1,2-Diaza-1,3-butadienes: just a nice class of compounds, or powerful tools in organic chemistry? Reviewing an experience

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Injection therapy in hip osteoarthritis: one year in review

Hip osteoarthritis affects a substantial and growing number of people worldwide. Its incidence and prevalence are increasing due to ageing and obesity. It is estimated that it affects between 10 and 18% of individuals over 60 years of age and up to 1 in 3 patients over the age of 85 with a substantial proportion of them experiencing persistent pain, loss of function and decline in health-related quality of life. Our work was aimed at updating the latest data on this field. We searched the following terms on PubMed: 'injection therapy', 'osteoarthritis' and 'hip'. We limited our search to the period from 1-1-2018 until 22-6-2019 and to the English language. We retrieved 31 works. We decided to divide the works into three groups: hyaluronic acid in hip OA, other therapies in hip OA and emerging radiological techniques to measure the efficacy of injection therapy. So far, in the literature there is no solid evidence that supports the efficacy of intra-articular infiltration therapies in hip osteoarthritis. The international guidelines reflect this lack of solid scientific evidence. We believe that only original works that show high-level evidence can highlight the benefits of these therapies

A Novel Solvent-free Approach to Imidazole containing Nitrogen-Bridgehead Heterocycles

A very simple domino reaction under solvent free conditions of various piridine-like heterocycles with 1,2-diaza-1,3-dienes produces in good yields imidazo[1,2-a]pyridines, imidazo[1,2-a]quinolines and imidazo[2,1-a]isoquinolines. The advantage of this one-pot transformation lies in the use of simple pyridine-like compounds without pre-functionalization of the starting heterocycles

Characterization of hematite nanowire arrays synthesized by atmospheric plasma.

Hematite synthesized by low pressure oxygen plasma has been shown previously to exhibit promising characteristics as a photo-anode for a photoelectrochemical water splitting cell. It is cheap, stable and has a 2.1 eV bandgap and exhibits a significant photoactivity due to the presence of a thin interfacial layer and oxygen vacancy planes throughout the sample. Unfortunately, due to the nature of vacuum systems, this process would be difficult to scale-up and as such atmospheric plasma synthesis was explored. Photoactive hematite nanowire arrays were synthesized using an atmospheric microwave plasma jet reactor. They exhibited all of the characteristics of those synthesized under low pressure except for poor photoactivity due to a thin amorphous oxide layer on the surface layer. This oxide layer was removed by hydrofluoric acid etching and subsequently produced a significant photoactivity. Further synthesis improvements have yielded hematite nanowire arrays with no amorphous oxide layer present. Removal of nanowires from the nanowire array decreased the subsequent photoactivity of the electrode, indicating that photoactivity is due to the nanowires present on the sample and not due to the thin interfacial layer. Testing at different light intensities under constant voltage shows that photoactivity of hematite nanowire arrays is linearly dependent on light intensity

Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study

We aimed to identify clinical predictors of long-term response to abiraterone (defined as >12 months drug exposure) in a retrospective cohort of metastatic castration-resistant prostate cancer patients treated in post-docetaxel setting at 24 Italian centers. The Cox proportional hazards model was used to analyze the association between clinical features and the duration of drug exposure. Results were expressed as hazard ratios (HR) with associated 95% confidence intervals (CI). A total of 143 patients met the inclusion criteria. Their median age was 73 years, median Gleason score 8 and median abiraterone exposure 20 months. At the univariate analysis, a significant correlation with the duration of abiraterone exposure was found for Gleason score (HR 0.82, 95% CI 0.71-0.96; p=0.012), PSA (HR 1.10, 95% CI 1.03-1.18; p=0.08) and lactic dehydrogenase levels (HR 1.22, 95% CI 1.02-1.46; p=0.027), while the association between lower alkaline phosphatase levels and treatment duration was marginally significant (HR 1.07, 95% CI 0.99-1.16; p=0.074). Only PSA and Gleason score were predictive of long-term treatment duration in the multivariate analysis. No other clinical factors resulted to be predictive of sustained response to abiraterone, including metastatic disease at diagnosis and visceral disease, suggesting that all subgroups of patients may derive a substantial clinical benefit from abiraterone treatment. These findings need to be validated in prospective, larger studies

Diagnóstico de la producción de plantas forestales en los viveros de la Municipalidad de Guatemala; evaluación del enraizamiento de matilisguate (Tabebuia rosea bertol) y servicios realizados en el Vivero Municipal Acatán, Zona 16, Ciudad De Guatemala, Guatemala, C.A.

El presente trabajo de investigación se orientó hacia la producción de plantas forestales de los viveros de la Municipalidad de Guatemala, referente a distintos criterios de selección del material al momento de plantarse en campo, así como principales modos de propagación que se utilizan en los viveros para abastecer a los distintos proyectos de jardinización y arborización urbana. Mediante el diagnóstico se puedo conoce la situación actual de los sistemas de producción de plantas forestales en los viveros, se determinaron las principales características de las especies forestales que se utilizan para arborización urbana, jardinización, criterios de selección y modos de propagación, encontrándose como principal medio de propagación la semilla y no otras alternativas que agilicen la obtención masal de plántulas de mayor tamaño en el menor tiempo posible. La investigación se dirigió a establecer el un método alternativo para la propagación vegetativa de una especie ampliamente utilizada para arborización urbana: Tabebuia rosea bertol. Se evaluó la respuesta al enraizamiento en vástago, en función de tres concentraciones del ácido Indol3Butírico y tres diámetros de estaca, en plantas en fase de vivero con material juvenil para propagar. La investigación tuvo una duración de 4 meses. El estudio se realizó en el Huerto y Vivero Urbano Municipal Acatán zona 16, ciudad de Guatemala. El resultado de la investigación, demostró que existe respuesta a la propagación vegetativa por la especie bajo estudio, la respuesta fue mayor para el caso de propagación por vástago de 2.5cm. de diámetro y 2500ppm del regulador. Los resultados se midieron en presencia de callo, de raíces, y de brotes; además, peso seco de raíces, altura de la planta. Este resultado es de importancia ya que permite obtener plantas de matilisguate de mayor tamaño en menos tiempo y esto se vería reflejado en el arbolado urbano

Salivary Gland Ultrasonography in Sjögren’s Syndrome: A European Multicenter Reliability Exercise for the HarmonicSS Project

Objectives: Salivary gland ultrasonography (SGUS) is increasingly applied for the management of primary Sjögren's syndrome (pSS). This study aims to: (i) compare the reliability between two SGUS scores; (ii) test the reliability among sonographers with different levels of experience. Methods: In the reliability exercise, two four-grade semi-quantitative SGUS scoring systems, namely De Vita et al. and OMERACT, were tested. The sonographers involved in work-package 7 of the HarmonicSS project from nine countries in Europe were invited to participate. Different levels of sonographers were identified on the basis of their SGUS experience and of the knowledge of the tested scores. A dedicated atlas was used as support for SGUS scoring. Results: Twenty sonographers participated in the two rounds of the reliability exercise. The intra-rater reliability for both scores was almost perfect, with a Light's kappa of 0.86 for the De Vita et al. score and 0.87 for the OMERACT score. The inter-rater reliability for the De Vita et al. and the OMERACT score was substantial with Light's Kappa of 0.75 and 0.77, respectively. Furthermore, no significant difference was noticed among sonographers with different levels of experience. Conclusion: The two tested SGUS scores are reliable for the evaluation of major salivary glands in pSS, and even less-expert sonographers could be reliable if adequately instructed.publishedVersio

The Geriatric G8 Score Is Associated with Survival Outcomes in Older Patients with Advanced Prostate Cancer in the ADHERE Prospective Study of the Meet-URO Network

Introduction: Androgen receptor pathway inhibitors (ARPIs) have been increasingly offered to older patients with prostate cancer (PC). However, prognostic factors relevant to their outcome with ARPIs are still little investigated. Methods and Materials: The Meet-URO network ADHERE was a prospective multicentre observational cohort study evaluating and monitoring adherence to ARPIs metastatic castrate-resistant PC (mCRPC) patients aged ≥70. Cox regression univariable and multivariable analyses for radiographic progression-free (rPFS) and overall survival (OS) were performed. Unsupervised median values and literature-based thresholds where available were used as cut-offs for quantitative variables. Results: Overall, 234 patients were enrolled with a median age of 78 years (73–82); 86 were treated with abiraterone (ABI) and 148 with enzalutamide (ENZ). With a median follow-up of 15.4 months (mo.), the median rPFS was 26.0 mo. (95% CI, 22.8–29.3) and OS 48.8 mo. (95% CI, 36.8–60.8). At the MVA, independent prognostic factors for both worse rPFS and OS were Geriatric G8 assessment ≤ 14 (p < 0.001 and p = 0.004) and PSA decline ≥50% (p < 0.001 for both); time to castration resistance ≥ 31 mo. and setting of treatment (i.e., post-ABI/ENZ) for rPFS only (p < 0.001 and p = 0.01, respectively); age ≥78 years for OS only (p = 0.008). Conclusions: Baseline G8 screening is recommended for mCRPC patients aged ≥70 to optimise ARPIs in vulnerable individuals, including early introduction of palliative care

The KCNQ1OT1 imprinting control region and non-coding RNA: new properties derived from the study of Beckwith–Wiedemann syndrome and Silver–Russell syndrome cases

A cluster of imprinted genes at chromosome 11p15.5 is associated with the growth disorders, Silver–Russell syndrome (SRS) and Beckwith–Wiedemann syndrome (BWS). The cluster is divided into two domains with independent imprinting control regions (ICRs). We describe two maternal 11p15.5 microduplications with contrasting phenotypes. The first is an inverted and in cis duplication of the entire 11p15.5 cluster associated with the maintenance of genomic imprinting and with the SRS phenotype. The second is a 160 kb duplication also inverted and in cis, but resulting in the imprinting alteration of the centromeric domain. It includes the centromeric ICR (ICR2) and the most 5′ 20 kb of the non-coding KCNQ1OT1 gene. Its maternal transmission is associated with ICR2 hypomethylation and the BWS phenotype. By excluding epigenetic mosaicism, cell clones analysis indicated that the two closely located ICR2 sequences resulting from the 160 kb duplication carried discordant DNA methylation on the maternal chromosome and supported the hypothesis that the ICR2 sequence is not sufficient for establishing imprinted methylation and some other property, possibly orientation-dependent, is needed. Furthermore, the 1.2 Mb duplication demonstrated that all features are present for correct imprinting at ICR2 when this is duplicated and inverted within the entire cluster. In the individuals maternally inheriting the 160 kb duplication, ICR2 hypomethylation led to the expression of a truncated KCNQ1OT1 transcript and to down-regulation of CDKN1C. We demonstrated by chromatin RNA immunopurification that the KCNQ1OT1 RNA interacts with chromatin through its most 5′ 20 kb sequence, providing a mechanism likely mediating the silencing activity of this long non-coding RNA

The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: a sub-analysis of the Meet-URO 15 study

Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era