Prediction of joint moments from kinematics using machine learning in children with congenital talipes equino varus and typically developing peers.

Background: Understanding joint loading and the crucial role of joint moments is essential for developing treatment strategies in gait analysis, which often requires the precise estimation of joint moments through an inverse dynamic approach. This process necessitates the use of a force plate synchronized with a motion capture system. However, effectively capturing ground reaction force in typically developing (TD) children and those with congenital talipes equino varus (CTEV) presents challenges, while the availability and high cost of additional force plates pose additional challenges. Therefore the study aimed to develop, train, and identify the most effective machine learning (ML) model to predict joint moments from kinematics for TD children and those with CTEV. Method: In a study at the Gait Lab, 13 children with bilateral CTEV and 17 TD children underwent gait analysis to measure kinematics and kinetics, using a 12-camera Qualisys Motion Capture System and an AMTI force plate. ML models were then trained to predict joint moments from kinematic data as input. Results: The random forest regressor and deep neural networks (DNN) proved most effective in predicting joint moments from kinematics for TD children, yielding better results. The Random Forest regressor achieved an average r of 0.75 and nRMSE of 23.03 % for TD children, and r of 0.74 and 23.82 % for CTEV. DNN achieved an average r of 0.75 and nRMSE of 22.83 % for TD children, and r of 0.76 and nRMSE of 23.9 % for CTEV. Conclusions: The findings suggest that using machine learning to predict joint moments from kinematics shows moderate potential as an alternative to traditional gait analysis methods for both TD children and those with CTEV. Despite its potential, the current prediction accuracy limitations hinder the immediate clinical application of these techniques for decision-making in a pediatric population.

Branched flows of flexural elastic waves in non-uniform cylindrical shells.

Propagation of elastic waves along the axis of cylindrical shells is of great current interest due to their ubiquitous presence and technological importance. Geometric imperfections and spatial variations of properties are inevitable in such structures. Here we report the existence of branched flows of flexural waves in such waveguides. The location of high amplitude motion, away from the launch location, scales as a power law with respect to the variance, and linearly with respect to the correlation length of the spatial variation in the bending stiffness. These scaling laws are then theoretically derived from the ray equations. Numerical integration of the ray equations also exhibit this behaviour-consistent with finite element numerical simulations as well as the theoretically derived scaling. There appears to be a universality for the exponents in the scaling with respect to similar observations in the past for waves in other physical contexts, as well as dispersive flexural waves in elastic plates.

Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis.

Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture is a key determinant of pathogenetic ECM structure-function in human fibrosis (Jones et al., 2018). Here, through human tissue, bioinformatic and ex vivo studies we provide evidence that hypoxia-inducible factor (HIF) pathway activation is a critical pathway for this process regardless of the oxygen status (pseudohypoxia). Whilst TGFß increased the rate of fibrillar collagen synthesis, HIF pathway activation was required to dysregulate post-translational modification of fibrillar collagen, promoting pyridinoline cross-linking, altering collagen nanostructure, and increasing tissue stiffness. In vitro, knockdown of Factor Inhibiting HIF (FIH), which modulates HIF activity, or oxidative stress caused pseudohypoxic HIF activation in the normal fibroblasts. By contrast, endogenous FIH activity was reduced in fibroblasts from patients with lung fibrosis in association with significantly increased normoxic HIF pathway activation. In human lung fibrosis tissue, HIF-mediated signalling was increased at sites of active fibrogenesis whilst subpopulations of human lung fibrosis mesenchymal cells had increases in both HIF and oxidative stress scores. Our data demonstrate that oxidative stress can drive pseudohypoxic HIF pathway activation which is a critical regulator of pathogenetic collagen structure-function in fibrosis.

Impact of COVID Pandemic on the Children with Cerebral Palsy.

Background: The COVID pandemic has been raging across the world for the past 18 months and has severely impacted healthcare and resources. Children with special needs have been adversely affected by the COVID pandemic, due to lack of formal schooling, access to rehabilitation and limited physical and social activity. The aim of this online survey was to understand the effect of the pandemic on the children with Cerebral Palsy (CP). Methods: An online survey was conducted using a nine parts questionnaire comprising 26 questions. Survey included questions pertaining to demographic data, ambulatory status, lack of access to physiotherapy, orthotic adjustment, surgery, deterioration of function, and behaviour. A simple binary answer was sought to cover all social strata of society. Results: Responses were received from 101 caregivers who participated in an online questionnaire. 25.7% had no therapy sessions, 74.2% were on therapy of which 23.7% had online sessions. The lockdown restrictions coupled with lack of rehabilitation and orthotic support led to deterioration in physical function in 54 children and worsening of deformity in 34. Changes in behavioural pattern was observed in 45 children. Conclusion: The survey revealed major disruptions in the care of Children with CP. The parents reported difficulties in managing the child therapy at home. There is always a possibility that the pandemic will result in a lockdown again, and hence our approach toward physical therapy assessment and rehabilitation needs to be towards home-based and family-centred care.

3D Printing of Functionally Graded Films by Controlling Process Parameters.

Scaffolds are often used in bioengineering to replace damaged tissues. They promote cell ingrowth and provide mechanical support until cells regenerate. Such scaffolds are often made using the additive manufacturing process, given its ability to create complex shapes, affordability, and the potential for patient-specific solutions. The success of the implant is closely related to the match of the scaffold mechanical properties to those of the host tissue. Many biological tissues show properties that vary in space. Therefore, the aim is to manufacture materials with variable properties, commonly referred to as functionally graded materials. Here we present a novel technique used to manufacture porous films with functionally graded properties using 3D printers. Such an approach exploits the control of a process parameter, without any hardware modification. The mechanical properties of the manufactured films have been experimentally tested and analytically characterized.

"Video Technique on Clinical Tests for DDH": New-Born to Walking Age.

INTRODUCTION: The early diagnosis of developmental Dysplasia of Hip (DDH) remains elusive. In the absence of symptoms, early signs need heightened awareness and an astute clinical examination. CLINICAL TESTS: Every newborn child must be examined for hip instability by the Barlow and Ortolani tests. Periodic examination of the lower limbs for limb length discrepancy, restricted hip abduction, thigh or gluteal crease asymmetry must alert the examiner to rule out hip dysplasia. In a walking child with unilateral DDH the limp is obvious, and the Trendelenburg sign is positive. In bilateral DDH, limitation of hip abduction and waddling gait with increased lumbar lordosis are the only early discernible signs. Often the care-giver or parents notice the subtle changes of limb asymmetry and bring to the notice of the primary care doctors. These early signs must not be ignored to prevent late presenting DDH. CONCLUSION: This article highlights the signs of DDH that every clinician dealing with children must be well-versed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43465-021-00528-w.

Hierarchical porosity in additively manufactured bioengineering scaffolds: Fabrication & characterisation.

Biomedical scaffolds with a high degree of porosity are known to facilitate the growth of healthy functioning tissues. In this study, scaffolds with hierarchical porosity are manufactured and their mechanical and thermal properties are characterised. Multi-scale porosity is achieved in scaffolds fabricated by Fused Deposition Modelling (FDM) in a novel way. Random intrinsic porosity at micron length scale obtained from particulate leaching is combined with the structured extrinsic porosity at millimeter length scales afforded by controlling the spacing between the struts. Polylactic acid (PLA) is blended with Polyvinyl alcohol (PVA) and an inorganic sacrificial phase, sodium chloride (NaCl), to produce pores at length scales of up to two orders of magnitude smaller than the inter-filament voids within 3D printed lattices. The specific elastic modulus and specific strength are maximised by optimising the polymer blends. The porosity level and pore size distribution of the foamy filaments within lattices are quantified statistically. Compression tests are performed on the porous samples and the observed mechanical response is attributed to the microstructure and density. Simple cellular solid models that possess power law are used to explain the measured trends and the dependence is associated with various mechanisms of elastic deformation of the cell walls. The relationship between pore architecture, pore connectivity, the blend material composition, and mechanical response of produced foams is brought out. Foams obtained using the PLA:PVA:NaCl 42%-18%-40% material blends show relatively high specific elastic modulus, specific strength and strain at failure. A quadratic power law relating the Young's modulus with the relative density is experimentally obtained, which is consistent with theoretical models for open-cell foams. 3D printing with blends, followed by leaching, produces structures with cumulative intrinsic and extrinsic porosity as high as 80%, in addition to good mechanical integrity.

Results of Rodding and Impact on Ambulation and Refracture in Osteogenesis Imperfecta: Study of 21 Children.

INTRODUCTION: Delay in presentation and surgical intervention is quite usual in osteogenesis imperfecta (OI) because of various local and cultural beliefs. The purpose of this study is to review the results of 21 children who had intramedullary rodding and its effect on ambulation and refracture. METHODS: We reviewed 21 children with a clinical diagnosis of OI. The mean age of children at presentation was 8.74 years (3-21 years). All children had recurrent fractures of long bones. Twenty eight femurs and 21 tibiae were stabilized with intramedullary rodding. Ambulatory status was assessed by the Hoffers and Bullock's (H and B) grading, and muscle power was recorded using the Medical Research Council, U. K., grade. Ten children had received intravenous bisphosphonates preoperatively. Postoperatively, the children were assessed for ambulatory status, pain, and ability for independent self-care. RESULTS: The mean followup period was 34 months (24-48 months). Rush rods were used in 20 femurs, the Fassier-Duval (FD) rods in 6 femurs, and in two cases, with narrow intramedullary canals, Kirshner (K) wires were used. For the tibiae, 15 children received rush rods and in 6 cases, an FD rod was used. The mean time to fracture union was 8 weeks (6-12 weeks). Before surgery, 13 children were in H and B Grade 4 (wheel-chair independent or carried by parents usually in a developing country), four were able to ambulate with a walking aid (H and B Grade 3b), and four children were able to walk about in the house without aids (H & B Grade 2). After the rodding procedure, the ambulatoty status improved in 11 (50%) children. Seven children (33%) became household physiologic walkers (H & B Grade 3b), three achieved independent ambulation with orthosis (H & B Grade 1b), and one child with mild OI could walk unaided (H & B Grade 1a). No child had deterioration in ambulatory status. Only two children had refractures at the distal end of the rod due to continual growth of bones. CONCLUSIONS: Intramedullary rodding treatment for recurrent fractures in children with OI improves their mobility potential. It also and prevents repeated cast application, disuse wasting, and osteopenia which can lead to deterioration in the quality of the long bones.

Nanoscale dysregulation of collagen structure-function disrupts mechano-homeostasis and mediates pulmonary fibrosis.

Matrix stiffening with downstream activation of mechanosensitive pathways is strongly implicated in progressive fibrosis; however, pathologic changes in extracellular matrix (ECM) that initiate mechano-homeostasis dysregulation are not defined in human disease. By integrated multiscale biomechanical and biological analyses of idiopathic pulmonary fibrosis lung tissue, we identify that increased tissue stiffness is a function of dysregulated post-translational collagen cross-linking rather than any collagen concentration increase whilst at the nanometre-scale collagen fibrils are structurally and functionally abnormal with increased stiffness, reduced swelling ratio, and reduced diameter. In ex vivo and animal models of lung fibrosis, dual inhibition of lysyl oxidase-like (LOXL) 2 and LOXL3 was sufficient to normalise collagen fibrillogenesis, reduce tissue stiffness, and improve lung function in vivo. Thus, in human fibrosis, altered collagen architecture is a key determinant of abnormal ECM structure-function, and inhibition of pyridinoline cross-linking can maintain mechano-homeostasis to limit the self-sustaining effects of ECM on progressive fibrosis.

Ex-vivo models of the Retinal Pigment Epithelium (RPE) in long-term culture faithfully recapitulate key structural and physiological features of native RPE.

The Retinal Pigment Epithelium (RPE) forms the primary site of pathology in several blinding retinopathies. RPE cultures are being continuously refined so that dynamic disease processes in this important monolayer can be faithfully studied outside the eye over longer periods. The RPE substrate, which mimics the supportive Bruch's membrane (BrM), plays a key role in determining how well in-vitro cultures recapitulate native RPE cells. Here, we evaluate how two different types of BrM substrates; (1) a commercially-available polyester transwell membrane, and (2) a novel electrospun scaffold developed in our laboratory, could support the generation of realistic RPE tissues in culture. Our findings reveal that both substrates were capable of supporting long-lasting RPE monolayers with structural and functional specialisations of in-situ RPE cells. These cultures were used to study autofluorescence and barrier formation, as well as activities such as outer-segment internalisation/trafficking and directional secretion of key proteins; the impairment of which underlies retinal disease. Hence, both substrates fulfilled important criteria for generating authentic in-vitro cultures and act as powerful tools to study RPE pathophysiology. However, RPE grown on electrospun scaffolds may be better suited to studying complex RPE-BrM interactions such as the formation of drusen-like deposits associated with early retinal disease.

Congenital muscular torticollis: Use of gaze angle and translational deformity in assessment of facial asymmetry.

BACKGROUND: Assessment of facial asymmetry is challenging in torticollis deformity. Neck tilt in toroticollis is associated with deviation of horizontal ocular gaze and translation of neck from the midline. These deviations can be assessed clinically and can be used as surrogate marker for facial asymmetry. MATERIALS AND METHODS: Thirty five children with congenital muscular torticollis (CMT) were classified into three grades of severity based on the new clinical score. The parameters included in the scoring system included rotational deficit, side flexion deficit, gaze angle (GA), and translational deformity (TD). Seven children had Grade I (mild), 18 had Grade II (moderate), and 10 had Grade III (severe) CMT. There were 21 girls and 14 boys with a mean age of 8.46 years (range 3-16 years). Twenty two children underwent a bipolar release, and 13 had unipolar surgery. Facial asymmetry (FA) signs were noted and based on GA and TD; all children had a deviation from the neutral angles (GA of 90° and 0 mm translation from the midsterna plumb line were considered neutral angle). The final outcome was based on the modified Cheng and Tang Score. RESULTS: The mean GA in Grade I, II, and III improved from 81.71 to 90, 72.77 to 89.16, and 66.60 to 88, respectively (Chi-square P < 0.0001). The TD improved from 15 mm to 0 mm, 25.83 mm to 3.05 mm, and 36.6 mm to 6 mm in Grade I, II, and III, respectively (Chi-square P < 0.05). The rotational and side flexion deficits also improved across all grades of severity but were not statistically significant (P < 0.911 and P < 0.04). Twenty four children had an excellent outcome with complete correction of their GA and TD. Four children with Grade II CMT and seven children with Grade III who had a residual translation of 5 mm or more and GA less than neutral horizontal had a good outcome. No child had problems with scar cosmesis or prominent lateral bands, and there was no recurrence of deformity at a mean followup of 28 months (range 24-32 months). CONCLUSION: The GA and TD can be used to assess FA in torticollis management and significant improvement can be expected even in severe cases.

Risk factors for early redislocation after primary treatment of developmental dysplasia of the hip: Is there a protective influence of the ossific nucleus?

BACKGROUND: Re-dislocation after primary treatment of developmental dysplasia of the hip is a serious complication. We analyzed the various risk factors that contribute to re-dislocation, and whether the bony ossific nucleus (ON) confers increased stability against re-dislocation. MATERIALS AND METHODS: Fifty-five children (60 hips) were classified into three treatment groups: Closed reduction (CR) in 15 children (17 hips), open reduction (OR) in 26 children (28 hips), and OR with bony surgery (ORB) in 14 children (15 hips). The mean age at initial treatment was 16 months (range 6-36 months). Fifty-one hips and 9 hips were Tonnis Grade 4 and 3, respectively. The mean preoperative acetabular index (AI) was 44.82° (range 32°-56°) for the study group. At initial treatment, bony ON was absent in 8 hips and present in 52 hips. RESULTS: No hip developed stiffness and pain after primary treatment. Although the AI index, Tonnis grade, and absence of ossific nucleus were higher in the re-dislocated groups, this was not statistically significant. Excluding the re-dislocations, four children had a fair outcome, 11 had good outcome, and 36 had excellent outcome as per McKay's criteria. In the CR group (17 hips), two children (2 hips) with absent ON had re-dislocation. In the OR group (28 hips), three re-dislocations were seen (three children) at 3, 5, and 7 months, respectively. Two of these had an absent bony ON. In the ORB group (15 hips), one late sub-luxation occurred in a child with absent ON. The mean preoperative AI for the re-dislocated and located group was 44.66° (range 42°-48°) and 44.53° (range 39°-56°), respectively. The postoperative AI was 34.53. CONCLUSION: The experience of the treating surgeon and technical factors play an overwhelming role in preventing early dislocation. The absence of ON should perhaps alert the surgeon for enhanced spica care, postoperative splinting, and meticulous intra-operative management.

Transphyseal Injury of Distal Humerus: A Commonly Missed Diagnosis in Neonates.

Distal humeral physeal injury is a rare entity in newborns. Lack of ossific nuclei of the distal humerus in neonates results in a diagnostic dilemma as the injury is radiologically not visible and is often mistaken as elbow dislocation. Ultrasonography and Magnetic resonance imaging help to clinch diagnosis in the early period where plain radiographs fail to detect this entity. This condition warrants high index of suspicion along with good clinical acumen for early diagnosis and immediate management with closed reduction and immobilization to avoid long term complications. We present a case of delayed diagnosis of distal humeral physeal separation in a neonate which was managed conservatively at our neonatal intensive care unit with a good outcome without functional deformity.

Neglected Anterior Dislocation of Shoulder: is surgery necessary? A Rare Case with review of literature.

INTRODUCTION: Shoulder joint is the most frequently dislocated joint. However, it is rarely neglected and treatment is sought immediately. Delayed or neglected shoulder dislocations are difficult to manage and require extensive procedures to obtain good functional outcome. Very few cases are described in literature showing neglected shoulder dislocation with good functional range of movement. We report a case with 3 years of neglected anterior shoulder dislocation with preserved joint function. CASE REPORT: A 40 years old gentleman presented withfracture distal end of the radius (left). On clinical examination we observed that he had anterior dislocation of his left shoulder which was confirmed on radiographic evaluation. He had history of seizures 3 years back, which may be the cause of dislocation which went unnoticed. On examination he had good range of motion without any pain. Patient could perform all routine activities with no major functional limitation. At three years after dislocation CT Scan showed neocavity formation. CONCLUSION: Neglected shoulder dislocation with preserved joint function without major functional limitation is a rare presentation. This condition should be kept in mind in patients with history of seizures. Proper evaluation and counseling of patients avoids extensive procedures and avoids complications of surgery. Observation can be a treatment option in patients with preserved range of movement especially involving non dominant handand having low functional demand. This report presents rare presentation of neglected shoulder dislocation highlighting its natural history and its outcome following conservative treatment.

Classification of relapse pattern in clubfoot treated with Ponseti technique.

BACKGROUND: Relapse of clubfoot deformity following correction by Ponseti technique is not uncommon. The relapsed feet progress from flexible to rigid if left untreated and can become as severe as the initial deformity. No definitive classification exists to assess a relapsed clubfoot. Some authors have used the Pirani score to rate the relapse while others have used descriptive terms. The purpose of this study is to analyze the relapse pattern in clubfeet that have undergone treatment with the Ponseti method and propose a simple classification for relapsed clubfeet. MATERIALS AND METHODS: Ninety-one children (164 feet) with idiopathic clubfeet who underwent treatment with Ponseti technique presented with relapse of the deformity. There were 68 boys and 23 girls. Mean age at presentation for casting was 10.71 days (range 7-22 days). Seventy three children (146 feet, 80%) had bilateral involvement and 18 (20%) had unilateral clubfeet. The mean Pirani Score was 5.6 and 5.5 in bilateral and unilateral groups respectively. Percutaneous heel cord tenotomy was done in 65 children (130 feet, 89%) in the bilateral group and in 12 children (66%) with unilateral clubfoot. RESULTS: Five relapse patterns were identified at a mean followup of 4.5 years (range 3-5 years) which forms the basis of this study. These relapse patterns were classified as: Grade IA: decrease in ankle dorsiflexion from15 degrees to neutral, Grade IB: dynamic forefoot adduction or supination, Grade IIA - rigid equinus, Grade IIB - rigid adduction of forefoot/midfoot complex and Grade III: combination of two or more deformities: Fixed equinus, varus and forefoot adduction. In the bilateral group, 21 children (38 feet, 28%) had Grade IA relapse. Twenty four children (46 feet, 34%) had dynamic intoeing (Grade IB) on walking. Thirteen children (22 feet, 16%) had true ankle equinus of varying degress (Grade IIA); eight children (13 feet, 9.7%) had fixed adduction deformity of the forefoot (Grade IIB) and seven children (14 feet, 10.7%) had two or more fixed deformities. In the unilateral group seven cases (38%) had reduced dorsiflexion (Grade IA), six (33%) had dynamic adduction (Grade IB), two (11%) had fixed equinus and adduction respectively (Grade IIA and IIB) and one (5%) child had fixed equinus and adduction deformity (Grade III). The relapses were treated by full time splint application, re-casting, tibialis anterior transfer, posterior release, corrective lateral closing wedge osteotomy and a comprehensive subtalar release. Splint compliance was compromised in both groups. CONCLUSION: Relapse pattern in clubfeet can be broadly classified into three distinct subsets. Early identification of relapses and early intervention will prevent major soft tissue surgery. A universal language of relapse pattern will allow comparison of results of intervention.

Utility of combined hip abduction angle for hip surveillance in children with cerebral palsy.

BACKGROUND: Spontaneous hip lateralization complicates the management of non-ambulatory children with cerebral palsy (CP). It can be diagnosed early using radiographs, but it involves standardization of positioning and exposure to radiation. Hence, the aim of this study was to assess the utility of Combined hip abduction angle (CHAA) in the clinical setting to identify those children with CP who were at greater risk to develop spontaneous progressive hip lateralization. MATERIALS AND METHODS: One hundred and three children (206 hips) with CP formed our study population. There were 48 boys and 55 girls aged 2-11 years (mean 5.03 years). 61 children were Gross Motor Function Classification System (GMFCS) level 5, while 42 were GMFCS level 4. Clinical measurements of CHAA were statistically correlated with radiographic measurements of Reimer's migration percentage (MP) for bivariate associations using χ(2) and t tests. RESULTS: CHAA is evaluated against MP which is considered as a reliable measure of hip subluxation. Thus, for CHAA, sensitivity was 74.07% and specificity was 67.35%. False-positive rate was 32.65% and false-negative rate was 25.93%. CONCLUSIONS: Our study shows that correlation exists between CHAA and MP, which has been proved to be useful for hip screening in CP children at risk of hip dislocation. CHAA is an easy, rapid, cost-effective clinical test which can be performed by paraclinical health practitioners (physiotherapists) and orthopedic surgeons.

Missed Monteggia fracture in children: Is annular ligament reconstruction always required?

BACKGROUND: Chronic (neglected) radiocapitellar joint dislocation is one of the feared complications of Monteggia fractures especially when associated with subtle fracture of the ulna bone. Many treatment strategies have been described to manage chronic Monteggia fracture and the need for annular ligament reconstruction is not always clear. The purpose of this study is to highlight the management of missed Monteggia fracture with particular emphasis on utility of annular ligament reconstruction by comparing the two groups of patients. MATERIALS AND METHODS: In a prospective study 12 patients with mean age of 7.4 years, who presented with neglected Monteggia fractures, were studied. All children underwent open reduction of the radiocapitellar joint. Five children (Group A) were treated with angulation-distraction osteotomy of ulna and annular ligament reconstruction and six cases (Group B) required only angulation-distraction osteotomy of ulna without ligament reconstruction. In one case an open reduction of the radiocapitellar joint was sufficient to reduce the radial head and this was included in Group B. The gap between injury and presentation was from 3 months to 18 months (mean 9 months). Ten patients were classified as Bado I, and one each as Bado II and III respectively. We used the Kim's criteria to score our results. RESULT: The mean follow-up period was 22 months. All ulna osteotomies healed uneventfully. The mean loss of pronation was 15 degree in Group A and 10 degree in Group B. Elbow flexion improved from the preoperative range and no child complained of pain, deformity and restriction of activity. The elbow score was excellent in 10 cases, and good in two cases. CONCLUSION: Distraction-angulation osteotomy of the ulna suffices in most cases of missed monteggia fracture and the need for annular ligament reconstruction is based on intraoperative findings of radial head instability.