Rejected

Hepatitis C virus (HCV) infections are more common among US veterans receiving care through Veterans Affairs (VA) Medical Centers than among the general population. Historically, HCV therapies had lower efficacy rates in VA patients, possibly due to common comorbidities such as psychiatric disorders and substance abuse. The direct-acting antivirals ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r +DSV) ± ribavirin (RBV) are approved in the US for HCV genotype (GT) 1-infected adults with or without cirrhosis. This study prospectively evaluated safety and efficacy of OBV/PTV/r +DSV ±RBV in VA patients with HCV GT1 infection.

Ustekinumab and briakinumab are monoclonal antibodies that target the standard p40 subunit of cytokines interleukin-12 and interleukin-23 (IL-12/23p40), which are involved in the pathogenesis of Crohn's disease (CD). A significant proportion of people with Crohn's disease fail conventional therapy or therapy with biologics (e.g. infliximab) or develop significant adverse events. Anti-IL-12/23p40 antibodies such as ustekinumab may be an effective alternative for these individuals.

Purinergic receptor is a potential drug target for neuropathic pain, Alzheimer disease, and prostate cancer. Focusing on the structure-based ligand discovery, docking analysis on the crystal structure of P2Y receptor (P2YR) with 923 derivatives of 1-indolinoalkyl 2-phenolic compound is performed to understand the molecular insights of the receptor. The structural model identified the top novel ligands, 426 (compound 1) and 636 (compound 2) having highest binding affinity with the docking score of -7.38 and -6.92. We have reported the interaction efficacy and the dynamics of P2YR protein with the ligands. The best hits synthesized were experimentally optimized as a potent P2Y agonists. These ligands exhibits anti-proliferative effect against the PC-3 and DU-145 cells (IC = 15 µM – 33 µM) with significant increase in the calcium level in dose- and time-dependent manner. Moreover, the activation of P2YR induced the apoptosis via Capase3/7 and ROS signaling pathway. Thus it is evidenced that the newly synthesized ligands, as a P2YR agonists could potentially act as a therapeutic drug for treating prostate cancer.

The α2 agonists, dexmedetomidine and clonidine, are used as sedative drugs during critical illness. These drugs may have anti-inflammatory effects, which might be relevant to critical illness, but a systematic review of published literature has not been published. We reviewed animal and human studies relevant to critical illness to summarise the evidence for an anti-inflammatory effect from α2 agonists.

Prolonged treatment with analgesic and sedative drugs in the pediatric intensive care unit (PICU) may lead to undesirable effects such as dependence and tolerance. Moreover, during analgosedation weaning, patients may develop clinical signs of withdrawal, known as withdrawal syndrome (WS). Some studies indicate that dexmedetomidine, a selective α2-adrenoceptor agonist, may be useful to prevent WS, but no clear evidence supports these data. The aims of the present study are to evaluate the efficacy of dexmedetomidine in reducing the occurrence of WS during analgosedation weaning, and to clearly assess its safety.

Prolonged latent phase of labor is associated with adverse maternal and neonatal outcomes. Preliminary data indicate that labor induction for prolonged latent phase may reduce cesarean delivery. We performed a study powered to Cesarean delivery to evaluate labor induction compared to expectant management in full term nulliparas hospitalized for persistent contractions but non-progressive to established labor after an overnight stay.

Resumen Introducción. El síndrome de Achenbach fue descrito en los años 50' por el médico alemán Walter Achenbach y corresponde a una entidad caracterizada por la aparición de equimosis o purpuras e incluso hematomas en los dedos de las manos y en algunas ocasiones de los pies. Cursa de forma benigna y es autolimitada. Métodos. Presentamos el caso de una mujer de 60 años a quien se diagnosticó este síndrome luego de realizar exámenes de laboratorio, anticuerpos e imágenes sin encontrar alteraciones en ellos, con mejoría luego de recibir analgesia y medios físicos. Resultados. El síndrome de Achenbach continúa siendo una entidad desconocida, con pocos reportes en la literatura. Hasta el año 2 016 se habían identificado 12 reportes de caso a nivel mundial concluyendo que es una patología que afecta principalmente a mujeres entre la quinta y sexta década de vida. Conclusión. Aunque esta entidad nosológica es benigna y su fisiopatología no está del todo clara, es importante que durante el abordaje inicial se consulte por episodios similares en el pasado y en caso de ser un evento agudo, buscar otras alteraciones como retardo en el llenado capilar, frialdad distal, ausencia de pulsos y de ese modo se descarte patología isquémica aguda con ayudas diagnosticas.   Resumo Introdução. Síndrome achenbach foi descrito no 50' pelo médico alemão Walter achenbach e corresponde a uma condição caracterizada pelo aparecimento de lesões ou roxo e hematomas mesmo nos dedos das mãos e dos pés, por vezes. Cursa de maneira benigna e é autolimitada. Métodos. Relatamos o caso de uma paciente de 60 anos que esta síndrome após a realização de testes de laboratório, anticorpos e imagens sem encontrar anormalidades nos mesmos, com melhora depois de receber analgesia e mídia física foi diagnosticado. Resultados. A síndrome de Achenbach continua sendo uma entidade desconhecida, com poucos relatos na literatura. Até o ano 2 016, 12 relatos de casos foram identificados em todo o mundo, concluindose que é uma patologia que acomete principalmente mulheres entre a quinta e a sexta década de vida. Conclusão. Embora esta entidade doença é benigna e sua fisiopatologia não é totalmente clara, é importante que, durante a abordagem inicial é consultado por episódios semelhantes no passado e deve ser um evento agudo, procure outros distúrbios, tais como enchimento capilar retardado, frio distal, ausência de pulsos e, assim, descartar a patologia isquêmica aguda com auxiliares de diagnóstico.   Abstract Introduction. The Achenbach syndrome was described in the '50s by the German physician Walter Achenbach and corresponds to an entity characterized by the appearance of ecchymosis or purpura and even bruises on the fingers and sometimes on the feet. It courses benignly and is self-limited.

We tested the popular, unproven theory that tinnitus is caused by resetting of auditory predictions towards a persistent low-intensity sound. Electroencephalographic mismatch negativity responses, which quantify the violation of sensory predictions, to unattended tinnitus-like sounds were greater in response to upward than downward intensity deviants in 26 unselected chronic tinnitus subjects with normal to severely-impaired hearing, and in 15 acute tinnitus subjects, but not in 26 hearing and age-matched controls (p < 0.001, ROC AUC 0.77), or in 20 healthy and hearing-impaired controls presented with simulated tinnitus. The findings support a prediction resetting model of tinnitus generation, and may form the basis of a convenient tinnitus biomarker, which we name Intensity Mismatch Asymmetry (IMA), that is usable across species, that is quick, tolerable and requires no training.In current models, perception is based around the generation of internal predictions of the environment, which are tested and updated using evidence from the senses. Here, we test the theory that auditory phantom perception (tinnitus) occurs when a default auditory prediction is formed in order to explain spontaneous activity in the subcortical pathway, rather than ignoring it as noise. We find that chronic tinnitus patients show an abnormal pattern of evoked responses to unexpectedly loud and quiet sounds that both supports this hypothesis and provides fairly accurate classification of tinnitus status at the individual subject level. This approach to objectively demonstrating the predictions underlying pathological perceptual states may also have a much wider utility, for instance in chronic pain.

Osteoarthritis (OA) is a most common orthopaedic condition, often complicated by inflammatory features.

Chronic pelvic pain affects approximately one-third of all women and is responsible for about 20% of all gynecological consultations. The authors report a rare case of symptomatic pelvic venous congestion in the presence of duplication of the inferior vena cava and inter-iliac communication through the right hypogastric vein that was treated via an endovascular approach with embolization of varicose pelvic veins. The published literature is reviewed.