Abnormal Formation Research Articles

Fibroblast Insights into the Pathogenesis of Ankylosing Spondylitis.

Emerging evidence has shown that ankylosing spondylitis fibroblasts (ASFs) act as crucial participants in inflammation and abnormal ossification in ankylosing spondylitis (AS). This review examines the investigations into ASFs and their pathological behavior, which contributes to inflammatory microenvironments and abnormal bone formation. The review spans the period from 2000 to 2023, with a primary focus on the most recent decade. Additionally, the review provides an in-depth discussion on studies on ASF ossification at the cellular level. ASFs organize immune functions by recruiting immune cells and influencing their differentiation and activation, thus mediate the inflammatory response in the early phase of disease. ASFs promote joint destruction at sites of cartilage and actively promote abnormal ossification by recruiting osteoblasts, differentiation into myofibroblasts or ossification directly. Many signaling pathways and cytokines such as Wnt signaling and BMP/TGF-β signaling are involved in ASF ossification. ASFs play a key role in AS inflammation and osteogenesis. Further studies are required to elucidate molecular mechanisms behind that and provide new targets and directions for AS diagnosis and treatment from a new perspective of fibroblasts.

Immunohistochemical detection of amyloid beta and tau proteins in the Monodelphis domestica brain

AbstractBackgroundAnimal models have been important for the understanding of Alzheimer’s disease and related dementias (ADRD). However, most of the research involving these diseases has been with rodents. Researchers have raised awareness about the need for alternative and feasible animal models in order to understand these types of diseases. To increase the knowledge of alternative animal models for the study of ADRD, the current study proposed the use of the Monodelphis domestica animal model to detect the presence of amyloid beta and tau proteins.MethodFixed brains from young adult Monodelphis were used in the present study. A standard immunohistochemistry (ABC‐DAB) staining protocol was used to detect amyloid beta and tau proteins. To detect the presence of amyloid beta, a 1:100 anti‐amyloid primary dilution was used; for tau protein, a 1:1000 anti‐tau primary dilution was utilized. Only the hippocampal region was selected for description and quantification. An Axioscan Z.1 microscope system was utilized to capture images, and image analysis was performed using ImageJ software.ResultThe area of the hippocampus of the first coronal section was 30262602.934 um2. The results from an amyloid‐beta dilution of 1:100 detected amyloid beta in a number of neurons in the hippocampus. Amyloid beta was also detected in the hippocampus of another brain section (total area: 7048008 um2). The negative control tissue did not reveal positive signal in neurons in the hippocampal area, suggesting low levels of non‐specific binding. The results for tau antibody are pending.ConclusionOur study revealed that in Monodelphis domestica animal model brain tissue, a 1:100 dilution resulted in identification of positive amyloid beta protein. However, no abnormal amyloid beta plaque formation was found with this animal model. A possible explanation was that a natural, non‐induced animal model was used in the study.

Role of Cytogenetics and Fluorescence In Situ Hybridization in the Laboratory Workup of Acute Myeloid Leukemias

AbstractA new understanding of acute myeloid leukemia as a varied group of unique biologic entity has emerged, as a result of the identification of various chromosomal aberrations and their association with clinical prognosis and diagnosis. Following induction treatment, cytogenetic examination can establish the presence of any residual malignant cells, it's recurrence, clonal evolution if any, or the formation of novel abnormalities. The G-banded karyotype has been the gold standard method for detecting all of these aberrations for years. The capacity to examine the entire genome through karyotype analysis quickly enabled the detection of deletions, duplications, and structural rearrangements across every chromosome, and the more frequent ones were associated with particular aberrant clinical symptoms. Fluorescence in situ hybridization (FISH) is a sensitive technology that aids in differential diagnosis or therapeutic planning and provides rapid results. Furthermore, the combination of cytogenetic and molecular profiling enables a more precise evaluation of disease prognosis, diagnosis, classification, risk stratification, and patient treatment. Interphase FISH analysis, in conjunction with G-banded chromosomal analysis, can be used as a major testing tool for the evaluation of hematological neoplasms. For accurate and consistent descriptions of genomic changes identified by karyotyping and FISH, a specified terminology is necessary. The International System for Human Cytogenomic Nomenclature is the main source and provides instructions for documenting cytogenetic and molecular findings in laboratory reports. This review discusses the two methods, karyotyping and FISH, their advantages and limitations, sample requirements, various FISH probes that are used, nomenclature for results reporting, and the necessary quality control measures.

Knockdown of TACC3 inhibits tumor cell proliferation and increases chemosensitivity in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant digestive tract tumor with limited clinical treatments. Transforming acidic coiled-coil-containing protein 3 (TACC3) is a component of the centrosome axis and a member of the TACC family, which affect mitosis and regulate chromosome stability and are involved in tumor development and progression. However, the role of TACC3 in PDAC remains elusive. In this study, by exploiting the TCGA database, we found that high TACC3 expression in PDAC is associated with poor prognosis. shRNA-mediated TACC3 knockdown caused S phase arrest of the cell cycle and inhibited proliferation in PDAC cell lines. Through RNA sequencing and protein co-immunoprecipitation combined with mass spectrometry, KIF11 was identified as a protein that interacts with TACC3. TACC3 stabilizes and regulates KIF11 protein expression levels in PDAC cells through physical interaction. Knockdown of TACC3 or KIF11 resulted in abnormal spindle formation during cell division both in vitro and in vivo. Pharmacological inhibition of TACC3 or KIF11 can suppress tumor cell proliferation and promote apoptosis. Our studies further demonstrated that high expression of TACC3 and KIF11 mediated the resistance of PDAC to gemcitabine, and deficiency of TACC3 or KIF11 increased the sensitivity of PDAC cells to chemotherapy. In conclusion, our study reveals the fundamental role of TACC3 expression in PDAC cell proliferation and chemoresistance, suggesting that TACC3 can be used as a molecular marker to evaluate the prognosis of PDAC.

Improvement of Inflammation and Abnormal Vascularization by TSP1 Treatment Combined with ADSCs Transplantation in Mice with Induced Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease with a certain degree of chronic inflammation and abnormal ovarian angiogenesis in reproductive women. Mesenchymal stem cells (MSCs) have potent immunomodulatory properties to regulate ovarian function, while thrombospondin 1 (TSP1) improves the abnormal formation of ovarian vessels. The present study investigated the efficacy of the combined use of adipose-derived mesenchymal stem cells (ADSCs) and TSP1 in PCOS mice. The PCOS model is established using dehydroepiandrosterone (DHEA) by subcutaneous injection. Ovarian apoptosis is assessed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Real-time quantitative PCR (RT-PCR) and western blotting are used to detect the expression of inflammatory factors and the levels of angiogenesis-related factors in ovarian tissues. Inflammatory cells count and ovarian angiogenesis are evaluated by immunofluorescence staining. This research shows that TSP1 and ADSCs treatment can significantly reduce the inflammatory state of PCOS mice, relieve the degree of ovarian cell apoptosis, optimize the ovarian histological manifestations, and restore the levels of related hormones. The proportion of CD31-positive cells in PCOS mice returned to near-normal levels. The synergistic use of ADSCs and TSP1 therapy can exert a more impressive effect by inhibiting the ovarian inflammatory response and regulating the balance of angiogenesis than the single application in PCOS mice.

Analysis of risk factors and pregnancy outcomes in pregnant women with subchorionic hematoma.

Subchorionic hemorrhage (SCH) or hematoma is one of the abnormal ultrasonic manifestations. At present, there are few studies on the pathogenesis of SCH, and its underlying mechanism is still unclear. It may be related to abnormal placenta formation and implantation, autoimmune dysfunction, and coagulation dysfunction. As a unique complication of pregnancy, SCH has a controversial effect on pregnancy outcome. The aim of the present study was to explore the possible etiology of SCH, especially its association with autoimmune dysfunctions, as well as the pregnancy outcomes of SCH patients. This retrospective cohort study was conducted at the Third Affiliated Hospital of Zhengzhou University. Patients with a singleton pregnancy of ≤14 weeks gestation from June 2021 to June 2022 were included. Patients with SCH detected by ultrasound were selected as the study group, while patients without SCH during the same period were chosen as the control group. Immunological indicators and pregnancy outcomes were primarily compared between the 2 groups. The decrease in protein S activity and antithrombin-III levels, the increase in homocysteine levels, and the presence of autoantibodies (such as lupus anticoagulant, anticardiolipin antibody, and antinuclear antibody spectrum) were found to be risk factors for SCH. SCH in the first trimester was associated with higher rates of premature rupture of membranes (13.5% vs 3.8%) and miscarriage (14.4% vs 6.4%). However, there were no significant differences in the rates of placental abruption, fetal distress, cesarean section, neonatal birth weight, and gestational age. The incidence of miscarriage was also significantly higher in patients with subchorionic hematoma (SCH) who tested positive for autoantibodies (28.2% vs 7.6%). There were no significant differences in other clinical characteristics and pregnancy outcomes between patients with SCH who had positive autoantibodies and those who did not. The occurrence of SCH may be related to maternal immune abnormalities. SCH may increase the risk of premature rupture of membranes and abortion. However, there is no correlation between the presence or absence of SCH and neonatal outcomes.

Characterization of Rickets Type II Model Rats to Reveal Functions of Vitamin D and Vitamin D Receptor.

Vitamin D has been known to exert a wide range of physiological effects, including calcemic, osteogenic, anticancer, and immune responses. We previously generated genetically modified (GM) rats and performed a comparative analysis of their physiological properties to elucidate the roles of vitamin D and vitamin D receptor (VDR). In this study, our primary goal was to investigate the manifestations of type II rickets in rats with the VDR(H301Q) mutation, analogous to the human VDR(H305Q). Additionally, we created a double-mutant rat with the VDR(R270L/H301Q) mutation, resulting in almost no affinity for 1,25-dihydroxy-vitamin D3 (1,25D3) or 25-hydroxy-vitamin D3 (25D3). Notably, the plasma calcium concentration in Vdr(R270L/H301Q) rats was significantly lower than in wild-type (WT) rats. Meanwhile, Vdr(H301Q) rats had calcium concentrations falling between those of Vdr(R270L/H301Q) and WT rats. GM rats exhibited markedly elevated plasma parathyroid hormone and 1,25D3 levels compared to those of WT rats. An analysis of bone mineral density in the cortical bone of the femur in both GM rats revealed significantly lower values than in WT rats. Conversely, the bone mineral density in the trabecular bone was notably higher, indicating abnormal bone formation. This abnormal bone formation was more pronounced in Vdr(R270L/H301Q) rats than in Vdr(H301Q) rats, highlighting the critical role of the VDR-dependent function of 1,25D3 in bone formation. In contrast, neither Vdr(H301Q) nor Vdr(R270L/H301Q) rats exhibited symptoms of alopecia or cyst formation in the skin, which were observed in the Vdr-KO rats. These findings strongly suggest that unliganded VDR is crucial for maintaining the hair cycle and normal skin. Our GM rats hold significant promise for comprehensive analyses of vitamin D and VDR functions in future research.

The spectrum of gastrointestinal functional bowel disorders in joint hypermobility syndrome and in an academic referral center.

Joint hypermobility syndrome (JHS) is a non-inflammatory hereditary disorder of connective tissue with varied clinical presentations, including frequent joint dislocations, hyperextensible skin, easy bruising, and abnormal paper-thin scar formation. Many of these patients have unexplained gastrointestinal (GI) symptoms. Our aim was to evaluate the prevalence of JHS in a tertiary gastroenterology motility clinic and the spectrum of functional bowel disorders in JHS patients. In this retrospective case series, we screened the medical records of 277 patients seen over 4 years at an academic GI Motility Center. The patients who met the criteria for JHS by Beighton hypermobility score were evaluated for the presence of functional GI disorders by Rome IV criteria. They also underwent gastric emptying study and glucose breath testing for small intestinal bacterial overgrowth. The prevalence of JHS in the study population was 9.7%. The mean age was 27 years, and 92.5% were female. The symptoms experienced by these patients include nausea/vomiting (89%), abdominal pain (70%), constipation (48%), and bloating (18.5%). The disorders associated with JHS include gastroparesis (52%), irritable bowel syndrome (55.5%), and gastroesophageal reflux disease (30%). Also, 10 patients (37%) were diagnosed with postural hypotension tachycardia syndrome secondary to autonomic dysfunction. Approximately 10% of patients with suspected functional bowel disorders have hypermobility syndrome. Hence, it is crucial to familiarize gastrointestinal practitioners with the criteria utilized to diagnose JHS and the methods to identify physical examination findings related to this condition.

Integrating Melt Electrowriting and Fused Deposition Modeling to Fabricate Hybrid Scaffolds Supportive of Accelerated Bone Regeneration.

Emerging additive manufacturing (AM) strategies can enable the engineering of hierarchal scaffold structures for guiding tissue regeneration. Here, the advantages of two AM approaches, melt electrowriting (MEW) and fused deposition modelling (FDM), are leveraged and integrated to fabricate hybrid scaffolds for large bone defect healing. MEW is used to fabricate a microfibrous core to guide bone healing, while FDM is used to fabricate a stiff outer shell for mechanical support, with constructs being coated with pro-osteogenic calcium phosphate (CaP) nano-needles. Compared to MEW scaffolds alone, hybrid scaffolds prevent soft tissue collapse into the defect region and support increased vascularization and higher levels of new bone formation 12 weeks post-implantation. In an additional group, hybrid scaffolds are also functionalized with BMP2 via binding to the CaP coating, which further accelerates healing and facilitates the complete bridging of defects after 12 weeks. Histological analyses demonstrate that such scaffolds support the formation of well-defined annular bone, with an open medullary cavity, smooth periosteal surface, and no evidence of abnormal ectopic bone formation. These results demonstrate the potential of integrating different AM approaches for the development of regenerative biomaterials, and in particular, demonstrate the enhanced bone healing outcomes possible with hybrid MEW-FDM constructs.

A novel DLX3 mutation causes tricho-dento-osseous syndrome with abnormal enamel structure and formation

ObjectiveThis study aimed to identify a DLX3 gene mutation in a family with atypical clinical manifestations of tricho-dento-osseous syndrome (TDO) and its impact on tooth enamel thickness, microhardness, structure and formation. DesignWhole-exome sequencing detected DLX3 mutations in the family. Micro-CT, Vickers hardness tester, energy dispersive spectrometer and scanning electron microscopy were performed on the deciduous teeth of the proband and controls. In vitro experiments preliminarily verified the effect of this mutation on ameloblast differentiation and suggested possible molecular mechanisms. ResultsWe found a new DLX3 frame-shift mutation (NM_005220.3: c.604_605del: p. S202 *) in this family. Compared with control teeth, the mutant enamel showed a significant decrease in thickness, hardness and calcium content and an increase in magnesium content. The enamel structure appeared disordered. In an immortalized ameloblast-lineage cell (ALC) line, this mutation affected ameloblast differentiation and downregulated the expression levels of enamel matrix protein (EMP) genes (Amelx, Tuft1, Klk4, Ambn, Odam). A luciferase reporter assay demonstrated that this mutation significantly reduced the transactivation activity of DLX3 on Amelx/Odam/Klk4. ConclusionWe found a new DLX3 mutation in a Chinese family with enamel dysplasia and that this mutation may affect ameloblast differentiation by inhibiting the transcriptional activity of Amelx/Odam/Klk4, thereby interfering with enamel formation. Our findings further expand the variation spectrum and enrich the evidence of molecular genetics of DLX3 mutations.

Nanoparticles green-formulated by Salvia leriifolia aqueous extract: Green synthesis, chemical characterization, and its application in improving the repair of damaged articular cartilage

Damaged cartilage has very low regenerative potential which has led to the search for novel tissue-engineering approaches to help treat cartilage defects. While various approaches have been reported, there is no perfect treatment currently. In this study, we evaluated the effects of green formulation of titanium nanoparticles by Salvia leriifolia on a model of knee joint injury in chicks. The NPs characterization was run by the techniques of ultraviolet–visible (UV–Vis), Fourier transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray crystallography (XRD), and energy-dispersive X-ray spectroscopy (EDS). The NPs materialized in spherical morphology with average size of less than 40 nm. The peaks at different 2 Theta values of 25.23, 37.73, 47.95, 54.93, and 62.66 are corresponded to planes of (101), (004), (200), (211), and (204) of TiO2. The peaks at 280, 328, and 459 nm show the surface plasmon resonance of the synthetic NPs. In the medicine experiments, primary cultured chondrocytes applied to assess the efficacy of nanoparticles on chondrogenesis. Then, using an animal mice knee model articular cartilage injury, we determined the functional recovery after nanoparticles transplantation by western blot, PCR, and histological analysis. The findings revealed that nanoparticles made notable effects on stimulating chondrogenesisand accelerated the recovery of injury-induced dysfunction by gait analysis when followed for 20 days. The application of nanoparticles suppressed the abnormal angiogenesis and fibrosis at the injury site, decreased the levels of inflammatory cytokines IL-1β, TNF-α, p-p65, and MMPs expression and up-regulated the expressions of Sox9 and Col2a1. Histochemical analysis revealed that there was more cartilage matrix synthesis and chondrocyte proliferation and less abnormal vasculature formation in the complexes containing nanoparticles presence.

Risk Factors for Penile Fracture After Intralesional Collagenase Clostridium histolyticum in Peyronie’s Disease

ObjectivesTo evaluate risk factors leading to corporal rupture after Collagenase Clostridium histolyticum (CCh). Peyronie's disease (PD) is a fibrotic condition of the penis characterized by abnormal plaque formation. Intralesional CCh is the only FDA approved medication for PD, however it can lead to corporal rupture, a potential surgical emergency. MethodsWe retrospectively reviewed medical records from Veterans diagnosed with PD who were under treatment with CCh using the Veterans Administration Informatics and Computing Infrastructure (VINCI). Using International Classification of Diseases and Current Procedural Terminology codes, we identified men who suffered a corporal rupture after CCh. Individual charts were reviewed to determine potential risk factors and events leading to corporal rupture. ResultsWe identified 17,647 veterans who were diagnosed with PD, of which 8.7% (1,541) received at least one injection of CCh for PD. Of them, 0.7% (11/1,541) veterans suffered corporal rupture. Within these 11 patients, the median number of CCH injections was 6 with a median initial curvature of 35º. Fracture occurred at a median of 8 days after CCH injection. The majority of fractures were secondary to spontaneous erections or sexual intercourse. Finally, six patients had their fracture repaired surgically while the remaining were managed conservatively. ConclusionsMost fractures occurred within 2 weeks of CCh injections and were associated with sexual intercourse and spontaneous morning erections.

Fractures in the ankylosed spine are associated with poor bone quality and lower hounsfield units

Study designRetrospective study IntroductionPatients with ankylosing spinal disorders have a higher risk of fractures, highlighting the need for bone health surveillance. Bone assessment by dual energy x-ray absorptiometry (DXA) is challenging due to abnormal bone formation but measurements by quantitative computed tomography (qCT) have demonstrated higher sensitivity and specificity. However, no studies have analyzed bone quality using qCT in the ankylosed spine population to assess three-column fracture characteristics and subsequent outcomes. Methods106 patients with 115 three-column fractures were identified from 1999 to 2020. Patient demographics, Charlson comorbidity index, and injury severity score were extracted. Bone quality measured in Hounsfield units (HU), fracture characteristics, neurologic injury, and mortality were obtained. ResultsMost injuries occurred in the thoracic spine (70.4%) following a ground level fall (60.5%). HU adjacent to the fracture (127 HU) was significantly lower than the mobile segments (173 HU) (p < 0.001). Fracture adjacent HU was significantly lower in AS patients compared to DISH (109 vs 150 HU, p = 0.02, respectively) and were lower in fractures that resulted in a non-union or revision surgery (88 vs 137 HU, p = 0.04). Patients with longer fused segments were associated with multilevel and displaced fractures. ConclusionsFracture adjacent HUs within the autofused segments were significantly lower than in the mobile segments, and longer fusion segments were associated with displaced, multilevel fractures. This study reinforces the importance of assessing patients for decreased HUs as well as better understand how the length of fused segments is associated with displaced, multilevel fractures. Level of evidenceLevel III.

Phenotypic Analysis of Preimplantation Lethality in Mice

Preimplantation development covers a period of ∼4.5 d from fertilization to implantation in the uterus. If a homozygous mutant phenotype causes the death of embryos during this period, simple culture methods are available that support preimplantation development to allow a thorough morphological assessment. Embryos are recovered from the oviducts or uterus and examined for gross morphology, cell number, and progression through cleavage stages. Blastocysts can also be cultured over the implantation period and undergo a process analogous to implantation in vitro. Different categories of phenotypes such as failure of compaction, abnormal blastocyst formation, or failure to hatch from the zona pellucida and failure to attach and outgrow in vitro are discussed in relation to what each phenotype might portend. Further experimental procedures such as isolation and assessment of blastocyst inner cell mass and analysis of induced implantation delay in vivo may also be appropriate. Additional assessment of preimplantation embryos can involve histology and localization of mRNA or proteins either in sections or whole embryos.

Smile Incision-Modified Technique for Better Scrotal Outcome in Surgical Management of Penile Paraffinoma

Introduction: Penile augmentation with foreign material injection is used to increase penile length, girth, or both. Most of these individuals develop complications due to an abnormal mass formation known as penile paraffinoma. Multiple surgical techniques for restoring penile function and correcting near-normal penile shape have been developed, but prior techniques have some post-operative complications. Methods: We explained the smile incision-modified technique for penile paraffinoma reconstruction using illustrations to describe step-by-step procedures. This study aimed to describe our modified surgical technique for reconstruction to correct complications due to disastrous consequences of failed penile augmentation. Results: A total of 16 patients aged 28–66 years (mean: 44.25 ± 2.63) were operated with a smile incision-modified technique from January 2017 until December 2020 in Semarang Dr. Kariadi tertiary hospital. There were no intraoperative complications observed. We found hematoma in 3 patients in a 1-week follow-up. After 2 weeks of post-operative surgery, all patients had no skin dehiscence or necrosis. Cosmetic appearance and functional improvement after reconstruction were acceptable by all patients. Conclusion: Penile paraffinoma reconstruction using the smile incision-modified technique was a feasible and effective technique to manage penile paraffinoma patients with good esthetic results and minor complications.

Dental and jawbone abnormalities linked to amelogenesis imperfecta: A retrospective and analytic study comparing panoramic radiographs.

Amelogenesis Imperfecta (AI) is a disorder of tooth development characterized by abnormal enamel formation. In order to detect other dental and jawbone abnormalities that could be associated with AI, a retrospective and analytic study was conducted comparing panoramic radiographs of AI and non-AI patients. Digital panoramic radiographs of 60 AI and 60 non-AI patients were examined. Abnormalities in dental number, size, shape, eruption, and in the shape of the dental arches were checked and blindly recorded by two experimented observers. Descriptive statistics using percentages and chi-square test with .05 level of significance value was used. Prevalence of supernumerary teeth, dental agenesis, microdontia, taurodontism, radicular dilacerations, dental inclusions, temporary teeth persistence, and pulp calcifications was significantly higher in AI patients compared to control patients. Prevalence of periapical images, cysts, and hypercementosis was lower in AI patients compared to control patients, with no statistically significant difference. A significant prevalence of mandibular hypoplasia was also noted in AI patients. In addition to enamel defect, panoramic radiography was useful in detecting other dental abnormalities and mandibular hypoplasia associated with AI and should therefore be systematically indicated for AI patients' care.

Bi-allelic truncating variants in CASP2 underlie a neurodevelopmental disorder with lissencephaly

Lissencephaly (LIS) is a malformation of cortical development due to deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. Thirty-one LIS-associated genes have been previously described. Recently, biallelic pathogenic variants in CRADD and PIDD1, have associated with LIS impacting the previously established role of the PIDDosome in activating caspase-2. In this report, we describe biallelic truncating variants in CASP2, another subunit of PIDDosome complex. Seven patients from five independent families presenting with a neurodevelopmental phenotype were identified through GeneMatcher-facilitated international collaborations. Exome sequencing analysis was carried out and revealed two distinct novel homozygous (NM_032982.4:c.1156delT (p.Tyr386ThrfsTer25), and c.1174 C > T (p.Gln392Ter)) and compound heterozygous variants (c.[130 C > T];[876 + 1 G > T] p.[Arg44Ter];[?]) in CASP2 segregating within the families in a manner compatible with an autosomal recessive pattern. RNA studies of the c.876 + 1 G > T variant indicated usage of two cryptic splice donor sites, each introducing a premature stop codon. All patients from whom brain MRIs were available had a typical fronto-temporal LIS and pachygyria, remarkably resembling the CRADD and PIDD1-related neuroimaging findings. Other findings included developmental delay, attention deficit hyperactivity disorder, hypotonia, seizure, poor social skills, and autistic traits. In summary, we present patients with CASP2-related ID, anterior-predominant LIS, and pachygyria similar to previously reported patients with CRADD and PIDD1-related disorders, expanding the genetic spectrum of LIS and lending support that each component of the PIDDosome complex is critical for normal development of the human cerebral cortex and brain function.

Prevalence of Oral Manifestation of Thalassemic Patients in Sulaymaniyah Thalassemia Center

Thalassemia is a genetic blood disorder characterized by abnormal hemoglobin formation, leading to chronic anemia. The objective of this study was to evaluate orofacial complications in thalassemia patients and to detect the blood profile among these patients. Patients and method included a total of 100 th alassemic patients who were enrolled in this study. Oral examination and dental status of each patient was carried out using OHI-simplified. In addition, each patient took a blood investigation (Hb, RBC, MCV, RDW, and ferritin). Result of this study showed that the majority of the patients were female (68%) of which 50 of them had major Thalassemia, with the most frequent age range was between 21-39 years. Patients had statistically higher frequencies of all oral manifestations (p &lt; 0.001 for all). Of which pale mucosa accounted for most frequency, 79%, followed by halitosis 39%, ulceration, brown pigmentation 33%, atrophic glossitis and actinic cheilitis 11%, hypomineralisation 8%, candidiasis and burning sensation 7%, geographic tongue and fissured tongue 6%, angular cheilitis 5%. Besides poor oral hygiene measure was 42%. Also, there was a significant positive correlation between most oral manifestations and blood transfusion. As a conclusion, thalassemia disease is associated with orofacial manifestation, which can adversely affect the oral health status of the patient. Therefore, dentists should understand the complications and management of the disease.

Analysis of miRNAs in Osteogenesis imperfecta Caused by Mutations in COL1A1 and COL1A2: Insights into Molecular Mechanisms and Potential Therapeutic Targets.

Osteogenesis imperfecta (OI) is a group of connective tissue disorders leading to abnormal bone formation, mainly due to mutations in genes encoding collagen type I (Col I). Osteogenesis is regulated by a number of molecules, including microRNAs (miRNAs), indicating their potential as targets for OI therapy. The goal of this study was to identify and analyze the expression profiles of miRNAs involved in bone extracellular matrix (ECM) regulation in patients diagnosed with OI type I caused by mutations in COL1A1 or COL1A2. Primary skin fibroblast cultures were used for DNA purification and sequence analysis, followed by analysis of miRNA expression. Sequencing analysis revealed mutations of the COL1A1 or COL1A2 genes in all OI patients, including four previously unreported. Amongst the 40 miRNAs analyzed, 9 were identified exclusively in OI cells and 26 in both OI patients and the controls. In the latter case, the expression of six miRNAs (hsa-miR-10b-5p, hsa-miR-19a-3p, hsa-miR-19b-3p, has-miR-204-5p, has-miR-216a-5p, and hsa-miR-449a) increased, while four (hsa-miR-129-5p, hsa-miR-199b-5p, hsa-miR-664a-5p, and hsa-miR-30a-5p) decreased significantly in OI cells in comparison to their expression in the control cells. The identified mutations and miRNA expression profiles shed light on the intricate processes governing bone formation and ECM regulation, paving the way for further research and potential therapeutic advancements in OI and other genetic diseases related to bone abnormality management.

Role of Genetics and Surgical Interventions for the Management of Cerebral Cavernous Malformations (CMM).

Cerebral cavernous malformations (CCMs) are comprised of tissue matter within the brain possessing anomalous vascular architecture. In totality, the dilated appearance of the cavernomatakes on a mulberry-like shape contributed by the shape and relation to vascular and capillary elements. Analyzing its pathophysiology along with its molecular and genetic pathways plays a vital role in whether or not a patient receives GKRS, medical management, or Surgery, the most invasive of procedures. To avoid neurological trauma, microsurgical resection of cavernomas canbe guided by the novel clinical application of a 3D Slicer with Sina/MosoCam. When cavernomas present in deep lesions with poor accessibility, gamma knife stereotactic radiosurgery (GKSR) is recommended. For asymptomatic and non-multilobal lesions, medical and symptom management is deemed standard, such as antiepileptic therapy. The two-hit hypothesis serves to explain the mutations in three key genes that are most pertinent to the progression of cavernomas: CCM1/KRIT1, CCM2/Malcavernin, and CCM3/PDCD10. Various exon deletions and frameshift mutations can cause dysfunction in vascular structure through loss and gain of function mutations. MEKK3 and KLF2/4 are involved in a protein kinase signaling cycle that promotes abnormal angiogenesis and cavernoma formation. In terms of potential treatments, RhoKinase inhibitors have shown to decrease endothelial to mesenchymal transition and CCM lesion development in mice models. All in all, understanding the research behind the molecular genetics in CCMs can foster personalized medicine and potentially create new neurosurgical and medicative treatments.