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Trichomonas vaginalis, a common sexually transmitted parasite that colonizes the human urogenital tract, secretes extracellular vesicles (TvEVs) that are taken up by human cells and are speculated to be taken up by parasites as well. While the crosstalk between TvEVs and human cells has led to insight into host:parasite interactions, roles for TvEVs in infection have largely been one-sided, with little known about the effect of TvEV uptake by T. vaginalis. Approximately 11% of infections are found to be coinfections of multiple T. vaginalis strains. Clinical isolates often differ in their adherence to and cytolysis of host cells, underscoring the importance of understanding the effects of TvEV uptake within the parasite population. To address this question, our lab tested the ability of a less adherent strain of T. vaginalis, G3, to take up fluorescently labeled TvEVs derived from both itself (G3-EVs) and TvEVs from a more adherent strain of the parasite (B7RC2-EVs). Here, we showed that TvEVs generated from the more adherent strain are internalized more efficiently compared to the less adherent strain. Additionally, preincubation of G3 parasites with B7RC2-EVs increases parasite aggregation and adherence to host cells. Transcriptomics revealed that TvEVs up-regulate expression of predicted parasite membrane proteins and identified an adherence factor, heteropolysaccharide binding protein (HPB2). Finally, using comparative proteomics and superresolution microscopy, we demonstrated direct transfer of an adherence factor, cadherin-like protein, from TvEVs to the recipient parasites surface. This work identifies TvEVs as a mediator of parasite:parasite communication that may impact pathogenesis during mixed infections.

Abstract Background Eating disorders (EDs) are associated with high morbidity and mortality, affecting predominantly young people and women. A delay in starting treatment is associated with chronic and more severe clinical courses; however, evidence on barriers and facilitators of access to care in Latin America is scarce. We aimed to identify barriers and facilitators of ED treatment in Chile from the perspective of patients, relatives, and health professionals. Methods Qualitative approach through semi-structured interviews with patients, their relatives, and health professionals. Participants were recruited from two ED centers in Santiago, Chile (one public and one private). Analysis was mainly based on Grounded Theory, using MAXQDA software. Results 40 interviews were conducted (n = 22 patients, 10 relatives, and 8 health professionals). The mean age of patients was 21.8 years, while the mean duration of untreated ED was 91.4 months (median 70 months). Five categories emerged with intersections between them: patient (P), family and social environment (FSE), health professionals (HP), healthcare system (HCS), and social and cultural context (SCC). Relevant barriers appeared within these categories and their intersections, highlighting a lack of professional knowledge or expertise, cultural ignorance or misinformation regarding EDs, and patient’s ego-syntonic behaviors. The main facilitators were patients’ and relatives’ psychoeducation, recognition of symptoms by family members, and parents taking the initiative to seek treatment. Conclusions This study provides information regarding access to treatment for patients living with EDs in Chile. A practical public health approach should consider the multi-causality of delay in treatment and promoting early interventions. Plain English Summary Eating disorders (EDs) may severely affect the daily functioning of people enduring them. A delay in starting treatment is associated with a disease that is more difficult to treat. To our knowledge, there are no published studies carried out in Latin America exploring factors influencing treatment initiation in EDs patients. This study aimed to identify facilitators of and barriers to treating patients with EDs in Chile. We interviewed patients (n = 22), their relatives (n = 10), and health professionals (n = 8) from a private and a public center in Santiago, Chile. Our analysis showed that the main barriers to starting treatment were the lack of professional knowledge in ED, the monetary cost of illness, and cultural misinformation. Facilitators were related to the role of the family in recognizing and addressing the disease while being educated in EDs by professionals. This study helps to provide data about treatment access in developing countries. While facilitators and barriers were similar to others reported in the literature, the untreated ED’s duration was longer. It is essential to address these barriers to provide access to treatment more efficiently and prevent severe and enduring forms of disease.

Abstract Background Narratives (including memoirs and novels) about eating disorders (EDs) are typically published with the intention to benefit readers, but survey evidence suggests that reading such narratives with an active ED may more often be harmful than helpful. To reduce the probability of inadvertent harm and learn more about how narrative reading and EDs interact, a pre-publication study was designed to determine whether or not a recovery memoir should be published. Methods 64 participants with a self-reported ED read either the experimental text (The Hungry Anorexic [HA]) or a control text (Ten Zen Questions [TZ]) over a roughly two-week period. All participants completed the Eating Disorder Examination Questionnaire (EDE-Q) and the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ) one week before and two weeks after reading, and answered three recurring open-ended questions at regular timepoints during and after the reading. Computational analysis of the free-text responses assessed text/response similarity and response characteristics on emotional, sensory, and action-effector dimensions. Both rating-scale and free-text data were analysed using mixed ANOVAs to test for effects of time and condition, and the university ethics board was notified in advance of the quantitative threshold for harmful effects that would prohibit the ED memoir from being published. Results On the two quantitative measures, there was an effect of time but not of condition: Significant improvement was found in both groups on the EDE-Q (with a medium-to-large effect size) and the ANSOCQ (with a very large effect size). In an ANCOVA analysis, no significant mediating effects were found for age, education, duration of professional support for the ED, or pre/post-reading BMI change. For the free-text responses, linguistic similarity measures indicated that HA responses most closely matched the text of HA, with the same being true for TZ. In a word-norm analysis, text condition significantly affected six emotional, sensory, and action-effector variables (interoception, olfaction, gustatory, mouth, torso, and hand/arm), mean scores for all of which were higher in HA responses than TZ responses. Close reading of readers’ responses explored two potential mechanisms for the positive effects of time but not condition: engagement with the during-reading prompts as part of the experimental setup and engagement with the texts’ dialogical form. Conclusions The ED memoir was found not to yield measurably harmful effects for readers with an ED, and will therefore be published. The finding that significant improvement on both quantitative measures was observed irrespective of text condition suggests that positive effects may be attributable to linguistic characteristics shared by the two texts or to elements of the reading and/or reflective processes scaffolded by both. The quantitative results and the free-text testimony have implications for our understanding of bibliotherapy, “triggering”, and the practicalities of responsible publishing.

Objective: To perform a retrospective, multicenter, external validation of the Cleveland Clinic malignancy probability prediction model for incidental pulmonary nodules. Patients and Methods: From July 1, 2022, to May 31, 2023, we identified 296 patients who underwent tissue acquisition at Mayo Clinic (MC) (n=198) and Loyola University Medical Center (n=98) with histopathology indicating malignant (n=195) or benign (n=101). Data was collected at initial radiographic identification (point 1) and at the time of intervention (point 2). Point 3 represented the most recent data. The areas under the receiver operating characteristics were calculated for each model per time point. Calibration was evaluated by comparing the predicted and observed rates of malignancy. Results: The areas under the receiver operating characteristics at time points 1, 2, and 3 for the MC model were 0.67 (95% CI, 0.61-0.74), 0.67 (95% CI, 0.58-0.77), and 0.70 (95% CI, 0.63-0.76), respectively. The Cleveland Clinic model (CCM) was 0.68 (95% CI, 0.61-0.74), 0.75 (95% CI, 0.65-0.84), and 0.72 (95% CI, 0.66-0.78), respectively. The mean ± SD estimated probability for malignant pulmonary nodules (PNs) at time points 1, 2, and 3 for the CCM was 64.2±25.9, 65.8±24.0, and 64.7±24.4, which resembled the overall proportion of malignant PNs (66%). The mean estimated probability of malignancy for the MC model at each time point was 38.3±27.4, 36.2±24.4, and 42.1±27.3, substantially lower than the observed proportion of malignancies. Conclusion: The CCM found discrimination similar to its internal validation and good calibration. The CCM can be used to augment clinical and shared decision-making when evaluating high-risk PNs.

Abstract Regulatory T cells (Tregs) are plastic cells playing a pivotal role in the maintenance of immune homeostasis. Tregs actively adapt to the microenvironment where they reside; as a consequence, their molecular and functional profiles differ among tissues and pathologies. In tumors, the features acquired by Tregs remains poorly characterized. Here, we observe that human tumor-infiltrating Tregs selectively overexpress CD74, the MHC class II invariant chain. CD74 has been previously described as a regulator of antigen-presenting cell biology, however its function in Tregs remains unknown. CD74 genetic deletion in human primary Tregs reveals that CD74KO Tregs exhibit major defects in the organization of their actin cytoskeleton and intracellular organelles. Additionally, intratumoral CD74KO Tregs show a decreased activation, a drop in Foxp3 expression, a low accumulation in the tumor, and consistently, they are associated with accelerated tumor rejection in preclinical models in female mice. These observations are unique to tumor conditions as, at steady state, CD74KO-Treg phenotype, survival, and suppressive capacity are unaffected in vitro and in vivo. CD74 therefore emerges as a specific regulator of tumor-infiltrating Tregs and as a target to interfere with Treg anti-tumor activity.

To identify medical phrases utilized by the critical care team that may have an unintended impact on the critically ill patient, we administered an anonymous survey to multi-professional critical care team members. We elicited examples of imprecise language that may have a negative emotional impact on the critically ill. Of the 1600 providers surveyed, 265 offered 1379 examples (912 unique) which were clustered into 5 categories. Medical jargon (eg, “riding the vent”) was most prevalent (n = 549). There were 217 negative suggestions (eg, “you will feel a stick and a burn”). Hyperboles (eg, “black cloud”) were common (n = 198) while homonyms (ie “he fibbed”) accounted for 150 examples. Phrases such as “code brown in there” were categorized as metonyms (n = 144). 121 metaphors/similes (eg, “rearranging deck chairs on the Titanic”) were provided. Phrases that have the potential to negatively impact critically ill patient perceptions are commonplace in critical care practice. Whether these everyday communication habits lead to an unintended nocebo effect on mental health outcomes of the critically ill deserves further study.

Objectives: The early initiation of the empirical antibiotic treatment and its impact on mortality in patients with bacteraemia has been extensively studied. However, information on the impact of precocity of the targeted antibiotic treatment is scarce. We aimed to study the impact of further delay in active antibiotic therapy on 30-day mortality among patients with bloodstream infection who had not received appropriate empirical therapy. Design: We worked with PROBAC cohort (prospective and compound by patients from 26 different Spanish hospitals). We selected a total of 1703 patients, who survived to day 2 without having received any active antibiotic therapy against the causative pathogen. Results: The 30-day mortality was 14% (238 patients). The adjusted odds of mortality increased for every day of delay, from 1.53 (95% confidence interval (CI) 1.13-2.08) for day 3 or after to 11.38 (95% CI 7.95-16.38) for day 6 or after. Conclusion: We concluded that among patients who had not received active treatment within the first 2 days of blood culture collection, additional delays in active targeted therapy were associated with increased mortality. These results emphasize the importance of active interventions in the management of patients with bloodstream infections.

In this article, deployable cylindrical vaults of reciprocal linkages with frustoconical ends are analysed. Deployable cylindrical vaults with quadrangular scissors modules have low stiffness in the longitudinal direction, which requires the use of stiffening bars after deployment. The truncated cone-shaped ends improve their stiffness but do not prevent bracing. However, if reciprocal knots are used, the mesh performance improves considerably. This article studies the design conditions of these vaults and their resistance to gravity, wind suction and wind loads in the transverse and longitudinal directions. We also study the different resistance behaviour of the mesh, depending on whether the roof is supported on the upper or lower joints. In all cases, model tests are carried out to check the validity of the proposed solutions. Both theoretical calculations and experimental tests demonstrate the viability and effectiveness of this type of structure.

Background: A nationwide, prospective, multicenter, cohort study (the Disease-Related caloric-protein malnutrition EChOgraphy (DRECO) study) was designed to assess the usefulness of ultrasound of the rectus femoris for detecting sarcopenia in hospitalized patients at risk of malnutrition and to define cut-off values of ultrasound measures. Methods: Patients at risk of malnutrition according to the Malnutrition Universal Screening Tool (MUST) underwent handgrip dynamometry, bioelectrical impedance analysis (BIA), a Timed Up and Go (TUG) test, and rectus femoris ultrasound studies. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were used to define categories of sarcopenia (at risk, probable, confirmed, severe). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the optimal diagnostic sensitivity, specificity, and predictive values of cut-off points of the ultrasound measures for the detection of risk of sarcopenia and probable, confirmed, and severe sarcopenia. Results: A total of 1000 subjects were included and 991 of them (58.9% men, mean age 58.5 years) were evaluated. Risk of sarcopenia was detected in 9.6% patients, probable sarcopenia in 14%, confirmed sarcopenia in 9.7%, and severe sarcopenia in 3.9%, with significant differences in the distribution of groups between men and women (p < 0.0001). The cross-sectional area (CSA) of the rectus femoris showed a significantly positive correlation with body cell mass of BIA and handgrip strength, and a significant negative correlation with TUG. Cut-off values were similar within each category of sarcopenia, ranging between 2.40 cm2 and 3.66 cm2 for CSA, 32.57 mm and 40.21 mm for the X-axis, and 7.85 mm and 10.4 mm for the Y-axis. In general, these cut-off values showed high sensitivities, particularly for the categories of confirmed and severe sarcopenia, with male patients also showing better sensitivities than women. Conclusions: Sarcopenia in hospitalized patients at risk of malnutrition was high. Cut-off values for the better sensitivities and specificities of ultrasound measures of the rectus femoris are established. The use of ultrasound of the rectus femoris could be used for the prediction of sarcopenia and be useful to integrate nutritional study into real clinical practice.

Pulmonary artery pseudoaneurysms (PAPs) are rare and life-threatening occurrences. We present a 57-year-old male patient with squamous cell lung cancer, who presented with hemoptysis. Bronchoscopy did not reveal ongoing bleeding. Imaging showed a left lower lobe tumor, a cavitary lesion communicating with the bronchus, and a pulmonary artery pseudoaneurysm. Successful embolization of the originating segmental branch of the pulmonary artery was performed. The pathogenesis of PAPs associated with primary lung malignancies remains poorly understood. We propose a four-step mechanism involving primary tumor expansion, central cavitary necrosis, direct arterial invasion, inflammatory response, vessel wall damage, pseudoaneurysm formation, and subsequent filling of the former cavitary lesion. This case emphasizes the importance of considering PAPs in primary lung malignancies, particularly in male patients with squamous cell pathology. Understanding the proposed pathogenic mechanism could lead to early detection, prompt intervention, and improved outcomes.

This paper presents baseline results from the NutriEcoMuscle study, a multicenter observational study conducted in Spain which focused on changes in nutritional status, body composition, and functionality in post-intensive care unit (ICU) COVID-19 patients following a nutritional intervention. Assessments at hospital discharge included Subjective Global Assessment (SGA), Global Leadership Initiative on Malnutrition (GLIM) criteria, the Barthel index, handgrip strength (HGS) and the Timed Up-and-Go test, bioelectrical impedance analysis (BIA), and nutritional ultrasound (US). The study involved 96 patients (71.9% male, mean age 58.8 years, mean BMI 28.8 kg/m2, 36.5% obese). All patients were malnourished at discharge according to GLIM and SGA. Functional status declined from admission up to hospital discharge. A total of 33.3% of patients had a low fat-free mass index (FFMI) and 29.5% had a low phase angle (PhA). Myosteatosis was observed in 83.7% of the population. There was a positive correlation between rectus femoris cross-sectional area, PhA, FFMI, and HGS. In conclusion, post-critically ill COVID-19 patients commonly suffer from malnutrition and reduced muscle mass, causing a loss of independence at hospital discharge. BIA and US could be valuable tools for assessing body composition in these patients. The NutriEcoMuscle study highlights the need for a thorough nutritional and morphofunctional status assessment of post-ICU patients.

No research has yet experimentally evaluated the role of narrative fiction in relation to eating disorders (EDs). This study used a between-participants design to assess vulnerability to EDs before and after reading two contemporary U.S. young adult sports novels. ED vulnerability was measured using the EAT-26 and a tailored questionnaire. The experimental group (n = 32) received the books with text-specific reading guides. The control group (n = 33) received only the novels. Our hypothesis was that post-reading measures would be lower (improved) in both groups, but more markedly in the experimental group. Scores were typically lower in the experimental group and higher in the control group, but these differences were not statistically significant after correction for multiple comparisons. These findings underline the need to expand empirical evidence on the effects of narrative reading in the context of EDs, while the innovative methods trialed here open up new methodological avenues. [ABSTRACT FROM AUTHOR]

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Background Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. Aims To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. Methods CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey–Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. Results A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02–3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00–1.62], moderate–severe activity in HBI [HR 1.79; 95% CI: 1.20–2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02–1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. Conclusion In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments. [ABSTRACT FROM AUTHOR]

Medial meniscal ramp injury has gained the attention of orthopaedic surgeons in recent years. It consists of a tear of the peripheral insertion of the posterior horn of the medial meniscus. Its prevalence in anterior cruciate ligament reconstruction varies between 9% and 40% according to different studies. Ramp lesions cannot always be diagnosed using magnetic resonance imaging scans. To identify ramp lesions, the arthroscope should be introduced into the posteromedial compartment of the knee during the routine examination of the knee (Gillquist maneuver). Not all authors advocate systematically repairing ramp injuries of the medial meniscus, especially when these injuries are small and stable. They have historically been repaired using an outside-in technique using a hook-type suture passed through a posteromedial portal. In this study, we present our all-inside suture technique without the use of a posteromedial portal. [Display omitted] [ABSTRACT FROM AUTHOR]

Pulmonary artery pseudoaneurysms (PAPs) are rare and life-threatening occurrences. We present a 57-year-old male patient with squamous cell lung cancer, who presented with hemoptysis. Bronchoscopy did not reveal ongoing bleeding. Imaging showed a left lower lobe tumor, a cavitary lesion communicating with the bronchus, and a pulmonary artery pseudoaneurysm. Successful embolization of the originating segmental branch of the pulmonary artery was performed. The pathogenesis of PAPs associated with primary lung malignancies remains poorly understood. We propose a four-step mechanism involving primary tumor expansion, central cavitary necrosis, direct arterial invasion, inflammatory response, vessel wall damage, pseudoaneurysm formation, and subsequent filling of the former cavitary lesion. This case emphasizes the importance of considering PAPs in primary lung malignancies, particularly in male patients with squamous cell pathology. Understanding the proposed pathogenic mechanism could lead to early detection, prompt intervention, and improved outcomes. [ABSTRACT FROM AUTHOR]