Virtual planning as a resource for correcting severe facial asymmetry ­ case report / Planejamento virtual como recurso para correção de assimetria facial severa ­ relato de caso

A hiperplasia hemimandibular é responsável por prejuízos estéticos, funcionais, motores e psicossociais. Com etiologia incerta, ocorre frente ao desequilíbrio de fatores regulatórios de crescimento presentes na camada cartilaginosa do côndilo. O relato objetiva descrever a tomada de decisões baseada em exames complementares específicos aliados à adequada intervenção cirúrgica da lesão. Paciente gênero feminino, 33 anos de idade, compareceu à clínica particular com queixa principal de "face assimétrica", foi requerido uma avaliação cintilográfica objetivando e confirmando a interrupção do crescimento condilar, descartando a hipótese de Osteocondroma e condilectomia. Após preparo ortodôntico prévio, os exames tomográficos foram utilizados na criação de um protótipo que foi impresso após a realização dos movimentos ósseos planejados. Mediante à reconstrução, foi concluído que a assimetria presente não seria totalmente corrigida somente através da intervenção ortognática, sendo necessária também uma osteotomia removendo parte da base do corpo e ângulo mandibular, através da confecção de um guia de corte, promovendo à reanatomização sem a necessidade de acesso extra oral submandibular, evitando uma cicatriz em face feminina. Paciente encontra-se em pós-operatório de 60 meses, sem queixas e satisfeita. Portanto, é evidenciado cada vez mais a influência positiva que o planejamento virtual pode trazer aos profissionais na otimização dos resultados cirúrgicos.

Hemimandibular hyperplasia is responsible for aesthetic, functional, motor, and psychosocial impairments. With an uncertain etiology, it occurs due to the imbalance of regulatory growth factors present in the cartilaginous layer of the condyle. The report aims to describe decision-making based on specific complementary exams combined with the appropriate surgical intervention for the condition. A 33-year-old female patient presented at a private clinic with the main complaint of "asymmetric face." A scintigraphic evaluation was requested to objectively confirm the interruption of condylar growth, ruling out the hypothesis of Osteochondroma and condylectomy. After prior orthodontic preparation, tomographic exams were used to create a prototype that was printed after planned bone movements. Through the reconstruction, it was concluded that the existing asymmetry would not be entirely corrected through orthognathic intervention alone, necessitating also an osteotomy to remove part of the base of the body and mandibular angle. This was done through the creation of a cutting guide, allowing for reanatomization without the need for submandibular extraoral access, thus avoiding a scar on the female face. The patient is 60 months postoperative, with no complaints and satisfied. Therefore, the increasingly positive influence of virtual planning on optimizing surgical outcomes for professionals is evident.

Intravascular delivery of an MK2 inhibitory peptide to prevent restenosis after angioplasty.

Peripheral artery disease is commonly treated with balloon angioplasty, a procedure involving minimally invasive, transluminal insertion of a catheter to the site of stenosis, where a balloon is inflated to open the blockage, restoring blood flow. However, peripheral angioplasty has a high rate of restenosis, limiting long-term patency. Therefore, angioplasty is sometimes paired with delivery of cytotoxic drugs like paclitaxel to reduce neointimal tissue formation. We pursue intravascular drug delivery strategies that target the underlying cause of restenosis - intimal hyperplasia resulting from stress-induced vascular smooth muscle cell switching from the healthy contractile into a pathological synthetic phenotype. We have established MAPKAP kinase 2 (MK2) as a driver of this phenotype switch and seek to establish convective and contact transfer (coated balloon) methods for MK2 inhibitory peptide delivery to sites of angioplasty. Using a flow loop bioreactor, we showed MK2 inhibition in ex vivo arteries suppresses smooth muscle cell phenotype switching while preserving vessel contractility. A rat carotid artery balloon injury model demonstrated inhibition of intimal hyperplasia following MK2i coated balloon treatment in vivo. These studies establish both convective and drug coated balloon strategies as promising approaches for intravascular delivery of MK2 inhibitory formulations to improve efficacy of balloon angioplasty.

TRPV4-ß-catenin axis is a novel therapeutic target for dry skin-induced chronic itch.

Dry skin induced chronic pruritus is an increasingly common and debilitating problem, especially in the elderly. Although keratinocytes play important roles in innate and adaptive immunity and keratinocyte proliferation is a key feature of dry skin induced chronic pruritus, the exact contribution of keratinocytes to the pathogenesis of dry skin induced chronic pruritus is poorly understood. In this study, we generated the acetone-ether-water induced dry skin model in mice and found that epidermal hyperplasia induced by this model is partly dependent on the ß-catenin signaling pathway. XAV939, an antagonist of ß-catenin signaling pathway, inhibited epidermal hyperplasia in dry skin model mice. Importantly, dry skin induced chronic pruritus also dramatically reduced in XAV939 treated mice. Moreover, acetone-ether-water treatment-induced epidermal hyperplasia and chronic itch were decreased in Trpv4-/- mice. In vitro, XAV939 inhibited hypo-osmotic stress induced proliferation of HaCaT cells, and hypo-osmotic stress induced proliferation of in HaCaT cells and primary cultured keratinocytes were also significantly reduced by blocking TRPV4 function. Finally, thymic stromal lymphopoietin release was examined both in vivo and in vitro, which was significantly inhibited by XAV939 treatment and Trpv4 deficiency, and anti-TSLP antibody treatment significantly decreased AEW-induced scratching behavior. Overall, our study revealed a unique ability of TRPV4 expressing keratinocytes in the skin, which critically mediated dry skin induced epidermal hyperplasia and chronic pruritus, thus provided novel insights into the development of therapies for chronic pruritus in the elderly.

GASTRIC POLYPOID HYPERPLASIA IN MORAY EELS (MURAENIDAE): EIGHT CASES.

Gastric and intestinal mucosal hyperplasia and polyps are identified as a cause of morbidity and mortality in moray eels. This report describes the clinical presentations, diagnostic procedures, and therapeutic interventions in eight moray eels diagnosed with gastric polypoid hyperplasia. All described cases were humanely euthanized or found deceased, and multifocal adenomatous hyperplasia and polyps extending from the gastric mucosal epithelium were identified in all cases. The moray eels diagnosed with adenomatous hyperplasia and polyps often exhibited anorexia, regurgitation, and occasional changes in buoyancy, and supportive care was unsuccessful in alleviating or resolving these signs.

Frontal Disconnection for Treating Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE) in the Frontal Lobe.

Malformation of cortical development is an important cause of drug-resistant epilepsy in young children. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) has been added to the last focal cortical dysplasia (FCD) classification and commonly involves the frontal lobe. The semiology at the onset of epilepsy is dominated by non-lateralizing infantile spasm; the boundaries of the malformation are usually difficult to determine by magnetic resonance imaging (MRI) and positron emission tomography (PET), and electroencephalography (EEG) findings are often widespread. Therefore, the traditional concept and strategy of preoperative evaluation to determine the extent of the epileptogenic zone by comprehensive anatomo-electro-clinical methods are difficult to implement. Frontal disconnection is an effective surgical method for the treatment of epilepsy, but there are few related reports. A total of 8 children with histo-pathologically confirmed MOGHE were retrospectively studied. MOGHE was located in the frontal lobe in all patients, and frontal disconnection was performed. The periinsular approach was used in the disconnective procedures, divided into several surgical steps: the partial inferior frontal gyrus resection, the frontobasal and intrafrontal disconnection, and the anterior corpus callosotomy. One patient presented with a short-term postoperative speech disorder, while another patient exhibited transient postoperative limb weakness. No long-term postoperative complications were observed. At 2 years after surgery, 75% of patients were seizure-free, with cognitive improvement in half of them. This finding suggested that frontal disconnection is an effective and safe surgical procedure for the treatment of MOGHE instead of extensive resection in the frontal lobe.

Conventional dendritic cells are more activated in the hyperplastic Thymus of myasthenia gravis patients.

INTRODUCTION: Dendritic cells (DCs) are crucial to form ectopic germinal centers (GCs) in the hyperplastic thymus (HT), which are typically found in anti-acetylcholine receptor autoantibody-positive myasthenia gravis (MG) patients. However, the characteristics of such DCs in the HT and their roles in thymic hyperplasia formation remain unclear. METHODS: We collected thymic tissue from MG patients and patients who underwent cardiac surgery. The tissues were cut into sections for immunohistochemistry and immunofluorescence or digested into a single cell suspension for flow cytometry. RESULTS: In addition to formation of ectopic GCs, we found that the proportion of the medulla in the thymic parenchyma was higher than that in the cortex (areacortex/areamedulla, 1.279 vs. 0.6576) in the HT of MG patients. The density of conventional dendritic cells (cDCs) in the HT was 131 ± 64.36 per mm2, whereas in normal thymic tissue, the density was 59.17 ± 22.54 per mm2. The more abundant cDCs expressed co-stimulatory molecules (CD80 and CD86) strongly. Moreover, the more abundant subset was mainly CD141+ DCs (cDC1s), accounting for an increase from 15% to 29%. However, these increased cDC1s appeared to be unrelated to Hassall's corpuscles and ectopic GCs. CONCLUSION: Thymic hyperplasia in MG patients is manifested as an increase in the proportion of the thymic medulla accompanied by increases in the density and functional activation as well as changes in the subset composition of cDCs.

New potential diagnostic markers for verrucous hyperplasia and verrucous carcinoma based on RNA-sequencing data.

Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma (SCC) characterized by its histological presentation as a low-grade tumor with no potential for metastasis, setting it apart from invasive SCC. However, distinguishing VC from its benign counterpart, verrucous hyperplasia (VH), is challenging due to their clinical and morphological similarities. Despite the importance of accurate diagnosis for determining treatment strategies, diagnosis of VH and VC relied only on lesion recurrence after resection. To address this challenge, we generated RNA profiling data from tissue samples of VH and VC patients to identify novel diagnostic markers. We analyzed differentially expressed (DE) mRNA and long non-coding RNA (lncRNA) in tissue samples from VH and VC patients. Additionally, ChIP-X Enrichment Analysis 3 (ChEA3) was conducted to identify the top five transcription factors potentially regulating the expression of DE mRNAs in VH and VC. Our analysis of mRNA and lncRNA expression profiles in VH and VC provides insights into the underlying molecular characteristics of these diseases and offers potential new diagnostic markers. The identification of specific DE genes and lncRNAs may enable clinicians to more accurately differentiate between VH and VC, leading to better treatment choices.

Papillary endothelial hyperplasia (Masson's tumor) of the breast: A diagnostic challenge.

Papillary endothelial hyperplasia (PEH) or Masson's tumor is a rare benign vascular tumor that usually appears in the soft tissues of the head and neck, trunk and extremities, being extremely rare in the breast. Its diagnosis can be a challenge, especially in the follow-up of patients with previous disease of breast carcinoma. We present the case of a 65-year-old patient, with a history of bilateral breast cancer and reconstruction with implants, who presented a Masson's tumor during follow-up. An ultrasound scan was performed, showing a well-circumscribed mass in the left breast, located in the posterior contour of the implant. Subsequently, magnetic resonance imaging (MR) depicted an enhancing tumor, without infiltration of adjacent structures. Finally, the definitive anatomopathological diagnosis was obtained after surgical excision.

[Long-term effect observation after 10 years of tonsillotomy （Histological analysis of one case of secondary operation）].

Objective:To investigate the long-term effect of partial tonsillectomy in children with tonsil hypertrophy. Methods:A total of 146 children with obstructive sleep apnea（OSA） who received surgical treatment for tonsil hyperplasia from January 2010 to January 2013 were selected and divided into the observation group（n=69） and the control group（n=77）. The observation group was received tonsillotomy（TT）, and the control group was received total tonsillectomy（TE）. Parental satisfaction and OSA quality of life questionnaire for children（OSA-18） were surveyed. Residual tonsil size was measured, and polysomnography（PSG） was monitored after 10 years. HE and immunohistochemical analysis were performed on tonsil tissues of one patient who performed a second operation after TT in 2017 year. Results:The results of questionnaire survey showed that the symptoms of respiratory obstruction were significantly improved in both groups, and the satisfaction of TT group was higher than that in the TE group. No increase in the number of respiratory tract infections was observed in all patients. In the TT group, nine cases（13.04%） had tonsil hyperplasia toⅡ°, and the remaining patients had tonsil hyperplasia to Ⅰ°. In addition, one case hadtonsil suppurative infection at the 14th month after surgery, and no recurrence or reoperation was found after treatment. There were seven cases in the TT group and eight cases in the TE group with occasional snoring and mouth breathing after surgery, but the PSG examination of the patients did not meet the diagnosis of OSA. The main causes were obesity and allergic rhinitis. Compared with the first operation, the cicatricial obstruction and infection of tonsil tissue in the second operation were not significantly changed, and the immunohistochemical results also demonstrated that the expression of CD20 was not changed, and the expression of CD3 was decreased. Conclusion:Both TT and TE can effectively improve the symptoms of OSA obstruction in children. TT has less trauma, less postoperative pain, faster recovery and lower rate of hyperplasia, which can be used as one of the main methods for the treatment of tonsil hypertrophy in children.

PTPN14 aggravates neointimal hyperplasia via boosting PDGFRß signaling in smooth muscle cells.

Smooth muscle cell (SMC) phenotypic modulation, primarily driven by PDGFRß signaling, is implicated in occlusive cardiovascular diseases. However, the promotive and restrictive regulation mechanism of PDGFRß and the role of protein tyrosine phosphatase non-receptor type 14 (PTPN14) in neointimal hyperplasia remain unclear. Our study observes a marked upregulation of PTPN14 in SMCs during neointimal hyperplasia. PTPN14 overexpression exacerbates neointimal hyperplasia in a phosphatase activity-dependent manner, while SMC-specific deficiency of PTPN14 mitigates this process in mice. RNA-seq indicates that PTPN14 deficiency inhibits PDGFRß signaling-induced SMC phenotypic modulation. Moreover, PTPN14 interacts with intracellular region of PDGFRß and mediates its dephosphorylation on Y692 site. Phosphorylation of PDGFRßY692 negatively regulates PDGFRß signaling activation. The levels of both PTPN14 and phospho-PDGFRßY692 are correlated with the degree of stenosis in human coronary arteries. Our findings suggest that PTPN14 serves as a critical modulator of SMCs, promoting neointimal hyperplasia. PDGFRßY692, dephosphorylated by PTPN14, acts as a self-inhibitory site for controlling PDGFRß activation.

Preoperative diagnosis of cervical cystic lesions using magnetic resonance imaging: a retrospective study.

BACKGROUND: We conducted this study to clarify the magnetic resonance imaging (MRI) characteristics of lobular endocervical glandular hyperplasia (LEGH) and Nabothian cysts. METHODS: This study included 48 patients who underwent hysterectomy at our institution between 2016 and 2020 for suspected LEGH. Histopathological studies confirmed the presence of 25 Nabothian cysts and 23 cases of LEGH. We retrospectively analyzed five characteristic MRI findings: (1) located at the upper cervical canal, (2) positioned within the cervical stroma, (3) not circumscribing the cervical canal, (4) low- to iso-intensity on T1-weighted images (T1WI), and (5) "cosmos" or "microcystic" pattern. We compared the diagnostic accuracy of these findings for LEGH and Nabothian cysts using sensitivity, specificity, and predictive values. Combinations of findings were also calculated. RESULTS: The characteristics "cosmos" or "microcystic" pattern, lesion not circumscribing the cervical canal, and low/iso-intensity on T1WI had a sensitivity and specificity greater than 50%. The sensitivity was 73.9% and specificity 84.0% when a combination of "cosmos" or "microcystic" pattern and lesion not circumscribing the cervical canal was present. CONCLUSION: The coexistence of a "cosmos" or "microcystic" pattern and not circumscribing the cervical canal was the most characteristic finding that distinguished LEGH from Nabothian cysts. When neither of these findings is present, Nabothian cyst can be suspected.

Does dexamethasone therapy affect intimal hyperplasia after injury in rat abdominal aorta models?

BACKGROUND: Intimal hyperplasia is a normal adaptive feature of arteries in response to injuries, which include invasive vascular interventions. Its development limits the long-term success of bypass grafts. Various pharmacological agents have been successfully employed in experimental models to reduce the degree of intimal hyperplasia. In our study, we investigated the efficacy of dexamethasone in reducing intimal hyperplasia in rat abdominal aortas after partial transection and primary repair. METHODS: In this study, 20 Wistar Albino rats were randomly selected and divided into four groups to compare the effects of low- and high-dose dexamethasone on intima and media thickness compared to the control. Group A (n=5) was the control group, where only skin incision and laparotomy were performed. For Group B (n=5), a median laparotomy was performed, the abdominal aorta was partially transected, and repaired with an 8.0 prolene suture. Doses of 0.1 mg/kg and 0.2 mg/kg dexamethasone were administered in Group C (n=5) and Group D (n=5), respectively. After two weeks, all rats were euthanized, and the repaired abdominal aortas were excised and examined histopathologically. Intima and media thicknesses were measured using the 'Olympus AnalySIS 5' program (Olympus Corporation, Japan) after digital photos were taken. RESULTS: Based on the measurements, we demonstrated that after transection and repair of the abdominal aorta, the intima/media ratio was not significantly different between the low-dose dexamethasone and non-dexamethasone groups. The intima/media ratio was significantly lower in the high-dose dexamethasone group than in the non-dexamethasone and low-dose dexamethasone groups. CONCLUSION: After vascular interventions, dexamethasone treatment may reduce intimal hyperplasia and increase patency by providing vascular remodeling.

Regulation of ClC-K/barttin by endocytosis influences distal convoluted tubule hyperplasia.

ClC-K/barttin channels are involved in the transepithelial transport of chloride in the kidney and inner ear. Their physiological role is crucial in humans because mutations in CLCNKB or BSND, encoding ClC-Kb and barttin, cause Bartter's syndrome types III and IV, respectively. In vitro experiments have shown that an amino acid change in a proline-tyrosine motif in the C-terminus of barttin stimulates ClC-K currents. The molecular mechanism of this enhancement and whether this potentiation has any in vivo relevance remains unknown. We performed electrophysiological and biochemical experiments in Xenopus oocytes and kidney cells co-expressing ClC-K and barttin constructs. We demonstrated that barttin possesses a YxxØ motif and, when mutated, increases ClC-K plasma membrane stability, resulting in larger currents. To address the impact of mutating this motif in kidney physiology, we generated a knock-in mouse. Comparing wild-type (WT) and knock-in mice under a standard diet, we could not observe any difference in ClC-K and barttin protein levels or localization, either in urinary or plasma parameters. However, under a high-sodium low-potassium diet, known to induce hyperplasia of distal convoluted tubules, knock-in mice exhibit reduced hyperplasia compared to WT mice. In summary, our in vitro and in vivo studies demonstrate that the previously identified PY motif is indeed an endocytic YxxØ motif in which mutations cause a gain of function of the channel. KEY POINTS: It is revealed by mutagenesis and functional experiments that a previously identified proline-tyrosine motif regulating ClC-K plasma membrane levels is indeed an endocytic YxxØ motif. Biochemical characterization of mutants in the YxxØ motif in Xenopus oocytes and human embryonic kidney cells indicates that mutants showed increased plasma membrane levels as a result of an increased stability, resulting in higher function of ClC-K channels. Mutation of this motif does not affect barttin protein expression and subcellular localization in vivo. Knock-in mice with a mutation in this motif, under conditions of a high-sodium low-potassium diet, exhibit less hyperplasia in the distal convoluted tubule than wild-type animals, indicating a gain of function of the channel in vivo.

Strategies for arterial graft optimization at the single-cell level.

Common arterial grafts used in coronary artery bypass grafting include internal thoracic artery (ITA), radial artery (RA) and right gastroepiploic artery (RGA) grafts; of these, the ITA has the best clinical outcome. Here, by analyzing the single-cell transcriptome of different arterial grafts, we suggest optimization strategies for the RA and RGA based on the ITA as a reference. Compared with the ITA, the RA had more lipid-handling-related CD36+ endothelial cells. Vascular smooth muscle cells from the RGA were more susceptible to spasm, followed by those from the RA; comparison with the ITA suggested that potassium channel openers may counteract vasospasm. Fibroblasts from the RA and RGA highly expressed GDF10 and CREB5, respectively; both GDF10 and CREB5 are associated with extracellular matrix deposition. Cell-cell communication analysis revealed high levels of macrophage migration inhibitory factor signaling in the RA. Administration of macrophage migration inhibitory factor inhibitor to mice with partial carotid artery ligation blocked neointimal hyperplasia induced by disturbed flow. Modulation of identified targets may have protective effects on arterial grafts.

Participation of ventricular trabeculae in neonatal cardiac regeneration leads to ectopic recruitment of Purkinje-like cells.

Unlike adult mammals, newborn mice can regenerate a functional heart after myocardial infarction; however, the precise origin of the newly formed cardiomyocytes and whether the distal part of the conduction system (the Purkinje fiber (PF) network) is properly formed in regenerated hearts remains unclear. PFs, as well as subendocardial contractile cardiomyocytes, are derived from trabeculae, transient myocardial ridges on the inner ventricular surface. Here, using connexin 40-driven genetic tracing, we uncover a substantial participation of the trabecular lineage in myocardial regeneration through dedifferentiation and proliferation. Concomitantly, regeneration disrupted PF network maturation, resulting in permanent PF hyperplasia and impaired ventricular conduction. Proliferation assays, genetic impairment of PF recruitment, lineage tracing and clonal analysis revealed that PF network hyperplasia results from excessive recruitment of PFs due to increased trabecular fate plasticity. These data indicate that PF network hyperplasia is a consequence of trabeculae participation in myocardial regeneration.

Distinct gut microbiomes in Thai patients with colorectal polyps.

BACKGROUND: Colorectal polyps that develop via the conventional adenoma-carcinoma sequence [e.g., tubular adenoma (TA)] often progress to malignancy and are closely associated with changes in the composition of the gut microbiome. There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway, such as hyperplastic polyps (HP). Exploration of microbiome alterations associated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis. AIM: To investigate gut microbiome signatures, microbial associations, and microbial functions in HP and TA patients. METHODS: Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps [control group (CT), n = 40], patients with HP (n = 52), and patients with TA (n = 60). Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA. Analytical techniques in this study included differential abundance analysis, co-occurrence network analysis, and differential pathway analysis. RESULTS: Colorectal cancer (CRC)-associated bacteria, including Streptococcus gallolyticus (S. gallolyticus), Bacteroides fragilis, and Clostridium symbiosum, were identified as characteristic microbial species in TA patients. Mediterraneibacter gnavus, associated with dysbiosis and gastrointestinal diseases, was significantly differentially abundant in the HP and TA groups. Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively, whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis (e.g., mevalonate); S. gallolyticus was a major contributor. Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients, whereas TA patients exhibited co-occurrence of CRC-associated bacteria. Furthermore, the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients. CONCLUSION: This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development, providing insights concerning the roles of microbial species, functional pathways, and microbial interactions in colorectal carcinogenesis.

It Is Time to Get to Know the Neuroendocrine Cell Hyperplasia of Infancy.

In the two decades that have elapsed since the initial proposal of neuroendocrine cell hyperplasia of infancy (NEHI), several hundred cases have been reported and researched. However, a comprehensive analysis of research progress remains absent from the literature. The present article endeavors to evaluate the current progress of NEHI research and offer a reference for the clinical management of this condition.