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Novel identifications of cerebral hemodynamics using BOLD fMRI in patients with sickle cell disease
No full textSickle cell disease (SCD) is a genetic blood disorder characterized by the production of abnormal hemoglobin known as hemoglobin S, which leads to reduced oxygen-carrying capacity of the blood. This reduced blood oxygenation can trigger cerebrovascular remodeling, leading to a higher risk of cerebrovascular disease and cognitive impairment. Despite growing evidence of the importance of cerebrovascular health in managing SCD, the lack of specific diagnostic tools makes this area an underutilized target in clinical care. In this cross-sectional study, we aimed to investigate the hemodynamic mechanisms of SCD through functional magnetic resonance imaging (fMRI) and their relationship with hematological parameters. In this pioneering study, we utilized the patterns of systemic low-frequency oscillations within the blood oxygen level-dependent fMRI signal to discern oxygen levels in the brain and characterize distinct blood flow patterns in patients with SCD. We formulated a unique model that revealed two blood flow patterns in SCD patients: firstly, an abnormal rapid flow pattern through arterio-venous shunting, where highly oxygenated blood reaches the superior sagittal sinus prematurely, circumventing most capillaries; secondly, a normal flow pattern, wherein normally oxygenated blood reaches the superior sagittal sinus after traversing through the capillaries. Our findings indicate that both flow patterns coexist in SCD patients, but in those with more severe blood abnormalities, the rapid flow pattern predominates. This study marks the first instance of employing fMRI to investigate the rich hemodynamic information in SCD patients. The results hold significant potential for the development of non-invasive hemodynamic biomarkers to gauge cerebrovascular health in SCD
Permanent first molar eruption failure in children: leading signs for early diagnosis
No full textBackground: This cross-sectional observational study seeks to determine the clinical differences in eruption failure of permanent first molars presenting in cases of ankylosis, failure due to mechanical obstruction (MFE), and failure due to genetic causes (PFE). A total of 34 patients between 7 and 12 years old (mean ± SD: 9.3 ± 1.28 years), with anomalies in the eruption of the first permanent molars, were selected based on clinical observation, the evaluation of orthopanoramic radiographs, and intra- and extra-oral photographs. Genetic testing was also conducted to identify variants of the PTH1R gene in 27 patients with clinical signs of PFE. The familial nature of the condition was investigated through anamnesis of the first-degree relatives.
Results: Out of the 34 patients, 3 were diagnosed with PFE, confirmed by the presence of PTH1R variants. Twelve patients showed clinical signs suggestive of MFE diagnosis. The remaining 19 cases, in which no variants of the PTH1R gene were found, were considered cases of ankylosis. Roots in ankylosed teeth were located in the basal bone and often dilacerated. The reduction of vertical growth of the alveolar bone was present in both PFE and ankylosis cases, but teeth were nearer to the basal bone in ankylosis cases. Infraocclusion of deciduous teeth was present in PFE and MFE cases. Asymmetry due to bilaterally unbalanced eruption of the teeth was present in six cases with ankylosis. Bilateral affection was noticed in one PFE case and 6 MFE cases. A descriptive statistical analysis using Fisher's exact test was employed to evaluate the significant association between variables.
Conclusions: The study highlighted some characteristic signs that help in early diagnosis of cases of PFE, MFE, and ankylosis. However, genetic testing remains necessary to understand the nature of the most dubious cases
Beyond the injection: delivery systems reshaping retinal disease management
No full textIntroduction: Intravitreal injections remain the standard for treating common retinal diseases including age-related macular degeneration (AMD), diabetic macular edema (DME) and diabetic retinopathy. However, frequent administration creates significant treatment burden due to limited drug half-life and the chronic nature of these conditions.
Areas covered: This review summarizes emerging drug delivery techniques and therapies for retinal disease that have achieved FDA approval within the past five years or have advanced to Phase 3 development, including intravitreal sustained-release platforms and alternative delivery routes (suprachoroidal, subretinal, topical, and subcutaneous). Specific innovations discussed include the ranibizumab port delivery system, EYP-1901 (Duravyu, vorolanib implant), KSI-301 (tarcocimab tedromer), KSI-501, OTX-TKI (Axpaxli, axitinib implant), 4D-150, revakinagene taroretcel-lwey (Encelto, NT-501, encapsulated cell therapy), Xipere (triamcinolone acetonide injectable suspension), AU-011 (belzupacap sarotalocan targeted delivery), ABBV-RGX-314, elamipretide, and OCS-01 (high concentration dexamethasone).
Expert opinion: Promising innovations include sustained-release intravitreal implants, topical and subcutaneous delivery systems, and targeted methods like suprachoroidal and subretinal injections, each with unique advantages and limitations. Challenges include overcoming the blood-retinal barrier, surgical complications with implantable devices, and ensuring patient adherence. Advances in smart delivery systems, drug formulations, and predictive models, alongside interdisciplinary collaboration, will be crucial in achieving personalized, effective, and sustainable retinal therapies
Cardiac Point of Care Ultrasound (POCUS) Used to Diagnose Infective Endocarditis Following Multiple Negative Echocardiograms
No full textInfective endocarditis (IE) is a life-threatening condition often diagnosed using the modified Duke's criteria, including bacteremia and pathognomonic echocardiographic findings. However, up to 30% of cases yield inconclusive results with transthoracic echocardiograms (TTE) or transesophageal echocardiograms (TEE). We present a case of a 68-year-old man with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia and recurrent fevers, in which multiple echocardiograms failed to detect valvular vegetations. However, an advanced cardiac point of care ultrasound (POCUS) examination identified a vegetation on the aortic valve, later confirmed by TTE and TEE. Although generalization is limited due to operator expertise and patient characteristics, this case demonstrates the utility of advanced cardiac POCUS in diagnosing IE in critically ill patients with negative initial echocardiograms. Incorporating advanced cardiac POCUS into routine diagnostic workflows may improve diagnostic accuracy and patient outcomes. Increasing use of advanced cardiac POCUS also highlights the importance of expanding proficiency among intensivists
Factors determining diversity of saproxylic arthropods in the fruiting bodies of the birch polypore fungus (Fomitopsis betulina)
No full textObjective: Certain basidiomycete fungi produce semi-stable fruiting bodies, known as brackets, that support a significant quality of saproxylic invertebrate biodiversity, especially in northern forests. The objective of this investigation was to assess the drivers of saproxylic diversity within the fruiting bodies of Fomitopsis betulina. We explore which factors are significant determinants of arthropod diversity and abundance, examining the effects of sporocarp size, height above the ground, and relative isolation from neighbouring sporocarps.
Results: We find that larger sporocarps support a greater number of arthropods, but diversity and species richness are determined by distance from nearest neighbour
International Society for Prenatal Diagnosis 2024 Debate 3—Cytogenetics Is a Dinosaur and Should Be Replaced by Molecular Technologies
No full textCytogenetic technologies such as G-banding chromosome and FISH analyses have long been the gold standard diagnostic test in prenatal genetic testing. However, unbiased next-generation sequencing technologies such as fetal exome or genome sequencing (ES/GS) are becoming widely accessible and increasingly utilized, particularly for fetuses with structural anomalies. Emerging studies are now establishing increased diagnostic yields from molecular technologies, but there remains a lack of consensus as to whether ES/GS should replace cytogenetic technologies and targeted genepanel screening as first-line tests for all prenatal diagnoses. This report is a summary of the debate on this topic presented at the 28th International Conference on Prenatal Diagnosis and Fetal Therapy. Both expert debaters discussed the advantages and disadvantages
Malaria Vaccines and Global Equity: A Scoping Review of Current Progress and Future Directions
No full textThe journey toward a viable malaria vaccine, initiated in 1965, reached a major milestone in 2021 with the WHO's endorsement of RTS,S/AS01, a recombinant protein-based malaria vaccine. This progress continued with the 2023 approval of the R21/Matrix-M vaccine, which is more cost-effective, more potent due it is higher protein content, and easier to manufacture. Though these achievements signal hope, malaria's intricate life cycle and its prevalence in underprivileged regions make vaccine development and equitable distribution challenging. This review explains the lifecycle of malaria and explores the evolution of various treatment strategies aimed at reducing malaria-related mortality. This scoping review aims to provide a comprehensive overview of malaria vaccines, examining their development, efficacy, safety, and implementation challenges. Using a structured literature search across PubMed, Web of Science, and Scopus, we identified key themes related to malaria vaccines trials, policy implications, and future research needs. Peer-reviewed publications on PubMed, Scopus, and Web of Science from 1970 to 2024 were searched without any limitations. Search and Boolean search terms were modified to include terms like "malaria vaccines", "malaria vaccination", "malaria immunisation", "malaria immunisation AND malaria-endemic countries", "malaria endemic low-income countries AND malaria control", "malaria public health control", "malaria chemoprophylaxis AND early diagnosis of malaria", "screening for malaria", and "laboratory diagnosis of malaria in endemic countries" in order to find pertinent studies. Preliminary insights suggest that although vaccines are crucial, comprehensive strategies involving health education, hygiene, and timely medical intervention remain essential to malaria control
Non‐Invasive Follicular Thyroid Neoplasm With Papillary‐Like Nuclear Features (NIFTPs)
No full textOver the past few years, follicular-patterned thyroid nodules with nuclear features of papillary thyroid carcinoma (PTC) have been further subclassified based on molecular profiling, histologic features, and clinical behavior. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) was established as a distinct entity in the 2017 4th edition of the WHO Classification of Tumors of Endocrine Organs due to its indolent clinical behavior and excellent prognosis. These tumors are characterized by a well-defined border, an exclusive follicular growth pattern, and PTC nuclear features. Molecularly, NIFTPs typically harbor RAS gene mutations, PAX8-PPARG rearrangements, or THADA gene fusions. In the 2022 5th edition of the WHO Classification, subcentimeter NIFTPs and oncocytic NIFTPs were introduced as new subtypes. In this review, we summarize the epidemiology, ultrasound features, histology/cytology, and molecular characteristics of NIFTP. As research continues to refine diagnostic criteria and management approaches, recognizing the distinct molecular and clinical features of NIFTP is essential for optimizing patient care and ensuring appropriate surgical management
Probing orthobunyavirus reassortment using Bunyamwera and Batai viruses as models
No full textReassortment is a critical evolutionary mechanism for segmented viruses, enabling the exchange of intact genome segments during co-infection and driving orthobunyavirus evolution; however, the molecular mechanisms underpinning this process remain unclear. With over 100 orthobunyavirus species, many of which are significant human and veterinary pathogens, understanding how reassortment influences transmissibility and virulence is essential for preempting the emergence of novel pathogens. Here, we use Bunyamwera virus (BUNV) and Batai virus (BATV) as models to explore orthobunyavirus reassortment through reverse genetics. We established the first reverse genetics system for BATV, generated reassortants, and employed minigenome assays to assess replication machinery compatibility. Additionally, we developed a novel hybridization chain reaction assay for high-resolution visualization of viral RNA segments. Our findings revealed that all six reassortants between BUNV and BATV are viable, exhibiting notable phenotypic differences in interferon-deficient (IFNAR-/-) mice. This work introduces essential tools and new insights into orthobunyavirus reassortment and pathogenesis, laying the groundwork for understanding this critical evolutionary process
Assessing Partnerships Fostered Through Community Engagement Initiatives
No full textThis project focused on evaluating participant satisfaction with HANDS in Autism® community engagement initiatives, particularly the “Let’s Talk LCC” events conducted between August 2024 and April 2025. These events, grounded in four core pillars—collaboration, information sharing, training, and dissemination—were assessed using survey data extracted from REDCap. After data cleaning and standardization, descriptive statistical analysis and Power BI visualizations were used to identify trends in participant satisfaction across various months, topics, and event types. Findings showed consistently higher satisfaction with interactive sessions and underscored the critical role of informatics in enhancing engagement strategies. This project strengthened skills in health data analysis, visualization, and cross-functional communication, while supporting data-driven recommendations for improving autism-focused community programs