Wide Variety Of Pathological Conditions Research Articles

Heart rate reactivity, recovery, and endurance of the incremental shuttle walk test in patients prone to heart failure.

Few randomized trials assessed the changes over time in the chronotropic heart rate (HR) reactivity (CHR), HR recovery (HRR) and exercise endurance (EE) in response to the incremental shuttle walk test (ISWT). We addressed this issue by analysing the open HOMAGE (Heart OMics in Aging) trial. In HOMAGE, 527 patients prone to heart failure were randomized to usual treatment with or without spironolactone (25-50mg/day). The current sub-study included 113 controls and 114 patients assigned spironolactone (~70% on beta-blockers), who all completed the ISWT at baseline and at Months 1 and 9. Within-group changes over time (follow-up minus baseline) and between-group differences at each time point (spironolactone minus control) were analysed by repeated measures ANOVA, unadjusted or adjusted for sex, age and body mass index, and additionally for baseline for testing 1 and 9month data. Irrespective of randomization, the resting HR and CHR did not change from baseline to follow-up, with the exception of a small decrease in the HR immediately post-exercise (-3.11b.p.m.) in controls at Month 9. In within-group analyses, HR decline over the 5min post-exercise followed a slightly lower course at the 1month visit in controls and at the 9month visits in both groups, but not at the 1month visit in the spironolactone group. Compared with baseline, EE increased by two to three shuttles at Months 1 and 9 in the spironolactone group but remained unchanged in the control group. In the between-group analyses, irrespective of adjustment, there were no HR differences at any time point from rest up to 5min post-exercise or in EE. Subgroup analyses by sex or categorized by the medians of age, left ventricular ejection fraction or glomerular filtration rate were confirmatory. Combining baseline and Months 1 and 9 data in both treatment groups, the resting HR, CHR and HRR at 1 and 5min averaged 61.5, 20.0, 9.07 and 13.8b.p.m. and EE 48.3 shuttles. Spironolactone on top of usual treatment compared with usual treatment alone did not change resting HR, CHR, HRR and EE in response to ISWT. Beta-blockade might have concealed the effects of spironolactone. The current findings demonstrate that the ISWT, already used in a wide variety of pathological conditions, is a practical instrument to measure symptom-limited exercise capacity in patients prone to developing heart failure because of coronary heart disease.

Overview of F18-FDG uptake patterns in retroperitoneal pathologies: imaging findings, pitfalls, and artifacts.

Retroperitoneum can be the origin of a wide variety of pathologic conditions and potential space for disease spread to other compartments of the abdomen and pelvis. Computed tomography (CT) and magnetic resonance imaging (MRI) are often the initial imaging modalities to evaluate the retroperitoneal pathologies, however given the intrinsic limitations, F18-FDG PET/CT provides additional valuable metabolic information which can change the patient management and clinical outcomes. We highlight the features of retroperitoneal pathologies on F18-FDG PET/CT and the commonly encountered imaging artifacts and pitfalls. The aim of this review is to characterizeprimary and secondary retroperitoneal pathologies based on their metabolic features, and correlate PET findings withanatomic imaging. Retroperitoneal pathologies can be complex, ranging from oncologic to a spectrum of non-oncologic disorders. While crosse-sectional imaging (CT and MRI) are often the initial imaging modalities to localize and characterize pathologies, metabolic information provided by F18-FDG PET/CT can change the management and clinical outcome in many cases.

JAK1/2 Regulates Synergy Between Interferon Gamma and Lipopolysaccharides in Microglia.

Microglia, the resident immune cells of the brain, regulate neuroinflammation which can lead to secondary neuronal damage and cognitive impairment under pathological conditions. Two of the many molecules that can elicit an inflammatory response from microglia are lipopolysaccharide (LPS), a component of gram-negative bacteria, and interferon gamma (IFNγ), an endogenous pro-inflammatory cytokine. We thoroughly examined the concentration-dependent relationship between LPS from multiple bacterial species and IFNγ in cultured microglia and macrophages. We measured the effects that these immunostimulatory molecules have on pro-inflammatory activity of microglia and used a battery of signaling inhibitors to identify the pathways that contribute to the microglial response. We found that LPS and IFNγ interacted synergistically to induce a pro-inflammatory phenotype in microglia, and that inhibition of JAK1/2 completely blunted the response. We determined that this synergistic action of LPS and IFNγ was likely dependent on JNK and Akt signaling rather than typical pro-inflammatory mediators such as NF-κB. Finally, we demonstrated that LPS derived from Escherichia coli, Klebsiella pneumoniae, and Akkermansia muciniphila can elicit different inflammatory responses from microglia and macrophages, but these responses could be consistently prevented using ruxolitinib, a JAK1/2 inhibitor. Collectively, this work reveals a mechanism by which microglia may become hyperactivated in response to the combination of LPS and IFNγ. Given that elevations in circulating LPS and IFNγ occur in a wide variety of pathological conditions, it is critical to understand the pharmacological interactions between these molecules to develop safe and effective treatments to suppress this process.

Poster 163: The Effect of Subacromial Epinephrine Injection on Visualization during Shoulder Arthroscopy

Objectives: Arthroscopic technique is used to treat an increasingly wide variety of pathologic conditions of the shoulder. Adequate visual clarity is imperative for the safety and efficacy of these procedures. Addition of epinephrine to arthroscopic irrigation fluid has been shown to improve surgeon-rated visual clarity, but also increases the cost of the procedure and carries the potential for rare, but serious, cardiovascular adverse events as the total dose increases. We utilize a preoperative subacromial injection containing epinephrine to improve visual clarity during arthroscopic shoulder surgery, thereby limiting the total dose of epinephrine added to the arthroscopic fluid. Methods: We performed a double-blinded, randomized controlled trial (institutional IRB approved and registered with clinicaltrials.gov) to include all adult patients undergoing arthroscopic shoulder surgery requiring visualization of the subacromial space in the seated upright (i.e., beach chair) position. We performed a preoperative injection into the subacromial space with bupivacaine alone for the control group versus a combination of bupivacaine and epinephrine for the study group. Epinephrine was also added to the first fifteen liters of arthroscopic fluid in all patients. Primary outcome was surgeon-rated visual clarity throughout the procedure using the visual analog score (VAS; 1 to 10). A power analysis determined the need for a minimum sample size in each group to ensure adequate power given that the minimal clinically significant difference in visual clarity score has been established in prior studies to be two points. Secondary outcomes included increase in pump pressure during the procedure to improve visualization, total operative time and intraoperative use of blood-pressure modulating medications. We documented any adverse events in the perioperative period in all patients. Results: Sixty patients (n = 60) were enrolled in the study, thirty (n = 30) randomized into each of the study and control groups. Rotator cuff repair was performed in 88% of cases (25 of 30 (83%) study; 28 of 30 (93%) control) with multiple procedures performed in each surgery in 85% of cases (24 of 30 (80%) study; 27 of 30 (90%) control). There was a small improvement in visual clarity that was neither statistically nor clinically significant (8.3 ± 1.4 study versus 7.5 ± 1.9 control, p = 0.09). There was no difference in need for increase in pump pressure to improve visualization (8 of 30 patients (27%) study versus 7 of 30 patients (23%) control, p = 1.0), total operative time (62.1 ± 19.4 min study versus 64.1 ± 31.0 min control, p = 0.86), or intraoperative use of blood-pressure modulating medications (20 of 30 patients (67%) study versus 17 of 30 (57%) control, p = 0.6). There were no perioperative adverse events in either the study or control group. Conclusions: Performing a preoperative injection of epinephrine into the subacromial space results in a small improvement in visual clarity that is neither statistically nor clinically significant during arthroscopic shoulder surgery. There was no difference in any of the secondary outcomes, including change in pump pressure to improve visualization, total operative time, or intraoperative use of blood- pressure modulating medications. However, there were no adverse events in either group, suggesting that the addition of a preoperative epinephrine injection is safe to perform.

Visualizing the anti-inflammatory cannabinoid Type-2 receptor

Visualizing the anti-inflammatory cannabinoid Type-2 receptor Medicinal chemists describe how small molecule probes allow for the detection of CB2R, and thereby enable the discovery of novel anti-inflammatory treatments. The G-protein-coupled receptor (GPCR) CB2R (1) is an essential constituent of the endocannabinoid system (ECS), a central lipid signalling system in all vertebrates (2). Preclinical studies have shown that CB2R activation is a general and robust principle to attenuate inflammation and associated tissue injury in a wide variety of pathological conditions. Strong accumulating evidence suggests that diseases such as heart disorders, gastrointestinal, liver, kidney, lung, neurodegenerative or neuroinflammatory diseases, pain, skin pathologies, rheumatoid arthritis, endometriosis and eye diseases might be therapeutically addressable by CB2R (3).

PET Criteria by Cancer Type from Imaging Interpretation to Treatment Response Assessment: Beyond FDG PET Score.

in recent years, the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) has emerged as a reliable diagnostic tool in a wide variety of pathological conditions. This review aims to collect and review PET criteria developed for interpretation and treatment response assessment in cases of non-[18F]fluorodeoxyglucose ([18F]FDG) imaging in oncology. A wide literature search of the PubMed/MEDLINE, Scopus and Google Scholar databases was made to find relevant published articles about non-[18F]FDG PET response criteria. The comprehensive computer literature search revealed 183 articles. On reviewing the titles and abstracts, 149 articles were excluded because the reported data were not within the field of interest. Finally, 34 articles were selected and retrieved in full-text versions. available criteria are a promising tool for the interpretation of non-FDG PET scans, but also to assess the response to therapy and therefore to predict the prognosis. However, oriented clinical trials are needed to clearly evaluate their impact on patient management.

Advanced Imaging of Ulnar Wrist Pain.

Ulnar-sided wrist pain can be a diagnostic challenge for clinicians and radiologists. The ulnar wrist has complex morphology and is composed of many small bone and soft tissue structures. Within these structures, a wide variety of pathologic conditions can occur. To successfully diagnose and treat these pathologic conditions, clinicians and radiologists must have a strong understanding of the advanced imaging techniques available to them. In this review, the authors present a brief review of the normal ulnar wrist anatomy, discuss the differential diagnosis of ulnar-sided wrist pain, and examine the indications for different advanced imaging modalities.

Fostering "Education": Do Extracellular Vesicles Exploit Their Own Delivery Code?

Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the characterization of EV surface membrane molecules and the mechanisms that mediate the addressability of specific EVs to different cell types and tissues. Identifying these mechanisms will help fulfill the diagnostic, prognostic, and therapeutic promises fueled by our growing knowledge of EVs. In this review, we first discuss published studies on the presumed EV “delivery code” and on the combinations of the hypothesized EV surface membrane “sender” and “recipient” molecules that may mediate EV targeting in intercellular communication. Then we briefly review the main experimental approaches and techniques, and the bioinformatic tools that can be used to identify and characterize the structure and functional role of EV surface membrane molecules. In the final part, we present innovative techniques and directions for future research that would improve and deepen our understandings of EV-cell targeting.

Xmrks the Spot: Fish Models for Investigating Epidermal Growth Factor Receptor Signaling in Cancer Research.

Studies conducted in several fish species, e.g., Xiphophorus hellerii (green swordtail) and Xiphophorus maculatus (southern platyfish) crosses, Oryzias latipes (medaka), and Danio rerio (zebrafish), have identified an oncogenic role for the receptor tyrosine kinase, Xmrk, a gene product closely related to the human epidermal growth factor receptor (EGFR), which is associated with a wide variety of pathological conditions, including cancer. Comparative analyses of Xmrk and EGFR signal transduction in melanoma have shown that both utilize STAT5 signaling to regulate apoptosis and cell proliferation, PI3K to modulate apoptosis, FAK to control migration, and the Ras/Raf/MEK/MAPK pathway to regulate cell survival, proliferation, and differentiation. Further, Xmrk and EGFR may also modulate similar chemokine, extracellular matrix, oxidative stress, and microRNA signaling pathways in melanoma. In hepatocellular carcinoma (HCC), Xmrk and EGFR signaling utilize STAT5 to regulate cell proliferation, and Xmrk may signal through PI3K and FasR to modulate apoptosis. At the same time, both activate the Ras/Raf/MEK/MAPK pathway to regulate cell proliferation and E-cadherin signaling. Xmrk models of melanoma have shown that inhibitors of PI3K and MEK have an anti-cancer effect, and in HCC, that the steroidal drug, adrenosterone, can prevent metastasis and recover E-cadherin expression, suggesting that fish Xmrk models can exploit similarities with EGFR signal transduction to identify and study new chemotherapeutic drugs.

Linking the Expression of Therapeutic Genes to Unfolded Protein Response: A New Option for Anti-Hepatitis B Virus Gene Therapy.

Tight control of transgene expression is key to ensure the efficacy of a wide range of gene therapy interventions, in which the magnitude and duration of gene expression have to be adjusted to therapeutic needs, thereby limiting secondary effects. The development of upgraded strategies to link transgene expression to pathological stress episodes is an unmet need in gene therapy. Here, we propose an expression strategy that associates transgene expression to an intracellular stress coping mechanism, the unfolded protein response. Specifically, we harnessed the cis elements required to sustain the noncanonical splicing of X-box binding protein 1 (XBP1) messenger RNA (mRNA) in response to the dysfunction of the endoplasmic reticulum (ER), a situation commonly known as ER stress, to drive the expression of heterologous genes. Since ER stress features a wide variety of pathological conditions, including viral infections, cancer, or metabolic disorders, this new expression module stimulates the synthesis of therapeutic genes as a response to cellular damage, and ensures their expression only when necessary. Validation of this inducible expression system was performed in vitro and in vivo, and its potential to limit/inhibit viral infections has been shown in proof-of principle experiments.

Histopathology of pulmonary lesions in autopsy cases

Introduction:Autopsies are carried out to establish the identity, cause of death, time of death and antemortem or postmortem nature of death. A wide variety of pathological conditions involve the lungs. Aim: To study the prevalence and pattern of lung lesions in autopsy cases, confirmed by histopathological examination. Material and Methods:This is an observational study carried out in the pathology department at tertiary care center. Lung tissues from autopsy cases were preserved in 10% formalin, processed and examined microscopically. A total of 500 cases were studied during a 4 year’s period from 2017 to 2020. Results:Among the 507 autopsy cases studied, lung specimen from 7 [1.38%] cases were autolyzed hence excluded from the present study. Out of 500 study cases, 70 cases [13.8%] showed unremarkable histopathology. Wide spectrum of microscopic findings was seen in the rest [84.81%] of the cases. Conclusion:Autopsy remains vital and important complimentary tool in identifying and understanding pulmonary lesions. Histopathological study of lungs at autopsy may reveal various lesions and their relative inputs toward death.

A five year study of lung lesions in medico-legal autopsies from a pathologist’s perspective

Introduction: A wide variety of pathologic conditions involve the lungs. The lungs are also involved in almost all terminal events of cardiovascular disease. Autopsy is important not only to determine the state of lungs at death but also to study the morphology of various diseases. Aims and objectives of study are to identify the histopathological spectrum of lung lesions and to find out the frequency of various lung pathologies in respect to age and sex. Materials and Methods: This was a retrospective study of medico legal autopsies over a period of five years. The lung tissue was fixed and processed. Routine paraffin sectioning was done followed by Haematoxylin and eosin (H and E) staining. Special stains were done when required. Relevant clinical, postmortem findings, gross and microscopic examination findings were recorded. Results: After thorough histopathological examinations, of total 412 cases, various pulmonary lesions were identified in 349 (84.6%) cases, in 23 (5.6%) of cases tissue was autolysed and 40 (9.8 %) of cases were histologically unremarkable. Most commonly affected age group was 30-49 years, with males being predominantly affected. The changes seen were - Congestion & edema 116 (33.2%), pneumonia 68(19.6%), interstitial changes 52 (15.1%), emphysema- 26 (7.5%), chronic venous congestion 30 (8.6%), abscess (1.1%), haemorrhage (6.4%) tuberculosis -11(3.3%), bronchiolitis- 3 (0.8%), asthama- 2(0.5%), ARDS- 7 (1.9%), lung cysts- 2 (0.5%) Conclusions: Though the pulmonary diseases are commonly encountered clinically, studying of lung tissues submitted for autopsy, not only gives us an insight into the histology of varying stages of different diseases but also is an important educative tool for the forensic pathologists. Keywords: Edema and congestion, Pneumonia, Tuberculosis, Autopsy, Histopathology.

Technical and Interpretive Pitfalls in Adrenal Imaging.

The adrenal gland may exhibit a wide variety of pathologic conditions. A number of imaging techniques can be used to characterize these, although it is not always possible to attain a definitive diagnosis radiologically. Incorrect diagnoses may be made if radiologists are not attentive to technical parameters and interpretive factors associated with adrenal gland imaging. Hence, an appreciation of the intricacies of adrenal imaging strategies and characterization is required; this can be aided by understanding the pitfalls of adrenal imaging. Technical pitfalls at CT may relate to the imaging parameters, including region of interest characteristics, tube voltage selection, and the timing of contrast material-enhanced imaging. With MRI, imaging acquisition technique and evaluation of the reference tissues used in chemical shift MRI are important considerations that can directly influence image interpretation. Interpretive errors may occur when evaluating adrenal washout at CT without considering other radiologic features, including the size of adrenal nodules, the presence of fat or calcification, the attenuation of nodules, and atypical imaging features. The characterization of an incidental adrenal lesion as benign or malignant does not end the role of the radiologist; consideration as to whether an adrenal lesion is associated with endocrine dysfunction is required. While imaging may not be optimal for establishing endocrine activity, there are imaging features from which radiologists may infer function. In cases of known endocrine activity, imaging can guide clinical management, including further investigations such as venous sampling. ©RSNA, 2020.

Oxidative Stress and Microvessel Barrier Dysfunction.

Clinical and experimental evidence indicate that increased vascular permeability contributes to many disease-associated vascular complications. Oxidative stress with increased production of reactive oxygen species (ROS) has been implicated in a wide variety of pathological conditions, including inflammation and many cardiovascular diseases. It is thus important to identify the role of ROS and their mechanistic significance in microvessel barrier dysfunction under pathological conditions. The role of specific ROS and their cross talk in pathological processes is complex. The mechanisms of ROS-induced increases in vascular permeability remain poorly understood. The sources of ROS in diseases have been extensively reviewed at enzyme levels. This review will instead focus on the underlying mechanisms of ROS release by leukocytes, the differentiate effects and signaling mechanisms of individual ROS on endothelial cells, pericytes and microvessel barrier function, as well as the interplay of reactive oxygen species, nitric oxide, and nitrogen species in ROS-mediated vascular barrier dysfunction. As a counter balance of excessive ROS, nuclear factor erythroid 2 related factor 2 (Nrf2), a redox-sensitive cell-protective transcription factor, will be highlighted as a potential therapeutic target for antioxidant defenses. The advantages and limitations of different experimental approaches used for the study of ROS-induced endothelial barrier function are also discussed. This article will outline the advances emerged mainly from in vivo and ex vivo studies and attempt to consolidate some of the opposing views in the field, and hence provide a better understanding of ROS-mediated microvessel barrier dysfunction and benefit the development of therapeutic strategies.

Differential Expression of Plasma Exo-miRNA in Neurodegenerative Diseases by Next-Generation Sequencing.

Neurodegenerative diseases encompass a wide variety of pathological conditions caused by a loss of neurons in the central nervous system (CNS) and are severely debilitating. Exosome contains bio-signatures of great diagnostic and therapeutic value. There is proof that exosomal proteins can be biomarkers for Alzheimer’s disease (AD) and Parkinson’s disease (PD). MicroRNAs in exosome has potential to be an important source of biomarkers for neurodegenerative diseases. Here, we report exosomal microRNA performance of human plasma in neurodegenerative diseases by small RNA sequencing. A wide range of altered exo-miRNA expression levels were detected in both AD and PD patients. Down-regulated miRNAs in AD samples were enriched in ECM-receptor interaction pathway and both up-/down-regulated miRNAs in PD samples were enriched in fatty acid biosynthesis pathway. Compared to the control, 8 miRNAs were found to be significantly elevated/declined in AD and PD samples, of which 4 miRNAs were newly identified. Additionally, two exosome isolating methods were compared and the reproducibility of plasma exo-miRNA expression was confirmed, suggesting the feasibility of large-scale clinical application of this method. This study revealed exo-miRNA expression levels in neurodegenerative diseases, proposed new biomarkers and their potential functional pathway for AD and PD, confirmed the reproductivity of exo-miRNA profiles by using a different exosome isolating method, and compared the results with plasma miRNA expression. Therefore, this study also provides a precedent for identifying exosomal biomarkers of neurodegenerative diseases in plasma by high-throughput sequencing and it could extend the therapeutic repertoire of exosomal biomarkers.

Oxidants, Antioxidants and Thiol Redox Switches in the Control of Regulated Cell Death Pathways.

It is well appreciated that biological reactive oxygen and nitrogen species such as hydrogen peroxide, superoxide and nitric oxide, as well as endogenous antioxidant systems, are important modulators of cell survival and death in diverse organisms and cell types. In addition, oxidative stress, nitrosative stress and dysregulated cell death are implicated in a wide variety of pathological conditions, including cancer, cardiovascular and neurological diseases. Therefore, much effort is devoted to elucidate the molecular mechanisms linking oxidant/antioxidant systems and cell death pathways. This review is focused on thiol redox modifications as a major mechanism by which oxidants and antioxidants influence specific regulated cell death pathways in mammalian cells. Growing evidence indicates that redox modifications of cysteine residues in proteins are involved in the regulation of multiple cell death modalities, including apoptosis, necroptosis and pyroptosis. In addition, recent research suggests that thiol redox switches play a role in the crosstalk between apoptotic and necrotic forms of regulated cell death. Thus, thiol-based redox circuits provide an additional layer of control that determines when and how cells die.

Lysosomal Abnormalities in Cardiovascular Disease.

The lysosome, a key organelle for cellular clearance, is associated with a wide variety of pathological conditions in humans. Lysosome function and its related pathways are particularly important for maintaining the health of the cardiovascular system. In this review, we highlighted studies that have improved our understanding of the connection between lysosome function and cardiovascular diseases with an emphasis on a recent breakthrough that characterized a unique autophagosome-lysosome fusion mechanism employed by cardiomyocytes through a lysosomal membrane protein LAMP-2B. This finding may impact the development of future therapeutic applications.

Computer-aided detection tool development for teaching chest radiograph pattern recognition to undergraduate radiography students: A context needs and capability analysis.

BackgroundMedical imaging (MI) education has experienced a shift aligned with the advances in technology and the role played by radiographers in pattern recognition. This has led to increased use of technology-enhanced teaching and simulated learning approaches (e.g. computer-aided detection [CAD] tools) which also support the increasing requirement to develop pattern-recognition skills at undergraduate level. However, the development of these approaches need to be explored and planned carefully to be context-relevant.AimThe aim of this study was to explore and describe the need for and capability of a CAD tool for teaching chest radiography pattern recognition in an undergraduate radiography programme.SettingThe setting was a university that offers MI education.MethodThe study employed a qualitative descriptive design with an interpretive research paradigm. Purposive sampling was used to recruit information-rich participants for a focus group interview. Information-rich participants were considered to be those who were involved in teaching clinical skills, such as those required in pattern recognition, to radiography students. Data were transcribed verbatim and analysed in a step-by-step approach.ResultsThree main themes emerged: (1) a structured approach to enhance implicit skills is critical in the CAD tool design; (2) an authentic tool which is able to simulate real-world experiences in image analysis is essential; and (3) a tool which encourages self-directed learning using a wide variety of pathological conditions would be ideal.ConclusionThe results of this study are essential in guiding radiography educators in designing CAD tools for teaching chest radiography pattern recognition.

Imaging Spectrum of Cavernous Sinus Lesions with Histopathologic Correlation.

Cavernous sinuses are paired interconnected venous plexuses situated in the floor of the middle cranial fossa on either side of the sella turcica and sphenoid sinus. They are lined by dura mater and consist of multiple venous channels within. The cavernous sinuses are intimately related to the internal carotid artery and its associated sympathetic plexus, the oculomotor nerve, the trochlear nerve, the abducens nerve, and the ophthalmic nerve. Cavernous sinuses are connected to the orbit, the pterygopalatine fossa, the infratemporal fossa, the nasopharynx, and the posterior cranial fossa by various foramina, fissures, and canals in the skull base. A multitude of structures in close relation to the cavernous sinus give rise to a myriad of possible pathologic conditions that can be broadly classified into (a) neoplastic, (b) vascular, (c) infective or inflammatory, or (d) miscellaneous lesions. These pathologic conditions can have overlapping clinical manifestations. Hence, imaging plays a crucial role in identifying the disease, assessing its extent, providing a pertinent differential diagnosis to guide further management, and suggesting a site or route for biopsy. MRI is the modality of choice to depict the cavernous sinuses, with CT and digital subtraction angiography playing supplementary roles in certain situations. In this article, the cavernous sinus lesions encountered in our institution during a 10-year period are reviewed. The purpose of the article is to (a) describe the anatomy of the cavernous sinus; (b) demonstrate the multimodality imaging spectrum of a wide variety of pathologic conditions involving the cavernous sinus, correlating with the histopathologic findings; (c) highlight important imaging clues for differential diagnosis; and (d) help the reader overcome potential pitfalls in interpretation. Online supplemental material is available for this article. ©RSNA, 2019.

Molecular signaling in bone cells: Regulation of cell differentiation and survival.

The achievement of proper bone mass and architecture, and their maintenance throughout life requires the concerted actions of osteoblasts, the bone forming cells, and osteoclasts, the bone resorbing cells. The differentiation and activity of osteoblasts and osteoclasts are regulated by molecules produced by matrix-embedded osteocytes, as well as by cross talk between osteoblasts and osteoclasts through secreted factors. In addition, it is likely that direct contact between osteoblast and osteoclast precursors, and the contact of these cells with osteocytes and cells in the bone marrow, also modulates bone cell differentiation and function. With the advancement of molecular and genetic tools, our comprehension of the intracellular signals activated in bone cells has evolved significantly, from early suggestions that osteoblasts and osteoclasts have common precursors and that osteocytes are inert cells in the bone matrix, to the very sophisticated understanding of a network of receptors, ligands, intracellular kinases/phosphatases, transcription factors, and cell-specific genes that are known today. These advances have allowed the design and FDA-approval of new therapies to preserve and increase bone mass and strength in a wide variety of pathological conditions, improving bone health from early childhood to the elderly. We have summarized here the current knowledge on selected intracellular signal pathways activated in osteoblasts, osteocytes, and osteoclasts.