Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis.

BACKGROUND: Thyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes. METHODS: A systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected. RESULTS: Six articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71-1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible. CONCLUSIONS: This systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022308006.

Assessing the cardiovascular effects of levothyroxine use in an ageing United Kingdom population (ACEL-UK) protocol: a cohort and target trial emulation study.

BACKGROUND: Subclinical hypothyroidism is diagnosed when serum thyroid stimulating hormone levels are higher whilst free thyroxine levels remain within their respective reference ranges. These reference ranges are uniformly applied in all adults, despite serum thyroid stimulating hormone levels naturally increasing with age. Research has found that mildly elevated thyroid stimulating hormone levels may be associated with some benefits in ageing patients, including reduced mortality and better cardiorespiratory fitness. Levothyroxine is typically prescribed to patients with hypothyroidism, but no conclusive evidence exists on whether levothyroxine therapy is beneficial or detrimental in older subclinical hypothyroid patients. Despite this, prescriptions for levothyroxine are increasing year-on-year. This study aims to determine if receiving levothyroxine affects the cardiovascular and bone health outcomes of subclinical patients in primary care aged 50 years and over. METHODS: This project includes a retrospective cohort analysis and a target trial emulation study using electronic patient records collected between 2006 and 2021 and recorded in The Health Improvement Network database. The primary outcome of this study is to compare the cardiovascular outcomes of subclinical hypothyroid patients aged over 50 years treated with levothyroxine compared to those untreated. Secondary outcomes are bone health and all-cause mortality outcomes. Descriptive and inferential statistics will both be employed to analyse the data. Secondary analysis will explore confounding factors, including age, sex, smoking status, body mass index, co-morbidities, and levothyroxine dosage. DISCUSSION: There needs to be a greater understanding of the potential risks of the current treatment for older patients with subclinical hypothyroidism in a primary care setting. We will investigate the clinical importance of this issue and whether older subclinical hypothyroid patients have poorer outcomes when treated. Clarifying this concern may help address the healthcare resource implications of ageing patients being misclassified as having mild hypothyroidism, as these patients are more likely to repeat their blood tests. This could reduce prescription wastage and improve patient outcomes and quality of life in the ageing population. TRIAL REGISTRATION: Not applicable.

Open retrieval management of inferior vena cava filter erosion resulting in symptomatic hydroureteronephrosis.

Inferior vena cava filters are effective for the management of thromboembolic disease but can erode into adjacent organ systems in rare instances. Endovascular retrieval of eroded filters has been the preferred management for this complication. We present a case for which endovascular retrieval was not appropriate because of filter orientation and erosion into the ureter and describe successful management using open retrieval of a permanent filter with erosion into the renal collecting system requiring reconstruction. Although minimally invasive retrieval is preferred over open repair, this approach should be considered when filter erosion is not amenable to endovascular retrieval.

Psychological Well-Being of Australian Actors and Performing Artists: Life Satisfaction and Negative Affect.

BACKGROUND: Anecdotal evidence and media reports suggest that actors and other performing artists experience high levels of depression, anxiety, and stress. However, no empirical study has examined the psychological well-being of this professional group. OBJECTIVE: The Australian Actors' Wellbeing Study (AWS) was conducted to examine the general wellbeing of Australian actors and performing artists. The present paper, reporting on data from the AWS, focuses on two aspects of respondents' psychological well-being: life satisfaction and the experience of negative affect. METHODS: An online survey including several questionnaires was distributed to the Equity Foundation membership representing Australian actors. We report results from the Satisfaction with Life Scale (SWLS) and the Depression Anxiety Stress Scales (DASS) and examine their associations with respondents' sociodemographic and occupational background, including their relationship status and any relationship stress, income from performing, and time taken away from performing. RESULTS: A sample of 782 Australian actors responded to the survey, with 582 participants completing the DASS and 568 the SWLS. Participants reported lower levels of life satisfaction and higher levels of depression, anxiety, and stress than found in the Australian general population. Being in a relationship was associated with better psychological well-being; however, work stress often impacted negatively on relationships. Income had little association with psychological well-being, unless the respondent felt under financial stress. Respondents who took extended periods of time away from performing reported less life satisfaction and more depression than others. CONCLUSION: Australian actors may be at a high risk for poor psychological health. Further research is necessary to establish causality among the variables we examined and to investigate protective factors that may increase well-being in the context of the performing arts industry.

Alcohol Use by Australian Actors and Performing Artists: A Preliminary Examination from the Australian Actors' Wellbeing Study.

BACKGROUND: Anecdotal and media reports suggest that actors and performing artists are vulnerable to high levels of alcohol use. However, little empirical research is available to document the extent and correlates of alcohol use amongst these artists, particularly in an Australian context. OBJECTIVE: This study investigated alcohol use in a sample of Australian actors and other performing artists and its associations with sociodemographic background, psychological wellbeing, and work stress. METHODS: An online survey was distributed to the Equity Foundation membership representing Australian actors and performing artists. The survey included questions on sociodemographic and occupational background and psychological wellbeing (DASS-21), as well as the AUDIT questionnaire to assess self-reported alcohol consumption. A sample of 620 performing artists responded to the survey, a large majority of whom were actors. RESULTS: Australian actors and performing artists appear to consume alcohol at levels that are higher than those found in the general Australian population. About 40% of men and 31% of women were classified as drinking alcohol at potentially harmful or hazardous levels. Alcohol use was not strongly associated with age, education, or income, but it had a relationship with poorer psychological wellbeing. About 50% of respondents reported that their alcohol drinking was related to work stress as a performer. This perception was more pronounced amongst those performers who reported drinking at harmful levels. CONCLUSIONS: Australian actors and performing artists appear to be an at-risk population for harmful or hazardous alcohol use.

Eating Disorder Symptoms in Australian Actors and Performing Artists.

AIMS: Anecdotal evidence suggests that actors and other performing artists are under great pressure to conform to idealized appearances and body types. The pursuit of such appearances may trigger eating disorder symptoms, such as unhealthy attitudes towards body weight and shape. Thus far, there has been no dedicated empirical study of the prevalence of such problems in Australian actors and performing artists specifically. Therefore, this study sought to examine eating disorder symptomatology in Australian actors and performing artists. METHODS: An online survey was distributed to the Equity Foundation membership representing Australian actors and performing artists, of whom 573 individuals completed the survey. This survey gauged demographic information and eating disorder symptoms using the psychometrically validated Eating Disorder Diagnostic Scale (EDDS). RESULTS: A large proportion of actors reported unhealthy attitudes such as 'feeling fat' even though they are of normal weight or underweight; reported an extreme fear of gaining weight; and evaluated their self-worth based on their body weight and shape, particularly women. Results also showed that 2.5% of women in the study met the diagnostic criteria for anorexia nervosa and 13% met diagnostic criteria for bulimia nervosa based on their scores on the EDDS. DISCUSSION: Performers may be a particularly at-risk population for the development and/or maintenance for a range of eating disorders.

Emergency Obstetrics for the Emergency Medicine Provider.

INTRODUCTION: Emergency medicine physicians must have the knowledge and skills to stabilize all life-and-limb-threatening conditions. These skills are especially important considering that the 1989 COBRA act clearly defines active labor as a condition unsuitable to transfer. Given this context, we thought it necessary to create a work that could be used to provide emergency physicians with the necessary skills to assist in deliveries both routine and complex. METHODS: The total time requirement for the workshop is 4 hours. Before the session begins, learners are asked to fill out a survey. Learners complete two 40-minute small-group sessions on the topics of normal vaginal delivery and shoulder dystocia with hands-on training with birthing manikins. After a short break learners complete a 65-minute small-group session for breech delivery with hands-on training. Each small-group session is preceded by a whole-group demonstration of required skills lasting 15 minutes as well a mini lecture on maternal hemorrhage and estimation of blood loss. RESULTS: Our workshop has been shown to successfully educate emergency physicians with a range of obstetric experience and improve their knowledge base and hands-on skills. One hundred percent of our learners felt this workshop was appropriate for them and met its stated goals. DISCUSSION: While this is not the first workshop to educate on obstetric deliveries and their possible complications, it is the first to be created with the emergency medicine provider as the intended audience and the first to create a curriculum around uncomplicated delivery, shoulder dystocia, breech delivery, and postpartum hemorrhage.

Autologous Fat Grafting as a Novel Approach to Parastomal Soft-tissue Volume Deficiencies.

SUMMARY: The aim of this study is to describe a novel approach to revise maladaptive soft-tissue contour around an ileostomy. A patient with permanent ileostomy suffered from significant defects in soft-tissue contour due to scarring and wound contraction. He underwent autologous fat grafting to achieve sealing of his stoma appliance and improve cosmesis. Due to numerous surgeries, the stoma appliance would not seal and required daily appliance changes. The patient received autologous fat grafting to augment the contour around stoma. A complete fitting of stoma was achieved. The patient is satisfied with stoma sealing and is changing his stoma appliance every 5-7 days without skin excoriation. Autologous fat transfer is an effective approach to treat a subset of stoma patients with complex subcutaneous defects.

RhoC promotes human melanoma invasion in a PI3K/Akt-dependent pathway.

Overexpression of the small GTPase, RhoC, in various human cancers has been correlated with high metastatic ability and poor prognosis. Rho-kinase (ROCK) is an important effector of Rho GTPases. The oncogenic serine/threonine kinase Akt (also known as PKB) is a downstream effector of phosphatidylinositol-3 kinase (PI3K). Akt activation contributes to the neoplastic phenotype by promoting cell cycle progression, increasing antiapoptotic functions, and enhancing tumor cell invasion. Rho signaling via ROCK has been previously shown either to activate or to downregulate PI3K/Akt. Using a human radial growth phase melanoma cell line, WM35, we have established stable transfectants that overexpress RhoC (called WM35RhoC). We found that overexpression of RhoC increased phosphorylated-Akt (Ser473/474/472, pAkt) expression and promoted cell invasion. Inhibition of RhoC with C3 transferase downregulated pAkt expression and decreased cell invasion in these cells. In addition, inhibition of PI3K, Akt, or ROCK partially decreased invasion. Further, inhibition of PI3K but not ROCK decreased the pAkt level. These results suggest that RhoC promotes invasion in part via activation of a PI3K/Akt pathway, in a manner independent of ROCK signaling. We propose that RhoC promotes melanoma progression via separate mechanisms that regulate the PI3K/Akt pathway and the ROCK signaling pathway.

Parvovirus LuIII transducing vectors packaged by LuIII versus FPV capsid proteins: the VP1 N-terminal region is not a major determinant of human cell permissiveness.

Human cell lines are permissive for LuIII, a member of the rodent group of autonomous parvoviruses. However, LuIII vectors pseudotyped with feline panleukopaenia virus (FPV) capsid proteins can transduce feline cells but not human cells. Feline transferrin receptor (FelTfR) functions as a receptor for FPV. Transfection of Rh18A, a human rhabdomyosarcoma cell line, with FelTfR enabled transduction by vector with FPV capsid. This was not true of other human lines, suggesting restriction at some additional, post-entry, level(s) in human cells other than Rh18A. It seemed a reasonable hypothesis that a second blockage might be in nuclear delivery mediated by the N-terminal region of the minor capsid protein, VP1. We therefore generated virions containing an LuIII-luciferase genome, packaged using chimaeric VP1 molecules (N-terminal region of LuIII VP1, fused with body of FPV, and vice versa) together with the major capsid protein, VP2, of FPV or LuIII. The virions were tested for ability to transduce feline and human cells. Our hypothesis predicted that the N-terminal region of LuIII VP1 should allow transduction of human cells expressing FelTfR, while the FPV N-terminal region should not allow transduction of human cells (except for Rh18A). The experimental results did not bear out either of these predictions. Therefore, the VP1 N-terminal region appears not to be a major determinant of permissiveness for LuIII, versus FPV, capsid in human cells.

Targeting diphtheria toxin A-chain transcription to activated endothelial cells using an E-selectin promoter.

Targeting the transcription of a toxin gene to activated endothelial cells might be used for inhibiting angiogenesis in solid tumors. As a model, we transiently transfected human endothelial cells (HUVEC) in culture with expression plasmids for the toxic A-chain of diphtheria toxin (DT-A), using electroporation (achieving approximately 70% transfection efficiency). Protein synthesis in HUVEC was highly sensitive to DT-A expression from constitutive viral promoters. E-selectin is strongly expressed on HUVEC activated by TNFalpha or TPA. We therefore tested a human E-selectin promoter (-547 to +33) for targeting transcription of DT-A or reporter genes to HUVEC. Luciferase reporters were efficiently expressed in HUVEC from this promoter, with or without an enhancer responsive to Ets-1. Expression was increased by TNF alpha or TPA. DT-A showed highly preferential expression (increased by TNF alpha or TPA) in HUVEC, compared with WI38 human fibroblasts. HUVEC expressing DT-A were killed via apoptosis. Overall expression levels were influenced by alternative 'backbone' sequences used in the expression plasmids. We propose that delivery of transcriptionally regulated expression plasmids for DT-A in vivo, using cationic lipids that show preferential accumulation in activated or proliferating endothelium, may offer a novel means of inhibiting undesired angiogenesis.

Autonomous parvovirus vectors.

Parvoviruses are small, icosahedral viruses (approximately 25 nm) containing a single-strand DNA genome (approximately 5 kb) with hairpin termini. Autonomous parvoviruses (APVs) are found in many species; they do not require a helper virus for replication but they do require proliferating cells (S-phase functions) and, in some cases, tissue-specific factors. APVs can protect animals from spontaneous or experimental tumors, leading to consideration of these viruses, and vectors derived from them, as anticancer agents. Vector development has focused on three rodent APVs that can infect human cells, namely, LuIII, MVM, and H1. LuIII-based vectors with complete replacement of the viral coding sequences can direct transient or persistent expression of transgenes in cell culture. MVM-based and H1-based vectors with substitution of transgenes for the viral capsid sequences retain viral nonstructural (NS) coding sequences and express the NS1 protein. The latter serves to amplify the vector genome in target cells, potentially contributing to antitumor activity. APV vectors have packaging capacity for foreign DNA of approximately 4.8 kb, a limit that probably cannot be exceeded by more than a few percent. LuIII vectors can be pseudotyped with capsid proteins from related APVs, a promising strategy for controlling tissue tropism and circumventing immune responses to repeated administration. Initial success has been achieved in targeting such a pseudotyped vector by genetic modification of the capsid. Subject to advances in production and purification methods, APV vectors have potential as gene transfer agents for experimental and therapeutic use, particularly for cancer therapy.