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Abstract Metabolic syndrome (MetS), as a set of medical conditions including hyperglycemia, hypertension, abdominal obesity, and dyslipidemia, represents a highly prevalent disease cluster worldwide. The individual components of MetS together increase the risk of MetS-related disorders. Recent research has demonstrated that bone, as an endocrine organ, releases several systemic cytokines (osteokines), including fibroblast growth factor 23 (FGF23), lipocalin 2 (LCN2), and sclerostin (SCL). This review not only summarizes current knowledge about MetS, osteokines and the most common MetS-related diseases with a detrimental impact on bone quality (type 2 diabetes mellitus: T2DM; cardiovascular diseases: CVDs; osteoporosis: OP), but also provides new interpretations of the relationships between osteokines and individual components of MetS, as well as between osteokines and MetS-related diseases mentioned above. In this context, particular emphasis was given on available clinical studies. According to the latest knowledge, FGF23 may become a useful biomarker for obesity, T2DM, and CVDs, as FGF23 levels were increased in patients suffering from these diseases. LCN2 could serve as an indicator of obesity, dyslipidemia, T2DM, and CVDs. The levels of LCN2 positively correlated with obesity indicators, triglycerides, and negatively correlated with high-density lipoprotein (HDL) cholesterol. Furthermore, subjects with T2DM and CVDs had higher LCN2 levels. SCL may act as a potential biomarker predicting the incidence of MetS including all its components, T2DM, CVDs, and OP. Elevated SCL levels were noted in individuals with T2DM, CVDs and reduced in patients with OP. The aforementioned bone-derived cytokines have the potential to serve as promising predictors and prospective treatment targets for MetS and MetS-related diseases negatively affecting bone quality.

Abstract Relationship between depressive disorder and autonomic nervous system has been already discussed. Reduced emotional regulation is supposed to be associated with prefrontal hypofunction and subcortical hyperactivity. The aim of this study was to determine the effect of vortioxetine on heart rate variability (HRV), a parameter of cardiac autonomic regulation, in depressed hospitalized paediatric patients and assess the clinical effectiveness of the drug in this population. We performed repeated polysomnography analyses at admission and after a short treatment in hospital (15.2 days on average) and measured various HRV parameters (RRi, pNN50, RMSSD, LF-HRV, HF-HRV) during wakefulness, N3 and REM sleep stages. Out of 27 study subjects, 67% have improved depression symptoms as well as anxiety and subjective sleep quality after short vortioxetine treatment. We have found a significant decrease in parasympathetic parameters pNN50, RMSSD and HF-HRV during N3 sleep phase, though not exclusively among vortioxetine responders. The anticipated increase in cardiovagal regulation after vortioxetine treatment was not demonstrated in this pilot study, possibly due to the drug’s multimodal mechanism and impact on the nucleus tractus solitarii, particularly its antagonism on 5HT-3 receptors. Application of selective drugs could further explain the effect of vortioxetine on HRV in depressed patients.

Bone tissue and breast tissue are interrelated, as demonstrated by breast microcalcifications, breast cancer bone metastases, bone morphogenetic proteins, and Wnt signaling. In addition, osteoblasts and osteoclasts represent an important switch of tumor cell dormancy during bone metastasis. Damage to both types of tissues mentioned above is highly prevalent, especially in postmenopausal women, and manifests itself in osteoporosis and breast cancer. Sea buckthorn (Elaeagnus rhamnoides L.), a botanical drug with high antioxidant, antitumor, anti-inflammatory, immunomodulatory, and regenerative properties, has great therapeutic potential due to the unique composition of its bioactive metabolites. This review aimed to summarize the current knowledge from in vitro and in vivo studies on the effect of sea buckthorn, as well as its most widespread flavonoids isorhamnetin, quercetin, and kaempferol, on bone and breast tissue health. In vitro studies have revealed the beneficial impacts of sea buckthorn and aforementioned flavonoids on both bone health (bone remodeling, mineralization, and oxidative stress) and breast tissue health (cancer cell proliferation, apoptosis, tumor growth, and metastatic behavior). In vivo studies have documented their protective effects against disturbed bone microarchitecture and reduced bone strength in animal models of osteoporosis, as well as against tumor expansion and metastatic properties in animal xenograft models. In any case, further research and clinical trials are needed to carefully evaluate the potential therapeutic benefits of sea buckthorn and its flavonoids. Based on the available information, however, it can be concluded that these bioactive metabolites favorably affect both bone and breast tissue health.

Background: Adolescent treatment resistant depression (TRD) is increasing in recent years. While ketamine showed rapid antidepressant effects in adult TRD studies, research on its effectiveness in adolescents is limited. Methods: This study examines the effects of intravenous ketamine vs. midazolam on depressive and anxiety symptomatology assessed by the Montgomery–Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and Children’s Depression Inventory (CDI) at two time points—2 h after initial infusion (T0+2h) and 24 h after the end of the treatment (Te+24h) in a sample of 55 adolescent TRD females (27 receiving ketamine, 28 midazolam). Results: At T0+2h, within-group comparisons revealed a significant reduction in MADRS and HAM-A scores compared to baseline in the ketamine and midazolam groups. At Te+24h, both groups demonstrated similar significant reductions in MADRS, HAM-A, and CDI scores compared to baseline. The MADRS assessment in the ketamine group showed 33% and 59% responders, and in the midazolam group, 14% and 46% responders at T0+2h and Te+24h, respectively. HAM-A evaluation in the ketamine group revealed 33% and 56% responders, and in the midazolam group, 11% and 39% responders at T0+2h and at Te+24h, respectively. CDI rating discovered 11% and 44% responders in the ketamine group and 4% and 21% responders in the midazolam group at T0+2h and Te+24h, respectively. Moreover, inner tension significantly decreased in ketamine compared to the midazolam group at Te+24h. Conclusions: Ketamine showed a reduction in depressive and anxiety symptoms during a short-term period with particular efficacy in alleviating inner tension over midazolam, suggesting its potential advantages in specific symptom relief in rarely studied adolescent TRD.

Non-linear pyroelectric energy harvesting using ferroelectric thin films exhibits high energy conversion, primarily due to their large breakdown field compared to bulks. Here, we report the pyroelectric energy conversion potential of lead scandium tantalate, Pb(Sc1/2Ta1/2)O3 (PST) thin film fabricated on a c-sapphire substrate using chemical solution deposition. To enable the application of high electric field and to assess the pyroelectric energy conversion performance, interdigitated electrodes were deposited on the PST thin film. A maximum harvested energy density of 9.1 J cm−3 per cycle was deduced from polarization measurements in films undergoing an Olsen cycle between 0 °C and 150 °C when the electric field was varied between 50 and 1500 kV/cm. Furthermore, PST thin films can reach up to 27 % of Carnot efficiency for a temperature interval of 10 K between 30 °C and 40 °C. This study highlights the significance of PST thin films for electro-thermal energy harvesting and promising opportunities for enhancing the conversion efficiency and power density using thin films or thin film multi-layer capacitors in the future for thermal energy harvesting.

The relationship between depression and insomnia is bidirectional and both conditions need to be treated adequately, especially in a vulnerable neurodevelopmental stage of adolescence. This study aimed to evaluate the effects of antidepressant treatment using vortioxetine (VOR) on the sleep architecture of depressed adolescents by using video-polysomnography (v-PSG), which has not been researched before. The v-PSG was performed on 30 adolescent in-patients (mean age of 15.0 years ± 1.5 SD, 21 girls) treated with VOR (dosage of 10/15/20 mg/day) administered orally once a day, before and after VOR treatment. The evaluated parameters were conventional sleep parameters, sleep fragmentation parameters, and selected spectral power indices. Symptoms of depression and insomnia before and after the treatment period were evaluated using valid and reliable questionnaires (the Children´s Depression Inventory and the Athens Insomnia Scale). Depressed adolescents showed higher REM latency and decreased REM sleep percentage after treatment than before the treatment period (p = 0.005, p = 0.009, respectively). Our study revealed REM suppression (increased REM latency and reduced REM sleep percentage), indicating altered sleep architecture as a potential result of VOR treatment, which seems to be dose-dependent.

Poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) P(VDF-TrFE-CFE) is a relaxor ferroelectric polymer, which exhibits a temperature-independent electrocaloric effect at room temperature. In this work, the electrocaloric effect in P(VDF-TrFE-CFE) film was directly analysed using infrared imaging. P(VDF-TrFE-CFE) 64.8%/27.4%/7.8% (in mole) film of (15 ± 1) μm thickness was deposited on polyethylene naphthalate substrate. Direct ECE of P(VDF-TrFE-CFE) film was measured from 15 to 35 °C at different electric fields. A maximum adiabatic temperature change (ΔTad) of 3.58 K was measured during the cooling cycle at a field of 100 V/μm at 30 °C. Finite element analysis of temperature dissipation through the sample estimated that the actual temperature change within P(VDF-TrFE-CFE) film was 4.3 K. Despite the thermal mass of the substrate, a substantial ECE was observed in P(VDF-TrFE-CFE) films. This electrocaloric terpolymer composition could be of interest for electrocaloric cooling applications.

Ketamine is a potential rapid-onset antidepressant characterized by sympathomimetic effects. However, the question of ketamine’s use in treating adolescents’ major depressive disorder (MDD) is still discussed. Thus, we aimed to study the acute effect of ketamine infusion treatment on sympathetic regulation using electrodermal activity (EDA) in addition to an assessment of depressive symptomatology in MDD adolescents. Twenty hospitalized adolescent girls with MDD (average age: 15.0 ± 1.46 yrs.) were examined before and two hours after a single intravenous infusion of ketamine. EDA was continuously recorded for 6 min, and depressive symptoms were assessed before and two hours after ketamine administration. The evaluated parameters included skin conductance level (SCL), nonspecific electrodermal responses (NS-SCRs), MADRS (questions no. 1–10, total score), and CDI (items A–E, total score). EDA parameters showed no significant changes after the ketamine treatment, and depressive symptoms were significantly reduced after the ketamine infusion. The analysis revealed a significant negative correlation between index SCL and CDI-A, CDI-E, and the total CDI score and between index NS-SCRs and MADRS no. 4 before the ketamine treatment. In conclusion, ketamine improved depressive symptomatology without a significant effect on EDA, indicating its potential safety and efficiency as an acute antidepressant intervention in adolescent MDD.

The skeleton is the third most common site of metastatic disease, which causes serious bone complications and short-term prognosis in cancer patients. Prostate and breast cancers are responsible for the majority of bone metastasis, resulting in osteolytic or osteoblastic lesions. The crosstalk between bone cells and their interactions with tumor cells are important in the development of lesions. Recently, both preclinical and clinical studies documented the clinical relevance of bone-derived factors, including osteocalcin (OC) and its undercarboxylated form (ucOC), fibroblast growth factor 23 (FGF23), sclerostin (SCL), and lipocalin 2 (LCN2) as prognostic tumor biomarkers and potential therapeutic targets in bone metastasis. Both OC and ucOC could be useful targets for the prevention of bone metastasis in breast cancer. Moreover, elevated OC level may be a metastatic marker of prostate cancer. FGF23 is particularly important for those forms of cancer that primarily affect bone and/or are characterized by bone metastasis. In other tumor entities, increased FGF23 level is enigmatic. SCL plays a significant role in the pathogenesis of both osteolytic and osteoblastic lesions, as its levels are high in metastatic breast and prostate cancers. Elevated expression levels of LCN2 have been found in aggressive subtypes of cancer. However, its role in anti-metastasis varies significantly between different cancer types. Anyway, all aforementioned bone-derived factors can be used as promising tumor biomarkers. As metastatic bone disease is generally not curable, targeting bone factors represents a new trend in the prevention of bone metastasis and patient care.

Understanding how context (e.g., host species, environmental conditions) drives disease susceptibility is an essential goal of disease ecology. We hypothesized that in bat white-nose syndrome (WNS), species-specific host–pathogen interactions may partly explain varying disease outcomes among host species. We characterized bat and pathogen transcriptomes in paired samples of lesion-positive and lesion-negative wing tissue from bats infected with Pseudogymnoascus destructans in three parallel experiments. The first two experiments analyzed samples collected from the susceptible Nearctic Myotis lucifugus and the less-susceptible Nearctic Eptesicus fuscus, following experimental infection and hibernation in captivity under controlled conditions. The third experiment applied the same analyses to paired samples from infected, free-ranging Myotis myotis, a less susceptible, Palearctic species, following natural infection and hibernation (n = 8 sample pairs/species). Gene expression by P. destructans was similar among the three host species despite varying environmental conditions among the three experiments and was similar within each host species between saprophytic contexts (superficial growth on wings) and pathogenic contexts (growth in lesions on the same wings). In contrast, we observed qualitative variation in host response: M. lucifugus and M. myotis exhibited systemic responses to infection, while E. fuscus up-regulated a remarkably localized response. Our results suggest potential phylogenetic determinants of response to WNS and can inform further studies of context-dependent host–pathogen interactions.

Abstract Background Emergence of both viral zoonoses from bats and diseases that threaten bat populations has highlighted the necessity for greater insights into the functioning of the bat immune system. Particularly when considering hibernating temperate bat species, it is important to understand the seasonal dynamics associated with immune response. Body temperature is one of the factors that modulates immune functions and defence mechanisms against pathogenic agents in vertebrates. To better understand innate immunity mediated by phagocytes in bats, we measured respiratory burst and haematology and blood chemistry parameters in heterothermic greater mouse-eared bats (Myotis myotis) and noctules (Nyctalus noctula) and homeothermic laboratory mice (Mus musculus). Results Bats displayed similar electrolyte levels and time-related parameters of phagocyte activity, but differed in blood profile parameters related to metabolism and red blood cell count. Greater mouse-eared bats differed from mice in all phagocyte activity parameters and had the lowest phagocytic activity overall, while noctules had the same quantitative phagocytic values as mice. Homeothermic mice were clustered separately in a high phagocyte activity group, while both heterothermic bat species were mixed in two lower phagocyte activity clusters. Stepwise regression identified glucose, white blood cell count, haemoglobin, total dissolved carbon dioxide and chloride variables as the best predictors of phagocyte activity. White blood cell counts, representing phagocyte numbers available for respiratory burst, were the best predictors of both time-related and quantitative parameters of phagocyte activity. Haemoglobin, as a proxy variable for oxygen available for uptake by phagocytes, was important for the onset of phagocytosis. Conclusions Our comparative data indicate that phagocyte activity reflects the physiological state and blood metabolic and cellular characteristics of homeothermic and heterothermic mammals. However, further studies elucidating trade-offs between immune defence, seasonal lifestyle physiology, hibernation behaviour, roosting ecology and geographic patterns of immunity of heterothermic bat species will be necessary. An improved understanding of bat immune responses will have positive ramifications for wildlife and conservation medicine.

Cadmium (Cd) is a widespread environmental pollutant which negatively affects bone health. The aim of this study was to investigate the impact of Cd exposure on cell parameters, expression of specific genes and mineralization in cultivated human osteoblasts. Osteoblasts were incubated without (control group) or with CdCl2 at final Cd concentrations of 0.1, 2, 5, 10, and 50 μM for 2, 4, 6 or 14 days. Cell viability, morphological changes, alkaline phosphatase activity, mineralization, and an expression of 10 genes associated with osteoblast-specific pathways, oxidative stress and cell death were determined. Osteoblast viability decreased at the highest Cd concentrations (5, 10 and 50 μM) after 4 days of treatment. Our findings specified the threshold of Cd exposure with morphological alterations to 5 μM Cd following 4 days of cultivation. Morphometric measurements revealed significantly decreased size of Cd-treated osteoblasts when compared to the control. The alkaline phosphatase activity was dose-dependent with a reduction at 5 μM Cd after 2 days. Cd concentration of 5 μM significantly down-regulated the expression of COL1A1, ALPL, BGLAP, and GPX1 genes. On the contrary, BAX and SOD1 genes were over-expressed at 0.1, 2, 5 μM Cd and TNFSF11 gene transcripts showed an increase at 0.1-2 μM Cd. No significant impact of Cd exposure on transcription levels of WNT5A, RUNX2, and CASP1 genes was detected. Cd at 0.1 μM stimulated the mineralization, while the dose of 1 μM Cd had no effect. In conclusion, Cd exposure had adverse impact on human osteoblasts viability, morphology and function. On molecular level, it was associated with bone matrix protein synthesis, bone remodelling, cell death, and response to oxidative stress. The lowest dose of Cd had the stimulatory effect on bone mineralization.

Cemtirestat, a bifunctional drug acting as an aldose reductase inhibitor with antioxidant ability, is considered a promising candidate for the treatment of diabetic neuropathy. Our study firstly examined the effects of prolonged cemtirestat treatment on bone parameters reflecting bone quality in non-diabetic rats and rats with streptozotocin (STZ)-induced diabetes. Experimental animals were assigned to four groups: non-diabetic rats, non-diabetic rats treated with cemtirestat, diabetic rats, and diabetic rats treated with cemtirestat. Higher levels of plasma glucose, triglycerides, cholesterol, glycated hemoglobin, magnesium, reduced femoral weight and length, bone mineral density and content, parameters characterizing trabecular bone mass and microarchitecture, cortical microarchitecture and geometry, and bone mechanical properties were determined in STZ-induced diabetic versus non-diabetic rats. Treatment with cemtirestat did not affect all aforementioned parameters in non-diabetic animals, suggesting that this drug is safe. In diabetic rats, cemtirestat supplementation reduced plasma triglyceride levels, increased the Haversian canal area and slightly, but insignificantly, improved bone mineral content. Nevertheless, the insufficient effect of cemtirestat treatment on diabetic bone disease does not support its use in the therapy of this complication of type 1 diabetes mellitus.

Osteoporosis and breast cancer are serious diseases that have become a significant socioeconomic burden. There are biochemical associations between the two disorders in terms of the amended function of estrogen, receptor activator of nuclear factor kappa beta ligand, oxidative stress, inflammation, and lipid accumulation. Honey as a functional food with high antioxidant and anti-inflammatory properties can contribute to the prevention of various diseases. Its health benefits are mainly related to the content of polyphenols. This review aims to summarize the current knowledge from in vitro, animal, and human studies on the use of honey as a potential therapeutic agent for osteoporosis and breast cancer. Preclinical studies have revealed a beneficial impact of honey on both bone health (microstructure, strength, oxidative stress) and breast tissue health (breast cancer cell proliferation and apoptosis, tumor growth rate, and volume). The limited number of clinical trials, especially in osteoporosis, indicates the need for further research to evaluate the potential benefits of honey in the treatment. Clinical studies related to breast cancer have revealed that honey is effective in increasing blood cell counts, interleukin-3 levels, and quality of life. In summary, honey may serve as a prospective therapeutic supplement for bone and breast tissue health.

Electrocaloric (EC) materials, presenting large adiabatic temperature change or isothermal entropy change under the application (or removal) of electric fields, offer an efficient alternative to caloric heat pumps for replacing hazardous gases used in traditional vapor-compression systems. Recently, a large EC temperature change of 5.5 K have been reported in Pb(Sc _0.5 Ta _0.5 )O _3 multilayer ceramic capacitors (Nair et al 2019 Nature 575 468) thanks to its strong first-order phase transition and a temperature span of 13 K has been reported in a prototype based on these capacitors (Torelló et al 2020 Science 370 125). However, the toxicity of lead forces researchers to find eco-friendly materials exhibiting competitive EC performances. Here, we study the EC effect in lead-free BaTiO _3 multilayer capacitors using an infrared camera. Unlike commercial BaTiO _3 capacitors, we prepared our samples without sacrifying the first-order phase transition in BaTiO _3 while a low amount of 0.2 mol% Mn was added as an acceptor dopant to improve electrical resistivity. Their EC adiabatic temperature variations show two peaks versus temperature, which match BaTiO _3 two first-order phase transitions, as observed by differential scanning calorimetry. We measured a temperature drop of ∼0.9 K over a temperature range of 70 K under 170 kV cm ^−1 , starting at 30 °C near the tetragonal-to-orthorhombic phase transition. Under the same electric field, a maximum temperature change of 2.4 K was recorded at 126 °C, at BaTiO _3 ’s Curie temperature. Our findings suggest that further optimized BaTiO _3 capacitors could offer a path for designing lead-free caloric cooling prototypes.

Ambient energy harvesting has great potential to contribute to sustainable development and address growing environmental challenges. Converting waste energy from energy-intensive processes and systems (e.g. combustion engines and furnaces) is crucial to reducing their environmental impact and achieving net-zero emissions. Compact energy harvesters will also be key to powering the exponentially growing smart devices ecosystem that is part of the Internet of Things, thus enabling futuristic applications that can improve our quality of life (e.g. smart homes, smart cities, smart manufacturing, and smart healthcare). To achieve these goals, innovative materials are needed to efficiently convert ambient energy into electricity through various physical mechanisms, such as the photovoltaic effect, thermoelectricity, piezoelectricity, triboelectricity, and radiofrequency wireless power transfer. By bringing together the perspectives of experts in various types of energy harvesting materials, this Roadmap provides extensive insights into recent advances and present challenges in the field. Additionally, the Roadmap analyses the key performance metrics of these technologies in relation to their ultimate energy conversion limits. Building on these insights, the Roadmap outlines promising directions for future research to fully harness the potential of energy harvesting materials for green energy anytime, anywhere.

Abstract Background This study aimed to examine femoral bone microstructure of mice after single and simultaneous administration to acrylamide and ethanol since both substances are often consumed separately and/or together by humans. Interactive effects of these toxins were analysed after one remodeling cycle. Methods Twenty clinically healthy adult mice were randomly divided into four groups following 2 weeks administration of toxins: A group - mice were fed with acrylamide (40 mg/kg bw); E group - mice were ethanol-fed (15% ethanol); AE group - mice were simultaneously fed with both toxins, and a C group – control (without acrylamide and/or ethanol supplementation). Generally, 2D and 3D imaging methods were used to determine cortical and trabecular bone tissues microstructure. Biochemical analyses of plasma parameters were also realized using commercially available ELISA tests and spectrophotometrically. Results Single and simultaneous exposure to acrylamide and ethanol affected only cortical bone microstructure. No significant changes in trabecular bone morphometry were detected among all groups. In mice from the A group, increased endocortical remodeling associated with a higher level of serum calcium and vasoconstriction of primary osteon’s vascular canals (POVC) were identified. On the contrary, increased cortical porosity consistent with a decreased relative bone volume, bone mineral density (BMD) and lower levels of alkaline phosphatase (ALP), glutathione (GSH), calcium in plasma and also with vasodilation of POVC were observed in the E group. In the AE group, the highest density of secondary osteons associated with a lower BMD and decreased levels of ALP, GSH were documented. The parameters of POVC and Haversian canals approximated to the C group. In addition, single and simultaneous exposure to both toxins caused liver disease consistent with a higher values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in plasma of all experimental groups. Conclusions Single administration to acrylamide and ethanol had negative effects on cortical bone structure of mice after one remodeling cycle. However, we identified possible antagonistic impact of these toxins on the structure of the cortical bone.

Abstract Background While commercial poultry and captive birds are exposed to antimicrobials through direct medication, environmental pollution may result in contamination of wild birds. Fluoroquinolones are commonly used medications to treat severe avian bacterial infections; however, their adverse effects on birds remain understudied. Here, we examine toxicity of enrofloxacin and marbofloxacin during the egg incubation period using the chicken (Gallus Gallus domesticus) as a model avian species. Laboratory tests were based on eggs injected with 1, 10 and 100 μg of fluoroquinolones per 1 g of egg weight prior to the start of incubation and monitoring of chick blood biochemistry, reproductive parameters and heart rate during incubation. Results Eggs treated with fluoroquinolones displayed reduced hatchability due to embryonic mortality, particularly on day 13 of incubation. Total hatching success showed a similar pattern, with a significantly reduced hatchability in low and high exposure groups treated with both enrofloxacin and marbofloxacin. From 15 to 67% of chicks hatching in these groups exhibited joint deformities. Hatching one-day pre-term occurred with a prevalence of 31 to 70% in all groups treated with fluoroquinolones. Embryonic heart rate, measured on days 13 and 19 of incubation, increased in all enrofloxacin-treated groups and medium and high dose groups of marbofloxacin-treated eggs. Blood biochemistry of chicks sampled at hatch from medium dose groups showed hypoproteinaemia, decreased uric acid and increased triglycerides. Chicks from the enrofloxacin-treated group displayed mild hyperglycaemia and a two-fold rise in the blood urea nitrogen to uric acid ratio. Principal components analysis based on blood biochemistry clearly separated the control bird cluster from both enrofloxacin- and marbofloxacin-treated birds. Conclusions Fluoroquinolones induce complex adverse effects on avian embryonic development, considerably reducing the performance of incubated eggs and hatching chicks. Cardiotoxicity, which quickens embryonic heart rate, meant that the total number of heart beats required for embryogenesis was achieved earlier than in the standard incubation period, resulting in pre-term hatching. Our data suggest that enrofloxacin has a higher potential for adverse effects than marbofloxacin. To conclude, care should be taken to prevent exposure of reproducing birds and their eggs to fluoroquinolones.

The extended microbial genome—the gut microbiome (GM)—plays a significant role in host health and disease. It is able to influence a number of physiological functions. During dysbiosis, GM is associated with the development of various chronic diseases with impaired bone quality. In general, GM is important for bone homeostasis and can affect it via several mechanisms. This review describes the roles of GM in bone homeostasis through influencing the immune and endocrine functions, short-chain fatty acids production, calcium absorption and the gut–brain axis. The relationship between GM composition and several bone-related diseases, specifically osteoporosis, osteoarthritis, rheumatoid arthritis, diabetes mellitus, obesity and bone cancer, is also highlighted and summarized. GM manipulation may become a future adjuvant therapy in the prevention of many chronic diseases. Therefore, the beneficial effects of probiotic therapy to improve the health status of individuals with aforementioned diseases are provided, but further studies are needed to clearly confirm its effectiveness. Recent evidence suggests that GM is responsible for direct and indirect effects on drug efficacy. Accordingly, various GM alterations and interactions related to the treatment of bone-related diseases are mentioned as well.

Lead scandium tantalate, Pb(Sc,Ta)O3, is an excellent electrocaloric material showing large temperature variations, good efficiency, and a broad operating temperature window. In form of multilayer ceramic capacitors integrated into a cooling device, the device can generate a temperature difference larger than 13 K. Here, we investigate Pb(Sc,Ta)O3 in form of thin films prepared using the sol–gel chemical solution deposition method. We report the detailed fabrication process of high-quality films on various substrates such as c-sapphire and fused silica. The main originality of this research is the use of interdigitated top electrodes, enabling the application of very large electric fields in PST. We provide structural and electrical characterisation, as well as electrocaloric temperature variation, using the Maxwell relation approach. Films do not show a B-site ordering. The temperature variation from 7.2 to 15.7 K was measured on the Pb(Sc,Ta)O3 film on a c-sapphire substrate under the electric field of 1330 kV/cm between 14.5 °C and 50 °C. This temperature variation is the highest reported so far in Pb(Sc,Ta)O3 thin films. Moreover, stress seems to have an effect on the maximum permittivity temperature and thus electrocaloric temperature variation with temperature in Pb(Sc,Ta)O3 films. Tensile stress induced by fused silica shifts the “transition” of Pb(Sc,Ta)O3 to lower temperatures. This study shows the possibility for electrocaloric temperature variation tuning with stress conditions.

White-nose syndrome (WNS) is a fungal disease caused by Pseudogymnoascus destructans that is devastating to Nearctic bat populations but tolerated by Palearctic bats. Temperature is a factor known to be important for fungal growth and bat choice of hibernation. Here we investigated the effect of temperature on the pathogenic fungal growth in the wild across the Palearctic. We modelled body surface temperature of bats with respect to fungal infection intensity and disease severity and were able to relate this to the mean annual surface temperature at the site. Bats that hibernated at lower temperatures had less fungal growth and fewer skin lesions on their wings. Contrary to expectation derived from laboratory P. destructans culture experiments, natural infection intensity peaked between 5 and 6°C and decreased at warmer hibernating temperature. We made predictive maps based on bat species distributions, temperature and infection intensity and disease severity data to determine not only where P. destructans will be found but also where the infection will be invasive to bats across the Palearctic. Together these data highlight the mechanistic model of the interplay between environmental and biological factors, which determine progression in a wildlife disease.

Abstract Background Spatiotemporal distribution patterns are important infectious disease epidemiological characteristics that improve our understanding of wild animal population health. The skin infection caused by the fungus Pseudogymnoascus destructans emerged as a panzootic disease in bats of the northern hemisphere. However, the infection status of bats over an extensive geographic area of the Russian Federation has remained understudied. Results We examined bats at the geographic limits of bat hibernation in the Palearctic temperate zone and found bats with white-nose syndrome (WNS) on the European slopes of the Ural Mountains through the Western Siberian Plain, Central Siberia and on to the Far East. We identified the diagnostic symptoms of WNS based on histopathology in the Northern Ural region at 11° (about 1200 km) higher latitude than the current northern limit in the Nearctic. While body surface temperature differed between regions, bats at all study sites hibernated in very cold conditions averaging 3.6 °C. Each region also differed in P. destructans fungal load and the number of UV fluorescent skin lesions indicating skin damage intensity. Myotis bombinus, M. gracilis and Murina hilgendorfi were newly confirmed with histopathological symptoms of WNS. Prevalence of UV-documented WNS ranged between 16 and 76% in species of relevant sample size. Conclusions To conclude, the bat pathogen P. destructans is widely present in Russian hibernacula but infection remains at low intensity, despite the high exposure rate.

Type 2 diabetes mellitus (T2DM) is the most widespread form of diabetes, characterized by chronic hyperglycaemia, insulin resistance, and inefficient insulin secretion and action. Primary care in T2DM is pharmacological, using drugs of several groups that include insulin sensitisers (e.g., biguanides, thiazolidinediones), insulin secretagogues (e.g., sulphonylureas, meglinides), alpha-glucosidase inhibitors, and the newest incretin-based therapies and sodium–glucose co-transporter 2 inhibitors. However, their long-term application can cause many harmful side effects, emphasising the importance of the using natural therapeutic products. Natural health substances including non-flavonoid polyphenols (e.g., resveratrol, curcumin, tannins, and lignans), flavonoids (e.g., anthocyanins, epigallocatechin gallate, quercetin, naringin, rutin, and kaempferol), plant fruits, vegetables and other products (e.g., garlic, green tea, blackcurrant, rowanberry, bilberry, strawberry, cornelian cherry, olive oil, sesame oil, and carrot) may be a safer alternative to primary pharmacological therapy. They are recommended as food supplements to prevent and/or ameliorate T2DM-related complications. In the advanced stage of T2DM, the combination therapy of synthetic agents and natural compounds with synergistic interactions makes the treatment more efficient. In this review, both pharmaceutical drugs and selected natural products, as well as combination therapies, are characterized. Mechanisms of their action and possible negative side effects are also provided.

The greater mouse-eared bat (Myotis myotis) is a flagship species for the protection of hibernation and summer maternity roosts in the Western Palearctic region. A range of pathogenic agents is known to put pressure on populations, including the white-nose syndrome fungus, for which the species shows the highest prevalence and infection intensity of all European bat species. Here, we perform analysis of blood parameters characteristic for the species during its natural annual life cycle in order to establish reference values. Despite sexual dimorphism and some univariate differences, the overall multivariate pattern suggests low seasonal variation with homeostatic mechanisms effectively regulating haematology and blood biochemistry ranges. Overall, the species displayed a high haematocrit and haemoglobin content and high concentration of urea, while blood glucose levels in swarming and hibernating bats ranged from hypo- to normoglycaemic. Unlike blood pH, concentrations of electrolytes were wide ranging. To conclude, baseline data for blood physiology are a useful tool for providing suitable medical care in rescue centres, for studying population health in bats adapting to environmental change, and for understanding bat responses to stressors of conservation and/or zoonotic importance.

This study examined for the first time whether bee bread (BB, consisting of monofloral rape bee pollen) could alleviate lipid derangements and reduced bone quality in Zucker diabetic fatty (ZDF) rats, which are considered an appropriate animal model for type 2 diabetes mellitus (T2DM) investigation. Adult ZDF rats were segregated into four groups: lean non-diabetic rats (L group), obese diabetic rats untreated (C group), and those treated with the BB at two doses (500 and 700 mg/kg body weight, respectively, B1 and B2 groups) for 10 weeks. Significantly reduced levels of total cholesterol and triglyceride were recorded in the B2 group versus the C group. In both BB-treated groups, significantly increased relative volume of trabecular bone and trabecular thickness, enhanced density of secondary osteons, accelerated periosteal bone apposition, and improved blood flow were observed. A positive effect of higher dose of BB on femoral weight and cortical bone thickness was also demonstrated. Our results suggest a promising potential of BB to ameliorate T2DM-related complications associated with lipid and bone damages.

Cornelian cherry (Cornus mas L.) is a medicinal plant with a range of biological features. It is often used as a nutritional supplement in the treatment of diabetes mellitus. Our study was aimed to first investigate the effects of Cornelian cherry pulp on bone quality parameters in Zucker diabetic fatty (ZDF) rats. Moreover, lipid-lowering properties of this fruit were also evaluated. Adult rats (n = 28) were assigned into four groups of seven individuals each: L group (non-diabetic lean rats), C group (diabetic obese rats), and E1 and E2 groups (diabetic obese rats receiving 500 and 1000 mg/kg body weight of Cornelian cherry pulp, respectively, for 10 weeks). Significantly lower levels of triglyceride, total cholesterol and alkaline phosphatase activity were determined in the E2 group versus the C group. A higher dose of Cornus mas also had a beneficial impact on femoral weight, cortical bone thickness, relative volume of trabecular bone and trabecular thickness. We observed elevated density of Haversian systems and accelerated periosteal bone apposition in both treated groups (E1 and E2). Our results clearly demonstrate that Cornelian cherry pulp has a favorable effect on lipid disorder and impaired bone quality consistent with type 2 diabetes mellitus in a suitable animal model.

While white-nose syndrome (WNS) has decimated hibernating bat populations in the Nearctic, species from the Palearctic appear to cope better with the fungal skin infection causing WNS. This has encouraged multiple hypotheses on the mechanisms leading to differential survival of species exposed to the same pathogen. To facilitate intercontinental comparisons, we proposed a novel pathogenesis-based grading scheme consistent with WNS diagnosis histopathology criteria. UV light-guided collection was used to obtain single biopsies from Nearctic and Palearctic bat wing membranes non-lethally. The proposed scheme scores eleven grades associated with WNS on histopathology. Given weights reflective of grade severity, the sum of findings from an individual results in weighted cumulative WNS pathology score. The probability of finding fungal skin colonisation and single, multiple or confluent cupping erosions increased with increase in Pseudogymnoascus destructans load. Increasing fungal load mimicked progression of skin infection from epidermal surface colonisation to deep dermal invasion. Similarly, the number of UV-fluorescent lesions increased with increasing weighted cumulative WNS pathology score, demonstrating congruence between WNS-associated tissue damage and extent of UV fluorescence. In a case report, we demonstrated that UV-fluorescence disappears within two weeks of euthermy. Change in fluorescence was coupled with a reduction in weighted cumulative WNS pathology score, whereby both methods lost diagnostic utility. While weighted cumulative WNS pathology scores were greater in the Nearctic than Palearctic, values for Nearctic bats were within the range of those for Palearctic species. Accumulation of wing damage probably influences mortality in affected bats, as demonstrated by a fatal case of Myotis daubentonii with natural WNS infection and healing in Myotis myotis. The proposed semi-quantitative pathology score provided good agreement between experienced raters, showing it to be a powerful and widely applicable tool for defining WNS severity.

Host traits and phylogeny can determine infection risk by driving pathogen transmission and its ability to infect new hosts. Predicting such risks is critical when designing disease mitigation strategies, and especially as regards wildlife, where intensive management is often advocated or prevented by economic and/or practical reasons. We investigated Pseudogymnoascus [Geomyces] destructans infection, the cause of white-nose syndrome (WNS), in relation to chiropteran ecology, behaviour and phylogenetics. While this fungus has caused devastating declines in North American bat populations, there have been no apparent population changes attributable to the disease in Europe. We screened 276 bats of 15 species from hibernacula in the Czech Republic over 2012 and 2013, and provided histopathological evidence for 11 European species positive for WNS. With the exception of Myotis myotis, the other ten species are all new reports for WNS in Europe. Of these, M. emarginatus, Eptesicus nilssonii, Rhinolophus hipposideros, Barbastella barbastellus and Plecotus auritus are new to the list of P. destructans-infected bat species. While the infected species are all statistically phylogenetically related, WNS affects bats from two suborders. These are ecologically diverse and adopt a wide range of hibernating strategies. Occurrence of WNS in distantly related bat species with diverse ecology suggests that the pathogen may be a generalist and that all bats hibernating within the distribution range of P. destructans may be at risk of infection.

Cyanogenic glycosides are present in several economically important plant foods. Amygdalin, one of the most common cyanoglucoside, can be found abundantly in the seeds of apples, bitter almonds, apricots, peaches, various beans, cereals, cassava and sorghum. Amygdalin has been used for the treatment of cancer, it shows killing effects on cancer cells by release of cyanide. However, its effect on bone structure has not been investigated to date. Therefore, the objective of this study was to determine a possible effect of amygdalin application on femoral bone microstructure in adult rabbits. Four month old rabbits were randomly divided into two groups of three animals each. Rabbits from E group received amygdalin intramuscularly at a dose 0.6 mg.kg-1 body weight (bw) (group E, n = 3) one time per day during 28 days. The second group of rabbits without amygdalin supplementation served as a control (group C, n = 3). After 28 days, histological structure of femoral bones in both groups of rabbits was analysed and compared. Rabbits from E group displayed different microstructure in middle part of the compact bone and near endosteal bone surface. For endosteal border, an absence of the primary vascular longitudinal bone tissue was typical. This part of the bone was formed by irregular Haversian and/or by dense Haversian bone tissues. In the middle part of substantia compacta, primary vascular longitudinal bone tissue was observed. Cortical bone thickness did not change between rabbits from E and C groups. However, rabbits from E group had a significantly lower values of primary osteons' vascular canals and secondary osteons as compared to the C group. On the other hand, all measured parameters of Haversian canals did not differ between rabbits from both groups. Our results demonstrate that intramuscular application of amygdalin at the dose used in our study affects femoral bone microstructure in rabbits.

Flavonoids are a group of plant metabolites with antioxidant effects. One of the most abundant flavonoids in the human diet is quercetin. It is found widely in fruits, vegetables and has a lot of beneficial effects on human health. Quercetin has a positive pharmacological effect on bone metabolism and it prevents the organism against bone loss. However, its impact on the size of basic structural units of the compact bone is still unknown. Therefore, the aim of present study was to investigate the impact of the quercetin on femoral bone microstructure in 5-month-old male rabbits. Five rabbits of Californian broiler line were randomly divided into two groups. In the experimental group (E group; n=3), animals were intramuscularly injected with quercetin at dose 1000 μg.kg-1 body weight (bw) for 90 days, 3 times per week. Two rabbits without quercetin administration served as a control group (C group). According to our results, intramuscular application of quercetin had an insignificant effect on cortical bone thickness in male rabbits. In these rabbits, changes in qualitative histological characteristics were present in the middle part of the compacta, where primary vascular longitudinal bone tissue was present and expanded there from the periosteum. Also, a lower number of secondary osteons was found in these animals. From the histomorphometrical point of view, significantly decreased sizes of primary osteons' vascular canals and secondary osteons (p

A lot of kinds of crops are susceptible to fungal attack, leading to considerable financial losses and damage the health of humans and animals. Patulin, a toxic fungal metabolite, can be found mainly in apple and apple products, with much less frequent contamination in other food products. Because of its high incidence and harmful health effects, patulin belongs to a class of mycotoxins, which are strictly monitored. However, its effect on bone structure is still unknown. This study was designed to investigate the impact of patulin on femoral bone structure in adult male rabbits. Four month-old male rabbits were randomly divided into two groups of three animals each. Rabbits from the experimental group (group A, n=3) were intramuscularly administered with patulin at dose 10 μg.kg-1 body weight (b.w.) twice a week for 4 weeks. The second group without patulin administration served as a control (group B, n=3). At the end of the experiment, body weight, femoral weight and length, cortical bone thickness and histological structure of femoral bones from all rabbits were determined. The results did not show any significant differences in body weight, femoral weight and length between experimental and control groups of rabbits. On the other hand, intramuscular application of patulin induced a significant increase in cortical bone thickness (p periosteum and also in the middle part of the femoral bone in these rabbits. The values for the primary osteons' vascular canals were significantly lower (p