especificidad de 100% o con un porcentaje cercano a esta cifra. Conclusión: La HSG-MR es una alternativa factible y segura de la HSG convencional o virtual, la histerosonografía y la cromotubación.

Objective: To determine the diagnostic performance of magnetic resonance hysterosalpingography (MRHSG) using laparoscopic chromotubation as a method of reference. Materials and methods: Twenty-two patients were included. The MRHSG was performed in a 1.5 Tesla MR scanner. Afterwards, patients underwent laparoscopic chromotubation. MR images were examined by two trained radiologists, and tubal patency was determined by consensus. A descriptive analysis was carried out, as well as an analysis of the diagnostic performance. Results: MRHSG had a 91% success rate. Exam duration of the examination was 49ą15min, with an injected volume 26ą 16cc, and pain scale 30ą 19 out of 100. Sensitivity and specificity of MRHSG was 100% for global and left Cotte, and 25% and 93.3% for right Cotte, respectively. Only 2 minor and no major complications were observed. Discussion: The initial results of MRHSG have shown high sensitivity and specificity. Even though other studies have analysed the potential of MRHSG with good results, the use of a flawed reference standard left a margin for a reasonable doubt as regards its true potential, thus preventing a solid evidence based recommendation. Nevertheless, if our results are compared to those published, a high level of agreement is observed in that positive spillage is correctly diagnosed with specificities near or at 100%. Conclusion: MRHSG is a feasible and safe alternative to conventional or virtual HSG, ultrasound-hysterography and chromotubation.

Radiofrecuencia pulsada sobre el nervio dorsal del pene: tratamiento eficaz para la neuralgia refractaria del pudendo / On the dorsal penile nerve pulsed radiofrecuency: effective treatment for refractory pudendal neuralgia

La neuralgia del pudendo se define como un síndrome doloroso neuropático, que involucra al dermatomo y a la inervación motora del nervio pudendo. Cualquier punto de su trayecto, desde su origen hasta sus ramificaciones terminales, es susceptible de sufrir diferentes grados de afectación o lesión. La localización del dolor puede ser perineal, rectal o en el área del clítoris/pene, presentándose de forma unilateral o bilateral; se agrava al sentarse y disminuye o desaparece al estar de pie; habitualmente respeta el descanso nocturno y puede asociarse a disfunción urinaria, anal e incluso sexual. Son múltiples las causas que pueden provocar la afectación del nervio pudendo, como partos, caídas, golpes directos y cirugías pélvicas. Esta patología constituye una entidad relativamente frecuente en las unidades de dolor crónico. Son varias las terapias utilizadas, incluyendo fármacos, bloqueos nerviosos del pudendo, cirugía descompresiva y neuromodulación de cordones posteriores medulares. Presentamos el caso de un paciente que, tras ser sometido a prostatectomía radical, consultó por dolor crónico continuo de tipo quemante junto a crisis lancinantes en parte distal derecha del pene (territorio del pudendo) y en el que aplicamos radiofrecuencia pulsada sobre el nervio dorsal derecho del pene obteniendo un buen resultado. Son varios los autores que han publicado tratamientos exitosos con radiofrecuencia pulsada del pudendo para el tratamiento de la neuralgia de dicho nervio, pero hasta ahora no se ha publicado ningún artículo de radiofrecuencia pulsada sobre los nervios dorsales del pene (AU)

Pudendal neuralgia is defined as a neuropathic pain syndrome, involving the dermatome and motor innervation of the pudendal nerve. Any point in its journey, from its origin to its terminal branches, is susceptible to varying levels of damage or injury. The location may be perineal pain, rectal or clitoral/penis area, presenting unilateral or bilateral. It is aggravated by sitting and diminishes or disappears when standing; usually respects people’s sleep and may be associated with urinary or anal dysfunction, and even sex. There are multiple causes that can lead to involvement of the pudendal nerve, such as births, falls, direct hits and pelvic surgeries. This disease is a relatively common condition in chronic pain units. There are several therapies used, including drugs, pudendal nerve blocks, decompressive spinal surgery and neuromodulation posterior columns. We report the case of a patient who, after undergoing radical prostatectomy, chronic pain consulted by continuous burning pain with lancinating type crisis penis right (territory of the pudendal) distal part and in which we apply on the nerve pulsed radiofrequency right dorsal penile obtaining a good result. There are several authors who have published successful treatments with pulsed radiofrequency to treat pudendal neuralgia of the nerve, but so far has not published any articles of pulsed radiofrequency of the dorsal nerves of the penis (AU)

[Retrograde intramedullary nail fixation for Charcot neuroarthropathy]. / Evaluación del uso del clavo centromedular retrógrado bloqueado para artrodesis de tobillo en pacientes con neuroartropatía de Charcot.

Charcot arthropathy is defined as an articular degenerative, chronic, progressive disease that affects one or more peripheral joints, develops as a result of a failure in the normal sensory perception (pain and proprioception) in the innervation of joints located in the foot and ankle, is characterized by destructive bone lesions without the presence of infection. Neuropathy is directly associated with diabetes mellitus type 1 and 2. Surgery is indicated when there is severe involvement of soft tissue, foot joints are unstable, at the presence of chronic or recurrent ulcers or when the foot and ankle can not fit to a normal shoe, and had limitation to perform activities of daily living. MATERIAL AND METHODS: Charcot arthropathy is defined as an articular degenerative, chronic, progressive disease that affects one or more peripheral joints, develops as a result of a failure in the normal sensory perception (pain and proprioception) in the innervation of joints located in the foot and ankle, is characterized by destructive bone lesions without the presence of infection. Neuropathy is directly associated with diabetes mellitus type 1 and 2. Surgery is indicated when there is severe involvement of soft tissue, foot joints are unstable, at the presence of chronic or recurrent ulcers or when the foot and ankle can not fit to a normal shoe, and had limitation to perform activities of daily living. DESIGN: observational, prospective, transversal, descriptive. SAMPLE: patients diagnosed with Charcot neuropathy type 3a of Brodsky. Surgically treated by ankle arthrodesis with an intramedullary blocked nail, from January 2010 to August 2015. RESULTS: 16 patients were analyzed. Preoperative AOFAS score was 35.0 ± 5.2 points. Postoperative follow-up period of 4 years to 7 months. Postoperative AOFAS scale showed an improvement of 40 points (p = 0.0001). CONCLUSIONS: The proposed treatment allows bone stabilization, resulting in a full foot plantar support and decreases the occurrence of chronic ulcers that are difficult to treat, and is an alternative method that avoids lead to amputation.

La artropatía de Charcot se define como un padecimiento articular degenerativo, crónico y progresivo que se caracteriza por lesiones óseas destructivas sin presencia de infección. La neuropatía está asociada directamente con la diabetes mellitus tipo 1 y 2. La cirugía está indicada cuando existe compromiso de partes blandas, inestabilidad de las articulaciones del tobillo y pie, cuando se desarrollan úlceras recurrentes o no es posible adecuar el tobillo o el pie a un calzado normal o en los pacientes que presentan deformidad severa, úlceras o dolor crónico y limitación para realizar las actividades de la vida diaria. El presente es un trabajo observacional, prospectivo, transversal y descriptivo de pacientes con diagnóstico de neuroartropatía de Charcot tipo 3a de Brodsky tratados quirúrgicamente mediante artrodesis de tobillo con clavo centromedular retrógrado bloqueado, del 1o de Enero de 2010 al 31 de Agosto de 2015. Se analizaron 16 pacientes. En el preoperatorio la media de la escala de AOFAS fue de 35.0 ± 5.2 puntos. Un seguimiento postoperatorio de cuatro años con un mínimo de siete meses. En el postoperatorio la escala de AOFAS mostró un incremento de 40 puntos hacia la mejoría (p = 0.0001). La técnica revisada logra la estabilización ósea, resultando en un pie con apoyo plantígrado que disminuye la aparición de úlceras crónicas y mejora el desarrollo en las actividades de la vida cotidiana.

Treatment With Darbepoetin During the First Year After Renal Transplantation: The Starting Point.

INTRODUCTION: Multiple factors are associated with post-transplantation anemia, and renal function is the main factor. The aims of this study were to compare the evolution of hemoglobin in the first year post-transplantation according to darbepoetin (DA) treatment, and factors related to it, to evaluate the difference between earlier versus delayed treatment, and to describe the dose change pattern. PATIENTS AND METHODS: We describe a retrospective study of cohorts in 462 transplant recipients (2004-2011). The variables reported were from donor, transplantation recipient, and DA treatment. RESULTS: In this study, 67.5% of patients were treated with DA, 32.5% were not. The comparison of hemoglobin in both groups during the first year showed a similar evolution with significant differences between consecutive measures until the second trimester. The hemoglobin of the treated group was significantly lower. The evolution of renal function was not different. Multivariate analysis related DA treatment to delayed graft function (DGF) and albuminuria in the first year. Patients with early versus delayed DA introduction did not show a difference regarding length of treatment, but the total dose in the delayed introduction was lower. The evolution of creatinine and hemoglobin was similar in both groups. CONCLUSION: The introduction of DA was related to DGF and albuminuria. The delayed introduction of DA meant the following: less total dose than earlier introduction, no difference in length of treatment, and a similar evolution in hemoglobin and renal function in both groups. The lack of guidelines about DA treatment in renal transplantation makes it difficult to establish a pattern of dose adjustment.

Merkel cell carcinoma and Merkel cell polyomavirus: a systematic review and meta-analysis.

Several observational studies have assessed the correlation between Merkel cell carcinoma and Merkel cell polyomavirus with variable results. The objective of this systematic review was to determine whether there is a correlation between Merkel cell carcinoma and Merkel cell polyomavirus. Studies assessing the relationship between Merkel cell carcinoma and Merkel cell polyomavirus from January 2008 to August 2014 were pooled from Medline, Embase, PubMed, Cochrane Database of Systemic Reviews and Google Scholar. From each study we collected the first author's last name, publication year, country of origin, type of study design, characteristics of participants, possible variables incorporated into the multivariable analyses and the risk ratio (RR) for Merkel cell carcinoma associated with Merkel cell polyomavirus combined with the corresponding 95% confidence interval (CI). Methodological assessment of the study was evaluated using the Newcastle-Ottawa scale. Crude RR was calculated from the data provided in each article. Meta-analyses for the global RR and for the proportion of positives in both case and control samples were performed. In addition, in order to explore the sources of heterogeneity among the studies, meta-regression and sensitivity analyses are also provided. A total of 22 studies were identified for the analysis. The pooled RR from random-effects analysis was determined to be 6.32 (95% CI, 4.02-9.93). Global proportions of positive samples were 0.79 (95% CI, 0.72-0.84) and 0.12 (95% CI, 0.08-0.19) in the case and control groups, respectively. The findings support the association between Merkel cell carcinoma and Merkel cell polyomavirus. However, a non-negligible percentage of positive results have been identified in controls. Some caution must be taken in the interpretation of these results because heterogeneity between studies was found.