Health literacy and cognitive function in people with diabetic foot ulcer with focus on knowledge, attitude, and practice in relation to foot self-care.

Introduction: Preventative foot self-care is vital for avoiding diabetic foot ulcer episodes and lowering the risk of amputations. Yet, it demands high levels of health literacy and cognitive function. Objective: To investigate health literacy and cognitive function in persons presenting with a diabetic foot ulcer. Methods: Participants with type 2 diabetes were recruited from the tertiary foot clinic at Steno Diabetes Center North Denmark. The European Health Literacy Survey Questionnaire and Addenbrooke's Cognitive Examination were applied. A semi-structured interview guide was developed to evaluate foot self-care knowledge, attitude, and practice. The qualitative data were analyzed with a deductive approach based on a qualitative thematic analysis model. Subsequently, an integrated analysis of the quantitative and qualitative results was conducted. Results: The participants (n = 12) had a mean age of 62.6 ± 8.4 years, and 11 were males. The mean diabetes duration was 15.9 ± 8.9 years. Eight participants had a recurrent diabetic foot ulcer. The health literacy level was sufficient in nine participants, and cognitive function was normal in five participants. Three different profiles related to foot self-care (proactive, active, or passive, respectively) were constructed by the final integrated analysis: a proactive profile refers to taking preventative action in concordance with knowledge and attitude, an active profile to taking action in response to a situation, but challenged by conflicting levels of knowledge and attitude, and a passive profile to not taking action. Conclusion: The study suggests that people presenting with a diabetic foot ulcer have different foot self-care profiles based on person-specific health literacy, cognitive function, and knowledge, attitude, and practice element characteristics, highlighting the need for individualized education and intervention strategy instead of a one-size-fits-all approach.

Time and change: a typology for presenting research findings in qualitative longitudinal research.

BACKGROUND: Qualitative longitudinal research (QLR) is an emerging methodology used in health research. The method literature states that the change in a phenomenon through time should be the focus of any QLR study, but in empirical studies, the analysis of changes through time is often poorly described, and the emphasis on time/change in the findings varies greatly. This inconsistency might depend on limitations in the existing method literature in terms of describing how QLR studies can present findings. The aim of this study was to develop and describe a typology of alternative approaches for integrating time and/or change in QLR findings. METHODS: In this method study, we used an adapted scoping review design. Articles were identified using EBSCOhost. In total, methods and results sections from 299 QLR articles in the field of health research were analyzed with inspiration from content analysis. RESULTS: We constructed a typology of three types and seven subtypes. The types were based on the underlying structural principles of how time/change was presented: Type A) Findings have a low utilization of longitudinal data, Type B) Findings are structured according to chronological time, and Type C) Findings focus on changes through time. These types differed in 1) the way the main focus was on time, change or neither; 2) the level of interpretation in the findings; and 3) how theoretical understandings of time/change were articulated in the articles. Each type encompassed two or three subtypes that represented distinct approaches to the aim and results presentation of QLR findings. CONCLUSIONS: This method study is the first to describe a coherent and comprehensive typology of alternative approaches for integrating time/change into QLR findings in health research. By providing examples of various subtypes that can be used for results presentations, it can help researchers make informed decisions suitable to their research intent.

Characterization of wooden breast myopathy: a focus on syndecans and ECM remodeling.

Introduction: The skeletal muscle deformity of commercial chickens (Gallus gallus), known as the wooden breast (WB), is associated with fibrotic myopathy of unknown etiology. For future breeding strategies and genetic improvements, it is essential to identify the molecular mechanisms underlying the phenotype. The pathophysiological hallmarks of WB include severe skeletal muscle fibrosis, inflammation, myofiber necrosis, and multifocal degeneration of muscle tissue. The transmembrane proteoglycans syndecans have a wide spectrum of biological functions and are master regulators of tissue homeostasis. They are upregulated and shed (cleaved) as a regulatory mechanism during tissue repair and regeneration. During the last decades, it has become clear that the syndecan family also has critical functions in skeletal muscle growth, however, their potential involvement in WB pathogenesis is unknown. Methods: In this study, we have categorized four groups of WB myopathy in broiler chickens and performed a comprehensive characterization of the molecular and histological profiles of two of them, with a special focus on the role of the syndecans and remodeling of the extracellular matrix (ECM). Results and discussion: Our findings reveal differential expression and shedding of the four syndecan family members and increased matrix metalloproteinase activity. Additionally, we identified alterations in key signaling pathways such as MAPK, AKT, and Wnt. Our work provides novel insights into a deeper understanding of WB pathogenesis and suggests potential therapeutic targets for this condition.

Patients' expectations of and experiences with psychosocial care needs in perioperative nursing: a descriptive study.

BACKGROUND: Meeting inpatients' psychosocial care needs is essential for their wellbeing, recovery, and positive experiences. This study aimed to describe and compare surgical inpatients' subjective perceptions of the importance of fundamental psychosocial and overall care received. METHODS: A descriptive study with a convenient sample was conducted from September 2019 to April 2020. A total of 194 surgical inpatients from Norway and Denmark answered a perioperative user participation questionnaire on the day of discharge. The questionnaire was previously face- and content validated. The questionnaire assessed patients' sociodemographic characteristics and four dimensions of fundamental care domains: Psychosocial, Relational, Physical, and System level. This study reports the results from the psychosocial domain. Descriptive statistics including frequencies, percentages, means, and standard deviations were used to analyze background information variables. The congruency between participants' expectations of and experiences with psychosocial care is presented. RESULTS: The inpatients expected (and experienced) the healthcare personnel to treat them with respect and dignity, and to be involved and informed throughout their perioperative care. The average ratings regarding these aspects of psychosocial care needs were 72.1-93.8%. There was congruency between patients' perceptions of the subjective importance (SI) of psychosocial fundamental care and their perceived reality (PR) of care. Congruency between high SI and high PR ranged from 59.1 to 92.2%, and congruency between low SI and low PR ranged from 0 to 6.6%. Incongruency between SI and PR varied between 5.9 and 39.6% and was mainly related to higher PR than SI. We found no association between education level, sex, length of stay, age, and patient expectations of or experiences with psychosocial care needs. CONCLUSIONS: Surgical inpatients in Norway and Denmark experience respectful and dignified treatment, and they feel involved and informed in their perioperative care. It is important to include patient perspectives in further research to avoid missed care and disconnection between what patients prefer and what healthcare personnel plan to do. Understanding patient preferences might also lead to less stress and workload for healthcare personnel.

Expansion of bovine skeletal muscle stem cells from spinner flasks to benchtop stirred-tank bioreactors for up to 38 days.

Introduction: Successful long-term expansion of skeletal muscle satellite cells (MuSCs) on a large scale is fundamental for cultivating animal cells for protein production. Prerequisites for efficient cell expansion include maintaining essential native cell activities such as cell adhesion, migration, proliferation, and differentiation while ensuring consistent reproducibility. Method: This study investigated the growth of bovine MuSC culture using low-volume spinner flasks and a benchtop stirred-tank bioreactor (STR). Results and discussion: Our results showed for the first time the expansion of primary MuSCs for 38 days in a bench-top STR run with low initial seeding density and FBS reduction, supported by increased expression of the satellite cell marker PAX7 and reduced expression of differentiation-inducing genes like MYOG, even without adding p38-MAPK inhibitors. Moreover, the cells retained their ability to proliferate, migrate, and differentiate after enzymatic dissociation from the microcarriers. We also showed reproducible results in a separate biological benchtop STR run.

Impact of microvessel patterns and immune status in NSCLC: a non-angiogenic vasculature is an independent negative prognostic factor in lung adenocarcinoma.

Introduction: Non-small cell lung carcinomas (NSCLC) exhibit different microvessel patterns (MVPs). Basal (BA), diffuse (DA) and papillary (PA) patterns show signs of angiogenesis (new blood vessels), while an alveolar pattern indicates that tumors are co-opting existing normal vessels (non-angiogenic alveolar, NAA). NAA tumor growth is known to exist in NSCLC, but little is known about its prognostic impact in different histological subgroups, and about associations between MVPs and immune cell infiltration. Methods: Detailed patterns of angiogenic and non-angiogenic tumor growth were evaluated by CD34 immunohistochemistry in whole tissue slides from 553 surgically treated patients with NSCLC stage I-IIIB disease. Associations with clinicopathological variables and markers related to tumor immunology-, angiogenesis- and hypoxia/metabolism were explored, and disease-specific survival (DSS) was analyzed according to histological subtypes. Results: The predominant MVP was angiogenic in 82% of tumors: BA 40%, DA 34%, PA 8%, while a NAA pattern dominated in 18%. A contribution of the NAA pattern >5% (NAA+), i.e., either dominant or minority, was observed in 40.1% of tumors and was associated with poor disease-specific survival (DSS) (p=0.015). When stratified by histology, a significantly decreased DSS for NAA+ was found for adenocarcinomas (LUAD) only (p< 0.003). In multivariate analyses, LUAD NAA+ pattern was a significant independent prognostic factor; HR 2.37 (CI 95%, 1.50-3.73, p< 0.001). The immune cell density (CD3, CD4, CD8, CD45RO, CD204, PD1) added prognostic value in squamous cell carcinoma (LUSC) and LUAD with 0-5% NAA (NAA-), but not in LUAD NAA+. In correlation analyses, there were several significant associations between markers related to tumor metabolism (MCT1, MCT4, GLUT1) and different MVPs. Conclusion: The NAA+ pattern is an independent poor prognostic factor in LUAD. In NAA+ tumors, several immunological markers add prognostic impact in LUSC but not in LUAD.

High Expression of IRS-1, RUNX3 and SMAD4 Are Positive Prognostic Factors in Stage I-III Colon Cancer.

Colon cancer is a common malignancy and a major contributor to human morbidity and mortality. In this study, we explore the expression and prognostic impact of IRS-1, IRS-2, RUNx3, and SMAD4 in colon cancer. Furthermore, we elucidate their correlations with miRs 126, 17-5p, and 20a-5p, which are identified as potential regulators of these proteins. Tumor tissue from 452 patients operated for stage I-III colon cancer was retrospectively collected and assembled into tissue microarrays. Biomarkers' expressions were examined by immunohistochemistry and analyzed using digital pathology. In univariate analyses, high expression levels of IRS1 in stromal cytoplasm, RUNX3 in tumor (nucleus and cytoplasm) and stroma (nucleus and cytoplasm), and SMAD4 in tumor (nucleus and cytoplasm) and stromal cytoplasm were related to increased disease-specific survival (DSS). In multivariate analyses, high expression of IRS1 in stromal cytoplasm, RUNX3 in tumor nucleus and stromal cytoplasm, and high expression of SMAD4 in tumor and stromal cytoplasm remained independent predictors of improved DSS. Surprisingly, with the exception of weak correlations (0.2 < r < 0.25) between miR-126 and SMAD4, the investigated markers were mostly uncorrelated with the miRs. However, weak to moderate/strong correlations (0.3 < r < 0.6) were observed between CD3 and CD8 positive lymphocyte density and stromal RUNX3 expression. High expression levels of IRS1, RUNX3, and SMAD4 are positive prognostic factors in stage I-III colon cancer. Furthermore, stromal expression of RUNX3 is associated with increased lymphocyte density, suggesting that RUNX3 is an important mediator during recruitment and activation of immune cells in colon cancer.

The Non-Human Primate in Safety Assessment of a Bifunctional Long-Acting Insulin Analogue.

Species selection plays a pivotal part during non-clinical safety assessment in drug development. If possible, use of non-human primates (NHPs) should be avoided due to ethical considerations. However, limiting factors as lack of pharmacologic activity in other species could necessitate use of NHPs. LAI-PCSK9i is a bi-functional molecule combining a long-acting insulin analogue with a PCSK9 inhibitor peptide aiming to provide glycaemic control and to reduce plasma LDL concentrations. The NHP was chosen for the safety assessment of LAI-PCSK9i being the most relevant species with basal levels and plasma lipid composition closest to humans, while the dog and initially also the minipig were deemed irrelevant due to lack of pharmacologic activity on LDL-lowering and biological differences in lipid profiles. An in vivo tolerability and toxicokinetic study of LAI-PCSK9i in NHPs showed recurrent and severe hypoglycaemia at very low doses. Therefore, the minipig was re-evaluated and a follow-up study thoroughly assessing blood glucose and cholesterol levels and clinical signs illustrated that minipigs dosed with LAI-PCSK9i, tolerated the compound and LAI-PCSK9i decreased glucose and LDL over time. This work underlines that careful consideration is required when selecting species during safety assessment in drug development. The tolerability issue in NHPs led to the subsequent selection of the minipig for safety evaluation of LAI-PCSK9i although as a suboptimal alternative, which unexpectedly had a measurable pharmacologic response on LDL lowering. In conclusion, the NHPs may be unsuitable as test species for safety assessment of long-acting insulin analogues due to high sensitivity to recurring hypoglycaemic episodes.

Development and validation of the perioperative care and user participation (POUP) questionnaire.

AIM: To validate a Perioperative User Participation questionnaire (POUP) that measures elective adult surgical patient experiences and evaluation of the significance of selected perioperative care items. MATERIALS AND METHODS: A generic perioperative user involvement questionnaire (POUP) was developed in the form of four psychometric scales based on the Fundamentals of Care (FoC) framework. The POUP is designed to capture patients' perceived and subjective importance of selected items of perioperative care. It was developed in Danish and comprehensive Danish-Norwegian translations were conducted. Face and content validation were conducted involving patients and expert nurses. The relevance of items was assessed by 68 patients, and the internal consistency of the scales was calculated. RESULTS: Danish and Norwegian patients assessed the POUP's face validity, and perioperative expert nurses reported no problems in clarity or ambiguity. However, a few reformulations of the questionnaire texts were suggested. None of the questions were reported as irrelevant or difficult to answer nor was any topic reported missing. Patients assessed all items as relevant, and the internal consistency for the three scales was between 0.8 and 0.9, and no differences between countries were found. CONCLUSION: The POUP questionnaire has four scales; the items are valid, but the scales need further statistical validation and refinement. At present, the POUP might provide insight into how elective adult surgical patients value the significance of perioperative care.

Dietary intake of micronized avian eggshell membrane in aged mice reduces circulating inflammatory markers, increases microbiota diversity, and attenuates skeletal muscle aging.

Introduction: Avian eggshell membrane (ESM) is a complex extracellular matrix comprising collagens, glycoproteins, proteoglycans, and hyaluronic acid. We have previously demonstrated that ESM possesses anti-inflammatory properties in vitro and regulates wound healing processes in vivo. The present study aimed to investigate if oral intake of micronized ESM could attenuate skeletal muscle aging associated with beneficial alterations in gut microbiota profile and reduced inflammation. Methods: Elderly male C57BL/6 mice were fed an AIN93G diet supplemented with 0, 0.1, 1, or 8% ESM. Young mice were used as reference. The digestibility of ESM was investigated using the static in vitro digestion model INFOGEST for older people and adults, and the gut microbiota profile was analyzed in mice. In addition, we performed a small-scale pre-clinical human study with healthy home-dwelling elderly (>70 years) who received capsules with a placebo or 500 mg ESM every day for 4 weeks and studied the effect on circulating inflammatory markers. Results and discussion: Intake of ESM in elderly mice impacted and attenuated several well-known hallmarks of aging, such as a reduction in the number of skeletal muscle fibers, the appearance of centronucleated fibers, a decrease in type IIa/IIx fiber type proportion, reduced gene expression of satellite cell markers Sdc3 and Pax7 and increased gene expression of the muscle atrophy marker Fbxo32. Similarly, a transition toward the phenotypic characteristics of young mice was observed for several proteins involved in cellular processes and metabolism. The digestibility of ESM was poor, especially for the elderly condition. Furthermore, our experiments showed that mice fed with 8% ESM had increased gut microbiota diversity and altered microbiota composition compared with the other groups. ESM in the diet also lowered the expression of the inflammation marker TNFA in mice and in vitro in THP-1 macrophages. In the human study, intake of ESM capsules significantly reduced the inflammatory marker CRP. Altogether, our results suggest that ESM, a natural extracellular biomaterial, may be attractive as a nutraceutical candidate with a possible effect on skeletal muscle aging possibly through its immunomodulating effect or gut microbiota.

Qualitative longitudinal research in health research: a method study.

BACKGROUND: Qualitative longitudinal research (QLR) comprises qualitative studies, with repeated data collection, that focus on the temporality (e.g., time and change) of a phenomenon. The use of QLR is increasing in health research since many topics within health involve change (e.g., progressive illness, rehabilitation). A method study can provide an insightful understanding of the use, trends and variations within this approach. The aim of this study was to map how QLR articles within the existing health research literature are designed to capture aspects of time and/or change. METHODS: This method study used an adapted scoping review design. Articles were eligible if they were written in English, published between 2017 and 2019, and reported results from qualitative data collected at different time points/time waves with the same sample or in the same setting. Articles were identified using EBSCOhost. Two independent reviewers performed the screening, selection and charting. RESULTS: A total of 299 articles were included. There was great variation among the articles in the use of methodological traditions, type of data, length of data collection, and components of longitudinal data collection. However, the majority of articles represented large studies and were based on individual interview data. Approximately half of the articles self-identified as QLR studies or as following a QLR design, although slightly less than 20% of them included QLR method literature in their method sections. CONCLUSIONS: QLR is often used in large complex studies. Some articles were thoroughly designed to capture time/change throughout the methodology, aim and data collection, while other articles included few elements of QLR. Longitudinal data collection includes several components, such as what entities are followed across time, the tempo of data collection, and to what extent the data collection is preplanned or adapted across time. Therefore, there are several practices and possibilities researchers should consider before starting a QLR project.

Production of food-grade microcarriers based on by-products from the food industry to facilitate the expansion of bovine skeletal muscle satellite cells for cultured meat production.

A major challenge for successful cultured meat production is the requirement for large quantities of skeletal muscle satellite cells (MuSCs). Commercial microcarriers (MCs), such as Cytodex®1, enable extensive cell expansion by offering a large surface-to-volume ratio. However, the cell-dissociation step post cell expansion makes the cell expansion less efficient. A solution is using food-grade MCs made of sustainable raw materials that do not require a dissociation step and can be included in the final meat product. This study aimed to produce food-grade MCs from food industry by-products (i.e., turkey collagen and eggshell membrane) and testing their ability to expand bovine MuSCs in spinner flask systems for eight days. The MCs' physical properties were characterized, followed by analyzing the cell adhesion, growth, and metabolic activity. All MCs had an interconnected porous structure. Hybrid MCs composed of eggshell membrane and collagen increased the mechanical hardness and stabilized the buoyancy compared to pure collagen MCs. The MuSCs successively attached and covered the entire surface of all MCs while expressing high cell proliferation, metabolic activity, and low cell cytotoxicity. Cytodex®1 MCs were included in the study. Relative gene expression of skeletal muscle markers showed reduced PAX7 and increased MYF5, which together with augmented proliferation marker MKI67 indicated activated and proliferating MuSCs on all MCs. Furthermore, the expression pattern of cell adhesion receptors (ITGb5 and SDC4) and focal adhesion marker VCL varied between the distinct MCs, indicating different specific cell receptor interactions with the various biomaterials. Altogether, our results demonstrate that these biomaterials are promising prospects to produce custom-fabricated food-grade MCs intended to expand MuSCs.

High expression of miR-17-5p and miR-20a-5p predicts favorable disease-specific survival in stage I-III colon cancer.

In many types of cancer, microRNAs (miRs) are aberrantly expressed. The aim of this study was to explore the prognostic impact of miR-17-5p and miR-20a-5p in colon cancer. Tumor tissue from 452 stage I-III colon cancer patients was retrospectively collected and tissue microarrays constructed. miR-17-5p and miR-20a-5p expression was evaluated by in situ hybridization and analyzed using digital pathology. Cell line experiments, using HT-29 and CACO-2, were performed to assess the effect of miR-17-5p and miR-20a-5p over expression on viability, invasion and migration. In multivariate analyses, high miR-17-5p expression in tumor (HR = 0.43, CI 0.26-0.71, p < 0.001) and high expression of miR-20a-5p in tumor (HR = 0.60, CI 0.37-0.97, p = 0.037) and stroma (HR = 0.63, CI 0.42-0.95, p = 0.027) remained independent predictors of improved disease-specific survival. In cell lines, over expression of both miRs resulted in mitigated migration without any significant effect on viability or invasion. In conclusion, in stage I-III colon cancer, high expression of both miR-17-5p and miR-20a-5p are independent predictors of favorable prognosis.

Expression of miR-24-1-5p in Tumor Tissue Influences Prostate Cancer Recurrence: The PROCA-life Study.

The role of miR-24-1-5p and its prognostic implications associated with prostate cancer are mainly unknown. In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), all men had a general health examination at study entry and were followed between 1994 and 2016. Patients with available tissue samples after a prostatectomy with curative intent were identified (n = 189). The tissue expression of miR-24-1-5p in prostate cancer was examined by in situ hybridization (ISH) in tissue microarray (TMA) blocks by semi-quantitative scoring by two independent investigators. Multivariable Cox regression models were used to study the associations between miR-24-1-5p expression and prostate cancer recurrence. The prostate cancer patients had a median age of 65.0 years (range 47−75 years). The Cancer of the Prostate Risk Assessment Postsurgical Score, International Society of Urological Pathology grade group, and European Association of Urology Risk group were all significant prognostic factors for five-year recurrence-free survival (p < 0.001). Prostate cancer patients with a high miR-24-1-5p expression (≥1.57) in the tissue had a doubled risk of recurrence compared to patients with low expression (HR 1.99, 95% CI 1.13−3.51). Our study suggests that a high expression of miR-24-1-5p is associated with an increased risk of recurrence of prostate cancer after radical prostatectomy, which points to the potential diagnostic and therapeutic value of detecting miR-24-1-5p in prostate cancer cases.

Overexpression of miR-20a-5p in Tumor Epithelium Is an Independent Negative Prognostic Indicator in Prostate Cancer-A Multi-Institutional Study.

OBJECTIVE: assessing the prognostic role of miR-20a-5p, in terms of clinical outcome, in a large multi-institutional cohort study. METHODS: Tissue microarrays from 535 patients' prostatectomy specimens were constructed. In situ hybridization was performed to assess the expression level of miR-20a-5p in different tissue subregions: tumor stroma (TS) and tumor epithelium (TE). In vitro analysis was performed on prostate cancer cell lines. RESULTS: A high miR-20a-5p expression was found negatively in association with biochemical failure in TE, TS and TE + TS (p = 0.001, p = 0.003 and p = 0.001, respectively). Multivariable analysis confirmed that high miR-20a-5p expression in TE independently predicts dismal prognosis for biochemical failure (HR = 1.56, 95% CI: 1.10-2.21, p = 0.014). Both DU145 and PC3 cells exhibited increased migration ability after transient overexpression of miR-20a-5p, as well as significant elevation of invasion in DU145 cells. CONCLUSION: A high miR-20a-5p expression in tumor epithelium is an independent negative predictor for biochemical prostate cancer recurrence.

Patient-reported outcome measures in the emergency department: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to identify and characterize validated patient-reported outcome measures used to assess adult patients' health status in the emergency department to support clinical decision-making and to develop individual care and treatment plans. INTRODUCTION: In recent years, the workload in emergency departments has increased and patient management is characterized by a fast pace. The accelerated approach may lead to unintentional negligence by health care professionals of patient-reported signs and symptoms in the emergency department. Thus, use of patient-reported outcome measures in the emergency department may improve health care professionals' attention to the needs and health status of patients. INCLUSION CRITERIA: Studies assessing adult patients' health status in the emergency department using patient-reported outcome measures will be considered. The patient-reported outcome measures should be self-reported, assisted by a proxy, or administered through interviews. Only studies reporting on the measurement properties of patient-reported outcome measures will be included. Moreover, health-related information retrieved using patient-reported outcome measures should be applicable at an individual patient level. METHODS: A systematic literature search will be performed primarily in the databases MEDLINE, Embase, CINAHL, and PsycINFO. Both published and unpublished sources of information will be considered. Studies published from 2000 onwards in Danish, Swedish, Norwegian, German, and English will be included. Using the JBI methodology for scoping reviews, two reviewers will independently perform the study selection and data extraction. The results will be presented in a tabular form together with a narrative summary.

Characterization of Collagen Structure in Normal, Wooden Breast and Spaghetti Meat Chicken Fillets by FTIR Microspectroscopy and Histology.

Recently, two chicken breast fillet abnormalities, termed Wooden Breast (WB) and Spaghetti Meat (SM), have become a challenge for the chicken meat industry. The two abnormalities share some overlapping morphological features, including myofiber necrosis, intramuscular fat deposition, and collagen fibrosis, but display very different textural properties. WB has a hard, rigid surface, while the SM has a soft and stringy surface. Connective tissue is affected in both WB and SM, and accordingly, this study's objective was to investigate the major component of connective tissue, collagen. The collagen structure was compared with normal (NO) fillets using histological methods and Fourier transform infrared (FTIR) microspectroscopy and imaging. The histology analysis demonstrated an increase in the amount of connective tissue in the chicken abnormalities, particularly in the perimysium. The WB displayed a mixture of thin and thick collagen fibers, whereas the collagen fibers in SM were thinner, fewer, and shorter. For both, the collagen fibers were oriented in multiple directions. The FTIR data showed that WB contained more ß-sheets than the NO and the SM fillets, whereas SM fillets expressed the lowest mature collagen fibers. This insight into the molecular changes can help to explain the underlying causes of the abnormalities.

Cognitive impairment in patients with chronic kidney disease-Next of kin's experiences.

BACKGROUND: Chronic kidney disease (CKD) has been associated with a progressive decline in cognitive functions. This may lead to significant consequences for the person with CKD physically, psychologically and socially and may affect the everyday lives of the family. OBJECTIVES: To explore the everyday life experiences of next of kin of persons with CKD and cognitive impairment (CI). DESIGN: A qualitative design with semi-structured individual interviews with next of kin of persons with CKD and CI to gather in-depth information about the everyday life experiences of the next of kin. Interviews were recorded, transcribed verbatim and analysed inductively based on qualitative thematic analysis. FINDINGS: Based on the analysis, four themes were constructed: CI evolves gradually and is multifaceted; balancing everyday life challenges; finding ways to deal with their situation and knowledge enables understanding. CONCLUSION: Next of kin took responsibility and developed strategies for making everyday life function for the person with CKD and CI, which required considerable structure and a number of actions. They needed information about the CI and developed strategies for how to protect the person with CKD from being exposed. To provide themselves a personal space, next of kin turned to family, friends and people in comparable situations. To identify and address unmet care needs, healthcare professionals must proactively demonstrate an increased focus on CI and focus on the potential care needs of the person with CKD and their next of kin.

Discovery of a Potent Adenine-Benzyltriazolo-Pleuromutilin Conjugate with Pronounced Antibacterial Activity against MRSA.

Conjugation of pleuromutilin is an attractive strategy for the development of novel antibiotics and the fight against multiresistant bacteria as the class is associated with low rates of resistance and cross-resistance development. Herein, the preparation of 35 novel (+)-pleuromutilin conjugates is reported. Their design was based on a synthetically more efficient benzyl adaption of a potent lead but still relied on the Cu(I)-catalyzed alkyne-azide [3 + 2] cycloaddition for conjugation onto pleuromutilin. Their antibacterial activity was evaluated against the multiresistant Staphylococcus aureus strain USA300 for which they displayed moderate to excellent activity. Compound 35, bearing a para-benzyladenine substituent, proved particularly potent against USA300 and additional strains of MRSA and displayed as importantly no cytotoxicity in four mammalian cell lines. Structure-activity relationship analysis revealed that the purine 6-amino is essential for high potency, likely because of strong hydrogen bonding with the RNA backbone of C2469, as suggested by a molecular model based on the MM-GBSA approach.