Retrospective Review of Positive Newborn Screening Results for Isovaleric Acidemia and Development of a Strategy to Improve the Efficacy of Newborn Screening in the UK

\ua9 2024 by the authors.Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0–9.6) and 4.0 (1.8–>70) \ub5mol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in ‘asymptomatic’ individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8–7.1) whilst ‘clinically affected’ patients (n = 7), showed a median (range) C5C of 13.9 (7.7–70) \ub5mol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 \ub5mol/L triggering urgent referral, and those >2.0 and <5.0 \ub5mol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder

Prevalence of hip dislocation among children with cerebral palsy in regions with and without a surveillance programme: a cross sectional study in Sweden and Norway

<p>Abstract</p> <p>Background</p> <p>Hip dislocation is a serious complication among children with cerebral palsy (CP). The aim of this study was to compare the prevalence of hip dislocation among children with CP in an area providing regular care with an area providing hip surveillance services.</p> <p>Methods</p> <p>This is a cross-sectional study in seven Norwegian counties providing regular care and one Swedish healthcare region where a hip surveillance programme was introduced in 1994. Data were provided by the Norwegian Cerebral Palsy Register and the CP Register in Southern Sweden. Children born 1996 - 2003 with moderate to severe CP, defined as Gross Motor Classification System (GMFCS) levels III - V, were included. In all, 119 Norwegian and 136 Swedish children fulfilled the criteria. In Norway, data on hip operations and radiographs of the hips were collected from medical records, while these data are collected routinely in the Swedish register. The hip migration percentage was measured on the recent radiographs. Hip dislocation was defined as a migration percent of 100%.</p> <p>Results</p> <p>The proportion of children at GMFCS levels III - V was 34% in the Norwegian and 38% in the Swedish population. In the Norwegian population, hip dislocation was diagnosed in 18 children (15.1%; CI: 9.8 - 22.6) compared with only one child (0.7%; 95% CI: 0.01 - 4.0) in Southern Sweden (p = < 0.001). Hip surgery was performed in 53 (44.5%) of the Norwegian children and in 43 (32%) of the Swedish children (p = 0.03). The total number of hip operations was 65 in Norway and 63 in Sweden. Norwegian children were first operated at a mean age of 7.6 years (SD: 2.9) compared with 5.7 years (SD: 2.3) in Sweden (p = 0.001).</p> <p>Conclusions</p> <p>The surveillance programme reduced the number of hip dislocations and the proportion of children undergoing hip surgery was lower. However, with the surveillance programme the first operation was performed at a younger age. Our results strongly support the effectiveness of a specifically designed follow-up programme for the prevention of hip dislocation in children with CP.</p

West Nile Virus–associated Flaccid Paralysis

The causes and frequency of acute paralysis and respiratory failure with West Nile virus (WNV) infection are incompletely understood. During the summer and fall of 2003, we conducted a prospective, population-based study among residents of a 3-county area in Colorado, United States, with developing WNV-associated paralysis. Thirty-two patients with developing paralysis and acute WNV infection were identified. Causes included a poliomyelitislike syndrome in 27 (84%) patients and a Guillain-Barré–like syndrome in 4 (13%); 1 had brachial plexus involvement alone. The incidence of poliomyelitislike syndrome was 3.7/100,000. Twelve patients (38%), including 1 with Guillain-Barré–like syndrome, had acute respiratory failure that required endotracheal intubation. At 4 months, 3 patients with respiratory failure died, 2 remained intubated, 25 showed various degrees of improvement, and 2 were lost to followup. A poliomyelitislike syndrome likely involving spinal anterior horn cells is the most common mechanism of WNV-associated paralysis and is associated with significant short- and long-term illness and death

Cholesterol Homeostasis in Two Commonly Used Human Prostate Cancer Cell-Lines, LNCaP and PC-3

BACKGROUND:Recently, there has been renewed interest in the link between cholesterol and prostate cancer. It has been previously reported that in vitro, prostate cancer cells lack sterol-mediated feedback regulation of the major transcription factor in cholesterol homeostasis, sterol-regulatory element binding protein 2 (SREBP-2). This could explain the accumulation of cholesterol observed in clinical prostate cancers. Consequently, perturbed feedback regulation to increased sterol levels has become a pervasive concept in the prostate cancer setting. Here, we aimed to explore this in greater depth. METHODOLOGY/PRINCIPAL FINDINGS:After altering the cellular cholesterol status in LNCaP and PC-3 prostate cancer cells, we examined SREBP-2 processing, downstream effects on promoter activity and expression of SREBP-2 target genes, and functional activity (low-density lipoprotein uptake, cholesterol synthesis). In doing so, we observed that LNCaP and PC-3 cells were sensitive to increased sterol levels. In contrast, lowering cholesterol levels via statin treatment generated a greater response in LNCaP cells than PC-3 cells. This highlighted an important difference between these cell-lines: basal SREBP-2 activity appeared to be higher in PC-3 cells, reducing sensitivity to decreased cholesterol levels. CONCLUSION/SIGNIFICANCE:Thus, prostate cancer cells are sensitive to changing sterol levels in vitro, but the extent of this regulation differs between prostate cancer cell-lines. These results shed new light on the regulation of cholesterol metabolism in two commonly used prostate cancer cell-lines, and emphasize the importance of establishing whether or not cholesterol homeostasis is perturbed in prostate cancer in vivo

Slip and hall current effects on Jeffrey fluid suspension flow in a peristaltic hydromagnetic blood micropump

The magnetic properties of blood allow it to be manipulated with an electromagnetic field. Electromagnetic blood flow pumps are a robust technology which provide more elegant and sustainable performance compared with conventional medical pumps. Blood is a complex multi-phase suspension with non-Newtonian characteristics which are significant in micro-scale transport. Motivated by such applications, in the present article a mathematical model is developed for magnetohydrodynamic (MHD) pumping of blood in a deformable channel with peristaltic waves. A Jeffery’s viscoelastic formulation is employed for the rheology of blood. A twophase fluid-particle (“dusty”) model is utilized to better simulate suspension characteristics (plasma and erythrocytes). Hall current and wall slip effects are incorporated to achieve more realistic representation of actual systems. A two-dimensional asymmetric channel with dissimilar peristaltic wave trains propagating along the walls is considered. The governing conservation equations for mass, fluid and particle momentum are formulated with appropriate boundary conditions. The model is simplified using of long wavelength and creeping flow approximations. The model is also transformed from the fixed frame to the wave frame and rendered non-dimensional. Analytical solutions are derived. The resulting boundary value problem is solved analytically and exact expressions are derived for the fluid velocity, particulate velocity, fluid/particle fluid and particulate volumetric flow rates, axial pressure gradient, pressure rise and skin friction distributions are evaluated in detail. Increasing Hall current parameter reduces bolus growth in the channel, particle phase velocity and pressure difference in the augmented pumping region whereas it increases fluid phase velocity, axial pressure gradient and pressure difference in the pumping region. Increasing the hydrodynamic slip parameter accelerates both particulate and fluid phase flow at and close to the channel walls, enhances wall skin friction, boosts pressure difference in the augmented pumping region and increases bolus magnitudes. Increasing viscoelastic parameter (stress relaxation time to retardation time ratio) decelerates the fluid phase flow, accelerates the particle phase flow, decreases axial pressure gradient, elevates pressure difference in the augmented pumping region and reduces pressure difference in the pumping region. Increasing drag particulate suspension parameter decelerates the particle phase velocity, accelerates the fluid phase velocity, strongly elevates axial pressure gradient and reduces pressure difference (across one wavelength) in the augmented pumping region. Increasing particulate volume fraction density enhances bolus magnitudes in both the upper and lower zones of the channel and elevates pressure rise in the augmented pumping region

Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial

Contains fulltext : 96247.pdf (publisher's version ) (Open Access)BACKGROUND: The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences.Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. METHODS/DESIGN: This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning).Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory.Study parameters are clinical consolidation, radiological consolidation evaluated by CT-scanning, functional status of the wrist, including assessment by means of the patient rated wrist evaluation (PRWE) questionnaire and quality of life using SF-36 health survey questionnaire.Primary endpoint is number of scaphoid unions at six weeks, secondary endpoints are time interval to clinical and radiological consolidation, number of non-unions, functional status at 52 weeks and non-adherence to the treatment protocol. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2064

Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

Background. Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design. A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion. This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration. Netherlands Trial Register (NTR1636)