Angiographic and Histopathological Characteristics of a Novel Polyacrylate Liquid Embolic Agent Compared to EVOH in a Large Animal Model.

PURPOSE: To study the in vivo safety and efficacy of a novel radiopaque non-adhesive polyacrylate peripheral liquid embolic system (PA, AMBER SEL-P) relative to ethylene vinyl alcohol copolymer (EVOH, OnyxTM) in a healthy swine endovascular model. MATERIALS AND METHODS: Twenty-five swine underwent rete mirabile and bilateral kidney embolization with PA or EVOH and were followed up for 24 hours (n=5) and 30 days (n=10), and 3 (n=10) months. Angiographic features (penetrability, radiopacity, catheter entrapment, fragmentation, occlusion, and vasospasm) were evaluated. Necropsy and histology were used to evaluate the non-target embolization, safety, target-embolization effectiveness by recanalization and to analyze the vascular response. RESULTS: No adverse events occurred during the embolization process or study period. The angiographic performance confirmed a significant positive effect of PA compared to EVOH in terms of penetrability (p=0.007), catheter entrapment (p=0.007), fragmentation (p=0.007), vascular occlusion (p=0.038), vasospasm (p=0.038), and follow-up vascular occlusion (p=0.038). Pre-necropsy angiography found no vascular recanalization in the organs treated with PA, while it was detected at 3 months in two samples treated with EVOH. Histologically, PA was classified as non-irritant compared with EVOH under the study conditions according to ISO 10993-6:2016 as modified. No systemic effects during necropsy were detected in the animals treated with these agents. CONCLUSION: This in vivo study concludes that the angiographic behavior of PA has advantages compared to EVOH. The embolization and biocompatibility of PA are similar to those of EVOH. PA is safe and effective for transarterial embolization in an acute, subacute, and chronic endovascular embolization model.

ELLIS Study: Comparative Analysis of Excimer Laser Coronary Angioplasty and Intravascular Lithotripsy on Drug-Eluting Stent as Assessed by Scanning Electron Microscopy.

BACKGROUND: Stent underexpansion is a significant challenge in percutaneous coronary intervention, critically impacting patient outcomes. While excimer laser coronary angioplasty (ELCA) and intravascular lithotripsy (IVL) are increasingly used to address this issue, their full impact on the integrity of drug-eluting stents remains unclear, raising concerns about their safety and efficacy. METHODS: This in vitro study assessed the effects of ELCA and IVL on the structural integrity of drug-eluting stents using scanning electron microscopy. Nine stents, 5 Onyx Frontier (with durable circumferential polymer coating) and 4 Cre8 (polymer-free), were implanted in a 3-dimensional coronary artery simulator following standardized protocols. After implantation, treatments with saline-ELCA, contrast-ELCA, IVL, and high-pressure balloon dilatation were applied. A comprehensive evaluation of the stent surface was performed at 60-fold magnification. RESULTS: Scanning electron microscopy analysis revealed significant differences in polymer damage between the techniques. High-pressure balloon dilatation and contrast-ELCA exhibited substantial polymer fragmentation and detachment compared with IVL, saline-ELCA, and conventional dilatation. High-pressure balloon dilatation demonstrated the highest incidence of polymer shaving and overcoating. No significant alterations were observed in polymer-free stents, regardless of the technique used. CONCLUSIONS: IVL and saline-ELCA applied immediately after stent implantation produce minimal polymer damage, whereas high-pressure balloon dilatation and contrast-ELCA cause significant damage to the polymer coating. The integrity of polymer-free drug-eluting stent appears stable regardless of the technique used. Further research is needed to validate these findings and explore their clinical implications.

Impact of APOE ε4 and ε2 on plasma neurofilament light chain and cognition in autosomal dominant Alzheimer's disease.

BACKGROUND: Apolipoprotein E (APOE) genotypes have been suggested to influence cognitive impairment and clinical onset in presenilin-1 (PSEN1) E280A carriers for autosomal dominant Alzheimer's disease (ADAD). Less is known about their impact on the trajectory of biomarker changes. Neurofilament light chain (NfL), a marker of neurodegeneration, begins to accumulate in plasma about 20 years prior to the clinical onset of ADAD. In this study we investigated the impact of APOE ε4 and ε2 variants on age-related plasma NfL increases and cognition in PSEN1 E280A mutation carriers. METHODS: We analyzed cross-sectional data from PSEN1 E280A mutation carriers and non-carriers recruited from the Alzheimer's Prevention Initiative Registry of ADAD. All participants over 18 years with available APOE genotype, plasma NfL, and neuropsychological evaluation were included in this study. APOE genotypes and plasma NfL concentrations were characterized for each participant. Cubic spline models using a Hamiltonian Markov chain Monte Carlo method were used to characterize the respective impact of at least one APOE ε4 or ε2 allele on age-related log-transformed plasma NfL increases. Linear regression models were estimated to explore the impact of APOE ε4 and ε2 variants and plasma NfL on a composite cognitive test score in the ADAD mutation carrier and non-carrier groups. RESULTS: Analyses included 788 PSEN1 E280A mutation carriers (169 APOE ε4 + , 114 ε2 +) and 650 mutation non-carriers (165 APOE ε4 + , 80 ε2 +), aged 18-75 years. APOE ε4 allele carriers were distinguished from ε4 non-carriers by greater age-related NfL elevations in the ADAD mutation carrier group, beginning about three years after the mutation carriers' estimated median age at mild cognitive impairment onset. APOE ε2 allele carriers had lower plasma NfL concentrations than ε2 non-carriers in both the ADAD mutation carrier and non-carrier groups, unrelated to age, and an attenuated relationship between higher NfL levels on cognitive decline in the ADAD mutation carrier group. CONCLUSIONS: APOE ε4 accelerates age-related plasma NfL increases and APOE ε2 attenuates the relationship between higher plasma NfL levels and cognitive decline in ADAD. NfL may be a useful biomarker to assess clinical efficacy of APOE-modifying drugs with the potential to help in the treatment and prevention of ADAD.

Multiple Biomarker Responses in Aegla castro Exposed to Copper: A Laboratory Approach.

Although some biomarkers have already been determined in aeglids collected in the field, data from laboratory exposures are scarce. To our knowledge, no studies have investigated oxidative stress biomarkers in aeglids exposed to metals in the laboratory, or performed hemocyte counts and the comet assay using gill and hepatopancreas of aeglids. Thus, we investigated the effects of acute Cu exposure on intermolt males of Aegla castro, collected from a reference stream, acclimated for 6 days in the laboratory, and then exposed to 11 µg L-1 of dissolved Cu (Cu 11) or only to water (CTR), for 24 h. Gill and hepatopancreas samples were used to determine Cu accumulation, DNA damage, and metallothionein content (MT), while hemolymph samples were used to determine Cu accumulation, DNA damage, and hemocyte counts. Muscle samples were used to determine Cu accumulation and acetylcholinesterase activity (AChE). Non-protein thiol content (NPSH), catalase (CAT), glutathione S-transferase activities (GST), lipoperoxidation (LPO), and protein carbonylation content (PCC) were measured only in the hepatopancreas. Aegla castro exposed to Cu accumulated this metal in gills and activated detoxification mechanisms, through increased MT content in the gill, and showed an immune response, evidenced by an increase in hyaline hemocytes. Therefore, gill and hemocytes appear to have a protective role in preventing the transport and bioavailability of Cu through the body. On the other hand, we observed a decrease in MT content in the hepatopancreas of crabs exposed to Cu, suggesting the excretion of MT in association with Cu bound to the sulfhydryl groups of this protein.

Liraglutide effects on epicardial adipose tissue micro-RNAs and intra-operative glucose control.

BACKGROUND AND AIM: Epicardial adipose tissue (EAT) plays a role in coronary artery disease (CAD). EAT has regional distribution throughout the heart and each location may have a different genetic profile and function. Glucagon like peptide-1 receptor analogs (GLP-1RAs) reduce cardiovascular risk. However, the short-term effects of GLP-1RA on microRNA (miRNA) profile of each EAT location is unknown. Objective was to evaluate if EAT miRNAs were different between coronary (CORO-EAT), left atrial EAT (LA-EAT) and subcutaneous fat (SAT), and liraglutide can modulate EAT miRNAs expression. METHODS AND RESULTS: This was a 12-week randomized, double-blind, placebo-controlled study in 38 patients with type 2 diabetes (T2DM) and coronary artery disease (CAD) who were started on either liraglutide or placebo for a minimum of 4 up to 12 weeks prior to coronary artery by-pass grafting (CABG). Fat samples were collected during CABG. miR16, miR155 and miR181a were significantly higher in CORO-EAT and in LA-EAT than SAT (p < 0.01 and p < 0.05) in overall patients. miR16 and miR181-a were significantly higher in CORO-EAT than SAT (p < 0.01), and miR155 and miR181a were higher in LA-EAT than SAT (p < 0.05) in the liraglutide group. Liraglutide-treated patients had better intra-op glucose control than placebo (146 ± 21 vs 160 ± 21 mg/dl, p < 0.01). CONCLUSIONS: Our study shows that CORO- and LA-miRNAs profiles were significantly different than SAT miRNAs in overall patients and miRNAs were significantly higher in CORO-EAT and LA-EAT than SAT in the liraglutide group. Pre-op liraglutide was also associated with better intra operative glucose control than placebo independently of weight loss.

What Women with HIV Know about Heart Health and Cardiovascular Risk and Intervention Preferences.

Cardiovascular disease (CVD) is a significant health concern influenced by various determinants. Stigma and resilience have emerged as factors in CVD development and management. Women with HIV (WWH) have higher CVD rates than women without HIV. To improve cardiovascular health for WWH, a comprehensive understanding of how these factors interact, the understanding about individual awareness and willingness to engage in risk-reduction interventions are needed. Methods: As part of a study examining CVD risk among WWH aged >35 years old, 90-min focus groups were conducted (May 2022) in the English language. Focus groups aimed to elicit participants' CVD risk knowledge and potential prevention strategies. Transcripts underwent a qualitative analysis. Results: Nineteen WWH participated in three focus groups. Participants experienced the following: (a) enacted stigma related to their HIV diagnosis (e.g., family, church member, healthcare staff); (b) a recent event (e.g., hospitalization of self/family, death in family, chest pain) triggered both heart health-promoting lifestyle changes and suboptimal health behaviors (e.g., COVID-19 pandemic: unhealthy snacking). Participants wanted to obtain more knowledge ("on a mission") about CVD risk. In total, 100% expressed willingness to take medication or embark on other lifestyle changes to prevent future CVD events. Although participants identified preventative heart health behaviors (e.g., eating healthy foods; exercising; limiting stress, substances, and smoking), misconceptions were also identified (e.g., "catching" heart disease). Conclusions: Understanding the interplay of the different factors related to heart health is needed both at the provider and the patient level to inform interventions that reduce CVD risk amongst racial/ethnic minoritized women with HIV, living in the Southern region of the US.

Factors affecting infant feeding choices with a focus on barriers to exclusive breastfeeding in Western Jamaica: a qualitative study.

BACKGROUND: Despite the many benefits of exclusive breastfeeding to infants and mothers, only 33% of Jamaican infants are exclusively breastfed up to the recommend six months. This study was conducted to identify factors affecting mothers' feeding choices focusing on barriers to exclusive breastfeeding of infants six weeks to less than six months old. METHODS: A qualitative study consisting of four focus group discussion sessions was conducted among 22 mothers attending postnatal clinics in western Jamaica from May to August 2016. The transcripts were coded by three independent coders and content analysis conducted to generate themes. RESULTS: Four themes were identified namely, perceived advantages of breastfeeding centered mainly on the benefits of breastfeeding for the infant and mother, perceived barriers of breastfeeding highlighting physical pain and fatigue, supplementing culturally acceptable complementary foods and herbal remedies, and cultural norms including perception of how breastfeeding affects a woman's body, societal sources of breastfeeding information, satiation of infants, and family and other support. Mothers overwhelmingly agreed that breastfeeding was inexpensive, allowed them to bond with their infants and was good for the overall health and intellectual development of the infants. They identified painful nipples, engorged breasts, lack of sleep, physical exhaustion and pressure to return to work as barriers to breastfeeding. Mothers named a number of complementary foods, such as pumpkin, carrots, potato, banana, and chocho (Chayote), that were culturally accepted for feeding infants in Jamaica and discussed herbs that were considered to aid in infants' nutrition and overall health. Other cultural factors that were noted to influence exclusive breastfeeding were mothers feeling that breastfeeding would help their bodies, especially their bellies, go back to their pre-maternity figure, sources of breastfeeding information in the society including the internet, belief that breast milk alone does not satisfy babies, and family and other support. CONCLUSION: Mothers in this study identified unique challenges to exclusive breastfeeding that if addressed, would help to increase exclusive breastfeeding so that the World Health Organization's exclusive breastfeeding recommendations can be achieved.

Comparative evaluation of local and downstream responses in two commercially available paclitaxel-coated balloons in healthy peripheral arteries of a swine model.

OBJECTIVE: To investigate the local, downstream, and systemic effects of 2 different paclitaxel-coated balloons. DESIGN: Preclinical study in healthy peripheral arteries of a swine model, with randomized allocation of the distribution of the devices: the test paclitaxel-coated balloon (PCB) (LuminorⓇ), a control PCB (IN.PACTⓇ), and a plain angioplasty balloon (OceanusⓇ), considering single (1×) and overlapping (3×) doses with simple blind histologic analysis. METHODS: Twenty animals underwent balloon angioplasty at 1× or 3× doses in the external and internal branches of both femoral arteries and were followed-up for 28 days. Postprocedural and follow-up angiography were carried out. Comprehensive necropsy and histology were used to evaluate the local, downstream and systemic effects. RESULTS: Angioplasty was successfully carried out in all animals. Significant protocol deviations appeared in 3 arteries (treated with Oceanus®) without clinical relevance. Those samples were excluded from the analysis. All the animals survived the follow-up period without major clinical issues. Local signs of drug toxicity were less marked with Luminor® than IN.PACT® at 1× dose, including endothelial loss (P = .0828), intima/media inflammation (P = .0004), transmural medial smooth muscle cell (SMC) loss (P = .0016), wall thickness loss (P = .0141), presence of fibrin in the vascular wall (P = .0054), and adventitial inflammation (P = .0080). A similar pattern was observed at the 3× dose for endothelial loss (P = .0011), intima/media inflammation (P < .0001), circumferential SMC loss (P = .0004), medial SMC replacement with proteoglycans (P = .0014), fibrin (P = .0034), and collagen content (P = .0205). Downstream vascular histologic changes were mild although more prevalent in the IN.PACT® 3× group (P = .006). No systemic effects of toxicity were detected in any of the samples analyzed. CONCLUSION: Luminor® showed better healing pattern (lower inflammation, and endothelial and muscular loss) than IN.PACT® balloon. The effect was evident at single and triple doses. The prevalence of downstream lesions, albeit low, was higher with the triple dose of IN.PACT® compared with Luminor®.

Ethnic differences in the patterns, sources, and reasons for cannabis use among cancer patients at an NCI-Designated Cancer Center.

OBJECTIVE: This study aims to describe patterns, sources, and reasons for cannabis use among cancer patients by ethnic group. METHODS: Data are from a cross-sectional study of 416 surveys collected via RedCap anonymously from adult cancer patients seen at a National Cancer Institute-designated comprehensive cancer center within the last 5 years. A harmonized survey was created with 11 other National Cancer Institute centers to assess cannabis use patterns, sources, and reasons for use. Sociodemographics and cancer details were also collected via self-report. Descriptive statistics by ethnic group were compared using χ2 and Fisher exact tests. RESULTS: Among the sample (age mean = 50.4 [15.7] years; 53% male; 8.3% lesbian, gay, bisexual, transgender, queer; 46.7% Hispanic and Latinx individuals), 69.6% reported lifetime use of cannabis, 33.7% began cannabis use after cancer diagnosis, 48.1% of those consuming cannabis did not have a prescription for cannabis, and 29.4% of cannabis users consumed daily. The frequency of cannabis use (P = .04) and reasons for cannabis use (P = .02) varied by ethnic group. Sleep and pain were the most prevalent reasons for use among the Hispanics and Latinx populations; pain, mental health management, and neuropathy were the most prevalent reasons for cannabis use among non-Hispanic White individuals. CONCLUSIONS: Patterns and reasons for cannabis use differed among cancer patients by ethnic group in this exploratory cross-sectional study aimed to provide data for more rigorous study. Understanding these distinctions are pivotal in conducting more rigorous studies that address the unique needs of diverse populations utilizing cannabis for managing cancer-related symptoms.

The association between breakfast frequency and diabetes incidence in middle-aged women: Results from the MTC study.

BACKGROUND AND AIMS: Breakfast consumption could have a synchronizer role in chronobiological functions. Across observational studies, the assessment of breakfast frequency consumption is heterogeneous, therefore consensus on the relation between of weekly frequency of breakfast consumption and the risk of diabetes is unclear. We examined the relation between weekly breakfast frequency consumption and the incidence of diabetes in middle-age women. METHODS AND RESULTS: Since baseline (2006-2008) we prospectively followed 71,373 women from the Mexican Teachers' Cohort. Participants were classified according to breakfast consumption frequency of 0, 1-3, 4-6, or 7 days/week. Diabetes was identified by self-report and clinical-administrative databases. We used Cox proportional hazards multivariable models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for breakfast frequency and diabetes adjusting for covariates. Stratified analyses were performed for age, birth weight, ethnicity, and physical activity. We identified 3613 new diabetes cases between baseline and 2014. The prevalence of daily breakfast consumers was 25%. The median follow-up was 2.2 years, interquartile range 1.8-3.8 years. Relative to women who skipped breakfast, those who consumed breakfast every day had a 12% lower risk of diabetes (multivariable HR = 0.88; 95% CI 0.78, 0.99; p-trend = 0.0018). One additional day per week of breakfast was associated with a lower risk of diabetes (HR = 0.98; 95% CI 0.97, 0.99). In stratified analysis, the observed inverse relation appeared to be stronger in women aged ≥40 years and in indigenous women. CONCLUSIONS: Breakfast frequency was inversely associated with the incidence of diabetes independently of lifestyle factors. Regular breakfast consumption may be a potential component of diabetes prevention.

Ovarian Sex Cord Stromal Tumor in a Free-Ranging Brown Bear (Ursus arctos).

Reports on neoplasms in bears are scarce, especially concerning ovarian tumors. A large primary ovarian neoplasm with multiple metastasis was found during the necropsy of a 14-year-old free-ranging Eurasian brown bear (Ursus arctos) from Northwestern Spain. Histopathology and immunohistochemistry allowed for the diagnosis of a sex cord stromal tumor. This is a complex group of neoplasms which differ in the predominant cell morphology and immunohistochemical features. The microscopic examination revealed two types of cells, one with eosinophilic cytoplasm, intermingled with larger vacuolated cells rich in lipids. The evaluation of the immunoreactivity to different markers, frequently used in the characterization of gonadal tumors (INHA, inhibin-alpha; PLAP, placental alkaline phosphatase; Ki-67; α-SMA, actin alpha-smooth muscle) and inflammation patterns (IBA1, ionized calcium-binding adapter molecule for macrophages; CD3 for T lymphocytes; CD20 for B lymphocytes), displayed significant INHA positive immunostaining of neoplastic cells, as well as inflammatory cell infiltration, mainly composed of macrophages and B lymphocytes. These findings were consistent with a malignant ovarian steroid cell tumor, not otherwise specified. The present study characterizes an unusual type of neoplasm, and also represents the first report of an ovarian sex cord stromal tumor in Ursidae.

Characterizing heart failure and its subtypes in people living with HIV.

OBJECTIVE: People living with HIV have an increased risk of heart failure (HF). There are different subtypes of HF. Knowledge about the factors differentiating HF subtypes in people with HIV is limited but necessary to guide preventive measures and treatment. METHODS: A retrospective review of medical records was undertaken in people with HIV aged ≥18 years who received care at the University of Miami/Jackson Memorial HIV Clinic between January 2017 and November 2019 (N = 1166). Patients with an echocardiogram available for review (n = 305) were included. HF was defined as a documented diagnosis of any HF subtype (n = 52). We stratified those with HF by their ejection fraction (EF) into HF with preserved EF (HFpEF), HF with borderline EF, or HF with reduced EF (HFrEF). RESULTS: The prevalence of HF was 4.5%. The cohort included 46.2% females and 75% self-identified African Americans. Those with HF had a higher prevalence of hypertension, prior myocardial infarction, angina, coronary artery disease, percutaneous coronary intervention, coronary artery bypass grafting, diastolic dysfunction, and left ventricle hypertrophy. People with HIV with HF with borderline EF exhibited more coronary artery disease than those with HFpEF. CONCLUSIONS: We characterize HF in people with HIV in South Florida and report the prevalence of HF and HF subtypes. Only a small percentage of patients had echocardiograms performed, suggesting an ongoing need for recognition of the increased risk of HF in people living with HIV, and raising the concern about lack of awareness contributing to underdiagnosis and missed treatment opportunities in this population.

Clima organizacional y gestión de la calidad en la Universidad Mayor de San Andrés Caso: División de títulos y diplomas / Organizational climate and quality management at the Major University of San Andrés Case: Division of degrees and diplomas / Gestão do clima organizacional e da qualidade na principal Universidade de San Andrés Caso: Divisão de graus e diplomas

El propósito del trabajo fue determinar la relación existente entre el clima organizacional y la gestión de la calidad en la División de Títulos y Diplomas (DTD), unidad administrativa de la Universidad Mayor de San Andrés (UMSA), institución pública y autónoma, responsable de la formación académica profesional, investigativa y social en la ciudad de La Paz. Para ello se empleó una metodología cuantitativa y un diseño correlacional transaccional; se elaboraron tres escalas que fueron validadas y confiabilizadas para luego ser aplicadas a funcionarios y usuarios de la DTD (seleccionados a través de muestras probabilísticas simples y censal); se contó también con una guía de entrevistas. Los resultados arrojan que en la DTD se cuenta con un clima organizacional participativo en el que resaltan el liderazgo, el trabajo en equipo y una visión positiva sobre sueldos y prestaciones recibidas; como debilidades resaltan el ambiente físico de trabajo, el diseño de puestos de trabajo y el desarrollo de carrera. La certificación en gestión de calidad es la mayor fortaleza a lo que se suma la orientación al cliente; la debilidad en gestión de calidad está centrada en la planificación. Finalmente se determinó que, si bien ambas variables están conectadas, el comportamiento de una no obedece exclusivamente al comportamiento de la otra, por lo que se infiere que existen otras variables que inciden en ellas, entre estas el compromiso, la normativa general institucional y el trato mismo que dispensa el usuario al funcionario.

The purpose of the work was to determine the relationship between the organizational climate and quality management in the Degrees and Diplomas Division (DTD), an administrative unit of the Universidad Mayor de San Andrés (UMSA), a public and autonomous institution, responsible for professional, investigative and social academic training in the city of La Paz. For this, a quantitative methodology and a transactional correlational design were used; Three scales were developed that were validated and made reliable and then applied to officials and users of the DTD (selected through simple probabilistic samples and census); There was also an interview guide. The results show that the DTD has a participatory organizational climate in which leadership, teamwork and a positive vision of salaries and benefits received stand out; as weaknesses they highlight the physical work environment, job design and career development. Certification in quality management is the greatest strength to which customer orientation is added; the weakness in quality management is focused on planning. Finally, it will be concluded that, although both variables are connected, the behavior of one does not obey exclusively to the behavior of the other, so it is inferred that there are other variables that affect them, among them the commitment, the general institutional regulations and the same treatment that dispenses the user to the officer.

O objetivo do trabalho foi determinar a relação entre o clima organizacional e a gestão da qualidade na Divisão de Graus e Diplomas (DTD), unidade administrativa da Universidade Mayor de San Andrés (UMSA), instituição pública e autônoma, responsável pela gestão profissional, formação acadêmica investigativa e social na cidade de La Paz. Para tanto, utilizou-se uma metodologia quantitativa e um desenho correlacional transacional; foram desenvolvidas três escalas que foram validadas e tornadas confiáveis ​​e depois aplicadas a funcionários e usuários da DTD (selecionados através de amostras probabilísticas simples e censo); havia também um guia de entrevista. Os resultados mostram que o DTD possui um clima organizacional participativo em que se destacam a liderança, o trabalho em equipe e uma visão positiva dos salários e benefícios recebidos; os pontos fracos incluem o ambiente físico de trabalho, a concepção do trabalho e o desenvolvimento da carreira. A certificação em gestão da qualidade é o maior ponto forte ao qual se soma a orientação para o cliente; A fraqueza na gestão da qualidade está focada no planejamento. Por fim, determinou-se que, embora ambos ases variáveis estejam conectadas, o comportamento de uma não obedece exclusivamente ao comportamento da outra, pelo que se infere que existem outras variáveis que as afetam, incluindo o comprometimento, as regulamentações institucionais gerais e o mesmo tratamento que o usuário dá ao funcionário.

Addressing the Missing Links in Cardiovascular Aging.

The aim of this manuscript is to provide a review of available options to enhance cardiovascular health and prevent cardiovascular disease (CVD) in the aging population using a systems-biology approach. These include the role of the gut microbiome, the early identification and removal of environmental toxins, and finally age related sex hormones and supplement replacement which all influence aging. Implementing such a comprehensive approach has the potential to facilitate earlier risk assessment, disease prevention, and even improve mortality. Further study in these areas will continue to advance our understanding and refine therapeutic interventions for a healthier cardiovascular aging process.

Loneliness, Methamphetamine Use, and Cardiovascular Risk Factors Among Sexual Minority Men in the COVID-19 Era.

BACKGROUND: Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV. METHOD: Participants were enrolled from August 2020 to February 2022 in a 6-month prospective cohort study. The study leveraged self-report baseline data from 103 SMM, with a subset of 56 SMM that provided a blood sample to measure markers of cardiovascular risk. RESULTS: Loneliness showed negative bivariate associations with total cholesterol and LDL cholesterol in the cardiometabolic subsample (n = 56). SMM with methamphetamine use (t(101) = 2.03, p < .05; d = .42) and those that screened positive for a stimulant use disorder (t(101) = 2.07, p < .05; d = .46) had significantly higher mean loneliness scores. In linear regression analyses, negative associations of loneliness with LDL and total cholesterol were observed only among SMM who used methamphetamine. CONCLUSION: We observed lower cholesterol in SMM reporting loneliness and methamphetamine use. Thus, in addition to the observed associations of loneliness with cholesterol, there are important medical consequences of methamphetamine use including cardiovascular risk, higher HIV acquisition risk and progression, as well as stimulant overdose death. This cross-sectional study underscores the need for clinical research to develop and test interventions targeting loneliness among SMM with stimulant use disorders.

Histological and Memory Alterations in an Innovative Alzheimer's Disease Animal Model by Vanadium Pentoxide Inhalation.

Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-ß (Aß) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aß plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.

How are we handling protein drugs in hospitals? A human factors and systems engineering approach to compare two hospitals and suggest a best practice.

Biopharmaceuticals are complex biological molecules that require careful storage and handling to ensure medication integrity. In this study, a work system analysis of real-world protein drug (PD) handling was performed with the following goals: identify main barriers and facilitators for successful adherence to accepted recommendations in PD handling, analyse differences in two organizations, and define a Best Current Practice in the real-life handling of PDs based on the results of the work system analysis. Observational study was held in two university hospitals in Spain and Sweden. Based on the Systems Engineering Initiative for Patient Safety (SEIPS) model, the tools chosen were: the PETT scan, in order to indicate the presence of barriers or facilitators for the PETT components (People, Environment, Tools, Tasks); the Tasks and tools matrices to construct a checklist to record direct observations during the real-life handling of biopharmaceuticals, and the Journey map to depict the work process. Observations were performed between March and November 2022. Each episode of direct observation included a single protein drug in some point of the supply chain and considered all the elements in the work system. Based on the results of the work system analysis and the literature review, the authors propose a list of items which could be assumed as Best Current Practice for PDs handling in hospitals. There were a total of 34 observations involving 19 PDs. Regarding People involved in the work process, there was a diversity of professionals with different previous training and knowledge, leading to an information gap. With respect to Environment, some structural and organizational differences between hospitals lead to risks related to the time exposure of PDs to room temperature and mechanical stress. Some differences also existed in the Tools and Tasks involved in the process, being especially relevant to the lack of compatibility information of PDs with new technologies, such as pneumatic tube system, robotic reconstitution, or closed-system transfer devices. Finally, 15 suggestions for best current practice are proposed. Main barriers found for compliance with accepted recommendations were related to the information gap detected in professionals involved in the handling of protein drugs, unmonitored temperature, and the lack of compatibility information of protein drugs with some new technologies. By applying a Human Factors and Systems Engineering Approach, the comparison of two European hospitals has led to a suggested list of Best Current Practices in the handling of protein drugs in a hospital.

Lower serum ferritin levels are associated with worse cognitive performance in aging.

OBJECTIVES: Iron is important for neurogenesis, synaptic development, and neurotransmitter synthesis. Serum ferritin (SF) is a reliable marker for assessing iron stores. Therefore, we evaluated the cognitive function associated with SF levels. We also assessed brain iron content using R2* Magnetic Resonance Imaging (MRI) and its association with SF levels. DESIGN: Data from three cross-sectional observational studies were used. Aging Imageomics (n = 1030) was conducted on aged subjects. Health Imageomics (n = 971) and IR0NMET (n = 175) were conducted in middle-aged subjects. SETTING AND PARTICIPANTS: Participants were enrolled at Dr. Josep Trueta University Hospital facilities. The three cohorts included a total of 2176 subjects (mean age, 52 years; 48% men). MEASUREMENTS: SF levels were measured by standard laboratory methods. Total Digits Span (TDS), and Phonemic Verbal Fluency (PVF) were used to assess executive function. Language function was assessed by semantic verbal fluency (SVF), attention by the Symbol Digit Modalities Test, and memory by the Memory Binding Tests - Total Free Recall and Total Delayed Free Recall. MRI was used to assess the iron content of the brain by R2*. RESULTS: In subjects aged 65 years or older, SF levels were associated with increased TDS (ß = 0.003, p = 0.02), PVF (ß = 0.004, p = 0.01), and SVF (ß = 0.004, p = 0.002) scores. After stratification by sex, these findings were significant only in men, where SF was associated with increased TDS (ß = 0.003, p = 0.01), PVF (ß = 0.004, p = 0.03), and SVF (ß = 0.004, p = 0.009) scores. In middle-aged subjects, SF was also associated with increased SVF scores (ß = 0.005, p = 0.011). Lastly, in men, SF levels were negatively associated with R2*, a surrogate marker of brain iron content, in both the left frontal inferior opercular area (r = -0.41, p = 0.005) and the right frontal inferior opercular area (r = -0.44, p = 0.002). CONCLUSIONS: SF is significantly and positively associated with cognition. In older people with low SF levels, iron supplementation may be a promising therapy to improve cognition.

Increased brain fractional perfusion in obesity using intravoxel incoherent motion (IVIM) MRI metrics.

OBJECTIVE: This research seeks to shed light on the associations between brain perfusion, cognitive function, and mental health in individuals with and without obesity. METHODS: In this study, we employed the noninvasive intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) technique to examine brain fractional perfusion (FP) in two groups: individuals with obesity (N = 72) and healthy controls (N = 66). Additionally, we investigated potential associations between FP, cognitive function, and depressive symptoms in the participants with and without obesity. Finally, artificial intelligence algorithms (Boruta analysis) were also used. RESULTS: Participants with obesity exhibited increased FP within dopaminergic brain circuits, particularly involving prefrontal cortex areas, anterior and posterior sections of the cingulate cortex, the right striatum, and the midbrain. Additionally, these individuals demonstrated lower working memory and higher depressive symptoms compared to the control group. Notably, higher FP in the inferior temporal and occipital cortices correlated with greater depressive symptoms, whereas increased FP in the right ventral caudate and the midbrain was associated with better working memory performance. A link between inflammatory and metabolic variables, with a particular emphasis on monocytes, and FP in obesity was also evidenced by Boruta analysis. CONCLUSIONS: Increased brain perfusion in individuals with obesity is associated with cognitive function and mental health through interaction with metabolic and inflammatory factors.

Unraveling the gut-brain connection: The association of microbiota-linked structural brain biomarkers with behavior and mental health.

AIM: The gut microbiota can influence human behavior. However, due to the massive multiple-testing problem, research into the relationship between microbiome ecosystems and the human brain faces drawbacks. This problem arises when attempting to correlate thousands of gut bacteria with thousands of brain voxels. METHODS: We performed brain magnetic resonance imaging (MRI) scans on 133 participants and applied machine-learning algorithms (Ridge regressions) combined with permutation tests. Using this approach, we were able to correlate specific gut bacterial families with brain MRI signals, circumventing the difficulties of massive multiple testing while considering sex, age, and body mass index as confounding factors. RESULTS: The relative abundance (RA) of the Selenomonadaceae, Clostridiaceae, and Veillonellaceae families in the gut was associated with altered cerebellar, visual, and frontal T2-mapping and diffusion tensor imaging measures. Conversely, decreased relative abundance of the Eubacteriaceae family was also linked to T2-mapping values in the cerebellum. Significantly, the brain regions associated with the gut microbiome were also correlated with depressive symptoms and attentional deficits. CONCLUSIONS: Our analytical strategy offers a promising approach for identifying potential brain biomarkers influenced by gut microbiota. By gathering a deeper understanding of the microbiota-brain connection, we can gain insights into the underlying mechanisms and potentially develop targeted interventions to mitigate the detrimental effects of dysbiosis on brain function and mental health.