Understanding and optimising gratitude interventions: the right methods for the right people at the right time.

OBJECTIVE: Gratitude has consistently been associated with various beneficial health-related outcomes, including subjective wellbeing, positive mental health, and positive physical health. In light of such effects, positive psychology researchers and practitioners have often implemented gratitude interventions in an attempt to build individuals' orientations toward appreciation and thankfulness. Recent meta-analyses and reviews have revealed, however, that these interventions often have mixed effects on gratitude or other health outcomes. With this issue in mind, we aimed to identify (a) contextual considerations that may impact the effectiveness of these approaches, and (b) recommendations for the optimisation of gratitude interventions. METHODS AND MEASURES: Seventeen mental health professionals or experienced health psychology researchers engaged in semi-structured interviews to address the research questions. RESULTS: Thematic analysis of the data resulted in three contextual themes-cultural considerations, personal characteristics, and life experience-that were discussed as factors likely to influence intervention effectiveness. With respect to recommendations, participants highlighted the importance of encouraging deep engagement in gratitude tasks, consistent repetition of those tasks, and the value of interpersonal expressions of gratitude. CONCLUSION: Discussion is centred on suggestions for future research on gratitude and on implications for the implementation of gratitude interventions.

Interventions in maternal syphilis care globally: A scoping review.

Infectious and Congenital Syphilis rates continue to rise globally. Current recommendations for syphilis screening and treatment may be insufficient, and there is a pressing need for improved programs and services to address the increase in cases. A scoping review was conducted to examine approaches to maternal syphilis screening and treatment. Theoretical underpinnings and the key characteristics of these interventions were studied to identify gaps in the existing literature to guide future research. Developing a modified version of the socio-ecological model to guide data analysis, we included 33 academic studies spanning 31 years, covering a range of interventions, programs, and policies globally. We highlight key facets of interventions aligning with the five levels of the modified model that include: individual, interpersonal, institutional, community and policy. In this review, we provide valuable insights into the characteristics and principles of maternal syphilis screening and treatment interventions.

Even with advances in care, there remain many similarities in interventions for the improved treatment and screening of maternal syphilis over the past 30 years.There is a need for meaningful research that engages community members in study and intervention development and considers the social determinants of health in the context of maternal syphilis care.Examining interventions in relation to the socio-ecological model may help guide policymakers, researchers, and clinicians in intervention development.

Audit tools for culturally safe and responsive healthcare practices with Aboriginal and Torres Strait Islander people: a scoping review.

Aboriginal and Torres Strait Islander people in Australia face disparities in accessing culturally safe and appropriate health services. While current cultural safety and responsiveness frameworks set standards for improving healthcare practices, ensuring accountability and sustainability of changes, necessitates robust mechanisms for auditing and monitoring progress. This study examined existing cultural safety audit tools, and facilitators and barriers to implementation, in the context of providing culturally safe and responsive healthcare services with Aboriginal and Torres Strait Islander people. This will assist organisations, interested in developing tools, to assess culturally responsive practice. A scoping review was undertaken using Medline, Scopus, CINAHL, Informit and PsychInfo databases. Articles were included if they described an audit tool used for healthcare practices with Aboriginal and Torres Strait Islander people. Selected tools were evaluated based on alignment with the six capabilities of the Indigenous Allied Health Australia (IAHA) Cultural Responsiveness in Action Framework. Implementation barriers and facilitators were identified. 15 papers were included. Audit tools varied in length, terminology, domains assessed and whether they had been validated or evaluated. Seven papers reported strong reliability and validity of the tools, and one reported tool evaluation. Implementation facilitators included: tool comprehensiveness and structure; effective communication; clear organisational responsibility for implementation; commitment to prioritising cultural competence; and established accountability mechanisms. Barriers included: the tool being time-consuming and inflexible; responsibility for implementation falling on a small team or single staff member; deprioritising tool use; and lack of accountability for implementation. Two of the six IAHA capabilities (respect for the centrality of cultures and inclusive engagement) were strongly reflected in the tools. The limited tool evaluation highlights the need for further research to determine implementation effectiveness and sustainability. Action-oriented tools, which comprehensively reflect all cultural responsiveness capabilities, are lacking and further research is needed to progress meaningful change within the healthcare system.

Impact of oral piercings on periodontal health - A systematic review.

AIM: Evidence on the impact of oral piercings on periodontal conditions is scarce. Thus, the aim of this systematic review was to evaluate the influence of oral piercings on periodontal health. MATERIALS AND METHODS: A systematic literature search was performed for studies published by 6 June 2023, using three electronic databases and a hand search. Clinical trials including ≥10 patients wearing ≥1 oral piercing and presenting data on probing pocket depths (PPDs) were considered. Primary outcomes were PPD, and secondary outcomes included clinical attachment loss (CAL), gingival recession, bleeding on probing (BOP), and plaque score (PI). A synthesis of results, using a vote-counting method, was applied. RESULTS: From 131 titles identified, eight studies, published between 2007 and 2022, were included. Out of these were six cross-sectional studies and two case series. A total of 236 lip piercings and 236 tongue piercings in overall 408 patients were analyzed. In patients with tongue piercings, teeth adjacent to the piercing showed increased PPD (3 of 5 studies), more CAL (3 of 4 studies), more gingival recessions (4 of 4 studies) and a higher BOP (2 of 3 studies) compared with control teeth. In patients with lip piercings, teeth adjacent to the piercing demonstrated more gingival recessions (3 of 4 studies) compared with control teeth. Time since piercing placement was associated with localized periodontal destruction in patients with tongue and/or lip piercings (4 of 7 studies). CONCLUSIONS: The available evidence from eight studies suggests negative effects of tongue piercings on several periodontal health parameters of adjacent teeth, while gingival recessions were frequently detected in patients with lip piercings.

Nano-Architecture of Persistent Focal DNA Damage Regions in the Minipig Epidermis Weeks after Acute γ-Irradiation.

Exposure to high acute doses of ionizing radiation (IR) can induce cutaneous radiation syndrome. Weeks after such radiation insults, keratinocyte nuclei of the epidermis exhibit persisting genomic lesions that present as focal accumulations of DNA double-strand break (DSB) damage marker proteins. Knowledge about the nanostructure of these genomic lesions is scarce. Here, we compared the chromatin nano-architecture with respect to DNA damage response (DDR) factors in persistent genomic DNA damage regions and healthy chromatin in epidermis sections of two minipigs 28 days after lumbar irradiation with ~50 Gy γ-rays, using single-molecule localization microscopy (SMLM) combined with geometric and topological mathematical analyses. SMLM analysis of fluorochrome-stained paraffin sections revealed, within keratinocyte nuclei with perisitent DNA damage, the nano-arrangements of pATM, 53BP1 and Mre11 DDR proteins in γ-H2AX-positive focal chromatin areas (termed macro-foci). It was found that persistent macro-foci contained on average ~70% of 53BP1, ~23% of MRE11 and ~25% of pATM single molecule signals of a nucleus. MRE11 and pATM fluorescent tags were organized in focal nanoclusters peaking at about 40 nm diameter, while 53BP1 tags formed nanoclusters that made up super-foci of about 300 nm in size. Relative to undamaged nuclear chromatin, the enrichment of DDR protein signal tags in γ-H2AX macro-foci was on average 8.7-fold (±3) for 53BP1, 3.4-fold (±1.3) for MRE11 and 3.6-fold (±1.8) for pATM. The persistent macro-foci of minipig epidermis displayed a ~2-fold enrichment of DDR proteins, relative to DSB foci of lymphoblastoid control cells 30 min after 0.5 Gy X-ray exposure. A lasting accumulation of damage signaling and sensing molecules such as pATM and 53BP1, as well as the DSB end-processing protein MRE11 in the persistent macro-foci suggests the presence of diverse DNA damages which pose an insurmountable problem for DSB repair.

Exploring the therapeutic potential of an antinociceptive and anti-inflammatory peptide from wasp venom.

Animal venoms are rich sources of neuroactive compounds, including anti-inflammatory, antiepileptic, and antinociceptive molecules. Our study identified a protonectin peptide from the wasp Parachartergus fraternus' venom using mass spectrometry and cDNA library construction. Using this peptide as a template, we designed a new peptide, protonectin-F, which exhibited higher antinociceptive activity and less motor impairment compared to protonectin. In drug interaction experiments with naloxone and AM251, Protonectin-F's activity was decreased by opioid and cannabinoid antagonism, two critical antinociception pathways. Further experiments revealed that this effect is most likely not induced by direct action on receptors but by activation of the descending pain control pathway. We noted that protonectin-F induced less tolerance in mice after repeated administration than morphine. Protonectin-F was also able to decrease TNF-α production in vitro and modulate the inflammatory response, which can further contribute to its antinociceptive activity. These findings suggest that protonectin-F may be a potential molecule for developing drugs to treat pain disorders with fewer adverse effects. Our results reinforce the biotechnological importance of animal venom for developing new molecules of clinical interest.

Does unionization and working under collective agreements promote health?

Health promoters recognize the social determinants of health (SDOH) shape health outcomes yet generally neglect how unionization and collective agreements (CAs) shape these SDOH. This is surprising since extensive evidence indicates unions and CAs influence wages and benefits, job security, working conditions and income inequality, which go on to affect additional SDOH of food and housing security, child development and social exclusion. We argue unions and CAs should be a health promotion focus by examining how they influence the SDOH and health outcomes in wealthy developed nations in four ways. First, we consider how union density (UD) and CA coverage (CAC) are associated with differences between wealthy western nations in percentage of low-waged workers, extent of income inequality, and low birthweight and infant mortality rates. Second, we bring together literature that shows greater UD and CAC within national sub-jurisdictions are associated over time with more equitable distribution of the SDOH and better health outcomes. Third, we document-also using available literature-how within nations, union membership and working under a CA shape the SDOH one experiences. Fourth, we carry out a Canadian case study-applying a political economy lens-to examine how power relations, working through economic and political systems, determine extent of unionization and CAC and the inclination of health promoters to consider these issues. Implications for health promoters are considered.

Protease inhibitor from Libidibia ferrea seeds attenuates inflammatory and nociceptive responses in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Libidibia ferrea (Mart. ex. Tul.) L.P. Queiroz is a Brazilian native tree locally known as jucá and pau-ferro, and it has been used in folk medicine for relieving, asthma, bronchitis, sore throat, rheumatism, enterocolitis and fever. The anti-inflammatory properties of L. ferrea were confirmed for its stem, fruit, leaves, bark and seeds extracts, however little is known about the natural compounds that may be associated with that response. AIM OF THIS STUDY: In a normal physiological condition, many enzymes play an important role in catalyzing biological functions. Among them, proteases are of great interest. Although they take part of many biological systems, as the inflammatory process, when deregulated, proteases may cause system malfunctions, such as under- or overproduction of cytokines, or immune cells activation. Thus, protease inhibitors prevent these immune responses by regulating proteases. The objective of this study was to evaluate the anti-inflammatory and anti-nociceptive response of a protease inhibitor purified from L. ferrea seeds (LfTI). MATERIALS AND METHODS: In vitro (5, 50 and 250 µg/mL of LfTI) and in vivo (0.6, 3 e 15 mg/kg of LfTI) assays were performed. Male Swiss mice weighing 18-25 g were used for cell harvesting and for the in vivo assays. The anti-inflammatory activity was analyzed in vitro by macrophage cytotoxicity, hydrogen peroxide (H2O2) production, and cell adhesion assays; and in vivo by leukocyte recruitment, nitric oxide (NO) production, vascular permeability, paw edema and mast cell degranulation assays. The anti-nociceptive activity was evaluated through abdominal writhing test induced by acetic acid and formalin sensitization. RESULTS: Our results showed that, in vitro, LfTI is not cytotoxic. Also, LfTI (50 µg/mL) inhibited macrophage H2O2 production (48.2%), and adhesion (48.4%). LfTI (0.6, 3 e 15 mg/kg) decreased polymorphonuclear cell recruitment dose-dependently, and it inhibited NO production (53%), vascular permeability (40.7%) and paw edema at 3 mg/kg at different time, but it did not inhibit mast cell degranulation. Besides, LfTI did not inhibit either the number of writhing or the licking time in the formalin test in the second phase (inflammatory). However, LfTI (3 mg/kg) inhibited licking time at the first phase (neurogenic) in the formalin sensitization (46.1%). CONCLUSIONS: Our results show that LfTI has anti-inflammatory and antinociceptive (neurogenic pain) effects, and these effects might be associated with the inhibition of inflammatory proteases and/or protease-activated receptors activation hindering.

Anadenanthera colubrina (Vell) Brenan: Ethnobotanical, phytochemical, pharmacological and toxicological aspects.

ETHNOPHARMACOLOGICAL RELEVANCE: Anadenanthera colubrina (Vell.) Brenan is an endemic tree to South America and different parts of it are used by the population for the treatment of various diseases, as well as in indigenous rituals. This species has high pharmacological potential but may present toxic potential due to the presence of psychotropic compounds. AIM OF THE STUDY: To review published studies with the species A. colubrina regarding ethnobotanical, phytochemical, pharmacological and toxicological aspects, as well as discuss perspectives for new research and protection of this species. MATERIALS AND METHODS: A literature review was performed by accessing published articles on databases such as: PubMed, Science Direct, Scielo, Scopus, Taylor and Francis online, Springer Link, National Center for Biotechnology Information (NCBI), ACS Publications, Chemspider and Google Scholar. The keywords used were: "Anadenanthera colubrina" or "Mimosa colubrina" or "Piptadenia colubrina" or "Piptadenia macrocarpa" or "Piptadenia grata" or "Anadenanthera macrocarpa" and "medicinal plants" or "pharmacological" or "phytochemicals" or "traditional use" or "toxicological" or "ethnobotanical" or "pre-clinical trial" or "clinical". Articles found by database searches and search engines were screened at four stages: (i) title screening, (ii) locality screening, (iii) abstract screening, and (iv) full text. Other articles found through supplementary searches were screened in the full text whenever available. Each article was assessed by three reviewers at the title and abstract screening stages, except for those found in Portuguese databases that were assessed by the native reviewer. RESULTS: This robust tree has been popularly useful for agroeconomic, medicinal and as a hallucinogen in religious rituals. According to the published studies, the main parts of the plant are the bark and seeds that are mostly used for respiratory conditions and as entheogens, respectively. It is a rich traditional herbal medicine with many pharmacological properties such as anti-inflammatory, antinociceptive, antidiarrheal, wound healing, antimicrobial, antitumoral, antioxidant, antiaddictive, insecticide and allelopathic that were described in in vitro and in vivo assays, and approximately 56 compounds were identified, suggesting a therapeutic potential for this species. Although most relate to medicinal uses, these are preliminaries and do not show the mechanism of action. The phytochemical assays showed the presence of phenolic compounds, flavonoids, triterpenes, steroids and alkaloids. Some of the compounds are anadanthoflavone, which is exclusive to this species, and no pharmacological or toxicological studies have yet demonstrated this compound. Another important compound is bufotenine which was isolated from seeds and is related to hallucinogenic and antiviral activity. The extracts made from leaves, bark, gum, and fruits appear to be safe, according to both in vivo and in vitro toxicology testing, which all shown low toxicity. Due to the presence of bufotenine in the seeds, it can be toxic, however, it was not found in toxicological assays with the seed extracts. CONCLUSIONS: Therefore, part of the studies confirms the popular use of A. colubrina, however, more assays with isolated compounds and with the different extracts are necessary to corroborate other uses and the mechanism of action of their pharmacological effects needs to discuss in more detail. Therefore, the present review would be identified the gaps and suggests further studies oriented to validate the popular use. Thus, it must be noted that the use of this species must be controlled in order to minimize the environmental impact, as most of the pharmacological potential was shown with the bark and seeds. Due to its wide use in folk medicine, it is part of the Brazilian medicinal species with priority for conservation.

Understanding parent perspectives on engagement with online youth-focused mental health programs.

OBJECTIVE: Online youth-focused health programs often include parent modules-that equip parents with skills to assist their child in improving their health-alongside youth-specific content. BRAVE Self-Help, an evidence-based program designed for children and teenagers with early signs of anxiety, is a popular Australian program that includes six parent modules. Despite its popularity and proven efficacy, BRAVE Self-Help shares the same challenge as many online self-help programs-that of low participant engagement. Using parents registered in BRAVE Self-Help as 'information rich' participants, we explored (a) factors that influenced parent engagement in online health programs, and (b) their recommendations for enhancing parent engagement. DESIGN AND OUTCOME MEASURE: We conducted semi-structured interviews with 14 parents registered in BRAVE Self-Help. Data were analysed through reflexive thematic analysis. RESULTS: Social-, family- and program-related factors drove parents' program engagement and recommendations. Social sub-themes related to the benefits of professional and community support in promoting more engagement. Family sub-themes included difficulties with program engagement due to competing priorities, perceptions that condition severity influenced engagement, and feelings that previously-acquired health knowledge reduced motivation to engage. Program sub-themes included perceived usefulness and ease-of-use. CONCLUSION: Program designers could target support systems, include flexible delivery options, and use iterative design processes to enhance parent engagement.

Repair of α-particle-induced DNA damage in peripheral blood mononuclear cells after internal ex vivo irradiation with 223Ra.

PURPOSE: As α-emitters for radiopharmaceutical therapies are administered systemically by intravenous injection, blood will be irradiated by α-particles that induce clustered DNA double-strand breaks (DSBs). Here, we investigated the induction and repair of DSB damage in peripheral blood mononuclear cells (PBMCs) as a function of the absorbed dose to the blood following internal ex vivo irradiation with [223Ra]RaCl2. METHODS: Blood samples of ten volunteers were irradiated by adding [223Ra]RaCl2 solution with different activity concentrations resulting in absorbed doses to the blood of 3 mGy, 25 mGy, 50 mGy and 100 mGy. PBMCs were isolated, divided in three parts and either fixed directly (d-samples) or after 4 h or 24 h culture. After immunostaining, the induced γ-H2AX α-tracks were counted. The time-dependent decrease in α-track frequency was described with a model assuming a repair rate R and a fraction of non-repairable damage Q. RESULTS: For 25 mGy, 50 mGy and 100 mGy, the numbers of α-tracks were significantly increased compared to baseline at all time points. Compared to the corresponding d-samples, the α-track frequency decreased significantly after 4 h and after 24 h. The repair rates R were (0.24 ± 0.05) h-1 for 25 mGy, (0.16 ± 0.04) h-1 for 50 mGy and (0.13 ± 0.02) h-1 for 100 mGy, suggesting faster repair at lower absorbed doses, while Q-values were similar. CONCLUSION: The results obtained suggest that induction and repair of the DSB damage depend on the absorbed dose to the blood. Repair rates were similar to what has been observed for irradiation with low linear energy transfer.

Design, synthesis and in vivo evaluation of 1,4-dioxo-2-butenyl aryl amine derivatives as a promising anti-inflammatory drug prototype.

Inflammation is a natural response of the organism to an infection, trauma, or cellular stress. Pain is the first symptom of acute and chronic inflammation. The standard class of medication to treat inflammatory pain is the nonsteroidal anti-inflammatory drug (NSAID). These drugs are associated with severe side effects such as gastric ulcers, gastritis, or internal bleeding. One of NSAIDs, Dipyrone® (metamizole) is largely used in many European and South American countries despite its dubious effectivity and its withdrawal from the market of several countries. Here, aiming to identify a new anti-inflammatory drug prototype based on Dipyrone® structure, a set of 27 molecules were virtually screened, and 4 compounds containing the active metabolite 4-aminoantipyrine and 1,4-dioxo-2-butenyl fragment were selected for docking, synthesis, and biological evaluation. The selection was based on the number of H-bonds and π- π stacking interactions between the inhibitor and the amino acids within the binding site of the enzyme. Carrageenan-induced paw edema, acetic acid-induced writhing, and formalin assays were used to evaluate inflammation and pain response. The selected compounds 1-4 inhibited the involvement of biogenic amines in the formation of paw edema. Compounds 1-4 also reduced pain in the inflammatory response phase. It has to be noted that 4-AA may cause agranulocytosis, which should be borne in mind when developing drug candidates of similar structure. Our new drug prototypes based on 4-aminoantipyrine and 1,4-dioxo-2-butenyl moieties open a gate for developing a prototype of nonsteroidal anti-inflammatory drugs.

Planar Proton Minibeam Irradiation Elicits Spatially Confined DNA Damage in a Human Epidermis Model.

Purpose: High doses of ionizing radiation in radiotherapy can elicit undesirable side effects to the skin. Proton minibeam radiotherapy (pMBRT) may circumvent such limitations due to tissue-sparing effects observed at the macro scale. Here, we mapped DNA damage dynamics in a 3D tissue context at the sub-cellular level. Methods: Epidermis models were irradiated with planar proton minibeams of 66 µm, 408 µm and 920 µm widths and inter-beam-distances of 2.5 mm at an average dose of 2 Gy using the scanning-ion-microscope SNAKE in Garching, GER. γ-H2AX + 53BP1 and cleaved-caspase-3 immunostaining revealed dsDNA damage and cell death, respectively, in time courses from 0.5 to 72 h after irradiation. Results: Focused 66 µm pMBRT induced sharply localized severe DNA damage (pan-γ-H2AX) in cells at the dose peaks, while damage in the dose valleys was similar to sham control. pMBRT with 408 µm and 920 µm minibeams induced DSB foci in all cells. At 72 h after irradiation, DNA damage had reached sham levels, indicating successful DNA repair. Increased frequencies of active-caspase-3 and pan-γ-H2AX-positive cells revealed incipient cell death at late time points. Conclusions: The spatially confined distribution of DNA damage appears to underlie the tissue-sparing effect after focused pMBRT. Thus, pMBRT may be the method of choice in radiotherapy to reduce side effects to the skin.

A bibliometric analysis of Health Promotion International content regarding unions, unionization and collective agreements.

A recent article brought together the health benefits of unionization and working under collective agreements. It was noted how Canadian health promotion texts, reports and statements made no mention of unionization and working under collective agreements as promoting health. This was seen as a significant omission and reasons for this were considered. In this article this analysis is extended to consider how contributors to the flagship health promotion journal Health Promotion International (HPI) conceptualize unions, unionization and working under collective agreements as promoting health. Of 2443 articles published in HPI since its inception, 87 or 3.6% make mention of unions, unionization, collective agreements or collective bargaining, with most saying little about their promoting health. Instead, 20 make cursory references to unions or merely see them as providing support and engagement opportunities for individuals. Forty-five depict unions or union members as involved in a health promotion programme or activity carried out by the authors or by government agencies. Only 33 articles explicitly mention unions, unionization or collective agreements as potentially health promoting, representing 1.3% of total HPI content since 1986. We conclude that the health promoting possibilities of unionization and working under collective agreements is a neglected area amongst HPI contributors. Reasons for this are explored and an Organisation for Economic Cooperation and Development report on the importance of collective bargaining is drawn upon to identify areas for health promotion research and action.

Lantana canescens (Kunth) inhibits inflammatory and hyperalgesic responses in murine models.

ETHNOPHARMACOLOGICAL RELEVANCE: Lantana canescens is popularly known in Brazil as "cidreirinha" or "chumbinho-branco". It is found in Pantanal biome and its flowers and leaves are used in traditional medicine to treat pain and inflammation. Information about this species is limited to the activity of isolated essential oils. Studies with different extracts, composition, and biological properties are still scarce. AIM OF THIS STUDY: The objective of this study was to evaluate the anti-inflammatory and anti-hyperalgesic activity of the hydroethanolic extract of L. canescens aerial parts. MATERIALS AND METHODS: The hydroethanolic extract L. canescens aerial parts (HELc) was analyzed using HPLC-DAD-EM. Male and female Swiss mice weighing 18-25 g were used in the in vivo assays. Acute toxicity was assessed (2000 mg/kg); anti-inflammatory activity through paw edema, mast cell degranulation and peritonitis, and anti-hyperalgesic activity through abdominal writhing assays induced by acetic acid and formalin sensitization, were evaluated using the doses of 3, 30 and 300 mg/kg. RESULTS: The phytochemical characterization of HELc confirmed the presence of glycosylated iridoids (theveside, theviridoside), verbascosides and flavonoids. The HELc did not present toxicity in the evaluated dose. HELc reduced formation of paw edema, degranulation of peritoneal mast cells and infiltration of polymorphonuclear cells into the animals peritoneal cavity. In addition, HELc decreased the number of abdominal writhing induced by acetic acid and the time of paw licking in the evaluation of formalin sensitization. CONCLUSIONS: These results confirm the anti-inflammatory and anti-hyperalgesic effects of hydroethanolic extract of L. canescens, validating the use of this plant in folk medicine.

Aortic root dimensions as a correlate for aortic regurgitation's severity.

To evaluate the prevalence of aortic regurgitation (AR) and associations between the individual aortic root components and AR severity in the general population. The study included the first 10,000 participants of the population-based Hamburg City Health Study (HCHS) of whom 8259 subjects, aged 62.23 ± 8.46 years (51.3% females), enrolled 2016-2018, provided echocardiographic data. 69 subjects with bicuspid valves and 23 subjects with moderate/severe aortic stenosis were excluded. Aortic root dimensions were measured using state-of-the-art cardiac ultrasound, including the aortic annulus, sinus of Valsalva, sinotubular junction (STJ), and ascending aorta, in diastole and systole. The distribution of AR was: 932 (11.4%) mild, 208 (2.5%) moderate, and 20 (0.24%) severe. Patients with moderate or severe AR were predominantly male at advanced age who had hypertension, coronary artery disease, atrial fibrillation, and renal dysfunction. Increasing AR severity correlated with higher absolute and indexed aortic root diameters (e.g., end-diastolic sinus of Valsalva for no-mild-moderate-severe AR in mm ± standard deviation: 34.06 ± 3.81; 35.65 ± 4.13; 36.13 ± 4.74; 39.67 ± 4.61; p < 0.001). In binary logistic regression analysis, all aortic root components showed significant associations with moderate/severe AR. Mid-systolic STJ showed the strongest association with moderate/severe AR (OR 1.33, 95% confidence interval 1.25-1.43, p < 0.001). AR was prevalent in 14.2%, of whom 2.8% showed moderate/severe AR. All assessed aortic root diameters correlated with the prevalence and severity of AR. STJ diameter had the strongest association with moderate/severe AR possibly reflecting the pathophysiological impact of an increasingly dilated STJ in the context of an ageing aorta.

Macrophage activation in vitro by Parachartergus fraternus venom.

Parachartergus fraternus wasp induces inflammation with a predominance of mononuclear cells, that can acquire macrophage functions at the sting site, amplifying the response. These cells can be activated by venomous animals and are involved in destruction of injurious agents and release of inflammatory mediators. The objective of this work was to evaluate the activity of P. fraternus venom (Pfv) on isolated murine macrophage function. The cells were obtained from peritoneal cavity of Swiss male mice and incubated with Pfv (2.5, 5 and 10 µg/mL). Cytotoxicity was determined using MTT assay. Adhesion and detachment were evaluated using violet crystal dye. Spreading was evaluated based on morphological parameters. Phagocytosis was performed with opsonized zymosan. Production of hydrogen peroxide (H2O2) and nitric oxide (NO) were quantified using the phenol red and Griess assays, respectively. Pfv at concentrations evaluated was not cytotoxic in MTT assay and did not cause macrophage detachment in cell culture plates. However, it increased adhesion of macrophage, spreading and phagocytosis of opsonized zymosan, as well as induced production of H2O2 and NO. Therefore, Pfv induces macrophage activation in vitro and the response of these cells can be correlated with the previously reported inflammatory process triggered by this wasp.

Genomic Adaption and Mutational Patterns in a HaCaT Subline Resistant to Alkylating Agents and Ionizing Radiation.

Sulfur mustard (SM) is a chemical warfare agent that can damage DNA via alkylation and oxidative stress. Because of its genotoxicity, SM is cancerogenic and the progenitor of many chemotherapeutics. Previously, we developed an SM-resistant cell line via chronic exposure of the popular keratinocyte cell line HaCaT to increasing doses of SM over a period of 40 months. In this study, we compared the genomic landscape of the SM-resistant cell line HaCaT/SM to its sensitive parental line HaCaT in order to gain insights into genetic changes associated with continuous alkylation and oxidative stress. We established chromosome numbers by cytogenetics, analyzed DNA copy number changes by means of array Comparative Genomic Hybridization (array CGH), employed the genome-wide chromosome conformation capture technique Hi-C to detect chromosomal translocations, and derived mutational signatures by whole-genome sequencing. We observed that chronic SM exposure eliminated the initially prevailing hypotetraploid cell population in favor of a hyperdiploid one, which contrasts with previous observations that link polyploidization to increased tolerance and adaptability toward genotoxic stress. Furthermore, we observed an accumulation of chromosomal translocations, frequently flanked by DNA copy number changes, which indicates a high rate of DNA double-strand breaks and their misrepair. HaCaT/SM-specific single-nucleotide variants showed enrichment of C > A and T > A transversions and a lower rate of deaminated cytosines in the CpG dinucleotide context. Given the frequent use of HaCaT in toxicology, this study provides a valuable data source with respect to the original genotype of HaCaT and the mutational signatures associated with chronic alkylation and oxidative stress.

Pro-inflammatory response induced by the venom of Parachartergus fraternus wasp.

The sting of different wasp species triggers local and systemic reactions in victims that can lead to death. Parachartergus fraternus is responsible for frequent accidents in Latin America; however, few studies have been conducted on this insect and its venom. In this study, the inflammatory process induced by the venom of the P. fraternus wasp (Pfv; 100, 200, and 400 µg/kg) was characterized. Mice were used to assess paw edema, vascular permeability, mast cell degranulation, leukocyte influx, nitric oxide (NO) production, expression of inflammatory genes, and histopathological changes. Pfv triggered edema formation with a peak dose of 200 µg/kg at 10 min. There was an increase in permeability in all periods and doses evaluated, with no differences between them. The 200 µg/kg dose induced mast cell degranulation in all periods, with a peak at 15 min. This same dose induced leukocyte influx with a predominance of mononuclear cells and triggered a peak in NO production in the 12th hour. The increase in COX-2, iNOS, and IFN-γ mRNA expression occurred after 1 and 6 h, and there was an increase in IL-10 expression after 48 h. In addition, Pfv triggered edema and induced an influx of macrophages and mast cells into the injection site. Therefore, Pfv induces an inflammatory process from the first 5 min of inoculation that can persist for up to 48 h.

Consumer, health professional and employment specialist experiences of an individual placement and support programme.

BACKGROUND: Individuals with severe mental illness (SMI) are under-represented in the workforce. The Individual Placement and Support (IPS) programme is an evidence-based intervention that co-locates an Employment Specialist in a community mental health team to support individuals with a SMI with their goal of finding work. Previous research predominantly explored IPS programme outcomes rather than stakeholder experiences. AIM: To explore programme stakeholder perspectives and experiences during the early stages of IPS programme implementation. METHODS: Qualitative descriptive methodology explored consumers (n = 11), health professionals and employment specialist (n = 11) perceptions and experiences of the IPS programme. Semi-structured interviews were conducted and thematically analysed. RESULTS: Three main themes emerged: enacting core care philosophies, IPS programme process and catalyst for supportive environments and relationships. The combination of IPS programme relationships, enactment of core care philosophies, and programme process promoted development of supportive environments and relationships for consumers participating in the programme. CONCLUSION: Findings suggest IPS processes promoted the enactment of person-centred and recovery-oriented care approaches and positively influenced care planning practices and service culture. SIGNIFICANCE: IPS directly tackles the compounding disadvantage resulting from unemployment for people with a SMI. At a service level, IPS can foster positive changes to care practices and service culture.