Is Raman the best strategy towards the development of non-invasive continuous glucose monitoring devices for diabetes management?

Diabetes has no well-established cure; thus, its management is critical for avoiding severe health complications involving multiple organs. This requires frequent glycaemia monitoring, and the gold standards for this are fingerstick tests. During the last decades, several blood-withdrawal-free platforms have been being studied to replace this test and to improve significantly the quality of life of people with diabetes (PWD). Devices estimating glycaemia level targeting blood or biofluids such as tears, saliva, breath and sweat, are gaining attention; however, most are not reliable, user-friendly and/or cheap. Given the complexity of the topic and the rise of diabetes, a careful analysis is essential to track scientific and industrial progresses in developing diabetes management systems. Here, we summarize the emerging blood glucose level (BGL) measurement methods and report some examples of devices which have been under development in the last decades, discussing the reasons for them not reaching the market or not being really non-invasive and continuous. After discussing more in depth the history of Raman spectroscopy-based researches and devices for BGL measurements, we will examine if this technique could have the potential for the development of a user-friendly, miniaturized, non-invasive and continuous blood glucose-monitoring device, which can operate reliably, without inter-patient variability, over sustained periods.

High-Throughput Live Imaging of Microcolonies to Measure Heterogeneity in Growth and Gene Expression.

Precise measurements of between- and within-strain heterogeneity in microbial growth rates are essential for understanding genetic and environmental inputs into stress tolerance, pathogenicity, and other key components of fitness. This manuscript describes a microscope-based assay that tracks approximately 105 Saccharomyces cerevisiae microcolonies per experiment. After automated time-lapse imaging of yeast immobilized in a multiwell plate, microcolony growth rates are easily analyzed with custom image-analysis software. For each microcolony, expression and localization of fluorescent proteins and survival of acute stress can also be monitored. This assay allows precise estimation of strains' average growth rates, as well as comprehensive measurement of heterogeneity in growth, gene expression, and stress tolerance within clonal populations.

Decanalizing thinking on genetic canalization.

The concept of genetic canalization has had an abiding influence on views of complex-trait evolution. A genetically canalized system has evolved to become less sensitive to the effects of mutation. When a gene product that supports canalization is compromised, the phenotypic impacts of a mutation should be more pronounced. This expected increase in mutational effects not only has important consequences for evolution, but has also motivated strategies to treat disease. However, recent studies demonstrate that, when putative agents of genetic canalization are impaired, systems do not behave as expected. Here, we review the evidence that is used to infer whether particular gene products are agents of genetic canalization. Then we explain how such inferences often succumb to a converse error. We go on to show that several candidate agents of genetic canalization increase the phenotypic impacts of some mutations while decreasing the phenotypic impacts of others. These observations suggest that whether a gene product acts as a 'buffer' (lessening mutational effects) or a 'potentiator' (increasing mutational effects) is not a fixed property of the gene product but instead differs for the different mutations with which it interacts. To investigate features of genetic interactions that might predispose them toward buffering versus potentiation, we explore simulated gene-regulatory networks. Similarly to putative agents of genetic canalization, the gene products in simulated networks also modify the phenotypic effects of mutations in other genes without a strong overall tendency towards lessening or increasing these effects. In sum, these observations call into question whether complex traits have evolved to become less sensitive (i.e., are canalized) to genetic change, and the degree to which trends exist that predict how one genetic change might alter another's impact. We conclude by discussing approaches to address these and other open questions that are brought into focus by re-thinking genetic canalization.

The Eating Disorder Examination Questionnaire: reliability and validity of the Italian version.

PURPOSE: To examine the validity and reliability of a new Italian language version of the latest edition of the Eating Disorder Examination Questionnaire (EDE-Q 6.0). METHODS: The sixth edition of the EDE-Q was translated into Italian and administered to 264 Italian-speaking inpatient and outpatient (257 females in their mid-20s) with eating disorder (75.4% anorexia nervosa) and 216 controls (205 females). RESULTS: Internal consistency was high for both the global EDE-Q and all subscale scores. Test-retest reliability was good to excellent (0.66-0.83) for global and subscale scores, and for items assessing key behavioral features of eating disorders (0.55-0.91). Patients with an eating disorder displayed significantly higher EDE-Q scores than controls, demonstrating the good criterion validity of the tool. Confirmatory factor analysis revealed a good fit for a modified seven-item three-factor structure. CONCLUSIONS: The study showed the good psychometric properties of the new Italian version of the EDE-Q 6.0, and validated its use in Italian eating disorder patients, particularly in young females with anorexia nervosa.

Residential cognitive-behavioral weight-loss intervention for obesity with and without binge-eating disorder: A prospective case-control study with five-year follow-up.

OBJECTIVE: The aim of this prospective case-control study was to compare the long-term effects of a residential cognitive-behavioral treatment (CBT) for weight loss in severely obese patients with and without binge-eating disorder (BED). METHODS: We assessed weight-loss outcomes and psychological impairment in 54 severely obese female patients with BED and 54 patients matched by age, gender, and body mass index (BMI) without BED admitted to a residential CBT program. Body weight was measured at baseline and at 6-month follow-up and was reported by patients in a telephone interview at 5-year follow-up. Depression, eating disorder psychopathology, general psychopathology, and quality of life were assessed using validated instruments at baseline and at 6-month follow-up. RESULTS: Obese patients with and without BED had similar weight loss at 6-month and 5-year follow-ups. Although both groups showed improved psychosocial variables, at 6 months the BED group maintained higher psychological impairment. Nevertheless, at 5-year follow-up more than half of the BED participants were no longer classifiable as having BED. DISCUSSION: The presence of BED does not affect weight-loss outcome in obese patients treated with the residential CBT for weight loss program considered. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:723-730).

Sponge mesoporous silica formation using disordered phospholipid bilayers as template.

Lecithin/dodecylamine/lactose mixtures in ethanol/aqueous media led to the formation of sponge mesoporous silica (SMS) materials by means of tetraethoxysilane (TEOS) as silica source. SMS materials show a "sponge-mesoporous" porosity with a pore diameter of about 5-6 nm, in accordance to the length of a lecithin bilayer. SMS synthesis was developed to create a new class of powerful biocatalysts able to efficiently encapsulate enzymes by adding a porosity control to the classical sol-gel synthesis and by using phospholipids and lactose as protecting agents for the enzymes. In the present study, the formation of SMS was investigated by using electron paramagnetic resonance (EPR) probes inserted inside phospholipid bilayers. The influence of progressive addition of each component (ethanol, dodecylamine, lactose, TEOS) on phospholipid bilayers was first examined; then, the time evolution of EPR spectra during SMS synthesis was studied. Parameters informative of mobility, structure, order, and polarity around the probes were extracted by computer analysis of the EPR line shape. The results were discussed on the basis of solids characterization by X-ray diffraction, nitrogen isotherm, transmission electron microscopy, and scanning electron microscopy. The results, together with the well-known ability of ethanol to promote membrane hemifusion, suggested that the templating structure is a bicontinuous phospholipid bilayer phase, shaped as a gyroid, resulting of multiple membrane hemifusions induced by the high alcohol content used in SMS synthesis. SMS synthesis was compared to hexagonal mesoporous silica (HMS) synthesis accomplished by adding TEOS to a dodecylamine/EtOH/water mixture. EPR evidenced the difference between HMS and SMS synthesis; the latter uses an already organized but slowly growing mesophase of phospholipids, never observed before, whereas the former shows a progressive elongation of micelles into wormlike structures. SMS-type materials represent a new class of biocompatible materials and open a bright perspective for biomolecule processing for pharmaceutical, biocatalysis, biosensors, or biofuel cell applications.

Synthesis of large-pore micelle-templated silico-aluminas at different alumina contents.

The EPR spectra of radical surfactant probes embedded in cetyltrimethylammonium bromide (CTAB) and trimethylbenzene (TMB) stable water emulsions (TMB/CTAB = 13) were analyzed to provide information on the kinetics of formation of micelle-templated silicoaluminas (MTSA) at 343 K, obtained by means of silica and alumina, solved in alkaline solutions, at different Si/Al ratios. Textural (surface area, pore volume, pore size, surfactant content) and structural characterization of both as-synthesized and calcined MTSA were performed by means of nitrogen sorption isotherms, TEM, and chemical analysis. This analysis showed that TMB worked as a swelling agent of the CTAB micelles, providing large-pore homogeneous and stable MTSA at TMB/CTAB = 13 for Si/Al from infinity to 10. A demixing of the emulsion occurs at Si/Al < 10: at Si/Al = 7, a double wide-and-narrow pore structure was formed; then, at Si/Al = 5, an amorphous material was obtained. At Si/Al > or = 10, the computer-aided analysis of the EPR spectra as a function of the synthesis time indicated the distribution of the probes in two different environments: "micellar" probes inserted in the surfactant aggregates, whose mobility decreases over the synthesis time, thus reporting on the progressive modification of the surfactant aggregates structure and the solid condensation, and "interacting" probes due to probe-surfactant heads electrostatically interacting with the charged surface sites induced by alumina incorporation in the silica network. This last fraction increases its relative amount over the synthesis time, informing about the condensation and structuration of the MTSA. Without alumina, the "interacting" component is absent in the EPR spectra because TMB preferentially interacts with the surfactant headgroups by cation-pi interactions, thus preventing the interactions of these headgroups with silanols. When alumina is added, the negatively charged silicoaluminate at the surface promotes the interaction of the ammonium headgroups with the surface, and some Na+ cations also interact with TMB by cation-pi interaction and contribute to decreasing the interaction of the headgroups with TMB. Therefore, increasing alumina contents promote electrostatic interactions between the positively charged surfactant heads and the negatively charged silicoaluminate groups. The strong interaction of the surfactants with the silicoaluminate surface allows the formation of a monolayerlike structure of surfactant, which is not observed in the absence of alumina. The synthesis is slowed by increasing alumina contents due to a destructuration effect of alumina in the MTSA formation.