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1.
Semina cienc. biol. saude ; 45(2): 211-222, jul./dez. 2024. tab
Article in Portuguese | LILACS | ID: biblio-1554836

ABSTRACT

As queimaduras provocam efeitos físicos e psicológicos devastadores nos indivíduos, sobretudo em crianças e adolescentes, e podem modificar a qualidade de vida da pessoa. O objetivo foi analisar o impacto das cicatrizes por queimaduras em crianças menores de oito anos na interação com amigos, família e escola, na perspectiva dos pais. Estudo quantitativo de corte transversal realizado com os pais de crianças <8 anos de idade, vítimas de queimaduras e internadas em um Centro de Tratamento de Queimados no norte do Paraná e acompanhadas ambulatorialmente, de 2017 a 2020. A coleta de dados ocorreu por meio de dois instrumentos: caracterização sociodemográfica e clínica; e Brisbane Burn Scar Impact Profile. Realizou-se análise descritiva e teste Qui-quadrado utilizando-se o SPSS®. Participaram 34 pais cujas crianças sofreram queimaduras, sendo 52,9% de 1 a 3 anos de idade, 58,8% sexo masculino, 82,2% por agente etiológico térmico e a internação foi de 73,5% devido à Superfície Corpórea Queimada ≤20%. Após a alta os pais identificaram que as cicatrizes de queimaduras tinham "um pouco" e "pouco" impacto nas cicatrizes nas relações de amizade e na interação social. Para os pais, prevaleceu a resposta "nada" de impacto, seguido por "um pouco" e "muito" na escola, nas brincadeiras, nos jogos e nas atividades diárias. Quanto às reações emocionais e ao humor, a maior parte dos pais considerou "nada". Nesse sentido, os pais responderam às questões quanto à própria percepção sobre as atividades diárias do seu filho e, em geral, a cicatriz de queimadura não impactou na qualidade de vida da criança.


Burns cause devastating physical and psychological effects on individuals, especially children and adolescents, and can change a person's quality of life. The objective was to analyze the impact of burn scars in children under eight years of age in the interaction with friends, family and school, from the parents' perspective. Quantitative cross-sectional study carried out with the parents of children <8 years old who were victims of burns and admitted to a Burn Treatment Center in northern Paraná and monitored on an outpatient basis, from 2017 to 2020. Data collection occurred using two instruments: sociodemographic and clinical characterization; Brisbane Burn Scar Impact Profile. Descriptive analysis and Chi-square test were performed using SPSS®. 34 parents participated whose children suffered burns, 52.9% aged 1 to 3 years old, 58.8% male, 82.2% due to thermal etiological agent and 73.5% hospitalization was due to Burned Body Surface ≤ 20%. After discharge, the parents identified that the burn scars had "a little" and "little" impact on the scars in friendship relationships and social interaction. For parents, the answer "nothing" of impact prevailed, followed by "a little" and "a lot" in school, play, games and daily activities. As for emotional reactions and mood, most parents considered "nothing" that impacted the child with burn scars. In this sense, parents answered questions regarding their own perception of their child's daily activities and, in general, the burn scar did not impact the child's quality of life.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool
2.
J Reprod Immunol ; 166: 104324, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39226672

ABSTRACT

PURPOSE: To investigate the risk factors for Caesarean Scar Diverticulum (CSD) with Chronic Endometritis (CE) and the correlation between CE and clinical symptoms of CSD. METHODS: The frequency of CE in 44 patients with CSD who underwent surgical treatment and 20 control women who underwent total hysterectomy was assessed and the clinical symptoms in the presence and absence of CE were compared. In accordance with the presence of one or more CD138-positive plasma cells per high-power field, CE was classified as mild or severe group. RESULTS: According to multivariate analysis, the presence of mild CE (OR 8.963, 95 % CI 2.177-36.907, p = 0.002) or severe CE (OR 21.773, 95 % CI 2.285-207.419, p = 0.007) was significantly associated with CSD. Mild CE (OR 12.390, 95 % CI 1.158-132.511, p = 0.037) or severe CE (OR 22.463, 95 % CI 1.657-304.541, P = 0.019) or depth of diverticulum (OR 1.294, 95 % CI 1.003-1.668, p = 0.047) was associated with prolonged menstruation in patients with CSD. The degree of CE in patients with CSD was positively correlated with the days of prolonged menstruation (r = 0.552, p < 0.001) and negatively correlated with haemoglobin level (r = -0.408, p = 0.038). CONCLUSIONS: CE was associated with CSD and its clinical symptoms, including prolonged menstruation and decreased haemoglobin. The severity of clinical symptoms of CSD is associated with endometrial inflammation.

3.
J Voice ; 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39227273

ABSTRACT

OBJECTIVE: Sex differences in response to trauma and physiologic stressors have been identified in numerous organ systems but have not yet been defined in the larynx. The objective of this study was to develop an endoscopic vocal fold injury model in rabbits and to compare structural and functional outcomes between male and female subjects. STUDY DESIGN: Basic science study. METHODS: Two male and two female rabbits underwent unilateral endoscopic cordectomy. Animals were intubated with a size 3-0 neonatal endotracheal tube, and laryngoscopy was performed with a 4 mm Hopkins rod telescope. While visualizing, a 2 mm cupped forceps grasped and resected the mid-membranous portion of the right true vocal fold. Larynges were then harvested after 8weeks. Excised larynx phonation with high-speed videography and kymography was used to assess vibrational quality. Tissue elastic (Young's) modulus was measured by indentation. RESULTS: Injured larynges phonated with fundamental frequencies between 237-415 Hz. In both males and females, the scarred vocal fold exhibited an increased Young's modulus compared to the contralateral nonoperated vocal fold. There were no notable differences in glottal closure pattern or vocal fold oscillation symmetry between sexes. CONCLUSION: We have demonstrated a model for vocal fold scarring in rabbits. Vibrational and structural outcomes were similar between the examined male and female larynges.

4.
Aesthetic Plast Surg ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39227470

ABSTRACT

BACKGROUND: Although deep inferior epigastric perforator (DIEP) flap breast reconstruction is the most widely used technique for autologous breast reconstruction, this technique leads to large scars in visible areas on breast and abdomen. So far, limited studies have thoroughly addressed the impact of breast and abdominal scars on satisfaction and Health-related Quality of Life (HR-QoL). OBJECTIVES: This research aimed to determine whether women with no/minor scar symptoms after undergoing DIEP-flap breast reconstruction differ in satisfaction and perceived HR-QoL from women with symptomatic scars. MATERIALS AND METHODS: In this cross-sectional survey study, women who had previously undergone DIEP-flap breast reconstruction completed an online survey. Patient-reported scar quality was assessed with the Patient and Observer Scar Assessment Scale (POSAS), and satisfaction and HR-QoL with BREAST-Q. Independent-samples t-tests were conducted to compare BREAST-Q scores between women with no/minor scar symptoms (POSAS overall opinion score 1-3) and women with symptomatic scars (POSAS overall opinion score 4-10). RESULTS: A total of 248 women completed the survey. Women with scar symptoms had significantly worse BREAST-Q scores on 'Satisfaction with breasts,' 'Physical well-being,' 'Psychosocial well-being' and, 'Sexual well-being' compared to women with no/minor scar symptoms (p ≤ 0.001). CONCLUSION: After DIEP-flap breast reconstructions, women with symptomatic breast and abdominal scars had a clinically relevant and statistically significant lower degree of satisfaction and HR-QoL compared to women who had no/minor scar symptoms. We therefore recommend to explicitly and repeatedly address inevitability of visible scars after DIEP-flap breast reconstruction, aiming to improve preoperative patient selection and post-operative expectation management. 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 .

6.
Mol Med ; 30(1): 134, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39223490

ABSTRACT

BACKGROUND: Epidermal remodeling and hypertrophy are hallmarks of skin fibrotic disorders, and keratinocyte to mesenchymal (EMT)-like transformations drive epidermis alteration in skin fibrosis such as keloids and hypertrophic scars (HTS). While phosphodiesterase 4 (PDE4) inhibitors have shown effectiveness in various fibrotic disorders, their role in skin fibrosis is not fully understood. This study aimed to explore the specific role of PDE4B in epidermal remodeling and hypertrophy seen in skin fibrosis. METHODS: In vitro experiments examined the effects of inhibiting PDE4A-D (with Roflumilast) or PDE4B (with siRNA) on TGFß1-induced EMT differentiation and dedifferentiation in human 3D epidermis. In vivo studies investigated the impact of PDE4 inhibition on HOCl-induced skin fibrosis and epidermal hypertrophy in mice, employing both preventive and therapeutic approaches. RESULTS: The study found increased levels of PDE4B (mRNA, protein) in keloids > HTS compared to healthy epidermis, as well as in TGFß-stimulated 3D epidermis. Keloids and HTS epidermis exhibited elevated levels of collagen Iα1, fibronectin, αSMA, N-cadherin, and NOX4 mRNA, along with decreased levels of E-cadherin and ZO-1, confirming an EMT process. Inhibition of both PDE4A-D and PDE4B prevented TGFß1-induced Smad3 and ERK1/2 phosphorylation and mesenchymal differentiation in vitro. PDE4A-D inhibition also promoted mesenchymal dedifferentiation and reduced TGFß1-induced ROS and keratinocyte senescence by rescuing PPM1A, a Smad3 phosphatase. In vivo, PDE4 inhibition mitigated HOCl-induced epidermal hypertrophy in mice in both preventive and therapeutic settings. CONCLUSIONS: Overall, the study supports the potential of PDE4 inhibitors, particularly PDE4B, in treating skin fibrosis, including keloids and HTS, shedding light on their functional role in this condition.


Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 4 , Fibrosis , Keloid , Keratinocytes , Phosphodiesterase 4 Inhibitors , Humans , Keloid/metabolism , Keloid/pathology , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 4/genetics , Keratinocytes/metabolism , Keratinocytes/drug effects , Phosphodiesterase 4 Inhibitors/pharmacology , Animals , Mice , Epidermis/metabolism , Epidermis/pathology , Transforming Growth Factor beta1/metabolism , Epithelial-Mesenchymal Transition/drug effects , Cell Differentiation/drug effects , Male
7.
Article in English | MEDLINE | ID: mdl-39244729

ABSTRACT

OBJECTIVE: The aim of the present study was to explore the relationship between the size of cesarean scar diverticulum (CSD) measured on preoperative magnetic resonance imaging (MRI) and adverse events during dilatation and curettage (D&C) procedure in patients with cesarean scar pregnancy (CSP). METHODS: The MRI of 197 CSP patients from October 2019 to August 2023 were retrospectively reviewed. The volume, area, and depth of CSD, residual myometrium thickness (RMT), and gestational sac diameter were recorded and tested for correlation with intraoperative estimated blood loss (EBL), and operation time and for any association with the intraoperative adverse events (intraoperative massive hemorrhage [39 cases] and D&C procedure failure [15 cases]). The Spearman test was used to characterize the correlation between the five MRI variables and both the EBL and operation time. The correlation between the five MRI variables and intraoperative adverse events was evaluated with student's t test and Mann-Whitney U test. Diagnostic power of the MRI variables was evaluated by the area under receiver operating characteristic curve (AUC). RESULTS: The volume, area, and depth of CSD and gestational sac diameter were positively correlated with both EBL and operation time, with the CSD volume having the highest correlation with them (r = 0.543 and 0.461, respectively). Conversely, the RMT displayed a negative correlation with the EBL and operation time. All five MRI variables were significantly associated with both intraoperative massive hemorrhage and D&C failure (all P < 0.001). The CSD volume demonstrated the highest AUC for diagnosing intraoperative massive hemorrhage and D&C failure at 0.893 (95% CI: 0.82-0.92) and 0.901 (95% CI: 0.85-0.94), respectively. The optimal cutoff values for CSD volume in predicting massive hemorrhage and D&C failure were determined to be 5.41 and 8.92 cm3, respectively, with corresponding sensitivities/specificities of 92.31/74.68 and 93.33/82.42, respectively. CONCLUSION: Quantifying the size of CSD based on preoperative MRI could aid in evaluating risk during D&C in CSP patients, with CSD volume possessing higher diagnostic efficacy than the other four MRI indicators.

8.
JACC Adv ; 3(10): 101214, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39246577

ABSTRACT

Most acquired and inherited cardiomyopathies are characterized by regional left ventricular involvement and nonischemic myocardial scars, often with a disease-specific pattern. Irrespective of the etiology and pathophysiological mechanisms, myocardial disorders are invariably associated with cardiac fibrosis, which contributes to dysfunction and electrical instability. Accordingly, cardiac magnetic resonance plays a central role in the diagnostic work-up and prognostic risk stratification of cardiomyopathies, particularly with the increasing correlation between genetic background and specific disease phenotype. Starting from pattern and distribution of myocardial fibrosis at cardiac magnetic resonance, we provide a practical regional atlas of nonischemic myocardial scar to guide the diagnostic approach to nonischemic cardiomyopathies.

9.
Aesthetic Plast Surg ; 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39218835

ABSTRACT

BACKGROUND: Botulinum toxin type A (BTXA) can improve wound healing and reduce scar formation; however, the exact dose required to prevent postoperative scarring across various anatomical sites remains unclear. This study aimed to investigate the effectiveness and optimal concentrations of BTXA for preventing postoperative scarring across various common surgical sites throughout the body. METHODS: In this prospective randomized controlled trial, 46 patients with benign skin tumors received injections of 1, 2.5, or 5 U/0.1 mL of BTXA or 0.9% saline immediately following surgical tumor excision on both sides of the incisions. Follow-ups were conducted at 7 days, 15 days, and 1, 3, and 6 months postoperatively. Patient-reported adverse events and standardized digital photographs were collected. Scar formation was assessed using the modified Stony Brook Scar Evaluation Scale (mSBSES). RESULTS: All 46 patients completed the trial without severe complications. The mSBSES scores were higher in the experimental groups at all follow-ups. The 5 U/0.1 mL BTXA dose group demonstrated optimal scar prevention at all high-risk sites for scar hyperplasia. No significant difference was observed between the 2.5 U/0.1 mL and 5 U/0.1 mL doses for intermediate-risk sites, while 1 U/0.1 mL dose was sufficient for low-risk sites. Overall, 86.5% of patients were satisfied with their treatments, with 16.3% being very satisfied. CONCLUSIONS: Early postoperative BTXA injection can reduce or prevent hypertrophic scarring, with optimal doses ranging from 1 to 5 U/0.1 mL depending on the surgical site, supporting broader clinical application of BTXA. The effectiveness of different concentrations of botulinum toxin type A (BTXA) in preventing postoperative scarring was compared, expanding the scope of previous research, which focused only on the head, face, and neck regions, to include the trunk and extremity areas. Different optimal injection strategies were determined based on different surgical sites and their risks of developing hypertrophic scars. The study demonstrates that BTXA not only reduces scar formation but also enhances patient satisfaction and reduces postoperative itching and pain, contributing to overall better postoperative outcomes. By establishing the efficacy and optimal dosing of BTXA for various surgical sites, this research supports the potential for broader clinical application of BTXA in aesthetic and reconstructive surgeries. LEVEL OF EVIDENCE I: 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 .

10.
Am J Reprod Immunol ; 92(3): e13924, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39221973

ABSTRACT

PROBLEM: Cesarean scar pregnancy (CSP) is characterized by a gestational sac fully or partially implanted in the scar from a previous cesarean section. Systemic immune-inflammation indices (SIIs) have recently been discussed as additional diagnostic markers in placenta accreta and preeclampsia. CSP shares a similar pathogenesis with these diseases, suggesting that assessing the SIIs and neutrophil-to-lymphocyte ratio (NLR) could enhance additional predictability in diagnosing CSP. METHOD OF STUDY: In this study, we analyzed the complete blood counts between 264 women who were confirmed with CSP by ultrasound and 295 women who underwent elective termination. RESULTS: The mean counts of total white cells and neutrophils were significantly higher, whereas the counts of monocytes, lymphocytes, and platelets were significantly lower in the CSP group compared to the control group (p < 0.001). Additionally, the SII, systemic inflammation response index (SIRI), or NLR was significantly higher in the CSP group compared to the control group (p < 0.0001). Given the limited effect of SII and SIRI on the increased risk of developing CSP, the optimal cut-off value for NLR in predicting CSP was 2.87 (area under the curve [AUC] 0.656, 68% sensitivity). The optimal cut-off value for NLR in predicting type 2 CSP was 2.91 (AUC 0.690, 71% sensitivity). CONCLUSIONS: Although ultrasound or magnetic resonance imaging images are a gold standard for visualizing the gestational sac's location in the diagnosis of CSP, assessing peripheral blood tests is cost-effective, and NLR may provide additional diagnosis value for CSP.


Subject(s)
Biomarkers , Cesarean Section , Cicatrix , Inflammation , Pregnancy, Ectopic , Humans , Female , Pregnancy , Cicatrix/immunology , Adult , Inflammation/immunology , Biomarkers/blood , Pregnancy, Ectopic/diagnosis , Pregnancy, Ectopic/immunology , Pregnancy, Ectopic/blood , Neutrophils/immunology , Lymphocytes/immunology
11.
Cureus ; 16(8): e66223, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39238696

ABSTRACT

We depict a unique case of a 39-year-old woman who presented to the emergency department with complaints of right upper quadrant pain. Work-up and a computed tomography (CT) scan revealed acute cholecystitis and the patient underwent laparoscopic cholecystectomy without complication. At this time, an incidental mass was discovered in the subcutaneous fat adjacent to the abdominal wall. The patient returned six months later with progressive, cyclic abdominal pain since her last hospital admission. Initial admission lab work was within normal limits and a urine pregnancy test was negative. Physical exam revealed tenderness around her previous cesarean section scar. Repeat CT revealed an enlarging, spiculated mass adherent to the abdominal wall. After imaging confirmation, the patient underwent complete open surgical excision for the removal of the mass. Post-surgical biopsy confirmed endometrial gland and stroma consistent with abdominal wall endometrioma. The patient was discharged with adjuvant therapy and recommended follow-up with the surgeon and her obstetrician-gynecologist. The radiological diagnosis, guidelines, and decision-making for initiating interventional treatment are discussed in this report. Our purpose in documenting this case is to present a rare diagnosis of an atypical location for an endometrioma on the abdominal wall, in a patient with prior cesarean delivery. Although this patient was treated with open excision, different interventional radiology treatments from radiofrequency ablation and focused ultrasound were discussed. In doing so, we hope to contribute to the systematic literature review on surgical excision as a treatment option for Pfannenstiel incision endometrioma.

12.
Europace ; 26(9)2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39230049

ABSTRACT

AIMS: Atrial fibrosis and autonomic remodelling are proposed pathophysiological mechanisms in atrial fibrillation (AF). Their impact on conduction velocity (CV) dynamics and wavefront propagation was evaluated. METHODS AND RESULTS: Local activation times (LATs), voltage, and geometry data were obtained from patients undergoing ablation for persistent AF. LATs were obtained at three pacing intervals (PIs) in sinus rhythm (SR). LATs were used to determine CV dynamics and their relationship to local voltage amplitude. The impact of autonomic modulation- pharmacologically and with ganglionated plexi (GP) stimulation, on CV dynamics, wavefront propagation, and pivot points (change in wavefront propagation of ≥90°) was determined in SR. Fifty-four patients were included. Voltage impacted CV dynamics whereby at non-low voltage zones (LVZs) (≥0.5 mV) the CV restitution curves are steeper [0.03 ± 0.03 m/s ΔCV PI 600-400 ms (PI1), 0.54 ± 0.09 m/s ΔCV PI 400-250 ms (PI2)], broader at LVZ (0.2-0.49 mV) (0.17 ± 0.09 m/s ΔCV PI1, 0.25 ± 0.11 m/s ΔCV PI2), and flat at very LVZ (<0.2 mV) (0.03 ± 0.01 m/s ΔCV PI1, 0.04 ± 0.02 m/s ΔCV PI2). Atropine did not change CV dynamics, while isoprenaline and GP stimulation resulted in greater CV slowing with rate. Isoprenaline (2.7 ± 1.1 increase/patient) and GP stimulation (2.8 ± 1.3 increase/patient) promoted CV heterogeneity, i.e. rate-dependent CV (RDCV) slowing sites. Most pivot points co-located to RDCV slowing sites (80.2%). Isoprenaline (1.3 ± 1.1 pivot increase/patient) and GP stimulation (1.5 ± 1.1 increase/patient) also enhanced the number of pivot points identified. CONCLUSION: Atrial CV dynamics is affected by fibrosis burden and influenced by autonomic modulation which enhances CV heterogeneity and distribution of pivot points. This study provides further insight into the impact of autonomic remodelling in AF.


Subject(s)
Atrial Fibrillation , Fibrosis , Heart Atria , Humans , Female , Male , Atrial Fibrillation/physiopathology , Atrial Fibrillation/surgery , Middle Aged , Heart Atria/physiopathology , Heart Atria/innervation , Aged , Action Potentials , Catheter Ablation , Atrial Remodeling , Heart Rate , Electrophysiologic Techniques, Cardiac , Autonomic Nervous System/physiopathology , Atrial Function, Left , Isoproterenol/pharmacology , Atropine/pharmacology , Time Factors , Heart Conduction System/physiopathology , Treatment Outcome
13.
J Invest Dermatol ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39236902

ABSTRACT

Post-natal cutaneous wound healing is characterized by development of collagen-rich scar lacking the architecture and functional integrity of unwounded tissue. Directing cell behaviors to efficiently heal wounds while minimizing scar formation remains a major wound management goal. Herein, we demonstrate type III collagen (Col3) as a critical regulator of re-epithelialization and scar formation during healing of Col3-enriched, regenerative (Acomys), scar-permissive (CD-1 Mus and wild-type Col3B6/B6 mice), and Col3-deficient, scar-promoting (Col3F/F, a murine conditional knockdown model) cutaneous wound models. We define a scar-permissive fibrillar collagen architecture signature characterized by elongated and anisotropically-aligned collagen fibers that is dose-dependently suppressed by Col3. Further, loss of Col3 alters how cells interpret their microenvironment - their mechanoperception - such that Col3-deficient cells display mechanically-active phenotypes in the absence of increased microenvironmental stiffness via upregulation and engagement of the profibrotic integrin α11. Further understanding Col3's role in regulating matrix architecture and mechanoresponses may inform clinical strategies that harness pro-regenerative mechanisms.

14.
Clin Transl Med ; 14(9): e70016, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39233335

ABSTRACT

BACKGROUND: Elevated extracellular matrix (ECM) accumulation is a major contributing factor to the pathogenesis of fibrotic diseases. Recent studies have indicated that N6-methyladenosine (m6A) RNA modification plays a pivotal role in modulating RNA stability and contribute to the initiation of various pathological conditions. Howbeit, the precise mechanism by which m6A influences ECM deposition remains unclear. METHODS: In this study, we used hypertrophic scars (HTSs) as a paradigm to investigate ECM-related diseases. We focused on the role of ALKBH5-mediated m6A demethylation within the pathological progression of HTSs and examined its correlation with clinical stages. The effects of ALKBH5 ablation on ECM components were studied both in vivo and in vitro. Downstream targets of ALKBH5, along with their underlying mechanisms, were identified using integrated high-throughput analysis, RNA-binding protein immunoprecipitation and RNA pull-down assays. Furthermore, the therapeutic potential of exogenous ALKBH5 overexpression was evaluated in fibrotic scar models. RESULTS: ALKBH5 was decreased in fibroblasts derived from HTS lesions and was negatively correlated with their clinical stages. Importantly, ablation of ALKBH5 promoted the expression of COL3A1, COL1A1, and ELN, leading to pathological deposition and reconstruction of the ECM both in vivo and in vitro. From a therapeutic perspective, the exogenous overexpression of ALKBH5 significantly inhibited abnormal collagen deposition in fibrotic scar models. As determined by integrated high-throughput analysis, key ECM components including COL3A1, COL1A1, and ELN are direct downstream targets of ALKBH5. By means of its mechanism, ALKBH5 inhibits the expression of COL3A1, COL1A1, and ELN by removing m6A from mRNAs, thereby decreasing their stability in a YTHDF1-dependent manner. CONCLUSIONS: Our study identified ALKBH5 as an endogenous suppressor of pathological ECM deposition, contributing to the development of a reprogrammed m6A-targeted therapy for HTSs.


Subject(s)
AlkB Homolog 5, RNA Demethylase , Extracellular Matrix , Fibrosis , AlkB Homolog 5, RNA Demethylase/metabolism , AlkB Homolog 5, RNA Demethylase/genetics , Extracellular Matrix/metabolism , Fibrosis/metabolism , Humans , Mice , Animals , Demethylation , Collagen Type III/metabolism , Collagen Type III/genetics , Collagen Type I/metabolism , Collagen Type I/genetics , Adenosine/analogs & derivatives , Adenosine/metabolism , Adenosine/genetics , Male , Collagen Type I, alpha 1 Chain/genetics , Collagen Type I, alpha 1 Chain/metabolism , Fibroblasts/metabolism
15.
Cureus ; 16(8): e66182, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39233982

ABSTRACT

Isthmocele is a myometrial defect in the uterine isthmus, often resulting from previous caesarean sections. With rising cesarean rates globally, including a significant increase in India, the prevalence of isthmocele has become a noteworthy clinical concern. Isthmocele can lead to symptoms such as abnormal uterine bleeding, dysmenorrhea, and secondary infertility, often detected through transvaginal ultrasound or MRI. Additionally, it can lead to caesarean scar pregnancy, a serious complication. The condition necessitates treatment, particularly in symptomatic cases or those planning future pregnancies. Early diagnosis and appropriate management are crucial for preventing complications and ensuring positive pregnancy outcomes. Here, we report a case that underscores the potential for successful pregnancy outcomes despite the presence of isthmocele, highlighting the need for tailored management strategies in such high-risk cases.

16.
J Biophotonics ; : e202300314, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39233496

ABSTRACT

Accurate characterization of mechanical properties is crucial in the evaluation of therapeutic effects for problematic skin conditions. A pilot study was carried out using a novel optical coherence elastography (OCE) device, combining mechanical characterization through suction-based deformation and imaging through optical coherence tomography. Using AI-assisted image segmentation and a power-law model, we were able to describe the mechanical behavior, comparing with measurements from the most commonly used commercial instrument (Cutometer) and subjective analyses of stiffness using the Patient and Observer Scar Assessment Scale. Twenty subjects were included with either keloids or hypertrophic scars. Measurements were fast and produced no discomfort. Mechanical and structural (epidermal thickness and rugosity) descriptors in pathologic skin conditions differed significantly from those in control tissue. We showed for the first time, the clinical feasibility of this novel suction-based OCE device in evaluating mechanical and structural properties in pathological skin conditions such as scars.

17.
Cureus ; 16(7): e65874, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39219911

ABSTRACT

INTRODUCTION: Pregnancy located outside the uterine cavity following a cesarean section has become more prevalent in recent years due to the increase in cesarean section delivery. This study sought to investigate the prevalence, determinants, and treatment options of scar site pregnancy among women who sought maternal and child health services in a hospital in Buraydah, Al-Qassim region, Saudi Arabia. METHODS: Utilizing a quantitative retrospective case-control design, 50 women were recruited and assigned to the two groups evenly. Demographic data and risk factors were assessed using a questionnaire, and data were analyzed using SPSS version 27 at a 95% confidence interval and presented in tables and figures. RESULTS: Fifty-eight percent of the participants were aged 35 years and above, with 38% reporting a parity of 1-3. Logistic regression revealed that parity (odds ratio (OR) = 10.975, 95% confidence interval (CI) = 0.887-135.861, and p-value = 0.062), the interval between the last and present pregnancies (OR = 0.056, 95% CI = 0.005-0.668, p-value = 0.023), intrauterine contraceptive device (IUCD) use in the last year (OR = 0.070, 95% CI = 0.006 -0.780, p-value = 0.031) were statistically significant in predicting cesarean scar pregnancy. Combined methotrexate and aspiration were the most prevalent treatment options for scar site pregnancy in this study. CONCLUSION: Scar site pregnancy is a maternal health complication that affects women across all healthcare settings, and its prevalence is not clear due to underdiagnosis and underreporting. The risk of scar site pregnancy increased with an increase in the number of childbirths (parity) and the interval between the last and current pregnancies.

18.
JID Innov ; 4(6): 100299, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39247523

ABSTRACT

Keloids are abnormal skin growths occurring in a significant portion of the global population. Despite their pervasiveness, the underlying pathophysiology of this scarring process is yet to be fully understood. In this review article, we delve into the current literature on the pathophysiological mechanisms of keloids. We take a top-down approach, first looking at host factors such as genetics and endocrine factors and then taking a more granular approach describing specific control factors such as germline keloid predisposition variants, epigenetics and transcriptomics, inflammatory and immune dysregulation, and the role of profibrotic and angiogenic cell signaling pathways. We then discuss current knowledge gaps, propose further research avenues, and explore potential future treatment options considering our increased understanding of keloid pathogenesis.

19.
Tissue Eng Regen Med ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39105875

ABSTRACT

BACKGROUND: Keloids and hypertrophic scars result from abnormal collagen accumulation and the inhibition of its degradation. Although the pathogenesis remains unclear, excessive accumulation of the extracellular matrix (ECM) is believed to be associated with the TGF-ß/SMAD pathway. Zinc-alpha-2-glycoprotein (ZAG) inhibits TGF-ß-mediated epithelial-to-mesenchymal transdifferentiation and impacts skin barrier functions. In this study, we investigated the potential of a small ZAG-derived peptide against hypertrophic scars and keloids. METHODS: The study examined cell proliferation and mRNA expression of collagen types I and III in human dermal fibroblast (HDF) cell lines and keloid-derived fibroblasts (KF) following ZAG peptide treatment. A rat incisional wound model was used to evaluate the effect of ZAG peptide in scar tissue. RESULTS: Significantly lower mRNA levels of collagen types I and III were observed in ZAG-treated fibroblasts, whereas matrix metalloproteinase (MMP)-1 and MMP-3 mRNA levels were significantly increased in HDFs and KFs. Furthermore, ZAG peptide significantly reduced protein expression of collagen type I and III, TGF-ß1, and p-Smad2/3 complex in KFs. Rat incisional scar models treated with ZAG peptide presented narrower scar areas and reduced immature collagen deposition, along with decreased expression of collagen type I, α-SMA, and p-Smad2/3. CONCLUSION: ZAG peptide effectively suppresses the TGF-ß and p-Smad2/3 pathway and inhibits excessive cell proliferation during scar formation, suggesting its potential therapeutic implications against keloids and hypertrophic scars.

20.
Rev Med Liege ; 79(7-8): 527-531, 2024 Jul.
Article in French | MEDLINE | ID: mdl-39129553

ABSTRACT

BACKGROUND: Cesarean scar pregnancy is a complicated and potentially life-threatening type of ectopic pregnancy. There is no gold standard for its management. The aim is to demonstrate the efficacy and safety of treatment by hysteroscopic tissue removal system after systemic methotrexate injection. METHODS: We report the case of a 27-year-old patient who had previously had a C-section and who presented herself to the emergency room with pelvic pain and metrorrhagia. The human chorionic gonadotrophin (hCG) serum level was positive. The exploration revealed an ectopic pregnancy on the cesarean scar. She benefited of 4 systemic injections of methotrexate. As the hCG became negative, endovaginal ultrasound confirmed the avascular nature of the mass. Surgical resection by mechanical morcellation hysteroscopy (TruClear™) was performed under general anaesthesia, visual control and ultrasound guidance. RESULTS: This procedure was successful. It was an ambulatory procedure and there were neither intra- nor postoperative complications. CONCLUSIONS: To our knowledge, this is the first time in Belgium that a hysteroscopic tissue removal system procedure has been used to treat a caesarean scar pregnancy. This technique seems to be safe for both the patient and the surgeon and could become a new approach for cesarean scar pregnancy management.


CONTEXTE: La grossesse sur cicatrice de césarienne est définie comme la présence d'un sac gestationnel dans une isthmocèle créée par une hystérotomie préalable. Il n'existe pas de gold standard concernant sa prise en charge. L'objectif est de démontrer l'efficacité et la sécurité du traitement par résection mécanique hystéroscopique des tissus après injection systémique de méthotrexate. Méthodes : Nous rapportons le cas d'une patiente de 27 ans ayant déjà eu une césarienne et qui s'est présentée aux urgences avec des douleurs pelviennes et des métrorragies. L'exploration révèle une grossesse sur la cicatrice de césarienne. Elle a bénéficié de 4 injections systémiques de méthotrexate. La résection des résidus trophoblastiques avasculaires a été réalisée par voie hystéroscopique en utilisant l'hystéroscope par action mécanique de type -TruClear™ et ce, sous contrôle échographique concomitant. Résultats : Cette procédure ambulatoire effectuée sous anesthésie générale a été un succès. Il n'y a eu aucune complication per- ou postopératoire. CONCLUSIONS: À notre connaissance, c'est la première fois qu'une résection par action mécanique des résidus trophoblastiques sur cicatrice de césarienne est réalisée en Belgique. Cette technique semble sûre pour la patiente et le chirurgien et pourrait devenir une nouvelle approche pour la prise en charge d'une grossesse sur cicatrice de césarienne.


Subject(s)
Abortifacient Agents, Nonsteroidal , Cesarean Section , Cicatrix , Hysteroscopy , Methotrexate , Pregnancy, Ectopic , Humans , Female , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Methotrexate/adverse effects , Pregnancy , Adult , Cesarean Section/adverse effects , Pregnancy, Ectopic/drug therapy , Pregnancy, Ectopic/surgery , Abortifacient Agents, Nonsteroidal/administration & dosage , Abortifacient Agents, Nonsteroidal/therapeutic use
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