Amyotrophic Lateral Sclerosis (ALS), neurodegenerative motor neuron disorder is characterized as multisystem disease with important contribution of genetic factors. The etiopahogenesis of ALS is not ...fully elucidate, but the dominant theory at present relates to RNA processing, as well as protein aggregation and miss-folding, oxidative stress, glutamate excitotoxicity, inflammation and epigenetic dysregulation. Additionally, as mitochondria plays a leading role in cellular homeostasis maintenance, a rising amount of evidence indicates mitochondrial dysfunction as a substantial contributor to disease onset and progression. The aim of this review is to summarize most relevant findings that link genetic factors in ALS pathogenesis with different mechanisms with mitochondrial involvement (respiratory chain, OXPHOS control, calcium buffering, axonal transport, inflammation, mitophagy, etc.). We highlight the importance of a widening perspective for better understanding overlapping pathophysiological pathways in ALS and neurodegeneration in general. Finally, current and potentially novel therapies, especially gene specific therapies, targeting mitochondrial dysfunction are discussed briefly.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Flexible intramedullary nailing provides advantages in limb lengthening and gradual deformity correction in combination with external fixation in patients with Ollier’s disease, fibrous dysplasia, ...osteogenesis imperfecta.•Hydroxyapatite-coated bent elastic nails in combination with external fixator are appropriate in limb lengthening of abnormal bone in children. Intramedullary nails left in situ after lengthening procedure should be applied for long-term reinforcement of lengthened bone in patients with abnormal bone. Osteoactive properties of intramedullary elastic implants are favorable for bone formation and as well as for stable position of nails without risks of migration in long-term follow-up.
Flexible intramedullary nailing (FIN) provides multiple advantages in limb lengthening and progressive deformity correction in combination with external fixation. The article presents brief literature review and authors’ experience in limb lengthening of abnormal bone (Ollier’s disease, fibrous dysplasia, osteogenesis imperfecta).
Titanium and, especially, hydroxyapatite-coated bent elastic nails in combination with external fixator are appropriate in limb lengthening of abnormal bone in children. FIN left in situ after lengthening procedure and external frame removal should be applied for long-term reinforcement of lengthened bone in patients with abnormal bone (metabolic bone disorders, skeletal dysplasias with compromised bone tissue development). The FIN respects bone biology, which is mandatory for good bone consolidation. Osteoactive properties of intramedullary elastic implants are favorable for bone formation and as well as for stable position of nails without risks of migration in long-term follow-up.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Diabetic neuropathy (DN), the most common chronic and progressive complication of diabetes mellitus (DM), strongly affects patients’ quality of life. DN could be present as peripheral, autonomous or, ...clinically also relevant, uremic neuropathy. The etiopathogenesis of DN is multifactorial, and genetic components play a role both in its occurrence and clinical course. A number of gene polymorphisms in candidate genes have been assessed as susceptibility factors for DN, and most of them are linked to mechanisms such as reactive oxygen species production, neurovascular impairments and modified protein glycosylation, as well as immunomodulation and inflammation. Different epigenomic mechanisms such as DNA methylation, histone modifications and non-coding RNA action have been studied in DN, which also underline the importance of “metabolic memory” in DN appearance and progression. In this review, we summarize most of the relevant data in the field of genetics and epigenomics of DN, hoping they will become significant for diagnosis, therapy and prevention of DN.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
: The immature skeleton in a pediatric population exposed to frequent physical activity might be extremely prone to injuries, with possible consequences later in adulthood. The main aim of this study ...is to present specific morphometric parameters and magnetic resonance imaging (MRI) morphological changes of the knee and patella in a physically active pediatric population. Additionally, we wanted to investigate the morphological risk factors for patellar instability.
The study included the MRI findings of 193 physically active pediatric patients with knee pain. The participants underwent sports activities for 5 to 8 h per week. Two divisions were performed: by age and by patellar type. We evaluated three age groups: group 1 (age 11-14), group 2 (age 15-17), and group 3 (age 18-21 years). In addition, participants were divided by the patellar type (according to Wiberg) into three groups. The following morphometric parameters were calculated: lateral trochlear inclination (LTI), the tibial tubercle-trochlear groove distance (TT-TG), trochlear facet asymmetry (TFA), Insall-Salvati index, modified Insall-Salvati index, Caton-Deschamps index, articular overlap, morphology ratio and contact surface ratio.
We found a statistically significant association between patellar type groups in LTI (
< 0.001), TFA (
< 0.001), Insal-Salvati (
= 0.001) index, and Caton-Deschamps index (
= 0.018). According to age groups, we found statistical significance in the Caton-Deschamps index (
= 0.039). The most frequent knee injury parameter, according to Wiberg, in physically active pediatric patients was patella type 2 in boys and type 3 in girls.
The MRI morphometric parameters observed in our study might be factors of prediction of knee injury in physically active children. In addition, it might be very useful in sports programs to improve the biomechanics of the knee in order to reduce the injury rate in sports-active children.
Pediatric stroke (PS) is an injury caused by the occlusion or rupture of a blood vessel in the central nervous system (CNS) of children, before or after birth. Hemiparesis is the most common motoric ...deficit associated with PS in children. Therefore, it is important to emphasize that PS is a significant challenge for rehabilitation, especially since the consequences may also appear during the child's growth and development, reducing functional capacity. The plasticity of the child's CNS is an important predecessor of recovery, but disruption of the neural network, specific to an immature brain, can have harmful and potentially devastating consequences. In this review, we summarize the complexity of the consequences associated with PS and the possibilities and role of modern rehabilitation. An analysis of the current literature reveals that Constraint-Induced Movement Therapy, forced-use therapy, repetitive transcranial magnetic stimulation, functional electrical stimulation and robot-assisted therapy have demonstrated at least partial improvements in motor domains related to hemiparesis or hemiplegia caused by PS, but they are supported with different levels of evidence. Due to the lack of randomized controlled studies, the optimal rehabilitation treatment is still debatable, and therefore, most recommendations are primarily based on expert consensuses, opinions and an insufficient level of evidence.
Purpose
The incidence of developmental dysplasia of the hip (DDH) is higher in Eastern Europeans and Middle Easterners. This study aimed to establish consensus among experts in this geographical area ...on the management of DDH before walking age.
Methods
Fourteen experienced orthopedic surgeons agreed to participate in a four-round online consensus panel by the Delphi method. The questionnaire included 31 statements concerning the prevention, diagnosis, and treatment of DDH before walking age.
Results
Consensus was established for 26 (84%) of 31 statements. Hip ultrasonography is the proper diagnostic tool under six months in DDH; universal newborn hip screening between three and six weeks is necessary; positive family history, breech presentation, female gender, and postnatal swaddling are the most important risk factors; Ortolani, Barlow tests, and limitation of abduction are the most important clinical findings; Pavlik harness is the first bracing preference; some Graf type IIa hips and all Graf type IIb and worse hips need abduction bracing treatment; the uppermost age limit for closed and open reductions is 12 months and 12–24 months, respectively; anatomic reduction is essential in closed and open reductions, postoperative MRI or CT is not always indicated; anterior approach open reduction is better than medial approach open reduction; forceful reduction and extreme positioning of the hips (> 60° hip abduction) are the two significant risk factors for osteonecrosis of the femoral head.
Conclusion
The findings of the present study may be useful for clinicians because a practical reference, based on the opinions of the multinational expert panel, but may not be applicable to all settings is provided.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background: Recognized as one of the most serious musculoskeletal deformities, occurring in 1–2 per 1000 newborns, 80% of clubfeet are idiopathic while 20% present with associated malformations. The ...etiopathogenesis of clubfoot is described as multifactorial, including both genetic and environmental risk factors. The aim of this study was to analyze possible genetic causes of isolated and syndromic clubfoot in Serbian children, as well as to correlate clinical and genetic characteristics that would provide insight into clubfoot etiopathogenesis and possibly contribute to global knowledge about clinical features of different genetically defined disorders. Methods: We evaluated 50 randomly selected, eligible children with clubfoot aged 3 to 16 years that were initially hospitalized and treated at University Children’s Hospital between November 2006 and November 2022. The tested parameters were gender, age, dominant foot, affected foot, degree of deformity, treatment, neuromuscular disorders, positive family history, and maternal smoking. According to the presence of defined genetic mutation/s by whole exome sequencing (WES), patients were separated into two groups: positive (with genetic mutation/s) and negative (without genetic mutation/s). Results: Seven patients were found to be positive, i.e., with genetic mutation/s. A statistically significant difference between categorical variables was found for families with a history of clubfoot, where more than half (57.14%) of patients with confirmed genetic mutation/s also had a family history of genetic mutation/s (p = 0.023). Conclusions: The results from this study further expand the genetic epidemiology of clubfoot. This study contributes to the establishment of genetic diagnostic strategies in pediatric patients with this condition, which can lead to more efficient genetic diagnosis.
Background and Objectives: Excessive use of the knee in patients with immature locomotor systems leads to a whole spectrum of morphological changes with possible consequences in adulthood. This study ...aimed to examine the morphological pattern in magnetic resonance imaging (MRI) that is associated with recurrent pain due to increased physical activity in children. Materials and Methods: This was a retrospective study conducted among pediatric patients treated at the University Children’s Hospital in Belgrade in 2018 and 2019. MRI findings of patients who reported recurrent pain in the knee joint during physical activity and who were without any pathological findings on both clinical examination and knee radiographs were included in the study. Results: MRI findings of 168 patients (73 boys and 95 girls, mean age 14.07 ± 3.34 years) were assessed. Meniscus and cartilage lesions were the most commonly detected morphological findings: meniscus lesions in 49.4%, cartilage ruptures in 44.6%, and cartilage edema in 26.2% of patients. The medial meniscus was more often injured in girls (p = 0.030), while boys were more prone to other joint injuries (p = 0.016), re-injury of the same joint (p = 0.036), bone bruises (p < 0.001), and ligament injuries (p = 0.001). In children older than 15 years, tibial plateau cartilage edema (p = 0.016), chondromalacia patellae (p = 0.005), and retropatellar effusion (p = 0.011) were detected more frequently compared to younger children. Conclusions: Children reporting recurrent knee pain due to increased physical activity, without any detected pathological findings on clinical examination and knee radiography, may have morphological changes that can be detected on MRI. Timely diagnosis of joint lesions should play a significant role in preventing permanent joint dysfunction in the pediatric population as well as in preventing the development of musculoskeletal diseases in adulthood.
: Idiopathic anterior knee pain is a common condition in adolescents and is mostly of unknown cause. The aim of this study was to examine the influence of the Q-angle and muscle strength on ...idiopathic anterior knee pain.
: Seventy-one adolescents (41 females and 30 males) diagnosed with anterior knee pain were included in this prospective study. The extensor strength in the knee joint and the Q-angle were monitored. The healthy extremity was used as a control. The Student's paired sample
-test was applied for testing the difference. Statistical significance was set at 0.05.
: There was no statistically significant difference in the Q-angle value between the idiopathic AKP and the healthy extremity (
> 0.05) within the entire sample. A statistically significant higher Q-angle of the idiopathic AKP knee (
< 0.05) was obtained in the female subgroup. No statistically significant difference (
> 0.05) was found in the male subgroup. Within the male subgroup, the strength of the extensors within the knee joint of the healthy extremity had statistically significant higher values than the strength of these muscles in the affected extremity (
< 0.05).
: A greater Q-angle is a risk factor linked to anterior knee pain within the female population. Decreased muscle strength of knee joint extensors is a risk factor linked to anterior knee pain in both sex subgroups.
Background: The forearm is the most common fracture site in childhood, accounting for every fourth pediatric fracture. It is well described that vitamin D is involved in the regulation of bone ...mineralization and skeletal homeostasis by the regulation of calcium absorption. The aim of our study was to determine the influence of 25-hydroxyvitamin D levels on forearm fracture falls in a pediatric population, depending on level of energy impact. Additionally, we also aimed to evaluate the correlation between 25-hydroxyvitamin D levels and other tested risk factors for pediatric fractures. Methods: We evaluated 50 eligible children aged 3 to 12 years with a forearm fracture. According to energy impact, patients were grouped into low-energy fractures (LEF) and high-energy fractures (HEF) groups. The general characteristics of the patients included age, gender, sport participation, and fractured bone and its localization. We analyzed 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium, magnesium, phosphate, C-reactive protein (CRP) levels, and body mass index (BMI). Results: There is a significant difference in the 25-hydroxyvitamin D levels distribution between LEF and HEF (p < 0.001) and PTH levels (p = 0.002). For magnesium levels, calcium levels, phosphate levels, and CRP levels, there were no significant differences in their frequency distribution. For the group of patients with LEF, there is a significantly positive correlation between 25-hydroxyvitamin D and calcium levels (p = 0.019) and a borderline significantly positive correlation between 25-hydroxyvitamin D and magnesium levels (p = 0.050). For the group of patients with HEF, there was only a significantly positive correlation between 25-hydroxyvitamin D and PTH levels (p < 0.001). Conclusions: Children with LEF were more frequently insufficient in 25-hydroxyvitamin D levels but had normal calcium levels, compared to the ones with HEF. These findings suggest that LEF and HEF in children might to a certain degree have different pathophysiological mechanisms.
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