Low-cost and effective fabrication of biocompatible nanofibers from silk and cellulose-rich materials

Here, we show the production of nanofibrous mats with controlled mechanical properties and excellent biocompatibility by combining fibroin with pure cellulose and cellulose-rich parsley powder agro-waste. To this end, trifluoroacetic acid was used as a common solvent for all of the involved biomaterials, achieving highly homogeneous blends that were suitable for the electrospinning technique. Morphological analysis revealed that the electrospun composite nanofibers were well-defined and defect-free, with a diameter in the range of 65–100 nm. Mechanical investigations demonstrated that the fibrous mats exhibited an increased stiffness when pure fibroin was combined with cellulose, whereas they possessed an increased flexibility when the parsley waste was added to fibroin. Lastly, the produced mats were highly biocompatible, as demonstrated by the promoted proliferation of fibroblast cells. The characteristics of the hybrid fibroin–cellulose nanofibers, in terms of nanoscale topography, mechanical propertie..

IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

Self-consumption of electricity produced with photovoltaic systems in apartment buildings - Update of the situation in various IEA PVPS countries

Over the last two decades, grid-connected solar photovoltaic systems have increased from a niche market to one of the leading power generation capacity additions annually. In 2019 the total worldwide installed photovoltaic electricity generation capacity exceeded 630 GW. It is forecasted that 1 TW will be reached by 2022. This further development is coupled with the question at what prices solar photovoltaic electricity can be provided and delivered to the customers. The installation of PV systems for self-consumption is already now an interesting option for many people but in general limited to those who have access to a rooftop they own or can use. Enabling residents of multi apartment buildings to commonly use electricity generated by a PV system (collective self-consumption) is a relatively new development and is still facing a lot of administrative and regulatory challenges. This paper provides an overview of existing regulatory schemes in IEA PVPS countries and presents and analysis of two self-consumption case studies.</p

Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner

Hematopoietic stem cells (HSCs) residing in specialized niches in the bone marrow are responsible for the balanced output of multiple short-lived blood cell lineages in steady-state and in response to different challenges. However, feedback mechanisms by which HSCs, through their niches, sense acute losses of specific blood cell lineages remain to be established. While all HSCs replenish platelets, previous studies have shown that a large fraction of HSCs are molecularly primed for the megakaryocyte-platelet lineage and are rapidly recruited into proliferation upon platelet depletion. Platelets normally turnover in an activation-dependent manner, herein mimicked by antibodies inducing platelet activation and depletion. Antibody-mediated platelet activation upregulates expression of Interleukin-1 (IL-1) in platelets, and in bone marrow extracellular fluid in vivo. Genetic experiments demonstrate that rather than IL-1 directly activating HSCs, activation of bone marrow Lepr+ perivascular niche cells expressing IL-1 receptor is critical for the optimal activation of quiescent HSCs upon platelet activation and depletion. These findings identify a feedback mechanism by which activation-induced depletion of a mature blood cell lineage leads to a niche-dependent activation of HSCs to reinstate its homeostasis

Intratumoral pan-ErbB targeted CAR-T for head and neck squamous cell carcinoma: interim analysis of the T4 immunotherapy study

Background: Locally advanced/recurrent head and neck squamous cell carcinoma (HNSCC) is associated with significant morbidity and mortality. To target upregulated ErbB dimer expression in this cancer, we developed an autologous CD28-based chimeric antigen receptor T-cell (CAR-T) approach named T4 immunotherapy. Patient-derived T-cells are engineered by retroviral transduction to coexpress a panErbB-specific CAR called T1E28ζ and an IL-4-responsive chimeric cytokine receptor, 4αβ, which allows IL-4-mediated enrichment of transduced cells during manufacture. These cells elicit preclinical antitumor activity against HNSCC and other carcinomas. In this trial, we used intratumoral delivery to mitigate significant clinical risk of on-target off-tumor toxicity owing to low-level ErbB expression in healthy tissues. // Methods: We undertook a phase 1 dose-escalation 3+3 trial of intratumoral T4 immunotherapy in HNSCC (NCT01818323). CAR T-cell batches were manufactured from 40 to 130 mL of whole blood using a 2-week semiclosed process. A single CAR T-cell treatment, formulated as a fresh product in 1–4 mL of medium, was injected into one or more target lesions. Dose of CAR T-cells was escalated in 5 cohorts from 1×107−1×109 T4+ T-cells, administered without prior lymphodepletion. // Results: Despite baseline lymphopenia in most enrolled subjects, the target cell dose was successfully manufactured in all cases, yielding up to 7.5 billion T-cells (67.5±11.8% transduced), without any batch failures. Treatment-related adverse events were all grade 2 or less, with no dose-limiting toxicities (Common Terminology Criteria for Adverse Events V.4.0). Frequent treatment-related adverse events were tumor swelling, pain, pyrexias, chills, and fatigue. There was no evidence of leakage of T4+ T-cells into the circulation following intratumoral delivery, and injection of radiolabeled cells demonstrated intratumoral persistence. Despite rapid progression at trial entry, stabilization of disease (Response Evaluation Criteria in Solid Tumors V.1.1) was observed in 9 of 15 subjects (60%) at 6 weeks post-CAR T-cell administration. Subsequent treatment with pembrolizumab and T-VEC oncolytic virus achieved a rapid complete clinical response in one subject, which was durable for over 3 years. Median overall survival was greater than for historical controls. Disease stabilization was associated with the administration of an immunophenotypically fitter, less exhausted, T4 CAR T-cell product. // Conclusions: These data demonstrate the safe intratumoral administration of T4 immunotherapy in advanced HNSCC

Zinc Polyaleuritate Ionomer Coatings as a Sustainable, Alternative Technology for Bisphenol A-Free Metal Packaging

Sustainable coatings for metal food packaging were prepared from ZnO nanoparticles (obtained by the thermal decomposition of zinc acetate) and a naturally occurring polyhydroxylated fatty acid named aleuritic (or 9,10,16-trihydroxyhexadecanoic) acid. Both components reacted, originating under specific conditions zinc polyaleuritate ionomers. The polymerization of aleuritic acid into polyaleuritate by a solvent-free, melt polycondensation reaction was investigated at different times (15, 30, 45, and 60 min), temperatures (140, 160, 180, and 200 °C), and proportions of zinc oxide and aleuritic acid (0:100, 5:95, 10:90, and 50:50, w/w). Kinetic rate constants calculated by infrared spectroscopy decreased with the amount of Zn due to the consumption of reactive carboxyl groups, while the activation energy of the polymerization decreased as a consequence of the catalyst effect of the metal. The adhesion and hardness of coatings were determined from scratch tests, obtaining values similar to robust polymers with high adherence. Water contact angles were typical of hydrophobic materials with values ≥94°. Both mechanical properties and wettability were better than those of bisphenol A (BPA)-based resins and most likely are related to the low migration values determined using a hydrophilic food simulant. The presence of zinc provided a certain degree of antibacterial properties. The performance of the coatings against corrosion was studied by electrochemical impedance spectroscopy at different immersion times in an aqueous solution of NaCl. Considering the features of these biobased lacquers, they can be potential materials for bisphenol A-free metal packagingPeer reviewe

O DESEMPENHO DA MARCHA DE HEMIPARÉTICOS CRÔNICOS E A CORRELAÇÃO COM A RECUPERAÇÃO E O NÍVEL DE COMPROMETIMENTO MOTOR FUNCIONAL

As a result of stroke, impairments such as hemiparesis, gait deficits, impaired motor function and physical deconditioning can occur. In which, gait is one of the most important functional limitations and this way the evaluation becomes important to determine the functional profile and consequently to develop an appropriate treatment. The objective of this study was to evaluate and correlate functional capacity with the level of motor and functional impairment in chronic hemiparetic. This is a cross-sectional study using the Six-Minute Walking Test (6MWT) to assess functional capacity and the Fugl Meyer Protocol (FM) to assess the level of motor and functional impairment. Twelve hemiparetic subjects were included. Statistical analysis revealed no significant correlation between the 6MWT and FM. We conclude that the present study revealed a non-correlation between functional capacity and motor impairment in chronic hemiparetic.Em decorrência ao Acidente Vascular Cerebral (AVC) podem ocorrer comprometimentos como hemiparesia, marcha deficitária, alteração na função motora e descondicionamento físico. No qual, a marcha é uma das limitações funcionais de maior destaque e desta forma a sua avaliação torna-se importante para determinar o perfil funcional e consequentemente elaborar um tratamento adequado. O objetivo deste estudo foi avaliar e correlacionar a capacidade funcional com o nível de comprometimento motor e funcional de hemiparéticos crônicos. Trata-se de um estudo transversal que utilizou o Teste de Caminhada de seis minutos (TC6) para avaliar a capacidade funcional e o Protocolo de Fugl Meyer (FM) para avaliar o nível de comprometimento motor e funcional. Participaram do estudo 12 hemiparéticos. A análise estatística não revelou correlação significante entre o TC6 e o FM. Concluímos que o presente estudo revelou a não correlação entre a capacidade funcional e o comprometimento motor de hemiparéticos crônicos

A WIC-Based Curriculum to Enhance Parent Communication with Healthcare Providers

The objectives describe a curriculum to support parent-provider communication about child development, and to demonstrate its impact and effectiveness when delivered by staff from the Special Supplemental Nutrition Program for Women, Infants and Children (WIC). A curriculum was developed by a university-WIC partnership for a WIC center-based health education class to teach parents about child development and how to talk to their child's doctor about development. During a 90-min training session, university pediatricians used this curriculum and trained WIC paraprofessionals to conduct a 20-30&nbsp;min center-based education session. WIC paraprofessionals completed an on-line survey to obtain their demographic characteristics, and their attitudes and perceptions about the training sessions and their experiences teaching the center-based health education session to parents. Approximately 500 WIC paraprofessionals received the 90-min training session across 60 centers in the Public Health Foundation Enterprises WIC Program in Southern California. About 250 WIC paraprofessionals completed the on-line survey and over 80&nbsp;% of WIC staff reported that they had learned new information about child development as a result of the training, and 87&nbsp;% of the WIC staff reported that the training was sufficient to feel comfortable teaching the class content to parents. We demonstrated the ability to build WIC paraprofessional capacity to promote parental participation in child developmental surveillance and communication with their child's doctor. With appropriate training, WIC staff are interested in supporting population-based efforts to improve parent-physician communication about child development that can complement WIC's existing maternal and child health topics