Vertical Transmission of Oropouche Virus in a Newly Affected Extra-Amazon Region: A Case Study of Fetal Infection and Death in Ceará, Brazil / Transmisión vertical del virus Oropouche en una región extraamazónica recientemente afectada: un estudio de caso de infección y muerte fetal en Ceará, Brasil / Transmissão vertical do vírus Oropouche em uma região extra-amazônica recentemente afetada: um estudo de caso de infecção fetal e morte no Ceará, Brasil

The recent geographic spread of Oropouche virus (OROV), coupled with an increase in cases and the emergence of previously unrecognized severe manifestations, has raised significant public health concerns. We report the case of a 40-year-old family farmer at 31 weeks of gestation who presented with fever, myalgia, and headache. OROV infection was confirmed by RT-qPCR, followed by nucleotide sequencing and phylogenomic inference, with other infections ruled out. Initially, maternal and fetal health assessments revealed no complications. However, within a week, the patient noted decreased fetal movements, and ultrasound confirmed fetal demise. Molecular diagnostics identified OROV RNA in multiple fetal tissues, confirming vertical transmission. This case highlights the urgent need to protect pregnant women against viral vectors and include OROV into the differential diagnosis of febrile illnesses. Furthermore, it is critical to further investigate the pathogenic mechanisms of this virus, which may lead to changes in public health policies and clinical guidelines.

La reciente propagación geográfica del virus Oropouche (OROV), junto con un aumento de casos y la aparición de manifestaciones graves no reconocidas previamente, ha suscitado importantes preocupaciones de salud pública. Informamos del caso de un agricultor familiar de 40 años de edad con 31 semanas de gestación que presentó fiebre, mialgia y dolor de cabeza. La infección por OROV se confirmó mediante RT-qPCR, y se descartaron otras infecciones. Inicialmente, las evaluaciones de salud materna y fetal no revelaron complicaciones. Sin embargo, en una semana, la paciente notó una disminución de los movimientos fetales y la ecografía confirmó la muerte fetal. Los diagnósticos moleculares identificaron ARN de OROV en múltiples tejidos fetales, lo que confirmó la transmisión vertical. Este caso destaca la necesidad urgente de proteger a las mujeres embarazadas contra los vectores virales e incluir OROV en el diagnóstico diferencial de enfermedades febriles. Además, es fundamental investigar más a fondo los mecanismos patogénicos de este virus, lo que puede conducir a cambios en las políticas de salud pública y las pautas clínicas.

A recente disseminação geográfica do vírus Oropouche (OROV), juntamente com um aumento de casos e o surgimento de manifestações graves não reconhecidas anteriormente, levantou preocupações significativas de saúde pública. Relatamos o caso de uma agricultora familiar de 40 anos com 31 semanas de gestação que apresentou febre, mialgia e dor de cabeça. A infecção por OROV foi confirmada por RT-qPCR, com outras infecções descartadas. Inicialmente, as avaliações de saúde materna e fetal não revelaram complicações. No entanto, dentro de uma semana, a paciente notou diminuição dos movimentos fetais, e o ultrassom confirmou a morte fetal. O diagnóstico molecular identificou o RNA do OROV em vários tecidos fetais, confirmando a transmissão vertical. Este caso destaca a necessidade urgente de proteger as mulheres grávidas contra vetores virais e incluir o OROV no diagnóstico diferencial de doenças febris. Além disso, é fundamental investigar mais profundamente os mecanismos patogênicos deste vírus, o que pode levar a mudanças nas políticas de saúde pública e diretrizes clínicas.

Identification of candidate causal variants and target genes at 41 breast cancer risk loci through differential allelic expression analysis.

Understanding breast cancer genetic risk relies on identifying causal variants and candidate target genes in risk loci identified by genome-wide association studies (GWAS), which remains challenging. Since most loci fall in active gene regulatory regions, we developed a novel approach facilitated by pinpointing the variants with greater regulatory potential in the disease's tissue of origin. Through genome-wide differential allelic expression (DAE) analysis, using microarray data from 64 normal breast tissue samples, we mapped the variants associated with DAE (daeQTLs). Then, we intersected these with GWAS data to reveal candidate risk regulatory variants and analysed their cis-acting regulatory potential. Finally, we validated our approach by extensive functional analysis of the 5q14.1 breast cancer risk locus. We observed widespread gene expression regulation by cis-acting variants in breast tissue, with 65% of coding and noncoding expressed genes displaying DAE (daeGenes). We identified over 54 K daeQTLs for 6761 (26%) daeGenes, including 385 daeGenes harbouring variants previously associated with BC risk. We found 1431 daeQTLs mapped to 93 different loci in strong linkage disequilibrium with risk-associated variants (risk-daeQTLs), suggesting a link between risk-causing variants and cis-regulation. There were 122 risk-daeQTL with stronger cis-acting potential in active regulatory regions with protein binding evidence. These variants mapped to 41 risk loci, of which 29 had no previous report of target genes and were candidates for regulating the expression levels of 65 genes. As validation, we identified and functionally characterised five candidate causal variants at the 5q14.1 risk locus targeting the ATG10 and ATP6AP1L genes, likely acting via modulation of alternative transcription and transcription factor binding. Our study demonstrates the power of DAE analysis and daeQTL mapping to identify causal regulatory variants and target genes at breast cancer risk loci, including those with complex regulatory landscapes. It additionally provides a genome-wide resource of variants associated with DAE for future functional studies.

Colocalised Genetic Associations Reveal Alternative Splicing Variants as Candidate Causal Links for Breast Cancer Risk in 10 Loci.

Genome-wide association studies (GWASs) have revealed numerous loci associated with breast cancer risk, yet the precise causal variants, their impact on molecular mechanisms, and the affected genes often remain elusive. We hypothesised that specific variants exert their influence by affecting cis-regulatory alternative splice elements. An analysis of splicing quantitative trait loci (sQTL) in healthy breast tissue from female individuals identified multiple variants linked to alterations in splicing ratios. Through colocalisation analysis, we pinpointed 43 variants within twelve genes that serve as candidate causal links between sQTL and GWAS findings. In silico splice analysis highlighted a potential mechanism for three genes-FDPS, SGCE, and MRPL11-where variants in proximity to or on the splice site modulate usage, resulting in alternative splice transcripts. Further in vitro/vivo studies are imperative to fully understand how these identified changes contribute to breast oncogenesis. Moreover, investigating their potential as biomarkers for breast cancer risk could enhance screening strategies and early detection methods for breast cancer.

The effect of flunixin meglumine on the premature regression of corpus luteum, recovery rate, and embryo production in superovulated Dorper ewes.

This study evaluated the use of flunixin meglumine to prevent the occurrence of premature corpus luteum (CL) regression in superovulated ewes, improving embryo recovery and viability. Ewes (n=23) submitted to conventional superovulatory protocol and laparoscopic artificial insemination were treated with 2.2 mg/kg/day of flunixin meglumine (FLU, n=12) or 1.5 mL saline solution (CONT, n=11) on Days 2, 3, and 4 (Day 0 = 48 h after device removal). Serum progesterone (P4) concentrations were measured (Day 1-6). Ultrasound (US, Days 3 and 6) and laparoscopic evaluation (Day 6) were performed to identify luteinized structures. In the US, laparoscopy, and P4 assessments, the percentage of ewes with premature CL regression differed (P<0.05) between CONT (54.5; 63.6; and 54.5 %) and FLU (0.0; 0.0; and 0.0 %), respectively. The US exams revealed the effect (P<0.05) of treatment on the number of regressing CL between CONT (1.4 ± 0.6) and FLU (0.0 ± 0.0). Greater (P<0.05) number of normal CLs (10.5 ± 1.8 vs. 4.4 ± 1.5), ova/embryos (9.1 ± 2.1 vs. 3.7 ± 1.3), viable embryos (5.1 ± 1.1 vs. 2.6 ± 1.2), and recovery rate (79.5 ± 9.6 vs. 41.3 ± 15.0 %) were observed in FLU compared to CONT, respectively. The embryo viability rate did not differ (P>0.05) between FLU (60.7 ± 10.5 %) and CONT (45.5 ± 16.1 %). In conclusion, the flunixin meglumine protocol was able to prevent the occurrence of premature CL regression in superovulated ewes, increasing the recovery rate and embryo production.

Intentional, inclusive, and interconnected: Looking forward with the leadership learning framework.

This article looks to explore four emergent themes from this special issue focused on the leadership learning framework: culturally relevant and socially just leadership foundations, intentional and unintentional leadership learning and socialization, the interconnectedness of each aspect of the leadership learning framework and using the theory-to-practice-to-theory approach to enhance model development. The article concludes with future directions, including the critical advancement of the entire leadership learning framework, by positing questions about each aspect of the framework.

Integrating culturally relevant leadership learning into the leadership learning framework.

By incorporating the culturally relevant leadership learning model (CRLL) into the leadership learning framework (LLF), this article provides leadership educators with an inclusive approach to leadership learning. The authors illustrate how educators can integrate the five dimensions of campus climate into leadership knowledge, observation, development, training, engagement, and metacognition. We describe practical ways to address leadership identity, efficacy, and capacity development for all college students, especially those belonging to traditionally underserved identities. Finally, the authors present a new visual for integrating CRLL into the LLF-a kaleidoscope leadership learning model.

Health literacy strengths and needs among migrant communities from Portuguese-speaking African countries in Portugal: a cross-sectional study.

Introduction: Health literacy among migrants is a matter of public health and social justice. Migrants from diverse backgrounds encounter challenges such as linguistic barriers, cultural disparities, restricted access to health services, and heterogeneous migration statuses. Addressing these challenges requires careful consideration of their unique experiences and needs to promote equitable health outcomes. This can hinder their ability to navigate the healthcare system, understand health information, and engage in health-promoting behaviours. However, there is still a significant gap in our understanding of health literacy within migrant communities. This study has a dual aim: to identify health literacy strengths and needs among migrants from Portuguese-speaking African Countries (PALOP) countries in the Lisbon Metropolitan Area and to examine associations between demographic, socioeconomic, migration and health condition characteristics and the health literacy domains. Methods: A cross-sectional survey was conducted. Data were collected from 506 PALOP migrants using the Health Literacy Questionnaire (HLQ). We also collected demographic, socioeconomic, migration, and health condition data. We employed multiple linear regression to understand the relationship between the HLQ nine domains and these characteristics. Results: The HLQ scores revealed distinct patterns of health literacy between the groups. Health literacy needs were particularly evident in the domains related to feeling understood and supported by healthcare providers and navigating the healthcare system. Conversely, higher scores and potential strengths were observed in actively managing one's health and understanding enough health information to make informed decisions. However, in these, the average scores suggest that a high proportion of people recognised difficulties. 'The results also indicated that a higher educational level was associated with increased health literacy. In contrast, low self-perceived health status, living alone, shorter duration of residence in Portugal, and being either undocumented or in the process of obtaining legal status were associated with lower health literacy. Conclusion: Our study highlights the importance of migration-related variables and self-reported health status in understanding health literacy among migrant communities. Factors such as length of stay and low self-perceived health status are associated with potentially disadvantageous levels of health literacy, which could exacerbate health inequalities. Assessing these variables is critical to identify gaps in health literacy and develop tailored interventions to reduce health inequalities.

Corrigendum: Leaf surfaces and neolithization - the case of Arundo donax L.

[This corrects the article DOI: 10.3389/fpls.2022.999252.].

Distinct transcriptional and prognostic impacts of TERT promoter mutations C228T and C250T in papillary thyroid carcinoma.

TERT promoter mutations C228T and C250T are associated with disease aggressiveness and poor clinical outcomes in patients with papillary thyroid carcinomas. However, very little is known about the transcriptional consequences of these mutations and whether they both carry similar oncogenic potential. Here we characterized the transcriptional disturbances and clinical outcomes associated with the presence of each of these two mutations using data derived from The Cancer Genome Atlas. We observed that tumors harboring the C228T mutation (n = 27) exhibited a 16-fold increase in TERT mRNA levels (P = 5.3 × 10-42), whereas C250T tumors (n = 8) showed only a two-fold increase in expression (P = 0.034). The C228T mutation was associated with the activation of signaling pathways controlling the cell cycle, cellular division, and extracellular matrix degradation. Univariate analysis demonstrated that the C228T mutation was associated with older age at diagnosis, large tumor size, lymph node invasion, and distant metastases at diagnosis. The C228T mutation was also associated with worse progression-free interval (PFI) in comparison to WT tumors (HR = 5,04; P < 0.001). This association remained significant in a multivariate analysis (HR = 3.74, P = 0.003) adjusting for BRAF-V600E status and ATA risk group. Our data indicate that TERT promoter mutations C228T and C250T have distinct transcriptional consequences in papillary thyroid carcinoma (PTC), suggesting a greater oncogenic potential for the C228T mutation. TERT promoter mutation C228T may be a useful prognostic marker to identify patients at high risk of distant recurrence. Clinical data for the C250T mutation is still limited, with no evidence up to date to confirm its prognostic significance.

Comprehensive investigation of factor structure and gender equivalence of the Beck Depression Inventory-II among nonclinical adolescents.

The Beck Depression Inventory-II (BDI-II) is a widely used tool for rating the severity of depressive symptoms. Studies on the factor structure of the BDI-II in adolescents have yielded controversial findings. Most studies have reported an oblique two-factor model that describes the 'cognitive' and 'somatic-affective' dimensions. However, there is variation in the item composition of each factor across studies. Alternative factor structures have been proposed, including one-factor, three-factor, hierarchical, and bifactor models. Additionally, there is limited data on measurement invariance across genders. This study aimed to examine hypothetical factor structures and gender equivalence of the BDI-II in a sample of Brazilian nonclinical adolescents (N = 1,184, aged 13-18 years, 59.1% females). Cross-validation of the BDI-II was performed through exploratory (EFA) and confirmatory factor analysis (CFA). Measurement invariance was evaluated using multigroup-CFA (MG-CFA). EFA suggested an oblique two-factor model depicting "affective-cognitive" and "somatic" dimensions. CFA tested competing models for the structure of BDI-II, including the simple one- and two-factor models, a bifactor model, and the EFA model along with its corresponding bifactor model. All models demonstrated adequate and similar fitness, well-defined factors, and good reliability. Bifactor analyses indicated a robust general factor with low reliable variance in total scores attributed to multidimensionality caused by the group factors in bifactor models. MG-CFA supported invariance across gender, suggesting that the same BDI-II construct could be applied to both female and male adolescents. This study provides evidence that the BDI-II could be used as a unidimensional measure of depressive symptoms in adolescents by researchers and clinicians.

Association between sex of the individual with untreated cleft lip and social judgement made by lay persons: A cross-sectional study.

OBJECTIVE: To assess whether there is an association between an individual's sex and social judgements made by lay persons regarding untreated cleft lip. MATERIALS AND METHODS: Lay individuals over 18 years old were recruited through an application to respond online to two questionnaires: a sociodemographic survey and the Brazilian Version of Lay Persons' Social Judgements about Cleft-lip Scale (B-LSojCleft-S). B-LSojCleft-S comprises 14 items evaluating social judgements made by laypersons concerning different types of untreated cleft lips in teenagers. The 14 items are linked to 8 images featuring untreated cleft lips and 1 image without a cleft (control). Higher scores represented more favourable social judgements. Independent samples t-test, paired, and multiple linear regression were conducted (P < 0.05). The study assessed judgements of untreated cleft lips in male and female adolescents using the B-LSojCleft-S. RESULTS: The mean age of the 217 participants was 37.78 ± 12.39 years, predominantly women (72.7%), married (47.7%), with a monthly income below three minimum wages (35.6%) in the majority of cases. Significantly higher social judgement scores were observed in the control group (no cleft) compared to any type of cleft (P < 0.001), with similar scores obtained for the same types of clefts with female or male images (P > 0.05). The participant's sex is associated with social judgement scores (F [1, 214] = 6.318, P = 0.013; adjusted R2 = 0.024), with females making more favourable judgements than males (P < 0.05). CONCLUSIONS: Individuals with cleft lips receive more negative social judgement scores, regardless of their own sex. Women make better social judgements than men.

Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Preliminary Latin American Experience.

Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12-82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0-100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1-49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7-50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.

Ultraviolet spectrophotometry as method to determine the concentration of ß-myrcene released from chitosan in aqueous medium.

Myrcene (ß-myrcene), found in essential oils from plant species such as hops and cannabis, has many advantageous properties, but its use is limited due to volatility and low solubility in water. One way to circumvent these limitations is to encapsulate the essential oils in a polymer matrix. However, these hydrophobic molecules are difficult to quantify when dispersed in water. Seeking to study the release of this terpene in drug release tests from polymeric matrices, this work aimed to develop an easy and cheap UV spectrophotometric method for the quantification of ß-myrcene in aqueous medium. To achieves this goal, samples were prepared in 0.05% (w/v) polysorbate 80 solution, with concentrations of ß-myrcene ranging from 0.01% to 0.1% (v/v), and were analyzed at 226 nm. Each sample was analyzed in triplicate and repeated on three different days, to evaluate the repeatability of the results. The results were subjected to Q, F and Student's t-tests. The regression parameters obtained for ß-myrcene were above 0.99 and through statistical analysis, it was possible to confirm the repeatability for the results. The values of the limits of detection and quantification indicated that the method is not affected by intrinsic factors of the equipment. The results of accuracy, robustness and selectivity showed recovery rates within acceptable limits. This demonstrates that the quantification of ß-myrcene in aqueous medium by UV spectrophotometry is feasible.

Active surveillance of nodal metastasis in differentiated thyroid carcinoma: a systematic review and meta-analysis.

PURPOSE: Cervical lymph nodes (LN) represent the most common site of recurrence in differentiated thyroid cancer (DTC), frequently requiring repeated interventions that contribute to increase morbidity to a usually indolent disease. Data on active surveillance (AS) of nodal metastasis are limited. Therefore, we performed a systematic review and meta-analysis to evaluate AS in nodal metastasis of DTC patients. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched up to July 2023 for studies including DTC patients with metastatic LN who were followed up with AS. The primary outcome was disease progression, according to the study's definition. Additional outcomes were LN enlargement ≥3 mm, occurrence of new cervical metastasis, and conversion from AS to surgical treatment. RESULTS: The search identified 375 studies and seven were included, comprising 486 patients with metastatic nodal DTC. Most were female (69.5%) and had papillary thyroid cancer (99.8%). The mean AS follow-up ranged from 28-86 months. Following each study's definition of progression, the pooled incidence was 28% [95% confidence interval (CI), 20-37%]. The pooled incidence of LN growth ≥ 3 mm was 21% [95% CI, 17-25%] and the emergence of new LN sites was 19% [95% CI, 14-25%]. Combining growth of 3 mm and the emergence of new LN criteria, we found an incidence of 26% [95% CI, 20-33%]. The incidence of neck dissection during AS was 18% [95% CI, 12-26%]. CONCLUSIONS: AS seems to be a suitable strategy for selected DTC patients with small nodal disease, avoiding or postponing surgical reintervention. PROSPERO REGISTRATION: CRD42023438293.

Not Only RET but NF1 and Chromosomal Instability Are Seen in Young Patients with Sporadic Medullary Thyroid Carcinoma.

Context: Genetic analysis of sporadic medullary thyroid carcinoma (MTC) has revealed somatic variants in RET, RAS, and occasionally other genes. However, around 20% of patients with sporadic MTC lack a known genetic driver. Objective: To uncover potential new somatic or germline drivers, we analyze a distinct cohort of patients with sporadic, very early-onset, and aggressive MTC. Methods: Germline and somatic DNA exome sequencing was performed in 19 patients, previously tested negative for germline RET variants. Results: Exome sequencing of 19 germline samples confirmed the absence of RET and identified an NF1 pathogenic variant in 1 patient. Somatic sequencing was successful in 15 tumors revealing RET variants in 80%, predominantly p.Met918Thr, which was associated with disease aggressiveness. In RET-negative tumors, pathogenic variants were found in HRAS and NF1. The NF1 germline and somatic variants were observed in a patient without a prior clinical diagnosis of neurofibromatosis type 1, demonstrating that the loss of heterozygosity of NF1 functions as a potential MTC driver. Somatic copy number alterations analysis revealed chromosomal alterations in 53.3% of tumors, predominantly in RET-positive cases, with losses in chromosomes 9 and 22 being the most prevalent. Conclusion: This study reveals that within a cohort of early-onset nonhereditary MTC, RET remains the major driver gene. In RET-negative tumors, NF1 and RAS are drivers of sporadic MTC. In addition, in young patients without a RET germline mutation, a careful clinical evaluation with a consideration of germline NF1 gene analysis is ideal to exclude Neurofibromatosis type 1 (NF1).

Survival Outcomes in Thyroid Cancer Patients with Co-Occurring Breast Cancer: Evidence of Mortality Risk Attenuation.

BACKGROUND: Previous studies have reported a strong correlation between breast cancer (BC) and thyroid cancer (TC) incidence. However, the clinical and oncological impact of these associations are not yet fully understood. Here, we aimed to explore the differences in clinicopathological characteristics between TC patients with and without BC, and the effect of a history of positive BC on TC survival. METHODS: We retrospectively compared the clinical characteristics and survival rates of patients with TC alone and those with TC and BC in a primary cohort at our institution and in a second cohort using the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: In our institutional cohort, survival rates were similar between patients with TC alone and those with TC-associated BC. However, using SEER data, we found that BC had a protective effect on TC patients and was associated with reduced TC mortality rates (hazard ratio [HR] = 0.72, 95% confidence interval [CI] 0.57 to 0.92; P = .026). After stratifying the TC patients according to co-occurring BC subtypes, we observed that higher survival rates were restricted to patients with coexisting luminal A BC (P = .015), which exhibit positive hormone receptors and do not express HER-2. CONCLUSION: These findings suggest that hormone pathways may play a role in the co-occurrence of thyroid and breast cancers. Patients with TC coexisting with luminal A BC have higher survival rates. However, further studies on the mechanisms underlying the association between BC and TC are warranted.

Differentiated thyroid carcinoma: what the nonspecialists needs to know.

Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Preventive nasal administration of flagellin restores antimicrobial effect of gentamicin and protects against a multidrug-resistant strain of Pseudomonas aeruginosa.

The increasing prevalence of multidrug-resistant Pseudomonas aeruginosa (PA) is a significant concern for chronic respiratory disease exacerbations. Host-directed drugs, such as flagellin, an agonist of toll-like receptor 5 (TLR5), have emerged as a promising solution. In this study, we evaluated the prophylactic intranasal administration of flagellin against a multidrug-resistant strain of PA (PAMDR) in mice and assessed the possible synergy with the antibiotic gentamicin (GNT). The results indicated that flagellin treatment before infection decreased bacterial load in the lungs, likely due to an increase in neutrophil recruitment, and reduced signs of inflammation, including proinflammatory cytokines. The combination of flagellin and GNT showed a synergistic effect, decreasing even more the bacterial load and increasing mice survival rates, in comparison to mice pre-treated only with flagellin. These findings suggest that preventive nasal administration of flagellin could restore the effect of GNT against MDR strains of PA, paving the way for the use of flagellin in vulnerable patients with chronic respiratory diseases.