Pathology Level Research Articles

Minimally-invasive trans-facet lumbar interbody fusion using a dual-dimension expandable cage: preliminary results of a multi-institutional retrospective study.

Minimally-invasive trans-facet lumbar interbody fusion (LIF) is an emerging technique that offers the advantages of being safe, enabling decompression, and facilitating patient recovery. An innovative cage that expands in two dimensions has been introduced to restore segmental lordosis and disc height while minimizing the risk of cage subsidence. This study aimed to report our surgical technique of trans-facet LIF utilizing the innovative cag and to report the early clinical outcomes. We retrospectively reviewed the medical records and radiographs of patients who underwent trans-facet LIF with dual-dimension expandable cages from two institutions: Duke University Hospital and Vail-Summit Orthopaedics and Neurosurgery. The analysis covered patient demographics, Oswestry Disability Index (ODI), visual analogue scale (VAS) for back pain, surgical data, complications, and radiographic parameters. Clinical outcomes were compared between pre- and one year post-operation, while radiographic outcomes were compared between pre- and three months post-operation. Twenty patients with a mean age of 61.2 years were included. Seventeen patients (85.0%) had spondylolisthesis, and L4/5 (68.2%) was the most common pathology level. Twelve patients (60.0%) underwent awake surgery, and the mean operative time was 164.5±36.1 minutes, with an estimated blood loss of 64.0±39.5 mL and a hospital stay of 1.75±1.2 days. Four patients (20.0%) experienced cage subsidence; however, none required additional surgery. The VAS score significantly improved from a preoperative average of 7.3±2.7 to 2.6±1.6 one year post-operation (P=0.02). The ODI score also showed a significant decrease, from 48.7±22.9 preoperatively to 16.4±11.1 one year postoperatively (P=0.03). Notably, 80% and 83.3% of patients achieved the minimum clinically important difference in VAS and ODI scores, respectively. The degree of spondylolisthesis was significantly reduced from a median of 5.9 mm preoperatively to 0 mm postoperatively (P<0.001). Additionally, both anterior and posterior disc heights significantly increased after surgery, from 9.8±4.7 to 15.1±2.6 mm (anterior) and from 4.9±3.3 to 10.5±2.2 mm (posterior) (P<0.001 for both). The mean segmental lordosis increased by 2.9 degrees and was associated with cage height (P=0.03), while spinopelvic parameters remained unchanged. Minimally-invasive trans-facet LIF with dual-dimension expandable cages demonstrates a substantial capacity for spondylolisthesis reduction and disc height restoration, and provides good short-term clinical outcomes. It may be the most appropriate method for deploying this large cage as it allows for a large, unobstructed pathway to the disc. However, future studies are needed to determine the long-term outcomes, including the arthrodesis rate.

Collagen integrity of the annulus fibrosus in degenerative disc disease individuals quantified with collagen hybridizing peptide.

Degenerative disc disease (DDD) is accompanied by structural changes in the intervertebral discs (IVD). Extra-cellular matrix degradation of the annulus fibrosus (AF) has been linked with degeneration of the IVD. Collagen is a vital component of the IVD. Collagen hybridizing peptide (CHP) is an engineered protein that binds to degraded collagen, which we used to quantify collagen damage in AF. This method was used to compare AF samples obtained from donors with no DDD to AF samples from patients undergoing surgery for symptomatic DDD. Fresh AF tissue was embedded in an optimal cutting temperature compound and cryosectioned at a thickness of 8 μm. Hematoxylin and Eosin staining was performed on sections for general histomorphological assessment. Serial sections were stained with Cy3-conjugated CHP and the mean fluorescence intensity and areal fraction of Cy3-positive staining were averaged for three regions of interest (ROI) on each CHP-stained section. Increases in mean fluorescence intensity (p = 0.0004) and percentage of positively stained area (p = 0.00008) with CHP were detected in DDD samples compared to the non-DDD samples. Significant correlations were observed between mean fluorescence intensity and percentage of positively stained area for both non-DDD (R = 0.98, p = 5E-8) and DDD (R = 0.79, p = 0.0012) samples. No significant differences were detected between sex and the lumbar disc level subgroups of the non-DDD and DDD groups. Only tissue pathology (non-DDD versus DDD) influenced the measured parameters. No three-way interactions between tissue pathology, sex, and lumbar disc level were observed. These findings suggest that AF collagen degradation is greater in DDD samples compared to non-DDD samples, as evidenced by the increased CHP staining. Strong positive correlations between the two measured parameters suggest that when collagen degradation occurs, it is detected by this technique and is widespread throughout the tissue. This study provides new insights into the structural alterations associated with collagen degradation in the AF that occur during DDD.

Comparison of Titanium Mesh Cage, Nano-Hydroxyapatite/Polyamide Cage, and 3D-Printed Vertebral Body for Anterior Cervical Corpectomy and Fusion.

A prospective non-randomized controlled study. To compare the clinical and radiographic outcomes of anterior cervical corpectomy and fusion (ACCF) using titanium mesh cages (TMC), nanohydroxyapatite/polyamide66 (n-HA/PA66) cages, and 3D-printed vertebral bodies (3d-VBs). Postoperative subsidence of TMCs in ACCF had been widely reported. Newer implants such as n-HA/PA66 cages and 3d-VBs using biocompatible titanium alloy powder (Ti6Al4V) had been introduced to address this issue, but their outcomes remain controversial. We enrolled 60 patients undergoing ACCF using TMCs, n-HA/PA66 cages, or 3d-VBs from January 2020 to November 2021. For each group, there were 20 patients. Follow-up was conducted for minimum two years. Clinical outcomes, including Japanese Orthopaedic Associationscores (JOA), Neck Disability Index (NDI) and Visual Analogue Scale (VAS) scores and radiographic outcomes, including FSU height, fusion rate, and cervical alignment were collected pre-operatively and at each follow-up. A loss of FSU height equal or greater than 3mm was deemed implant subsidence. One-way analysis of variance was used for comparisons of mean values at different time points within the same group, with pairwise comparisons performed using the LSD method. The Mann-Whitney test was used for comparisons between groups. Categorical data such as gender, smoking status, implant subsidence and pathology level were analyzed using the chi-square test. Postoperative function of spinal unit (FSU) height loss at 2 years differed significantly among the TMC, n-HA/PA66, and 3d-VB groups, measuring 3.07±1.25mm, 2.11±0.73mm, and 1.46±0.71mm, respectively (P<0.001). The rates of implant subsidence were 45%, 20%, and 10%, respectively (P=0.031). All patients obtained solid fusion at 2-year follow-up. We observed statistically significant differences in VAS and JOA scores at 3 months postoperatively, and JOA scores at 2 years postoperatively among the three groups. At two-year follow-up, the n-HA/PA66 and the 3d-VBs groups exhibited less FSU height loss, lower subsidence rates and demonstrated better cervical lordosis than the TMC group. No severe postoperative complications were observed in any of the patients, and no patient required reoperation. At two-year follow-up after ACCF, the n-HA/PA66 and the 3d-VBs groups exhibited less FSU height loss, lower subsidence rates and demonstrated better cervical lordosis than the TMC group. Longer term observation of implant subsidence in ACCF using TMC, n-HA/PA66, and 3d-VB, is necessary. Therapeutic Level III.

Functional Outcomes of Therapeutic Selective Nerve Root Block for Single-Segment Lumbar Spinal Stenosis: A Retrospective Study.

BACKGROUND Functional evaluation after therapeutic selective nerve root block (SNRB) has been rarely reported. We explored functional outcomes of SNRB for single-segment lumbar spinal stenosis (LSS). MATERIAL AND METHODS Data for 117 patients with single-segment LSS who underwent single therapeutic SNRB were retrospectively collected between January 2019 and December 2021. Functional outcomes were assessed using Oswestry Disability Index (ODI) and Japanese Orthopaedic Association (JOA) scores preoperatively, and 3 days, and 3, 6, and 12 months after SNRB, which were compared in subgroups stratified by age, sex, BMI, sedentary time, hypertension, diabetes, affected side, pathology level, intervertebral disk. Correlation between ODI and JOA was analyzed using univariate linear regression analysis. RESULTS Clinical symptoms of LSS significantly improved within 12 months after SNRB, especially at 6 months (P<0.05). ODI scores in each subgroup gradually decreased within 6 months after SNRB, and JOA scores gradually increased. Most subgroup analyses revealed significantly increased ODI scores and decreased JOA scores at 12 months after SNRB, compared with 6-month scores (P<0.05). Notably, ODI and JOA scores at 12 months after SNRB were not significantly different than those before SNRB in patients with BMI >25 or sedentary time >8 h (P>0.05). A significant correlation existed between ODI and JOA scores (P<0.05). CONCLUSIONS Therapeutic SNRB was an effective treatment for alleviating LSS within at least 6 months. Changing sedentary habits with appropriate exercise and controlling weight with a healthy diet can improve the effectiveness of SNRB, especially in patients for whom conservative treatment is ineffective and who are unsuitable for surgical treatment.

Evaluation of osteomeatal complex by cone-beam computed tomography in patients with maxillary sinus pathology and nasal septum deviation

BackgroundThis study aimed to determine if there is a relationship between the presence of maxillary sinus pathology, nasal septum deviation and various lengths of the osteomeatal complex.MethodsA total of 223 CBCT images were included in the study. The lengths of the osteomeatal complex (maxillary sinus ostium width, infundibulum length, maxillary sinus ostium height) were analyzed. The presence of maxillary sinus pathology, nasal septum deviation, age, sex, right-left, septum deviation level, and the relationship between pathology level and all variables were evaluated.ResultsThe average maxillary sinus ostium width, ostium height and infundibulum length were 3.06 ± 0.70 mm, 30.10 ± 5.43 mm and 8.82 ± 1.86 mm, respectively. Ostium width was significantly higher in the healthy group than in the groups evaluated in the presence of deviation and pathology. A significant difference was found in infundibulum length only between the healthy condition and the condition evaluated in the presence of deviation. No significant difference was observed between the groups in terms of ostium height. In all groups, ostium height and infundibulum length were significantly higher in men than in women. The age group with the highest average ostium height was found in the 35–44 age group (p < 0.001).ConclusionIdentifying normal and abnormal conditions in the osteomeatal complex area is important for diagnosing the cause of a patient's complaint, guiding the surgical procedures to be performed, and preventing possible complications that may arise during surgical procedures.

Cerebral-cognitive reserve: concept and functions of the cerebral-cognitive reserve

IntroductionThe modern understanding of AD allows us to consider it through the constructs of “vulnerability” and “stability” of the brain as a dynamic system of dialectical interaction between the pathogenic process and the protective process that prevents neurodegeneration. The concept of cognitive reserve (CR) is based on observations of discrepancy between the degree of brain pathology and the severity of clinical manifestations. The concept of “reserve” was proposed to describe the resistance of the brain to a developing damage caused by a pathological process. Stern (2002) considered CR as a protective factor that modifies the impact of brain pathology on cognitive function. The researchers have defined CR as an ability to optimize cognitive function through differential involvement of structures or neural networks of the brain into brain activity.ObjectivesA systematic review of scientific studies has been conductedMethodsThe review includes an analysis of full-text literature sources.ResultsSeveral possible directions of CR influence on cognitive functions have been described:1)CR may reduce the risk of MCI or dementia through mechanisms, which do not depend on the level of neurodegenerative pathological changes in the brain.2)CR can interact with the markers of brain pathology or healthaffectingthe future cognitive decline or risk of progression. It has been found that smaller volumes or thickness in some AD vulnerable areas of the brain represent a stronger risk factor for cognitive impairment in people with low CR than in people with higher CR. CR protective effects on clinical outcomes reduce as the number of damaged neurons increases.3)The protective effect of CR increasesduring late AD onset and at a low rate of the damaged substrate accumulation.4)CR changes the relationship between genetic factors and aging withclinical and cognitive outcomes. The relationship between age and AD pathology level or age-related structural changes in the brain may weaken in people with higher CR ConclusionsThe concept of cerebral-cognitive reserve actualizes the problem of the search for compensatory mechanisms of cognitive deficit in AD, the assessmentof the structure of the reserve, the development and implementationof programs to maintain the reserve, the preventionof its depletion, starting from the preclinical stage of the disease, which can prevent the transformation of preclinical manifestations of AD into cognitive disordersDisclosure of InterestNone Declared

Late diagnostics of hereditary nephrogenic diabetes insipidus: clinical case

Diabetes insipidus belongs to the group of rare heterogeneous diseases, it can manifest at any age and is distinguished by a variety of etiological factors, pathogenetic mechanisms and clinical variants of the debut and course. A significant water-electrolyte imbalance in this type of diabetes is its "calling card". The article presents a description of a clinical case of a preschool patient with early verification and late diagnosis of hereditary nephrogenic diabetes insipidus as a result of the lack of alertness of primary care specialists. Low awareness of parents about the essence of the pathology, insufficient sanitary and cultural level of the family and, as a result, a low level of parental compliance create additional risks for achieving a long-term remission. This case reflects the importance of a thorough history taking, which makes it possible to suspect the hereditary nature of the disease from the first days of a child's life at the outpatient stage. Carrying out timely diagnostics both at the regional and federal levels for further development of treatment tactics, recommendations and a follow-up plan is a necessary step towards improving the patient's quality of life.

Cortisol, cognition, and Alzheimer’s disease biomarkers among memory clinic patients

AbstractBackgroundChronic stress has been studied as a potential lifestyle risk factor for Alzheimer's disease (AD). Prolonged stress can lead to alterations in diurnal patterns of cortisol. This study aims to investigate the relationship between diurnal cortisol patterns, cognition, and AD biomarkers in memory clinic patients.MethodParticipants diagnosed with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or AD dementia were recruited from Karolinska University Hospital memory clinic in Sweden (n=155). Baseline cognition was measured using five cognitive domains (memory, working memory, processing speed, perceptual reasoning, overall cognition), operationalized as average z‐scores. Diurnal cortisol patterns were assessed using five salivary cortisol measures: awakening levels, cortisol awakening response, bedtime levels, the ratio of awakening to bedtime cortisol levels (AM/PM ratio), and total daily output. AD biomarkers Aβ42, total tau (T‐Tau), and phosphorylated tau (P‐Tau) were measured from cerebrospinal fluid. Cognition was measured at follow‐up (average 32 months) in a subsample of participants (n=57).ResultAwakening cortisol levels were significantly higher in AD dementia compared with SCI. Greater cortisol awakening response was associated with better memory performance (OR= 1.57, 95% CI: [1.10 – 2.23]), while a greater AM/PM ratio (OR= 2.21, 95% CI: [1.15 – 4.25]) and lower bedtime cortisol levels (OR= .64, 95% CI: [.40 – 1.01]) were associated with better overall cognition. Cortisol measures were not associated with cognitive decline during follow‐up or with AD biomarkers in the full sample. However, in stratified analyses, higher awakening cortisol levels were associated with lower CSF Aβ42 in amyloid‐positive participants (b= ‐60.13; 95% CI [‐102.73 ‐ ‐17.52]), while higher bedtime cortisol levels (b= .09; 95% CI [.02 ‐ .17]) and a lower AM/PM ratio (b= ‐.12; 95% CI [‐.23 ‐ ‐.02]) were associated with higher CSF T‐Tau in amyloid‐negative participants.ConclusionThis study shows that diurnal cortisol patterns are associated with cognitive performance in memory clinic patients. In people without amyloid pathology, cortisol may affect cognition through neurodegeneration‐related mechanisms, leading to the observed correlation with T‐Tau. Meanwhile, in amyloid‐positive participants, the greater pathology level may affect cortisol patterns. Further research should investigate the complex relationship between cortisol, cognition, and brain pathology.

Osteopontin as a Predictor of Adverse Events in Patients with Comorbid Pathology

Information about the results of the examination of 78 women aged 50 to 65 years is given. The nature of comorbid pathology was studied: chronic heart failure, type 2 diabetes mellitus and osteoporosis. It has been established that osteopontin is an independent risk factor for the development of adverse cardiovascular events and bone fractures in women with comorbid pathology. During 36 months of prospective follow-up, patients with comorbid pathology and OPN level &gt;21.4 ng/ml were significantly more likely to have adverse cardiovascular events and osteoporotic fractures. In patients of the 2nd group with an AKI level of &gt;21.4 ng/ml compared with the group with an AKI concentration of ≤21.4 ng/ml, the risk of cumulative (combined frequency of the combined end point of cardiovascular events) was increased (OR = 6.200 [95% CI 2.258-17.024; p=0.001]). Separate analysis showed a significant increase in the risk of adverse events within 36 months at an AKI concentration of &gt;21.4 ng/ml: progression of CHF (OR=4.073 [95% CI 1.575–10.531; p=0.023]) and osteoporotic bone fractures (OR=0 .81 [95% CI 0.72-0.90; p=0.01]); risks of MI (OR=4.343 [95% CI 0.463-40.751; p=0.162]), stroke (OR=1.178 [95% CI 0.315-31.860; p=0.498]), and decompensation of CHF (OR=1.938 [95% CI 0.696-5.391; p=0.083]) increased insignificantly. The level of acute renal failure &gt;21.4 ng/ml (sensitivity-83%, specificity-62%) makes it possible to predict the onset of adverse cardiovascular events in patients with coronary artery disease with type 2 diabetes and osteoporosis with a high probability.

Supplementation of conventional anti-diabetic therapy with alpha-lipoic acid prevents early development and progression of diabetic nephropathy

BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease. Current pharmacological interventions only retard DN progression. Alpha-lipoic acid (ALA) is a potent antioxidant with beneficial effect in other diabetic complications. This study investigates whether ALA supplementation prevents early development and progression of DN. MethodFifty-eight male Sprague-Dawley rats were randomly assigned to healthy control and diabetic groups and subjected to overnight fasting. Type 2 diabetes mellitus (T2DM) was induced in diabetic group by intraperitoneal administration of nicotinamide (110 mg/kg) and streptozotocin (55 mg/kg). On day 3 after T2DM induction, diabetic rats received oral daily administration of ALA (60 mg/kg), gliclazide (15 mg/kg), ramipril (10 mg/kg) or drug combinations for 6 weeks. Untreated diabetic rats served as diabetic control. Blood, kidneys and pancreas were harvested for biochemical and histological analyses. ResultInduction of T2DM resulted in hypoinsulinemia, hyperglycemia and renal pathology. ALA supplementation maintained β-cell function, normoinsulinemia and normoglycemia in diabetic rats, and prevented renal pathology (PAS, KIM-1, plasma creatinine, total protein, blood urea nitrogen, uric acid and urine albumin/creatinine ratio) and triglycerides level compared to diabetic control (p < 0.001). Additionally, ALA supplementation significantly prevented elevated serum and tissue malondialdehyde, collagen deposition, α-SMA expression, apoptosis and serum IL-1β and IL-6 levels while it markedly increased renal glutathione content and plasma HDL-C compared to diabetic control group (p < 0.001). ConclusionALA supplementation prevents early development and progression of DN by exerting anti-hyperglycemic, antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic effects. Our findings provide additional option for clinical treatment of DN in T2DM patients.

Abstract P1-02-09: Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer (ILC)

Abstract Background. ILC represents the second most common histological type of breast cancer (BC), accounting for approximately 15% of all invasive BCs. Loss of cell-cell adhesion due to genomic alterations of CDH1,. the gene coding for E-cadherin, is the hallmark of ILC. So far, in the WHO guidelines, it is essential to recognize the dispersed or linear discohesive cells but it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC) for diagnosing ILC. Recent central pathology revisions of clinical trials have demonstrated overdiagnosis of ILC in local pathological diagnosis, as only ~60% of the locally diagnosed ILCs were confirmed by central pathology. To understand the possible underlying reasons, we undertook a worldwide survey on the currently used histopathological diagnostic criteria for ILC. Materials and Methods. A survey was drafted using the online tool SurveyMonkey by a panel of pathologists and researchers from the European Lobular Breast Cancer Consortium (ELBCC). This survey was circulated to pathologists from December 14, 2020 until July, 1 2021. The main goals were to register the use of E-cadherin as a diagnostic marker for ILC and the systematic reporting of the ILC subtypes. Results. A total of 149 entries were recorded from 34 different countries from 6 continents. Pathologists declared working in a large tertiary (30%, 44/149) or university hospital (56%, 84/149), with an average yearly volume of BC samples &amp;gt;300 in 111/149 (74%) and &amp;gt;500 in 80/149 (54%) respondents. 117/149 (79%) are specialized in breast pathology. About half of the pathologists systematically perform IHC for ILC diagnosis (52%, 77/149), whilst others only perform staining in case of doubt (43%, 64/149) or for differentiating DCIS from LCIS (3%, 4/149). There was no association between the systematic use of IHC, the volume of BC samples, the type of institution (academic, large tertiary, private), and the number of pathologists in the institution. Concerning the use of IHC, 141/145(97%) participants use E-cadherin, 35/145 (24%) use β-catenin and 49/145 (34%) use p120-catenin. The majority (50%, 73/145) uses only E-cadherin, 13% (19/145) use E-cadherin in combination with β-catenin or 23% (33/145) use E-cadherin with p120-catenin, while 11% (16/145) use all 3 antibodies. For E-cadherin, 11 different clones were reported, of which the NCH-38 is the most frequently used (45%, 39/86), followed by Clone 36 (17%, 15/86) and EP700Y (16%, 14/86). Heterogeneity is reported regarding the used concentration per clone. The most frequently used modality of antigen retrieval is the heat induced one. Similar findings were observed for β-catenin and p120-catenin with each 4 different clones reported, again with variable concentrations. Only 4/104 (4%) respondents reported to perform DNA sequencing for CDH1 for diagnosing ILC. Most special lobular types are systematically reported by the vast majority of the pathologists: classic (149/149, 100%), pleomorphic (140/149, 94%), solid (108/149, 72%), histiocytoid/apocrine (90/149, 60%), alveolar (90/149, 60%), trabecular (54/149, 36%), mixed non-classic (54/149, 36%) and mucinous (51/149, 34%). Conclusions. We report the results of the first worldwide survey concerning diagnosis of ILC in pathological practice. The results demonstrate that ~half of the institutions systematically perform E-cadherin IHC to support the diagnosis of ILC. There is a great variability in E-cadherin antibody clones used as well as their concentrations, which might result in differences in staining results and their interpretation. As ILC-specific therapeutic avenues are currently being explored, some of which already in the context of clinical trials, it is of utmost importance to further improve the standardization of ILC diagnosis at the pathology level. Citation Format: Maxim De Schepper, Anne Vincent-Salomon, Matthias Christgen, Karen Van Baelen, Hitoshi Tsuda, Sasagu Kurozumi, Maria Jose Brito, Gabor Cserni, Stuart Schnitt, Denis Larsimont, Janina Kulka, Pedro Luis Fernandez, Paula Rodriguez, Ana Aula, Cristina Mendelez, Mieke Van Bockstal, Aniko Kovacs, Zsuzsanna Varga, Jelle Wesseling, Rohit Bhargava, Pia Boström, Camille Franchet, Blessing Zambuko, Gustavo Matute, Anca Berghian, Paul van Diest, Steffi Oesterreich, Patrick WB Derksen, Giuseppe Floris, Christine Desmedt. Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer (ILC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-02-09.

Hydroxysafflor yellow A (HSYA) improve scars by vivo and vitro study

The purpose of this research was to evaluate HSYA’ effects and mechanisms to improve Scars Induced by Anticoagulant Injection by vivo and vitro study. New Zealand rabbits were divided into Normal control (NC), Anticoagulant, Anticoagulant+HSYA-Low, Anticoagulant+HSYA-Middle and Anticoagulant+HSYA-High. Measuring TGF-β1 and IL-1β concentration by Elisa assay; evaluating pathology and fibrosis level by HE and Masson staining, measuring collage I, collage III, TLR4 and NF-κB(p65) protein expression by IHC assay. Relative gene expression (Collage I, Collage III, TLR4 and NF-κB(p65)) were evaluated by RT-qPCR assay. Relative proteins expression (Collage I, Collage III, TLR4 and NF-κB(p65)) were evaluated by WB assay. And using TGF-β1 to stimulate cell to make cell model. Compared with NC group, TGF-β1 and IL-1β concentration were significantly increased (P < 0.001); The pathology and fibrosis level were significantly deteriorated, meanwhile, Collage I, Collage III, TLR4 and NF-κB(p65) proteins and gene expression were significantly up-regulation in Anticoagulant group (P < 0.001). With HSYA supplement, TGF-β1 and IL-1β concentration were significantly depressed, Pathology and fibrosis levels were significantly improved, Collage I, Collage III, TLR4 and NF-κB(p65) proteins and gene expressions were significantly improved with dose-dependent (P < 0.05). HSYA could improve anticoagulant injury induced subcutaneous scar via regulation TLR4/NF-κB(p65).

Анализ результатов по калу на скрытую кровь при диспансеризации населения в районах Республики Татарстан за 2018-2019 гг.

Purpose. The work was aimed at analyzing the fecal occult blood (FOB) test results obtained during oncoscreening for colorectal cancer due to prophylactic medical examination of the population of some municipal districts of the Republic of Tatarstan (RT) in 2018 and 2019, as well as assessing the distribution of the examined patients by gender, age, and pathology detectability for different RT regions. Material and methods. Materials for examination were stool samples taken into special vials manufactured by Sentinel Diagnostics (Italy). Materials were taken in laboratories of regional hospitals and outpatient departments. Fecal occult blood tests were performed on a AU-680 and AU-480 Beckman Coulter biochemical analyzers in the RT oncology dispensary laboratory by the immunochemical (immunoturbodimetric latex) method for quantitative determination of hemoglobin content in the stool. The reagents were supplied by Sentinel FOB Gold NG. Reference values were 0–50 ng/ml. Results. A comparative analysis of the data for two years showed the increase in inclusion of population into prophylactic medical examination from 4,2% up to 6,9% predominantly thanks to women, as well as the decrease in the revealed FOB pathology from 8,7% down to 7,7% both within men and women. The maximum increase in the amount of the examined population from 8,5% in 2018 up to 18,3% in 2019 occurred in the Atninsky municipal district. The averaged maximum abnormal level within women (12,1%) was revealed in the Vysokogorsky municipal district, but within men (16,0%) — in the Sabinsky municipal district. A two-fold increase in the abnormal level within men occurred in the Alkeyevsky, Buinsky, and Sarmanovsky municipal districts, but within women — in the Kaybitsky municipal district. Most frequently, for every fourth patient in average, exceeded reference values were observed for the total age of 60-69 and more then 70. For the age of 50-59, a permanently low abnormal level was revealed both within men (2% in 2018 and 3% in 2019) and women (3% and 3% respectively). The abnormal level over the average for the Republic within men of the age of 40-49 was revealed in seven municipal districts. The abnormal level over the average was observed within all population of the age of 40 to 50 in the Apastovsky municipal district. A positive dynamics (a decrease in pathology level below the average) within population of all age groups was observed in four municipal districts (the Drozhzhanovsky, Rybno-Slobodsky, Sarmanovsky, and Mamadyshsky districts).

World´s COVID-19 anti-pandemic measures in the context of postural and spine disorders in primary school children in Slovakia.

This study was aimed to estimate the effect of one-year persistence of COVID-19 anti-pandemic measures on the posture and spine in children of younger school age in Slovakia. A total of 135 children aged between 6 and 9 years participated in this study. The examination of posture and spine was carried out in 4 schools in 4 different districts in Slovakia. The posture was evaluated in February 2020, before anti-pandemic restrictions and in period from May 2021, after one year of anti-pandemic restrictions. Modified methodology according to Napoleon Wolanski was used to evaluate the posture. For the entire study group, the mean posture disorder level score before anti-pandemic restrictions was 5.667 (±1.75) and it rose to 7.844 (±0.64). Prevalence of posture disorders rose from 71.11 % to 91.3 % in the study group. The most affected segments were lumbar spine and pelvis, followed by deformities of the thoracis spinae. The mean pathology level score for entire group in these segments rose as followed: in the lumbar spine from 0.6 (±0.61) to 1.022 (±0.75); in the pelvis from 0.444 (±0.54) to 0.772 (±0.73) and in the thoracis spine from 0.378 (±0.53) to 0.578 (±0.61). Study confirmed a worsening of the posture and spine in school children after a one year of strict anti-pandemic measures. As postural changes increased by 20 % during the year, it seems necessary to implement appropriate preventives programs for children, which could have the potential to improve their postural state (Tab. 2, Fig. 1, Ref. 37). Text in PDF www.elis.sk Keywords: anti-pandemic restriction, e-learning, COVID-19, postural disorders, spine deformities.

APOE-e4 alters the microglial phenotype in the presence of Alzheimer's disease pathology compared to APOE-e3.

APOE is the largest genetic risk factor for late-onset Alzheimer's disease (AD) with the APOE-e4 allele conferring an increased risk for AD compared to the APOE- e3 allele. While APOE in the brain is a lipid transporter produced by astrocytes, research has shown that APOE can impact diverse biochemical pathways. Interestingly, APOE isoforms have also been shown to modulate levels of neuroinflammation in the brain, yet the exact impact on inflammation remains unknown. As microglia are considered to be a primary source of brain inflammation, this study explores how APOE isoforms impact microglial morphology and activation state in human brains. Two methods were used in this study to assess the impact of APOE isoforms on microglia in human brain sections. First, NanoString Digital Spatial Profiling (DSP) was used to investigate protein levels of inflammatory markers specific for microglia on fixed tissue in the hippocampus with AD pathology in both APOE- e3 (n=7) and APOE- e4 (n=8) subjects. Immunohistochemistry (IHC) was then performed using samples from APOE- e3/3 (n=33 control n=23 AD), APOE- e4/4 (n=19 AD), and APOE-e3/4 (n=15 control) subjects from the University of Kentucky AD Research Center. IBA-1 IHC was used to investigate microglial activation and morphology differences between APOE isoforms. Using both DSP and IHC, the results indicate that APOE isoforms play a role in the microglial changes seen in the presence of AD pathology- both in activation state and morphology. The DSP experiments showed significant changes in microglial markers throughout the hippocampal region between APOE- e3 and APOE- e4. Of interest, in APOE-e3 subjects, we show an alteration of the microglial phenotype based on pathology level, however, in APOE-e4 subjects, this change due to pathology is reduced. Additionally, in the IHC experiments we found changes in microglial morphology and activation that parallel those seen in DSP. The findings from this study suggest that with APOE- e3, microglia are able to respond in the presence of AD pathology. By contrast, APOE- e4 microglia cannot produce an appropriate response to AD pathology. Overall, these findings help highlight the role of the APOE isoforms in AD and neuroinflammation.

Experience of Application of Magnetic Resonance Myelography Methods in Patients with Neurological and Neurosurgical Pathology

Purpose — to study the possibilities of clinical application of MR-myelography techniques in static and dynamic modes in patients with various neurological and neurosurgical pathologies accompanied by CSF dynamics disorders. On the Philips 1.5 and 3.0 T MRI scanners, an extended protocol for examination of patients with cerebrospinal fluid disorders was presented. The protocol includes, in addition to routine sequences (T1-, T2-WI, FLAIR), thin-slice MP-myelography in a static mode (CSF-DRIVE, 3DMYUR) with soft tissues signal suppression. Also, a cinema-technique of MR myelography (CSF-PCA) in the optimal projection and a phase-contrast method with a quantitative assessment of the cerebrospinal fluid flow at the pathology level and at adjacent levels were performed. The assessment of the diagnostic significance of the proposed research protocol was carried out. The extended study protocol was applied in patients with idiopathic normotensive hydrocephalus, obstructive hydrocephalus, Chiari malformation type I, in patients with syringomyelia at the level of the cervical spinal cord and showed high efficiency in assessing of cerebrospinal fluid dynamics in patients with a neurological and neurosurgical profile. The use of extended approach allows to more fully evaluate the state of the cerebrospinal fluid system, the patency of the cerebrospinal fluid (the presence of additional septa / membranes, partial / complete stenosis and narrowing), as well as preand postoperative morpho-functional changes.

Phenotype-Based HPLC-Q-TOF-MS/MS Coupled With Zebrafish Behavior Trajectory Analysis System for the Identification of the Antidepressant Components in Methanol Extract of Anshen Buxin Six Pills

Phenotype screening has become an important tool for the discovery of active components in traditional Chinese medicine. Anshen Buxin Six Pills (ASBX) are a traditional Mongolian medicine used for the treatment of neurosis in clinical settings. However, its antidepressant components have not been explicitly identified and studied. Here, the antidepressant effect of ASBX was evaluated in adult zebrafish. High performance liquid chromatography-mass spectrometry (HPLC-Q-TOF-MS/MS) was combined with zebrafish behavior trajectory analysis to screen and identify the antidepressant-active extract fraction and active components of ASBX. Finally, the antidepressant effect of the active ingredients were verified by the behavior, pathology, biochemical indices and protein level of adult fish. The novel tank driving test (NTDT) showed that ASBX can effectively improve the depressive effect of reserpine on zebrafish. Petroleum ether and dichloromethane extracts of ASBX were screened as antidepressant active extracts. Costunolide (COS) and dehydrocostus lactone (DHE) were screened as the active components of ASBX. COS had been shown to significantly improve the depressive behavior, nerve injury and neurotransmitter levels (5-hydroxytryptamine (5-HT) and norepinephrine (NE)) of zebrafish by inhibiting the high expression of serotonin transporter and norepinephrine transporter induced by reserpine suggesting the antidepressant effect of COS may be related to its effect on 5-HT and NE pathways. This study provided a phenotype based screening method for antidepressant components of traditional Chinese medicines, so as to realize the separation, identification and activity screening of components at the same time.

Relationship Between Oxidative Stress, Tau Level and Antioxidant Mechanisms of the KEAP-1/NRF-2/HO-1 in Children with Hydrocephalus.

Hydrocephalus is a complex neurologic disorder that has a widespread impact on the central nervous system and a multifactor disease which affects the CSF dynamics and causes severe neurological impairments in children. The pathophysiology of hydrocephalus is not fully understood. However, increasing evidence suggests that oxidative stress may be an important factor in the pathogenesis of hydrocephalus. The purpose of this study is to investigate the relationship of the KEAP-1/NRF-2/HO-1 pathway, one of the main regulators of the antioxidant system in the hydrocephalus pathology, on oxidative stress and tau protein level. The study included 32 patients with hydrocephalus and 32 healthy controls. KEAP-1, NRF-2, HO-1, TAU, and MPO levels are measured using ELISA method TAS, TOS, and Total THIOL colorimetric method. KEAP-1, TAS, and Total THIOL levels were found significantly lowerer in the hydrocephalus group than in the control group. Nevertheless, it was identified that in the hydrocephalus group that the NRF-2, HO-1, TAU, MPO, TOS, and OSI levels were significantly elevated. In conclusion, although the KEAP-1/NRF-2/HO-1 pathway is activated in patients with hydrocephalus, it is identified that the antioxidant defense system is insufficient and ultimately leads to elevated oxidative stress. The elevation in the tau level may be an indicator of oxidative stress induced neurodegenerative damage.

The Republic of Buryatia population malignant neoplasms rate

The degree of morbidity of the population of the Republic of Buryatia with malignant neoplasms without subdivision by localization from 1996 to 2019 was analyzed according to the data of the Republican Clinical Oncological Dispensary. Material and methods. The data on the incidence of malignant neoplasms in the population of municipalities of the Buryat Republican Clinical Oncological Dispensary, expressed in intensive («rough») indicators (PI) per 100 thousand population (ppm, 0/0000) have been analyzed. The zoning of the incidence of the population has been based on the approach of medico-geographical typification of the territory. The range of indicators of the incidence of cancer in the population served as the basis for identifying four types of territories by the levels of cancer pathology: low – medium – high – very high. The dynamics of morbidity was analyzed by the average indicators of four 5-year periods (1996–2000, 2001–2005, 2006–2010, 2011–2015) and one 4-year period (2016–2019). Cartographic processing of the material was performed using Paint.NET. The comparison of morbidity in 21 municipal districts has been carried out. In period 1, there were 4 districts with low pathology (90–134 people): Okinsky, Muisky, Tunkinsky, Zakamensky districts, and with very high pathology (225–277 cases) – 4 districts: Pribaikalsky, Kabansky, Zaigraevsky, Bauntovsky. In the second period, the Okinsky, Tunkinsky, Dzhidinsky districts had low rates (100–158 cases), and the North-Baikalsky, Ivolginsky, Selenginsky, Kurumkansky, Mukhorshibirsky districts had very high level (257 and more). In the third period: low incidence rate (100–150 cases) has been determined in Muisky, Kizhinginsky districts, very high rate (274–331 cases) – in Bauntovsky, Kabansky, Zaigraevsky, Tarbagataisky districts. In the fourth period: low pathology rate (155–212 people) was in Okinsky, Zakamensky, Muisky, Eravninsky, Ivolginsky districts, very high level (329 cases) was in Bauntovsky district. In the last four years: low case rate (138–204) was only in Okinsky district, very high pathology level (339–405 people) was in 5 districts, to Bauntovsky, Kabansky, Pribaikalsky districts were added the northern districts: Severo-Baikalsky and Barguzinsky. Territories with high indicators of malignant neoplasms include: Pribaikalsky (393.5 ± 39.9 0/0000), Kabansky (397.5 ± 21.9 0/0000), Zaigraevsky (318.2 ± 13.6 0/0000), Bauntovsky (403.6 ± 51.6 0/ 0000); with reduced ones – Zakamensky (241.1 ± 17.4 0/0000), Tunkinsky (215.9 ± 6.8 0/0000), Eravinsky (214.3 ± 16.5 0/0000), Okinsky (137.8 ± 6.1 0/0000) districts. The malignant neoplasms incidence of the population of the Republic Buryatia is high, and it is growing every year.

Correlation of the squat-and-smile test against other patient-reported outcome scores in knee pathology

ABSTRACT BACKGROUND: The use of patient-reported outcome measures (PROMs) for knee pathology may be affected by socioeconomic factors, language barriers and time constraints in busy outpatient clinics. The squat-and-smile test (SST) is an example of such a test that has previously been validated for femur fractures. The aim of this study was to validate the SST against other PROMs in patients with knee pathology METHODS: Patients presenting to a subspecialist knee clinic in a large hospital in sub-Saharan Africa were approached to participate. They were asked to squat and the depth of the squat as well as the need to support themselves were classified into four categories. To describe their pain, participants also selected one of three smiley faces (unhappy, neutral, smiling). These test scores were correlated to the patient's Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Lysholm score and EQ-5D scores RESULTS: Seventy patients (median age 53.4 years) were included. The squat depth correlated moderately with the KOOS score (r=0.56) and poorly with the EQ-5D and Lysholm scores (r=0.46; r=0.43). The need for squat support had poor correlations with the KOOS, EQ-5D and Lysholm scores (r=0.29; r=0.31; r=0.31), as did the smiley face component (r=0.40; r=0.32; r=0.30 CONCLUSION: For patients with knee pathology, the squat depth correlates moderately with other PROMs. It could therefore be used in settings for which conventional PROMs have limited application. Support needed to squat, and a visual analogue scale of smiley faces, had poor correlation when compared to other knee PROMs and should not be used for the assessment of knee pathology Level of evidence: Level 4 Keywords: squat and smile, KOOS, PROM, smiley faces, outcome score