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Calcified Tissue International Jun 2024In 2023 following extensive consultation with key stakeholders, the expert Nosology Working Group of the International Skeletal Dysplasia Society (ISDS) published the... (Review)
Review
In 2023 following extensive consultation with key stakeholders, the expert Nosology Working Group of the International Skeletal Dysplasia Society (ISDS) published the new Dyadic Nosology for Genetic Disorders of the Skeleton. Some 770 entities were delineated associated with 552 genes. From these entities, over 40 genes resulting in distinct forms of Osteogenesis Imperfecta (OI) and Bone Fragility and/or Familial Osteoporosis were identified. To assist clinicians and lay stake holders and bring the considerable body of knowledge of the matrix biology and genomics to people with OI as well as to clinicians and scientists, a dyadic nosology has been recommended. This combines a genomic co-descriptor with a phenotypic naming based on the widely used Sillence nosology for the OI syndromes and the many other syndromes characterized in part by bone fragility.This review recapitulates and explains the evolution from the simple Congenita and Tarda subclassification of OI in the 1970 nosology, which was replaced by the Sillence types I-IV nosology which was again replaced in 2009 with 5 clinical groups, type 1 to 5. Qualitative and quantitative defects in type I collagen polypeptides were postulated to account for the genetic heterogeneity in OI for nearly 30 years, when OI type 5, a non-collagen disorder was recognized. Advances in matrix biology and genomics since that time have confirmed a surprising complexity both in transcriptional as well as post-translational mechanisms of collagens as well as in the many mechanisms of calcified tissue homeostasis and integrity.
PubMed: 38942908
DOI: 10.1007/s00223-024-01248-7 -
Molecular and Cellular Endocrinology Jun 2024Polycystic ovary syndrome (PCOS) is a type of follicular dysplasia with an unclear pathogenesis, posing certain challenges in its diagnosis and treatment. Cancer...
Polycystic ovary syndrome (PCOS) is a type of follicular dysplasia with an unclear pathogenesis, posing certain challenges in its diagnosis and treatment. Cancer susceptibility candidate 15 (CASC15), a long non-coding RNA closely associated with tumour development, has been implicated in PCOS onset and development. Therefore, this study aimed to investigate the molecular mechanisms underlying PCOS by downregulating CASC15 expression in both in vitro and in vivo models. We explored the potential regulatory relationship between CASC15 expression and PCOS by examining cell proliferation, cell cycle dynamics, cell autophagy, steroid hormone secretion capacity, and overall ovarian function in mice. We found that CASC15 expression in granulosa cells derived from patients with PCOS was significantly higher than those of the normal group (P < 0.001). In vitro experiments revealed that downregulating CASC15 significantly inhibited cell proliferation, promoted apoptosis, induced G1-phase cell cycle arrest, and influenced cellular autophagy levels. Moreover, downregulating CASC15 affected the follicular development process in newborn mouse ovaries. In vivo studies in mice demonstrated that disrupting CASC15 expression improved PCOS-related symptoms such as polycystic changes and hyperandrogenism, and significantly affected ovulation induction and embryo implantation in pregnant mice. Overall, CASC15 was highly expressed in granulosa cells of patients with PCOS and its downregulation improved PCOS-related symptoms by influencing granulosa cell function and follicular development in mice.
PubMed: 38942281
DOI: 10.1016/j.mce.2024.112322 -
Gene Jun 2024This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473...
This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473 and its downstream targets on FGR progression in trophoblast cells. Placental vascular distribution, placental vascular index (VI), CD34 expression, and histological changes were compared between control and FGR groups. FGR-related differentially expressed genes (DEGs) were analyzed and validated by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in placentae. In vitro experiments examined the regulatory relationships among LINC00473, miR-5189-5p, and StAR, followed by investigations into their impacts on cell proliferation and apoptosis. FGR placentae exhibited irregular shapes, uneven parenchymal echo, stromal dysplasia, ischemic infarction, and variable degrees of thickening in some cases. FGR samples showed less prominent mother vessel lakes, significantly lower VI, and decreased CD34 expression. Hematoxylin & eosin (H&E) staining revealed placental fibrosis, fibrin adhesion, infarction, and interstitial dysplasia in FGR. LINC00473, miR-5189-5p, and StAR were identified as DEG, with qPCR demonstrating a significant increase in LINC00473 and a decrease in miR-5189-5p in FGR, while both qPCR and IHC indicated a significant increase in StAR expression. LINC00473 served as an endogenous sponge against miR-5189-5p in human HTR-8/SV neo cells, and StAR expression was regulated by both LINC00473 and miR-5189-5p. Dysregulation of these genes affected cell proliferation and apoptosis. Pathological changes in the placenta are significant contributors to FGR, with placental microblood flow potentially serving as an indicator for monitoring its progression. LINC00473 and its downstream targets may modulate trophoblasts proliferation and apoptosis, thus influencing the onset of FGR, suggesting novel avenues for diagnosis and treatment.
PubMed: 38942180
DOI: 10.1016/j.gene.2024.148727 -
Endoscopy Jun 2024Introduction The role of endoscopic submucosal dissection (ESD) in the treatment of Barrett's associated neoplasia (BEN) has been evolving. We examined the efficacy and...
Introduction The role of endoscopic submucosal dissection (ESD) in the treatment of Barrett's associated neoplasia (BEN) has been evolving. We examined the efficacy and safety of ESD and EMR for BEN. Methods A database search was performed for studies reporting efficacy and safety outcomes of ESD and EMR for BEN. Pooled proportional and comparative meta-analyses were performed. Results 47 studies (23 ESD, 19 EMR, and 5 comparative) were included. Mean lesion size for ESD and EMR were 22.5 mm and 15.8 mm respectively. Majority of lesions were Paris type IIa. Pooled analysis for ESD showed en-bloc resection, R0 resection, curative resection, and local recurrence rates of 98%, 78%, 65%, and 2%, respectively. Complete eradication of dysplasia (CE-D) and complete eradication of intestinal metaplasia (CE-IM) were achieved in 94% and 59% of cases. Pooled rates of perforation, intraprocedural bleeding (IPB), delayed bleeding (DB), and stricture were 1%, 1%, 2%, and 10%, respectively. Pooled analysis for EMR showed en-bloc resection, R0 resection, curative resection, and local recurrence rates of 37%, 67%, 62%, and 6%, respectively. CE-D and CE-IM were achieved in 94% and 76% of cases. Pooled rates of perforation, IPB, DB, and stricture were 0.1%, 1%, 0.4%, and 7.7%, respectively. The mean procedure time for ESD and EMR were 111.3 and 22.3 mins respectively. Comparative analysis showed higher en-bloc and R0 resection rates with ESD compared to EMR, with comparable adverse events. Conclusion ESD and EMR both can be employed to treat BEN depending on the lesion type, size, and expertise.
PubMed: 38942058
DOI: 10.1055/a-2357-6111 -
Clinical Oral Investigations Jun 2024The COHQoL is a set of questionnaires used to evaluate the impact of oral health on children's quality of life. Although the CPQ8-10 and the P-CPQ have been translated...
OBJECTIVES
The COHQoL is a set of questionnaires used to evaluate the impact of oral health on children's quality of life. Although the CPQ8-10 and the P-CPQ have been translated and validated in French, the CPQ11-14 14 has not yet been validated. The aim was to develop a French version of the CPQ11-14 16-items.
MATERIALS AND METHODS
The French version of CPQ11-14 was obtained by a forward-backward translation process and pretested. The final version was tested on children aged 11-14 and divided into three groups: children with orofacial clefts, children with rare dental diseases other than clefts, and children without anomalies. We conducted a cross-sectional study and evaluated the reliability with test-retest and internal consistency, and the questionnaire validity with construct validity and discriminant validity. We performed an Exploratory Factory Analysis (EFA).
RESULTS
187 children tested the questionnaire. The ICC of the test-retest was 0.76 and the Cronbach's alpha was 0.77. The correlation between the CPQ11-14 and self-assessment of oral health and general well-being was > 0.2. Patients with orofacial clefts and rare diseases had significantly higher scores for overall short-form CPQ11-14. The EFA revealed six factors.
CONCLUSION
The French CPQ11-14 is valid to assess the impact of oral health on children's quality of life.
CLINICAL RELEVANCE
The translation of this questionnaire into French will enable us to assess the impact of oral health on the quality of life of adolescents. This questionnaire complements the 8-10 years version of the CPQ, as well as the parental version that can be used in conjunction with the questionnaire.
Topics: Humans; Child; Surveys and Questionnaires; Female; Adolescent; Male; Cross-Sectional Studies; Quality of Life; Reproducibility of Results; Oral Health; France; Translations; Cleft Palate; Cleft Lip
PubMed: 38940970
DOI: 10.1007/s00784-024-05793-1 -
Alternative Therapies in Health and... Jun 2024The objective of this study is to develop a prediction model for the pathological upgrading of low-grade dysplasia (LGD) in gastric mucosa. The study aims to compare the...
OBJECTIVE
The objective of this study is to develop a prediction model for the pathological upgrading of low-grade dysplasia (LGD) in gastric mucosa. The study aims to compare the performance of a traditional model based on clinical and endoscopic factors with an enhanced model that incorporates AMACR staining of biopsy tissues.
METHODS
The study utilized a training dataset of 405 LGD cases to establish and compare the traditional and enhanced prediction models. Factors associated with upgrading were identified, and the traditional model was based on these factors. The enhanced model incorporated AMACR staining. The models' performances were evaluated using the area under the curve (AUC), bootstrap resampling, and decision curve analysis. External validation was performed using 171 LGD cases. Statistical techniques such as logistic regression and resampling methods were employed to assess the models' predictive abilities and robustness.
RESULTS
In the training dataset, the traditional model achieved an AUC of 0.824 (95% confidence interval [CI]: 0.783-0.865) for predicting pathological upgrading. However, the enhanced model, which incorporated AMACR staining, exhibited a significantly improved performance with an AUC of 0.878 (95% CI: 0.843-0.913). This increase in AUC by 0.054 (95% CI: 0.015-0.093) demonstrates a statistically significant enhancement provided by the inclusion of AMACR staining in the prediction model for pathological upgrading of LGD lesions in gastric mucosa.
CONCLUSION
The findings of this study highlight the practical implications of the enhanced prediction model incorporating AMACR staining for low-grade gastric mucosal dysplasia (LGD). The significantly improved performance of the enhanced model in predicting pathological upgrading emphasizes its potential to revolutionize the management and treatment strategies for patients with LGD. By providing a more accurate prediction of upgrading, the enhanced model enables early intervention and timely decision-making, leading to improved outcomes and prognosis for patients. The incorporation of AMACR staining in the prediction model holds promise for enhancing diagnostic strategies and reducing the incidence of postoperative pathological upgrading. This research underscores the importance of leveraging advanced techniques to improve the early detection rate of gastric cancer and ultimately benefit patient care.
PubMed: 38940773
DOI: No ID Found -
The Laryngoscope Jun 2024This study aimed to compare the pharyngocutaneous fistula (PCF) between patients who underwent reconstruction using cervical fascia after total laryngectomy and those...
OBJECTIVE
This study aimed to compare the pharyngocutaneous fistula (PCF) between patients who underwent reconstruction using cervical fascia after total laryngectomy and those who did not and to investigate the factors affecting PCF rates.
METHODS
We retrospectively compared 22 patients operated between February 2021 and March 2023 who received cervical fascia flap as the study group and 21 patients operated between January 2018 and March 2023 who did not receive fascia flap as the control group. The study included patients who underwent total laryngectomy for Stage 3 and 4 squamous cell laryngeal cancer.
RESULTS
We included 43 patients, with 22 (51.2%) and 21 patients (48.8%) in the study and control groups, respectively. The age and sex were not different between the two groups (p = 0.471, p = 0.176, respectively). The distribution of patients as per sex, smoking, alcohol use, chronic obstructive pulmonary disease, diabetes mellitus, coronary artery disease, and multiple comorbidities was similar in both groups (p > 0.05). PCF was observed in one patient (4.5%) and seven patients (33.3%) in the study and control groups, respectively. The PCF rate was significantly lower in the study group (p = 0.021). When the relationship between flap use and risk factors was compared by correlation analysis, a moderate negative relationship was found between flap use and PCF (p = 0.015, r = -0.370).
CONCLUSION
The use of a cervical fascia flap is effective in reducing fistula rates after total laryngectomy. Its main advantages include being technically simpler than alternative techniques, locally available, cost-effective.
LEVEL OF EVIDENCE
Level 3 Laryngoscope, 2024.
PubMed: 38940495
DOI: 10.1002/lary.31606 -
Clinical Genetics Jun 2024HDR syndrome is a rare disease characterized by hypoparathyroidism, deafness, and renal dysplasia. An autosomal dominant disease caused by heterozygous pathogenic GATA3...
HDR syndrome is a rare disease characterized by hypoparathyroidism, deafness, and renal dysplasia. An autosomal dominant disease caused by heterozygous pathogenic GATA3 variants, the penetrance of each associated condition is variable. Literature reviews have provided some answers, but many questions remain, in particular what the relationship is between genotype and phenotype. The current study examines 28 patients with HDR syndrome combined with an exhaustive review of the literature. Some conditions such as hearing loss are almost always present, while others described as rare initially, do not seem to be so rare after all (genital malformations and basal ganglia calcifications). By modeling pathogenic GATA3 variants found in HDR syndrome, we found that missense variations appear to always be located in the same area (close to the two Zinc Finger domain). We describe new pathogenic GATA3 variants, of which some seem to always be associated with certain conditions. Many audiograms were studied to establish a typical audiometric profile associated with a phenotype in HDR. As mentioned in the literature, hearing function should always be assessed as early as possible and follow up of patients with HDR syndrome should include monitoring of parathyroid function and vesicoureteral reflux in order to prevent complications.
PubMed: 38940299
DOI: 10.1111/cge.14583 -
JAAD Case Reports Jul 2024
PubMed: 38938698
DOI: 10.1016/j.jdcr.2024.05.007 -
Oral Diseases Jun 2024Oral leukoplakia (OL) is one of the most common and investigated oral potentially malignant disorders (OPMD). Preventing OSCC occurrence should be the primary outcome in...
Surgical treatment compared with "wait and see" in patients affected by oral leukoplakia to prevent oral cancer: Preliminary data from a multicenter randomized controlled trial.
OBJECTIVE
Oral leukoplakia (OL) is one of the most common and investigated oral potentially malignant disorders (OPMD). Preventing OSCC occurrence should be the primary outcome in the clinical management of OL. Surgical removal of OL is performed by most clinicians, although its effectiveness in reducing OSCC onset has still not been established by randomized controlled trials (RCT). Wait and see approach is characterized by frequent clinical examinations and periodical biopsies of OL, avoiding unnecessary surgical procedures. This is the first multicenter RCT in literature aiming at comparing the effectiveness of surgical removal and the "wait and see" approach in preventing OSCC onset in patients affected by dysplastic and non-dysplastic OL.
METHODS
Two Italian referral care centres for oral diseases were involved in this multicenter two-arm RCT comparing the surgical removal of OL (group A) and the "wait and see" approach (group B), with the aim of reducing oral cancer onset.
RESULTS
This report shows preliminary data on the first 161 patients, with a mean follow-up of 19.14 ± 11.25 months. Eight cases of OSCC occurred (6 out 8 involving the tongue): one case in group A and seven cases in group B. Moreover, OL recurred in 13 (20%) cases after surgical excision.
CONCLUSIONS
Within the limitations of this preliminary report, these initial data underline the increased risk of OSCC onset in the case of OL of the tongue in the presence of epithelial dysplasia in group B ("wait and see") compared to group A (surgery). This RCT is currently ongoing at the same clinical departments, with the aim of enrolling 310 patients and collecting data at 5-year follow-up, in order to achieve conclusive results, in an evidence-based medicine approach.
PubMed: 38938085
DOI: 10.1111/odi.15058