In addition, females were associated more with rivers due to their higher water demands. The differences in habitat selection between Siberian ibex males and females depend on multiple considerations, but only a limited number of key factors determine their actual distribution.Laguerre-Gaussian (LG) beams contain a helical phase front with a doughnut-like intensity profile. We use the LG beam to introduce a rather simple method for generation of a vector beam (VB), a beam with spatially-dependent polarization in the beam cross section, via the nonlinear magneto-optical rotation (NMOR). We consider the NMOR of the polarization of a linearly polarized probe field passing through an inverted Y-type four-level quantum system interacting with a LG control field and a static magnetic field. It is shown that the polarization of the transmitted field is spatially distributed by the orbital angular momentum (OAM) of the LG control field, leading to generation of the VB with azimuthally symmetric polarization distribution. We show that the polarization and intensity distributions of the VB spatially vary by changing the OAMs of the LG control field. Moreover, the radial index of the LG control field has a major role in more spatially polarization distributing of the VB. It is shown that the intensity of the generated VBs in different points of the beam cross section can be controlled by the OAM as well as the radial index of the LG control field. However, the VB with highly spatially distributed can be generated for higher values of the radial index of LG control field. The analytical calculations determine the contribution of the different nonlinear (cross-Kerr effect) phenomena on the generation of the VB. We show that the VB is mainly generated via birefringence induced by the applied fields. Finally, we use asymmetric LG (aLG) beams for making the VBs with asymmetric polarization distribution. It is shown that by applying aLG beams, the azimuthal symmetry of the polarization distribution breaks and the asymmetric polarization distribution can be controlled by OAM and radial index of the aLG control field. The obtained results may find more interesting applications in fiber/free space optical communication to enhance the capacity of the information transmission.3,4-Methylenedioxymethamphetamine (MDMA) is currently being evaluated by the Food and Drug Administration (FDA) for the treatment of post-traumatic stress disorder (PTSD). If MDMA is FDA-approved it will be important to understand what medications may pose a risk of drug-drug interactions. The goal of this study was to evaluate the risks due to MDMA ingestion alone or in combination with other common medications and drugs of abuse using the FDA drug safety surveillance data. To date, nearly one thousand reports of MDMA use have been reported to the FDA. The majority of these reports include covariates such as co-ingested substances and demographic parameters. Univariate and multivariate logistic regression was employed to uncover the contributing factors to the reported risk of death among MDMA users. Several drug classes (MDMA metabolites or analogs, anesthetics, muscle relaxants, amphetamines and stimulants, benzodiazepines, ethanol, opioids), four antidepressants (bupropion, sertraline, venlafaxine and citalopram) and olanzapine demonstrated increased odds ratios for the reported risk of death. Future drug-drug interaction clinical trials should evaluate if any of the other drug-drug interactions described in our results actually pose a risk of morbidity or mortality in controlled medical settings.The potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8-1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia.Much of our understanding of motor control deficits in children with developmental coordination disorder (DCD) comes from upper limb assessments focusing on the dominant limb. Here, using two robotic behavioural tasks, we investigated motor control in both the dominant and non-dominant limbs of children with DCD. Twenty-six children with diagnosed DCD (20 males; mean age 10.6 years ± 1.3 years) and 155 controls were included in this cross-sectional study. Participants completed a visually guided reaching task with their dominant and non-dominant limbs and a bimanual object hitting task. Motor performance was quantified across nine parameters. We determined the number of children with DCD who fell outside of the typical performance range of the controls on these parameters and compared the DCD and control groups using ANCOVAs, accounting for age. Children with DCD demonstrated impairments in six out of nine parameters; deficits were more commonly noted in the non-dominant limb. Interestingly, when looking at individual performance, several children with DCD performed in the range of controls. These findings indicate that children with DCD display deficits in motor control in both the dominant and non-dominant limb and highlight the importance of including detailed assessments of both limbs when investigating children with DCD. They also demonstrate the variability in motor control performance evidenced by children with DCD.Ankylosing spondylitis cervical spine fractures (ASCFs) are particularly unstable and need special consideration when selecting appropriate internal fixation technology. However, there is a lack of related biomechanical studies. This study aimed to investigate the biomechanical influence of the pattern, length, and density of instrumentation for the treatment of ASCF. Posterior, anterior, and various combined fixation approaches were constructed using the finite element model (FEM) to mimic the surgical treatment of ASCFs at C5/6. The rate of motion change (RMC) at the fractured level and the internal stress distribution (ISD) were observed. The results showed that longer segments of fixation and combined fixation approaches provided better stability and lowered the maximal stress. The RMC decreased more significantly when the length increased from 1 to 3 levels (302% decrease under flexion, 134% decrease under extension) than from 3 to 5 levels (22% decrease under flexion, 23% decrease under extension). Longer fixation seems to be more stable with the anterior/posterior approach alone, but 3-level posterior fixation may be the most cost-effective option. It is recommended to perform surgery with combined approaches, which provide the best stability. Long skipped-screwing posterior fixation is an alternative technique for use in ASCF patients.Horizontal gene transfer (HGT), the movement of heritable materials between distantly related organisms, is crucial in eukaryotic evolution. However, the scale of HGT in choanoflagellates, the closest unicellular relatives of metazoans, and its possible roles in the evolution of animal multicellularity remains unexplored. We identified at least 175 candidate HGTs in the genome of the colonial choanoflagellate Salpingoeca rosetta using sequence-based tests. The majority of these were orthologous to genes in bacterial and microalgal lineages, yet displayed genomic features consistent with the rest of the S. rosetta genome-evidence of ancient acquisition events. Putative functions include enzymes involved in amino acid and carbohydrate metabolism, cell signaling, and the synthesis of extracellular matrix components. Functions of candidate HGTs may have contributed to the ability of choanoflagellates to assimilate novel metabolites, thereby supporting adaptation, survival in diverse ecological niches, and response to external cues that are possibly critical in the evolution of multicellularity in choanoflagellates.Glioblastoma multiforme is the most common primary brain tumor and among the most lethal types of cancer. Several mono-target small molecule-inhibitors have been investigated as novel therapeutics, thus far with poor success. In this study we investigated the anticancer effects of SB747651A, a multi-target small-molecule inhibitor, in three well characterized patient-derived glioblastoma spheroid cultures and a murine orthotopic xenograft model. Concentrations of 5-10 µM SB747651A reduced cell proliferation, spheroid formation, migration and chemoresistance, while apoptotic cell death increased. Investigation of oncogenic kinase signaling showed decreased phosphorylation levels of mTOR, CREB, GSK3 and GYS1 leading to altered glycogen metabolism and formation of intracellular reactive oxygen species. Expression levels of cancer stemness marker SOX2 were reduced in treated tumor cells and SB747651A treatment significantly prolonged survival of mice with intracranial glioblastoma xenografts, while no adverse effects were observed in vivo at doses of 25 mg/kg administered 5 days/week for 8 weeks. These findings suggest that SB747651A has anticancer effects in glioblastoma. The cancer-related pathophysiological mechanisms targeted by SB747651A are shared among many types of cancer; however, an in-depth clarification of the mechanisms of action in cancer cells is important before further potential application of SB747651A as an anticancer agent can be considered.Current treatments of plantar fasciitis are based on the premise that the Achilles tendon (AT) and plantar fascia (PF) are mechanically directly linked, which is an area of debate. The aim of this study was to assess the morphological relationship between the AT and PF. Nineteen cadaveric feet were x-ray imaged, serially sectioned and plastinated for digital image analyses. Measurements of the AT and PF thicknesses and cross-sectional areas (CSA) were performed at their calcaneal insertion. The fiber continuity was histologically assessed in representative subsamples. Strong correlations exist between the CSA of the AT and PF at calcaneal insertion and the CSA of PF’s insertional length (r = 0.80), and between the CSAs of AT’s and PF’s insertional lengths. Further correlations were observed between AT and PF thicknesses (r = 0.62). This close morphological relationship could, however, not be confirmed through x-ray nor complete fiber continuity in histology. This study provides evidence for a morphometric relationship between the AT and PF, which suggests the presence of a functional relationship between these two structures following the biological key idea that the structure determines the function. The observed morphological correlations substantiate the existing mechanical link between the AT and PF via the posterior calcaneus and might explain why calf stretches are a successful treatment option for plantar heel pain.Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of cognitive dysfunction. We previously showed that patients with metabolic syndrome (MetS) had significantly higher plasma levels of electronegative very-low-density lipoprotein (VLDL) than did healthy controls. However, the effects of electronegative-VLDL on the brain and cognitive function remain unclear. In this study, VLDL isolated from healthy volunteers (nVLDL) or patients with MetS (metVLDL) was administered to mice by means of tail vein injection. Cognitive function was assessed by using the Y maze test, and plasma and brain tissues were analyzed. We found that mice injected with metVLDL but not nVLDL exhibited significant hippocampus CA3 neuronal cell loss and cognitive dysfunction. In mice injected with nVLDL, we observed mild glial cell activation in the medial prefrontal cortex (mPFC) and hippocampus CA3. However, in mice injected with metVLDL, plasma and brain TNF-α and Aβ-42 levels and glial cell activation in the mPFC and whole hippocampus were higher than those in control mice. In conclusion, long-term exposure to metVLDL induced levels of TNF-α, Aβ-42, and glial cells in the brain, contributing to the progression of cognitive dysfunction. Our findings suggest that electronegative-VLDL levels may represent a new therapeutic target for cognitive dysfunction.Silver nanoparticles (AgNPs) exhibit strong antimicrobial properties against many pathogens. Traditionally employed chemical methods for AgNPs synthesis are toxic for the environment. Here, we report a quicker, simpler, and environmentally benign process to synthesize AgNPs by using an aqueous 'root extract’ of Salvadora persica (Sp) plant as a reducing agent. The synthesized Salvadora persica nano particles (SpNPs) showed significantly higher antimicrobial efficacy compared to earlier reported studies. We characterized SpNPs using UV-Vis spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FE-SEM), Dynamic Light Scattering (DLS) and X-ray powder diffraction (P-XRD). UV-Vis spectrum showed the highest absorbance at 420 nm. FTIR analysis depicts presence of bond stretching including OH- (3300 cm-1), C=N- (2100 cm-1) and NH- (1630 cm-1) which are attributed in the involvement of phenolics, proteins or nitrogenous compomany antimicrobial applications including wound healing, water purification, air filtering and other biomedical applications.Electrocardiogram (ECG) recordings, lasting hours before epileptic seizures, have been studied in the search for evidence of the existence of a preictal interval that follows a normal ECG trace and precedes the seizure’s clinical manifestation. The preictal interval has not yet been clinically parametrized. Furthermore, the duration of this interval varies for seizures both among patients and from the same patient. In this study, we performed a heart rate variability (HRV) analysis to investigate the discriminative power of the features of HRV in the identification of the preictal interval. HRV information extracted from the linear time and frequency domains as well as from nonlinear dynamics were analysed. We inspected data from 238 temporal lobe seizures recorded from 41 patients with drug-resistant epilepsy from the EPILEPSIAE database. Unsupervised methods were applied to the HRV feature dataset, thus leading to a new perspective in preictal interval characterization. Distinguishable preictal behaviour was exhibited by 41% of the seizures and 90% of the patients. Half of the preictal intervals were identified in the 40 min before seizure onset. The results demonstrate the potential of applying clustering methods to HRV features to deepen the current understanding of the preictal state.Mutations in the GBA1 gene encoding glucocerebrosidase (GCase) are linked to Gaucher (GD) and Parkinson’s Disease (PD). Since some GD and PD patients develop ocular phenotypes, we determined whether ocular phenotypes might result from impaired GCase activity and the corresponding accumulation of glucosylceramide (GluCer) and glucosylsphingosine (GluSph) in the Gba1D409V/D409V knock-in (Gba KI/KI; „KI”) mouse. Gba KI mice developed age-dependent pupil dilation deficits to an anti-muscarinic agent; histologically, the iris covered the anterior part of the lens with adhesions between the iris and the anterior surface of the lens (posterior synechia). This may prevent pupil dilation in general, beyond an un-responsiveness of the iris to anti-muscarinics. Gba KI mice displayed atrophy and pigment dispersion of the iris, and occlusion of the iridocorneal angle by pigment-laden cells, reminiscent of secondary open angle glaucoma. Gba KI mice showed progressive thinning of the retina consistent with retinal degeneration. GluSph levels were increased in the anterior and posterior segments of the eye, suggesting that accumulation of lipids in the eye may contribute to degeneration in this compartment. We conclude that the Gba KI model provides robust and reproducible eye phenotypes which may be used to test for efficacy and establish biomarkers for GBA1-related therapies.Despite increasing incidence, treatment for hepatoblastoma has not changed significantly over the past 20 years. Chemotherapeutic strategies continue to rely on cisplatin, as it remains the most active single agent against hepatoblastoma. However, chemoresistance remains a significant challenge with 54-80% of patients developing resistance to chemotherapy after 4-5 cycles of treatment. Stem cell-like cancer cells (SCLCCs) are a subset of cells thought to play a role in chemoresistance and disease recurrence. We have previously demonstrated that Proviral Integration site for Moloney murine leukemia virus (PIM) kinases, specifically PIM3, play a role in hepatoblastoma cell proliferation and tumor growth and maintain the SCLCC phenotype. Here, we describe the development of a cisplatin-resistant hepatoblastoma xenograft model of the human HuH6 cell line and a patient-derived xenograft, COA67. We provide evidence that these cisplatin-resistant cells are enriched for SCLCCs and express PIM3 at higher levels than cisplatin-naïve cells. We demonstrate that PIM inhibition with AZD1208 sensitizes cisplatin-resistant hepatoblastoma cells to cisplatin, enhances cisplatin-mediated apoptosis, and decreases the SCLCC phenotype seen with cisplatin resistance. Together, these findings indicate that PIM inhibition may be a promising adjunct in the treatment of hepatoblastoma to effectively target SCLCCs and potentially decrease chemoresistance and subsequent disease relapse.Vertical sleeve gastrectomy (VSG) is one of the most commonly performed clinical bariatric surgeries for the remission of obesity and diabetes. Its effects include weight loss, improved insulin resistance, and the improvement of hepatic steatosis. Epidemiologic studies demonstrated that vitamin D deficiency (VDD) is associated with many diseases, including obesity. To explore the role of vitamin D in metabolic disorders for patients with obesity after VSG. We established a murine model of diet-induced obesity + VDD, and we performed VSGs to investigate VDD’s effects on the improvement of metabolic disorders present in post-VSG obese mice. We observed that in HFD mice, the concentration of VitD3 is four fold of HFD + VDD one. In the post-VSG obese mice, VDD attenuated the improvements of hepatic steatosis, insulin resistance, intestinal inflammation and permeability, the maintenance of weight loss, the reduction of fat loss, and the restoration of intestinal flora that were weakened. Our results suggest that in post-VSG obese mice, maintaining a normal level of vitamin D plays an important role in maintaining the improvement of metabolic disorders.Multifunctional nanoparticles are discussed as versatile probes for homogeneous immunoassays for in-vitro diagnostics. Top-down fabrication allows to combine and tailor magnetic and plasmonic anisotropic properties. The combination of nanoimprint lithography, thin film deposition, and lift-off processing provides a top-down fabrication platform, which is both flexible and reliable. Here, we discuss the material compositions and geometrical designs of monodisperse multicomponent nanoparticles and their consequences on optical and magnetic properties. The rotational hydrodynamics of nanoparticles is measured and considered under the influence of magnetic shape anisotropy in the framework of the Stoner-Wohlfarth theory. The plasmon-optical properties are explained by discrete-dipole finite-element simulations. Rotational dynamical measurements of imprinted nanoprobes for two test proteins demonstrate the applicability as highly sensitive biomolecular nanoprobes.The purpose of this study was to analyze corneal sub-basal nerve plexus (SBNP) density and morphology and their relationships with corneal parameters and refractive status. In this single center study, in vivo confocal microscopy (IVCM) was performed in 76 eyes of 38 healthy subjects aged 19-87 (mean age 34.987 ± 1.148). Nerve fiber analysis was performed using Confoscan 4 microscope with semi-automated software (Nidek Technologies, Italy) The nerve fiber length (NFL) µm/mm2, nerve fiber density (NFD) no./mm2, tortuosity coefficient (TC), and nerve beadings density (NBD) no./mm were considered. Relationship between SBNP parameters and corneal curvature, thickness, diameter, and refraction were analyzed. Additionally, the association with gender, laterality and age were determined. NFL was inversely correlated with age (r = - 0.528, p  0.005). SBNP fiber length decreases with age, myopic refractive error and cylindrical power. SBNP fiber density reduces with age and myopic refractive error. Corneal nerve parameters are not influenced by gender or laterality.Nearly a third of patients with high-grade serous ovarian cancer (HGSC) do not respond to initial therapy and have an overall poor prognosis. However, there are no validated tools that accurately predict which patients will not respond. Our objective is to create and validate accurate models of prediction for treatment response in HGSC. This is a retrospective case-control study that integrates comprehensive clinical and genomic data from 88 patients with HGSC from a single institution. Responders were those patients with a progression-free survival of at least 6 months after treatment. Only patients with complete clinical information and frozen specimen at surgery were included. Gene, miRNA, exon, and long non-coding RNA (lncRNA) expression, gene copy number, genomic variation, and fusion-gene determination were extracted from RNA-sequencing data. DNA methylation analysis was performed. Initial selection of informative variables was performed with univariate ANOVA with cross-validation. Significant variables (p  less then  0.05) were included in multivariate lasso regression prediction models. Initial models included only one variable. Variables were then combined to create complex models. Model performance was measured with area under the curve (AUC). Validation of all models was performed using TCGA HGSC database. By integrating clinical and genomic variables, we achieved prediction performances of over 95% in AUC. Most performances in the validation set did not differ from the training set. Models with DNA methylation or lncRNA underperformed in the validation set. Integrating comprehensive clinical and genomic data from patients with HGSC results in accurate and robust prediction models of treatment response.We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN_MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In patients with high risks for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiation-related mortality risk could not outweigh the ~ 8% disease-specific survival benefit of WB + LN_MI radiotherapy in any of the assessed treatments.The rapid growth and development of technology has had significant implications for healthcare, personalized medicine, and our understanding of biology. In this work, we leverage the miniaturization of electronics to realize the first demonstration of wireless detection and communication of an electronic device inside a cell. This is a significant forward step towards a vision of non-invasive, intracellular wireless platforms for single-cell analyses. We demonstrate that a 25 [Formula see text]m wireless radio frequency identification (RFID) device can not only be taken up by a mammalian cell but can also be detected and specifically identified externally while located intracellularly. The S-parameters and power delivery efficiency of the electronic communication system is quantified before and after immersion in a biological environment; the results show distinct electrical responses for different RFID tags, allowing for classification of cells by examining the electrical output noninvasively. This versatile platform can be adapted for realization of a broad modality of sensors and actuators. This work precedes and facilitates the development of long-term intracellular real-time measurement systems for personalized medicine and furthering our understanding of intrinsic biological behaviors. It helps provide an advanced technique to better assess the long-term evolution of cellular physiology as a result of drug and disease stimuli in a way that is not feasible using current methods.Previous studies have shown the effect of refined grains on various cancers; however, data on the link between rice consumption and brain cancer are scarce. We aimed to investigate the relationship between rice consumption and glioma in Iranian adults. Current hospital-based case-control study was done in Tehran between 2009 and 2011. Cases were individuals with pathologically confirmed glioma in a maximally 1 month of the disease diagnosis (n = 128). Controls were individuals, aged between 20 and 75 years, who were hospitalized or were outpatients referred to other wards of the same hospital (n = 256). Cases and controls were frequently matched in terms of age and gender. Usual dietary intakes of participants, including rice consumption, during the preceding year were examined using a Block-format validated semi-quantitative 126-item food frequency questionnaire. Compared with participants in the lowest tertile of rice consumption ( less then  181 g/day), those in the highest tertile (≥ 279 g/day) had 2.47 times greater chance for having glioma (OR 2.47, 95% CI 1.44-4.23). This relationship was also seen when potential confounders including demographic variables, energy and dietary intakes as well as body mass index were taking into account; such that individuals in the top tertile of rice consumption had 2.46 times greater odds of glioma compared with those in the bottom tertile (OR 2.46, 95% CI 1.01-5.97). We found that rice consumption was positively associated with risk of glioma in adults. Further prospective studies are required to confirm this finding.Staphylococcus aureus is the cause of serious vascular infections such as sepsis and endocarditis. These infections are notoriously difficult to treat, and it is believed that the ability of S. aureus to invade endothelial cells and persist intracellularly is a key mechanism for persistence despite ongoing antibiotic treatment. Here, we used dual RNA sequencing to study the simultaneous transcriptional response of S. aureus and human endothelial cells during in vitro infections. We revealed discrete and shared differentially expressed genes for both host and pathogen at the different stages of infection. While the endothelial cells upregulated genes involved in interferon signalling and antigen presentation during late infection, S. aureus downregulated toxin expression while upregulating genes related to iron scavenging. In conclusion, the presented data provide an important resource to facilitate functional investigations into host-pathogen interaction during S. aureus invasive infection and a basis for identifying novel drug target sites.Antifreeze proteins (AFPs) inhibit ice growth by adsorbing onto specific ice planes. Microbial AFPs show diverse antifreeze activity and ice plane specificity, while sharing a common molecular scaffold. To probe the molecular mechanisms responsible for AFP activity, we here characterized the antifreeze activity and crystal structure of TisAFP7 from the snow mold fungus Typhula ishikariensis. TisAFP7 exhibited intermediate activity, with the ability to bind the basal plane, compared with a hyperactive isoform TisAFP8 and a moderately active isoform TisAFP6. Analysis of the TisAFP7 crystal structure revealed a bound-water network arranged in a zigzag pattern on the surface of the protein’s ice-binding site (IBS). While the three AFP isoforms shared the water network pattern, the network on TisAFP7 IBS was not extensive, which was likely related to its intermediate activity. Analysis of the TisAFP7 crystal structure also revealed the presence of additional water molecules that form a ring-like network surrounding the hydrophobic side chain of a crucial IBS phenylalanine, which might be responsible for the increased adsorption of AFP molecule onto the basal plane. Based on these observations, we propose that the extended water network and hydrophobic hydration at IBS together determine the TisAFP activity.Creutzfeldt-Jakob Disease (CJD) is a fatal, currently incurable, neurodegenerative disease. The search for candidate treatments would be greatly facilitated by the availability of human cell-based models of prion disease. Recently, an induced pluripotent stem cell derived human cerebral organoid model was shown to take up and propagate human CJD prions. This model offers new opportunities to screen drug candidates for the treatment of human prion diseases in an entirely human genetic background. Here we provide the first evidence that human cerebral organoids can be a viable model for CJD drug screening by using an established anti-prion compound, pentosan polysulfate (PPS). PPS delayed prion propagation in a prophylactic-like treatment paradigm and also alleviated propagation when applied following establishment of infection in a therapeutic-like treatment paradigm. This study demonstrates the utility of cerebral organoids as the first human 3D cell culture system for screening therapeutic drug candidates for human prion diseases.The eligibility of reperfusion therapy has been expanded to increase the number of patients. However, it remains unclear the reperfusion therapy will be beneficial in stroke patients with various comorbidities. We developed a reperfusion comorbidity index for predicting 6-month mortality in patients with acute stroke receiving reperfusion therapy. The 19 comorbidities included in the Charlson comorbidity index were adopted and modified. We developed a statistical model and it was validated using data from a prospective cohort. Among 1026 patients in the retrospective nationwide reperfusion therapy registry, 845 (82.3%) had at least one comorbidity. As the number of comorbidities increased, the likelihood of mortality within 6 months also increased (p  less then  0.001). Six out of the 19 comorbidities were included for developing the reperfusion comorbidity index on the basis of the odds ratios in the multivariate logistic regression analysis. This index showed good prediction of 6-month mortality in the retrospective cohort (area under the curve [AUC], 0.747; 95% CI, 0.704-0.790) and in 333 patients in the prospective cohort (AUC, 0.784; 95% CI, 0.709-0.859). Consideration of comorbidities might be helpful for the prediction of the 6-month mortality in patients with acute ischemic stroke who receive reperfusion therapy.Amyloid plaques are small (~ 50 μm), highly-dense aggregates of amyloid beta (Aβ) protein in brain tissue, supposed to play a key role in pathogenesis of Alzheimer’s disease (AD). Plaques´ in vivo detection, spatial distribution and quantitative characterization could be an essential marker in diagnostics and evaluation of AD progress. However, current imaging methods in clinics possess substantial limits in sensitivity towards Aβ plaques to play a considerable role in AD screening. Contrast enhanced X-ray micro computed tomography (micro CT) is an emerging highly sensitive imaging technique capable of high resolution visualization of rodent brain. In this study we show the absorption based contrast enhanced X-ray micro CT imaging is viable method for detection and 3D analysis of Aβ plaques in transgenic rodent models of Alzheimer’s disease. Using iodine contrasted brain tissue isolated from the Tg-F344-AD rat model we show the micro CT imaging is capable of precise imaging of Aβ plaques, making possible to further analyze various aspects of their 3D spatial distribution and other properties.CD73 is a cell surface ecto-5′-nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute to TNBC progression. This was done by inhibiting CD73 with adenosine 5′-(α, β-methylene) diphosphate (APCP) in MDA-MB-231 or 4T1 TNBC cells or through shRNA-silencing (sh-CD73). Effects of such inhibition on cell behavior was then studied in normoxia and hypoxia in vitro and in an orthotopic mouse model in vivo. CD73 inhibition, through shRNA or APCP significantly decreased cellular viability and migration in normoxia. Inhibition of CD73 also resulted in suppression of hypoxia-induced increase in viability and prevented cell protrusion elongation in both normoxia and hypoxia in cancer cells. Sh-CD73 4T1 cells formed significantly smaller and less invasive 3D organoids in vitro, and significantly smaller orthotopic tumors and less lung metastases than control shRNA cells in vivo. CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial-mesenchymal transition.To meet the present and forecasted market demand, bacterial alkaline phosphatase (ALP) production must be increased through innovative and efficient production strategies. Using sugarcane molasses and biogenic apatite as low-cost and easily available raw materials, this work demonstrates the scalability of ALP production from a newfound Bacillus paralicheniformis strain APSO isolated from a black liquor sample. Mathematical experimental designs including sequential Plackett-Burman followed by rotatable central composite designs were employed to select and optimize the concentrations of the statistically significant media components, which were determined to be molasses, (NH4)2NO3, and KCl. Batch cultivation in a 7-L stirred-tank bioreactor under uncontrolled pH conditions using the optimized medium resulted in a significant increase in both the volumetric and specific productivities of ALP; the alkaline phosphatase throughput 6650.9 U L-1, and µ = 0.0943 h-1; respectively, were obtained after 8 h that, ameliorated more than 20.96, 70.12 and 94 folds compared to basal media, PBD, and RCCD; respectively. However, neither the increased cell growth nor enhanced productivity of ALP was present under the pH-controlled batch cultivation. Overall, this work presents novel strategies for the statistical optimization and scaling up of bacterial ALP production using biogenic apatite.The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9-/- and Gal-9wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9-/- mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9-/- mice receiving Gal-9-/- or Gal-9wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9wt/wt mice receiving Gal-9-/- BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity.Over one billion adults worldwide are estimated to suffer from sleep apnea, a condition with wide-reaching effects on brain health. Sleep apnea causes cognitive decline and is a risk factor for neurodegenerative conditions such as Alzheimer’s disease. Rodents exposed to intermittent hypoxia (IH), a hallmark of sleep apnea, exhibit spatial memory deficits associated with impaired hippocampal neurophysiology and dysregulated adult neurogenesis. We demonstrate that IH creates a pro-oxidant condition that reduces the Tbr2+ neural progenitor pool early in the process, while also suppressing terminal differentiation of adult born neurons during late adult neurogenesis. We further show that IH-dependent cell-autonomous hypoxia inducible factor 1-alpha (HIF1a) signaling is activated in early neuroprogenitors and enhances the generation of adult born neurons upon termination of IH. Our findings indicate that oscillations in oxygen homeostasis, such as those found in sleep apnea, have complex stage-dependent influence over hippocampal adult neurogenesis.The pathophysiology behind thrombus formation in paroxysmal atrial fibrillation (AF) patients is very complex. This can be due to left atrial (LA) flow changes, remodeling, or both. We investigated differences for cardiovascular magnetic resonance (CMR)-derived LA 4D flow and remodeling characteristics between paroxysmal AF patients and patients without cardiac disease. In this proof-of-concept study, the 4D flow data were acquired in 10 patients with paroxysmal AF (age = 61 ± 8 years) and 5 age/gender matched controls (age = 56 ± 1 years) during sinus rhythm. The following LA and LA appendage flow parameters were obtained flow velocity (mean, peak), stasis defined as the relative volume with velocities  less then  10 cm/s, and kinetic energy (KE). Furthermore, LA global strain values were derived from b-SSFP cine images using dedicated CMR feature-tracking software. Even in sinus rhythm, LA mean and peak flow velocities over the entire cardiac cycle were significantly lower in paroxysmal AF patients compared to controls [(13.1 ± 2.4 cm/s vs. 16.7 ± 2.1 cm/s, p = 0.01) and (19.3 ± 4.7 cm/s vs. 26.8 ± 5.5 cm/s, p = 0.02), respectively]. Moreover, paroxysmal AF patients expressed more stasis of blood than controls both in the LA (43.2 ± 10.8% vs. 27.8 ± 7.9%, p = 0.01) and in the LA appendage (73.3 ± 5.7% vs. 52.8 ± 16.2%, p = 0.04). With respect to energetics, paroxysmal AF patients demonstrated lower mean and peak KE values (indexed to maximum LA volume) than controls. No significant differences were observed for LA volume, function, and strain parameters between the groups. Global LA flow dynamics in paroxysmal AF patients appear to be impaired including mean/peak flow velocity, stasis fraction, and KE, partly independent of LA remodeling. This pathophysiological flow pattern may be of clinical value to explain the increased incidence of thromboembolic events in paroxysmal AF patients, in the absence of actual AF or LA remodeling.Antibiotic resistances progressively cause treatment failures, and their spreading dynamics reached an alarming level. Some strains have already been classified as highly critical, e.g. the ones summarised by the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.). To restrain this trend and enable effective medication, as much information as possible must be obtained in the least possible time. Here, we present a DNA microarray-based assay that screens for the most important sepsis-relevant 44 pathogenic species, 360 virulence factors (mediate pathogenicity in otherwise non-pathogenic strains), and 409 antibiotic resistance genes in parallel. The assay was evaluated with 14 multidrug resistant strains, including all ESKAPE pathogens, mainly obtained from clinical isolates. We used a cost-efficient ligation-based detection platform designed to emulate the highly specific multiplex detection of padlock probes. Results could be obtained within one day, requiring approximately 4 h for amplification, application to the microarray, and detection.Proper maternal care is an essential factor of reproductive success in mammals, involving a repertoire of behaviors oriented toward the feeding and care of the offspring. Among the neurotransmitters involved in the initiation of these behaviors, serotonin (5-HT) seems to play an important role. Here we compared pup-oriented maternal behaviors in mice with constitutive 5-HT depletion, the tryptophan hydroxylase 2-knock-out (Tph2-KO) and the Pet1-KO mice. We report that the only common pup-oriented defect in these 2 hyposerotoninergic models is a defective nursing in parturient mice and altered nursing-like (crouching) behavior in virgin mice, while pup retrieval defects are only present in Tph2-KO. Despite a normal mammary gland development and milk production, the defect in appropriate nursing is responsible for severe growth retardation and early lethality of pups born to hyposerotonergic dams. This nursing defect is due to acute rather constitutive 5-HT depletion, as it is reproduced by adult knockdown of Tph2 in the dorsal raphe nucleus in mothers with a prior normal maternal experience. We conclude that 5-HT innervation from the dorsal raphe is required for both the initiation and maintenance of a normal nursing behavior. Our findings may be related to observations of reduced maternal/infant interactions in human depression.Quantification of iron is an important step to assess the iron burden in patients suffering from iron overload diseases, as well as tremendous value in understanding the underlying role of iron in the pathophysiology of these diseases. Current iron determination of total or labile iron, requires extensive sample handling and specialized instruments, whilst being time consuming and laborious. Moreover, there is minimal to no overlap between total iron and labile iron quantification methodologies-i.e. requiring entirely separate protocols, techniques and instruments. Herein, we report a unified-ferene (u-ferene) assay that enables a 2-in-1 quantification of both labile and total iron from the same preparation of a biological specimen. We demonstrate that labile iron concentrations determined from the u-ferene assay is in agreement with confocal laser scanning microscopy techniques employed within the literature. Further, this assay offers the same sensitivity as the current gold standard, inductively coupled plasma mass spectrometry (ICP-MS), for total iron measurements. The new u-ferene assay will have tremendous value for the wider scientific community as it offers an economic and readily accessible method for convenient 2-in-1 measurement of total and labile iron from biological samples, whilst maintaining the precision and sensitivity, as compared to ICP-MS.Dismal prognosis of glioblastoma (GBM) prompts for the identification of response predictors and therapeutic resistance mechanisms of current therapies. The authors investigated the impact of c-Met, HGF, VEGFR2 expression and microvessel density (MVD) in GBM patients submitted to second-line chemotherapy with bevacizumab. Immunohistochemical expression of c-Met, HGF, VEGFR2, and MVD was assessed in tumor specimens of GBM patients treated with bevacizumab, after progression under temozolomide. Survival analysis was evaluated according to the expression of the aforementioned biomarkers. c-Met overexpression was associated with a time-to-progression (TTP) after bevacizumab of 3 months (95% CI, 1.5-4.5) compared with a TTP of 7 months (95% CI, 4.6-9.4) in patients with low or no expression of c-Met (p = 0.05). VEGFR2 expression was associated with a TTP after bevacizumab of 3 months (95% CI, 1.8-4.2) compared with a TTP of 7 months (95% CI, 5.7-8.3) in patients with no tumoral expression of VEGFR2 (p = 0.009). Concomitant c-Met/VEGFR2 overexpression was associated with worse overall survival (13 months) compared with concomitant c-Met/VEGFR2 negative expression (19 months; p = 0.025). Our data support the hypothesis that c-Met and VEGFR2 overexpression have a role in the development of glioblastoma early resistance and might predict poorer responses to anti-angiogenic therapies.Local Xylocarpus granatum leaves were extracted by ethyl acetate solvent and characterized by TLC fingerprinting and 2D 1H NMR spectroscopy to contain phenolic compounds as well as several organic and amino acids as metabolic byproducts, such as succinic acid and acetic acid. Traces of flavonoids and other non-categorized phenolic compounds exhibited intermediate antioxidant activity (antioxidant IC50 84.93 ppm) as well as anticancer activity against HeLa, T47D, and HT-29 cell lines; which the latter being most effective against HT-29 with Fraction 5 contained the strongest activity (anticancer IC50 23.12 ppm). Extracts also behaved as a natural growth factor and nonlethal towards brine shrimps as well as human adipose-derived stem cell hADSC due to antioxidative properties. A stability test was performed to examine how storage conditions factored in bioactivity and phytochemical structure. Extracts were compared with several studies about X. granatum leaves extracts to evaluate how ethnogeography and ecosystem factored on biologically active compounds. Further research on anticancer or antioxidant mechanism on cancer cells is needed to determine whether the extract is suitable as a candidate for an anticancer drug.In functional near infrared spectroscopy (fNIRS), deconvolution analysis of oxy and deoxy-hemoglobin concentration changes allows estimating specific hemodynamic response functions (HRF) elicited by neuronal activity, taking advantage of the fNIRS excellent temporal resolution. Diffuse optical tomography (DOT) is also becoming the new standard reconstruction procedure as it is more accurate than the modified Beer Lambert law approach at the sensor level. The objective of this study was to assess the relevance of HRF deconvolution after DOT constrained along the cortical surface. We used local personalized fNIRS montages which consists in optimizing the position of fNIRS optodes to ensure maximal sensitivity to subject specific target brain regions. We carefully evaluated the accuracy of deconvolution when applied after DOT, using realistic simulations involving several HRF models at different signal to noise ratio (SNR) levels and on real data related to motor and visual tasks in healthy subjects and from spontaneous pathological activity in one patient with epilepsy. We demonstrated that DOT followed by deconvolution was able to accurately recover a large variability of HRFs over a large range of SNRs. We found good performances of deconvolution analysis for SNR levels usually encountered in our applications and we were able to reconstruct accurately the temporal dynamics of HRFs in real conditions.This study aimed to consolidate current knowledge of wildlife brucellosis in Africa and to analyse available predictors of infection. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Information on species, test used, test results, area, rainfall, livestock and wildlife contact and year of study were extracted. This systematic review revealed 42 prevalence studies, nine disease control articles and six articles on epidemiology. Brucella abortus, Brucella melitensis, Brucella inopinata and Brucella suis were reported in wildlife. The prevalence studies revealed serological evidence of brucellosis in buffalo, antelope (positive in 14/28 species), carnivores (4/12) and other species (7/20) over the last five decades. Buffalo populations were more likely to be infected and had a higher seroprevalence than other species; the pooled seroprevalence was 13.7% (95% CI 10.3-17.3%) in buffalo, 7.1% (95% CI 1.1-15.5%) in carnivores and 2.1% (95% CI 0.1-4.9%) in antelope. Wildlife in high rainfall areas (≥ 800 mm) were more likely to be infected, and infected populations showed higher seroprevalence in high rainfall areas and in studies published after 2000. Domestic animal contact was associated with increased seroprevalence in antelope and carnivore species, but not in buffalo, supporting the hypothesis that buffalo may be a reservoir species.Sexual selection, including mate choice and intrasexual competition, is responsible for the evolution of some of the most elaborated and sexually dimorphic traits in animals. Although there is sexual dimorphism in the shape of human faces, it is not clear whether this is similarly due to mate choice, or whether mate choice affects only part of the facial shape difference between men and women. Here we explore these questions by investigating patterns of both facial shape and facial preference across a diverse set of human populations. We find evidence that human populations vary substantially and unexpectedly in both the magnitude and direction of facial sexually dimorphic traits. In particular, European and South American populations display larger levels of facial sexual dimorphism than African populations. Neither cross-cultural differences in facial shape variation, sex differences in body height, nor differing preferences for facial femininity and masculinity across countries, explain the observed patterns of facial dimorphism.