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Journal of Indian Association of... 2023Diphallia (penile duplication) is a rare congenital malformation with an incidence of about 1 per 5-6 million newborns. The severity of diphallia varies from a small...
Diphallia (penile duplication) is a rare congenital malformation with an incidence of about 1 per 5-6 million newborns. The severity of diphallia varies from a small accessory penile-like tissue to complete true penile duplication with other deformities, usually involving the urogenital, gastrointestinal, and musculoskeletal systems. Pseudodiphallia, as a rare kind of diphallia, is characterized by a small accessory penile-like tissue without a normal penile anatomy structure. A 5.5-year-old male child was brought to the pediatric surgery outpatient department by the parents with complaint of difficulty in retracting the prepucial foreskin and the presence of some growth near the glans. There were no other complaints in specific. Clinical examination revealed foreskin retractable with difficulty and small conical lump smaller than the original glans approximately size ~1 cm diameter at the base attached horizontally at the left side of the original glans at the coronal sulcus and visible incomplete clefting in between the 2 glans visible from the aerial view. After approval from anesthetist, the patient was operated under general anesthesia by excision of pseudodiphallia. Urethral catheterization and circumcision of the penis after taking informed parental consent. Postoperatively, the period was uneventful. The patient responded well to the symptomatic treatment and was orally allowed on the same day evening. Urinary catheter was removed on 5 postoperative day. The patient was discharged on oral symptomatic medication and was advice for follow-up.
PubMed: 38173637
DOI: 10.4103/jiaps.jiaps_30_23 -
IScience Jul 2023Collagen XII, belonging to the fibril-associated collagens, is a homotrimeric secreted extracellular matrix (ECM) protein encoded by the gene. Mutations in the human...
Collagen XII, belonging to the fibril-associated collagens, is a homotrimeric secreted extracellular matrix (ECM) protein encoded by the gene. Mutations in the human gene cause an Ehlers-Danlos/myopathy overlap syndrome leading to skeletal abnormalities and muscle weakness. Here, we studied the role of collagen XII in joint pathophysiology by analyzing collagen XII deficient mice and human patients. We found that collagen XII is widely expressed across multiple connective tissue of the developing joint. Lack of collagen XII in mice destabilizes tendons and the femoral trochlear groove to induce patellar subluxation in the patellofemoral joint. These changes are associated with an ECM damage response in tendon and secondary quadriceps muscle degeneration. Moreover, patellar subluxation was also identified as a clinical feature of human patients with collagen XII deficiency. The results provide an explanation for joint hyperlaxity in mice and human patients with collagen XII deficiency.
PubMed: 37485359
DOI: 10.1016/j.isci.2023.107225 -
Cell Death & Disease Aug 2023Peptidylarginine deiminase (PADI) 2 catalyzes the post-translational conversion of peptidyl-arginine to peptidyl-citrulline in a process called citrullination. However,...
Peptidylarginine deiminase (PADI) 2 catalyzes the post-translational conversion of peptidyl-arginine to peptidyl-citrulline in a process called citrullination. However, the precise functions of PADI2 in bone formation and homeostasis remain unknown. In this study, our objective was to elucidate the function and regulatory mechanisms of PADI2 in bone formation employing global and osteoblast-specific Padi2 knockout mice. Our findings demonstrate that Padi2 deficiency leads to the loss of bone mass and results in a cleidocranial dysplasia (CCD) phenotype with delayed calvarial ossification and clavicular hypoplasia, due to impaired osteoblast differentiation. Mechanistically, Padi2 depletion significantly reduces RUNX2 levels, as PADI2-dependent stabilization of RUNX2 protected it from ubiquitin-proteasomal degradation. Furthermore, we discovered that PADI2 binds to RUNX2 and citrullinates it, and identified ten PADI2-induced citrullination sites on RUNX2 through high-resolution LC-MS/MS analysis. Among these ten citrullination sites, the R381 mutation in mouse RUNX2 isoform 1 considerably reduces RUNX2 levels, underscoring the critical role of citrullination at this residue in maintaining RUNX2 protein stability. In conclusion, these results indicate that PADI2 plays a distinct role in bone formation and osteoblast differentiation by safeguarding RUNX2 against proteasomal degradation. In addition, we demonstrate that the loss-of-function of PADI2 is associated with CCD, thereby providing a new target for the treatment of bone diseases.
Topics: Animals; Mice; Citrullination; Osteogenesis; Chromatography, Liquid; Core Binding Factor Alpha 1 Subunit; Tandem Mass Spectrometry; Cleidocranial Dysplasia; Mice, Knockout
PubMed: 37648716
DOI: 10.1038/s41419-023-06101-7 -
The Indian Journal of Radiology &... Apr 2024Vascular complications in athletes are common and mimic musculoskeletal injuries such as muscle sprains, fractures, and cartilage abnormalities. They include traumatic... (Review)
Review
Vascular complications in athletes are common and mimic musculoskeletal injuries such as muscle sprains, fractures, and cartilage abnormalities. They include traumatic vascular injuries and more subtle pathologies like entrapment syndromes, pseudoaneurysms, arterial occlusions, and venous thrombosis. Such vascular complications may be occult on imaging and can be difficult for a musculoskeletal radiologist to diagnose, resulting in a lack of timely diagnosis and potentially limb-threatening consequences. Although the final diagnosis may require multidisciplinary input from orthopaedic, sports and exercise medicine, and vascular and interventional radiology inputs, a musculoskeletal radiologist with prior knowledge of such conditions can be the first to diagnose such conditions aiding the athlete's performance. A musculoskeletal radiologist should pay due attention to anatomical courses of vascular channels and look for potential causes of vascular compression, aberrant myotendinous bands, accessory muscles, etc., before concluding a computed tomography (CT) or magnetic resonance imaging (MRI) as normal. Doppler ultrasound, CT, or MR angiography are commonly employed techniques for primary evaluation, whereas digital subtraction angiography is generally reserved for troubleshooting as advanced dynamic imaging.
PubMed: 38549894
DOI: 10.1055/s-0043-1777014 -
BMC Medical Genomics Oct 2023Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of...
BACKGROUND
Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of prenatal WES and to investigate the pathogenic variants in structurally abnormal fetuses.
METHODS
We recruited 144 fetuses with structural anomalies between 14 and 2020 and 15 December 2021 in the study. Genetic screening was performed by WES combined with karyotyping and chromosomal microarray analysis. The molecular diagnostic yield of prenatal WES for each type of fetal structural anomaly and the identified pathogenic genes and mutations were reported.
RESULTS
In this study, we retrospectively analyzed the clinical and genetic data of 145 structurally anomalous fetuses. These cases were classified into 9 phenotypic classes based on antenatal ultrasound findings. Thirty-eight pathogenic variants in 24 genes were identified in 35 of the 145 cases, including 14 novel variants in 13 genes (EP300, MYH3, TSC2, MMP9, CPLANE1, INVS, COL1A1, EYA1, TTC21B, MKS1, COL11A2, PDHA1 and L1CAM). Five additional pathogenic variants were classified as incidental findings. Our study showed that the overall diagnosis rate of WES was 28.1% (27/96) in the parent-fetus trio cases and 16.3% (8/49) in the proband-only cases. Fetuses with musculoskeletal anomalies had the highest diagnostic yield (51.4%, 19/37). In addition, FGFR3 and COL1A1 were the most common pathogenic genes.
CONCLUSIONS
Our work expands the mutation spectrum of the genes associated with fetal structural anomalies and provides valuable information for future parental genetic counselling and pregnancy management of the structurally anomalous fetuses.
Topics: Female; Humans; Pregnancy; East Asian People; Exome Sequencing; Fetus; Pregnancy Trimester, First; Prenatal Diagnosis; Retrospective Studies; Ultrasonography, Prenatal; Congenital Abnormalities
PubMed: 37880672
DOI: 10.1186/s12920-023-01697-3 -
The Yale Journal of Biology and Medicine Jun 2024Joint hypermobility syndromes, particularly chronic pain associated with this condition, including Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum... (Review)
Review
Chronic Pain and Joint Hypermobility: A Brief Diagnostic Review for Clinicians and the Potential Application of Infrared Thermography in Screening Hypermobile Inflamed Joints.
Joint hypermobility syndromes, particularly chronic pain associated with this condition, including Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD), present diagnostic challenges due to their multifactorial origins and remain poorly understood from biomechanical and genomic-molecular perspectives. Recent diagnostic guidelines have differentiated hEDS, HSD, and benign joint hypermobility, providing a more objective diagnostic framework. However, incorrect diagnoses and underdiagnoses persist, leading to prolonged journeys for affected individuals. Musculoskeletal manifestations, chronic pain, dysautonomia, and gastrointestinal symptoms illustrate the multifactorial impact of these conditions, affecting both the physical and emotional well-being of affected individuals. Infrared thermography (IRT) emerges as a promising tool for joint assessment, especially in detecting inflammatory processes. Thermal distribution patterns offer valuable insights into joint dysfunctions, although the direct correlation between pain and inflammation remains challenging. The prevalence of neuropathies among hypermobile individuals accentuates the discordance between pain perception and thermographic findings, further complicating diagnosis and management. Despite its potential, the clinical integration of IRT faces challenges, with conflicting evidence hindering its adoption. However, studies demonstrate objective temperature disparities between healthy and diseased joints, especially under dynamic thermography, suggesting its potential utility in clinical practice. Future research focused on refining diagnostic criteria and elucidating the underlying mechanisms of hypermobility syndromes will be essential to improve diagnostic accuracy and enhance patient care in this complex and multidimensional context.
Topics: Humans; Thermography; Joint Instability; Chronic Pain; Ehlers-Danlos Syndrome; Inflammation; Infrared Rays
PubMed: 38947102
DOI: 10.59249/WGRS1619 -
EBioMedicine Sep 2023Hip minimum joint space width (mJSW) provides a proxy for cartilage thickness. This study aimed to conduct a genome-wide association study (GWAS) of mJSW to (i) identify... (Meta-Analysis)
Meta-Analysis
The identification of distinct protective and susceptibility mechanisms for hip osteoarthritis: findings from a genome-wide association study meta-analysis of minimum joint space width and Mendelian randomisation cluster analyses.
BACKGROUND
Hip minimum joint space width (mJSW) provides a proxy for cartilage thickness. This study aimed to conduct a genome-wide association study (GWAS) of mJSW to (i) identify new genetic determinants of mJSW and (ii) identify which mJSW loci convey hip osteoarthritis (HOA) risk and would therefore be of therapeutic interest.
METHODS
GWAS meta-analysis of hip mJSW derived from plain X-rays and DXA was performed, stratified by sex and adjusted for age and ancestry principal components. Mendelian randomisation (MR) and cluster analyses were used to examine causal effect of mJSW on HOA.
FINDINGS
50,745 individuals were included in the meta-analysis. 42 SNPs, which mapped to 39 loci, were identified. Mendelian randomisation (MR) revealed little evidence of a causal effect of mJSW on HOA (OR 0.98 [95% CI 0.82-1.18]). However, MR-Clust analysis suggested the null MR estimates reflected the net effect of two distinct causal mechanisms cancelling each other out, one of which was protective, whereas the other increased HOA susceptibility. For the latter mechanism, all loci were positively associated with height, suggesting mechanisms leading to greater height and mJSW increase the risk of HOA in later life.
INTERPRETATIONS
One group of mJSW loci reduce HOA risk via increased mJSW, suggesting possible utility as targets for chondroprotective therapies. The second group of mJSW loci increased HOA risk, despite increasing mJSW, but were also positively related to height, suggesting they contribute to HOA risk via a growth-related mechanism.
FUNDING
Primarily funded by the Medical Research Council and Wellcome Trust.
Topics: Humans; Genome-Wide Association Study; Osteoarthritis, Hip; Joints; Cluster Analysis; Mendelian Randomization Analysis
PubMed: 37619450
DOI: 10.1016/j.ebiom.2023.104759 -
Foot (Edinburgh, Scotland) Jun 2024The adult cavus foot represents a challenging clinical problem, with varied aetiology and complex, 3-dimensional deformities. Thus far, the cavus foot has eluded a... (Review)
Review
AIMS
The adult cavus foot represents a challenging clinical problem, with varied aetiology and complex, 3-dimensional deformities. Thus far, the cavus foot has eluded a unified classification. The aim of this paper was to appraise the literature to identify classification systems which guide the operative management of neurological cavus feet in adults.
METHODS
As the aim of this paper was broad, a scoping review was conducted. The review was conducted in line with published frameworks. Our principal research question was 'what classification systems that guide surgical management currently exist for neurological cavus feet in adults'. We searched CINAHL, Embase, OVID, Proquest, Pubmed, Scopus and Web of Science databases using MESH and non-MESH terms. Two authors independently reviewed abstracts / papers and a data extraction sheet was used to collect the relevant data.
RESULTS
A total of 1140 articles were initially screened, identifying 125 articles for which a full text review was performed. Only three articles met all our inclusion criteria. All these articles reported an anatomical classification with suggestions for treatment based on the classification. All were considered to comprise Level V evidence, and none reported outcomes of treatment based on the classification.
CONCLUSIONS
There is currently a paucity of robust classifications to guide treatment in neurological cavus feet in adults. The few classifications systems that exist are varied and do not as yet have sufficient evidence to support their widespread use. Further work is required, aimed at identifying specific features of cavus feet that would guide operative treatment.
Topics: Humans; Adult; Talipes Cavus
PubMed: 38678805
DOI: 10.1016/j.foot.2024.102098 -
Journal of Applied Biomechanics Oct 2023In this review, we elaborate on how musculoskeletal (MSK) modeling combined with dynamic movement simulation is gradually evolving from a research tool to a promising in... (Review)
Review
In this review, we elaborate on how musculoskeletal (MSK) modeling combined with dynamic movement simulation is gradually evolving from a research tool to a promising in silico tool to assist medical doctors and physical therapists in decision making by providing parameters relating to dynamic MSK function and loading. This review primarily focuses on our own and related work to illustrate the framework and the interpretation of MSK model-based parameters in patients with 3 different conditions, that is, degenerative joint disease, cerebral palsy, and adult spinal deformities. By selecting these 3 clinical applications, we also aim to demonstrate the differing levels of clinical readiness of the different simulation frameworks introducing in silico model-based biomarkers of motor function to inform MSK rehabilitation and treatment, with the application for adult spinal deformities being the most recent of the 3. Based on these applications, barriers to clinical integration and positioning of these in silico technologies within standard clinical practice are discussed in the light of specific challenges related to model assumptions, required level of complexity and personalization, and clinical implementation.
PubMed: 37348849
DOI: 10.1123/jab.2023-0029