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CSF1R-related disorder (CSF1R-RD) is a neurodegenerative condition that predominantly affects white matter due to genetic alterations in the CSF1R gene, which is expressed by microglia. We studied an elderly man with a hereditary, progressive dementing disorder of unclear etiology. Standard genetic testing for leukodystrophy and other neurodegenerative conditions was negative. Brain autopsy revealed classic features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), including confluent white matter degeneration with axonal spheroids and pigmented glial cells in the affected white matter, consistent with CSF1R-RD. Subsequent long-read sequencing identified a novel deletion in CSF1R that was not detectable with short-read exome sequencing. To gain insight into potential mechanisms underlying white matter degeneration in CSF1R-RD, we studied multiple brain regions exhibiting varying degrees of white matter pathology. We found decreased CSF1R transcript and protein across brain regions, including intact white matter. Single nuclear RNA sequencing (snRNAseq) identified two disease-associated microglial cell states: lipid-laden microglia (expressing GPNMB, ATG7, LGALS1, LGALS3) and inflammatory microglia (expressing IL2RA, ATP2C1, FCGBP, VSIR, SESN3), along with a small population of CD44+ peripheral monocyte-derived macrophages exhibiting migratory and phagocytic signatures. GPNMB+ lipid-laden microglia with ameboid morphology represented the end-stage disease microglia state. Disease-associated oligodendrocytes exhibited cell stress signatures and dysregulated apoptosis-related genes. Disease-associated oligodendrocyte precursor cells (OPCs) displayed a failure in their differentiation into mature myelin-forming oligodendrocytes, as evidenced by upregulated LRP1, PDGFRA, SOX5, NFIA, and downregulated NKX2-2, NKX6.2, SOX4, SOX8, TCF7L2, YY1, ZNF488. Overall, our findings highlight microglia–oligodendroglia crosstalk in demyelination, with CSF1R dysfunction promoting phagocytic and inflammatory microglia states, an arrest in OPC differentiation, and oligodendrocyte depletion. [ABSTRACT FROM AUTHOR]

Objectives: The role of migration in the cultural development of central Mexico has long been debated. Archaeological models suggest that central Mexico likely experienced increased migration during the Epiclassic period (600–900 CE) and that migrants may have originated in northwestern Mexico. While previous biodistance analyses of Classic and Postclassic populations have come to similar conclusions, none have incorporated Epiclassic skeletal populations. This study uses multi‐scalar biodistance analyses to directly evaluate archaeological Epiclassic migration models within central Mexico. Materials and Methods: This study uses finite mixture and relationship (R) matrix analyses of cervicometric tooth dimensions to reconstruct patterns of biological affinity among Classic and Epiclassic Mesoamerican populations (n = 333), including at the central Mexican Epiclassic shrine site of Non‐Grid 4 where the remains of at least 180 individuals were interred. Results: Estimated inter‐site phenotypic distances demonstrate support for some degree of both biological continuity and extra‐local gene flow within central Mexican populations during the Classic‐Epiclassic transition. Furthermore, estimated phenotypic distances and finite mixture posterior probabilities indicate central Mexican Epiclassic populations were biologically diverse, originating from various source populations throughout Mesoamerica, including the Bajío region, the Malpaso Valley, and the Oaxaca Valley. Discussion: Results suggest that emphasizing both local and extra‐local gene flow rather than population replacement may be more appropriate to understand central Mexican population structure during the Classic‐Epiclassic transition. Moreover, analyses support previous archaeological migration models positing that Epiclassic migrants into central Mexico originated in northwestern Mexico, but also find evidence of Epiclassic migrants originating from previously unanticipated locales like southern Mexico. [ABSTRACT FROM AUTHOR]

Autocatalysis and self‐assembly are key processes in developmental biology and are involved in the emergence of life. In the last decade both of these features were extensively investigated by chemists with the final goal to design synthetic living systems. Herein, we describe the autonomous growth of a self‐assembled soft material, that is, a supramolecular hydrogel, able to sustain its own formation through an autocatalytic mechanism that is not based on any template effect and emerges from a peptide (hydrogelator) self‐assembly. A domino sequence of events starts from an enzymatically triggered peptide generation followed by self‐assembly into catalytic nanofibers that induce and amplify their production over time, resulting in a 3D hydrogel network. A cascade is initiated by traces (10−18 m) of a trigger enzyme, which can be localized allowing for a spatial resolution of this autocatalytic buildup of hydrogel growth, an essential condition on the route towards further cell‐mimic designs. [ABSTRACT FROM AUTHOR]

Autocatalysis and self‐assembly are key processes in developmental biology and are involved in the emergence of life. In the last decade both of these features were extensively investigated by chemists with the final goal to design synthetic living systems. Herein, we describe the autonomous growth of a self‐assembled soft material, that is, a supramolecular hydrogel, able to sustain its own formation through an autocatalytic mechanism that is not based on any template effect and emerges from a peptide (hydrogelator) self‐assembly. A domino sequence of events starts from an enzymatically triggered peptide generation followed by self‐assembly into catalytic nanofibers that induce and amplify their production over time, resulting in a 3D hydrogel network. A cascade is initiated by traces (10−18 m) of a trigger enzyme, which can be localized allowing for a spatial resolution of this autocatalytic buildup of hydrogel growth, an essential condition on the route towards further cell‐mimic designs. [ABSTRACT FROM AUTHOR]

A combinatorial approach using a one-bead-one-compound method and a screening based on a SOD-activity assay was set up for the discovery of an efficient peptidyl copper complex. The complex exhibited good stability constants, suitable redox potentials and excellent intrinsic activity. This complex was further assayed in cells for its antioxidant properties and showed beneficial effects when cells were subjected to oxidative stress. [ABSTRACT FROM AUTHOR]

Inspired by biology, one current goal in supramolecular chemistry is to control the emergence of new functionalities arising from the self‐assembly of molecules. In particular, some peptides can self‐assemble and generate exceptionally catalytically active fibrous networks able to underpin hydrogels. Unfortunately, the mechanical fragility of these materials is incompatible with process developments, relaying this exciting field to academic curiosity. Here, we show that this drawback can be circumvented by enzyme‐assisted self‐assembly of peptides initiated at the walls of a supporting porous material. We applied this strategy to grow an esterase‐like catalytically active supramolecular hydrogel (CASH) in an open‐cell polymer foam, filling the whole interior space. Our supported CASH material is highly efficient towards inactivated esters and enables the kinetic resolution of racemates. This hybrid material is robust enough to be used in continuous flow reactors, and is reusable and stable over months. [ABSTRACT FROM AUTHOR]

Inspired by biology, one current goal in supramolecular chemistry is to control the emergence of new functionalities arising from the self‐assembly of molecules. In particular, some peptides can self‐assemble and generate exceptionally catalytically active fibrous networks able to underpin hydrogels. Unfortunately, the mechanical fragility of these materials is incompatible with process developments, relaying this exciting field to academic curiosity. Here, we show that this drawback can be circumvented by enzyme‐assisted self‐assembly of peptides initiated at the walls of a supporting porous material. We applied this strategy to grow an esterase‐like catalytically active supramolecular hydrogel (CASH) in an open‐cell polymer foam, filling the whole interior space. Our supported CASH material is highly efficient towards inactivated esters and enables the kinetic resolution of racemates. This hybrid material is robust enough to be used in continuous flow reactors, and is reusable and stable over months. [ABSTRACT FROM AUTHOR]

Spring relative gravimeters are considered too unstable to provide useful information on long‐term gravity variations. In this paper, we prove that the new generation of spring gravimeter gPhoneX can reach long‐term stability at the μGal level (10 nm s−2) when the verticality of the gravimeter is maintained, if the instrumental drift can be correctly estimated. We conducted two comparisons with different gPhoneXs in different observatories and environmental conditions. In the "Walferdange Underground Laboratory for Geodynamics" in Luxembourg, we compared time series from the gPhoneX (with and without tilt control), with data from a superconducting gravimeter. We found an agreement at the μGal level when the tilt control is switched on. We validated this result by repeating the experiment at the "Geodesy in Karstic Environment" observatory in the south of France. The fit between the superconducting gravimeter and the gPhoneX hourly values gives similar results at all frequencies over 276 days of measurements. The linear correlation coefficient between the gPhoneX and superconducting gravimeter reaches 0.99, with a misfit of 6.0 nm s−2. We demonstrated that tilt‐controlled gPhoneXs are suitable for long‐term gravity monitoring. Key Points: gPhoneXs are suitable for long‐term gravity monitoring when the tilts are actively controlled [ABSTRACT FROM AUTHOR]

The diffusion of adequate peptide through an enzyme-embedded host hydrogel leads to the in situ start-up and growth of an interpenetrated fibrous network. Based on the enzyme-assisted self-assembly concept, both chemistry and mechanical features of the hybrid hydrogel can be tuned. [ABSTRACT FROM AUTHOR]

Aims Evaluate the participation of IL-17 pathway in T1D pathogenesis. T helper 17 cells are potent, highly inflammatory cells that produce interleukin 17A (IL-17A), considered a mediator of various immune disorders. However, their role in Type 1 diabetes (T1D) pathogenesis in humans is not totally elucidated. Methods The expression of IL-17 Receptor A (IL-17RA) in peripheral T lymphocytes and IL-17A serum levels in recent-onset patients with T1D were compared with healthy controls. IL-17A gene variants were evaluated in a greater cohort. Results Patients with recent-onset T1D (less than 6 months of diagnosis) exhibited lower expression of IL-17RA in CD3+ T (% of cells = 31.3% × 43.6%; p = .041) and CD4+ T cells (11.1% × 25.2%; p = .0019) and lower number of IL-17RA in CD4+ T cells (MFI = 1.16 × 4.56; p = .03) than controls. IL-17RA expression in CD8+ T cells and IL-17A serum levels were similar in both groups. The coding regions and boundary intron sequences of IL17A were sequenced. Seventeen allelic variants, including three novel variants in exon 3 (3′UTR n) were identified, but no one was associated with T1D susceptibility, as well as the resulting haplotypes and diplotypes. The expression of IL-17RA was not correlated with metabolic variables (glucose and HbA1c levels) or pancreatic autoantibodies titers. Conclusions The lower expression of IL-17RA in CD3+ and CD4+ T cells suggests a reduced effect of IL-17A in immune response of recent-onset T1D patients, at least at peripheral tissues. IL-17A allelic variants were not related with T1D susceptibility. [ABSTRACT FROM AUTHOR]

Electrodes are ideal substrates for surface localized self-assembly processes. Spatiotemporal control over such processes is generally directed through the release of ions generated by redox reactions occurring specifically at the electrode. The so-used gradients of ions proved their effectiveness over the last decade but are in essence limited to material-based electrodes, considerably reducing the scope of applications. Herein is described a strategy to enzymatically generate proton gradients from non-conductive surfaces. In the presence of oxygen, immobilization of glucose oxidase (GOx) on a multilayer film provides a flow of protons through enzymatic oxidation of glucose by GOx. The confined acidic environment located at the solid-liquid interface allows the self-assembly of Fmoc-AA-OH (Fmoc=fluorenylmethyloxycarbonyl and A=alanine) dipeptides into β-sheet nanofibers exclusively from and near the surface. In the absence of oxygen, a multilayer nanoreactor containing GOx and horseradish peroxidase (HRP) similarly induces Fmoc-AA-OH self-assembly. [ABSTRACT FROM AUTHOR]

Electrodes are ideal substrates for surface localized self-assembly processes. Spatiotemporal control over such processes is generally directed through the release of ions generated by redox reactions occurring specifically at the electrode. The so-used gradients of ions proved their effectiveness over the last decade but are in essence limited to material-based electrodes, considerably reducing the scope of applications. Herein is described a strategy to enzymatically generate proton gradients from non-conductive surfaces. In the presence of oxygen, immobilization of glucose oxidase (GOx) on a multilayer film provides a flow of protons through enzymatic oxidation of glucose by GOx. The confined acidic environment located at the solid-liquid interface allows the self-assembly of Fmoc-AA-OH (Fmoc=fluorenylmethyloxycarbonyl and A=alanine) dipeptides into β-sheet nanofibers exclusively from and near the surface. In the absence of oxygen, a multilayer nanoreactor containing GOx and horseradish peroxidase (HRP) similarly induces Fmoc-AA-OH self-assembly. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the impact of ambient temperature changes on the gravity reading of spring-based relative gravimeters. Controlled heating experiments using two Scintrex CG5 gravimeters allowed us to determine a linear correlation ( R $$^{2}>$$ 0.9) between ambient temperature and gravity variations. The relation is stable and constant for the two CG5 we used: −5 nm/s $$^{2}/^\circ $$ C. A linear relation is also seen between gravity and residual sensor temperature variations ( R $$^{2}>$$ 0.75), but contrary to ambient temperature, this relation is neither constant over time nor similar between the two instruments. The linear correction of ambient temperature on the controlled heating time series reduced the standard deviation at least by a factor of 2, to less than 10 nm/s $$^{2}$$ . The laboratory results allowed for reprocessing the data gathered on a field survey that originally aimed to characterize local hydrological heterogeneities on a karstic area. The correction of two years of monthly CG5 measurements from ambient temperature variations halved the standard deviation (from 62 to 32 nm/s $$^{2}$$ ) and led us to a better hydrological interpretation. Although the origin of this effect is uncertain, we suggest that an imperfect control of the sensor temperature may be involved, as well as a change of the properties of an electronic component. [ABSTRACT FROM AUTHOR]

In this paper we present the potential of a new compact superconducting gravimeter (GWR iGrav) designed for groundwater monitoring. At first, 3 yr of continuous gravity data are evaluated and the performance of the instrument is investigated. With repeated absolute gravity measurements using a Micro-g Lacoste FG5, the calibration factor (-894.8 nm s-2 V-1) and the long-term drift of this instrument (45 nm s-2 yr-1) are estimated for the first time with a high precision and found to be respectively constant and linear for this particular iGrav. The low noise level performance is found similar to those of previous superconducting gravimeters and leads to gravity residuals coherent with local hydrology. The iGrav is located in a fully instrumented hydrogeophysical observatory on the Durzon karstic basin (Larzac plateau, south of France). Rain gauges and a flux tower (evapo-transpiration measurements) are used to evaluate the groundwater mass balance at the local scale. Water mass balance demonstrates that the karst is only capacitive: all the rainwater is temporarily stored in the matrix and fast transfers to the spring through fractures are insignificant in this area. Moreover, the upper part of the karst around the observatory appears to be representative of slow transfer of the whole catchment. Indeed, slow transfer estimated on the site fully supports the low-flow discharge at the only spring which represents all groundwater outflows from the catchment. In the last part of the paper, reservoir models are used to characterize the water transfer and storage processes. Particular highlights are done on the advantages of continuous gravity data (compared to repeated campaigns) and on the importance of local accurate meteorological data to limit misinterpretation of the gravity observations. The results are complementary with previous studies at the basin scale and show a clear potential for continuous gravity time-series assimilation in hydrological simulations, even on heterogeneous karstic systems. [ABSTRACT FROM AUTHOR]

Regular physical activity has been increasingly valued, both from the therapeutic point of view and aesthetic. Thus, the Pilates® method has become a popular form of exercise for conditioning and rehabilitation, contemplated to improve body contour and muscle tone. The present study aims to investigate the effects of the method in perimetry waist / hip and on the skin folds, checking BMI and ICQ. The sample was randomly selected and constituted 20 women, aged between 20 and 57 years old, with a BMI greater than 20 and less than 30, The subjects were submitted to an assessment by applying physical therapy Assessment Protocol in Adiposity Located - PAFAL. Thus, there was perimetry waist and pre posttreatment hip. The Pilates® exercise program in the soil emphasized strengthening muscles: the shoulder girdle, triceps, abdomen and thigh. For data analysis, we used the SPSS17.0 for Windows by comparing the pre and post-treatment variables using paired t test. Statistically significant differences were observed after treatment with the Pilates® method, with clinical improvement in the anthropome-tric variables. Fold scapular 2.9/2.2 cm; Abdominal 3,1/2, 1cm; triceps 2.7 / 2,1cm; thigh 2.5 / 2.0 cm; perimetry waist 78,5/ 6,7cm and hip 100.3/98,4cm. Thus, it was demonstrated in this study that the practice of Pilates® method in the soil, after 2 months of treatment caused a reduction of skin folds however, there was no change in body mass index (BMI) and waist / hip ratio (WHR). [ABSTRACT FROM AUTHOR]

Organisations are finding it increasingly more difficult to keep abreast with the pace of change. The continuous rise in the number of business opportunities and the increase in global competition require firms to combine internal and external learning processes to renew and reconfigure existing capabilities and knowledge to enable them to meet environmental demands and to innovate. This study aims to unravel the complex linkage between internal learning capacity and absorptive capacity and at exploring the joint effect of both knowledge generation processes on innovation capacity. This study also proposes innovation capacity as an antecedent of business performance. Using data from 952 industrial Spanish firms and the technique of structural equation modelling, we provide evidence on the joint effect of internal learning capacity and absorptive capacity on innovation capacity. We also show that innovation capacity acts as a catalyst for the effect of learning capacities on business performance. [ABSTRACT FROM AUTHOR]

Abstract During mysid culture, Artemia nauplii are traditionally used as food, with the high price of Artemia cysts adding significantly to production costs. In contrast, rotifers (Brachionis plicatilis) are cheaper to produce. As the effects of feeding rotifers to mysids is not well known, the effects of a partial and a total replacement of Artemia nauplii with rotifers were tested in a flowthrough culture system. Mysids used in this study were identified as Leptomysis sp. The three diets tested were: (1) 33% Artemia nauplii + 66% rotifers; (2) 100% Artemia nauplii; and (3) 100% rotifers. Production was similar for diets 1 and 2 (P > 0.05), but significantly lower for diet 3 (P < 0.01). Survival of spawning adults fed diets 1 and 2 was the same (P > 0.05), but spawning adults fed diet 3 (rotifers alone) had significantly lower survival (P < 0.05). In a similar way, hatchling survival was the same for diets 1 and 2 (P > 0.05), but hatchlings fed rotifers alone (diet 3) had significantly lower survival (P < 0.05). In 34 days, mysids fed diets 1, 2 and 3 grew up to 6.7 mm, 6.6 mm and 5.2 mm respectively. Surprisingly, mysid growth was similar among the three diets for 20 days. After 20 days, mysids fed 100% rotifers grew less than mysids fed the other diets. In general, the production, survival and growth of mysids fed the rotifer-exclusive diet was significantly lower than those of the other diets (P < 0.05). Based on the results, the following feeding regime is recommended: (1) feed rotifers during the first 20 days of the life cycle and then (2) feed a diet of Artemia nauplii (33%) and rotifers (66%). This will enhance the large-scale culture of mysids by reducing the cost of their production. [ABSTRACT FROM AUTHOR]

Hydrogel coating is highly suitable in biomaterial design. It provides biocompatibility and avoids protein adsorption leading to inflammation and rejection of implants. Moreover, hydrogels can be loaded with biologically active compounds. In this field, hyaluronic acid has been largely studied as an additional component since this polysaccharide is naturally present in extracellular matrix. Strategies to direct hydrogelation processes exclusively from the surface using a fully biocompatible approach are rare. Herein we have applied the concept of localized enzyme-assisted self-assembly to direct supramolecular hydrogels in the presence of HA. Based on electronic and fluorescent confocal microscopy, rheological measurements and cell culture investigations, this work highlights the following aspects: (i) the possibility to control the thickness of peptide-based hydrogels at the micrometer scale (18–41 µm) through the proportion of HA (2, 5 or 10 mg/mL); (ii) the structure of the self-assembled peptide nanofibrous network is affected by the growing amount of HA which induces the collapse of nanofibers leading to large assembled microstructures underpinning the supramolecular hydrogel matrix; (iii) this changing internal architecture induces a decrease of the elastic modulus from 2 to 0.2 kPa when concentration of HA is increasing; (iv) concomitantly, the presence of HA in supramolecular hydrogel coatings is suitable for cell viability and adhesion of NIH 3T3 fibroblasts. [ABSTRACT FROM AUTHOR]

In an earlier paper the professions were identified as a primarily Anglo- Saxon phenomenon, and associated with economic under-performance. The present paper goes further by questioning the theoretical interpretations of professionalism in the writings of some of the founding fathers, and occasionally of their translators. We variously question here Weber's restricted concept of the entrepreneur, Parsons's rendering of these ideas in English, the assumption that science in general has had a Newtonian character, and that association with science produces a rational disposition in human actors. The view expressed here is that these various misapprehensions - about entrepreneurialism, professionalism, rationality and science - derive from a desire to impose order, to oversimplify phenomena as systems, and to focus on that which may be described and codified, to the neglect of voluntaristic and problematic dimensions. [ABSTRACT FROM AUTHOR]

There tends to be more extensive occupational specialization outside the core production area in British manufacturing companies than in German ones. This appears to be associated with the emphasis in Britain on professionalism in industry, a concept which is largely absent in Germany. The British approach is seen to have unfavourable consequences for the status of production and of manufacturing industry in general, with quite likely depressing effects on its performance. The origins of the contrast between Britain and Germany are explored by reference to the development of post-school vocational education in the two countries, and this leads to the conclusion that strategic choices about contemporary work organization were in effect made at a societal level a century ago. The analysis indicates that industrial policy cannot be confined to changes within the industrial sector atone. [ABSTRACT FROM AUTHOR]

Discusses the concepts and relationships of Homo and Machina, fictional names given by the author to man and machine respectively in the context of industrial revolution. Different phases of economic, industrial and scientific revolutions; Features and types of machines; Human traits and articulation trap; Karl Marx's theory; Link between active man and active machine; Francis Bacon's history of marvel.

It has been proposed, and accepted, commonly, often as part of a whiggish tale of humanity breaking the shackles of the past, that an Early Modem Europe paved the way, with its Scientific Revolution, for an "industrial condition' to come. Yet interpretations of that 'revolution' have involved making some suspect general conclusions about a new. standard 'rationality' of conduct and a new norm suitable for constructed science, Furthermore, commonly-accepted generalizations about the advent and spread of Industrial Revolution are not well supported by the available evidence, especially where the case has been linked to an indistinct 'science.' [ABSTRACT FROM AUTHOR]

A need for new antidepressants is necessary since traditional antidepressants have several flaws. Neuropeptide Y(NPY) Y1 receptor (NPYY1R) and galanin (GAL) receptor 2 (GALR2) interact in several regions of the limbic system, including the hippocampus. The current study assesses the antidepressant effects induced by GALR2 and NPYY1R coactivation, together with the evaluation of cell proliferation through 5‐Bromo‐2'‐deoxyuridine expression within the dentate gyrus of the ventral hippocampus (vDG). We employed in situ proximity ligation assay to manifest GALR2/NPYY1R heteroreceptor complexes. Additionally, the expression pattern of GALR2 and the activation of the extracellular‐regulated kinases (ERK) pathway after GALR2 and NPYY1R costimulation in cell cultures were examined. GALR2 and NPYY1R coactivation resulted in sustained antidepressant behaviors in the FST after 24 h, linked to increased cell proliferation in the vDG. Moreover, an increased density of GALR2/NPYY1R heteroreceptor complexes was observed in vDG, on doublecortin‐expressing neuroblasts. Recruitment of the GALR2 expression to the plasma membrane was observed upon the coactivation of GALR2 and NPYY1R in cell cultures, presumably associated to the enhanced effects on the activation of ERK pathway. GALR2 may promote the GALR2/NPYY1R heteroreceptor complexes formation in the ventral hippocampus. It may induce a transformation of cell proliferation toward a neuronal lineage by enhancement of ERK pathway. Thus, it may give the mechanism for the antidepressant behavior observed. These results may provide the basis for the development of heterobivalent agonist pharmacophores, targeting GALR2/NPYY1R heteromers, especially in the neuronal precursor cells of the dentate gyrus in the ventral hippocampus for the novel treatment of depression. [ABSTRACT FROM AUTHOR]

A letter to the editor about spinal myoclonus in a patient who received intradural anaesthesia with prilocaine is presented.

Most of water reservoirs are underground and therefore challenging to monitor. This is particularly the case of karst aquifers which knowledge is mostly based on sparse spatial and temporal observations. In this study, we propose a new approach, based on a supervised machine learning algorithm, the Random Forests, and continuous seismic noise records, that allows the prediction of the underground river water height. The study site is a karst aquifer in the Jura Mountains (France). An underground river is accessible through an artificial shaft and is instrumented by a hydrological probe. The seismic noise generated by the river is recorded by two broadband seismometers, located underground (20 m depth) and at the surface. The algorithm succeeds in predicting water height thanks to signal energy features. Even weak river-induced noise such as recorded at the surface can be detected and used by the algorithm. Its efficiency, expressed by the Nash–Sutcliffe criterion, is above 95 per cent and 53 per cent for data from the underground and surface seismic stations, respectively. [ABSTRACT FROM AUTHOR]

Objectives: To determine the rates at which women received screening Papanicolaou tests, clinical breast examinations, and mammography and to determine the extent to which these women might be expected to respond to screening recommendations from their physicians.Design: Random-digit-dial telephone interviews conducted in January 1993.Setting: Fifteen counties in southeastern Minnesota.Subjects: A sample of 1019 women who completed the telephone interview.Main Outcome Measures: Self-reported Papanicolaou test, clinical breast examination, and mammography screening rates, with verification from medical records for a randomly selected subsample of 200 respondents who reported having had a test within 1 year of the interview.Results: For women aged 18 years and older, 60% (95% confidence interval, +/- 3.4%) reported having had a Papanicolaou test within the preceding year. For women 40 years of age and older, 57% (95% confidence interval, +/- 3.5%) reported having had a clinical breast examination in the past year, and 46% (95% confidence interval, +/- 3.6%) reported having had a screening mammogram within 1 year. The verified 1-year Papanicolaou test and mammogram rates were 35% and 33%, respectively. More than 90% of the respondents expressed a willingness to have these tests if their physicians were to advise them that the tests were indicated. However, 53% and 54% of the respondents, respectively, said that they either did not care or did not want their physicians to remind them when they were due for a Papanicolaou test or a mammogram.Conclusions: Although self-reported screening rates in this population meet Healthy People 2000 goals, verified rates were significantly below target levels. A substantial proportion of women in this population remain ambivalent about participating in cancer detection programs. [ABSTRACT FROM AUTHOR]

Background: The voltage gated K+ channels Kv1.3 and Kv1.5 contribute to the orchestration of cell proliferation. Kinases participating in the regulation of cell proliferation include protein kinase B (PKB/Akt). The present study thus explored whether PKB/Akt modifies the abundance and function of Kv1.3 and Kv1.5. Methods: Kv1.3 or Kv1.5 was expressed in Xenopus laevis oocytes with or without wild-type PKB/Akt, constitutively active T308D/S473DPKB/Akt or inactive T308A/S473APKB/Akt. The channel activity was quantified utilizing dual electrode voltage clamp. Moreover, HAtagged Kv1.5 protein was determined utilizing chemiluminescence. Results: Voltage gated K+ currents were observed in Kv1.3 or Kv1.5 expressing oocytes but not in water-injected oocytes or in oocytes expressing PKB/Akt alone. Co-expression of PKB/Akt or T308D/S473DPKB/Akt, but not coexpression of T308A/S473APKB/Akt significantly increased the voltage gated current in both Kv1.3 and Kv1.5 expressing oocytes. As shown for Kv1.5, co-expression of PKB/Akt enhanced the channel protein abundance in the cell membrane. In Kv1.5 expressing oocytes voltage gated current decreased following inhibition of carrier insertion by brefeldin A (5 µM) to similarly low values in the absence and presence of PKB/Akt, suggesting that PKB/Akt stimulated carrier insertion into rather than inhibiting carrier retrieval from the cell membrane. Conclusion: PKB/Akt up-regulates both, Kv1.3 and Kv1.5 K+ channels. [ABSTRACT FROM AUTHOR]

Drug delivery systems that release hydrophobic drugs with zero-order kinetics remain rare and are often complicated to use. In this work, we present a gellified emulsion (emulgel) that comprises oil droplets of a hydrolyzable oil entrapped in a hydrogel. In the oil, we incorporate various hydrophobic drugs and, because the oil hydrolyzes with zero-order kinetics, the release of the drugs is also linear. We tune the release period from three hours to 50 h by varying the initial oil concentration. We show that the release rate is tunable by varying the initial drug concentration. Our quantitative understanding of the system allows for predicting the drug release kinetics once the drug's partition coefficient between the oil and the aqueous phase is known. Finally, we show that our drug delivery system is fully functional after storing it at −20 °C. Cell viability studies show that the hydrolyzable oil and its hydrolysis product are non-toxic under the employed conditions. With its simplicity and versatility, our system is a promising platform for the zero-order release of the drug. [Display omitted] • Emulsions of hydrolyzable oils can deliver hydrophobic drugs with zero-order kinetics. • The drug release rate and period can be tuned. • The formulation can be stored. • The hydrolyzable oils and hydrolysis products are not toxic for cells. • Various drugs can be release linearly with this system. [ABSTRACT FROM AUTHOR]

The emergence of bacterial strains resistant to antibiotics is a major issue in the medical field. Antimicrobial peptides are widely studied as they do not generate as much resistant bacterial strains as conventional antibiotics and present a broad range of activity. Among them, the homopolypeptide poly(l -arginine) presents promising antibacterial properties, especially in the perspective of its use in biomaterials. Linear poly(l -arginine) has been extensively studied but the impact of its 3D structure remains unknown. In this study, the antibacterial properties of newly synthesized branched poly(l -arginine) peptides, belonging to the family of multiple antigenic peptides, are evaluated. First, in vitro activities of the peptides shows that branched poly(l -arginine) is more efficient than linear poly(l -arginine) containing the same number of arginine residues. Surprisingly, peptides with more arms and more residues are not the most effective. To better understand these unexpected results, interactions between these peptides and the membranes of Gram positive and Gram negative bacteria are simulated thanks to molecular dynamic. It is observed that the bacterial membrane is more distorted by the branched structure than by the linear one and by peptides containing smaller arms. This mechanism of action is in full agreement with in vitro results and suggest that our simulations form a robust model to evaluate peptide efficiency towards pathogenic bacteria. [Display omitted] • 3D structures of branched polyarginine impact on their antibacterial properties. • Shorter polyarginine are not those with the most antimicrobial activities. • Polyarginines destabilize the outer membrane of Gram-positive or -negative bacteria. • Molecular simulations improve the understanding of polycation mechanisms against bacteria. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships with sex, age, lipid profile, C-reactive protein, and Brain-derived neurotrophic factor (BDNF) genotype in a sample of 648 healthy participants over 50 years of age with a comprehensive neuropsychological assessment. Our results showed that APOE ε2 carriers performed better in the Verbal Memory (p = .002) and Fluency Domains (p = .001). When we studied the effect of sex, we observed that the beneficial effect of APOE ε2 on the normalized values of these cognitive domains occurred only in females (β = 0.735; 95% confidence interval, 0.396-1.074; p = 3.167·10-5 and β = 0.568; 95% confidence interval, 0.276-0.861; p = 1.853·10-4, respectively). Similarly, the sex-specific effects of APOE ε2 were further observed on lipidic and inflammation biomarkers. In the whole sample, APOE ε2 carriers showed significantly lower levels of total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. These differences were found only among females. Furthermore, total cholesterol and low-density lipoprotein cholesterol mediated the protective effect of APOE ε2 on cognition in the whole sample and total cholesterol in females, providing candidate physiological mechanisms for the observed genetic effects. Our results show that the neuroprotective role of APOE ε2 in cognition varies with sex and that the lipidic profile partially mediates this protection. Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories (1). Complex interactions between heritability, environmental influence, and cognitive functions in aging have been highlighted (2). In particular, genetic differences explain around 15%-25% of the variance in life expectancy (3). Therefore, the identification of susceptibility genes and their biological effects on cognitive aging is required to establish interindividual differences in this process and promote early personalized interventions to delay cognitive decline and minimize the financial burden of aging in the health care system. [ABSTRACT FROM AUTHOR]

Objective: To assess the effectiveness of Extracorporeal Shock Wave Therapy for reducing spasticity and improving functionality of the upper limb in stroke survivors. Data sources: A systematic review of MEDLINE, Cochrane Central Register of Controlled Trials, CINAHL, PEDro, REHABDATA, Scielo, Scopus, Web of Science, Tripdatabase and Epistemonikos from 1980 to April 2020 was carried out. Review methods: The bibliography was screened to identify randomized controlled clinical trials that applied extracorporeal shock waves to upper limb spastic muscles in post-stroke individuals. Two reviewers independently screened references, selected relevant studies, extracted data and assessed risk of bias using the PEDro scale. The primary outcome was spasticity and functionality of the upper limb. Results: A total of 1,103 studies were identified and 16 randomized controlled trials were finally included (764 individuals) were analyzed. A meta-analysis was performed and a beneficial effect on spasticity was found. The mean difference (MD) on the Modified Ashworth Scale for comparison extracorporeal shock wave versus sham was −0.28; with a 95% confidence interval (CI) from −0.54 to −0.03. The MD of the comparison of extracorporeal shock wave plus conventional physiotherapy versus conventional physiotherapy was −1.78; 95% CI from −2.02 to −1.53. The MD for upper limb motor-function using the Fugl Meyer Assessment was 0.94; 95% CI from 0.42 to 1.47 in the short term and 0.97; 95% CI from 0.19 to 1.74 in the medium term. Conclusion: The extracorporeal shock wave therapy is effective for reducing upper limb spasticity. Adding it to conventional therapy provides an additional benefit. [ABSTRACT FROM AUTHOR]

A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different (Mn1-R9 < Mn1-MPP < Mn1-RW9 < Mn1), as well as their subcellular distribution. In addition, the three functionalized-complexes display a better anti-inflammatory activity than Mn1 when assayed at 10 μM. This improvement is due to a combination of an anti-inflammatory effect of the peptidyl moiety itself, and of the SOD mimic for Mn1-RW9 and Mn1-MPP. In contrast, the enhanced anti-inflammatory activity of Mn1-R9 is solely due to the SOD mimic. [ABSTRACT FROM AUTHOR]

Aim The recent epidemic of Zika Virus in the United States has necessitated screening for the presence of this agent in high-risk transplant solid organ donors to avoid the transmission to potential recipients. In this study, we performed a retrospective analysis of Cadaver Donors from Auxilio Mutuo Hospital (HAM) in Puerto Rico. Methods One hundred fifty-six (156) serum samples from Deceased Donors were obtained from Puerto Rico. Aliquots of serum, were maintained at −20 °C since collection. There were 38 samples from 2014, 62 from 2015, and 56 from 2016. These samples were tested with the RealStar® Zika Virus RT-PCR Kit U.S.® kit (Altona Diagnostics), and Anti-Zika Virus ELISA IgG and IgM kits (EUROIMMUN). These assays were validated with a separate group of freshly obtained Zika-positive samples from an ambulatory clinic at HAM. Results Of the 156 total deceased donor specimens retrospectively tested, none were positive for PCR, 2 were positive for IgM, and 22 were positive or borderline for IgG. The breakdown over the 3-year period indicated an increase in long-term exposure, as indicated by the increase in IgG positive samples. In 2014, only 5.2% were positive. However, by 2015 19.4% of the samples were positive. This indicates that almost 20% of the Deceased Donors tested had some contact with the Zika Virus (or a related Flavivirus , such as Dengue or West Nile). Of the positive IgG samples, only 2 were positive for IgM, indicating the exposure was likely more than 3 months prior. The results of the PCR study were not surprising, as we have seen in our laboratory, the long-term storage of serum for later RNA-based PCR testing has been unsuccessful. Conclusions Zika testing utilizing PCR-based assays in conjunction with serological assays in areas of known infection is essential, especially when servicing solid organ transplant programs. The use of donors potentially infected with Zika virus could have a significant impact in transplant success as there are some indications that immunocompromised individuals may develop more severe symptoms or illnesses. The correct storage of serum samples is crucial to obtain reliable results of this test. [ABSTRACT FROM AUTHOR]

The wine industry produces large quantities of wastewater that often contains high levels of organic matter and nutrients, like nitrogen and phosphorous. In particular, nitrogen pollution can be harmful, even at low levels, since infants are vulnerable to nitrates in drinking water, and excess nitrogen can harm the health of soils and waterways. Herein, an innovative compact, modular, and mobile treatment wetland (TW) using cork by product as the only granular media was used to treat the final effluents from the Codorniu winery (Sant Sadurní d'Anoia, Spain). The TW was operated during two 5-month periods with or without intermittent induced aeration (40 min cycles, 90 L/min air flow rate). Nitrate (N-NO 3) and total nitrogen (TN) removal were higher (52.8% and 46.8%, respectively, p < 0.05) during TW operation under aerated-condition. Additionally, q PCR analysis of 16S rRNA, nir S and nos Z genes revealed that intermittent induced aeration facilitates N-NO 3 reduction by the stimulation of denitrifying bacteria in the TW biofilm (11.4% increase in nir S copies number/g cork sample, p < 0.05) as well as increasing the number of heterotrophic bacteria adhered to cork (25.5% increase in 16S rRNA copies number/g cork sample, p < 0.05). Moreover, SEM images demonstrated the suitability of cork as a resistant filter media for TW after long-term system operation (1.5 years). In conclusion, our results suggest that aeration improved nitrogen compounds removal compared to the non-aerated period, without affecting phosphorous elimination. Additionally, residual cork is presented here in a circular bioeconomy view, as a suitable filling media to treat winery wastewater that can provide additional carbon source to increase C/N rate stimulating denitrification, as well as a reliable organic substrate for biomass growth. [Display omitted] • Cork filled TW could be an appropriate technology to treat and/or remediate winery wastewater with high nitrate content. • The induced aeration in a vertical TW using cork as filter medium showed higher removal rates for NO 3 -N and TN. • The saturated-aerated vertical TW increased microbial abundance with the presence of the denitrification genes nir S and nos Z. • The nir S genes showed higher relative abundance than nos Z. [ABSTRACT FROM AUTHOR]

Background Umbilical cord blood transplantation ( CBT) is an established alternative source of stem cells in the setting of unrelated transplantation. When compared with other sources, single-unit CBT ( sCBT) is associated with a delayed hematologic recovery, which may lead to a higher infection-related mortality ( IRM). Co-infusion with the sCBT of CD34+ peripheral blood stem cells from a third-party donor ( TPD) ( sCBT + TPDCD34+) has been shown to markedly accelerate leukocyte recovery, potentially reducing the IRM. However, to our knowledge, no comparative studies have focused on severe infections and IRM with these 2 sCBT strategies. Methods A total of 148 consecutive sCBT (2000-2010, median follow-up 4.5 years) were included in a multicenter retrospective study to analyze the incidence and risk factors of IRM and severe viral and invasive fungal infections ( IFIs). Neutrophil engraftment occurred in 90% of sCBT ( n = 77) and 94% sCBT + TPDCD34+ ( n = 71) recipients at a median of 23 and 12 days post transplantation, respectively ( P < 0.01). Results The 4-year IRM was 24% and 20%, respectively ( P = 0.7), with no differences at day +30 (5% and 4%, respectively) and day +100 (10% and 8%, respectively). In multivariate analysis early status of the underlying malignancy, cytomegalovirus ( CMV)-seronegative recipient and high CD34+ cell content in the cord blood unit before cryostorage (≥1.4 × 105/kg) were protective of IRM. Among the causes of IRM, bacterial infections and IFIs were more common in sCBT (15% vs. 4%), while CMV disease and parasitic infections were more common in the sCBT + TPDCD34+ cohort (5% vs. 16%). Conclusion These data show that sCBT supported with TPDCD34+ cells results in much shorter periods of post-transplant leukopenia, but the short- and long-term rates of IRM were comparable to those of sCBT, presumably because immune recovery is equally delayed in both graft types. [ABSTRACT FROM AUTHOR]

Among the strategies to optimize engraftment of cord blood (CB) stem cell transplantation (SCT), single CB with the coinfusion of CD34 + stem cells from an HLA-mismatched auxiliary donor (haplo-cord) provides a valid alternative for adult patients without a suitable donor. A total of 132 high-risk adult patients with hematological malignancies from 3 Spanish institutions underwent myeloablative haplo-cord SCT. The median age was 37 years and median weight was 70 kg; 37% had active disease. The median number of postprocessing CB total nucleated and CD34 + cells was 2.4 × 10 7 /kg (interquartile range [IQR], 1.8 to 2.9) and 1.4 × 10 5 /kg (IQR, .9 to 2), respectively. Neutrophil engraftment occurred in a median of 11.5 days (IQR, 10.5 to 16.5) and platelet engraftment at 36 days (IQR, 25.5 to 77). Graft failure was 2% overall and only 9% for CB. Cumulative incidence of acute graft-versus-host disease (GHVD) grades II to IV was 21% and cumulative incidence of chronic GVHD was 21%. Median follow-up was 60 months (range, 3.5 to 163). Overall survival was 43.5%, event-free survival was 38.3%, nonrelapse mortality was 35%, and relapse was 20% at 5 years. Myeloablative haplo-cord SCT results in fast engraftment of neutrophils and platelets, low incidences of acute and chronic GVHD, and favorable long-term outcomes using single CB units with relatively low cell content. Moreover, CB cell dose had no impact on CB engraftment and survival in this study. Therefore, haplo-cord SCT expands donor availability while reducing CB cell dose requirements. [ABSTRACT FROM AUTHOR]

Abstract: Both alterations in neurodevelopment and aversive experiences during childhood and adolescence seem important risk factors for schizophrenia. Animal models reproducing these alterations mimic some of the symptoms, constituting a valid approach to study the etiopathology of this disorder. Among these models, the perinatal injection of N-methyl-d-aspartate receptor antagonists and the postweaning social isolation rearing are among the most widely used. Our aim is to combine them in a “double hit” model, which should produce a wider spectrum of alterations. Lister Hooded rats have been subjected to a single injection of MK-801 at postnatal day 7 and socially isolated from postweaning to adulthood. These animals presented increased body weight gain and volume reductions in their medial prefrontal cortex (mPFC) and hippocampus. They also showed an increased number of activated pyramidal neurons and alterations in the numbers of parvalbumin and calbindin expressing interneurons in the mPFC. The expressions of the polysialylated form of the neural cell adhesion molecule and GAD67 are decreased in the mPFC. The mRNA level of calbindin was decreased, while that of calretinin was increased in the mPFC. The mRNA level of ERbB4, a gene associated to schizophrenia, was also altered in this region. All these structural and neurochemical alterations, specially in cortical inhibitory circuits, are similar to those found in schizophrenic patients and are more numerous than in each of the single models. Consequently, the present “double hit” model may be a better tool to study the neurobiological basis of schizophrenia and to explore new therapeutic approaches. [Copyright &y& Elsevier]

The article focuses on the comparison between the diagnostic accuracy of self-administered screening tests and examination methodology of general practitioner for diagnosing mood disorders. It mentions that mood disorders include depressive and bipolar disorders most commonly occurring in the U.S. It states that treatment options for mood disorders are available at primary care facilities which are not timely employed due to late diagnosis.

Abstract: A regiospecific and high diastereoselective synthesis of trans-glycidic amides coming from a common pseudoephedrine sulfonium salt 2 precursor is presented. This is the first example in where the diastereoselectivity is controlled by a chiral noncyclic amide fragment. The epoxidation reaction provides alkyl or aryl glycidic amides in good to excellent yields and exclusive trans selectivity. Finally, through of a chemospecific 6-exo-tet ring closure of trans-epoxyamides we access to morpholin-3-ones densely functionalized with excellent chemical and stereochemical yields. [Copyright &y& Elsevier]

Background aims Cord blood (CB) transplants with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC) have been shown to result in 'bridge' engraftment with prompt neutrophil recovery and high final rates of CB engraftment and full chimerism. This strategy overcomes the limitation posed by low cellularity of CB units for unrelated transplants in adults. Enhancement of adaptive immunity reconstitution without increasing risks of graft-versus-host disease (GvHD) is required to optimize results further. Our objectives were to evaluate co-infusion of mesenchymal stromal cells (MSC) from the same TPD regarding tolerance, CB engraftment and effects on acute (a)GvHD, both preventive and therapeutic. Methods Ex vivo-expanded bone marrow MSC were infused at the time of the transplant or the in case of refractory aGvHD. Results Nine patients received 1.04-2.15×106/kg (median 1.20) MSC immediately after CB and TPD MHSC. Neither immediate adverse side-effects nor significant differences regarding CB engraftment or aGvHD development were observed. Four patients developed grade II aGvHD, refractory to steroids in two. These reached complete remission after therapeutic infusions of MSC. Conclusions In recipients of 'dual CB/TPD MHSC transplants', MSC infusions were therapeutically effective for severe aGvHD but no significant differences in CB engraftment and incidence of severe aGvHD were observed following their prophylactic use. Although results of this study alone cannot conclusively determine the application of MSC in CB transplantation, we believe that, in this setting, the best use of MSC could be as pre-emptive treatment for aGvHD. [ABSTRACT FROM AUTHOR]