Development Of Pathology Research Articles

Three-dimensional assessment of subchondral arc and hip joint coverage angles in the asymptomatic young adult hip.

The primary objective of this study was to develop a custom algorithm to assess three-dimensional (3D) acetabular coverage of the femoral head based on surface models generated from computed tomography (CT) imaging. The secondary objective was to apply this algorithm to asymptomatic young adult hip joints to assess the regional 3D acetabular coverage variability and understand how these novel 3D metrics relate to traditional two-dimensional (2D) radiographic measurements of coverage. The algorithm developed automatically identifies the lateral- and medial-most edges of the acetabular lunate at one-degree intervals around the acetabular rim based on local radius of curvature. The acetabular edges and the center of a best-fit sphere to the femoral head are then used to compute the mean 3D subchondral arc angles and hip joint coverage angles in five acetabular octants. This algorithm was applied to hip models generated from pelvis/hip CT imaging or abdomen/pelvis CT angiograms of 50 patients between 17 and 25 years of age who had no history of congenital or developmental hip pathology, neuromuscular conditions, or bilateral pelvic and/or femoral fractures. Corresponding 2D acetabular coverage measures of lateral center edge angle (LCEA) and acetabular arc angle (AAA) were assessed on the patients' clinical or digitally reconstructed radiographs. The 3D subchondral arc angle in the superior region (58.0 [54.6-64.8] degrees) was significantly higher (p < 0.001) than all other acetabular subregions. The 3D hip joint coverage angle in the superior region (26.2 [20.7-28.5] degrees) was also significantly higher (p < 0.001) than all other acetabular subregions. 3D superior hip joint coverage angle demonstrated the strongest correlation with 2D LCEA (r = 0.649, p < 0.001), while 3D superior-anterior subchondral arc angle demonstrated the strongest correlation with 2D AAA (r = 0.718, p < 0.001). The 3D coverage metrics in the remaining acetabular regions did not strongly correlate with typical 2D radiographic measures. The discrepancy between standard 2D measures of radiographic acetabular coverage and actual 3D coverage identified on advanced imaging indicates potential discord between anatomic coverage and the standard clinical measures of coverage on 2D imaging. As 2D measurement of acetabular coverage is increasingly used to guide surgical decision-making to address acetabular deformities, this work would suggest that 3D measures of acetabular coverage may be important to help discriminate local coverage deficiencies, avoid inconsistencies resulting from differences in radiographic measurement techniques, and provide a better understanding of acetabular coverage in the hip joint, potentially altering surgical planning and guiding surgical technique.

β-sitosterol alleviates pulmonary arterial hypertension by altering smooth muscle cell phenotype and DNA damage/cGAS/STING signaling

BackgroundPulmonary arterial smooth muscle cells (PASMCs) have a neoplastic phenotype characterized by hyperproliferative and anti-apoptotic features that contribute to pulmonary hypertension (PH) development. DNA-sensing adapter protein stimulator of interferon genes (STING) regulate the phenotypic switch of vessel smooth muscle cells. β-sitosterol (SITO) is a nutrient derived from plants that inhibits vascular smooth muscle cell proliferation without notable toxicity. However, the effect of SITO on cancer-like PH-associated pulmonary vascular remodeling and the specific mechanism has not yet be studied. PurposeThis study investigated the in vitro and in vivo effects of SITO against PH, and its underlying mechanisms. MethodsThe therapeutic efficacy of SITO was assessed, and its underlying mechanisms were explored in hypoxia-induced and platelet-derived growth factor (PDGF)-BB-stimulated primary PASMCs and in a monocrotaline (MCT)-induced preclinical PH rat model. SITO or sildenafil (SID) were administered after the MCT intraperitoneal injection. Pulmonary parameters, right heart function, morphology, and PASMCs were cultured for verification. The expression levels of DNA damage/cyclic GMP–AMP synthase (cGAS)/STING were determined using immunofluorescence and Western blotting. STING agonists that interfere with PASMCs were used to determine whether STING mediates the effects of SITO. ResultsSITO prevented PASMCs proliferation, promoted apoptosis and suppressed phenotypic switching in a dose-dependent manner in vitro and in vivo. In vivo results in rats demonstrated that four weeks of intragastric SITO administration effectively mitigated the MCT-induced elevation of hemodynamic parameters, improved right cardiac function, and reduced pulmonary arteries remodeling. Mechanistically, DNA damage and cGAS/STING/nuclear factor kappa-B signaling activation were observed in rats with PH and cultured PASMCs. SITO exhibited protective effects by suppressing the DNA damage, potentially via inhibiting the expression level of the cGAS/STING signaling pathway. Pharmacological overexpression of STING abolished the anti-proliferative effects of SITO treatment in hypoxia-induced and PDGF-stimulated PASMCs by downregulating PCNA. ConclusionSITO may be an attractive agent for PH vascular remodeling by inhibiting proliferation and modulating the phenotypic switch in PASMCs via the DNA damage/cGAS/STING signaling pathway. This study provides a novel therapeutic agent and mediator of the pathological development of PASMCs and PH.

Erosive Tooth Wear and Associated Risk Indicators in Schoolchildren from Rural and Urban Areas of the State of Mexico: A Cross-Sectional Study.

Limited access to health services and low educational levels are factors in the rural population that are associated with the development of oral pathologies. However, the specific risk indicators contributing to erosive tooth wear (ETW) in these populations remain unclear. The objective of this study was to identify risk indicators associated with the prevalence of erosive tooth wear (ETW) in schoolchildren aged 8-12 years from rural and urban areas in the State of Mexico. A cross-sectional study was carried out in public schools in rural and urban areas. The prevalence of ETW was evaluated using the Basic Erosive Wear Examination (BEWE). The risk indicators studied were gastroesophageal reflux, vomiting, vitamin C, food, beverages, dental hygiene, bruxism, and hyposalivation. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). The prevalence of ETW was higher in the rural area (77.3%) compared to the urban area (51.2%) (p = 0.001). The odds of presenting ETW were more than twice in schoolchildren from rural areas compared to those from urban areas (OR: 2.25, 95% CI: 1.11-3.98). Risk indicators varied between rural and urban populations, with different factors such as the consumption of fresh tomato sauce, orange, tangerine, atole (artisanal corn-based drink), and teeth grinding in the rural area, and lemon, soft drink, fruit juice consumption, and the simplified oral hygiene index in the urban area (p < 0.05). To prevent ETW, strategies offering tailored dietary and hygiene advice should be proposed, considering the specific conditions of each geographic area.

Clinical assessment of the respiratory system in pregnant women on the background of nicotine addiction

Smoking is not only a modifiable risk factor for adverse pregnancy outcomes, it is primarily a risk factor for the development of pathology of the respiratory system, eventually turning into chronic obstructive pulmonary disease (COPD). The high prevalence of tobacco smoking among pregnant women, confirmed by numerous studies, demonstrates the underestimation of the high risks of COPD development. The present study substantiates the relevance of timely detection of pathological changes in the bronchi in smokers in primary care and the formation of motivations to quit smoking. It is the desired pregnancy that can cause complete cessation of smoking, thereby reducing the risks of developing not only the pathology of the smoker's lungs, but also the pathology of the fetus.

The Role of DNMT Methyltransferases and TET Dioxygenases in the Maintenance of the DNA Methylation Level.

This review deals with the functional characteristics and biological roles of enzymes participating in DNA methylation and demethylation as key factors in epigenetic regulation of gene expression. The set of enzymes that carry out such processes in human cells is limited to representatives of two families, namely DNMT (DNA methyltransferases) and TET (DNA dioxygenases). The review presents detailed information known today about each functionally important member of these families and describes the catalytic activity and roles in the mammalian body while also providing examples of dysregulation of the expression and/or activity of these enzymes in conjunction with the development of some human disorders, including cancers, neurodegenerative diseases, and developmental pathologies. By combining the up-to-date information on the dysfunction of various enzymes that control the DNA "methylome" in the human body, we hope not only to draw attention to the importance of the maintenance of a required DNA methylation level (ensuring epigenetic regulation of gene expression and normal functioning of the entire body) but also to help identify new targets for directed control over the activity of the enzymes that implement the balance between processes of DNA methylation and demethylation.

Pre-implant surgery complexity for achieving implant-supported prosthetic rehabilitation in oligodontia patients: a retrospective study

IntroductionOligodontia is a rare dental developmental pathology that requires prolonged, complex and multidisciplinary treatment. Although bone augmentation is frequently required during a complete implant treatment of oligodontia. Therefore, we evaluated the ability to predict pre-implant surgery complexity based on age, number of missing teeth, and number of implants required to achieve implant-supported prosthetic rehabilitation.Material and methodsThis retrospectively registered study included all patients who underwent surgical treatment for oligodontia in our Oral and Maxillofacial Surgery Department between January 2012 and May 2023. Demographic data, number and location of missing teeth, pre- and per-implant surgical procedures, and the number of planned implants were recorded. A quantitative variable called “complexity score of pre-implant surgery” was created. This 10-point score was calculated by adding one point for each preimplant surgical procedure registered. A simple linear regression was calculated to explain the number of targeted implants based on number of missing teeth. A multiple linear regression model was used to explain the complexity score of pre-implant surgery and age, number of missing teeth and number of targeted implants.Results119 oligodontia patients were included in the study. The median number of tooth agenesis was 10. A total of 825 implants were placed, 14 (1.7%) of which failed. A significant regression equation was used (F(1,118) = 1098,338; p < 0.0001) to explain the number of targeted implants based on number of missing teeth, with a R2 of 0.903. A significant regression equation was found (F(3,116) = 107,229; p < 0.0001) to explain the complexity score of pre-implant surgery and age, number of missing teeth and number of targeted implants, with a R2 of 0.735.DiscussionThese results based on patient data indicate that age, number of missing teeth and number of targeted implants could reliably explain the complexity of pre-implant surgery.

Connectome-based predictive modeling of brain pathology and cognition in Autosomal Dominant Alzheimer's Disease.

Autosomal Dominant Alzheimer's Disease (ADAD) through genetic mutations can result in near complete expression of the disease. Tracking AD pathology development in an ADAD cohort of Presenilin-1 (PSEN1) E280A carriers' mutation has allowed us to observe incipient tau tangles accumulation as early as 6 years prior to symptom onset. Resting-state functional Magnetic Resonance Imaging (fMRI) and Positron-Emission Tomography (PET) scans were acquired in a group of PSEN1 carriers (n=32) and non-carrier family members (n=35). We applied Connectome-based Predictive Modeling (CPM) to examine the relationship between the participant's functional connectome and their respective tau/amyloid-β levels and cognitive scores (word list recall). CPM models strongly predicted tau concentrations and cognitive scores within the carrier group. The connectivity patterns between the temporal cortex, default mode network, and other memory networks were the most informative of tau burden. These results indicate that resting-state fMRI methods can complement PET methods in early detection and monitoring of disease progression in ADAD.

Effect of diet-induced obesity and non-drug options of its correction on the functional and morphological liver characteristics in female Wistar rats

A nonalcoholic fatty liver disease is one of the unfavorable consequences of obesity. However, experimental studies on the mechanisms of this pathology development are being carried out mainly on male rodents, and the data on the development of fatty hepatosis in females are insufficient.The aim of the study was to investigate the effect of diet-induced obesity and non-drug options for its correction on the morphological liver characteristics and liver metabolic parameters in female Wistar rats. Experiments were conducted on sexually mature female Wistar rats and included the study of morphological and biochemical parameters of the liver functional state in animals kept on standard diet (StD, 16 weeks), on a high-calorie diet (HCD, 16 weeks) when switching to a standard diet (HCD/StD, 8/8 weeks), when the physical activity in the form of treadmill running was included (StD + running, HCD + running and HCD/StD + running, 8/8 weeks).Long-term use of HCD in female rats caused visceral obesity, liver fatty dystrophy with disruption of organ histoarchitectonics, shifts in hepatic metabolism and increased lipid peroxidation. Correction of diet-induced obesity by switching to StD led to a complete or partial normalization of the studied indices. In the “HCD + running” group, metabolic disorders are often more pronounced than in the “HCD” group. The transition to HCD/StD + running promoted the most complete restoration of metabolism and histostructure of the liver with regeneration signs of the organ.Thus, an optimal correction of visceral obesity, fatty liver dystrophy and its metabolism is impossible without diet normalization in female Wistar rats. An additional regenerating effect with respect to the liver histostructure is achieved with a combined variant of correction ‒ transition to a balanced diet and moderate physical activity.

Deep-ultraviolet Fourier ptychography (DUV-FP) for label-free biochemical imaging via feature-domain optimization

We present deep-ultraviolet Fourier ptychography (DUV-FP) for high-resolution chemical imaging of biological specimens in their native state without exogenous stains. This approach uses a customized 265-nm DUV LED array for angle-varied illumination, leveraging the unique DUV absorption properties of biomolecules at this wavelength region. We implemented a robust feature-domain optimization framework to overcome common challenges in Fourier ptychographic reconstruction, including vignetting, pupil aberrations, stray light problems, intensity variations, and other systematic errors. By using a 0.12 numerical aperture low-resolution objective lens, our DUV-FP prototype can resolve the 345-nm linewidth on a resolution target, demonstrating at least a four-fold resolution gain compared to the captured raw images. Testing on various biospecimens demonstrates that DUV-FP significantly enhances absorption-based chemical contrast and reveals detailed structural and molecular information. To further address the limitations of conventional FP in quantitative phase imaging, we developed a spatially coded DUV-FP system. This platform enables true quantitative phase imaging of biospecimens with DUV light, overcoming the non-uniform phase response inherent in traditional microscopy techniques. The demonstrated advancements in high-resolution, label-free chemical imaging may accelerate developments in digital pathology, potentially enabling rapid, on-site analysis of biopsy samples in clinical settings.

Clinical and translational mode of single-cell measurements: An artificial intelligent single-cell.

With rapid development and mature of single-cell measurements, single-cell biology and pathology become an emerging discipline to understand the disease. However, it is important to address concerns raised by clinicians as to how to apply single-cell measurements for clinical practice, translate the signals of single-cell systems biology into determination of clinical phenotype, and predict patient response to therapies. The present Perspective proposes a new system coined as the clinical artificial intelligent single-cell (caiSC) with the dynamic generator of clinical single-cell informatics, artificial intelligent analyzers, molecular multimodal reference boxes, clinical inputs and outs, and AI-based computerization. This system provides reliable and rapid information for impacting clinical diagnoses, monitoring, and prediction of the disease at the single-cell level. The caiSC represents an important step and milestone to translate the single-cell measurement into clinical application, assist clinicians' decision-making, and improve the quality of medical services. There is increasing evidence to support the possibility of the caiSC proposal, since the corresponding biotechnologies associated with caiSCs are rapidly developed. Therefore, we call the special attention and efforts from various scientists and clinicians on the caiSCs and believe that the appearance of the caiSCs can shed light on the future of clinical molecular medicine.

Image stitching algorithm for super-resolution localization microscopy combined with fluorescence noise prior.

Super-resolution panoramic pathological imaging provides a powerful tool for biologists to observe the ultrastructure of samples. Localization data can maintain the essential ultrastructural information of biological samples with a small storage space, and also provides a new opportunity for stitching super-resolution images. However, the existing image stitching methods based on localization data cannot accurately calculate the registration offset of sample regions with no or few structural points and thus lead to registration errors. Here, we proposed a stitching framework called PNanoStitcher. The framework fully utilizes the distribution characteristics of the background fluorescence noise in the stitching region and solves the stitching failure in sample regions with no or few structural points. We verified our method using both simulated and experimental datasets, and compared it with existing stitching methods. PNanoStitcher achieved superior stitching results on biological samples with no structural and few structural regions. The study provides an important driving force for the development of super-resolution digital pathology.

CAUSES OF MORBIDITY AND MORTALITY IN STELLER SEA LIONS (EUMETOPIAS JUBATUS) UNDER PROFESSIONAL CARE IN NORTH AMERICAN AQUARIUMS FROM 1979 TO 2021.

To date, published comprehensive pathology investigations documented in Steller sea lions (SSL; Eumetopias jubatus) are from free-ranging populations, whereas health data from those under professional care in aquariums are currently lacking. A retrospective review of gross and histopathologic reports of SSL under human care in North American aquariums from 1979 to 2021 (n = 20) was performed. Associations between age, sex, or birth origin (born in aquariums versus the wild) with cause of death (COD) and comorbidities were explored. Age was significantly associated with development of endocrine organ pathology (P = 0.011). A relationship between age and both cardiovascular and ocular disease was suggested by the data, but did not reach significance (P = 0.058). Ocular disease was significantly associated with being born in aquariums (P = 0.022). The most common COD was neoplasia (n = 10), which was significantly associated with aged animals (P = 0.038). Less frequent COD included sepsis (confirmed, n = 2; suspected, n = 3), cardiomyopathy (n = 1), clostridial enteritis (n = 1), Sarcocystis spp. (n = 1), complication secondary to sedation (n = 1), and unknown (n = 1). This is the first report documenting the high prevalence of neoplasia in SSL, with tumors found incidentally in three individuals, frequent metastasis (10/13, 77%), and many cases of multiple primary malignancies (6/13, 46%). These data expand upon the current understanding of disease in SSL, highlight this species' predisposition to neoplasia with increasing longevity, and underscore the need for heightened screening in aged animals, which may ultimately serve to elevate the care of SSL under professional care in aquariums.

Association Between Intracranial Aneurysms and Genes

Ruptured intracranial aneurysm(IA) leads to aneurysmal subarachnoid hemorrhage(aSAH), which is the most severe type of stroke. Besides age, sex, and alcohol consumption, family history is considered an important risk factor. Approximately 5% of the Japanese population is affected by unruptured cerebral aneurysms. However, their developmental processes and pathologies remain unclear. Familial cerebral aneurysms account for 10% of all cerebral aneurysm cases, and somatic gene mutations are believed to be involved in their development. This review summarizes the recent findings from family-based, genome-wide association, sequencing, and somatic gene mutation studies on IA.

The Role of Mast Cell-Neuron Tandem in the Regulation of Cardiac Function in Cardiovascular Pathologies

This review is consisted of new data about participation of mast cells (MCs) in the regulation of cardiac function in the development of some cardiovascular pathologies. In norm the number of MCs in the heart is very small compared to their number in barrier tissues. They are responsible for homeostasis of cardiac tissue and ensuring the interaction of the organ with the nervous and endocrine systems throughout the life of the organism. Pathological processes in the heart are accompanied by the development of inflammation reaction. MCs fulfil a significant role in the all stages of inflammation. The number of MCs significantly increases against the background of myocardial infarction development, fibrotic heart disease and vascular atherosclerosis. Their contribution to the pathogenesis of the disease is ambiguous, because on the one hand it is aimed at tissue adaptation to damage, and on the other hand - avalanche-like synthesis and release of mediators from activated MCs aggravates the course of the process. As a result, MCs change their secretory profile, interfere in the realization of cardiac functions against the background of inflammation, but at the same time modulate afferent information flow from the heart and efferent influences of the nervous system. The coordinated work of the system loses its stability, which can lead to severe consequences for the vital activity of the whole organism. The analysis of the current state of the problem indicates that the heart activity depends on the functional state of MCs, their complex interaction with the nervous system both in the norm and, especially, against the background of pathological processes development.

Investigation of pulmonary artery and circulating endothelin-1 expression in dogs with pulmonary hypertension secondary to myxomatous mitral valve disease.

Pulmonary hypertension (PH) is a condition characterized by abnormally elevated pressure in the pulmonary vasculature. It is a common complication of myxomatous mitral valve disease (MMVD) in dogs. Several vasoactive substances, including endothelin-1 (ET-1), have been suggested to contribute to pathological changes in the pulmonary arteries of patients with PH. This study aimed to examine the local and systemic expression of ET-1 in dogs with PH secondary to MMVD. Lung tissues were collected from 20 client-owned dogs during the first stage of the study and divided into three groups: normal dogs (n = 5), MMVD dogs (n = 8), and MMVD+PH dogs (n = 7). The expression of ET-1 and endothelin A receptor (ETAR) in the pulmonary arteries was determined using immunohistochemistry. Blood samples were collected from 61 client-owned dogs for the second stage of the study and divided into three groups: normal (n = 22), MMVD (n = 20), and MMVD+PH (n = 19). Plasma ET-1 concentration was measured using a sandwich enzyme-linked immunosorbent assay. There was no difference in ET-1 and ETAR expression in the pulmonary arteries among the three groups. Similarly, there was no difference in the plasma ET-1 concentration between the groups. In addition, no correlation was found between the immunohistochemical expression of ET-1 and ETAR and the thickness of the pulmonary arteries or between the plasma ET-1 level and echocardiographic variables. The lack of difference in the expression of ET-1 and ETAR in the pulmonary arteries and in the circulating ET-1 concentration among the studied groups suggests that ET-1 may not be related to the pathological development of PH secondary to MMVD in dogs. Due to the small sample size in this study, further research is needed to confirm these findings.

Apolipoprotein E in Alzheimer's Disease: Focus on Synaptic Function and Therapeutic Strategy.

Synaptic dysfunction is a critical pathological feature in the early phase of Alzheimer's disease (AD) that precedes typical hallmarks of AD, including beta-amyloid (Aβ) plaques and neurofibrillary tangles. However, the underlying mechanism of synaptic dysfunction remains incompletely defined. Apolipoprotein E (APOE) has been shown to play a key role in the pathogenesis of AD, and the ε4 allele of APOE remains the strongest genetic risk factor for sporadic AD. Itiswidelyrecognizedthat APOE4 accelerates the development of Aβ andtau pathology in AD. Recent studies have indicated that APOE affects synaptic function through a variety of pathways. Here, we summarize the mechanism of modulating synapses by various APOE isoforms and demonstrate the therapeutic potential by targeting APOE4 for AD treatment.

PRIMARY PREVENTION OF CARDIOVASCULAR DISEASES AND WAYS OF IMPROVING RISK ASSESSMENT OF THEIR DEVELOPMENT IN CLINICAL PRACTICE

Introduction. Cardiovascular diseases are a global problem and one of the main causes of death worldwide. Aim. To highlight and analyze modern approaches to the use in routine practice of risk factors for the development of cardiovascular pathology, which is appropriate for further clinical decision-making based on a meta-analysis of literary sources, clinical guidelines and the results of multicenter studies. Materials and methods. The search and selection of publications, systematic reviews and current recommendations is carried out using PubMed and Google Scholar databases, their detailed analysis and description. Results and discussion. The article provides data on primary prevention, which includes assessment and implementation of measures to reduce the overall risk of developing cardiovascular diseases in patients. Methods for assessing individual total or relative risk (use of SCORE and SCORE 2 scales, various risk calculators, etc.) taking into account the level of cholesterol and its various fractions are given. The importance of taking into account additional independent risk factors for the development of cardiovascular diseases is also considered. The possibility of taking into account the level of lipoprotein (a), high-density lipoprotein, and high-sensitivity C-reactive protein to improve the accuracy of predicting cardiovascular risk is discussed. Attention is paid to the possibility of using such "non-metabolic" factors as environmental pollution, psychosocial stress and stressful conditions, sleep disorders and obstructive sleep apnea syndrome, family history and genetic factors to change the risk category. Conclusions. The results of the conducted analysis prove that the given methods and importance of detection of subclinical atherosclerosis especially in patients with low or medium (marginal) cardiovascular risk. The use of both primary and secondary risk factors may be appropriate to inform decisions about changes in the calculated risk of such patients, the use and effectiveness of specific cardiac treatments, and the implementation of preventive measures such as statin therapy.

Evaluation of the effectiveness of a hyperlipidic-hyperglycemic diet in inducing weight gain and dyslipidemia in wistar rats

Hyperlipidic and hyperglycemic diets, called cafeteria diets, are important factors that favor the development of pathologies and comorbidities such as obesity, type 2 diabetes mellitus, neoplasms, and cardiovascular diseases. Thus, their use in experimental studies that aim to understand the factors that encompass the pathophysiology and treatment of obesity and the comorbidities involved has increased in recent years. Taking that into consideration, the aim of this study was to analyze the effectiveness of a high-fat-hyperglycemic (HHD) diet in inducing weight gain and dyslipidemia in Wistar rats. In this study, 22 rats were divided into 2 groups, and exposed to standard and high-fat-hyperglycemic diets for 11 weeks. After that, euthanasia was carried out along with collection of blood samples for analysis of the following parameters of the lipid profile: triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c), and TG/HDL-c ratio. A more expressive weight gain was found in the rats that received HHD (p=0.006) in relation to the group maintained on the standard diet. Furthermore, no statistically detected alterations were found in the levels of TG, TC, LDL-c, HDL-c, and TG-HDL-c ratio. Analysis of the results indicated that HHD was effective in inducing weight gain in rats. However, there was no significant influence on the lipid profile.

Steroid profiling in human primary teeth via liquid chromatography-tandem mass spectrometry for long-term retrospective steroid measurement.

Steroid hormones are important modulators of many physiological processes, and measurements of steroids in blood, saliva, and urine matrices are widely used to assess endocrine pathologies and stress. However, these matrices cannot be used to retrospectively assess early-life stress and developmental endocrine pathologies, because they do not integrate steroid levels over the long term. A novel biological matrix in which to measure steroids is primary teeth (or "baby teeth"). Primary teeth develop early in life and accumulate various endogenous molecules during their gradual formation. Here, we developed and validated the first assay to measure steroids in human primary teeth using liquid chromatography-tandem spectrometry (LC-MS/MS). Our assay is highly sensitive, specific, accurate, and precise. It allows for the simultaneous quantification of 17 steroids in primary teeth (16 of which have not been examined previously in primary teeth). Overall, steroid levels in primary teeth were relatively low, and 8 steroids were quantifiable. Levels of dehydroepiandrosterone, cortisol, and progesterone were the highest of the 17 steroids examined. Next, we used this assay to perform steroid profiling in primary teeth from males and females. The same 8 steroids were quantifiable, and no sex differences were found. Levels of androgens (androstenedione and testosterone) were positively correlated, and levels of glucocorticoids (cortisol, cortisone, corticosterone, 11-dehydrocorticosterone) were also positively correlated. These data demonstrate that multiple steroids can be quantified by LC-MS/MS in human primary teeth, and this method potentially provides a powerful new way to retrospectively assess early-life stress and developmental endocrine pathologies.

Persistent Post COVID-19 Endothelial Dysfunction and Oxidative Stress in Women.

The assessment of endothelial dysfunction and free radical homeostasis parameters were performed in 92 women, aged 45 to 69 years, divided into the following groups: women without COVID-19 (unvaccinated, no antibodies, control); women with acute phase of COVID-19 infection (main group, COVID-19+); 12 months post COVID-19+; women with anti-SARS-CoV-2 IgG with no symptoms of COVID-19 in the last 12 months (asymptomatic COVID-19). Compared to the control, patients of the main group had lower glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, decreased advanced glycation end products (AGEs) level, higher glutathione reductase (GR) activity, and higher glutathione S transferases pi (GSTpi), thiobarbituric acid reactants (TBARs), endothelin (END)-1, and END-2 concentrations (all p ≤ 0.05). The group with asymptomatic COVID-19 had lower 8-OHdG and oxidized glutathione (GSSG) levels, decreased total antioxidant status (TAS), and higher reduced glutathione (GSH) and GSH/GSSG levels (all p ≤ 0.05). In the group COVID-19+, as compared to the group without clinical symptoms, we detected lower GPx and SOD activities, decreased AGEs concentration, a higher TAS, and greater GR activity and GSTpi and TBARs concentrations (all p ≤ 0.05). The high content of lipid peroxidation products 12 months post COVID-19+, despite decrease in ENDs, indicates long-term changes in free radical homeostasis. These data indicate increased levels of lipid peroxidation production contribute, in part, to the development of free radical related pathologies including long-term post COVID syndrome.