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Inflammatory responses in small vessels play an important role in the development of cardiovascular diseases, including hypertension, stroke, and small vessel disease. This involves various complex molecular processes including oxidative stress, inflammasome activation, immune-mediated responses, and protein misfolding, which together contribute to microvascular damage. In addition, epigenetic factors, including DNA methylation, histone modifications, and microRNAs influence vascular inflammation and injury. These phenomena may be acquired during the aging process or due to environmental factors. Activation of proinflammatory signaling pathways and molecular events induce low-grade and chronic inflammation with consequent cardiovascular damage. Identifying mechanism-specific targets might provide opportunities in the development of novel therapeutic approaches. Monoclonal antibodies targeting inflammatory cytokines and epigenetic drugs, show promise in reducing microvascular inflammation and associated cardiovascular diseases. In this article, we provide a comprehensive discussion of the complex mechanisms underlying microvascular inflammation and offer insights into innovative therapeutic strategies that may ameliorate vascular injury in cardiovascular disease., Competing Interests: Disclosures None.

Introduction: The phenomenon known as periodic limb movements in sleep (PLMS) has been linked to a change in autonomic nervous system (ANS) activity and its effect on circulatory regulation. Autonomic dysfunction or dysregulation in patients with PLMS has been described in some domains; however, any relationship between heart rate variability (HRV) and PLMS has not been clearly established. HRV analysis is a recognised, non-invasive research method that describes the influence of the ANS on heart rate (HR). The aim of our study was to further investigate the dysregulation of autonomic HR control in patients with PLMS., Material and Methods: We undertook a retrospective analysis of the polysomnographic (PSG), demographic and medical data of five patients with a total number of 1,348 PLMS. We analysed HR, HRV HF, systolic blood pressure (SBP), and diastolic blood pressure (DBP) for 10 heartbeats before the series of PLMS and 10 consecutive heartbeats as beat-to-beat measurements. The presented method of using successive, short, 10 RR interval segments refers to the time-frequency measurement, which is very clear and useful for presenting changes in the calculated parameters over time and thereby illustrating their dynamics. This method allowed us to assess dynamic changes in HRV HF during successive PLMS series. Statistical analysis was performed using IBM SPSS Statistics (v. 28.0.0.0). The Kruskal-Wallis test was performed to find statistically significant changes from baseline., Results: No statistically significant changes in HR, SBP, or DBP were found in our group, although an increase in the value of the HRV HF was noted, suggesting an increase in intracardiac parasympathetic activity during the subsequent series of PLMS., Conclusions: Our study indicates an increase in parasympathetic activity during the appearance of successive PLMS, which, with the simultaneous lack of changes in HR, may suggest an increase in sympathetic activity, and therefore the appearance of so-called 'autonomic co-activation' resulting in the possibility of life-threatening cardiac events., Clinical Implications: Our findings add to the literature information regarding HRV in PLMS, and highlight the need for further studies to elucidate the effects of these conditions on the ANS, and on cardiovascular health.

Microcirculation is pervasive and orchestrates a profound regulatory cross-talk with the surrounding tissue and organs. Similarly, it is one of the earliest biological systems targeted by environmental stressors and consequently involved in the development and progression of ageing and age-related disease. Microvascular dysfunction, if not targeted, leads to a steady derangement of the phenotype, which cumulates comorbidities and eventually results in a nonrescuable, very high-cardiovascular risk. Along the broad spectrum of pathologies, both shared and distinct molecular pathways and pathophysiological alteration are involved in the disruption of microvascular homeostasis, all pointing to microvascular inflammation as the putative primary culprit. This position paper explores the presence and the detrimental contribution of microvascular inflammation across the whole spectrum of chronic age-related diseases, which characterise the 21st-century healthcare landscape. The manuscript aims to strongly affirm the centrality of microvascular inflammation by recapitulating the current evidence and providing a clear synoptic view of the whole cardiometabolic derangement. Indeed, there is an urgent need for further mechanistic exploration to identify clear, very early or disease-specific molecular targets to provide an effective therapeutic strategy against the otherwise unstoppable rising prevalence of age-related diseases., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

We first want to thank the authors of the excellent review for their contributions to summarizing the confounders associated with critical flicker fusion frequency (CFFF) [...].

The regular cardiac response to immersion of the face in cold water is reduction in heart rate (HR). The highly individualized and unpredictable course of the cardiodepressive response prompted us to investigate the relationship between the cardiac response to face immersion and the resting HR. The research was conducted with 65 healthy volunteers (37 women and 28 men) with an average age of 21.13 years (20-27 years) and a BMI of 21.49 kg/m 2 (16.60-28.98). The face-immersion test consisted of stopping breathing after maximum inhaling and voluntarily immersing the face in cold water (8-10 °C) for as long as possible. Measurements included determination of minimum, average, and maximum HR at rest and minimum and maximum HR during the cold-water face-immersion test. The results indicate a strong relationship between the cardiodepressive reaction of the immersion of the face and the minimum HR before the test, as well as a relationship between the maximum HR during the test and the maximum HR at rest. The results also indicate a strong influence of neurogenic HR regulation on the described relationships. The parameters of the basal HR can, therefore, be used as prognostic indicators of the course of the cardiac response of the immersion test.

New imaging sequences and biophysical models allow adopting magnetic resonance imaging (MRI) for in vivo myelin mapping in humans. Understanding myelination and remyelination processes in the brain is fundamental from the perspective of proper design of physical exercise and rehabilitation schemes that aim to slow down demyelination in the aging population and to induce remyelination in patients with neurodegenerative diseases. Therefore, in this review we strive to provide a state-of-the art summary of the existing MRI studies in humans focused on the effects of physical activity on myelination/remyelination. We present and discuss four cross-sectional and four longitudinal studies and one case report. Physical activity and an active lifestyle have a beneficial effect on the myelin content in humans. Myelin expansion can be induced in humans throughout the entire lifespan by intensive aerobic exercise. Additional research is needed to determine (1) what exercise intensity (and cognitive novelty, which is embedded in the exercise scheme) is the most beneficial for patients with neurodegenerative diseases, (2) the relationship between cardiorespiratory fitness and myelination, and (3) how exercise-induced myelination affect cognitive abilities., 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 © 2023 Kujawa, Marcinkowska, Grzywińska, Waśkow, Romanowski, Szurowska, Winklewski and Szarmach.)

Scuba diving as a recreational activity is becoming increasingly popular. However, the safety of this activity, especially in the out-of-comfort zone, has been discussed worldwide. The latest publications bring conclusions regarding negative effects on cognitive functions. We compare the acute and chronic effects of diving on cognitive functioning depending on the type of dive performed, including recreational, technical and saturation diving. However, the results of research show that acute and chronic effects on cognitive functions can be negative. While acute effects are reversible after the ascent, chronic effects include white matter lesions in magnetic resonance imaging scans. We believe that more investigations should be performed to determine the chronic effects that could be observed after a few months of observations in a group of regular, intense divers. In addition, publications referring to technical divers are very limited, which is disquieting, as this particular group of divers seems to be neglected in research concerning the effects of diving on cognitive functions.

Stroke is a life-threatening condition in which accurate diagnoses and timely treatment are critical for successful neurological recovery. The current acute treatment strategies, particularly non-invasive interventions, are limited, thus urging the need for novel therapeutical targets. Arginine vasopressin (AVP) receptor antagonists are emerging as potential targets to treat edema formation and subsequent elevation in intracranial pressure, both significant causes of mortality in acute stroke. Here, we summarize the current knowledge on the mechanisms leading to AVP hyperexcretion in acute stroke and the subsequent secondary neuropathological responses. Furthermore, we discuss the work supporting the predictive value of measuring copeptin, a surrogate marker of AVP in stroke patients, followed by a review of the experimental evidence suggesting AVP receptor antagonists in stroke therapy. As we highlight throughout the narrative, critical gaps in the literature exist and indicate the need for further research to understand better AVP mechanisms in stroke. Likewise, there are advantages and limitations in using copeptin as a prognostic tool, and the translation of findings from experimental animal models to clinical settings has its challenges. Still, monitoring AVP levels and using AVP receptor antagonists as an add-on therapeutic intervention are potential promises in clinical applications to alleviate stroke neurological consequences.

A characteristic feature of the cardiac response to diving is the uncertainty in predicting individual course. The aim of the study was to determine whether resting regulatory heart rate determinants assessed before diving may be predictors of cardiac response in a simulated diving test. The research was conducted with 65 healthy volunteers (37 women and 28 men) with an average age of 21.13 years (20-27 years) and a BMI of 21.49 kg/m 2 (16.60-28.98). The simulated diving test consisted of stopping breathing after maximum inhaling and voluntarily immersing the face in water (8-10 °C) for as long as possible. The measurements included heart rate variability (HRV) analysis before diving and determination of the course of the cardiac response to diving-minimum and maximum heart rate (HR). The results indicate that minimum HR during diving (MIN_div) is dependent on the short-term HRV measures, which proves the strong influence of the parasympathetic system on the MIN_div. The lack of dependence of MIN_div on short-term HRV in women may be associated with differences in neurogenic HR regulation in women and men. In conclusion, cardiac response to simulated diving is strictly dependent on the autonomic regulation of the heart rhythm under resting conditions. The course of the cardiac response to diving and its relationship with resting HRV appears to be gender dependent.

The aim of this review is to summarise current knowledge about flickering light and the underlying processes that occur during its processing in the brain. Despite the growing interest in the topic of flickering light, its clinical applications are still not well understood. Studies using EEG indicate an appearing synchronisation of brain wave frequencies with the frequency of flickering light, and hopefully, it could be used in memory therapy, among other applications. Some researchers have focused on using the flicker test as an indicator of arousal, which may be useful in clinical studies if the background for such a relationship is described. Since flicker testing has a risk of inducing epileptic seizures, however, every effort must be made to avoid high-risk combinations, which include, for example, red-blue light flashing at 15 Hz. Future research should focus on the usage of neuroimaging methods to describe the specific neuropsychological and neurophysiological processes occurring in the brain during the processing of flickering light so that its clinical utility can be preliminarily determined and randomised clinical trials can be initiated to test existing reports.

The arginine vasopressin (AVP), a neurohypophysial hormone, is synthesized within specific sites of the central nervous system and axonally transported to multiple areas, acting as a neurotransmitter/ neuromodulator. In this context, AVP acts primarily through vasopressin receptors A and B and is involved in regulating complex social and cognition behaviors and basic autonomic function. Many earlier studies have shown that AVP as a neuromodulator affects synaptic plasticity. This review updates our current understanding of the underlying molecular mechanisms by which AVP affects synaptic plasticity. Moreover, we discuss AVP modulatory effects on event-related potentials and blood oxygen level-dependent responses in specific brain structures, and AVP effects on the network level oscillatory activity. We aimed at providing an overview of the AVP effects on the brain from the synaptic to the network level., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Thank you very much for your interest and comments [...].

Hyperbaric oxygen therapy (HBOT) is a modality of treatment in which patients inhale 100% oxygen inside a hyperbaric chamber pressurised to greater than 1 atmosphere. The aim of this review is to discuss neuropsychological findings in various neurological disorders treated with HBOT and to open new perspectives for therapeutic improvement. A literature search was conducted in the MEDLINE (via PubMed) database from the inception up 10 May 2020. Eligibility criteria included original articles published in English. Case studies were excluded. Full-text articles were obtained from the selected studies and were reviewed on the following inclusion criteria (1) performed cognitive processes assessment (2) performed HBOT with described protocol. Two neuropsychologists independently reviewed titles, abstracts, full texts and extracted data. The initial search retrieved 1024 articles, and a total of 42 studies were finally included after applying inclusion and exclusion criteria. The search yielded controversial results with regard to the efficiency of HBOT in various neurological conditions with cognitive disturbance outcome. To the best of our knowledge this is the first state-of-the art, systematic review in the field. More objective and precise neuropsychological assessment methods are needed to exact evaluation of the efficacy of HBOT for neuropsychological deficits. Future studies should widen the assessment of HBOT effects on different cognitive domains because most of the existing studies have focussed on a single process. Finally, there is a need for further longitudinal studies., (© 2021. The Author(s).)

Aim of the Study: The aim of this study was to assess the diagnostic value of diffusion tensor imaging (DTI) in patients with symptoms of cervical myelopathy. Detailed goals included determining the diagnostic effectiveness of quantitative parameters, i.e. fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in the diagnosis of cervical myelopathy, and the correlation between these parameters and clinical symptoms., Clinical Rationale for the Study: The demonstration of an ischaemic focus in the spinal cord by standard magnetic resonance imaging (MRI) methods is associated with already accomplished spinal cord damage, and of course limited treatment options. Therefore, finding a new examination protocol that allows early diagnosis of myelopathic focus, before the onset of full neurological symptoms, has become a priority in the diagnosis and treatment of spine diseases. Such an examination increases the chances of correctly qualifying the patient for conservative vs. surgical treatment., Material and Methods: Between 2013 and 2017, 128 adults with clinical signs of cervical myelopathy were examined, and were divided into four symptomatic subgroups. A control group consisted of 37 healthy volunteers. DTI values were measured at the level of C2/C3, and at the most severe stenosis of the spine., Results: In patients with cervical spondylotic myelopathy (CSM), the ADC values were significantly higher (p < 0.001), and FA values were significantly lower (p < 0.001), than in healthy volunteers at the stenotic level. There were significant differences in DTI parameters between the clinical subgroups (p < 0.001)., Conclusions and Clinical Implications: Changes in DTI parameters indicate a microstructural disorder of the core which is not visible in a structural MRI. FA and ADC values measured at the level of the most severe stenosis of the spinal canal allow the differentiation of patients with myelopathy of varying degrees of clinical severity. Extending standard MRI to include assessment of FA and ADC may be helpful in deciding treatment modalities (conservative vs. surgical) for patients with visible canal stenosis without full neurological symptoms. This may be useful in selecting patients for urgent rehabilitative treatment. This study is a starting point for further research, i.e. an evaluation of the extent of FA and ADC lesion withdrawal after surgical treatment.

Introduction: We hypothesized that, based on magnetic resonance enterography (MRE) and the apparent diffusion coefficient (ADC), measured in the affected parts of the intestine, it is possible to effectively differentiate active and chronic phases of Crohn's disease., Aim: To create a multidimensional diagnostic model for differentiating between the phases of Crohn's disease., Material and Methods: This study included 125 patients - 55 women (aged 19 to 66 years) and 70 men (aged 12 to 67 years) - who underwent MRE and ADC measurement for the first time., Results: The group of potential explanatory variables comprised 11 variables, including the thickness and length of the occupied section, number of lymph nodes, layered bowel wall enhancement, total transitions on fat tissue, and features of restricted diffusion. The final discrimination model was based on 2 variables: ADC (A) and layered bowel wall enhancement (W). Active Crohn's disease was defined as -6.339 + 4.747 × W + 0.008 × A, while chronic Crohn's disease was defined as -11.365 + 2.812 × W + 0.012 × A. Definitive diagnosis was based on histological examination of material collected during ileocolonoscopy in 96 patients, surgery with subsequent histopathological examination in 17 patients, and capsule endoscopy in 12 patients., Conclusions: The predictive model described here could identify the active form of Crohn's disease with a probability of 93.06% and the chronic form with a probability of 75.57%. The use of classic MRE layered bowel wall enhancement and a DWI-based ADC metric eliminates the main shortcomings of both approaches., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

Objectives: To evaluate the effect of L-carnitine (LC) in combination with leucine supplementation on muscle strength and muscle hypertrophy in aged women participating in a resistance exercise training (RET) program., Design/setting/participants: Thirty-seven out of sixty (38.3% dropout) healthy women aged 60-75 years (mean 67.6 ± 0.7 years) completed the intervention in one of three groups. One of the supplemented groups received 1 g of L-carnitine-L-tartrate in combination with 3 g of L-leucine per day (LC+L group; n = 12), and the second supplemented group received 4 g of L-leucine per day (L group; n = 13). The control group (CON group; n = 12) received no supplementation., Intervention: All three groups completed the same RET protocol involving exercise sessions twice per week for 24 weeks., Measurements: Before and after the experiment, participants performed isometric and isokinetic muscle strength testing on the Biodex dynamometer. The cross-sectional areas of the major knee extensors and total thigh muscles were assessed using magnetic resonance imaging. Fasting serum levels of insulin-like growth factor-1 (IGF-1), myostatin and decorin, and plasma levels of total carnitine (TC) and trimethylamine-N-oxide (TMAO) levels were measured., Results: The 24-week RET significantly increased muscle strength and muscle volume, but the group and time interactions were not significant for the muscle variables analyzed. Plasma total carnitine increased only in the LC+L group (p = 0.009). LC supplementation also caused a significant increase in plasma TMAO, which was higher after the intervention in the LC+L group than in the L (p &lt; 0.001), and CON (p = 0.005) groups. The intervention did not change plasma TMAO concentration in the L (p = 0.959) and CON (p = 0.866) groups. After the intervention serum decorin level was higher than before in both supplemented groups combined (p = 0.012), still not significantly different to post intervention CON (p = 0.231). No changes in serum IGF-1 and myostatin concentrations and no links between the changes in blood markers and muscle function or muscle volume were observed., Conclusions: LC combined with leucine or leucine alone does not appear to improve the effectiveness of RET.

Background: The aim of the study was to investigate the effect of mild cerebral hypoxia on haemoglobin oxygenation (HbO 2 ), cerebrospinal fluid dynamics and cardiovascular physiology. To achieve this goal, four signals were recorded simultaneously: blood pressure, heart rate / electrocardiogram, HbO 2  from right hemisphere and changes of subarachnoid space (SAS) width from left hemisphere. Signals were registered from 30 healthy, young participants (2 females and 28 males, body mass index = 24.5 ± 2.3 kg/m 2 , age 30.8 ± 13.4 years)., Results: We analysed the recorded signals using wavelet transform and phase coherence. We demonstrated for the first time that in healthy subjects exposed to mild poikilokapnic hypoxia there were increases in very low frequency HbO 2 oscillations (< 0.052 Hz) in prefrontal cortex. Additionally, SAS fluctuation diminished in the whole frequency range which could be explained by brain oedema., Conclusions: Consequently the study provides insight into mechanisms governing brain response to a mild hypoxic challenge. Our study supports the notion that HbO 2 and SAS width monitoring might be beneficial for patients with acute lung disease., (© 2021. The Author(s).)

This review presents the current knowledge of the usage of critical flicker fusion frequency (CFF) in human and animal model studies. CFF has a wide application in different fields, especially as an indicator of cortical arousal and visual processing. In medicine, CFF may be helpful for diagnostic purposes, for example in epilepsy or minimal hepatic encephalopathy. Given the environmental studies and a limited number of other methods, it is applicable in diving and hyperbaric medicine. Current research also shows the relationship between CFF and other electrophysiological methods, such as electroencephalography. The human eye can detect flicker at 50-90 Hz but reports are showing the possibility to distinguish between steady and modulated light up to 500 Hz. Future research with the use of CFF is needed to better understand its utility and application.

Background: The goal of this study was to assess the effect of melatonin on blood redox systems in mice simultaneously exposed to ethanol and low-dose lipopolysaccharide (LPS)., Methods: Oxidative stress parameters were assessed in eight groups: untreated control, melatonin (10 mg kg -1 , 10 days), LPS (injected once intraperitoneally at a dose of 150 μg per mouse), LPS with previous melatonin treatment, acute ethanol-induced stress (AES, 0.75 g kg -1 per day, 10 days), AES with previous melatonin treatment, LPS- and AES-induced toxicity, and melatonin treatment., Results: Both ethanol and LPS induced oxidative stress. The combination of these two factors was even more toxic to the organism. Melatonin stabilized erythrocyte membranes and decreased the high level of free radical oxidation at the initial and final stages. Furthermore, melatonin limited protein damage through maintenance in the functional ability of the blood redox system to counteract pathological conditions., Conclusions: Melatonin limited the negative effects associated with alcohol consumption and low-intensity inflammation.

The precise mechanisms connecting the cardiovascular system and the cerebrospinal fluid (CSF) are not well understood in detail. This paper investigates the couplings between the cardiac and respiratory components, as extracted from blood pressure (BP) signals and oscillations of the subarachnoid space width (SAS), collected during slow ventilation and ventilation against inspiration resistance. The experiment was performed on a group of 20 healthy volunteers (12 females and 8 males; BMI=22.1±3.2 kg/m2; age 25.3±7.9 years). We analysed the recorded signals with a wavelet transform. For the first time, a method based on dynamical Bayesian inference was used to detect the effective phase connectivity and the underlying coupling functions between the SAS and BP signals. There are several new findings. Slow breathing with or without resistance increases the strength of the coupling between the respiratory and cardiac components of both measured signals. We also observed increases in the strength of the coupling between the respiratory component of the BP and the cardiac component of the SAS and vice versa. Slow breathing synchronises the SAS oscillations, between the brain hemispheres. It also diminishes the similarity of the coupling between all analysed pairs of oscillators, while inspiratory resistance partially reverses this phenomenon. BP-SAS and SAS-BP interactions may reflect changes in the overall biomechanical characteristics of the brain.

Substance use disorders pose a common medical, social and financial problem. Among the pathomechanisms of substance use disorders, the disruption and increased permeability of the blood-brain barrier has been recently revealed. Physical exercise appears to be a relatively inexpensive and feasible way to implement behavioral therapy counteracting the blood-brain barrier impairment. Concomitantly, there are also studies supporting a potential protective role of selected substances of abuse in maintaining the blood-brain barrier integrity. In this review, we aim to provide a summary on the modulatory influence of physical exercise, a non-pharmacological intervention, on the blood-brain barrier alterations caused by substances of abuse. Further studies are needed to understand the precise mechanisms that underlie various effects of physical exercise in substance use disorders., (Copyright © 2020. Published by Elsevier Ltd.)

The aim of the study was to compare simultaneously recorded a NIR-T/BSS and NIRS signals from healthy volunteers. NIR-T/BSS is a device which give an ability to non-invasively detect and monitor changes in the subarachnoid space width (SAS). Experiments were performed on a group of 30 healthy volunteers (28 males and 2 females, age 30.8 ± 13.4 years, BMI = 24.5 ± 2.3 kg/m 2 ). We analysed recorded signals using analysis methods based on wavelet transform (WT) for the wide frequency range from 0.0095 to 2 Hz. Despite the fact that both devices use a similar radiation source both signals are distinct from each other. We found statistically significant differences for WT amplitude spectra between both signals. Additionally, we showed different relationships of both signals to blood pressure. Collectively, based on the present findings and those of previous studies, we can conclude that the combination of NIR-T/BSS or NIRS signals and time-frequency analysis opens new frontiers in science, and give possibility to understand and diagnosis of various neurodegenerative and ageing related diseases to improve diagnostic procedures and patient prognosis.

A high-fat diet (HFD) induces changes in gut microbiota leading to activation of pro-inflammatory pathways, and obesity, as a consequence of overnutrition, exacerbates inflammation, a known risk factor not only for cancer. However, experimental data showed that the composition of dietary fat has a greater impact on the pathogenesis of cancer than the total fat content in isocaloric diets. Similarly, human studies did not prove that a decrease in total fat intake is an effective strategy to combat cancer. Saturated fat has long been considered as harmful, but the current consensus is that moderate intake of saturated fatty acids (SFAs), including palmitic acid (PA), does not pose a health risk within a balanced diet. In regard to monounsaturated fat, plant sources are recommended. The consumption of plant monounsaturated fatty acids (MUFAs), particularly from olive oil, has been associated with lower cancer risk. Similarly, the replacement of animal MUFAs with plant MUFAs decreased cancer mortality. The impact of polyunsaturated fatty acids (PUFAs) on cancer risk depends on the ratio between ω-6 and ω-3 PUFAs. In vivo data showed stimulatory effects of ω-6 PUFAs on tumour growth while ω-3 PUFAs were protective, but the results of human studies were not as promising as indicated in preclinical reports. As for trans FAs (TFAs), experimental data mostly showed opposite effects of industrially produced and natural TFAs, with the latter being protective against cancer progression, but human data are mixed, and no clear conclusion can be made. Further studies are warranted to establish the role of FAs in the control of cell growth in order to find an effective strategy for cancer prevention/treatment.

Aim: The intensive care unit (ICU) environment contributes to the development of sleep disturbances. Sleep disturbances, sleep fragmentation, and multiple awakening episodes lead to the circadian rhythm disorder, which increases the risk of delirium. Melatonin and melatonin receptor agonist is widely used agent in the therapy of sleep disturbances. However, there is also some for its efficacy in ICU delirium. Enteral melatonin and ramelteon supplementation eliminates (partially) the delirium inducing factors., Methods: PubMed/MEDLINE, OVID, Embase, Cochrane Library, and Web of Science databases were searched using adequate key words. We reviewed the literature on the role of melatonin and ramelteon in the prevention of sleep disturbances and delirium in intensive care units and analysed the methods of melatonin therapy in an ICU setting. Review followed the PRISMA statement. A review written protocol was not drafted., Results: Originally 380 studies were searched in five scientific databases. After rejecting the duplicate results, 125 results were obtained. Finally, 10 scientific studies were included in the review. In selected articles, the leading topics analysed were the role of melatonin and ramelteon in the prevention of delirium and sleep disorders. In addition, the noted effect of therapy with these agents on reducing the ventilation time of mechanical time and the demand for psychoactive substances in the ICU environment., Conclusion: Reduction of either the incidence or the severity of delirium course is possible by eliminating its risk factors. Risk factors are directly related to sleep disorders. To reduce the problem, therefore, a holistic approach to the source is necessary. The efficacy of melatonin therapy in an ICU setting requires confirmation in studies including a greater number of participants as the impact of melatonin on these factors is yet to be fully elucidated. However, the prognosis is predictive because this concept provides patients with a minimally invasive and natural form of therapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

l-carnitine supplementation has been used for cardiovascular health protection for a long time. Recently, trimethylamine-N-oxide (TMAO), which is an end product of l-carnitine metabolism via the activity of microbiota, has been identified as a cardiovascular disease (CVD) biomarker. The aim of this study was to assess the effect of 6 months of l-carnitine supplementation in a group of aged women engaged in a regular physical training. Platelet mitochondrial DNA methylation, an emerging and innovative biomarker, lipid profile and TMAO levels have been measured. TMAO increased after l-carnitine supplementation (before 344.3 ± 129.8 ng/mL vs. after 2216.8 ± 1869.0 ng/mL; n = 9; paired t-test, p = 0.02). No significant effects on TMAO were exerted by training alone ( n = 9) or by l-leucine supplementation ( n = 12). TMAO levels after 6 months of l-carnitine supplementation were associated with higher low-density lipoprotein-cholesterol (LDL-c) (Spearman Rho = 0.518, p = 0.003) and total cholesterol (TC) (Spearman Rho = 0.407, p = 0.026) levels. l-carnitine supplementation increased D-loop methylation in platelets (+6.63%; paired t-test, p = 0.005). D-loop methylation was not directly correlated to the TMAO augmentation observed in the supplemented group, but its increase inversely correlated with TC (Pearson coefficient = -0.529, p = 0.029) and LDL-c (Pearson coefficient = -0.439, p = 0.048). This evidence supports the hypothesis that the correlation between l-carnitine, TMAO and atherosclerosis might be more complex than already postulated, and the alteration of mitochondrial DNA (mtDNA) methylation in platelets could be involved in the pathogenesis of this multifactorial disease.

Negative intrathoracic pressure (nITP) is generated by the respiratory muscles during inspiration to overcome inspiratory resistance, thus enabling lung ventilation. Recently developed noninvasive techniques have made it possible to assess the effects of nITP in real time in several physiological aspects such as systemic blood pressure (BP), intracranial pressure (ICP), and cerebral blood flow (CBF). It has been shown that nITP from 0 to -20 cmH 2 O elevates BP and diminishes ICP, which facilitates brain perfusion. The effects of nITP from -20 to -40 cmH 2 O on BP, ICP, and CBF remain largely unrecognized, yet even nITP at -40 cmH 2 O may facilitate CBF by diminishing ICP. Importantly, nITP from -20 to -40 cmH 2 O has been documented in adults in commonly encountered obstructive sleep apnea, which justifies research in this area. Recent revelations about interactions between ICP and BP have opened up new fields of research in physiological regulation and the pathophysiology of common diseases, such as hypertension, brain injury, and respiratory disorders. A better understanding of these interactions may translate directly into new therapies in various fields of clinical medicine.

High-altitude intolerance and consequently high-altitude sickness, is difficult to predict. Liver is an essential organ in glucose and lipid metabolism, and may play key role in the adaptation to high altitude. In response to extreme high altitude, mitochondrial respiration exhibits changes in substrate metabolism, mitochondrial electron transport chain activity, and respiratory coupling. We determined the cobalt chloride (CoCl 2 ) effects on liver mitochondrial plasticity and oxygen uptake in rats with low resistance (LR) and high resistance (HR) to extreme hypobaric hypoxia. The polarographic method proposed by Chance and Williams was used as a simple and effective tool to trace mitochondrial functionality and oxygen consumption. HR rats had more efficient processes of NADH- and FAD-generated mitochondrial oxidation. CoCl 2 promoted more efficient NADH-generated and diminished less efficient FAD-generated mitochondrial respiratory reactions in HR rats. CoCl 2 diminished both aerobic and anaerobic processes in LR rats. Glutamate and pyruvate substrates of NADH-generated mitochondrial pathways were highly affected by CoCl 2 . Red blood cells acted as cobalt depots in HR and LR rats. We have unveiled several mechanisms leading to differentiated mitochondrial respiratory responses to hypobaric hypoxia in LR and HR rats. Our study strongly supports the existence of adaptive liver mitochondrial plasticity to extreme hypoxia.

The aim of the study was to assess cardiac and respiratory blood pressure (BP) and subarachnoid space (SAS) width oscillations during the resting state for slow and fast breathing and breathing against inspiratory resistance. Experiments were performed on a group of 20 healthy volunteers (8 males and 12 females; age 25.3 ± 7.9 years; BMI = 22.1 ± 3.2 kg/m 2 ). BP and heart rate (HR) were measured using continuous finger-pulse photoplethysmography. SAS signals were recorded using an SAS monitor. Oxyhaemoglobin saturation (SaO 2 ) and end-tidal CO 2 (EtCO 2 ) were measured using a medical monitoring system. Procedure 1 consisted of breathing spontaneously and at controlled rates of 6 breaths/minute and 6 breaths/minute with inspiratory resistance for 10 minutes. Procedure 2 consisted of breathing spontaneously and at controlled rates of 6, 12 and 18 breaths/minute for 5 minutes. Wavelet analysis with the Morlet mother wavelet was applied for delineation of BP and SAS signals cardiac and respiratory components. Slow breathing diminishes amplitude of cardiac BP and SAS oscillations. The overall increase in BP and SAS oscillations during slow breathing is driven by the respiratory component. Drop in cardiac component of BP amplitude evoked by slow-breathing may be perceived as a cardiovascular protective mechanism to avoid target organ damage. Further studies are warranted to assess long-term effects of slow breathing.

Objectives: We tested the hypothesis that computed tomography (CT) perfusion markers of cerebral microcirculation would improve 36 months after internal carotid artery stenting for symptomatic carotid stenosis while results obtained 6-8 weeks after the stenting procedure would yield a predictive value., Methods: We recruited consecutive eligible patients with >70% symptomatic carotid stenosis with a complete circle of Willis and normal vertebral arteries to the observational cohort study. We detected changes in the cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and permeability surface area-product (PS) before and after carotid stenting. We have also compared the absolute differences in the ipsilateral and contralateral CT perfusion markers before and after stenting. The search for regression models of "36 months after stenting" results was based on a stepwise analysis with bidirectional elimination method., Results: A total of 34 patients completed the 36 months follow-up (15 females, mean age of 69.68±S.D. 7.61 years). At 36 months after stenting, the absolute values for CT perfusion markers had improved: CBF (ipsilateral: +7.76%, contralateral: +0.95%); CBV (ipsilateral: +5.13%, contralateral: +3.00%); MTT (ipsilateral: -12.90%; contralateral: -5.63%); TTP (ipsilateral: -2.10%, contralateral: -4.73%) and PS (ipsilateral: -35.21%, contralateral: -35.45%). MTT assessed 6-8 weeks after stenting predicted the MTT value 36 months after stenting (ipsilateral: R2=0.867, contralateral R2=0.688)., Conclusions: We have demonstrated improvements in CT perfusion markers of cerebral microcirculation health that persist for at least 3 years after carotid artery stenting in symptomatic patients. MTT assessed 6-8 weeks after stenting yields a predictive value.

In this narrative review, a theoretical framework on the crosstalk between physical exercise and blood-brain barrier (BBB) permeability is presented. We discuss the influence of physical activity on the factors affecting BBB permeability such as systemic inflammation, the brain renin-angiotensin and noradrenergic systems, central autonomic function and the kynurenine pathway. The positive role of exercise in multiple sclerosis and Alzheimer's disease is described. Finally, the potential role of conditioning as well as the effect of exercise on BBB tight junctions is outlined. There is a body of evidence that regular physical exercise diminishes BBB permeability as it reinforces antioxidative capacity, reduces oxidative stress and has anti-inflammatory effects. It improves endothelial function and might increase the density of brain capillaries. Thus, physical training can be emphasised as a component of prevention programs developed for patients to minimise the risk of the onset of neuroinflammatory diseases as well as an augmentation of existing treatment. Unfortunately, despite a sound theoretical background, it remains unclear as to whether exercise training is effective in modulating BBB permeability in several specific diseases. Further research is needed as the impact of exercise is yet to be fully elucidated.

Percutaneous vertebroplasty is a treatment option in vertebral compression fractures (VCF). The aim of the study was to propose the mathematical calculation of the "optimum volume" of acrylic cement filling of the vertebral body, depending on the severity of a fracture. Two hundred computed tomography (CT) scans of vertebral columns in healthy adult Caucasians were analyzed. Vertebral body width (VBW), vertebral body depth (VBD), vertebral body height (VBH), and vertebral body volume (VBV) were measured. The "optimum volume" of cement injections in mild (25% collapse) and moderate (40% collapse) VCF were calculated. We found that moving caudally from Th 11 to L 2 , the mean values of the examined parameters increased: VBH from 22.6 to 26.0 mm, VBW from 34.0 to 39.5 mm, VBD from 28.1 to 30.9 mm, and VBV from 17.1 to 24.8 cm 3 . The calculated hypothetical "optimum volume" of cement injection increased from 7.4 to 10.0 cm 3 in mild VCF and from 5.9 to 7.8 cm 3 in moderate VCF, with some variability depending on the vertebral level and gender. These values are akin to those present in other past studies. We conclude that morphometric measurements, based on CT images, are a reliable source of practical anatomical savvy, which may be of help in spine surgery.

The aim of the study was to assess blood pressure-subarachnoid space (BP-SAS) width coupling properties using time-frequency bispectral analysis based on wavelet transforms during handgrip and cold tests. The experiments were performed on a group of 16 healthy subjects (F/M; 7/9) of the mean age 27.2 ± 6.8 years and body mass index of 23.8 ± 4.1 kg/m 2 . The sequence of challenges was first handgrip and then cold test. The handgrip challenge consisted of a 2-min strain, indicated by oral communication from the investigator, at 30% of maximum strength. The cold test consisted of 2 min of hand immersion to approximately wrist level in cold water of 4 °C, verified by a digital thermometer. Each test was preceded by 10 min at baseline and was followed by 10-min recovery recordings. BP and SAS were recorded simultaneously. Three 2-min stages of the procedure, baseline, test, and recovery, were analyzed. We found that BP-SAS coupling was present only at cardiac frequency, while at respiratory frequency both oscillators were uncoupled. Handgrip and cold test failed to affect BP-SAS cardiac-respiratory coupling. We showed similar handgrip and cold test cardiac bispectral coupling for individual subjects. Further studies are required to establish whether the observed intersubject variability concerning the BP-SAS coupling at cardiac frequency has any potential clinical predictive value.

Transpedicular stabilization is a frequently used spinal surgery for fractures, degenerative changes, or neoplastic processes. Improper screw fixation may cause substantial vascular or neurological complications. This study seeks to define detailed morphometric measurements of the pedicle (height, width, and surface area) in the aspects of screw length and girth selection and the trajectory of its implantation, i.e., sagittal and transverse angle of placement. The study was based on CT examinations of 100 Caucasian patients (51 women and 49 men) aged 27-75 with no anatomical, degenerative, or post-traumatic spine changes. The results were stratified by gender and body side, and they were counter compared with the available literature database. Pedicle height decreased from L1 to L4, ranging from 15.9 to 13.3 mm. Pedicle width increased from L1 to L5, extending from 6.1 to 13.2 mm. Pedicle surface area increased from L1 to L5, ranging from 63 to 140 mm 2 . Distance from the point of entry into the pedicle to the anterior surface of the vertebral body, defining the maximum length of a transpedicular screw, varied from 54.0 to 50.2 mm. Variations concerning body sides were inappreciable. A transverse angle of screw trajectory extended from 20° to 32°, shifting caudally from L1 to L5, with statistical differences in the L3-L5 segments. A sagittal angle varied from 10° to 12°, without such definite relations. We conclude that the L1 and L2 segments display the most distinct morphometric similarities, while the greatest differences, in both genders, are noted for L3, L4, and L5. The findings enable the recommendation of the following screw diameters: 4 mm for L1-L2, 5 mm for L3, 6 mm for L4-L5, and the length of 50 mm. We believe the study has extended clinical knowledge on lumbar spine morphometry, essential in the training physicians engaged in transpedicular stabilization.

In this study we hypothesized that the alleviation of neurological symptoms long after internal carotid artery (ICA) stenting may be related to sustained improvement of cerebral perfusion. Thirty-four subjects (F/M; 15/19) with >70% stenosis of a single internal carotid artery and neurological symptoms, who underwent a carotid artery stenting procedure, were studied. Brain computed tomography perfusion (CTP) imaging was performed before and 3 years after ICA stenting. The following relative variables were compared: cerebral blood flow (rCBF), cerebral blood volume (rCBV), mean transit time (rMTT), time to peak (rTTP), and permeability surface area product (rPS). A survey also was conducted to compare the patients' clinical symptoms. Overall, we found that a trend toward rMTT decline was the only persisting change after ICA stenting. We then stratified the patients into the subgroups of <2%, 2-5%, and > 5% rMTT decline and found that those with a rMTT decline >2% reported a prominent reduction in subjective clinical symptoms such as headache, dizziness, tinnitus, blurred vision, transient blindness, a sense of gravity of the head, and pain in the eyeballs. We conclude that a shortened mean rMTT, likely reflecting improved cerebral microcirculation, underlies the improvement of neurological symptoms in patients with ICA stenosis.

Lipopolysaccharide (LPS) administration in an in vivo experimental mice model causes oxidative damage in the liver, muscle, and kidney. We aimed to determine specific mechanisms underlying melatonin's antioxidant protective role. Assays were carried out in quadruplicate in the control, melatonin (10 mg/kg, 10 days), acute LPS administration (once 150 μg), and LPS + melatonin groups. LPS stimulated lipid peroxidation processes (dienes and malondialdehyde) and antioxidant enzyme concentrations (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) were assessed in all investigated tissues. Protein oxidation processes (measured as aldehyde and kenotic carbonyl protein derivatives) were enhanced by LPS in the kidney and liver but not in muscle. Melatonin reversed LPS-induced changes, with the exception of muscle protein oxidation. LPS-induced oxidative stress resulted in augmented early-stage diene conjugated and end-stage malondialdehyde lipid peroxidation processes and affected antioxidant activity in liver, kidney, and muscle tissues. LPS activated protein oxidation processes in the kidney and liver. Melatonin ameliorated oxidative damage in the liver, kidney, and partially in the muscle. Melatonin modulates oxidative stress-induced states. Potential synergism between melatonin and systemic inflammation in terms of oxidative modification of muscle proteins needs to be clarified in further studies.

The aim of the study was to elucidate the effects of melatonin administration (10 mg/kg, 10 days) in a model of inflammation and oxidative stress induced by low-dose bacterial lipopolysaccharide (LPS, once 150 μg). Assays were carried out in quadruplicate in the control, melatonin (10 mg/kg, 10 days), acute LPS administration (once 150 μg) and LPS plus melatonin groups. Blood morphological examination was performed. Erythrocyte resistance to haemolytic agents, ceruloplasmin, diene conjugates, malondialdehyde, oxidatively modified protein concentrations, total antioxidant capacity and antioxidant enzyme activity in plasma were measured. LPS administration in mice resulted in white blood cell (WBC) depletion, erythrocyte cell membrane impairment and oxidative stress in plasma characterised by lipid and protein oxidative processes, decreased antioxidative defence and augmented ceruloplasmin concentrations. Melatonin treatment provided to LPS-exposed animals restored WBC counts, ameliorated erythrocyte membrane damage and decreased overall oxidative stress in plasma. Melatonin provides multilevel protection in animals exposed to low-dose LPS.

Oxidative stress is involved in the development of various cancers. In the present study, the effect of long-term administration of peroral antidiabetic metformin and pineal hormone melatonin on liver antioxidant and aerobic status in female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N-nitrosourea was evaluated. Both substances were administered in a preventive and curative manner (12 days before and 16 weeks after the carcinogen application). Carcinogen administration induced oxidative stress: the level of thiobarbituric acid reactive substances (TBARS) considered as a marker of reactive oxygen species (ROS) generation in liver increased as well as the level of oxidatively modified protein content (OMP; aldehyde and ketone derivates). Metformin administration restored succinate dehydrogenase and lactate dehydrogenase activity and associated ROS production and OMP content to the level of intact rats, with predominant activation of superoxide dismutase (SOD) and glutathione reductase (GR). Melatonin alone and in combination with metformin also decreased TBARS content. OMP content decreased in all groups receiving chemoprevention. The rise in total antioxidant capacity after melatonin and particularly metformin and melatonin combination might result from the initiation of anaerobic metabolism and increasing SOD, GR, and glutathione peroxidase activity. Long-term administration of metformin and melatonin exerts antioxidant properties in liver, especially in combination.

The available studies on cerebrovascular reactivity and cerebral oxygenation in obstructive sleep apnoea (OSA) patients brought conflicting results, yet the overall evidence suggests that resting state cerebral perfusion is diminished in these patients. Interestingly, in a group of healthy professional breath-hold divers who are exercising very long apnoeas - episodes corresponding to the ones observed in patients with OSA - demonstrated that cerebral oxygenation may remain stable at the expense of extreme sympathetic nervous system (SNS) activation. In the present review we address several mechanisms that could potentially explain these discrepancies. We focus in depth on mechanisms of central SNS reinforcement in OSA including dysfunctional baroreflex response, and inflammatory processes within the brain centres controlling the cardiovascular system. Additionally, novel insights into physiology of cerebral blood flow regulation are proposed, including the role of short-term blood pressure changes, heart rate fluctuations and baroreflex alterations. Finally, a potential role of increased blood flow pulsatility in cerebrospinal fluid circulation changes and its influence on SNS drive is highlighted. The presented review provides insights into how sympathetic nervous system reinforcement in OSA promotes maladaptive mechanisms that could alter cerebral perfusion regulation, and result in functional and structural cerebral changes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The use of the diffusion tensor imaging (DTI) is rapidly growing in the neuroimaging field. Nevertheless, rigorously performed quantitative validation of DTI pathologic metrics remains very limited owing to the difficulty in co-registering quantitative histology findings with magnetic resonance imaging. The aim of this review is to summarize the existing state-of-the-art knowledge with respect to axial (λ ║ ) and radial (λ ┴ ) diffusivity as DTI markers of axonal and myelin damage, respectively. First, we provide technical background for DTI and briefly discuss the specific organization of white matter in bundles of axonal fibers running in parallel; this is the natural target for imaging based on diffusion anisotropy. Second, we discuss the four seminal studies that paved the way for considering axial (λ ║ ) and radial (λ ┴ ) diffusivity as potential in vivo surrogate markers of axonal and myelin damage, respectively. Then, we present difficulties in interpreting axial (λ ║ ) and radial (λ ┴ ) diffusivity in clinical conditions associated with inflammation, edema, and white matter fiber crossing. Finally, future directions are highlighted. In summary, DTI can reveal strategic information with respect to white matter tracts, disconnection mechanisms, and related symptoms. Axial (λ ║ ) and radial (λ ┴ ) diffusivity seem to provide quite consistent information in healthy subjects, and in pathological conditions with limited edema and inflammatory changes. DTI remains one of the most promising non-invasive diagnostic tools in medicine.

Abnormal cerebrospinal fluid (CSF) pulsatility has been implicated in patients suffering from various diseases, including multiple sclerosis and hypertension. CSF pulsatility results in subarachnoid space (SAS) width changes, which can be measured with near-infrared transillumination backscattering sounding (NIR-T/BSS). The aim of this study was to combine NIR-T/BSS and wavelet analysis methods to characterise the dynamics of the SAS width within a wide range of frequencies from 0.005 to 2 Hz, with low frequencies studied in detail for the first time. From recordings in the resting state, we also demonstrate the relationships between SAS width in both hemispheres of the brain, and investigate how the SAS width dynamics is related to the blood pressure (BP). These investigations also revealed influences of age and SAS correlation on the dynamics of SAS width and its similarity with the BP. Combination of NIR-T/BSS and time-frequency analysis may open up new frontiers in the understanding and diagnosis of various neurodegenerative and ageing related diseases to improve diagnostic procedures and patient prognosis.

The aim of this study was to assess regional perfusion at baseline and regional cerebrovascular resistance (CVR) to delayed acetazolamide challenge in subjects with chronic carotid artery stenosis. Sixteen patients (ten males) aged 70.94±7.71 with carotid artery stenosis ≥ 90% on the ipsilateral side and ≤ 50% on the contralateral side were enrolled into the study. In all patients, two computed tomography perfusion examinations were carried out; the first was performed before acetazolamide administration and the second 60 minutes after injection. The differences between mean values were examined by paired two-sample t-test and alternative nonparametric Wilcoxon's test. Normality assumption was examined using W Shapiro-Wilk test. The lowest resting-state cerebral blood flow (CBF) was observed in white matter (ipsilateral side: 18.4±6.2; contralateral side: 19.3±6.6) and brainstem (ipsilateral side: 27.8±8.5; contralateral side: 29.1±10.8). Grey matter (cerebral cortex) resting state CBF was below the normal value for subjects of this age: frontal lobe - ipsilateral side: 30.4±7.0, contralateral side: 33.7±7.1; parietal lobe - ipsilateral side: 36.4±11.3, contralateral side: 42.7±9.9; temporal lobe - ipsilateral side: 32.5±8.6, contralateral side: 39.4±10.8; occipital lobe - ipsilateral side: 24.0±6.0, contralateral side: 26.4±6.6). The highest resting state CBF was observed in the insula (ipsilateral side: 49.2±17.4; contralateral side: 55.3±18.4). A relatively high resting state CBF was also recorded in the thalamus (ipsilateral side: 39.7±16.9; contralateral side: 41.7±14.1) and cerebellum (ipsilateral side: 41.4±12.2; contralateral side: 38.1±11.3). The highest CVR was observed in temporal lobe cortex (ipsilateral side: +27.1%; contralateral side: +26.1%) and cerebellum (ipsilateral side: +27.0%; contralateral side: +34.6%). The lowest CVR was recorded in brain stem (ipsilateral side: +20.2%; contralateral side: +22.2%) and white matter (ipsilateral side: +18.1%; contralateral side: +18.3%). All CBF values were provided in milliliters of blood per minute per 100 g of brain tissue (ml/100g/min). Resting state circulation in subjects with carotid artery stenosis is low in all analysed structures with the exception of insula and cerebellum. Acetazolamide challenge yields relatively uniform response in both hemispheres in the investigated population. Grey matter is more reactive to acetazolamide challenge than white matter or brainstem.

In the cerebrospinal fluid (CSF) circulation, two components can be distinguished: bulk flow (circulation) and pulsatile flow (back and forth motion). CSF pulsatile flow is generated by both cardiac and respiratory cycles. Recent years have seen increased interest in cardiac- and respiratory-driven CSF pulsatility as an important component of cerebral homeostasis. CSF pulsatility is affected by cerebral arterial inflow and jugular outflow and potentially linked to white matter abnormalities in various diseases, such as multiple sclerosis or hypertension. In this review, we discuss the physiological mechanisms associated with CSF pulsation and its clinical significance. Finally, we explain the concept of using the oscillations of subarachnoid space width as a surrogate for CSF pulsatility.

The aim of this study was to determine the effects of long-term administration of the oral antidiabetic metformin or the pineal hormone melatonin, and a combination thereof, in preventing oxidative stress in the heart tissue of female Sprague-Dawley rats with mammary tumors induced by N-methyl-N-nitrosourea (NMU) (50 mg/kg) given on the 42nd postnatal day. Metformin and melatonin were administered 12 days before and 16 weeks after the carcinogen. During the experiment, all animals were fed a high fat diet (10% total fat, 2.5% from lard, and 7.5% from palm oil). The findings are that mammary carcinogenesis generated oxidative stress. Reactive oxygen species (ROS) content, estimated from thiobarbituric acid reactive substances (TBARS), oxidatively modified protein content (aldehyde and ketone derivatives), and the activity of the antioxidant enzymes superoxide dismutase, glutathione reductase, and glutathione peroxidase were all augmented. Metformin caused a decrease in oxidative stress in the heart, accompanied by a decrease in diene conjugates, the elimination of ROS (stable total antioxidant status), and the activation of catalase and glutathione reductase. Melatonin caused an increase in total antioxidant status and a substantial reduction in ROS as estimated from aldehyde and ketone derivatives, lipid peroxidation at the initial (diene conjugates) and terminal stages (TBARS), and increased catalase and glutathione peroxidase activities. Metformin and melatonin combined reversed the effects of NMU on oxidative stress. In conclusion, melatonin reduces the level of oxidative stress in the heart tissue, caused by NMU carcinogenesis and a high fat diet, significantly stronger than metformin.

This study seeks to define the role of predictive values of the motor speed, inhibition control, and fluid and crystallized intelligence in estimating the cortical thickness in healthy elderly. Forty-six older healthy subjects (37 women, 9 men) over 60 years of age were included in the study. The participants were examined on 3.0 T MRI scanners. The protocol included standard anatomical sequences, to exclude brain pathology, and a high-resolution T1-weighted sequence used to estimate the cortical thickness. The neuropsychological protocol included fluid intelligence assessment (Raven Progressive Matrices), crystalized intelligence assessment (information or vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R)), and executive functioning (Color Traits Test). The findings unraveled several interdependencies. The higher the intelligence, the thicker was the grey matter in nine regions of both hemispheres, but also some paradoxical reversed associations were found in four areas; all of them were localized along different sections of the cingulate gyrus in both hemispheres. An inverse association was found between crystallized intelligence and the thickness of the pars opecularis of the right hemisphere. The better the executive functioning, the thicker was the grey matter of a given region. The better the motor performance, the thicker was the grey matter of the rostral middle frontal area of the left hemisphere and the lingual gyrus of both hemispheres. In conclusion, the associations unraveled demonstrate that the neural mechanisms underlying healthy aging are complex and heterogenic across different cognitive domains and neuroanatomical regions. No brain aging theory seems to provide a suitable interpretative framework for all the results. A novel, more integrative approach to the brain aging should be considered.

Aims: The aim of the study was to examine the effects of melatonin impact on changes in haematological profile, biomarkers of oxidative stress (dienes conjugates, malondialdehyde (MDA), oxidatively modified protein levels, total antioxidant capacity and antioxidant enzyme activity) in liver, muscle, kidney and erythrocytes, and glycated haemoglobin (HBA1c) in mice during acute ethanol stress., Methods: Assays were carried out in quadruplicate: control, melatonin (10 mg/kg, 10 days), acute ethanol stress (0.75 g/kg/day, 10 days) and acute ethanol stress plus melatonin groups., Results: Acute ethanol stress caused a significant increase in the total number of white blood cells (WBC), especially neutrophils in the blood, and HBA1c levels vs. control mice. The correlation between lipid peroxidation and the glycated haemoglobin level was shown (r = 0.93, P = 0.007). Ethanol reduced the antioxidant capacity by increasing reactive oxygen species (ROS) production and the level of oxidatively modified protein content, diene conjugates and MDA. Melatonin administration in animals during acute ethanol stress reduced antioxidant stress biomarkers, WBC, HBA1c levels and ROS production., Conclusions: Melatonin had protective effects on liver, kidney and muscle tissues by preventing the intensive lipid peroxidation processes in initial (diene conjugation production) and late stages (MDA level), and significantly reduced the level of aldehyde and ketone protein derivatives. Furthermore, melatonin restored elevated WBC count and HBA1c level and diminished ROS production., Short Summary: Ethanol reduces antioxidant capacity and leads to exaggerated reactive oxygen species production and consequent increases in oxidatively modified proteins. Melatonin exerts protective effects by preventing the intensive lipid peroxidation processes. Melatonin significantly reduces the level of aldehyde and ketone protein derivatives, restores glycated haemoglobin level and white blood cell count., (© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

During apnoea, the pial artery is subjected to two opposite physiological processes: vasoconstriction due to elevated blood pressure and vasorelaxation driven by rising pH in the brain parenchyma. We hypothesized that the pial artery response to apnoea may vary, depending on which process dominate. Apnoea experiments were performed in a group of 19 healthy, non-smoking volunteers (9 men and 10 women). The following parameters were obtained for further analysis: blood pressure, the cardiac (from 0.5 to 5.0Hz) and slow (<0.5Hz) components of subarachnoid space width, heart rate, mean cerebral blood flow velocity in the internal carotid artery, pulsatility and resistivity index, internal carotid artery diameter, blood oxygen saturation and end-tidal carbon dioxide. The experiment consisted of three apnoeas, sequentially: 30s, 60s and maximal apnoea. The breath-hold was separated for 5minute rest. The control process is sophisticated, involving internal cross-couplings and cross-dependences. The aim of work was to find a mathematical dependence between data. Unexpectedly, the modelling revealed two different reactions, on the same experimental procedure. As a consequence, there are two subsets of cardiac subarachnoid space width responses to breath-hold in humans. A positive cardiac subarachnoid space width change to apnoea depends on changes in heart rate and cerebral blood flow velocity. A negative cardiac subarachnoid space width change to apnoea is driven by heart rate, mean arterial pressure and pulsatility index changes. The described above two different reactions to experimental breath-hold provides new insights into our understanding of the complex mechanisms governing the adaptation to apnoea in humans. We proposed a mathematical methodology that can be used in further clinical research., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Objective: Respiration is known to affect cerebrospinal fluid (CSF) movement. We hypothesised that increased inspiratory resistance would affect the dynamic relationship between blood pressure (BP) changes and subarachnoid space width (SAS) oscillations., Methods: Experiments were performed in a group of 20 healthy volunteers undergoing controlled intermittent Mueller Manoeuvres (the key characteristic of the procedure is that a studied person is subjected to a controlled, increased inspiratory resistance which results in marked potentiation of the intrathoracic negative pressure). BP and heart rate (HR) were measured using continuous finger-pulse photoplethysmography; oxyhaemoglobin saturation with an ear-clip sensor; end-tidal CO2 with a gas analyser; cerebral blood flow velocity (CBFV), pulsatility and resistive indices with Doppler ultrasound. Changes in SAS were recorded with a new method i.e. near-infrared transillumination/backscattering sounding. Wavelet transform analysis was used to assess the BP and SAS oscillations coupling., Results: Initiating Mueller manoeuvres evoked cardiac SAS component decline (-17.8%, P<0.001), systolic BP, diastolic BP and HR increase (+6.3%, P<0.001; 6.7%, P<0.001 and +2.3%, P<0.05, respectively). By the end of Mueller manoeuvres, cardiac SAS component and HR did not change (+2.3% and 0.0%, respectively; both not statistically significant), but systolic and diastolic BP was elevated (+12.6% and +8.9%, respectively; both P<0.001). With reference to baseline values there was an evident decrease in wavelet coherence between BP and SAS oscillations at cardiac frequency in the first half of the Mueller manoeuvres (-32.3%, P<0.05 for left hemisphere and -46.0%, P<0.01 for right hemisphere) which was followed by subsequent normalization at end of the procedure (+3.1% for left hemisphere and +23.1% for right hemisphere; both not statistically significant)., Conclusions: Increased inspiratory resistance is associated with swings in the cardiac contribution to the dynamic relationship between BP and SAS oscillations. Impaired cardiac performance reported in Mueller manoeuvres may influence the pattern of cerebrospinal fluid pulsatility.

Failure of the blood-brain barrier (BBB) is a critical event in the development and progression of diseases such as acute ischemic stroke, chronic ischemia or small vessels disease that affect the central nervous system. It is not known whether BBB breakdown in subjects with chronic carotid artery stenosis can be restrained with postoperative recovery of cerebral perfusion. The aim of the study was to assess the short-term effect of internal carotid artery stenting on basic perfusion parameters and permeability surface area-product (PS) in such a population. Forty subjects (23 males) with stenosis of >70% within a single internal carotid artery and neurological symptoms who underwent a carotid artery stenting procedure were investigated. Differences in the following computed tomography perfusion (CTP) parameters were compared before and after surgery: global cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP) and PS. PS acquired by CTP is used to measure the permeability of the BBB to contrast material. In all baseline cases, the CBF and CBV values were low, while MTT and TTP were high on both the ipsi- and contralateral sides compared to reference values. PS was approximately twice the normal value. CBF was higher (+6.14%), while MTT was lower (-9.34%) on the contralateral than on the ipsilateral side. All perfusion parameters improved after stenting on both the ipsilateral (CBF +22.66%; CBV +18.98%; MTT -16.09%, TTP -7.62%) and contralateral (CBF +22.27%, CBV +19.72%, MTT -14.65%, TTP -7.46%) sides. PS decreased by almost half: ipsilateral -48.11%, contralateral -45.19%. The decline in BBB permeability was symmetrical on the ipsi- and contralateral sides to the stenosis. Augmented BBB permeability can be controlled by surgical intervention in humans.