Climate change is likely to profoundly modulate the burden of infectious diseases. However, attributing health impacts to a changing climate requires being able to associate changes in infectious ...disease incidence with the potentially complex influences of climate. This aim is further complicated by nonlinear feedbacks inherent in the dynamics of many infections, driven by the processes of immunity and transmission. Here, we detail the mechanisms by which climate drivers can shape infectious disease incidence, from direct effects on vector life history to indirect effects on human susceptibility, and detail the scope of variation available with which to probe these mechanisms. We review approaches used to evaluate and quantify associations between climate and infectious disease incidence, discuss the array of data available to tackle this question, and detail remaining challenges in understanding the implications of climate change for infectious disease incidence. We point to areas where synthesis between approaches used in climate science and infectious disease biology provide potential for progress.
It remains unclear whether structural brain abnormalities in schizophrenia are caused by genetic and/or disease-related factors. Structural brain abnormalities have been found in nonpsychotic ...first-degree relatives of patients with schizophrenia, but results are inconclusive. This large magnetic resonance imaging study examined brain structures in patients with schizophrenia, their nonpsychotic siblings, and healthy control subjects using global and focal brain measurements.
From 155 patients with schizophrenia, their 186 nonpsychotic siblings, and 122 healthy controls (including 25 sibling pairs), whole-brain scans were obtained. Segmentations of total brain, gray matter (GM), and white matter of the cerebrum, lateral and third ventricle, and cerebellum volumes were obtained. For each subject, measures of cortical thickness and GM density maps were estimated. Group differences in volumes, cortical thickness, and GM density were analyzed using Structural Equation Modeling, hence controlling for familial dependency of the data.
Patients with schizophrenia, but not their nonpsychotic siblings, showed volumetric differences, cortical thinning, and reduced GM density as compared with control subjects.
This study did not reveal structural brain abnormalities in nonpsychotic siblings of patients with schizophrenia compared with healthy control subjects using multiple imaging methods. Therefore, the structural brain abnormalities observed in patients with schizophrenia are for the largest part explained by disease-related factors.
(ProQuest: ... denotes formulae and/or non-USASCII text omitted; see image).A combination is presented of all inclusive deep inelastic cross sections previously published by the H1 and ZEUS ...collaborations at HERA for neutral and charged current ... scattering for zero beam polarisation. The data were taken at proton beam energies of 920, 820, 575 and 460 GeV and an electron beam energy of 27.5 GeV. The data correspond to an integrated luminosity of about 1 fb... and span six orders of magnitude in negative four-momentum-transfer squared, ..., and Bjorken x. The correlations of the systematic uncertainties were evaluated and taken into account for the combination. The combined cross sections were input to QCD analyses at leading order, next-to-leading order and at next-to-next-to-leading order, providing a new set of parton distribution functions, called HERAPDF2.0. In addition to the experimental uncertainties, model and parameterisation uncertainties were assessed for these parton distribution functions. Variants of HERAPDF2.0 with an alternative gluon parameterisation, HERAPDF2.0AG, and using fixed-flavour-number schemes, HERAPDF2.0FF, are presented. The analysis was extended by including HERA data on charm and jet production, resulting in the variant HERAPDF2.0Jets. The inclusion of jet-production cross sections made a simultaneous determination of these parton distributions and the strong coupling constant possible, resulting in ... An extraction of ... and results on electroweak unification and scaling violations are also presented.
Cerebral strokes can disrupt descending commands from motor cortical areas to the spinal cord, which can result in permanent motor deficits of the arm and hand. However, below the lesion, the spinal ...circuits that control movement remain intact and could be targeted by neurotechnologies to restore movement. Here we report results from two participants in a first-in-human study using electrical stimulation of cervical spinal circuits to facilitate arm and hand motor control in chronic post-stroke hemiparesis ( NCT04512690 ). Participants were implanted for 29 d with two linear leads in the dorsolateral epidural space targeting spinal roots C3 to T1 to increase excitation of arm and hand motoneurons. We found that continuous stimulation through selected contacts improved strength (for example, grip force +40% SCS01; +108% SCS02), kinematics (for example, +30% to +40% speed) and functional movements, thereby enabling participants to perform movements that they could not perform without spinal cord stimulation. Both participants retained some of these improvements even without stimulation and no serious adverse events were reported. While we cannot conclusively evaluate safety and efficacy from two participants, our data provide promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke.
Abstract The aim of this study was to compare the use of beta-tricalcium phosphate (β-TCP) (chronOS) with autogenous bone grafts alone in maxillary sinus elevation surgery. The test samples were ...β-TCP alone, β-TCP mixed with autogenous bone grafts (1:1), and autogenous bone grafts alone. Twelve maxillary sinuses were grafted with β-TCP (group 1), nine with β-TCP + autogenous bone graft (group 2), and 12 with autogenous bone graft (group 3). After 6 months, biopsies were obtained concurrent to the placement of dental implants; these were subjected to histomorphometric analysis and immunohistochemical analysis for runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor (VEGF). The average bone formation in group 1 was 46.3 ± 11.6% in the pristine bone region, 47.6 ± 9.9% in the intermediate region, and 44.8 ± 22.1% in the apical region; in group 2, values were 35.0 ± 15.8%, 32.5 ± 13.7%, and 32.8 ± 16.0%, respectively; in group 3, values were 43.1 ± 16.0%, 31.0 ± 13.0%, and 46.1 ± 16.3%, respectively. Immunostaining of samples in group 2 showed high cellular activity and immature bone; this differed from groups 1 and 3, in which mature bone was demonstrated. Thus, this study showed that β-TCP presents the same behaviour as autogenous bone graft, which makes it a good bone substitute.
Colorectal cancer (CRC) contains considerable heterogeneity; therefore, models of the disease must also reflect the multifarious components. Compared to traditional 2D models, 3D cellular models, ...such as tumor spheroids, have the utility to determine the drug efficacy of potential therapeutics. Monoculture spheroids are well-known to recapitulate gene expression, cell signaling, and pathophysiological gradients of avascularized tumors. However, they fail to mimic the stromal cell influence present in CRC, which is known to perturb drug efficacy and is associated with metastatic, late-stage colorectal cancer. This study seeks to develop a cocultured spheroid model using carcinoma and noncancerous fibroblast cells. We characterized the proteomic profile of cocultured spheroids in comparison to monocultured spheroids using data-independent acquisition with gas-phase fractionation. Specifically, we determined that proteomic differences related to translation and mTOR signaling are significantly increased in cocultured spheroids compared to monocultured spheroids. Proteins related to fibroblast function, such as exocytosis of coated vesicles and secretion of growth factors, were significantly differentially expressed in the cocultured spheroids. Finally, we compared the proteomic profiles of both the monocultured and cocultured spheroids against a publicly available data set derived from solid CRC tumors. We found that the proteome of the cocultured spheroids more closely resembles that of the patient samples, indicating their potential as tumor mimics.
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