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Type 2 diabetes mellitus (T2DM) is one of the most common modern “disease of affluence”, characterized by hyperglycemia resulting from defective insulin secretion by pancreatic β cells and/or impaired tissue sensitivity to insulin. In Poland, the incidence of this metabolic disease is 5–8% and is still increasing. The consequences of the development of T2DM include, among others: changes in cardiovascular system, retinopathy, nephropathy and neuropathy. Due to medical progress, it is easier to control glycemia, as well as to predict the occurrence of this disease or the dynamics of its development and consequences. The molecules discussed in the article: growth differentiation factor 15 (GDF-15), mesencephalic astrocyte-derived neurotrophic factor (MANF) and fetuin-A, represent great promise both in the diagnosis and treatment of not only T2DM, but also obesity, which often accompanies T2DM. Most of the studies reported in the literature were performed on animal models, mainly mouse. This article presents arguments supporting the potential usefulness of the above-mentioned paracrine factors for prognostic, diagnostic and therapeutic purposes.

Obesity is a chronic disease that constitutes a global problem and a serious challenge to public health. In the course of this disease, excessive accumulation of fat tissue occurs in the body, which not only leads to an increased risk of health complications, but also negatively affects the quality of life. Fat cells – adipocytes – are responsible for the biosynthesis and release of adipokines, among others, leptin, visfatin, chemerin and omentin-1. They are active biological substances, including mediators of inflammation, which may lead to the development of metabolic disorders in the body. The above-mentioned properties of the described adipokines make it possible to potentially use them as diagnostic and therapeutic factors in the course of obesity and its accompanying disorders such as insulin resistance, type 2 diabetes mellitus, and cardiometabolic complications. Despite significant progress in understanding the role played by the discussed adipokines, further research is necessary to precisely describe the mechanisms of action and to determine the precise relationship between their plasma concentrations and state of diseases.

Currently, steatohepatitis has been designated as metabolic dysfunction-associated steatohepatitis (MASLD). MASLD risk factors mainly include metabolic disorders but can also include genetic, epigenetic, and environmental factors. Disease entities such as obesity, diabetes, cardiovascular disease, and MASLD share similar pathomechanisms and risk factors. Moreover, a bidirectional relationship is observed between the occurrence of certain chronic diseases and MASLD. These conditions represent a global public health problem that is responsible for poor quality of life and high mortality. It seems that paying holistic attention to these problems will not only help increase the chances of reducing the incidence of these diseases but also assist in the prevention, treatment, and support of patients.

Paweł Sokal,1 Damian Palus,1 Magdalena Jabłońska,2 Oskar Puk,2 Sara Kieronska-Siwak1 1Department of Neurosurgery and Neurology, Faculty of Health Sciences, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, 85-168, Poland; 2Doctoral School Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, 85-168, PolandCorrespondence: Paweł Sokal, Department of Neurosurgery and Neurology, Faculty of Health Sciences, Collegium Medicum Nicolaus Copernicus University, Ujejskiego 75, Bydgoszcz, 85-168, Poland, Email pawel.sokal@cm.umk.plPurpose: Central neuropathic pain (CNP) following spinal cord injury (SCI) presents a formidable therapeutic challenge, affecting over 50% of the patients post-SCI. For those who experience CNP, conventional treatments often prove insufficient. Spinal cord stimulation (SCS) emerges as a potential intervention for chronic pain after SCI that is unresponsive to pharmacotherapy and supportive measures. However, the efficacy of SCS in alleviating CNP is notably limited. The objective of our study was to evaluate novel stimulation paradigms in SCS for patients with severe CNP after SCI, based on our extensive experience.Patients and Methods: From a pool of 112 patients treated with SCS for chronic neuropathic pain in the Department of Neurosurgery and Neurology, we selected eight individuals (4 males and 4 females) with CNP for our case series. Burst and high frequency SCS was applied. The assessment involved utilizing the Numeric Rating Scale (NRS), the Neuropathic Pain Symptom Inventory (NPSI), and the EQ-5D quality of life scale before surgery and during a 12-month follow-up period.Results: Over the course of the one-year follow-up, only two patients experienced satisfactory relief from pain, demonstrating the effectiveness of the stimulation. Moreover, high-frequency and burst SCS failed to show improvement in the remaining six patients.Conclusion: Our findings suggest that, despite the incorporation of new stimulation paradigms such as burst stimulation and high-frequency stimulation, SCS does not exhibit significant effectiveness in treating neuropathic pain in patients after SCI. These findings highlight the ongoing challenge of treating CNP and emphasize the importance of investigating alternative therapeutic strategies for this group.Keywords: spinal cord stimulation, central neuropathic pain, spinal cord injury, burst stimulation, high-frequency stimulation

Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9–17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p

Summary: Background: Healthcare-associated infections (HAI) and antimicrobial use (AMU) are drivers for antimicrobial resistance, and robust data are required to inform interventions and track changes. We aimed to estimate the prevalence of HAI and AMU at Port Moresby General Hospital (PMGH), the largest hospital in Papua New Guinea. Methods: We did a point prevalence survey (PPS) on HAI and AMU at PMGH in May 2023 using the European Centre for Disease Prevention and Control (ECDC) PPS protocol. We included all critical care patients and randomly sampled half of the patients in other acute-care wards. We calculated weighted HAI and AMU prevalence estimates to account for this sampling strategy. Weighted HAI estimates were also calculated for an expanded definition that included physician diagnosis. Findings: Of 361 patients surveyed in 18 wards, the ECDC protocol identified 28 HAIs in 26 patients, resulting in a weighted HAI prevalence of 6.7% (95% CI: 4.6, 9.8). Surgical site infections (9/28, 32%) were the most common HAI. When adding physician diagnosis to the ECDC definitions, more skin and soft tissue, respiratory, and bloodstream HAIs were detected, and the weighted HAI prevalence was 12.4% (95% CI: 9.4, 16.3). The prevalence of AMU was 66.5% (95%CI: 61.3, 71.2), and 73.2% (263/359) of antibiotics were from the World Health Organization Access group. Interpretation: This is the first reported hospital PPS of HAI and AMU in Papua New Guinea. These results can be used to prioritise interventions, and as a baseline against which future point prevalence surveys can be compared. Funding: Australian Government Department of Foreign Affairs and Trade and Therapeutic Guidelines Limited Australia.

One of the branches of traditional Chinese medicine (TCM) is herbal medicine. In this paper, we focus on the biological activity of substances belonging to flavonoids and specific examples of their impact on various body systems. Flavonoids are a group of chemical compounds included in plant materials, honey, propolis or mushrooms used in TCM. Chrysin, galangin, kaempferol and fisetin are examples of flavonoids showing, among others, antioxidant, anti-inflammatory or antibacterial properties, which are the subject of various scientific studies aimed at examining their potential therapeutic effect.

Abstract Background The global nutrition transition is associated with increased consumption of ultra-processed snack foods and sugar-sweetened beverages (UPF/SSB), contributing to the double burden of child obesity and undernutrition. Methods This cross-sectional study describes the prevalence of maternal and child UPF/SSB consumption and the factors associated with frequent consumption in a convenience sample of 749 children ages 6 months through 6 years and their mothers participating in a community-based child oral health program in five informal settlement communities in Mumbai, India. Mothers were interviewed regarding maternal and child oral health and nutrition characteristics, including consumption of beverages and foods associated with tooth decay—milk, soda, tea with sugar, sweets, and chips/biscuits—using standardized questionnaires. Spearman correlations were used to assess for associations between various social factors and the frequency of maternal and child consumption of the five food categories. Chi-square tests were used to assess differences in child consumption patterns by age groups. Results Though reported soda consumption was low among both mothers and children, nearly 60% of children consumed sweets and chips/biscuits daily, four to five times the rate of mothers. Factors associated with children’s frequent consumption of UPF/SSB included lower maternal education level, frequent maternal consumption of UPF/SSB, greater number of household members, greater amount of money given to the child, and closer proximity to a store. Conclusion Our findings demonstrate social factors that may promote UPF/SSB consumption. The nutritional dangers of sugary drinks and non-nutritious snacks for mothers and young children should be addressed across maternal–child health, education, and social service programs. Early childhood nutrition interventions should involve the entire family and community and emphasize the need to limit children’s consumption of unhealthy foods and beverages from an early age.

CD4+ CD25+ FOXP3+ T regulatory cells (Tregs) are a subset of the immunomodulatory cell population that can inhibit both innate and adaptive immunity by various regulatory mechanisms. In hepatic microenvironment, proliferation, plasticity, migration, and function of Tregs are interrelated to the remaining immune cells and their secreted cytokines and chemokines. In normal conditions, Tregs protect the liver from inflammatory and auto-immune responses, while disruption of this crosstalk between Tregs and other immune cells may result in the progression of chronic liver diseases and the development of hepatic malignancy. In this review, we analyze the deviance of this protective nature of Tregs in response to chronic inflammation and its involvement in inducing liver fibrosis, cirrhosis, and hepatocellular carcinoma. We will also provide a detailed emphasis on the relevance of Tregs as an effective immunotherapeutic option for autoimmune diseases, liver transplantation, and chronic liver diseases including liver cancer.

Abstract Diabetes mellitus (DM) is a well-known risk factor for atrial fibrillation (AF), but the mechanism(s) by which DM affects AF prevalence remains unclear. This study aims to evaluate the impact of diabetes mellitus severity (expressed as its known duration), antihyperglycemic treatment regimen and glycaemic control on AF prevalence. From the representative sample of 3014 participants (mean age 77.5, 49.1% female) from the cross-sectional NOMED-AF study, 881 participants (mean age 77.6 ± 0.25, 46.4% female) with concomitant DM were involved in the analysis. AF was screened using a telemonitoring vest for a mean of 21.9 ± 9.1 days. The mean DM duration was 12 ± 0.35 years, but no significant impact of DM timespan on AF prevalence was observed. No differences in the treatment pattern (oral medication vs insulin vs both oral + insulin) among the study population with and without AF were shown (p = 0.106). Metabolic control reflected by HbA1c levels showed no significant association with AF and silent AF prevalence (p = 0.635; p = 0.094). On multivariate analyses, age (Odds Ratio (OR) 1.35, 95%CI: 1.18–1.53, p

This paper aims to assess the level of credit risk (from the perspective of default risk) among Polish households associated with the physical risks of climate change. In order to determine the potential impact of the physical risk of climate change on household credit risk, we conducted CAWI interviews with 1,006 borrowers residing in different Polish voivodeships (to account for heterogeneity of credit exposures to extreme weather events). According to these respondents, wildfires and storms in Poland are the greatest source of physical risk of climate change. In the event of a wildfire or storm, approximately 13% of borrowers would not be able to repay their loans while not being insured, which potentially increases banks’ credit risk and exposes banks to losses. However, we find that households underestimate the credit risk that could arise from a drought.

Abstract Background Deoxyguanosine kinase deficiency is mainly manifested by hepatic and neurological damage, hence it belongs to the hepatocerebral form of mitochondrial deoxyribonucleic acid depletion syndrome. The association between deoxyguanosine kinase deficiency and recurrent spontaneous pneumothorax has not currently been reported. Case presentation A 12-year-old Russian boy with deoxyguanosine kinase deficiency, a recipient of a liver transplant with amyotrophy secondary to his mitochondriopathy, presented with recurrent spontaneous bilateral pneumothorax refractory to drainage and surgery. Conclusion To our knowledge, this is the first documented case of deoxyguanosine kinase deficiency associated with recurrent spontaneous pneumothorax, which could be considered a late complication of deoxyguanosine kinase deficiency. At this point, this is only an association and further studies and research need to be performed to help confirm the pathogenesis of this association.

Although copious research has documented elevated stress and burnout in teachers worldwide during the COVID-19 pandemic, few studies have provided empirical evidence of effective interventions to support post-pandemic educator recovery and resilience. Attention to educator well-being is essential not only to healthy schools, but also to preventing teacher shortages. In the current study, Canadian educators (n = 621) who participated in a school-based mental health intervention program offered by a national mental health organization demonstrated significantly higher levels of well-being and recovery post-intervention than pre-intervention. Moreover, when compared with a control group (n = 86), the intervention group demonstrated significantly higher levels of connectedness, recovery, well-being, and resilience, although no differences in organizational commitment were demonstrated. Implications on teacher attrition and shortages are discussed.

Introduction: Deep Brain Stimulation (DBS) and Spinal Cord Stimulation (SCS) represent burgeoning treatments for diverse neurological disorders. This systematic review aims to consolidate findings on the immunological and endocrine effects of DBS and SCS, shedding light on the intricate mechanisms of neuromodulation. Materials and methods: This systematic review, aligned with PRISMA protocols, synthesizes findings from 33 references—20 on DBS and 13 on SCS—to unravel the immunological and endocrine impacts of neuromodulation. Results: DBS interventions exhibited divergent effects on cytokines, with an increase in hepcidin levels and a variable impact on the IL-6/IL-10 ratio. While some studies reported elevated IL-6, animal studies consistently demonstrated a reduction in IL-1β and IL-6, with no significant changes in TNF-α and an increase in IL-10. Noteworthy hormonal changes included decreased corticosterone and ACTH concentrations and increased oxytocin levels following DBS of the hypothalamus. SCS mirrored similar effects on interleukins, indicating a reduction in IL-6 and IL-1β and an increase in IL-10 levels. Additionally, SCS led to reduced VEGF levels and elevated expression of neurotrophic factors such as BDNF and GDNF, particularly under burst stimulation. Conclusions: Both DBS and SCS exert anti-inflammatory effects, manifesting as a decrease in pro-inflammatory cytokines alongside the stimulation of anti-inflammatory cytokine synthesis. These findings, observed in both animal and human models, imply that neurostimulation may modify the trajectory of neurological diseases by modulating local immune responses in an immunomodulatory and endocrine manner. This comprehensive exploration sets the stage for future research endeavors in this evolving domain.

A series of novel CoFe2O4 – xBaTiO3 (x = 0.6–0.9) phosphate-bonded multifunctional ceramic composites were synthesized and studied both in ‘Salisbury screen’ geometry and as free-standing films in the frequency range of 25–54 GHz and temperature interval of 120–500 K. Experiments prove that the studied system is prospective for shielding applications in both modes providing total transmission losses of the free-standing sample layer of 40 dB for x = 0.9 dominated by absorption and more than 40 dB of reflection losses at resonant conditions in the Salisbury screen geometry. It was demonstrated that the electromagnetic response of multiferroic composite ceramics in microwaves is very sensitive to the temperature changes in the application's significant temperature range, i.e. 150 – 400 K. Notably, a small, i.e. 5 – 10 K, temperature variation drastically changes the shielding efficiency of the Salisbury screen (SER). In particular, SER ≥ 40 dB is achieved in the range of 302–309 K for the sample with x = 0.9, outside of the range SE rapidly decreases to 10–15 dB. The impact of temperature has to be considered for the efficient use of shielding materials in Ka and V bands for different applications.

Nigella sativa L. (family Ranunculaceae), also known as black cumin, has been used in cuisine around the world for many years. Due to its health-promoting properties, it can be used not only in the food industry but also in medicine. The main bioactive compound contained in the black cumin extract is thymoquinone (TQ), which has a special therapeutic role. The results of research in recent years confirmed its hypoglycemic, hypolipemic, and hepatoprotective effects, among others. In addition, the results of laboratory tests also indicate its immunomodulatory and anticancer effects, although there is still a lack of data on the mechanisms of how they are involved in the fight against cancer. Including this plant material in one’s diet can be both an element of prophylaxis and therapy supporting the treatment process, including pharmacological treatment. However, attention should be paid to its potential interactions with drugs used in the treatment of chronic diseases.

Currently, metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are considered to be the main causes of fibrosis. In turn, fibrosis may lead to the development of hepatocellular carcinoma or advanced cirrhosis, i.e., potentially life-threatening conditions. It is likely that therapy aimed at reducing the risk of developing hepatic steatosis and inflammation could be helpful in minimizing the threat/probability of organ fibrosis. In recent years, increasing attention has been paid to the influence of nutraceuticals in the prevention and treatment of liver diseases. Therefore, the aim of this review was to describe the precise role of selected ingredients such as vitamin C, beta-carotene, omega-3 fatty acids, and curcumin. It is likely that the use of these ingredients in the treatment of patients with MASLD/MASH, along with behavioral and pharmacological therapy, may have a beneficial effect on combating inflammation, reducing oxidative stress, and thereby preventing liver damage.

The problem of treating inflammatory bowel disease continues to be a topic of great interest for researchers. Despite the complexity surrounding their treatment and strategies to prolong periods of remission, there is a promising exploration of various compounds that have potential in combating inflammation and alleviating symptoms. Selenium, calcium, magnesium, zinc, and iron are among these compounds, offering a glimpse of hope in the treatment of IBD. These essential minerals not only hold the promise of reducing inflammation in these diseases, but also show the potential to enhance immune function and possibly influence the balance of intestinal microflora. By potentially modulating the gut microbiota, they may help support overall immune health. Furthermore, these compounds could play a crucial role in mitigating inflammation and minimising complications in patients with IBD. Furthermore, the protective effect of these compounds against mucosal damage in IBD and the protective effect of calcium itself against osteoporosis in this group of patients are notable.

Quinoline and isoquinoline moieties occur in many natural and synthetic compounds exhibiting high biological activity. The purpose of this study was to analyze the chemical structures of 5,8-quinolinedione and 5,8-isoquinoline derivatives using FT-IR spectroscopy supplemented with theoretical DFT calculations. Spectroscopic measurements were conducted using the attenuated total reflection (ATR) mode in the frequency range of 4000–400 cm−1. An analysis of FT-IR spectra was carried out, assigning the characteristic vibration frequencies of various functional groups to individual peaks. It was found that the experimental and calculated FT-IR spectra showed a good correlation for all the compounds under study. The most significant difference in the spectra occurred in the region of carbonyl bands. For compounds with the 5,8-quinolinedione moiety, two separated C=O vibration peaks were observed, while for compounds with the 5,8-isoquinolinedione moiety, the carbonyl vibrations created only one peak. This difference makes it possible to distinguish between the 5,8-quinolinedione and 5,8-isoquinolinedione derivatives.

Abstract The carotid body chemoreceptors (CBC) play an important role in the adaptive counter‐regulatory response to hypoglycaemia by evoking the CBC‐mediated sympathetic neuronal system to restore normoglycaemia. Ex vivo studies have shown varied responses of insulin‐induced hypoglycaemia on CBC function, and several in vivo studies have indirectly established the role of CBCs in restoring normoglycaemia in both animals and humans. However, a direct effect of insulin and/or insulin‐induced hypoglycaemia on CBC activity is not established in animal models. Therefore, the aim of this study was to evaluate in vivo effects of insulin and insulin‐induced hypoglycaemia on CBC activity and cardiorespiration in a preclinical large animal model. The carotid sinus nerve (CSN) activity and cardiorespiratory responses to sodium cyanide (NaCN; 25 µg/kg) were compared before (euglycaemic) and after (hypoglycaemic) intracarotid administration of insulin (12.5–100 µU/dogs) in beagle dogs. Insulin administration increased CSN activity and minute ventilation (V̇E) with significant (P

Summary: Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation at both the global and the transcript-specific levels. In this study, we characterized translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) by polysome profiling. We demonstrate that protein synthesis increases during exit from pluripotency and is then globally repressed during later steps of hepatogenic maturation. This global downregulation of translation is accompanied by a decrease in the abundance of protein components of the translation machinery, which involves a global reduction in translational efficiency of terminal oligopyrimidine tract (TOP) mRNA encoding translation-related factors. Despite global translational repression during hepatogenic differentiation, key hepatogenic genes remain efficiently translated, and the translation of several transcripts involved in hepatospecific functions and metabolic maturation is even induced. We conclude that, during hepatogenic differentiation, a global decrease in protein synthesis is accompanied by a specific translational rewiring of hepatospecific transcripts.

Abstract The slice-wise multiplication of two tensors is required in a variety of tensor decompositions (including PARAFAC2 and PARATUCK2) and is encountered in many applications, including the analysis of multidimensional biomedical data (EEG, MEG, etc.) or multi-carrier multiple-input multiple-output (MIMO) systems. In this paper, we propose a new tensor representation that is not based on a slice-wise (matrix) description, but can be represented by a double contraction of two tensors. Such a double contraction of two tensors can be efficiently calculated via generalized unfoldings. It leads to new tensor models of the investigated system that do not depend on the chosen unfolding (in contrast to matrix models) and reveal the tensor structure of the data model, such that all possible unfoldings can be seen at the same time. As an example, we apply this new concept to the design of new receivers for multi-carrier MIMO systems in wireless communications. In particular, we consider MIMO-orthogonal frequency division multiplexing (OFDM) systems with and without Khatri–Rao coding. The proposed receivers exploit the channel correlation between adjacent subcarriers, require the same amount of training symbols as traditional OFDM techniques, but have an improved performance in terms of the symbol error rate. Furthermore, we show that the spectral efficiency of the Khatri–Rao-coded MIMO-OFDM can be increased by introducing cross-coding such that the “coding matrix” also contains useful information symbols. Considering this transmission technique, we derive a tensor model and two types of receivers for cross-coded MIMO-OFDM systems using the double contraction of two tensors.

Thermostable heat-insulating composite materials based on solid magnesium phosphate and calcium phosphate binders, fly-ash and glass hollow microspheres have been developed and proposed. Thermal and phase transformations have been studied as well as strength characteristics of the initial composites and products of their thermal treatment up to 1000 °C have been determined. It is shown that the prepared phosphate composites are thermally stable in the temperature range of 20 –1000 °С, have a density 0.4 – 0.6 g/cm3 , thermal conductivity 0.11– 0.19 W/(m ⋅ K) and show sufficiently high strength properties (compressive strength 1.4 –3.2 MPa).

In this study, authors use combinatory bacteriophage-antibiotic therapy, as treatment for extensively drug-resistant Pseudomonas aeruginosa infection in a toddler post liver transplantation. They report on the clinical and microbiological improvement, and present their investigation on how bacterial phage resistance did not result in therapeutic failure.

Background & Aims: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis. Methods: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22–24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0–4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs). Results: In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22–24 of PEDFIC 2 in sBAs was -201 μmol/L (p

SARS-CoV-2 mRNA vaccination generates protective B cell responses targeting the SARS-CoV-2 spike glycoprotein. Whereas anti-spike memory B cell responses are long lasting, the anti-spike humoral antibody response progressively wanes, making booster vaccinations necessary for maintaining protective immunity. Here, we qualitatively investigated the plasmablast responses by measuring from single cells within hours of sampling the affinity of their secreted antibody for the SARS-CoV-2 spike receptor binding domain (RBD) in cohorts of BNT162b2-vaccinated naive and COVID-19–recovered individuals. Using a droplet microfluidic and imaging approach, we analyzed more than 4,000 single IgG-secreting cells, revealing high interindividual variability in affinity for RBD, with variations over 4 logs. High-affinity plasmablasts were induced by BNT162b2 vaccination against Hu-1 and Omicron RBD but disappeared quickly thereafter, whereas low-affinity plasmablasts represented more than 65% of the plasmablast response at all time points. Our droplet-based method thus proves efficient at fast and qualitative immune monitoring and should be helpful for optimization of vaccination protocols.

Bioavailability describes the properties that determine the passage of a compound through biological barriers. In many cases, bioavailability depends on the lipophilicity of the compound. In this study, the lipophilicity as well as other bioavailability properties of the mono- and bistriazole derivatives of betulin are presented. The lipophilicity was determined using RP-TLC and theoretical methods. The experimental lipophilicity of mono- and bistriazole derivatives is in the range from 4.39 to 7.85 and from 3.75 to 8.83, respectively. The lipophilicity of mono- and bistriazoles is similar, and the logPTLC depends on the type of substituent at the triazole ring. The introduction of a substituent with oxygen and nitrogen atoms decreases lipophilicity. Comparing the experimental and theoretical lipophilicity shows that the milogP and XLOGP3 programs best reproduce the experimental values. The in silico-determined pharmacokinetic parameters show that monotriazole derivatives could be used as oral drugs while bistriazoles show low availability after oral administration. Triazoles could be used as transdermal drugs. The analysis of in silico bioavailability parameters shows that the type of substituent at the triazole ring influences the pharmacokinetic properties, while the number of triazole rings slightly affects the bioavailability properties of the compound.

Lead poses severe effects on living organisms, and since Pb2+ ions tend to accumulate in different organs, it is crucial to monitor Pb2+ concentration in samples such as water and soil. One of the approaches is the utilization of biosensors combined with aptamer-based layers for the electrochemical detection of lead ions. Herein, we present the studies of applying miniaturized screen-printed transducers as solid surfaces to fabricate aptamer layers. As the research is the direct continuation of our previous studies regarding the use of gold disk electrodes, the working parameters of elaborated aptasensors were defined, including the range of linear response (10–100 nM), selectivity as well as stability, regeneration, and feasibility of application for the analysis of real samples. This was achieved using voltammetric techniques including cyclic and square-wave voltammetry in the presence of methylene blue redox indicator.

The intestinal microbiota is a community of microorganisms inhabiting the human intestines, potentially influencing both physiological and pathophysiological processes in the human body. Existing evidence suggests that nutrients can influence the modulation of the gut microbiota. However, there is still limited evidence regarding the effects of vitamin and mineral supplementation on the human gut microbiota through epigenetic modification. It is plausible that maintaining an adequate dietary intake of vitamin D, iron, fibre, zinc and magnesium may have a beneficial effect on alleviating inflammation in the body, reducing oxidative stress, and improving the condition of the intestinal microbiota through various epigenetic mechanisms. Moreover, epigenetics involves alterations in the phenotype of a cell without changing its fundamental DNA sequence. It appears that the modulation of the microbiota by various nutrients may lead to epigenetic regulation. The correlations between microbiota and epigenetics are potentially interdependent. Therefore, the primary objective of this review is to identify the complex relationships between diet, gut microbiota, and epigenetic regulation. These interactions could play a crucial role in systemic health.

As a form of immunomodulatory therapeutics, mesenchymal stromal/stem cells (MSCs) from umbilical cord (UC) tissue were assessed for their dynamic interplay with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on the cell ratio of the cocultures as well as the presence of an inflammatory setting underlying their plasticity. UC-MSCs significantly increased the expression of IL-17A and RORγt but differentially modulated T cell expression of IL-23R. In parallel, the secretion profile of the fifteen factors (IL1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α) involved in the Th-17 immune response pathway was substantially altered during these cocultures. The modulation of these factors demonstrates the capacity of UC-MSCs to sense and actively respond to tissue challenges. Protein network and functional enrichment analysis indicated that several biological processes, molecular functions, and cellular components linked to distinct Th-17 signaling interactions are involved in several trophic, inflammatory, and immune network responses. These immunological changes and interactions with the Th-17 pathway are likely critical to tissue healing and may help to identify molecular targets that will improve therapeutic strategies involving UC-MSCs.

Mateusz Krakowiak,1 Natalia Rulewska,2 Marcin Rudaś,1 Maciej Broda,1 Michał Sabramowicz,1 Andrzej Jaremko,1 Krzysztof Leki,3 Paweł Sokal1 1Department of Neurosurgery and Neurology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland; 2Students’ Scientific Circle at the Department of Neurosurgery, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland; 3Centre for Statistical Analysis, Nicolaus Copernicus University, Toruń, PolandCorrespondence: Paweł Sokal, Department of Neurosurgery and Neurology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland, Tel/Fax +48 523655505, Email pawel.sokal@cm.umk.plAim: Interspinous process device (IPD) placement is an attractive treatment option for lumbar spinal and foraminal stenosis. The goal of the treatment is to release the stress on facets joints as well as decompress the nerve roots by enlarging the intervertebral foramina and narrowed canal recesses.Purpose: To evaluate possible structural changes in the lumbar spine after implantation of an IPD on operated and adjacent segments.Patients and Methods: Twenty-two patients were enrolled in the study. Preoperative MRI scans of the lumbar spine evaluated recess and foraminal stenosis prior to the application of an IPD. CT exams were performed and morphometric measurements were made to assess the size of intervertebral foramina after implantation on the operated and adjacent segments.Results: Statistically significant enlargements in diameter and surface area of the intervertebral foramen were seen at the operating level. On the right and left sides, foraminal enlargement after the procedure was 1 mm in diameter. The average enlargement of the foramina surface area at the level of implantation was 10 mm2. The median interspinous distance was significantly enlarged by 3.5 mm. No significant changes in adjacent segments were observed. Clinical improvement was confirmed by the Oswestry Disability Index (ODI) and visual analog scale (VAS). Preoperative disability was reduced (mean ODI from 70.5 (12.25) to 49.5 (23.75)), as well as back pain (mean VAS from 8.0 (1.7) to 4.4 (2.6)) and pain in lower limbs (mean VAS from 7.4 (1.9) to 3.8 (2.9)).Conclusion: Decompression surgery using an IPD is effective in the treatment of lumbar foraminal and canal stenosis. It provides relief of symptoms in short-term observation through enlargement of intervertebral foramina and decompression of neural roots. It reduces overload of facet joints of the operated segment and does not decrease the size of the intervertebral foramina and disc heights of adjacent segments.Keywords: interspinous device, low lumbar back pain, lumbar decompression, spinal canal stenosis, foraminal stenosis

In the present work, potentiometric sensors with polymer membranes used for chlorhexidine (CHXD) determination were developed. The polymer membranes were plasticized with bis(2-ethylheksyl)sebacate (DOS) or 2-nitrophenyloctyl ether (o-NPOE). The active compounds used in the membrane were cyclodextrins, crown ethers, and ion exchangers. The best-constructed electrode was based on neutral heptakis(2,3,6-tri-O-benzoyl)-β-cyclodextrin with lipophilic salt (KTpClBP)—potassium tetrakis(4-chlorophenyl) borate—dissolved in plasticizer, DOS. The presented electrode is characterized by an average cationic slope of 30.9 ± 2.9 mV decade−1 within a linear range of 1 × 10−6 to 1 × 10−3 mol × L−1, while the value of the correlation coefficient is 0.9970 ± 0.0026. The response time was about 5 s when increasing the sample concentration and about 10 s when diluting the sample. The electrode potential is independent of the pH within a range of 4.0–9.5. The polymeric membrane sensor was successfully applied for assays of chlorhexidine digluconate in pure samples and pharmaceutical samples. The relative error from three replicate measurements was determined to be 1.1%. and the accuracy was RSD = 0.3–1.1%.

The molecular structure of 3-diethoxyphosphoryl-28-[1-(1-deoxy-β-D-glucopyranosyl)-1H-1,2,3-triazol-4-yl]carbonylbetulin was investigated through various experimental and theoretical methods. X-ray diffraction, Hirshfeld surface, experimental and calculated FT-IR spectra analysis, molecular electrostatic potential (MEP) and molecular orbital (HOMO and LUMO) were used for the analyses. It was found that the introduction of a triazole substituent affects the arrangement of molecules in the crystal structure and the formation of hydrogen bonds. The Hirshfeld surface analysis shows that the red regions are concentrated near groups, which create hydrogen bonds, which means that the hydrogen bonds are strong. The analysis of HOMO and LUMO orbitals and the chemical reactivity descriptors shows that the compound is kinetically and chemically stable. A molecular electrostatic potential map was used to analyze the electrophilic and nucleophilic area in the molecule.

Head and neck cancer (HNC) therapy is limited; therefore, new solutions are increasingly being sought among flavonoids, which exhibit numerous biological properties, including potential anticancer activity. However, because they are mostly insoluble in water, are unstable and have low bioavailability, they are subjected to chemical modification to obtain new derivatives with better properties. This study aimed to synthesize and analyze new propargyloxy derivatives of galangin, kaempferol and fisetin, and to evaluate their anticancer activity against selected HNC cell lines. The obtained derivatives were assessed by spectroscopic analysis; next, their anticancer activity was evaluated using a flow cytometer and real-time cell analysis. The results showed that only the fisetin derivative was suitable for further analysis, due to the lack of crystal formation of the compound. The fisetin derivative statistically significantly increases the number of cells in the G2/M phase (p < 0.05) and increases cyclin B1 levels. A statistically significant increase in the number of apoptotic cells after being exposed to the tested compound was also observed (p < 0.05). The data indicate that the obtained fisetin derivative exhibits anticancer activity by affecting the cell cycle and increasing apoptosis in selected HNC lines, which suggests its potential use as a new medicinal agent in the future.

Highlights Using the satellite-detected tropospheric NO2 concentrations, we observed an association between individual exposure to NO2 and symptoms of Acute Respiratory Infections (ARIs) among children under 5 years old in Senegal. This is the first population-based epidemiological study conducted in Senegal that investigated the adverse health effect of early childhood exposure to ambient concentrations of NO2 on ARIs in children.

BackgroundHyperglycemia (HG) and prediabetes are rarely sought in pediatric liver (LT) and renal (RT) transplantation, yet their presence indicates a high risk of diabetes and cardiovascular disease. The objectives of our DIABGRAFT study were to retrospectively (rDIABGRAFT) and longitudinally (pDIABGRAFT) characterize HG and (pre)diabetes in a cohort of children with LT or/and RT.MethodsWe retrospectively analyzed risk factors of HG from 195 children with LT from 2012 to 2019 and twenty children with RT from 2005 to 2019 at Cliniques universitaires Saint-Luc. In addition, we prospectively followed four LT and four RT children to evaluate the evolution of their glucose metabolism.ResultsOur rDIABGRAFT study showed that 25% and 35% of LT and RT children respectively presented transient HG and 20% of RT developed diabetes. The occurrence of HG was associated with the use of glucocorticoids and with acute events as graft rejection and infection. In our pDIABGRAFT cohort, biological markers of diabetes were in the normal range for HbA1C, fasting glucose and insulin levels. However, oral glucose tolerance test and glucose sensors showed insulin resistance, impaired glucose tolerance and HG in the post-prandial afternoon period.ConclusionOur study shows that children with LT and RT were more at risk of developing HG when glucocorticoids were required and that HbA1C and fasting glucose lack sensitivity for early detection of glucose intolerance. Also, measurement of glycemia immediately after the transplantation and in postprandial period is key to detect dysglycemia since insulin resistance prevailed in our cohort.ClinicalTrials.gov IDNCT05464043.

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p

Background. Traumatic brain injury (TBI) is the main cause of disability in the world. Prehospital diagnosis of patients requiring rapid neurosurgical intervention and the earliest possible introduction of procedures preventing secondary brain injuries (SBI) are crucial. Methodology and Study Population. The authors of this paper assumed that certain age groups with specific injuries are more likely to require urgent neurosurgical intervention compared with patients who did not require such an intervention. Out of 54,814 head CT scans, based on the inclusion criteria, 7,864 were selected for the study. Data such as sex, age, the mechanism of injury, comorbid trauma, and abnormal findings in the examination of patients qualified for urgent neurosurgical intervention were analyzed in order to find statistically significant factors through a comparison with all head trauma patients. Results. Patients qualified for urgent neurosurgical intervention were significantly older compared with the others (63 years vs. 49 years). Patients transferred from the emergency department directly to the operating room were more often admitted to the hospital due to the fall (64.1% vs. 45.1%, p=0.004). The following were observed much more commonly among the patients qualified for urgent neurosurgical intervention than in the entire study group of subjects with traumatic brain injury (TBI), e.g., calf deformity (2.2% vs. 0.1%, p=0.019) and bleeding from the mouth (4.3% vs. 0.0%, p

IntroductionAlagille syndrome (ALGS) is an autosomal dominant disease characterized by a multisystem involvement including bile duct paucity and cholestasis, caused by JAG1 or NOTCH2 mutations in most of the cases. Jagged1-Notch2 interactions are known to be crucial for intrahepatic biliary tract development, but the Notch signaling pathway is also involved in the juxtacrine transmission of senescence and in the induction and modulation of the senescence-associated secretory phenotype (SASP).AimOur aim was to investigate premature senescence and SASP in ALGS livers.MethodsLiver tissue from ALGS patients was prospectively obtained at the time of liver transplantation (n = 5) and compared to control livers (n = 5).ResultsWe evidenced advanced premature senescence in the livers of five JAG1 mutated ALGS pediatric patients through increased senescence-associated beta-galactosidase activity (pConclusionsWe demonstrate for the first time that ALGS livers display important premature senescence despite Jagged1 mutation, underlying the complexity of senescence and SASP development pathways.

Introduction Alagille syndrome (ALGS) is an autosomal dominant disease characterized by a multisystem involvement including bile duct paucity and cholestasis, caused by JAG1 or NOTCH2 mutations in most of the cases. Jagged1-Notch2 interactions are known to be crucial for intrahepatic biliary tract development, but the Notch signaling pathway is also involved in the juxtacrine transmission of senescence and in the induction and modulation of the senescence-associated secretory phenotype (SASP). Aim Our aim was to investigate premature senescence and SASP in ALGS livers. Methods Liver tissue from ALGS patients was prospectively obtained at the time of liver transplantation (n = 5) and compared to control livers (n = 5). Results We evidenced advanced premature senescence in the livers of five JAG1 mutated ALGS pediatric patients through increased senescence-associated beta-galactosidase activity (pConclusions We demonstrate for the first time that ALGS livers display important premature senescence despite Jagged1 mutation, underlying the complexity of senescence and SASP development pathways.

Twenty teachers took part in bi-weekly interviews over the course of the 2020–2021 school year and again one year later during the COVID-19 pandemic. Comparative findings on teachers’ experiences indicated varied circumstances and a wide array of perspectives on coping during this protracted and stressful time. While some teachers demonstrated flourishing and resilience, the majority experienced a tipping point toward burnout. A small group languished, relating indicators of burnout and post-traumatic stress. Given the dynamic findings, a continuum of awareness is suggested that might assist teachers and administrators in critically assessing the range and dimensions of coping exhibited during the pandemic or subsequent stressful periods of time. With information of this nature available, we propose that school organizations could be better informed to provide supports and resources and improve worklife balance and well-being of teachers.

Introduction and objective It is widely known that the ageing process is associated with the occurrence of morphological, anatomical, and functional changes within the brain. Consequently, memory, elective attention and concentration may be impaired, and thus the quality of daily life may deteriorate. Reduced mental efficiency increases the susceptibility of the brain to neurodegenerative disorders, such as Alzheimer›s disease (AD) or Parkinson›s disease (PD). One of the main aims of this study was to examine the impact of diet composition and the use of various nutritional strategies, such as calorie restriction (CR) and intermittent fasting, (IF) on brain health. Review methods An electronic search strategy was used, including MeSH and key words. Brief description of the state of knowledge There are nutritional factors, including the amount of energy supplied and diet composition, which are important in brain functioning, especially during ageing. Based on research from recent years many strategies have been developed, the use of which could delay the neurological ageing process and the development of associated disorders and age-related pathologies. This research has focused mainly on nutritional interventions that delay (neurological) ageing, especially CR and IF. Particularly, altering the proportion of macronutrients appears to have an impact on life expectancy and longevity; a growing body of evidence shows that modulation of macronutrient proportions can affect brain ageing and cognition and, consequently, delay brain ageing and reduce the risk of developing neurodegenerative diseases, such as dementia. Summary There is a need for further randomized studies taking into account various factors, such as: genetic background or the severity of the disease, due to which it will be possible to develop appropriate strategies to prevent dementia in the elderly.

Abstract Thoracic aortic diseases contribute to a major part of cardiac surgeries. The severity of pathologies varies significantly from emergency and life-threatening to conservatively managed conditions. Life-threatening conditions include type A aortic dissection and rupture. Aortic aneurysm is an example of a conservatively managed condition. Pathologies that affect the arterial wall can have a profound impact on the presentation of such cases. Several risk factors have been identified that increase the risk of emergency presentations such as connective tissue disease, hypertension, and vasculitis. The understanding of aortic pathologies is essential to improve management and clinical outcomes.

Thermostable composite materials based on solid magnesium phosphate and calcium phosphate, as well as hybrid calcium magnesium phosphate binders have been developed and investigated. Thermal and phase transformations of the phosphate composites have been studied. Strength characteristics of composite materials have been determined in the temperature range of 20–1000 °C. It is shown that the obtained phosphate composites have high strength properties (compressive strength reaches 120–130 MPa) and are characterised by high thermal stability in the temperature range up to 1000 °С. The low weight loss of the studied composites (no more than 10 %) and the absence of significant thermal effects indicate that they are promising for use as a thermostable matrix for obtaining functional composite materials.

Background. The dynamic development and change of rural lifestyle patterns towards urban patterns has been noticeable since the second half of the 20th century. Nutrition, as well as the lifestyle in urban and rural areas, has undergone a process of urbanization, which is evidenced by the following an increasing number of overweight people. Objective. The aim of the study was to compare eating habits and frequency of consumption of selected groups of products between the urban and rural residents from the Subcarpathian voivodeship. Material and methods. The survey was carried out on a sample of 279 persons from urban and rural areas of Subcarpathian voivodeship. In this study, the diagnostic survey method consisting of 3 (different) parts was used. To check the significance of differences, U Mann-Whitney and Kruskal-Wallis tests were used; whereas correlations between variables were determined by the Spearman's rank of correlation coefficient and Pearson's chi-quadrat test. Results. In the part concerning eating habits, statistically significant differences occurred among others; for the circumstances of eating meals, the most commonly consumed snacks, food processing techniques and the most frequently selected fat. In the part concerning the frequency of consumption of individual product groups, significant differences occurred among others; for dairy products, grain products, fast food, alcohol. There was a correlation between the frequency of consumption of individual products and socioeconomic status. Conclusions. The quality of the diet and eating habits of urban and rural residents of Subcarpathian voivodeship does not differ significantly. The detected differences in eating habits were more influenced by the education and socioeconomic status of the examined group than the place of residence.

Abstract Background The global burden of atrial fibrillation (AF) and diabetes mellitus (DM) is constantly rising, leading to an increasing healthcare burden of stroke. AF often remains undiagnosed due to the occurrence in an asymptomatic, silent form, i.e., silent AF (SAF). The study aims to evaluate the relationships between DM and AF prevalence using a mobile long-term continuous ECG telemonitoring vest in a representative Polish and European population ≥ 65 years for detection of AF, symptomatic or silent. Methods A representative sample of 3014 participants from the cross-sectional NOMED-AF study was enrolled in the analyses (mean age 77.5, 49.1% female): 881 (29.2%) were diagnosed with DM. AF was screened using a telemonitoring vest for a mean of 21.9 ± 9.1days. Results Overall, AF was reported in 680 (22.6%) of the whole study population. AF prevalence was higher among subjects with concomitant DM (DM+) versus those without DM (DM−) [25%, 95% CI 22.5-27.8% vs 17%; 95% CI 15.4–18.5% respectively, p

The purpose of the study was to determine the global competence of 115 Canadian teacher candidates using a new measurement tool. Non-parametric tests indicated several differences in self-reported global competence within individual indicators across the three areas of Exploring, Engaging, and Acting with global competence. Two indicators showed that male teacher candidates reported higher levels of global competence than did females in the Exploring and Acting areas. Teacher candidates intending to teach in middle and senior high school reported higher levels in one indicator within the Acting area. Moreover, Canadian-born teacher candidates reported higher levels of Engaging and Acting than did non-Canadian-born students across six indicators total. While there were no differences across the three areas by age, results showed that higher levels of experience in their teacher education program were associated with greater global competence across all three areas as indicated by five indicators total, with three at the Acting stage. Implications for teacher education are discussed.

Abstract Involution of a rapidly involuting congenital hemangioma is an unknown cause of neonatal ascites. As involution phase is completed by 14 months after birth, conservative management with diuretics and drainage is possible and may avoid surgical resection.

Oral health is integral to overall health and is often neglected, especially in low- and middle-income countries (LMICs). Oral disease, including untreated dental caries, affects nearly 3.5 billion people globally, contributing to poor health and quality of life. To examine the relationship between the utilization of general healthcare and oral healthcare, we conducted an exploratory cross-sectional study of first-visit interview data collected from a convenience sample of 3,422 low-income mothers and 4,324 children aged 6 months through 6 years participating in a community-based oral health and nutrition program in five LMICs (Ecuador, El Salvador, India, Nepal, and Vietnam) from 2006–2015. We used descriptive and exploratory association analysis to identify patterns of oral healthcare utilization for mothers and children compared to medical care utilization, specifically maternal prenatal care and child immunizations. Overall, 89.6% of the mothers had received prenatal care for at least one child, but only 76.4% had ever received dental care and 50% were currently suffering from oral health symptoms, primarily oral pain. Mothers who received prenatal care were significantly more likely to have accessed dental care compared to those who had not received prenatal care (OR = 2.62, 95% CI: 2.06, 3.32). Overall, 95.4% of the children had current immunizations, but only 30.1% had ever received dental care, and 32.4% were currently suffering from oral pain. Children whose immunizations were up-to-date were more likely to have received dental care, with a significant association in Ecuador (OR = 3.29, 95% CI: 2.06, 5.30). Compared to utilization of general healthcare, oral healthcare was under-utilized by mothers and children in our sample from five LMICs. Integration of prevention- and treatment-oriented oral healthcare into primary medical care services, particularly prenatal care and child immunizations, could help increase access to oral healthcare and improve women's and children's oral health.