Amorfrutin B Compromises Hypoxia/Ischemia-induced Activation of Human Microglia in a PPARγ-dependent Manner: Effects on Inflammation, Proliferation Potential, and Mitochondrial Status.

Amorfrutin B is a selective PPARγ modulator that we demonstrated to be a promising neuroprotective compound in cellular models of stroke and perinatal asphyxia. Although neuronal mechanisms of amorfrutin B-evoked neuroprotection have been identified, none of them reflects the actions of the compound on microglia, which play a pivotal role in brain response to hypoxia/ischemia. Here, we provide evidence for amorfrutin B-induced effects on human microglia subjected to hypoxia/ischemia; the compound counteracts inflammation, and influences mitochondrial status and proliferation potential in a PPARγ-dependent manner. Post-treatment with amorfrutin B decreased the IBA1 fluorescence intensity, reduced caspase-1 activity, and downregulated IL1B/IL-1ß and TNFA but not IL10/IL-10 expression, which was upregulated. Amorfrutin B also stimulated PPARγ signaling, as evidenced by increased mRNA and/or protein levels of PPARγ and PGC1α. In addition, amorfrutin B reversed the hypoxia/ischemia-evoked effects on mitochondria-related parameters, such as mitochondrial membrane potential, BCL2/BCL2 expression and metabolic activity, which were correlated with diminished proliferation potential of microglia. Interestingly, the inhibitory effect of amorfrutin B on the proliferation potential and mitochondrial function of microglia is opposite to the stimulatory effect of amorfrutin B on mouse neuronal survival, as evidenced by increased neuronal viability and reduced neurodegeneration. In summary, this study showed for the first time that amorfrutin B compromises hypoxia/ischemia-induced activation of human microglia in a PPARγ-dependent manner, which involves inhibiting inflammation, normalizing mitochondrial status, and controlling proliferation potential. These data extend the protective potential of amorfrutin B in the pharmacotherapy of hypoxic/ischemic brain injury, targeting not only neurons but also activated microglia.

Raman Spectroscopy for the Time since Deposition Estimation of a Menstrual Bloodstain.

Forensic chemistry plays a crucial role in aiding law enforcement investigations by applying analytical techniques for the analysis of evidence. While bloodstains are frequently encountered at crime scenes, distinguishing between peripheral and menstrual bloodstains presents a challenge. This is due to their similar appearance post-drying. Raman spectroscopy has emerged as a promising technique capable of discriminating between the two types of bloodstains, offering invaluable probative information. Moreover, estimating the time since deposition (TSD) of bloodstains aids in crime scene reconstruction and prioritizing what evidence to collect. Despite extensive research focusing on TSD estimations, primarily in peripheral bloodstains, a crucial gap exists in determining the TSD of menstrual bloodstains. This study demonstrates how Raman spectroscopy effectively analyzes biological samples like menstrual blood, showing similar aging patterns to those of peripheral blood and provides proof-of-concept models for determining the TSD of menstrual blood. While this work shows promising results for creating a universal model for bloodstain age determination, further testing with more donors needs to be conducted before the implementation of this method into forensic practice.

Lung Lesions: Differential Diagnoses Beyond Cancer.

BACKGROUND Lung cancer is the most common malignant neoplasm diagnosed worldwide. Early diagnosis and treatment are of great importance for patient's prognosis. A wide variety of pulmonary conditions display clinical and radiological presentation similar to that of lung cancer, and the awareness of their existence can help in making correct diagnoses. CASE REPORT This article presents a description of 4 patients with an insidious type of lesions mimicking pulmonary carcinomas. The first patient was referred to Department with a tumor-like lesion in the right lung. After CT of the chest and core-needle biopsy, the lesion turned out to be an ectopic thyroid tissue. The second patient reported a dry cough and weight loss. A lung nodule mass was revealed in chest CT and the patient was diagnosed with pulmonary tuberculoma. The remaining 2 patients, despite the suspicion of lung cancer, were subsequently diagnosed with a post-traumatic pleural hematoma and diffuse large B cell lymphoma. CONCLUSIONS Low-dose computed tomography of the chest plays a significant role in the diagnosis of newly detected lesions in the lungs. However, due to the similarity of the image of cancer to that of other diseases, the ultimate diagnosis should be based on the interpretation of full imaging diagnostic tests, clinical presentation, and histopathological examination of the material obtained from the lesion. Analysis of cases enables us to expand our understanding of the diseases that need to be considered in differential diagnosis of a patient with a detected tumor-like lesion in the lungs.

Impact of COVID-19 on antibiotic usage in primary care: a retrospective analysis.

The COVID-19 pandemic has contributed to many changes in the medical practice, including a wider access to tele-consultations. It not only influenced the type of treatment but also shed light on mistakes often made by doctors, such as the abuse of antibiotics. This study aimed to evaluate the antibiotic treatment, and the impact of the COVID-19 pandemic on antibiotic prescribing during a GP's visit. The retrospective medical history analysis involved data from a first-contact medical center (Pantamed, Olsztyn, Poland), from 1 January 2018 to 31 May 2023. Quantities of prescribed antibiotics were assessed and converted into the so-called active list for a given working day of adult patients (> 18 years of age). Statistical analysis based on collective data was performed. During the COVID-19 pandemic, a decline in the number of medical consultations has been observed, both remotely via tele-medicine and in personal appointments, compared to the data from before the pandemic: n = 95,251 versus n = 79,619. Also, during the COVID-19 pandemic, there was a decrease in the total amount of prescribed antibiotics relative to the data before the pandemic (2.44 vs. 4.54; p > 0.001). The decrease in the quantities of prescribed antibiotics did not depend on the way doctor consultations were provided. The COVID-19 pandemic has contributed to changing the family doctors' management of respiratory infections. The ability to identify the etiological agent-the SARS-COV2 virus-contributed to the reduction of the antibiotics use.

Bioinformatic analysis of endometrial miRNA expression profile at day 26-28 of pregnancy in the mare.

The establishment of the fetomaternal interface depends on precisely regulated communication between the conceptus and the uterine environment. Recent evidence suggests that microRNAs (miRNAs) may play an important role in embryo-maternal dialogue. This study aimed to determine the expression profile of endometrial miRNAs during days 26-28 of equine pregnancy. Additionally, the study aimed to predict target genes for differentially expressed miRNAs (DEmiRs) and their potential role in embryo attachment, adhesion, and implantation. Using next-generation sequencing, we identified 81 DEmiRs between equine endometrium during the pre-attachment period of pregnancy (day 26-28) and endometrium during the mid-luteal phase of the estrous cycle (day 10-12). The identified DEmiRs appear to have a significant role in regulating the expression of genes that influence cell fate and properties, as well as endometrial receptivity formation. These miRNAs include eca-miR-21, eca-miR-126-3p, eca-miR-145, eca-miR-451, eca-miR-491-5p, members of the miR-200 family, and the miRNA-17-92 cluster. The target genes predicted for the identified DEmiRs are associated with ion channel activity and sphingolipid metabolism. Furthermore, it was noted that the expression of mucin 1 and leukemia inhibitory factor, genes potentially regulated by the identified DEmiRs, was up-regulated at day 26-28 of pregnancy. This suggests that miRNAs may play a role in regulating specific genes to create a favorable uterine environment that is necessary for proper attachment, adhesion, and implantation of the embryo in mares.

Heat and cold stress increases the risk of paroxysmal supraventricular tachycardia.

Paroxysmal supraventricular tachycardia (PSVT) is a common arrhythmia in adults. Its occurrence depends on the presence of the reentry circuit and the trigger of the paroxysm. Stress, emotional factors, and comorbidities favour the occurrence of such an episode. We hypothesized that the occurrence of PSVT follows extreme thermal episodes. The retrospective analysis was based on the data collected from three hospital emergency departments in Poland (Olsztyn, Radom, and Wroclaw) involving 816 admissions for PSVT in the period of 2016-2021. To test the hypothesis, we applied the Universal Climate Thermal Index (UTCI) to objectively determine exposure to cold or heat stress. The risk (RR) for PSVT increased to 1.37 (p = 0.006) in cold stress and 1.24 (p = 0.05) in heat stress when compared to thermoneutral conditions. The likelihood of PSVT during cold/heat stress is higher in women (RR = 1.59, p< 0.001 and RR = 1.36, p = 0.024, respectively) than in men (RR = 0.64 at p = 0.088 and RR = 0.78, p = 0.083, respectively). The susceptibility for PSVT was even higher in all groups of women after exclusion of perimenopausal group of women, in thermal stress (RR = 1.74, p< 0.001, RR = 1.56, p = 0.029, respectively). Females, particularly at the perimenopausal stage and men irrespective of age were less likely to develop PSVT under thermal stress as compared to thermoneutral conditions. Progress in climate change requires searching for universal methods and tools to monitor relationships between humans and climate. Our paper confirms that the UTCI is the universal tool describing the impact of thermal stress on the human body and its high usefulness in medical researches.

Exploring the efficacy of artificial neural networks in predicting lung cancer recurrence: a retrospective study based on patient records.

Background: Lung cancer remains a significant public health concern, accounting for a considerable number of cancer-related deaths worldwide. Neural networks have emerged as a promising tool that can aid in the diagnosis and treatment of various cancers. Consequently, there has been a growing interest in exploring the potential of artificial intelligence (AI) methods in medicine. The present study aimed to evaluate the effectiveness of a neural network in predicting lung cancer recurrence. Methods: The study employed retrospective data from 2,296 medical records of patients diagnosed with lung cancer and admitted to the Warminsko-Mazurskie Center for Lung Diseases in Olsztyn, Poland. The statistical software STATISTICA 7.1, equipped with the Neural Networks module (StatSoft Inc., Tulsa, USA), was utilized to analyze the data. The neural network model was trained using patient information regarding gender, treatment, smoking status, family history, and symptoms of cancer. Results: The study employed a multilayer perceptron neural network with a two-phase learning process. The network demonstrated high predictive ability, as indicated by the percentage of correct classifications, which amounted to 87.5%, 89.1%, and 89.9% for the training, validation, and test sets, respectively. Conclusions: The findings of this study support the potential usefulness of a neural network-based predictive model in assessing the risk of lung cancer recurrence. Further research is warranted to validate these findings and to explore AI's broader implications in cancer diagnosis and treatment.

Telemedicine in Primary Practice in the Age of the COVID-19 Pandemic-Review.

Background and Objectives: In the era of the COVID-19 pandemic, telemedicine, so far underestimated, has gained in value. Currently, telemedicine is not only a telephone or chat consultation, but also the possibility of the remote recording of signals (such as ECG, saturation, and heart rate) or even remote auscultation of the lungs. The objective of this review article is to present a potential role for, and disseminate knowledge of, telemedicine during the COVID-19 pandemic. Material and Methods: In order to analyze the research material in accordance with PRISMA guidelines, a systematic search of the ScienceDirect, Web of Science, and PubMed databases was conducted. Out of the total number of 363 papers identified, 22 original articles were subjected to analysis. Results: This article presents the possibilities of remote patient registration, which contributes to an improvement in remote diagnostics and diagnoses. Conclusions: Telemedicine is, although not always and not by everyone, an accepted form of providing medical services. It cannot replace direct patient-doctor contact, but it can undoubtedly contribute to accelerating diagnoses and improving their quality at a distance.

The potential role of miRNAs and regulation of their expression in the development of mare endometrial fibrosis.

Mare endometrial fibrosis (endometrosis), is one of the main causes of equine infertility. Despite the high prevalence, both ethology, pathogenesis and the nature of its progression remain poorly understood. Recent studies have shown that microRNAs (miRNAs) are important regulators in multiple cellular processes and functions under physiological and pathological circumstances. In this article, we reported changes in miRNA expression at different stages of endometrosis and the effect of transforming growth factor (TGF)-ß1 on the expression of the most dysregulated miRNAs. We identified 1, 26, and 5 differentially expressed miRNAs (DEmiRs), in categories IIA (mild fibrosis), IIB (moderate fibrosis), and III (severe fibrosis) groups compared to category I (no fibrosis) endometria group, respectively (Padjusted < 0.05, log2FC ≥ 1.0/log2FC ≤ - 1.0). This study indicated the potential involvement of miRNAs in the regulation of the process associated to the development and progression of endometrosis. The functional enrichment analysis revealed, that DEmiRs target genes involved in the mitogen-activated protein kinases, Hippo, and phosphoinositide-3-kinase (PI3K)-Akt signalling pathways, focal adhesion, and extracellular matrix-receptor interaction. Moreover, we demonstrated that the most potent profibrotic cytokine-TGF-ß1-downregulated novel-eca-miR-42 (P < 0.05) expression in fibroblasts derived from endometria at early-stage endometrosis (category IIA).

Involvement of the peroxisome proliferator-activated receptor gamma (Pparγ) and matrix metalloproteinases-2 and -9 (Mmp-2 and -9) in the mechanism of action of di(2-ethylhexyl)phthalate (DEHP) in cultured mouse brain astrocytes and neurons.

Di(2-ethylhexyl)phthalate (DEHP) is one of the most widely used phthalates in industry. It has been shown that, after entering the body, DEHP has the ability to cross the blood-placenta and blood-brain barriers. One of the proposed mechanisms of action of DEHP is the activation of peroxisome proliferator-activated receptors (PPARs). Many different functions of PPARγ in cells have been demonstrated, one of which is the modulation of the activation of matrix metalloproteinases (MMPs). The aim of this study was to investigate the role of Pparγ, Mmp-2, and Mmp-9 in the mechanism of action of DEHP. The experiments were performed on in vitro primary murine neurons and astrocytes. The results showed that DEHP has a pro-apototic effect on neurons, causing an increase in caspase-3 activity and in the number of apoptotic bodies. However, in astrocytes, the increase in caspase-3 activity was not related to the apoptosis process, as no increase in the formation of apoptotic bodies was observed. Moreover, DEHP increased the proliferation of astrocytes, which was confirmed by the increase in the amount and expression of the Ki-67 protein. In astrocytes, DEHP decreased the expression of the Pparγ and Mmp-9 proteins but increased the expression of the Mmp-2 protein. In DEHP neurons, it increased the expression of the Pparγ protein but decreased the expression of the Mmp-2 and Mmp-9 proteins.

Experimental Models to Study the Functions of the Blood-Brain Barrier.

The purpose of this paper was to discuss the achievements of in vitro modeling in terms of the blood-brain barrier [BBB] and to create a clear overview of this research area, which is useful in research planning. The text was divided into three main parts. The first part describes the BBB as a functional structure, its constitution, cellular and noncellular components, mechanisms of functioning and importance for the central nervous system, in terms of both protection and nourishment. The second part is an overview of parameters important in terms of establishing and maintaining a barrier phenotype that allows for formulating criteria of evaluation of the BBB in vitro models. The third and last part discusses certain techniques for developing the BBB in vitro models. It describes subsequent research approaches and models, as they underwent change alongside technological advancement. On the one hand, we discuss possibilities and limitations of different research approaches: primary cultures vs. cell lines and monocultures vs. multicultures. On the other hand, we review advantages and disadvantages of specific models, such as models-on-a-chip, 3D models or microfluidic models. We not only attempt to state the usefulness of specific models in different kinds of research on the BBB but also emphasize the significance of this area of research for advancement of neuroscience and the pharmaceutical industry.

Three-Dimensional Echocardiography and Global Longitudinal Strain in Follow-Up After Multisystem Inflammatory Syndrome in Children: Six-Month, Single-Center, Prospective Study.

OBJECTIVE: To assess the potential long-term cardiac effects after multisystem inflammatory syndrome in children (MIS-C) with cardiovascular involvement in the acute phase. STUDY DESIGN: Our prospective study involved children consecutively diagnosed with MIS-C between October 2020 and February 2022 and followed 6 weeks and 6 months after the disease. In patients with severe cardiac involvement during the acute phase, an additional check-up after 3 months was scheduled. In all patients at all check-ups, 3-dimensional echocardiography and global longitudinal strain (GLS) were used to assess ventricular function. RESULTS: The study enrolled 172 children aged 1-17 years (median, 8 years). The means of ejection fraction (EF) and GLS for both ventricles were within normal limits after 6 weeks with no relationship with initial severity: left ventricular EF (LVEF) 60% (59%-63%), LV GLS -21.08% (-18.63% to -23.2%), right ventricular (RV) EF 64% (62%-67%), and RV GLS -22.8% (-20.5% to -24.5%). Further, statistically significant improvement of LV function was observed after 6 months-LVEF 63% (62%-65%) and LV GLS -22.55% (-21.05% to -24.25%; P < .05); however, RV function remained unchanged. The group with severe cardiac involvement showed LV function recovery pattern with no significant improvement between 6 weeks and 3 months after MIS-C, while still improving between 3 and 6 months after discharge. CONCLUSIONS: LV and RV function is within normal limits 6 weeks after MIS-C regardless of severity of cardiovascular involvement; LV function improves further between 6 weeks and 6 months after the disease. The long-term prognosis is optimistic with full recovery of cardiac function.

The Role of Aquaporin 5 (AQP5) in Lung Adenocarcinoma: A Review Article.

Aquaporins (AQPs) are selective, transmembrane proteins, which are primarily responsible for the transport of water and small molecules. They have been demonstrated to play a key role in the development and progression of cancer. Lung adenocarcinoma is the most common primary lung cancer diagnosed in patients in Europe and the USA. The research done so far has provided firm evidence that some AQPs can be biomarkers for various diseases. The objective of this review article is to present a potential role of AQP5 in the development of lung adenocarcinoma. Original papers discussing the involvement of AQP5 in carcinogenesis and containing relevant clinical data were identified. In order to analyze the research material in accordance with PRISMA guidelines, a systematic search of the ScienceDirect, Web of Science, and Pubmed databases was conducted. Out of the total number of 199 papers identified, 14 original articles were subject to analysis. This article presents the pathophysiological role of AQP5 in the biology of lung adenocarcinoma as well as its prognostic value. The analysis substantiates the conclusion that the prognostic value of AQP5 in lung cancer requires further research. Another aim of this paper is to disseminate knowledge about AQPs among clinicians.

Assessment of the Function of Respiratory Muscles in Patients after COVID-19 Infection and Respiratory Rehabilitation.

OBJECTIVES: The MIP (maximum inspiratory pressure) and MEP (maximum expiratory pressure) are sensitive indicators of respiratory muscle function. The aim of the study was to assess the function of respiratory muscles in patients after COVID-19 infection, before and after hospitalisation at the Pulmonary Rehabilitation Ward. MATERIALS AND METHODS: The study was conducted on a group of 19 people with laboratory-confirmed COVID-19 infection, who, in the period from 1 February to 31 May 2021, were hospitalised at the Independent Public Pulmonary Hospital and underwent respiratory rehabilitation in hospital conditions. A statistical analysis was performed using the STATISTICA package, ver. 10. A respiratory pressure meter (RP Check) was used to measure muscle strength. Measurements were performed twice on each patient-before admission and after hospitalisation in the Pulmonary Rehabilitation Ward. RESULTS: We show that conducting pulmonary rehabilitation contributes to the increase in MIP and MEP, which are associated with increased strength of the inspiratory and expiratory muscles. The average value of MIP increased by 11.95 cmH2O and MEP by 26.16 cmH2O. The improvement was visible in both female and male patients. CONCLUSIONS: Pulmonary rehabilitation contributes to the improvement of respiratory muscle function indicators among patients after COVID-19 infection. Assessment of the MIP and MEP indices is a simple and quick way to reliably assess the function of the respiratory muscles.

Fast and Noninvasive Hair Test for Preliminary Diagnosis of Mood Disorders.

The main objective of this study was to develop a test for the fast and noninvasive prediagnosis of mood disorders based on the noninvasive analysis of hair samples. The database included 75 control subjects (who were not diagnosed with depression) and 40 patients diagnosed with mood disorders such as depression or bipolar disorder. Both women and men, aged 18-65 years, participated in the research. After taking the hair samples, they were washed (methanol-water-methanol by shaking in a centrifuge for two min) and air-dried in a fume hood. Each hair collection was analyzed using Fourier transform infrared spectroscopy attenuated total reflection (ATR-FTIR) spectroscopy. Subsequently, the results obtained were analyzed based on chemometric methods: hierarchical cluster analysis (HCA) and principal component analysis (PCA). As a results of the research conducted, potential differences were noticed. There was a visible change in the spectra intensity at around 2800-3100 cm-1 and smaller differences around 1460 cm-1; the bands can be assigned to protein vibrations. However, these are preliminary studies that provide a good basis for the development of a test for the initial diagnosis of mood disorders.

Cardiovascular Anomalies among 1005 Fetuses Referred to Invasive Prenatal Testing-A Comprehensive Cohort Study of Associated Chromosomal Aberrations.

This retrospective cohort study comprehensively evaluates cardiovascular anomalies (CVAs) and associated extracardiac structural malformations (ECMs) among 1005 fetuses undergoing invasive prenatal testing at a single tertiary Polish center in the context of chromosomal aberrations detected in them by array comparative genomic hybridization (aCGH) and G-band karyotyping. The results of our study show that CVAs are among the most common malformations detected in fetuses undergoing invasive prenatal testing, as they affected 20% of all cases seen in our department. Septal defects predominated among fetuses with numerical aberrations, while conotruncal defects were the most common findings among fetuses with pathogenic copy number variants (CNVs). In 61% of cases, CVAs were associated with ECMs (the diagnosis was confirmed postnatally or in cases of pregnancy termination by means of autopsy). The most common ECMs were anomalies of the face and neck, followed by skeletal defects. In total, pathogenic chromosomal aberrations were found in 47.5% of CVAs cases, including 38.6% with numerical chromosomal aberrations. Pathogenic CNVs accounted for 14.5% of cases with CVAs and normal karyotype. Thus, our study highlights the importance of assessing the anatomy of the fetus, and of the genetic testing (preferably aCGH) that should be offered in all CVA and ECM cases.

Effects of Tobacco Smoking on the Survivability of Patients with Multiple Cancers and Single Lung Cancer.

Lung cancer is the leading cause of death worldwide among men and women. Tobacco smoking is the number one risk factor for lung cancer. The aim of our study was to evaluate the survivability of patients with single lung cancer in relation to the survival time in patients with multiple neoplasms whose last neoplasm was a lung cancer. A retrospective analysis was con-ducted of data from medical histories of patients hospitalized at the Pulmonary Hospital in Olsztyn (Poland) from 2012 to 2017, with a lung cancer diagnosis as the first or subsequent cancer. The total longevity of women with diagnosed multiple cancers was found to be shorter than that of men: 67.60 years (SD: 7.77) and 69.91 years (SD: 7.97), respectively. Among the ex-smokers, the longevity of men (68.93 years) was longer than that of women (66.18 years). Survival time, counted from the diagnosis of both the first and subsequent cancer, was longer among patients with multiple cancers than among patients with single lung cancer (p = 0.000). Women's survivability was worse than men's in the case of multiple cancers and in the group of people who quit smoking (p = 0.037; p = 0.000). To conclude, smoking tobacco affects the survival of patients with lung cancer. Smoking cessation improves overall survival.

A rare case of hemimegalencephaly diagnosed prenatally.

Hemimegalencephaly (HME), or unilateral megalencephaly, is a rare congenital brain malformation defined as overgrowth of one cerebral hemisphere or part of it resulting from abnormal cortical development and neuronal migration. However, cortical developmental abnormalities are rarely diagnosed prenatally. This is the reason for our study, in which we describe and compare ultrasound and MRI findings in a fetus with HME.

Hepatorenal Syndrome and Other Post-Liver Transplantation Complications: Case Studies and Literature Review.

Hepatorenal syndrome (HRS) was originally defined as a renal dysfunction caused by a decreased renal perfusion due to hemodynamic disturbances in the arterial circulation and an excessive activity of endogenous vasoactive systems in the course of cirrhosis. Considering the latest research, this syndrome may have a more complex pathomechanism. Equally often as in cirrhosis, HRS develops after orthotopic liver transplantation (OLTx) and worsens the prognosis significantly increasing mortality rates in this patient population. The prevalence of renal complications after OLTx and their negative prognostic impact on the survival of both the graft and the recipient prompted the authors of this work to analyze in detail 2 cases of HRS after OLTx to indicate the multiplicity of factors contributing to the pathophysiology of this syndrome. Attention was paid to risk factors for HRS found in the anamnesis before OLTx, especially a pre-existing renal dysfunction. In both cases early post-OLTx complications associated with the transplantation procedure were described: destabilization of the circulatory system, transfusions of blood products, prolonged stay at an intensive care unit, and necessity of introducing continuous renal replacement therapy. In the later period after the OLTx, infections (bacterial, fungal, viral) and drug nephrotoxicity, including the activity of immunosuppressants (tacrolimus), contributed primarily to the renal function impairment.