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Urine-based immunoassay is a non-invasive method with demonstrated utility in detecting anti-SARS-CoV-2 antibodies in unvaccinated patients with COVID-19. To evaluate urine’s potential for serological surveys in a real-world setting, SARS-CoV-2 serology was performed on urine samples from vaccinated individuals, both with and without prior confirmed COVID-19. (1) Methods: An in-house indirect ELISA was used to measure antibodies against recombinant spike (S) and nucleocapsid (N) proteins of SARS-CoV-2 in urine and paired serum from 149 individuals vaccinated with Janssen AD26.COV2.S, an S protein-based COVID-19 vaccine. (2) Results: Anti-S and anti-N levels were higher in the urine and serum of participants with confirmed prior COVID-19 compared to those without prior infection. Urinary anti-S effectively distinguished vaccinated individuals with (AUC = 0.96) and without (AUC = 0.88) prior infection from negative controls (non-vaccinated, non-previously infected individuals) (p < 0.0001). Among vaccinated participants, urinary anti-S and anti-N identified prior infection, with AUC values of 0.73 (p < 0.0001) and 0.60 (p = 0.03), respectively, being recorded. (3) Conclusions: Findings indicate that urinary anti-SARS-CoV-2 antibodies reflect AD26.COV2.S vaccination and previous COVID-19. To further advance the methodology, studies with larger sample sizes and a greater diversity of COVID-19 vaccines are required.

The treatment of tegumentary leishmaniasis (TL) faces significant challenges, including drug toxicity, high costs, and the emergence of resistant strains. These limitations highlight the urgent need for novel antileishmanial agents and therapeutic strategies. This study evaluated blue light-emitting diode (LED) phototherapy as an alternative approach to inhibit Leishmania stationary promastigotes and treat infected mammalian models. In vitro assays using Leishmania amazonensis , L. braziliensis , and L. infantum demonstrated that blue LED significantly inhibited parasite growth during and after treatment, with inhibition levels comparable to those achieved with amphotericin B (AmpB). Treatment of infected macrophages with blue LED substantially reduced infection rates and amastigote recovery across all three parasite species. Ultrastructural analyses revealed the destruction of internal organelles and alterations to the surface membranes of all Leishmania species following blue LED exposure. In in vivo experiments, L. amazonensis -infected BALB/c mice were treated with AmpB, blue LED alone, combination of blue LED plus AmpB, or saline as a control. Animals treated with blue LED, particularly in combination with AmpB, exhibited significant reductions in parasite loads in infected tissues such as lesions, spleens, livers, and draining lymph nodes, as confirmed by limiting dilution assays and qPCR. Additionally, these treatments induced a robust antileishmanial Th1-type immune response, characterized by increased production of IFN-γ, IL-12, nitrite, and IgG2a antibodies. These findings suggest that blue LED phototherapy holds promise as a potential therapeutic strategy for TL and warrants further investigation in future studies.

Current treatment for visceral leishmaniasis (VL) is associated with toxicity, a high cost, and the emergence of drug-resistant parasite strains. Moreover, no human vaccine is available. In this context, immunotherapeutics combining vaccination and chemotherapy have emerged as a promising alternative. In this study, we combined a recombinant chimeric protein (ChimT) with the adjuvant 3-O-desacyl–monophosphoryl lipid A (MPLA) and the antileishmanial drug miltefosine (Milt) and used it to treat Leishmania infantum-infected mice. Parasitological, immunological, and toxicological assays were performed at 1 and 30 days post treatment. The ChimT/MPLA/Milt combination was the most effective therapeutic regimen, inducing robust Th1-type cellular and humoral immune responses, as demonstrated by increased levels of IFN-γ, IL-12, and TNF-α cytokines, nitrite, and IgG2a antibodies. These responses were associated with significant reductions in parasite load across various organs. Furthermore, the treatment showed low renal and hepatic toxicity at both evaluation time points. By contrast, ChimT alone, ChimT/MPLA, and Milt induced lower immunological and parasitological responses when compared with the ChimT/MPLA/Milt group. The results observed at 1 and 30 days post treatment demonstrated the potential of ChimT/MPLA/Milt combination against VL.

We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13–17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included (n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact (n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 (n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 (n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms (p < 0.001). Class 3 (n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month (p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.

Adenomyosis and leiomyomas are common benign uterine disorders characterized by abnormal cellular proliferation. The BCL6 protein, a transcriptional repressor implicated in cell proliferation and oncogenesis, has been linked to the pathogenesis of endometriosis. This study investigates BCL6 expression in adenomyosis, leiomyomas, and normal myometrium using immunohistochemistry and deep learning neural networks. We analyzed paraffin blocks from total hysterectomies performed between 2009 and 2017, confirming diagnoses through pathological review. Immunohistochemistry was conducted using an automated system, and BCL6 expression was quantified using Fiji-ImageJ software. A supervised deep learning neural network was employed to classify samples based on DAB staining. Our results show that BCL6 expression is significantly higher in leiomyomas compared to adenomyosis and normal myometrium. No significant difference in BCL6 expression was observed between adenomyosis and controls. The deep learning neural network accurately classified samples with a high degree of precision, supporting the immunohistochemical findings. These findings suggest that BCL6 plays a role in the pathogenesis of leiomyomas, potentially contributing to abnormal smooth muscle cell proliferation. The study highlights the utility of automated immunohistochemistry and deep learning techniques in quantifying protein expression and classifying uterine pathologies. Future studies should investigate the expression of BCL6 in adenomyosis and endometriosis to further elucidate its role in uterine disorders.

Background: Health and fitness apps have potential benefits to improve self-management and disease control among patients with asthma. However, inconsistent use rates have been reported across studies, regions, and health systems. A better understanding of the characteristics of users and nonusers is critical to design solutions that are effectively integrated in patients’ daily lives, and to ensure that these equitably reach out to different groups of patients, thus improving rather than entrenching health inequities. Objective: This study aimed to evaluate the use of general health and fitness apps by patients with asthma and to identify determinants of usage. Methods: A secondary analysis of the INSPIRERS observational studies was conducted using data from face-to-face visits. Patients with a diagnosis of asthma were included between November 2017 and August 2020. Individual-level data were collected, including age, gender, marital status, educational level, health status, presence of anxiety and depression, postcode, socioeconomic level, digital literacy, use of health services, and use of health and fitness apps. Multivariate logistic regression was used to model the probability of being a health and fitness app user. Statistical analysis was performed in R. Results: A total of 526 patients attended a face-to-face visit in the 49 recruiting centers and 514 had complete data. Most participants were ≤40 years old (66.4%), had at least 10 years of education (57.4%), and were in the 3 higher quintiles of the socioeconomic deprivation index (70.1%). The majority reported an overall good health status (visual analogue scale [VAS] score>70 in 93.1%) and the prevalence of anxiety and depression was 34.3% and 11.9%, respectively. The proportion of participants who reported using health and fitness mobile apps was 41.1% (n=211). Multivariate models revealed that single individuals and those with more than 10 years of education are more likely to use health and fitness mobile apps (adjusted odds ratio [aOR] 2.22, 95%CI 1.05-4.75 and aOR 1.95, 95%CI 1.12-3.45, respectively). Higher digital literacy scores were also associated with higher odds of being a user of health and fitness apps, with participants in the second, third, and fourth quartiles reporting aORs of 6.74 (95%CI 2.90-17.40), 10.30 (95%CI 4.28-27.56), and 11.52 (95%CI 4.78-30.87), respectively. Participants with depression symptoms had lower odds of using health and fitness apps (aOR 0.32, 95%CI 0.12-0.83). Conclusions: A better understanding of the barriers and enhancers of app use among patients with lower education, lower digital literacy, or depressive symptoms is key to design tailored interventions to ensure a sustained and equitable use of these technologies. Future studies should also assess users’ general health-seeking behavior and their interest and concerns specifically about digital tools. These factors may impact both initial engagement and sustained use.

ObjectivesAnxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms.MethodsThis is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen’s kappa. Two multivariable logistic regressions were built.ResultsAccording to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression.ConclusionAt least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.

ObjectiveWe aimed to compare patient’s and physician’s ratings of inhaled medication adherence and to identify predictors of patient-physician discordance.DesignBaseline data from two prospective multicentre observational studies.Setting29 allergy, pulmonology and paediatric secondary care outpatient clinics in Portugal.Participants395 patients (≥13 years old) with persistent asthma.MeasuresData on demographics, patient-physician relationship, upper airway control, asthma control, asthma treatment, forced expiratory volume in one second (FEV1) and healthcare use were collected. Patients and physicians independently assessed adherence to inhaled controller medication during the previous week using a 100 mm Visual Analogue Scale (VAS). Discordance was defined as classification in distinct VAS categories (low 0–50; medium 51–80; high 81–100) or as an absolute difference in VAS scores ≥10 mm. Correlation between patients’ and physicians’ VAS scores/categories was explored. A multinomial logistic regression identified the predictors of physician overestimation and underestimation.ResultsHigh inhaler adherence was reported both by patients (median (percentile 25 to percentile 75) 85 (65–95) mm; 53% VAS>80) and by physicians (84 (68–95) mm; 53% VAS>80). Correlation between patient and physician VAS scores was moderate (rs=0.580; p<0.001). Discordance occurred in 56% of cases: in 28% physicians overestimated adherence and in 27% underestimated. Low adherence as assessed by the physician (OR=27.35 (9.85 to 75.95)), FEV1 ≥80% (OR=2.59 (1.08 to 6.20)) and a first appointment (OR=5.63 (1.24 to 25.56)) were predictors of underestimation. An uncontrolled asthma (OR=2.33 (1.25 to 4.34)), uncontrolled upper airway disease (OR=2.86 (1.35 to 6.04)) and prescription of short-acting beta-agonists alone (OR=3.05 (1.15 to 8.08)) were associated with overestimation. Medium adherence as assessed by the physician was significantly associated with higher risk of discordance, both for overestimation and underestimation of adherence (OR=14.50 (6.04 to 34.81); OR=2.21 (1.07 to 4.58)), while having a written action plan decreased the likelihood of discordance (OR=0.25 (0.12 to 0.52); OR=0.41 (0.22 to 0.78)) (R2=44%).ConclusionAlthough both patients and physicians report high inhaler adherence, discordance occurred in half of cases. Implementation of objective adherence measures and effective communication are needed to improve patient-physician agreement.

Intravenous synthetic prostacyclin analogs (iPCAs), such as epoprostenol, treprostinil and iloprost have been widely used for the treatment of pulmonary arterial hypertension (PAH). Despite having good outcomes, continuous infusion of iPCAs has been associated with some adverse effects. Bloodstream infection (BSI) is one of the most severe complications, although poorly recognized, especially under iloprost administration, which few studies have addressed. This study aimed to compare the BSI incidence rates between intravenous iloprost and epoprostenol administration. Patients with pulmonary hypertension (PH) functional class III or IV receiving intravenous iloprost or epoprostenol through Hickman catheter, between 2004 and 2019, were retrospectively selected from two PH treatment centers. From a total of 36 patients (13 for iloprost and 23 for epoprostenol), 75% (n = 27) fulfilled the PAH criteria, mainly belonging to the idiopathic group. Overall BSI rate was 1.5/1000 days of treatment (3.38 and 0.09/1000 days for iloprost and epoprostenol, respectively). Patients receiving iloprost were at a higher risk of developing BSI than those receiving epoprostenol (HR: 12.5; 95% CI: 1.569–99.092). A higher mortality rate from BSI was also identified in the iloprost group (p = 0.04). Twenty-seven patients developed BSI, with 92% of them requiring hospitalization. A total of 29 agents were found, 10 Gram-positive (mainly Staphylococcus aureus; n = 5) and 19 Gram-negative (mainly Pseudomonas aeruginosa; n = 6) bacteria. Iloprost administration was linked to a significantly higher incidence of BSI, worse prognosis, and more BSI-related deaths than epoprostenol. BSI due to Gram-negative, commensal, low-virulence bacteria was also higher in the iloprost group. In short, physicians should be aware when prescribing iPCA to guarantee their patients’ safety and best medical care.

Despite recent advances in assisted reproduction techniques and recent knowledge regarding embryo and endometrium quality, implantation and birth rates remain low. The objective of this study was to investigate whether clomiphene citrate alters endometrial maturation in infertile patients. In a prospective self-matched cohort study, we assessed the ovulation of women in spontaneous and stimulated cycles (with clomiphene citrate). We determined the ovulation day by ultrasound scanning. In both cycles, we took four blood samples (BS1 - at early proliferative phase, BS2 - at mid proliferative phase, BS3 - after ovulation and BS4 - at mid luteal phase) to determine the serum concentrations of FSH, LH, estradiol and progesterone. We retrieved an endometrial biopsy five days after ovulation, followed by blinded analysis and classification according to Noyes criteria, in both cycles. Twenty-two participants completed the study. There were significant differences in FSH BS3 (p=0.001), in LH BS3 and BS4 (p<0.001 and p=0.049, respectively), in estradiol BS2, BS3 and BS4 (p<0.001, p=0.024 and p<0.001, respectively) and in progesterone BS3 and BS4 (p=0.028 and p<0.001, respectively). Considering Noyes criteria, there was a one-day delay when comparing the stimulated cycle with the spontaneous cycle (p=0.004), and a two-day delay when comparing the stimulated cycle with the biopsy day. This study indicates that ovarian stimulation with clomiphene citrate delays the endometrial maturity, and could possibly impair the implantation process due to asynchrony.