Conectar
by Evan R. Polzer, Ryan Holliday, Carly M. Rohs, Suzanne M. Thomas, Christin N. Miller, Joseph A. Simonetti, Lisa A. Brenner, Lindsey L. Monteith
AimsFirearms have become an increasingly common method of suicide among women Veterans, yet this population has rarely been a focus in firearm suicide prevention research. Limited knowledge is available regarding the preferences, experiences, or needs of women Veterans with respect to firearm lethal means counseling (LMC), an evidence-based suicide prevention strategy. Understanding is necessary to optimize delivery for this population.
MethodOur sample included forty women Veterans with lifetime suicidal ideation or suicide attempt(s) and firearm access following military separation, all enrolled in the Veterans Health Administration. Participants were interviewed regarding their perspectives, experiences, and preferences for firearm LMC. Data were analyzed using a mixed inductive-deductive thematic analysis.
ResultsWomen Veterans’ firearm and firearm LMC perspectives were shaped by their military service histories and identity, military sexual trauma, spouses/partners, children, rurality, and experiences with suicidal ideation and attempts. Half reported they had not engaged in firearm LMC previously. For those who had, positive aspects included a trusting, caring relationship, direct communication of rationale for questions, and discussion of exceptions to confidentiality. Negative aspects included conversations that felt impersonal, not sufficiently comprehensive, and Veterans’ fears regarding implications of disclosure, which impeded conversations. Women Veterans’ preferences for future firearm LMC encompassed providers communicating why such conversations are important, how they should be framed (e.g., around safety and genuine concern), what they should entail (e.g., discussing concerns regarding disclosure), whom should initiate (e.g., trusted caring provider) and where they should occur (e.g., safe spaces, women-specific groups comprised of peers).
DiscussionThis study is the first to examine women Veterans’ experiences with, and preferences for, firearm LMC. Detailed inquiry of the nuances of how, where, why, and by whom firearms are stored and used may help to facilitate firearm LMC with women Veterans.
by Alexia Loste, Marc Clément, Sandrine Delbosc, Kevin Guedj, Jean Sénémaud, Anh-Thu Gaston, Marion Morvan, Guillaume Even, Grégory Gautier, Alexander Eggel, Michel Arock, Emanuele Procopio, Catherine Deschildre, Liliane Louedec, Jean-Baptiste Michel, Lydia Deschamps, Yves Castier, Raphaël Coscas, Jean-Marc Alsac, Pierre Launay, Giuseppina Caligiuri, Antonino Nicoletti, Marie Le Borgne
AimsIgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression.
Methods and resultsThrough histological assays conducted on human surgical samples from AAA patients, we uncovered that activated MCs were enriched at sites of unhealed haematomas, due to subclinical aortic wall fissuring, in close proximity to adventitial IgE+ TLO B cells. Remarkably, in vitro the IgEs deriving from these samples enhanced MC production of IL-4, a cytokine which favors IgE class-switching and production by B cells. Finally, the role of MCs in aneurysmal progression was further analysed in vivo in ApoE-/- mice subjected to angiotensin II infusion aneurysm model, through MC-specific depletion after the establishment of dissecting aneurysms. MC-specific depletion improved intramural haematoma healing and reduced aneurysmal progression.
ConclusionsOur data suggest that MC located close to aortic wall fissures are activated by adventitial TLO B cell-produced IgEs and participate to their own activation by providing support for further IgE synthesis through IL-4 production. By preventing prompt repair of aortic subclinical fissures, such a runaway MC activation loop could precipitate aneurysmal progression, suggesting that MC-targeting treatments may represent an interesting adjunctive therapy for reducing AAA progression.
by Wim Van Neer, Mircea Udrescu, Joris Peters, Bea De Cupere, Stéphane Pasquali, Stéphanie Porcier
Since predynastic times, baboons (Papio hamadryas and Papio anubis) were important in ancient Egypt for ritual and religious purposes. These species did not occur naturally in Egypt and therefore had to be imported, but little is known about their exact provenance and the conditions in which they were kept through time. Here, we analyse the skeletal remains of a collection of baboon mummies coming from Thebes (Egypt), representing a minimum of 36 individuals, from a palaeopathological and demographic point of view. The pathological cases are described, figured where relevant, and the discussion attempts to understand their aetiology. The prevalence of the different types of deformations and pathologies is compared with that of other captive baboon populations from more or less contemporary (Tuna el-Gebel and Saqqara) or older (predynastic Hierakonpolis) sites. This is combined with observations on the age and sex distribution and the proportion of hamadryas and anubis baboons to draw conclusions about the conditions of keeping, possible breeding on-site, provenance of the animals and the trade routes used for import. As in Tuna el-Gebel and Saqqara, the baboons from Gabbanat el-Qurud suffered from numerous metabolic diseases due to chronic lack of sunlight and an unbalanced diet. This and the demographic data suggest that there was a local breeding population derived from animals captured downstream from the Sudanese Nile Valley (for anubis) and from the Horn of Africa or the southern part of the Arabian Peninsula (for hamadryas). A new series of radiocarbon dates is provided, placing the baboons from Gabbanat el-Qurud between the end of the Third Intermediate Period and the beginning of the Late Period.by Ana Rubio-Garcia, Aldert L. Zomer, Ruoshui Guo, John W. A. Rossen, Jan H. van Zeijl, Jaap A. Wagenaar, Roosmarijn E. C. Luiken
Animal rehabilitation centres provide a unique opportunity to study the microbiome of wild animals because subjects will be handled for their treatment and can therefore be sampled longitudinally. However, rehabilitation may have unintended consequences on the animals’ microbiome because of a less varied and suboptimal diet, possible medical treatment and exposure to a different environment and human handlers. Our study describes the gut microbiome of two large seal cohorts, 50 pups (0–30 days old at arrival) and 23 weaners (more than 60 days old at arrival) of stranded harbour seals admitted for rehabilitation at the Sealcentre Pieterburen in the Netherlands, and the effect of rehabilitation on it. Faecal samples were collected from all seals at arrival, two times during rehabilitation and before release. Only seals that did not receive antimicrobial treatment were included in the study. The average time in rehabilitation was 95 days for the pups and 63 days for the weaners. We observed that during rehabilitation, there was an increase in the relative abundance of some of the Campylobacterota spp and Actinobacteriota spp. The alpha diversity of the pups’ microbiome increased significantly during their rehabilitation (p-valueby Soeurette Policar, Alana Sharp, Joanne Isidor Hyppolite, Gérald Marie Alfred, Eva Steide, Leïnadine Lucien, Naiké Ledan, Matthew Kavanagh
BackgroundFailure to retain people living with HIV (PLHIV) in care remains a significant barrier to achieving epidemic control in Haiti, with as many as 30% lost from care within one year of starting treatment. Community-led monitoring (CLM) is an emerging approach of improving healthcare and accountability to service users, through a cycle of monitoring and advocacy. In 2020, a CLM program was launched in Haiti to identify barriers to retention and advocating for better health services.
MethodsData from the community-led monitoring program in Haiti were analyzed, from a sample of 65 healthcare facilities in the Nord, Artibonite, and Ouest departments collected from April 2021 to February 2022. Qualitative data from six community-based focus groups and 45 semi-structured individual interviews were analyzed.
ResultsConfidentiality and stigmatization emerged as barriers to care, particularly due to the separation of PLHIV from other patients in view of community members. To avoid identification, patients described traveling long distances, with the reimbursement of transportation costs described as being insufficient or unavailable. Costs of non-HIV clinical services were a frequent concern and respondents described a need for clinics to provide food during all patient visits. Stock-outs were a regular challenge; by contrast, treatment literacy did not emerge as a major barrier to retention.
ConclusionsThese findings represent the first instance, to our knowledge, of original data from a community-led monitoring program being published in any country. These findings suggest that improving treatment retention for PLHIV is dependent on improving the acceptability and affordability of healthcare services. Ensuring confidentiality is critical, particularly where stigma is high. Retention could be improved by systematically strengthening patient confidentiality protections throughout the healthcare system, providing patients with sufficient travel compensation and other incentives, and delivering wraparound services provided for free. Addressing these challenges will require ongoing advocacy for community-developed recommendations and solutions.
by Peng Wang, Onno J. Arntz, Johanna F. A. Husch, Van der Kraan P. M., Jeroen J. J. P. van den Beucken, Fons A. J. van de Loo
Mesenchymal stromal/stem cell derived-extracellular vesicles (MSC-EVs) have gained interest as drug delivery nanoparticles, having immunoregulatory and potentiating tissue repair property. To maintain growth of MSCs and obtain pure MSC-derived EVs, the culture media should contain fetal bovine serum (FBS) devoid of EVs, as the presence of FBS EVs confounds the properties of MSC-EVs. Therefore, we tested three methods: 18h ultracentrifugation (UC) and ultrafiltration (UF), which are common FBS EV depletion methods in current MSC-EV research, and polyethylene glycol (PEG) precipitation to obtain three EV depleted FBS (EVdFBS) batches, and compared them to FBS and commercial (Com) EVdFBS on human adipose stem cell (hADSC) growth, differentiation, enrichment of EVs in hADSC supernatant and their biological function on collagen metabolism. Our comparative study showed UC and UF vary in terms of depletion efficiency and do not completely deplete EVs and affects the growth-promoting quality of FBS. Specifically, FBS EV depletion was comparable between PEG (95.6%) and UF (96.6%) but less by UC (82%), as compared to FBS. FBS protein loss was markedly different among PEG (47%), UF (87%), and UC (51%), implying the ratio of EV depletion over protein loss was PEG (2.03), UF (1.11), and UC (1.61). A significant decrease of TGFβ/Smad signaling, involving in MSC growth and physiology, was observed by UF. After 96 hours of exposure to 5% FBS or 5% four different EVdFBS cell growth media, the osteogenesis ability of hADSCs was not impaired but slightly lower mRNA expression level of Col2a observed in EVdFBS media during chondrogenesis. In consistent with low confluency of hADSCs observed by optical microscope, cell proliferation in response to 5% UF EVdFBS media was inhibited significantly. Importantly, more and purer ADSCs EVs were obtained from ADSCs cultured in 5% PEG EVdFBS media, and they retained bioactive as they upregulated the expression of Col1a1, TIMP1 of human knee synovial fibroblast. Taken together, this study showed that PEG precipitation is the most efficient method to obtain EV depleted FBS for growth of MSCs, and to obtain MSC EVs with minimal FBS EV contamination.by Bushra Sabri, Chakra Budhathoki, Allison M. McFall, Shruti H. Mehta, David D. Celentano, Sunil S. Solomon, Aylur K. Srikrishnan, Santhanam Anand, Canjeevaram K. Vasudevan, Gregory M. Lucas
Lifetime exposures to violence among men who have sex with men (MSM) are associated with multiple psychosocial health risks and can affect engagement and outcomes of HIV treatment. This study a) explored relationships between levels of exposures to violence and HIV care continuum outcomes among MSM living with HIV in India, and b) identified psychosocial correlates of HIV care continuum outcomes among MSM living with HIV and those with lifetime cumulative exposures to violence (CVE). CVE referred to exposures to violence in both childhood and adulthood. This cross-sectional analysis used survey data collected between August 2016 and May 2017 from 1763 men who have sex with men living with HIV across 10 cities in India, using respondent-driven sampling. We found that higher levels of violence exposure were significantly associated with lower awareness of HIV positive status, and lower likelihood of initiating antiretroviral therapy. Compared with MSM living with HIV that had no CVE, those with CVE were more likely to report perpetration of interpersonal violence, alcohol misuse, depressive symptoms, and HIV transmission risk behaviors and to have two to four co-occurring psychosocial problems. In multivariable analysis with the subset of MSM with CVE, psychosocial correlates significantly associated with at least one HIV care continuum outcome were HIV transmission risk behaviors, perpetration of interpersonal violence, depression, and alcohol misuse. The findings highlight the need for integrating care for lifetime violence exposures and associated behavioral problems in HIV care settings for men who have sex with men living with HIV in India.by Yufeng Zhang, Keith D. Aaronson, Jonathan Gryak, Emily Wittrup, Cristian Minoccheri, Jessica R. Golbus, Kayvan Najarian
BackgroundTimely referral for advanced therapies (i.e., heart transplantation, left ventricular assist device) is critical for ensuring optimal outcomes for heart failure patients. Using electronic health records, our goal was to use data from a single hospitalization to develop an interpretable clinical decision-making system for predicting the need for advanced therapies at the subsequent hospitalization.
MethodsMichigan Medicine heart failure patients from 2013–2021 with a left ventricular ejection fraction ≤ 35% and at least two heart failure hospitalizations within one year were used to train an interpretable machine learning model constructed using fuzzy logic and tropical geometry. Clinical knowledge was used to initialize the model. The performance and robustness of the model were evaluated with the mean and standard deviation of the area under the receiver operating curve (AUC), the area under the precision-recall curve (AUPRC), and the F1 score of the ensemble. We inferred membership functions from the model for continuous clinical variables, extracted decision rules, and then evaluated their relative importance.
ResultsThe model was trained and validated using data from 557 heart failure hospitalizations from 300 patients, of whom 193 received advanced therapies. The mean (standard deviation) of AUC, AUPRC, and F1 scores of the proposed model initialized with clinical knowledge was 0.747 (0.080), 0.642 (0.080), and 0.569 (0.067), respectively, showing superior predictive performance or increased interpretability over other machine learning methods. The model learned critical risk factors predicting the need for advanced therapies in the subsequent hospitalization. Furthermore, our model displayed transparent rule sets composed of these critical concepts to justify the prediction.
ConclusionThese results demonstrate the ability to successfully predict the need for advanced heart failure therapies by generating transparent and accessible clinical rules although further research is needed to prospectively validate the risk factors identified by the model.
by Matthias Bosman, Dustin N. Krüger, Kasper Favere, Guido R. Y. De Meyer, Constantijn Franssen, Emeline M. Van Craenenbroeck, Pieter-Jan Guns
Apart from cardiotoxicity, the chemotherapeutic agent doxorubicin (DOX) provokes acute and long-term vascular toxicity. Dexrazoxane (DEXRA) is an effective drug for treatment of DOX-induced cardiotoxicity, yet it remains currently unknown whether DEXRA prevents vascular toxicity associated with DOX. Accordingly, the present study aimed to evaluate the protective potential of DEXRA against DOX-related vascular toxicity in a previously-established in vivo and ex vivo model of vascular dysfunction induced by 16 hour (h) DOX exposure. Vascular function was evaluated in the thoracic aorta in organ baths, 16h after administration of DOX (4 mg/kg) or DOX with DEXRA (40 mg/kg) to male C57BL6/J mice. In parallel, vascular reactivity was evaluated after ex vivo incubation (16h) of murine aortic segments with DOX (1 μM) or DOX with DEXRA (10 μM). In both in vivo and ex vivo experiments, DOX impaired acetylcholine-stimulated endothelium-dependent vasodilation. In the ex vivo setting, DOX additionally attenuated phenylephrine-elicited vascular smooth muscle cell (VSMC) contraction. Importantly, DEXRA failed to prevent DOX-induced endothelial dysfunction and hypocontraction. Furthermore, RT-qPCR and Western blotting showed that DOX decreased the protein levels of topoisomerase-IIβ (TOP-IIβ), a key target of DEXRA, in the heart, but not in the aorta. Additionally, the effect of N-acetylcysteine (NAC, 10 μM), a reactive oxygen species (ROS) scavenger, was evaluated ex vivo. NAC did not prevent DOX-induced impairment of acetylcholine-stimulated vasodilation. In conclusion, our results show that DEXRA fails to prevent vascular toxicity resulting from 16h DOX treatment. This may relate to DOX provoking vascular toxicity in a ROS- and TOP-IIβ-independent way, at least in the evaluated acute setting. However, it is important to mention that these findings only apply to the acute (16h) treatment period, and further research is warranted to delineate the therapeutic potential of DEXRA against vascular toxicity associated with longer-term repetitive DOX dosing.by Lucie Barthe, Vanessa Soldan, Luis F. Garcia-Alles
Bacterial micro-compartments (BMC) are complex macromolecular assemblies that participate in varied metabolic processes in about 20% of bacterial species. Most of these organisms carry BMC genetic information organized in operons that often include several paralog genes coding for components of the compartment shell. BMC shell constituents can be classified depending on their oligomerization state as hexamers (BMC-H), pentamers (BMC-P) or trimers (BMC-T). Formation of hetero-oligomers combining different protein homologs is theoretically feasible, something that could ultimately modify BMC shell rigidity or permeability, for instance. Despite that, it remains largely unknown whether hetero-oligomerization is a widespread phenomenon. Here, we demonstrated that the tripartite GFP (tGFP) reporter technology is an appropriate tool that might be exploited for such purposes. Thus, after optimizing parameters such as the size of linkers connecting investigated proteins to GFP10 or GFP11 peptides, the type and strength of promoters, or the impact of placing coding cassettes in the same or different plasmids, homo-oligomerization processes could be successfully monitored for any of the three BMC shell classes. Moreover, the screen perfectly reproduced published data on hetero-association between couples of CcmK homologues from Syn. sp. PCC6803, which were obtained following a different approach. This study paves the way for mid/high throughput screens to characterize the extent of hetero-oligomerization occurrence in BMC-possessing bacteria, and most especially in organisms endowed with several BMC types and carrying numerous shell paralogs. On the other hand, our study also unveiled technology limitations deriving from the low solubility of one of the components of this modified split-GFP approach, the GFP1-9.by Gerben A. van Kleef, Florian Wanders, Annelies E. M. van Vianen, Rohan L. Dunham, Xinkai Du, Astrid C. Homan
Norms play an important role in upholding orderly and well-functioning societies. Indeed, violations of norms can undermine social coordination and stability. Much is known about the antecedents of norm violations, but their social consequences are poorly understood. In particular, it remains unclear when and how norm violators gain or lose influence in groups. Some studies found that norm violators elicit negative responses that curtail their influence in groups, whereas other studies documented positive consequences that enhance violators’ influence. We propose that the complex relationship between norm violation and influence can be understood by considering that norm violations differentially shape perceptions of dominance and prestige, which tend to have opposite effects on voluntary influence granting, depending on the type of norm that is violated. We first provide correlational (Study 1) and causal (Study 2) evidence that norm violations are associated with dominance, and norm abidance with prestige. We then examine how dominance, prestige, and resultant influence granting are shaped by whether local group norms and/or global community norms are violated. In Study 3, protagonists who violated global (university) norms but followed local (sorority/fraternity) norms were more strongly endorsed as leaders than protagonists who followed global norms but violated local norms, because the former were perceived not only as high on dominance but also on prestige. In Study 4, popular high-school students were remembered as violating global (school) norms while abiding by local (peer) norms. In Study 5, individuals who violated global (organizational) norms while abiding by local (team) norms were assigned more leadership tasks when global and local norms conflicted (making violators “rebels with a cause”) than when norms did not conflict, because the former situation inspired greater prestige. We discuss implications for the social dynamics of norms, hierarchy development, and leader emergence.by Ivana Radovic, Igor Krdzic, Ana Jovanovic, Danka Vukasinovic, Ivan Soldatovic, Masa Petrovic, Ana Tomic, Tanja Jesic-Petrovic, Aleksandar Matejic, Bojana Salovic, Ilic-Zivojinovic Jelena
ObjectiveTranscultural adaptation and validation of FACIT-TS-PS questionnaire to Serbian language.
MethodsStandard forward and backward translation from English to Serbian language was performed. Pilot testing of FACIT-TS-PS was conducted on 12 patients with a confirmed diagnosis of malignant tumor. The study included 154 patients with malignant disease. The Questionnaire of Patient Satisfaction was used as a validated tool to evaluate concurrent validity of FACIT-TS-PS questionnaire. Reproducibility was tested on 30 subjects who answered the questionnaire for the second time two weeks later.
ResultsThree FACIT-TS-PS subscales (Physician Communication, Treatment Staff Communication and Nurse Communication) demonstrated satisfactory construct validity using Cronbach’s alpha, the remaining two subscales (Technical Competence and Confidence & Trust) showed high ceiling effect. Treatment Staff Communication subscale showed large floor effect. Concurrent validity was demonstrated by correlation with the two dimensions of the Questionnaire of Patient Satisfaction. Satisfactory reproducibility was demonstrated on 30 patients who filled the questionnaire for the second time two weeks after initial interview.
ConclusionThe Serbian version of FACIT-TS-PS with the omission of Treatment Staff Communication subscale could be used as a valid instrument to assess patient and treatment satisfaction in chronically ill patients in the Serbian population. Omission of Treatment Staff Communication subscale is necessary because it contains questions not relevant for patients in Serbian healthcare system.
by Ivana Bozicevic, Tatjana Nemeth Blazic, Mirjana Lana Kosanovic Licina, Tatjana Marijan, Tomislav Mestrovic, Tihana De Zan, Aleksandar Stulhofer
To determine the prevalence of genital Chlamydia trachomatis (chlamydia) infection, knowledge about chlamydia and experience of previous testing for chlamydia, we carried out a national probability-based survey in emerging adults aged 18–25 years in Croatia in 2021–2022. Participants (n = 1197), members of a national online panel, completed a web-based questionnaire that collected information on socio-demographics, sexual behaviours and knowledge about sexually transmitted infections (STIs). Urine specimens from a sample of sexually experienced participants were self-collected and tested for chlamydia using Cobas 4800 CT/NG test. To achieve broad representativeness of the emerging adult population in the country, we applied post-hoc weighting for gender and age. Multivariable ordinary least squares linear regression was used to determine correlates of knowledge about chlamydia infection and binomial logistic regression to assess correlates of the willingness to test for chlamydia. Among 448 participants who sent in their urine specimens chlamydia prevalence was 2.5% (95% CI 1.2–5.1) in women and 1.0% (0.3–3.2%) in men. A total of 8.0% of women and 4.7% men reported testing for chlamydia prior to the survey. About a quarter of the sample was characterized by not answering correctly any of the six questions related to knowledge about chlamydia, while only 9.6% had five or six correct answers. In the multivariable analysis, significantly higher odds of willingness to test for chlamydia were found in females compared to males (OR = 1.34, p = 0.024), those with better knowledge about the infection (OR = 1.11, p = 0.005), and those with lower religiosity (OR = 0.91, p = 0.017). In conclusion, prevalence of chlamydia in emerging adults in Croatia is considerable. Efforts to control this infection should focus on primary prevention and targeted testing combined with effective case management strategies.by Alan Cervantes-Guzmán, Kyle McPherson, Jimena Olveres, Carlos Francisco Moreno-García, Fabián Torres Robles, Eyad Elyan, Boris Escalante-Ramírez
Cardiovascular diseases related to the right side of the heart, such as Pulmonary Hypertension, are some of the leading causes of death among the Mexican (and worldwide) population. To avoid invasive techniques such as catheterizing the heart, improving the segmenting performance of medical echocardiographic systems can be an option to early detect diseases related to the right-side of the heart. While current medical imaging systems perform well segmenting automatically the left side of the heart, they typically struggle segmenting the right-side cavities. This paper presents a robust cardiac segmentation algorithm based on the popular U-NET architecture capable of accurately segmenting the four cavities with a reduced training dataset. Moreover, we propose two additional steps to improve the quality of the results in our machine learning model, 1) a segmentation algorithm capable of accurately detecting cone shapes (as it has been trained and refined with multiple data sources) and 2) a post-processing step which refines the shape and contours of the segmentation based on heuristics provided by the clinicians. Our results demonstrate that the proposed techniques achieve segmentation accuracy comparable to state-of-the-art methods in datasets commonly used for this practice, as well as in datasets compiled by our medical team. Furthermore, we tested the validity of the post-processing correction step within the same sequence of images and demonstrated its consistency with manual segmentations performed by clinicians.
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