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This study evaluated the bioaccessibility of essential (Ca, Cu, Fe, K, Mg, Mn, Mo, Na and Zn) and non-essential (Al, Ba, Cr, Sr and V) elements in food supplements (vitamins and/or minerals and botanicals). Extraction using in-vitro methods (Unified BARGE Method-UBM and INFOGEST) was evaluated allowing a comparison of protocols and using inductively coupled plasma optical emission spectrometry (ICP OES). Bioaccessibility values revealed differences among the elements in different types of food supplements. The limits of quantification (LOQs) obtained for some elements were relatively high for both methods due to the composition of the digests, which drastically impaired bioaccessibility assessment. As a result, most elements presented fractions lower than the LOQ, regardless of the sample. This is an important limitation promoted by interferences when analyzing these extracts by ICP-based techniques. A simple extraction using 1 mol L-1 HCl was evaluated, considering that HCl is present in the solutions used in both protocols. Leaching was observed for the same elements using only the HCl solution.
The human microbiome comprises the microorganisms inhabiting the body, with the oral cavity representing the second most densely colonized site after the colon. Periodontal disease-associated oral bacteria are more common in patients with kidney disorders than in the general population. Oral dysbiosis disrupts host-microbiota homeostasis and promotes destructive periodontal inflammation, which has been linked to chronic kidney disease (CKD). However, current interventional evidence, including randomized controlled trials, remains limited by small sample sizes, short follow-up, heterogeneous periodontal interventions, inconsistent renal endpoints, limited blinding, and inadequate adjustment for confounders such as smoking, glycemic control, and medication use. Thus, causality between oral microbiota modulation and CKD progression remains unproven. This review synthesizes current evidence on the mechanisms by which oral microbiota influence various forms of nephropathy, with a particular focus on the impact of periodontitis (PD) on the progression of renal disease.This review summarizes evidence on mechanisms by which oral microbiota and periodontitis may contribute to nephropathy and renal disease progression. Oral dysbiosis may affect CKD through systemic inflammation, endothelial dysfunction, and oxidative stress. It may also promote abnormal IgA1 glycosylation in IgA nephropathy and contribute to immune dysregulation and persistent inflammation in glomerulonephritis. Periodontitis-associated oral dysbiosis may contribute to renal disease pathogenesis and progression. Clarifying these mechanisms could support preventive and therapeutic strategies for patients with nephropathy.
Chronic kidney disease-mineral and bone disorder is a major contributor to skeletal fragility in patients with chronic kidney disease and after kidney transplantation. Alterations in mineral metabolism begin early during CKD and persist through later stages, leading to a markedly increased fracture risk that may precede renal failure. Bone fragility in CKD arises from the interplay of primary osteoporosis, secondary causes, and CKD-specific disturbances in bone turnover and mineralisation. CKD related bone disease and post-transplant bone loss are characterised not only by reduced bone mineral density but also by impaired bone quality, driven by abnormalities in trabecular and cortical microarchitecture, collagen properties, and mineral composition. Immunosuppressive therapy further exacerbates skeletal vulnerability after kidney transplantation. Recent guidelines have therefore adopted the term CKD-associated osteoporosis to emphasise the need for integrated diagnostic and therapeutic approaches. Diagnosis remains challenging because BMD alone fails to capture alterations in bone turnover and mineralisation that critically influence fracture risk and treatment response. Although bone biopsy remains the reference standard, limited availability has led to increased reliance on bone turnover markers, particularly those not cleared by the kidneys. Combined assessment of parathyroid hormone and BTMs improves discrimination of turnover states and supports individualised clinical decision-making. A pragmatic approach could be based on an integrated evaluation of CKD-MBD parameters, BTM trends, and baseline and follow-up imaging. Therapeutic management becomes increasingly complex in advanced CKD, where fracture risk is high, and evidence for osteoporosis treatments is limited. Antiresorptive, osteoanabolic, and dual-action agents have distinct effects on bone modelling and remodelling, with important implications for efficacy and safety. Despite progress, no consensus exists on optimal treatment strategies. Emerging sequential and combination therapies remain insufficiently studied in advanced CKD and transplant populations, underscoring the need for robust clinical evidence.
Primary care is a pivotal part of the health care system. While in the 1990's it was considered a success story, nowadays it is a crisis sector. This paper aims to discover the reasons behind this, evaluating the human resources as well. The age distribution of family physicians is presented and the input and output of residency programmes (vocational training) and elements of the undergraduate education and governmental efforts for improvement are discussed. Based on national data, the components of financing and primary care provision are presented, as well as laboratory and radiological investigations and relevant expenditures are displayed. Fundamental and conceptional changes are needed in the whole health care system. New and innovative structures of primary care provision are required, besides appropriate financing, without uniformity. The problems of human resources could be solved with appropriate financing, wider professional competences and restructuring the undergraduate education. Orv Hetil. 2026; 167(26): 1018-1026. Az egészségügyi rendszer fontos szintje az alapellátás, amelynek működésében hazánkban komoly problémák vannak. Az 1990-es években sikerágazatnak számító terület mára válságágazattá vált. Ennek okait próbálja meg feltárni a kézirat, áttekintve a magyar alapellátás humánerőforrás-helyzetét is. Bemutatja a háziorvosok korösszetételét, az orvoshiány enyhítésére tett kormányzati támogatásokat, a szakorvosképzés adatait és az egyetemi oktatás szakmaspecifikus elemeit. Országos adatok alapján elemzi a háziorvosi finanszírozás összetevőit, a háziorvosi ellátások komponenseit. Bemutatja a háziorvosok által indikált laboratóriumi és képalkotó vizsgálatok számát, költségét. A megoldást az egészségügyi rendszer elkerülhetetlen, koncepcionális átalakításán belül, az alapellátásnak az innovatív elemeket tartalmazó és ezeket finanszírozni képes áttervezésében, nem pedig az uniformizálásában keresi. A humánerőforrás helyzetének javítása sem képzelhető el a finanszírozás és a kompetenciák jelentős bővítése és a képzési rendszer átalakítása nélkül. Orv Hetil. 2026; 167(26): 1018–1026.
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Reactive oxygen species (ROS) play a complex dual role in cancer biology. At physiological levels, ROS act as signaling molecules that drive tumorigenesis, metastasis, and therapy resistance by activating oncogenic pathways, such as NF-κB and PI3K/AKT, and fostering an immunosuppressive microenvironment. Conversely, excessive ROS accumulation overwhelms antioxidant defenses, triggering oxidative stress that can selectively eliminate tumor cells. Consequently, manipulating the delicate redox equilibrium has emerged as a pivotal strategy for cancer treatment. This review systematically examines the multifaceted functions of ROS, bridging the gap between fundamental redox biology and clinical application within the Predictive, Preventive, and Personalized Medicine (3PM) framework. Beyond molecular mechanisms, we evaluated the rationale for utilizing mitochondrial redox signatures as intrinsic biological sensors to identify suboptimal health conditions (SHC) and prevent the health-to-disease transition. We elucidate the regulatory networks governing ROS production and elimination, highlighting their dual function in promoting genomic instability versus inducing distinct cell death modalities, including apoptosis, autophagy, necroptosis, and ferroptosis. Special attention is given to ROS-mediated remodeling of the tumor microenvironment (TME), where oxidative stress facilitates immunosuppression. Importantly, we provide expert recommendations on integrating digital health monitoring and patient stratification into clinical oncology. By emphasizing mitochondrial rejuvenation and individualised protection, this review discusses how proactive interventions can restore homeostasis and improve long-term outcomes, offering a cost-effective alternative to reactive treatments.
Objectives: Endocrine neoplasms, as a general rule, show systemic, neuro-inflammatory and metabolic consequences, known as paraneoplastic syndrome. The comorbidity of thyroid tumors with neurological and autoimmune diseases prompt looking for common neuro-immuno-endocrine mechanisms of these disorders. While most TCs are well described, there is a gap in the literature after the isolation of oncocytic/Hürthle cell carcinoma (HCC), as a unique type due to immunoendocrine and metabolic features (low TSH-receptor expression and radioiodine avidity). The aim of this study was to collect clearly defined reports of HCC (as a separate entity) and to attempt determining common clinical symptoms and the usefulness of various diagnostic techniques (comprehensive critical review). This may be an introduction to modern treatment (patient-centered care) since the main cause of mortality is not local progression or metastases. Results: Until now, due to misnomenclature and data misinterpretation, HCC has been treated according to general standards (with overuse of TSH-ST and RIA). High thyroglobulin level, decreased total thyroxin (with normal FT3 and spontaneous decrease in TSH), hypercalcemia, as well as the "reverse flip-flop" phenomenon, as common symptoms, indicate the neuroendocrine origin of HCC. Sparse, well-documented lymph node metastases are another feature, although from few studies. Most studies omit the N stage. Whole-body 131iodine and 18F-fluorodeoxyglucose scintigraphy may be useful before FNAB. Fine-needle aspiration biopsy (FNAB), as a "gold standard" in early diagnosis of thyroid nodules, delays HCC diagnosis because of the inability to determine a benign/malignant nature. Conclusions: Final HCC outcome may be affected by various overlapping immunoendocrine factors (paraneoplastic effects). Due to very few thyroid function tests performed in HCC, we have proposed a set of basic laboratory analyses, core biopsy in HCC differentiation, and diagnostic chain for standardization. According to the review, adaptation and treatment of HCC based on existing standards for other thyroid cancers seem to be insufficient, and the risks outweigh the benefits. The key recommendations resulting from the 5th edition of the WHO Classification of Endocrine Neoplasms are only the beginning of refuting many myths and biases.
N-ary Knowledge Graphs (NKGs), containing facts with more than two entities, are prevalent in the real world. Link Prediction in NKGs (LPN) is to predict missing elements in facts therein, which helps populate and enrich the NKGs. Existing LPN methods implicitly assume that NKGs remain static. However, real-world NKGs usually grow, frequently introducing new facts over time. When new facts emerge, existing LPN methods need to be fine-tuned with new data or retrained on the entire dataset, often resulting in knowledge forgetting or requiring a lot of training time. Consequently, this paper introduces a new task, i.e., Continual Link Prediction in growing NKGs (CLPN), aiming to predict missing elements in facts in growing NKGs. To conduct CLPN, we propose a Continual N-ary knowledge Reasoner, called ConNR. ConNR includes an embedding generation module to initialize embeddings of the unseen elements, a embedding update module to globally update embeddings of all elements, and a fact decoder that captures the semantics of new facts and predicts missing elements. To evaluate CLPN, we have carefully constructed five datasets with different NKG growth scenarios. Experimental results on all these datasets demonstrate the superior performance of ConNR over existing representative models.
Aim: to distinguish such outwardly similar legal phenomena in the form of irreversible transfer of a child from one person to another, such as child trafficking and surrogacy, primarily paid (commercial). Materials and Methods: In order to achieve the stated objective, the study employed a set of general scientific and specialized methods of cognition, including comparative law, the formal-logical method, historical method etc. More than 3 thousand records of the Unified Register of Pre-Trial Investigations on the registration and results of pre-trial investigation of criminal proceedings on the facts of human trafficking, including on the facts of illegal surrogacy, were processed. 5 court verdicts from the Unified Register of Court Decisions were analyzed, and 6 criminal proceedings on such facts, in which the investigator or prosecutor made a decision to close them, were also studied. Conclusions: Due to significant differences from both the objective and subjective sides, surrogacy and child trafficking are different legal agreements, which makes it necessary to assess all the factual circumstances in each specific case when qualifying the act.
Science is the best way to produce facts about reality. The best, at least, that limited human beings have devised so far. Yet, not even scientists quite seem to understand how scientific knowledge is generated. This is not only a philosophical but also a practical problem, as our misunderstandings affect the quality of our research and limit the directions it can take. In light of this, it may be good if we reflected a bit more on how we do science - to become better researchers through philosophy. Here, I provide an accessible introduction to a philosophical approach that achieves precisely this: William Wimsatt's multi-perspectival realism. It disabuses us of widespread but misleading myths and idealizations about science, such as the idea that everything in the world can be reduced to a fundamental level, or that we can approach a "view from nowhere" - complete and objectively detached knowledge of the world. Wismatt proposes an alternative view based on his thorough studies of actual research practice. It cuts deeply into the layered yet messy structure of reality, and the improvised but potent tools we have available, as limited and evolved beings, to explore it. Wimsatt reframes science as an irregular yet adaptive process rather than a cumulative repository of unalterable facts. His philosophy provides a workable and grounded middle way between radical skepticism and naïve belief in the objective truth of science. It explains how knowledge is conceptually constructed by humans, but still connects us to reality in a trustworthy way. We need such a new view of science, not only to improve our research practices and outcomes but, more generally, to gain a more realistic understanding of ourselves, the world, and our place and role within it.
Our systematic evidence map aimed to identify lung-related epidemiological estimates to populate the International Respiratory Coalition's Lung Facts website. We highlight important evidence gaps, suggest how they could be filled, and provide bespoke societal cost estimates to inform resource allocation. We examined 14 lung conditions across 53 World Health Organization Europe countries, seeking incidence, prevalence, mortality, years of life lost, years lived with disability, and disability-adjusted life year (DALY) estimates by age/sex. Global Burden of Disease (GBD) study estimates were obtained for nine GBD-included lung conditions: asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, lower respiratory infections, lung cancer/tracheal, bronchus and lung cancer, tuberculosis, mesothelioma, COVID-19 and pulmonary arterial hypertension. Systematic searches of bibliographic databases were necessary for five non-GBD-included lung conditions: cystic fibrosis, obstructive sleep apnoea (OSA), influenza, alpha-1 antitrypsin deficiency (A1AD) and bronchiectasis. All-age country-specific DALY estimates were multiplied by gross domestic product per capita as a proxy for a country's wealth and prosperity to estimate societal costs. Complete data for nine lung conditions for all countries were extracted from GBD, enabling societal cost estimation. Significant gaps were found for A1AD (only prevalence for 24 countries) and bronchiectasis (incidence, prevalence and mortality for between one and five countries), with more, but incomplete, estimates for cystic fibrosis, OSA and influenza. More epidemiological evidence is required for A1AD, bronchiectasis, cystic fibrosis, OSA, and influenza. Inclusion in the GDB study could help address these gaps. Lung Facts provides comprehensive lung-related epidemiological and societal cost estimates covering 53 countries to support policy-makers advocating for respiratory interventions.
Knowledge of past cultures relies heavily on surviving written material. Over the centuries, texts were copied, altered, and often lost, leaving scholars to reconstruct partial genealogies-stemmata-from shared innovations between surviving copies. Yet, a general understanding of the processes shaping textual transmission remains elusive. Within the broader topic of cultural evolution, text transmission provides a favorable context for integrating formal modeling with empirical evidence: explicitly identified items (texts), transmitted through deliberate manual replication, have left tangible artifacts (manuscripts)-traces of a dynamical, cultural, and historical process. Rethinking textual transmission through a complexity science approach, this study combines stochastic models and simulations, informed by historical scholarship, with empirical data from a corpus of circa 2,000 medieval manuscripts spanning four centuries. Our framework quantifies how variation in copying and destruction rates influences survival or extinction, and reproduces key stylized facts observed empirically in reconstructed stemmata, such as imbalance, a feature debated for over a century. Further, this approach provides broad trends estimates suggesting that up to 60%; of texts and more than 95%; of manuscripts may have been lost. Our findings highlight the role of drift in cultural transmission, while providing a formal basis to integrate drivers such as cultural selection and historical contingencies (eg the Black Death). It bridges philology and cultural evolution approaches, while providing a theoretical and empirical framework applicable to numerous other traditions-eg Classical literature, legal and scientific texts, religious canons-where replication and loss also shape what endures.
Food pleasure and worry may operate differently across cultural contexts; however, no studies have examined food pleasure or worry and eating-related outcomes among Mexican Americans. This study explored whether: (1) food pleasure/worry were associated with individual-level cultural attributes; (2) food pleasure/worry were associated with eating-related outcomes; and (3) relationships between food pleasure/worry and eating-related outcomes were moderated by cultural attributes. Data were collected with 3,329 Mexican American adults recruited through online panels to complete an online survey between November and December 2022. Participants had unique IP addresses, were aged 18-100, lived in the U.S., were able to read in English or Spanish, and had Mexican heritage. The survey assessed food pleasure, food worry, six cultural attributes (e.g., language use), and five eating-related outcomes believed to be associated with eating pleasure (e.g., sugary drink consumption) or nutrition monitoring (e.g., use of Nutrition Facts labels). Most participants rated food pleasure as important (83.6%) and had no food worry (83.1%). Rating food pleasure as important (vs. not) was associated with more Latino-oriented cultural attributes, higher sugary drink intake, consuming food prepared outside the home, and greater importance of sugary drinks at social gatherings. Having food worry (vs. not) was associated with being foreign-born, lower sugary drink intake, lower importance of sugary drinks at social gatherings, and greater likelihood of using Nutrition Facts labels. There was no strong evidence of moderation by cultural attributes. Food pleasure was associated with more obesogenic behaviors, and food worry was associated with more nutrition monitoring behaviors. More nuanced measurement of these food attitudes is needed to elucidate how food pleasure and worry influence eating behaviors, as well as whether nutrition interventions should target these food attitudes to promote healthy eating among Mexican American adults.
The currently known favorable properties of soybean have become the target of fraud in meat production. The use of plant-based raw materials in the adulteration of meat products is increasingly recognized by consumers, manufacturers, and researchers. However, the toxicity of soybeans has not been addressed. This article aimed to focus on the following: detection, quantification of soybean adulteration in meat products, analyzing how other adulterants could impact cholesterol levels in the products, and discussing how soybean adulteration could cause conditions such as allergies and toxicity. Utilizing immunohistochemical techniques, 450 different meat product samples were analyzed. Highlighting the confirmed soybean adulteration by analyzing cholesterol levels using HPLC. Results showed that, across all tested cases, soybean toxic doses ranged from 62% to 85%. Meanwhile, there were no indications on their respective nutritional facts labels. Surprisingly, the cholesterol levels were lower than those reported by previous investigators.
In this study, part of RAND's Gun Policy in America initiative, researchers systematically review the scientific literature that has examined the likely effects of various gun laws. In the fifth edition of this study, the authors incorporate more-recent research in their synthesis of the available scientific data regarding the effects of 18 state firearm policies on firearm injuries and deaths, violent crime, suicides, the gun industry, defensive gun use, and other outcomes. By highlighting where scientific evidence is accumulating, the authors hope to build consensus around a shared set of facts that have been established through a transparent, nonpartisan, and impartial review process. In so doing, they also illuminate areas in which more and better information could make important contributions to establishing fair and effective gun policies.