Characterizing morphological alterations in blood related disorders through Atomic Force Microscopy.

Atomic Force Microscopy (AFM) is a very flexible method that can create topographical images from a range of materials and image surfaces. Significantly, AFM has emerged as an invaluable tool for dissecting the morphology and biochemical aspects of body cells and tissues. The high-resolution imaging capabilities of AFM enable researchers to discern alterations in cell morphology and understand the underlying mechanisms of diseases. It contributes to understanding disease etiology and progression. In the context of this review, our focus will be directed towards elucidating the pivotal role of AFM in analysis of blood related disorders. Through detailed comparisons with normal cells, we delve into the alterations in size, shape, and surface characteristics induced by conditions such as cancer, diabetes, anaemia, and infections caused by pathogens. In essence, various work described in this article highlights to bridge the gap between traditional microscopy and in-depth analysis of blood-related pathologies, which in turn offers valuable perspectives for both research and clinical applications in the field.

Surface engineered nanohybrids in plasmonic photothermal therapy for cancer: Regulatory and translational challenges.

Plasmonic materials as non-invasive and selective treatment strategies are gaining increasing attention in the healthcare sector due to their remarkable optical and electronic properties, where the interface between matter and light becomes enhanced and highly localized. Some attractive applications of plasmonic materials in healthcare include drug delivery to target specific tissues or cells, hence reducing the side effects of the drug and improving their efficacy; enhancing the contrast and resolution in bioimaging; and selectively heating and destroying the cancerous cells while parting the healthy cells. Despite such advancements in photothermal therapy for cancer treatment, some limitations are still challenging. These include poor photothermal conversion efficiency, heat resistance, less accumulation in the tumor microenvironment, poor biosafety of photothermal agents, damage to the surrounding healthy tissues, post-treatment inflammatory responses, etc. Even though the clinical application of photothermal therapy is primarily restricted due to poor tissue penetration of excitation light, enzyme therapy is hindered due to less therapeutic efficacy. Several multimodal strategies, including chemotherapy, radiotherapy, photodynamic therapy, and immunotherapy were developed to circumvent these side effects associated with plasmonic photothermal agents for effective mild-temperature photothermal therapy. It can be prophesied that the nanohybrid platform could pave the way for developing cutting-edge multifunctional precise nanomedicine via an ecologically sustainable approach towards cancer therapy. In the present review, we have highlighted the significant challenges of photothermal therapy from the laboratory to the clinical setting and their struggle to get approval from the Food and Drug Administration (FDA).

Patient-derived organoids for precision oncology: a platform to facilitate clinical decision making.

BACKGROUND: Despite recent advances in research, there are still critical lacunae in our basic understanding of the cause, pathogenesis, and natural history of many cancers, especially heterogeneity in patient response to drugs and mediators in the transition from malignant to invasive phenotypes. The explication of the pathogenesis of cancer has been constrained by limited access to patient samples, tumor heterogeneity and lack of reliable biological models. Amelioration in cancer treatment depends on further understanding of the etiologic, genetic, biological, and clinical heterogeneity of tumor microenvironment. Patient-derived organoids recapitulate the basic features of primary tumors, including histological complexity and genetic heterogeneity, which is instrumental in predicting patient response to drugs. METHODS: Human iPSCs from healthy donors, breast and ovarian cancer patients were successfully differentiated towards isogenic hepatic, cardiac, neural and endothelial lineages. Multicellular organoids were established using Primary cells isolated from tumor tissues, histologically normal tissues adjacent to the tumors (NATs) and adipose tissues (source of Mesenchymal Stem Cells) from ovarian and breast cancer patients. Further these organoids were propagated and used for drug resistance/sensitivity studies. RESULTS: Ovarian and breast cancer patients' organoids showed heterogeneity in drug resistance and sensitivity. iPSCs-derived cardiomyocytes, hepatocytes and neurons showed donor-to-donor variability of chemotherapeutic drug sensitivity in ovarian cancer patients, breast cancer patients and healthy donors. CONCLUSION: We report development of a novel integrated platform to facilitate clinical decision-making using the patient's primary cells, iPSCs and derivatives, to clinically relevant models for oncology research.

Derivation of Breast Cancer Patient Derived Human Induced Pluripotent Stem Cell Line (YBLi006-A) with FANC-BRCA Gene Mutations: A Resource for Precision & Personalized Medicine.

Fanconi anemia complementation group I (FANCI) is located on the chromosome 15q26.1 locus and becomes ubiquitinated following DNA damage. 3.06% of patients with breast cancer have altered FANCI gene. We generated an iPSC line (YBLi006-A) from peripheral blood mononuclear cells (PBMCs) of a patient carrying a mutation in FANCIgene (NM_001376911.1, NM_001376910.1, NM_001113378.2; c.80G > T, c.257C > T, c.2225G > C; p.Gly27Val, p.Ala86Val, p.Cys742Ser) using non-integrating Sendai virus technology. This unique breast cancer patient-derived-iPSC line will be resourceful to analyze the entire coding sequence and splicing sites ofFANCIin high-risk familial breast cancer.

Gamut of Extratesticular Scrotal Masses: Anatomic Approach to Sonographic Differential Diagnosis.

The commonly taught tenet that intratesticular lesions are always malignant and extratesticular scrotal lesions are always benign is a simplistic statement that erroneously minimizes the significance of extratesticular scrotal masses and their diagnosis. Yet, disease in the extratesticular space is commonly encountered by clinicians and radiologists and is often a source of uncertainty in diagnosis and management. Given the embryologically rooted complex anatomy of this region, a wide range of pathologic conditions is possible. Radiologists may not be familiar with some of these conditions; further, many of these lesions can have a specific sonographic appearance, allowing accurate diagnosis that can minimize surgical intervention. Lastly, malignancies can occur in the extratesticular space-although this is less common than in the testicles-and proper recognition of findings that warrant additional imaging or surgery is critical in optimizing outcomes. The authors present a compartmental anatomic framework for differential diagnosis of extratesticular scrotal masses and provide a comprehensive illustrative display of many of the pathologic conditions that can be encountered to familiarize radiologists with the sonographic appearances of these lesions. They also review management of these lesions and scenarios where US may not be definitive in diagnosis and selective use of scrotal MRI can be helpful. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Multimodality imaging of renal lymphoma and its mimics.

Lymphomatous involvement of the genitourinary system, particularly the kidneys, is commonly detected on autopsies; yet on conventional diagnostic imaging renal lymphoma is significantly underestimated and underreported, in part due to its variable imaging appearance and overlapping features with other conditions. We present a spectrum of typical and atypical appearances of renal lymphoma using multimodality imaging, while reviewing the roles of imaging in the detection, diagnosis, staging, and surveillance of patients with lymphoma. We also illustrate a breadth of benign and malignant entities with similar imaging features confounding the diagnosis of renal lymphoma, emphasizing the role of percutaneous image-guided biopsy. Understanding the spectrum of appearances of renal lymphoma and recognizing the overlapping entities will help radiologists improve diagnostic confidence and accuracy.

Multimodality Imaging after Liver Transplant: Top 10 Important Complications.

Patients who have undergone liver transplant are now regularly seen in day-to-day radiology practice. All surgical techniques for liver transplant require arterial, portal venous, hepatic venous and caval, and biliary anastomoses. This review is focused on the 10 "not to be missed" complications of liver transplant that affect the health and life of the graft and graft recipient. Arterial complications are the most common and devastating. Early hepatic artery thrombosis may be catastrophic because the biliary tree is solely dependent on the hepatic artery after transplant and collateral vessels have not yet formed. In contrast, delayed hepatic artery thrombosis may be more insidious as collateral arteries develop. US findings of delayed hepatic artery thrombosis may be similar to those of hepatic artery stenosis and celiac artery stenosis. Splenic artery steal syndrome is an increasingly recognized cause of graft ischemia. Venous complications are much less common. Hepatic venous and caval complications are notable for their increased incidence in living-donor and pediatric transplants. Biliary complications often result from arterial ischemia. Biliary cast syndrome is a notable example in which ischemic biliary mucosa sloughs into and obstructs the duct lumens. Neoplasms also may occur within the hepatic graft and may be due to recurrent malignancy, posttransplant lymphoproliferative disorder, or metastases. US is the initial imaging modality of choice, particularly in the acute postoperative setting. Further evaluation with contrast-enhanced US, CT, or MRI; catheter angiography; endoscopic retrograde cholangiopancreatography; and/or nuclear medicine studies is performed as needed. An invited commentary by Bhargava is available online. Online supplemental material is available for this article. ©RSNA, 2022.

A pictorial review of ultrasonography of the FIGO classification for uterine leiomyomas.

Uterine leiomyomas are the most common gynecological and pelvic neoplasm, reported in up to 80 percent of women by age 50. While the majority are asymptomatic, uterine leiomyomas, depending on size, number, and location can result in bulk symptoms, abnormal uterine bleeding (AUB), infertility or recurrent pregnancy loss. Ultrasonography (USG) remains first-line for the diagnosis of leiomyomas and is the most appropriate imaging modality for the initial assessment of abnormal uterine bleeding. In an effort to standardize nomenclature and identify causes of AUB, the International Federation of Gynecology and Obstetrics (FIGO) developed a classification system based on the acronym PALM-COEIN (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified). For the L category of leiomyoma, when present, a secondary and tertiary subclassification system is described distinguishing submucosal masses from others and categorizing the relationship of the mass to the endometrium and serosa. With advancements in newer minimally to non-invasive techniques developed for the management of leiomyomas, uniform characterization, mapping, and classification of leiomyomas is necessary to decide the optimal therapeutic approach. While this classification system has recently been reviewed on MR, to our knowledge, it has not been reviewed on ultrasound in the radiology literature. We hereby present a pictorial review of USG images of all the FIGO categories of leiomyomas to provide a standard guide for radiology reporting.

"Tram-line" Calcifications in Granulomatosis with Polyangiitis.

Nephrocalcinosis consists of deposition of calcium in the renal parenchyma. Renal cortical calcification is a rare entity in comparison to calcium deposits in the medulla and is seen only in a handful of pathologies with corresponding characteristic patterns on imaging. Thin linear calcifications may get deposited in the peripheral renal cortex suggestive of cortical necrosis due to a vascular insult (vasculitis), and rarely due to glomerulonephritis. This pattern of calcification has also been referred to as the "tramline" or "railroad track" sign.

Ultrasound Findings of Benign Scrotal Lesions: A Pictorial Review.

Ultrasound is an essential tool in evaluating the underlying etiology of scrotal lesions, which range from traumatic, infectious, inflammatory, congenital, and neoplastic conditions. Understanding the sonographic characteristics of benign scrotal masses is essential for a radiologist to determine whether conservative management is appropriate or if more aggressive follow-up or treatment is necessary. While surgical intervention may sometimes be necessary, combining the clinical presentation and imaging appearance can sometimes lead to a confident radiologic diagnosis that spares the patient from surgery. Examples of benign scrotal lesions and their ultrasound appearance are illustrated in this review.

Chapter 5 Ultrasound Characteristics of Benign vs Malignant Cervical Lymph Nodes.

With approximately 800 lymph nodes in the body, and more than one-third found within the head and neck, lymph nodes are a common site for neck pathology. Differentiation between benign and malignant lymph nodes is critical in accurate prognosis; similarly, treatment hinges on accurate identification of the etiology of the pathologic process. Key gray-scale and color Doppler ultrasound criteria can help accurately distinguish between benign and malignant lymph nodes.

Carboxyl-ester lipase maturity-onset diabetes of the young is associated with development of pancreatic cysts and upregulated MAPK signaling in secretin-stimulated duodenal fluid.

Carboxyl-ester lipase (CEL) maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes and pancreatic exocrine dysfunction due to mutations in the CEL gene encoding CEL. The pathogenic mechanism for diabetes development is unknown. Since CEL is expressed mainly in pancreatic acinar cells, we asked whether we could find structural pancreatic changes in CEL-MODY subjects during the course of diabetes development. Furthermore, we hypothesized that the diseased pancreas releases proteins that are detectable in pancreatic fluid and potentially reflect activation or inactivation of disease-specific pathways. We therefore investigated nondiabetic and diabetic CEL-mutation carriers by pancreatic imaging studies and secretin-stimulated duodenal juice sampling. The secretin-stimulated duodenal juice was studied using cytokine assays, mass spectrometry (MS) proteomics, and multiplexed MS-based measurement of kinase activities. We identified multiple pancreatic cysts in all eight diabetic mutation carriers but not in any of the four nondiabetic mutation carriers or the six healthy controls. Furthermore, we identified upregulated mitogen-activated protein kinase (MAPK) target proteins and MAPK-driven cytokines and increased MAPK activity in the secretin-stimulated duodenal juice. These findings show that subjects with CEL-MODY develop multiple pancreatic cysts by the time they develop diabetes and that upregulated MAPK signaling in the pancreatic secretome may reflect the pathophysiological development of pancreatic cysts and diabetes.

Phosphorylation by p38 mitogen-activated protein kinase promotes estrogen receptor α turnover and functional activity via the SCF(Skp2) proteasomal complex.

The nuclear hormone receptor estrogen receptor α (ERα) mediates the actions of estrogens in target cells and is a master regulator of the gene expression and proliferative programs of breast cancer cells. The presence of ERα in breast cancer cells is crucial for the effectiveness of endocrine therapies, and its loss is a hallmark of endocrine-insensitive breast tumors. However, the molecular mechanisms underlying the regulation of the cellular levels of ERα are not fully understood. Our findings reveal a unique cellular pathway involving the p38 mitogen-activated protein kinase (p38MAPK)-mediated phosphorylation of ERα at Ser-294 that specifies its turnover by the SCF(Skp2) proteasome complex. Consistently, we observed an inverse relationship between ERα and Skp2 or active p38MAPK in breast cancer cell lines and human tumors. ERα regulation by Skp2 was cell cycle stage dependent and critical for promoting the mitogenic effects of estradiol via ERα. Interestingly, by the knockdown of Skp2 or the inhibition of p38MAPK, we restored functional ERα protein levels and the control of gene expression and proliferation by estrogen and antiestrogen in ERα-negative breast cancer cells. Our findings highlight a novel pathway with therapeutic potential for restoring ERα and the responsiveness to endocrine therapy in some endocrine-insensitive ERα-negative breast cancers.

Computed tomography mimics of acute appendicitis: predictors of appendiceal disease confirmed at pathology.

PURPOSE: Imaging and pathology findings are used to analyze the capability of computed tomography (CT) to distinguish between acute appendicitis and radiological mimickers. MATERIALS AND METHODS: A retrospective review of 5861 patients undergoing abdominopelvic CT from 2000 to 2008 for suspicion of acute appendicitis was performed. Appendix diameter, surrounding inflammation, appendicolith, and location were assessed. Only those cases were included where patients underwent surgery for acute appendicitis on CT findings. Pathology specimens were examined and those indicative of acute appendicitis were identified. Statistical analysis was performed to correlate pathology and CT signs. RESULTS: A total of 969 of the 5681 patients were included in the study. Acute appendicitis was verified in 870/969 (89%) cases, while 99/969 (11%) demonstrated either chronic findings (i.e., fibrosis [32%], granulomatous disease [16%], lymphoid hyperplasia [11%]) or no abnormality. In regression models, appendiceal diameter >7 mm (odds ratio [OR] = 3.98, P < 0.0001) and mesenteric fat stranding (OR = 6.04, P < 0.0001) were associated with acute appendicitis. Nearly 87% (754/870) of acute appendicitis cases showed both signs on CT, compared with 53% (52/99) of those with other pathologic finding (P < 0.0001). In cases with non-appendicitis findings, 39% (39/99) had only one of these signs compared with 13% (112/870) of those with acute appendicitis (P < 0.0001). CONCLUSION: Diseases of the appendix other than acute appendicitis may manifest with isolated radiological findings and should be considered as part of the differential diagnosis in cases of borderline acute appendicitis.

Traumatic ectopic dislocation of testis.

Traumatic ectopic dislocation of testis is a rare occurrence and usually occurs following a motorcycle collision, in what is referred to as "fuel tank injury". Early identification and subsequent surgical management is of utmost importance to maintain normal spermatogenesis in the dislocated testis. In appropriate clinical setting, scrotal ultrasound examination with gray-scale and color flow Doppler imaging is the method of choice for diagnosis. Computed tomography of the abdomen is a useful adjunct procedure. We report a case of traumatic testicular dislocation with partial testicular torsion following a motorcycle collision, diagnosed with imaging, and subsequently confirmed on surgery.

Cystic duct remnant syndrome.

Post-cholecystectomy syndrome (PCS) is a common manifestation in patients with cholecystectomy. The patients exhibit a heterogeneous group of symptoms, such as upper abdominal pain, vomiting, gastrointestinal disorders, jaundice, and dyspepsia. Choledocholithiasis, biliary dyskinesia, and dilation of cystic duct remnants are common causes of these symptoms. The symptoms can recur after a symptom-free period following cholecystectomy or they can persist after surgery. Ultrasonography, computed tomography (CT), and magnetic resonance imaging scan, which are non-invasive methods of imaging, have a high sensitivity in detecting the causes of PCS. We report a case of an 84-year-old lady who came to the Ultrasound Department with recurrent episodes of abdominal pain following cholecystectomy. The gray-scale sonography showed a dilated cystic structure, which was confirmed as the duct remnant in follow-up contrast-enhanced CT.

Bilateral testicular epidermoid cysts.

Testicular epidermoid cysts are the most common benign tumors of the testes, but account for only 1-2% of all testicular tumors. In a young man presenting with a testicular mass, a high index of suspicion must be maintained for the malignant testicular germ cell tumor, which is 50-times more common than testicular epidermoid cyst. Bilateral testicular epidermoid cysts are a very rare condition, with only a few reports in the literature. It is extremely important in this condition to make a correct pre-operative diagnosis on imaging to enable a testis-sparing surgery.