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The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.

Introduction Deliberate exposure to medical ionising radiation should be as low as reasonably practicable but the reduction of radiation from CT should be balanced against diagnostic image quality. The ability of ultra-low-dose CT (uLDCT: similar radiation to chest X-ray) to demonstrate low contrast abnormalities (emphysema and interstitial lung abnormality (ILA)) is unclear.The aim of this cross-sectional study was to analyse the lung parenchymal findings from uLDCT scans against physiological measures of respiratory function.Methods WA Asbestos Review Programme participants were eligible if they had an uLDCT scan and lung function assessment between Janary and December 2018. All scans were performed using a single CT machine and reported using a standardised, semiquantitative synoptic report which includes emphysema and linear fibrosis (ILA) scores.Results Of 1344 participants, median (IQR) age was 72.0 (65.0–78.0) years, the majority were males (84.9%) with mixed occupational asbestos exposure (68.1%). There were 721 (53.6%) with no abnormality, 158 (11.8%) with emphysema, 465 (34.6%) with ILA. Mean radiation dose was 0.12 mSv. There was statistically significant between group differences for all physiological parameters of lung function compared with controls. For instance, the emphysema score significantly correlated with obstructive forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio (r=0.512), per cent predicted FEV1 (r=0.24) and lower diffusion of carbon monoxide (DLCO) (r=0.337). Multivariate modelling demonstrated that increasing age, emphysema and fibrosis scores predicted reduced DLCO (adjusted R2=0.30).Discussion uLDCT-detected parenchymal lung abnormalities correlate strongly with significant changes on lung function testing suggesting the observed CT abnormalities are of physiological and clinical significance.

Abstract This paper proposes a smartphone-based method for measuring Blood Pressure (BP) using the oscillometric method. For oscillometry, it is necessary to measure (1) the pressure applied to the artery and (2) the local blood volume change. This is accomplished by performing an oscillometric measurement at the finger’s digital artery, whereby a user presses down on the phone’s camera with steadily increasing force. The camera is used to capture the blood volume change using photoplethysmography. We devised a novel method for measuring the force applied of the finger without the use of specialized smartphone hardware with a technique called Vibrometric Force Estimation (VFE). The fundamental concept of VFE relies on a phenomenon where a vibrating object is dampened when an external force is applied on to it. This phenomenon can be recreated using the phone’s own vibration motor and measured using the phone’s Inertial Measurement Unit (IMU). A cross device reliability study with three smartphones of different manufacturers, shape, and prices results in similar force estimation performance across all smartphone models. In an N = 24 proof of concept study of the BP measurement, the smartphone technique achieves a mean absolute error of 9.21 mmHg and 7.77 mmHg of systolic and diastolic BP, respectively, compared to an FDA approved BP cuff. The vision for this technology is not necessarily to replace existing BP monitoring solutions, but rather to introduce a downloadable smartphone software application that could serve as a low-barrier hypertension screening measurement fit for widespread adoption.

Background Protein biomarkers that reflect different pathophysiological pathways have been associated with the risk of adverse cardiovascular events. However, it is uncertain whether these associations are sustained with increasing years after the biomarkers are measured. Methods and Results In this cohort study, 7745 patients with coronary heart disease who participated in the LIPID (Long‐Term Intervention With Pravastatin in Ischemic Disease) trial, BNP (B‐type natriuretic peptide), troponin I, cystatin‐C, C‐reactive protein, d‐dimer and midregional proadrenomedullin were measured at baseline and after 1 year. Discrimination of plasma biomarker concentrations for cardiovascular death were evaluated in landmark analyses from 1 year for the next 5 years of the randomized trial, and for 10 additional years after trial completion. All 6 biomarkers were associated with risk of cardiovascular death (n=1903) both during and after the clinical trial (each P

El Estado Colombiano, a partir de la Constitución de 1991, se declaró como un Estado Social de Derecho en donde los valores de los Derechos Humanos se convierten en un pilar fundamental en la construcción de una sociedad incluyente y respetuosa de la diferencia étnica. En ese sentido, el artículo tiene como objetivo describir los desarrollos legislativos, particularmente, leyes y decretos en los cuales se materializan las acciones afirmativas en función de garantizar el derecho a la educación de las minorías étnicas desde sus realidades y particularidades culturales en Colombia, lo cual es fundamental para el cumplimiento de los demás derechos, como la identidad, la salud, entre otros. Para ello, se realiza una investigación cualitativa centrada en el análisis documental, tomando como referente las leyes y decretos publicados a partir de la Constitución Política de 1991. El análisis documental es una metodología de investigación que utiliza documentos como fuente de información. Los documentos pueden ser de diversos tipos, como libros, artículos, informes, etc. El análisis documental permite al investigador obtener información sobre un tema específico, comprender diferentes perspectivas sobre un problema y desarrollar nuevas ideas. Los resultados evidencian los avances jurídicos en dicha materia. Sin embargo, también se manifiestan las debilidades de las mismas que han conllevado a dificultades para que la población pueda acceder de forma eficaz al gozo y disfrute de la educación, desde su diversidad étnica.

Purpose To explore the lived experiences and motivations of individuals engaged in weight management, focusing on psychological, societal, health-related, and personal factors influencing their motivations. Methods A descriptive exploratory approach, guided by the Self-Determination Theory (SDT), was followed and semi-structured interviews were conducted with ten adults actively involved in weight management. Thematic analysis identified key themes across four domains: (i) psychological motivation (extrinsic and intrinsic), (ii) societal influence (body image, social norms, media influence), (iii) health consciousness (priority of health, health concerns), and (iv) family support and past weight management experiences (learned habits, supportive environment). Results The findings revealed a nuanced interplay of intrinsic and extrinsic motivations, societal expectations, health priorities, and the impact of family support on weight management. Aligning with SDT, the study emphasizes the role of autonomy, competence, and relatedness in shaping individual motivations for weight management. Conclusions The study provides valuable insights for tailoring interventions aimed at enhancing well-being by addressing the psychological, societal, health-conscious, and familial factors that influence motivations in weight management.

The genus Passiflora (Passifloraceae) comprises about 500 species. The Passiflora edulis stands out because of its economic and medicinal importance. It is widely planted in tropical and subtropical regions worldwide, especially in South America, the Caribbean, South Africa, and Asia. The aqueous extract of Passiflora edulis Sims f. edulis (Gulupa) leaves is used in traditional medicine for its soothing and tranquilizing effects on the central nervous system. Therefore, evaluating its safety for human use is a fundamental requirement to continue the development of new therapies within the framework of regulatory, preclinical, and clinical guidelines. Here, the sub-acute toxicity study was conducted following the Organization for Economic Cooperation and Development (OECD) guideline 407 for 28 days in Wistar albino rats. The study showed that 1000 mg/kg/day of the aqueous extract in 10 adult Wistar rats (five males and five females) was well tolerated. The hematological results are at normal levels. However, monocytopenia and eosinopenia were observed with a significant difference (P

Knowledge about determinants of addiction in people taking addictive substances is poor and needs to be supplemented. The novelty of this paper consists in the analysis of innovative aspects of current research about relationships between determinants of addiction in Polish patients taking addictive substances and rare available data regarding the relationships between these factors from studies from recent years from other environments, mainly in Europe, and on the development of genetic determinants of physiological responses. We try to explain the role of the microelements Mn, Fe, Cu, Co, Zn, Cr, Ni, Tl, Se, Al, B, Mo, V, Sn, Sb, Ag, Sr, and Ba, the toxic metals Cd, Hg, As, and Pb, and the rare earth elements Sc, La, Ce, Pr, Eu, Gd, and Nd as factors that may shape the development of addiction to addictive substances or drugs. The interactions between factors (gene polymorphism, especially ANKK1 (TaqI A), ANKK1 (Taq1 A-CT), DRD2 (TaqI B, DRD2 Taq1 B-GA, DRD2 Taq1 B-AA, DRD2-141C Ins/Del), and OPRM1 (A118G)) in patients addicted to addictive substances and consumption of vegetables, consumption of dairy products, exposure to harmful factors, and their relationships with physiological responses, which confirm the importance of internal factors as determinants of addiction, are analyzed, taking into account gender and region. The innovation of this review is to show that the homozygous TT mutant of the ANKK1 TaqI A polymorphism rs 1800497 may be a factor in increased risk of opioid dependence. We identify a variation in the functioning of the immune system in addicted patients from different environments as a result of the interaction of polymorphisms.

Image classification is increasingly being utilized on construction sites to automate project monitoring, driven by advancements in reality-capture technologies and artificial intelligence (AI). Deploying real-time applications remains a challenge due to the limited computing resources available on-site, particularly on remote construction sites that have limited telecommunication support or access due to high signal attenuation within a structure. To address this issue, this research proposes an efficient edge-computing-enabled image classification framework for support of real-time construction AI applications. A lightweight binary image classifier was developed using MobileNet transfer learning, followed by a quantization process to reduce model size while maintaining accuracy. A complete edge computing hardware module, including components like Raspberry Pi, Edge TPU, and battery, was assembled, and a multimodal software module (incorporating visual, textual, and audio data) was integrated into the edge computing environment to enable an intelligent image classification system. Two practical case studies involving material classification and safety detection were deployed to demonstrate the effectiveness of the proposed framework. The results demonstrated the developed prototype successfully synchronized multimodal mechanisms and achieved zero latency in differentiating materials and identifying hazardous nails without any internet connectivity. Construction managers can leverage the developed prototype to facilitate centralized management efforts without compromising accuracy or extra investment in computing resources. This research paves the way for edge “intelligence” to be enabled for future construction job sites and promote real-time human-technology interactions without the need for high-speed internet.

Background Use of personal sensing to predict mental health risk has sparked interest in adolescent psychiatry, offering a potential tool for targeted early intervention.Objectives We investigated the preferences and values of UK adolescents with regard to use of digital sensing information, including social media and internet searching behaviour. We also investigated the impact of risk information on adolescents’ self-understanding.Methods Following a Design Bioethics approach, we created and disseminated a purpose-built digital game (www.tracingtomorrow.org) that immersed the player-character in a fictional scenario in which they received a risk assessment for depression Data were collected through game choices across relevant scenarios, with decision-making supported through clickable information points.Findings The game was played by 7337 UK adolescents aged 16–18 years. Most participants were willing to personally communicate mental health risk information to their parents or best friend. The acceptability of school involvement in risk predictions based on digital traces was mixed, due mainly to privacy concerns. Most participants indicated that risk information could negatively impact their academic self-understanding. Participants overwhelmingly preferred individual face-to-face over digital options for support.Conclusions The potential of digital phenotyping in supporting early intervention in mental health can only be fulfilled if data are collected, communicated and actioned in ways that are trustworthy, relevant and acceptable to young people.Clinical implications To minimise the risk of ethical harms in real-world applications of preventive psychiatric technologies, it is essential to investigate young people’s values and preferences as part of design and implementation processes.

Objective To capture UK medical students’ self-reported knowledge and harm assessment of psychedelics and to explore the factors associated with support for changing the legal status of psychedelics to facilitate further clinical research.Design Cross-sectional, anonymous online survey of UK medical students using a non-random sampling method.Setting UK medical schools recognised by the General Medical Council.Participants 132 medical students who had spent an average of 3.8 years (SD=1.4; range: 1–6) in medical school.Results Most students (83%) reported that they were aware of psychedelic research and only four participants (3%) said that they were not interested in learning more about this type of research. Although medical students’ harm assessment of psychedelics closely aligned with that of experts, only 17% of students felt well-educated on psychedelic research. Teachings on psychedelics were only rarely encountered in their curriculum (psilocybin: 14.1 (SD=19.9), scale: 0 (never) to 100 (very often)). Time spent at medical schools was not associated with more knowledge about psychedelics (r=0.12, p=0.129). On average, this sample of medical students showed strong support for changing the legal status of psychedelics to facilitate further research into their potential clinical applications (psilocybin: 80.2 (SD=24.8), scale: 0 (strongly oppose) to 100 (strongly support)). Regression modelling indicated that greater knowledge of psychedelics (p

Abstract Oral history indicates that a large wooden trough held in storage at the University of Kentucky’s William S. Webb Museum of Anthropology was a component of the saltpeter mining operation in Mammoth Cave in the late 18th and early 19th centuries, worked largely by enslaved persons. We used multiple heritage science methods, including radiocarbon wiggle-match dating, tree-ring dating, scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM–EDS), and optical scanning, combined with historical research, to examine the trough. Our analysis supports the oral history of the trough as an artifact of the mining system in Mammoth Cave. This case study illustrates how heritage science methods can provide corroboration for the origins and biographies of poorly documented historical artifacts.

Bone regeneration is a complex multicellular process involving the recruitment and attachment of osteoprogenitors and their subsequent differentiation into osteoblasts that deposit extracellular matrixes. There is a growing demand for synthetic bone graft materials that can be used to augment these processes to enhance the healing of bone defects resulting from trauma, disease or surgery. P-15 is a small synthetic peptide that is identical in sequence to the cell-binding domain of type I collagen and has been extensively demonstrated in vitro and in vivo to enhance the adhesion, differentiation and proliferation of stem cells involved in bone formation. These events can be categorized into three phases: attachment, activation and amplification. This narrative review summarizes the large body of preclinical research on P-15 in terms of these phases to describe the mechanism of action by which P-15 improves bone formation. Knowledge of this mechanism of action will help to inform the use of P-15 in clinical practice as well as the development of methods of delivering P-15 that optimize clinical outcomes.

Abstract In recent times, widely understood spine diseases have advanced to one of the most urgetn problems where quick diagnosis and treatment are needed. To diagnose its specifics (e.g. to decide whether this is a scoliosis or sagittal imbalance) and assess its extend, various kind of imaging diagnostic methods (such as X-Ray, CT, MRI scan or ST) are used. However, despite their common use, some may be regarded as (to a level) invasive methods and there are cases where there are contraindications to using them. Besides, which is even more of a problem, these are very expensive methods and whilst their use for pure diagnostic purposes is absolutely valid, then due to their cost, they cannot rather be considered as tools which would be equally valid for bad posture screening programs purposes. This paper provides an initial evaluation of the alternative approach to the spine diseases diagnostic/screening using inertial measurement unit and we propose policy-based computing as the core for the inference systems. Although the methodology presented herein is potentially applicable to a variety of spine diseases, in the nearest future we will focus specifically on sagittal imbalance detection.

Smartphone camera photoplethysmography (cPPG) enables non-invasive pulse oximetry and hemoglobin concentration measurements. However, the aesthetic-driven non-linearity in default image capture and preprocessing pipelines poses challenges for consistency and transferability of cPPG across devices. This work identifies two key parameters—tone mapping and sensor threshold—that significantly impact cPPG measurements. We propose a novel calibration method to linearize camera measurements, thus enhancing consistency and transferability of cPPG across devices. A benchtop calibration system is also presented, leveraging a microcontroller and LED setup to characterize these parameters for each phone model. Our validation studies demonstrate that, with appropriate calibration and camera settings, cPPG applications can achieve 74% higher accuracy than with default settings. Moreover, our calibration method proves effective across different smartphone models (N=4), and calibrations performed on one phone can be applied to other smartphones of the same model (N=6), enhancing consistency and scalability of cPPG applications.

Background CD8+ T cells are a highly diverse population of cells with distinct phenotypic functions that can influence immunotherapy outcomes. Further insights on the roles of CD8+ specificities and TCR avidity of naturally arising tumor-specific T cells, where both high and low avidity T cells recognizing the same peptide-major histocompatibility complex (pMHC) coexist in the same tumor, are crucial for understanding T cell exhaustion and resistance to PD-1 immunotherapy.Methods CT26 models were treated with anti-PD-1 on days 3, 6 and 9 following subcutaneous tumor implantation generating variable responses during early tumor development. Tetramer staining was performed to determine the frequency and avidity of CD8+ T cells targeting the tumor-specific epitope GSW11 and confirmed with tetramer competition assays. Functional characterization of high and low avidity GSW11-specific CD8+ T cells was conducted using flow cytometry and bulk RNA-seq. In vitro cytotoxicity assays and in vivo adoptive transfer experiments were performed to determine the cytotoxicity of high and low avidity populations.Results Treatment success with anti-PD-1 was associated with the preferential expansion of low avidity (Tetlo) GSW11-specific CD8+ T cells with Vβ TCR expressing clonotypes. High avidity T cells (Tethi), if present, were only found in progressing PD-1 refractory tumors. Tetlo demonstrated precursor exhausted or progenitor T cell phenotypes marked by higher expression of Tcf-1 and T-bet, and lower expression of the exhaustion markers CD39, PD-1 and Eomes compared with Tethi, whereas Tethi cells were terminally exhausted. Transcriptomics analyses showed pathways related to TCR signaling, cytotoxicity and oxidative phosphorylation were significantly enriched in Tetlo found in both regressing and progressing tumors compared with Tethi, whereas genes related to DNA damage, apoptosis and autophagy were downregulated. In vitro studies showed that Tetlo exhibits higher cytotoxicity than Tethi. Adoptive transfer of Tetlo showed more effective tumor control than Tethi, and curative responses were achieved when Tetlo was combined with two doses of anti-PD-1.Conclusions Targeting subdominant T cell responses with lower avidity against pMHC affinity neoepitopes showed potential for improving PD-1 immunotherapy. Future interventions may consider expanding low avidity populations via vaccination or adoptive transfer.

Legal reform is a necessity. Regulatory arrangement is one aspect of the legal reform program within the framework of national legal development. Regulation is the solution and foundation of law enforcement and government policies, thereby creating legal certainty and order and providing benefits to the community. However, regulation is an obstacle to development due to overlapping regulations, hyper regulations, conflicts of interest and authority. It can be seen that there is a judicial review of existing laws in the Constitutional Court and 1,765 regional regulations have been canceled. The legal reform program is carried out based on the Regulation of the Minister of Administrative and Bureaucratic Reform concerning the Road Map for Bureaucratic Reform 2020-2024. The regulation mandates the need to create a Legal Reform Index to measure the success of Legal Reform. This research was conducted to provide an overview of regulations and the formation of regulations as well as the implementation of regulatory policies for Government Agencies. This research is juridical-empirical and used a qualitative approach. From the results of this study, it was found that there are regulations in Indonesia that require amalgamation, simplification, and revocation. Considering this situation, legal reform is needed. This determination is seen from the Legal Reform Index. Policy Measurement of the legal reform index is useful for ensuring the quality of good laws and regulations following the principles, rules and objectives of the ideal formation and arrangement of laws and regulations.

Just as psychedelic-assisted psychotherapy (PAP) represents a clinical innovation that may need to be accommodated with corresponding theoretical and methodological innovations, there is growing awareness that the tools, normative frameworks, and standard practices of our clinical ethics may also need to be adapted, renewed, or replaced to accommodate its unusual features. Drawing on L. A. Paul's work on “Transformative Experience,” I argue that the acute and long-term effects that are repeatedly reported following the administration of psychedelic drugs, including in clinical contexts, are epistemically inaccessible at the point of deciding to take them. By virtue of both the so-called “mystical” experiences that frequently arise during PAP, and the long-term shifts to outlooks, values, and priorities that can follow treatment, the processes of decision-making that are normatively expected of patients run aground. If this framing is correct, then prospective patients cannot meet the requirement of understanding that is one of the principal analytic components of informed consent. The role of understanding in supporting two functions of informed consent—avoiding unauthorized trespass against patients and supporting values-aligned decision-making—is explored, and I argue that, while the normative standard for the first function may be met by extant suggestions for enhancing the consenting process for PAP, the latter function remains unattainable. In light of this, the consequences for the ethical preparation of prospective patients are considered.

ObjectiveLactation consultants (LCs) positively impact chestfeeding rates by providing in-person support to struggling parents. In Brazil, LCs are a scarce resource and in high demand, risking chestfeeding rates across many communities nationwide. The transition to remote consultations during the COVID-19 pandemic made LCs face several challenges to solve chestfeeding problems due to limited technical resources for management, communication, and diagnosis. This study investigates the main technological issues LCs have in remote consultations and what technology features are helpful for chestfeeding problem-solving in remote settings.MethodsThis paper implements qualitative investigation through a contextual study (n=10) and a participatory session (n=5) to determine stakeholders’ preferences for technology features in solving chestfeeding problems.FindingsThe contextual study with LCs in Brazil characterized (1) the current appropriation of technologies that help during consultations, (2) technology limitations that affect LCs’ decision-making, (3) challenges and benefits of remote consultations, and (4) cases that are easy and difficult to solve remotely. The participatory session brings LCs’ perceptions on (1) components for an effective remote evaluation, (2) preferred elements by professionals when providing remote feedback to parents, and (3) feelings about using technology resources for remote consultations.ConclusionFindings suggest that LCs adapted their methodologies for remote consultations, and the perceived benefits of this modality show interest in continuing to provide remote care as long as more integrative and nurturing applications are offered to their clients. We learned that fully remote lactation care might not be the main objective for overall populations in Brazil, but as a hybrid mode of care that benefits parents by having both modalities of consultations available to them. Finally, remote support helps reduce financial, geographic, and cultural barriers in lactation care. However, future research must identify how generalized solutions for remote lactation care can be, especially for different cultures and regions.

Multiple myeloma is an incurable plasma cell malignancy with only a 53% 5-year survival rate. There is a critical need to find new multiple myeloma vulnerabilities and therapeutic avenues. Herein, we identified and explored a novel multiple myeloma target: the fatty acid binding protein (FABP) family. In our work, myeloma cells were treated with FABP inhibitors (BMS3094013 and SBFI-26) and examined in vivo and in vitro for cell cycle state, proliferation, apoptosis, mitochondrial membrane potential, cellular metabolism (oxygen consumption rates and fatty acid oxidation), and DNA methylation properties. Myeloma cell responses to BMS309403, SBFI-26, or both, were also assessed with RNA sequencing (RNA-Seq) and proteomic analysis, and confirmed with western blotting and qRT-PCR. Myeloma cell dependency on FABPs was assessed using the Cancer Dependency Map (DepMap). Finally, MM patient datasets (CoMMpass and GEO) were mined for FABP expression correlations with clinical outcomes. We found that myeloma cells treated with FABPi or with FABP5 knockout (generated via CRISPR/Cas9 editing) exhibited diminished proliferation, increased apoptosis, and metabolic changes in vitro. FABPi had mixed results in vivo, in two pre-clinical MM mouse models, suggesting optimization of in vivo delivery, dosing, or type of FABP inhibitors will be needed before clinical applicability. FABPi negatively impacted mitochondrial respiration and reduced expression of MYC and other key signaling pathways in MM cells in vitro. Clinical data demonstrated worse overall and progression-free survival in patients with high FABP5 expression in tumor cells. Overall, this study establishes the FABP family as a potentially new target in multiple myeloma. In MM cells, FABPs have a multitude of actions and cellular roles that result in the support of myeloma progression. Further research into the FABP family in MM is warrented, especially into the effective translation of targeting these in vivo.

Diffuse correlation spectroscopy is a non-invasive optical modality used to measure cerebral blood flow in real time, and it has important potential applications in clinical monitoring and neuroscience. As such, many research groups have recently been investigating methods to improve the signal-to-noise ratio, imaging depth, and spatial resolution of diffuse correlation spectroscopy. Such methods have included multispeckle, long wavelength, interferometric, depth discrimination, time-of-flight resolution, and acousto-optic detection strategies. In this review, we exhaustively appraise this plethora of recent advances, which can be used to assess limitations and guide innovation for future implementations of diffuse correlation spectroscopy that will harness technological improvements in the years to come.

Abstract It is becoming increasingly clear that the field of empirical bioethics requires methodological innovations that can keep up with the scale and pace of contemporary research in health and medicine. With that in mind, we have recently argued for Design Bioethics—the use of purpose‐built, engineered research tools that allow researchers to investigate moral decision‐making in ways that are embodied and contextualized. In this paper, we outline the development, testing and implementation of a novel prototype tool in the Design Bioethics Workshop—with each step illustrated with collected data. Titled ‘Tracing Tomorrow’ (www.tracingtomorrow.org), the tool is a narrative game to investigate young people's values and preferences in the context of digital phenotyping for mental health. The process involved (1) Working with young people to discover, validate and define the morally relevant cases or problems, (2) Building and testing the game concept in collaboration with relevant groups and game developers, (3) Developing prototypes that were tested and iterated in partnership with groups of young people and game developers and (4) Disseminating the game to young people to collect data to investigate research questions. We argue that Design Bioethics yields tools that are relevant, representative and meaningful to target populations and provide improved data for bioethics analysis. Patient or Public Contribution In planning and conducting this study, we consulted with young people from a diverse range of backgrounds, including the NeurOX Young People's Advisory Group, the What Lies Ahead Junior Researchers Team, Censuswide youth participants and young people from the Livity Youth Network.

ObjectivesThe SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this.MethodsIn this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1st November 2020 and 30th January 2021 were sequenced. We matched sequence data to clinical outcomes as the Alpha variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death.ResultsOur cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus pre-Alpha variants).ConclusionsThe Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.

Summary: PIP (Poly Implant Prothèse, France) implants were readily employed for breast reconstruction until withdrawn from the market in 2010. These implants have an early and increased risk of rupture compared to non-PIP implants. This report outlines a significant cutaneous manifestation of PIP-implant rupture not previously described in the literature. This patient developed significant cutaneous xanthomatous inflammation with sinus tract formation that has yet to resolve despite explantation. Further investigation is warranted to elucidate the aetiology of this clinical sign and the optimal management of the cutaneous manifestation.

Background: Lenvatinib is an approved first-line treatment for unresectable hepatocellular carcinoma (uHCC). We evaluated the safety and efficacy of lenvatinib versus sorafenib in patients with uHCC who deteriorated to Child-Pugh class B (CP-B) on treatment. Methods: We retrospectively evaluated patients from REFLECT who deteriorated to CP-B versus those who remained Child-Pugh class A (CP-A) within 8 weeks after randomization. Best overall response and objective response rate (ORR) per modified Response Evaluation Criteria In Solid Tumors (mRECIST) were assessed from baseline. Progression-free survival (PFS) per mRECIST and overall survival (OS) were assessed beginning at week 8. Results: Patients with CP-B versus CP-A classification receiving lenvatinib had ORRs of 28.3 and 42.9%, respectively; patients with CP-B versus CP-A classification receiving sorafenib had ORRs of 8.5 and 12.9%, respectively. Median PFS and OS (landmark analyses beginning at week 8) in patients receiving lenvatinib were 3.7 months [95% confidence interval (CI): 1.8–7.4] and 6.8 months (95% CI: 2.6–10.3) in the CP-B subgroup versus 6.5 months (95% CI: 5.6–7.4) and 13.3 months (95% CI: 11.6–16.1) in the CP-A subgroup, respectively. Median PFS and OS in patients receiving sorafenib were 0.5 months (95% CI: 0.1–3.6) and 4.5 months (95% CI: 2.9–6.1) in the CP-B subgroup versus 3.6 months (95% CI: 2.7–3.7) and 12.0 months (95% CI: 10.2–14.0) in the CP-A subgroup, respectively. The most common treatment-emergent adverse events in the lenvatinib cohort were hypertension (both subgroups) and decreased appetite (CP-B subgroup). Conclusion: Results suggest that patients with uHCC whose liver function deteriorates to CP-B after initiation of therapy may continue to receive lenvatinib. Trial registration: ClinicalTrials.gov, NCT01761266, https://clinicaltrials.gov/ct2/show/NCT01761266 .

Background The plasma concentration of B‐type natriuretic peptide (BNP) is a strong predictor of adverse cardiovascular events. The aim of this study was to determine whether the association between plasma BNP concentration and cardiovascular mortality is sustained or diminishes with increasing time after BNP is measured. Methods and Results Six thousand seven hundred forty patients with a history of myocardial infarction or unstable angina who participated in the LIPID (Long‐Term Intervention with Pravastatin in Ischemic Disease) trial had plasma BNP concentration measured at baseline and after 1 year. Associations with cardiovascular mortality were evaluated in landmark analyses 1 to 1 BNP measurement improves long‐term risk prediction.

Pada tahun 1908 Nusakambangan telah ditetapkan sebagai rumah bagi mereka yang menjalani masa hukuman dan selanjutnya pada tahun 1912 ditetapkan sebagai “pulau penjara” oleh Pemerintah Hindia Belanda. Penetapan Nusakambangan sebagai pilot project percepatan pelaksanaan Revitalisasi Pemasyarakatan dilakukan dalam upaya memaksimalkan pembinaan narapidana. Nusakambangan memiliki lahan sangat luas yang dapat dimanfaatkan sesuai dengan tugas dan fungsi pemasyarakatan. Di lahan sangat luas tersebut terdapat delapan unit kerja Pemasyarakatan. Hingga saat ini pemanfaatan lahan belum optimal, baik dalam perencanaan, pemanfaatan, pengelolaan, maupun pengawasan. Selain itu, juga belum memiliki organisasi pengkoordinasi unit kerja pemasyarakatan dan pengolahan lahan. Tulisan ini membahas pemanfaatan Nusakambangan saat ini, serta model organisasi pengelolaan Nusakambangan dalam rangka mendukung tugas dan fungsi Pemasyarakatan. Penelitian ini merupakan penelitian deskriptif analisis dengan pendekatan kualitatif. Hasil analisis diperoleh bahwa Nusakambangan saat ini dimanfaatkan sebagai kawasan terpadu revitalisasi pembinaan narapidana berbasis pada pemanfaatan lahan produktif. Model organisasi yang akan dibentuk sebagai pengkoordinasi unit kerja Pemasyarakatan di Nusakambangan serta dapat melakukan tugas dan fungsi pemanfaatan dan pengelolaan lahan. Untuk itu diperlukan regulasi yang jelas dalam pengelolaan Nusakambangan, mensertifikasi aset Barang Milik Negara di Nusakambangan, dan mengoptimalkan redistribusi narapidana. Serta perlu membentuk unit kerja dengan model sebagai pengkoordinasi unit kerja pemasyarakatan dan pengelolaan lahan Nusakambangan.

Background Elevated plasma cystatin C levels reflect reduced renal function and increased cardiovascular risk. Less is known about whether the increased risk persists long‐term or is independent of renal function and other important biomarkers. Methods and Results Cystatin C and other biomarkers were measured at baseline (in 7863 patients) and 1 year later (in 6106 patients) in participants in the LIPID (Long‐Term Intervention with Pravastatin in Ischemic Disease) study, who had a previous acute coronary syndrome. Outcomes were ascertained during the study (median follow‐up, 6 years) and long‐term (median follow‐up, 16 years). Glomerular filtration rate (GFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration equations (first GFR‐creatinine, then GFR‐creatinine‐cystatin C). Over 6 years, in fully adjusted multivariable time‐to‐event models, with respect to the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, for comparison of Quartile 4 versus 1 of baseline cystatin C, the hazard ratio was 1.37 (95% CI, 1.07–1.74; P=0.01), and for major cardiovascular events was 1.47 (95% CI, 1.19–1.82; P

ABSTRAK Hak untuk mengeksploitasi suatu ciptaan terletak pada Pencipta dan/atau Pemegang Hak Cipta. Salah satu pengalihan hak eksploitasi dari pencipta kepada pemegang hak cipta dengan memberikan izin atau lisensi berdasarkan suatu perjanjian. Berkaitan dengan lisensi mengumumkan lagu dan/ atau Musik di Indonesia dilakukan oleh Lembaga Manajemen Kolektif yang pengaturannya masih multitafsir yang dapat mengakibatkan terjadinya konflik. Penelitian ini bertujuan untuk mengekplorasi proses Lisensi atas Pengumuman Karya Cipta Lagu dan/atau Musik dan menganalisis Implementasi pengelolaan Royalti atas Pengumuman Karya Cipta Lagu dan/atau Musik. Penelitian ini merupakan penelitian hukum empiris yang bersifat deskriptif. Berdasarkan penelitian ini diperoleh hasil bahwa sangat diperlukan lembaga yang dapat mewakili para pencipta lagu dan pemegang hak terkait untuk melaksanakan lisensi yang dapat membantu menjembatani kerja sama antara pencipta atau pemegang hak cipta dengan pengguna. Namun, pelaksanaan pengelolaan royalti pengumuman Karya Cipta Lagu dan/atau Musik belum berjalan dengan lancar. Hal ini disebabkan karena kesadar- an hukum masyarakat pengguna hak cipta masih sangat kurang serta belum maksimalnya sosiali- sasi yang dilakukan oleh Lembaga Manajemen Kolektif.

Pathogenic IgA1 metalloproteases block the initial host immune response by cleaving host IgA1. Using cryoEM, the authors here provide structural insights into the substrate recognition mechanism of Streptococcus pneumoniae IgA1 protease, and develop a protease-inhibiting antibody.

Permohonan pengangkatan calon penerjemah tersumpah di Kementerian Hukum dan Hak Asasi Manusia telah mengalami peningkatan. Untuk menindaklanjuti hal ini telah diterbitkan ketentuan yang menjadi dasar dalam teknis pengangkatan, pemantauan, dan pemberhentian penerjemah tersumpah. Namun, pengaturan terhadap kualifikasi penerjemah tersumpah hingga sat ini belum ada. Sehubungan dengan banyaknya permintaan dokumen resmi yang diminta oleh sebagian negara tujuan yang mengharuskan untuk diterjemahkan dalam bahasa setempat, maka diperlukan penerjemah yang benar-benar memahami atau menguasai bahasa asal dari dokumen yang diterjemahkan. Secara profesi seorang penerjemah harus dapat bertanggung jawab terhadap hasil terjemahannya. Untuk itu perlu adanya suatu pengaturan yang jelas tentang penerjemah tersumpah sehingga kedudukannya menjadi jelas dan diakui oleh masyarakat serta dapat melakukan praktik dengan baik. Penelitian ini merupakan penelitian hukum empiris. Analisis pengaturan terkait profesi penerjemah tersumpah dan praktik penerjemah tersumpah dengan menggunakan pendekatan kualitatif. Dari hasil analisis perlu dipertimbangkan pengaturan mengenai syarat Perguruan Tinggi yang dapat melakukan ujian kualifikasi penerjemah dan perlu diadakannya jurusan yang khusus mengenai penerjemah resmi tersumpah di setiap Perguruan Tinggi atau program kuliah kerja lapangan, agar bisa mengakomodir para calon penerjemah resmi tersumpah.

Abstract Aims/Introduction To develop a new non‐invasive risk score for undiagnosed diabetes in Chinese people, and to evaluate the incident diabetes risk in those with high‐risk scores, but no diabetes on initial testing. Materials and Methods A total of 2,609 participants with no known diabetes (aged 25–74 years) who underwent oral glucose tolerance tests in Hong Kong (HK) were investigated for independent risk factors of diabetes to develop a categorization point scoring system, the Non‐invasive Diabetes Score (NDS). This NDS was validated in a cross‐sectional study of 2,746 participants in Shaanxi, China. HK participants tested to not have diabetes at baseline were assessed for subsequent incident diabetes rates. Results In the HK cohort, hypertension, age and body mass index were the key independent risk factors selected to develop the NDS, with ≥28 out of 50 NDS points considered as high risk. The area under the receiver operating characteristic curve for undiagnosed diabetes was 0.818 and 0.720 for the HK and Shaanxi cohort, respectively. The negative predictive value was 97.4% (HK) and 95.8% (Shaanxi); the number needed to screen to identify one case of diabetes was five (HK) and 11 (Shaanxi), respectively. Among those that tested non‐diabetes at baseline, individuals with NDS ≥28 had a threefold risk of incident diabetes during the subsequent 20.9 years, compared with those with NDS

Background: The impact of residential setting on the performance of older adults on commonly used instruments of mobility has not been closely investigated. Objective: This study aimed to (1) explore whether mobility test performance differed between those who lived in urban and rural communities, and (2) report preliminary reference values for these tests according to residential setting. Methods: The study used a descriptive design. Individuals who were aged 60 years and above, had no significant disability, and resided in urban and rural areas in the Philippines (n=180), participated in the study. Researchers measured mobility performance using the 10-Meter Walk Test (10MWT) (both comfortable gait velocity (CGV) and fast gait velocity (FGV)), Five Times Sit to Stand Test (FTSST), and Six-Minute Walk Test (6MWT). Preliminary reference values for the mobility tests were presented as means, standard deviations, and 95% confidence intervals. Scores were compared based on residential setting (urban versus rural). Results: Urban-dwellers scored consistently better compared to their rural counterparts on the CGV, FGV, FTSST, and 6MWT using independent samples t-test (p

Faculty are increasingly interested in engaging in the scholarship of teaching and learning (SoTL) across disciplines, necessitating educational development support. While many institutions utilize one-time workshops and faculty communities offering professional development funding, the case study presented in this article takes a different approach. The aim of the Engaged Teacher-Scholar (ETS) program is to support faculty growth in a process of becoming ETS leaders across the university campus. ETS leaders advance an individual SoTL research project and are trained to develop a plan for and offer professional development events to their department, college, and university related to SoTL. The article presents an overview of the program’s objectives, organization, and outcomes over four years of implementation. The article concludes with implications for implementation at other institutions.

The article addresses the issue of transformations in contemporary culture, which deviates from traditional values. globalism and domination of popular culture have consequences in preferences and behavior of residents of local communities. negative aspects of individualism in culture can be balanced by the activities of cultural institutions in the nearest place of residence. The text shows cultural and animation activities in social perception in a small urban-rural commune. it is noteworthy that residents’ social capital is animated and formed by local institutions in cultural and educational work.

Podstawową tezą niniejszej pracy jest polemiczne stanowisko Tadeusza Micińskiego wobec tradycji interpretacji kerygmatu Ewangelii według św. Jana. Analizując obecność tej w Ewangelii w jego powieści Xiądz Faust, koncentruję się na kilkunastu najważniejszych odwołaniach do tej księgi nowotestamentowej, widocznych w tekście powieści. Wśród nich znajdują się drobne, rozsiane po różnych rozdziałach aluzje, służące obrazowaniu i poetyckiej intensyfikacji przekazu. Niewiele tu takich odniesień, które podejmują (konstruktywnie lub destruktywnie) dialog z Janowym przekazem. Szczególnie rozgałęzione treściowo jest modyfikacja sceny spotkania Chrystusa z Samarytanką przy studni w Sychar. W sposobach uobecniania Janowej Ewangelii daje się zauważyć przedmiotowe wykorzystywanie epizodów w niej zawartych dla potrzeb imaginarium poetyckiego powieści. Nie ma tu, niestety, choćby najbardziej podstawowego dialogu z Księgą, a nieznaczne imitacje polemiczne należą do rzadkości. Warte jednakże odnotowania jest Micińskiego korzystanie z Jana, gdyż unaocznia ono pewne, wspólne dla lektury całego dziedzictwa biblijnego w Xiędzu Fauście prawidłowości tak w zakresie poetyki, jak też w zakresie idei i swoistej teologumenii tej powieści.

Abstract Background Women with gestational diabetes have low diet quality. We evaluated the effectiveness of a group-based lifestyle modification program for improvement of dietary quality in women with previous gestational diabetes predominantly within their first postnatal year. Methods Women were randomised to intervention (n = 284) or usual care (n = 289). Dietary data was collected at baseline and twelve months using a food frequency questionnaire and recoded into the Australian Recommended Food Score (ARFS). Mixed model analyses investigated the intervention effect on ARFS (per-protocol-set (PPS) excluded women without the minimum intervention exposure). Results Baseline mean total ARFS was low (31.8 ± 8.9, maximum score = 74) and no significant changes were seen in total ARFS (Cohen’s D = − 0.06). 2% reduction in alcohol for intervention (0.05, 0.26) compared with − 1% for usual care (Odds ratio: 0.68; 95%CI 0.46, 0.99). Dairy ARFS sub-category significantly improved (low fat/saturated fat foods) in the intervention group over time compared with usual care for the PPS analysis (dairy + 0.28 in intervention (95%CI 0.08, 0.48) compared with + 0.02 in usual care (95%CI -0.14, 0.18) (group-by-treatment interaction p = 0.05, Cohen’s D = 0.14)). Conclusions Engaging with the intervention improved aspects of diet quality that aligned with minimum intervention exposure, but the total diet quality remains low. Further research is needed to improve diabetes prevention program engagement. Trial registration Australian New Zealand Clinical Trials Registry ANZCTRN12610000338066, April 2010.

Pencanangan wilayah bebas dari korupsi di Kementerian Hukum dan Hak Asasi Manusia dimulai sejak tahun 2004 sampai sekarang. Namun, dari 814 unit kerja hanya satu unit kerja yang telah memperoleh predikat Wilayah Bebas dari Korupsi pada tahun 2016, yaitu Lembaga Pemasyarakatan Perempuan Semarang. Kemudian, pada tahun 2018 menjadi 11 satuan kerja yang predikat Wilayah Bebas dari Korupsi. Untuk percepatan pemberantasan dan pencegahan korupsi dilakukan gerakan revolusi mental “Ayo Kerja, Kami PASTI“. Untuk itu dianalisis Aktualisasi Tata Nilai ‘PASTI’ dalam pelaksanaan tugas dan fungsi dari satuan kerja dengan menggunakan pendekatan kualitatif. Setelah pendeklarasian Tata Nilai ‘PASTI’ sikap dan tindakan yang dilakukan berbeda dengan sebelum pendeklarasian, seperti sikap tepat waktu. Ketaatan terhadap jam masuk kerja dan jam keluar kerja sudah lebih tepat waktu, serta penyelesaian pekerjaan sesuai dengan aturan yang ditetapkan. Unit kerja telah mengimplementasikan seluruh ‘aturan disiplin’/’kode etik’/’kode perilaku’ pegawai yang ditetapkan organisasi namun belum membuat inovasi yang sesuai dengan karakteristik unit kerja. Masih ada unit kerja yang belum melengkapi Standar Operasi Prosedur dan masih kurangnya data pendukung di setiap kegiatan yang dilakukan. Serta belum adanya dukungan khusus anggaran dan reward bagi unit kerja penerima predikat wilayah bebas dari korupsi

ABSTRAK Layanan jasa hukum berupa pemberian legalisasi yang diselenggarakan oleh Direktorat Jenderal Administrasi Hukum Umum. Pemberian legalisasi merupakan jawaban terhadap pemenuhan kebutuhan layanan hukum serta diharapkan dapat memberikan kepastian hukum kepada masyarakat pengguna. Penelitian ini bertujuan untuk menganalisis kepastian hukum pemberian legalisasi tanda tangan pejabat. Penelitian ini merupakan penelitian hukum empirik dengan pendekatan kualitatif. Data dan informasi diperoleh melalui wawancara. Hasil dari penelitian ini menegaskan bahwa pemberian legalisasi tanda tangan pejabat dapat memberikan kepastian hukum kepada para pengguna. Legalisasi tanda tangan pejabat yang merupakan kewenangan Kementerian Hukum dan Hak Asasi Manusia agar tidak ditafsirkan sebagai persetujuan terhadap keseluruhan isi dokumen yang dilegalisasi, melainkan sebatas pengesahan tanda tangan pejabat yang menandatangani dokumen yang dilegalisasi. Perlunya peningkatan kesadaran pejabat pemerintah atau pejabat umum yang diangkat pemerintah untuk segera mengirimkan spesimen tanda tangan untuk dicatat dalam database Direktorat Jenderal Administrasi Hukum Umum. Untuk itu perlu dilakukan sosialisasi materi legalisasi hukum perdata umum untuk dilaksanakan di daerah.

Feature detection is a vital aspect of computer vision applications, but adverse environments, distance and illumination can affect the quality and repeatability of features or even prevent their identification. Invariance to these constraints would make an ideal feature attribute. Here we propose the first exploitation of consistently occurring thermal signatures generated by a moving platform, a paradigm we define as passively user-generated thermal invariant features (PUGTIFs). In this particular instance, the PUGTIF concept is applied through the use of thermal footprints that are passively and continuously user generated by heat differences, so that features are no longer dependent on the changing scene structure (as in classical approaches) but now maintain a spatial coherency and remain invariant to changes in illumination. A framework suitable for any PUGTIF has been designed consisting of three methods: first, the known footprint size is used to solve for monocular localisation and thus scale ambiguity; second, the consistent spatial pattern allows us to determine heading orientation; and third, these principles are combined in our automated thermal footprint detector (ATFD) method to achieve segmentation/feature detection. We evaluated the detection of PUGTIFs in four laboratory environments (sand, grass, grass with foliage, and carpet) and compared ATFD to typical image segmentation methods. We found that ATFD is superior to other methods while also solving for scaled monocular camera localisation and providing user heading in multiple environments.

Oxidative stress, which is associated with metabolic and anthropometric perturbations, leads to reactive oxygen species production and decrease in plasma adiponectin concentration. We investigated pharmacodynamically the pathophysiological role and potential implication of exogenously administered adiponectin with full and partial peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists on modulation of oxidative stress, metabolic dysregulation, and antioxidant potential in streptozotocin-induced spontaneously hypertensive rats (SHR). Group I (WKY) serves as the normotensive control, whereas 42 male SHRs were randomized equally into 7 groups (n=6); group II serves as the SHR control, group III serves as the SHR diabetic control, and groups IV, V, and VI are treated with irbesartan (30 mg/kg), pioglitazone (10 mg/kg), and adiponectin (2.5 μg/kg), whereas groups VII and VIII received cotreatments as irbesartan+adiponectin and pioglitazone+adiponectin, respectively. Diabetes was induced using an intraperitoneal injection of streptozotocin (40 mg/kg). Plasma adiponectin, lipid contents, and arterial stiffness with oxidative stress biomarkers were measured using an in vitro and in vivo analysis. Diabetic SHRs exhibited hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and increased arterial stiffness with reduced plasma adiponectin and antioxidant enzymatic levels (P

Introducción: La pancreatitis aguda se considera un proceso inflamatorio del páncreas, el cual resulta de la activación de enzimas digestivas liberadas por esta glándula. Esta entidad patológica está asociada con múltiples etiologías. Caso: varón de 37 años de edad con cuadro de dolor abdominal en hipogastrio irradiado a la espalda. En el examen físico se encontró taquicárdico, hipertenso, con dolor abdominal a la palpación profunda sin signos de irritación peritoneal. Los paraclínicos mostraban una elevación de los reactantes de fase aguda y amilasa pancreática, los estudios imagenológicos mostraban signos de pancreatitis aguda. Discusión: la pancreatitis asociada con hipertrigliceridemia se presenta entre el 0,5 % al 1 % de los casos. La tríada inicial del manejo es dieta absoluta, hidratación intravenosa y analgésicos. En el caso de la hipertrigliceridemia, se puede manejar con hipolipemiantes orales o, en caso de niveles mayores de 1000 mg/dL, se puede usar el recambio plasmático, el cual tiene buena efectividad y disminuye los valores a rangos de normalidad en el 80 % de los casos con la primera sesión.

Hieronim ze Strydonu, przedstawiany jest najczęściej jako wielki egzegeta i znawca oraz tłumacz Pisma Świętego. Niekiedy przypomina się również o jego znaczących dokonaniach w sporach teologicznych. Tymczasem sam Hieronim w swoich licznych pismach i działaniach, przedstawia się sobie współczesnym i potomnym jako bardzo wymagający od siebie i od drugich asceta. Praktykując mniszy styl życia na pustyni i poświęcając się pracy naukowej, dążył do jak najlepszego poznania Jezusa Chrystusa, aby Go jak najlepiej naśladować i przez swoje osobiste doświadczenia z Nim się jednoczyć. Dlatego też te dwie drogi, czyli studium Biblii oraz pokutę i wyrzeczenie, uznaje za najlepsze w tym celu. Poza tym – jak często podkreśla – wzajemnie się warunkujące i wspomagające. W jego teologii ascetycznej do głosu dochodzą tematy związane z zasługującym charakterem chrześcijańskiego umartwienia. Podstawę tego Strydończyk dostrzega w swoim bardzo wyraźnym wychyleniu eschatologicznym. Stanowi ono podstawowe kryterium w określaniu przez niego marnością wszystkiego co doczesne ze względu na to co wieczne i duchowe. Chrystocentrycznie rozumiana przez niego idea Królestwa Bożego, obecnego już w doczesności, staje się najważniejszym argumentem w wymaganiu od chrześcijan życia właściwego pełnej realizacji tej rzeczywistości w niebie. Najlepiej temu służy – w jego przekonaniu – wyrzeczenie aż po ofiarę z własnego życia. Najlepiej zaś to tłumaczy taka właśnie droga Zbawiciela, wzywającego do wspólnego z Nim życia w chwale nieba, przez wspólne z Nim umartwienie na ziemi.

Oxidative stress is involved in the pathogenesis of a number of diseases including hypertension and renal failure. There is enhanced expression of nicotinamide adenine dinucleotide (NADPH oxidase) and therefore production of hydrogen peroxide (H2O2) during renal disease progression. This study investigated the effect of apocynin, an NADPH oxidase inhibitor and catalase, an H2O2 scavenger on Cyclosporine A (CsA) nephrotoxicity in Wistar-Kyoto rats. Rats received CsA (25mg/kg/day via gavage) and were assigned to vehicle, apocynin (2.5mmol/L p.o.), catalase (10,000U/kg/day i.p.) or apocynin plus catalase for 14 days. Renal functional and hemodynamic parameters were measured every week, and kidneys were harvested at the end of the study for histological and NADPH oxidase 4 (NOX4) assessment. Oxidative stress markers and blood urea nitrogen (BUN) were measured. CsA rats had higher plasma malondialdehyde (by 340%) and BUN (by 125%), but lower superoxide dismutase and total antioxidant capacity (by 40%, all P

Pioglitazone, a therapeutic drug for diabetes, possesses full PPAR-γ agonist activity and increase circulating adiponectin plasma concentration. Plasma adiponectin concentration decreases in hypertensive patients with renal dysfunctions. Present study investigated the reno-protective, altered excretory functions and renal haemodynamic responses to adrenergic agonists and ANG II following separate and combined therapy with pioglitazone in diabetic model of hypertensive rats. Pioglitazone was given orally [10mg/kg/day] for 28 days and adiponectin intraperitoneally [2.5μg/kg/day] for last 7 days. Groups of SHR received either pioglitazone or adiponectin in combination. A group of Wistar Kyoto rats [WKY] served as normotensive controls, whereas streptozotocin administered SHRs served as diabetic hypertensive rats. Metabolic data and plasma samples were taken on day 0, 8, 21 and 28. In acute studies, the renal vasoconstrictor actions of Angiotensin II [ANGII], noradrenaline [NA], phenylephrine [PE] and methoxamine [ME] were determined. Diabetic SHRs control had a higher basal mean arterial blood pressure than the WKY, lower RCBP and plasma adiponectin, higher creatinine clearance and urinary sodium excretion compared to WKY [all P

Replication of bone marrow niches is essential for the evaluation of the toxicity and efficacy of multiple drug candidates and understanding of cell development. Recreation of the complex biological environment of bone marrow in a suitable format for such studies can be accomplished using bone-mimetic constructs based on three-dimensional (3D) nanocomposite-coated cell scaffolds with inverted colloidal crystal geometry. Layer-by-layer (LBL) assembled nanocomposites combine the mechanical properties and surface topography of bone with the transparency of 3D cell matrices. Such rare combination of properties allows for discrimination and control of complex biological processes such as differentiation of bone marrow stromal cells. LBL biomimetic nanocomposites open the pathway toward better understanding of the interactions between stromal cells and the extracellular matrix in the bone marrow microenvironment, in order to achieve the accurate engineering of the bone marrow niches.