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Introduction: The use of robotic systems in the surgical domain has become groundbreaking for patients and surgeons in the last decades. While the annual number of robotic surgical procedures continues to increase rapidly, it is essential to provide the surgeon with innovative training courses along with the standard specialization path. To this end, simulators play a fundamental role. Currently, the high cost of the leading VR simulators limits their accessibility to educational institutions. The challenge lies in balancing highfidelity simulation with cost-effectiveness; however, few cost-effective options exist for robotic surgery training. Methods: This paper proposes the design, development and user-centered usability study of an affordable user interface to control a surgical robot simulator. It consists of a cart equipped with two haptic interfaces, a VR visor and two pedals. The simulations were created using Unity, which offers versatility for expanding the simulator to more complex scenes. An intuitive teleoperation control of the simulated robotic instruments is achieved through a high-level control strategy. Results and Discussion: Its affordability and resemblance to real surgeon consoles make it ideal for implementing robotic surgery training programs in medical schools, enhancing accessibility to a broader audience. This is demonstrated by the results of an usability study involving expert surgeons who use surgical robots regularly, expert surgeons without robotic surgery experience, and a control group. The results of the study, which was based on a traditional Peg-board exercise and Camera Control task, demonstrate the simulator's high usability and intuitive control across diverse user groups, including those with limited experience. This offers evidence that this affordable system is a promising solution for expanding robotic surgery training. [ABSTRACT FROM AUTHOR]

Neurogenesis is the process by which new brain cells are formed. This crucial event emerges during embryonic life and proceeds in adulthood, and it could be influenced by environmental pollution. Non-combustion-derived magnetite represents a portion of the coarse particulate matter (PM) contributing to air and water pollution in urban settings. Studies on humans have reported that magnetite and other iron oxides have significant damaging effects at a central level, where these particles accumulate and promote oxidative stress. Similarly, magnetite nanoparticles can cross the placenta and damage the embryo brain during development, but the impact on neurogenesis is still unknown. Furthermore, an abnormal Fe cation concentration in cells and tissues might promote reactive oxygen species (ROS) generation and has been associated with multiple neurodegenerative conditions. In the present study, we used zebrafish as an in vivo system to analyze the specific effects of magnetite on embryonic neurogenesis. First, we characterized magnetite using mineralogical and spectroscopic analyses. Embryos treated with magnetite at sub-lethal concentrations showed a dose–response increase in ROS in the brain, which was accompanied by a massive decrease in antioxidant genes (sod2, cat, gsr, and nrf2). In addition, a higher number of apoptotic cells was observed in embryos treated with magnetite. Next, interestingly, embryos exposed to magnetite displayed a decrease in neural staminal progenitors (nestin, sox2, and pcna markers) and a neuronal marker (elavl3). Finally, we observed significative increases in apoeb (specific microglia marker) and interleukin-1b (il1b), confirming a status of inflammation in the brain embryos treated with magnetite. Our study represents the very first in vivo evidence concerning the effects of magnetite on brain development. [ABSTRACT FROM AUTHOR]

Nitrogen-based fertilizers represent the most common fertilization tools, particularly used in crop food agriculture, despite the low cost-efficiency and the high negative environmental impact. At present, there is still inadequate information available about the effects of urea on human health; nevertheless, previous studies in animals observed that high urea concentration exposure can damage different tissues, including the brain. In several vertebrates, a crucial factor involved in neuronal cell formation is represented by the gas molecule, nitric oxide (NO), derived from the conversion of arginine to citrulline through the enzymatic activity of nitric oxide synthases (NOS). In zebrafish, three different isoforms of the NOS gene are known: nos1, nos2a, and nos2b. In the present study we show that nos1 represents the unique isoform with a stable high expression in the brain and spinal cord during all the embryonic stages of zebrafish development. Then, by using a specific transgenic zebrafish line, Tg(HuC:GFP), to mark neuronal cells, we observed nos1 to be specifically expressed in neurons. Interestingly, we observed that urea exposure at sub-lethal doses affected cell proliferation and the number of nos1-expressing cells, inducing apoptosis. Consistently, brain NO levels were observed to be reduced in urea-treated animals compared to untreated ones. This finding represents the first evidence that urea exposure affects the expression of a key gene involved in neuronal cell formation during embryonic development. [ABSTRACT FROM AUTHOR]

Neonatal resuscitation is an uncommon, albeit critical task that is more likely to succeed if performed properly and promptly. In this context, simulation is an appropriate way for training and assessing the abilities of all medical staff involved in delivery room care. Recent studies have shown that learning is enhanced if the simulation experience is realistic and engaging. Hence, Virtual Reality can be beneficial for newborn resuscitation training. However, the difficulty of providing realistic haptic interaction limits its use. To overcome this constraint, we have designed RiNeo MR, a simulator for newborn life support training, combining a sensorized manikin to monitor in real time resuscitation skills, with a Virtual Reality application. The system includes a Virtual Reality headset, Leap Motion to track the user's hands, sensorized bag valve mask, and manikin to monitor head and mask positioning, ventilation, and chest compression. RiNeo MR can be used in two modalities: 2D to let the trainee practice resuscitation manoeuvres on the physical manikin, while receiving real time feedback; 3D that allows the user to be immersed in a virtual environment and practice in an hospital-like setting. In the 3D mode, virtual and real manikins are overlapped and communicate in real time. Tests on 16 subjects (11 controls without medical expertise and 5 paediatric residents) demonstrated that the simulator is well tolerated in terms of discomfort. Moreover, the simulator is high rated for user experience and system usability, suggesting that RiNeo MR can be a promising tool to improve newborn life support training. RiNeo MR is a proof of concept of a mixed-reality newborn life support simulator that can be a promising tool to spread newborn resuscitation high-quality training among healthcare providers involved in perinatal medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: Fertility, in males and females, is linked to the correct formation of sexual line cells (spermatozoa and oocytes) through a physiological process called meiosis. In all vertebrates, meiosis is orchestrated by different molecular effectors, and among these, we focused our attention on CLASP2, a protein involved in cytoskeleton function. In several animal models, such as mice, flies, or frogs, this protein is known to participate in spermatozoa maturation. However, in fish, nothing was known about the presence of CLASP2 in sexual organs or whether it could have a role in spermatozoa formation. To investigate this point, we used two excellent vertebrate aquatic models: guppy and zebrafish. Our results open a window to knowledge about male sex cell formation effectors in fish. Considering the great affinity between zebrafish and humans, the study of CLASP2 in fish spermatogenesis could uncover a new target of male fertility in humans. Cytoplasmic linker-associated protein-2 (CLASP2) is a member of the CLIP-associating proteins (CLASPs) family involved in the structure and function of microtubules and Golgi apparatus. Several studies performed using different mammalian and non-mammalian model organisms reported that CLASP2 controls microtubule dynamics and the organization of microtubule networks. In Drosophila and mice, an important role of CLASP2 during the development of germ cell lines has been uncovered. However, no study has clearly defined its role during fish germ cell differentiation. In the present study, we used two excellent aquatic animal models among teleost fish: zebrafish (Danio rerio) and guppy (Poecilia reticulata). Using qPCR, we found that the clasp2 transcript level is significantly high in the testis of both fish. Then, by in situ hybridization, we localized the clasp2 transcript in the spermatozoa of zebrafish and the spermatozeugmata of guppy. Our data suggest a potential role for this gene in the last stage of spermiogenesis in fish. [ABSTRACT FROM AUTHOR]

Introduction: The Stop the Bleed campaign provided civilians with tourniquet application training and increased the demand for tourniquets among the general population, which led to the development of new commercially available devices. However, most widely available tourniquets have not undergone testing by regulatory bodies and their efficacy remains unknown. Study Objective: This study aimed to compare the efficacy and performance of Combat Application Tourniquets (CAT) versus uncertified tourniquets. Methods: This study compared 25 CAT with 50 commercially available "look-alike" tourniquets (LA-TQ) resembling the CAT. The CAT and the LA-TQ were compared for cost, size, and tested during one-hour and six-hour applications on a manikin's leg. The outcomes were force applied, force variation during the application, and tourniquet rupture rate. Results: The LA-TQ were cheaper (US$6.07 versus US$27.19), shorter, and had higher inter-device variability than the CAT (90.1 [SE = 0.5] cm versus 94.5 [SE = 0.1] cm; P <.001). The CAT applied a significantly greater force during the initial application when compared to the LA-TQ (65 [SE = 3] N versus 14 [SE = 1] N; P <.001). While the initial application force was maintained for up to six hours in both groups, the CAT group applied an increased force during one-hour applications (group effect: F [1,73] = 105.65; P <.001) and during six-hour applications (group effect: F [1,12] = 9.79; P =.009). The rupture rate differed between the CAT and the LA-TQ (0% versus 4%). Conclusion: The LA-TQ applied a significantly lower force and had a higher rupture rate compared to the CAT, potentially affecting tourniquet performance in the context of public bleeding control. These findings warrant increased layperson education within the framework of the Stop the Bleed campaign and further investigations on the effectiveness of uncertified devices in real-world applications. [ABSTRACT FROM AUTHOR]

In vertebrates, neurotrophins and their receptors play a fundamental role in the central and peripheral nervous systems. Several studies reported that each neurotrophin/receptor signalling pathway can perform various functions during axon development, neuronal growth, and plasticity. Previous investigations in some fish species have identified neurotrophins and their receptors in the spinal cord under physiological conditions and after injuries, highlighting their potential role during regeneration. In our study, for the first time, we used an excellent animal model, the zebrafish (Danio rerio), to compare the mRNA localization patterns of neurotrophins and receptors in the spinal cord. We quantified the levels of mRNA using qPCR, and identified the transcription pattern of each neurotrophin/receptor pathway via in situ hybridization. Our data show that ngf/trka are the most transcribed members in the adult zebrafish spinal cord. [ABSTRACT FROM AUTHOR]

Unrestrained ketogenesis leads to life-threatening ketoacidosis whose incidence is high in patients with diabetes. While insulin therapy reduces ketogenesis this approach is sub-optimal. Here, we report an insulin-independent pathway able to normalize diabetic ketogenesis. By generating insulin deficient male mice lacking or re-expressing Toll-Like Receptor 4 (TLR4) only in liver or hepatocytes, we demonstrate that hepatic TLR4 in non-parenchymal cells mediates the ketogenesis-suppressing action of S100A9. Mechanistically, S100A9 acts extracellularly to activate the mechanistic target of rapamycin complex 1 (mTORC1) in a TLR4-dependent manner. Accordingly, hepatic-restricted but not hepatocyte-restricted loss of Tuberous Sclerosis Complex 1 (TSC1, an mTORC1 inhibitor) corrects insulin-deficiency-induced hyperketonemia. Therapeutically, recombinant S100A9 administration restrains ketogenesis and improves hyperglycemia without causing hypoglycemia in diabetic mice. Also, circulating S100A9 in patients with ketoacidosis is only marginally increased hence unveiling a window of opportunity to pharmacologically augment S100A9 for preventing unrestrained ketogenesis. In summary, our findings reveal the hepatic S100A9-TLR4-mTORC1 axis in non-parenchymal cells as a promising therapeutic target for restraining diabetic ketogenesis. Excess ketogenesis can lead to ketoacidosis, a serious complication in patients with diabetes. Here the authors report an insulin independent pathway, the hepatic nonparenchymal S100A9-TLR4-mTORC1 axis, that is able to normalize diabetic ketogenesis and pre-clinical data to suggest potential for development of S100A9 based adjunctive therapy to insulin. [ABSTRACT FROM AUTHOR]

The use of augmented reality (AR) and virtual reality (VR) for life support training is increasing. These technologies provide an immersive experience that supports learning in a safe and controlled environment. This review focuses on the use of AR and VR for emergency care training for health care providers, medical students, and nonprofessionals. In particular, we analyzed (1) serious games, nonimmersive games, both single-player and multiplayer; (2) VR tools ranging from semi-immersive to immersive virtual and mixed reality; and (3) AR applications. All the toolkits have been investigated in terms of application goals (training, assessment, or both), simulated procedures, and skills. The main goal of this work is to summarize and organize the findings of studies coming from multiple research areas in order to make them accessible to all the professionals involved in medical simulation. The analysis of the state-of-the-art technologies reveals that tools and studies related to the multiplayer experience, haptic feedback, and evaluation of user's manual skills in the foregoing health care-related environments are still limited and require further investigation. Also, there is an additional need to conduct studies aimed at assessing whether AR/VR-based systems are superior or, at the minimum, comparable to traditional training methods. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that, in rested subjects, extensive practice in a motor learning task increased both electroencephalographic (EEG) theta power in the areas involved in learning and improved the error rate in a motor test that shared similarities with the task. A nap normalized both EEG and performance changes. We now ascertain whether extensive visual declarative learning produces results similar to motor learning. Thus, during the morning, we recorded high-density EEG in well rested young healthy subjects that learned the order of different visual sequence task (VSEQ) for three one-hour blocks. Afterward, a group of subjects took a nap and another rested quietly. Between each VSEQ block, we recorded spontaneous EEG (sEEG) at rest and assessed performance in a motor test and a visual working memory test that shares similarities with VSEQ. We found that after the third block, VSEQ induced local theta power increases in the sEEG over a right temporo-parietal area that was engaged during the task. This local theta increase was preceded by increases in alpha and beta power over the same area and was paralleled by performance decline in the visual working memory test. Only after the nap, VSEQ learning rate improved and performance in the visual working memory test was restored, together with partial normalization of the local sEEG changes. These results suggest that intensive learning, like motor learning, produces local theta power increases, possibly reflecting local neuronal fatigue. Sleep may be necessary to resolve neuronal fatigue and its effects on learning and performance. [ABSTRACT FROM AUTHOR]

Beta oscillations (13.5−25 Hz) over the sensorimotor areas are characterized by a power decrease during movement execution (event-related desynchronization, ERD) and a sharp rebound after the movement end (event-related synchronization, ERS). In previous studies, we demonstrated that movement-related beta modulation depth (peak ERS-ERD) during reaching increases within 1-h practice. This increase may represent plasticity processes within the sensorimotor network. If so, beta modulation during a reaching test should be affected by previous learning activity that engages the sensorimotor system but not by learning involving other systems. We thus recorded high-density EEG activity in a group of healthy subjects performing three 45-min blocks of motor adaptation task to a visually rotated display (ROT) and in another performing three blocks of visual sequence-learning (VSEQ). Each block of either ROT or VSEQ was followed by a simple reaching test (mov) without rotation. We found that beta modulation depth increased with practice across mov tests. However, such an increase was greater in the group performing ROT over both the left and frontal areas previously involved in ROT. Importantly, beta modulation values returned to baseline values after a 90-min of either nap or quiet wake. These results show that previous practice leaves a trace in movement-related beta modulation and therefore such increases are cumulative. Furthermore, as sleep is not necessary to bring beta modulation values to baseline, they could reflect local increases of neuronal activity and decrease of energy and supplies. [ABSTRACT FROM AUTHOR]

Stroke survivors show greater postural oscillations and altered muscular activation compared to healthy controls. This results in difficulties in walking and standing, and in an increased risk of falls. A proper control of the trunk is related to a stable walk and to a lower falling risk; to this extent, rehabilitative protocols are currently working on core stability. The main objective of this work was to evaluate the effectiveness of trunk and balance training performed with a new robotic device designed for evaluation and training of balance and core stability, in improving the recovery of chronic stroke patients compared with a traditional physical therapy program. Thirty chronic stroke patients, randomly divided in two groups, either underwent a traditional rehabilitative protocol, or a robot-based program. Each patient was assessed before and after the rehabilitation and at 3-months follow-up with clinical and robot-based evaluation exercises focused on static and dynamic balance and trunk control. Results from clinical scores showed an improvement in both groups in balance and trunk control. Robot-based indices analysis indicated that the experimental group showed greater improvements in proprioceptive control, reactive balance and postural control in unstable conditions, compared to the control group, showing an improved trunk control with reduced compensatory strategies at the end of the training. Moreover, the experimental group had an increased retention of the benefits obtained with training at 3 months follow up. These results support the idea that such robotic device is a promising tool for stroke rehabilitation. [ABSTRACT FROM AUTHOR]

During movement, modulation of beta power occurs over the sensorimotor areas, with a decrease just before its start (event-related desynchronization, ERD) and a rebound after its end (event-related synchronization, ERS). We have recently found that the depth of ERD-to-ERS modulation increases during practice in a reaching task and the following day decreases to baseline levels. Importantly, the magnitude of the beta modulation increase during practice is highly correlated with the retention of motor skill tested the following day. Together with other evidence, this suggests that the increase of practice-related modulation depth may be the expression of sensorimotor cortex's plasticity. Here, we determine whether the practice-related increase of beta modulation depth is equally present in a group of younger and a group of older subjects during the performance of a 30-minute block of reaching movements. We focused our analyses on two regions of interest (ROIs): the left sensorimotor and the frontal region. Performance indices were significantly different in the two groups, with the movements of older subjects being slower and less accurate. Importantly, both groups presented a similar increase of the practice-related beta modulation depth in both ROIs in the course of the task. Peak latency analysis revealed a progressive delay of the ERS peak that correlated with the total movement time. Altogether, these findings support the notion that the depth of beta modulation in a reaching movement task does not depend on age and confirm previous findings that only ERS peak latency but not ERS magnitude is related to performance indices. [ABSTRACT FROM AUTHOR]

The main diagnostic tools for primary and metastatic central nervous system (CNS) tumors are the anamnestic neurological examination and the imaging tests, which are expensive and lack specificity. In recent years, the shell of macromolecules which forms on nanoparticles (NPs) when they are exposed to human blood, also known as hard corona (HC), became a powerful tool in diagnostics. Indeed, HC can act as a "nano-concentrator" of serum proteins and can detect minor changes in the protein concentration at the very early stages of disease development. In this paper, we characterized lipid NP HC formed in blood samples from patients affected by meningeal tumors. We found that the HCs of meningeal tumor patients could be discriminated from those of healthy subjects. Our results show that emerging HC-based technologies will pave the way for early diagnosis of CNS cancer. [ABSTRACT FROM AUTHOR]

Beta power over the sensorimotor areas starts decreasing just before movement execution (event-related desynchronization, ERD) and increases post-movement (event-related synchronization, ERS). In this study, we determined whether the magnitude of beta ERD, ERS and modulation depth are linked to movement characteristics, such as movement length and velocity. Brain activity was recorded with a 256-channels EEG system in 35 healthy subjects performing fast, uncorrected reaching movements to targets located at three distances. We found that the temporal profiles of velocity were bell-shaped and scaled to the appropriate target distance. However, the magnitude of beta ERD, ERS and modulation depth, as well as their timing, did not significantly change and were not related to movement features. [ABSTRACT FROM AUTHOR]

Prep1 is a homeodomain transcription factor which has an important role in hindbrain development. Prep1 expression is also kept in adult mouse brain and in particular within the olfactory bulbs. Moreover, many Prep1 neurons co-localize with Calbindin-positive periglomerular interneurons in olfactory glomerular layer. However, Prep1 function in this brain region is still unknown. In this study, we show that Prep1 hypomorphic heterozygous (Prep1i/+) mice express low levels of protein and feature a 30% reduction of olfactory bulb area, compared to WT mice. In addition, Prep1i/+ mice olfactory bulb histological analysis indicated a 20% lower cytochrome C oxidase activity within the glomerular layer, accompanied by a reduced number of periglomerular interneurons, compared to the WT littermates. Consistently, olfactory perception test highlighted that Prep1 hypomorphic heterozygous mice display a scant ability to distinguish odors, which significantly impacts on feeding behavior, as Prep1i/+ mice revealed a reduced preference for high-fat food. Analysis of BDNF signaling, which represents the main molecular mediator of olfactory plasticity, showed that Prep1i/+ mouse olfactory bulbs feature a 30% reduction of TrkB receptor levels and a decreased activation of ERK1/2. Similarly, overexpression of Prep1 in mouse neuronal cells (N2A) caused an increase of TrkB expression levels, BDNF-induced ERK phosphorylation, and cell viability, compared to control cells. We conclude that Prep1 deficiency alters olfactory morpho-functional integrity and olfaction-mediated eating behavior by affecting BDNF-TrkB signaling. Prep1 could, therefore, play a crucial role in behavioral dysfunctions associated to impaired responsiveness to BDNF. [ABSTRACT FROM AUTHOR]

Recently we found that modulation depth of beta power during movement increases with practice over sensory-motor areas in normal subjects but not in patients with Parkinson's disease (PD). As such changes might reflect use-dependent modifications, we concluded that reduction of beta enhancement in PD represents saturation of cortical plasticity. A few questions remained open: What is the relation between these EEG changes and retention of motor skills? Would a second task exposure restore beta modulation enhancement in PD? Do practice-induced increases of beta modulation occur within each block? We thus recorded EEG in patients with PD and age-matched controls in two consecutive days during a 40-min reaching task divided in fifteen blocks of 56 movements each. The results confirmed that, with practice, beta modulation depth over the contralateral sensory-motor area significantly increased across blocks in controls but not in PD, while performance improved in both groups without significant correlations between behavioral and EEG data. The same changes were seen the following day in both groups. Also, beta modulation increased within each block with similar values in both groups and such increases were partially transferred to the successive block in controls, but not in PD. Retention of performance improvement was present in the controls but not in the patients and correlated with the increase in day 1 modulation depth. Therefore, the lack of practice-related increase beta modulation in PD is likely due to deficient potentiation mechanisms that permit between-block saving of beta power enhancement and trigger mechanisms of memory formation. [ABSTRACT FROM AUTHOR]

Background: In the evaluation of Stereo-Electroencephalography (SEEG) signals, the physicist's workflow involves several operations, including determining the position of individual electrode contacts in terms of both relationship to grey or white matter and location in specific brain regions. These operations are (i) generally carried out manually by experts with limited computer support, (ii) hugely time consuming, and (iii) often inaccurate, incomplete, and prone to errors. Results: In this paper we present SEEG Assistant, a set of tools integrated in a single 3DSlicer extension, which aims to assist neurosurgeons in the analysis of post-implant structural data and hence aid the neurophysiologist in the interpretation of SEEG data. SEEG Assistant consists of (i) a module to localize the electrode contact positions using imaging data from a thresholded post-implant CT, (ii) a module to determine the most probable cerebral location of the recorded activity, and (iii) a module to compute the Grey Matter Proximity Index, i.e. the distance of each contact from the cerebral cortex, in order to discriminate between white and grey matter location of contacts. Finally, exploiting 3DSlicer capabilities, SEEG Assistant offers a Graphical User Interface that simplifies the interaction between the user and the tools. SEEG Assistant has been tested on 40 patients segmenting 555 electrodes, and it has been used to identify the neuroanatomical loci and to compute the distance to the nearest cerebral cortex for 9626 contacts. We also performed manual segmentation and compared the results between the proposed tool and gold-standard clinical practice. As a result, the use of SEEG Assistant decreases the post implant processing time by more than 2 orders of magnitude, improves the quality of results and decreases, if not eliminates, errors in post implant processing. Conclusions: The SEEG Assistant Framework for the first time supports physicists by providing a set of open-source tools for post-implant processing of SEEG data. Furthermore, SEEG Assistant has been integrated into 3D Slicer, a software platform for the analysis and visualization of medical images, overcoming limitations of command-line tools. [ABSTRACT FROM AUTHOR]

The basement membrane collagen IV-degrading matrix metalloproteinases -2 and -9 (MMPs) are most often linked to the malignant phenotype of tumor cells by playing a critical role in invasion, metastasis, angiogenesis, and vasculogenesis. We verified the activity of these two MMPs in the sera of patients affected by brain tumors (20 gliomas, 28 meningiomas and 20 metastasis) by zymography. The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. Zymography showed four dominant gelatinolytic bands of 240, 130, 92 (MMP-9) and 72 (MMP-2) kDa. No statistically significant variations of MMP-2 proteolytic activity between patients and healthy individuals were observed. On the contrary, MMP-9 (both monomeric and multimeric forms) lytic activities were significantly higher in tumors specimens compared to healthy controls (p < 0.001). Moreover, MMP-9 immunohistochemistry revealed: (1) a strong reactivity in neoplastic vessels of high-grade gliomas showing an inverse correlation with serum multimeric gelatinolytic activity; (2) a cytoplasmatic reactivity in meningiomas with a significantly increase in atypical meningioma compared with low-grade ones (p = 0.036); (3) a positive correlation between MMP-9 and Ki-67 (Sperman Rho coefficient r = 0.418 and p = 0.034). Our results suggest that serum and tissue MMP-9 might provide clinicians additional objective information in intracranial neoplasms. Finally, it should be possible to use MMP-9 as a target for new forms of therapy. Nevertheless, due to the small number of patients included in the study, the conclusion may not be transferable to the general population and therefore further evaluations are needed. [ABSTRACT FROM AUTHOR]

Obesity is characterized by a disruption in energy balance regulation that results in an excess accumulation of body fat. Its increasing prevalence poses a major public health concern because it is a risk factor for a host of additional chronic conditions, including type 2 diabetes, hypertension, and cardiovascular disease. Obesity is increasingly recognized as a growing cause of cancer risk. In particular excessive adipose expansion during obesity causes adipose dysfunction and inflammation that can regulate tumor growth. In obesity, dysregulated systemic metabolism and inflammation induce hyperinsulinemia, hyperglycemia, dyslipidemia, and enhance sex hormone production with increased secretion of proinflammatory adipokine that impact breast cancer development and progression. This review describes how adipose inflammation that characterizes obesity is responsible of microenvironment to promote cancer, and discuss how steroid hormones, that are essential for the maintenance of the normal development, growth and differentiation of the cells, influence the induction and progression of breast cancer. J. Cell. Physiol. 232: 69-77, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Matrix metallo-proteinases (MMPs) are a family of zinc-dependent endopeptidases, capable of degrading all the molecular components of extracellular matrix. A class of MMPs is gelatinases which includes gelatinase A or MMP-2 (72 kDa) and gelatinase B or MMP-9 (92 kDa), which have been shown to play critical roles in pathophysiology of many human disease and, in particular, cancer progression. For these reasons they obtained a great interest as potential non-invasive biomarker in providing useful clinical information in cancer diagnosis and therapy. A sensitive and unexpensive method for analysis of gelatinases is the gelatine zymography, which allows to measure the relative amounts of active and inactive enzymes in body fluids and tissue extracts. The procedure involves the electrophoretic separation of proteins under denaturing but non reducing conditions through a polyacrylamide gel containing a synthetic substrate (gelatin). The aim of this mini-review has been to describe the general principles of gelatine zymography technique, underling the main advantages and disadvantages. Even though an improvement of this method is necessary for a better applicability in laboratory medicine, gelatine zymography represents the most convenient method to detect the activity of the different gelatinases from a wide range of biological samples. [ABSTRACT FROM AUTHOR]

The present study was aimed to evaluate the malvidin's protective effects on damage induced by 30 min bilateral common carotid artery occlusion (BCCAO) and 60 min reperfusion (RE) in rat pial microcirculation. Rat pial microcirculation was observed using fluorescence microscopy through a closed cranial window. Western blotting analysis was performed to investigate the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) and matrix metalloproteinase 9 (MMP-9) expression. Moreover, MMP-9 activity was evaluated by zymography. Finally, neuronal damage and radical oxygen species (ROS) formation were assessed. In all animals, pial arterioles were classified in five orders of branching according to Strahler's method. In hypoperfused rats, 30 min BCCAO and 60 min RE caused a decrease in arteriolar diameter, an increase in microvascular leakage and leukocyte adhesion, accompanied by decreased capillary perfusion and red blood cell velocity (VRBC). Moreover, marked neuronal damage and evident ROS generation were detected. Conversely, malvidin administration induced arteriolar dilation in dose-related manner, reducing microvascular leakage as well as leukocyte adhesion. Capillary perfusion and VRBC were protected. Nitric oxide (NO) synthase inhibition significantly attenuated malvidin's effects on arteriolar diameter. Western blotting analysis revealed an increase in eNOS and p-eNOS expression, while zymography indicated a decrease in MMP-9 activity after malvidin's administration. Furthermore, malvidin was able to prevent neuronal damage and to decrease ROS generation. In conclusion, malvidin protects rat pial microcirculation against BCCAO/RE injury, preventing blood-brain impairment and neuronal loss. Malvidin's effects appear to be mediated by eNOS activation and scavenger activity. [ABSTRACT FROM AUTHOR]

The identification of biomarkers in urine or serum samples from patients with bladder cancer is urgently required for the development of non-invasive methods for the diagnosis of bladder carcinoma and to facilitate follow-up surveillance, to combat the high progression and recurrence rates of this type of cancer. The current study measured the content of matrix metalloproteinase (MMP)-2 and -9, as well as tissue inhibitor of metalloproteinase (TIMP)-1 and -2 in the urine and sera of 41 patients with bladder cancer by ELISA. The association between levels of MMP-2 and -9 and TIMP-1 and -2, and tumor grade and stage were investigated to verify whether these molecules are involved in tumor differentiation. Statistical analysis of the data revealed that urinary TIMP-1 levels were significantly higher in the high grade group compared with those of the low grade samples (P=0.022). The results also revealed a significantly differing distribution of TIMP-1 expression between Ta and T1 stage specimens (P=0.040). The corresponding area under the curves (AUCs) were 0.72, with a sensitivity of 0.70 and specificity of 0.75. In addition, neutrophil gelatinase-associated lipocalin (NGAL) and MMP-9/NGAL complex levels in the sera were measured. All molecules evaluated were detected in the sera of the patients studied. In particular, tumors staged as non-muscle invasive (Ta and T1), demonstrated significantly higher NGAL levels compared with those of muscle invasive (>T1) bladder cancer (32.8 ng/ml vs. 16.2 ng/ml; P=0.029). The discriminatory ability of NGAL expression was confirmed by receiver operating characteristic curve analysis that revealed an AUC of 0.75, a sensitivity of 0.88 and a specificity of 0.67. These data indicated that urinary TIMP-1 and serum NGAL may be useful non-invasive biomarkers to provide clinical information for bladder cancer disease management. Multicenter, prospective studies are required to confirm these preliminary results. [ABSTRACT FROM AUTHOR]

Metabolic disorders are very common in the population worldwide and are among the diseases with the highest health utilization and costs per person. Despite the ongoing efforts to develop new treatments, currently, for many of these disorders, there are no approved therapies, resulting in a huge economic hit and tension for society. In this review, we recapitulate the recent advancements in stem cell (gene) therapy as potential tools for the long-term treatment of both inherited (lysosomal storage diseases) and acquired (diabetes mellitus, obesity) metabolic disorders, focusing on the main promising results observed in human patients and discussing the critical hurdles preventing the definitive jump of this approach from the bench to the clinic. [ABSTRACT FROM AUTHOR]

Tens of millions suffer from insulin deficiency (ID); a defect leading to severe metabolic imbalance and death. The only means for management of ID is insulin therapy; yet, this approach is sub-optimal and causes life-threatening hypoglycemia. Hence, ID represents a great medical and societal challenge. Here we report that S100A9, also known as Calgranulin B or Myeloid-Related Protein 14 (MRP14), is a leptin-induced circulating cue exerting beneficial anti-diabetic action. In murine models of ID, enhanced expression of S100A9 alone (i.e. without administered insulin and/or leptin) slightly improves hyperglycemia, and normalizes key metabolic defects (e.g. hyperketonemia, hypertriglyceridemia, and increased hepatic fatty acid oxidation; FAO), and extends lifespan by at least a factor of two. Mechanistically, we report that Toll-Like Receptor 4 (TLR4) is required, at least in part, for the metabolic-improving and pro-survival effects of S100A9. Thus, our data identify the S100A9/TLR4 axis as a putative target for ID care. Insulin replacement is a valuable therapy for insulin deficiency, however, other therapies are being investigated to restore metabolic homeostasis. Here, the authors identify S100A9 as a leptin induced circulating cue that improves glucose and lipid homeostasis and extends survival in insulin deficient mice. [ABSTRACT FROM AUTHOR]