Climate Influence on Emerging Risk Areas for Rift Valley Fever Epidemics in Tanzania.
Rift Valley Fever (RVF) is a climate-related arboviral infection of animals and humans. Climate is thought to represent a threat toward emerging risk areas for RVF epidemics globally. The objective of this study was to evaluate influence of climate on distribution of suitable breeding habitats for Culex pipiens complex, potential mosquito vector responsible for transmission and distribution of disease epidemics risk areas in Tanzania. We used ecological niche models to estimate potential distribution of disease risk areas based on vectors and disease co-occurrence data approach. Climatic variables for the current and future scenarios were used as model inputs. Changes in mosquito vectors' habitat suitability in relation to disease risk areas were estimated. We used partial receiver operating characteristic and the area under the curves approach to evaluate model predictive performance and significance. Habitat suitability for Cx. pipiens complex indicated broad-scale potential for change and shift in the distribution of the vectors and disease for both 2020 and 2050 climatic scenarios. Risk areas indicated more intensification in the areas surrounding Lake Victoria and northeastern part of the country through 2050 climate scenario. Models show higher probability of emerging risk areas spreading toward the western parts of Tanzania from northeastern areas and decrease in the southern part of the country. Results presented here identified sites for consideration to guide surveillance and control interventions to reduce risk of RVF disease epidemics in Tanzania. A collaborative approach is recommended to develop and adapt climate-related disease control and prevention strategies.


BN-PVDF/rGO-PVDF Laminate Nanocomposites for Energy Storage Applications.
The increasing demand for high energy storage devices calls for concurrently enhanced dielectric constants and reduced dielectric losses of polymer dielectrics. In this work, we rationally design dielectric composites comprising aligned 2D nanofillers of reduced graphene oxide (rGO) and boron nitride nanosheets (BNNS) in a polyvinylidene fluoride (PVDF) matrix through a novel press-and-fold technique. Both nanofillers play different yet complementary roles: while rGO is designed to enhance the dielectric constant through charge accumulation at the interfaces with polymer, BNNS suppress the dielectric loss by preventing the mobility of free electrons. The microlaminate containing eight layers each of rGO/PVDF and BNNS/PVDF films exhibits remarkable dielectric performance with a dielectric constant of 147 and an ultralow dielectric loss of 0.075, due to the synergistic effect arising from the alternatingly electrically conductive and insulating films. Consequently, a maximum energy density of 3.5 J/cm3-about 18 times the bilayer composite counterpart-is realized. The high thermal conductivities of both nanofillers and their alignment endow the microlaminate with an excellent in-plane thermal conductivity of 6.53 Wm-1K-1, potentially useful for multifunctional applications. This work offers a simple but effective approach to fabricating a composite for high dielectric energy storage using two different 2D nanofillers.


Infectious complications of pentostatin therapy.
Managing the infectious complications associated with pentostatin (Nipent), used alone or in combination with other agents in patients with low-grade lymphomas, poses a significant problem for clinicians. Since there is limited experience with these therapies, definitive treatment recommendations concerning prophylaxis cannot be made. The panel members discussed the use of valacyclovir (Valtrex) to provide prophylaxis for herpes zoster, trimethoprim/sulfamethoxazole for Pneumocystis, and acyclovir (Zovirax) for varicella zoster. They also considered combinations of pentostatin with agents such as interferon, rituximab (Rituxan), and chlorambucil (Leukeran) and their effect on the immune system. The biology of B and T cells was discussed, with an emphasis on clinical application.


Deep-sea biodiversity in the Mediterranean Sea: the known, the unknown, and the unknowable.
Deep-sea ecosystems represent the largest biome of the global biosphere, but knowledge of their biodiversity is still scant. The Mediterranean basin has been proposed as a hot spot of terrestrial and coastal marine biodiversity but has been supposed to be impoverished of deep-sea species richness. We summarized all available information on benthic biodiversity (Prokaryotes, Foraminifera, Meiofauna, Macrofauna, and Megafauna) in different deep-sea ecosystems of the Mediterranean Sea (200 to more than 4,000 m depth), including open slopes, deep basins, canyons, cold seeps, seamounts, deep-water corals and deep-hypersaline anoxic basins and analyzed overall longitudinal and bathymetric patterns. We show that in contrast to what was expected from the sharp decrease in organic carbon fluxes and reduced faunal abundance, the deep-sea biodiversity of both the eastern and the western basins of the Mediterranean Sea is similarly high. All of the biodiversity components, except Bacteria and Archaea, displayed a decreasing pattern with increasing water depth, but to a different extent for each component. Unlike patterns observed for faunal abundance, highest negative values of the slopes of the biodiversity patterns were observed for Meiofauna, followed by Macrofauna and Megafauna. Comparison of the biodiversity associated with open slopes, deep basins, canyons, and deep-water corals showed that the deep basins were the least diverse. Rarefaction curves allowed us to estimate the expected number of species for each benthic component in different bathymetric ranges. A large fraction of exclusive species was associated with each specific habitat or ecosystem. Thus, each deep-sea ecosystem contributes significantly to overall biodiversity. From theoretical extrapolations we estimate that the overall deep-sea Mediterranean biodiversity (excluding prokaryotes) reaches approximately 2805 species of which about 66% is still undiscovered. Among the biotic components investigated (Prokaryotes excluded), most of the unknown species are within the phylum Nematoda, followed by Foraminifera, but an important fraction of macrofaunal and megafaunal species also remains unknown. Data reported here provide new insights into the patterns of biodiversity in the deep-sea Mediterranean and new clues for future investigations aimed at identifying the factors controlling and threatening deep-sea biodiversity.


Proper use of serum antibody titres against Epstein-Barr virus in nasopharyngeal carcinoma: IgA/virus capsid antigen for diagnosis and EBV-related nuclear antigen-2 for follow-up.
Sera from patients with nasopharyngeal carcinoma (NPC) show high titres of IgA antibodies to Epstein-Barr viral capsid antigen (IgA/VCA). We reported previously that the serum titres for Epstein-Barr virus-related nuclear antigen-2 (EBNA2) correlated with NPC patients' prognosis. To investigate which is better for diagnosing NPC and predicting patient prognosis, the titration of serum IgA/VCA or EBNA2, we examined the same serum titres. Sixteen cases of NPC in which serum EBNA2 antibody titres had been tested, were investigated for the serum IgA/VCA antibody titres before and after radiation treatment. All NPC cases showed positive reactions with indirect immunofluorescence staining, and the median titre was 252. Twelve normal controls, 5 mesopharyngeal carcinoma patients, 4 hypopharyngeal carcinoma patients, 4 laryngeal carcinoma patients and 6 malignant lymphoma were also examined, but they showed negative or relatively low titres. A follow-up study revealed that IgA/VCA titres remained mostly stable. These results indicate a close relationship between IgA/VCA and NPC, however, prognosis correlated better with EBNA2 titres than with IgA/VCA titres.


[The role of introns in evolution].
The article describes the role of introns in eukaryotic evolution. Polymorhpsms generated in intronic regions included in the reading frame splice isoforms can alter the properties of the alternative product. It provides a framework to adapt to changing conditions of life. This is the basis for the adaptation of eukaryotes to changing conditions of life, that by evolution is fixed at the level of populations and species. The article describes the mechanisms of the dynamics properties of the eukaryotic genome, and the role of associative combinations in the genesis of multifactorial diseases.


EnsCat: clustering of categorical data via ensembling.
Clustering is a widely used collection of unsupervised learning techniques for identifying natural classes within a data set. It is often used in bioinformatics to infer population substructure. Genomic data are often categorical and high dimensional, e.g., long sequences of nucleotides. This makes inference challenging: The distance metric is often not well-defined on categorical data; running time for computations using high dimensional data can be considerable; and the Curse of Dimensionality often impedes the interpretation of the results. Up to the present, however, the literature and software addressing clustering for categorical data has not yet led to a standard approach. We present software for an ensemble method that performs well in comparison with other methods regardless of the dimensionality of the data. In an ensemble method a variety of instantiations of a statistical object are found and then combined into a consensus value. It has been known for decades that ensembling generally outperforms the components that comprise it in many settings. Here, we apply this ensembling principle to clustering. We begin by generating many hierarchical clusterings with different clustering sizes. When the dimension of the data is high, we also randomly select subspaces also of variable size, to generate clusterings. Then, we combine these clusterings into a single membership matrix and use this to obtain a new, ensembled dissimilarity matrix using Hamming distance. Ensemble clustering, as implemented in R and called EnsCat, gives more clearly separated clusters than other clustering techniques for categorical data. The latest version with manual and examples is available at https://github.com/jlp2duke/EnsCat .


Family caregivers' experiences with community services: a qualitative analysis.
Researchers of family caregiving have presented mixed results in evaluating the effectiveness of community services in reducing family caregiver stress and have indicated that many caregivers use limited services or access services late in their caregiving experience. The purpose of this study was to describe the experience of the use of community services, including benefits and barriers, by family caregivers of relatives with Alzheimer's disease or a related disorder. Community services included assistance with caregiving or related tasks and educational or emotional support that was provided by health professionals or community service providers. In this qualitative descriptive study, a convenience sample of 21 family caregivers was interviewed. Open-ended questions were used to explore the caregivers' experiences with community services. Transcribed data were analyzed using qualitative content-analysis techniques. Results indicated that family caregivers received benefits of renewal, sense of community, and new knowledge and believed that their patient benefited from the services. Barriers to service use included care receiver resistance, reluctance of the caregiver, hassles for the caregiver, concerns over quality, and concerns over finances. These findings provide direction for community nurses and other health professionals in targeting interventions that will meet the expressed needs of caregivers.


A model-based evaluation of sorptive reactivities of hydrous ferric oxide and hematite for U(VI).
The sorption of uranyl onto hydrous ferric oxide (HFO) or hematite was measured by discontinuously titrating the suspensions with uranyl at pH 5.9, 6.8, and 7.8 under Pco2 = 10(-35)atm (sorption isotherms). Batch reactors were used with equilibration times up to 48 days. Sorption of 1 microM uranyl onto HFO was also measured versus pH (sorption edge). A diffuse double layer surface complexation model was calibrated by invoking three sorption species that were consistent with spectroscopic evidence for predominance of bidentate complexes at neutral pH and uranyl-carbonato complexes: > SOH:UO2OH(+1), (> SO)2: UO2CO3(-2), and (> SO)2:(UO2)3(OH)5(-1). The model was consistent with previously published isotherm and edge data. The model successfully predicted sorption data onto hematite, only adjusting for different measured specific surface area. Success in application of the model to hematite indicates that the hydrated surface of hematite has similar sorptive reactivity as HFO.


Myocardial ischaemia and ventricular arrhythmias precipitated by physiological concentrations of adrenaline in patients with coronary heart disease.
The clinical and haemodynamic effects of adrenaline infusion (30 ng kg-1 min-1) producing plasma adrenaline concentrations in the range seen during acute myocardial infarction and of placebo were investigated in a crossover design in 14 patients with stable coronary heart disease. Adrenaline infusion resulted in electrocardiographic evidence of myocardial ischaemia (greater than or equal to 1 mm (0.1 mV) horizontal or downsloping ST segment depression) in 10 patients and angina in four, although the mean (SEM) increase in heart rate was modest (14 (2) beats/min) and mean coronary vascular resistance fell from 1.56 (0.21) to 1.16 (0.14) mm Hg min ml-1 (p less than 0.005). New or increasingly frequent or complex ventricular arrhythmias occurred in five patients. Placebo infusion had no effect on the variables measured. Supine bicycle exercise during infusion of the saline placebo was associated with a similar degree of ST segment depression (0.9 (0.2) mm) as adrenaline infusion at rest (0.9 (0.1) mm) but exercise performed during adrenaline infusion (10 patients) resulted in more pronounced ST segment depression (1.9 (0.3) mm) (p less than 0.005) than either intervention alone. Angina occurred in three of 11 patients during control exercise and in six of 10 during the combination of adrenaline infusion and exercise. Such potentially adverse consequences of low dose adrenaline infusion in patients with stable coronary heart disease are consistent with the suggestion that adrenal activation is detrimental during acute myocardial infarction, being both arrhythmogenic and proischaemic.


Lives of Skin Lesions in Monkeypox: Histomorphological, Immunohistochemical, and Clinical Correlations in a Small Case Series.
Monkeypox (mpox), a former rare viral zoonosis, has increasingly made it into the public eye since the major outbreak that started in May 2022. Mpox presents with skin lesions that change over time and go through different stages (macular, papular, pustular, and early and late ulceration). In this study, we evaluated skin biopsies of all stages. Therefore, five biopsies from four patients were analyzed histologically, immunohistochemically with anti-Vaccinia virus antibodies, and electron-microscopically. Notably, the early macular stage only showed subtle viropathic changes; it did not express of Orthopoxvirus proteins in immunohistochemistry and therefore can easily be missed histologically. In later stages, immunohistochemistry with anti-Vaccinia virus antibodies might be useful to distinguish mpox from differential diagnoses such as herpes virus infections. In the ulcerative stages, the identified occlusive vasculopathic changes could be an explanation for the severe pain of the lesions reported by some patients. Despite the small number of samples examined, our analysis suggests that the histological findings of mpox are highly dependent on the stage of the biopsied lesion. Therefore, knowledge of all different stages of histology is necessary to reliably diagnose mpox histologically, especially when molecular testing is not available.


Clinicopathological characterization of Pick's disease versus frontotemporal lobar degeneration with ubiquitin/TDP-43-positive inclusions.
Although frontotemporal lobar degeneration with ubiquitin/TDP-43-positive inclusions (FTLD-TDP) and Pick's disease are common pathological substrates in sporadic FTLD, clinical differentiation of these diseases is difficult. We performed a retrospective review of medical records and semiquantitative examination of neuronal loss of 20 sporadic FTLD-TDP and 19 Pick's disease cases. Semantic dementia as the first syndrome developed only in FTLD-TDP patients. Impaired speech output in the early stage was five times more frequent in Pick's disease than in FTLD-TDP. The total frequency of asymmetric motor disturbances (e.g., parkinsonism, pyramidal signs, and contracture) during the course was significantly more frequent in FTLD-TDP (78%) than in Pick's disease cases (14%). Asymmetric pyramidal signs were found in 7 of 13 FTLD-TDP cases with corticospinal tract degeneration similar to primary lateral sclerosis. Frontotemporal dementia as the first syndrome was noted in both FTLD-TDP (28%) and Pick's disease cases (64%); however, only FTLD-TDP cases subsequently developed asymmetric motor disturbances, and some of the cases further exhibited hemineglect. Concordant with these clinical findings, degeneration in the temporal cortex, caudate nucleus, putamen, globus pallidus, substantia nigra, and corticospinal tract was significantly more severe in FTLD-TDP, and degeneration in the frontal cortex tended to be more severe in Pick's disease. Given these findings, the initial impairment of semantic memory or comprehension and subsequent asymmetric motor disturbances in sporadic FTLD patients predict sporadic FTLD-TDP rather than Pick's disease, while initial behavioral symptoms or non-fluent aphasia without subsequent asymmetric motor disturbances predict Pick's disease rather than sporadic FTLD-TDP.


Ammonium loss microbiologically mediated by Fe(III) and Mn(IV) reduction along a coastal lagoon system.
Anaerobic ammonium oxidation, associated with both iron (Feammox) and manganese (Mnammox) reduction, is a microbial nitrogen (N) removal mechanism recently identified in natural ecosystems. Nevertheless, the spatial distributions of these non-canonical Anammox (NC-Anammox) pathways and their environmental drivers in subtidal coastal sediments are still unknown. Here, we determined the potential NC-Anammox rates and abundance of dissimilatory metal-reducing bacteria (Acidomicrobiaceae A6 and Geobacteraceae) at different horizons (0-20 cm at 5 cm intervals) of subtidal coastal sediments using the 15N isotope-tracing technique and molecular analyses. Sediments were collected across three sectors (inlet, transition, and inner) in a coastal lagoon system (Bahia de San Quintin, Mexico) dominated by seagrass meadows. The positive relationship between 30N2 production rates and dissimilatory Fe and Mn reduction provided evidence for Feammox's and Mnammox's co-occurrence. N loss through NC-Anammox was detected in subtidal sediments, with potential rates of 0.07-0.62 μg N g-1 day-1. NC-Anammox process in vegetated sediments tended to be higher than those in adjacent unvegetated ones. NC-Anammox rates showed a subsurface peak (between 5 and 15 cm) in the vegetated sediments but decreased consistently with depth in the adjacent bare bottoms. Thus, the presence/absence of seagrasses and sediment characteristics, particularly the availability of organic carbon and microbiologically reducible Fe(III) and Mn(IV), affected the abundance of dissimilatory metal-reducing bacteria, which mediated NC-Anammox activity and the associated N removal. An annual loss of 32.31 ± 3.57 t N was estimated to be associated with Feammox and Mnammox within the investigated area, accounting for 2.8-4.7% of the gross total import of reactive N from the ocean into the Bahia de San Quintin. Taken as a whole, this study reveals the distribution patterns and controlling factors of the NC-Anammox pathways along a coastal lagoon system. It improves our understanding of the coupling between N and trace metal cycles in coastal environments.


Implementation of Oxy-Fuel Combustion (OFC) Technology in a Gasoline Direct Injection (GDI) Engine Fueled with Gasoline-Ethanol Blends.
Nowadays, to mitigate the global warming problem, the requirement of carbon neutrality has become more urgent. Oxy-fuel combustion (OFC) has been proposed as a promising way of carbon capture and storage (CCS) to eliminate carbon dioxide (CO2) emissions. This article explores the implementation of OFC technology in a practical gasoline direct injection (GDI) engine fueled with gasoline-ethanol blends, including E0 (gasoline), E25 (25% ethanol, 75% is gasoline in mass fraction), and E50 (50% ethanol, 50% is gasoline in mass fraction). The results show that with a fixed spark timing, φCA50 (where 50% fuel is burned), of E50 and E25 is about 4.5 and 1.9° later than that of E0, respectively. Ignition delay (θF) and combustion duration (θC) can be extended with the increase of the ethanol fraction in the blended fuel. With the increase of the oxygen mass fraction (OMF) from 23.3 to 29%, equivalent brake-specific fuel consumption (BSFCE) has a benefit of 2.12, 1.65, and 1.51% for E0, E25, and E50, respectively. The corresponding increase in brake-specific oxygen consumption (BSOC) is 21.83, 22.42, and 22.58%, respectively. Meanwhile, θF, θC, and the heat release rate (HRR) are not strongly affected by the OMF. With the increase of the OMF, the increment of θF is 0.7, 1.8, and 2.2° for E0, E25, and E50, respectively. θC is only extended by 1, 1.1, and 1.4°, respectively. Besides, by increasing the intake temperature (T I) from 298 to 358 K under all of the fuel conditions, BSFCE and BSOC present slight growth trends; θF and θC are slightly reduced; in the meantime, φCA50, φPmax (crank angle of peak cylinder pressure), and the position of the HRR peak are advanced by nearly 1°.


Modified Dakin's solution for cutaneous vibrio infections.
Vibrio species, specifically Vibrio vulnificus, are known to be endemic to warm saltwater environments. As a human pathogen they are capable of causing severe, progressive, necrotizing infections. The lesions are bullous in nature and often require wide surgical debridement due to the aggressiveness of this organism. The literature supports prophylactic antibiotic therapy for those with preexisting hepatic dysfunction or immunocompromise. The authors routinely implement prophylactic antibiotic coverage with doxycycline 100 mg every 12 hours for vibrio in patients with wounds exposed to or acquired in saltwater. In addition, they institute topical therapy with 0.025% sodium hypochlorite solution (modified Dakin's), based on their in vitro study of vibrio sensitivity to antimicrobials. Over the past 2 years, the authors have treated 10 patients with this protocol for cutaneous vibrio infections confirmed by quantitative cultures. None of these patients experienced progression of infection requiring operative debridement-contrary to the aggressive nature of this organism documented in other reports.


The challenge of diet, exercise and lifestyle modification in the management of the obese diabetic patient.
Type 2 diabetes is associated with many comorbid medical conditions including obesity, neuropathy, microvascular pathology and atherosclerotic arterial disease. Due to its complications and chronicity, reducing risk factors such as obesity and sedentary lifestyle through lifestyle modification is crucial to the long-term health of patients with type 2 diabetes. Patients must learn how to adopt lifelong, low-fat eating habits and regular activity patterns, with formal treatments focusing on weight loss, increased physical activity and low-fat, low-saturated fat diets. In this article we review the efficacy of lifestyle modification programmes for obese diabetic patients. In addition, we discuss barriers to lifestyle changes and methods for improving long-term adherence. Finally, we present information on how this approach has been adapted to a group of Mexican Americans in the USA, a population at high risk for type 2 diabetes, obesity and sedentary lifestyle.


The tumor immune microenvironment in pancreatic cancer and its potential in the identification of immunotherapy biomarkers.
Pancreatic cancer (PC) has an extremely poor prognosis, even with surgical resection and triplet chemotherapy treatment. Cancer immunotherapy has been recently approved for tumor-agnostic treatment with genome analysis, including in PC. However, it has limited efficacy. In addition to the low tumor mutation burden, one of the difficulties of immunotherapy in PC is the presence of abundant stromal cells in its microenvironment. Among stromal cells, cancer-associated fibroblasts (CAFs) play a major role in immunotherapy resistance, and CAF-targeted therapies are currently under development, including those in combination with immunotherapies. Meanwhile, microbiomes and tumor-derived exosomes (TDEs) have been shown to alter the behavior of distant receptor cells in PC. This review discusses the role of CAFs, microbiomes, and TDEs in PC tumor immunity. Elucidating the mechanisms by which CAFs, microbiomes, and TDEs are involved in the tumorigenesis of PC will be helpful for developing novel immunotherapeutic strategies and identifying companion biomarkers for immunotherapy. Spatial single-cell analysis of the tumor microenvironment will be useful for identifying biomarkers of PC immunity. Furthermore, given the complexity of immune mechanisms, artificial intelligence models will be beneficial for predicting the efficacy of immunotherapy.


Electron paramagnetic resonance study of ferroelectric phase transition and dynamic effects in a Mn2+ doped [NH4][Zn(HCOO)3] hybrid formate framework.
We present an X- and Q-band continuous wave (CW) and pulse electron paramagnetic resonance (EPR) study of a manganese doped [NH4][Zn(HCOO)3] hybrid framework, which exhibits a ferroelectric structural phase transition at 190 K. The CW EPR spectra obtained at different temperatures exhibit clear changes at the phase transition temperature. This suggests a successful substitution of the Zn2+ ions by the paramagnetic Mn2+ centers, which is further confirmed by the pulse EPR and 1H ENDOR experiments. Spectral simulations of the CW EPR spectra are used to obtain the temperature dependence of the Mn2+ zero-field splitting, which indicates a gradual deformation of the MnO6 octahedra indicating a continuous character of the transition. The determined data allow us to extract the critical exponent of the order parameter (β = 0.12), which suggests a quasi two-dimensional ordering in [NH4][Zn(HCOO)3]. The experimental EPR results are supported by the density functional theory calculations of the zero-field splitting parameters. Relaxation time measurements of the Mn2+ centers indicate that the longitudinal relaxation is mainly driven by the optical phonons, which correspond to the vibrations of the metal-oxygen octahedra. The temperature behavior of the transverse relaxation indicates a dynamic process in the ordered ferroelectric phase.


The size and structure of the DNA genome of symbiont xenosome particles in the ciliate Parauronema acutum.
The size and structure of the DNA genome of xenosomes, bacterial endosymbionts of the marine hymenostome ciliate, Parauronema acutum 110-3, were investigated. Renaturation kinetic measurements, determined optically and by hydroxyapatite chromatography, suggested a genome size of 0.34 x 10(9) daltons. Sedimentation rate measurements of DNA gently released from the symbionts yielded molecules of comparable size. The analytical complexity, determined chemically, was 3.03 x 10(9) daltons. Consistent with these and other data is a model for the structure of the symbiont genome in which the DNA exists in the form of nine circularly permuted, double-stranded DNA molecules of unique sequence, each of molecular weight 0.34 x 10(9). It is suggested that xenosomes and certain symbionts found in ciliated protozoa may be extant forms of once free-living bacteria that have adapted to the intracellular environment.


One-step assembly of zein/caseinate/alginate nanoparticles for encapsulation and improved bioaccessibility of propolis.
The design of zein-based nanoparticles to encapsulate bioactive molecules has gained great attention in recent years. However, the use of ethanol to dissolve zein presents flammability concerns and the scale-up production of zein-based nanoparticles is also a concern. In our study, propolis loaded zein/caseinate/alginate nanoparticles were fabricated using a facile one-step procedure: a well-blended solution was prepared containing deprotonated propolis, soluble zein, dissociated sodium caseinate micelles (NaCas) and alginate at alkaline pH, and then this alkaline solution was added to 0.1 M citrate buffer (pH 3.8) to fabricate composite nanoparticles without using organic solvents and sophisticated equipment. During acidification, the alginate molecules adsorbed on the zein/NaCas surfaces by electrostatic complexation, which improved the stability towards aggregation of zein/NaCas nanoparticles under gastrointestinal (GI) or acidic pH. The nanoparticles prepared under the optimized method (method 3 sample) were of spherical morphology with a particle size around 208 nm and a negative zeta potential around -27 mV. The encapsulation efficiency (EE) and loading capacity (LC) of propolis reached 86.5% and 59.6 μg mg-1 by zein/NaCas/alginate nanoparticles, respectively. These nanoparticles were shown to be stable towards aggregation over a wide range of pH values (2-8) and salt concentrations (0-300 mM NaCl). Compared to free propolis, the bioaccessibility of propolis encapsulated with nanoparticles was increased to 80%. Our results showed a promising clean and scalability strategy to encapsulate hydrophobic nutraceuticals for applications in foods, supplements, and pharmaceuticals.


The acute phase of mild traumatic brain injury is characterized by a distance-dependent neuronal hypoactivity.
The consequences of mild traumatic brain injury (TBI) on neuronal functionality are only now being elucidated. We have now examined the changes in sensory encoding in the whisker-recipient barrel cortex and the brain tissue damage in the acute phase (24 h) after induction of TBI (n=9), with sham controls receiving surgery only (n=5). Injury was induced using the lateral fluid percussion injury method, which causes a mixture of focal and diffuse brain injury. Both population and single cell neuronal responses evoked by both simple and complex whisker stimuli revealed a suppression of activity that decreased with distance from the locus of injury both within a hemisphere and across hemispheres, with a greater extent of hypoactivity in ipsilateral barrel cortex compared with contralateral cortex. This was coupled with an increase in spontaneous output in Layer 5a, but only ipsilateral to the injury site. There was also disruption of axonal integrity in various regions in the ipsilateral but not contralateral hemisphere. These results complement our previous findings after mild diffuse-only TBI induced by the weight-drop impact acceleration method where, in the same acute post-injury phase, we found a similar depth-dependent hypoactivity in sensory cortex. This suggests a common sequelae of events in both diffuse TBI and mixed focal/diffuse TBI in the immediate post-injury period that then evolve over time to produce different long-term functional outcomes.


A beta-galactosidase gene is expressed during mature fruit abscission of 'Valencia' orange (Citrus sinensis).
beta-galactosidases have been detected in a wide range of plants and are characterized by their ability to hydrolyse terminal non-reducing beta-D-galactosyl residues from beta-D-galactosides. These enzymes have been detected in a wide range of plant organs and tissues. In a search for differentially expressed genes during the abscission process in citrus, sequences encoding beta-galactosidase were identified. Three cDNA fragments of a beta-galactosidase gene were isolated from a cDNA subtraction library constructed from mature fruit abscission zones 48 h after the application of a mature fruit-specific abscission agent, 5-chloro-3-methyl-4-nitro-1H-pyrazole (CMN-pyrazole). Based on sequence information derived from these fragments, a full-length cDNA of 2847 nucleotides (GenBank accession number AY029198) encoding beta-galactosidase was isolated from mature fruit abscission zones by 5'- and 3'-RACE approaches. The beta-galactosidase cDNA encoded a protein of 737 amino acid residues with a calculated molecular weight of 82 kDa. The deduced protein was highly homologous to plant beta-galactosidases expressed in fruit ripening. Southern blot analysis demonstrated that at least two closely related beta-galactosidase genes were present in 'Valencia' orange. Temporal expression patterns in mature fruit abscission zones indicated beta-galactosidase mRNA was detected 48 h after treatment of CMN-pyrazole and ethephon in mature fruit abscission zones. beta-galactosidase transcripts were detected in leaf abscission zones only after ethephon application. The citrus beta-galactosidase was expressed in stamens and petals of fully opened flowers and young fruitlets. The results suggest that this beta-galactosidase may play a role during abscission as well as early growth and development processes in flowers and fruitlets.


Effectiveness, Morbidity, and Costs of Transcrestal and Lateral Sinus Floor Elevation at Sites with Different Residual Bone Heights: A Re-Analysis of Data from a Parallel-Arm Randomized Trial.
To comparatively evaluate transcrestal sinus floor elevation (tSFE) and lateral sinus floor elevation (lSFE) at sites with different residual bone heights (RBHs). A re-analysis of data from a parallel-arm, randomized trial comparatively evaluating tSFE and lSFE was performed. Within each RBH interval (< 4 mm or ≥ 4 mm), tSFE and lSFE groups were compared for chair time, surgery-related costs, morbidity, and radiographic parameters (including the proportion of the implant surface in direct contact with the radiopaque area [totCON%]). The intention-to-treat (ITT) population consisted of 29 and 28 patients in the tSFE and lSFE groups, respectively. Irrespective of RBH, both tSFE and lSFE lead to a median totCON% of 100%. At sites with RBH < 4 mm, pain severity was significantly higher at days 0 and 1 in the tSFE group, with no intergroup difference in the dose of analgesics. LSFE was associated with a significantly higher frequency of bruising and greater cost. At sites with RBH ≥ 4 mm, a significantly lower frequency of postoperative signs/symptoms, less chair time, and lower costs were observed in the tSFE group. The selection of tSFE or lSFE within the investigated RBH intervals seems to be supported by differences in chair time, costs, and morbidity between the two techniques. At sites with RBH < 4 mm, clinicians preferring tSFE should encourage the administration of analgesics according to a predefined plan in the early postoperative phase. At sites with RBH ≥ 4 mm, tSFE should be preferred to lSFE due to reduced chair time, costs, and morbidity.


TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG).
The optimal management of patients with resectable gastric cancer continues to evolve in Western countries. Following publication of the US Intergroup 0116 and UK Medical Research Council MAGIC trials, there are now two standards of care for adjuvant therapy in resectable gastric cancer, at least in the Western world: postoperative chemoradiotherapy and perioperative epirubicin/cisplatin/fluorouracil (ECF) chemotherapy. We hypothesize that adding chemoradiation to standard perioperative ECF chemotherapy will achieve further survival gains. We also believe there are advantages to administering chemoradiation in the preoperative rather than postoperative setting. In this article, we describe the TOPGEAR trial, which is a randomised phase III trial comparing control arm therapy of perioperative ECF chemotherapy with experimental arm therapy of preoperative chemoradiation plus perioperative ECF chemotherapy. Eligible patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either perioperative chemotherapy alone (3 preoperative and 3 postoperative cycles of ECF) or perioperative chemotherapy plus preoperative chemoradiation. In the chemoradiation arm, patients receive 2 cycles of ECF plus chemoradiation prior to surgery, and then following surgery 3 further cycles of ECF are given. The trial is being conducted in two Parts; Part 1 (phase II component) has recruited 120 patients with the aim of assessing feasibility, safety and preliminary efficacy of preoperative chemoradiation. Part 2 (phase III component) will recruit a further 632 patients to provide a total sample size of 752 patients. The primary endpoint of the phase III trial is overall survival. The trial includes quality of life and biological substudies, as well as a health economic evaluation. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique. TOPGEAR is an international, intergroup collaboration led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. It addresses a globally significant question that will help inform future international standards for clinical practice in resectable gastric cancer. Australian New Zealand Clinical Trials Registry: ACTRN12609000035224 . Registered 30 May 2009.


ASL-MRICloud: An online tool for the processing of ASL MRI data.
Arterial spin labeling (ASL) MRI is increasingly used in research and clinical settings. The purpose of this work is to develop a cloud-based tool for ASL data processing, referred to as ASL-MRICloud, which may be useful to the MRI community. In contrast to existing ASL toolboxes, which are based on software installation on the user's local computer, ASL-MRICloud uses a web browser for data upload and results download, and the computation is performed on the remote server. As such, this tool is independent of the user's operating system, software version, and CPU speed. The ASL-MRICloud tool was implemented to be compatible with data acquired by scanners from all major MRI manufacturers, is capable of processing several common forms of ASL, including pseudo-continuous ASL and pulsed ASL, and can process single-delay and multi-delay ASL data. The outputs of ASL-MRICloud include absolute and relative values of cerebral blood flow, arterial transit time, voxel-wise masks indicating regions with potential hyper-perfusion and hypo-perfusion, and an image quality index. The ASL tool is also integrated with a T1 -based brain segmentation and normalization tool in MRICloud to allow generation of parametric maps in standard brain space as well as region-of-interest values. The tool was tested on a large data set containing 309 ASL scans as well as on publicly available ASL data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study.


Identification and validation of an individualized autophagy-clinical prognostic index in gastric cancer patients.
The purpose of this study is to perform bioinformatics analysis of autophagy-related genes in gastric cancer, and to construct a multi-gene joint signature for predicting the prognosis of gastric cancer. GO and KEGG analysis were applied for differentially expressed autophagy-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. In order to optimize the prognosis evaluation system of gastric cancer, we established a prognosis model integrating autophagy-related genes. We used single factor Cox proportional risk regression analysis to screen genes related to prognosis from 204 autophagy-related genes in The Atlas Cancer Genome (TCGA) gastric cancer cohort. Then, the generated genes were applied to the Least Absolute Shrinkage and Selection Operator (LASSO). Finally, the selected genes were further included in the multivariate Cox proportional hazard regression analysis to establish the prognosis model. According to the median risk score, patients were divided into high-risk group and low-risk group, and survival analysis was conducted to evaluate the prognostic value of risk score. Finally, by combining clinic-pathological features and prognostic gene signatures, a nomogram was established to predict individual survival probability. GO analysis showed that the 28 differently expressed autophagy-related genes was enriched in cell growth, neuron death, and regulation of cell growth. KEGG analysis showed that the 28 differently expressed autophagy-related genes were related to platinum drug resistance, apoptosis and p53 signaling pathway. The risk score was constructed based on 4 genes (GRID2, ATG4D,GABARAPL2, CXCR4), and gastric cancer patients were significantly divided into high-risk and low-risk groups according to overall survival. In multivariate Cox regression analysis, risk score was still an independent prognostic factor (HR = 1.922, 95% CI = 1.573-2.349, P < 0.001). Cumulative curve showed that the survival time of patients with low-risk score was significantly longer than that of patients with high-risk score (P < 0.001). The external data GSE62254 proved that nomograph had a great ability to evaluate the prognosis of individual gastric cancer patients. This study provides a potential prognostic marker for predicting the prognosis of GC patients and the molecular biology of GC autophagy.


Conformation of polygalacturonase-II from Aspergillus carbonarius--a spectroscopic study.
Solution conformation of polygalacturonase from Aspergillus carbonarius was determined by spectroscopy. UV absorption, second derivative, near-UV CD, fluorescence emission spectra and fluorescence quenching measurements suggest that the tryptophan fluorophores are in a hydrophobic environment. Of the nine tryptophan residues, only one is exposed to the solvent. In the near UV region the enzyme exhibits very weak CD bands, the far UV CD spectrum has a minimum at 218 nm; the enzyme is rich in parallel beta structure. Modification of solvent exposed tryptophan by N-bromosuccinimide resulted in the complete loss of enzyme activity. The enzyme is very sensitive towards urea induced unfolding, with complete loss of activity at 3 M urea concentration.


[Music and chronic muscular-skeletal pain: the evocative potential of mental images].
Ninety women with diagnosed fibromyalgia, work-related repetitive strain injury/osteoarticular diseases (RSI) and diseases related to the spinal column were submitted to individual listening of three musical pieces. Data were obtained by means of interviews and pain intensity was evaluated by the verbal numeric scale (0-10) before and after listening to the music. The mental images were quantified by analyzing the drawings made during each listening session. The three groups presented a statistically significant reduction in pain intensity at the end of the listening session (p<0.001). The mental images did not differ in quantity, between Ravel and Wagner. The Mix presented quantitatively lower results. The musical structures related to the production of images and the observed therapeutic effect suggests that structural analyses may contribute to the use of music by nursing.


Angiotensin II AT(1) blockade normalizes cerebrovascular autoregulation and reduces cerebral ischemia in spontaneously hypertensive rats.
Angiotensin II, through stimulation of AT(1) receptors, not only controls blood pressure but also modulates cerebrovascular flow. We sought to determine whether selective AT(1) antagonists could be therapeutically advantageous in brain ischemia during chronic hypertension. We pretreated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto controls with the AT(1) antagonist candesartan (CV-11974), 0.5 mg/kg per day, for 3 to 14 days, via subcutaneously implanted osmotic minipumps. We analyzed cerebral blood flow by laser-Doppler flowmetry, cerebral stroke in SHR after occlusion of the middle cerebral artery with reperfusion, and brain AT(1) receptors by quantitative autoradiography. Candesartan treatment normalized blood pressure and the shift toward higher blood pressures at both the upper and lower limits of cerebrovascular autoregulation in SHR. Candesartan pretreatment of SHR for 14 days partially prevented the decrease in blood flow in the marginal zone of ischemia and significantly reduced the volume of total and cortical infarcts after either 1 or 2 hours of middle cerebral artery occlusion with reperfusion, relative to untreated SHR, respectively. This treatment also significantly reduced brain edema after 2 hours of middle cerebral artery occlusion with reperfusion. In SHR, candesartan markedly decreased AT(1) binding in areas inside (nucleus of the solitary tract) and outside (area postrema) the blood-brain barrier and in the middle cerebral artery. Pretreatment with an AT(1) antagonist protected hypertensive rats from brain ischemia by normalizing the cerebral blood flow response, probably through AT(1) receptor blockade in cerebral vessels and in brain areas controlling cerebrovascular flow during stroke.


Production and Characterization of a Novel Bilayer Nanocomposite Scaffold Composed of Chitosan/Si-nHap and Zein/POSS Structures for Osteochondral Tissue Regeneration.
Osteochondral tissue is hard to regenerate after injuries or degenerative diseases. Traditional treatments still have disadvantages, such as donor tissue availability, donor site morbidity, implant loss, and limited durability of prosthetics. Thus, recent studies have focused on tissue engineering strategies to regenerate osteochondral defects with different scaffold designs. Scaffolds have been developed from monolayer structures to bilayer scaffolds to repair the cartilage-bone interface and to support each tissue separately. In this study, Si-substituted nanohydroxyapatite particles (Si-nHap) and silica-based POSS nanocages were used as reinforcements in different polymer layers to mimic a cartilage-bone tissue interface. Chitosan and zein, which are widely used biopolymers, are used as polymer layers to mimic the structure. This study reports the development of a bilayer scaffold produced via fabrication of two different nanocomposite layers with different polymer-inorganic composites in order to satisfy the complex and diverse regenerative requirements of osteochondral tissue. The chitosan/Si-nHap microporous layer and the zein/POSS nanofiber layer were designed to mimic a bone-cartilage tissue interface. Bilayer scaffolds were characterized with SEM, compression, swelling, and biodegradation tests to determine morphological, physical, and mechanical properties. The results showed that the bilayer scaffold had a structure composed of microporous and nanofiber layers joined at a continuous interface with appropriate mechanical properties. Furthermore, in vitro cell culture studies have been performed with LDH, proliferation, fluorescence imaging, and ALP activity assays using osteosarcoma and chondrosarcoma cell lines. ALP expression levels provide a good illustration of the improved osteogenic potential of a porous chitosan/Si-nHap layer due to the Si-doped nHap incorporation. Histological data showed that both fiber and porous layers that mimic the cartilage and bone sections exhibit homogeneous cell distribution and matrix formation. Histochemical staining was used to determine the cell proliferation and ECM formation on each layer. In vitro studies indicated that zein-POSS/chitosan/Si-nHap nanocomposite bilayer scaffolds showed promising results for osteochondral regeneration.


Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive.
Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson's disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model.


Physical capability predicts mortality in late mid-life as well as in old age: Findings from a large British cohort study.
Low physical capability predicts mortality, perhaps by association with co-morbidity. However, few studies include participants <70years old with lower co-morbidity burdens compared to older adults. We examined relationships between usual walking speed (UWS), timed chair stands speed, grip strength, standing balance and all-cause mortality in 8477 participants aged 48-92years enrolled in the European Prospective Investigation of Cancer-Norfolk study. Participants (55.1% female) were followed up for 6.0 years (inter-quartile range 4.6, 7.5). Associations were examined using Cox proportional hazards regression by age-group (<70years versus ≥70years) and then in the whole cohort adjusted for age, sex, anthropometry, history of diabetes/stroke/myocardial infarction/cancer, smoking, alcohol intake, socioeconomic status, television viewing time and physical activity. Age and sex adjusted associations were similar in younger and older participants (Pinteraction all >0.05) and those with lower physical capability had higher mortality risk. For example, in those <70years old hazard ratios (95% confidence interval) for mortality in the third, second and lowest sex-specific quartiles of UWS compared to the highest were 1.21 (0.75, 1.96), 2.11 (1.35, 3.28) and 2.91 (1.84, 4.62) and in participants ≥70years old were 1.19 (0.73, 1.95), 2.09 (1.35, 3.24) and 2.64 (1.73, 4.02) respectively. In the whole cohort, strong associations between all physical capability tests and mortality persisted after multivariable adjustment and after excluding participants with co-morbidity. Physical capability was independently predictive of future mortality risk with similar associations in late mid-life, when co-morbidity burden is lower, as at older age.


Neurocognitive endophenotypes for bipolar disorder identified in multiplex multigenerational families.
Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, a strategy for identifying risk genes is to identify and map quantitative intermediate phenotypes or endophenotypes. To adjudicate neurocognitive endophenotypes for bipolar disorder. All participants underwent diagnostic interviews and comprehensive neurocognitive evaluations. Neurocognitive measures found to be heritable were entered into analyses designed to determine which test results are impaired in affected individuals, are sensitive to the genetic liability for the illness, and are genetically correlated with affection status. Central valley of Costa Rica; Mexico City, Mexico; and San Antonio, Texas. Seven hundred nine Latino individuals participated in the study. Of these, 660 were members of extended pedigrees with at least 2 siblings diagnosed as having bipolar disorder (n = 230). The remaining subjects were community control subjects drawn from each site who did not have a personal or family history of bipolar disorder or schizophrenia. Neurocognitive test performance. Two of the 22 neurocognitive variables were not significantly heritable and were excluded from subsequent analyses. Patients with bipolar disorder were impaired on 6 cognitive measures compared with nonrelated healthy controls. Nonbipolar first-degree relatives were impaired on 5 of these, and the following 3 tests were genetically correlated with affection status: Digit Symbol Coding Task, Object Delayed Response Task, and immediate facial memory. This large-scale extended pedigree study of cognitive functioning in bipolar disorder identifies measures of processing speed, working memory, and declarative (facial) memory as candidate endophenotypes for bipolar disorder.


Bronchial artery embolization for hemoptysis in young patients with cystic fibrosis.
To review the authors' 15-year experience with bronchial artery embolization (BAE) for treatment of hemoptysis in young patients with cystic fibrosis. By searching the 1985-1999 radiology database, the authors identified 23 young patients who had been referred to the radiology department for angiography. Twenty of these patients underwent BAE. The 23 medical records were retrospectively reviewed with regard to embolization agents used, embolization success rates, number of repeat embolizations, survival times, and causes of death. BAE was performed on 38 occasions in 20 patients. The mean age of patients at first BAE was 15 years (age range, 7-19 years). The majority (n = 34 [89%]) of BAEs were performed by using polyvinyl alcohol. The immediate success rate after BAE (ie, no recurrent bleeding within 24 hours) was 95% (36 of 38 BAEs). Eleven (55%) patients required more than one BAE, and the median time between first and second embolizations was 4 months (range, 5 days to 61 months). Three patients died as a consequence of severe hemoptysis during induction of anesthesia with intermittent positive pressure ventilation in preparation for BAE. The median survival duration after the first BAE (Kaplan-Meier estimate) was 84 months (average follow-up, 61 months; range, 5 days to 169 months). BAE had a high success rate for short-term control of bleeding; however, more than half the patients required repeat embolization during the long-term follow-up.


Domains and Methods Used to Assess Home Telemonitoring Scalability: Systematic Review.
The COVID-19 pandemic catalyzed the adoption of home telemonitoring to cope with social distancing challenges. Recent research on home telemonitoring demonstrated benefits concerning the capacity, patient empowerment, and treatment commitment of health care systems. Moreover, for some diseases, it revealed significant improvement in clinical outcomes. Nevertheless, when policy makers and practitioners decide whether to scale-up a technology-based health intervention from a research study to mainstream care delivery, it is essential to assess other relevant domains, such as its feasibility to be expanded under real-world conditions. Therefore, scalability assessment is critical, and it encompasses multiple domains to ensure population-wide access to the benefits of the growing technological potential for home telemonitoring services in health care. This systematic review aims to identify the domains and methods used in peer-reviewed research studies that assess the scalability of home telemonitoring-based interventions under real-world conditions. The authors followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines and used multiple databases (PubMed, Scopus, Web of Science, and EconLit). An integrative synthesis of the eligible studies was conducted to better explore each intervention and summarize relevant information concerning the target audience, intervention duration and setting, and type of technology. Each study design was classified based on the strength of its evidence. Lastly, the authors conducted narrative and thematic analyses to identify the domains, and qualitative and quantitative methods used to support scalability assessment. This review evaluated 13 articles focusing on the potential of scaling up a home telemonitoring intervention. Most of the studies considered the following domains relevant for scalability assessment: problem (13), intervention (12), effectiveness (13), and costs and benefits (10). Although cost-effectiveness was the most common evaluation method, the authors identified seven additional cost analysis methods to evaluate the costs. Other domains were less considered, such as the sociopolitical context (2), workforce (4), and technological infrastructure (3). Researchers used different methodological approaches to assess the effectiveness, costs and benefits, fidelity, and acceptability. This systematic review suggests that when assessing scalability, researchers select the domains specifically related to the intervention while ignoring others related to the contextual, technological, and environmental factors, which are also relevant. Additionally, studies report using different methods to evaluate the same domain, which makes comparison difficult. Future work should address research on the minimum required domains to assess the scalability of remote telemonitoring services and suggest methods that allow comparison among studies to provide better support to decision makers during large-scale implementation.


Low coherent hybrid detection technique for differential mode delay in a multimode optical fiber.
We present a low coherent hybrid detection technique for the differential model delay (DMD) measurement of a conventional optical multimode fiber with a modified Mach-Zehnder interferometer. A low coherent hybrid detection technique enhances mode coupling between guided modes and the reference mode to easily resolve the modal distribution. An optical spectrum analyzer and a broadband source were used to obtain time-resolved optical beat signals. The measured interference signal was Fourier transformed to obtain time-delay information. A scanning offset launching method was used to excite every available mode in a multimode fiber (MMF). Measurements of a conventional 8-m-long MMF demonstrated the validity of our proposed method. The experimental results of our proposed method agree well with results obtained using a conventional time domain measurement method. Our proposed method can be used to measure the DMD in a short length of optical MMF with a temporal resolution better than 0.72 ps when using an 8-m-long single-mode fiber as a reference.


Seagrass ecosystem trajectory depends on the relative timescales of resistance, recovery and disturbance.
Seagrass ecosystems are inherently dynamic, responding to environmental change across a range of scales. Habitat requirements of seagrass are well defined, but less is known about their ability to resist disturbance. Specific means of recovery after loss are particularly difficult to quantify. Here we assess the resistance and recovery capacity of 12 seagrass genera. We document four classic trajectories of degradation and recovery for seagrass ecosystems, illustrated with examples from around the world. Recovery can be rapid once conditions improve, but seagrass absence at landscape scales may persist for many decades, perpetuated by feedbacks and/or lack of seed or plant propagules to initiate recovery. It can be difficult to distinguish between slow recovery, recalcitrant degradation, and the need for a window of opportunity to trigger recovery. We propose a framework synthesizing how the spatial and temporal scales of both disturbance and seagrass response affect ecosystem trajectory and hence resilience.


The effects of low-shear stress on Adherent-invasive Escherichia coli.
The impact of low-shear stress (LSS) was evaluated on an Adherent-invasive Escherichia coli clinical isolate (AIEC strain O83:H1) from a Crohn's disease patient. High-aspect ratio vessels (HARVs) were used to model LSS conditions to characterize changes in environmental stress resistance and adhesion/invasive properties. Low-shear stress-grown cultures exhibited enhanced thermal and oxidative stress resistance as well as increased adherence to Caco-2 cells, but no changes in invasion were observed. An AIEC rpoS mutant was constructed to examine the impact of this global stress regulator. The absence of RpoS under LSS conditions resulted in increased sensitivity to oxidative stress while adherence levels were elevated in comparison with the wild-type strain. TnphoA mutagenesis and rpoS complementation were carried out on the rpoS mutant to identify those factors involved in the LSS-induced adherence phenotype. Mutagenesis results revealed that one insertion disrupted the tnaB gene (encoding tryptophan permease) and the rpoS tnaB double mutant exhibited decreased adherence under LSS. Complementation of the tnaB gene, or medium supplemented with exogenous indole, restored adhesion of the rpoS tnaB mutant under LSS conditions. Overall, our study demonstrated how mechanical stresses such as LSS altered AIEC phenotypic characteristics and identified novel functions for some RpoS-regulated proteins.


A promising engineering strategy for water electro-oxidation iridate catalysts via coordination distortion.
Here, we study the relationship between the coordination structure of IrO6 and OER activity in a wide range of oxides with systematic comparisons. The results reveal that distorted IrO6 is more conducive to OER activity. Specifically, for a given material, regulating the transformation of the IrO6 octahedron from D4h compression to D4h elongation causes electrons near the EF level to become more delocalized, which is very beneficial for reducing the energy of the rate determining step. Our findings will guide the design and preparation of more efficient iridium-based OER catalysts.


Urogenital schistosomiasis in women of reproductive age and pregnant mothers in Kwale County, Kenya.
Generally, women residing in areas endemic for urinary schistosomiasis may suffer from female genital schistosomiasis which is acquired during childhood. The objective of this cross-sectional study was to estimate the prevalence and intensity of infection of Schistosoma haematobium in women of reproductive age (16-45 years) and to investigate whether S. haematobium had any effect on kidney function. A total of 394 women of known pregnancy status (158 pregnant and 236 non-pregnant) were recruited from five villages (known for their high prevalence of infection of S. haematobium) in Kwale County. Serum samples were analysed to determine levels of urea and creatinine as proxy indicators of kidney function. Data revealed that pregnant women did not, on average, have a higher prevalence or intensity of infection of urinary schistosomiasis than non-pregnant women. During pregnancy, the level of prevalence and intensity of infection of S. haematobium was highest in the first trimester (0-13 weeks), dropped in the second trimester (14-26 weeks) and rose again in the third trimester (27-40 weeks). In addition, 24.8% of women were infected with hookworm, while none were diagnosed with malaria parasites. Of 250 samples analysed for serum urea and creatinine, none had significant levels of pathology, either in pregnant or non-pregnant women. Despite World Health Organization (WHO) recommendations that pregnant women should be treated with praziquantel after the first trimester, in practice this has not been the case in many countries, including Kenya. In view of this, healthcare providers should be informed to consider treatment of pregnant women infected with schistosomiasis during antenatal visits and whenever there is mass drug administration as recommended by the WHO.


NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment.
Approximately 25-50 million Americans, 30 million Europeans, and 8% of the Australian population have a rare disease. Rare diseases are thus a common problem for clinicians and account for enormous healthcare costs worldwide due to the difficulty of establishing a specific diagnosis. In this article, we review the milestones achieved in our understanding of rare diseases since the emergence of next-generation sequencing (NGS) technologies and analyze how these advances have influenced research and diagnosis. The first half of this review describes how NGS has changed diagnostic workflows and provided an unprecedented, simple way of discovering novel disease-associated genes. We focus particularly on metabolic and neurodevelopmental disorders. NGS has enabled cheap and rapid genetic diagnosis, highlighted the relevance of mosaic and de novo mutations, brought to light the wide phenotypic spectrum of most genes, detected digenic inheritance or the presence of more than one rare disease in the same patient, and paved the way for promising new therapies. In the second part of the review, we look at the limitations and challenges of NGS, including determination of variant causality, the loss of variants in coding and non-coding regions, and the detection of somatic mosaicism variants and epigenetic mutations, and discuss how these can be overcome in the near future.


The "Eve" procedure: the transfer of vascularized seventh rib, fascia, cartilage, and serratus muscle to reconstruct difficult defects.
Very few microvascular units entertain the possibility of simultaneous vascularized transfer of bone, cartilage, muscle, and gliding fascia. In exceptionally complex conditions with loss of an essential joint, adjacent bone and functional muscle, reconstruction of all these structures at once may be necessary. At the same time, gliding tissue is often required to cover tendons. Reconstruction in one sitting prevents formation of dense scar tissue due to multiple interventions. Additionally, less bone resorption is seen if vascularized bone is used. Therefore, a more undisturbed tissue composition at the end is guaranteed. Moreover, rapid rehabilitation of moving function is possible with improvement in the final result. Finally, morbidity is lowered by using a single donor site, and costs are minimalized. We present four unique cases in which the seventh rib including the costochondral junction with overlying serratus muscle, branches of the thoracicus longus nerve, and adjacent fascia have been transferred as a microvascular unit to reconstruct two severely damaged hands and two other complex injuries. In analogy with the Bible story of the creation of "the woman," it is called the "Eve" procedure. The vascularized rib was used to reconstruct a first and fourth metacarpal bone, the ascending ramus of the mandible, and the clavicle. The rib cartilage was sculptured in four cases to reconstruct an articular surface. The serratus muscle served as coverage and filling for lost tissues. It also was used as a soft bed for facial nerve repair. In two cases muscle reinnervation was performed. The fascia provided gliding tissue surrounding reconstructed tendons or articular surfaces. In all cases a high degree of function was obtained with a good cosmesis. Rehabilitation was uneventful, and no reinterventions have been necessary. Donor-site morbidity was low. Therefore, this flap proved to be successful in complex injuries where bone, cartilage, muscle, and gliding tissue were needed simultaneously. Dynamic reconstruction was attempted in two cases and was successful in one.


Mucosal immunization of cynomolgus macaques with two serotypes of live poliovirus vectors expressing simian immunodeficiency virus antigens: stimulation of humoral, mucosal, and cellular immunity.
Poliovirus live virus vectors are a candidate recombinant vaccine system. Previous studies using this system showed that a live poliovirus vector expressing a foreign antigen between the structural and nonstructural proteins generates both antibody and cytotoxic T-lymphocyte responses in mice. Here we describe a novel in vitro method of cloning recombinant polioviruses involving a hybrid-PCR approach. We report the construction of recombinant vectors of two different serotypes of poliovirus-expressing simian immunodeficiency virus (SIV) antigens and the intranasal and intravenous inoculations of four adult cynomolgus macaques with these poliovirus vectors expressing the SIV proteins p17(gag) and gp41(env). All macaques generated a mucosal anti-SIV immunoglobulin A (IgA) response in rectal secretions. Two of the four macaques generated mucosal antibody responses detectable in vaginal lavages. Strong serum IgG responses lasting for at least 1 year were detected in two of the four monkeys. SIV-specific T-cell lymphoproliferative responses were detected in three of the four monkeys. SIV-specific cytotoxic T lymphocytes were detected in two of the four monkeys. This is the first report of poliovirus-elicited vaginal IgA or cytotoxic T lymphocytes in any naturally infectable primate, including humans. These findings support the concept that a live poliovirus vector is a potentially useful delivery system that elicits humoral, mucosal, and cellular immune responses against exogenous antigens.


Improved Denoising of Structural Vibration Data Employing Bilateral Filtering.
With the continuous advancement of data acquisition and signal processing, sensors, and wireless communication, copious research work has been done using vibration response signals for structural damage detection. However, in actual projects, vibration signals are often subject to noise interference during acquisition and transmission, thereby reducing the accuracy of damage identification. In order to effectively remove the noise interference, bilateral filtering, a filtering method commonly used in the field of image processing for improving data signal-to-noise ratio was introduced. Based on the Gaussian filter, the method constructs a bilateral filtering kernel function by multiplying the spatial proximity Gaussian kernel function and the numerical similarity Gaussian kernel function and replaces the current data with the data obtained by weighting the neighborhood data, thereby implementing filtering. By processing the simulated data and experimental data, introducing a time-frequency analysis method and a method for calculating the time-frequency spectrum energy, the denoising abilities of median filtering, wavelet denoising and bilateral filtering were compared. The results show that the bilateral filtering method can better preserve the details of the effective signal while suppressing the noise interference and effectively improve the data quality for structural damage detection. The effectiveness and feasibility of the bilateral filtering method applied to the noise suppression of vibration signals is verified.


[Therapy of monosymptomatic nocturnal enuresis in childhood and adolescence: what is the evidence?].
Nocturnal enuresis (bedwetting) is one of the most frequent urological symptoms in children, affecting about 20% of five year olds. It is a heterogeneous disorder with a whole variety of etiologic factors (genetic, endocrinological, neurobiological), particularly a dysfunction of the lower urinary tract. Despite the prevalence of enuresis many questions regarding the complex pathophysiological mechanisms remain unanswered. While nocturnal enuresis per se is clearly not a disease, psychosocial problems have been reported in up to 40% of affected children. Management strategies comprise behavioural and pharmacological approaches, either in isolation or combined. Although expectations were high, especially with pharmacological interventions, the results are usually disappointing with high recurrence rates. Extensive analyses of the available literature on the efficacy of enuresis treatment modalities reveal a poor quality of many trials with a whole range of methodological flaws. Therefore, further comparative studies of adequate methodological quality are needed.


[Non-neoplastic polyps of the colon].
Non-neoplastic colon polyps are benign lesions with normal histology components, we present our experience with colonoscopy polypectomy in 10 years. We resected 187 polyps in 96 patients (50 males) with medium age of 49.3 years and range 2-82. Most common indication was hemorrhage (37%) taking out the hyperplastic polyps who were found in asymptomatic patients with the highest frequency (41%). Juvenile polyps follows with 25%. 71% polyps were unique but hamaetomatous polyps of Peutz-Jeghers syndrome were multiple (39%). Juvenile (retention) polyps were found among the youngest patients (average 13.2 years) and frequently had hemorrhage (21-25). Lipomas were found in elder patients (range 52.5 years). We had no major complications with hemorrhage or mortality, minor complications were found in 3.09%.


A 5-year prospective clinical study of submerged and nonsubmerged Paragon system implants in the edentulous mandible.
The aim of this investigation was to evaluate the clinical outcome of two different surgical protocols in the edentulous mandible: submerged and nonsubmerged. Further, the Paragon dental implant with a titanium plasma-sprayed surface was evaluated. Twenty-nine consecutively treated patients with 168 implants supporting fixed prostheses were included. All but 3 patients were provided 6 implants, placed via nonsubmerged healing on one side and submerged healing on the other. Data were collected from patient records and radiographs. Twenty-four patients participated in the 5-year clinical follow-up examination. After 5 years, all patients still had their mandibular fixed prostheses in function. Cumulative survival rates were 100% for prostheses and 99.4% for implants. However, 3 implants fractured in 1 patient. One submerged implant was lost before loading but no further implants were lost during follow-up. The radiographic bone loss was small for all implants with a mean of 0.14 mm (standard deviation [SD]: 0.37) at 1 year and 0.42 mm (SD: 0.48) at 5 years for nonsubmerged implants and 0.17 mm (SD: 0.32) at 1 year and 0.51 mm (SD: 0.33) at 5 years for submerged implants. Nineteen implants (including the 3 that fractured) presented annual bone loss exceeding 0.2 mm after the first year, yielding a cumulative success rate of 86.2% after 5 years. Single-stage surgery was shown to have the same predictability as two-stage surgery in the anterior edentulous mandible. Paragon implants with a titanium plasma-sprayed surface showed a fracture rate of 2.2% and a success rate of 86.2% after 5 years.


Mice lacking both granulocyte colony-stimulating factor (CSF) and granulocyte-macrophage CSF have impaired reproductive capacity, perturbed neonatal granulopoiesis, lung disease, amyloidosis, and reduced long-term survival.
Mice lacking granulocyte colony-stimulating factor (G-CSF) are neutropenic with reduced hematopoietic progenitors in the bone marrow and spleen, whereas those lacking granulocyte-macrophage colony-stimulating factor (GM-CSF) have impaired pulmonary homeostasis and increased splenic hematopoietic progenitors, but unimpaired steady-state hematopoiesis. These contrasting phenotypes establish unique roles for these factors in vivo, but do not exclude the existence of additional redundant functions. To investigate this issue, we generated animals lacking both G-CSF and GM-CSF. In the process of characterizing the phenotype of these animals, we further analyzed G-CSF- and GM-CSF-deficient mice, expanding the recognized spectrum of defects in both. G-CSF-deficient animals have a marked predisposition to spontaneous infections, a reduced long-term survival, and a high incidence of reactive type AA amyloidosis. GM-CSF-deficient mice have a modest impairment of reproductive capacity, a propensity to develop lung and soft-tissue infections, and a similarly reduced survival as in G-CSF-deficient animals. The phenotype of mice lacking both G-CSF and GM-CSF was additive to the features of the constituent genotypes, with three novel additional features: a greater degree of neutropenia among newborn mice than in those lacking G-CSF alone, an increased neonatal mortality rate, and a dominant influence of the lack of G-CSF on splenic hematopoiesis resulting in significantly reduced numbers of splenic progenitors. In contrast to newborn animals, adult mice lacking both G-CSF and GM-CSF exhibited similar neutrophil levels as G-CSF-deficient animals. These findings demonstrate that the additional lack of GM-CSF in G-CSF-deficient animals further impairs steady-state granulopoiesis in vivo selectively during the early postnatal period, expand the recognized roles of both G-CSF and GM-CSF in vivo, and emphasize the utility of studying multiply deficient mouse strains in the investigation of functional redundancy.


[Selective serotonin reuptake inhibitors in major depressive disorder in children and adolescents (ratio of benefits/risks)].
Major depressive disorder in children and adolescents is associated with high risk of suicide and persistent functional impairment. While psychological treatments are used as a first line treatment in mild and moderately severe depression in this age group, the number of prescriptions for antidepressant medication (SSRI) has grown in recent years. Recently, FDA and MHRA advised that most of SSRI should not be used to treat MDD under the age of 18 years. They may increase the risk of suicidal thoughts and self harm. We reviewed the recent literature on efficacy and suicide risks of SSRI in depressed young people. Conflicting findings of SSRI efficacy have been reported in clinical studies. The discrepancies could be related to the heterogeneous samples and the absence of a standard definition of treatment effectiveness. In randomised placebo-controlled antidepressant clinical trials (RCT), the assessment of treatment effectiveness is commonly made with the CDRS-R (improvement of 20% or 30% or 40%) and CGI. SSRI demonstrated significantly, but modest, improvement compared with placebo in CGI score of 1 or 2: 10% more for sertraline, 16.8% more for paroxetine and between 16 to 24% more for fluoxetine. In adults, RCT studies have shown placebo response rates of 30% to 50%, drug response rates of 45% to 50% and drug-placebo differences of 18% to 25%. The highest placebo response rates, in young people, may be related to the highly selected group not representative of the general population of depressed patients and/or to the high youths' sensibility of psychotherapy. Patients participating in antidepressant clinical trials have a low BDI and CDI in Emslie's study for example (2002). In adults, previous reports suggest that SSRI use is associated with increased suicidal risk. But the analyse of 48 277 depressed patients participating in RCT for nine FDA approved antidepressants fail to support an overall difference in suicide risk between antidepressants (SSRI) and placebo treated subjects. An inverse relationship between regional change in use of antidepressants (increased) and suicide (decreased) is found in young -people in United States from 1990 and 2000. We can not draw a conclusion from few studies with few -participants. None suicide have been reported in pharmacological studies. And the link between "suicidality" and MDD can not be excluded. The instruments of assessment in depressed young patients are based on extensions of adult procedures. Whereas clinical picture of MDD in children, adolescents and adults have some differences. Depressed youngsters have more pronounced mood lability. Depressed adolescents have more anhedonia than depressed children. Future investigations into the efficacy and safety of treatments for children and adolescents depression should use specific instruments directly built on phenomenological and clinical picture of depressed children and adolescents. Comparison studies of pharmacotherapy, specific psychotherapies (not only CBT) and combined therapies are necessary to identify the adolescents who will benefit the most from specific or combined therapies. Further studies into the factors that influence treatment outcome including clinical picture (clinical dimensions, severity, duration, co morbidity), genetic factor, age, and i-llness course may help identify appropriate treatments for children and adolescents with MDD. Studies should include patients more severely ill, with associated psychiatric troubles, treatment resistance, history of relapses... In clinical studies, the link between "suicidality" and some clinical dimensions (which take part in clinical picture or not) must be analysed by assessing anhedonia, hopelessness feel, impulsive trait, borderline personality, familial inter-action, biological indices. New treatment should be expand and their efficacy and safety must be study: St John's worth, Bright light therapy, Trans-cranial Magnetic Stimulation. suicide and MDD have a strongest relation and it must be investigate syste-matically during the course of MDD. The suicide risk increases in the context of past history of suicide attempts, hopelessness, psychosis, impulsivity traits, substance abuse, familial dysfunction, life events, open access of arms. The use of SSRI in depressed children and adolescents is also the question of the quality and the support of the consultant and the mode of the prescription.


Drug-related problems in older people after hospital discharge and interventions to reduce them.
Drug-related problems in older people during care transitions have become a major public health problem since they threaten patient safety. The objective of our paper is to investigate the extent and frequency of drug-related problems (discontinuity, adherence, errors, interactions and adverse events) after hospital discharge and the efficacy of interventions intended to reduce them. We included 20 studies in the review. All of them underlined the high frequency and complexity of drug-related problems in older people after hospital discharge. Interventions proposed to improve care transitions led to diverse and sometimes contradictory results, but the findings suggested that combining hospital discharge measures with home follow-up strategies is of value. We conclude that it is not possible to estimate the frequency of drug-related problem through a review of selected articles or to evaluate the efficacy of the proposed interventions. More research is needed in this field to reduce uncertainty and generate evidence-based recommendations for physicians.


Seasonal variations in daily rhythms of activity in athletic horses.
Circadian rhythms reflect extensive programming of biological activity that meets and exploits the challenges and opportunities offered by the periodic nature of the environment. In the present investigation, we recorded the total activity of athletic horses kept at four different times of the year (vernal equinox, summer solstice, autumn equinox and winter solstice), to evaluate the presence of seasonal variations of daily activity rhythms. Athletic Thoroughbred horses were kept in individual boxes with paddock. Digitally integrated measure of total activity of each mare was continuously recorded by actigraphy-based data loggers. Horse total activities were not evenly distributed over the day, but they were mainly diurnal during the year. Daily activity rhythms showed clear seasonal variations, with the highest daily amount of activity during the vernal equinox and the lowest during the winter solstice. Interestingly, the amount of activity during either photophase or scotophase changed significantly throughout the year. Circadian analysis of horse activities showed that the acrophase, the estimated time at which the peak of the rhythm occurs, did not change during the year, it always occurred in the middle of the photoperiod. Analysing the time structure of long-term and continuously measured activity and feeding could be a useful method to critically evaluate athletic horse management systems in which spontaneous locomotor activity and feeding are severely limited. Circadian rhythms are present in several elements of sensory motor and psychomotor functions and these would be taken into consideration to plan the training schedules and competitions in athletic horses.


Kinematic features of unrestrained vertical arm movements.
Unrestrained human arm trajectories between point targets have been investigated using a three-dimensional tracking apparatus, the Selspot system. Movements were executed between different points in a vertical plane under varying conditions of speed and hand-held load. In contrast to past results which emphasized the straightness of hand paths, movement regions were discovered in which the hand paths were curved. All movements, whether curved or straight, showed an invariant tangential velocity profile when normalized for speed and distance. The velocity profile invariance with speed and load is interpreted in terms of simplification of the underlying arm dynamics, extending the results of Hollerbach and Flash (Hollerbach, J. M., and T. Flash (1982) Biol. Cybern. 44: 67-77).


ARGO 2.0: a Hybrid NLP/ML Framework for Diagnosis Standardization.
A relevant problem in medicine is the standardization of the diagnosis associated with a clinical case. Although diagnosis formulation is an intrinsically subjective and uncertain process, its standardization may take benefit from digital solutions automating the routines at the basis of such a decision. In this work, we propose ARGO 2.0: a framework for the development of decision support systems for diagnosis formulation. The framework can read free-text reports and store their clinically relevant information as personalized electronic Case Report Forms. A hybrid strategy, exploiting the synergy of Natural Language Processing and Machine Learning techniques, is used to automatically suggest a diagnosis in a standardized fashion. ARGO 2.0 has been designed to be template-independent and easily tailored to specific medical fields. We here demonstrate its feasibility in hemo lympho-pathology, by detailing its implementation, object of an ongoing validation campaign in a standing medical institute. ARGO 2.0 achieved an average Accuracy of 95.07%, an average precision of 94.85%, an average Recall of 96.31% and a F-Score of 95.32% onto the test set, outperforming both its embedded components, based on Natural Language Processing and Machine Learning.


ATP inhibition of proliferation of immortalized human fibroblasts is greater than that of normal human diploid fibroblasts.
It is known that cancers develop by a multi-step process. Normal cells are first immortalized, and then transformed into tumorigenic cells. Normal human cells are very rarely immortalized, but once they are, they are relatively easily transformed into tumorigenic cells. This indicates that the immortalization step plays a critical part in the development of human cancers. Thus, elucidation of the mechanisms of this step would shed light on the process of carcinogenesis in human cells. To understand the causes of immortalization, it is important to determine the differences in cellular phenotype between immortalized and normal human cells. In this study, we found that immortalized human fibroblasts were more sensitive to the growth inhibitory effects of ATP than normal human fibroblasts. ADP was as effective as ATP, but AMP, adenosine, and phosphoric acid were not. These results indicate that a high-energy bound of ATP and ADP may contribute to the growth inhibition of the cells. When the immortalized cells were pulse-labeled with [32P]-ATP, 30-, 31-, 33- and 40-kDa membrane fraction proteins were more prominently labeled in the immortalized cells than in the normal cells. At present, the characteristics of these proteins are being investigated.


Rapid control of reproductive behaviour by locally synthesised oestrogens: focus on aromatase.
Oestrogens activate nucleus- and membrane-initiated signalling. Nucleus-initiated events control a wide array of physiological and behavioural responses. These effects generally take place within relatively long periods of time (several hours to days). By contrast, membrane-initiated signalling affects a multitude of cellular functions in a much shorter timeframe (seconds to minutes). However, much less is known about their functional significance. Furthermore, the origin of the oestrogens able to trigger these acute effects is rarely examined. Finally, these two distinct types of oestrogenic actions have often been studied independently such that we do not exactly know how they cooperate to control the same response. The present review presents a synthesis of recent work carried out in our laboratory that aimed to address these issues in the context of the study of male sexual behaviour in Japanese quail, which is a considered as a suitable species for tackling these issues. The first section presents data indicating that 17β-oestradiol, or its membrane impermeable analogues, acutely enhances measures of male sexual motivation but does not affect copulatory behaviour. These effects depend on the activation of membrane-initiated events and local oestrogen production. The second part of this review discusses the regulation of brain oestrogen synthesis through post-translational modifications of the enzyme aromatase. Initially discovered in vitro, these rapid and reversible enzymatic modulations occur in vivo following variations in the social and environment context and therefore provide a mechanism of acute regulation of local oestrogen provision with a spatial and time resolution compatible with the rapid effects observed on male sexual behaviour. Finally, we discuss how these distinct modes of oestrogenic action (membrane- versus nucleus-initiated) acting in different time frames (short- versus long-term) interact to control different components (motivation versus performance) of the same behavioural response and improve reproductive fitness.


Neuromuscular Training Improves Movement Competency and Physical Performance Measures in 11-13-Year-Old Female Netball Athletes.
Hopper, A, Haff, EE, Barley, OR, Joyce, C, Lloyd, RS, and Haff, GG. Neuromuscular training improves movement competency and physical performance measures in 11-13-year-old female netball athletes. J Strength Cond Res 31(5): 1165-1176, 2017-The purpose of this study was to examine the effects of a neuromuscular training (NMT) program on movement competency and measures of physical performance in youth female netball players. It was hypothesized that significant improvements would be found in movement competency and physical performance measures after the intervention. Twenty-three junior female netball players (age, 12.17 ± 0.94 years; height, 1.63 ± 0.08 m; weight, 51.81 ± 8.45 kg) completed a test battery before and after a 6-week training intervention. Thirteen of these athletes underwent 6 weeks of NMT, which incorporated plyometrics and resistance training. Trained athletes showed significant improvements in 20-m sprint time, 505 agility time, countermovement jump height, and peak power (p ≤ 0.05, g > 0.8). In addition, trained athletes significantly improved their score in the Netball Movement Screening Tool (NMST) (p < 0.05, g > -1.30); while the athletes also demonstrated increased reach in the anterior and posteromedial directions for the right leg and left leg, and in the posterolateral direction for the left leg only in the Star Excursion Balance Test (SEBT) (p < 0.05, g > -0.03). Control subjects did not exhibit any significant changes during the 6-week period. Significant negative correlations were found between improved score on the NMST and decreased 5-, 10-, and 20-m sprint time, and 505 change of direction time (r > 0.4, p ≤ 0.05). Results of the study affirm the hypothesis that a 6-week NMT intervention can improve performance and movement competency in youth netball players.


Evaluation and targeting of amyloid precursor protein (APP)/amyloid beta (Aβ) axis in amyloidogenic and non-amyloidogenic pathways: A time outside the tunnel.
In Alzheimer disease (AD), amyloid precursor protein (APP) and production of amyloid beta (Aβ) which is generated by amyloidogenic pathway is implicated in neurotoxicity and neuronal cell deaths. However, physiological Aβ level is essential to improves neuronal survival, attenuates neuronal apoptosis and has neuroprotective effect. In addition, physiological APP level has neurotrophic effect on the central nervous system (CNS). APP has a critical role in the brain growth and development via activation of long-term potentiation (LTP) and acceleration of neurite outgrowth. Moreover, APP is cleaved by α secretase to form a neuroprotective soluble APP alpha (sAPPα) in non-amyloidogenic pathway. Consequently, this mini-review purposes to highlight the possible beneficial role of APP and Aβ. In addition, this mini-review discussed the modulation of APP processing and Aβ production.


A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial.
Artemisinin-based combination therapies (ACTs) are the mainstay for the management of uncomplicated malaria cases. However, up-to-date data able to assist sub-Saharan African countries formulating appropriate antimalarial drug policies are scarce. Between 9 July 2007 and 19 June 2009, a randomized, non-inferiority (10% difference threshold in efficacy at day 28) clinical trial was carried out at 12 sites in seven sub-Saharan African countries. Each site compared three of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), or chlorproguanil-dapsone-artesunate (CD+A). Overall, 4,116 children 6-59 mo old with uncomplicated Plasmodium falciparum malaria were treated (1,226 with AL, 1,002 with ASAQ, 413 with CD+A, and 1,475 with DHAPQ), actively followed up until day 28, and then passively followed up for the next 6 mo. At day 28, for the PCR-adjusted efficacy, non-inferiority was established for three pair-wise comparisons: DHAPQ (97.3%) versus AL (95.5%) (odds ratio [OR]: 0.59, 95% CI: 0.37-0.94); DHAPQ (97.6%) versus ASAQ (96.8%) (OR: 0.74, 95% CI: 0.41-1.34), and ASAQ (97.1%) versus AL (94.4%) (OR: 0.50, 95% CI: 0.28-0.92). For the PCR-unadjusted efficacy, AL was significantly less efficacious than DHAPQ (72.7% versus 89.5%) (OR: 0.27, 95% CI: 0.21-0.34) and ASAQ (66.2% versus 80.4%) (OR: 0.40, 95% CI: 0.30-0.53), while DHAPQ (92.2%) had higher efficacy than ASAQ (80.8%) but non-inferiority could not be excluded (OR: 0.35, 95% CI: 0.26-0.48). CD+A was significantly less efficacious than the other three treatments. Day 63 results were similar to those observed at day 28. This large head-to-head comparison of most currently available ACTs in sub-Saharan Africa showed that AL, ASAQ, and DHAPQ had excellent efficacy, up to day 63 post-treatment. The risk of recurrent infections was significantly lower for DHAPQ, followed by ASAQ and then AL, supporting the recent recommendation of considering DHAPQ as a valid option for the treatment of uncomplicated P. falciparum malaria. ClinicalTrials.gov NCT00393679; Pan African Clinical Trials Registry PACTR2009010000911750


Gold nanoparticles functionalized with deep-cavity cavitands: synthesis, characterization, and photophysical studies.
In this report, we present methods of functionalization of AuNP's with deep-cavity cavitands that can include organic molecules. Two types of deep-cavity cavitand-functionalized AuNP's have been synthesized and characterized, one soluble in organic solvents and the other in water. Functionalized AuNP soluble in organic solvents forms a 1:1 host-guest complex where the guest is exposed to the exterior solvents. The one soluble in water forms a 2:1 host-guest complex where the guest is protected from solvent water. Phosphorescence from thiones and benzil included within heterocapsules attached to AuNP was quenched by gold atoms present closer to the guests included within deep-cavity cavitands. During this investigation, we have synthesized four new deep-cavity cavitands. Of these, two thiol-functionalized hosts allowed us to make stable AuNP's. However, AuNP's protected with two amine-functionalized cavitands tended to aggregate within a day.


Building better fibrin knob mimics: an investigation of synthetic fibrin knob peptide structures in solution and their dynamic binding with fibrinogen/fibrin holes.
Fibrin polymerizes via noncovalent and dynamic association of thrombin-exposed "knobs" with complementary "holes." Synthetic knob peptides have received significant interest as a means for understanding fibrin assembly mechanisms and inhibiting fibrin polymerization. Nevertheless, the inability to crystallize short peptides significantly limits our understanding of knob peptide structural features that regulate dynamic knob:hole interactions. In this study, we used molecular simulations to generate the first predicted structure(s) of synthetic knobs in solution before fibrin hole engagement. Combining surface plasmon resonance (SPR), we explored the role of structural and electrostatic properties of knob "A" mimics in regulating knob:hole binding kinetics. SPR results showed that association rates were most profoundly affected by the presence of both additional prolines as well as charged residues in the sixth to seventh positions. Importantly, analyzing the structural dynamics of the peptides through simulation indicated that the 3Arg side chain orientation and peptide backbone stability each contribute significantly to functional binding. These findings provide insights into early fibrin protofibril assembly dynamics as well as establishing essential design parameters for high-affinity knob mimics that more efficiently compete for hole occupancy, parameters realized here through a novel knob mimic displaying a 10-fold higher association rate than current mimics.