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Copyright of Revista Andaluza de Medicina del Deporte is the property of Centro Andaluza de Medicina del Deporte and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The Raphe Pallidus (RPa) is a brainstem nucleus containing sympathetic premotor neurons that control thermogenesis and modulate cardiovascular function. It receives inputs from various hypothalamic areas, including the Lateral Hypothalamus (LH), a heterogeneous region intricately involved in several autonomic and behavioral functions. A key subpopulation of neurons in the LH expresses orexin/hypocretin, a neuropeptide which is crucially involved in the regulation of the wake-sleep states and feeding behavior. The RPa receives orexinergic projections from the LH and orexinergic signalling in the RPa has been shown to enhance thermogenesis in the anaesthetized rat, but only in the presence of an already existing thermogenic drive, without significantly affecting cardiovascular function. The present work was aimed at exploring the effects on thermoregulation and autonomic function and the possible role in the modulation of the wake-sleep states and feeding behavior of orexin injection in the RPa in the free-behaving rat. In order to assess the influence of an already present thermogenic drive on orexinergic signalling in the RPa, animals were studied at three different ambient temperatures (Ta, 10°C, 24°C, and 32°C). We found that orexin injection into the RPa variably affected the wake-sleep states, autonomic functions, motor activity, and feeding behavior, at the different Tas. In particular, in the first post-injection hour, we observed an increase in wakefulness, which was large at Ta 24°C and Ta 10°C and rather mild at Ta 32°C. Deep brain temperature was increased by orexin injection at Ta 10°C, but not at either Ta 24°C or Ta 32°C. Moreover, an increase in mean arterial blood pressure occurred at Ta 24°C, which was probably masked by the high baseline levels at Ta 10°C and was completely absent at Ta 32°C. Finally, an enhancement in feeding behavior was observed at Ta 24°C and 10°C only. In accordance with what observed in anaesthetized rats, orexinergic signalling in the RPa seems to be ineffective in the absence of any thermogenic drive. Moreover, the effects observed on the wake-sleep states and feeding behavior introduce the RPa as a novel player in the central neural network promoting wakefulness and feeding., 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 © 2024 Hitrec, Del Vecchio, Alberti, Luppi, Martelli, Occhinegro, Piscitiello, Taddei, Tupone, Amici and Cerri.)

About 1-2% of people worldwide suffer from epilepsy, which is characterized by unpredictable and intermittent seizure occurrence. Despite the fact that the exact origin of temporal lobe epilepsy is frequently unknown, it is frequently linked to an early triggering insult like brain damage, tumors, or Status Epilepticus (SE). We used an experimental approach consisting of electrical stimulation of the amygdaloid complex to induce two behaviorally and structurally distinct SE states: Type I (fully convulsive), with more severe seizure behaviors and more extensive brain damage, and Type II (partial convulsive), with less severe seizure behaviors and brain damage. Our goal was to better understand how the various types of SE impact the hippocampus leading to the development of epilepsy. Despite clear variations between the two behaviors in terms of neurodegeneration, study of neurogenesis revealed a comparable rise in the number of Ki-67 + cells and an increase in Doublecortin (DCX) in both kinds of SE., (© 2023 The Authors.)

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7's miRNAs into EVs. In multiple patient cohorts, we observed increased levels of let-7a-5p and let-7d-5p in EVs derived from the blood of premenopausal ER+ BC patients, and elevated EV levels in patients with high BMI, both conditions associated with higher levels of 17β-estradiol. In brief, we identified a unique estrogen-driven mechanism by which ER+ BC cells eliminate tumor suppressor miRNAs in EVs, with effects on modulating tumor-associated macrophages in the microenvironment.

The ability to vary the characteristics of one's voice is a critical feature of human communication. Understanding whether and how animals change their calls will provide insights into the evolution of language. We asked to what extent the vocalizations of penguins, a phylogenetically distant species from those capable of explicit vocal learning, are flexible and responsive to their social environment. Using a principal components (PCs) analysis, we reduced 14 vocal parameters of penguin's contact calls to four PCs, each comprising highly correlated parameters and which can be categorized as fundamental frequency, formant frequency, frequency modulation, and amplitude modulation rate and duration. We compared how these differed between individuals with varying degrees of social interactions: same-colony versus different-colony, same colony over 3 years and partners versus non-partners. Our analyses indicate that the more penguins experience each other's calls, the more similar their calls become over time, that vocal convergence requires a long time and relative stability in colony membership, and that partners' unique social bond may affect vocal convergence differently than non-partners. Our results suggest that this implicit form of vocal plasticity is perhaps more widespread across the animal kingdom than previously thought and may be a fundamental capacity of vertebrate vocalization.

People who use drugs (PWUDs) are generally considered "hard-to-treat" patients, due to adherence to HCV antiviral therapy or re-infection concerns. Linkage-to-care still remains a significant gap for HCV elimination, worsened by the COVID-19 pandemic. To reduce time-to-treat and improve treatment adherence, we have developed a patient-tailored model-of-care, decentralized within the addiction center and supervised remotely by hepatologists. From January 2017 to December 2020, patients were enrolled in one addiction care center in Southern Italy, where a complete hepatologic assessment, including blood chemistry, ultrasound, and transient elastography examination, was provided. DAAs treatment has been adapted on clinical features, also performing a daily administration during an outpatient visit, and monitored remotely by specialists via telemedicine interactions. Adherence was evaluated on the accomplishment of therapy or on the percentage of attended visits. From a total of 690 PWUDs, 135 had an active HCV infection and were enrolled in the study. All patients started the treatment within 3 weeks after HCV diagnosis. Six drop-outs were recorded, obtaining a sustained virological response at week 12 (SVR12) in 98.5% of PWUDs. There were only two cases of treatment failure, one of which is re-infection. No differences were found between the SVR12 rates before and during the COVID-19 pandemic. We obtained a high SVR12 rate, providing a comprehensive assessment within the addiction care center, tailoring the drug administration with a hepatologic remote stewardship. Our therapeutic model should improve the time-to-treat and treatment adherence in PWUDs.

People who use drugs (PWUDs) are a crucial population in the global fight against viral hepatitis. The difficulties in linkage to care, the low adherence to therapy, the frequent loss to follow-up and the high risk of re-infection make the eradication process of the hepatitis C virus (HCV) really hard in this viral reservoir. Several management and treatment models have been tested with the aim of optimizing the HCV care cascade in PWUDs. Models of decentralization of the care process and integration of services seem to provide the highest success rates. Giving this, telemedicine could favor the decentralization of diagnostic-therapeutic management, key for the implementation of linkage to care, reduction of waiting times, optimization of adherence and results and reduction of the costs. The purpose of this literature review is to examine the role and possible impact of telemedicine in optimizing the HCV care cascade, comparing the different care models that have shown to improve the linkage to care and therapeutic adherence in this special population.

Extracellular vesicles (EVs) mediate the cross-talk between cancer cells and the cells of the surrounding Tumour Microenvironment (TME). Professional killer cells include Natural Killer (NK) cells and CD8+ Cytotoxic T-lymphocytes (CTLs), which represent some of the most effective immune defense mechanisms against cancer cells. Recent evidence supports the role of EVs released by NK cells and CTLs in killing cancer cells, paving the road to a possible therapeutic role for such EVs. This review article provides the state-of-the-art knowledge on the role of NK- and CTL-derived EVs as anticancer agents, focusing on the different functions of different sub-types of EVs. We also reviewed the current knowledge on the effects of cancer-derived EVs on NK cells and CTLs, identifying areas for future investigation in the emerging new field of EV-mediated immunotherapy of cancer., Competing Interests: The authors do not have any conflicts of interest to declare., (© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Background: Clinical and experimental evidence indicates that olfactory stimulation modulates limbic seizures, either blocking or inducing ictal activity. Objective: We aim to evaluate the behavioral and electroencephalographic (EEGraphic) effects of dihydro-2,4,5-trimethylthiazoline (TMT) olfactory exposure on limbic seizures induced by amygdala rapid kindling (ARK). Materials and Methods: Wistar male rats (280-300 g) underwent stereotaxic surgery for electrode implantation in piriform cortex (PC), hippocampal formation (HIP), and amygdaloid complex (AMYG). Part of the animals was exposed to a saturated chamber with water or TMT, while others had ARK and olfactory exposure prior to the 21st stimulus. Behavioral responses were measured by traditional seizure severity scales (Racine and Pinel and Rovner) and/or by sequential analysis/neuroethology. The electrographic activity of epileptogenic limbic networks was quantified by the occurrence of the first and second EEG afterdischarges, comparing the 1st and 21st stimulus. The spectral analysis [Fast Fourier Transform (FFT)] of the first afterdischarge was performed at the 21st stimulus. Results: TMT olfactory exposure reduced the seizure severity in kindled rats, altering the displayed behavioral sequence. Moreover, TMT decreased the occurrence of first and second afterdischarges, at the 21st stimulus, and altered the spectral features. Conclusions: Both behavioral and EEGraphic evaluations indicated that TMT, a potent molecule with strong biological relevance, in fact, "predator odor," suppressed the epileptiform activity in limbic networks., (Copyright © 2020 Delfino-Pereira, Bertti-Dutra, Del Vecchio, de Oliveira, Medeiros, Cestari, Santos, Moraes, Rosa, Mendes and Garcia-Cairasco.)

There is limited research examining the physical tasks that Brazilian special policemen groups can perform in the line of duty. The aims of this study were to (a) identify the occupational tasks of specialist police personnel serving in the Rapid Response Group (GRR) and Tactical Operations Command (COT), and to profile the frequency, difficulty, and importance of these tasks, and (b) to explore the current physical training these special operations police units (SOPUs) officers undertake to maintain their operational fitness. Univariate analysis for numerical variables (mean and standard deviation (SD)), as well as the absolute and relative frequencies for categorical variables were performed. Two Brazilian SOPUs performed a questionnaire with demographic, performance, and physical training sections. A total of 78 respondents (24 of the GRR and 54 of the COT) completed the survey. "Standing and/or sitting with complete equipment for long periods in different climatic conditions", and "lifting/pushing/pulling heavier objects" were the most frequent and difficult occupational tasks of both SOPUs, respectively. "Shooting a long weapon" and "breaking a door" were the most important for GRR and COT, respectively. All officers undertook regular physical training (~9 h/week), in an unstructured manner, without supervision, and planning of physical training is carried out autonomously (COT) or a mixture of autonomously and directed (GRR), with the main objectives of developing aerobic endurance and muscle strength. It is important that SOPUs teams train their members' physical capabilities to perform the tasks identified in this study, as well as follow a structured, supervised, and planned physical training program.

Objective: Electrohypersensitive people attribute various symptoms to exposure of radiofrequency electromagnetic fields (RF-EMF); sleep disturbance is the most frequently cited. However, laboratory experiments have yielded conflicting results regarding sleep alterations. Our hypothesis was that exposure to RF-EMF alone would lead to slight or non-significant effects but that co-exposure to RF-EMFs and other environmental constraints (such as noise) would lead to significant effects., Methods: 3-week-old male Wistar rats (4 groups, n = 12 per group) were exposed for 5 weeks to continuous RF-EMF (900 MHz, 1.8 V/m, SAR = 30 mW/kg) in the presence or absence of high-level noise (87.5 dB, 50-20000 Hz) during the rest period. After 5 weeks of exposure, sleep (24 h recording), food and water intakes, and body weight were recorded with or without RF-EMF and/or noise. At the end of this recording period, sleep was scored during the 1 h resttime in the absence of noise and of RF-EMF exposure., Results: Exposure to RF-EMF and/or noise was associated with body weight gain, with hyperphagia in the noise-only and RF-EMF + noise groups and hypophagia in the RF-EMF-only group. Sleep parameters recording over 24 h highlighted a higher frequency of active wakefulness in the RF-EMF-only group and a lower non-rapid eye movement/rapid eye movement sleep ratio during the active period in the noise-only group. There were no differences in sleep duration in either group. During the 1-h, constraint-free sleep recording, sleep rebound was observed in the noise-only group but not in the RF-EMF-only and RF-EMF + noise groups., Conclusion: Our study showed effects of RF-EMF, regardless of whether or not the animals were also exposed to noise. However, the RF-EMF + noise group presented no exacerbation of those effects. Our results did not support the hypothesis whereby the effects of RF-EMF on physiological functions studied are only visible in animals exposed to both noise and RF-EMF., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Noise is an environmental factor that has been associated with metabolic and sleep disorders. Sleep is a vital function, since it underpins physiologic processes and cognitive recovery and development. However, the effects of chronic noise exposure on the developing organism are still subject to debate., Objective: The objective of the present study was to assess the effects of subchronic, high-level noise exposure on sleep, apnea, and homeostasis in juvenile rats., Methods: Twenty-four 3-wk-old male Wistar rats were exposed to noise [[Formula: see text], [Formula: see text]] for 5 wk and 2 d during the 12-h rest period. Data on sleep stages, food and water intake, apnea, and body and organ weight were recorded., Results: Five weeks of high-level noise exposure were associated with hyperphagia ([Formula: see text]), body weight gain ([Formula: see text]), a heavier thymus ([Formula: see text]), and heavier adrenal glands ([Formula: see text]). A sleep analysis highlighted microstructural differences in the active period: in particular, the mean daily amount of rapid eye movement (REM) sleep as a proportion of total sleep time (TST) was higher. The mean daily amount of non-REM (NREM) sleep was lower in the exposed group, meaning that the intergroup difference in the TST was not significant. During a 1-h, noise-free plethysmographic recording during the rest period, the mean total amount of active wakefulness (AW) was lower in the exposed group (by 9.1 min), whereas the mean duration of an episode of REM sleep was higher (by 1.8 min), and the TST was higher (by 10.7 min)., Discussion: Subchronic exposure of juvenile rats to high-intensity noise during the rest period was associated with some small but significant sleep disturbances, greater food and water intakes, greater body weight gain, and greater thymus and adrenal gland weights. The main effects of noise exposure on sleep were also observed in the 1-h plethysmography session after 5 wk of exposure. https://doi.org/10.1289/EHP4045.

Manual scoring of polysomnography data is labor-intensive and time-consuming, and most existing software does not account for subjective differences and user variability. Therefore, we evaluated a supervised machine learning algorithm, Somnivore TM , for automated wake-sleep stage classification. We designed an algorithm that extracts features from various input channels, following a brief session of manual scoring, and provides automated wake-sleep stage classification for each recording. For algorithm validation, polysomnography data was obtained from independent laboratories, and include normal, cognitively-impaired, and alcohol-treated human subjects (total n = 52), narcoleptic mice and drug-treated rats (total n = 56), and pigeons ( n = 5). Training and testing sets for validation were previously scored manually by 1-2 trained sleep technologists from each laboratory. F -measure was used to assess precision and sensitivity for statistical analysis of classifier output and human scorer agreement. The algorithm gave high concordance with manual visual scoring across all human data (wake 0.91 ± 0.01; N1 0.57 ± 0.01; N2 0.81 ± 0.01; N3 0.86 ± 0.01; REM 0.87 ± 0.01), which was comparable to manual inter-scorer agreement on all stages. Similarly, high concordance was observed across all rodent (wake 0.95 ± 0.01; NREM 0.94 ± 0.01; REM 0.91 ± 0.01) and pigeon (wake 0.96 ± 0.006; NREM 0.97 ± 0.01; REM 0.86 ± 0.02) data. Effects of classifier learning from single signal inputs, simple stage reclassification, automated removal of transition epochs, and training set size were also examined. In summary, we have developed a polysomnography analysis program for automated sleep-stage classification of data from diverse species. Somnivore enables flexible, accurate, and high-throughput analysis of experimental and clinical sleep studies.

Since the establishment of the Sanger sequencing method, scientists around the world focused their efforts to progress in the field to produce the utmost technology. The introduction of next-generation sequencing (NGS) represents a revolutionary step and promises to lead to massive improvements in our understanding on the role of nucleic acids functions. Cancer research began to use this innovative and highly performing method, and interesting results started to appear in colorectal cancer (CRC) analysis. Several studies produced high-quality data in terms of mutation discovery, especially about actionable or less frequently mutated genes, epigenetics, transcriptomics. Analysis of results is unveiling relevant perspectives aiding to evaluate the response to therapies. Novel evidences have been presented also in other directions such as gut microbiota or CRC circulating tumor cells. However, despite its unquestioned potential, NGS poses some issues calling for additional studies. This review intends to offer a view of the state of the art of NGS applications to CRC through examination of the most important technologies and discussion of recent published results.

Background: One of the goals for training in combat sports is to mimic real situations. For mixed martial arts (MMA), simulated sparring matches are a frequent component during training, but a there is a lack of knowledge considering the differences in sparring and competitive environments., Objectives: The main objective of this study was to compare biochemical responses to sparring and official MMA matches., Materials and Methods: Twenty five male professional MMA fighters were evaluated during official events (OFF = 12) and simulated matches (SIM = 13). For both situations, blood samples were taken before (PRE) and immediately after (POST) matches. For statistical analysis, two-way analysis of variance (time x group and time x winner) were used to compare the dependent parametric variables. For non-parametric data, the Kruskal-Wallis test was used and differences were confirmed by Mann-Whitney tests., Results: No significant differences were observed among the groups for demographic variables. The athletes were 26.5 ± 5 years with 80 ± 10 kg, 1.74 ± 0.05 m and had 39.4 ± 25 months of training experience. Primary results indicated higher blood glucose concentration prior to fights for OFF group (OFF= 6.1 ± 1.2 mmol/L and SIM= 4.4 ± 0.7 mmol/L; P < 0.01) and higher ALT values for OFF group at both time points (OFF: PRE = 41.2 ± 12 U/L, POST = 44.2 ± 14.1 U/L; SIM: PRE = 28.1 ± 13.8 U/L, POST = 30.5 ± 12.5 U/L; P = 0.001). In addition, the blood lactate showed similar responses for both groups (OFF: PRE= 4 [3.4 - 4.4] mmol/L, POST= 16.9 [13.8 - 23.5] mmol/L; SIM: PRE = 3.8 [2.8 - 5.5] mmol/L, POST= 16.8 [12.3 - 19.2] mmol/L; P < 0.001)., Conclusions: In conclusion, MMA official and simulated matches induce similar high intensity glycolytic demands and minimal changes to biochemical markers of muscle damage immediately following the fights. Glycolytic availability prior to the fights was raised exclusively in response to official matches.

Background: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Non-alcoholic fatty liver disease (NAFLD) is a frequent chronic liver disorder in developed countries. NAFLD can progress through the more severe non alcoholic steatohepatitis (NASH), cirrhosis and, lastly, HCC. Genetic and epigenetic alterations of coding genes as well as deregulation of microRNAs (miRNAs) activity play a role in HCC development. In this study, the C57BL/6J mouse model was long term high-fat (HF) or low-fat (LF) diet fed, in order to analyze molecular mechanisms responsible for the hepatic damage progression., Methods: Mice were HF or LF diet fed for different time points, then plasma and hepatic tissues were collected. Histological and clinical chemistry assays were performed to assess the progression of liver disease. MicroRNAs' differential expression was evaluated on pooled RNAs from tissues, and some miRNAs showing dysregulation were further analyzed at the individual level., Results: Cholesterol, low and high density lipoproteins, triglycerides and alanine aminotransferase increase was detected in HF mice. Gross anatomical examination revealed hepatomegaly in HF livers, and histological analysis highlighted different degrees and levels of steatosis, inflammatory infiltrate and fibrosis in HF and LF animals, demonstrating the progression from NAFLD through NASH. Macroscopic nodules, showing typical neoplastic features, were observed in 20% of HF diet fed mice. Fifteen miRNAs differentially expressed in HF with respect to LF hepatic tissues during the progression of liver damage, and in tumors with respect to HF non tumor liver specimens were identified. Among them, miR-340-5p, miR-484, miR-574-3p, miR-720, whose expression was never described in NAFLD, NASH and HCC tissues, and miR-125a-5p and miR-182, which showed early and significant dysregulation in the sequential hepatic damage process., Conclusions: In this study, fifteen microRNAs which were modulated in hepatic tissues and in tumors during the transition NAFLD-NASH-HCC are reported. Besides some already described, new and early dysregulated miRNAs were identified. Functional analyses are needed to validate the results here obtained, and to better define the role of these molecules in the progression of the hepatic disease.

Background: Hepatocellular carcinoma (HCC) is an aggressive epithelial tumor which shows very poor prognosis and high rate of recurrence, representing an urgent problem for public healthcare. MicroRNAs (miRNAs/miRs) are a class of small, non-coding RNAs that attract great attention because of their role in regulation of processes such as cellular growth, proliferation, apoptosis. Because of the thousands of potential interactions between a single miR and target mRNAs, bioinformatics prediction tools are very useful to facilitate the task for individuating and selecting putative target genes. In this study, we present a chemically-induced HCC mouse model to identify differential expression of miRNAs during the progression of the hepatic injury up to HCC onset. In addition, we describe an established bioinformatics approach to highlight putative target genes and protein interaction networks where they are involved., Results: We describe four miRs (miR-125a-5p, miR-27a, miR-182, miR-193b) which showed to be differentially expressed in the chemically-induced HCC mouse model. The miRs were subjected to four of the most used predictions tools and 15 predicted target genes were identified. The expression of one (ANK3) among the 15 predicted targets was further validated by immunoblotting. Then, enrichment annotation analysis was performed revealing significant clusters, including some playing a role in ion transporter activity, regulation of receptor protein serine/threonine kinase signaling pathway, protein import into nucleus, regulation of intracellular protein transport, regulation of cell adhesion, growth factor binding, and regulation of TGF-beta/SMAD signaling pathway. A network construction was created and links between the selected miRs, the predicted targets as well as the possible interactions among them and other proteins were built up., Conclusions: In this study, we combined miRNA expression analysis, obtained by an in vivo HCC mouse model, with a bioinformatics-based workflow. New genes, pathways and protein interactions, putatively involved in HCC initiation and progression, were identified and explored.

Neurons within the lateral hypothalamus (LH) are thought to be able to evoke behavioural responses that are coordinated with an adequate level of autonomic activity. Recently, the acute pharmacological inhibition of LH has been shown to depress wakefulness and promote NREM sleep, while suppressing REM sleep. These effects have been suggested to be the consequence of the inhibition of specific neuronal populations within the LH, i.e. the orexin and the MCH neurons, respectively. However, the interpretation of these results is limited by the lack of quantitative analysis of the electroencephalographic (EEG) activity that is critical for the assessment of NREM sleep quality and the presence of aborted NREM-to-REM sleep transitions. Furthermore, the lack of evaluation of the autonomic and thermoregulatory effects of the treatment does not exclude the possibility that the wake-sleep changes are merely the consequence of the autonomic, in particular thermoregulatory, changes that may follow the inhibition of LH neurons. In the present study, the EEG and autonomic/thermoregulatory effects of a prolonged LH inhibition provoked by the repeated local delivery of the GABAA agonist muscimol were studied in rats kept at thermoneutral (24°C) and at a low (10°C) ambient temperature (Ta), a condition which is known to depress sleep occurrence. Here we show that: 1) at both Tas, LH inhibition promoted a peculiar and sustained bout of NREM sleep characterized by an enhancement of slow-wave activity with no NREM-to-REM sleep transitions; 2) LH inhibition caused a marked transitory decrease in brain temperature at Ta 10°C, but not at Ta 24°C, suggesting that sleep changes induced by LH inhibition at thermoneutrality are not caused by a thermoregulatory impairment. These changes are far different from those observed after the short-term selective inhibition of either orexin or MCH neurons, suggesting that other LH neurons are involved in sleep-wake modulation.

Nausea is a prominent symptom and major cause of complaint for patients receiving anticancer chemo- or radiation therapy. The arsenal of anti-nausea drugs is limited, and their efficacy is questionable. Currently, the development of new compounds with anti-nausea activity is hampered by the lack of physiological correlates of nausea. Physiological correlates are needed because common laboratory rodents lack the vomiting reflex. Furthermore, nausea does not always lead to vomiting. Here, we report the results of studies conducted in four research centers to investigate whether nausea is associated with any specific thermoregulatory symptoms. Two species were studied: the laboratory rat, which has no vomiting reflex, and the house musk shrew (Suncus murinus), which does have a vomiting reflex. In rats, motion sickness was induced by rotating them in their individual cages in the horizontal plane (0.75 Hz, 40 min) and confirmed by reduced food consumption at the onset of dark (active) phase. In 100% of rats tested at three centers, post-rotational sickness was associated with marked (~1.5°C) hypothermia, which was associated with a short-lasting tail-skin vasodilation (skin temperature increased by ~4°C). Pretreatment with ondansetron, a serotonin 5-HT3 receptor antagonist, which is used to treat nausea in patients in chemo- or radiation therapy, attenuated hypothermia by ~30%. In shrews, motion sickness was induced by a cyclical back-and-forth motion (4 cm, 1 Hz, 15 min) and confirmed by the presence of retching and vomiting. In this model, sickness was also accompanied by marked hypothermia (~2°C). Like in rats, the hypothermic response was preceded by transient tail-skin vasodilation. In conclusion, motion sickness is accompanied by hypothermia that involves both autonomic and thermoeffector mechanisms: tail-skin vasodilation and possibly reduction of the interscapular brown adipose tissue activity. These thermoregulatory symptoms may serve as physiological correlates of nausea.

Cancer is a multistep process characterized by various and different genetic lesions which cause the transformation of normal cells into tumor cells. To preserve the genomic integrity, eukaryotic cells need a complex DNA damage/repair response network of signaling pathways, involving many proteins, able to induce cell cycle arrest, apoptosis, or DNA repair. Chemotherapy and/or radiation therapy are the most commonly used therapeutic approaches to manage cancer and act mainly through the induction of DNA damage. Impairment in the DNA repair proteins, which physiologically protect cells from persistent DNA injury, can affect the efficacy of cancer therapies. Recently, increasing evidence has suggested that microRNAs take actively part in the regulation of the DNA damage/repair network. MicroRNAs are endogenous short noncoding molecules able to regulate gene expression at the post-transcriptional level. Due to their activity, microRNAs play a role in many fundamental physiological and pathological processes. In this review we report and discuss the role of microRNAs in the DNA damage/repair and cancer.

Unlabelled: A role for the occipital or retrosplenial cortex in nociceptive processing has not been demonstrated yet, but connections from these cortices to brain structures involved in descending pain-inhibitory mechanisms were already demonstrated. This study demonstrated that the electrical stimulation of the occipital or retrosplenial cortex produces antinociception in the rat tail-flick and formalin tests. Bilateral lesions of the dorsolateral funiculus abolished the effect of cortical stimulation in the tail-flick test. Injection of glutamate into the same targets was also antinociceptive in the tail-flick test. No rats stimulated in the occipital or retrosplenial cortex showed any change in motor performance on the Rota-rod test, or had epileptiform changes in the EEG recording during or up to 3 hours after stimulation. The antinociception induced by occipital cortex stimulation persisted after neural block of the retrosplenial cortex. The effect of retrosplenial cortex stimulation also persisted after neural block of the occipital cortex. We conclude that stimulation of the occipital or retrosplenial cortex in rats leads to antinociception activating distinct descending pain-inhibitory mechanisms, and this is unlikely to result from a reduced motor performance or a postictal phenomenon., Perspective: This study presents evidence that stimulation of the retrosplenial or occipital cortex produces antinociception in rat models of acute pain. These findings enhance our understanding of the role of the cerebral cortex in control of pain., (Copyright © 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Introduction: One important aggression to human biology is constituted by metallic mercury intoxication, mainly expressed by neuropsychiatric disorders., Objective: To explore interaction between the domains of Quality of Life (QoL.) and neuro-muscular evidences in intoxicated people by the metal within an urban-industrial environment., Material and Methods: 47 patients have been assessed, through SF36 application and semiological tests. Multiple regression was performed and, to test parameters estimated in adjustments, Student t test was used., Results: Although there are low scores present in the instrument, there have been noticed good results in physical capacities. Muscular strength seems to be an influencing variable on physical and social functioning and mental health (p<0.05). Motor coordination influence on Vitality (p <0.05) was also remarked. As to equilibrium, it presents a negative interaction (p <0.03) with social functioning., Conclusions: Neuropsychiatric disorders influence negatively QoL perception, making people to subestime their motor performances. Complementarily, it is distinguished strength as physical capacity that presents positive interaction with the subjective perception of QV.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), encoded by the OLR1 gene, is a scavenger receptor that plays a fundamental role in the pathogenesis of atherosclerosis. LOX-1 activation is associated with apoptosis of endothelial cells, smooth muscle cells (SMCs), and macrophages. This process is an important underlying mechanism that contributes to plaque instability and subsequent development of acute coronary syndromes. Independent association genetic studies have implicated OLR1 gene variants in myocardial infarction (MI) susceptibility. Because single nucleotide polymorphisms (SNPs) linked to MI are located in intronic sequences of the gene, it remains unclear as to how they determine their biological effects. Using quantitative real-time PCR and minigene approach, we show that intronic SNPs, linked to MI, regulate the expression of a new functional splicing isoform of the OLR1 gene, LOXIN, which lacks exon 5. Macrophages from subjects carrying the "non-risk" disease haplotype at OLR1 gene have an increased expression of LOXIN at mRNA and protein level, which results in a significant reduction of apoptosis in response to oxLDL. Expression of LOXIN in different cell types results in loss of surface staining, indicating that truncation of the C-terminal portion of the protein has a profound effect on its cellular trafficking. Furthermore, the proapoptotic effect of LOX-1 receptor in cell culture is specifically rescued by the coexpression of LOXIN in a dose-dependent manner. The demonstration that increasing levels of LOXIN protect cells from LOX-1 induced apoptosis sets a groundwork for developing therapeutic approaches for prevention of plaque instability.

Sequence comparisons of multiple acyltransferase (AT) domains from modular polyketide synthases (PKSs) have highlighted a correlation between a short sequence motif and the nature of the extender unit selected. When this motif was specifically altered in the bimodular model PKS DEBS1-TE of Saccharopolyspora erythraea, the products included triketide lactones in which acetate extension units had been incorporated instead of propionate units at the predicted positions. We also describe a cassette system for convenient construction of hybrid modular PKSs based on the tylosin PKS in Streptomyces fradiae and demonstrate its use in domain and module swaps.

Purpose: We studied, by means of video-EEG and neo-Timm histochemistry, the behavioral, electrophysiologic, and structural characteristics of seizures induced by intrahippocampal microinjection of pilocarpine (HIP-PILO), a selective model of temporal lobe epilepsy (TLE)., Methods: We investigated the behavioral and electrophysiologic (hippocampus and amygdala EEG) evaluation of status epilepticus (SE) induced by HIP-PILO and the consequent spontaneous recurrent seizures (SRSs). We evaluated hippocampal structural rearrangements after SE by means of neo-Timm staining., Results: HIP-PILO induced SE in 17 (71%) of 24 animals. Although three animals displayed spontaneous remission of SE (not used in analysis) before the established SE duration (90 min), none of those undergoing SE died. Of SE animals, 10 (71%) of 14 had SRSs. All animals with SE had clear-cut mossy fiber sprouting (MFS) in the inner molecular layer of the dentate gyrus and epileptiform activity in hippocampus and amygdala., Conclusions: HIP-PILO rats displayed SE, SRS, MFS, and limbic epileptiform activity, without animal loss after SE. Thus, our data support this as a selective and efficient model of TLE.