Failure Of Fusion Research Articles

Genital Examination of the Prepubertal Female: Essentials for Pediatric Nurse Practitioners.

Genital Examination of the Prepubertal Female: Essentials for Pediatric Nurse Practitioners.

Delayed Complete Chorioamniotic Membrane Separation in the Third Trimester Following a Motor Vehicle Collision

Complete separation of the amnion and chorion is a rare pregnancy complication. The proposed causes for chorioamniotic separation are failure of fusion,spontaneous separation, and iatrogenically from invasive prenatal pro-cedures. We present the first reported case of delayed complete chorioamniotic separation following a motor vehicle collision. Close fol-low-up with serial fetal ultrasounds resulted in a favorable outcome

An amphipathic helix in Brl1 is required for nuclear pore complex biogenesis in S. cerevisiae.

The nuclear pore complex (NPC) is the central portal for macromolecular exchange between the nucleus and cytoplasm. In all eukaryotes, NPCs assemble into an intact nuclear envelope (NE) during interphase, but the process of NPC biogenesis remains poorly characterized. Furthermore, little is known about how NPC assembly leads to the fusion of the outer and inner NE, and no factors have been identified that could trigger this event. Here, we characterize the transmembrane protein Brl1 as an NPC assembly factor required for NE fusion in budding yeast. Brl1 preferentially associates with NPC assembly intermediates and its depletion halts NPC biogenesis, leading to NE herniations that contain inner and outer ring nucleoporins but lack the cytoplasmic export platform. Furthermore, we identify an essential amphipathic helix in the luminal domain of Brl1 that mediates interactions with lipid bilayers. Mutations in this amphipathic helix lead to NPC assembly defects, and cryo-electron tomography analyses reveal multilayered herniations of the inner nuclear membrane with NPC-like structures at the neck, indicating a failure in NE fusion. Taken together, our results identify a role for Brl1 in NPC assembly and suggest a function of its amphipathic helix in mediating the fusion of the inner and outer nuclear membranes.

CircJag1 promotes apoptosis of ethylene thiourea-exposed anorectal malformations through sponging miR-137-3p by regulating Sox9 and suppressing Wnt/β-catenin pathway during the hindgut development of rat embryos.

Anorectal malformations (ARMs) are common birth defects involving congenital structural anomalies of the gastrointestinal tract. As an important component of non-coding RNAs, circular RNAs (circRNAs) widely participate in the digestive system development; however, the specific molecular mechanism of their involvement in ARM occurrence remains obscure. Herein, we generated rat models of ARMs induced by ethylene thiourea. A novel circRNA (circJag1) was screened and identified by RNA-Seq, which is remarkably upregulated in hindgut tissues of ARM rat embryos. In vivo experiments, colocation analysis via fluorescence in situ hybridization, and immunofluorescence further demonstrated that the disordered circJag1/miR-137-3p/Sox9 expression caused a spatiotemporal imbalance in the urorectal septum (URS) of ARMs. In vitro, functional assays confirmed that circJag1 upregulation resulted in the degradation of nuclear β-catenin, C-myc, and Cyclin D1 in rat intestinal epithelial cells, as well as the promotion of apoptosis and suppression of cell proliferation. Mechanistically, dual-luciferase reporter assay and RNA immunoprecipitation assay indicated that circJag1 acted as a miR-137-3p sponge, thereby inhibiting its repressive effect on its target Sox9. Further experiments showed that a loss of Sox9 abolished the circJag1-mediated increase in apoptosis. In conclusion, aberrantly high circJag1 expression promotes epithelial apoptosis by suppressing the canonical Wnt/β-catenin pathway via the miR-137-3p/Sox9 axis, which leads to fusion failure of the URS and cloacal membrane, and eventually contributed to ARMs. Our achievements might boost the comprehension of ARM pathogenesis and could provide a novel candidate target for the development of therapies for ARMs to complement surgical treatment.

The ORF7a protein of SARS-CoV-2 initiates autophagy and limits autophagosome-lysosome fusion via degradation of SNAP29 to promote virus replication

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1‐mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the SNAP29 protein at aspartic acid residue 30 (D30), ultimately impairing complete autophagy. Importantly, SARS-CoV-2 infection-induced accumulated autophagosomes promote progeny virus production, whereby ORF7a downregulates SNAP29, ultimately resulting in failure of autophagosome fusion with lysosomes to promote viral replication. Taken together, our study reveals a mechanism by which SARS-CoV-2 utilizes the autophagic machinery to facilitate its own propagation via ORF7a.

135 Type 2 Mayer-Rokitansky-Kuster-Hauser syndrome with unicornuate non communicating uterus and cervical hypoplasia: A rare association

Introduction. Faced with primary amenorrhea in a teenage girl with well-developed secondary sexual characteristics, a congenital anatomical defect must be ruled out first. Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) which results from a failure of fusion of the Müllerian ducts in the embryo, resulting in total utero-vaginal agenesis or uterine hypoplasia with partial vaginal atresia in patients with 46, XX karyotype, is a diagnosis to consider.

MTHFR C677T rs1801133 GENE POLYMORPHISM AS A RISK FACTOR FOR NONSYNDROMIC CLEFT PALATE ONLY AMONG DEUTERO MALAY SUB RACE IN INDONESIA

Nonsyndromic cleft palate only (NS CPO) is a congenital malformation that arises from palatal fusion failure process at the seventh week of palatogenesis with a prevalence of 1:1000 live birth worldwide. The MTHFR C677T rs1801133 gene polymorphism is one candidate gene that can be associated with NS CPO. This study aims to determine the risk factor for NS CPO through MTHFR C677T rs1801133 analysis among the Deutero Malay subrace of the Indonesian population. This study was a case-control design, using samples from venous blood of 50 NS CPO subjects and 51 healthy control subjects. After DNA was extracted, followed by PCR, the PCR-RFLPs method was performed using the HinfI restriction enzyme. The Chi-Square test was used with the Kolmogorov Smirnov and Exact Fisher alternatives. The results showed that CT genotype (OR=2,960, p<0.05) of MTHFR C677T rs1801133 gene polymorphism can increase the risk of NS CPO. MTHFR C677T rs1801133 gene polymorphism is a risk factor associated with NS CPO among the Deutero Malay subrace in the Indonesian population.

Complete Sternal Cleft

Background: Sternal cleft is a rare chest wall anomaly with a reported incidence of 1 in 100,000 live births. It results from failure of midline fusion during embryonic development. It can present as an isolated anomaly or be associated with other malformations. The condition is easily diagnosed in a neonate due to the paradoxical movements of the chest. Early surgical repair in the neonatal period is the treatment of choice to improve respiratory dynamics and prevent recurrent respiratory infection with their sequelae. Case Report: We report a case of a neonate who was diagnosed to have absence of sternum at birth due to the mediastinal bulge with paradoxical chest wall movements. The diagnosis was later confirmed on imaging studies and the neonate was successfully managed conservatively and later referred to tertiary centre for surgical repair. Conclusion: Paradoxical movements of the thorax in a newborn should alert the physician towards possibility of sternal cleft.

The Tbx6 Transcription Factor Dorsocross Mediates Dpp Signaling to Regulate Drosophila Thorax Closure

Movement and fusion of separate cell populations are critical for several developmental processes, such as neural tube closure in vertebrates or embryonic dorsal closure and pupal thorax closure in Drosophila. Fusion failure results in an opening or groove on the body surface. Drosophila pupal thorax closure is an established model to investigate the mechanism of tissue closure. Here, we report the identification of T-box transcription factor genes Dorsocross (Doc) as Decapentaplegic (Dpp) targets in the leading edge cells of the notum in the late third instar larval and early pupal stages. Reduction of Doc in the notum region results in a thorax closure defect, similar to that in dpp loss-of-function flies. Nine genes are identified as potential downstream targets of Doc in regulating thorax closure by molecular and genetic screens. Our results reveal a novel function of Doc in Drosophila development. The candidate target genes provide new clues for unravelling the mechanism of collective cell movement.

Bone Fusion Morphology after Circumferential Minimally Invasive Spine Surgery Using Lateral Lumbar Interbody Fusion and Percutaneous Pedicle Screws without Bone Grafting in the Thoracic Spine: A Retrospective Study.

Background and Objectives: This study aimed to investigate the process and morphology of thoracic and lumbosacral bone fusion in patients with adult spinal deformity (ASD) who underwent circumferential minimally invasive spine surgery (CMIS) by lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screws (PPSs) without bone grafting in the thoracic spine and who have risk factors for bone fusion failure in the thoracic spine. Materials and Methods: This retrospective study included 61 patients with spinal deformities (46 women and 15 men) who underwent CMIS with LLIF and PPSs at our hospital after 2016 and completed a 3-year postoperative follow-up. The rate and morphology of bone fusion and rod fracture rate in the thoracic and lumbosacral vertebrae were evaluated. Patients were divided into the thoracic spine spontaneous bone fusion group and the bone fusion failure group. The data of various spinopelvic parameters and the incidence of complications were compared. The vertebral body conditions in the thoracic spine were classified as less degenerative (type N), osteophyte (type O), and diffuse idiopathic skeletal hyperostosis (DISH) (type D). Results: After three postoperative years, the bone fusion rates were 54%, 95%, and 89% for the thoracic, lumbar, and lumbosacral spine, respectively. Screw loosening in the thoracic vertebrae was significantly higher in the bone fusion failure group, while no significant differences were observed in the spinopelvic parameters, Oswestry Disability Index (ODI), and rate of proximal junctional kyphosis and rod fractures. Type N vertebral body condition and screw loosening were identified as risk factors for spontaneous bone fusion failure in the thoracic spine. Conclusion: This study indicated that spontaneous bone fusion is likely to be obtained without screw loosening, and even if bone fusion is not obtained, there is no effect on clinical results with the mid-term (3-year) results of CMIS without bone grafting in the thoracic spine.

Cement discoplasty for managing lumbar spine pseudarthrosis in elderly patients: a less invasive alternative approach for failed posterior lumbar spine interbody fusion.

A retrospective cohort study was performed to evaluate pseudoarthrosis treatment results by injection of cement in disc space of failed fusion in posterior lumbar interbody fusion in patients above 65years. Forty-five patients above 65years with symptomatic pseudarthrosis after lumbar spine fusion were treated by cement injection in the affected disc space. There were 30 females and 15 males. The mean age at the operation was 74 ± 6.5years (range 65-89). Discoplasty was performed after the primary fusion operations after a mean of 14 ± 1.3months (range 12-24). The mean preoperative VAS was 7.5 (range 6-9), and ODI was 36 (range 30-45). Cement injection was done at one level in most of the cases (35 patients). In seven cases, two injection levels were done, and in three cases, three levels. Twenty-three patients had discoplasty only, while 22 had discoplasty and screws change, including 14 cases of extension of the instrumentation. The mean postoperative follow-up was 32 ± 6.5months. The VAS improved to 3.5 (range 2-5) (p = 0.02) and ODI to 12.3 (range 5-35) (p = 0.001). Reoperation was indicated in two (4%) patients by screws loosening. Asymptomatic cement leakage occurred in the paravertebral space in seven cases (15.5%). Cement discoplasty offers a less invasive reliable surgical solution in elderly patients with symptomatic lumbar pseudarthrosis in the elderly patients. In cases with screw loosening, discoplasty should be combined with screw revision.

Double uterus in young women delivered by Caesarean Section: five cases from South Sudan and Ethiopia

Double uterus (uterus didelphys) is the second least common congenital anomaly of the female genital tract resulting from failure of fusion of the two Müllerian ducts during embryological development, leading to duplication of the uterus and the cervix. The condition may be associated with abnormalities of the Wolffian duct such as ipsilateral renal agenesis. Presence of a double uterus increases obstetric complications. We report five cases of young women with uterus didelphys who were delivered by Caesarean Section for obstetric indications.

Revisiting the embryogenesis of lip and palate development.

Clefts of the lip and palate (CLP), the major causes of congenital facial malformation globally, result from failure of fusion of the facial processes during embryogenesis. With a prevalence of 1 in 500-2500live births, CLP causes major morbidity throughout life as a result of problems with facial appearance, feeding, speaking, obstructive apnoea, hearing and social adjustment and requires complex, multi-disciplinary care at considerable cost to healthcare systems worldwide. Long-term outcomes for affected individuals include increased mortality compared with their unaffected siblings. The frequent occurrence and major healthcare burden imposed by CLP highlight the importance of dissecting the molecular mechanisms driving facial development. Identification of the genetic mutations underlying syndromic forms of CLP, where CLP occurs in association with non-cleft clinical features, allied to developmental studies using appropriate animal models is central to our understanding of the molecular events underlying development of the lip and palate and, ultimately, how these are disturbed in CLP.

Prevalence of os acromiale in an indigenous East African population: a computerized tomography scan-based study

Background: Failure of fusion to any of the acromion physes at maturity may lead to an os acromiale. A radiological review into the prevalence of os acromiale in an indigenous East African population was performed using computer tomography (CT) imaging. The study aimed to demonstrate a lower prevalence of os acromiale in an urban population compared with cadaveric studies.
 Methods: This was a cross-sectional study with consecutive sampling. CT scans of both shoulders obtained for non-shoulder pathology were used for the analysis. CT scanning was performed at a tertiary referral hospital from January 2019 to July 2020.
 Results: Nine hundred eighty-two CT studies were eligible for the review. There were148 os acromiale identified that were either pre-acromiale or meso-acromiale. The study found a 15% prevalence of os acromiale among an ethnic East African population, of which almost 40% were meso-acromiale and 60% were pre-acromiale, with no meta-acromiale.
 Conclusion: The prevalence of os acromiale found in this study is similar to that observed in earlier cadaveric studies.
 

Complication Avoidance in Surgical Management of Vertebral Column Tumors

The surgical management of spinal tumors has grown increasingly complex as treatment algorithms for both primary bone tumors of the spine and metastatic spinal disease have evolved in response to novel surgical techniques, rising complication rates, and additional data concerning adjunct therapies. In this review, we discuss actionable interventions for improved patient safety in the operative care for spinal tumors. Strategies for complication avoidance in the preoperative, intraoperative, and postoperative settings are discussed for approach-related morbidities, intraoperative hemorrhage, wound healing complications, cerebrospinal fluid (CSF) leak, thromboembolism, and failure of instrumentation and fusion. These strategies center on themes such as pre-operative imaging review and medical optimization, surgical dissection informed by meticulous attention to anatomic boundaries, and fastidious wound closure followed by thorough post-operative care.

Comparison of Unilateral Versus Bilateral Lateral Rectus Recession for Small Angle Intermittent Exotropia: Outcomes and Surgical Dose-Responses.

To compare the surgical outcomes of unilateral lateral rectus recession to bilateral lateral rectus recession for small angle intermittent exotropia. This was a retrospective cohort study of pediatric patients with an intermittent exotropia between 16 and 20 prism diopters (PD) who underwent unilateral lateral rectus recession or bilateral lateral rectus recession at a single tertiary care pediatric hospital. The primary outcome was success (exotropia < 10 PD of esotropia < 5 PD, no decrease in stereopsis > 0.6 log arcsec, and no reoperation) at 12 months postoperatively. Secondary outcomes included survival analysis of time to surgical failure, surgical dose-response, and improvement in central fusion or stereopsis. At 12 months, successful outcomes were achieved in 13 of 27 patients (46%) in the bilateral lateral rectus recession group and 19 of 28 patients (70%) in the unilateral lateral rectus recession group, which was not a statistically significant difference (P = .10). Survival analysis showed a trend toward a higher rate of failure in the bilateral lateral rectus recession group compared to the unilateral lateral rectus recession group (P = .04). The mean surgical dose-response was 1.7 PD/mm at 1 week and 1.0 PD/mm at 12 months for the bilateral lateral rectus recession group, and 2.0 PD/mm at 1 week postoperatively and 1.4 PD/mm at 12 months postoperatively for the unilateral lateral rectus recession group. There were no cases of long-term postoperative lateral incomitance in either group. Unilateral lateral rectus recession and bilateral lateral rectus recession have similar success rates for small angle intermittent exotropia after at least 12 months of follow-up. Randomized controlled trials in surgical management of intermittent exotropia should consider unilateral lateral rectus recession as a treatment arm. [J Pediatr Ophthalmol Strabismus. 2022;59(5):350-355.].

Extended spinal dysraphism: Rachischisis or myeloschisis

Myeloschisis (rachischisis) is a rare congenital malformation linked to incomplete development of the spine and characterized by posterior opening of the vertebrae [1,2]. It is spread over more than one floor or even the entire spine and incompatible with life. Its diagnosis is clinical, confirmed by ultrasound and cross-sectional imaging [2]. This anomaly in its thoracic location is rare. There are two types: Segmentation and development defects [4]. Developmental defects include hemi vertebrae and failure of neural tube fusion which in turn includes the simple cleft of the posterior arch of the vertebrae (spina bifida) [3]. It can involve one or more vertebral arches, determining extensive spinal dysraphism. Certain factors favor their appearance. According to the literature, only one article published in 1972 by Levy et al, which reported an incidence of 0.01% of thoracic spina bifida [3]. We report the case of a 33-day-old female infant born at term in breech presentation, with a pregnancy that was not well followed. There was a notion of taking fenugreek during pregnancy. Hospitalized for meningitis, with a dysmorphic face, clinically presented a dorsolumbar spina bifida (Figure 1). She had received antibiotic therapy and regular dressings since her admission. A cerebral-medullary scan was performed and showed a progressive opening of the spinous processes from the cervical and dorsal spine, more marked at the height of the spinous process of the fourth dorsal vertebra to distality, with issue of meningeal structures and spinal cord. Conflicts of interest: The authors declare that they have no conflicts of interest.

Early Results and Patient-Reported Outcome Measures (PROMS) of an Intraosseous Device for Arthrodesis of the First Tarso-Metatarsal (TMT) Joint.

We describe a new surgical technique for arthrodesis of the first tarso-metatarsal (TMT) joint using an intraosseous fixation device and the early results including patient-reported outcome measures (PROMS). Seventeen consecutive procedures with this method were included. Indication for surgery was hallux valgus. The average age was 42years (range 26-65). PROMS were collected and the patients were asked to fill out a satisfaction questionnaire. A retrospective review of radiographs and electronic medical notes was conducted. Overall fusion rate was 94%. Complications included a case of failed fusion, a superficial wound infection and a deep vein thrombosis (DVT). At a mean follow-up of 24months (range 10-38) radiographic results demonstrated significant improvement in the intermetatarsal angle or IMA (11.7 ± 2.8 degrees to 6.9 ± 2.4 degrees, P < 0.001) and hallux valgus angle or HVA (28.1 ± 7.3 degrees to 12.2 ± 4.3 degrees, P < 0.001). The mean visual analog scale (VAS) score improved significantly from a mean of 7.6 (SD 0.85) preoperatively, to a mean of 2.1 (SD 1.83) post-operatively (P < 0.0001). The Manchester-Oxford Foot Questionnaire (MOXFQ) significantly improved from a mean of 35.8 (SD 10.2), to a mean of 9.2 (SD 17) (P < 0.0001). The final result was satisfactory for 88% of the patients. The early results show intraosseous fixation to be a safe and efficient method for the fusion of the first TMT joint providing good patient satisfaction.

Deletion of the initial methionine codon of the Tmem95 gene causes subfertility, but not complete infertility, in male mice.

Dear Editor,In mammals, sperm izumo sperm-egg fusion 1 (IZUMO1) and oocyte IZUMO1 receptor (JUNO) interaction plays a pivotal role in the recognition of gametes prior to membrane fusion through multiple intermolecular reactions [1–3]. Although many of the factors involved in gamete fusion have recently been identified, their specific contributions remain largely unknown [1]. Among them, transmembrane protein 95 (TMEM95) was initially identified as a responsible gene for male subfertility in Fleckvieh bulls by a genome-wide association study [4, 5]. Furthermore, in 2020, two research teams reported that CRISPR/Cas9-mediated Tmem95 disruption caused complete sterility in male mice due to gamete fusion failure [6, 7]. In order to analyze the phenotype, we newly produced a TMEM95 knockout mouse line. We designed a single guide RNA to target the initial methionine codon for the Tmem95 gene since this gene has some alternative splicing...

Revision First Metatarsophalangeal Joint Fusion for Non-Union, Implant Failures, and Failed Hallux Valgus Correction: Does the Indication Matter?

Category:Midfoot/Forefoot; BunionIntroduction/Purpose:The most common indications for revision of 1st Metatarsophalangeal (MTP) joint surgery are symptomatic failures of prior fusion, failed hallux valgus correction, and failed MTP arthroplasty implants. The outcome of revision 1st MTP fusion has rarely been studied. The purpose of this study was to compare the clinical, radiographic, and patient-reported outcomes of revision MTP fusion for different indications.Methods:A retrospective chart review was performed for patients who underwent revision 1st MTP fusion between January 2015 and December 2019 in a single-center, by 4 fellowship-trained foot and ankle surgeons. The complication, revision, and non- union rates as well as VAS and PROMIS scores and pre-operative and post-operative radiographs were analyzed and compared between the different indication groups. Univariate and multivariate analysis and logistic regression models were used to obtain odds ratio of the explanatory variables for outcome measures.Results:A total of 79 cases of revision MTP fusion were included. Thirty-eight cases of hallux valgus corrections salvage, 22 failed MTP arthroplasty implants, 6 failed polyvinyl alcohol hydrogel implants, 13 prior MTP fusion non-unions. The mean follow-up time was 350 days (Median 226, SD 306). Seven cases (8.9%) required structural iliac-crest bone graft during the revision. Seven cases (8.9%) required allograft augmentation. The overall complication rate was 40.7%. Fifteen patients (18.5%) were classified as Clavien-Dindo grade 3, which represents a complication that may require a revision surgery (i.e. non-union, deep infection, loss of correction). Eventually, 7 cases (8.9%) underwent further revision surgery. The logistic regression model demonstrated that indication for revision was not significantly related to union rate (p=0.280). Visual-Analogue-Scale significantly improved at 6 weeks, 3 months, and at last follow-up in all indications for revision (p=0.001). PROMIS-10 Physical and PROMIS-10 Mental did not change significantly during follow-up (p=0.860, p=0.589).Conclusion:Treatment of 1st MTP joint surgery failures is a clinical challenge in orthopaedic surgery. In our study, revision of 1st MTP joint surgery with MTP fusion had higher non-union rates and higher overall complication rates compared to primary 1st MTP fusion. Nevertheless, revision rates remained comparable to primary 1st MTP fusion. Complication rates and patient- reported outcomes were similar between the different indications for revision groups. Visual-analogue-scale improved significantly during follow-up in all groups. Diabetes mellitus had a significant impact on non-union rates and overall complication rates.