Synthesis of novel structural hybrids between aza-heterocycles and azelaic acid moiety with a specific activity on osteosarcoma cells

Nine compounds bearing pyridinyl (or piperidinyl, benzimidazolyl, benzotriazolyl) groups bound to an azelayl moiety through an amide bond were synthesized. The structural analogy with some histone deacetylase inhibitors inspired their syntheses, seeking new selective histone deacetylase inhibitors (HDACi). The azelayl moiety recalls part of 9-hydroxystearic acid, a cellular lipid showing antiproliferative activity toward cancer cells with HDAC as a molecular target. Azelayl derivatives bound to a benzothiazolyl moiety further proved to be active as HDACi. The novel compounds were tested on a panel of both normal and tumor cell lines. Non-specific induction of cytotoxicity was observed in the normal cell line, while three of them induced a biological effect only on the osteosarcoma (U2OS) cell line. One of them induced a change in nuclear shape and size. Cell-cycle alterations are associated with post-transcriptional modification of both H2/H3 and H4 histones. In line with recent studies, revealing unexpected HDAC7 function in osteoclasts, molecular docking studies on the active molecules predicted their proneness to interact with HDAC7. By reducing side effects associated with the action of the first-generation inhibitors, the herein reported compounds, thus, sound promising as selective HDACi

Conductive photo-activated porphyrin-ZnO nanostructured gas sensor array

Chemoresistors working at room temperature are attractive for low-consumption integrated sensors. Previous studies show that this feature can be obtained with photoconductive porphyrins-coated ZnO nanostructures. Furthermore, variations of the porphyrin molecular structure alter both the chemical sensitivity and the photoconductivity, and can be used to define the sensor characteristics. Based on these assumptions, we investigated the properties of an array of four sensors made of a layer of ZnO nanoparticles coated with porphyrins with the same molecular framework but different metal atoms. The array was tested with five volatile organic compounds (VOCs), each measured at different concentrations. Results confirm that the features of individual porphyrins influence the sensor behavior, and the differences among sensors are enough to enable the discrimination of volatile compounds disregarding their concentration. © 2017 by the authors; Licensee MDPI, Basel, Switzerland

How pain affect real life of children and adults with achondroplasia: a systematic review

The clinical features of achondroplasia can cause acute self-limited pain that can develop into chronic pain. Pain causes a low quality of life, in terms of physical, emotional, social, and school functioning in both adult and children with achondroplasia. We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement to describe prevalence, assessment tools, causes and management strategies of pain in this rare disease. We found that shoulder and knee pain is typically referred during infancy, while knee pain is generally referred around 5-6 years of age. The prevalence of general pain in adolescence can be as high as 90%. Chronic pain in the achondroplasia population increases with age, with up to 70% of adults reporting general pain and back pain. Recognizing the multiple determinants of acute and chronic pain in patients with achondroplasia may enable physicians to better understand and manage this burden, particularly with the advent of new drugs that may modify some of the known features of achondroplasia

• ROTHSCHILD ET AL. Recent Trends in Optical Lithography Recent Trends in Optical Lithography

■ The fast-paced evolution of optical lithography has been a key enabler in the dramatic size reduction of semiconductor devices and circuits over the last three decades. Various methods have been devised to pattern at dimensions smaller than the wavelength used in the process. In addition, the patterning wavelength itself has been reduced and will continue to decrease in the future. As a result, it is expected that optical lithography will remain the technology of choice in lithography for at least another decade. Lincoln Laboratory has played a seminal role in the progress of optical lithography; it pioneered 193-nm lithography, which is used in advanced production, and 157-nm lithography, which is under active development. Lincoln Laboratory also initiated exploration of liquidimmersion lithography and studied the feasibility of 121-nm lithography. Many of the challenges related to practical implementation of short-wavelength optical lithography are materials-related, including engineering of new materials, improving on existing materials, and optimizing their photochemistry. This article examines the technical issues facing optical lithography and Lincoln Laboratory’s contributions toward their resolution. Optical lithography, the technology of patterning, has enabled semiconductor devices to progressively shrink since the inception of integrated circuits more than three decades ago. Throughout the 1980s and 1990s, the trend of miniaturization continued unabated and even accelerated. Current semiconductor devices are being mass produced with 130-nm dense features; by 2007 these devices will have 65-nm dense features. Optical lithography has been, and will remain for the foreseeable future, the critical technology that makes this trend possible. (To learn the fundamentals of optical lithography, see the sidebar entitled “Optical Lithograph

What to expect of feeding abilities and nutritional aspects in achondroplasia patients: a narrative review

Achondroplasia is an autosomal dominant genetic disease representing the most common form of human skeletal dysplasia: almost all individuals with achondroplasia have identifiable mutations in the fibroblast growth factor receptor type 3 (FGFR3) gene. The cardinal features of this condition and its inheritance have been well-established, but the occurrence of feeding and nutritional complications has received little prominence. In infancy, the presence of floppiness and neurological injury due to foramen magnum stenosis may impair the feeding function of a newborn with achondroplasia. Along with growth, the optimal development of feeding skills may be affected by variable interactions between midface hypoplasia, sleep apnea disturbance, and structural anomalies. Anterior open bite, prognathic mandible, retrognathic maxilla, and relative macroglossia may adversely impact masticatory and respiratory functions. Independence during mealtimes in achondroplasia is usually achieved later than peers. Early supervision of nutritional intake should proceed into adolescence and adulthood because of the increased risk of obesity and respiratory problems and their resulting sequelae. Due to the multisystem involvement, oral motor dysfunction, nutrition, and gastrointestinal issues require special attention and personalized management to facilitate optimal outcomes, especially because of the novel therapeutic options in achondroplasia, which could alter the progression of this rare disease