Microphase separation of highly amphiphilic, low N polymers by photoinduced copper-mediated polymerization, achieving sub-2 nm domains at half-pitch

The lower limit of domain size resolution using microphase separation of short poly(acrylic acid) homopolymers equipped with a short fluorinated tail, posing as an antagonist 'A block' in pseudo AB block copolymers has been investigated. An alkyl halide initiator with a fluorocarbon chain was utilized as a first 'A block' in the synthesis of low molecular weight polymers (1400-4300 g mol -1) using photoinduced Cu(ii)-mediated polymerization allowing for very narrow dispersity. Poly(tert-butyl acrylate) was synthesized and subsequently deprotected to give very low degrees of polymerization (N), amphiphilic polymers with low dispersity (D = 1.06-1.13). By exploiting the high driving force for demixing and the well-defined 'block' sizes, we are able to control the nanostructure in terms of domain size (down to 3.4 nm full-pitch) and morphology. This work demonstrates the simple and highly controlled synthesis of polymers to push the boundaries of the smallest achievable domain sizes obtained from polymer self-assembly

Stem cell modeling of nervous system tumors

Nervous system tumors, particularly brain tumors, represent the most common tumors in children and one of the most lethal tumors in adults. Despite decades of research, there are few effective therapies for these cancers. Although human nervous system tumor cells and genetically engineered mouse models have served as excellent platforms for drug discovery and preclinical testing, they have limitations with respect to accurately recapitulating important aspects of the pathobiology of spontaneously arising human tumors. For this reason, attention has turned to the deployment of human stem cell engineering involving human embryonic or induced pluripotent stem cells, in which genetic alterations associated with nervous system cancers can be introduced. These stem cells can be used to create self-assembling three-dimensional cerebral organoids that preserve key features of the developing human brain. Moreover, stem cell-engineered lines are amenable to xenotransplantation into mice as a platform to investigate the tumor cell of origin, discover cancer evolutionary trajectories and identify therapeutic vulnerabilities. In this article, we review the current state of human stem cell models of nervous system tumors, discuss their advantages and disadvantages, and provide consensus recommendations for future research

Patient-derived iPSC-cerebral organoid modeling of the 17q11.2 microdeletion syndrome establishes CRLF3 as a critical regulator of neurogenesis

Neurodevelopmental disorders are often caused by chromosomal microdeletions comprising numerous contiguous genes. A subset of neurofibromatosis type 1 (NF1) patients with severe developmental delays and intellectual disability harbors such a microdeletion event on chromosome 17q11.2, involving the NF1 gene and flanking regions (NF1 total gene deletion [NF1-TGD]). Using patient-derived human induced pluripotent stem cell (hiPSC)-forebrain cerebral organoids (hCOs), we identify both neural stem cell (NSC) proliferation and neuronal maturation abnormalities in NF1-TGD hCOs. While increased NSC proliferation results from decreased NF1/RAS regulation, the neuronal differentiation, survival, and maturation defects are caused by reduced cytokine receptor-like factor 3 (CRLF3) expression and impaired RhoA signaling. Furthermore, we demonstrate a higher autistic trait burden in NF1 patients harboring a deleterious germline mutation in the CRLF3 gene (c.1166T\u3eC, p.Leu389Pro). Collectively, these findings identify a causative gene within the NF1-TGD locus responsible for hCO neuronal abnormalities and autism in children with NF1

Absolut “copper catalyzation perfected”; robust living polymerization of NIPAM : Guinness is good for SET-LRP

The controlled polymerization of N-isopropyl acrylamide (NIPAM) is reported in a range of international beers, wine, ciders and spirits utilizing Cu(0)-mediated living radical polymerization (SET-LRP). Highly active Cu(0) is first formed in situ by the rapid disproportionation of [Cu(I)(Me6-Tren)Br] in the commercial water–alcohol mixtures. Rapid, yet highly controlled, radical polymerization follows (Đ values as low as 1.05) despite the numerous chemicals of diverse functionality present in these solvents e.g. alpha acids, sugars, phenols, terpenoids, flavonoids, tannins, metallo-complexes, anethole etc. The results herein demonstrate the robust nature of the aqueous SET-LRP protocol, underlining its ability to operate efficiently in a wide range of complex chemical environments

Five years of the #RSCPoster Twitter conference

The #RSCPoster Twitter conference is an annual, 24 hour poster conference held each March on Twitter. This original conference format has enabled hundreds of participants to share their research, with 32 million measurable impressions of #RSCPoster in 2020, participation growing each year and inspiring new conferences. Here, we will give a brief outline of the history, technicalities and content of the event

The socioeconomic burden of chronic lung disease in low-resource settings across the globe - an observational FRESH AIR study

BACKGROUND: Low-resource settings are disproportionally burdened by chronic lung disease due to early childhood disadvantages and indoor/outdoor air pollution. However, data on the socioeconomic impact of respiratory diseases in these settings are largely lacking. Therefore, we aimed to estimate the chronic lung disease-related socioeconomic burden in diverse low-resource settings across the globe. To inform governmental and health policy, we focused on work productivity and activity impairment and its modifiable clinical and environmental risk factors. METHODS: We performed a cross-sectional, observational FRESH AIR study in Uganda, Vietnam, Kyrgyzstan, and Greece. We assessed the chronic lung disease-related socioeconomic burden using validated questionnaires among spirometry-diagnosed COPD and/or asthma patients (total N = 1040). Predictors for a higher burden were studied using multivariable linear regression models including demographics (e.g. age, gender), health parameters (breathlessness, comorbidities), and risk factors for chronic lung disease (smoking, solid fuel use). We applied identical models per country, which we subsequently meta-analyzed. RESULTS: Employed patients reported a median [IQR] overall work impairment due to chronic lung disease of 30% [1.8-51.7] and decreased productivity (presenteeism) of 20.0% [0.0-40.0]. Remarkably, work time missed (absenteeism) was 0.0% [0.0-16.7]. The total population reported 40.0% [20.0-60.0] impairment in daily activities. Breathlessness severity (MRC-scale) (B = 8.92, 95%CI = 7.47-10.36), smoking (B = 5.97, 95%CI = 1.73-10.22), and solid fuel use (B = 3.94, 95%CI = 0.56-7.31) were potentially modifiable risk factors for impairment. CONCLUSIONS: In low-resource settings, chronic lung disease-related absenteeism is relatively low compared to the substantial presenteeism and activity impairment. Possibly, given the lack of social security systems, relatively few people take days off work at the expense of decreased productivity. Breathlessness (MRC-score), smoking, and solid fuel use are potentially modifiable predictors for higher impairment. Results warrant increased awareness, preventive actions and clinical management of lung diseases in low-resource settings from health policymakers and healthcare workers

Household air pollution and respiratory health in rural Crete, Greece: a cross-sectional FRESH AIR study

Breathing polluted air is a risk to respiratory conditions. During the Greek financial crisis, the use of household fireplaces/wood stoves shifted from mostly decorative to actual domestic heating, resulting in increased indoor smoke production. We aimed to evaluate household air pollution (HAP), fuel use and respiratory symptoms in rural Crete, Greece. PM2.5 and CO were measured in 32 purposively selected rural households (cross-sectional study) at periods reflecting lesser (baseline) versus extensive (follow-up) heating. Clinical outcomes were assessed using questionnaires. Mean PM2.5 were not significantly different between measurements (36.34 mu g/m(3) vs. 54.38 mu g/m(3), p = 0.60) but exceeded the WHO air quality guidelines. Mean and maximal CO levels were below the WHO cut-offs (0.56 ppm vs. 0.34 ppm, p = 0.414 and 26.1 ppm vs. 9.72 ppm, p = 0.007, respectively). In total, 90.6% of households were using wood stoves or fireplaces for heating, but half also owned clean fuel devices. The differences between devices that were owned versus those that were used were attributed to financial reasons. In both cases, the most frequent respiratory symptoms were phlegm (27.3% vs. 15.2%; p = 0.34) and cough (24.2% vs. 12.1%; p = 0.22). Our findings demonstrate the magnitude of HAP and confirm the return to harmful practices during Greece's austerity. Upon validation, these results can support strategies for fighting fuel poverty, empowering communities and strengthening local health systems.Prevention, Population and Disease management (PrePoD)Public Health and primary car

Can integrated care help in meeting the challenges posed on our health care systems by COVID-19? Some preliminary lessons learned from the european VIGOUR project

The COVID-19 pandemic puts health and care systems under pressure globally. This current paper highlights challenges arising in the care for older and vulnerable populations in this context and reflects upon possible perspectives for different systems making use of nested integrated care approaches adapted during the work of the EU-funded project VIGOUR