Associations between Sperm Epigenetic Age and Semen Parameters: An Evaluation of Clinical and Non-Clinical Cohorts.

The well-documented relationship between chronological age and the sperm methylome has allowed for the construction of epigenetic clocks that estimate the biological age of sperm based on DNA methylation, which we previously termed sperm epigenetic age (SEA). Our lab demonstrated that SEA is positively associated with the time taken to achieve pregnancy; however, its relationship with semen parameters is unknown. A total of 379 men from the Longitudinal Investigation of Fertility and Environment (LIFE) study, a non-clinical cohort, and 192 men seeking fertility treatment from the Sperm Environmental Epigenetics and Development Study (SEEDS) were included in the study. Semen analyses were conducted for both cohorts, and SEA was previously generated using a machine learning algorithm and DNA methylation array data. Association analyses were conducted via multivariable linear regression models adjusting for BMI and smoking status. We found that SEA was not associated with standard semen characteristics in SEEDS and LIFE cohorts. However, SEA was significantly associated with higher sperm head length and perimeter, the presence of pyriform and tapered sperm, and lower sperm elongation factor in the LIFE study (p < 0.05). Based on our results, SEA is mostly associated with defects in sperm head morphological factors that are less commonly evaluated during male infertility assessments. SEA shows promise to be an independent biomarker of sperm quality to assess male fecundity.

Ventilator-associated pneumonia in Polish intensive care unit dedicated to COVID-19 patients.

BACKGROUND: Healthcare-Associated Infections (HAI) are most frequently associated with patients in the Intensive Care Unit (ICU). Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), led to ICU hospitalization for some patients. METHODS: The study was conducted in 2020 and 2021 at a hospital in southern Poland. The Healthcare-Associated Infections Surveillance Network (HAI-Net) of the European Centre for Disease Prevention and Control (ECDC) was used for HAI diagnosis. The aim of this case-control study was to retrospectively assess the epidemiology of HAIs in ICU patients, distinguishing between COVID-19 and non-COVID-19 cases. RESULTS: The study included 416 ICU patients: 125 (30%) with COVID-19 and 291 (70%) without COVID-19, p < 0.05. The mortality rate was 80 (64%) for COVID-19 patients and 45 (16%) for non-COVID-19 patients, p < 0.001. Ventilator-Associated Pneumonia (VAP) occurred in 40 cases, with an incidence rate density of 6.3/1000 patient-days (pds): 14.1/1000 pds for COVID-19 patients vs. 3.6/1000 pds for non-COVID-19 patients. Odds Ratio (OR) was 2.297, p < 0.01. Acinetobacter baumannii was the most often isolated microorganism in VAP, with 25 cases (incidence rate 8.5%): 16 (18.2%) in COVID-19 patients vs. 9 (4.4%) in non-COVID-19 patients. OR was 4.814 (1.084-4.806), p < 0.001. CONCLUSIONS: Patients treated in the ICU for COVID-19 faced twice the risk of VAP compared to non-COVID-19 patients. The predominant microorganism in VAP cases was Acinetobacter baumannii.

miRNA Studies in Glaucoma: A Comprehensive Review of Current Knowledge and Future Perspectives.

Glaucoma, a neurodegenerative disorder that leads to irreversible blindness, remains a challenge because of its complex nature. MicroRNAs (miRNAs) are crucial regulators of gene expression and are associated with glaucoma and other diseases. We aimed to review and discuss the advantages and disadvantages of miRNA-focused molecular studies in glaucoma through discussing their potential as biomarkers for early detection and diagnosis; offering insights into molecular pathways and mechanisms; and discussing their potential utility with respect to personalized medicine, their therapeutic potential, and non-invasive monitoring. Limitations, such as variability, small sample sizes, sample specificity, and limited accessibility to ocular tissues, are also addressed, underscoring the need for robust protocols and collaboration. Reproducibility and validation are crucial to establish the credibility of miRNA research findings, and the integration of bioinformatics tools for miRNA database creation is a valuable component of a comprehensive approach to investigate miRNA aberrations in patients with glaucoma. Overall, miRNA research in glaucoma has provided significant insights into the molecular mechanisms of the disease, offering potential biomarkers, diagnostic tools, and therapeutic targets. However, addressing challenges such as variability and limited tissue accessibility is essential, and further investigations and validation will contribute to a deeper understanding of the functional significance of miRNAs in glaucoma.

Cadmium Toxicity and Health Effects-A Brief Summary.

Cadmium (Cd) is a ductile metal in the form of a blueish or silvery-white powder. It is naturally found in soil (about 0.2 mg/kg), minerals, and water. Cd belongs to the group of toxic, carcinogenic, and stimulating elements. Its biological half-life in the human body ranges from 16 to even 30 years on average. Some lung diseases (such as emphysema, asthma, and bronchitis) and high blood pressure are thought to be related to slow poisoning. The symptoms of cadmium poisoning may vary depending on the time of exposure, the type of diet, and the age and health status of the exposed people. For non-smokers and non-occupational exposures, the only source of exposure is diet. The FAO/WHO recommends that the tolerable cadmium intake for an adult is approximately 0.4-0.5 mg/week (60-70 µg per day). Cadmium is primarily absorbed through the respiratory system (about 13-19% of Cd from the air), but it can also enter through the digestive system (about 10-44%), when dust is mixed and swallowed with saliva. The amount of accumulated Cd ranges from 0.14 to 3.2 ppm in muscles, 1.8 ppm in bones, and 0.0052 ppm in the blood. People who are most frequently exposed to heavy metals should be continuously monitored in order to maintain a healthy lifestyle, as well as to implement effective preventive measures and improve public health.

Blood concentrations of new synthetic opioids.

PURPOSE: Over the last decade, there has been a significant growth in the market and number of new psychoactive substances (NPS). One of the NPS groups that has grown rapidly in recent years, bringing a new set of problems, consists of new synthetic opioids. The extreme potency of these compounds poses a high risk of acute poisoning, as an overdose can cause respiratory depression. Most of the information regarding human pharmacokinetics of new opioids is based on toxicological case reports and the data on concentrations of new opioids in human blood are scarce. The interpretation of results usually requires a comparison to previously published cases; therefore, a referenced compilation of previously published concentration data would be useful. METHODS: The data were collected by searching the PubMed and Scopus databases and by using the Google search engine. All the available data from articles and reports that measured new opioid concentrations in plasma, serum, or whole blood were included in the data analysis. RESULTS: The presented tables list the observed concentrations in fatal and nonfatal cases involving 37 novel synthetic opioids. CONCLUSIONS: Blood levels of new opioids are extremely difficult to interpret. Low blood concentrations of these substances do not rule out acute poisoning as their high potency creates a risk of respiratory depression even at low doses. Opioid tolerance, frequent presence of other drugs, and additional diseases make it impossible to define concentration ranges, especially the minimum fatal concentrations. This report provides quick access to the source articles quantifying novel synthetic opioids.

Investigation of estrogen-like effects of parabens on human neutrophils.

This study investigated the estrogen-like effects and mechanism of action most commonly used parabens: methyl- (MeP), ethyl- (EtP), propyl- (PrP) and butylparaben (BuP) in human neutrophils. Neutrophils were isolated from 50 blood donors, pre-incubated with antagonists of estrogen receptor α (ERα), ERß and G-protein coupled estrogen receptor 1 (GPER), then incubated with MeP, EtP, PrP, BuP and 17ß-estradiol (E2; 10 nM). Cytotoxic effect was evaluated by MTT test. Neutrophils apoptosis, necrosis and NETs formation were assessed in flow cytometry and confocal microscopy. The ability of the neutrophils for chemotaxis, phagocytosis, NADPH oxidase activity and generation of superoxide anion was assessed in Boyden's chamber, Park's method with latex, the NBT test, and reduction of cytochrome C, respectively. The total nitric oxide concentration was measured in neutrophils supernatants by the Griess reaction. The expression of cathepsin G, neutrophil elastase, proteinase 3, ERα, ERß and GPER was assessed in Western blot method. In our research, parabens did not cause a cytotoxic effect on human neutrophils nor affect their lifespan. Parabens exposure did not change neutrophils functions (chemotaxis, phagocytosis, NETs formation and oxygen-dependent killing mechanism) and expression of estrogen receptors. Our results suggest that parabens do not cause estrogen receptor-mediated neutrophils-related effects at concentrations measured in the plasma of individuals using products preserved with parabens.

Long-term spatial and population-structured planning of non-pharmaceutical interventions to epidemic outbreaks.

In this paper, we consider the problem of planning non-pharmaceutical interventions to control the spread of infectious diseases. We propose a new model derived from classical compartmental models; however, we model spatial and population-structure heterogeneity of population mixing. The resulting model is a large-scale non-linear and non-convex optimisation problem. In order to solve it, we apply a special variant of covariance matrix adaptation evolution strategy. We show that results obtained for three different objectives are better than natural heuristics and, moreover, that the introduction of an individual's mobility to the model is significant for the quality of the decisions. We apply our approach to a six-compartmental model with detailed Poland and COVID-19 disease data. The obtained results are non-trivialand sometimes unexpected; therefore, we believe that our model could be applied to support policy-makers in fighting diseases at the long-term decision-making level.

Adhesion molecules: a way to understand lupus.

Systemic lupus erythematosus is a connective disease in which all vitally important organs may be affected. The etiology of the disease is largely unknown and almost all immunological mechanisms have been proposed as the pathophysiological background of the disease. Among them, endothelial damage and dysfunction seem to play a pivotal role. Endothelial damage can be accurately measured using adhesion molecules such asintercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), platelet endothelial cell adhesion molecule (PECAM) and selectins. In this review we discuss the role of well-known cellular adhesion molecules as pathogenic factors in disease development as well as disease activity biomarkers.

High prevalence of steroid-induced glucose intolerance with normal fasting glycaemia during low-dose glucocorticoid therapy: an oral glucose tolerance test screening study.

OBJECTIVES: To evaluate the prevalence and risk factors of new-onset glucose metabolism impairment using an oral glucose tolerance test (OGTT) in patients with normal fasting glycaemia on long-term glucocorticoid (GC) treatment. METHODS: An OGTT was performed in 150 patients without a previous history of pre-diabetes or diabetes who were diagnosed with inflammatory rheumatic diseases and treated with GCs >3 months. All participants underwent clinical and biochemical evaluation for risk factors of diabetes: age, sex, current and cumulative dose of steroids, treatment duration, waist circumference, BMI, Homeostatic Model Assessment for Insulin Resistance, fasting insulin concentration, family history of diabetes, CRP, 28-joint DAS with CRP, type of connective tissue disease and trunk fat percentage measured by DXA. Logistic regression analysis was conducted to evaluate the association between the presence of impaired glucose tolerance (IGT) in the OGTT and analysed risk factors. RESULTS: A total of 102 patients (68%) had fully normal glucose tolerance. Diabetes, isolated impaired fasting glucose, isolated IGT and combined impaired fasting glucose + IGT was diagnosed in 3.3, 4.67, 19.33 and 4.67% of patients, respectively; 20% of participants had IGT or diabetes despite normal fasting glucose concentration. The median cumulative dose and current dose (5 mg) of GCs and treatment duration were similar compared with the normal glucose tolerance group. In a multivariate logistic regression model, only older age (particularly ≥50 years of age) and trunk fat percentage remained significant factors predicting IGT or diabetes in the OGTT. CONCLUSION: New-onset GC-induced glucose intolerance, even in patients on long-term low-dose treatment, is prevalent despite normal fasting glucose concentration and patients should be screened with an OGTT despite the absence of classic risk factors of diabetes.

Controversy around parabens: Alternative strategies for preservative use in cosmetics and personal care products.

Parabens usage as preservatives in cosmetics and personal care products have been debated among scientists and consumers. Parabens are easy to production, effective and cheap, but its safety status remains controversial. Other popular cosmetics preservatives are formaldehyde, triclosan, methylisothiazolinone, methylchloroisothiazolinone, phenoxyethanol, benzyl alcohol and sodium benzoate. Although their high antimicrobial effectiveness, they also exhibit some adverse health effects. Lately, scientists have shown that natural substances such as essential oils and plant extracts present antimicrobial potential. However, their use in cosmetic is a challenge. The present review article is a comprehensive summary of the available methods to prevent microbial contamination of cosmetics and personal care products, which can allow reducing the use of parabens in these products.

Sex-dependent dysregulation of human neutrophil responses by bisphenol A.

BACKGROUND: In the present study, we aimed to investigate selected functions of human neutrophils exposed to bisphenol A (BPA) under in vitro conditions. As BPA is classified among xenoestrogens, we compared its action and effects with those of 17ß-estradiol (E2). METHODS: Chemotaxis of neutrophils was examined using the Boyden chamber. Their phagocytosis and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity were assessed via Park's method with latex beads and Park's test with nitroblue tetrazolium. To assess the total concentration of nitric oxide (NO), the Griess reaction was utilized. Flow cytometry was used to assess the expression of cluster of differentiation (CD) antigens. The formation of neutrophil extracellular traps (NETs) was analyzed using a microscope (IN Cell Analyzer 2200 system). Expression of the investigated proteins was determined using Western blot. RESULTS: The analysis of results obtained for both sexes demonstrated that after exposure to BPA, the chemotactic capacity of neutrophils was reduced. In the presence of BPA, the phagocytic activity was found to be elevated in the cells obtained from women and reduced in the cells from men. Following exposure to BPA, the percentage of neutrophils with CD14 and CD284 (TLR4) expression, as well as the percentage of cells forming NETs, was increased in the cells from both sexes. The stimulatory role of BPA and E2 in the activation of NADPH oxidase was observed only in female cells. On the other hand, no influence of E2 on the expression of CD14 and CD284, chemotaxis, phagocytosis, and the amount of NET-positive neutrophils was found for both sexes. The study further showed that BPA intensified NO production and iNOS expression in the cells of both sexes. In addition, intensified expression of all tested PI3K-Akt pathway proteins was observed in male neutrophils. CONCLUSIONS: The study demonstrated the influence of BPA on neutrophil functions associated with locomotion and pathogen elimination, which in turn may disturb the immune response of these cells in both women and men. Analysis of the obtained data showed that the effect of this xenoestrogen on the human neutrophils was more pronounced than E2.

Adrenal metastases - long-term results of surgical treatment, single-centre experience.

INTRODUCTION: The adrenal gland is a frequent site of metastases in different types of cancer. The aim of this study was to assess the results of metastatic adrenalectomy in a single institution and to identify factors for survival. MATERIAL AND METHODS: A retrospective, single-centre analysis of outcomes of 39 patients (22 male, 17 female) with adrenal metastases who underwent surgery within 14 years (2004-2017) was performed. The median age at the time of adrenal surgery was 64.8 years (range 49-79 years). RESULTS: In our study group non-small cell lung cancer (NSCLC) was the most frequent primary tumour type (15 pts), followed by renal cell carcinoma (RCC) (14 pts) and colon cancer (6 pts). Most of the metastases - 36 (92%) - were metachronous (> 6 months). All synchronous metastases were NSCLC. The mean time from primary cancer to adrenalectomy was 42.3 months (range 1-176) and was statistically longer for RCC. In 3 patients (8%) metastases were bilateral and both adrenal glands were removed. In all patients, surgery was limited to the adrenal gland, and no major complications of surgery were observed. The median overall survival after metastasectomy was 18 months (3-81) and was statistically longer for colon cancer - 29.5 months (p = 0.012). In patients who died, tumours were significantly bigger than in survivors, 76.5 mm vs. 52.5 mm (p = 0.026). CONCLUSIONS: Surgery for adrenal metastasis is safe and indications for this procedure should be individualized. In selected patients, surgical removal of adrenal metastasis was associated with longer survival.

Microbial Turnover of Glyphosate to Biomass: Utilization as Nutrient Source and Formation of AMPA and Biogenic NER in an OECD 308 Test.

Environmental fate assessment of chemicals involves standardized simulation tests with isotope-labeled molecules to balance transformation, mineralization, and formation of nonextractable residues (NER). Methods to predict microbial turnover and biogenic NER have been developed, having limited use when metabolites accumulate, the chemicals are not the only C source, or provide for other macroelements. To improve predictive capability, we extended a recently developed method for microbial growth yield estimation to account for incomplete degradation and multiple-element assimilation and combined it with a dynamic model for fate description in soils and sediments. We evaluated the results against the unique experimental data of 13C3-15N co-labeled glyphosate turnover with AMPA formation in water-sediment systems (OECD 308). Balancing 13C- and 15N- fluxes to biomass showed a pronounced shift of glyphosate transformation from full mineralization to AMPA formation. This may be explained by various hypotheses, for example, the limited substrate turnover inherent to the batch conditions of the test system causing microbial starvation or inhibition by P release. Modeling results indicate initial N overload due to the lower C/N ratio in glyphosate compared to average cell composition leading to subsequent C demand and accumulation of AMPA.

Perceptual audio processing stethoscope.

Stethoscopes are used to transmit body sounds related to various physiological processes to ears of a physician, providing basic or supportive information for eventual diagnosis. Unfavorably, the dominant frequency components of most of the auscultation signals are localized close to the lower frequency limits of the human auditory system, restricting the achievable selectivity and specificity. The present study introduces an approach that aims at overcoming the existing limitations. A signal processing scheme utilizing knock rejection, dynamic compressor, and pseudo-stereo synthesizer blocks is described, along with hardware implementation and results of the initial subjective evaluation.

Prediction of the Formation of Biogenic Nonextractable Residues during Degradation of Environmental Chemicals from Biomass Yields.

Degradation tests with radio or stable isotope labeled compounds enable the detection of the formation of nonextractable residues (NER). In PBT and vPvB assessment, remobilisable NER are considered as a potential risk while biogenic NER from incorporation of labeled carbon into microbial biomass are treated as degradation products. Relationships between yield, released CO2 (as indicator of microbial activity and mineralization) and microbial growth can be used to estimate the formation of biogenic NER. We provide a new approach for calculation of potential substrate transformation to microbial biomass (theoretical yield) based on Gibbs free energy and microbially available electrons. We compare estimated theoretical yields of biotechnological substrates and of chemicals of environmental concern with experimentally determined yields for validation of the presented approach. A five-compartment dynamic model is applied to simulate experiments of 13C-labeled 2,4-D and ibuprofen turnover. The results show that bioNER increases with time, and that most bioNER originates from microbial proteins. Simulations with precalculated input data demonstrate that precalculation of yields reduces the number of fit parameters considerably, increases confidence in fitted kinetic data, and reduces the uncertainty of the simulation results.

Sound differences between electronic and acoustic stethoscopes.

BACKGROUND: The area of application of electronic stethoscopes in medical diagnostics covers the scope of usability of the acoustic stethoscopes, from which they have evolved and which they could potentially replace. However, the principle of operation of these two groups of diagnostic devices is substantially different. Thus, an important question arises, regarding the differences in parameters of the transmitted sound and their potential diagnostic consequences in clinical practice. METHODS: In order to answer this question, heart auscultation signals are recorded using various stethoscopes and divided into short fragments based on the analysis of the synchronized recordings of electrocardiogram signals. Next, a dedicated algorithm is used to extract representative datasets for each case, which are then analyzed for their acoustic parameters. Four different electronic stethoscopes were investigated, together with an acoustic stethoscope as a reference point. RESULTS: The determined acoustic characteristics of the considered stethoscopes differ significantly between each other. CONCLUSIONS: The differences in sound transmitted by various stethoscope models may translate into significant differences in quality of the obtained diagnosis. It is also pointed out, that the terminology and application guidelines regarding the electronic stethoscopes are misleading and should be changed.

The effect of ethanol and N-nitrosodimethylamine on the iNOS-dependent NO production in human neutrophils. Role of NF-κB.

1. The objective of study was to determine the influence of ethanol and/or N-nitrosodimethyloamine (NDMA) on the inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production by human neutrophils and determination of the role of NF-κB in this process. 2. Isolated polymorphonuclear leukocytes (PMNs) derived from 15 human volunteers were incubated in the presence of ethanol and/or NDMA. Expression of the tested proteins were evaluated using the Western blot method. Total NO metabolites was assayed in the cell cultures by Griess reaction. 3. In neutrophils exposed to ethanol or NDMA was observed an increased NF-κB-dependent NO production mediated by iNOS with the contribution of MAP kinases: p38 and JNK. An inhibiting effect of NF-κB signaling pathway on the MAP kinases was observed, which are involved in the iNOS-dependent NO production. By the simultaneous effect, ethanol and NDMA caused stronger generation of NO by neutrophils without the contribution of iNOS. Inhibition of NF-κB in cells simultaneously exposed to the xenobiotics caused a decreased expression of MAP kinases. 4. Individual and simultaneous effect of ethanol and NDMA may cause disorders in the response of immune system. However, the joint effect of the tested substances results in uncontrolled interactions, leading to cascading disorders of signal transduction.

[Adrenal gangliuoneuroma - features of 10 cases in own material]. / Adrenal gangliuoneuroma ­ features of 10 cases in own material.

Adrenal ganglioneuroma is a rare benign neuroblastic tumor. Most of adrenal ganglioneuromas are asymptomatic and discovered incidentally during imaging examinations performed for many different indications. Proper preoperative diagnosis is challenging and most of this masses are described as being poor lipid adenomas or pheochromocytomas. AIM: The aim of the study was to present experience of referral center with this rare adrenal pathologies. MATERIALS AND METHODS: Analysis of our data - 374 adrenalectomies performed over last 13 years (2004-2016) in patients referred to our department from different endocrinological centers. Date of all patients were reviewed retrospectively in order to focus on adrenal ganlioneuroma. RESULTS: Among this patients histopathological report confirmed 10 adrenal ganglioneuromas (2,67% of cases, median age 51 years, range 39-74), diagnosed in 4 men and 6 women. Preoperative CT tumors were described as homogenous masses with mean attenuation on unenhanced images 28 (19-39 HU). In 5 patients (50%), progressive enhancement on delayed-phase postcontrast imaging was observed. 7 right and 3 left adrenalectomies was performed (laparoscopic approach in 50% of cases) Mean size of the resected tumors in histopatogical report was 47mm ( 5-85 ). CONCLUSIONS: Proper preoperative diagnosis of adrenal ganglioneuroma is challenging. In our series all diagnosis was made by histopathological examination. Surgery is indicated because it's difficult to distinguish adrenal gangioneuroma from other adrenal malignances. Radical excision is a definitive cure and may be done safely by laparoscopy.

Experimental validation of the tuneable diaphragm effect in modern acoustic stethoscopes.

PURPOSE: The force with which the diaphragm chestpiece of a stethoscope is pressed against the body of a patient during an auscultation examination introduces the initial stress and deformation to the diaphragm and the underlying tissues, thus altering the acoustic parameters of the sound transmission path. If the examination is performed by an experienced physician, he will intuitively adjust the amount of the force in order to achieve the optimal sound quality. However, in case of becoming increasingly popular auto-diagnosis and telemedicine auscultation devices with no such feedback mechanisms, the question arises regarding the influence of the possible force mismatch on the parameters of the recorded signal. DESIGN: The present study describes the results of the experimental investigations on the relation between pressure applied to the chestpiece of a stethoscope and parameters of the transmitted bioacoustic signals. The experiments were carried out using various stethoscopes connected to a force measurement system, which allowed to maintain fixed pressure during auscultation examinations. The signals were recorded during examinations of different volunteers, at various auscultation sites. RESULTS: The obtained results reveal strong individual and auscultation-site variability. CONCLUSIONS: It is concluded that the underlying tissue deformation is the primary factor that alters the parameters of the recorded signals.

Acoustic characterization of stethoscopes using auscultation sounds as test signals.

The present study introduces a detailed methodology which can be applied for objective evaluation and comparison of the acoustic parameters of medical stethoscopes using auscultation sounds as test signals. The described approach allows taking into account the acoustic coupling between the body of an auscultated patient and the chest piece of a stethoscope. Information obtained from additional, synchronized electrocardiography measurements is used to extract short, specific fragments of recordings, defined as acoustic events. Analysis of the spectral characteristics of many acoustic events allows us to compare the acoustic properties of various stethoscopes and to estimate the measurement uncertainty. The exemplary results of the comparative evaluation of acoustic properties of bell and diaphragm-type chest pieces of a single stethoscope are presented. The results show that the frequency characteristics of the signals obtained using both examined chest pieces under the conditions of the performed examinations are very similar.