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A STEDable BF<sub>2</sub>-azadipyrromethene fluorophore for nuclear membrane and associated endoplasmic reticulum imaging
No full textThe endoplasmic reticulum and the internal nuclear compartments are intrinsically connected through the nuclear membrane, pores and lamina. High resolution imaging of each of these cellular features concurrently remains a significant challenge. To that end we have developed a new molecular nuclear membrane-endoplasmic reticulum (NM-ER) staining fluorophore with emission maxima at 650 nm. NM-ER is compatible with fixed and live cell imaging and stimulated emission depletion microscopy (STED) showing significant improvement in resolution when compared to comparable confocal laser scanning microscopy. The imaging versatility of NM-ER was illustrated through its compatible use with other fluorophores for co-imaging with DNA, nuclear pores and lamina allowing cellular abnormalities to be identified. NM-ER alone, or in use with other nuclear region labels could be an important tool for the investigation of nuclear transport and associated cellular processes.</p
A novel workflow for multi-modal imaging of musculoskeletal tissues
No full textAccording to the World Health Organization (WHO) musculoskeletal conditions are a leading contributor to disability worldwide. This fact is often somewhat overlooked, since musculoskeletal conditions are less likely to be associated with mortality. Nonetheless, treatments, therapies and management of these conditions are extremely costly to national healthcare systems. As with all systemic conditions, biomedical imaging of relevant tissues plays a major role in understanding the fundamental biological processes involved in musculoskeletal health. However, the skeletal system with its relatively large proportion of dense, opaque (often mineralised) tissues can often be more challenging to image, and recently important advances have been made in imaging these complex musculoskeletal tissues. Thus, we here describe a novel workflow in which recent advanced imaging techniques have been modified and optimised for use in musculoskeletal tissues (specifically bone and cartilage). This will allow for investigations, of different phases of these tissues, at new and higher resolutions. Furthermore, the process has been designed to fit with the existing and standard processes which are typically used with these samples (i.e. μCT imaging and standard histology). The additional modalities which have been included here are second harmonic generation (SHG) imaging, tissue clearing, specifically the Passive Clear Lipid-exchanged Acrylamide-hybridised Rigid Imaging Tissue hYdrogel (CLARITY) method known as PACT, and then imaging of these tissues with confocal, multiphoton and light-sheet microscopy. This paper serves to introduce a combination of existing new methods and improvements in imaging of musculoskeletal tissues.</p
A systematic review of determinants of breast cancer risk among women with benign breast disease
No full textBenign breast disease (BBD) is associated with heterogeneous breast cancer risk. Identifying key breast cancer risk factors for this population may inform breast cancer prevention or early detection strategies. We systematically searched literature databases PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify studies reporting associations of demographic, lifestyle, reproductive, and radiological factors with risk of breast cancer among women with biopsy-confirmed BBD. 67 studies met eligibility criteria. Variation was observed for study time period, exposure measurement, comparison groups, outcomes, and adjustment for confounders, precluding meta-analysis. The literature suggested positive risk associations for age at biopsy, family history, mammographic breast density, and time since biopsy, and no association for body mass index, alcohol, smoking, age at menarche, and use of hormonal contraceptives. More research is needed to understand risk factor associations among women with BBD, particularly studies that account for heterogeneity within BBD and breast cancer.</p
Non-cardiogenic pulmonary oedema provoked by acetazolamide
No full textA 61-year-old male was brought to the Emergency Department with severe shortness of breath, a throbbing headache, sweating, nausea, vomiting and diarrhoea after the administration of an acetazolamide tablet (250 mg) at a private ophthalmology clinic. On presentation, a chest X-ray was performed, showing diffuse alveolar opacities bilaterally, indicating pulmonary oedema, as seen in CT chest also. However, his echocardiogram revealed a normal ejection fraction with no signs of ischemia. He was subsequently diagnosed with non-cardiogenic pulmonary oedema (NCPE) and was immediately started on high-flow oxygen, later requiring mechanical ventilation. The patient was admitted to the Critical Care Unit with supportive treatment, including IV fluids and antibiotics, without steroid administration. Four days later, he was extubated and subsequently discharged from the ICU, followed by discharge from the hospital. Our case revolves around a rare yet potentially fatal episode of NCPE secondary to Acetazolamide use.</p
Adverse drug reactions and events in an Ageing PopulaTion risk Prediction (ADAPTiP) tool: the development and validation of a model for predicting adverse drug reactions and events in older patients
No full textPurpose: Older people are at an increased risk of developing adverse drug reactions (ADR) and adverse drug events (ADE). This study aimed to develop and validate a risk prediction model (ADAPTiP) for ADR/ADE in older populations.Methods: We used the adverse drug reactions in an Ageing PopulaTion (ADAPT) cohort (N = 798; 361 ADR-related admissions; 437 non-ADR-related admissions), a cross-sectional study designed to examine the prevalence and risk factors for ADR-related hospital admissions in patients aged ≥ 65 years. Twenty predictors (categorised as sociodemographic-related, functional ability-related, disease-related, and medication-related) were considered in the development of the model. The model was developed using multivariable logistic regression and was internally validated by fivefold cross-validation. The model was externally validated in a separate prospective cohort from the Centre for Primary Care Research (CPCR) study of ADES. The cross-validated and externally validated model performance was evaluated by discrimination and calibration.Results: The final prediction model, ADAPTiP, included nine predictors: age, chronic lung disease, the primary presenting complaints of respiratory, bleeding and gastrointestinal disorders and syncope on hospital admission and antithrombotics, diuretics, and renin-angiotensin-aldosterone system drug classes. ADAPTiP demonstrated good performance with cross-validated area under the curve of 0.75 [95% CI 0.72;79] and 0.83 [95% CI 0.80;0.87] in the external validation.Conclusion: Using accessible information from medical records, ADAPTiP can help clinicians to identify those older people at risk of an ADR/ADE who should be monitored and/or have their medications reviewed to avoid potentially harmful prescribing.</p
The use of the SPAIRE technique in cases of cemented hemiarthroplasty in the management of displaced intracapsular neck of femur fractures – a pair-matched control study versus a direct lateral approach
No full textIntroduction The aim of this study was to analyze and compare clinical, radiological and mortality outcomes of patients who underwent cemented hip hemiarthroplasty for displaced neck of femur fractures using a SPAIRE technique when compared to a pair-matched control cohort who underwent the same procedure using the direct lateral approach.Methods A retrospective review of patients who underwent cemented hip hemiarthroplasty for displaced neck of femur fractures by a single surgeon using a SPAIRE technique over a two-year period between July 2019 and July 2021 was performed. These were subsequently pair matched in a 5:1 ratio for age, gender, ASA grade and residential status with a control group who underwent cemented hip hemiarthroplasty by 4 other surgeons using a direct lateral approach. Mobility levels, residential status, radiological outcomes as well as mortality data were analyzed and compared.Results The study included a total of 240 patients (40 and 200 pair-matched to SPAIRE and control groups respectively), with a mean age of 81.0 ± 8.2 years (63–99) and a mean follow-up of 12 ± 3 months (3–30). There was no significant difference for mean age, gender, ASA grade and residential status between the two groups. Overall, there was no significant difference in any of the radiological or mortality outcome scores assessed between the SPAIRE and control groups (p > 0.05 for all). There was a significantly lower number of patients in the SPAIRE group who dropped a level of mobility from their pre-injury baseline at 30-days post-operatively (8.1 % versus 31.6 %; p = 0.003). However, this appeared to have resolved at 120-day follow-up with no significant differences between the groups in terms of those acquiring a new baseline mobility at 120-days post-operatively (2.7 % versus 13.2 %, p = 0.09).Conclusion In cases of cemented hip hemiarthroplasty for displaced intracapsular neck of femur fractures, the SPAIRE technique appears to offer patients an earlier return to levels of baseline pre-injury mobility when compared to a direct lateral approach. This study found that both techniques result in similarly acceptable clinical, radiological and mortality related outcomes in this high-risk patient cohort.</p
Evaluating interdisciplinary breastfeeding and lactation knowledge, attitudes and skills: an evaluation of a professional graduate programme for healthcare professionals
No full textBreastfeeding theoretical and skills training is important for health care professionals engaging with the mother infant dyad to increase breastfeeding exclusivity and duration. The aim of this study was to evaluate the knowledge, attitudes and practices (KAPs) of health care professionals following completion of a university professional graduate programme in breastfeeding and lactation. A pre and post-educational study design was used. All students enrolled in a six month programme were invited to complete an online anonymous survey at two time points: January 2023 and July 2023. Ethical approval (LS-C-23-17) was obtained in January 2023. Descriptive statistics were utilised to report percentages and means, and independent T tests were used to report mean differences between variables on knowledge, attitude and practices. All students completed the module. The pre survey participant response rate was n = 55 (92.82%) and the post survey participant response rate n = 33 (60%). Comparison of the pre and post questionnaire report nine statistically significant results following completion of the university breastfeeding and lactation programme. Knowledge scores increased specifically with higher mean knowledge scores for reporting "I am confident with my knowledge about breastfeeding" and statistically significant mean difference of 0.29 following completion of the module (95% CI, 0.13 to 0.45) (t (64) = 3.59, p = 0.001). The programme evaluation identifies the importance of a professional graduate breastfeeding and lactation education programme for interdisciplinary health care professionals increasing knowledge, attitudes and practices and ultimately increasing breastfeeding rates in the short and long term, with improved maternal and child health outcomes.</p
Sharing knowledge on implementing mental health and wellbeing projects for veterans and first responders
No full textPurpose: The aim of this study was to describe the knowledge to action and knowledge transfer approaches used in an international mental health research funding program and its outcomes. A key goal of the evaluation was to maximise organisational learning and knowledge sharing to inform future implementation projects.Methods: A series of interactive knowledge sharing workshops focused on five key themes: peer support; psychoeducation; the involvement of family, friends, and significant others; retreat, residential, or group-based programs; and organisational change. Qualitative descriptive analysis was used to code, summarise and describe themes.Findings: Key learnings that influenced the success of mental health initiatives include building relationships across all organisational levels, involving Veterans and First Responders with lived experience in the design and implementation process, and understanding the unique workplace culture and operations.Conclusion: Our findings highlight the need for collaborative, informed approaches tailored to the culture, organisation and mental health support needs of Veteran and First Responder. These insights enhance understanding of the factors that impact the successful implementation of mental health prevention and support programs for those exposed to work-related trauma.</p
Sonographic features of active Charcot neuro-osteoarthropathy: a case series
No full textAims: To describe the sonographic features of active Charcot neuro-osteoarthropathy (CNO) and assess the potential role of ultrasound in identifying those with active CNO.Methods: Using a prospective case-series study design we assessed the sonographic features of 14 patients with a diagnosis of diabetes presenting with clinical signs and symptoms suspicious for active CNO. Patients had standard weight-bearing plain X-Ray and, where possible, MRI to evaluate the presence of active CNO. Ultrasound was performed bilaterally to assess for subcutaneous oedema, intra-articular and peri-articular colour flow. The spectral waveform morphology, peak systolic velocity and resistive index of the dorsalis pedis arteries of both feet were also documented.Results: Following clinical and radiological (X-ray and MRI) assessment, 50% (n = 7) were diagnosed with active CNO. Of those with a confirmed diagnosis, ≥3 sonographic features suggestive of active CNO were observed.Conclusions: Ultrasound combined with clinical presentation and medical history may support decision making around the diagnosis of CNO at the bedside.</p
Evaluation of the Role of Glycans of the Biomolecular Corona and Development of Well-Characterised Glyco-Nanoparticles for Biomedical Applications
No full textNanoparticles (NPs) have gained great attention in medicine thanks to their advantageous properties that make them excellent candidates for application in modern medicine. In particular, the NP surface can be tailored and modified with targeting moieties to increase the localisation in diseased areas. Despite these advantages, several drawbacks are decreasing the implementation of clinical trials and there is a need to tackle several issues.Upon intravenous injection, NPs encounter biological barriers resulting in macrophage uptake and liver accumulation and low circulation half-time. Additionally, their surface is dramatically altered by the adsorption of biomolecules with high affinity towards the NP surface, which can dramatically affect the NPs’ biodistribution and accumulation, thus their therapeutic efficacy. In the last decades, several studies have been focused on the correlation between the NP physico-chemical properties, corona formation and biological outcome, and it has become a regulatory burden as this phenomenon is too complex to be studied and it has too many variables. As the protein corona is formed by glycosylated plasma proteins, it is possible to speculate that these glycans become part of the corona. Additionally, glycans modulate several biological processes, including protein clearance and inflammation. Several studies have focused on the development of NPs with longer circulation half-time. A typical approach is the surface functionalisation with stealth polymers, such as PEG. However, increasing studies have shown that PEG can lead to complement activation, pseudo-allergies and to the development of anti-PEG antibodies. Therefore, there is the need to develop biocompatible polymers.In this thesis, I have carried out a deep corona characterisation using citrate gold NPs, where I have identified the glycan types on the corona proteins and I have shown with different techniques that these glycans are biologically accessible and capable of interacting with specific receptors. I have also evaluated whether glycans can be used as biomolecules to increase the NP circulation half-life by attenuating the protein corona formation, and increase the nanomaterial biocompatibility by masking PEG and modulate the immunological response. I have developed a novel platform for characterisation.</p