Lab-on-a-chip platforms based on highly sensitive nanophotonic Si biosensors for single nucleotide DNA testing

In order to solve the drawbacks of sensitivity and portability in optical biosensors we have developed ultrasensitive and miniaturized photonic silicon sensors able to be integrated in a "lab-on-a-chip" microsystem platform. The sensors are integrated Mach-Zehnder interferometers based on TIR optical waveguides (Si/SiO2/Si3N4) of micro/nanodimensions. We have applied this biosensor for DNA testing and for detection of single nucleotide polymorphisms at BRCA-1 gene, involved in breast cancer development, without target labeling. The oligonucleotide probe is immobilized by covalent attachment to the sensor surface through silanization procedures. The hybridization was performed for different DNA target concentrations showing a lowest detection limit at 10 pM. Additionally, we have detected the hybridization of different concentrations of DNA target with two mismatching bases corresponding to a mutation of the BRCA-1 gene. Following the way of the lab-on-a-chip microsystem, integration with the microfluidics has been achieved by using a novel fabrication method of 3-D embedded microchannels using the polymer SU-8 as structural material. The optofluidic chip shows good performances for biosensing

Evaluation of Textural and Sensory Properties on Typical Spanish Small Cakes Designed Using Alternative Flours

[EN] The objective of this study was to evaluate the effect of wheat flour substitution with toasted corn, quinoa, and sorghum flours on the overall perception and texture of typical Spanish small cakes named madeleine. In order to evaluate these characteristics, a texture profile analysis (TPA) and a sensory analysis were carried out. TPA showed that the replacement of wheat flour by sorghum flour did not affect significantly texture parameters of cakes. Hedonic sensory tests were also conducted revealing that the cake prepared with sorghum flour was highly appreciated by the consumers as it got scores similar to traditional cakes made with wheat flour.Casas Moreno, MDM.; Barreto Palacios, VJ.; González Carrascosa, R.; Iborra Bernad, MDC.; Andrés Bello, MD.; Martínez Monzó, J.; García-Segovia, P. (2015). Evaluation of Textural and Sensory Properties on Typical Spanish Small Cakes Designed Using Alternative Flours. Journal of Culinary Science and Technology. 13(1):19-28. doi:10.1080/15428052.2014.952475S1928131Baldwin, R. R., Baldry, R. P., & Johansen, R. G. (1972). Fat systems for bakery products. Journal of the American Oil Chemists’ Society, 49(8), 473-477. doi:10.1007/bf02582482Beleia, A., Miller, R. A., & Hoseney, R. C. (1996). Starch Gelatinization in Sugar Solutions. Starch - Starke, 48(7-8), 259-262. doi:10.1002/star.19960480705Brannan, G. L., Setser, C. S., Kemp, K. E., Seib, P. A., & Roozeboom, K. (2001). Sensory Characteristics of Grain Sorghum Hybrids with Potential for Use in Human Food. Cereal Chemistry Journal, 78(6), 693-700. doi:10.1094/cchem.2001.78.6.693Cauvain, S. P., & Young, L. S. (Eds.). (2006). Baked Products. doi:10.1002/9780470995907Chieh, C. (s. f.). Water. Bakery Products, 211-232. doi:10.1002/9780470277553.ch11Conforti, F. D. (s. f.). Cake Manufacture. Bakery Products, 393-410. doi:10.1002/9780470277553.ch22Ghotra, B. S., Dyal, S. D., & Narine, S. S. (2002). Lipid shortenings: a review. Food Research International, 35(10), 1015-1048. doi:10.1016/s0963-9969(02)00163-1Kiosseoglou, V., & Paraskevopoulou, A. (s. f.). Eggs. Bakery Products, 161-172. doi:10.1002/9780470277553.ch8Lai, H.-M., & Lin, T.-C. (s. f.). Bakery Products: Science and Technology. Bakery Products, 3-68. doi:10.1002/9780470277553.ch1Lau, M. ., Tang, J., & Paulson, A. . (2000). Texture profile and turbidity of gellan/gelatin mixed gels. Food Research International, 33(8), 665-671. doi:10.1016/s0963-9969(00)00111-3LINDLEY, M. G. (1987). Sucrose in baked products. Nutrition Bulletin, 12(1), 41-45. doi:10.1111/j.1467-3010.1987.tb00011.xMastromatteo, M., Chillo, S., Iannetti, M., Civica, V., & Del Nobile, M. A. (2011). Formulation optimisation of gluten-free functional spaghetti based on quinoa, maize and soy flours. International Journal of Food Science & Technology, 46(6), 1201-1208. doi:10.1111/j.1365-2621.2011.02613.xOreopoulou, V. (s. f.). Fat Replacers. Bakery Products, 193-210. doi:10.1002/9780470277553.ch10Peressini, D., Pin, M., & Sensidoni, A. (2011). Rheology and breadmaking performance of rice-buckwheat batters supplemented with hydrocolloids. Food Hydrocolloids, 25(3), 340-349. doi:10.1016/j.foodhyd.2010.06.012Sanz, T., Salvador, A., Baixauli, R., & Fiszman, S. M. (2009). Evaluation of four types of resistant starch in muffins. II. Effects in texture, colour and consumer response. European Food Research and Technology, 229(2), 197-204. doi:10.1007/s00217-009-1040-1Taylor, J. R. N., Schober, T. J., & Bean, S. R. (2006). Novel food and non-food uses for sorghum and millets. Journal of Cereal Science, 44(3), 252-271. doi:10.1016/j.jcs.2006.06.009Wilderjans, E., Luyts, A., Brijs, K., & Delcour, J. A. (2013). Ingredient functionality in batter type cake making. Trends in Food Science & Technology, 30(1), 6-15. doi:10.1016/j.tifs.2013.01.001Wilderjans, E., Pareyt, B., Goesaert, H., Brijs, K., & Delcour, J. A. (2008). The role of gluten in a pound cake system: A model approach based on gluten–starch blends. Food Chemistry, 110(4), 909-915. doi:10.1016/j.foodchem.2008.02.079Wilson, N. L. W. (2011). How the Cookie Crumbles: A Case Study of Gluten-Free Cookies and Random Utility. American Journal of Agricultural Economics, 94(2), 576-582. doi:10.1093/ajae/aar081Zhu, J.-H., Yang, X.-Q., Ahmad, I., Li, L., Wang, X.-Y., & Liu, C. (2008). Rheological properties of κ-carrageenan and soybean glycinin mixed gels. Food Research International, 41(3), 219-228. doi:10.1016/j.foodres.2007.11.00

Resolving Structure and Mechanical Properties at the Nanoscale of Viruses with Frequency Modulation Atomic Force Microscopy

Structural Biology (SB) techniques are particularly successful in solving virus structures. Taking advantage of the symmetries, a heavy averaging on the data of a large number of specimens, results in an accurate determination of the structure of the sample. However, these techniques do not provide true single molecule information of viruses in physiological conditions. To answer many fundamental questions about the quickly expanding physical virology it is important to develop techniques with the capability to reach nanometer scale resolution on both structure and physical properties of individual molecules in physiological conditions. Atomic force microscopy (AFM) fulfills these requirements providing images of individual virus particles under physiological conditions, along with the characterization of a variety of properties including local adhesion and elasticity. Using conventional AFM modes is easy to obtain molecular resolved images on flat samples, such as the purple membrane, or large viruses as the Giant Mimivirus. On the contrary, small virus particles (25–50 nm) cannot be easily imaged. In this work we present Frequency Modulation atomic force microscopy (FM-AFM) working in physiological conditions as an accurate and powerful technique to study virus particles. Our interpretation of the so called “dissipation channel” in terms of mechanical properties allows us to provide maps where the local stiffness of the virus particles are resolved with nanometer resolution. FM-AFM can be considered as a non invasive technique since, as we demonstrate in our experiments, we are able to sense forces down to 20 pN. The methodology reported here is of general interest since it can be applied to a large number of biological samples. In particular, the importance of mechanical interactions is a hot topic in different aspects of biotechnology ranging from protein folding to stem cells differentiation where conventional AFM modes are already being used

Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)

Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear. Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese. Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire. Results: The mHealth intervention produced a greater loss of body weight (–1.97 kg, 95% CI –2.39 to –1.54) relative to standard counselling at 3 months (–1.13 kg, 95% CI –1.56 to –0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; –1.84 kg, 95% CI –2.48 to –1.20), percentage of body fat (PBF; –1.22%, 95% CI –1.82% to 0.62%), and BMI (–0.77 kg/m2, 95% CI –0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of –1.18 kg (95% CI –2.30 to –0.06) and BMI of –0.47 kg/m2 (95% CI –0.80 to –0.13), whereas the obese group only experienced a change in BMI of –0.53 kg/m2 (95% CI –0.86 to –0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of –1.03 kg (95% CI –1.74 to –0.33), PBF of –0.76% (95% CI –1.32% to –0.20%), and BMI of –0.5 kg/m2 (95% CI –0.83 to –0.19). Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Efficient computation of two-electron reduced density matrices via selected configuration interaction

We create an approach to efficiently calculate two-electron reduced density matrices (2-RDMs) using selected configuration interaction wavefunctions. This is demonstrated using the specific example of Monte Carlo configuration interaction (MCCI). The computation of the 2-RDMs is accelerated by using ideas from fast implementations of full configuration interaction (FCI) and recent advances in implementing the Slater-Condon rules using hardware bitwise operations. This method enables a comparison of MCCI and truncated CI 2-RDMs with FCI values for a range of molecules, which includes stretched bonds and excited states. The accuracy in energies, wavefunctions, and 2-RDMs is seen to exhibit a similar behavior. We find that MCCI can reach sufficient accuracy of the 2-RDM using significantly fewer configurations than truncated CI, particularly for systems with strong multireference character

Towards high-resolution X-ray scattering as a probe of electron correlation

X-ray scattering cross sections are calculated using a range of increasingly correlated methods: Hartree&ndash;Fock (HF), complete active space self-consistent field (CASSCF), Monte Carlo configuration interaction (MCCI), and full configuration interaction (FCI). Even for the seemingly straightforward case of ground state Ne, the accuracy of the total scattering is significantly better with a more correlated wavefunction. Scanning the bond distance in ground state CO shows that the total scattering signal tracks the multireference character. We examine the convergence of the elastic, inelastic, and total scattering of O3. Overall, the inelastic and total components are found to be the most sensitive to the strength of correlation. Our results suggest that highly accurate measurement of X-ray scattering could provide a sensitive probe of pair-wise correlation between electrons.</p