The role of gamma globulin, complement component 1q, factor B, properdin, body temperature, C-reactive protein and serum amyloid alpha to the activity and the function of the human complement system and its pathways.

The complement system plays a crucial role in orchestrating the activation and regulation of inflammation within the human immune system. Three distinct activation pathways-classical, lectin, and alternative-converge to form the common lytic pathway, culminating in the formation of the membrane-attacking complex that disrupts the structure of pathogens. Dysregulated complement system activity can lead to tissue damage, autoimmune diseases, or immune deficiencies. In this study, the antimicrobial activity of human serum was investigated by using a bioluminescent microbe probe, Escherichia coli (pEGFPluxABCDEamp). This probe has previously been used to determine the antimicrobial activity of complement system and the polymorphonuclear neutrophils. In this study, blocking antibodies against key serum activators and components, including IgG, complement component 1q, factor B, and properdin, were utilized. The influence of body temperature and acute phase proteins, such as C reactive protein (CRP) and serum amyloid alpha (SAA), on the complement system was also examined. The study reveals the critical factors influencing complement system activity and pathway function. Alongside crucial factors like C1q and IgG, alternative pathway components factor B and properdin played pivotal roles. Results indicated that the alternative pathway accounted for approximately one third of the overall serum antimicrobial activity, and blocking this pathway disrupted the entire complement system. Contrary to expectations, elevated body temperature during inflammation did not enhance the antimicrobial activity of human serum. CRP demonstrated complement activation properties, but at higher physiological concentrations, it exhibited antagonistic tendencies, dampening the response. On the other hand, SAA enhanced the serum's activity. Overall, this study sheds a light on the critical factors affecting both complement system activity and pathway functionality, emphasizing the importance of a balanced immune response.

Reliability and validity of the adapted Finnish version of the early onset scoliosis questionnaire (EOSQ-24).

BACKGROUND: EOSQ-24 is a disease specific patient-reported outcome score used to assess the quality of life in patients with early-onset scoliosis. The aim of this study was to translate and cross-culturally adapt the English version of the EOSQ-24 to Finnish language and to assess the reliability and validity of the translation. METHODS: Cross-cultural adaptation and cross-cultural validation were performed to the Finnish translation of the EOSQ-24. Patients and/or their caretakers were then recruited to assess the psychometric properties of the translation. We assessed the internal consistency, test-retest reliability, floor and ceiling effects, and discriminative abilities. One-hundred-and-three patients filled the questionnaire. RESULTS: EOSQ-24 was successfully translated into Finnish. The translation showed excellent internal consistency (Cronbach alpha 0.94), satisfactory item-total correlations ranging from 0.6 to 0.9, and moderate to strong inter item correlations. Test-retest reliability ranged from 0.7 to 0.96 indicating good to excellent agreement. Patients with neuromuscular and syndromic scoliosis reported lower EOSQ-24 scores when compared to patients' idiopathic and congenital scoliosis. There was a significant negative correlation between major curve and EOSQ-24 scores in patients with idiopathic early onset scoliosis. CONCLUSION: The internal consistency and test-retest reliability of the measure were found to be satisfactory. A marked ceiling effect was observed, indicating a potential source of error.

Severe Untreated Scoliosis and Early Onset Breast Cancer in a Patient with Neurofibromatosis Associated with a Nonsense Variant of NF1 Gene.

Background: Neurofibromatosis 1 (NF1) is a relatively common genetic disorder linked to skeletal abnormalities and elevated risk of cancer. Early onset scoliosis is common in patients with NF1 although severe scoliosis is rare. Scoliosis complicates the normal development and growth and may lead to thoracic insufficiency syndrome. The increased risk for breast cancer in young NF1 female patients has been recently identified. Case Presentation: We describe a NF1 patient with dystrophic scoliosis symptoms emerged at childhood. At 37 years of age major scoliosis curve in the thoracolumbar region was 80 degrees. The patient was diagnosed with breast cancer at the age of 37 years, histologically the breast cancer was ductal, hormone receptor positive and Her2-positive. Results: A novel pathogenic variant in NF1 p.(Trp2348*) was identified by next-generation sequencing method. The patient did not have pathogenic variants in BRCA genes or in other currently known hereditary breast cancer genes. Conclusion: Here, we describe a novel pathogenic variant in NF1 named p.(Trp2348*) which may cause severe dystrophic scoliosis and deteriorate the quality of life and physical function, as well as Her-2 positive breast cancer. Untreated dystrophic scoliosis in patients with NF1 may result in significant spinal deformity and deteriorate the quality of life and physical function. Genetic counseling is recommended in all patients with NF1. Patients need routine follow-up throughout life. Multidisciplinary consulting is warranted in patients with neurofibromatosis 1.

Association Between Lenke Classification, The Extent of Lumbar Spinal Fusion, and Health-Related Quality of Life After Instrumented Spinal Fusion for Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Prospective cohort study. SUMMARY OF BACKGROUND DATA: Lenke classification is used to define the curve type in adolescent idiopathic scoliosis (AIS). The association of Lenke classification and long-term postoperative health-related quality of life (HRQoL) remains unclear. OBJECTIVE: The purpose of this study was to assess the association between Lenke classification and HRQoL in patients who underwent spinal fusion for AIS. MATERIALS AND METHODS: In all, 146 consecutive patients (mean age 15.1 yr) operated for AIS between 2007 and 2019 with a minimum 2-year follow-up were included. Fifty-three (36%) patients reached the 10-year follow-up. Their HRQoL was assessed with the SRS-24 questionnaire preoperatively, at six months, two years, and 10 years after surgery. RESULTS: The preoperative major curve was the largest in Lenke 3 (mean 63 ° ) and 4 (mean 62 ° ) groups and the lowest in Lenke 5 groups (mean 48 ° , P <0.05). These curves were corrected to a mean of 15 ° with no differences between groups. We found no evidence of differences between the preoperative HRQoL scores between the Lenke groups. The self-image domain of SRS-24 was lower in patients with isolated major thoracolumbar scoliosis (Lenke 5) when compared with double-thoracic (Lenke 2) group at the two-year follow-up (mean [95% CI] 3.6 [3.3-3.9] vs. 4.3 [4.1-4.6]). The postoperative satisfaction domain was lower in Lenke 5 group when compared with main thoracic (Lenke 1) group (mean [95% CI] 3.8 [3.5-4.0] vs. 4.3 [4.2-4.5]) and Lenke 2 group (mean 4.4, 95% CI 4.2-4.6) at the two-year follow-up. The mean total score of SRS-24 at the 10-year follow-up was highest in Lenke 1 group (mean 4.06, 95% CI 3.79-4.33) and lowest in Lenke 6 group (mean 2.92, 95% CI 2.22-3.61). CONCLUSIONS: Lenke classification and especially its curve type (major thoracic vs. major thoracolumbar scoliosis) was associated with long-term health-related quality of life after instrumented spinal fusion for AIS.

Comparison of magnetic resonance imaging findings among sciatica patients classified as centralizers or non-centralizers.

OBJECTIVE: To compare if the degenerative findings from MRI differ between the sciatica patients classified as centralizers (CEN) and non-centralizers (Non-CEN) according to the McKenzie Method of mechanical diagnosis and therapy. STUDY DESIGN: A cross-sectional study. METHODS: Patients (N = 100) referred to a spine clinic of a single tertiary hospital for specialist consultation for sciatica. The McKenzie-based assessment was performed by the mechanical diagnosis and therapy-trained physiotherapists. Clinical data and prevalence of lumbar MRI findings were compared between the groups. RESULTS: There was no significant difference in leg pain intensity between the groups. The Non-CEN had significantly more intense back pain, mean 56 (SD 30) and were more disabled 44 (SD 15) compared to the CEN mean 41 (SD 25) and mean 31 (11), measured with a visual analogue scale (0-100), and the Oswestry Disability Index (0-100), respectively. The CEN had more severe degenerative findings on MRI than the Non-CEN: vertebral end-plate changes were 63% and 43%; mean Pfirrmann's disc degeneration lumbar summary score was 12.8, and 10.6; and severity score of total damage was 12.0 and 10.1, respectively. There were differences neither in disc contour changes nor nerve root stenosis on MRI. CONCLUSIONS: Sciatica patients classified as non-centralizers had significantly more severe back pain, and were significantly more disabled than centralizers, who instead had more severe degenerative findings on MRI. Thus, classification to non-centralizers by the McKenzie method seems not predict higher incidence of degenerative findings on MRI compared to centralizers.

Traumatic Hip Dislocation in Pediatric Patients: Clinical Case Series and a Narrative Review of the Literature with an Emphasis on Primary and Long-Term Complications.

Traumatic hip dislocation is a rare injury in pediatric populations. Dislocation may be associated with low-energy trauma, such as a minor fall. Traumatic hip dislocation is associated with severe complications, such as avascular necrosis of the femoral head. Timely diagnosis and reposition decrease the rate of complications. In this study we retrospectively assessed traumatic hip dislocations in pediatric patients during a 10-year timespan in a university hospital. There were eight cases of traumatic hip dislocations. All patients had a minimum follow-up of two years and were followed with MRI scans. One patient developed avascular necrosis during the follow-up which resolved conservatively. There were no other significant complications. In conclusion, traumatic hip dislocation is a rare injury which is associated with severe complications. Patients in our case series underwent a timely reposition. The complication rate was similar to previous reports.

Occupational Risk Factors for Hoarseness Among Police Officers in Finland.

PURPOSE: Police officers have many work-related risks. In Finland, hoarseness and other respiratory symptoms and related risk factors have not been investigated on a national level. In many of the work tasks carried out by the police, an excellent physical and mental condition is essential. METHOD: Our aim was to determine the prevalence of hoarseness and related respiratory symptoms and to investigate eventual occupational risk factors associated with hoarseness. We also compared different work tasks and remediation procedures in three police stations with indoor air problems. MATERIAL: In all, 767 persons completed a nation-wide e-mail survey. The study population is approximately 11% of the total police force in Finland. Half of the study population were men. In three cities, we evaluated the outcome of different type of remediation methods after the moisture damaged buildings were renovated. The prevalence of hoarseness was compared in different work tasks and the risk associated with indoor air, work-related stress, and background factors were estimated. Information on the remediation was obtained from the employer. RESULTS: Altogether, 30.5% of the respondents had hoarseness and 15.5% had work-related stress. Almost 9% were smokers and 43% had pets at home. Of all the respondents, 13% had asthma. Hoarseness was not related to work-related stress. The strongest risk factors for hoarseness were asthma and exposure to mold odor, dusts and cold temperatures after adjusting for age, gender, smoking and pet-owning. When three renovation techniques were compared, the best results were found in the building with a thorough remediation and the removal of mold from the building. CONCLUSIONS: We conclude that the exposure to irritant gases, fumes, and bioaerosols should be minimized whenever possible in order to avoid incident asthma and voice problems.

Beam-Like rods do not Provide Additional Improvement to Thoracic Kyphosis Restoration when Compared to Sagittal Reinforced rods in Adolescents Undergoing Spinal Fusion with Pedicle Screw Instrumentation for Idiopathic Scoliosis.

OBJECTIVE: Operative treatment of adolescent idiopathic scoliosis (AIS) with posterior spinal fusion aims for three-dimensional correction of coronal curve and thoracic kyphosis. Our aim was to compare two different designs of asymmetrical rods in adolescents who underwent a posterior spinal fusion with pedicle screw instrumentation for AIS with an emphasis on thoracic kyphosis restoration. METHODS: This study was made with 76 consecutive adolescents (mean age 15.6 years, SD 2.0). Thirty-nine patients were operated with sagittal reinforced rods and 37 patients were operated with beam-like rods. The clinical and radiological results were assessed preoperatively, postoperatively, and during the follow-up visits at the outpatient clinic 6 months and 2 years after the surgery. RESULTS: At the last follow-up, the mean (SD) major thoracic curves were 13° (6.2°) and 13° (6.0°) (P = 0.717). Correction percentages were 75% in the sagittal reinforced group and 73% in the beam-like rod group (P = 0.517). The mean (SD) thoracic kyphosis was 24° (11°) and 22° (7.8°) at the two year follow-up in the sagittal reinforced rod group and beamlike rod group (P = 0.517). There was a slight negative correlation between the major curve correction and thoracic kyphosis change in both groups, although this was not statistically significant (R = -0.19, P = 0.094 in the sagittal reinforced rod group, R=-0.16, P = 0.180 in the beam like rod group). CONCLUSIONS: There are no significant differences in the coronal or sagittal deformity restoration in adolescent patients who underwent a posterior spinal fusion with sagittal reinforced rods and beam-like rods for adolescent idiopathic scoliosis.

Health-related quality of life outcomes in adolescent Scheuermann's kyphosis patients treated with posterior spinal fusion: A comparison with age- and sex-matched controls.

Purpose: To assess the health-related quality of life and radiographic outcomes of surgically treated adolescent Scheuermann's kyphosis patients after minimum of 2-year follow-up and to compare the health-related quality of life with age- and sex-matched healthy controls. Methods: Twenty-two consecutive adolescents (mean age = 16.7 years) undergoing posterior spinal fusion for Scheuermann's kyphosis were included and matched by age and sex with two healthy controls. The health-related quality of life was evaluated using the Scoliosis Research Society-24 questionnaire. Radiographic parameters were measured for comparison preoperatively and at 6 months and 2-year follow-ups. The health-related quality of life parameters were compared with healthy controls at 2 years of follow-up. Results: The mean maximal thoracic kyphosis improved from 79° (range = 75°-90°) to 55° (range = 45°-75°) (p < 0.001), and the mean lumbar lordosis was reduced from 71° (range = 51°-107°) to 52° (range = 34°-68°) (p < 0.001) after 2 years postoperatively. Incidence of proximal junctional kyphosis (PJK) was 18%. The scores of the Scoliosis Research Society-24 improved, with statistical significance observed in pain and self-image domains from preoperative to 2-year follow-up (p = 0.002 in both domains). The self-image and function were significantly lower in the operated patients at their 2-year follow-up visit compared to controls (p = 0.023 for self-image and p < 0.001 for function). Conclusion: Instrumented posterior spinal fusion improves the health-related quality of life of Scheuermann's kyphosis patients during the 2-year follow-up. The greatest improvement is observed in pain and self-image domains. The health-related quality of life in pain and activity domains reaches the level of healthy individuals, while function and self-image remain at a statistically lower level.

Intraoperative 3D Imaging Reduces Pedicle Screw Related Complications and Reoperations in Adolescents Undergoing Posterior Spinal Fusion for Idiopathic Scoliosis: A Retrospective Study.

Widely used surgical treatment for adolescent idiopathic scoliosis (AIS) is posterior spinal fusion using pedicle screw instrumentation (PSI). Two-dimensional (2D) or three-dimensional (3D) navigation is used to track the screw positioning during surgery. In this study, we evaluated the screw misplacement, complications, and need for reoperations of intraoperative 3D as compared to 2D imaging in AIS patients. There were 198 adolescents, of which 101 (51%) were evaluated with 2D imaging and 97 (49%) with 3D imaging. Outcome parameters included radiographic correction, health-related quality of life (HRQOL), complications, and reoperations. The mean age was 15.5 (SD 2.1) years at the time of the surgery. Forty-four (45%) patients in the 3D group and 13 (13%) patients in the 2D group had at least one pedicle screw repositioned in the index operation (p < 0.001). Six (6%) patients in the 2D group, and none in the 3D group had a neurological complication (p = 0.015). Five (5%) patients in the 2D group and none in the 3D group required reoperation (p = 0.009). There were no significant differences in HRQOL score at two-year follow-up between the groups. In conclusion, intraoperative 3D imaging reduced pedicle screw-related complications and reoperations in AIS patients undergoing PSI as compared with 2D imaging.

Alcohol intoxication and lack of helmet use are common in electric scooter-related traumatic brain injuries: a consecutive patient series from a tertiary university hospital.

PURPOSE: Clinicians have increasingly encountered traumatic brain injuries (TBI) related to electric scooter (ES) accidents. In this study, we aim to identify the modifiable risk factors for ES-related TBIs. METHODS: A retrospective cohort of consecutive patients treated for ES-related traumatic brain injuries in a tertiary university hospital between May 2019 and September 2021 was identified and employed for the study. The characteristics of the accidents along with the clinical and imaging findings of the injuries were collected from the patient charts. RESULTS: During the study period, 104 TBIs related to ES accidents were identified. There was a high occurrence of accidents late at night and on Saturdays. In four cases, the patient's helmet use was mentioned (3.8%). Seventy-four patients (71%) were intoxicated. At the scene of the accident, seventy-seven (74%) of the patients had a Glasgow Coma Scale score of 13-15, three patients (3%) had a score of 9-12, and two patients (2%) had a score of 3-8. The majority (83%) of TBIs were diagnosed as concussions. Eighteen patients had evidence of intracranial injuries in the imagining. Two patients required neurosurgical procedures. The estimated population standardized incidence increased from 7.0/100,000 (95% CI 3.5-11/100,000) in 2019 to 27/100,000 (95% CI 20-34/100,000) in 2021. CONCLUSIONS: Alcohol intoxication and the lack of a helmet were common in TBIs caused by ES accidents. Most of the accidents occurred late at night. Targeting these modifiable factors could decrease the incidence of ES-related TBIs.

Structural and Construct Validity of the Foot and Ankle Ability Measure (FAAM) With an Emphasis on Pain and Functionality After Foot Surgery: A Multicenter Study.

The Foot and Ankle Ability Measure (FAAM) is a patient-reported outcome measure that is available in several languages. We aim to assess the structural and construct validity of the FAAM with an emphasis on pain and functionality after foot surgery. The activities of daily living (ADL) and Sports subscales of the Finnish version of the FAAM were completed by 182 patients who underwent operative treatment for disorders of the foot. Convergent validity was assessed by principal component analysis using Spearman's correlation coefficient between the FAAM subscales and the principal components (Function-PC and Pain-PC) derived from validated patient-reported outcome measures. Subscales were studied for floor and ceiling effects, internal consistency and unidimensionality. Internal consistency was examined with Cronbach's alpha and the subscale structure with exploratory factor analysis. FAAM-ADL had high correlation with the Function-PC (r = 0.87, 95% confidence interval [CI] 0.81-0.91) and the Pain-PC (r = 0.75, 95% CI 0.65-0.83). FAAM-Sports had moderate correlation (r = 0.64, 95% CI 0.50-0.74) with the Function-PC and high correlation (r = 0.74, 95% CI 0.64-0.82) with the Pain-PC. No floor or ceiling effects were observed. Cronbach's alpha was 0.97 (95% CI 0.96-0.98) for the ADL and 0.93 (95% CI 0.91-0.95) for the Sports subscales. The results supported the unidimensionality of the FAAM-Sports. Within the ADL subscale, 3 factors were identified, suggesting a 3-factor model for the FAAM overall. Results highlighted the inter-relationship of pain and physical function. Further research on longitudinal validity is needed.

Traumatic Rupture and Herniation of the Peroneus Tertius Muscle Leading to Compartment Syndrome and Entrapment of the Superficial Peroneal Nerve: A Case Report.

We present a patient with compartment syndrome and entrapment of the superficial peroneal nerve due to a direct hit to the lateral part of the right lower extremity. The diagnosis of evolving compartment syndrome was made without delay and the patient was quickly taken to the operating theater. Intraoperatively, the entrapment of the superficial peroneal nerve caused by rupture and herniation of the peroneus tertius muscle was surprisingly observed at the site, where the nerve pierces the anterior compartment. The nerve was successfully released in conjunction with fasciotomies of the anterior and lateral compartments. Meticulous diagnosis of compartment syndrome is critical to prevent ischemic injury to muscles and nerves. Recognition of anatomy and anatomical variations is important to prevent iatrogenic injury in unusual circumstances.

Indoor-related microbe damage induces complement system activation in building users.

In this comparative study, serum complement system antimicrobial activity was measured from 159 serum samples, taken from individuals from microbe-damaged (70 samples) and from reference buildings (89 samples). Antimicrobial activity was assessed using a probe-based bacterial Escherichia coli-lux bioluminescence system and comparison was made at a group level between the experimental and reference group. The complement activity was higher in users of microbe-damaged buildings compared with the reference group and the significant (P < 0.001) increase in activity was found in the classical reaction pathway. This study strengthens our notion that exposure to indoor-related microbe damage increases the risk for systemic subclinical inflammation and creates a health risk for building users.

Investigating the short- and long-term effects of antibacterial agents using a real-time assay based on bioluminescent E. coli-lux.

We have previously established that the E. coli-lux assessment is a convenient tool for rapid measurements of the kinetical features of short-term toxicity caused by various factors. In this study, kinetic measurements of seven specifically acting model antibacterials (i.e., polymyxin B, chloramphenicol, nalidixic acid, kanamycin, deoxynivalenol, erythromycin and tetracycline) and two metals (AgNO3 and CdCl2) against E. coli-lux through a bioluminescence- and optical density-based real-time assay that combined short- and long-term toxicity assessments were performed. Bacteria were exposed to antibacterials and the effects were reported as the half-maximum effective concentration (EC50) after 30 min and 10 h. Regarding the 10-hour endpoints, all reference compounds, except deoxynivalenol, showed dose-response inhibition in the studied concentration range. The analysis of chloramphenicol, kanamycin, erythromycin, tetracycline and nalidixic acid clearly revealed the limitations of short-term inhibition tests. No significant differences were observed between the results obtained from luminescence inhibition and growth inhibition assays. The kinetical data from measurements provide differentiation between bacteriostatic and bactericidal mechanisms of various types of antibacterial agents. The combined assessment of short- and long-term effects reduces the risk of the underestimation of toxicity due to an inaccurate endpoint selection. The cost-efficient and fully automated E. coli-lux assessment technique may offer possibilities for high-throughput screening procedures.

Indoor exposure to Streptomyces albus and Aspergillus versicolor elevates the levels of spore-specific IgG, IgG1 and IgG3 serum antibodies in building users - A new ELISA-based assay for exposure assessment.

Moisture-indicative microbes in buildings are associated with a variety of symptoms, ranging from mild irritation to severe clinical illnesses. These symptoms are caused principally by dried, dormant and dead microbe material like spores, mycelium and microbe metabolites, leading to the activation of the immune system and formation of the antigen-specific immunoglobulins. This activation presumably takes place through the respiratory track and is a normal immune reaction against pathogenic invaders. During continuous exposure, a prolonged state of inflammation will follow, and this forms a considerable health risk for a building's occupant. A new ELISA system utilizing spores from two species Streptomyces albus and Aspergillus versicolor as an antigen was developed to reveal the related immunological processes. In 159 persons, microbial exposure was observed to increase the levels of spore-specific IgG, IgG1 and IgG3 serum antibody levels of individuals residing in microbe-dense buildings compared with the control reference buildings. No differences were detected in the levels of S. albus- and A. versicolor-specific serum IgA or IgM levels.

A real-time-based in vitro assessment of the oxidative antimicrobial mechanisms of the myeloperoxidase-hydrogen peroxide-halide system.

Mammals have evolved a special cellular mechanism for killing invading microbes, which is called the phagocytosis. Neutrophils are the first phagocytosing cells that migrate into the site of infection. In these cells, hypochlorite (HOCl) and other hypohalites, generated in the myeloperoxidase (MPO)-hydrogen peroxide (H2O2)-halide system is primarily responsible for oxidative killing. Here, we present a method for assessing these oxidative mechanisms in an in vitro cell-free system in a kinetical real-time-based manner by utilizing a bioluminescent bacterial probe called Escherichia coli-lux. The E. coli-lux method provides a practical tool for assessing the effects of various elementary factors in the MPO-H2O2-halide system. Due to the reported versatile intracellular pH and halide concentration during the formation of the phagolysosome and respiratory burst, the antimicrobial activity of the MPO-H2O2-halide system undergoes extensive alterations. Here, we show that at a physiological pH or lower, the antimicrobial activity of MPO is high, and the system effectively enhances the H2O2-dependent oxidative killing of E. coli by chlorination. The HOCl formed in this reaction is a prominent microbe killer. During the respiratory burst, there is a shift to a more alkaline environment. At pH 7.8, the chlorinating activity of MPO was shown to be absent, and the activity of the HOCl decreased. At this higher pH, the activity of H2O2 is enhanced and high enough to kill E. coli without the participation of MPO, and the lowered chloride concentration seemed still to enhance the H2O2-dependent killing capacity.