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Background: Ochratoxin A (OTA) is widely recognized for its broad spectrum of toxic effects and is classified as a potential human carcinogen, placed in group 2B by the International Agency for Research on Cancer (IARC). Its presence in food and beverages poses a significant health hazard. Extensive research has documented the efficient absorption and distribution of OTA throughout the body via the bloodstream and tissues, underscoring the associated health risk. Additionally, ongoing studies aim to clarify the link between OTA exposure and carcinogenesis. The obtained results indicate a strong correlation between OTA and renal cell carcinoma (RCC), with potential associations with other malignancies, including hepatocellular carcinoma (HCC), gallbladder cancer (GBC), and squamous cell carcinoma (SCC). OTA is implicated in oxidative stress, lipid peroxidation, apoptosis, DNA damage, adduct formation, miRNA deregulation, and distributions in the cell cycle, all of which may contribute to carcinogenesis. Conclusions: Despite significant research efforts, the topic remains inexhaustible and requires further investigation. The obtained results do not yield definitive conclusions, potentially due to species-specific differences in the animal models used and challenges in extrapolating these results to humans. In our review, we delve deeper into the potential mechanisms underlying OTA-induced carcinogenesis and discuss existing limitations, providing directions for future research.

Apitoxin therapy (BVT-bee venom therapy) is an emerging complementary treatment utilizing bee venom for various medical conditions. This review explores the potential and therapeutic mechanisms of bee venom, focusing on its chemical composition and the methods for its extraction and purification to enhance safety while maintaining bioactivity. Bee venom contains amphipathic peptides such as melittin and apamin, enzymes like phospholipase A2, and bioamines including histamine and catecholamines, contributing to its pleiotropic effects. The therapeutic applications of bee venom span anti-inflammatory, analgesic, antimicrobial, antiviral, neuroprotective, anti-arthritic, and anti-cancer activities. Clinical and laboratory studies have demonstrated its efficacy in treating chronic and autoimmune diseases, pain management, and improving quality of life. The immunogenic properties of bee venom necessitate ongoing research to mitigate allergic reactions, ensuring its safe and effective use in medical practice. This review summarizes the current state of research on bee venom therapy, highlighting its potential benefits and future research directions.

Despite the significant changes that unfold during the subacute phase of stroke, few studies have examined recovery abilities during this critical period. As neuroinflammation subsides and tissue degradation diminishes, the processes of neuroplasticity and angiogenesis intensify. An important factor in brain physiology and pathology, particularly neuroplasticity, is matrix metalloproteinase 9 (MMP-9). Its activity is modulated by tissue inhibitors of metalloproteinases (TIMPs), which impede substrate binding and activity by binding to its active sites. Notably, TIMP-1 specifically targets MMP-9 among other matrix metalloproteinases (MMPs). Our present study examines whether MMP-9 may play a beneficial role in psychological functions, particularly in alleviating depressive symptoms and enhancing specific cognitive domains, such as calculation. It appears that improvements in depressive symptoms during rehabilitation were notably linked with baseline MMP-9 plasma levels (r = -0.36, p = 0.025), and particularly so with the ratio of MMP-9 to TIMP-1, indicative of active MMP-9 (r = -0.42, p = 0.008). Furthermore, our findings support previous research demonstrating an inverse relationship between pre-rehabilitation MMP-9 serum levels and post-rehabilitation motor function. Crucially, our study emphasizes a positive correlation between cognition and motor function, highlighting the necessity of integrating both aspects into rehabilitation planning. These findings demonstrate the potential utility of MMP-9 as a prognostic biomarker for delineating recovery trajectories and guiding personalized treatment strategies for stroke patients during the subacute phase.

Pathogens and their toxins can cause various diseases of different severity. Some of them may be fatal, and therefore early diagnosis and suitable treatment is essential. There are numerous available methods used for their rapid screening. Conventional laboratory-based techniques such as culturing, enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) are dominant. However, culturing still remains the "gold standard" for their identification. These methods have many advantages, including high sensitivity and selectivity, but also numerous limitations, such as long experiment-time, costly instrumentation, and the need for well-qualified personnel to operate the equipment. All these existing limitations are the reasons for the continuous search for a new solutions in the field of bacteria identification. For years, research has been focusing on the use of immunosensors in various types of toxin- and pathogen-detection. Compared to the conventional methods, immunosensors do not require well-trained personnel. What is more, immunosensors are quick, highly selective and sensitive, and possess the potential to significantly improve the pathogen and toxin diagnostic-processes. There is a very important potential use for them in various transport systems, where the risk of contamination by bioagents is very high. In this paper, the advances in the field of immunosensor usage in pathogenic microorganism- and toxin-detection, are described.

Ionizing radiation (IR) can pass through the human body easily, potentially causing severe damage to all biocomponents, which is associated with increasing oxidative stress. IR is employed in radiotherapy; however, in order to increase safety, it is necessary to minimize side effects through the use of radioprotectors. Water-soluble derivatives of fullerene exhibit antiradical and antioxidant properties, and these compounds are regarded as potential candidates for radioprotectors. We examined the ability of fullerenol C60(OH)36 to protect human erythrocytes, including the protection of the erythrocytal antioxidant system against high-energy electrons. Human erythrocytes irradiated with high-energy [6 MeV] electrons were treated with C60(OH)36 (150 µg/mL), incubated and haemolyzed. The radioprotective properties of fullerenol were determined by examining the antioxidant enzymes activity in the hemolysate, the concentration of -SH groups, as well as by determining erythrocyte microviscosity. The irradiation of erythrocytes (650 and 1300 Gy) reduces the number of thiol groups; however, an attenuation of this harmful effect is observed (p < 0.05) in the presence of C60(OH)36. Although no significant effect of fullerenol was recorded on catalase activity, which was preserved in both control and test samples, a more active protection of other enzymes was evident. An irradiation-induced decrease in the activity of glutathione peroxidase and glutathione reductase became an increase in the activity of those two enzymes in samples irradiated in the presence of C60(OH)36 (p < 0.05 and p < 0.05, respectively). The fourth studied enzyme, glutathione transferase, decreased (p < 0.05) its activity in the irradiated hemolysate treated with C60(OH)36, thus, indicating a lower level of ROS in the system. However, the interaction of fullerenol with the active centre of the enzyme cannot be excluded. We also noticed that radiation caused a dose-dependent decrease in the erythrocyte microviscosity, and the presence of C60(OH)36 reduced this effect (p < 0.05). Overall, we point to the radioprotective effect of C60(OH)36 manifested as the protection of the antioxidant enzymes of human erythrocytes against IR-induced damage, which has not been the subject of intense research so far.

Stroke as the most frequent cause of disability is a challenge for the healthcare system as well as an important socio-economic issue. Therefore, there are currently a lot of studies dedicated to stroke recovery. Stroke recovery processes include angiogenesis and neuroplasticity and advances in neuroimaging techniques may provide indirect description of this action and become quantifiable indicators of these processes as well as responses to the therapeutical interventions. This means that neuroimaging and neurophysiological methods can be used as biomarkers-to make a prognosis of the course of stroke recovery and define patients with great potential of improvement after treatment. This approach is most likely to lead to novel rehabilitation strategies based on categorizing individuals for personalized treatment. In this review article, we introduce neuroimaging techniques dedicated to stroke recovery analysis with reference to angiogenesis and neuroplasticity processes. The most beneficial for personalized rehabilitation are multimodal panels of stroke recovery biomarkers, including neuroimaging and neurophysiological, genetic-molecular and clinical scales.

An increasing number of people experience disorders related to the central nervous system (CNS). Thus, new forms of therapy, which may be helpful in repairing processes' enhancement and restoring declined brain functions, are constantly being sought. One of the most relevant physiological processes occurring in the brain for its entire life is neuroplasticity. It has tremendous significance concerning CNS disorders since neurological recovery mainly depends on restoring its structural and functional organization. The main factors contributing to nerve tissue damage are oxidative stress and inflammation. Hence, marine carotenoids, abundantly occurring in the aquatic environment, being potent antioxidant compounds, may play a pivotal role in nerve cell protection. Furthermore, recent results revealed another valuable characteristic of these compounds in CNS therapy. By inhibiting oxidative stress and neuroinflammation, carotenoids promote synaptogenesis and neurogenesis, consequently presenting neuroprotective activity. Therefore, this paper focuses on the carotenoids obtained from marine sources and their impact on neuroplasticity enhancement.

Ngari virus (NRIV) has been mostly detected during concurrent outbreaks of Rift Valley fever virus (RVFV). NRIV is grouped in the genus Orthobunyavirus within the Bunyaviridae family and RVFV in the genus Phlebovirus in the family Phenuiviridae . Both are zoonotic arboviruses and can induce hemorrhagic fever displaying the same clinical picture in humans and small ruminants. To investigate if NRIV and its parental viruses, Bunyamwera virus (BUNV) and Batai virus (BATV), played a role during the Mauritanian RVF outbreak in 2015/16, we analyzed serum samples of sheep and goats from central and southern regions in Mauritania by quantitative real-time RT-PCR, serum neutralization test (SNT) and ELISA. 41 of 458 samples exhibited neutralizing reactivity against NRIV, nine against BATV and three against BUNV. Moreover, complete virus genomes from BUNV could be recovered from two sheep as well as two NRIV isolates from a goat and a sheep. No RVFV-derived viral RNA was detected, but 81 seropositive animals including 22 IgM-positive individuals were found. Of these specimens, 61 samples revealed antibodies against RVFV and at least against one of the three orthobunyaviruses. An indirect ELISA based on NRIV/BATV and BUNV derived Gc protein was established as complement to SNT, which showed high performance regarding NRIV, but decreased sensitivity and specificity regarding BATV and BUNV. Moreover, we observed high cross-reactivity among NRIV and BATV serological assays. Taken together, the data indicate the co-circulation of at least BUNV and NRIV in the Mauritanian sheep and goat populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cichon, Barry, Stoek, Diambar, Ba, Ziegler, Rissmann, Schulz, Haki, Höper, Doumbia, Bah, Groschup and Eiden.)

Background : Fullerenols (water-soluble derivatives of fullerenes), such as C 60 (OH) 36 , are biocompatible molecules with a high ability to scavenge reactive oxygen species (ROS), but the mechanism of their antioxidant action and cooperation with endogenous redox machinery remains unrecognized. Fullerenols rapidly distribute through blood cells; therefore, we investigated the effect of C 60 (OH) 36 on the antioxidant defense system in erythrocytes during their prolonged incubation. Methods : Human erythrocytes were treated with fullerenol at concentrations of 50-150 µg/mL, incubated for 3 and 48 h at 37 °C, and then hemolyzed. The level of oxidative stress was determined by examining the level of thiol groups, the activity of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, and glutathione transferase), and by measuring erythrocyte microviscosity. Results : The level of thiol groups in stored erythrocytes decreased; however, in the presence of higher concentrations of C 60 (OH) 36 (100 and 150 µg/mL), the level of -SH groups increased compared to the control. Extending the incubation to 48 h caused a decrease in antioxidant enzyme activity, but the addition of fullerenol, especially at higher concentrations (100-150 µg/mL), increased its activity. We observed that C 60 (OH) 36 had no effect on the microviscosity of the interior of the erythrocytes. Conclusions : In conclusion, our results indicated that water-soluble C 60 (OH) 36 has antioxidant potential and efficiently supports the enzymatic antioxidant system within the cell. These effects are probably related to the direct interaction of C 60 (OH) 36 with the enzyme that causes its structural changes.

Cognitive function decline is strictly related to age, resulting in the loss of the ability to perform daily behaviors and is a fundamental clinical neurodegeneration symptom. It has been proven that an adequate diet, comprehensive nutrition, and a healthy lifestyle may significantly inhibit neurodegenerative processes, improving cognitive functions. Therefore, intensive research has been conducted on cognitive-enhancing treatment for many years, especially with substances of natural origin. There are several intervention programs aimed at improving cognitive functions in elderly adults. Cognitive functions depend on body weight, food consumed daily, the quality of the intestinal microflora, and the supplements used. The effectiveness in the prevention of dementia is particularly high before the onset of the first symptoms. The impact of diet and nutrition on age-associated cognitive decline is becoming a growing field as a vital factor that may be easily modified, and the effects may be observed on an ongoing basis. The paper presents a review of the latest preclinical and clinical studies on the influence of natural antioxidants on cognitive functions, with particular emphasis on neurodegenerative diseases. Nevertheless, despite the promising research results in animal models, the clinical application of natural compounds will only be possible after solving a few challenges.

Aphasia is one of the most common clinical features of functional impairment after a stroke. Approximately 21-40% of stroke patients sustain permanent aphasia, which progressively worsens one's quality of life and rehabilitation outcomes. Post-stroke aphasia treatment strategies include speech language therapies, cognitive neurorehabilitation, telerehabilitation, computer-based management, experimental pharmacotherapy, and physical medicine. This review focuses on current evidence of the effectiveness of impairment-based aphasia therapies and communication-based therapies (as well as the timing and optimal treatment intensities for these interventions). Moreover, we present specific interventions, such as constraint-induced aphasia therapy (CIAT) and melodic intonation therapy (MIT). Accumulated data suggest that using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) is safe and can be used to modulate cortical excitability. Therefore, we review clinical studies that present TMS and tDCS as (possible) promising therapies in speech and language recovery, stimulating neuroplasticity. Several drugs have been used in aphasia pharmacotherapy, but evidence from clinical studies suggest that only nootropic agents, donepezil and memantine, may improve the prognosis of aphasia. This article is an overview on the current state of knowledge related to post-stroke aphasia pharmacology, rehabilitation, and future trends.

Nutrition and rehabilitation are crucial in post-stroke recovery, especially in the elderly. Since stroke is the leading cause of long-term disability, there is a need to promote special, individually tailored nutrition strategies targeting older patients with low motor ability. Chronic stroke survivors have higher risk of developing nutrition-related chronic diseases, such as sarcopenia, anemia, type 2 diabetes mellitus and osteoporosis. Moreover, reduced motor activity, cognitive impairment and depression might be aggravated by poor malnutrition status. Accumulated data suggest that nutritional supplements and neuroprotective diets can be associated with better effectiveness of post-stroke rehabilitation as well as brain recovery. Therefore, this review focuses on preventive strategies that can improve dietary intake and change dietary patterns. We highlight the importance of neuroprotective diets, the problem of dysphagia and the role of nutrition in rehabilitation. This article focuses on potential nutritional supplements and neuroprotective diets that may have an impact on functional recovery during and after rehabilitation. Moreover, a new approach to post-stroke neuroplasticity including the use of agents from marine sources such as fucoxanthin and tramiprosate as compounds that might be used as potential neuroprotectants with antioxidative and anti-inflammatory properties is introduced.

Malnutrition is a serious problem in post-stroke patients. Importantly, it intensifies with hospitalization, and is related to both somatic and psychological reasons, as well as is associated with the insufficient knowledge of people who accompany the patient. Malnutrition is a negative prognostic factor, leading to a reduction in the quality of life. Moreover, this condition significantly extends hospitalization time, increases the frequency of treatment in intensive care units, and negatively affects the effectiveness of rehabilitation. Obtaining growing data on the therapeutic effectiveness of new compounds of natural origin is possible through the use of pharmacodynamic and analytical methods to assess their therapeutic properties. The proper supply of nutrients, as well as compounds of natural origin, is an important element of post-stroke therapy, due to their strong antioxidant, anti-inflammatory, neuroprotective and neuroplasticity enhancing properties. Taking the above into account, in this review we present the current state of knowledge on the benefits of using selected substances of natural origin in patients after cerebral stroke.

Several key issues impact the clinical practice of stroke rehabilitation including a patient's medical history, stroke experience, the potential for recovery, and the selection of the most effective type of therapy. Until clinicians have answers to these concerns, the treatment and rehabilitation are rather intuitive, with standard procedures carried out based on subjective estimations using clinical scales. Therefore, there is a need to find biomarkers that could predict brain recovery potential in stroke patients. This review aims to present the current state-of-the-art stroke recovery biomarkers that could be used in clinical practice. The revision of biochemical biomarkers has been developed based on stroke recovery processes: angiogenesis and neuroplasticity. This paper provides an overview of the biomarkers that are considered to be ready-to-use in clinical practice and others, considered as future tools. Furthermore, this review shows the utility of biomarkers in the development of the concept of personalized medicine. Enhancing brain neuroplasticity and rehabilitation facilitation are crucial concerns not only after stroke, but in all central nervous system diseases.

The present preliminary case-control study was undertaken to detect the potential association of six single nucleotide polymorphisms (SNPs) in oxidative stress-related genes: SOD2 (c.47T > C; rs4880), CAT (c.-89A > T; rs7943316), GPX4 (c.660T > A; rs713041), NOS1 (g.117803515C > T; rs1879417) and NOS2 (c.1823C > T; rs2297518 and c.-227G > C; rs10459953) and the occurrence of a stroke. The SNPs were determined using the TaqMan ® Allelic Discrimination Assay in 107 patients with strokes and 107 age- and sex-matched individuals who had not experienced cerebrovascular accidents. The T alleles of the rs4880 were positively correlated with a stroke (bootstrap OR 1.31; 1.07-1.59 95% CI). In the case of the rs713041, an association with the T allele was found (bootstrap OR 1.36; 1.12-1.67). In addition, the occurrence of a stroke was associated with the presence of the C allele of the rs1879417 (bootstrap OR 1.32; 1.09-1.61). We also found that the C/C genotype and C allele of the rs2297518 increased the risk of a stroke (bootstrap ORs 7.00; 4.34-11.29 and 4.96; 3.88-6.34, respectively). Moreover, the C allele of the rs10459953 was associated with an increased occurrence of this disease (bootstrap OR 1.31; 1.08-1.60). These results indicated that genetics variants in the SOD2 , GPX4 , NOS1 and NOS2 might be associated with susceptibility to strokes in the Polish population.

Arthropod-borne Batai virus (BATV) is an Orthobunyavirus widely distributed throughout European livestock and has, in the past, been linked to febrile diseases in humans. In Germany, BATV was found in mosquitoes and in one captive harbor seal, and antibodies were recently detected in various ruminant species. We have, therefore, conducted a follow-up study in ruminants from Saxony-Anhalt, the most affected region in Eastern Germany. A total of 325 blood samples from apparently healthy sheep, goats, and cattle were tested using a BATV-specific qRT-PCR and SNT. Even though viral RNA was not detected, the presence of antibodies was confirmed in the sera of all three species: sheep (16.5%), goats (18.3%), and cattle (41.4%). Sera were further analyzed by a glycoprotein Gc-based indirect ELISA to evaluate Gc-derived antibodies as a basis for a new serological test for BATV infections. Interestingly, the presence of neutralizing antibodies was not directly linked to the presence of BATV Gc antibodies. Overall, our results illustrate the high frequency of BATV infections in ruminants in Eastern Germany.

Neuroplasticity is a complex physiological process occurring in the brain for its entire life. However, it is of particular importance in the case of central nervous system (CNS) disorders. Neurological recovery largely depends on the ability to reestablish the structural and functional organization of neurovascular networks, which must be pharmacologically supported. For this reason, new forms of therapy are constantly being sought. Including adjuvant therapies in standard treatment may support the enhancement of repair processes and restore impaired brain functions. The common hallmark of nerve tissue damage is increased by oxidative stress and inflammation. Thus, the studies on flavonoids with strong antioxidant and anti-inflammatory properties as a potential application in neuro intervention have been carried out for a long time. However, recent results have revealed another important property of these compounds in CNS therapy. Flavonoids possess neuroprotective activity, and promote synaptogenesis and neurogenesis, by, among other means, inhibiting oxidative stress and neuroinflammation. This paper presents an overview of the latest knowledge on the impact of flavonoids on the plasticity processes of the brain, taking into account the molecular basis of their activity.

Apoptosis in acute stroke is associated with a negative prognosis and is correlated with the severity of the neurological deficit. However, there is no evidence that indicates that, in the subacute phase of the stroke, the apoptosis process might activate neuroplasticity. Therefore, in this study, we investigated the effect of an extremely low frequency electromagnetic field (ELF-EMF) on the molecular mechanism of apoptosis, as used in the rehabilitation of post-stroke patients. Patients with moderate stroke severity ( n = 48), 3-4 weeks after incident, were enrolled in the analysis and divided into ELF-EMF and non-ELF-EMF group. The rehabilitation program in both groups involves the following: kinesiotherapy-30 min; psychological therapy-15 min; and neurophysiological routines-60 min. Additionally, the ELF-EMF group was exposed to an ELF-EMF (40 Hz, 5 mT). In order to assess the apoptosis gene expression level, we measured the mRNA expression of BAX , BCL - 2 , CASP8 , TNFα , and TP53 . We found that ELF-EMF significantly increased the expression of BAX , CASP8 , TNFα , and TP53 , whereas the BCL-2 mRNA expression after ELF-EMF exposition remained at a comparable level in both groups. Thus, we suggest that increasing the expression of pro-apoptotic genes in post-stroke patients promotes the activation of signaling pathways involved in brain plasticity processes. However, further research is needed to clarify this process.

The abnormal activation of the tryptophan catabolites pathway (TRYCATs) is observed in patients suffering from cerebrovascular disease, including stroke. A previous study confirmed that lower bioavailability of tryptophan for serotonin synthesis was characterized in the patients during the acute stroke phase. Interestingly, according to various studies, polymorphisms of the genes involved in the TRYCATs pathway may modulate the risk of stroke occurrence. Therefore, this study aimed to investigate the association between the occurrence of TPH1, TPH2, KAT1, KAT2 and IDO1 polymorphisms and the risk of stroke development.The following 10 polymorphisms of the genes encoding enzymes of the TRYCATs pathway were selected: c.804-7C > A (rs10488682), c.-1668T > A (rs623580), c.803+221C > A (rs1800532), c.-173A > T (rs1799913) - TPH1 , c.-1449C > A (rs7963803), and c.-844G > T (rs4570625) - TPH2 . c.*456G > A of KAT1 (rs10988134), c.975-7T > C of KAT2 (rs1480544), c.-1849C > A (rs3824259) and c. -1493G > C (rs10089084) of IDO1 . The study was carried out on DNA isolated from the peripheral blood taken from 107 patients after a stroke and 107 healthy volunteers. All DNA samples were genotyped using TaqMan probes. The genotypes of eight studied polymorphisms modulated the risk of stroke. No significant difference in genotype and allele frequencies of the c.804-7C > A - TPH1 (rs10488682) and c.*456G > A - KAT1 (rs10988134) polymorphisms were found between patients and controls. Having performed haplotype and gen-gen analyses, it was possible to determine that patients after a stroke and controls differed in terms of the frequency of selected genotypes and haplotypes. Among the studied polymorphisms, eight SNPs were linked with stroke risk modulation. The results obtained confirmed our hypothesis regarding the involvement of the TRYCATs pathway in the pathogenesis of stroke., Competing Interests: The authors declare no competing financial and/or non-financial interests.

In humans, genetic variants of DLGAP1-4 have been linked with neuropsychiatric conditions, including autism spectrum disorder (ASD). While these findings implicate the encoded postsynaptic proteins, SAPAP1-4, in the etiology of neuropsychiatric conditions, underlying neurobiological mechanisms are unknown. To assess the contribution of SAPAP4 to these disorders, we characterized SAPAP4-deficient mice. Our study reveals that the loss of SAPAP4 triggers profound behavioural abnormalities, including cognitive deficits combined with impaired vocal communication and social interaction, phenotypes reminiscent of ASD in humans. These behavioural alterations of SAPAP4-deficient mice are associated with dramatic changes in synapse morphology, function and plasticity, indicating that SAPAP4 is critical for the development of functional neuronal networks and that mutations in the corresponding human gene, DLGAP4, may cause deficits in social and cognitive functioning relevant to ASD-like neurodevelopmental disorders.

Background: To investigate i) the effects of Trolox® or mannitol, which represent two different classes of antioxidants, on oxidative changes generated in manually isolated red blood cells (RBCs) from citrate-phosphate-dextrose (CPD) preserved whole blood, followed by up to 20 days refrigerated storage, and ii) whether Trolox supplemented to the blood bank-manufactured saline-adenine-glucose-mannitol (SAGM) preserved RBC units would offer better storage conditions compared with SAGM alone., Methods: The percentage of hemolysis and extracellular activity of lactate dehydrogenase (LDH) was measured to assess RBC membrane integrity. Lipid peroxidation, reduced glutathione (GSH) levels and total antioxidant capacity (TAC) were quantified by thiobarbituric acid-reactive substances (TBARS), Ellman's reagent and 2, 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS .+ ) based assay, respectively., Results: Trolox was little more effective than mannitol in protecting against progressive RBC hemolysis. Trolox (0.125-3.125 mmol/l) inhibited storage-induced leakage of LDH, lipid peroxidation, and to a lesser extent GSH depletion. Mannitol at these concentrations neither inhibited TBARS formation nor prevented GSH depletion. RBC units stored in SAGM-Trolox had significantly lower hemolysis, LDH leakage, and lipid peroxidation level compared to RBCs stored in SAGM., Conclusion: There is evidence of the beneficial effects of supplementing RBC-additive solutions with membrane-interacting antioxidants such as vitamin E analogues.

Objectives: To investigate the effects of sodium ascorbate (SA) (5-3125 μM) and a combination of SA and Trolox (25 and 125 μM) on oxidative changes generated in red blood cells (RBCs) followed by up to 20 days refrigerated storage., Methods: RBCs were isolated from CPD-preserved human blood. Percentage of hemolysis and extracellular activity of lactate dehydrogenase (LDH) were measured to assess the RBC membrane integrity. Lipid peroxidation (LPO), glutathione (GSH) and total antioxidant capacity (TAC) were quantified by thiobarbituric acid-reactive substances, Ellman's reagent and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) [Formula: see text]-based assay, respectively., Results: SA failed to reduce the storage-induced hemolysis and RBC membrane permeability. Addition of SA resulted in a concentration-independent LPO inhibition and increased TAC. A combination of SA/Trolox supplemented to the RBC medium significantly inhibited hemolysis, LDH leakage, LPO, GSH depletion and enhanced TAC., Discussion: The effects of vitamin C action are closely concentration-dependent and may be modulated by a variety of compounds (e.g. Hb degradation products) released from RBCs during the prolonged storage, changing its properties from anti- to pro-oxidative. The two different class antioxidants (SA/Trolox) could possibly cooperate to be good potential RBC storage additives ensuring both antiradical and membrane stabilizing protection.

Overall, diseases of the vascular system are rarely observed entities among nonhuman primates that are commonly associated with systemic infections, septicemia or bacteremia. Rhesus monkeys infected with simian immunodeficiency virus (SIV) may develop a chronic occlusive arteriopathy of unknown etiology in late stages of the disease. This SIV associated arteriopathy is the only well-known specific vascular entity described in nonhuman primates. We herein report a unique case of granulomatous arteritis in a grey mouse lemur affecting multiple organs, which is not comparable to other disease entities formerly described in nonhuman primates. The features of the entity most closely resemble disseminated visceral giant cell arteritis in humans. A concise description of the disease is given, and the differential diagnoses are discussed. An idiopathic pathogenesis is suspected., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2017 Nicole Cichon et al.)

Optimal behavior and survival result from integration of information across sensory systems. Modulation of network activity at the level of primary sensory cortices has been identified as a mechanism of cross-modal integration, yet its cellular substrate is still poorly understood. Here, we uncover the mechanisms by which individual neurons in primary somatosensory (S1) and visual (V1) cortices encode visual-tactile stimuli. For this, simultaneous extracellular recordings were performed from all layers of the S1 barrel field and V1 in Brown Norway rats in vivo and units were clustered and assigned to pyramidal neurons (PYRs) and interneurons (INs). We show that visual-tactile stimulation modulates the firing rate of a relatively low fraction of neurons throughout all cortical layers. Generally, it augments the firing of INs and decreases the activity of PYRs. Moreover, bimodal stimulation shapes the timing of neuronal firing by strengthening the phase-coupling between neuronal discharge and theta-beta band network oscillations as well as by modulating spiking onset. Sparse direct axonal projections between neurons in S1 and V1 seem to time the spike trains between the two cortical areas and, thus, may act as a substrate of cross-modal modulation. These results indicate that few cortical neurons mediate multisensory effects in primary sensory areas by directly encoding cross-modal information by their rate and timing of firing.

Cognitive deficits represent a major burden of neuropsychiatric disorders and result in part from abnormal communication within hippocampal-prefrontal circuits. While it has been hypothesized that this network dysfunction arises during development, long before the first clinical symptoms, experimental evidence is still missing. Here, we show that pre-juvenile mice mimicking genetic and environmental risk factors of disease (dual-hit GE mice) have poorer recognition memory that correlates with augmented coupling by synchrony and stronger directed interactions between prefrontal cortex and hippocampus. The network dysfunction emerges already during neonatal development, yet it initially consists in a diminished hippocampal theta drive and consequently, a weaker and disorganized entrainment of local prefrontal circuits in discontinuous oscillatory activity in dual-hit GE mice when compared with controls. Thus, impaired maturation of functional communication within hippocampal-prefrontal networks switching from hypo- to hyper-coupling may represent a mechanism underlying the pathophysiology of cognitive deficits in neuropsychiatric disorders., (© The Author 2016. Published by Oxford University Press.)

The coactivation of prefrontal and hippocampal networks in oscillatory rhythms is critical for precise information flow in mnemonic and executive tasks, yet the mechanisms governing its development are still unknown. Here, we demonstrate that already in neonatal rats, patterns of discontinuous oscillatory activity precisely entrain the firing of prefrontal neurons and have distinct spatial and temporal organization over cingulate and prelimbic cortices. Moreover, we show that hippocampal theta bursts drive the generation of neonatal prefrontal oscillations by phase-locking the neuronal firing via axonal pathways. Consequently, functional impairment of the hippocampus reduces the prefrontal activity. With ongoing maturation continuous theta-gamma oscillations emerge and mutually entrain the prejuvenile prefrontal-hippocampal networks. Thus, theta-modulated communication within developing prefrontal-hippocampal networks may be relevant for circuitry refinement and maturation of functional units underlying information storage at adulthood., (Copyright © 2011 Elsevier Inc. All rights reserved.)