From structure to clinic: Design of a muscarinic M1 receptor agonist with potential to treatment of Alzheimer's disease.

Current therapies for Alzheimer's disease seek to correct for defective cholinergic transmission by preventing the breakdown of acetylcholine through inhibition of acetylcholinesterase, these however have limited clinical efficacy. An alternative approach is to directly activate cholinergic receptors responsible for learning and memory. The M1-muscarinic acetylcholine (M1) receptor is the target of choice but has been hampered by adverse effects. Here we aimed to design the drug properties needed for a well-tolerated M1-agonist with the potential to alleviate cognitive loss by taking a stepwise translational approach from atomic structure, cell/tissue-based assays, evaluation in preclinical species, clinical safety testing, and finally establishing activity in memory centers in humans. Through this approach, we rationally designed the optimal properties, including selectivity and partial agonism, into HTL9936-a potential candidate for the treatment of memory loss in Alzheimer's disease. More broadly, this demonstrates a strategy for targeting difficult GPCR targets from structure to clinic.

Faithful to the Marseille tradition: Unique and intriguing-that's how Marseillevirus packs its DNA.

Not only does Marseillevirus bear the name of the city where it was identified, it also encompasses its values and what makes Marseille a wonderful city. Marseillevirus is unique and intriguing. As such, Bryson et al. in this issue of Molecular Cell reveal how virion-associated Marseillevirus DNA is packed with nucleosomes.

Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia.

N6-methyladenosine (m6A) is an abundant internal RNA modification1,2 that is catalysed predominantly by the METTL3-METTL14 methyltransferase complex3,4. The m6A methyltransferase METTL3 has been linked to the initiation and maintenance of acute myeloid leukaemia (AML), but the potential of therapeutic applications targeting this enzyme remains unknown5-7. Here we present the identification and characterization of STM2457, a highly potent and selective first-in-class catalytic inhibitor of METTL3, and a crystal structure of STM2457 in complex with METTL3-METTL14. Treatment of tumours with STM2457 leads to reduced AML growth and an increase in differentiation and apoptosis. These cellular effects are accompanied by selective reduction of m6A levels on known leukaemogenic mRNAs and a decrease in their expression consistent with a translational defect. We demonstrate that pharmacological inhibition of METTL3 in vivo leads to impaired engraftment and prolonged survival in various mouse models of AML, specifically targeting key stem cell subpopulations of AML. Collectively, these results reveal the inhibition of METTL3 as a potential therapeutic strategy against AML, and provide proof of concept that the targeting of RNA-modifying enzymes represents a promising avenue for anticancer therapy.

Highlights from the 2023 International Meeting on the Molecular Biology of Hepatitis B virus.

Since its discovery in 1965, our understanding of the hepatitis B virus (HBV) replication cycle and host immune responses has increased markedly. In contrast, our knowledge of the molecular biology of hepatitis delta virus (HDV), which is associated with more severe liver disease, is less well understood. Despite the progress made, critical gaps remain in our knowledge of HBV and HDV replication and the mechanisms underlying viral persistence and evasion of host immunity. The International HBV Meeting is the leading annual scientific meeting for presenting the latest advances in HBV and HDV molecular virology, immunology, and epidemiology. In 2023, the annual scientific meeting was held in Kobe, Japan and this review summarises some of the advances presented at the Meeting and lists gaps in our knowledge that may facilitate the development of new therapies.

Endoparasitic helminth fauna and diet of Geophagus sveni (Pisces) in Upper Paraná River basin.

In freshwater ecosystems, parasite infection patterns are influenced by factors including spatial-temporal variations, host diet, and habitat. Fish often change diets, affecting their parasite communities. This study focused on non-native host fish Geophagus sveni, aiming to characterize diet and endoparasitic helminth fauna patterns in the invaded area, investigating spatial and seasonal possible differences of endoparasite infections and correlating with host diet, in São José dos Dourados River and Tietê River areas. The host fish were collected in these areas during the dry and rainy season using gillnets. The endoparasites were collected and preserved in alcohol and identified using taxonomic methods, and stomach contents were examined for diet analysis. Parasitism descriptors were calculated and evaluated spatially and seasonally by ANOVA and the Kruskal-Wallis tests. PERMANOVA assessed G. sveni diet differences, and RDA correlated the endohelminth abundance with the host diet. Two endoparasites were recorded: metacercariae of Austrodiplostomum compactum (Trematoda) and larvae and adults of Raphidascaris (Sprentascaris) lanfrediae (Nematoda). Spatial differences were observed for the mean abundance and prevalence of R. (S.) lanfrediae and A. compactum prevalence. Seasonal variations of parasitic descriptors occurred for the nematode in the Tietê River area. The detritus and aquatic insects were the most consumed items by G. sveni. Detritus consumption positively correlates with nematode abundance. The findings indicate that factors such as artificial channels and rainfall, which can influence resource availability, may affect the fish's diet and potentially influence the structure of its endoparasite community. The study emphasizes the importance of understanding trophic chain-transmitted parasites and calls for further research in Neotropical environments.

Design of customizable personal protective equipment for 3-D printing: Performance evaluation of N95 respirators using computational fluid dynamics.

3-D printing the structural components of facemasks and personal protective equipment (PPE) based on 3-D facial scans creates a high degree of customizability. As a result, the facemask fits more comfortably with its user's specific facial characteristics, filters contaminants more effectively with its increased sealing effect, and minimizes waste with its cleanable and reusable plastic structure compared to other baseline models. In this work, 3-D renditions of the user's face taken with smartphone laser scanning techniques were used to generate customized computer-aided design (CAD) models for the several components of an N95 respirator, which are each designed with considerations for assembly and 3-D printing constraints. Thorough analyses with computational fluid dynamics (CFD) simulations were carried out to verify the respirator's efficiency in filtering airborne contaminants to comply with industry safety guidelines and generate data to showcase the relationships between various input and output design parameters. This involved a comparative study to identify the ideal cross-sectional geometry of exposed filter fabric, a sensitivity study to evaluate the respirator's ability to protect the user in various scenarios, and the 3-D printing of several prototypes to estimate printing time, cost of materials, and comfort level at the user's face. Results showed that the combination of different digital tools can increase efficiency in the design, performance assessment, and production of customized N95-rated respirators.

Valorization of baobab seeds (Adansonia digitata) as a coffee-like beverage: evaluation of roasting time on bioactive compounds.

The baobab tree (Adansonia digitata) can be found in sub-Saharan Africa, and its fruit presents high nutritional value. However, baobab seeds are often discarded and their potential remains underutilized. This study aimed to investigate the effect of roasting time (30/55/80/105 min at 200 °C) on the physical-chemical properties of baobab seeds and the bioactive compounds in a coffee-like beverage. The results showed a decrease in moisture, Aw (water activity), and hardness of baobab seeds with increasing roasting time. These changes resulted from moisture loss, caramelization, and Maillard reactions, which also affected appearance when compared with unroasted baobab seeds. The pH of the beverage decreased to a value of around 6.01 after 105 min of roasting. The total phenolic content and antioxidant activity of the beverage increased with roasting time, reaching 851.2 mg GAE/100 g (after 80 min) and 18.9 mmol Fe2+/100 g (after 55 min), respectively. The caffeine content remained stable around 16 mg/100 g from 55 to 105 min, lower than that of unroasted coffee beans and decaffeinated coffee. These findings suggest the potential for valorizing baobab seeds in the development of a new coffee-like beverage with lower caffeine content.

A retrospective study in tumour characteristics and clinical outcomes of overweight and obese women with breast cancer.

INTRODUCTION: Obesity and breast cancer are two major pathologies closely associated with increasing incidence and mortality rates, especially amongst women. The association between both diseases have been thoroughly discussed but much is still to uncover. AIM: The aim of this study is to analyse tumour characteristics and clinical outcomes of overweight and obese women to disclosure potential associations and better understand the impact of obesity in breast cancer. MATERIALS AND METHODS: Clinicopathological information of 2246 women were extracted from the institutional database of comprehensive cancer centre in Portugal diagnosed between 2012 and 2016. Women were stratified according to body mass index as normal, overweight, and obese. Patients' demographic information and tumour features (age, family history, topographic localization, laterality, histological type, and receptor status) were taken as independent variables and overall survival, tumour stage, differentiation grade and bilaterality were considered clinical outcomes. RESULTS: The main results reveal that overweight and obesity are predominantly associated with worse outcomes in breast cancer patients. Obese patients present larger (p-value: 0.002; OR 1.422; 95% CI 1.134-1.783) and more poorly differentiated tumours (p-value: 0.002; OR 1.480; 95% CI 1.154-1.898) and tend to have lower overall survival although without statistical significance (p-value: 0.117; OR 1.309; 95% CI 0.934-1.833). Overweighted women are more likely to have bilateral breast cancer (p-value: 0.017; OR 3.076; 95% CI 1.225-7.722) than obese women. The results also reveal that overweight women present less distant metastasis (p-value: 0.024; OR 0.525; 95%CI 0.299-0.920). Topographic localization and laterality did not achieve statistical significance.

Thromboelastography-Guided Therapy Enhances Patient Blood Management in Cirrhotic Patients: A Meta-analysis Based on Randomized Controlled Trials.

Patients with cirrhosis often have abnormal hemostasis, with increased risk of hemorrhage and thrombosis. Thromboelastography provides a rapid assessment of the coagulation status and can guide product transfusions in adult patients with cirrhosis. This study aimed to determine whether the use of thromboelastography in adult patients with cirrhosis decreases blood product use and impacts adverse events or mortality compared with standard practice. A registered (PROSPERO CRD42020192458) systematic review and meta-analysis was conducted for randomized controlled trials (RCTs) comparing thromboelastography-guided hemostatic management versus standard practice (control). Co-primary outcomes were the number of transfused platelet units and fresh frozen plasma (FFP) units. Secondary outcomes were mortality, adverse events, utilization of individual blood products, blood loss or excessive bleeding events, hospital/intensive care unit stay, and liver transplant/intervention outcomes. The search identified 260 articles, with five RCTs included in the meta-analysis. Platelet use was five times lower with thromboelastography versus the control, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03-0.90]; p = 0.04), but FFP use did not differ significantly. Thromboelastography was associated with less blood product (p < 0.001), FFP + platelets (p < 0.001), and cryoprecipitate (p < 0.001) use. No differences were reported in bleeding rates or longer term mortality between groups, with the thromboelastography group having lower mortality at 7 days versus the control (relative risk [95% CI] = 0.52 [0.30-0.91]; p = 0.02). Thromboelastography-guided therapy in patients with cirrhosis enhances patient blood management by reducing use of blood products without increasing complications.

Searching for bacteria able to metabolize polycyclic aromatic sulfur compounds in 12-years periodically fed bioreactor.

Biodesulfurization is a promising alternative for removing sulfur molecules from the polycyclic aromatic sulfur compounds (PASC) found in petroleum. PASC consists of recalcitrant molecules that can degrade fuel quality and cause a range of health and environmental problems. Therefore, identifying bacteria capable of degrading PASC is essential for handling these recalcitrant molecules. Microorganisms in environments exposed to petroleum derivatives have evolved specific enzymatic machinery, such as the 4S pathway associated with the dszABC genes, which are directly linked to sulfur removal and utilization as nutrient sources in the biodesulfurization process. In this study, bacteria were isolated from a bioreactor containing landfarm soil that had been periodically fed with petroleum for 12 years, using a medium containing dibenzothiophene (DBT), 4.6-dimethylbenzothiophene, 4-methylbenzothiophene, or benzothiophene. This study aimed to identify microorganisms capable of degrading PASC in such environments. Among the 20 colonies isolated from an inoculum containing DBT as the sole sulfur source, only four isolates exhibited amplification of the dszA gene in the dszABC operon. The production of 2-hydroxybiphenyl (HPB) and a decrease in DBT were detected during the growth curve and resting cell assays. The isolates were identified using 16S rRNA sequencing belonging to the genera Stutzerimonas and Pseudomonas. These isolates demonstrated significant potential for biodesulfurization and/or degradation of PASC. All isolates possessed the potential to be utilized in the biotechnological processes of biodesulfurization and degradation of recalcitrant PASC molecules.

Consumption of sweetened beverages is associated with the incidence of type 2 diabetes in Brazilian adults (CUME project).

BACKGROUND AND AIM: To evaluate the association between the energy consumption of sweetened beverages (SBs) adjusted for daily energy intake and the incidence of type 2 diabetes. METHODS AND RESULTS: This was a prospective study with 2480 type 2 diabetes mellitus (T2DM)-free Cohort of Universities of Minas Gerais (CUME) participants at baseline and 2-4 years of follow-up. A longitudinal analysis was performed with generalized equation estimation to verify the effect of SB consumption, adjusted for sociodemographic and lifestyle variables, on the incidence of T2DM. The incidence of T2DM was 2.78%. The median calorie intake of daily SB consumption adjusted for energy was 47.7 kcal/day. Participants with the highest consumption of SBs (≥47.7 kcal/day) were 63% (odds ratio [OR] = 1.63; p value-0.049) more likely to acquire T2DM over time compared to the lowest consumption (<47.7 kcal/day). CONCLUSIONS: Higher energy consumption from SBs favored a higher incidence of T2DM among CUME participants. The results reinforce the need for marketing restrictions on these foods and taxation to reduce the consumption of these beverages to prevent T2DM and other chronic noncommunicable diseases.

Off-label use of a vena caval filter in the SVC in an adolescent with upper deep vein thrombosis.

Vena caval filters remain as a useful tool in patients with deep vein thrombosis and contraindications to anticoagulation. Although they are rarely used in paediatric patients, they have been shown to be safe and effective when used in the inferior vena cava.In this case report, we describe the off-label use of a retrievable vena caval filter in the superior vena cava in an adolescent with acute lymphoblastic leukaemia with extensive thrombosis of the right upper neck veins as a means to reduce the risk of pulmonary embolism.

Characterisation and long-term follow-up of children with Brugada syndrome: experience from a tertiary paediatric referral centre.

AIMS: Brugada syndrome is an inherited condition, which typically presents in young adults. It can also be diagnosed in children, but data in this group remain scarce. This study aims to describe the clinical features, management, and follow-up of children with personal or family history of Brugada syndrome. METHODS: Retrospective study of consecutive patients with Brugada history followed up in a tertiary paediatric referral centre between 2009 and 2021. Patients were assessed according to the phenotype: positive (with variable genotype) or negative (with positive genotype). RESULTS: Thirty patients were included (mean age at diagnosis 7 ± 6 years, 53% male). Within the positive phenotype (n = 16), 81% were male, and 88% had spontaneous type 1 ECG pattern. A genetic test was performed in 88% and was positive in 57%. Fourteen patients had a negative phenotype-positive genotype, 79% female, all diagnosed during family screening; 43% mentioned family history of sudden cardiac death. Although most of the patients were asymptomatic, the prevalence of rhythm/conduction disturbances was not negligible, particularly if a positive phenotype. No clinically significant events were reported in the negative phenotype patients. Three patients were hospitalised due to an arrhythmic cause, all in patients with a positive phenotype. CONCLUSION: In our study, the documentation of rhythm and conduction disturbances was not infrequent, especially in patients with a positive phenotype. Despite the significant family history, phenotype negative patients had no relevant events during follow-up. Nevertheless, the management of these patients is not clear cut, and a personalised therapeutic strategy with close follow-up is essential.

An Interpretable Digital Twin for Self-Aware Industrial Machines.

This paper presents a proposed three-step methodology designed to enhance the performance and efficiency of industrial systems by integrating Digital Twins with particle swarm optimization (PSO) algorithms while prioritizing interpretability. Digital Twins are becoming increasingly prevalent due to their capability to offer a comprehensive virtual representation of physical systems, thus facilitating detailed simulations and optimizations. Concurrently, PSO has demonstrated its effectiveness for real-time parameter estimation, especially in identifying both standard and unknown components that influence the dynamics of a system. Our methodology, as exemplified through DC Motor and Hydraulic Actuator simulations, underscores the potential of Digital Twins to augment the self-awareness of industrial machines. The results indicate that our approach can proficiently optimize system parameters in real-time and unveil previously unknown components, thereby enhancing the adaptive capacities of the Digital Twin. While the reliance on accurate data to develop Digital Twin models is a notable consideration, the proposed methodology serves as a promising framework for advancing the efficiency of industrial applications. It further extends its relevance to fault detection and system control. Central to our approach is the emphasis on interpretability, ensuring a more transparent understanding and effective usability of such systems.

Interleukin-6, tumor necrosis factor-α, and CD5 immunolabeling of new experimental endodontic sealer and repair material.

The aim of this study was to evaluate the biocompatibility and immunoinflammatory response of the Sealepox and Sealepox-RP, based on interleukin (IL)-6, tumor necrosis factor (TNF)-α, and CD5 immunolabelling. The ProRoot MTA (PRMTA) was used for comparison. Polyethylene tubes (1.0-mm internal, 1.6-mm external diameter, and 10.0-mm length; ISO 10993) with or without (control) materials were randomly implanted in the dorsum of 35 rats (4 per rat). After 7, 15, 30, 60, and 90 days (n = 7), the tubes were removed for histological and immunohistochemical analysis. The Kruskal-Wallis and Dunn's test for non-parametric data and, ANOVA and Tukey test for parametric data were used (P < 0.05). Hematoxylin and eosin staining revealed that the concentration of inflammatory cells decreased over time with no differences between groups in all periods (P > 0.05). Regarding IL-6 immunostaining, there was no difference at 7 days (P > 0.05); all groups decreased over time, being faster for the PRMTA group and also, with no differences between groups in the last period (P > 0.05). For TNF-α, at 7 days there was no difference between groups (P > 0.05); there was an increase at 15 days for PRMTA and, at 30 and 60 days, for PRMTA and Sealepox compared to the control (P < 0.05). At 90 days, Sealepox RP showed the lowest immunostaining being similar to the control (P > 0.05). Regarding CD5 cells, at 7 days, there was high immunostaining for PRMTA compared to the control (P < 0.05); and significant reduction over time with difference for all groups at 30 and 60 days. (P < 0.05); Sealepox was similar to the control in all periods (P > 0.05). Sealepox RP showed the highest immunostaining at 15 days, being different from the control and PRMTA (P < 0.05); in the other periods it was similar to the control (P > 0.05). It can be concluded that Sealepox and Sealepox-RP were biocompatible and demonstrated similar immunoinflammatory response regarding IL-6, TNF-α, and CD5 compared to PRMTA.

Quality Standard for Rehabilitation of Young Deaf Children Receiving Cochlear Implants.

Background and objectives: More and more children with severe-to-profound hearing loss are receiving cochlear implants (CIs) at an early age to improve their hearing and listening abilities, speech recognition, speech intelligibility, and other aspects of spoken language development. Despite this, the rehabilitation outcomes can be very heterogeneous in this population, not only because of issues related to surgery and fitting or the specific characteristics of the child with his/her additional disabilities but also because of huge differences in the quality of the support and rehabilitation offered by the therapist and the family. These quality standards for the rehabilitation of young deaf children receiving CIs are developed within the European KA202 Erasmus+ project "VOICE"-vocational education and training for speech and language therapists and parents for the rehabilitation of children with CIs, Ref. No.: 2020-1-RO01-KA202-080059. Material and methods: To develop these quality standards, we used the input from the face-to-face interviews of 11 local rehabilitation experts in CIs from the four partner countries of the project and the outcomes of the bibliographic analysis of 848 publications retrieved from six databases: Pub Med, Psych Info, CINAHL, Scopus, Eric, and Cochrane. Based on all this information, we created a first set of 32 quality standards over four domains: general, fitting, rehabilitation, and for professionals. Further on, the Delphi method was used by 18 international rehabilitation experts to discuss and agree on these standards. Results: The results from the literature analysis and the interviews show us that more than 90% of the consulted international experts agreed on 29 quality standards. They focus on different aspects of rehabilitation: the multidisciplinary team, their expertise and knowledge, important rehabilitation topics to focus on, and programming issues related to rehabilitation. Conclusions: These quality standards aim to optimize the activity of speech rehabilitation specialists so that they reach the optimal level of expertise. Also presented is the necessary equipment for the IC team to carry out the rehabilitation sessions in good conditions. This set of quality standards can be useful to ensure the appropriate postoperative care of these children. As a result, the rehabilitation process will be more relaxed, and therapists will have the opportunity to focus more on the specific needs of each child, with the provision of quality services, which will result in better results. This theme is particularly complex and dependent on multifactorial aspects of medicine, education, speech therapy, social work, and psychology that are very intricate and interdependent.

Analysis of T cell receptor clonotypes in tumor microenvironment identifies shared cancer-type-specific signatures.

Despite the conventional view that a truly random V(D)J recombination process should generate a highly diverse immune repertoire, emerging reports suggest that there is a certain bias toward the generation of shared/public immune receptor chains. These studies were performed in viral diseases where public T cell receptors (TCR) appear to confer better protective responses. Selective pressures generating common TCR clonotypes are currently not well understood, but it is believed that they confer a growth advantage. As very little is known about public TCR clonotypes in cancer, here we set out to determine the extent of shared TCR clonotypes in the intra-tumor microenvironments of virus- and non-virus-driven head and neck cancers using TCR sequencing. We report that tumor-infiltrating T cell clonotypes were indeed shared across individuals with the same cancer type, where the majority of shared sequences were specific to the cancer type (i.e., viral versus non-viral). These shared clonotypes were not particularly enriched in EBV-associated nasopharynx cancer but, in both cancers, exhibited distinct characteristics, namely shorter CDR3 lengths, restricted V- and J-gene usages, and also demonstrated convergent V(D)J recombination. Many of these shared TCRs were expressed in patients with a shared HLA background. Pattern recognition of CDR3 amino acid sequences revealed strong convergence to specific pattern motifs, and these motifs were uniquely found to each cancer type. This suggests that they may be enriched for specificity to common antigens found in the tumor microenvironment of different cancers. The identification of shared TCRs in infiltrating tumor T cells not only adds to our understanding of the tumor-adaptive immune recognition but could also serve as disease-specific biomarkers and guide the development of future immunotherapies.

The Brazilian Zika virus strain causes birth defects in experimental models.

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.

The role of viscoelastic testing in assessing peri-interventional platelet function and coagulation.

We carried out a literature search in MEDLINE (PubMed) and EMBASE literature databases to provide a concise review of the role of viscoelastic testing in assessing peri-interventional platelet function and coagulation. The search identified 130 articles that were relevant for the review, covering the basic science of VHA and VHA in clinical settings including cardiac surgery, cardiology, neurology, trauma, non-cardiac surgery, obstetrics, liver disease, and COVID-19. Evidence from these articles is used to describe the important role of VHAs and platelet function testing in various peri-interventional setups. VHAs can help us to comprehensively assess the contribution of platelets and coagulation dynamics to clotting at the site-of-care much faster than standard laboratory measures. In addition to standard coagulation tests, VHAs are beneficial in reducing allogeneic transfusion requirements and bleeding, in predicting ischemic events, and improving outcomes in several peri-interventional care settings. Further focused studies are needed to confirm their utility in the peri-interventional case.

Pachydermodactyly: the role of ultrasonography, superb microvascular imaging, and elastography in diagnosis.

Pachydermodactyly is a rare and benign superficial fibromatosis characterized by painless and progressive swelling of periarticular soft tissues of the proximal interphalangeal (PIP) joints, most commonly of both hands. There is no tenderness, warmth, morning stiffness, or reduced range of motion associated. Our purpose is to highlight the diagnostic utility of ultrasonography, superb microvascular imaging (SMI), and elastography in pachydermodactyly. We report the case of a 15-year-old adolescent white boy, with a 6-month history of insidious and progressive, asymptomatic swelling of the lateral and dorsal regions of the metacarpophalangeal (MCP), and PIP joints of both hands. Articular ultrasonography showed thickening of the skin around the lateral regions of the PIP and MCP joints, with no synovitis, hydrarthrosis, or muscle, tendon, or bone changes. Strain elastography revealed lower elasticity in the aforementioned skin regions, corresponding to increased tissue hardness due to hyperkeratosis. No SMI or Doppler signals were detected in epidermal or dermal tissues, as well as in tendons, joints, and bone. This case report shows that ultrasonography, SMI, and elastography may play a significant role in the accurate diagnosis of pachydermodactyly and exclusion of alternative conditions. These imaging modalities have no ionizing radiation; they are fast, inexpensive, and performed on site. They do not require usage of contrast agents and thus can eliminate the need of invasive procedures such as skin biopsy. They also contribute to reduce health care costs with unnecessary complementary tests and inappropriate treatment.