Extending depolarized DLS measurements to turbid samples.

The application of dynamic light scattering to soft matter systems has strongly profited from advanced approaches such as the so-called modulated 3D cross correlation technique (Mod3D-DLS) that suppress contributions from multiple scattering, and can therefore be used for the characterization of turbid samples. Here we now extend the possibilities of this technique to allow for depolarized light scattering (Mod3D-DDLS) and thus obtain information on both translational and rotational diffusion, which is important for the characterization of anisotropic particles. We describe the required optical design and test the performance of the approach for increasingly turbid samples using well defined anisotropic colloidal models systems. Our measurements demonstrate that 3D-DDLS experiments can be performed successfully for samples with a reduced transmission due to multiple scattering as low as 1%. We compare the results from this approach with those obtained by standard DDLS experiments, and point out the importance of using an appropriate optical design when performing depolarized dynamic light scattering experiments with turbid systems.

COVID-19 and the state: Exploring a puzzling relationship in the early stages of the pandemic.

During the first year of the Covid-19 pandemic, it was wealthier countries with stronger institutions that suffered the highest numbers of cases and fatalities. Many weaker countries were instead praised for more effective pandemic response. What explains this seeming puzzle? We re-consider these relationships in the cross-country data, drawing on measures of the state, Covid's health impact and pandemic response. In brief, our analysis suggests that, when appropriate additional factors are taken into account, the expected relationship between state effectiveness and pandemic health outcomes in fact is clear. We also offer insight into how different dimensions of the state influence policy and outcomes and how particular countries compare with others.

Practical Impact of New Diastolic Recommendations on Noninvasive Estimation of Left Ventricular Diastolic Function and Filling Pressures.

BACKGROUND: In 2016, an update of the 2009 recommendations for the evaluation of left ventricular (LV) diastolic function (DF) was released by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. The aims of this study were to assess the concordance between the 2016 and 2009 recommendations and to test the impact of the consideration of "myocardial disease" recommended in the 2016 update on the evaluation of diastolic dysfunction (DD) and LV filling pressures in patients with normal and reduced LV ejection fractions referred to a general echocardiography laboratory. METHODS: A total of 1,508 outpatients referred to an echocardiography laboratory during a predefined 5-month period were prospectively enrolled. All patients underwent targeted clinical history and Doppler echocardiographic examination. DD and LV filling pressures were assessed according to 2009 and 2016 recommendations. Concordance was calculated using the κ coefficient and overall proportion of agreement. RESULTS: Overall proportion of agreement between the two recommendations was 64.7% (κ = 0.43). Comparing the 2009 and 2016 recommendations, 47.5% and 36.1% patients, respectively, had DD (P < .0001), and 22.7% and 12.6% had elevated LV filling pressures (P < .0001). This difference remained significant in the setting of patients with normal LV ejection fractions (21.6% vs 10.7%, P < .0001). In the application of the 2016 recommendations, whether or not the presence of "myocardial disease" was considered, the prevalence of indeterminate diastolic function was, respectively, 7.3% versus 13.7%, while patients in whom the DD grade could not be determined were 8.1% versus 14.4% (P < .0001 for all). CONCLUSIONS: Considering the presence of myocardial disease when applying the 2016 recommendations resulted in a lower prevalence of inconclusive diagnosis.

Cardiac Changes in Patients on Long-Term Parenteral Nutrition.

Patients with short bowel syndrome (SBS) on long-term home parenteral nutrition (HPN) chronically receive high fluid volumes directly into the right atrium (RA) through the superior vena cava. We retrospectively evaluated cardiac function measured by routine transthoracic echocardiography (TTE) in a population of 26 SBS patients on long-term HPN and compared their data on echocardiograph-derived right heart structure and function, with those of a control group of 26 patients also bearing a central venous catheter (CVC) for other reasons. Results showed that body weight and BMI were significantly higher in the control group. The echocardiographic estimate of RA pressure was higher in HPN patients than in controls (p = 0.01). An increased estimate of RA pressure indicates the need to consider TTE in the follow-up of long-term HPN patients to detect functional impairment early.

Dynamic Light Scattering of Biopharmaceutics-Can Analytical Performance Be Enhanced by Laser Power?

BACKGROUND: Dynamic light scattering (DLS) is an important tool to characterize colloidal systems and adequate sizing is particularly critical in the field of protein formulations. Among the different factors that can influence the measurement result, the effect of laser power has so far not been studied thoroughly. METHODS: The sensitivity of a DLS instrument was first considered on a theoretical level, followed by experiments using DLS instruments, equipped with two different lasers of (nominal) 45 mW, and 100 mW, respectively. This work analyzes dilute colloidal dispersions of lysozyme as model protein. RESULTS: Theoretical findings agreed with experiments in that only enhanced laser power of 100 mW laser allowed measuring a 0.1 mg/mL protein dispersion in a reliable manner. Results confirmed the usefulness of the presented theoretical considerations in improving a general understanding of the limiting factors in DLS. CONCLUSIONS: Laser power is a critical aspect regarding adequate colloidal analysis by DLS. Practical guidance is provided to help scientists specifically with measuring dilute samples to choose both an optimal instrument configuration as well as a robust experimental procedure.

Impact of Vitamin D deficiency on subclinical carotid atherosclerosis: a pooled analysis of cohort studies.

Context: Vitamin D deficiency patients have an increased cardiovascular (CV) morbidity and mortality. Carotid intima-media thickness (IMT) and carotid plaques are markers of subclinical atherosclerosis and predictors of CV events. Objective: To perform a meta-analysis of studies evaluating the impact of Vitamin D deficiency on common carotid artery IMT (CCA-IMT) and on the prevalence of carotid plaques. Data Sources: Studies were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results: Twenty-one studies (3,777 Vitamin D deficiency patients and 4,792 controls) with data on CCA-IMT and 6 studies (1,889 Vitamin D deficiency patients and 2,883 controls) on the prevalence of carotid plaques were included. Compared to controls, Vitamin D deficiency patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.043 mm; 95%CI: 0.030, 0.056; P<0.001), and an increased prevalence of carotid plaques (Odds Ratio [OR]: 2.29, 95%CI: 1.03-5.11; P=0.043) with an attributable risk of 35.9%. When selecting studies specifically including patients with diabetes, the prevalence of carotid plaques in Vitamin D deficiency patients than in controls resulted higher (OR: 3.27; 95%CI: 1,62-6.62; P=0.001). A significant difference in CCA-IMT was confirmed when comparing patients with Vitamin D insufficiency to controls (MD: 0.011; 95%CI: 0.010-0.012, P<0.001). Sensitivity analyses substantially confirmed results and regression models showed that with the exception of LDL-cholesterol, HDL-cholesterol, triglycerides and the prevalence of hypercholesterolemia, all the other clinical and demographic co-variates significantly impacted on the difference in CCA-IMT between Vitamin D deficiency patients and controls. Conclusions: Both Vitamin D deficiency and Vitamin D insufficiency are associated with subclinical atherosclerosis, potentially suggesting an increased CV risk in these clinical settings.

Determinants of myocardial mechanics in top-level endurance athletes: three-dimensional speckle tracking evaluation.

AIMS: The determinants of systolic function in the performing heart are not completely understood. Aim of the study was to assess the contributors of left ventricular (LV) strain components, using 3D speckle tracking echocardiography (STE) in endurance athletes. METHODS AND RESULTS: A total of 36 top-level male endurance athletes (AT) and 36 age-matched sedentary normal controls (NC) underwent standard and real-time 3D echocardiography. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were assessed using 3D STE. AT had significantly higher GLS (-22.1 ± 4.4 vs. -18.4 ± 3.5%; P < 0.0001), GCS (-17.9 ± 2.4 vs. -16.0 ± 3.2; P = 0.006), and GAS (-35.5 ± 6.7 vs. -30.2 ± 4.9; P < 0.0001), while GRS did not differ significantly with NC. At separate multiple linear regression analyses, heart rate emerged as independent predictor of GLS (ß = -0.37, P < 0.002), GCS (ß = -0.32, P = 0.007), GAS (ß = -0.37, P < 0.001), and GRS (ß = -0.29, P = 0.019); LV mass was independently associated with GLS (ß = 0.34, P = 0.009) and GAS (ß = 0.41, P < 0.001) but not with GCS and GRS, while diastolic blood pressure predicted GCS (ß = -0.46, P < 0.0001), GAS (ß = -0.28; P = 0.006), and GRS (ß = -0.42, P < 0.001). No independent correlation emerged for body surface area and stroke volume. By replacing LV mass with end-diastolic volume, the latter showed independent association with GCS (ß = -0.65, P = 0.028) and with GRS (ß = -0.60, P < 0.05). CONCLUSION: AT have an increased myocardial function at rest when compared with NC, this being elicited mainly by subendocardial and mid-wall fibres. Sinus bradycardia, LV mass, and afterload are independent determinants of supernormal myocardial deformation at rest.

Whole-grain pasta reduces appetite and meal-induced thermogenesis acutely: a pilot study.

In epidemiological studies, the intake of foods rich in dietary fiber is associated with a reduced risk of developing overweight and type 2 diabetes. This work aims to identify acute strategies to regulate appetite and improve glucose control by using different pasta meals. Hence, 4 different isocaloric lunch meals, consisting of (i) refined-grain pasta (RG+T), (ii) whole-grain pasta (WG+T), (iii) lemon juice-supplemented refined-grain pasta (LRG+T), and (iv) refined-grain pasta with legumes (RG+L), were administered to 8 healthy participants in a crossover design. On the test days, participants underwent baseline measurements, including appetite sensation, blood sample, and resting energy expenditure (EE), after which the test lunch was served. Subjective appetite was assessed and a blood sample was taken each hour for 240 min, and postprandial EE was measured for 3 h. In repeated-measures analysis of covariance (ANCOVA), postprandial fullness (p = 0.001) increased and hunger (p = 0.038) decreased. WG+T had a lower EE than did both LGR+T (p = 0.02) and RG+L (p < 0.001). Likewise, meal-induced thermogenesis was lower for WG+T compared with RG+L (58 ± 81 kJ vs 248 ± 188 kJ; p < 0.05). Plasma glucose (p = 0.001) was lower for RG+T, and triacylglycerols (p = 0.02) increased for LRG+T; however, insulin, C-peptide, and ghrelin were comparable in all other meals. In conclusion, our study indicates that acute consumption of whole-grain pasta may promote fullness and reduce hunger, lowering postprandial thermogenesis, and adding lemon juice to the pasta or legumes does not appear to affect appetite. However, none of pasta meal alterations improved the postprandial metabolic profile.

[Radionuclide imaging of neurendocrine tumors: biological basis and diagnostic results]. / Imaging con radionuclidi dei tumori neuroendocrini: basi biologiche e risultati diagnostici.

Many radiopharmaceuticals have been successfully used in nuclear medicine to detect neuroendocrine tumors, and many of them are based on a specific mechanism of uptake, while others are non-specific probes. This "review" focuses on the clinical applications of metaiodobenzylguanidine, (111)In-pentreotide and positron emission tomography (PET) tracers. New avances in diagnostic imaging will be discussed. Molecular imaging serves these diagnostic functions and provides powerful means for non-invasively detecting disease.

[Effectiveness of conventional diagnostic radiology and nuclear medicine in the treatment of pain from bone metastases]. / Efficacia della radiodiagnostica convenzionale e della medicina nucleare nel trattamento del dolore osseo da metastasi.

Bone is one of the most common metastasis sites from solid tumors. Bone pain due to metastatic neoplastic growth is due to tumor infiltration and expansion of bone membranes. Treatment of acute and chronic pain represents one of the greatest problems in clinical oncology, requiring a multidisciplinary approach. This review focuses on the effectiveness of conventional diagnostic radiology and nuclear medicine for the detection, management and treatment of pain from bone metastasis.

Evidence of brown fat activity in constitutional leanness.

BACKGROUND: Brown adipose tissue (BAT) was considered essentially nonexistent in adults until recent evidence obtained using 18-fluorodeoxyglucose (18-FDG) positron emission tomography/computed tomography. It seems to play a role in whole body metabolism, but it has not been evaluated in underweight conditions, such as in young females with constitutional leanness (CL) or anorexia nervosa (AN). SUBJECTS AND METHODS: Thirty-eight subjects were evaluated from October 2011 to March 2012 : 7 CL (21.7 ± 3.6 y, body mass index [BMI] 16.2 ± 1.0 kg/m(2)), 7 AN (23.4 ± 4.5 y, BMI 15.5 ± 0.8), 3 of the 7 AN after stable refeeding (R-AN, 21.3 ± 1.5 y, BMI 18.8 ± 1.1), and 24 normal weight (NW) women (25.6 ± 3.9 y, BMI 22.2 ± 1.5). Fasting resting metabolic rate and respiratory quotient were measured by indirect calorimetry, body composition by bioimpedentiometry (only in CL, AN, and refed AN), and BAT activity by 18-FDG positron emission tomography/computed tomography scan, all in standardized conditions. RESULTS: All CL (100%), none of the AN and refed AN (0%), and 3 of the 24 NW (12%) subjects showed FDG uptake. Average FDG maximum standardized uptake value was 11.4 + 6.7 g/mL in CL and 5.5 ± 1.2 g/mL (min 3.7, max 8.3) in the 3 NW subjects. In CL, the maximum standardized uptake value was directly correlated to resting metabolic rate, corrected for fat-free mass, and inversely correlated with respiratory quotient. CONCLUSION: BAT activity has been shown in CL in resting thermoneutral conditions and may exert a role against adipose tissue deposition.

[Multimodal imaging in bone metastases]. / Imaging multimodale delle metastasi ossee: le nuove frontiere della medicina nucleare.

The skeleton is one main sites of metastasis of solid tumors, and metastatic bone disease are most common malignant disease of the bone. The diagnosis and assessment of bone metastases require integrated multimodality combined approach of different diagnostic methods, including both different radionuclides that radiological techniques such as X-rays, CT and MRI. In this scenario the nuclear medicine gives a significant contribution to the evaluation of skeletal metastases. In this article we will analyze the main approaches.

[Peptide imaging: the somatostatine model]. / Imaging recettoriale con analoghi della somatostatina.

Radiolabeled cell-surface peptide receptor-binding molecules are emerging as an important class of radiopharmaceuticals. Main approach has been the use of 111In Octreotide as functional imaging to find NETs. In some tumor types, it is considered the diagnostic gold standard. This article focuses on the current status of peptide-receptor scintigraphy in different tumors, in other oncologic and non oncologic applications and on future developments in these fields.

[New diagnostic imaging approaches in multiple myeloma]. / Nuovi approcci alla diagnostica per immagini nel mieloma multiplo.

Multiple myeloma (MM) is a neoplastic monoclonal proliferation of plasma cells, mainly involving bone marrow. To properly stage and manage patients with MM the clinician needs at first a complete skeletal survey. Today none of diagnostic imaging methods is able to answer alone to all questions in staging, treatment and follow up. Bone scintigraphy is affected by a low sensitivity. Tc-99m MIBI has been proposed in staging and in follow-up , with most relevant clinical information deriving from the correlation of its whole body uptake's distribution with extent and activity of the disease. PET - FDG has been proposed in MM for its skill to detect whole-body metabolic active disease, producing relevant information in staging and prognosis. First studies demonstrated that PET-FDG is more sensitive than other imaging modalities for localizing extra medullary sites of disease.

Novel self-associative and multiphasic nanostructured soft carriers based on amphiphilic hyaluronic acid derivatives.

The purpose of the present study was to investigate the physicochemical properties in aqueous media of amphiphilic hyaluronic acid (HA) derivatives obtained by reaction of HA's hydroxyl groups with octenyl succinic anhydride (OSA). The self-associative properties of the resulting octenyl succinic anhydride-modified hyaluronic acid (OSA-HA) derivatives were studied by fluorescence spectroscopy using Nile Red as fluorophore. The morphology, size and surface charge of the OSA-HA assemblies were determined by transmission electron microscopy, dynamic light scattering and by measuring their electrophoretic mobility, respectively. OSA-HA was shown to spontaneously self-associate in aqueous media into negatively charged spherical and multiphasic nanostructures with a hydrodynamic diameter between 170 and 230nm and to solubilize hydrophobic compounds such as Nile Red. This was a good indication that OSA-HA could be used as building block for the formulation of soft nanocarriers towards the encapsulation and controlled delivery of hydrophobic active ingredients or drugs.

Electrostatic stabilization of charged colloidal particles with adsorbed polyelectrolytes of opposite charge.

Repulsive electrostatic double-layer forces are responsible for the stabilization of charged colloidal particles in the presence of adsorbed polyelectrolytes of opposite and high line charge densities. This mechanism is revealed by studies of electrophoretic mobility and colloidal stability performed with dynamic light scattering as a function of the polyelectrolyte dose and the ionic strength for two different types of latex particles and four different types of polyelectrolytes. The dependence of these quantities is very similar for bare charged latex particles and the same particles in the presence of the different oppositely charged polyelectrolytes. Positively charged particles in the presence of anionic polyelectrolytes behave analogously to negatively charged particles in the presence of cationic polyelectrolytes.

Stability of negatively charged latex particles in the presence of a strong cationic polyelectrolyte at elevated ionic strengths.

Sulfate-terminated latex particles were investigated in the presence of poly(diallyldimethyl ammonium chloride) (PDADMAC) at pH 4.0 in aqueous KCl electrolyte solutions by dynamic light scattering and electrophoresis, in particular, at high ionic strengths. The polyelectrolyte adsorbs to the latex particles quantitatively until the adsorption plateau is reached. The adsorbed amount at this plateau and the corresponding layer thickness increase with increasing ionic strength. The resulting layers have a thickness of several nanometers. Colloidal stability is qualitatively consistent with electrostatic double layer forces, especially since the system can be fully destabilized at high ionic strengths even at high polyelectrolyte doses. Additional attractive forces due to lateral charge heterogeneities seem to contribute to the destabilization of the system, even for the adsorbed layers in the saturated state. However, this layer does not provide any additional stabilization mechanism due to steric repulsion forces, since the adsorbed polyelectrolyte layers are thin and laterally heterogeneous even in their saturated state.

Structure of an adsorbed polyelectrolyte monolayer on oppositely charged colloidal particles.

An adsorbed layer of a cationic polyelectrolyte, poly(diallyldimethyl-ammonium) chloride (PDADMAC) on negatively charged colloidal latex particles was investigated by small-angle neutron scattering (SANS) and dynamic light scattering (DLS). SANS gives a layer thickness of 8 +/- 1 A and a polymer volume fraction of 0.31 +/- 0.05 within the film. DLS gives a somewhat larger thickness of 18 +/- 2 A, and the discrepancy is likely due to the inhomogeneous nature of the layer and the existence of polymer tails or loops protruding into solution. These results show that a highly charged polyelectrolyte adsorbs on an oppositely charged colloidal particle in a flat configuration due to the attractive forces acting between the polyelectrolyte and the substrate.

Synthesis of planar five-connected nodal ligands.

Synthetic routes to a penta(4-pyridyl)cyclopentadienyl ligand are explored. The most successful route uses a palladium-catalysed pentapyridation of di(tert-butyl)phosphinoferrocene by using a procedure developed by Hartwig. The same method allows the synthesis of cyclopentadiene ligands substituted with 4-benzaldehydes or 4-phenylthiols. The pyridine ligands are formally five-connected nodes that may be linked by linear coordination metals to give closed spherical complexes of composition [(metal)(30)(ligand)(12)] as shown by molecular modelling. Experiment shows that the ligand complexes copper(I) and silver(I) with the expected 1:2.5 stoichiometry, and the (1)H NMR spectrum of the resulting product shows the ligands to be equivalent. NMR diffusion and light-scattering measurements support the formation of a species with a hydrodynamic radius of the order of 15 A, in agreement with the modelling studies. The resulting complex would be topologically identical to the C(60) fullerene structure.

Diffusion NMR spectroscopy for the characterization of the size and interactions of colloidal matter: the case of vesicles and nanoparticles.

We report the application of the pulse gradient spin-echo (PGSE) NMR technique (PGSE NMR) to the analysis of large colloidal materials, specifically vesicles formed from macromolecular amphiphiles and nanoparticles. Measurements of size and size distribution were demonstrated to be comparable to those obtained through dynamic light scattering or hydrodynamic chromatography. In comparison to these more common analytical methods, the use of PGSE NMR is particularly advantageous in that, as a spectroscopic technique, it adds chemical selectivity to the study of physical dimensions. In this way, chemically different species contemporarily present in a sample may be individually studied. In addition, we demonstrate the use of PGSE NMR to probe the existence of equilibria between macroamphiphiles present in solution and those present in vesicles or on the surface of nanoparticles. This feature in particular opens exciting possibilities for the characterization of the phase behavior and of the surface adsorption phenomena of colloids.