Notes

Properly modulating cold weather initialized cost transfer within natural semiconductors by simply precise potential hurdle design.
The protein was purified to homogeneity. In vivo and in vitro substrate analyses revealed that MaWSD5 is able to synthesize WE but no triacylglycerols. The protein produces WE from saturated and monounsaturated mid- and long-chain substrates. Arabidopsis thaliana seeds expressing a fatty acid reductase from Marinobacter aquaeolei VT8 and MaWSD5 produce WE. Main WE synthesized are 201/181 and 201/201. This makes MaWSD5 a suitable candidate for industrial WE production in planta.Background As the coronavirus (COVID-19) pandemic spreads globally, hospitals are rushing to adapt their facilities which may not have been designed to deal with infections adequately. We present the management of a patient with suspected COVID-19 pneumonia. Case A 66-years-old man presented to the hospital and his recent travel history, infective symptoms and CXR made him a possible COVID-19 suspect. Emergency surgery was decided considering the septic condition. The patient was transported to operating theatre with supplemental oxygen over a face mask and plastic covering over the trolley. Rapid sequence intubation was performed by an experienced anesthetist using a videolaryngoscope. After surgery, the patient remained intubated to avoid re-intubation due to initial presentation of respiratory distress. Droplet, contact and airborne infection precautions were instituted. Conclusions Our objective was to facilitate surgical management of patients with known or suspected COVID-19 while minimising risk of nosocomial transmission to healthcare workers and other patients.3D bioprinting is an emerging biofabrication process for the production of adherent cell-based products, including engineered tissues and foods. While process innovations are rapidly occurring in the area of process monitoring, which can improve fundamental understanding of process-structure-property relations as well as product quality by closed-loop control techniques, in-line sensing of the bioink composition remains a challenge. Here, we present that hollow multifunctional fibers enable in-line impedimetric sensing of bioink composition and exhibit selectivity for real-time classification of cell type, viability, and state of differentiation during bioprinting. Continuous monitoring of the fiber impedance magnitude and phase angle response from 102 to 106 Hz during microextrusion 3D bioprinting enabled compositional and quality analysis of alginate bioinks that contained fibroblasts, neurons, or mouse embryonic stem cells (mESCs). Fiber impedimetric responses associated with the bioinks that contained differentiated mESCs were consistent with differentiation marker expression characterized by immunocytochemistry. 3D bioprinting through hollow multifunctional fiber impedimetric sensors enabled classification of stem cells as stable or randomly differentiated populations. This work reports an advance in monitoring of 3D bioprinting processes in terms of in-line sensor-based bioink compositional analysis using fiber technology and provides a non-invasive sensing platform for achieving future quality-controlled bioprinted tissues and injectable stem-cell therapies.Chitosan nanofibrous membranes have immense potential in tissue engineering and drug delivery applications because of their high degree of biocompatibility, their ability to mimic the extracellular matrix and increased surface area. However, their use is often limited due to their extreme hydrophilic nature causing them to lose their nanofibrous structure. In this study, chitosan membranes were modified either by acylation reactions using fatty acids of different chain lengths or tert-butyloxycarbonyl(tBOC) protecting groups to increase the hydrophobicity of the membranes and protect the nanofibrous structure. The modified membranes were characterized using scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, water contact angle and elemental analysis to confirm the addition of the modification groups. These membranes were then evaluated to control the release of a hydrophobic osteogenic drug-simvastatin (SMV). The interaction between SMV and the polymer were detell studies showed that SMV from 75 to 600ng/ml range possessed osteogenic potential in a dose dependent manner and the amount of SMV released from the most hydrophobic FA treated membranes was not cytotoxic and supported osteogenic differentiation. This study demonstrates our ability to control the release of a hydrophobic drug from chitosan membranes based on the clinical need.Neuroinflammation is a crucial mechanism in many neurological disorders. Injury to the peripheral sensory nerves leads to a neuroinflammatory response in the somatosensory pathway, from dorsal root ganglia (DRG) to the spinal cord, contributing to neuropathic pain. How the immune reaction is initiated peripherally and propagated to the spinal cord remains less clear. Here, we find that ciliary neurotrophic factor (CNTF), highly expressed in Schwann cells, mediates neuroinflammatory response through the activating signal transducer and activator of transcription 3 (STAT3) and inducing interleukin 6 (IL-6) in sensory neurons. Cntf deficiency attenuates neuroinflammation in DRG and the spinal cord with alleviated pain post-injury. Recombinant CNTF applied to the sensory nerves recapitulates neuroinflammation in the DRG and spinal cord, with consequent pain development. We delineate the CNTF-STAT3-IL-6 axis in mediating the onset and progression of the inflammatory cascade from the periphery to the spinal cord with therapeutic implications for neuropathic pain.Background Management of hundreds of analytes obtained from the molecular multiplex techniques currently available may represent a challenge for clinicians in daily clinical practice. Objectives The aim of the study was to describe a comprehensive and simple approach to assess such complex molecular results, to display relevant disease-specific signatures at a glance, and to facilitate their interpretation. Method A total of 6,332 consecutive allergic patients, categorized based on clinical symptoms reported at the time of the first visit before IgE testing, were evaluated through ImmunoCAP ISAC112®. Results and conclusions The occurrence of bronchial asthma is associated with polcalcin, serum albumin, or lipocalin reactivity. Higher risk of severe reaction to food is linked to tropomyosin or nonspecific lipid transfer protein reactivity (in the absence of plant pathogenesis-related proteins [PR-10] or profilin sensitization). We used radar graphic display to highlight, at a glance, the molecular reactivity profiles associated with relevant disease-specific patterns.Background Excessive androgenesis in the skin promotes sebaceous hyperproduction which is the onset of acne vulgaris pathogenesis. Free fatty acids and lipids accumulation in the glandular infundibulum culminates in microbiota imbalance, triggering inflammatory response and follicular hyperkeratinization. Aims The purpose of this work was to present an alternative cosmetic treatment for acne skin care, focusing on the prevention of sebaceous gland dysregulation. Methods Insulin-stimulated human sebocytes were treated with non-cytotoxic concentrations of a DTRW cosmetic formulation. After 6 days of incubation, cell lysates were collected for testosterone, 5α-reductase and dyhidrotestosterone (DHT) quantitation. In parallel, cells were stained with Oil Red O to measure sebum production. Results Human sebocytes were incubated with insulin to mimic a seborrheic microenvironment with overproduction of intracellular lipids and fatty acids. Concomitant incubation of cell cultures with DRTW was able to promote a 52.97% reduction in intracellular lipid content. The anti-androgenic properties of DRTW had been proved by the reductions of testosterone (↓59.90%), 5α reductase (↓59.34%) and DHT (↓55.98%) levels in sebocyte cultures also stimulated with insulin. Conclusion The results indicate a promising action of DRTW cosmetic formulation in preventing the development of acne lesions by mechanisms involving the modulation of cutaneous androgenesis and consequently the control of sebum overproduction, considered one of the leading cause of acne.Objectives The purpose of the present study was to estimate the trends and state of research of periprosthetic joint infection (PJI). Methods Publications on PJI published between 1998 and 2018 were searched from the Web of Science database and analyzed using bibliometrics. The Altmetric score and Research Interest score were combined to provide a weighted count. The scope of the Altmetric score includes >16 weighted composite scores from websites such as Twitter, Facebook and YouTube, whereas the Research Interest score is calculated from information derived from ResearchGate. Results A total of 3245 documents were published. The largest contribution was made by the United States (US), with the most contributive institution the Rothman Institute. The most relative articles were published by the Journal of Arthroplasty, whereas the highest citation frequency journal was Clinical Orthopaedics and Related Research. There was a positive correlation between citation counts and Research Interest scores, while the Altmetric Attention score showed a negative value for highly cited articles. Conclusions Based on the current trends of globalization, there is a rising trend in publications on PJI, with the largest annual contributions made by the US. The most influential contributors are researchers from the US and Europe. Twitter is used as a platform to communicate knowledge by most PJI researchers. More recent research will focus on the diagnosis and risk factors of PJI.Since the seventies, positron emission tomography (PET) has become an invaluable medical molecular imaging modality with an unprecedented sensitivity at the picomolar level, especially for cancer diagnosis and the monitoring of its response to therapy. More recently, its combination with X-ray computed tomography (CT) or magnetic resonance (MR) has added high precision anatomic information in fused PET/CT and PET/MR images, thus compensating for the modest intrinsic spatial resolution of PET. Nevertheless, a number of medical challenges call for further improvements in PET sensitivity. These concern in particular new treatment opportunities in the context personalized (also called precision) medicine, such as the need to dynamically track a small number of cells in cancer immunotherapy or stem cells for tissue repair procedures. A better signal-to-noise ratio (SNR) in the image would allow detecting smaller size tumours together with a better staging of the patients, thus increasing the chances of putting can11C radiopharmaceuticals. The present roadmap article toward the advent of 10 ps TOF-PET addresses the status and current/future challenges along the development of TOF-PET with the objective to reach this mythic 10 ps frontier that will open the door to real-time volume imaging virtually without tomographic inversion. The medical impact and prospects to achieve this technological revolution from the detection and image reconstruction point-of-views, together with a few perspectives beyond the TOF-PET application are discussed.Context Residency programs invest considerable time and resources in candidate interviews due to their perceived ability to reveal important social traits. However, studies examining the ability of interviews to predict resident performance have shown mixed findings, and the role that the interview plays in candidate evaluation remain unclear. This mixed methods study, conducted in an anesthesiology residency program at a large academic medical center, examines how interviews contributed to candidate assessment as well as whether the addition of behavioral questions to interviews altered their role in the evaluation process. Methods During 2018-2019 residency selection season in the Department of Anesthesiology & Critical Care at the University of Pennsylvania, independent ratings for each interviewee were collected from faculty interviewers. Consensus ratings subsequently established by committee were also collected. Committee meetings were audio-recorded and transcribed for qualitative analysis. Behavioral the interviews from providing discrete assessments of interpersonal qualities-even when behavioral questions were included. In the continued effort to perform well-rounded assessments of resident candidates, further research and reflection on the role of interviewing in evaluation is necessary.MicroRNAs are regulatory molecules that can be packaged into exosomes to modulate cellular response of recipients. While the role of exosomes during viral infection is beginning to be appreciated, the involvement of exosomal miRNAs in immunoregulation in invertebrates has not been addressed. Here, we observed that exosomes released from WSSV-injected mud crabs could suppress viral replication by inducing apoptosis of hemocytes. Besides, miR-137 and miR-7847 were found to be less packaged in mud crab exosomes during viral infection, with both miR-137 and miR-7847 shown to negatively regulate apoptosis by targeting the apoptosis-inducing factor (AIF). Our data also revealed that AIF translocated to the nucleus to induce DNA fragmentation, and could competitively bind to HSP70 to disintegrate the HSP70-Bax (Bcl-2-associated X protein) complex, thereby activating the mitochondria apoptosis pathway by freeing Bax. The present finding therefore provides a novel mechanism that underlies the crosstalk between exosomal miRNAs and apoptosis pathway in innate immune response in invertebrates.Background As the climate of medical care continually shifts, more is expected of surgical specialists than ever before. The rate of burnout amongst providers appears to be increasing, while the career longevity' of the modern physician continues to rise to meet the growing demands of our patient population. Spinal surgery is a demanding field, requiring significant amounts of mental and physical fortitude. We intend to highlight issues that cause debility in this cohort of providers. Methods This study surveyed the members of the North American Spine Society (NASS) to better ascertain the issues that plague our profession, in relation to physical and mental debility. The survey included multiple-choice questions regarding demographics, burnout, and health status, among other physical and mental health concerns. Results We achieved a 19% response rate. Eighty percent of responders highlighted physical debility, and psychological, social, and/or behavioral debility (e.g., burnout) was reported by 39% of respondents. Conclusions This study highlights the need to improve the work environment and maintain physician health. While this report sheds light on the problems affecting our colleagues, there is much work that is needed to improve on them. Often the medical philosophy is to ignore one's own personal discomfort in the quest to help patients. In an era where physician career longevity is needed, these issues must be identified and addressed.Microfluidic artificial lungs (µALs) have the potential to improve the treatment and quality of life for patients with acute or chronic lung injury. In order to realize the full potential of this technology (including as a destination therapy), the biocompatibility of these devices needs to be improved to produce long-lasting devices that are safe for patient use with minimal or no systemic anticoagulation. Many studies exist which probe coagulation and thrombosis on polydimethyl siloxane (PDMS) surfaces, and many strategies have been explored to improve surface biocompatibility. As the field of µALs is young, there are few studies which investigate biocompatibility of functioning µALs; and even fewer which were performed in vivo. Here, we use both in vitro and in vivo models to investigate two strategies to improve µAL biocompatibility 1) a hydrophilic surface coating (polyethylene glycol, PEG) to prevent surface fouling, and 2) the addition of nitric oxide (NO) to the sweep gas to inhibit platelet activatioetime. Statement of Significance The development of microfluidic artificial lungs (µALs) can potentially have a massive impact on the treatment of patients with acute and chronic lung impairments. Before these devices can be deployed clinically, the biocompatibility of µALs must be improved and more comprehensively understood. This work explores two strategies for improving biocompatibility, a hydrophilic surface coating (polyethylene glycol) for general surface passivation and the addition of nitric oxide (NO) to the sweep gas to quell platelet and leukocyte activation. These two strategies are investigated separately and as a combined device treatment. Devices are challenged with clottable blood using in vitro testing and in vivo testing in rabbits. This is the first study to our knowledge that allows statistical comparisons of biocompatible µALs in animals, a key step towards eventual clinical use.Skin damaged during sea battles is vulnerable to seawater immersion and bacterial infection. Scaffolds with effective biological function are highly desired for treatment of naval combat wound injuries. Herein, we prepared composite scaffolds of CS/GEL/GMs-CIP. The chitosan (CS) and gelatin (GEL) were cross-linked by genipin as matrix, and then gelatin microspheres loading ciprofloxacin hydrochloride (GMs-CIP) were add. From in vitro characterization results, CS/GEL/GMs-CIP had high water absorption ability, proper porosity, satisfactory fracture resistance, and flexibility. Furthermore, CS/GEL/GMs-CIP composite scaffold had excellent biocompatibility. Antibacterial experiments confirmed that CS/GEL/GMs-CIP had a significant inhibitory effect on E. coli, S. aureus and P. aeruginosa. The in vivo wound healing was evaluated using animal wound infection model of seawater immersion, and it was observed that the prepared composite scaffolds accelerated wound healing, reepithelialization, collagen deposition. Further analysis of wound tissue indicated that the expression of anti-inflammatory factor (TGF-β1) was up-regulated, but the serum endotoxin levels and expression of pro-inflammatory factor (TNF-a, IL-6, and IL-1β) were down-regulated. In summary, we believe that CS/GEL/GMs-CIP composite scaffold may serve as a promising multifunctional dressing for healing with open trauma wound infections and wound with seawater immersion.In chronic HIV infection, virus-specific cytotoxic CD8 T cells showed expression of checkpoint receptors and impaired function. Therefore, restoration of CD8 T cell function is critical in cure strategies. Here, we show that in vitro blockade of PD-L1 (Avelumab) in combination with recombinant human IL-15 (rhIL-15) synergistically enhanced cytokine secretion by proliferating HIVGag-specific CD8 T cells. In addition, these CD8 T cells have a CXCR3+PD1-/low phenotype, suggesting a potential to traffic into peripheral tissues. In vitro, proliferating CD8 T cells express PD-L1 suggesting that anti-PD-L1 treatment also targets virus-specific CD8 T cells. All together these data indicate that rhIL-15/Avelumab combination therapy could be a useful strategy to enhance CD8 T cell function in cure strategies.Few authors in the Western literature have acquired such a monumental reputation as Thomas Mann and Fyodor Dostoyevsky; although with different backgrounds and aesthetic peculiarities, their writings converge thematically in their frequent relationship with disease. From Dostoyevsky's struggle with epilepsy to Mann's descriptions of tuberculosis and cholera, many are the examples found in their body of work describing medical afflictions. One noteworthy similarity in their works is the presence of hallucinations with Mephistopheles-like devilish entities, possibly caused by neurological diseases in Mann's case, concerning the main character of Doctor Faustus, caused by neurosyphilis, while for Dostoyevsky, concerning one of the titular Brothers Karamazov, by delirium tremens. In both cases, the authors leave room for ambiguity, with the characters themselves casting doubts on whether their experiences were indeed caused by their disease or by an actual supernatural being. In this, we may find an interesting intersection between neurology and the literature.Background The glucose metabolism of cancer cells differs from that of noncancerous cells. Transketolase-like protein 1 (TKTL1) and glucose transporter 1 (GLUT1) both play a role in this process. These biochemical tumor markers are overexpressed in several types of human cancer. Objective We sought to determine if TKTL1 and/or GLUT1 expression predicts prognosis in gastric cancer. Methods In this retrospective study, we selected 284 patients who underwent surgery for gastric cancer at the Helsinki University Hospital. We used immunohistochemistry to assess the expression of TKTL1 and GLUT1, combined with clinicopathological data. Results Positive expression of TKTL1 was associated with positive expression of GLUT1, age over 65 years, male gender, advanced stage (II-IV), and advanced tumors (T2-T4). Patients with a positive expression of TKTL1 had a poorer prognosis than those with no expression (p = 0.042, Breslow test). GLUT1 positivity was associated with higher age and with the intestinal type of gastric cancer but did not carry any prognostic value. Conclusion In conclusion, our study showed that positive expression of TKTL1 correlates with a poor prognosis in gastric cancer.In this paper, we describe the application of the 4D biofabrication approach for the fabrication of artificial nerve graft. Bilayer scaffolds consisting of uniaxially aligned polycaprolactone-poly(glycerol sebacate) (PCL-PGS) and randomly aligned methacrylated hyaluronic acid (HA-MA) fibers were fabricated using electrospinning and further used for the culture of PC-12 neuron cells. Tubular structures form instantly after immersion of fibrous bilayer in an aqueous buffer and the diameter of obtained tubes can be controlled by changing bilayer parameters such as the thickness of each layer, overall bilayer thickness, and medium counterion concentration. Designed scaffolds showed a self-folded scroll-like structure with high stability after four weeks of real-time degradation. The significance of this research is in the fabrication of a tuneable tubular nerve guide conduits that can simplify the current existing clinical treatment of neural injuries.Radiation chemists have been routinely using high-dose microsecond-pulsed irradiation for almost 60 years, involving many thousands of studies, in the technique of "pulse radiolysis". This involves dose rates broadly similar to the FLASH regimen now attracting interest in radiotherapy and radiobiology. Using the experience gained from radiation chemistry, two scenarios are examined here that may provide a mechanistic basis for any differential response in normal tissues versus tumors in FLASH radiotherapy. These are 1. possible depletion of a chemical critical to the response to radiation, and 2. radical-radical reactions as a possible cause of effects occurring mainly with high-intensity pulsed radiation. The evidence for changes in relative levels of so-called "reactive oxygen species" produced after irradiation using FLASH versus conventional irradiation modalities is also examined.Introduction Metastatic breast cancer has poor prognosis due to limited therapeutic options. Protein kinase dysregulations have a major role in breast cancer progression and metastasis. In this study, we investigated the anti-cancer activity of sorafenib, a multikinase inhibitor, which targets receptor tyrosine kinases in breast cancer. Although treatment with sorafenib has increased the patient survival and inhibited metastatic migration in hepatocellular carcinoma, its role in breast cancer migration, metastasis, and intracellular signaling modulation is unknown. Methods Breast cancer cell lines MCF7 and MDA-MB-231 were treated with sorafenib and its effect on proliferation, migration, invasion and gene expression was analyzed. Results We found that sorafenib has an anti-proliferative and cytotoxic effect on breast cancer cells. Importantly, sorafenib inhibited the migration and invasion of breast cancer cells in vitro. Mechanistically, sorafenib increased mitochondrial superoxide production, suppressed breast cancer stem cell self-renewal, inhibited epithelial mesenchymal transition and ERK signaling. Conclusion Thus, sorafenib has anti-cancer activity against breast cancer cells and could improve the survival of breast cancer patients by inhibiting their invasive and metastatic properties.Recently, organic dyes with aggregation-induced emission (AIE) have attracted much attention in bioimaging and diagnostics. Relatively, the application of traditional dyes has diminished because of aggregation-caused quenching (ACQ). In this work, we compare the imaging ability of nanoparticle formulations of these two kinds of dyes. Boron dipyrromethene (BODIPY) was chosen as a representative of the ACQ dyes, and an aggregation-induced emission (AIE) dye BPMT was used for comparison. BODIPY and BPMT were entrapped into PEG5k-PLA10k to form BODIPY-loaded NPs (BNPs) and BPMT-loaded NPs (ANPs), respectively. In vivo and ex vivo imaging demonstrated that BNP1 with ultralow BODIPY load (0.07%) can effectively accumulate in tumor tissues and enable long-term noninvasive imaging. In contrast, ANP4 with high BPMT load (1.6%) has poor bioimaging ability. In general, our work has certain reference significance for the application of ACQ dyes and AIEgens in bioimaging, diagnostics, and theranostics.Pulmonary typical carcinoid (TC) is a low-grade, rare lung cancer of neuroendocrine origin. Currently, there is very little information available about the immune cell composition in TC tumors. Here, we analyzed by flow cytometry resected tumors from four never-smoker female patients with TC. Twelve distinct immune cell types were identified in TC tumors. The most abundant immune cells were CD8+ T cells, CD4+ T cells, B cells, and macrophages, which represented 19.8%, 17.7%, 11.5%, and 11% of all tumor-infiltrating CD45+ leukocytes, respectively. Natural killer (NK) cells (8.9%) and neutrophils (3.9%) were also common. Three types of dendritic cells (DCs) were identified (plasmacytoid DCs, CD1c+ DCs, and CD141+ DCs) which together constituted 1.4% of all immune cells in TC tumors. Small populations of basophils (1.3%), mast cells (0.8%), and eosinophils (0.6%) were also present. Notably, the percentage of leukocytes (of all living cells) was much lower in TC tumors compared to high-grade non-small cell lung cancer (NSCLC) tumors, and also compared to non-cancerous lung tissue. We conclude that TC tumors are relatively non-inflammatory, although the immune landscape was found to be very complex.Coronavirus disease-2019 (COVID-19) pandemic is the biggest global health threat in the 21st century. We describe a case of a patient with suspected COVID-19 who needed urgent coronary artery interrogation, in which we utilized robotic assistance to minimize the risk of exposure to COVID-19 and reduced personal protective equipment needed by the procedural team.As sessile organisms, plants are exposed to multiple abiotic stresses commonly found in nature. To survive, plants have developed complex responses that involve genetic, epigenetic, cellular, and morphological modifications. Among different environmental cues, salt stress has emerged as a critical problem contributing to yield losses and marked reductions in crop production. Moreover, as the climate changes, it is expected that salt stress will have a significant impact on crop production in the agroindustry. On a mechanistic level, salt stress is known to be modulated by the crosstalk of many signaling molecules such as phytohormones, with auxin having been described as a key mediator of the process. Auxin plays an important role in plant developmental responses and stress, modulating a complex balance of biosynthesis, transport, and signaling that among other things, finely tune physiological changes in plant architecture and Na+ accumulation. In this review, we describe our current knowledge on auxin's role in modulating the salt-stress response. We also discuss current and potential biotechnological approaches to tackling salt stress.We have prepared a candidate biocompatible construct for skin wound healing based on electrospun polycaprolactone (PCL) nanofibrous membranes. The membrane material was loaded either with L-arginine or with alaptide, or with a mixture of both bioactive components. Alaptide is a spirocyclic synthetic dipeptide, an analogue of melanocyte-stimulating hormone release-inhibiting factor. L-arginine is an amino acid with a basic guanidine side chain. It is a direct precursor of nitric oxide, which plays a pivotal role in skin repair. The presence and the distribution of the additives were proved with HPLC, FTIR and Raman spectroscopy. The influence of L-arginine and alaptide on the morphology of the membrane was characterized using SEM. No statistically significant correlation between fiber diameter and drug concentration was observed. The membranes were then tested in vitro for their cytotoxicity, using primary human dermal fibroblasts, in order to obtain the optimal concentrations of the additives for in vivo tests in a rat model. The membranes with the highest concentration of L-arginine (10 wt. %) proved to be cytotoxic. The membranes with alaptide in concentrations from 0.1 to 2.5 wt.%, and with the other L-arginine concentrations (1 and 5 wt.%) did not show high toxicity. In addition, there was no observed improvement in cell proliferation on the membranes. The in vivo experiments revealed that membranes with 1.5 wt.% of alaptide or with 1.5 wt.% of alaptide in combination with 5 wt.% of L-arginine markedly accelerated the healing of skin incisions, and particularly the healing of skin burns, i.e. wounds of relatively large extent. These results indicate that our newly-developed nanofibrous membranes are promising for treating wounds with large damaged areas, where a supporting material is needed.Wastewater has become one of the most important and least expensive water for the agriculture sector, as well as an alternative to the overexploitation of water resources. However, inappropriate treatment before its reuse can result in a negative impact on the environment, such as the presence of pathogens. This poses an increased risk for environmental safety, which can subsequently lead to an increased risk for human health. Among all the emerging wastewater pathogens, bacteria of the genus Helicobacter are some of the most disturbing ones, since they are directly related to gastric illness and hepatobiliary and gastric cancer. Therefore, the aim of this study was to determine the presence of potentially pathogenic Helicobacter spp. in treated wastewater intended for irrigation. We used a next generation sequencing approach, based on Illumina sequencing in combination with culture and other molecular techniques (qPCR, FISH and DVC-FISH), to analyze 16 wastewater samples, with and without an enrichment step. By culture, one of the direct samples was positive for H. pylori. FISH and DVC-FISH techniques allowed for detecting viable Helicobacter spp., including H. pylori, in seven out of eight samples of wastewater from the tertiary effluents, while qPCR analysis yielded only three positive results. When wastewater microbiome was analyzed, Helicobacter genus was detected in 7 samples. The different molecular techniques used in the present study provided evidence, for the first time, of the presence of species belonging to the genus Helicobacter such as H. pylori, H. hepaticus, H. pullorum and H. suis in wastewater samples, even after disinfection treatment.Background Demographic changes and shorter hospital stays have made community-based homecare nursing an increasingly important part of the healthcare organisation. This development may also impact the secondary healthcare system. Optimal use of resources is key to meeting the future challenges. Nevertheless, the research-based knowledge on homecare nursing is scarce. The aim of this study was to examine factors related to homecare nursing tasks that could have been performed by ancillary health professionals. Methods A population-based survey involving all homecare nurses in the homecare services in one municipality in Denmark was performed. The nurses registered all contacts during daytime for one week using a registration form with a series of items to identify factors related to possible substitution of nurse-performed tasks. Statistical analyses were used to identify associations between specific factors and potential substitution of the performing type of healthcare professional. The study was approved by and is registered at VIA University College in accordance with the General Data Protection Regulation of the EU. Results Homecare nurses registered 941 representative visits in the municipality. Substitution by ancillary health professionals was considered a possibility by the nurses in 28.3% of the cases. When adjusting for age, gender, type of visit, need for extra healthcare services and vulnerability, we established that the nurses more often found that ancillary health professionals could have provided the care in unplanned visits and in visits to patients above 90 years of age. Conclusions The results indicate potential for optimising the available nursing resources as substitution by ancillary health professionals was considered possible in numerous visits. In view of the increasing demands for community-based homecare nursing, it is important to make the most of the available resources in the future. Substitution of nurses for some tasks could be a feasible solution.Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans. Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network. In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans. Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.Due to their ease of fabrication and mechanical flexibility, silver nanowire transparent electrodes have been touted as a promising replacement for metal oxides such as indium tin oxide (ITO). Here we study an additional advantage their high transparency in the near-infrared region (NIR) which is highly desirable for some applications. For electrodes that are 96% transparent in the visible, ones made from ITO are only 35% transparent at a wavelength of 2500 nm, but those made from silver nanowires maintain a transparency as high as 94%. Experiments and modelling show that to minimize the transparency drop from the visible to the NIR, the nanowires should be sparse and larger in diameter, This is found to be attributed to both the larger average spacing between nanowires in such networks and the lower absoprtion losses of larger diameter nanowires in the NIR.Introduction Cadmium (Cd) is a heavy metal, which is widespread in the environment and has been hypothesized to be a metalloestrogen and a breast cancer risk factor. Mammographic density (MD) reflects the composition of the breast and was proposed to be used as a surrogate marker for breast cancer. The aim of our study was to investigate association between cadmium concentration in urine and mammographic density. Methods A cross-sectional study included 517 women aged 40-60 years who underwent screening mammography in Łódź, Poland. Data were collected through personal interviews and anthropometric measurements. Spot morning urine samples were obtained. The examination of the breasts included both craniocaudal and mediolateral oblique views. Raw data ("for processing") generated by the digital mammography system were analysed using Volpara Imaging Software, The volumetric breast density(%) and fibrograndular tissue volume(cm3) were determined. Cadmium concentration in urine was analysed using the standard ICP-MS method. Results After adjusting for key confounders including age, BMI, family breast cancer, mammographic device, season of the year of mammography, and age at menarche, an inverse association of Cd and volumetric breast density was found, which was attenuated after further adjustment for smoking. Associations of Cd with dense volume were null. Conclusions These findings suggest that Cd is not positively associated with breast density, a strong marker of breast cancer risk, when examined in a cross-sectional fashion.Adenosine-to-inosine RNA editing is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes that deaminate adenosine to inosine. Although many RNA editing sites are known, few trans regulators have been identified. We perform BioID followed by mass spectrometry to identify trans regulators of ADAR1 and ADAR2 in HeLa and M17 neuroblastoma cells. We identify known and novel ADAR-interacting proteins. Using ENCODE data, we validate and characterize a subset of the novel interactors as global or site-specific RNA editing regulators. Our set of novel trans regulators includes all four members of the DZF-domain-containing family of proteins ILF3, ILF2, STRBP, and ZFR. We show that these proteins interact with each ADAR and modulate RNA editing levels. We find ILF3 is a broadly influential negative regulator of editing. This work demonstrates the broad roles that RNA binding proteins play in regulating editing levels, and establishes DZF-domain-containing proteins as a group of highly influential RNA editing regulators.The clinical usage of Doxorubicin (DOX) is limited due to its cardiotoxicity. Although the precise mechanism remains unclear, there is an increasing body of evidence that has demonstrated that mitophagy is responsible for DOX-induced cardiotoxicity. In the present study, Parkin, a key protein for mitophagy initiation, was revealed to be downregulated in mouse hearts and in H9c2 cells upon DOX treatment. Enforced expression of Parkin led to mitophagy activation and attenuated cell apoptosis in H9c2 cells. Parkin transgenic mice inhibited DOX-induced cardiotoxicity. Furthermore, Yes-associatd protein, as a transcription co-activator, regulated the gene expression of Parkin, and in turn Parkin overexpression protected against cell apoptosis induced by DOX treatment. Taken together, enhanced mitophagy mediated by YAP/Parkin pathway protects against DOX-induced cardiotoxicity in mouse heart. These studies revealed the complex pathological process of DOX-induced cardiotoxicity and provided novel insight into potential chemotherapy targets.Water availability is arguably the most important environmental factor limiting crop growth and productivity. Erratic precipitation patterns and increased temperatures resulting from climate change will likely make drought events more frequent in many regions, increasing the demand on freshwater resources and creating major challenges for agriculture. Addressing these challenges through increased irrigation is not always a sustainable solution so there is a growing need to identify and/or breed drought tolerance crop varieties in order to maintain sustainability in the context of climate change. Grapes, a major fruit crop of economic importance, have emerged as a model perennial fruit crop for the study of drought tolerance. This review synthesizes the most recent results on grapevine drought responses, the impact of water deficit on fruit yield and composition, and the identification of drought tolerant varieties. Given the existing gaps in our knowledge of the mechanisms underlying grapevine drought responses this review aims to answer the following question How can we move towards a more integrative definition of grapevine drought tolerance?Titrating analgesic and sedative drugs in pediatric intensive care remains a challenge for caregivers due to the lack of pharmacodynamic knowledge in this population. The aim of the current study is to explore the concentration-effect relationship for morphine-associated oversedation after cardiac surgery in children aged 3 months to 3 years. Data on morphine dosing, as well as morphine plasma concentrations, were available from a previous study on the pharmacokinetics of morphine after cardiac surgery in children. Oversedation was defined as scores below 11 on the validated COMFORT-behavioral scale. Population pharmacokinetic-pharmacodynamic modeling was performed in NONMEM 7.3. The probability of oversedation as a function of morphine concentration was best described using a step function in which the EC50 was 46.3 ng/mL. At morphine concentrations below the EC50 , the probability of oversedation was 2.9% (0.4& to 18%), whereas above the EC50 percentages were 13% (1.9% to 52%) (median value [95% prediction interval from interindividual variability]). Additionally, the risk of oversedation was found to be increased during the first hours after surgery (P less then .001) and was significantly lower during mechanical ventilation (P less then .005). We conclude that morphine concentrations above approximately 45 ng/mL may increase the probability of oversedation in children after cardiac surgery. The clinician must evaluate, on a case-by-case basis, whether the analgesic benefits arising from dosing regimen associated with such concentrations outweigh the risks.The majority of oligomeric proteins form clusters which have rotational or dihedral symmetry. Despite the many advantages of symmetric packing, protein oligomers are only nearly symmetric, and the origin of this phenomenon is still in need to be fully explored. Here we apply near-symmetry analyses by the Continuous Symmetry Measures methodology of protein homomers to their natural state, namely their structures in solution. NMR-derived structural data serves us for that purpose. We find that symmetry deviations of proteins are by far higher in solution, compared to the crystalline state; that much of the symmetry distortion is due to amino acids along the interface between the subunits; that the distortions are mainly due to hydrophilic amino acids; and that distortive oligomerization processes such as the swap-domain mechanism can be identified by the symmetry analysis. Most of the analyses were carried out on distorted C2-symmetry dimers, but C3 and D2 cases were analyzed as well. Our NMR analysis supports the idea that the crystallographic B-factor represents non-classical crystals, in which different conformers pack in the crystal, perhaps from the conformers which the NMR analysis provides.Background Policymakers worldwide are considering requiring warnings for sugary drinks. A growing number of experimental studies have examined sugary drink warnings' impacts, but no research to our knowledge has synthesized this literature. To inform ongoing policy debates, this study aimed to identify the effects of sugary drink warnings compared with control conditions. Methods and findings We systematically searched 7 databases on June 21, 2019, and October 25, 2019. We also searched reference lists of relevant articles. Two investigators independently screened titles, abstracts, and full texts to identify peer-reviewed articles that used an experimental protocol to examine the effects of sugary drink warnings compared to a control condition. Two investigators independently extracted study characteristics and effect sizes from all relevant full-text articles. We meta-analyzed any outcome assessed in at least 2 studies, combining effect sizes using random effects meta-analytic procedures. Twenty-three exper a population-level strategy for changing behavior, as well as emotions, perceptions, and intentions. Protocol registry PROSPERO ID 146405.Neonatally transplanted human glial progenitor cells (hGPCs) can myelinate the brains of myelin-deficient shiverer mice, rescuing their phenotype and survival. Yet, it has been unclear whether implanted hGPCs are similarly able to remyelinate the diffusely demyelinated adult CNS. We, therefore, ask if hGPCs could remyelinate both congenitally hypomyelinated adult shiverers and normal adult mice after cuprizone demyelination. In adult shiverers, hGPCs broadly disperse and differentiate as myelinating oligodendrocytes after subcortical injection, improving both host callosal conduction and ambulation. Implanted hGPCs similarly remyelinate denuded axons after cuprizone demyelination, whether delivered before or after demyelination. RNA sequencing (RNA-seq) of hGPCs back from cuprizone-demyelinated brains reveals their transcriptional activation of oligodendrocyte differentiation programs, while distinguishing them from hGPCs not previously exposed to demyelination. These data indicate the ability of transplanted hGPCs to disperse throughout the adult CNS, to broadly myelinate regions of dysmyelination, and also to be recruited as myelinogenic oligodendrocytes later in life, upon demyelination-associated demand.CRISPR genome engineering has become a powerful tool to functionally investigate the complex mechanisms of immune system regulation. While decades of work have aimed to genetically reprogram innate immunity, the utility of current approaches is restricted by poor knockout efficiencies or limited specificity for mature cell lineages in vivo. Here, we describe an optimized strategy for non-viral CRISPR-Cas9 ribonucleoprotein (cRNP) genomic editing of mature primary mouse innate lymphocyte cells (ILCs) and myeloid lineage cells that results in an almost complete loss of single or double target gene expression from a single electroporation. Furthermore, we describe in vivo adoptive transfer mouse models that can be utilized to screen for gene function during viral infection using cRNP-edited naive natural killer (NK) cells and bone-marrow-derived conventional dendritic cell precursors (cDCPs). This resource will enhance target gene discovery and offer a specific and simplified approach to gene editing in the mouse innate immune system.The influence of 3D microenvironments on apoptosis susceptibility remains poorly understood. Here, we studied the susceptibility of cancer cell spheroids, grown to the size of micrometastases, to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Interestingly, pronounced, spatially coordinated response heterogeneities manifest within spheroidal microenvironments In spheroids grown from genetically identical cells, TRAIL-resistant subpopulations enclose, and protect TRAIL-hypersensitive cells, thereby increasing overall treatment resistance. TRAIL-resistant layers form at the interface of proliferating and quiescent cells and lack both TRAILR1 and TRAILR2 protein expression. In contrast, oxygen, and nutrient deprivation promote high amounts of TRAILR2 expression in TRAIL-hypersensitive cells in inner spheroid layers. COX-II inhibitor celecoxib further enhanced TRAILR2 expression in spheroids, likely resulting from increased ER stress, and thereby re-sensitized TRAIL-resistant cell layers to treatment. Our analyses explain how TRAIL response heterogeneities manifest within well-defined multicellular environments, and how spatial barriers of TRAIL resistance can be minimized and eliminated.A 77 year old gentleman, normally fit and well, was admitted with acute confusion. On admission GCS was 14/15, vital signs were within the normal limits and bilateral crepitation at the lung base. Head CT scan normal. CXR showed some air space opacification. Investigations revealed hyponatraemia, raised CRP and positive for COVID-19. Treated with antibiotics and intravenous saline, sodium returned to normal. Delirium remained unchanged four weeks post incidence. Neurological manifestations were documented in patients with COVID-19, however no report has shown delirium as a primary manifestation. This case illustrates acute confusion may be the only presenting symptom of COVID-19 without overt lung disease.Introduction The Neutrophil-to-Lymphocyte Ratio (NLR) has been investigated as an independent predictive marker for clinical outcomes in vascular diseases. This study aimed to investigate the peri-interventional behavior of NLR in patients with ruptured and unruptured intracranial aneurysms (IAs). Methods 117 patients with IAs, who were treated at our department and had available complete data, were retrospectively identified during a ten-year period. Routine laboratory parameters, including the neutrophil and lymphocytes counts, were evaluated before and after treatment. Results The baseline NLR showed significant differences between patients with ruptured and unruptured IAs (6.3 vs. 1.8; p less then 0.001). In patients with ruptured IAs, the baseline NLR decreased significantly during the follow-up visits, while in unruptured IAs, the NLR remained low. Furthermore, higher baseline NLR values could also be observed in patients with ruptured IAs and fatal outcome than in surviving patients (8.0 vs. 5.4; p=0.220). In patients with poor functional outcome, defined as modified Rankin Score ≥3, the NLR was significantly higher before treatment (p=0.047), at day 10 (p=0.025) and one month after treatment (p=0.001). Conclusions The peri-interventional NLR was significantly different between patients with ruptured and unruptured IAs. In patients with ruptured IAs, elevated baseline NLR levels were associated with poor postoperative functional outcomes and decreased postoperatively, implying the potential prognostic value of NLR in patients with IAs.Objective To adapt the Reaching Performance Scale for Stroke (RPSS) for the Wolf Motor Function Test (WMFT) "Lift Can" (Can) and "Hand to Box" (Box) items. Design Retrospective analysis of video-recorded WMFT assessment performed by three raters on two occasions; SETTING N/A; PARTICIPANTS 29 participants with mild to moderate upper extremity impairment, less then 3 months post stroke INTERVENTIONS N/A MAIN OUTCOME MEASURES Inter- and intra-rater agreement, concurrent validity of Wolf Motor Function Test-Reaching Performance Scale for Stroke (WMFT-RPSS) RESULTS Mean (SD) inter-rater Gwet's agreement coefficient (AC2) was 0.61 (0.05) for Can WMFT-RPSS and 0.56 (0.03) for Box. Mean (SD) intra-rater AC2 for Can was 0.63 (0.05) and 0.70 (0.04) for Box. WMFT-RPSS Can and Box scores correlated with log mean WMFT time (C -0.73, B -0.48), Functional Ability Scale (C 0.87, B 0.62), Upper Extremity Fugl-Meyer Motor Score (C 0.69, B 0.51), and item movement rate (C 0.74, B 0.71), (all, p less then 0.05). Mean (SD) WMFT-RPSS score across the 29 participants was 12.
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