Tissue Overgrowth Research Articles

HPV infection and endometrial polyps: insights from a case-control study

BackgroundEndometrial polyps are common benign lesions characterized by localized overgrowths of endometrial tissue within the uterine cavity. The etiology and pathogenesis of these polyps remain unclear. Human papillomavirus (HPV) infection, known for its association with various genital tract conditions, has been investigated concerning endometrial polyps, although research in this area is limited.MethodsA case-control study involving 62 premenopausal women was conducted, with endometrial polyp cases and control groups matched for age and BMI. Biopsy samples were collected for HPV testing using polymerase chain reaction (PCR). Clinical and demographic data were collected and analyzed for associations between HPV presence and endometrial polyps.ResultsResults showed a higher prevalence of HPV (all types) in cases (4, 12.9%) compared to controls (1, 3.2%), with low-risk HPV being the most prevalent genotype detected and HPV 16 tested positive in one case diagnosed with polyp. While no significant association was found between HPV infection and the presence of endometrial polyps, the study suggests a potential role for HPV in their development. Interestingly, HPV presence in endometrial polyps was unrelated to histopathological features, patients’ age, or BMI.ConclusionThis study provides insights into the potential involvement of HPV infection in the development of endometrial polyps. Despite no significant association found, the prevalence of HPV in these polyps suggests a possible contributory role. Further research with larger sample sizes and more robust methodologies is warranted to clarify this association and its clinical implications.

Creation of 6-10mm Diameter Transjugular Intrahepatic Portosystemic Shunts Using a Novel TIPS Stent Graft in a Swine Model

PurposeTo assess the delivery, function, and patency of a new expanded polytetrafluoroethylene encapsulated TIPS stent- graft ("Liverty") in an animal model. Materials and MethodsTIPS were created in 2 successive groups: 14 single & 10 overlapping devices, in swine weighing 52-64kg. Explants occurred at 30 (n=10) and 60 (n=14) days. These were evaluated by histomorphometry and histopathologic evaluations, and electron microscopy. ResultsSeven 6mm, five 7mm, and twelve 10mm diameter TIPS were created using varied human TIPS access sets without complications; both sheathed and unsheathed advancement and deployment of the devices within liver tracts. One animal was sacrificed at 35d due to encephalopathy; remainder survived to endpoints. 22/24 TIPS were patent at 30 and 60-day endpoints; Mean stenosis at 30 days was 13.3% +/- 10.1%, and for 60 days was 18.44% ± 5.04%. Two shunts were occluded by tissue overgrowth at unstented native hepatic vein end and downgrowth into TIPS. Histology and electron microscopy showed well-apposed, incorporated devices lined with smooth, uniform neointimal tissue averaging 0.48mm (single devices) and 0.74mm thick (overlapped devices) with minimal adventitial inflammation. ConclusionThe new Liverty TIPS stent graft was straightforward to deploy for TIPS creation and resulted in patent 6,7, and 10mm diameter shunts in both single and overlapping configurations. One- and 2-month histology showed desired tissue healing without in-stent stenosis.

Massive Localized Lymphedema, Wound Care Without Major Surgical Excision: A Case Report

ABSTRACT Massive localized lymphedema (MLL) is a benign overgrowth of lymphoproliferative tissue that is primarily observed in adults with class III obesity. Patients present with a painless mass that has usually been present for a considerable period. Consultation of a healthcare professional typically takes place when MLL-related complaints interfere with daily living. Massive localized lymphedema is often termed “pseudosarcoma” due to its clinical similarity to sarcoma. Surgical excision is necessary to improve mobility, prevent recurrent infections, and rule out malignancy, but can be high-risk for individuals with class III obesity and multiple comorbidities. In this report, the authors present the case of a 47-year-old woman with a body mass index of 73 kg/m2 and MLL of the right medial thigh. She was successfully diagnosed and managed by local necrosectomy, wound debridement, maggot debridement therapy, and negative-pressure wound therapy by using a vacuum-assisted closure device. The diagnosis of MLL can be challenging because of its similarity to sarcoma; its pathogenesis and management are not completely elucidated. Despite surgery being the best described treatment, such an intervention itself can be challenging because patients often have multiple comorbidities and delayed diagnosis. The authors recommend that clinicians should consider nonsurgical treatment of MLL in high-risk patients who have necrotic wounds with fluid loss. The use of less invasive methods such as maggot debridement therapy followed by negative-pressure wound therapy can be useful in high-risk patients.

Roles of PDGF/PDGFR signaling in various organs.

Platelet-derived growth factors (PDGFs) ligands and their corresponding receptors, PDGF receptor (PDGFR)α and PDGFRβ, play a crucial role in controlling diverse biological functions, including cell growth, viability and migration. These growth factors bind to PDGFRs, which are receptor tyrosine kinases present on the surface of target cells. The interaction between PDGFs and PDGFRs induces receptor dimerization and subsequent activation through auto-phosphorylation, which in turn triggers a cascade of intracellular signaling pathways. PDGF/PDGFR signaling is essential for maintaining normal physiological functions, including tissue regeneration and growth. However, dysregulation of this signaling pathway leads to pathological conditions, including fibrosis, atherosclerosis, and cancer development in various organs. The pathological impact of PDGF/PDGFR signaling primarily stems from its capacity to promote excessive cell proliferation, enhanced migration, and increased extracellular matrix deposition, resulting in tissue overgrowth, scarring, and abnormal vessel formation. These processes are integral to the pathogenesis of fibrotic, neoplastic, and vascular disorders. Therefore, understanding these pathways is crucial for developing targeted treatments designed to inhibit PDGF/PDGFR signaling in these diseases. This review delves into the dual role of PDGF/PDGFR signaling in both physiological and pathophysiological contexts across different organs and provides insights into current pharmacological therapies designed to target the PDGF signaling pathway. INTRODUCTION Platelet-derived growth factors (PDGFs) are key signaling molecules that interact with specific cell to modulate various cellular responses. Upon binding to their receptors (PDGFRs), PDGFs initiate dimerization and tyrosine phosphorylation, which activates downstream signaling pathways. The PDGF signaling network comprises four ligands-PDGF-A, PDGF-B, PDGFC, and PDGF-D, that interact with two receptors, PDGFRα and PDGFRβ [1-6]. PDGFRα exhibits broader ligand specificity, binding to PDGF-A, PDGF-B, PDGF-C homodimers, and PDGFAB heterodimers, whereas PDGFRβ specifically binds to PDGFB and PDGF-D homodimers. Under both physiological and pathol.

Intrusion and retraction with an innovative crane spring

Today, one of the most common lines of treatment for gummy smiles is the use of temporary anchorage devices (TADs). One of the major issues with the TADs is the unpredictability of stability during treatment. Additional to the loosening of TAD, gingival tissue overgrowth, especially when placed above the attached gingiva, is a persistent issue. During the process of intrusion and retraction, the point of force attachment in relation to the center of resistance is of prime importance to achieve the correct and required vector of force. This, at most times, is not achievable with TADs due to the interference of the roots of teeth. Thus, an alternative to TADs with the convenience of placing the point of force attachment anywhere in the buccal vestibule is discussed here in. This article describes the design and action of an innovative spring (Crane spring) wherein the point of force attachment can be varied to suit the biomechanics apart from delivering light and continuous forces using looped mechanics. The spring is of a simple design and can be easily constructed. It is highly efficient with intrusion and retraction.

7518 A Case of Delayed Diagnosis of Acromegaly Associated with Uncontrolled Diabetes

Abstract Disclosure: A. Mahmoudabadi: None. S. Patel: None. Background: Acromegaly is a rare disorder characterized by an excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) levels, typically due to a GH-secreting pituitary adenoma. This consequently leads to complications such as acral and soft tissue overgrowth, visual disturbance, insulin resistance, and dyslipidemia. In this case, we describe a patient who presented to the endocrinology clinic for uncontrolled diabetes and was subsequently diagnosed with acromegaly. Clinical Case: This is a 47-year-old male with a history of heart failure, hypertension, and type 2 diabetes mellitus (DM) who presented to the clinic with uncontrolled DM. He had failed to achieve adequate blood sugar control despite being compliant with metformin, dapagliflozin, and insulin degludec. Physical examination revealed frontal bossing, prognathism, macroglossia, and a deep voice. On further questioning, he had noticed these changes since five years prior. Anthropometry and laboratory tests were as follows: Height, 180 cm; body weight 107.5 kg; body mass index (BMI), 33.05 kg/m2 and A1c level of 15.0%. Suspicion of acromegaly was confirmed based on biochemical and imaging findings. Fasting growth hormone (GH), at 58 mU/L (reference range 0-10), and insulin-like growth factor 1 (IGF-1), at 857 nmol/L (reference range 81-263), were markedly elevated. Pituitary magnetic resonance imaging (MRI) showed a sellar and suprasellar mass (2.6 × 2.2 × 2.2 cm) extending and compressing the optic chiasm. He eventually underwent a transsphenoidal adenomectomy with neurosurgery. Following surgery, his insulin requirements went from a total daily dose of about 100 units to an inpatient dose of 30 units by his last day of admission. Conclusion: Acromegaly is prevalent in less than 3% of patients with DM, but higher rates of DM are seen in acromegalic patients with higher IGF-1 levels and longer duration of disease. The diagnosis of acromegaly can often be delayed due to missed findings on routine physical examination. This can lead to increased morbidity, mortality, and complications such as uncontrolled DM, witnessed in our patient. Surgical management of acromegaly is the mainstay of treatment and can lead to improvement of glycemic control and insulin sensitivity. Fortunately, our patient could undergo surgery, but delayed diagnosis can prevent patients from surgery if the pituitary tumor becomes too large or unresectable. Ultimately, this case highlights the importance of a thorough physical examination and keeping a wide differential diagnosis when evaluating patients with uncontrolled DM, as failure to diagnose acromegaly at an early stage may have devastating consequences on patient outcomes. Presentation: 6/3/2024

YAP promotes global mRNA translation to fuel oncogenic growth despite starvation.

Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) play fundamental roles in stem/progenitor cell expansion during homeostasis, and their dysregulation often leads to tissue overgrowth. Here, we show that YAP activation is sufficient to overcome the restriction of global protein synthesis induced by serum starvation, enabling cells to sustain proliferation and survival despite an unfavorable environment. Mechanistically, YAP/TAZ selectively promoted the mTORC1-dependent translation of mRNAs containing 5' terminal oligopyrimidine (5'TOP) motifs, ultimately increasing the cellular polysome content. Interestingly, DNA damage-inducible transcript 4 (DDIT4), a negative regulator of mTORC1, was upregulated by serum starvation but repressed by YAP/TAZ. DDIT4 was sufficient to suppress the translation and transformative potential of uveal melanoma cells, which are often serum unresponsive due to G protein mutations. Our findings reveal a vital role for protein synthesis as a key modality of YAP/TAZ-induced oncogenic transformation and indicate the potential for targeting mTORC1 or translation to treat YAP/TAZ-driven malignancies.

Characterization of testicular embryonic-type neuroectodermal tumor and embryonic-type neuroectodermal tissue admixed with mature neuro-glial tissue using a broad immunohistochemical panel.

Embryonic-type neuroectodermal tumor (ENT) is a somatic-type malignancy characterized by overgrowth of embryonic-type neuroectodermal tissue (EtNT). In germ cell tumors, EtNT is frequently intermingled with other components that may exhibit significant morphologic overlap [mature neuro-glial tissue (MNGT), nephroblastomatous tissues, and primitive endodermal-type glands]. Therefore, the quantification of EtNT (crucial for the diagnosis of ENT) can be challenging. In this study, we investigated the immunohistochemical profile of ENT, EtNT, and MNGT using a broad immunohistochemical panel. We found that SOX2 was the most sensitive marker for EtNT (100%), but it also stained MNGT (28.6%). GFAP and S100 were relatively sensitive (71.4%) and highly specific (GFAP 100%, S100 85.8%) for MNGT, whereas synaptophysin stained both. Combining our results with those of previous studies, we propose that a combination of SOX11, SOX2, GFAP, S100, AFP, villin, CDX2, PAX8, and nuclear WT1 may help to identify and quantify EtNT in germ cell tumors.

Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis.

Tumor suppressor genes play critical roles in normal tissue homeostasis, and their dysregulation underlies human diseases including cancer. Besides human genetics, model organisms such as Drosophila have been instrumental in discovering tumor suppressor pathways that were subsequently shown to be highly relevant in human cancer. Here we show that hyperplastic disc (Hyd), one of the first tumor suppressors isolated genetically in Drosophila and encoding an E3 ubiquitin ligase with hitherto unknown substrates, and Lines (Lin), best known for its role in embryonic segmentation, define an obligatory tumor suppressor protein complex (Hyd-Lin) that targets the zinc finger-containing oncoprotein Bowl for ubiquitin-mediated degradation, with Lin functioning as a substrate adaptor to recruit Bowl to Hyd for ubiquitination. Interestingly, the activity of the Hyd-Lin complex is directly inhibited by a micropeptide encoded by another zinc finger gene, drumstick (drm), which functions as a pseudosubstrate by displacing Bowl from the Hyd-Lin complex, thus stabilizing Bowl. We further identify the epigenetic regulator Polycomb repressive complex1 (PRC1) as a critical upstream regulator of the Hyd-Lin-Bowl pathway by directly repressing the transcription of the micropeptide drm Consistent with these molecular studies, we show that genetic inactivation of Hyd, Lin, or PRC1 resulted in Bowl-dependent hyperplastic tissue overgrowth in vivo. We also provide evidence that the mammalian homologs of Hyd (UBR5, known to be recurrently dysregulated in various human cancers), Lin (LINS1), and Bowl (OSR1/2) constitute an analogous protein degradation pathway in human cells, and that OSR2 promotes prostate cancer tumorigenesis. Altogether, these findings define a previously unrecognized tumor suppressor pathway that links epigenetic program to regulated protein degradation in tissue growth control and tumorigenesis.

Endoplasmic Reticulum Stress-Mediated Cell Death in Renal Fibrosis.

The endoplasmic reticulum (ER) is indispensable for maintaining normal life activities. Dysregulation of the ER function results in the accumulation of harmful proteins and lipids and the disruption of intracellular signaling pathways, leading to cellular dysfunction and eventual death. Protein misfolding within the ER disrupts its delicate balance, resulting in the accumulation of misfolded or unfolded proteins, a condition known as endoplasmic reticulum stress (ERS). Renal fibrosis, characterized by the aberrant proliferation of fibrotic tissue in the renal interstitium, stands as a grave consequence of numerous kidney disorders, precipitating a gradual decline in renal function. Renal fibrosis is a serious complication of many kidney conditions and is characterized by the overgrowth of fibrotic tissue in the glomerular and tubular interstitium, leading to the progressive failure of renal function. Studies have shown that, during the onset and progression of kidney disease, ERS causes various problems in the kidneys, a process that can lead to kidney fibrosis. This article elucidates the underlying intracellular signaling pathways modulated by ERS, delineating its role in triggering diverse forms of cell death. Additionally, it comprehensively explores a spectrum of potential pharmacological agents and molecular interventions aimed at mitigating ERS, thereby charting novel research avenues and therapeutic advancements in the management of renal fibrosis.

3D printing and intelligent technology increase convenience, reliability, and patient acceptance of ostomy nursing: a randomized controlled trial.

Traditional ostomy bags commonly cause skin allergy and inflammation around the stoma, as well as leakage. This study aimed to examine the effect of a 3D-printed ostomy bag with sensors and stimulators on stoma nursing. This is a randomized controlled trial. This trial involved 113 distinct individuals who undergo colorectal cancer surgery and intestinal obstruction surgery, with resulting stoma. The date of trial registration was January 17, 2019, and the date of first recruitment was May 1, 2019. Patients were randomized into two groups: intelligent 3D-printed ostomy bag (3D group, n = 57) and Coloplast one-piece pouching systems (control group, n = 56). The shape of ostomy and the surrounding skin of all the 57 patients of the 3D group was scanned by a handheld 3D scanner. Then, the ostomy bag chassis (also known as skin barrier) was 3D printed and an intelligent device adhered to the ostomy bag. The wearing time, leakage rate, the Discoloration, Erosion, and Tissue Overgrowth (DET) score, and the Acceptance of Illness Scale (AIS) were observed. In the 3D-printed bag group, the time to wear (0.7 ± 0.4m) was significantly shorter than that of the control group (9.1 ± 3.5m). The leakage rate of 3D-printed bag (1.75%) was significantly lower than that of the control group (16.1%). The DET score for the 3D-printed bag group was also lower than that of the control group, and the AIS score for the 3D-printed bag group was higher than that of the control group. The 3D-printed ostomy bags and the linked computer program can significantly reduce wearing time, leakage rate, and stoma complications. This may improve the quality of home ostomy care for patients and reduce the incidence of skin complications around the stoma.Registration number: ChiCTR1900020752.

Direct activation of PI3K in osteoblasts and osteocytes strengthens murine bone through sex-specific actions on cortical surfaces.

Intracellular phosphoinositide 3-kinase (PI3K) signaling is activated by multiple bone-active receptors. Genetic mutations activating PI3K signaling are associated with clinical syndromes of tissue overgrowth in multiple organs, often including the skeleton. While one formation is increased by removing the PI3K inhibitor (phosphatase and TENsin homolog deleted on chromosome 10 (PTEN)), the effect of direct PI3K activation in the osteoblast lineage has not been reported. We introduced a known gain-of-function mutation in Pik3ca, the gene encoding the p110α catalytic subunit of PI3K, in osteocytes and late osteoblasts using the dentin matrix protein-1 Cre (Dmp1Cre) mouse and assessed the skeletal phenotype. Femur shape was grossly normal, but cortical thickness was significantly greater in both male and female Dmp1Cre.Pik3caH1047R mice, leading to almost doubled bone strength at 12wk of age. Both sexes had smaller marrow areas from 6wk of age. Female mice also exhibited greater cross-sectional area, which continued to increase until 24wk of age, resulting in a further increase in bone strength. Although both male and female mice had increased endocortical mineralizing surface, only female mice had increased periosteal mineralizing surface. The bone formed in the Dmp1Cre.Pik3caH1047R mice showed no increase in intracortical remodeling nor any defect in cortical bone consolidation. In contrast, on both endocortical and periosteal surfaces, there was more lamellar bone formation, including highly organized osteocyte networks extending along the entire surface at a greater thickness than in control mice. In conclusion, direct activation of PI3Kα in cells targeted by Dmp1Cre leads to high cortical bone mass and strength with abundant lamellar cortical bone in female and male mice with no increase in intracortical remodeling. This differs from the effect of PTEN deletion in the same cells, suggesting that activating PI3Kα in osteoblasts and osteocytes may be a more suitable target to promote formation of lamellar bone.

P-284 Large-scale genome-wide association study (GWAS) to determine the genetic underpinnings of female genital tract polyps (FGT)

Abstract Study question Can a large-scale GWAS meta-analysis identify the genomic risk loci and associated candidate genes for FGT polyps? Summary answer We identified ten genomic risk loci, with two exonic missense variants in PRIM1 and COL17A1 genes, highlighting the shared mechanisms with cancerous processes. What is known already Small-scale candidate gene studies have focused on biological processes such as oestrogen stimulation and inflammation to clarify the biology behind FGT polyps. However, the exact mechanism for the development of polyps is still elusive. At the same time, a genome-wide approach, which has become the gold standard in complex disease genetics, has never been used to uncover the genetics of the FGT polyps. Study design, size, duration We performed a genome wide association study (GWAS) meta-analysis including a total of 25,100 women with FGT polyps (International Classification of Disease, ICD-10 diagnosis code N84) and 207,193 female controls (without N84 code) of European ancestry from the FinnGen study (11,092 cases and 94,394 controls) and the Estonian Biobank (EstBB, 14,008 cases and 112,799 controls). Participants/materials, setting, methods A meta-analysis and functional annotation of GWAS signals were performed using the Functional mapping and annotation of genetic associations (FUMA) tool. Gene prioritization for the identified variants was conducted using the variant-to-gene (V2G) score from the OpenTarget genetics portal, followed by FUMA analysis. To determine associations with other phenotypes, we performed a look-up of associated variants across multiple traits, a genetic correlation analysis, and a phenome-wide association study (PheWAS) with ICD10 diagnosis codes. Main results and the role of chance Our GWAS meta-analysis revealed ten significant (P < 5 x 10-8) genomic risk loci. Two signals, rs2277339 (P = 7.6 x 10-10) and rs1265005 (P = 1.1 x 10-9) (in linkage disequilibrium (LD) with rs805698 r2 = 0.75), are exonic missense variants in PRIM1, and COL17A1 genes, respectively. Based on the literature, these genes may play a role in cellular proliferation. Several of the identified genomic loci had previously been linked to endometrial cancer and/or uterine fibroids. Thus, highlighting the shared mechanisms underlying tissue overgrowth and cancerous processes, which may be relevant to the development of polyps. Genetic correlation analysis revealed a negative correlation between sex hormone-binding globulin (SHBG) and the risk of FGT polyps (rg = -0,21, se = 0.04, P = 2.9 x 10-6), and on the phenotypic level (PheWAS), the strongest associations were observed with endometriosis, leiomyoma of the uterus and excessive, frequent and irregular menstruation. Limitations, reasons for caution In this study, we focused broadly on FGT polyps and did not differentiate between the polyp subtypes. The prevalence of FGT polyps led us to assume that most women included in the study had endometrial polyps. Wider implications of the findings The study findings have the potential to significantly enhance our understanding of the genetic mechanisms involved, paving the way for future functional follow-up, which in turn could improve the diagnosis, risk assessment, and targeted treatment options, since surgery is the only line of treatment available for diagnosed polyps. Trial registration number not applicable

Modern approaches to the creation of 2D and 3D cellular models for the study of lung fibrosis

Lung fibrosis is a consequence of many influences leading to damage to lung tissue and the development of subsequent inflammation. Fibrosis is an overgrowth of connective tissue, which can lead to a violation of the architectonics of the lungs and reduce their functionality up to a fatal outcome. At the same time, the mechanisms underlying fibrogenesis are currently insufficiently studied. In this regard, the task of studying them does not lose its relevance, and its solution requires the development of models of lung fibrosis that can reflect all the key processes of fibrogenesis.The in vivo model using animals has multiple undeniable advantages, but at the same time it has strict ethical limitations and does not reflect all the mechanisms of lung fibrosis inherent in the human body. At the same time, in vitro research, scientists can afford to use biomaterials not only of animals, but also of humans, and build cellular systems based on them — from 2D to 3D models. Modeling of pulmonary fibrosis is mainly based on the use of the main types of cells involved in the development of pulmonary fibrosis, such as myofibroblasts, fibroblasts, alveolocytes and others. Some models are also based on a specific fibrosis-associated extracellular matrix and further study of the interaction of cells with each other and with the matrix. It should be borne in mind that different models display individual nuances of the native processes of lung fibrogenesis, which requires the research community to use a wide range of models. Taking into account the multifactorial pathogenesis of pulmonary fibrosis, it is important to understand the totality of the processes taking place in order to obtain the completeness of the real picture, close to the picture in vivo, and therefore the multicomponence of models is important. This review focuses on the analysis of various models of lung fibrosis in vitro in two-dimensional and three-dimensional systems, shows approaches to their creation, key differences, main advantages and disadvantages of models, both particular and general.

Genotype-histotype-phenotype correlations in hyperinsulinemic hypoglycemia.

Hyperinsulinemic hypoglycemia (HH) of pancreatic origin includes congenital hyperinsulinism (CHI), insulinoma, insulinomatosis, and adult-onset non-insulinoma persistent hyperinsulinemic hypoglycemia syndrome (NI-PHHS). In this review, we describe the genotype-histotype-phenotype correlations in HH and their therapeutic implications. CHI can occur from birth or later on in life. Histologically, diffuse CHI shows diffuse beta cell hypertrophy with a few giant nuclei per islet of Langerhans, most frequently caused by loss-of-function mutations in ABCC8 or KCNJ11. Focal CHI is histologically characterized by focal adenomatous hyperplasia consisting of confluent hyperplastic islets, caused by a paternal ABCC8/KCNJ11 mutation combined with paternal uniparental disomy of 11p15. CHI in Beckwith-Wiedemann syndrome is caused by mosaic changes in the imprinting region 11p15.4-11p15.5, leading to segmental or diffuse overgrowth of endocrine tissue in the pancreas. Morphological mosaicism of pancreatic islets is characterized by occurence of hyperplastic (type 1) islets in one or a few lobules and small (type 2) islets in the entire pancreas. Other rare genetic causes of CHI show less characteristic or unspecific histology. HH with a predominant adult onset includes insulinomas, which are pancreatic insulin-producing endocrine neoplasms, in some cases with metastatic potential. Insulinomas occur sporadically or as part of multiple endocrine neoplasia type 1 due to MEN1 mutations. MAFA mutations may histologically lead to insulinomatosis with insulin-producing neuroendocrine microadenomas or neuroendocrine neoplasms. NI-PHHS is mainly seen in adults and shows slight histological changes in some patients, which have been defined as major and minor criteria. The genetic cause is unknown in most cases. The diagnosis of HH, as defined by genetic, histological, and phenotypic features, has important implications for patient management and outcome.

Proteus Syndrome: Case Report and Updated Literature Review.

Proteus syndrome (PS) is an exceptionally uncommon genetic disorder that has been documented in only approximately 250 cases in the literature spanning the past four decades. It is characterized by a disproportionate, asymmetric overgrowth of all types of tissues, provoked by a somatic activating mutation in serine/threonine protein kinase 1. We report a case of PS in a two-year-old female patient with the following clinical features: unilateral overgrowth of connective tissue in the right buttock and right foot, where multiple surgeries were performed to achieve a desirable aesthetic outcome and ensure psychological comfort of the young patient. The insights provided by this case underscore the pivotal role of obtaining pleasing aesthetic outcomes in the surgical management of untreatable genetic disorders, with the aim of nurturing psychological contentment in affected children.

Sialyllactose preserves residual hearing after cochlear implantation

In individuals with hearing loss, protection of residual hearing is essential following cochlear implantation to facilitate acoustic and electric hearing. Hearing preservation requires slow insertion, atraumatic electrode and delivery of the optimal quantity of a pharmacological agent. Several studies have reported variable hearing outcomes with osmotic pump-mediated steroid delivery. New drugs, such as sialyllactose (SL) which have anti-inflammatory effect in many body parts, can prevent tissue overgrowth. In the present study, the positive effects of the pharmacological agent SL against insults were evaluated in vitro using HEI-OC1 cells. An animal model to simulate the damage due to electrode insertion during cochlear implantation was used. SL was delivered using osmotic pumps to prevent loss of the residual hearing in this animal model. Hearing deterioration, tissue fibrosis and ossification were confirmed in this animal model. Increased gene expressions of inflammatory cytokines were identified in the cochleae following dummy electrode insertion. Following the administration of SL, insertion led to a decrease in hearing threshold shifts, tissue reactions, and inflammatory markers. These results emphasize the possible role of SL in hearing preservation and improve our understanding of the mechanism underlying hearing loss after cochlear implantation.

Dissolvable microneedles loaded with asiaticoside nanocrystals stabilized by Panax Notoginseng saponins for hypertrophic scar treatment

Hypertrophic scars (HS) are fibroproliferative disorders caused by overgrowth of connective tissue during wound repair, for which effective treatment is lacking. Although Asiaticoside (AS) facilitates scarless wound healing, its low permeability through the skin and poor solubility in water pose major barriers to clinical application. Dissolvable microneedles (DMNs) have emerged as a potent transdermal drug delivery technique capable of penetrating the stratum corneum barrier. However, due to the lipid-soluble nature of AS, it is incompatible with water-soluble microneedle matrices. This incompatibility could result in an uneven dispersion of drugs, making the creation of DMNs loaded with AS challenging. In this study, a pharmacodynamic molecule called Panax Notoginseng Saponins (PNS), which similarly encourages scarless wound healing, was used as a stabilizer. Asiaticoside-Panax Notoginseng Saponin (AS-PNS-NCs) were prepared by solvent evaporation coupled with ultrasonication to improve the water solubility of AS. The average particle size was 158.70 ± 10.99 nm, Polydispersity index (PDI) was 0.18 ± 0.012, and Zeta potential was −15.5 ± 1.08 mV. A centrifugal filling technique was then used to create AS-PNS-NCs-DMNs. After 24 h of in vitro transdermal drug release, the cumulative transdermal release of AS-PNS-NCs-DMNs of 319.00 ± 50.01 μg and skin retention of 80.61 ± 48.46 μg were significantly higher than those of AS-PNS-NCs- Gels (134.84 ± 27.66 μg and 5.23 ± 1.86 μg, respectively). Furthermore, it was demonstrated that AS-PNS-NCs-DMNs may suppress human skin fibroblasts (HSF) in vitro migration rate and proliferative activity. In rabbit ear keloid model, AS-PNS-NCs-DMNs (containing AS 1536.49 ± 93.14 μg/patch) reduced the collagen volume fraction (CVF) and improved the collagen fiber arrangement by inhibiting the overexpression of transforming growth factor-β1 (TGF-β1) and α-Smooth muscle actin (α-SMA) at the scar site, resulting in a reduction of scar thickness. It is demonstrated that AS-PNS-NCs-DMNs can effectively inhibit scar proliferation.

A Three-Dimensional Approach To Male Chest Enhancement: A Surgical Algorithm Based On 300 Cases.

Gynecomastia is defined as a benign condition of the male caused by tissue overgrowth (Blau and Hazani in Plast Reconstruct Surg 135(2): 425-432, 2015). Its incidence ranges widely in the world population, ranging from 32 to 65% (Innocenti et al. in Ann Plast Surg 78(5):492-496, 2017). Pseudogynecomastia is a condition characterized by deposits of adipose tissue with alteration of the profile of the male thorax. It appears clinically similar to gynecomastia (Hoyos et al. in Plast Reconstr Surg 147:1072-1083, 2021). Several classification systems that characterize the severity of male breast hypertrophy have been described in the literature, and many surgical algorithms have been formulated for its treatment (Holzmer et al. in Plast Reconstruct Surg-Global Open 8:e3161, 2020). The purpose of this original article is to provide a comprehensive surgical algorithm for the management of male chest enhancement based on severity, as defined by the Moschella scale (Tambasco et al. in J Plast Reconstruct Aesthet Surg 90:99-100, 2024). A total of 300 patients treated for bilateral breast hypertrophy are included and reviewed in this retrospective study. Patients have been diversified according to the Moschella scale. For each grade up to grade III, two subgroups were distinguished: A) pinch test less than 0.7 cm and B) pinch test greater than 0.7 cm. For Grade IV, we distinguished: subgroup A) where the distance between the inframammary fold and the nipple was < 3 cm; and subgroup B) where the distance between the inframammary fold and the nipple was > 3 cm. We developed an algorithm, based on this experience, to help to choose the best surgical techniques to perform a three-dimensional result. All patients were treated using multiple surgical techniques. In all cases, we made a reduction in the hypertrophy of the chest, obtaining the three dimensionality. Associate techniques include ultrasound-assisted liposuction (UAL) and helium plasma radiofrequency technology (HPRF). A round block mastectomy (RBm) or skin-reducing mastectomy T inverted (SRM Tinv) is reserved only in limited cases.Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Case study- Jalaukavacharan-Leech Therapyin management of Vranagranthi (Keloid)

Keloid is a type of scar that results from the overgrowth of dense fibrous tissue which is usually develops after healing of a skin injury. In other words, it represents an abnormal scar formation. The tissue extends beyond the borders of the original wound and does not usually regress spontaneously. It causes cosmetic deformity, itching, pain, and stress ultimately resulting in compromised quality of life and diminished functional performance. The treatment of Keloid is often difficult because there is an associated high risk of recurrence. Vrana represents a vast part of Shalyatantra and the pathogenesis of Keloid is similar to Vrana granthi which has been explained as a growth of mass at the site of Vrana following dietetic complications or any physical irritation in a Vrana patient. Jalaukavacharana (leech therapy) is a parasurgical type of Raktamokshana and is considered as the most unique and effective method of bloodletting. Leeches are widely used in most disorders ranging from skin disease with evidence of successful results. In the present paper, an effort has been made to case of keloid that have been conducted in Ayurveda as para surgical procedure.