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LoRa is a long-range, low-power, low-bitrate, wireless telecommunications system, promoted as an infrastructure solution for the Internet of Things: end-devices use LoRa across a single wireless hop to communicate to gateway(s), connected to the Internet and which act as transparent bridges and relay messages between these end-devices and a central network server. This paper provides an overview of LoRa and an in-depth analysis of its functional components. The physical and data link layer performance is evaluated by field tests and simulations. Based on the analysis and evaluations, some possible solutions for performance enhancements are proposed.

Glycosaminoglycans (GAGs) are essential polysaccharides in normal physiology and disease. However, understanding of the contribution of specific GAG structures to specific biological functions is limited, largely because of the great structural heterogeneity among GAGs themselves, as well as technical limitations in the structural characterization and chemical synthesis of GAGs. Here we describe a cell-based method to produce and display distinct GAGs with a broad repertoire of modifications, a library we refer to as the GAGOme. By using precise gene editing, we engineered a large panel of Chinese hamster ovary cells with knockout or knock-in of the genes encoding most of the enzymes involved in GAG biosynthesis, to generate a library of isogenic cell lines that differentially display distinct GAG features. We show that this library can be used for cell-based binding assays, recombinant expression of proteoglycans with distinct GAG structures, and production of distinct GAG chains on metabolic primers that may be used for the assembly of GAG glycan microarrays.

Background Research questionnaires are not always translated appropriately before they are used in new temporal, cultural or linguistic settings. The results based on such instruments may therefore not accurately reflect what they are supposed to measure. This paper aims to illustrate the process and required steps involved in the cross-cultural adaptation of a research instrument using the adaptation process of an attitudinal instrument as an example. Methods A questionnaire was needed for the implementation of a study in Norway 2007. There was no appropriate instruments available in Norwegian, thus an Australian-English instrument was cross-culturally adapted. Results The adaptation process included investigation of conceptual and item equivalence. Two forward and two back-translations were synthesized and compared by an expert committee. Thereafter the instrument was pretested and adjusted accordingly. The final questionnaire was administered to opioid maintenance treatment staff (n=140) and harm reduction staff (n=180). The overall response rate was 84%. The original instrument failed confirmatory analysis. Instead a new two-factor scale was identified and found valid in the new setting. Conclusions The failure of the original scale highlights the importance of adapting instruments to current research settings. It also emphasizes the importance of ensuring that concepts within an instrument are equal between the original and target language, time and context. If the described stages in the cross-cultural adaptation process had been omitted, the findings would have been misleading, even if presented with apparent precision. Thus, it is important to consider possible barriers when making a direct comparison between different nations, cultures and times.

OBJECTIVE:The aim of this study was to investigate the prospective association between social capital in the workplace and self-reported job performance, work engagement, and psychological well-being. METHODS:Survey data on 538 employees in the dairy industry were analyzed using linear multilevel regression analysis. Social capital was analyzed as individual-level and aggregated team-level variables. Follow-up time was approximately 2 years. Analyses were adjusted for age, sex, outcome measured at T1, and random effects at team level. RESULTS:Individual-level social capital at T1 predicted self-reported job performance, and psychological well-being at T2. Changes in individual-level and team-level social capital from T1 to T2 were significantly associated with self-reported job performance, work engagement, and psychological well-being at T2. CONCLUSIONS:Social capital in the workplace is associated with relevant outcomes for work organizations. Workplace interventions to enhance social capital are recommended.

Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is of high value for disease monitoring and molecular characterization. Despite the development of many new CTC isolation platforms in the last decade, their isolation and detection has remained a challenge due to the lack of specific and sensitive markers. In this feasibility study, we present a method for CTC isolation based on the specific binding of the malaria rVAR2 protein to oncofetal chondroitin sulfate (ofCS). We show that rVAR2 efficiently captures CTCs from hepatic, lung, pancreatic, and prostate carcinoma patients with minimal contamination of peripheral blood mononuclear cells. Expression of ofCS is present on epithelial and mesenchymal cancer cells and is equally preserved during epithelial–mesenchymal transition of cancer cells. In 25 stage I–IV prostate cancer patient samples, CTC enumeration significantly correlates with disease stage. Lastly, rVAR2 targets a larger and more diverse population of CTCs compared to anti-EpCAM strategies. Isolation of circulating tumor cells (CTCs) allows for non-invasive disease monitoring and characterization. Here the authors describe an alternative CTC isolation method based on the ability of the malaria rVAR2 protein to specifically bind oncofetal chondroitin sulfate, which is expressed by all cancer cells

During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells.

Background Veterinarians have a high prevalence of mental health disorders, such as depression. Previous research suggests that veterinarians are highly exposed to emotional demands at work and that these emotional demands are associated with adverse mental health outcomes. However, little is known about the consequences of the simultaneous exposure to emotional demands and other types of job demands in clinical veterinary practice. In this cross-sectional study, we investigate the combined effect of simultaneous exposure to emotional demands and other types of job demands on the risk of depression. We invited 1,757 employees in clinical veterinary practice in Denmark to participate in an online survey in the spring of 2022. Results We obtained response from 885 employees (50.4%). Mean age was 38.2 years and 90.2% of the sample identified as women. The majority of the respondents worked in small animal practice (80.6%). We assessed psychosocial job demands (emotional demands, quantitative demands, role conflicts, work pace, and threats) and depressive symptoms in the study questionnaire, and defined depression as a score of ≥ 21 on the Major Depression Inventory. Data were analyzed using logistic regression analysis. 15.1% of the participants had an indication of depression. Results showed an increased risk of depression for participants reporting high emotional demands in combination with high quantitative demands (OR:8.37; 95%CI:4.31–16.24), high role conflicts (OR:8.95; 95%CI:4.71–16.99), threats at work (OR:7.06; 95%CI:4.06–12.28) and high work pace (OR:14.24; 95%CI:6.51–31.15). The combined effects indicated additive but not synergistic interaction. Conclusions Combinations of emotional demands and other types of job demands are associated with an increased risk of depression among employees in clinical veterinary practice in Denmark. The results have implications for preventing negative health-related consequences of adverse psychosocial working conditions among employees in clinical veterinary practice. Preventive strategies and initiatives to promote a healthy psychosocial work environment and well-being among veterinary employees are discussed, and we further encourage employers and relevant authorities in veterinary practice to prioritize efforts to enhance the psychosocial work environment and employee well-being in clinical veterinary practice.

Placental malaria can have severe consequences for both mother and child and effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA and the glycosaminoglycan chondroitin sulfate A (CS) abundantly present in the intervillous space. Here, we report cryo-EM structures of the VAR2CSA ectodomain at up to 3.1 Å resolution revealing an overall V-shaped architecture and a complex domain organization. Notably, the surface displays a single significantly electropositive patch, compatible with binding of negatively charged CS. Using molecular docking and molecular dynamics simulations as well as comparative hydroxyl radical protein foot-printing of VAR2CSA in complex with placental CS, we identify the CS-binding groove, intersecting with the positively charged patch of the central VAR2CSA structure. We identify distinctive conserved structural features upholding the macro-molecular domain complex and CS binding capacity of VAR2CSA as well as divergent elements possibly allowing immune escape at or near the CS binding site. These observations will support rational design of second-generation placental malaria vaccines. In placental malaria, interactions between parasite protein VAR2CSA and human glycosaminoglycan chondroitin sulfate A (CS) sequesters infected red blood cells in the placenta. Here, the authors provide cryo-EM structures of VAR2CSA and placental CS, identifying molecular interactions that could guide design of placental malaria vaccines.

Background For patients receiving daily opioid agonist treatment (OAT) for opioid dependence, several countries relaxed treatment guidelines at the beginning of the COVID-19 pandemic. This involved longer take-home intervals for methadone and buprenorphine doses as well as a reduction in supervised dosing and drug screening. To date, little is known about the medium or long-term experience of OAT deregulation. Therefore, we conducted a survey to explore how OAT providers perceived greater flexibility in OAT service delivery at the end of the second year of the pandemic. Methods Nationwide cross-sectional study of twenty-three OAT units in 19 publicly funded hospital trusts in Norway. OAT units were sent a 29-item online questionnaire comprising closed-format and open-ended questions on treatment provider experiences and changes in OAT service delivery during the past 12 months (January to December 2021). Results Twenty-three (of whom female: 14; 60.8%) managers or lead physicians of OAT units completed the questionnaire reporting that, in 2021, most OAT units (91.3%, n  = 21) still practiced some adjusted approaches as established in the beginning of the pandemic. The most common adaptions were special protocols for COVID-19 cases (95.7%, n  = 22), increased use of telephone- (91.3%, n  = 21) and video consultations (87.0%, n  = 20), and longer take-home intervals for OAT medications (52.2%, n  = 12). The use of depot buprenorphine also increased substantially during the pandemic. According to the OAT providers, most patients handled flexible treatment provision well. In individual cases, patients’ substance use was identified as key factor necessitating a reintroduction of supervised dosing and drug screening. Collaboration with general practitioners and municipal health and social services was generally perceived as crucial for successful treatment delivery. Conclusions Overall, the Norwegian OAT system proved resilient in the second year of the COVID-19 pandemic, as its healthcare workforce embraced innovation in technology (telemedicine) and drug development (depot buprenorphine). According to our nationally representative sample of OAT providers, most patients were compliant with longer take-home doses of methadone and buprenorphine. Our findings suggest that telemedicine can be useful as adjunct to face-to-face treatment and provide greater flexibility for patients.