refractory

The use of soluble and highly oxidizing Ag(III) in the form of the tetrahydroxoargentate ion Ag(OH)4(-) is reported for the oxidation of surrogate organic recalcitrant dyes (i.e., rhodamine 6G (Rh6G) and fluorescein (Fl)). The possible use of Ag(OH)4(-) for the treatment of these and other refractory compounds is assessed. Such dyes were selected due to their common occurrence, stability, refractory nature, the relatively high toxicity of Rh6G, and their structural similarity to Fl. Several reaction intermediates/products were identified...

Despite expressing high levels of Polycomb group proteins, embryonic stem cells (ESCs) are refractory to H3K27 trimethylation, notably at super-enhancers regulating key pluripotency genes. In this issue of Molecular Cell, Wang et al. (2017) report that the histone chaperone Spt6 prevents H3K27 trimethylation of key ESC super-enhancers.

BACKGROUND: Prior work has described 5 domains within the 22-item Sino-Nasal Outcomes Test (SNOT-22) that allow for stratification of symptoms into similar clusters and that can be used to direct therapy. Although the outcomes of various interventions on these symptom domains have been reported, minimal clinically important difference (MCID) values have not been investigated, which has limited clinical interpretation of these results. METHODS: This study was designed as a secondary analysis of a prospective, multi-institutional, observational cohort...

Pyridoxine dependent epilepsy (PDE) is caused by likely pathogenic variants in ALDH7A1 (PDE-ALDH7A1) and inherited autosomal recessively. Neurotoxic alpha-amino adipic semialdehyde (alpha-AASA), piperideine 6-carboxylate and pipecolic acid accumulate in body fluids. Neonatal or infantile onset seizures refractory to anti-epileptic medications are clinical features. Treatment with pyridoxine, arginine and lysine-restricted diet does not normalize neurodevelopmental outcome or accumulation of neurotoxic metabolites...

The ketogenic diet (KD) is increasingly used to treat epilepsy refractory to antiepileptic drugs and other neurological disorders. In animal models, the KD was found to increase the threshold to seizures induced by different convulsive stimulations. However, in models in which suprathreshold stimuli were used, a paradoxical seizure worsening was consistently observed in KD-fed animals. To better define this phenomenon, we characterized the electrographic response to seizures induced in mice which were treated with the KD, and then corneally stimulated at 6-Hz in four different sessions...

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a chronic debilitating psychiatric disorder, with significant proportion of patients failing to respond with current first-line treatments. The present study assesses the safety and effectiveness of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over left-orbitofrontal cortex (Lt-OFC) as a potential augmentation strategy in treatment of patients with medication-refractory OCD in real-world clinical setting. The present report also aims to examine the factors affecting response to rTMS and the durability of effects produced by rTMS over 1 month of follow-up period...

Type II diabetes mellitus (T2DM) is the prevalent type of diabetes, including 90% of the cases world-wide. Helicobacter pylori plays a pathogenic role in the development of T2DM. The host genetic factors have a significant impact on the clinical outcome and anatomical distribution of H. pylori infection and polymorphisms in several genes such as tumor necrotic factor (TNF)-α and mannose-binding lectin (MBL) and are considered to increase the risk for the development of T2DM. In this study, we investigate the prevalence rate of H...

Amnestic syndromes are acknowledged to be associated to bilateral hippocampal damage. We briefly report the case of a young man who underwent anterior left temporal lobectomy for a medically refractory temporal lobe epilepsy due to hippocampal sclerosis with an excellent seizure and neuropsychological outcome. Approximately 10 years later, he presented with a subacute severe global amnesia and MRI findings of a damage involving the contralateral mesial temporal lobe structures. A diagnosis of a possible autoimmune encephalitis was made...

Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is a subtype of non-Hodgkin lymphoma with a poor prognosis. Although first-line treatments for patients with localized ENKTL have been established, there is no gold standard treatment for patients with advanced ENKTL and refractory and/or relapsed disease. Anti-CD30 antibody-based therapy, including brentuximab vedotin (BV), has been shown to target malignant lymphomas with CD30 expression. In particular, this therapeutic agent has recently been suggested to be effective for Hodgkin lymphoma and mature T-cell lymphoma...

BACKGROUND: Faecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown. AIMS: To establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success...

PURPOSE: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, has been described following treatment of acute lymphoblastic leukemia (ALL) with the anti-metabolite 6-thioguanine (6-TG). Previous studies incorporating daily 6-TG into maintenance chemotherapy demonstrated a high incidence of SOS, typically presenting after prolonged exposures to 6-TG. 6-TG continues to be used as a single, 14-day burst during intensification; however, SOS associated with brief courses of 6-TG is poorly described...

Hodgkin lymphoma (HL) is curable in 70-80% of patients with first-line therapy. However, relapses occur in a minority of patients with favorable early stage disease and are more frequent in patients with advanced HL. Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) for patients with chemotherapy-sensitive disease is a standard treatment sequence for relapsed or refractory (rel/ref) HL. Patients who achieve complete response prior to ASCT have better survival outcomes...

β-Ti alloys have low elastic modulus, good specific strength and high corrosion resistance for biomaterial applications. Noble elements, such as Nb, Ta and Mo, are used to obtain β-Ti due to their chemical biocompatibility. However, due to their refractory nature, β-Ti requires specific processing routes. Powder metallurgy (P/M) allows for the development of new β-Ti alloys with decreasing costs, but dealing with high-elemental-content alloys can lead to a lack of diffusion and grain growth. One method to refine the structure and improve mechanical properties is a severe plastic deformation technique through high-pressure torsion (HPT)...

The effects of background noise on speech-evoked cortical auditory evoked potentials (CAEPs) can provide insight into the physiology of the auditory system. The purpose of this study was to determine background noise effects on neural coding of different phonemes within a syllable. CAEPs were recorded from 15 young normal-hearing adults in response to speech signals /s/, /ɑ/, and /sɑ/. Signals were presented at varying signal-to-noise ratios (SNRs). The effects of SNR and context (in isolation or within syllable) were analyzed for both phonemes...

Imatinib has clinical activity in chronic graft-versus-host disease (cGvHD), a significant complication of allogeneic hematopoietic cell transplant. Nilotinib is a tyrosine kinase inhibitor that targets the same receptors as imatinib but with different affinities. We tested the hypothesis that nilotinib is safe and has clinical activity in cGvHD. 33 participants were enrolled in a phase 1/2 dose escalation and dose extension clinical trial of nilotinib for the treatment of steroid refractory or dependent cGvHD (ClinicalTrials...

OBJECTIVE: Recent data published on biological therapy in axial spondyloarthritis (axSpA) since the last publication of the recommendations of the Spanish Society of Rheumatology (SER) has led to the generation of a review of these recommendations based on the best possible evidence. These recommendations should be a reference for rheumatologists and those involved in the treatment of patients with axSpA. METHODS: Recommendations were drawn up following a nominal group methodology and based on systematic reviews...

It is challenging to understand mechanisms of drug resistance in Mycobacterium tuberculosis (MTB) due to the large variability in resistance associated genes. Efflux pump genes contribute to drug resistance and thus add to this complexity. Efflux pump gene protein superfamilies have been characterized by genome analysis of drug resistant strains and through in vitro transcriptional studies. However, there is limited information regarding efflux pump genes in extensively drug resistant (XDR) tuberculosis (TB) isolates...

Chimeric Antigen Receptor (CAR) T cells that have been engineered to target CD19 have shown great promise in patients with relapsed and refractory B cell acute lymphocytic leukemia with remission rates of 70-90%. Some remissions have successfully bridged patients to a curable allogeneic stem cell transplant, some responses have been durable without further treatment, and some patients have achieved durable remissions for relapsed ALL after allogeneic stem cell transplant. Cytokine release syndrome, correlating with the in vivo activation and expansion of T cells, and neurologic toxicity are the most significant side effects and approaches to better understand and manage these events are the subject of ongoing clinical trials...

Despite significant improvements in outcome of newly diagnosed B-precursor ALL, the results in relapsed or refractory adult ALL are overall poor. Large retrospective studies revealed significant differences in terms of outcome, with particularly poor response rates in early or refractory relapses, whereas late relapses usually respond very well to repeated standard induction. Particularly new immunotherapy compounds like the CD19 bispecific antibody Blinatumomab and the conjugated CD22 antibody Inotuzumab yielded promising response rates compared to standard therapies in randomised trials...

Older adults with Philadelphia chromosome negative (Ph-),-B-cell acute lymphoblastic leukemia (ALL) have the highest rates of treatment failure and treatment complications with current therapy, and, thus, there is no standard treatment for these patients. Approximately 16 percent of patients with newly diagnosed Ph- B-cell ALL are aged 60 years or older [1]. The five-year overall survival for this older cohort of patients is approximately 20 percent, and there has been no improvement in their survival in decades [2]...