Etiopatogenia e tratamento da osteonecrose dos maxilares induzida por medicamentos: aspectos essenciais ao dentista / Etiopathogenesis and treatment of medication-related osteonecrosis of the jaw: essential aspects for the dentist

A osteonecrose dos maxilares induzida por medicamentos (MRONJ) caracteriza-se por exposição óssea ou osso que pode ser sondado através de fístula intra ou extraoral, em região maxilofacial, e que não cicatriza dentro de oito semanas. A MRONJ é uma condição rara e debilitante que pode causar dor, disfagia e odor desagradável na cavidade oral, afetando pacientes com histórico ou sob uso contínuo de terapia antirreabsortiva, isolada ou associada a imunomoduladores ou drogas antiangiogênicas, mas sem histórico de radioterapia nos maxilares. O objetivo desta revisão narrativa de literatura é compilar os principais aspectos sobre a etiopatogenia da MRONJ e as opções terapêuticas disponíveis. A etiologia da MRONJ é multifatorial, complexa, e não está totalmente compreendida, não havendo um tratamento definitivo, mas diversas modalidades terapêuticas que visam o controle da dor e da progressão da osteonecrose. Conclui-se com essa revisão que o entendimento da etiopatogenia da MRONJ pelo cirurgião-dentista lhe permite adotar medidas preventivas, bem como o conhecimento das modalidades terapêuticas disponíveis lhe possibilita oferecer o manejo adequado para seu paciente, conforme o estágio da doença.

Medication-related osteonecrosis of the jaw (MRONJ) is characterized by exposed bone or bone that can be probed through an intra or extraoral fistula, in the maxillofacial region, which does not heal within eight weeks. MRONJ is a rare and debilitating condition that can cause pain, dysphagia and unpleasant odor in the oral cavity, affecting patients with a history or continuous use of antiresorptive therapy, alone or associated with immunomodulators or antiangiogenic drugs, but without a history of radiotherapy to the jaws. The aim of this narrative literature review is to compile the main aspects about the etiopathogenesis of MRONJ and the available therapeutic options. The etiology of MRONJ is multifactorial, complex, and is not fully understood, with no definitive treatment, but several therapeutic modalities that aim to control pain and the progression of osteonecrosis. It is concluded from this review that the understanding of the etiopathogenesis of MRONJ by the dental surgeon allows him to adopt preventive measures, as well as the knowledge of the therapeutic modalities available allows him to offer the appropriate management for his patient, depending on the stage of the disease.

Medical Students' Impression of Surgical Pathology as a Career in Saudi Arabia.

BACKGROUND AND OBJECTIVES: Surgical/anatomical pathologists study diseases to provide accurate diagnoses, identify pathogens, and participate in treatment. However, there is a need for more surgical pathologists worldwide due to low recruitment rates. One contributing factor is the medical students' interest and knowledge about surgical pathology as a career option. Understanding medical students' knowledge and perceptions about surgical pathologist jobs is crucial for future physicians, as it influences collaboration with pathologists and impacts patient care outcomes. This study aims to evaluate medical students' knowledge of surgical pathologists' jobs in Saudi Arabian medical colleges, which will help identify gaps in knowledge and develop targeted interventions to promote interest in surgical pathology as a career. For simplicity, in this study, we refer to anatomical/surgical pathology as "pathology". METHODS AND RESULTS: A cross-sectional study was done in Saudi Arabia with a total of 478 medical students examining their perception of pathologist's job using a validated questionnaire distributed through social media platforms. The study revealed that 322 (67%) had no interest and did not consider becoming pathologists in the future, and 194 (40%) chose lack of patient contact as the main reason for not joining this field. However, 15% of the students think that pathologists have flexible lifestyle. CONCLUSION: Our study shows that many students are not interested in pathology as a career, with varied responses revealing uncertainty about pathologists' roles. To spark interest, universities should involve students in laboratories and decision-making processes, prioritize understanding pathologists' roles, and emphasize their impact on patients' lives.

Maude Abbott: "A Feminine Misfit in an Exclusive Male Environment" and Her Strategies for Success.

Maude Abbott was a pioneering female Canadian physician who became a world authority on medical museums and congenital heart disease. Abbott spent almost all her career in highly sexist, discriminatory work environments. This paper reviews Abbott's life and accomplishments, but, more importantly, analyzes her pathway to success in the masculine world of early 20th-century academic pathology. Abbott, though well-trained as a pathologist, never provided clinical service, but instead worked as museum curator at McGill University. She established the International Association of Medical Museums (predecessor to the International Academy of Pathology), edited its journal, and essentially ran the organization. Abbott, surrounded by influential males, dealt differently with each. In general, she recognized that male doctors believed women lacked the gravitas to lead major initiatives but that she could circumnavigate this supposed impediment by co-leading projects with male counterparts, preferably ones too busy to get in her way. She repeatedly used this approach, and by doing most of the work but sharing credit, succeeded in gaining reputation, accomplishment, and advancement. Abbott's pioneering work on congenital heart disease established her as one of the founders of pediatric pathology, and, overall, her career promoted the entry of women physicians into the pathology profession.

Socioeconomic and medical determinants of state-level subjective cognitive decline in the United States.

INTRODUCTION: It is important to understand the socioeconomic and medical determinants of subjective cognitive decline (SCD) at a population level in the United States. METHODS: The primary outcomes are state-level rates of SCD and SCD-related functional impairment in adults aged ≥ 45, both measured in the Behavioral Risk Factor Surveillance System from 2016 to 2022. The exposures are state-level rates of poverty, unemployment, homelessness, college education, racial and ethnic minorities, uninsurance, smoking, hypertension, diabetes, and obesity as well as household income and physician density. RESULTS: The strongest state-level associations with rates of SCD were the prevalence of diabetes (rho = 0.64), hypertension (rho = 0.59), and poverty (rho = 0.58; all p < 0.001), and with SCD-related functional impairment were prevalence of poverty (rho = 0.71), diabetes (rho = 0.68), and hypertension (rho = 0.53; all p < 0.001). DISCUSSION: This study highlights critical links between SCD and socioeconomic and medical determinants in adults aged ≥ 45 in the United States, including the prevalence of poverty, diabetes, and hypertension. HIGHLIGHTS: State-level analysis reveals socioeconomic and medical risk factors for subjective cognitive decline (SCD) at a population level. The prevalence of poverty is a critical contributor to the state-level prevalence of SCD. The prevalence of diabetes and hypertension are also strong state-level determinants of SCD. Addressing the burden of cognitive decline at the population level necessitates targeting socioeconomic and medical factors.

Standardization through education of molecular pathology: a spotlight on the European Masters in Molecular Pathology.

Despite advancements in precision medicine, many cancer patients globally, particularly those in resource-constrained environments, face significant challenges in accessing high-quality molecular testing and targeted therapies. The considerable heterogeneity in molecular testing highlights the urgent need to harmonize practices across Europe and beyond, establishing a more standardized and consistent approach in MP laboratories. Professionals, especially molecular pathologists, must move beyond traditional education to cope with this heterogeneity. This perspective addresses critical issues in molecular pathology (MP), such as limited access to high-quality molecular testing, leading to disparities in cancer treatment, and the consequences of inconsistent practices. Recognizing the necessity for a standardized framework for education to address these issues, educational programs play a pivotal role in updating professionals' skills to achieve standardization in MP. European experts from the Steering Committee, the Pathology Section of the European Union of Medical Specialists, and the European Society of Pathology have proposed creating a comprehensive Master's degree program called the "European Masters in Molecular Pathology" (EMMP). This program emerges as a strategic response to the demand for a specialized and standardized framework for education in MP, catering to professionals who concurrently work and study. The program's design aligns with evidence-based education methods, ensuring effective learning and engagement while integrating computational pathology to analyze complex molecular data, enhance diagnostic accuracy, and improve treatment outcomes. EMMP's structured curriculum, strategic partnerships, and regular updates underscore its significance in standardizing MP practices. Exploring future developments, this perspective delves into technology integration and interdisciplinary collaboration, anticipating ongoing advances and harmonization. Challenges and future directions in MP education are discussed, emphasizing the necessity for dynamic curriculum updates, seamless technology integration, and interdisciplinary cooperation. This perspective underscores EMMP's pivotal role in preparing pathologists for this dynamic field, advocating continuous advancements in education and training to uphold excellence in MP practices and maintain the highest patient care standards.

The future of multimodal artificial intelligence models for integrating imaging and clinical metadata: a narrative review.

With the ongoing revolution of artificial intelligence (AI) in medicine, the impact of AI in radiology is more pronounced than ever. An increasing number of technical and clinical AI-focused studies are published each day. As these tools inevitably affect patient care and physician practices, it is crucial that radiologists become more familiar with the leading strategies and underlying principles of AI. Multimodal AI models can combine both imaging and clinical metadata and are quickly becoming a popular approach that is being integrated into the medical ecosystem. This narrative review covers major concepts of multimodal AI through the lens of recent literature. We discuss emerging frameworks, including graph neural networks, which allow for explicit learning from non-Euclidean relationships, and transformers, which allow for parallel computation that scales, highlighting existing literature and advocating for a focus on emerging architectures. We also identify key pitfalls in current studies, including issues with taxonomy, data scarcity, and bias. By informing radiologists and biomedical AI experts about existing practices and challenges, we hope to guide the next wave of imaging-based multimodal AI research.

Galileo-an Artificial Intelligence tool for evaluating pre-implantation kidney biopsies.

BACKGROUND: Pre-transplant procurement biopsy interpretation is challenging, also because of the low number of renal pathology experts. Artificial intelligence (AI) can assist by aiding pathologists with kidney donor biopsy assessment. Herein we present the "Galileo" AI tool, designed specifically to assist the on-call pathologist with interpreting pre-implantation kidney biopsies. METHODS: A multicenter cohort of whole slide images acquired from core-needle and wedge biopsies of the kidney was collected. A deep learning algorithm was trained to detect the main findings evaluated in the pre-implantation setting (normal glomeruli, globally sclerosed glomeruli, ischemic glomeruli, arterioles and arteries). The model obtained on the Aiforia Create platform was validated on an external dataset by three independent pathologists to evaluate the performance of the algorithm. RESULTS: Galileo demonstrated a precision, sensitivity, F1 score and total area error of 81.96%, 94.39%, 87.74%, 2.81% and 74.05%, 71.03%, 72.5%, 2% in the training and validation sets, respectively. Galileo was significantly faster than pathologists, requiring 2 min overall in the validation phase (vs 25, 22 and 31 min by 3 separate human readers, p < 0.001). Galileo-assisted detection of renal structures and quantitative information was directly integrated in the final report. CONCLUSIONS: The Galileo AI-assisted tool shows promise in speeding up pre-implantation kidney biopsy interpretation, as well as in reducing inter-observer variability. This tool may represent a starting point for further improvements based on hard endpoints such as graft survival.

Epistemic Trust: a Keyword for Contemporary Clinical Practice and Psychopathology.

The increasing integration of eclectic knowledge from fields not directly related to clinical psychology is coherent with a current tendency to employ alternative ideas to investigate psychopathology in the light of a more phenomenological perspective. The concept of epistemic trust may provide the gateway to alternative causal models for personality psychopathology that links poor mentalizing environment to a more general lack of social support. People who have been denied the ability to trust the information circulating in their more proximate environment may showcase a remarkable disadvantage in terms of social adjustment that relate to early insecure attachment experiences. Research assumes that patients who have been suffering an epistemic deficient environment in infancy could be trapped into a vicious cycle of suffering, loneliness and inability to seek or accept help. Although most contributes cited in this brief article deal with epistemic trust as potential tool for social learning from a theoretical point of view, the recent introduction of systematic measures of epistemic trust as a dimensional personality variable outlines a likely future increase in the use of new questionnaires and protocols for clinical assessment and treatment monitoring expressively focused on epistemic trust. The benefits of adopting such a holistic etiological paradigm in personality pathology are outlined, as proposed by the many works that advocate a more equitable clinical practice that assume individual development in the context of an unequal social world, that is believed to determine the child's evolutionary trajectory from the very first stages of life. In the same vein, the importance of fostering an authentic relationship of trust between patient and therapist as a fundamental element of the therapeutic alliance, as well as a driving force for salutogenesis at the community level, is vividly highlighted.

PViT-AIR: Puzzling vision transformer-based affine image registration for multi histopathology and faxitron images of breast tissue.

Breast cancer is a significant global public health concern, with various treatment options available based on tumor characteristics. Pathological examination of excision specimens after surgery provides essential information for treatment decisions. However, the manual selection of representative sections for histological examination is laborious and subjective, leading to potential sampling errors and variability, especially in carcinomas that have been previously treated with chemotherapy. Furthermore, the accurate identification of residual tumors presents significant challenges, emphasizing the need for systematic or assisted methods to address this issue. In order to enable the development of deep-learning algorithms for automated cancer detection on radiology images, it is crucial to perform radiology-pathology registration, which ensures the generation of accurately labeled ground truth data. The alignment of radiology and histopathology images plays a critical role in establishing reliable cancer labels for training deep-learning algorithms on radiology images. However, aligning these images is challenging due to their content and resolution differences, tissue deformation, artifacts, and imprecise correspondence. We present a novel deep learning-based pipeline for the affine registration of faxitron images, the x-ray representations of macrosections of ex-vivo breast tissue, and their corresponding histopathology images of tissue segments. The proposed model combines convolutional neural networks and vision transformers, allowing it to effectively capture both local and global information from the entire tissue macrosection as well as its segments. This integrated approach enables simultaneous registration and stitching of image segments, facilitating segment-to-macrosection registration through a puzzling-based mechanism. To address the limitations of multi-modal ground truth data, we tackle the problem by training the model using synthetic mono-modal data in a weakly supervised manner. The trained model demonstrated successful performance in multi-modal registration, yielding registration results with an average landmark error of 1.51 mm (±2.40), and stitching distance of 1.15 mm (±0.94). The results indicate that the model performs significantly better than existing baselines, including both deep learning-based and iterative models, and it is also approximately 200 times faster than the iterative approach. This work bridges the gap in the current research and clinical workflow and has the potential to improve efficiency and accuracy in breast cancer evaluation and streamline pathology workflow.

α-Synuclein pathology disrupts mitochondrial function in dopaminergic and cholinergic neurons at-risk in Parkinson's disease.

BACKGROUND: Pathological accumulation of aggregated α-synuclein (aSYN) is a common feature of Parkinson's disease (PD). However, the mechanisms by which intracellular aSYN pathology contributes to dysfunction and degeneration of neurons in the brain are still unclear. A potentially relevant target of aSYN is the mitochondrion. To test this hypothesis, genetic and physiological methods were used to monitor mitochondrial function in substantia nigra pars compacta (SNc) dopaminergic and pedunculopontine nucleus (PPN) cholinergic neurons after stereotaxic injection of aSYN pre-formed fibrils (PFFs) into the mouse brain. METHODS: aSYN PFFs were stereotaxically injected into the SNc or PPN of mice. Twelve weeks later, mice were studied using a combination of approaches, including immunocytochemical analysis, cell-type specific transcriptomic profiling, electron microscopy, electrophysiology and two-photon-laser-scanning microscopy of genetically encoded sensors for bioenergetic and redox status. RESULTS: In addition to inducing a significant neuronal loss, SNc injection of PFFs induced the formation of intracellular, phosphorylated aSYN aggregates selectively in dopaminergic neurons. In these neurons, PFF-exposure decreased mitochondrial gene expression, reduced the number of mitochondria, increased oxidant stress, and profoundly disrupted mitochondrial adenosine triphosphate production. Consistent with an aSYN-induced bioenergetic deficit, the autonomous spiking of dopaminergic neurons slowed or stopped. PFFs also up-regulated lysosomal gene expression and increased lysosomal abundance, leading to the formation of Lewy-like inclusions. Similar changes were observed in PPN cholinergic neurons following aSYN PFF exposure. CONCLUSIONS: Taken together, our findings suggest that disruption of mitochondrial function, and the subsequent bioenergetic deficit, is a proximal step in the cascade of events induced by aSYN pathology leading to dysfunction and degeneration of neurons at-risk in PD.

NLRP3 inflammasome activation and pyroptosis are dispensable for tau pathology.

Background: Neuroinflammation is widely recognized as a key factor in the pathogenesis of Alzheimer's disease (AD), alongside ß-amyloid deposition and the formation of neurofibrillary tangles. The NLR family pyrin domain containing 3 (NLRP3) inflammasome, part of the innate immune system, has been implicated in the neuropathology of both preclinical amyloid and tau transgenic models. Activation of the NLRP3 pathway involves an initial priming step, which increases the expression of Nlrp3 and interleukin (IL)-1ß, followed by the assembly of the NLRP3 inflammasome complex, comprising NLRP3, ASC, and caspase-1. This assembly leads to the proteolytic maturation of the pro-inflammatory cytokines IL-1ß and IL-18. Additionally, the NLRP3 inflammasome induces Gasdermin D (GSDMD) cleavage, forming membrane pores through which IL-1ß and IL-18 are secreted. Inhibition of NLRP3 has been shown to enhance plaque clearance by modulating microglial activation. Furthermore, blocking NLRP3 in tau transgenic mice has been found to reduce tau phosphorylation by affecting the activity of certain tau kinases and phosphatases. Methods: In this study, organotypic brain slice cultures from P301S transgenic mice were treated with lipopolysaccharide (LPS) plus nigericin as a positive control or exposed to tau seeds (K18) to evaluate NLRP3 inflammasome activation. The effect of tau seeding on NLRP3 activity was further examined using Meso Scale Discovery (MSD) assays to measure IL1ß secretion levels in the presence and absence of NLRP3 inhibitors. The role of NLRP3 activity was investigated in full-body Nlrp3 knockout mice crossbred with the tau transgenic P301S model. Additionally, full-body and microglia-selective Gsdmd knockout mice were crossbred with P301S mice, and tau pathology and neurodegeneration were evaluated at early and late stages of the disease using immunohistochemistry and biochemical assays. Results: Activation of the NLRP3 pathway was observed in the mouse organotypic slice culture (OSC) model following stimulation with LPS and nigericin or exposure to tau seeds. However, Nlrp3 deficiency did not mitigate tauopathy or neurodegeneration in P301S mice in vivo, showing only a minor effect on plasma neurofilament (NF-L) levels. Consistently, Gsdmd deficiency did not alter tau pathology in P301S mice. Furthermore, neither full-body nor microglia-selective Gsdmd deletion had an impact on neuronal pathology or the release of pro-inflammatory cytokines. Conclusion: The absence of key components of the NLRP3 inflammasome pathway did not yield a beneficial effect on tau pathology or neurodegeneration in the preclinical Tau-P301S mouse model of AD. Nonetheless, organotypic slice cultures could serve as a valuable ex vivo mechanistic model for evaluating NLRP3 pathway activation and pharmacological inhibitors.

Rat shoulder contracture models: Techniques, evaluation, pathophysiology, and applications in developing treatment interventions.

Studies on the pathophysiology of shoulder contracture and development of interventions have greatly benefited from the use of animal models. This narrative review comprehensively analyzes research on established rat model of shoulder contracture and new treatment approaches. This review evaluated existing literature on the available techniques for inducing contracture models, assessed these models, conducted pathological analyses, and explored their application in developing new treatment interventions. Our review highlights the usefulness of different rat shoulder contracture models, including external immobilization, internal immobilization, and intra-articular injection models, each with varying levels of success. Pathological analyses have demonstrated similarities to the human condition. The effective models have been instrumental in developing new treatment interventions, including recombinant human relaxin-2, platelet-rich plasma, collagenase clostridium histolyticum, and peroxisome proliferator-activated receptor-γ agonists. Therefore, rat shoulder contracture models serve as valuable tools for researchers to establish an effective animal model foundation for investigating the etiology and potential treatment.

Graduated responsibility and competency-based education in pathology residency programs: a five-year semi-longitudinal landscape assessment on autonomy and supervision.

Pathology residency training has been criticized for having too little opportunities for resident autonomy. As graduate medical education moves to competency-based models measuring competency and giving autonomy for specific tasks will be important. To determine how much autonomy residents are currently granted we surveyed pathology residency directors with regard to a list of usual pathology tasks and compared responses with those of a similar survey from 2018. Among the 29 programs whose directors responded, we found a considerable range within which some programs give much autonomy and others very little. Most programs did not describe measuring competency before granting performance of specific activities. We urge that restrictive programs examine the more permissive programs to see how they can move toward granting more autonomy.

Ultrasound-Guided Glucocorticoid Injection as a Treatment for Rotator Cuff Calcific Tendinopathy: A Case Report.

Rotator cuff calcific tendinopathy (RCCT) is a common disorder of the rotator cuff causing shoulder pain and dysfunction. RCCT is characterized by calcium deposition on and around the tendons of the rotator cuff muscles. Treatment is typically conservative, consisting of anti-inflammatory drugs (NSAIDs) and physical therapy, although certain patients require more invasive treatment. If first-line treatments do not resolve the pain, second-line treatments such as glucocorticoid injections, extracorporeal shock wave therapy (ESWT), barbotage, and surgery may be considered; however, there is no gold standard treatment for these refractory cases. In this case study, a 36-year-old female patient with confirmed RCCT achieved symptom remission with ultrasound-guided methylprednisolone injection followed by adjunctive physical therapy. Ultrasonography enabled precise, targeted delivery of steroids to the calcified lesions, with near 100% resolution of deposits on repeat radiography. With additional physical therapy, the patient was completely pain-free with a full range of motion and the ability to perform daily activities. This case report demonstrates that ultrasound-guided glucocorticoid injection can be an efficacious treatment option for refractory cases of RCCT.

Turmeric supplement-associated hepatitis: a clinicopathological series of 11 cases highlighting pan-lobular and zone 3 injury.

AIMS: Although turmeric is commonly ingested and well tolerated, there is increasing evidence that over-the-counter turmeric supplements can cause drug-induced liver injury. We sought to thoroughly characterise clinicopathological features of patients for whom liver injury was attributed clinically to turmeric supplements. METHODS AND RESULTS: We identified 11 patients via retrospective pathology archive review: 10 females (91%) and one male, with a median age of 58 years (range = 37-66 years). Six patients (55%) were asymptomatic with abnormal liver function tests, while five patients (45%) presented with malaise and/or jaundice. Ten patients (91%) showed predominant transaminase abnormalities, while one exhibited predominant alkaline phosphatase elevation. Histologically, biopsies showed acute hepatitis (eight cases, 73%, including five pan-lobular and three zone 3-predominant inflammation), scattered lobular aggregates of histiocytes (two; 18%) and a chronic hepatitis pattern of injury (one; 9%). Mild bile duct injury was present in five biopsies (45%). All patients stopped ingesting turmeric supplements after presenting with liver injury, and four patients additionally received steroid therapy; liver function tests normalised in all patients. Roussel Uclaf causality assessment method (RUCAM) analysis estimated the likelihood of turmeric supplement-associated liver injury to be probable (eight cases) and possible (three). CONCLUSIONS: Histological features in the 'possible' cases were consistent with drug-induced injury, highlighting the added benefit of histological analysis relative to RUCAM analysis isolation. This study underscores the need to obtain a full history of over-the-counter medications and supplements when investigating aetiologies for liver injury, including supplements purportedly containing innocuous compounds such as turmeric.

Spatial Transcriptomics Unravel the Tissue Complexity of Oral Pathogenesis.

Spatial transcriptomics (ST) is a cutting-edge methodology that enables the simultaneous profiling of global gene expression and spatial information within histological tissue sections. Traditional transcriptomic methods lack the spatial resolution required to sufficiently examine the complex interrelationships between cellular regions in diseased and healthy tissue states. We review the general workflows for ST, from specimen processing to ST data analysis and interpretations of the ST dataset using visualizations and cell deconvolution approaches. We show how recent studies used ST to explore the development or pathogenesis of specific craniofacial regions, including the cranium, palate, salivary glands, tongue, floor of mouth, oropharynx, and periodontium. Analyses of cranial suture patency and palatal fusion during development using ST identified spatial patterns of bone morphogenetic protein in sutures and osteogenic differentiation pathways in the palate, in addition to the discovery of several genes expressed at critical locations during craniofacial development. ST of salivary glands from patients with Sjögren's disease revealed co-localization of autoimmune antigens with ductal cells and a subpopulation of acinar cells that was specifically depleted by the dysregulated autoimmune response. ST of head and neck lesions, such as premalignant leukoplakia progressing to established oral squamous cell carcinomas, oral cancers with perineural invasions, and oropharyngeal lesions associated with HPV infection spatially profiled the complex tumor microenvironment, showing functionally important gene signatures of tumor cell differentiation, invasion, and nontumor cell dysregulation within patient biopsies. ST also enabled the localization of periodontal disease-associated gene expression signatures within gingival tissues, including genes involved in inflammation, and the discovery of a fibroblast subtype mediating the transition between innate and adaptive immune responses in periodontitis. The increased use of ST, especially in conjunction with single-cell analyses, promises to improve our understandings of craniofacial development and pathogenesis at unprecedented tissue-level resolution in both space and time.

Texture analysis can predict response to etoposide-doxorubicin-cisplatin in patients with adrenocortical carcinoma.

BACKGROUND: The adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy originating from the adrenal cortex. These patients usually undergo chemotherapy with etoposide, doxorubicin, cisplatin and mitotane (EDP-M) in case of locally advanced or metastatic ACC. Computed tomography (CT) radiomics showed to be useful in adrenal pathologies. The study aimed to analyze the association between response to EDP-M treatment and CT textural features at diagnosis in patients with locally advanced or metastatic ACCs. METHODS: We enrolled 17 patients with advanced or metastatic ACC who underwent CT before and after EDP-M therapy. The response to treatment was evaluated according to RECIST 1.1, Choi, and volumetric criteria. Based on the aforementioned criteria, the patients were classified as responders and not responders. Textural features were extracted from the biggest lesion in contrast-enhanced CT images with LifeX software. ROC curves were drawn for the variables that were significantly different (p < 0.05) between the two groups. RESULTS: Long-run high grey level emphasis (LRHGLE_GLRLM) and histogram kurtosis were significantly different between responder and not responder groups (p = 0.04) and the multivariate ROC curve combining the two features showed a very good AUC (0.900; 95%IC: 0.724-1.000) in discriminating responders from not responders. More heterogeneous tissue texture of initial staging CT in locally advanced or metastatic ACC could predict the positive response to EDP-M treatment. CONCLUSIONS: Adrenal texture is able to predict the response to EDP-M therapy in patients with advanced ACC.

Multifaceted roles of mitochondria in asthma.

Mitochondria are essential organelles within cells, playing various roles in numerous cellular processes, including differentiation, growth, apoptosis, energy conversion, metabolism, and cellular immunity. The phenotypic variation of mitochondria is specific to different tissues and cell types, resulting in significant differences in their function, morphology, and molecular characteristics. Asthma is a chronic, complex, and heterogeneous airway disease influenced by external factors such as environmental pollutants and allergen exposure, as well as internal factors at the tissue, cellular, and genetic levels, including lung and airway structural cells, immune cells, granulocytes, and mast cells. Therefore, a comprehensive understanding of the specific responses of mitochondria to various external environmental stimuli and internal changes are crucial for elucidating the pathogenesis of asthma. Previous research on mitochondrial-targeted therapy for asthma has primarily focused on antioxidants. Consequently, it is necessary to summarize the multifaceted roles of mitochondria in the pathogenesis of asthma to discover additional strategies targeting mitochondria in this context. In this review, our goal is to describe the changes in mitochondrial function in response to various exposure factors across different cell types and other relevant factors in the context of asthma, utilizing a new mitochondrial terminology framework that encompasses cell-dependent mitochondrial characteristics, molecular features, mitochondrial activity, function, and behavior.

A Cadaveric Study of the Rotator Cable: Interrogating the Suspension Bridge Model.

Purpose The objective of this cadaveric study was to describe the anatomical relationships between the rotator cuff muscles and the rotator cable. Methods In 30 formaldehyde-fixed shoulders from 20 cadavers, the rotator cuff and rotator cable were dissected and the glenohumeral joint opened. The orientation and attachments of the rotator cable to the rotator cuff muscles were described, and the severity of any osteoarthritis, labral pathology, and rotator cuff pathology present was documented. The width and thickness of the infraspinatus attachments to the rotator cable were measured. Results The infraspinatus muscle was noted to be more loosely adherent to the rotator cable, while the supraspinatus and teres minor were tightly adherent to the cable. Specifically, the superior-most portion of the infraspinatus was found to be less tightly adherent than the inferior-most portion in 26 of the 30 shoulders studied. The thickness/width ratio of the inferior-most portion of infraspinatus was significantly different in shoulders with more-than-minimal osteoarthritis and labral pathology (p=0.048 and p=0.041, respectively). Conclusion While the supraspinatus and teres minor muscles were tightly adherent to the cable in all shoulders, the degree of attachment of the superior-most portion of the infraspinatus muscle was notably less in 26 of the 30 shoulders studied. This could mean that only the inferior portion of the infraspinatus participates in stress shielding through the cable or be a compensatory response to increased load on the tendon. This work is expected to provide insight into the function of the rotator cable and the different functions of the infraspinatus.

A case of immunocompetent intracranial cryptococcoma in which intraoperative rapid pathological diagnosis and polymerase chain reaction led to early treatment: What to know to avoid misdiagnosis as brain tumor.

Background: Cryptococcal infections of the central nervous system are infrequent in immunocompetent hosts and usually present as meningitis. However, a fungal mass called a cryptococcoma may form, requiring caution in therapeutic intervention. Here, we report a rare case in which treatment of intraventricular cryptococcoma in an immunocompetent patient was facilitated by rapid pathological diagnosis. Case Description: A 58-year-old previously healthy man was admitted to our hospital with fever, headache, and gradually worsening hearing loss over 1 month. Cerebrospinal fluid analysis showed moderately elevated levels of protein and lymphocytic cells and decreased glucose. In addition, ß2-microglobulin was highly elevated. Magnetic resonance imaging showed homogeneously enhanced lesions in lateral ventricles of the left and right hemispheres and the subarachnoid space, and 18F-fluorodeoxyglucose positron emission tomography revealed abnormal uptake corresponding to the lesion. A surgical excision was performed to achieve a definitive diagnosis. Intraoperative rapid pathology, including immunohistochemistry (IHC), yielded negative results for malignant tumor, suggesting the possibility of inflammatory granuloma. Additional targeted pathological diagnosis was immediately performed. Paraffin-embedded histopathological examination showed fibrocaseous granuloma and numerous fungal spores. Cryptococcus neoformans within the granuloma were suggested by Fontana-Masson and Grocott staining and confirmed by polymerase chain reaction (PCR), leading to a diagnosis of cryptococcoma. Antifungal agents were started 3 days postoperatively. The patient has since been doing well, with no recurrence. Conclusion: This pathology can be difficult to distinguish from a brain tumor, so early pathological diagnosis, including rapid pathology with IHC and PCR, may be crucial.