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Social ulighed i oldtiden:Social ulighed i oldtiden
No full textSocial ulighed i oldtiden og i forhistorien er meget svært at undersøge, da det, hvis skritflige kilder mangler, kun kan gøres gennem fragmenterede indirekte spor. Derfor må arkæologerne have brede, men klare, definitioner på velstand og ulighed, og ofte trække inspiration til fortolkning fra etnografiske eksempler, som dog sjældent kan anvendes én til én på f.eks. Europas forhistorie. Denne artikel giver et overblik over nogle af de udbredte metoder til at undersøge social ulighed i forhistorien, samt nogle eksempler fra Europa
The Recycling Collagen Receptor uPARAP Is a Unique Mediator of Stromal Drug Delivery to Carcinoma Cells
No full textThe genetic instability of cancer cells leads to cellular resistance against most targeted cancer drugs. Cancer-associated fibroblasts (CAF) infiltrate all carcinomas and are genetically stable. Using antibody–drug conjugates (ADC), we exploit the unique properties of a rapidly recycling endocytic receptor, uPARAP, to achieve highly efficient CAF-mediated drug delivery and killing of carcinomas. This receptor is generally not present on carcinoma cells and is only expressed in a restricted group of mesenchymal cancer cell types, which are sensitive to uPARAP-directed ADCs. However, we show that uPARAP is highly expressed in CAFs in all carcinoma types examined. This property is recapitulated in mouse xenograft carcinoma models. In these models, despite the absence of uPARAP on the carcinoma cells, uPARAP-targeting ADCs with clinically validated payloads, monomethyl auristatin E and deruxtecan, eradicated tumors with remarkable efficiency. Systemic treatment with anti-uPARAP ADC led to the permanent eradication of tumors in mice carrying subcutaneous xenografts with human EBC-1 lung carcinoma cells. A pronounced repression of tumor growth and a strongly increased mouse survival rate were also obtained with human HT29 colon adenocarcinoma cells, both when these tumors were growing subcutaneously and after the homing of tumor cells to bone from the circulation. CAFs were largely refractory to ADC treatment and retained a high expression of uPARAP. uPARAP-expressing fibroblasts could also process an anti-uPARAP ADC in vitro and deliver the cytotoxic component to carcinoma cells. The current bystander mechanism may be exploited in the majority of the most prevalent solid cancers, thus making uPARAP an extraordinarily versatile target for ADC-based cancer treatment.</p
Phenotypic Spectrum of Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) in Denmark:A Case Series Characterizing the First Danish Families With the <i>APC </i>Promotor 1B Variant c.-191T > C
No full textGastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare autosomal dominantly inherited gastric cancer syndrome that is characterized by fundic gland polyposis of the stomach (> 100) and an increased risk of gastric cancer. The genetic cause is recognized as a pathogenic variant in the promotor 1B of the APC gene. Presently, there are no established clinical criteria, and current guidelines are based on limited evidence. In this report, we identified two families with GAPPS. Family I had a family history of gastric cancer, and we identified seven family members with GAPPS. The diagnosis was verified by endoscopic findings of polyposis and genetic analysis identifying a variant in the promotor 1B of the APC gene, NM_001127511.3: c.-191T > C. In Family II, the same pathogenic variant, NM_001127511.3: c.-191T > C, was detected as an incidental finding in a 61-year-old patient with hepatocellular carcinoma, clear cell renal carcinoma, and small cell lung cancer. An esophagogastroduodenoscopy (EGD) at the age of 59 had revealed only one small fundic polyp. This is the first report of patients with GAPPS from Denmark, and it emphasizes the variable phenotypic expression and subsequently the difficulty of surveillance and genetic counseling in these patients and their families.</p
Digital Health Citizenship:a Spectrum from Invited to Uninvited Participation
No full textThe term ‘digital health citizenship’ is increasingly being used normatively to highlight the potential of digital technologies to enhance patient empowerment and im-prove the efficiency of healthcare delivery. Drawing on science and technology studies (STS) this chapter provides alternative perspectives to evaluate the participatory practices emerging alongside the sociotechnical changes in healthcare. I suggest that we understand digital health citizenship as a spectrum of participation that spans from invited individual uptake of digital tools to critical collective mobilisation against established institutions. Case studies on the use of digital self-care tools in the Danish healthcare system and the global #wearenotwaiting movement among individuals with type 1 diabetes exemplify the spectrum of digital-enabled participation, highlighting both invited participation within formal healthcare structures and the emergence of ‘device activist’ mobilisation outside traditional institutional boundaries. The chapter underscores the need for a nuanced understanding of digital health citizenship as a negotiated order, recognising the affordances of digital technologies and the diverse ways in which individuals and collectives engage with and contest these
A New Chitosan-Based Nanoformulation of <i>Lavandula dentata</i> Essential Oil for Sustainable Control of Green Citrus Aphids
No full textThe green citrus aphid (Aphis spiraecola) poses a serious threat to citrus production worldwide, primarily through the transmission of phytoviruses and the resulting yield losses in untreated orchards. Overreliance on synthetic insecticides such as Acetamiprid has led to increased resistance and environmental contamination (DT50 >120 days in soil). In this study, we present a novel nanoformulation of Lavandula dentata essential oils, chemically characterized by GC-MS, which is composed mainly of eucalyptol (12.8%), β-pinene (5.7%), linalool (4.7%), camphene (4.4%), and α-pinene (4.0%). Nanoparticles were synthesized via optimized ionotropic gelation (0.4% chitosan in 1% acetic acid, 0.3% TPP crosslinking, 1500 rpm, 60 min), yielding a high production rate (83.6% ± 1.2%), encapsulation efficiency (99.2% ± 0.5%), and loading capacity (21.3% ± 0.8%). Dynamic light scattering (DLS) revealed uniform particle sizes (41.8 ± 3.1 nm) with excellent colloidal stability (+39.4 ± 1.8 mV zeta potential, PDI 0.57 ± 0.03). SEM imaging confirmed spherical morphology, smooth surfaces of nanoparticles, while unloaded controls appeared irregular and significantly larger (90.2 ± 5.6 nm). EDX analysis further validated successful encapsulation, with oil-loaded particles showing a 6.7% increase in carbon content attributable to essential oil hydrocarbons, alongside preserved phosphorus signals from chitosan–TPP crosslinking. FTIR spectra exhibited characteristic peak shifts, including a 15 cm−1 displacement of the carbonyl stretch (1740 cm−1) and the emergence of new P–O–C vibrations (930–950 cm−1), confirming the presence of molecular interactions. In controlled bioassays (25°C ± 1°C, 65% ± 5% RH), the nanoformulation demonstrated enhanced insecticidal activity, with LC50 decreasing from 0.43 mg/mL (48 h) to 0.25 mg/mL (72 h), representing a 42% increase in efficacy. Complete mortality (100%) was achieved at 0.5 mg/mL within 90 h, whereas unencapsulated oil lost 82% of its activity within 24 h due to volatility. The formulation also demonstrated excellent photostability (< 8% degradation after 72 h UV exposure) and low mammalian toxicity (OECD 208 LD50 > 2000 mg/kg), offering a sustainable solution with 3.8 times longer residual activity than conventional sprays. These findings establish chitosan nanoencapsulation as a promising strategy for enhancing the stability and effectiveness of botanical insecticides in integrated pest management
Ca<sup>2+</sup>/calmodulin-driven functions mediated by extracellular vesicles:a physiopathological perspective
No full textExtracellular vesicles (EVs), including exosomes and microvesicles, secreted by a wide range of eukaryotic cells, are now well-established mediators of intercellular communication, acting through their uptake by recipient cells at local or distant sites. This occurs after delivering their cargo, a variety of RNAs, lipids, and proteins, which regulate many cellular functions in health and disease states. Among the exosomal cargos, the Ca2+-sensor protein calmodulin (CaM), as well as several Ca2+/CaM-regulated proteins, are frequently found in EVs, potentially playing important roles in the function of target cells. In addition, RNAs, which control the expression (mRNAs) or downregulation (miRNAs, lncRNAs) of Ca2+/CaM-regulated systems, are present in EVs, contributing to Ca2+ signaling processes when transferred into target cells. We discuss the involvement of exosomal CaM signaling systems in the pathophysiology of some high-incidence diseases affecting the heart and the nervous system. In this group, the contribution of Ca²⁺/CaM-regulated systems to tumor cells behavior in a wide range of organs is explored in more detail. In addition, some diseases of the kidneys, lungs, liver, the immune system, the eyes and the pancreas are considered. Finally, we highlight selected examples in which isolated exosomes modulating Ca²⁺/CaM pathways have been investigated as potential therapeutic agents.</p
The visual system of the longest-living vertebrate, the Greenland shark
No full textThe Greenland shark (Somniosus microcephalus) is the longest-living vertebrate and inhabits the exceptionally dim and cold waters of the Arctic deep sea. Due to its extreme lifespan, harsh environmental conditions, and prevalent corneal parasitisation, the Greenland shark has previously been thought to have impaired or degenerated vision. Here, we present genomic, transcriptomic, histological and functional evidence that the Greenland shark retains an intact visual system well-adapted for life in dim light. Histology and in vitro opsin expression revealed visual adaptations typical of deep-sea species, including densely packed, elongated rods and a short-wavelength shift in rod visual pigment sensitivity compared to shallow-water sharks. In situ hybridisation confirmed the presence of essential visual cell types: rods, M & uuml;ller glia, and bipolar, amacrine, and ganglion cells. Moreover, despite being over a century old, the examined specimens showed no obvious signs of retinal degeneration. Using whole genome and retinal RNA-sequencing, we further show that dim-light (rod-based) vision genes are intact and robustly expressed, while many bright-light (cone-based) vision genes have become pseudogenized and/or are no longer expressed. Finally, we identify robust expression of DNA repair-associated genes in the retina, which may help support long-term maintenance of retinal integrity over the Greenland shark's extreme lifespan
Pharmacogenetic Predictors of Postoperative Opioid-Related Adverse Events:A Systematic Review
No full textBACKGROUNDS/AIMS: This systematic review aimed to assess associations between genotypes and the risk of experiencing postoperative opioid-related adverse drug events (ORADEs).METHODS: Following PRISMA guidelines and registered with PROSPERO, we searched MEDLINE, Embase and CENTRAL for studies assessing genetic predictors of ORADEs within 24 h postoperatively. Eligible studies included English-written retrospective and prospective cohort studies as well as randomised trials. Risk of bias was assessed using the QUIPS tool. Data were extracted in duplicate, and relative risks with 95% confidence intervals were calculated. Meta-analyses were conducted when ≥ 2 studies assessed the same genetic predictor and ORADE relationship.RESULTS: Of the 119 523 citations, 27 studies (5279 patients) met inclusion criteria. All included studies ranked high risk of bias. Of the 28 investigated predictors, 17 significantly increased or decreased ORADE risk in individual studies. Of the 31 meta-analyses, only two demonstrated significant associations (p < 0.05; COMT rs4680 AA and nausea, and CYP2D6 IM and hyperhidrosis).CONCLUSION: While finding two significant associations, we would expect one to two significant associations at random given the 31 meta-analyses. Findings were limited by heterogeneity, few studies and small sample sizes. The current evidence does not suggest that genotypes should have a central place in the risk stratification of the occurrence of postoperative ORADEs.</p
Divine Policy: The Impact of Religion in Government
No full textCan policies shape personal values and beliefs? To examine, we exploit the staggered introduction of faith-based initiatives across US states. Our difference-in-differences analysis reveals that the initiatives strengthened religiosity and conservative-religious social views, such as attitudes against homosexuals. The evidence points to causal effects; we find no systematic differences prior to implementation, the results are robust to restricting comparison to contiguous counties and to conducting triple-differences estimation exploiting treatment heterogeneity. A key explanation, in line with standard models of religion and supported by data on nonprofit organizations, is that the initiatives facilitated the establishment of faith-based organizations
EULAR points to consider and consensus definitions for difficult-to-manage and treatment-refractory psoriatic arthritis
No full textObjectives: This study aimed to develop evidence-based points to consider (PtC) and consensus definitions of difficult-to-manage (D2M) and treatment-refractory (TR) psoriatic arthritis (PsA). Methods: A multidisciplinary international European Alliance of Associations for Rheumatology (EULAR) task force (TF) of 27 members, including rheumatologists, dermatologists, health practitioners, and patient partners, was established, and the EULAR standardised operating procedures, including a systematic literature review and a consensus process, were followed. Results: The TF formulated 4 overarching principles addressing the proportion of patients with PsA with an unsatisfactory treatment response despite the best standard of care, and for which the causes are likely multifactorial. Six PtC highlight criterion relevant for subsequent definitions including failure to achieve or maintain response to ≥2 biological/targeted synthetic disease-modifying antirheumatic drugs with ≥2 different mechanisms of action; management of signs and symptoms perceived as problematic by the rheumatologist and/or the patient, and evidence of persistent disease activity in the presence of extramusculoskeletal manifestations and/or comorbidities and/or objective evidence of inflammatory activity. Finally, the following 2 definitions were developed: (1) D2M PsA, an umbrella term including drivers such as inflammation, comorbidities, psychosocial or other factors, incorporating (2) TR PsA, defined by persistent disease activity and objective evidence of active inflammation. Conclusions: EULAR proposes 2 consensus definitions to identify a D2M PsA population, including a TR subgroup. These definitions should now be tested in research studies to understand disease pathogenesis and improve care for people living with PsA.</p