An immortalised mesenchymal stem cell line maintains mechano-responsive behaviour and can be used as a reporter of substrate stiffness

The mechanical environment can influence cell behaviour, including changes to transcriptional and proteomic regulation, morphology and, in the case of stem cells, commitment to lineage. However, current tools for characterizing substrates’ mechanical properties, such as atomic force microscopy (AFM), often do not fully recapitulate the length and time scales over which cells ‘feel’ substrates. Here, we show that an immortalised, clonal line of human mesenchymal stem cells (MSCs) maintains the responsiveness to substrate mechanics observed in primary cells, and can be used as a reporter of stiffness. MSCs were cultured on soft and stiff polyacrylamide hydrogels. In both primary and immortalised MSCs, stiffer substrates promoted increased cell spreading, expression of lamin-A/C and translocation of mechano-sensitive proteins YAP1 and MKL1 to the nucleus. Stiffness was also found to regulate transcriptional markers of lineage. A GFP-YAP/RFP-H2B reporter construct was designed and virally delivered to the immortalised MSCs for in situ detection of substrate stiffness. MSCs with stable expression of the reporter showed GFP-YAP to be colocalised with nuclear RFP-H2B on stiff substrates, enabling development of a cellular reporter of substrate stiffness. This will facilitate mechanical characterisation of new materials developed for applications in tissue engineering and regenerative medicine

Caracterización y evaluación de los recursos naturales de la microcuenca cunyatupe

The microriver basin of Cunyatupe, located to the north of the city of Huaraz, in the department of Ancash-Peru; it presents/displays 5 zones of life, in addition to be within the White Mountain range of the Valley of Huaylas it has water in sufficient amount, to suitably maintain all the existing natural resources in this. With respect to the characterization of the microriver basin one was the following natural resources: Water, which it includes/understands a fluvial network that mainly has its origin in the different easts caused by the excessive erosion from cárcavas, Hidrobiológico where it was observed the presence of seaweed and worms like (Rhabditis Diplogasteroides, Dichotomosiphon, etc), Cattle dealer with bovine, ovine, equinos and pig greater cattles that is to say, Agricultural with the presence of cultivables species nutritional altoandinos like: barley, Pope, maize, wheat among others, fruit like: quince, apple, pacay and uvilla, Genetic or genetic aromatic like; Robust (Route graveolens), Ishmuna or muña (Minthostachys spp), etc, and genetic forages like: wild barley (Nassella Sp), Kikuyo (Pennisetum clandestinum), ichu (Stipa ichu), etc and finally, biological diversity with the presence of small lizards colilarga (Psammodromus algyrus), black picaflor (Metallura phoebe), among others inside d ela fauna and in addition species to flora lsecshi (cortaderia Sp), maguey (American Agave), ferns (Polistichium Sp), etc, Ecological where one took encuenta the zones from life among others, and finally the Forest resource where they honor the eucalyptus (Eucalyptus Sp), alder (Alnus Sp), pine (Pinus Sp), capulí (Serotina Prunus), quenual (Polylepis Sp), etc. In the evaluation of the natural resources of the microriver basin one was grounds by capacity of greater use of class I to the VIII, with problems due to badly the related handling of water to its contamination, due to the raising of cattles, and badly use of the irrigation water, that causes the erosion.ike: retama (spartium junceum),La microcuenca de Cunyatupe, ubicada al norte de la provincia de Huaraz, en el departamento de Ancash-Perú, presenta cinco zonas de vida. Además por hallarse dentro de la Cordillera Blanca del Callejón de Huaylas tiene agua en cantidad suficiente, para mantener adecuadamente todos los recursos naturales existentes en ella. Con respecto a la caracterización de la microcuenca, se encontraron los siguientes recursos naturales: Agua, que comprende una red fluvial que tiene su origen en las diferentes nacientes ocasionadas principalmente por la erosión excesiva de cárcavas, Hidrobiológico donde se observó la presencia de algas y gusanos como el Rhabditis diplogasteroides, Dichotomosiphon, etc., Ganadero con ganados mayores, es decir, vacunos, ovinos, equinos y porcinos, Agrícola con la presencia de especies cultivables alimenticias altoandinas como: cebada, papa, maíz, entre otros; frutales como: membrillo, manzana, pacae y uvilla, Genético, ya sea genéticos aromáticos como: ruda (Ruta graveolens), Ishmuna o muña (Minthostachys spp.), etc., y genéticos forrajes como: Kikuyo (Pennisetum clandestinum), ichu (Stipa ichu), etc., y finalmente, Diversidad biológica con la presencia de lagartijas colilarga (Psammodromus algyrus), picaflor negro (Metallura phoebe), entre otros, dentro de la fauna, y además especies de flora como: retama (Spartium junceum), secshi (Cortaderia Sp.), maguey (Agave americana), helechos (Polistichium Sp.), etc., Ecológico, donde se tomó en cuenta las zonas de vida, entre otros, y finalmente el recurso Forestal donde destacan el eucalipto (Eucalyptus Sp.), aliso (Alnus Sp.), pino (Pinus Sp.), capulí (Prunus serotina), quenual (Polylepis Sp.), etc. En la evaluación de los recursos naturales de la microcuenca, se encontraron suelos por capacidad de uso mayor de la clase II al VIII, con problemas debido al mal manejo de agua relacionados a su contaminación, debido a la crianza de ganados, y mal uso del agua de riego, que ocasiona la erosión

The SARS-CoV-2 Ivermectin Navarra-ISGlobal Trial (SAINT) to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission in low risk, non-severe COVID-19 patients in the first 48 hours after symptoms onset: A structured summary of a study protocol for a randomized control pilot trial

Objectives: The primary objective is to determine the efficacy of a single dose of ivermectin, administered to low risk, non-severe COVID-19 patients in the first 48 hours after symptom onset to reduce the proportion of patients with detectable SARS-CoV-2 RNA by Polymerase Chain Reaction (PCR) test from nasopharyngeal swab at day 7 post-treatment

Twenty questions about design behavior for sustainability, report of the International Expert Panel on behavioral science for design

How behavioral scientists, engineers, and architects can work together to advance how we all understand and practice design—in order to enhance sustainability in the built environment, and beyond.https://www.nature.com/documents/design_behavior_for_sustainability.pdfPublished versio

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial.

Background Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. Methods Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022. Findings All patients recruited completed the trial (median age, 26 [IQR 19-36 in the ivermectin and 21-44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77-1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001). Interpretation Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials. Funding ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra

Factors contributing to delays in diagnosis of breast cancers in Ghana, West Africa

BACKGROUND: Late diagnoses and poor prognoses of breast cancer are common throughout Africa. METHODS: To identify responsible factors, we utilized data from a population-based case-control study involving 1,184 women with breast malignancies conducted in three hospitals in Accra and Kumasi, Ghana. Interviews focused on potential breast cancer risk factors as well as factors that might contribute to presentation delays. We calculated odds ratios (OR) and 95% confidence intervals (CI) comparing malignances with biopsy masses larger than 5 cm. (62.4% of the 1,027 cases with measurable lesions) to smaller lesions. RESULTS: In multivariate analyses, strong predictors of larger masses were limited education (OR=1.96, 95% CI 1.32–2.90 <primary vs. ≥senior secondary school), being separated/divorced or widowed (1.75, 1.18–2.60 and 2.25, 1.43–3.55, respectively, vs. currently married), delay in care seeking after onset of symptoms (2.64, 1.77–3.95 for ≥12 vs. ≤2 months), care having initially been sought from someone other than a doctor/nurse (1.86, 0.85–4.09), and frequent use of herbal medications/treatment (1.51, 0.95–2.43 for ≥3x/day usage vs. none),. Particularly high risks associated with these factors were found among less educated women; for example, women with less than junior secondary schooling who delayed seeking care for breast symptoms for 6 months or longer were at nearly 4-times the risk of more educated women who promptly sought assistance. CONCLUSIONS: Our findings suggest that additional communication, particularly among less educated women, could promote earlier breast cancer diagnoses. Involvement of individuals other than medical practitioners, including traditional healers, may be helpful in this process

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease