Results From Finland's 2022 Para Report Card on Physical Activity for Children and Adolescents With Disabilities.

Finland's 2022 Para Report Card on Physical Activity for Children and Adolescents With Disabilities includes a summary of results and grades for 10 physical activity indicators and highlights how these grades are interpreted by stakeholders. The disability classification was based on the UNICEF/Washington Group on Disability Statistics measure, Generalized Anxiety Disorder (GAD7) measure, or education status. Data between 2017 and 2021 were reviewed by 24 physical activity specialists using benchmarks adapted for data on disabilities from the Active Healthy Kids Global Alliance. The grades were assigned as follows: Overall Physical Activity, C+; Organized Sport, C; Active Play, D; Active Transportation, B; Family and Peers, C+; School, B; Community and Environment, C-; Government, A-; sedentary behavior and physical fitness were graded as incomplete. Stakeholder focus-group discussions highlighted the need for multidisciplinary cooperation and increasing competence of specialists working with children to promote a physically active lifestyle for all children.

Novel non-neutral mitochondrial DNA mutations found in childhood acute lymphoblastic leukemia.

Mitochondria produce adenosine triphosphate (ATP) for energy requirements via the mitochondrial oxidative phosphorylation (OXPHOS) system. One of the hallmarks of cancer is the energy shift toward glycolysis. Low OXPHOS activity and increased glycolysis are associated with aggressive types of cancer. Mitochondria have their own genome (mitochondrial DNA [mtDNA]) encoding for 13 essential subunits of the OXPHOS enzyme complexes. We studied mtDNA in childhood acute lymphoblastic leukemia (ALL) to detect potential pathogenic mutations in OXPHOS complexes. The whole mtDNA from blood and bone marrow samples at diagnosis and follow-up from 36 ALL patients were analyzed. Novel or previously described pathogenic mtDNA mutations were identified in 8 out of 36 patients. Six out of these 8 patients had died from ALL. Five out of 36 patients had an identified poor prognosis genetic marker, and 4 of these patients had mtDNA mutations. Missense or nonsense mtDNA mutations were detected in the genes encoding subunits of OXPHOS complexes, as follows: MT-ND1, MT-ND2, MT-ND4L and MT-ND6 of complex I; MT-CO3 of complex IV; and MT-ATP6 and MT-ATP8 of complex V. We discovered mtDNA mutations in childhood ALL supporting the hypothesis that non-neutral variants in mtDNA affecting the OXPHOS function may be related to leukemic clones.

Venous thrombosis in children and adolescents with Hodgkin lymphoma in Sweden.

INTRODUCTION: Pediatric patients with Hodgkin lymphoma (HL) have several risk factors for venous thromboembolism (VTE). Although these patients are occasionally treated with thromboprophylaxis, no guidelines are implemented in Sweden. Scarce data from adult patients indicate an increased risk of VTE, but pediatric data is largely missing. Given the favorable overall survival of HL, there should reasonably be more focus on preventing complications. MATERIALS AND METHODS: We conducted a retrospective cohort study, including all patients registered in the Childhood Cancer Registry under the age of 18years diagnosed with HL between January 2005 and December 2015 in Sweden. RESULTS: Data was retrieved from the medical records of all 163 patients (100%) at six Swedish pediatric cancer centers. The incidence of VTE was 7.7% (symptomatic VTE 3.9%). The median follow-up was 3.4years (range 0.3-10.5). Only five patients (3.1%) were treated with thromboprophylaxis. All VTE events occurred in the older age category (11-17years) and all but one (92.7%) had a mediastinal mass. While the VTE did not significantly affect the treatment of HL, it caused increased morbidity and 2/12 developed a post-thrombotic syndrome. No significant risk factors for VTE were identified. CONCLUSIONS: VTE is a relatively common complication of HL and its treatment, causing increased acute and long-term morbidity. However, due to limited number of events we could not demonstrate risk-factors for VTE that would identify patients who might benefit from thromboprophylaxis.

The classification of osteonecrosis in patients with cancer: validation of a new radiological classification system.

AIM: To validate a new, non-joint-specific radiological classification system that is suitable regardless of the site of the osteonecrosis (ON) in patients with cancer. MATERIAL AND METHODS: Critical deficiencies in the existing ON classification systems were identified and a new, non-joint-specific radiological classification system was developed. Seventy-two magnetic resonance imaging (MRI) images of patients with cancer and ON lesions were graded, and the validation of the new system was performed by assessing inter- and intra-observer reliability. RESULTS: Intra-observer reliability of ON grading was good or very good, with kappa values of 0.79-0.86. Interobserver agreement was lower but still good, with kappa values of 0.62-0.77. Ninety-eight percent of all intra- or interobserver differences were within one grade. Interobserver reliability of assessing the location of ON was very good, with kappa values of 0.93-0.98. CONCLUSION: All the available radiological ON classification systems are joint specific. This limitation has spurred the development of multiple systems, which has led to the insufficient use of classifications in ON studies among patients with cancer. The introduced radiological classification system overcomes the problem of joint-specificity, was found to be reliable, and can be used to classify all ON lesions regardless of the affected site.

The Psychometric Properties of the Farsi Version of "Hospital Survey on Patient Safety Culture" In Iran's Hospitals.

BACKGROUND: If you want to start a long journey towards patient safety, you should create a good culture of patient safety among employees alongside structural interventions. The first step in doing so is the assessment of current culture in the organization using different tools. One of the most commonly used instruments of measuring patient safety culture is Hospital Survey of Patient Safety culture (HSOPS). The aim of this study was to assess the validity and reliability of Farsi version of this questionnaire for the first time in Iran's hospitals. METHODS: We purposefully selected four hospitals out of seven general Tehran University of Medical Sciences affiliated hospitals. Then a 420 sample of staff of these hospitals were taken randomly. Staff was asked to complete the questionnaire. Confirmative factor analysis, correlation coefficient, Cronbach's alpha were employed in statistical analyses. RESULTS: Factor loadings for almost all questions were acceptable. Factors jointly explained 77.8% of the variance in the responses. The Cronbach's alpha coefficient was between 0.57 and 0.8. The study revealed that over 70% of employees were working at their hospitals more than 40 hours a week and also more than half of the employees were not reporting errors. CONCLUSION: Farsi version of HSOPS with 12 dimensions and 42 questions is a valid and reliable questionnaire to measure patient safety culture for the first time in Iran hospitals. This tool will be helpful in tracking improvements and in heightening awareness on patient safety culture in Iran.

Cervical spinal cord deformation during simulated head-first impact injuries.

The relationship between bony spinal column and spinal cord injury during an injury event is not well understood. While several studies have measured spinal canal occlusion during axial impact, there has been limited work done to quantify the spinal cord compression or deformation during simulated injury. Because the cord is a viscoelastic solid it may provide resistance to bone fragments, ligaments or other elements that move into the canal and impinge it during column injury. This would differentiate the measurement of cord compression from the measurement of occlusion of an empty canal. In the present study, a novel method of visualizing and quantifying spinal cord deformation during dynamic head-first impact of ex vivo human cervical spine specimens (N=6) was developed. A radiodense, biofidelic surrogate spinal cord was imaged in the spinal canal using high speed cineradiography at 1000 frames per second. The dorsal-ventral diameter of the cord was measured at 1.5mm increments along its length for each frame of the radiographic footage. The resulting cord deformations were used to determine the theoretical neurological outcome of the impact based on published in vivo ferret studies. The corresponding probability of recovery for the spinal cord deformations in these tests ranged between 8% for atlantoaxial dislocation injury and 95% for mid-cervical spine hyperextension injury (based on the ferret data). Clinically relevant spinal column fracture patterns were produced in this study.

Effects of a germ-free environment on gut immune regulation and diabetes progression in non-obese diabetic (NOD) mice.

AIMS/HYPOTHESIS: Microbial factors influence the development of diabetes in NOD mice. Studies in germ-free animals have revealed important roles of microbiota in the regulation of Th17 and forkhead box P3 (FOXP3)(+) T regulatory (Treg) activation in the intestine. However, the effects of intestinal microbiota in immune regulation and diabetes development in NOD mice are still poorly understood. METHODS: A colony of germ-free NOD mice was established to evaluate the effects of intestinal microbiota on regulatory immunity in the gut, and on the development of insulitis and diabetes in NOD mice. RESULTS: Diabetes developed in roughly equal numbers in germ-free and specific pathogen-free NOD mice. Insulitis was accentuated in germ-free NOD mice; yet insulin preservation was unaltered. Germ-free NOD mice showed increased levels of Il17 (also known as Il17a) mRNA in the colon, and of Th17 and Th1 cells in the mesenteric and pancreatic lymph nodes, while Foxp3 mRNA and FOXP3(+) Tregs were reduced. In the islet infiltrates, FOXP3(+)CD4(+) T cells were slightly increased in germ-free mice. B cells appeared less activated in the peritoneum and were less abundant in islet infiltrates. CONCLUSIONS/INTERPRETATION: These results indicate that lack of intestinal microbiota promotes an imbalance between Th1, Th17 and Treg differentiation in the intestine. This imbalance is associated with accelerated insulitis, but intact recruitment of FOXP3(+) Tregs into islets, suggesting: (1) a microbial dependence of local induction of Treg in the gut and draining lymph nodes; but (2) a potentially compensatory function of naturally occurring Tregs in the islets, which may help control diabetogenic T cells.

Giant enhancement of second-harmonic generation in multiple diffraction orders from sub-wavelength resonant waveguide grating.

We demonstrate a purely dielectric resonant waveguide structure that enhances the efficiency of second-harmonic generation by a factor of at least 5500 compared to a flat reference surface in the same geometry. We also show that the structure emits second-harmonic radiation in four different directions when the sample is illuminated with fundamental radiation incident at the resonant angle of the sample.

Sweating impairment in patients with multiple sclerosis.

OBJECTIVES: To measure sweating in patients with multiple sclerosis (MS). MATERIALS AND METHODS: Sweating was measured by an evaporimeter after a heating stimulus in 29 MS patients and in 15 healthy control subjects. RESULTS: The MS patients sweated markedly less than the controls. After 10 min of heating the sweating was significantly lower in the forehead (P = 0.034), feet (right, P = 0.033; left, P = 0.037) and legs (right, P = 0.043; left, P = 0.029) of the MS patients than in those of the controls. After 15 min of heating the difference was statistically significant only in the feet (right, P = 0.043; left, P = 0.029). The Expanded Disability Status Scale score correlated inversely with sweating at 15 min of heating in the left hand (r = 0.42, P < 0.05), and in the left (r = 0.36, P < 0.05) and right foot (r = 0.37, P < 0.05). CONCLUSIONS: MS is associated with an impairment in thermoregulatory sweating which seems to be related to the disease severity.

Sympathetic skin responses in multiple sclerosis.

OBJECTIVES: This study assessed the sympathetic skin responses (SSRs) and their correlation with brain lesion volumes in patients with multiple sclerosis (MS). MATERIALS AND METHODS: The SSRs were measured in 27 patients with MS and 27 healthy controls. The volumes of the proton density-weighted MS lesions in the brain were measured using MRI. RESULTS: The SSRs were abnormal in 52% of the patients with MS, but absent only in clinically severe MS. The total lesion volume in the whole brain correlated significantly with both the severity of MS expressed by the EDSS score (P < 0.001) and the decreased SSR amplitudes in the feet (P < 0.01). Focal lesion volumes in the temporal lobe (P < 0.01), in the pons (P < 0.01) and in the cerebellum (P < 0.01) were also separately associated with abnormal SSR reflexes. CONCLUSIONS: Sudomotor regulation failure in MS is associated with certain focal MS lesions.

Scholastic achievements of children with brain tumors at the end of comprehensive education: a nationwide, register-based study.

BACKGROUND: Cancer treatment may affect school performance. Scholastic achievements after childhood brain tumors have not been previously reported on the level of actual grades. PATIENTS AND METHODS: Patients with brain tumor (n = 300) were identified from the Finnish Cancer Registry. Population controls (n = 1,473) were matched for age, gender, and place of living. Their ninth grade school reports were obtained from Statistics Finland. Age at diagnosis and cranial irradiation (CRT) were considered in analyses, and the level of parental education was taken into model as a covariate. RESULTS: Six percent of patients did not finish their comprehensive school at the usual age. Patients had lower overall averages than their controls (95% CI for the difference -0.30, -0.16). Girls differed from their controls independently of the age at diagnosis or CRT. Boys treated with CRT at school age, but not before school age, had poorer results than their controls (95% CI -0.65, -0.18). The grades of patients were significantly lower in each school subject, and differed most in foreign language. Young girls with CRT had greatest differences from their controls (95% CI -1.73, -0.86) in this subject. In mathematics, patients diagnosed before school age had greatest difference from their controls. In their mother tongue, patients differed less from their controls. CONCLUSIONS: Few patients with brain tumor missed the ninth grade certificate at the age of 16. Grades in foreign language (representing verbal performance) were most affected. However, the patients fared poorer than controls in each subject. The difference was most pronounced among girls. Girls were more sensitive to the adverse effects of irradiation.

Modelling the bioelectric behaviour of halo pin-patient structures during magnetic resonance imaging.

Bioelectric compatibility of electrically conductive halo fixation devices and magnetic resonance (MR) imaging has been largely based on resulting image quality. Previous studies have focused primarily on improving image quality and, although the electrical characteristics of the system during imaging may have been noted, they have not been studied in depth. Utilizing both a theoretical and experimental approximation, this study focuses on the bioelectric characteristics of the pin-patient structures typically enountered in clinical halo fixation systems. Results indicate that the halo pin-patient system can be modelled using a resistor-inductor-capacitor circuit and that simple attempts at improving compatibility through increasing interface resistance by the use of insulated pins may not be an effective approach to improving halo instrumentation compatibility with new, stronger magnetic and higher-frequency resonance imaging systems.

Cardiovascular autonomic dysfunction correlates with brain MRI lesion load in MS.

OBJECTIVE: The aim of the present study was to investigate the cardiovascular autonomic control in clinically definite multiple sclerosis (MS) patients with a standardised battery of cardiovascular tests and to correlate these findings with the brain magnetic resonance imaging (MRI) lesion load. METHODS: Fifty-one patients with MS and 50 healthy controls were studied. Brain MRI was performed in all patients showing typical MS lesions. The cardiovascular tests were carried out using a standardised battery. RESULTS: Heart rate (HR) responses to deep breathing (P < 0.05) and tilt table testing (P < 0.001) were significantly decreased in MS patients when compared to those of the controls. Blood pressure (BP) responses in the tilt table test were also impaired in MS patients (diastolic P < 0.001, systolic P < 0.05). Of the different brain areas investigated the total volume of the midbrain MRI lesions (P < 0.05) was the one most clearly associated with the impaired BP responses. CONCLUSIONS: MS results in both reduced HR variation and decreased BP reactions indicating disturbed cardiovascular regulation. In particular, the midbrain lesions found in MS are associated with cardiovascular dysfunction.

Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials.

BACKGROUND: The objective was to evaluate whether motor nervous pathways are affected when patients are treated for childhood acute lymphoblastic leukemia (ALL). PROCEDURE: Thirty-two children with ALL were studied at the end of treatment by means of motor evoked potentials (MEPs) elicited by magnetic stimulation (MS) transcranially and peripherally and underwent a detailed neurological examination. Thirty-two healthy children matched with them for age, sex, and height served as a control group. RESULTS: The latencies of the MEPs were significantly prolonged along the entire motor nervous pathway in the patients with ALL compared with the healthy controls, indicating demyelination in the thick motor fibres. The MEP amplitudes of the distal extremities elicited by stimulation at the brachial plexus and LV spinal level were significantly lowered in the patients treated for ALL, also indicating anatomical or functional loss of descending motor fibres and/or muscle fibres. The MEP amplitudes elicited by cortical MS showed wider variation and no clear abnormalities were found. Neurological signs and symptoms were common after treatment: 41% of the patients had depressed deep tendon reflexes, 31% had fine motor difficulties and 63% gross motor difficulties, and 34% had dysdiadochokinesia. The conduction delay within the peripheral nerve was related to the post-therapeutic interval after administration of vincristine and the lesions within the CNS to the number of injections of intrathecal methotrexate. CONCLUSIONS: The present results show adverse effects of the ALL treatment on the entire motor nervous pathways. In our experience, the measurement of MEPs by MS provides an objective, painless, and practical tool for assessing the treatment-related neurotoxicity in both the CNS and the peripheral nerves. These disturbances in the motor nervous pathways at the end of treatment raise the question of the long-term effects of ALL treatment on the motor nerve tracts, and have led us to employ MEPs to study these effects in long-term survivors of ALL.

White matter changes on MRI during treatment in children with acute lymphoblastic leukemia: correlation with neuropsychological findings.

BACKGROUND: Treatment of childhood acute lymphoblastic leukemia (ALL) may cause structural and functional brain damage. To find out the incidence of white matter changes during therapy, a prospective MRI study was designed, and the findings were correlated with neuropsychological evaluation. PROCEDURE: Thirty-three children with ALL underwent serial cranial MRI before, during, and after therapy. Twenty-eight of these children underwent also neuropsychological assessment at the end of treatment. They all received intravenous and intrathecal methotrexate for central nervous system (CNS) therapy, 15 patients received cranial irradiation in addition. RESULTS: Transient high-intensity white matter changes were observed by MRI in three children 9% (95% CI, 2-24%) who received chemotherapy only. The high-intensity changes were most prominent in the frontal lobes in two of these children. The children with white matter changes were significantly younger than those with normal MRI (2.8 vs. 7.4 years; mean). There was no correlation between neuropsychological tests and white matter changes, except in attention and in tests referring to the frontal areas in general. CONCLUSIONS: White matter changes are occasionally observed during therapy with the current Nordic protocols. Young children may be more susceptible to developing white matter changes after repeated intravenous methotrexate injections. There is no systematic correlation between neuropsychological deficits and MRI findings.

Cerebral glucose metabolism in survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Cranial radiation therapy (CRT) has been suggested to be a principal factor responsible for long term neurocognitive deficits in survivors of acute lymphoblastic leukemia (ALL). However, neither reduction of the irradiation dose nor the elimination of irradiation entirely appear to have abolished neurocognitive impairment in long term ALL survivors. Positron emission tomography (PET) and [(18)F]-fluorodeoxyglucose (FDG) can be used to quantitate cerebral glucose metabolism, a potential indicator of treatment-induced adverse central nervous system (CNS) effects. The purpose of this study was to assess whether CRT is associated with defects in cerebral glucose metabolism in long term ALL survivors. The authors also studied whether chemotherapy and/or the severity of disease have deleterious effects on glucose metabolism. METHODS: Forty long-term survivors of childhood ALL were studied using FDG PET. All subjects went through an elaborate neurocognitive assessment. In 20 of these children, the prophylactic treatment of the CNS had been CRT combined with methotrexate (MTX), and it was MTX only in the remaining 20 children. RESULTS: No major differences were found in the regional cerebral glucose utilization or in neurocognitive performance between the irradiated and nonirradiated groups. A high leukocyte count at the time of diagnosis was found to be associated inversely with cerebral glucose utilization. CONCLUSIONS: CRT does not appear to affect cerebral glucose metabolism in long term survivors of ALL. By contrast, the association between the leukocyte count and glucose utilization implies that disease severity may be partly responsible for adverse CNS effects in long term survivors of childhood ALL.

Cerebral blood flow and glucose metabolism in long-term survivors of childhood acute lymphoblastic leukaemia.

Central nervous system treatment for childhood acute lymphoblastic leukaemia (ALL) has been reported to cause changes in cerebral blood flow and glucose metabolism. Little is known about the association of these functional changes with neuropsychological defects and structural changes. The aim of the present study was to assess the relationship between changes in regional cerebral blood flow and glucose utilisation in long-term survivors of ALL, and the association of these functional abnormalities with neurocognitive and structural defects. 8 survivors of childhood ALL were studied with single photon emission tomography (SPECT) using Tc99m-ethyl cysteinate dimer (ECD) as tracer and with positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) as tracer. 8 healthy controls also underwent FDG-PET. All subjects also underwent magnetic resonance imaging and neuropsychological assessment 5 years after cessation of the therapy. Focal cerebral blood flow abnormalities were found in ECD-SPECT in 5 of the 8 survivors. Glucose utilisation appeared normal in the corresponding regions. However, glucose utilisation was decreased in thalamus and cerebellum in the survivors of ALL as compared with healthy controls. 3 patients had severe and 5 patients mild neurocognitive difficulties. The changes in cerebral blood flow and FDG uptake did not correspond neuroanatomically with the neurocognitive defects. Focal defects in cerebral blood flow in long-term survivors of ALL are not associated with changes in local cerebral glucose utilisation. Neurocognitive difficulties are not consistently associated with either changes in cerebral blood flow or with decreased glucose utilisation. Therefore, based on the present set of studies FDG-PET and ECD-SPECT cannot yet be recommended for the evaluation of long-term neurocognitive defects associated with treatment of ALL.

Bioelectric properties of human cystic fibrosis and non-cystic fibrosis fetal tracheal xenografts in SCID mice.

We measured, the bioelectric properties of 14 cystic fibrosis (CF) and 33 non-CF human fetal tracheal xenografts in severe combined immunodeficiency (SCID) mice. All xenografts exhibited a mature airway-type epithelium irrespective of their gestational age, duration of engraftment, and genotype. The in vivo potential difference and the in vitro baseline short-circuit current (Isc) were significantly higher in non-CF than in CF xenografts. In non-CF xenografts, sequential addition of amiloride, forskolin, and ATP resulted in a 39.4% decrease, a 24.1% increase, and a 43.6% increase in Isc, respectively. In CF xenografts, forskolin had no significant effect on Isc, whereas amiloride- and ATP-induced changes in Isc were proportionally higher than in non-CF xenografts (-60.0 and +68.8%, respectively). These results indicate that the bioelectric properties of non-CF xenografts are similar to those of postnatal airways and that CF xenografts exhibit lower baseline electrogenic activity than non-CF xenografts but similar regulation of ion transport processes to postnatal CF airways. This model of mature human fetal tracheal mucosa may help gain insight into early CF airway pathogenesis.