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Lung cancer remains a significant health challenge, characterized by aberrant tissue growth within the pulmonary system. Early carcinogenic events often involve genomic instability and the emergence of a mutator phenotype. In this study, we aimed to explore the mutator phenotype in 89 patients diagnosed with non-small-cell lung cancer (NSCLC). RNA isolation from formalin-fixed paraffin-embedded (FFPE) tissue samples was performed using the Promega ReliaPrep RNA Miniprep System, facilitating gene amplification relevant to cancer through the Archer® FusionPlexComprehensiveThyroid and Lung (CTL) kit. Next-generation sequencing (NGS) on the Illumina NextSeq platform enabled comprehensive analysis of target areas. Utilizing Archer Analysis software, secondary analyses involving data cleansing, alignment, and variant/fusion identification were executed against the human reference genome hg19 (GRCh37). Expression patterns were visualized using HeatMap graphics. Our findings revealed a notable presence of KRAS gene mutations in approximately 20% of NSCLC patients. Among these mutations, the G12C variant was predominant at 50%, followed by G12V and G12D variants at 11.2% each. Notably, patients harboring the G12C variant responded favorably to sotorasib medication. These results underscore the importance of mutational profiling and targeted therapeutic approaches in managing NSCLC, particularly highlighting the promising efficacy of sotorasib in G12C-mutated cases. [ABSTRACT FROM AUTHOR]

Summary: Adipose tissue is a large endocrine organ that serves numerous physiological functions. As we age, adipose tissue remodels and can develop functional changes that alters its phenotype, potentially contributing to metabolic and cardiovascular disorders. Aging adipose tissue is characterized by regional redistribution of fat, accumulation of senescent cells, fibrosis, and decline in adipocyte differentiation capacities, which collectively impact adipose tissue function and whole body health. A notable transformation involves increased accumulation of intra‐abdominal visceral adipose tissue and ectopic fat around internal organs such as the heart, blood vessels, liver, and kidneys that alter their functions. Other changes associated with aging include alterations in adipokine secretion and changes in adipocyte size and numbers. Aging adipocytes play a role in mediating chronic inflammation, metabolic dysfunction, and insulin resistance. Visceral adipose tissue, which increases in volume with aging, is in particular associated with inflammation, angiogenic dysfunction, and microvascular abnormalities, and mediators released by visceral fat may have adverse consequences systemically in multiple target organs, including the cardiovascular system. Understanding mechanisms underlying adipose tissue aging and its impact on cardiovascular health are important for developing interventions and treatments to promote healthy aging and reduce cardiometabolic disease risk. [ABSTRACT FROM AUTHOR]

Ectopic thyroid tissue along the line of descent of thyroid from foramen caecum along thyroglossal duct to the normal anatomic location in neck has been reported. Ectopic thyroid tissue in adrenal gland (ETTAG) is rarely encountered and very few cases have been reported in literature. The most common differential diagnosis to be considered when thyroid follicles are noted in adrenal gland are metastasis from a thyroid malignancy or a teratoma or an ectopic thyroid tissue in adrenal gland. We present a case of an adrenal incidentaloma in a young pregnant female which was diagnosed to be ectopic thyroid tissue in adrenal gland. The review of literature of similar cases of this rare embryological aberrance is discussed. To our knowledge, only 16 such cases have been documented in literature and our case is the first one from Indian subcontinent and the largest documented with respect to size. [ABSTRACT FROM AUTHOR]

Endometriosis is characterized by the ectopic proliferation of endometrial cells, posing considerable diagnostic and therapeutic challenges. Our study investigates AGPAT4's involvement in endometriosis pathogenesis, aiming to unveil new therapeutic targets. Our investigation by analyzing eQTL data from GWAS for preliminary screening. Subsequently, within the GEO dataset, we utilized four machine learning algorithms to precisely identify risk-associated genes. Gene validity was confirmed through five Mendelian Randomization methods. AGPAT4 expression was measured by Single-Cell Analysis, ELISA and immunohistochemistry. We investigated AGPAT4's effect on endometrial stromal cells using RNA interference, assessing cell proliferation, invasion, and migration with CCK8, wound-healing, and transwell assays. Protein expression was analyzed by western blot, and AGPAT4 interactions were explored using AutoDock. Our investigation identified 11 genes associated with endometriosis risk, with AGPAT4 and COMT emerging as pivotal biomarkers through machine learning analysis. AGPAT4 exhibited significant upregulation in both ectopic tissues and serum samples from patients with endometriosis. Reduced expression of AGPAT4 was observed to detrimentally impact the proliferation, invasion, and migration capabilities of endometrial stromal cells, concomitant with diminished expression of key signaling molecules such as Wnt3a, β-Catenin, MMP-9, and SNAI2. Molecular docking analyses further underscored a substantive interaction between AGPAT4 and Wnt3a.Our study highlights AGPAT4's key role in endometriosis, influencing endometrial stromal cell behavior, and identifies AGPAT4 pathways as promising therapeutic targets for this condition. [ABSTRACT FROM AUTHOR]

Routine histopathology of tonsillectomy specimens is not standard practice due to cost and resource constraints. This study aimed to evaluate the prevalence of abnormal histopathologies in tonsillectomy specimens to determine the necessity of routine histopathology. A prospective observational study was conducted from January 2014 to August 2016 at a general tertiary care center after approval of Institutional Ethics Committee (IEC). Patients scheduled for tonsillectomy surgery as per the AAOHNS 2011 criteria were included in the study. All tonsillectomy specimens were sent for histopathology, and abnormal findings were documented. Statistical analysis was performed. A total of 111 patients were enrolled in this study, and 222 tonsillectomy specimens were analyzed. The most common finding was chronic tonsillitis, which justified the selection criteria in 91.89% of patients. Two patients with chronic tonsillitis were also found to have actinomycosis present on the surface without parenchymal tissue reaction. Abnormal histopathological findings were observed in 9 (8.10%) of patients, leading to further investigations or treatment in 8 cases. These abnormalities included chronic granuloma, non-Hodgkin's lymphoma, early squamous cell carcinoma, and one choristoma. Tonsillar asymmetry, recent onset of symptoms and older age were found to be significantly correlated with abnormal histopathology and malignancy. Routine histopathology in tonsillectomy specimens helps to identify important findings that may require additional treatment. Based on the study we strongly recommend routine histopathology of tonsillectomy specimen. When significant cost constraints exist, risk-based approach can be adopted. Factors such as older age, asymmetry of tonsils, referred otalgia, duration of symptoms (recent onset) and a history of addiction should be considered for proceeding with histopathology. [ABSTRACT FROM AUTHOR]

Choristomas are aggregates of microscopically normal tissues in aberrant locations. They can be cartilage, bone, glial tissue, salivary gland, and thyroid tissue. Cartilaginous choristomas of the oral cavity are rare and occur most commonly on the tongue and less often in sites such as the soft palate and gingiva. We report two cases of cartilaginous choristoma in young females presenting with recurrent tonsillitis. Histopathological examination showed the presence of mature island of hyaline cartilage surrounded by lymphoid hyperplasia. Level of Evidence: Level 4 [ABSTRACT FROM AUTHOR]

Background: Endometriosis is well known as a chronic inflammatory disease. The development of endometriosis is heavily influenced by the estrogen receptor β (ERβ), while NOD-like receptors (NLRs) family CARD domain-containing 5 (NLRC5) exhibits anti-inflammatory properties during endometriosis. However, whether NLRC5-mediated anti-inflammation is involved in the ERβ-mediated endometriosis is still uncertain. This study aimed to assess that relation. Methods: Nine cases of eutopic endometrial tissue and ten cases of ectopic endometrial tissue were collected from patients with endometriosis, and endometrial samples from ten healthy fertile women were analyzed, and the expression levels of ERβ were quantified using immunohistochemistry (IHC). Subsequently, we constructed mouse model of endometriosis by intraperitoneal injection. We detected the expression of ERβ, NLRC5, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-10 and measured the volume of ectopic lesions in mice with endometriosis. In vitro, human endometrial stromal cells (hESCs) were transfected respectively with ERβ-overexpressing and NLRC5-overexpressing plasmids. We then assessed the expression of ERβ and NLRC5 using quantitative real-time PCR (qRT-PCR) and western blot analysis. Furthermore, we measured the concentrations of TNF-α, IL-6, and IL-10 in the cell culture supernatant through enzyme-linked immunosorbent assay (ELISA). Additionally, we evaluated the migration and invasion ability of hESCs using transwell and wound healing assays. Results: Inhibition of NLRC5 expression promotes the development of ectopic lesions in mice with endometriosis, upregulates the expression of pro-inflammatory factors TNF-α and IL-6, and downregulates the expression of anti-inflammatory factor IL-10. The high expression of NLRC5 in endometriosis depended on the ERβ overexpression. And ERβ promoted the migration of hESCs partially depend on inflammatory microenvironment. Lastly, NLRC5 overexpression inhibited ERβ-mediated development and inflammatory response of endometriosis. Conclusions: Our results suggest that the innate immune molecule NLRC5-mediated anti-inflammation participates in ERβ-mediated endometriosis development, and partly clarifies the pathological mechanism of endometriosis, expanding our knowledge of the specific molecules related to the inflammatory response involved in endometriosis and potentially providing a new therapeutic target for endometriosis. [ABSTRACT FROM AUTHOR]

The organoid nevus syndrome is a rare neurocutaneous syndrome typified by cutaneous sebaceous nevus, seizures and epibulbar choristomas. The condition is associated with multiple ocular abnormalities. Herein, the authors aim to study and report the ophthalmic features of cases diagnosed with organoid nevus syndrome. The authors retrospectively evaluated the records of patients with the organoid nevus syndrome who had presented to a tertiary care eye hospital in northern India. The ocular features were studied and entered in MS excel and the data were evaluated. Data of 13 patients with the organoid nevus syndrome were found. All 13 patients had cutaneous features in the form of Sebaceous nevus of Jadasson, 8 patients had alopecia of the scalp area, 2 had history seizures and 10 had arachnoid cysts on neuroimaging of the head. All 13 patients had a complex choristoma involving the ocular surface. We conclude that the most common ophthalmologic features associated with organoid nevus are complex choristoma of the bulbar surface, scleral coat calcification and upper eyelid coloboma. [ABSTRACT FROM AUTHOR]

A compelling correlation method linking microbial communities and host gene expression in tissues is currently absent. A novel pipeline is proposed, dubbed Transcriptome Analysis of Host‐Microbiome Crosstalk (TAHMC), designed to concurrently restore both host gene expression and microbial quantification from bulk RNA‐seq data. Employing this approach, it discerned associations between the tissue microbiome and host immunity in the context of Crohn's disease (CD). Further, machine learning is utilized to separately construct networks of associations among host mRNA, long non‐coding RNA, and tissue microbes. Unique host genes and tissue microbes are extracted from these networks for potential utility in CD diagnosis. Experimental validation of the predicted host gene regulation by microbes from the association network is achieved through the co‐culturing of Faecalibacterium prausnitzii with Caco‐2 cells. Collectively, the TAHMC pipeline accurately recovers both host gene expression and microbial quantification from CD RNA‐seq data, thereby illuminating potential causal links between shifts in microbial composition as well as diversity within CD mucosal tissues and aberrant host gene expression. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the expression and role of Endoglin (ENG) in endometriosis (EM). Material and methods: In this study, quantitative real-time polymerase chain reaction, western blot and immunohistochemistry were used to examine the expression of ENG in tissues. Cellular experiments were performed to evaluate the effect of ENG on cellular biological function. Western blot was used to examine the expression of epithelial to mesenchymal transition-related proteins. Results: The expression of ENG was significantly higher in the ectopic endometriotic tissues than that in eutopic endometriotic tissues. Knockdown of ENG inhibited cell viability, migration and invasion, and induced cell apoptosis in hEM15A cells. Additionally, silenced ENG caused increased levels of E-cadherin and decreased levels of N-cadherin, vimentin, MMP-2 and MMP-9. Conclusions: These results confirmed that ENG may be involved in the development of endometriosis by promoting EMT process, revealing a new insight into the pathogenesis of endometriosis and contributing to the exploration of molecular therapeutic strategies against endometriosis. [ABSTRACT FROM AUTHOR]

This article from Veterinary Pathology provides images and descriptions of various pulmonary diseases in animals. It includes images and information on diseases such as bovine tuberculosis, bronchial cartilage hypoplasia, subpleural macrophage foci, pulmonary endometriosis, and enzootic calcinosis. The article aims to educate readers about these diseases and their characteristics. [Extracted from the article]

A choledochal cyst (CC) is one of the rare congenital diseases of the biliary tract and is more common in females. The association of ectopic pancreatic and splenic tissue with CC is an extremely rare condition. An 11-year-old girl child presented with a vague abdominal lump and intermittent dull abdominal pain for 5 months with early satiety and weight loss in the current case scenario. Her laboratory findings were normal. A type IV CC was discovered on ultrasonography, and the distal common bile duct displayed significant cystic dilatation on magnetic resonant cholangiopancreatography. After the CC was surgically removed, it was sent for histopathological examination. Sections revealed dual heterotropic elements, which included pancreatic and splenic tissues in a CC. It was very uncommon for both to exist independently in the CC and in this instance, both were observed together. This will be the first documented case, in which the CC contained dual ectopic tissue from the spleen and pancreas. Ectopic splenic tissue in the CC has never been documented in the literature. It is crucial to be aware of this entity when splenic or pancreatic tissue experiences changes due to inflammation, even though its clinical significance is uncertain. In the ectopic rests, bleeding, blockage, and malignant transformation are the possible outcomes.

The entity commonly referred to as chondrolipoma is a rare and enigmatic breast lesion with unclear histogenesis and a complete lack of molecular characterization. It is uncertain whether it represents a hamartoma, choristoma, or a distinct neoplasm, including possibly a variant of mammary-type myofibroblastoma. We report two additional chondrolipomatous lesions of the breast. The lesions had varying histologic and immunohistochemical features similar to myofibroblastoma, including the loss of retinoblastoma (Rb) protein expression in one lesion. Molecular analysis by chromosomal microarray analysis performed on a second lesion did not demonstrate a loss of 13q14 or 16q typical of myofibroblastoma. Our findings further support the concept that at least a subset of breast lesions that historically have been classified as chondrolipoma are related to myofibroblastoma. However, the lack of myofibroblastoma-specific molecular alterations in one lesion suggests chondrolipomas may also have varying origins. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy. Methods: Female rats were selected to establish a castration model and then underwent different volumes of ovarian tissue transplantation. Group I served as the sham operation group. The transplantation group was divided into five subgroups based on the calculated ratio of ovarian weight to body weight in normal female rats, δ = (2.52 ± 0.17) x10-4: Group II: transplanted ovarian volume was δ; Group III: 0.75δ; Group IV: 0.5δ; Group V: 0.25δ; Group VI: without ovarian transplantation. The post-transplant oestrous cycle recovery was observed, and blood samples were collected every 2 weeks to measure serum hormone levels. Histological evaluation was performed at the end of the observation period. Results: Rats in Group V exhibited disrupted oestrous cycles after transplantation, which were significantly longer than those in Group I. Rats in Groups II, III, and IV showed no cyclic changes. At 6 weeks post-transplantation, rats in Group V had lower E2 and AMH levels and higher FSH levels compared to Group I. The uterine wet weight and the number of normal follicles in Group V were significantly lower than those in Group I, but the number of atretic follicles was higher than in Group I. Conclusion: The larger ovarian tissue transplantation resulted in a faster recovery with a higher survival rate of the uterus and normal follicles, compared to smaller ovarian tissue transplantation. [ABSTRACT FROM AUTHOR]

Ectopic eruption of the permanent first molar can lead to malocclusion if left untreated. Despite several reported etiologic factors and treatment options, ectopic eruption caused by an improper restoration on an adjacent tooth and a simple solution have never been documented. Case report: An 8-year-old boy presented with an entrapped ectopic permanent mandibular first molar under the poorly adapted margin of a preformed metal crown (PMC) on the adjacent primary second molar. Replacement with a PMC that had well-contoured margins followed by inserting a separating module between the proximal contact of the two teeth resulted in successful management of this situation in 1 month. Conclusion: This simple approach with good interdisciplinary communication is practical for correcting eruption problems due to a poorly adapted PMC, with long-term satisfactory results. To avoid subsequent malocclusion and unnecessary treatments, dental practitioners must be vigilant when manipulating PMCs and assessing the marginal adaptation prior to their cementation. [ABSTRACT FROM AUTHOR]

Muscle stem cells (MuSCs) are specialized cells that reside in adult skeletal muscle poised to repair muscle tissue. The ability of MuSCs to regenerate damaged tissues declines markedly with aging and in diseases such as Duchenne muscular dystrophy, but the underlying causes of MuSC dysfunction remain poorly understood. Both aging and disease result in dramatic increases in the stiffness of the muscle tissue microenvironment from fibrosis. MuSCs are known to lose their regenerative potential if cultured on stiff plastic substrates. We sought to determine whether MuSCs harbor a memory of their past microenvironment and if it can be overcome. We tested MuSCs in situ using dynamic hydrogel biomaterials that soften or stiffen on demand in response to light and found that freshly isolated MuSCs develop a persistent memory of substrate stiffness characterized by loss of proliferative progenitors within the first three days of culture on stiff substrates. MuSCs cultured on soft hydrogels had altered cytoskeletal organization and activity of Rho and Rac guanosine triphosphate hydrolase (GTPase) and Yes-associated protein mechanotransduction pathways compared to those on stiff hydrogels. Pharmacologic inhibition identified RhoA activation as responsible for the mechanical memory phenotype, and single-cell RNA sequencing revealed a molecular signature of the mechanical memory. These studies highlight that microenvironmental stiffness regulates MuSC fate and leads to MuSC dysfunction that is not readily reversed by changing stiffness. Our results suggest that stiffness can be circumvented by targeting downstream signaling pathways to overcome stem cell dysfunction in aged and disease states with aberrant fibrotic tissue mechanics. [ABSTRACT FROM AUTHOR]

Mammary‐type tissue in the vulva was first described in 1872 but has been rarely reported in the literature. This tissue was previously considered as ectopic breast tissue that occurs as a result of incomplete regression of the milk line. Similar to native breast tissue, ectopic mammary tissue is hormone‐sensitive and can develop benign changes, such as fibroadenoma, as well as malignant changes. A more recent theory suggests that these benign and malignant mammary‐type entities arise from mammary‐like anogenital glands, which constitute normal vulvar components. We report a case of a 41‐year‐old woman who presented with a chronic asymptomatic cyst on the left vulva that eventually became uncomfortable, especially on standing. The cyst was located on the labium minus, measuring 1.0 × 0.5 cm, with no identified erythema or other skin abnormalities. Excision of the lesion and subsequent microscopic examination showed a circumscribed mass with a nodular overgrowth of epithelial and stromal components, resembling a mammary fibroadenoma with pseudoangiomatous stromal hyperplasia. We bring to attention this rare diagnosis and the importance of considering it in the presence of a vulvar lesion. The malignant and recurrence potential of mammary‐type tissue necessitates excision with clear margins and close monitoring of these patients. [ABSTRACT FROM AUTHOR]

Though aetiology of lateral neck masses is complex, branchial cleft cyst is the second most common congenital lesions of the neck next only to thyroglossal duct cysts. Rarely ectopic thyroid tissue within a branchial cleft cyst may develop into primary papillary carcinoma, and even more rarely it may harbour metastases of primary thyroid papillary carcinoma. We report a rare case of lateral cystic neck mass in a 24-year-old female patient diagnosed as metastatic PTC. The patient was diagnosed after she underwent surgical excision of branchial cleft cyst. Later prospectively the patient underwent total thyroidectomy which revealed papillary thyroid micro invasive carcinoma. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Perforation of Meckel's diverticulum (MD) is rare, particularly by foreign body. High index of suspicion and thorough intraoperative assessment is needed in patients undergoing surgery for acute appendicitis, specifically when appendix appears normal. Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract. While often asymptomatic, it can present with several complications. Perforation due to foreign body ingestion is rare but can have severe consequences if late diagnosis occurs. A 13‐year‐old male, initially suspected of acute appendicitis, was eventually diagnosed with perforation of MD by a wood splinter‐like foreign body after intraoperative assessment. Histological analysis revealed ectopic colonic tissue within the MD, a finding whose implications are not well understood, in contrast with the well‐established complications associated with ectopic gastric and pancreatic tissues. This case highlights the diagnostic challenges of MD, which can mimic acute appendicitis, emphasizing the need for high suspicion when faced with atypical clinical presentation such as foreign body‐induced perforation. Although surgical resection of asymptomatic MD remains controversial, we recommend a case‐specific approach based on risk factors to guide decision‐making on surgical resection for asymptomatic MD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ectopic prostatic tissue in female patients is rare. It is theorized that the presence of prostatic tissue in female patients is likely a Wolffian remnant or transformation of hormonally mediated tissue of the uterus, cervix, Skene's gland, and, rarely, periurethral tissue. Due to the increase in the use of testosterone and gender-affirming therapies, it is important to understand the role of testosterone in mediating the presence of ectopic prostatic tissue. CASE: We present a case of ectopic prostatic tissue in a urethral diverticulum in a female patient with exposure to testosterone hormone therapy and review the literature on this finding. CONCLUSION: Although rare, ectopic prostatic tissue should be considered in the differential diagnosis of anterior vaginal cysts, especially in the setting of testosterone supplementation. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary sequestration is a rarely reported phenomenon where aberrant lung tissue exists independently from the rest of the tracheobronchial network. Complications may include hemothorax; however, there is a paucity of descriptions of this condition in the literature. Case Report: We describe a case of a pulmonary intralobar sequestration resulting in atraumatic tension hemothorax. A 73-year-old woman presented to our facility in extremis and with complaints of acute-onset flank pain. Her evaluation was notable for a large pulmonary sequestration with a presumed, moderate-sized effusion; however, initial review did not reveal an obvious underlying cause for her symptoms. Shortly after her arrival to the emergency department (ED) she experienced a cardiac arrest. On secondary review of her computed tomographic angiography, it was determined that what was previously thought to be a pleural effusion was a large hemothorax. Following this finding, a finger thoracostomy was performed, which resulted in the immediate evacuation of hemothorax. The thoracostomy was then converted into an ED thoracotomy to assess for active hemorrhage with brief return of spontaneous circulation. Prior to proceeding with emergent operative intervention, the patient’s spouse requested that all further resuscitative efforts cease, and the patient was allowed to expire. In a review of the case, it was determined that the patient suffered from cardiac arrest due to a spontaneous hemothorax secondary to a large intralobar pulmonary sequestration. Conclusion: Pulmonary intralobar sequestration can result in spontaneous hemorrhage with fatal results. Early and correct interpretation of imaging and surgical intervention are crucial in ED management. [ABSTRACT FROM AUTHOR]

Adenomyosis is characterized by ectopic proliferation of endometrial tissue within the myometrium. Histologically, this condition is marked by the presence of islands of benign endometrial glands surrounded by stromal cells. The myometrium appears thinner, and cross-sectional analysis often reveals signs of recent or chronic hemorrhage. The ectopic endometrial tissue may respond to ovarian hormonal stimulation, exhibiting proliferative or secretory changes during the menstrual cycle, potentially leading to bleeding, uterine swelling, and pain. Adenomyosis can appear as either a diffuse or focal condition. It is crucial to understand that adenomyosis involves the infiltration of the endometrium into the myometrium, rather than its displacement. The surgical management of adenomyosis is contingent upon its anatomical extent. The high incidence of the disease and the myths that develop around it increase the need to study its characteristics and its association with pregnancy and potential obstetric complications. These complications often require quick decisions, appropriate diagnosis, and proper counseling. Therefore, knowing the possible risks associated with adenomyosis is key to decision making. Pregnancy has a positive effect on adenomyosis and its painful symptoms. This improvement is not only due to the inhibition of ovulation, which inhibits the bleeding of adenomyotic tissue, but also to the metabolic, hormonal, immunological, and angiogenic changes associated with pregnancy. Adenomyosis affects pregnancy through disturbances of the endocrine system and the body's immune response at both local and systemic levels. It leads to bleeding from the adenomyotic tissue, molecular and functional abnormalities of the ectopic endometrium, abnormal placentation, and destruction of the adenomyotic tissue due to changes in the hormonal environment that characterizes pregnancy. Some of the obstetric complications that occur in women with adenomyosis in pregnancy include miscarriage, preterm delivery, placenta previa, low birth weight for gestational age, obstetric hemorrhage, and the need for cesarean section. These complications are an understudied field and remain unknown to the majority of obstetricians. These pathological conditions pose challenges to both the typical progression of pregnancy and the smooth conduct of labor in affected women. Further multicenter studies are imperative to validate the most suitable method for concluding labor following surgical intervention for adenomyosis. [ABSTRACT FROM AUTHOR]

It has been shown using proton magnetic resonance spectroscopy (1H MRS) that, in a group of females, whole‐body insulin resistance was more closely related to accumulation of saturated intramyocellular lipid (IMCL) than to IMCL concentration alone. This has not been investigated in males. We investigated whether age‐ and body mass index‐matched healthy males differ from the previously reported females in IMCL composition (measured as CH2:CH3) and IMCL concentration (measured as CH3), and in their associations with insulin resistance. We ask whether saturated IMCL accumulation is more strongly associated with insulin resistance than other ectopic and adipose tissue lipid pools and remains a significant predictor when these other pools are taken into account. In this group of males, who had similar overall insulin sensitivity to the females, IMCL was similar between sexes. The males demonstrated similar and even stronger associations of IMCL with insulin resistance, supporting the idea that a marker reflecting the accumulation of saturated IMCL is more strongly associated with whole‐body insulin resistance than IMCL concentration alone. However, this marker ceased to be a significant predictor of whole‐body insulin resistance after consideration of other lipid pools, which implies that this measure carries no more information in practice than the other predictors we found, such as intrahepatic lipid and visceral adipose tissue. As the marker of saturated IMCL accumulation appears to be related to these two predictors and has a much smaller dynamic range, this finding does not rule out a role for it in the pathogenesis of insulin resistance. [ABSTRACT FROM AUTHOR]

Background: Ectopic liver tissue (ELT) is a developmental abnormality in which liver tissue develops at an extrahepatic site without connection to the true liver. It is a rare entity with an incidence of 0.24–0.56% according to data described in laparoscopic or autopsy studies. The detailed mechanism behind the development of ELT is poorly understood. ELT predominantly has an asymptomatic nature, even by means of radiological studies the diagnosis of ELT without surgery or autopsy is difficult. ELT has been reported mostly to be found frequently on the gallbladder and rarely on the gastrohepatic ligament. ELT has increased the potential risk of HCC which makes the resection crucial. Due to its variations anatomically, ELT recognition should gain clinical importance and surgeons need to be aware of these possible disparities. Case presentation. We present a 59-year-old female from Western Tanzania was presented to us with 2-month history of painless upper abdominal swelling. An abdominal CT scan was performed, and it revealed a large mass located at the gastrohepatic region with blood supply mainly from the left hepatic artery and omentum. Technically difficult excision of 17 × 12 cm tumor at gastrohepatic ligament was performed, with uneventful recovery. Post-operative histology results revealed capsulated hepatic parenchyma without the biliary components and limited sinusoids with tissue degeneration. To date, no complications happened during follow-up for one year. Conclusion: ELT is a rare entity with a predominantly asymptomatic nature. Preoperatively diagnosis is difficult even with images. It has anatomical variation and is hardly found along the gastrohepatic ligament. ELT has increased the potential risk of HCC which makes the resection crucial. Increased awareness of this congenital anomaly may result in increased detection rates. [ABSTRACT FROM AUTHOR]

Oxidative phosphorylation is becoming increasingly important in the induction and development of endometriosis. Recently, it has been reported that ring finger protein 43 (RNF43) is involved in the process of oxidative phosphorylation, but the mechanism remains unclear. Our investigation is to delve into the roles of RNF43 in endometriosis and elucidate the related mechanisms. We found RNF43 was downregulated in ectopic endometrial tissue and primary ectopic endometrial stromal cells (ECESCs). Knockdown of RNF43 enhanced cell viability and migration by activating oxidative phosphorylation in eutopic endometrial stromal cells (EUESCs), while overexpression of RNF43 led to the opposite results. Moreover, RNF43 reinforced the ubiquitination and degradation of NADH dehydrogenase Fe‐S protein 1 (NDUFS1) by interacting with it. Likewise to RNF43 overexpression, NDUFS1 silencing inhibited cell viability, migration, and oxidative phosphorylation in ECESCs. NDUFS1 was a downstream target of RNF43, mediating its biological role in endometriosis. Interestingly, the expression and stability of RNF43 mRNA were regulated by the Methyltransferase‐like 3 (METTL3)/IGF2BP2 m6A modification axis. The results of rat experiments showed decreased RNF43 expression and increased NDUFS1 expression in endometriosis rats, which was enhanced by METTL3 inhibition. Those observations indicated that m6A methylation‐mediated RNF43 negatively affects viability and migration of endometrial stromal cells through regulating oxidative phosphorylation via NDUFS1. The discovery of METTL3/RNF43/NDUFS1 axis suggested promising therapeutic targets for endometriosis. [ABSTRACT FROM AUTHOR]

The historical control database of a multinational laboratory services provider was queried for all histopathologic findings in New Zealand White rabbits which were used as control animals during a ten-year period (2011-2020). The query included all evaluated tissues, with or without microscopic findings, in studies conducted for safety testing for regulatory approval by the U.S. Food and Drug Agency (FDA) or the U.S. Environmental Protection Agency. A second query included studies conducted in the United Kingdom for control rabbits used in studies compliant with the Healthcare Products Regulatory Agency (MHRA) and/or the European Medicines Agency (EMA), which provide regulatory oversight in the United Kingdom and European Union, respectively. Infiltrates of inflammatory (mixed or mononuclear) cells were commonly noted in various organs including heart, digestive tract, muscle, thyroid, kidney, urinary bladder, eyelid, ocular structures, harderian gland, lacrimal gland, and lung. Mineralization was noted in aorta, kidney, urinary bladder, and ovary. Also noted were degeneration/necrosis in the myocardium, and intramuscular injection sites of the skin, degeneration/regeneration of muscle and diaphragm, ectopic tissue in the pancreas and thyroid, basophilic foci in salivary gland, increased/decreased vacuolation in adrenal gland, increased/decreased lymphocytic cellularity of lymph nodes, intrasinusoidal erythrocytes in lymph nodes, thymic atrophy, increased adipocytes in bone marrow, inflammatory cell foci in the liver and gall bladder, lacrimal gland atrophy, renal tubule basophilia, degeneration/regeneration, and dilatation; oviduct cyst; in the testis, degeneration/atrophy, cellular debris, dilatation, decreased sperm and segmental hypoplasia of seminiferous tubules; and squamous metaplasia of the testis and seminal vesicle. [ABSTRACT FROM AUTHOR]

Ectopic thyroid tissue is a rare congenital anomaly, with the presence of three simultaneous ectopic foci being exceedingly rare. We describe a case of a totally asymptomatic 26-year-old male discovered to have triple ectopic thyroid following incidental elevated thyroid-stimulating hormone (TSH) levels. Subsequent ultrasonography of the neck showed an absent thyroid gland in its conventional location. A Technetium-99m pertechnetate (Tc-99m) thyroid scan showed three distinct foci of radiotracer uptake in the upper cervical, lingual, and sublingual regions, corresponding to triple ectopic thyroid. An extensive review of the literature was conducted to provide a broader understanding and deeper insights into this uncommon condition. This case underscores the pivotal role of Technetium-99m thyroid scanning in diagnosing triple ectopic thyroid, particularly in instances where the orthotopic thyroid gland is absent. A comprehensive understanding of this rare entity is indispensable for radiologists and clinicians, enabling accurate diagnosis and informed decision-making regarding the appropriate therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a chronic estrogen dependent condition involving deposition of ectopic endometrial-like tissue, typically on the ovaries, pelvic peritoneum, and sometimes extra-pelvic regions. Despite being one of the common causes of infertility, endometriosis often remains underdiagnosed and imposes considerable emotional and financial burdens on those affected. Materials and Methods: 80 patients presented to the OPD of Department of Obstetrics and Gynaecology of Shadan Institute of Medical Science, over 12 months period, i.e., from January 2023 to December 2023. Results: The prevalence of endometriosis in present study was 35%. Most of the patients with endometriosis belonged to the age group of 31-40 years. Ovaries, followed by Pouch of Douglas were the most common sites of endometrial implants. Most of the patients had Stage III (moderate) endometriosis. Out of 28 patients, 26 patients underwent laparoscopic ablation and 2 were on conservative treatment. 16 patients reported successful pregnancies after treatment (20%). Conclusion: The study concludes that early detection and management of endometriosis is associated with higher rates of successful conceptions. [ABSTRACT FROM AUTHOR]

This article report a 40‐year‐old male patient who underwent total thyroidectomy and forearm auto‐transplantation in another hospital for secondary hyperparathyroidism. After 4 years of follow‐up, the level of parathyroid hormone continued to increase, and ultrasound showed nodules in the neck and right forearm, which were considered to be of parathyroid origin. Technetium 99m sestamibi single photon emission computed tomography and computed tomography (Tc‐99m‐MIBI SPECT/CT) imaging showed increased radioactive uptake in the submuscular soft tissue nodule of the right medial forearm, maximum standardized uptake value (SUVmax) is 0.98, which was identified as transplanted functioning parathyroid tissue. No parathyroid imaging activity was found in the neck. The patient then underwent partial removal of ectopic parathyroid tissue from the right forearm. Pathological examination confirmed parathyroid tissue, and removal was followed by a rapid decline in serum parathyroid hormone levels. [ABSTRACT FROM AUTHOR]

Ectopic breast tissue, which results from incomplete regression of the mammary line during embryogenesis, is observed in 0.2%-6% of the population. Carcinoma development in ectopic breast tissue, especially in the abdominal or chest wall, is rare. Here we present the unusual case of a 38-year-old woman with invasive ductal carcinoma in the ectopic breast tissue on the left side of the chest wall and concurrent fibroadenoma in the ectopic breast tissue on the right side. We also describe the US and MR findings of these masses. [ABSTRACT FROM AUTHOR]

Background and Objectives: Thyroid ectopy represents a rare disease with an incidence of 0.3–1/100,000. It occurs due to the defective embryological process of the thyroid gland development. The thyroid ectopic tissue may suffer malignant transformation. This review aims to shed light on the roles that I-131 SPECT/CT (radioiodine 131 single-photon emission tomography fused with computed tomography) and F-18 PET/CT (fluorodeoxyglucose F18 positron emission tomography fused with computer tomography) may play in managing patients with ectopic thyroid carcinoma. Materials and Methods: A total number of 47 articles were identified on the PubMed and Google Scholar databases, and 3 other articles were selected from articles identified in the references cited in the retrieved articles. After refining the selection, the inclusion and exclusion criteria were applied, resulting in 10 articles that were included in the review. Results: The cases of ectopy included in this review were localised as follows: four cases in the thyroglossal duct, two cases in the mediastinum, one case in the oesophagus, one case in the thorax, one case with a pre-tracheal location, and one case with a latero-cervical location. In all the cases, F-18 FDG PET/CT was used as a diagnostic tool. In one case, F-18 FDG PET/CT was combined with I-131 SPECT/CT and MRI (magnetic resonance imaging). In one case, it was combined with 68 Ga-FAPI PET/CT (Ga-68 radiolabelled FAP inhibitor positron emission tomography fused with computer tomography). The maximum SUVs (standardised uptake values) ranged from 5.5 to 25 g/mL. Conclusions: F-18 PET/CT and I-131 SPECT/CT hybrid nuclear imaging is of great value in assessing ectopic thyroid carcinoma. F-18 FDG PET/CT plays an important role in the primary tumour evaluation and distant disease detection. Ga-68 FAPIs are a promising alternative. I-131 SPECT/CT adds important information related to the anatomical characterization of primary and distant iodine-avid lesions. [ABSTRACT FROM AUTHOR]

A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells. First, we examine the unique characteristics of differentiated cell division, focusing on why differentiated cells are more susceptible than stem cells to accumulating mutations. Next, we investigate why the evolution of multicellularity in animals likely required plastic differentiated cells that maintain the capacity to return to the cell cycle and required the tumor suppressor p53. Finally, we examine an example of an evolutionarily conserved program for the plasticity of differentiated cells, paligenosis, which helps explain the origins of cancers that arise in adults. Altogether, we highlight new perspectives for understanding the development of cancer and new strategies for preventing carcinogenic cellular transformations from occurring. This review summarises emerging views on how differentiated cells become cancer cells and contribute to malignancies due to accumulating mutations, aberrant tissue repair programs and hijacked cell state plasticity. [ABSTRACT FROM AUTHOR]

The high prevalence of endometriosis, its impact on menstrual and reproductive functions, obstetric complications, and the quality of life of women in the reproductive age determines the urgency of the problem. The objective: to assess the prevalence of inflammatory changes in foci of heterotopic endometrium in patients with endometriosis and adenomyosis. Materials and methods. 92 women of reproductive age – from 21 to 46 years old – who applied for surgical treatment for symptomatic adenomyosis (47 women – 1st group) and ovarian endometriosis (45 patients – 2nd group), and 30 practically healthy women of the same age (control group) were examined. Histological examination of adenomyosis and ovarian endometriosis biopsies was performed using a light microscope at magnifications of 40 and 100. For immunohistochemical examination, primary and secondary antibodies were used to determine CD34, CD68, and CD138 markers. Results. In patients with adenomyosis and ovarian endometriosis the following concomitant gynecological pathologies as uterine fibroids, endometrial hyperplasia, chronic endometritis, chronic abnormal uterine bleeding, the frequency of which is significantly higher in adenomyosis, were diagnosed. This may indicate the pathogenetic role of chronic inflammation in the development of these pathological conditions. In patients with adenomyosis the positive expression of CD68 in the epithelial component of heterotopias was determined in 8 (17.0±5.6%) women, and in 4 (8.9±4.2%) women with ovarian endometriosis, which indicated a low phagocytic activity. During the assessment of CD34 expression in vessel walls and the stromal component of endometrioid heterotopias, a positive reaction was determined in 16 (34.0±6.9%) patients with adenomyosis and in 10 (22.2±6.2%) patients with ovarian endometriosis, which reflects the processes of neoangiogenesis and the activity of the pathological process. Positive expression of CD138 in endometrioid heterotopias prevailed in the group of patients with adenomyosis – 12 (25.5±6.4%) cases versus 4 (8.9±4.2%) cases in the group of patients with ovarian endometriosis (p<0.05). This confirmed the histological results and clinical data regarding the presence of chronic endometritis and isthmocele. Conclusions. The identified inflammatory changes, weak phagocytic activity and signs of neoangiogenesis in foci of heterotopic endometrium are more significant in patients with adenomyosis, which is confirmed by clinical and morphological data. [ABSTRACT FROM AUTHOR]

Background and objectives: B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal ectopic lymphoid tissue (mELT) in the murine model experimental autoimmune encephalomyelitis (EAE). While mELT can be examined in EAE, it is not accessible in vivo in MS patients. Our key objectives were to compare the immune cells in cerebrospinal fluid (CSF), which is accessible in patients, with those in mELT, and to study the effects of aCD20 mAbs on CSF and mELT in EAE. Methods: Applying single cell RNA sequencing, we compared gene expression profiles in immune cells from (1) CSF with mELT and (2) aCD20 mAbs treated with control treated mice in a spontaneous 2D2xTh EAE model. Results: The immune cell composition in CSF and mELT was very similar. Gene expression profiles and pathway enrichment analysis revealed no striking differences between the two compartments. aCD20 mAbs led not only to a virtually complete depletion of B cells in the CSF but also to a reduction of naïve CD4+ T cells and marked increase of macrophages. No remarkable differences in regulated genes or pathways were observed. Discussion: Our results suggest that immune cells in the CSF may serve as a surrogate for mELT in EAE. Future studies are required to confirm this in MS patients. The observed increase of macrophages in B cell depleted CSF is a novel finding and requires verification in CSF of aCD20 mAbs treated MS patients. Due to unresolved technical challenges, we were unable to study the effects of aCD20 mAbs on mELT. This should be addressed in future studies. [ABSTRACT FROM AUTHOR]

AbstractIntroduction: We investigated the role of E-cadherin and Ber-EP4 in tubal pregnancy by comparing their expressions in epithelial and trophoblastic cells both in ectopic tubal and intrauterine pregnancies. Methods: The Formalin-fixed paraffin embedded blocks of 17 intrauterine and 17 tubal pregnancies were immunohistochemically stained with E-cadherin and Ber-EP4. Results: E-cadherin was expressed in the epithelium, villous and extravillous trophoblast in tubal and intrauterine pregnancies but not in the syncytiotrophoblast. The staining intensity was lower in the extra-villous trophoblast in tubal ectopic pregnancies compared with intrauterine pregnancies. Ber-EP4 was expressed in the epithelium of tubal and intrauterine pregnancies and only in villous cytotrophoblast. The intensity of staining in tubal pregnancy was higher than in intrauterine pregnancy. Discussion: The loss of E-cadherin expression in extra-villous trophoblast and increased expression of Ber-EP4 in the villous cytotrophoblast may play a role in the formation of tubal pregnancy by allowing the blastocyst to attach to the tubal epithelium. [ABSTRACT FROM AUTHOR]

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that can give rise to the formation of vascular lesions in affected individuals. These lesions, whether occurring spontaneously or as a result of trauma, have the potential to cause severe and even fatal hemorrhage. Case description: We presented a case demonstrating the most extensive hematoma ever documented in a patient with NF1, resulting from a minor trauma. He experienced hemodynamic instability due to severe anemia. Arteriography revealed a rupture in the intercostal artery, which was successfully treated through interventional embolization to stop the hemorrhage. Additionally, we implemented a refined surgical approach, beginning with suturing, followed by the meticulous resection of necrotic and aberrant tissues, thereby markedly diminishing bleeding. Conclusion: Minor trauma may cause severe bleeding in patients with NF1, which can be life-threatening. Timely diagnosis of NF1 and effective hemostatic techniques are key to successful treatment. [ABSTRACT FROM AUTHOR]

Introduction: Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still under debate. Methods: Prevailing retrograde menstruation model predicts that ectopic endometrial cells migrate and develop into ovarian chocolate cyst. However, other models were also proposed. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. Results: A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.Because DNA methylation states exhibit a tissue specific pattern, we profiled the DNA methylation for ovarian cysts and paired eutopic endometrial and ovarian tissues from four patients. Surprisingly, DNA methylation profiles showed the ovarian cysts were closely grouped with normal ovarian but not endometrial tissues. Conclusions: These results suggested alterative origin of ovarian cysts or strong epigenetic reprogramming of infiltrating endometrial cells after seeding the ovarian tissue. The data provide contributing to the pathogenesis and pathophysiology of endometriosis. [ABSTRACT FROM AUTHOR]

Ectopic/accessory liver tissue is a rare developmental anomaly thought to be due to abnormal development of the liver during embryogenesis. Most patients with ectopic liver tissue are asymptomatic, and the condition is usually discovered incidentally during intraabdominal surgery or autopsy. In rare symptomatic cases, patients' presentations can range from mild liver function test abnormalities to severe abdominal pain or discomfort secondary to torsion and ischemia. Here, we report 2 patients with ectopic liver tissue identified incidentally during cholecystectomy: one with histologic manifestations of sickle cell congestion and the other with steatohepatitis. A possible relationship between ectopic liver tissue and gallbladder and biliary diseases, such as cholecystitis, has been proposed. To the best of our knowledge, ectopic liver tissue with sickle cell congestion has not been reported previously. [ABSTRACT FROM AUTHOR]

Foregut duplication cyst is most commonly seen in the posterior mediastinum without communication with adjacent organs or presence of other malformations and typically shows ectopic gastric or respiratory epithelium. The finding of ectopic pancreatic tissue is extremely rare. A 15-year-old female patient presented with elevated blood pressure, intermittent right flank pain for 18 months. An abdominal MRI revealed a 4 cm right cystic retroperitoneal mass, initially thought to arise from the right adrenal gland. Intraoperatively, the mass was centered in the retroperitoneum between the right adrenal gland and kidney, without attachments to these organs and no communication with other structures, and it was completely excised. Gross examination revealed a 3.5 cm well-circumscribed solid and cystic mass with orange–white cut surface and cloudy fluid surrounded by variable amounts of adipose tissue. On microscopic examination, the cysts were lined by respiratory and gastric antral/oxyntic-type mucosa, surrounded by muscularis mucosae, submucosal tissue, muscularis propria, and perienteric tissue. Within the muscular propria, exocrine pancreatic tissue was also noted. The patient is well with 7-months of follow up. This case is the first one reporting gastric, respiratory, and pancreatic epithelia. [ABSTRACT FROM AUTHOR]

Anatomically, normal cells found in an abnormal site are known as choristoma. When any two of the three-cell lineage of the mullerian duct, that is endosalpinx, endocervix and endometrium, are found at an abnormal location, it is termed mullerian choristoma or mullerianosis. Mullerianosis histologically reveals glands of varying sizes lined by cervical, tubal and endometrial cells. Individual cell lineages like endometriosis of the ovary, endosalpingiosis and endocervicosis of the urinary bladder are common. But mullerianosis is quite rare, and as per literature, only about 20 cases have been reported. We report a mullerianosis involving the liver and lung in a 41-year-old female that mimicked metastatic biliary cystadenocarcinoma. It is the first case reported in literature where there is simultaneous involvement of the liver and lung by mullerianosis. The diagnosis was made with the help of histopathology and immunohistochemistry in the resected specimens. [ABSTRACT FROM AUTHOR]

A submucosal heterotopic gastric gland (SHGG) is characterized by benign ectopic gastric tissue within the submucosa. Neoplasms arising from SHGGs are rare, and their definitive diagnosis via endoscopic biopsy is often challenging. We report the case of a 74‐year‐old man undergoing screening esophagogastroduodenoscopy, which revealed a subepithelial lesion with a central orifice in the upper body of the stomach. Endoscopic submucosal dissection (ESD) was performed because the endoscopic biopsy revealed a suspected pyloric gland adenoma. Pathological examination of the resected specimen confirmed SHGG with focal dysplasia. The patient recovered uneventfully and remained free of recurrence over a 5‐year follow‐up period. This case highlights the utility of ESD in both the treatment and accurate pathological diagnosis of neoplasms arising from SHGGs. [ABSTRACT FROM AUTHOR]

Heterotopia is defined as the presence of a tissue outside of its natural location. Ectopic or heterotopic pancreatic tissue is a form of choristoma and is considered an embryological abnormality. Stomach, duodenum, jejunum and spleen are common localizations. The gallbladder is a very rare localization. In this case report, ectopic pancreatic tissue observed in the gallbladder of a 41-year-old patient who is diagnosed with chronic calculous cholecystitis who underwent surgery is discussed in the light of current literature. [ABSTRACT FROM AUTHOR]

Background: Ectopic pancreatic tissue, also referred to as heterotopic pancreas, is defined as the presence of pancreatic tissue in an organ outside the pancreas. Ectopic pancreatic tissue, a rare embryologic abnormality, has been reported in the stomach, duodenum, colon, and Meckel diverticulum and is usually discovered incidentally. Case Report: We report a case of ectopic pancreatic tissue in the gallbladder of a 37-year-old female who underwent a cholecystectomy after a clinical diagnosis of chronic cholecystitis. Histopathologic findings were chronic cholecystitis with cholesterolosis and pyloricmetaplasia. The gallbladder wall showed ectopic pancreatic tissue composed of acini, ducts, and islets of Langerhans. The histopathologic examination confirmed the diagnosis of ectopic pancreatic tissue. Conclusion: Making a preoperative diagnosis of ectopic pancreatic tissue is clinically and radiologically challenging. Meticulous histopathologic examination is required for the diagnosis of this rare condition. [ABSTRACT FROM AUTHOR]

Maxillary canines are the second most commonly impacted teeth. Two thirds of these impacted canines are palatal, and one third are labially impacted. Maxillary labial impactions comprise approximately 0.33% to 0.75% of the general population. Like palatal impactions, preventive and interceptive methods can be employed to help the impacted tooth erupt and avoid surgical uncovering. Early extraction of appropriate primary teeth and palatal expansion has helped some of these impactions erupt spontaneously. Most labially impacted canines are positioned "in the slot," in a midalveolar location between the lateral incisor and first premolar. If they do not erupt after preventive or interceptive means, they can be managed with simple closed-eruption uncovering techniques. The most difficult labial impactions are ectopically positioned. These are usually horizontally positioned, mesial to the lateral incisor. They can be very apically positioned, near the base of the nose and near the midline. The rarest labial impaction occurs between the central and lateral incisors or between the premolars. These are extremely rare and require special orthodontic and uncovering techniques. All of these ectopic impactions require a technique that leaves the impacted tooth uncovered so the orthodontist can employ the proper mechanics to move these teeth without damage to adjacent structures. This article elucidates the surgical uncovering techniques and the orthodontic mechanics to successfully move these teeth and minimize root resorption, bone loss, and recession. [ABSTRACT FROM AUTHOR]

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease driven by gain-of-function variants in activin receptor–like kinase 2 (ALK2), the most common variant being ALK2R206H. In FOP, ALK2 variants display increased and dysregulated signaling through the bone morphogenetic protein (BMP) pathway resulting in progressive and permanent replacement of skeletal muscle and connective tissues with heterotopic bone, ultimately leading to severe debilitation and premature death. Here, we describe the discovery of BLU-782 (IPN60130), a small-molecule ALK2R206H inhibitor developed for the treatment of FOP. A small-molecule library was screened in a biochemical ALK2 binding assay to identify potent ALK2 binding compounds. Iterative rounds of structure-guided drug design were used to optimize compounds for ALK2R206H binding, ALK2 selectivity, and other desirable pharmacokinetic properties. BLU-782 preferentially bound to ALK2R206H with high affinity, inhibiting signaling from ALK2R206H and other rare FOP variants in cells in vitro without affecting signaling of closely related homologs ALK1, ALK3, and ALK6. In vivo efficacy of BLU-782 was demonstrated using a conditional knock-in ALK2R206H mouse model, where prophylactic oral dosing reduced edema and prevented cartilage and heterotopic ossification (HO) in both muscle and bone injury models. BLU-782 treatment preserved the normal muscle-healing response in ALK2R206H mice. Delayed dosing revealed a short 2-day window after injury when BLU-782 treatment prevented HO in ALK2R206H mice, but dosing delays of 4 days or longer abrogated HO prevention. Together, these data suggest that BLU-782 may be a candidate for prevention of HO in FOP. Editor's summary: Fibrodysplasia ossificans progressiva results in ectopic bone formation through heterotopic ossification (HO), which causes fused joints and early death. Gain-of-function variants in the gene encoding the activin receptor–like kinase 2 (ALK2) protein cause the disorder. Davis et al. screened a library of small-molecule kinase inhibitors and developed a compound, BLU-782, to inhibit ALK2 and prevent HO in a mouse model expressing the most common disease-causing variant of ALK2 in humans. Muscle pinch or bone break caused HO in the mice, and prophylactic treatment with BLU-782 prevented HO formation in the injured tissue. BLU-782 treatment was required starting 2 days after injury and no later than 4 days after injury to prevent HO in these mice. This study characterizes a promising potential therapy to prevent HO in fibrodysplasia ossificans progressiva. —Brandon Berry [ABSTRACT FROM AUTHOR]

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities. [ABSTRACT FROM AUTHOR]

Viscoelastic transformation of tissue drives aberrant cellular functions and is an early biomarker of disease pathogenesis. Tissues scale a range of viscoelastic moduli, from biofluids to bone. Moreover, viscoelastic behavior is governed by the frequency at which tissue is probed, yielding distinct viscous and elastic responses modulated over a wide frequency band. Existing tools do not quantify wideband viscoelastic spectra in tissues, leaving a vast knowledge gap. We present wideband laser speckle rheological microscopy (WB-SHEAR) that reveals elastic and viscous response over sub-megahertz frequencies previously not investigated in tissue. WB-SHEAR uses an optical, noncontact approach to quantify wideband viscoelastic spectra in specimens spanning a range of moduli from low-viscosity fibrin to highly elastic bone. Via laser scanning, micromechanical imaging is enabled to access wideband viscoelastic spectra in heterogeneous tumor specimens with high spatial resolution (25 micrometers). The ability to interrogate the viscoelastic landscape of diverse biospecimens could transform our understanding of mechanobiological processes in various diseases. [ABSTRACT FROM AUTHOR]

This document discusses a rare condition called neuromuscular choristoma (NMC) that is characterized by the presence of well-differentiated smooth muscle cells mixed with nerve fascicles. Patients with NMC can develop desmoid-type fibromatosis (DTF), which is a non-metastatic neoplasm that can compress or invade nervous structures. The document describes the imaging features of NMC and DTF, including the use of contrast-enhanced CT and MRI. The diagnosis of NMC associated with DTF is confirmed through biopsy and resection of the affected areas. Treatment typically involves chemotherapy and radiotherapy. [Extracted from the article]

Vulval fibroadenoma is a rare benign tumor arising from the ectopic breast tissue or mammary-like anal glandular tissue. Although it is a common breast neoplasm, its genital location makes it notable, with less than a hundred cases being reported in the literature so far. It is commonly known to present in the reproductive age group, similar to its breast counterpart, with its histogenesis being a frequent topic of discussion. Despite being benign and largely infrequent, these vulval neoplasms continue to be important reasons for medical consultation. We present one such case of vulval fibroadenoma presenting as an enlarged lymph node in a 37-year-old female. [ABSTRACT FROM AUTHOR]