Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

ERS International Congress 2023: highlights from the Respiratory Intensive Care Assembly.

Early career members of Assembly 2 (Respiratory Intensive Care) attended the 2023 European Respiratory Society International Congress in Milan, Italy. The conference covered acute and chronic respiratory failure. Sessions of interest to our assembly members and to those interested in respiratory critical care are summarised in this article and include the latest updates in respiratory intensive care, in particular acute respiratory distress syndrome and mechanical ventilation.

Fields of flowers with few strikes: how oligolectic bees manage their foraging behavior on Calibrachoa elegans (Solanaceae).

In specialized plant-pollinator associations, partners may exhibit adaptive traits, which favor the maintenance of the interaction. The association between Calibrachoa elegans (Solanaceae) and its oligolectic bee pollinator, Hexantheda missionica (Colletidae), is mutualistic and forms a narrowly specialized pollination system. Flowers of C. elegans are pollinated exclusively by this bee species, and the bees restrict their pollen resources to this plant species. The pollen presentation schedules of C. elegans were evaluated at the population level to test the hypothesis that H. missionica females adjust their foraging behavior to the resource offering regime of C. elegans plants. For this, the number of new flowers and anthers opened per hour (as a proxy for pollen offering) was determined, and pollen advertisement was correlated with the frequency of flower visits during the day. Preferences of female bees for flowers of different stages were also investigated, and their efficiency as pollinators was evaluated. Pollen offering by C. elegans was found to be partitioned throughout the day through scattered flower openings. Females of H. missionica indeed adjusted their foraging activity to the most profitable periods of pollen availability. The females preferred new, pollen-rich flowers over old ones and gathered pollen and nectar selectively according to flower age. Such behaviors must optimize female bee foraging efficiency on flowers. Female bees set 93% of fruit after a single visit. These findings guarantee their importance as pollinators and the persistence of the specialized plant-pollinator association.

[Trauma Injuries Associated with Rope Bullfights in the Azores: A Cross-Sectional Study]. / Trauma Associado às Touradas à Corda nos Açores: Um Estudo Transversal.

INTRODUCTION: The aim of the study was to describe trauma injuries associated with rope bullfights in the Azores, Portugal, regarding the cause of the incident, trauma mechanism, most affected anatomical areas, and injury severity. METHODS: Two-year cross-sectional study in the local hospital with prospective data collection. Patients who were consecutively admitted to the local hospital's emergency department with trauma injuries from the bull's direct impact or from falls either during the bull's escape or when handling the rope, were included. Data on general demographics, lesion characteristics, treatments, need for hospitalization and mortality were collected. RESULTS: Fifty-six incidents and 80 trauma injuries were identified. The main cause of trauma was the bull's direct impact (37; 66.07%) and the mechanism of injury was blunt trauma in all patients (100%; 56). Head and neck injuries (27; 33.75%) were the most common. The median Injury Severity Score at the emergency department admission was 4. Major trauma was noted in five patients (8.92%). Ten patients (17.85%) needed hospitalization with a median hospital stay of seven days. Three of the 10 hospitalized patients (30%) were previously admitted to the intensive care unit. Surgery was performed in six patients (10.71%). CONCLUSION: The main cause of trauma was the bull's direct impact, and the mechanism of injury was blunt trauma. The most affected anatomical areas were the head and neck. These findings are a wake-up call to the impact of these events regarding the economic costs they entail, the costs for the health of the local population, the safety measures currently implemented and the availability of the necessary means to treat these patients.

Introdução: O objetivo deste estudo foi caracterizar as lesões traumáticas tauromáquicas ocorridas nas touradas à corda nos Açores no que diz respeito à causa do incidente, mecanismo de trauma, área anatómica mais afetada e gravidade das lesões. Métodos: Estudo unicêntrico, transversal, com a colheita prospetiva de dados realizada durante dois anos. Foram incluídos os doentes que consecutivamente recorreram ao serviço de urgência do hospital local por lesões traumáticas ocorridas por trauma direto com o animal ou quedas aquando da fuga ou manuseio da corda. Foram colhidos dados demográficos gerais, características da lesão, tratamentos efetuados, necessidade de internamento hospitalar e mortalidade. Foi realizada uma análise estatística descritiva com recurso ao software estatístico SPSS. Resultados: Registaram-se 56 admissões hospitalares e 80 lesões traumáticas. A principal causa de traumatismo foi o trauma direto com o animal (37; 66,07%) e o mecanismo de lesão foi o trauma fechado (56; 100%). As áreas anatómicas mais afetadas foram a cabeça e pescoço (27; 33,75%). A mediana de Injury Severity Score foi de 4 à admissão hospitalar. Cinco doentes (8,92%) apresentaram trauma major. Dez doentes (17,85%) necessitaram de internamento hospitalar com uma mediana de dias de internamento de sete (IIQ 4,5 dias). Três (30%) dos doentes internados necessitaram de internamento em unidade de cuidados intensivos. Seis doentes (10,71%) foram submetidos a cirurgia. Conclusão: A principal causa de traumatismo foi o trauma direto com o animal e o mecanismo de lesão foi o trauma fechado. As áreas anatómicas mais afetadas foram a cabeça e pescoço. Estes dados constituem um alerta para o impacto destes eventos no que diz respeito aos custos económicos que acarretam, aos custos para a saúde da população local, às medidas de segurança atualmente implementadas e à disponibilidade dos meios necessários para tratar estes doentes.

How young radiologists use contrast media and manage adverse reactions: an international survey.

OBJECTIVES: To collect real-world data about the knowledge and self-perception of young radiologists concerning the use of contrast media (CM) and the management of adverse drug reactions (ADR). METHODS: A survey (29 questions) was distributed to residents and board-certified radiologists younger than 40 years to investigate the current international situation in young radiology community regarding CM and ADRs. Descriptive statistics analysis was performed. RESULTS: Out of 454 respondents from 48 countries (mean age: 31.7 ± 4 years, range 25-39), 271 (59.7%) were radiology residents and 183 (40.3%) were board-certified radiologists. The majority (349, 76.5%) felt they were adequately informed regarding the use of CM. However, only 141 (31.1%) received specific training on the use of CM and 82 (18.1%) about management ADR during their residency. Although 266 (58.6%) knew safety protocols for handling ADR, 69.6% (316) lacked confidence in their ability to manage CM-induced ADRs and 95.8% (435) expressed a desire to enhance their understanding of CM use and handling of CM-induced ADRs. Nearly 300 respondents (297; 65.4%) were aware of the benefits of contrast-enhanced ultrasound, but 249 (54.8%) of participants did not perform it. The preferred CM injection strategy in CT parenchymal examination and CT angiography examination was based on patient's lean body weight in 318 (70.0%) and 160 (35.2%), a predeterminate fixed amount in 79 (17.4%) and 116 (25.6%), iodine delivery rate in 26 (5.7%) and 122 (26.9%), and scan time in 31 (6.8%) and 56 (12.3%), respectively. CONCLUSION: Training in CM use and management ADR should be implemented in the training of radiology residents. CRITICAL RELEVANCE STATEMENT: We highlight the need for improvement in the education of young radiologists regarding contrast media; more attention from residency programs and scientific societies should be focused on training about contrast media use and the management of adverse drug reactions. KEY POINTS: • This survey investigated training of young radiologists about use of contrast media and management adverse reactions. • Most young radiologists claimed they did not receive dedicated training. • An extreme heterogeneity of responses was observed about contrast media indications/contraindications and injection strategy.

The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

Difficulties in emotion regulation and well-being in breast cancer.

Objective: Breast cancer is responsible for disruptive changes in women's lives, causing them to experience diverse and intense negative emotions that can affect their perception of well-being. The present study aimed to characterize difficulties in emotion regulation (ER), according to Gratz and Roemer's multidimensional assessment, in women with breast cancer and to relate them with General Well-Being and its different domains: Physical, Social/Familial, Emotional, and Functional. Method: Ninety-five Portuguese women with breast cancer aged between 32 and 75 years answered a sociodemographic and clinical questionnaire and the Portuguese versions of the Difficulties in Emotion Regulation Scale and the Functional Assessment of Cancer Therapy - General. Data were collected in an oncology public hospital. Results: In general, difficulties in ER presented negative correlations with General Well-Being and its domains. The multiple regression analysis findings indicated that two specific types of difficulties, Limited Access to ER Strategies and Lack of Emotional Clarity, play a significant role in predicting well-being, especially in the Emotional domain, which was most compromised in these patients. Conclusions: These difficulties should be approached within psycho-oncological interventions as they are essential contributors to improving emotional and general well-being and fostering psychological adaptation to breast cancer.

Pomegranate extract in polyphosphate-fluoride mouthwash reduces enamel demineralization.

OBJECTIVES: To evaluate the anti-demineralizing effect of a mouthwash comprising pomegranate peel extract (PPE 3%), sodium trimetaphosphate (TMP 0.3%), and fluoride (F 225 ppm) in an in situ study, and to assess its irritation potential in an ex vivo study. METHODS: This double-blind crossover study was conducted in four phases with 7 days each. Twelve volunteers used palatal appliances containing enamel blocks, which were subjected to cariogenic challenges. The ETF formulation (PPE + TMP + F, pH 7.0), TF formulation (TMP + F, pH 7.0), deionized water (W, pH 7.0), and essential oil commercial mouthwash (CM, 220 ppm F, pH 4.3) were dropped onto the enamel twice daily. The percentage of surface hardness loss, integrated loss of subsurface hardness, calcium, phosphorus, and fluoride in enamel and biofilms were determined. In addition, alkali-soluble extracellular polysaccharide concentrations were analyzed in the biofilms. The irritation potential was evaluated using the hen's egg chorioallantoic membrane test through the vascular effect produced during 300-s of exposure. RESULTS: ETF was the most efficacious in preventing demineralization. It also showed the highest concentrations of calcium and phosphorus in the enamel and in the biofilm, as well as the lowest amount of extracellular polysaccharides in the biofilm. In the eggs, ETF produced light reddening, whereas CM led to hyperemia and hemorrhage. CONCLUSIONS: The addition of PPE to formulations containing TMP and F increased its anti-demineralizing property, and this formulation presented a lower irritation potential than the CM. CLINICAL RELEVANCE: ETF can be a promising alternative alcohol-free mouthwash in patients at high risk of caries.

The influence of subclinical active inflammation on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patients.

BACKGROUND AND AIMS: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment. METHODS: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model. RESULTS: The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in all its different definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression. CONCLUSION: In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.

Lifestyle and quality of life in children and adolescents during the covid-19 social distancing period.

OBJECTIVE: To evaluate the lifestyle and quality of life in Brazilian children and adolescents during the COVID-19 social distancing period in 2020. METHODS: This cross-sectional study evaluated children and adolescents (2-18 years of age) and their parents, who voluntarily participated in an online survey. Snowball sampling was used to recruit participants during the first 6 months of the pandemic. A questionnaire was used to characterize the study population. The PedsQL 4.0 and the EUROHIS-QOL 8-item index were used to assess the quality of life (QoL) in children/adolescents and parents, respectively. Data were analyzed using SPSS 18.0 statistical program through the ANOVA with post hoc Bonferroni analysis, student's t test, and the generalized estimating equation. RESULTS: Mean screen time increased from 2h pre-pandemic to 5h during the pandemic (p < 0.001), which was associated with a decline in PedSQL4.0 scores (from 75.7 ± 2.6 to 71.3 ± 13.7, p < 0.001). Unhealthy eating habits increased from 11% to 34% and were associated with worse QoL scores compared with improved or unchanged eating habits during the pandemic (69.7 ± 13.3 vs 72.80 ± 13.4 vs 76.4 ± 12.6; p < 0.001). Poor sleep quality increased from 9% to 31.7% and was associated with worse QoL scores compared to improved or unchanged sleep quality during the pandemic (67.3 ± 13.1 vs 74.5 ± 13.1 vs 76.8 ± 12.2; p < 0.05). Physical exercise was associated with better PedSQL4.0 scores (77.5 ± 12.3 vs 72.5 ± 14.4; p < 0.001). Children aged 2-4y old had the best QoLscores. CONCLUSIONS: Pandemic-related social distancing promoted significant lifestyle changes in children and adolescents, increasing screen time, reducing physical activity, and worsening food and sleep quality, which resulted in worse QoL scores.

Internalizing problems in individuals with reading, mathematics and unspecified learning difficulties: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to examine if individuals with reading difficulties (RD), mathematics difficulties (MD), or unspecified learning difficulties (ULD) experience internalizing problems (i.e., anxiety, depression, somatic complaints, and social withdrawal) to the same extent, and if the effect sizes are influenced by moderators (age, internalizing problems type, anxiety type, rater type, selection criteria, and attention control). We reviewed 2,806 studies published in English between January 2000 and April 2023. Our final sample consisted of 96 studies that reported effect sizes or data to calculate them (a total of 120 unique samples, 83,260 participants, age range = 7.3 - 34.8 years). Risk of bias and sensitivity were assessed. A random-effects model analysis revealed a significant and moderate overall effect size (Hedge's g = -.54), indicating that individuals with RD, MD or ULD experience more internalizing problems than their chronological-age (CA) controls. Follow-up analyses showed that neither learning difficulties type nor age of participants were significant moderators, but selection criteria (diagnosis versus screening) and internalizing problems type were. These findings suggest that individuals with RD do not differ from those with MD or ULD in internalizing problems, and all fare poorly compared to CA controls.

Lifestyle and quality of life in children and adolescents during the covid-19 social distancing period

Abstract Objective To evaluate the lifestyle and quality of life in Brazilian children and adolescents during the COVID-19 social distancing period in 2020. Methods This cross-sectional study evaluated children and adolescents (2-18 years of age) and their parents, who voluntarily participated in an online survey. Snowball sampling was used to recruit participants during the first 6 months of the pandemic. A questionnaire was used to characterize the study population. The PedsQL 4.0 and the EUROHIS-QOL 8-item index were used to assess the quality of life (QoL) in children/adolescents and parents, respectively. Data were analyzed using SPSS 18.0 statistical program through the ANOVA with post hoc Bonferroni analysis, student's t test, and the generalized estimating equation. Results Mean screen time increased from 2h pre-pandemic to 5h during the pandemic (p <0.001), which was associated with a decline in PedSQL4.0 scores (from 75.7 ± 2.6 to 71.3 ± 13.7, p <0.001). Unhealthy eating habits increased from 11% to 34% and were associated with worse QoL scores compared with improved or unchanged eating habits during the pandemic (69.7 ± 13.3 vs 72.80 ± 13.4 vs 76.4 ± 12.6; p <0.001). Poor sleep quality increased from 9% to 31.7% and was associated with worse QoL scores compared to improved or unchanged sleep quality during the pandemic (67.3 ± 13.1 vs 74.5 ± 13.1 vs 76.8 ± 12.2; p <0.05). Physical exercise was associated with better PedSQL4.0 scores (77.5 ± 12.3 vs 72.5 ± 14.4; p <0.001). Children aged 2-4y old had the best QoLscores. Conclusions Pandemic-related social distancing promoted significant lifestyle changes in children and adolescents, increasing screen time, reducing physical activity, and worsening food and sleep quality, which resulted in worse QoL scores.

Multidisciplinary Development and Initial Validation of a Clinical Knowledge Base on Chronic Respiratory Diseases for mHealth Decision Support Systems.

Most mobile health (mHealth) decision support systems currently available for chronic obstructive respiratory diseases (CORDs) are not supported by clinical evidence or lack clinical validation. The development of the knowledge base that will feed the clinical decision support system is a crucial step that involves the collection and systematization of clinical knowledge from relevant scientific sources and its representation in a human-understandable and computer-interpretable way. This work describes the development and initial validation of a clinical knowledge base that can be integrated into mHealth decision support systems developed for patients with CORDs. A multidisciplinary team of health care professionals with clinical experience in respiratory diseases, together with data science and IT professionals, defined a new framework that can be used in other evidence-based systems. The knowledge base development began with a thorough review of the relevant scientific sources (eg, disease guidelines) to identify the recommendations to be implemented in the decision support system based on a consensus process. Recommendations were selected according to predefined inclusion criteria: (1) applicable to individuals with CORDs or to prevent CORDs, (2) directed toward patient self-management, (3) targeting adults, and (4) within the scope of the knowledge domains and subdomains defined. Then, the selected recommendations were prioritized according to (1) a harmonized level of evidence (reconciled from different sources); (2) the scope of the source document (international was preferred); (3) the entity that issued the source document; (4) the operability of the recommendation; and (5) health care professionals' perceptions of the relevance, potential impact, and reach of the recommendation. A total of 358 recommendations were selected. Next, the variables required to trigger those recommendations were defined (n=116) and operationalized into logical rules using Boolean logical operators (n=405). Finally, the knowledge base was implemented in an intelligent individualized coaching component and pretested with an asthma use case. Initial validation of the knowledge base was conducted internally using data from a population-based observational study of individuals with or without asthma or rhinitis. External validation of the appropriateness of the recommendations with the highest priority level was conducted independently by 4 physicians. In addition, a strategy for knowledge base updates, including an easy-to-use rules editor, was defined. Using this process, based on consensus and iterative improvement, we developed and conducted preliminary validation of a clinical knowledge base for CORDs that translates disease guidelines into personalized patient recommendations. The knowledge base can be used as part of mHealth decision support systems. This process could be replicated in other clinical areas.

18 Months of Treatment with Triheptanoin in 2 Patients with Long Chain Fatty Acid Oxidation Disorders.

INTRODUCTION: Long-chain fatty acid oxidation disorders (LC-FAOD) are inborn errors of metabolism, also identified in newborn screening in Portugal. They interfere with adequate energy utilization, namely by muscles, heart, and liver. Treatment aims to maintain patients in an anabolic state, with increased caloric intake, using carbohydrates and medium-chain fatty acids. Treatment with triheptanoin (THP), a synthetic seven-carbon fatty acid triglyceride compound with an anaplerotic effect that increases energy availability to the cell, has been advocated as an efficacious and safe therapy in LC-FAOD. METHODS: Retrospective revision of clinical records of 2 LC-FAOD patients comparing number, severity and admissions for rhabdomyolysis crises, maximum CK values and weight gain in a period of 18 months before and after treatment with THP. RESULTS/CASE REPORT: Patient 1 is a 12 year old male with VLCADD, with main manifestation being rhabdomyolysis crises. After he started THP we found a decrease in admissions (6 to 2), less rhabdomyolysis crises treated at home (5 to 3), and lower maximum CK values (72352 U/L to 13.000U/L). He had a large increase in weight - 13kg in 18 months. He was able to start pool exercises with no rhabdomyolysis associated. Patient 2 is an 8 year old male with LCAHDD, with main manifestations being rhabdomyolysis crises and retinopathy. After he started THP we found a decrease in admissions (4 to 1), no rhabdomyolysis crises treated at home, and lower maximum CK values (100.000U/L to 19848 U/L). He also increased his weight - 7kg in 18 months. He plays football in school and swims with no rhabdomyolysis associated. In both patients, no major side effects were observed. CONCLUSION: In our patients, we could observe a reduction in the number of admissions, and less severe rhabdomyolysis crises after THP use. The weight gain was significant. There were no major side effects. Despite regarding only two patients, our findings are in line with the latest literature on THP and LC-FAOD, reinforcing the utility of THP as one more tool in the treatment of these disorders with rhabdomyolysis as the main manifestation. The weight increase is an issue to be aware of and to address from the start of the treatment.

Characterization of the RofA regulon in the pandemic M1global and emergent M1UK lineages of Streptococcus pyogenes.

The standalone regulator RofA is a positive regulator of the pilus locus in Streptococcus pyogenes. Found in only certain emm genotypes, RofA has been reported to regulate other virulence factors, although its role in the globally dominant emm1 S. pyogenes is unclear. Given the recent emergence of a new emm1 (M1UK) toxigenic lineage that is distinguished by three non-synonymous SNPs in rofA, we characterized the rofA regulon in six emm1 strains that are representative of the two contemporary major emm1 lineages (M1global and M1UK) using RNAseq analysis, and then determined the specific role of the M1UK-specific rofA SNPs. Deletion of rofA in three M1global strains led to altered expression of 14 genes, including six non-pilus locus genes. In M1UK strains, deletion of rofA led to altered expression of 16 genes, including nine genes that were unique to M1UK. Only the pilus locus genes were common to the RofA regulons of both lineages, while transcriptomic changes varied between strains even within the same lineage. Although introduction of the three SNPs into rofA did not impact gene expression in an M1global strain, reversal of three SNPs in an M1UK strain led to an unexpected number of transcriptomic changes that in part recapitulated transcriptomic changes seen when deleting RofA in the same strain. Computational analysis predicted that interactions with a key histidine residue in the PRD domain of RofA would differ between M1UK and M1global. RofA is a positive regulator of the pilus locus in all emm1 strains but effects on other genes are strain- and lineage-specific, with no clear, common DNA binding motif. The SNPs in rofA that characterize M1UK may impact regulation of RofA; whether they alter phosphorylation of the RofA PRD domain requires further investigation.

Advancing hospital-based health technology assessment: evaluating genomic panel contracting strategies for blood tumors through a multimethodology.

INTRODUCTION: The adoption of genomic technologies in the context of hospital-based health technology assessment presents multiple practical and organizational challenges. OBJECTIVE: This study aimed to assist the Instituto Português de Oncologia de Lisboa Francisco Gentil (IPO Lisboa) decision makers in analyzing which acute myeloid leukemia (AML) genomic panel contracting strategies had the highest value-for-money. METHODS: A tailored, three-step approach was developed, which included: mapping clinical pathways of AML patients, building a multicriteria value model using the MACBETH approach to evaluate each genomic testing contracting strategy, and estimating the cost of each strategy through Monte Carlo simulation modeling. The value-for-money of three contracting strategies - "Standard of care (S1)," "FoundationOne Heme test (S2)," and "New diagnostic test infrastructure (S3)" - was then analyzed through strategy landscape and value-for-money graphs. RESULTS: Implementing a larger gene panel (S2) and investing in a new diagnostic test infrastructure (S3) were shown to generate extra value, but also to entail extra costs in comparison with the standard of care, with the extra value being explained by making available additional genetic information that enables more personalized treatment and patient monitoring (S2 and S3), access to a broader range of clinical trials (S2), and more complete databases to potentiate research (S3). CONCLUSION: The proposed multimethodology provided IPO Lisboa decision makers with comprehensive and insightful information regarding each strategy's value-for-money, enabling an informed discussion on whether to move from the current Strategy S1 to other competing strategies.

Psychometric analysis of the body responsiveness questionnaire in the Portuguese population.

Body responsiveness refers to the tendency to be attuned to the body's needs and use interoceptive information to guide behavior. Despite its potential beneficial effect on the development of positive body image, this construct is currently understudied. To boost research in this area, we examined the factor structure, gender invariance, and psychometric properties of a Portuguese translation of the Body Responsiveness Questionnaire (BRQ). A total of 650 men and women (aged 18-80 years) completed the Portuguese BRQ. To assess its convergent validity, participants also completed measures of body appreciation, emotion regulation, depression symptoms, and psychological quality of life. Exploratory factor analysis indicated a two-factor structure of the BRQ, which was upheld using confirmatory factor analysis: "Importance of Interoceptive Awareness" (ω = .85-.87) and "Perceived Connection" between body and mind (ω = .71-.74). BRQ scores had partial scalar invariance across gender, and no significant gender differences. Convergent and known-groups validity was supported. Participants with overweight/obesity (vs. normal weight) and middle-aged adults (vs. young adults) assigned higher importance to body signals to guide behavior. The Portuguese version of the BRQ is a psychometrically sound measure of body responsiveness and it may contribute to a comprehensive assessment of positive body image to guide intervention.