Facial Sebaceous Hyperplasia in an Adolescent With Hypohidrotic Ectodermal Dysplasia.

We report on a 13-year-old boy diagnosed with hypohidrotic ectodermal dysplasia (HED) due to a pathogenic variant in ectodysplasin A (EDA). He exhibited multiple whitish, millimetric papules clustered on the nasal ala, forehead, temporal, and zygomatic arch areas. Histological examination revealed numerous hyperplastic sebaceous lobules within the upper dermis. The occurrence of sebaceous papules in this distribution among HED patients has rarely been reported. An association with the blockage of the Wnt/ß-catenin pathway due to EDA malfunction has been speculated.

Understanding and using experiences of social care to guide service improvements: translating a co-design approach from health to social care.

Background: Local authorities need to find new ways of collecting and using data on social care users' experiences to improve service design and quality. Here we draw on and adapt an approach used in the healthcare improvement field, accelerated experience-based co-design, to see if it can be translated to social care. We use loneliness support as our exemplar. Objectives: To understand how loneliness is understood and experienced by members of the public and characterised by social care and voluntary sector staff; to identify service improvements around loneliness support; to explore whether accelerated experience-based co-design is effective in social care; and to produce new resources for publication on Socialcaretalk.org. Design and methods: Discovery phase: in-depth interviews with a diverse sample of people in terms of demographic characteristics with experience of loneliness, and 20 social care and voluntary staff who provided loneliness support. Production of a catalyst film from the public interview data set. Co-design phase: exploring whether the accelerated experience-based co-design approach is effective in one local authority area via a series of three workshops to agree shared priorities for improving loneliness support (one workshop for staff, another for people with experience of local loneliness support, and a third, joint workshop), followed by 7-monthly meetings by two co-design groups to work on priority improvements. A process evaluation of the co-design phase was conducted using interviews, ethnographic observation, questionnaires and other written material. Results: Accelerated experience-based co-design demonstrated strong potential for use in social care. Diverse experiences of participants and fuzzy boundaries around social care compared to health care widened the scope of what could be considered a service improvement priority. Co-design groups focused on supporting people to return to pre-pandemic activities and developing a vulnerable passenger 'gold standard' award for taxi drivers. This work generated short-term 'wins' and longer-term legacies. Participants felt empowered by the process and prospect of change, and local lead organisations committed to take the work forward. Conclusions: Using an exemplar, loneliness support, that does not correspond to a single pathway allowed us to comprehensively explore the use of accelerated experience-based co-design, and we found it can be adapted for use in social care. We produced recommendations for the future use of the approach in social care which include identifying people or organisations who could have responsibility for implementing improvements, and allowing time for coalition-building, developing trusted relationships and understanding different perspectives. Limitations: COVID-19 temporarily affected the capacity of the local authority Project Lead to set up the intervention. Pandemic work pressures led to smaller numbers of participating staff and had a knock-on effect on recruitment. Staff turnover within Doncaster Council created further challenges. Future work: Exploring the approach using a single pathway, such as assessing eligibility for care and support, could add additional insights into its transferability to social care. Trial registration: This trial is registered as Current Controlled Trials ISRCTN98646409. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR128616) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 27. See the NIHR Funding and Awards website for further award information.

Local councils need to find new ways of using people's experiences of social care to improve services. We explored whether a way of improving health services can improve social care services. 'Experience-based co-design' is a complicated name. It means working with people who use health or social care services to improve that service, and interviewing people as part of this process. Accelerated experience-based co-design uses existing interviews instead of new interviews. To see if the approach works in social care, we chose the topic of loneliness because many of us experience loneliness. We worked with Doncaster City Council because it has been focusing on loneliness. We interviewed 37 people across England and recorded what they said about loneliness. We made a film about their experiences that showed examples of good or poor care. We call these touch points. We held three workshops in Doncaster. Workshop 1 was with people who work in social care as paid workers or volunteers, and workshop 2 was with people who use social care services. In both workshops, people made a list of types of support that needed improvement. Both groups attended workshop 3, watched the film and decided what to focus on from the two lists. Two groups were set up to work on improving support for loneliness in Doncaster. Each group met seven times. One focused on taxi services, and the other group focused on supporting people to do activities they did before the pandemic. A researcher attended these meetings and talked with everyone involved to see how this approach worked. At the end, there was a celebration event. We found that loneliness is complicated. We found the approach to improving support does work in social care, but it needs some changes because social care is not like health care. We suggest ways the approach can be done differently.

The impact of suicide registers and other monitoring systems on suicide prevention: A scoping review.

BACKGROUND: Decreasing suicide mortality has become an overarching goal for societies worldwide. Suicide registers and other monitoring systems are a valuable source of information that can be used for addressing the suicide phenomenon and evaluating preventative interventions. AIMS: This scoping review provides an overview of literature published in the last decade that has focussed on the operations (functioning) and characteristics of suicide registers and other suicide monitoring systems. METHODS: Four electronic databases were searched in 2020 for identifying published material from January 2010 to October 2020. The searches were updated in October 2023 to include material from 2020 to date. Grey literature through Google searches and mental health commissions websites and the reference lists of selected documents were also searched. RESULTS: Twenty-five articles were included in this review. Nearly half the articles were from the United States, followed by Australia. Nine countries were identified as having used suicide registers or suicide-specific monitoring systems to inform suicide prevention. Monitoring mechanisms varied across the countries examined. No article provided evidence that definitively linked suicide registers or other monitoring systems for suicide with the prevention of suicide or reduction in suicide rates. However, a variety of benefits of suicide monitoring for preventative and public health interventions were identified. CONCLUSIONS: The number of nations with surveillance systems for suicide prevention is low. Further, there is a lack of consistency in the systematic collection, analysis and interpretation of suicide-related information across the countries examined. Efforts to establish high-quality suicide surveillance systems that can be accessed in a timely and easy manner are needed to inform tailored strategies for suicide prevention.

Improving support and planning ahead for older people with learning disabilities and family carers: a mixed-methods study.

Background: People with learning disabilities are living longer. Despite government policy to encourage people to lead supported lives in their community, family carers often maintain support due to dissatisfaction with services. This can lead to people moving from the family home in a crisis. Objectives: (1) Find out what is known about health needs and resources for older people with learning disabilities (aged ≥ 40 years); (2) identify exemplars of good services for older people with learning disabilities; (3) explore service exemplars through ethnographic case studies; (4) evaluate support for older people with learning disabilities and their families through co-producing and testing future planning tools and (5) co-produce recommendations and resources. Design and methods: Work package 1 rapid scoping reviews - three reviews focused on the health and social care needs of older people with learning disabilities and 'behaviours that challenge others', and family carers, and the co-ordination of support for this group. Work package 2 scoping and mapping exemplars of good practice - analysis of published service standards to assess excellence criteria, by mapping services, interviews (n = 30), survey (n = 9) and informal discussion with commissioners. Work package 3 ethnography of case studies of exemplar provision; independent supported living (n = 4); residential/nursing home (n = 2); day activities (n = 1), Shared Lives (n = 2). Fieldwork (20 days per model), interviews (n = 77) with older people with learning disabilities, family carers, support staff and commissioners. Work package 4 - co-producing and testing resources for older people with learning disabilities and their families involved interviews and focus groups with 36 people with learning disabilities, parents, and siblings, and experience-based co-design with 11 participants. Eight families evaluated the resources. Work package 5 - three stakeholder workshops co-produced service recommendations. Findings: The reviews confirmed an inadequate evidence base concerning the experiences and support of family carers and older people with learning disabilities and 'behaviours that challenge others'. Criteria of excellence were produced, and a shortlist of 15 services was identified for consideration in work package 3. The ethnographic work found that environmental, organisational and social factors were important, including supporting independence and choice about who people live with, matching staff to people, consistent relationships and adapting to ageing. Practices of institutionalisation were observed. In work package 4, we found that families were worried about the future and unsupported to explore options. 'Planning Ahead' cards and a booklet to record discussions were produced, and the evaluation was positively rated. Finally, formative discussion informed recommendations. Outputs include training packages, a carers' forum, a film, a podcast and academic papers. Conclusions: There is little focus on older people with learning disabilities and family carers. Services vary in their approach to planning for older-age support. Families are unsupported to plan, leaving people without choice. 'Behaviours that challenge others' was found to be unhelpful terminology. Recommendations: A new strategy is recommended for older people with learning disabilities and family carers that encompasses commissioning practices, professional input and peer learning, proactive support in ageing well and excellent service design. Limitations: The COVID-19 pandemic created recruitment challenges. Reliance on providers for recruitment resulted in a lack of diversity in work package 3. Families' plans, and therefore change, may be frustrated by insufficient service resources. Future work: Given the lack of focus in this area, there is a range of future work to consider: experiences of older people with learning disabilities from diverse ethnic backgrounds; supporting people to age and die 'in place'; best practice regarding designing/commissioning services, including housing; the role of social workers; access to nature; accessing mainstream support; and evaluation of the 'Planning Ahead' cards. Trial registration: This trial is registered as ISRCTN74264887. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR129491) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 16. See the NIHR Funding and Awards website for further award information.

People with learning disabilities are living longer, but most live with their families, who are also getting older. This is because there are not enough suitable places for people with learning disabilities to live, and family carers worry that the person will not get the right support and have a good life. Our research aimed to improve support for people with learning disabilities and their family carers to plan ahead for a good life. We focused on people who are labelled with 'behaviours that challenge others'. We read what has been written about this area. We looked for and found examples of excellent support for older people with learning disabilities. Researchers and people with learning disabilities and family carers spent time hanging out with people where they live or spend their days to see what support they get. Then we had three meetings with everyone involved and discussed our research findings with people with learning disabilities, family carers, and professionals. We found that people can be supported to live good lives as they grow older. This can be living alone or with people they choose, and it means having staff they like and who like them and being supported to be active. However, we found that ageing of people with learning disabilities is often ignored, and some people were not living good lives. We also found that the label of 'behaviours that challenge others' is unhelpful. We worked with people with learning disabilities and family carers to make a set of cards with pictures and questions to help people plan ahead for a good life. We produced resources and made recommendations to create a new plan for older people with learning disabilities to support people to lead good lives. This is very important because there is a lack of attention to and support for people with learning disabilities as they age.

Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease.

Pompe disease (PD) is a progressive myopathy caused by the aberrant accumulation of glycogen in skeletal and cardiac muscle resulting from the deficiency of the enzyme acid alpha-glucosidase (GAA). Administration of recombinant human GAA as enzyme replacement therapy (ERT) works well in alleviating the cardiac manifestations of PD but loses sustained benefit in ameliorating the skeletal muscle pathology. The limited efficacy of ERT in skeletal muscle is partially attributable to its inability to curb the accumulation of new glycogen produced by the muscle enzyme glycogen synthase 1 (GYS1). Substrate reduction therapies aimed at knocking down GYS1 expression represent a promising avenue to improve Pompe myopathy. However, finding specific inhibitors for GYS1 is challenging given the presence of the highly homologous GYS2 in the liver. Antisense oligonucleotides (ASOs) are chemically modified oligomers that hybridize to their complementary target RNA to induce their degradation with exquisite specificity. In the present study, we show that ASO-mediated Gys1 knockdown in the Gaa -/- mouse model of PD led to a robust reduction in glycogen accumulation in skeletal and cardiac muscle. In addition, combining Gys1 ASO with ERT further reduced glycogen content in muscle, eliminated autophagic buildup and lysosomal dysfunction, and improved motor function in Gaa -/- mice. Our results provide a strong foundation for further validation of the use of Gys1 ASO, alone or in combination with ERT, as a therapy for PD. We propose that early administration of Gys1 ASO in combination with ERT may be the key to preventative treatment options in PD.

Impact of Flash Glucose Monitoring on the Fear of Hypoglycemia Phenomenon in Adults with Type 1 Diabetes.

Objective: To assess the clinical impact of flash glucose monitoring (FGM) systems on fear of hypoglycemia (FoH) and quality of life in adults with type 1 diabetes mellitus (T1DM). Methods: Prospective quasi-experimental study with a 12-month follow-up. People with T1DM (18-80 years old) and self-monitoring by blood capillary glycemia controls were included. The FH15 questionnaire, a survey validated in Spanish in a comparable study population, was used to diagnose FoH with a cutoff point of 28 points. Results: A total of 181 participants were included, with a FoH prevalence of 69% (n = 123). A mean reduction in FH15 score of -4 points (95% confidence interval [-5.5 to -3]; P < 0.001) was observed, along with an improvement in quality of life (EsDQOL-test (Diabetes Quality of Life, Spanish version), -7 points [-10; -4], P < 0.001) and satisfaction with treatment (Diabetes Treatment Satisfaction questionnaire, self-reported version [DTSQ-s] test, +4.5 points [4; 5.5], P < 0.001). At the end of the follow-up, 64.2% of the participants saw an improved FoH intensity, compared to 35.8% who scored the same or higher. This improvement in FoH status was associated with a higher time-in-range at the end of the follow-up (P = 0.003), as well as a lower time spent in hyperglycemia (P = 0.005). In addition, it was linked to participants with a high baseline FoH levels (P < 0.001) and those who were university degree holders (P = 0.07). Conclusions: FGM is associated with an overall reduction of FoH in adults with T1DM and with an increase in their quality of life. Nevertheless, a significant percentage of patients may experience an increase of this phenomenon leading to clinical repercussions and a profound impact on quality of life.

Idiopathic calcinosis cutis in an infant: The importance of a wait-and-see approach.

A healthy 2-year-old girl presented with multiple asymptomatic subcutaneous nodules on both legs. Histologically demonstrated calcium deposition within the dermis and subcutaneous tissue consistent with calcinosis cutis. Laboratory abnormalities, underlying genetic conditions, and potential triggering factors were ruled out. The lesions resolved over an 18-month period without treatment, emphasizing the importance of the wait-and-see approach in idiopathic cases of calcinosis cutis.

The Melatonin Derivative ITH13001 Prevents Hypertension and Cardiovascular Alterations in Angiotensin II-Infused Mice.

Inflammatory mechanisms and oxidative stress seem to contribute to the pathogenesis of hypertension. ITH13001 is a melatonin-phenyl-acrylate hybrid that moderately induces the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) and has a potent oxidant scavenging effect compared with other derivatives of its family. Here we investigated the effect of ITH13001 on hypertension and the associated cardiovascular alterations. Angiotensin II (AngII)-infused mice were treated with ITH13001 (1 mg/kg per day, i.p.) for 2 weeks. The ITH13001 treatment prevented: 1) the development of hypertension, cardiac hypertrophy, and increased collagen and B-type natriuretic peptide (Bnp) expression in the heart; 2) the reduction of elasticity, incremental distensibility, fenestrae area, intraluminal diameter, and endothelial cell number in mesenteric resistance arteries (MRA); 3) the endothelial dysfunction in aorta and MRA; 4) the plasma and cardiovascular oxidative stress and the reduced aortic nitric oxide (NO) bioavailability; 5) the increased cardiac levels of the cytokines interleukin (IL)-1ß, IL-6, and C-C motif chemokine ligand 2 (Ccl2), the T cell marker cluster of differentiation 3 (Cd3), the inflammasome NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), the proinflammatory enzymes inducible nitric oxide synthase (iNOS) and COX-2, the toll-like receptor 4 (TLR4) adapter protein myeloid differentiation primary response 88 (MyD88), and the nuclear factor kappa B (NF-κB) subunit p65; 6) the greater aortic expression of the cytokines tumor necrosis factor alpha (Tnf-α), Ccl2 and IL-6, Cd3, iNOS, MyD88, and NLRP3. Although ITH13001 increased nuclear Nrf2 levels and heme oxygenase 1 (HO-1) expression in vascular smooth muscle cells, both cardiac and vascular Nrf2, Ho-1, and NADPH quinone dehydrogenase 1 (Nqo1) levels remained unmodified irrespective of AngII infusion. Summarizing, ITH13001 improved hypertension-associated cardiovascular alterations independently of Nrf2 pathway activation, likely due to its direct antioxidant and anti-inflammatory properties. Therefore, ITH13001 could be a useful therapeutic strategy in patients with resistant hypertension. SIGNIFICANCE STATEMENT: Despite the existing therapeutic arsenal, only half of the patients treated for hypertension have adequately controlled blood pressure; therefore, the search for new compounds to control this pathology and the associated damage to end-target organs (cerebral, cardiac, vascular, renal) is of particular interest. The present study demonstrates that a new melatonin derivative, ITH13001, prevents hypertension development and the associated cardiovascular alterations due to its antioxidant and anti-inflammatory properties, making this compound a potential candidate for treatment of resistant hypertensive patients.

Association Between VDR and CYP24A1 Polymorphisms, Atopic Dermatitis, and Biochemical Lipid and Vitamin D Profiles in Spanish Population: Case-Control Study.

BACKGROUND: Atopic dermatitis (AD) is the most prevalent inflammatory skin disorder, characterized by impaired epidermal barrier function and an altered immune response, both of which are influenced by vitamin D deficiency. Single-nucleotide polymorphisms (SNPs) in VDR and CYP24A1 have been previously associated with AD. OBJECTIVE: We sought to characterize the associations between the VDR and CYP24A1 polymorphisms and the vitamin D and lipid biochemical profile in children diagnosed with AD. METHODS: A total of 246 participants (143 patients with AD and 103 healthy controls) were enrolled in this study. Genotyping for polymorphisms in VDR (rs2239185, rs1544410, rs7975232, rs2238136, rs3782905, rs2239179, rs1540339, rs2107301, rs2239182, and rs731236) and CYP24A1 (rs2248359 and rs2296241) was performed by allele-specific polymerase chain reaction using integrated fluidic circuit technology. Serum levels of calcium, phosphorus, and vitamin D were measured, and the biochemical lipid profile was determined. RESULTS: Among VDR SNPs, rs2239182 exerted a protective effect against the development of AD, whereas rs2238136 was identified as a risk factor for AD. The GCC haplotype (rs2239185-G, rs1540339-C, and rs2238136-C) appeared to protect against the development of AD. rs2239182-CC was associated with higher 25(OH)D concentrations, whereas rs2238136-TT, rs2239185-GA, and rs2248359-TT were present in a large proportion of patients with serum vitamin D deficiency. rs2239185-AA, rs2239182-CC, and rs1540339-CC were associated with higher serum total cholesterol; rs2239182-TT was associated with lower low-density lipoprotein cholesterol; and rs2239182-TC with lower high-density lipoprotein cholesterol. Both CYP24A1 SNPs (rs2296241-AA and rs2248359-TT) were associated with higher high-density lipoprotein cholesterol levels. CONCLUSIONS: The VDR SNP rs2238136 is a risk factor for AD and other SNPs in VDR and CYP24A1, which may lead to alterations in biochemical parameters that influence the risk of AD. Our findings highlight the complex genetic basis to AD and indicate that interrelationships between different genetic factors can lead to alterations in vitamin D metabolism or lipid profiles, which in turn may influence the development of AD.

Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma.

Hereditary palmoplantar keratodermas (PPKs) are a clinically and genetically heterogeneous group of disorders characterized by excessive epidermal thickening of palms and soles. Several genes have been associated with PPK including PERP, a gene encoding a crucial component of desmosomes that has been associated with dominant and recessive keratoderma. We report a patient with recessive erythrokeratoderma (EK) in which whole exome sequencing (WES) prioritized by human phenotype ontology (HPO) terms revealed the presence of the novel variant c.153C > A in the N-terminal region the PERP gene. This variant is predicted to have a nonsense effect, p.(Cys51Ter), resulting in a premature stop codon. We demonstrated a marked reduction in gene expression in cultured skin fibroblasts obtained from the patient. Despite the PERP gene is expressed at low levels in fibroblasts, our finding supports a loss-of-function (LoF) mechanism for the identified variant, as previously suggested in recessive EK. Our study underscores the importance of integrating HPO analysis when using WES for molecular genetic diagnosis in a clinical setting, as it facilitates continuous updates regarding gene-clinical feature associations.

Effects of enzyme replacement therapy on bone density in late onset Pompe disease.

Pompe disease is an autosomal recessive disorder caused by a deficiency of α-glucosidase, resulting in the accumulation of glycogen in smooth, cardiac, and skeletal muscles, leading to skeletal muscle dysfunction, proximal muscle weakness, and early respiratory insufficiency. Although many patients exhibit decreased bone mineral density (BMD) and increased fractures, there is currently no official protocol for surveillance and management of osteoporosis and osteopenia in late onset Pompe disease (LOPD). Enzyme replacement therapy (ERT) has therapeutic effects on muscle function; however, very few studies report on the effect of ERT on bone mineralization in LOPD patients. Our study included 15 Pompe patients from 25 to 76 years of age on ERT for variable durations. Progressive impact of ERT on BMD of the hips and spine, and the frequency of osteopenia or osteoporosis was studied using DEXA scanning, and correlations were made with age of initiation of ERT, duration of ERT and six-minute walk test. We found a significant positive correlation between the age of ERT initiation and age of the subject, with increases in the Z-scores for the femur and lumbar region. Females had a significantly higher risk for developing osteoporosis compared to males. These results highlight the significance of ERT on reducing progression of osteoporosis in LOPD patients.

Humane orientation, work-family conflict, and positive spillover across cultures.

Although cross-national work-family research has made great strides in recent decades, knowledge accumulation on the impact of culture on the work-family interface has been hampered by a limited geographical and cultural scope that has excluded countries where cultural expectations regarding work, family, and support may differ. We advance this literature by investigating work-family relationships in a broad range of cultures, including understudied regions of the world (i.e., Sub-Saharan Africa, Southern Asia). We focus on humane orientation (HO), an overlooked cultural dimension that is however central to the study of social support and higher in those regions. We explore its moderating effect on relationships between work and family social support, work-family conflict, and work-family positive spillover. Building on the congruence and compensation perspectives of fit theory, we test alternative hypotheses on a sample of 10,307 participants from 30 countries/territories. We find HO has mostly a compensatory role in the relationships between workplace support and work-to-family conflict. Specifically, supervisor and coworker supports were most strongly and negatively related to conflict in cultures in which support is most needed (i.e., lower HO cultures). Regarding positive spillover, HO has mostly an amplifying role. Coworker (but not supervisor) support was most strongly and positively related to work-to-family positive spillover in higher HO cultures, where providing social support at work is consistent with the societal practice of providing support to one another. Likewise, instrumental (but not emotional) family support was most strongly and positively related to family-to-work positive spillover in higher HO cultures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Regulation by Nrf2 of IL-1ß-induced inflammatory and oxidative response in VSMC and its relationship with TLR4.

Introduction: Vascular oxidative stress and inflammation play an important role in the pathogenesis of cardiovascular diseases (CVDs). The proinflammatory cytokine Interleukin-1ß (IL-1ß) participates in the vascular inflammatory and oxidative responses and influences vascular smooth muscle cells (VSMC) phenotype and function, as well as vascular remodelling in cardiovascular diseases. The Toll-like receptor 4 (TLR4) is also involved in the inflammatory response in cardiovascular diseases. A relationship between Interleukin-1ß and Toll-like receptor 4 pathway has been described, although the exact mechanism of this interaction remains still unknown. Moreover, the oxidative stress sensitive transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) promotes the transcription of several antioxidant and anti-inflammatory genes. Nuclear factor-erythroid 2-related factor 2 activators have shown to possess beneficial effects in cardiovascular diseases in which oxidative stress and inflammation are involved, such as hypertension and atherosclerosis; however, the molecular mechanisms are not fully understood. Here, we analysed the role of Toll-like receptor 4 in the oxidative and inflammatory effects of Interleukin-1ß as well as whether nuclear factor-erythroid 2-related factor 2 activation contributes to vascular alterations by modulating these effects. Materials: For this purpose, vascular smooth muscle cells and mice aortic segments stimulated with Interleukin-1ß were used. Results: Interleukin-1ß induces MyD88 expression while the Toll-like receptor 4 inhibitor CLI-095 reduces the Interleukin-1ß-elicited COX-2 protein expression, reactive oxygen species (ROS) production, vascular smooth muscle cells migration and endothelial dysfunction. Additionally, Interleukin-1ß increases nuclear factor-erythroid 2-related factor 2 nuclear translocation and expression of its downstream proteins heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and superoxide dismutase-2, by an oxidative stress-dependent mechanism; moreover, Interleukin-1ß reduces the expression of the nuclear factor-erythroid 2-related factor 2 inhibitor Keap1. The nuclear factor-erythroid 2-related factor 2 activator tert-butylhydroquinone (tBHQ) reduces the effects of Interleukin-1ß on the increased reactive oxygen species production and the expression of the proinflammatory markers (p-p38, p-JNK, p-c-Jun, COX-2), the increased cell proliferation and migration and prevents the Interleukin-1ß-induced endothelial dysfunction in mice aortas. Additionally, tert-butylhydroquinone also reduces the increased MyD88 expression, NADPHoxidase activity and cell migration induced by lipopolysaccharide. Conclusions: In summary, this study reveals that Toll-like receptor 4 pathway contributes to the prooxidant and proinflammatory Interleukin-1ß-induced effects. Moreover, activation of nuclear factor-erythroid 2-related factor 2 prevents the deleterious effects of Interleukin-1ß, likely by reducing Toll-like receptor 4-dependent pathway. Although further research is needed, the results are promising as they suggest that nuclear factor-erythroid 2-related factor 2 activators might protect against the oxidative stress and inflammation characteristic of cardiovascular diseases.

An Integrated Approach to Workplace Mental Health: A Scoping Review of Instruments That Can Assist Organizations with Implementation.

This study aimed to identify instruments that may assist organizations with implementing an integrated approach to workplace mental health using three activities from the knowledge to action (KTA) framework. A scoping review of published and grey literature, supported by stakeholder (business end-user and researcher) consultation, identified work-specific instruments that were relevant to at least one of the three domains of an integrated approach to workplace mental health: 'prevent harm', 'promote the positive', and 'respond to problems'. A total of 207 instruments were located, and 109 instruments met eligibility criteria. 10 instruments were located that were relevant to multiple domains, however most instruments (n = 72) were relevant to the 'prevent harm' domain. Instruments relevant to the 'promote the positive' (n = 14) and 'respond to problems' (n = 13) domains were limited. Most instruments found were suitable for the 'monitor, review and improve' KTA activity. Further development of instruments that can assist with 'promote the positive' and 'respond to problems' strategies are required, specifically those instruments that can assist organizations with the 'identify gaps and opportunities' and 'identify priorities and design new/enhanced interventions' KTA activities.

Marina Observation of Sea Turtles: Establishing a Database of Intracoastal Waterway Green Sea Turtles in Northeast Florida.

As conservation efforts regarding green sea turtles, Chelonia mydas, continue, it is imperative to document behaviors and foraging habits/habitats of understudied populations. We have conducted an 18-month study dedicated to photographing the local population feeding alongside floating docks within the Guana Tolomato Matanzas estuary to determine the capability of matching head scale patterns efficiently through a pattern matching program: HotSpotter. To date, 195 unique sea turtles have been identified between two different marinas located in St. Augustine, FL. Of these, 98 were spotted more than once, with 39 of them being "tracked" for longer than a year. Temperature trends were also monitored in conjunction, showing that more individuals appeared during the warmer months of the year. The evidence, overall, indicates that these locations host a resident population of green sea turtles, leading to the need for a discussion on potential threats originating from the usage of these marinas by humans.

Ichthyosis.

The ichthyoses are a large, heterogeneous group of skin cornification disorders. They can be inherited or acquired, and result in defective keratinocyte differentiation and abnormal epidermal barrier formation. The resultant skin barrier dysfunction leads to increased transepidermal water loss and inflammation. Disordered cornification is clinically characterized by skin scaling with various degrees of thickening, desquamation (peeling) and erythema (redness). Regardless of the type of ichthyosis, many patients suffer from itching, recurrent infections, sweating impairment (hypohidrosis) with heat intolerance, and diverse ocular, hearing and nutritional complications that should be monitored periodically. The characteristic clinical features are considered to be a homeostatic attempt to repair the skin barrier, but heterogeneous clinical presentation and imperfect phenotype-genotype correlation hinder diagnosis. An accurate molecular diagnosis is, however, crucial for predicting prognosis and providing appropriate genetic counselling. Most ichthyoses severely affect patient quality of life and, in severe forms, may cause considerable disability and even death. So far, treatment provides only symptomatic relief. It is lifelong, expensive, time-consuming, and often provides disappointing results. A better understanding of the molecular mechanisms that underlie these conditions is essential for designing pathogenesis-driven and patient-tailored innovative therapeutic solutions.