Fluorescent tags are commonly used for imaging of proteins and peptides during biological events; however, the large size of dyes can disrupt protein structure and function, and typically require the ...use of a chemical spacer. Herein, we report the synthesis of a new class of fluorescent unnatural α-amino acid, containing carbazole side-chains designed to mimic l-tryptophan and thus, readily incorporated into peptides. The amino acids were constructed using a Negishi cross-coupling reaction as the key step and exhibited strong fluorescent emission, with high quantum yields in both organic solvents and water. Compatible with solid phase peptide synthesis, the carbazole amino acids were used to replace tryptophan in a β-hairpin model peptide and shown to be a close structural mimic with retention of conformation. They were also found to be effective fluorescent molecular reporters for biological events. Incorporation into a proline-rich ligand of the WW domain protein demonstrated that the fluorescent properties of a carbazole amino acid could be used to measure the protein-protein binding interaction of this important biological signalling process.
Abstract
Background
Research by the Irish Hospice Foundation reports 43% of Irish deaths occur in hospital. The aim of this study was to review in-hospital deaths in a university teaching hospital to ...examine whether escalation of care and resuscitation instructions were documented clearly where death was a likely outcome during hospitalisation.
Methods
Medical records from 50 deaths in 2018 were reviewed. A proforma was designed to record detail on: demographics, if death was expected, and if resuscitation status, ceiling of care and discussion of these with the patient or family were clearly documented.
Results
50 patients were included, median age 83.5 years. In 84%, end of life was anticipated by the medical team. 74% of patients were seen by palliative care. The most common cause of death was pneumonia/respiratory sepsis (46%) and median length of stay was 13 days. 3 patients (6%) had cardiac arrest calls.
A clear ceiling of care was recorded in 46% of cases. Goals of care were documented as discussed with the patient in 2% of cases and family in 78%. Resuscitation status was recorded as discussed with family in 62% and the patient in 4%.
Resuscitation status was documented in 96% of cases; 60% by the primary team, 36% by on-call staff. In only 54% of cases the name, position and Medical Council number of the person recording resuscitation status were all clearly written. Resuscitation status was correctly documented on the Early Warning Score chart in 32% of cases.
Conclusion
Clear documentation around treatment escalation plans is needed in patients admitted to an acute hospital. Resuscitation status and ceiling of care, if appropriate, should be decided and documented by the primary team where possible and discussed with the patient/family. This study showed a need to improve documentation and discussion with patients and families approaching end of life.
Objective
We used qualitative data to evaluate how religious and interfaith couples may view the influences of fidelity and/or loyalty on their marriage.
Background
Religion often regulates beliefs ...surrounding marriage and sexuality. Religion tends to support fidelity to marital vows. Previous quantitative studies indicated that higher religiosity is linked with higher levels of marital stability and satisfaction.
Method
Using semistructured interviews with 261 married couples (N = 522) who were identified as both religious and relational exemplars, the potential connections and processes between religion, relationships, and fidelity or integrity were examined.
Results
Three core themes emerged from systematic team‐based analyses: (1) integrity and/or fidelity strengthened marital quality and stability, (2) integrity and/or fidelity were core marital values and virtues, and (3) religion taught, developed, and motivated marital integrity and fidelity. Three subthemes were identified under this final theme: (3a) religious lifestyle, (3b) religious beliefs, and (3c) commitment to God. Contradictory voices that expressed and described challenges to marital integrity and fidelity are presented.
Conclusion
Couples discussed how their faiths' teachings on integrity and/or fidelity strengthened marital quality and stability, added to their core marital values and virtues, and motivated marital integrity and/or fidelity through a religious lifestyle, religious beliefs and morals, and commitment to God that built commitment and fidelity to spouse.
Implications
Therapists and educators who recognize that these deeply held values contribute to couples' stability and satisfaction within their relationship may be able to ask, understand, and harness religious strengths to facilitate commonalities and satisfaction.
Objective: Weight loss has been found to improve the symptoms of asthma in children who are overweight. However, many paediatric weight management programmes do not address the challenges associated ...with living with asthma. The aim of this study was to explore the views and experiences of paediatric healthcare professionals concerning weight management advice and support offered to families of children living with asthma. Methods: In-depth individual interviews with 10 healthcare professionals who work with a paediatric asthma population (n = 4 Respiratory Consultants, 3 Respiratory Nurses, 3 General Paediatricians). Data were analysed using a Framework approach. Results: Healthcare professionals highlighted that families' perceptions of weight, their approach to physical activity and nutrition, the family's social context and perceptions of asthma and asthma treatment all influence weight management in children living with asthma. Initiating weight management conversations and referring to weight management support were perceived as challenging. It was thought that tailoring weight management to the needs of children living with asthma and locating support within the community were important to the success of a family-centred intervention. Conclusions: The results highlight the added complexity of responding to excessive weight in a paediatric population with asthma. Training and referral guidance for healthcare professionals may help overcome weight management support challenges. Addressing family beliefs about the factors influencing paediatric asthma and exploring families' motivations for behaviour change may enhance engagement with weight management.
Hyperphosphatemia and II
o hyperparathyroidism are common and severe complications of chronic renal failure. Reduced dietary phosphorus has been shown to be an effective treatment in reducing serum ...phosphate and serum PTH. 2
′-Phosphophloretin inhibited small intestine apical membrane Na
+/phosphate cotransport and reduced serum phosphate in adult rats. 2
′-PP and phosphoesters of phloretin were tested for inhibition of human small intestine brush border membrane alkaline phosphatase activity and for inhibition of Na
+-dependent phosphate uptake. The IC
50’s for inhibition of alkaline phosphatase suggested an order of inhibitory potency of 4-PP > phloretin > 4
′-PP > 2
′-PP. Inhibition of Na
+-dependent phosphate uptake followed the sequence 2
′-PP
≫
4
′-PP > 4-PP > phloretin. These results are consistent with 2
′-PP being a specific inhibitor of human intestinal brush border membrane Na
+/phosphate cotransport.
This study aimed to establish the differences in parental attitudes toward feeding and activity, as well as child eating and activity levels, between families of children living with and without ...asthma. Parents of children and young people aged between 10 and 16 years living both with asthma (n = 310) and without asthma (n = 311) completed measures for parental feeding, parental attitudes toward child exercise, child eating, child activity level and asthma control. Children living with asthma had a significantly higher BMIz (BMI standardised for weight and age) score, were significantly more likely to emotionally overeat and desired to drink more than their peers without asthma. Parents of children with asthma reported greater use of food to regulate emotions, restriction of food for weight control, monitoring of child activity, pressure to exercise and control over child activity. When asthma symptoms were controlled, parental restriction of food for weight management predicted greater child BMIz scores, and higher child activity predicted lower child BMIz scores. These relationships were not found to be significant for children with inadequately controlled asthma. Differences in parental attitudes toward feeding and exercise, and child eating and exercise behaviors, between families may help to explain the increased obesity risk for children with asthma.
Immunohistochemistry remains the overwhelming technique of choice for test biomarker evaluation in both clinical or research settings when using formalin-fixed, paraffin embedded tissue sections. ...However, validations can be complex with significant issues about specificity, sensitivity and reproducibility. The vast array of commercially available antibodies from many vendors may also lead to non-standard approaches which are difficult to cross-reference. In contrast mRNA detection, by in situ hybridization (ISH) with sequence specific probes, offers a realistic alternative, with less validation steps and more stringent and reproducible assessment criteria. In the present study mRNA ISH was evaluated in prospectively and retrospectively collected FFPE samples within a cancer biobank setting. Three positive control probes, POLR2A, PPIB and UBC were applied to FFPE sections from a range of tumour types in FFPE whole-face (prospective collection) or TMA (retrospective collection) formats and evaluated semi-quantitatively and by image analysis. Results indicate that mRNA can be robustly evaluated by ISH in prospectively and retrospectively collected tissue samples. Furthermore, for 2 important test biomarkers, PD-L1 and c-MET, we show that mRNA ISH is a technology that can be applied with confidence in the majority of tissue samples because there are quantifiable levels of control probes indicating overall mRNA integrity.
The Black Caribbean population have a disproportionately high burden of sexually transmitted infections (STIs) compared with other ethnic groups. The aim of this study was to explore barriers to ...engagement with STI testing within a UK-based young adult Black Caribbean community.
Semi-structured interviews were carried out with 14 young adults from the Black Caribbean community and six sexual healthcare professionals. Data were analysed thematically. A focus group of five young adults was conducted to refine themes.
Data analysis generated three themes: (1) culturally embedded stigma; (2) historically embedded mistrust; and (3) lack of knowledge. Perceived as 'dirty', particularly for females, infection with STIs was stigmatised by religious conceptions of 'purity' and shame. This presented challenges in terms of cultural acceptability of talking about STI testing with partners, friends, and family. Legacies of colonialism, medical racism and malpractice compromised young people's trust in medical intervention and confidentiality of data management. A lack of knowledge related to STIs and their treatment, and in how to access and perform STI tests further served as a barrier. Culturally tailored interventions targeting these factors and delivered by radio, podcasts and social media were highlighted as having potential to improve engagement with STI testing.
Engagement with STI testing by young adults from the Black Caribbean community is impacted by historically and culturally embedded teachings, practices and beliefs inherited through generations. Targeting these factors within culturally tailored interventions may be effective for increasing STI-testing, and thus reducing rates of STI-infection in this population.
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