NO

The global spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has challenged most countries worldwide. It was quickly recognized that reduced activities (lockdowns) during the Coronavirus Disease of 2019 (COVID-19) pandemic produced major changes in air quality. Our objective was to assess the impacts of COVID-19 lockdowns on groundlevel PM2.5, NO2, and O3 concentrations on a global scale. We obtained data from 34 countries, 141 cities, and 458 air monitoring stations on 5 continents (few data from Africa). On a global average basis, a 34.0% reduction in NO2 concentration and a 15.0% reduction in PM2.5 were estimated during the strict lockdown period (until April 30, 2020). Global average O3 concentration increased by 86.0% during this same period. Individual country and continent-wise comparisons have been made between lockdown and business-as-usual periods. Universally, NO2 was the pollutant most affected by the COVID-19 pandemic. These effects were likely because its emissions were from sources that were typically restricted (i.e., surface traffic and non-essential industries) by the lockdowns and its short lifetime in the atmosphere. Our results indicate that lockdown measures and resulting reduced emissions reduced exposure to most harmful pollutants and could provide global-scale health benefits. However, the increased O3 may have

Status epilepticus (SE) has functional and structural consequences resulting in brain damage. The present study aims to investigate the role of taurine and green tea extract in the neuroprotection against oxidative stress and changes in acetylcholinesterase (AChE) and Na + ,K + -ATPase activities during SE induced by pilocarpine in the hippocampus of adult male rats. Animals received an oral administration of either taurine (100 mg/kg) or green tea extract containing 100 mg/kg epigallocatechin gallate for 3 days before the induction of SE with pilocarpine (380 mg/kg, i.p.) and were sacrificed 1 h after pilocarpine injection. Data indicated that a state of oxidative stress has evolved during SE as evident from the significant increase in lipid peroxidation level and significant decrease in reduced glutathione (GSH) level. Significant decreases in AChE and Na + ,K + -ATPase activities were also recorded. Pretreatment of rats with taurine exaggerated the increase in lipid peroxidation and failed to prevent the decrease in Na + ,K + -ATPase activity resulting from pilocarpine. However, taurine pretreatment prevented the reduced activity of hippocampal

In the present study, a series of labdane derivatives (2e9) were prepared from labdanediol (1) and their potential as anti-inflammatory agents were evaluated on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. All compounds were able to inhibit LPS-induced nitric oxide (NO), although compounds 1, 2, 5, 8 and 9 exhibited the most potent effects with a range of IC 50 values of 5e15 mM. Similarly to the inhibitory effects on NO release, these labdane derivatives also inhibited prostaglandin E 2 (PGE 2 ) production. However, analysis of cell viability demonstrated that effects on NO release and (PGE 2 ) production of compounds 1, 8 and 9 were due to citotoxicity, whereas compound 2 and 5 did not show any effect in the survival of RAW 264.7 macrophages. In addition to these in vitro data, compound 5 also showed anti-inflammatory activity in vivo, when tested in mice. They prevented the extent of swelling in the TPA-induced ear edema model and inhibited MPO activity, showing similar potency to that of the widely used anti-inflammatory drug indomethacin. These results indicate that compound 2 and in particular compound 5 might be used for the design of new anti-inflammatory agents.

The most common method used to quantify lipopolysaccharide (LPS) in polysaccharide samples is the Limulus amebocyte lysate (LAL) test. It is a very sensitive and simple, although not accurate with samples containing carbohydrates, such as widely distributed (1 → 3)-linked ␤-glucans. Another method, the Polymyxin B assay, suffers interference with samples containing negatively charged polysaccharides. We have now developed a method to detect and quantify LPS in carbohydrate-containing samples, using GC-MS of derived acetylated 3-OH fatty acid methyl esters. The method proved to be robust, highly specific and sensitive, allowing detection of LPS at 1 ng, 100 times less than the amount of LPS frequently used as positive control in immunological experiments. In order to demonstrate the applicability of the method, 14 polysaccharide samples were analyzed. On two of them, the presence of LPS was detected at concentrations of 16.1 and 12.7 ng/300 g polysaccharide.

Enzymatically derived NO and extracellular ATP are receiving greater attention due to their role as messengers in the CNS during different physiological and pathological processes. Ionotropic (P2XR) and metabotropic (P2YR) purinergic receptors mediate ATP effects and are present throughout the body. Particularly P2XR are crucial for brain plasticity mechanisms, and are involved in the pathogenesis of different CNS illnesses. NO does not have a specific receptor and its actions are directly dependent on the production on demand by different nitric oxide synthase isoforms. NO synthesizing enzymes are present virtually in all tissues, and NO influences multifarious physiological and pathological functions. Interestingly, various are the tissue and organs modulated by both ATP and NO, such as the immune, brain and vascular systems. Moreover, direct interactions between purinergic and nitrergic mechanisms outside the CNS are well documented, with several studies also indicating that ATP and NO do participate to the same CNS functions. In the past few years, further experimental evidence supported the physiological and pathological relevance of ATP and NO direct interactions in the CNS. The aim of the present review is to provide an account of the available information on the interplay between purinergic and nitrergic systems, focussing on the CNS. The already established relevance of ATP and NO in different pathological processes would predict that the knowledge of ATP/NO cross-talk mechanisms would support pharmacological approaches toward the development of novel ATP/NO combined pharmacological agents. #

Background: Protozoan parasites of the genus Leishmania cause a number of important diseases in humans and undergo a complex life cycle, alternating between a sand fly vector and vertebrate hosts. The parasites have a remarkable capacity to avoid destruction in which surface molecules are determinant for survival. Amongst the many surface molecules of Leishmania, the glycoconjugates are known to play a central role in host-parasite interactions and are the focus of this review. Scope of the review: The most abundant and best studied glycoconjugates are the Lipophosphoglycans (LPGs) and glycoinositolphospholipids (GIPLs). This review summarizes the main studies on structure and biological functions of these molecules in New World Leishmania species. Major conclusions: LPG and GIPLs are complex molecules that display inter-and intraspecies polymorphisms. They are key elements for survival inside the vector and to modulate the vertebrate immune response during infection. General significance: Most of the studies on glycoconjugates focused on Old World Leishmania species. Here, it is reported some of the studies involving New World species and their biological significance on host-parasite interaction. This article is part of a Special Issue entitled Glycoproteomics.

Seeds contain the embryo as a new plant in miniature and have two major functions, reproduction and dispersal. Seed formation completes the process of plant reproduction and, with seed germination, the next plant generation starts. Given the ever-increasing environmental pollution with metal(loid)s, it is perhaps surprising that relatively few reports detail the impacts of metals on seed metabolism, viability and germination in comparison to the numerous publications on the effects of metals in vegetative tissues, particularly roots and shoots. This review provides information on metal(loid) homeostasis, detoxification and tolerance in relation to seed metabolism and performance. The delivery of metals from the mother plant into seeds and their implications on seed development are discussed, as are their uptake upon seed imbibition and subsequent effects on seed germination. Implications for seeds and seedlings on the biochemical and molecular level are discussed and finally, applied aspects are considered regarding the use of seeds for soil and water purification, and in phytoremediation programmes. We conclude with a perspective on future metal research in relation to seed biology.

Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, effectively reduces plasma cholesterol both in monotherapy or combined with a statin. However, its effect on atherosclerosis plaque progression is certainly unknown. MicroRNAs are short non-encoding RNA molecules dynamically implicated in monocytic differentiation which is considered an essential process during atherosclerosis development. The purpose of this study was to investigate the effect of ezetimibe on monocyte/macrophage differentiation as well as the implication of microRNAs (miRNAs) in this process. THP-1 differentiation with PMA became cells adherent to the plastic surface, and induced the expression of macrophage surface markers (CD11a, CD11b and ICAM-1) and miR-155, miR-222, miR-424 and miR-503. In the presence of ezetimibe, the adhesive capacity of THP-1 cells was decreased in a dose-dependent manner (P < 0.05) and the expression of CD11a, CD11b and ICAM-1 was almost totally inhibited (P < 0.05). The expression of miR-155, miR-222, miR-424 and miR-503 was reduced by 55%, 100%, 75% and 100%, respectively (P < 0.05). Further mechanistic studies demonstrated that ezetimibe suppressed the PMA-induced phosphorylation of ERK/MAPK and inhibited the NF-B activity, which are upstream signalling molecules in the differentiation process. In conclusion, ezetimibe inhibits PMA-induced THP-1 cell differentiation into macrophage-like cells in association with the inhibition of miRNA pathways. Our study suggests that inhibition of miRNAs might form a novel mechanism of anti-atherosclerotic effect of ezetimibe.

The most common electronic equipment used is cell phones. With advancement in communicationtechnology, the requirement of cell phones has increased manifold. A cell phone typically transmits and receives signals in the frequency range of 0.9 to 3GHz. This article provides a simple circuit to detect the presence of an activated cell phone by detecting these signals.

Dehydroepiandrosterone (DHEA) is synthesized in the brain and several studies have shown that this steroid is a modulator of synaptic transmission. The effect of DHEA, and its sulfate ester DHEAS, on glutamate and GABA neurotransmission has been extensively studied but some effects on other neurotransmitter systems, such as dopamine, serotonin and nitric oxide, have also been reported. This review summarizes studies showing the effect of DHEA and DHEAS on neurotransmitter systems at different levels (metabolism, release, reuptake, receptor activation), as well as the activation of voltage-gated ion channels and calcium homeostasis, showing the variety of effects that these steroids exert on those systems, allowing the discussion of its mechanisms of action and its relevance to psychiatric disorders.

Although yohimbine (YOH) has been available for the treatment of male erectile dysfunction (ED) for longer than Viagra 1 , there is a perception that little is known about the clinical performance of the drug. This review attempts, by comprehensive analysis of the literature, to cover the clinical, pharmacological, and therapeutic profiles of YOH, relevant to its potential utility in the management of patients with ED. Relatively few well-designed studies have been completed. From these, however, it can be concluded that YOH as monotherapy possesses only modest efficacy in ED patients. In acute and chronic (long-term) studies, YOH has been found to be relatively free of side effects over the dose range predicted to be effective in ED. At much higher doses, the most frequently observed effects, consistent with the primary pharmacological action of the drug, are elevation of blood pressure, a slight anxiogenic action, and increased frequency of urination. These side effects are all easily reversible on termination of YOH therapy. There is increasing evidence that the erectogenic action of YOH can be augmented by concomitant administration of agents that augment the release and/or action of nitric oxide in the corpus cavernosum. YOH has yet to be studied in female sexual dysfunction. Overall, the benefit risk profile of YOH would indicate that it has potential, more probably as part of a combination strategy, e.g., with a drug that enhances the nitric oxide pathway, in the treatment of ED.

Cannabinoids, including the bioactive constituents of the marijuana plant, their synthetic analogs, and endogenous lipids with cannabinoid-like activity, produce their biological effects by interacting with specific receptors. To date, two G protein-coupled cannabinoid receptors have been identified by molecular cloning, CB 1 receptors mainly expressed in the brain and mediating most of the neurobehavioral effects of cannabinoids and CB 2 receptors expressed by immune and hematopoietic tissues. Recent findings indicate that some cannabinoid effects are not mediated by either CB 1 or CB 2 receptors, and in some cases there is compelling evidence to implicate additional receptors in these actions. These include transient receptor potential vanilloid 1 (TRPV 1 ) receptors and as-yet-unidentified receptors implicated in the endothelium-dependent vasodilator effect of certain cannabinoids and in the presynaptic inhibition of glutamatergic neurotransmission in the hippocampus. The case for these additional receptors is being reviewed here. D

A B S T R A C T Peptide and protein (P/P) drugs have been identified as showing great promises for the treatment of various neurodegenerative diseases. A major challenge in this regard, however, is the delivery of P/P drugs over the blood-brain barrier (BBB). Intense research over the last 25 years has enabled a better understanding of the cellular and molecular transport mechanisms at the BBB, and several strategies for enhanced P/P drug delivery over the BBB have been developed and tested in preclinical and clinicalexperimental research. Among them, technology-based approaches (comprising functionalized nanocarriers and liposomes) and pharmacological strategies (such as the use of carrier systems and chimeric peptide technology) appear to be the most promising ones. This review combines a comprehensive overview on the current understanding of the transport mechanisms at the BBB with promising selected strategies published so far that can be applied to facilitate enhanced P/P drug delivery over the BBB. ß

Background: Asthma affects more than 17 million people in the United States;1/3 of these are children. Children are particularly vulnerable to airborne pollution because of their narrower airways and because they generally breathe more air per pound of body weight than adults, increasing their exposure to air pollutants. However, the results from previous studies on the association between motor vehicle emissions and the development of childhood wheeze and asthma are conflicting. Therefore, we conducted a meta-analysis to clarify their potential relationship. Methods: MEDLINE, Highwire, and The Cochrane Library databases were searched for relevant studies. Adjusted odds ratio (OR) with corresponding 95% confidence interval (CI) for the association between traffic air pollutants and wheeze or asthma were retrieved from individual studies and pooled to generate summary effect estimates (meta-OR) in STATA 11.1. Results: Nineteen studies were included in the meta-analysis. Exposure to nitrogen dioxide (meta-OR: 1.05, 95% CI: 1.00-1.11), nitrous oxide (meta-OR: 1.02, 95% CI: 1.00-1.04), and carbon monoxide (meta-OR: 1.06, 95% CI: 1.01-1.12) were positively associated with a higher prevalence of childhood asthma. Exposure to sulfur dioxide (meta-OR: 1.04, 95% CI: 1.01-1.07) was positively associated with a higher prevalence of wheeze in children. Exposure to nitrogen dioxide was positively associated with a higher incidence of childhood asthma (meta-OR: 1.14, 95% CI: 1.06-1.24), and exposures to particulate matter was positively associated with a higher incidence of wheeze in children (meta-OR: 1.05, 95% CI: 1.04-1.07). Conclusions: Living or attending schools near high traffic density roads exposes children to higher levels of motor vehicle air pollutants, and increases the incidence and prevalence of childhood asthma and wheeze.

For many years, methylparaben (MP) has been used as a preservative in cosmetics. In this study, we investigated the effects of ultraviolet-B (UVB) exposure on MP-treated human skin keratinocytes. HaCaT keratinocyte was cultured in MP-containing medium for 24 h, exposed to UVB (15 or 30 mJ/cm 2 ) and further cultured for another 24 h. Subsequent cellular viability was quantified by MTT-based assay and cell death was qualified by fluorescent microscopy and flow cytometry. Oxidative stress, nitric oxide (NO) production and cellular lipid peroxidation were measured using fluorescent probes. In addition, activation of nuclear factor kappa B and activator protein-1 was assessed by electro-mobility gel-shift assay. Practical concentrations of MP (0.003%) had a little or no effect on cellular viability, oxidative stress, NO production, lipid peroxidation and activation of nuclear transcription factors in HaCaT keratinocytes. Low-dose UVB also had little or no effect on these parameters in HaCaT keratinocytes. However, UVB exposure significantly increased cell death, oxidative stress, NO production, lipid peroxidation and activation of transcription factors in MP-treated HaCaT keratinocytes. These results indicate that MP, which has been considered a safe preservative in cosmetics, may have harmful effects on human skin when exposed to sunlight.

Ethnopharmacological relevance: Zingiber officinale Rosc. (Zingiberaceae) has been traditionally used in Ayurvedic, Chinese and Tibb-Unani herbal medicines for the treatment of various illnesses that involve inflammation and which are caused by oxidative stress. Although gingerols and shogaols are the major bioactive compounds present in Zingiber officinale, their molecular mechanisms of actions and the relationship between their structural features and the activity have not been well studied. Aim of the study: The aim of the present study was to examine and compare the antioxidant and antiinflammatory activities of gingerols and their natural analogues to determine their structure-activity relationship and molecular mechanisms. Materials and methods: The in vitro activities of the compounds [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol were evaluated for scavenging of 1,1-diphenyl-2-picyrlhydrazyl (DPPH), superoxide and hydroxyl radicals, inhibition of N-formyl-methionyl-leucyl-phenylalanine (f-MLP) induced reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN), inhibition of lipopolysaccharide induced nitrite and prostaglandin E 2 production in RAW 264.7 cells. Results: In the antioxidant activity assay, [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol exhibited substantial scavenging activities with IC 50 values of 26.3, 19.47, 10.47 and 8.05 M against DPPH radical, IC 50 values of 4.05, 2.5, 1.68 and 0.85 M against superoxide radical and IC 50 values of 4.62, 1.97, 1.35 and 0.72 M against hydroxyl radical, respectively.

Mitochondria are essential organelles for cellular integrity and functionality maintenance and their imparement is implicated in the development of a wide range of diseases, including metabolic, cardiovascular, degenerative and hyperproliferative pathologies. The identification of different compounds able to interact with mitochondria for therapeutic purposes is currently becoming of primary importance. Indeed, it is well known that foods, particularly those of vegetable origin, present several constituents with beneficial effects on health. This review summarizes and updates the most recent findings concerning the mechanisms through which different dietary compounds from plant foods affect mitochondria functionality in healthy and pathological in vitro and in vivo models, paying particular attention to the pathways involved in mitochondrial biogenesis and apoptosis.

 Lingkungan yang baik dan sehat sebagai bagian HAM; Lingkungan yang baik dan sehat sebagai bagian HAM;  Pendidikan LH, akses informasi, partisipasi dan keadilan; Pendidikan LH, akses informasi, partisipasi dan keadilan;  Pendidikan LH, akses informasi, partisipasi dan keadilan; Pendidikan LH, akses informasi, partisipasi dan keadilan; (pasal (pasal 65 65 UU PPLH) UU PPLH) KEWAJIBAN MASYARAKAT DALAM PPLH KEWAJIBAN MASYARAKAT DALAM PPLH   Memelihara kelestarian fungsi LH serta pengendalian pencemaran Memelihara kelestarian fungsi LH serta pengendalian pencemaran dan/atau kerusakan LH; dan/atau kerusakan LH;   Setiap orang yang melakukan usaha/kegiatan berkewajiban : Setiap orang yang melakukan usaha/kegiatan berkewajiban :   Setiap orang yang melakukan usaha/kegiatan berkewajiban : Setiap orang yang melakukan usaha/kegiatan berkewajiban :  Memberikan informasi terkait dengan PPLH secara benar, akurat, Memberikan informasi terkait dengan PPLH secara benar, akurat, terbuka, dan tepat waktu; terbuka, dan tepat waktu; terbuka, dan tepat waktu; terbuka, dan tepat waktu;  Menjaga keberlanjutan fungsi LH; Menjaga keberlanjutan fungsi LH;  Mentaati ketentuan baku mutu LHdan/atau kriteria baku kerusakan Mentaati ketentuan baku mutu LHdan/atau kriteria baku kerusakan LH. LH. LH. LH.

Nutrition exerts a life-long impact on human health, and the interaction between nutrition and health has been known for centuries. The recent literature has suggested that nutrition could differently influence the health of male and female individuals. Until the last decade of the 20th century, research on women has been neglected, and the results obtained in men have been directly translated to women in both the medicine and nutrition fields. Consequently, most modern guidelines are based on studies predominantly conducted on men. However, there are many sex-gender differences that are the result of multifactorial inputs, including gene repertoires, sex steroid hormones, and environmental factors (e.g., food components). The effects of these different inputs in male and female physiology will be different in different periods of ontogenetic development as well as during pregnancy and the ovarian cycle in females, which are also age dependent. As a result, different strategies have evolved to maintain male and female body homeostasis, which, in turn, implies that there are important differences in the bioavailability, metabolism, distribution, and elimination of foods and beverages in males and females. This article will review some of these differences underlying the impact of food components on the risk of developing diseases from a sex-gender perspective.

Aegle marmelos, a plant indigenous to India has been used by the inhabitants of the Indian subcontinent for over 5000 years. The leaves, bark, roots, fruits and seeds are used extensively in the Indian traditional system of medicine the Ayurveda and in various folk medicine to treat myriad ailments. Bael fruits are of dietary use and the fruit pulp is used to prepare delicacies like murabba, puddings and juice. Bael fruits are also used in the treatment of chronic diarrhea, dysentery, and peptic ulcers, as a laxative and to recuperate from respiratory affections in various folk medicines. Scientific studies have validated many of the ethnomedicinal uses and reports indicate that the fruit possesses broad range of therapeutic effects that includes free radical scavenging, antioxidant, inhibition of lipid peroxidation, antibacterial, antiviral, anti-diarrheal, gastroprotective, anti-ulcerative colitis, hepatoprotective, antidiabetic, cardioprotective and radioprotective effects. For the first time, this review critically assesses the nutritional values, phytochemistry and preclinical pharmacological properties of the bael fruit. Attempts are also made at emphasizing the dietary and pharmaceutical potential of bael fruit that has been largely underutilized and neglected.

The blood-brain barrier (BBB) is a dynamic and complex interface between blood and the central nervous system that strictly controls the exchanges between the blood and brain compartments, therefore playing a key role in brain homeostasis and providing protection against many toxic compounds and pathogens. In this review, the unique properties of brain microvascular endothelial cells and intercellular junctions are examined. The specific interactions between endothelial cells and basement membrane as well as neighboring perivascular pericytes, glial cells and neurons, which altogether constitute the neurovascular unit and play an essential role in both health and function of the central nervous system, are also explored. Some relevant pathways across the endothelium, as well as mechanisms involved in the regulation of BBB permeability, and the emerging role of the BBB as a signaling interface are addressed as well. Furthermore, we summarize some of the experimental approaches that can be used to monitor BBB properties and function in a variety of conditions and have allowed recent advances in BBB knowledge. Elucidation of the molecular anatomy and dynamics of the BBB is an essential step for the development of new strategies directed to maintain or restore BBB integrity and barrier function and ultimately preserve the delicate interstitial brain environment.

We construct a two-variable analogue of Perrin-Riou's p-adic regulator map for the Iwasawa cohomology of a crystalline representation of the absolute Galois group of Qp, over a Galois extension whose Galois group is an abelian p-adic Lie group of dimension 2.

Neurodegenerative diseases constitute a worldwide health problem. Metals like iron and copper are essential for life, but they are also involved in several neurodegenerative mechanisms such as protein aggregation, free radical generation and oxidative stress.

En la edad pediátrica el concepto de unidad integral donde las partes se complementan entre sí y la afección de una de ellas repercute en las demás, marca el impacto de la prevención al priorizar lo importante sobre lo urgente. Esto responsabiliza a los profesionales de la salud a tener una visión completa e interdisciplinaria para garantizar la calidad de vida como proyecto futuro del niño.

Warburg effect Aerobic glycolysis Glycolytic inhibitors Targeted drug delivery to cancer Delocalized lipophilic cations Inhibitors of mitochondrial electron transport chain Biosynthetic alterations in cancer cells Mitochondrial redox system Mitochondrial apoptotic machinery Triphenylphosphonium compounds Cancer cells are characterized by self-sufficiency in the absence of growth signals, their ability to evade apoptosis, resistance to anti-growth signals, sustained angiogenesis, uncontrolled proliferation, and invasion and metastasis. Alterations in cellular bioenergetics are an emerging hallmark of cancer. The mitochondrion is the major organelle implicated in the cellular bioenergetic and biosynthetic changes accompanying cancer. These bioenergetic modifications contribute to the invasive, metastatic and adaptive properties typical in most tumors. Moreover, mitochondrial DNA mutations complement the bioenergetic changes in cancer. Several cancer management therapies have been proposed that target tumor cell metabolism and mitochondria. Glycolytic inhibitors serve as a classical example of cancer metabolism targeting agents. Several TCA cycle and OXPHOS inhibitors are being tested for their anticancer potential. Moreover, agents targeting the PDC/PDK (pyruvate dehydrogenase complex/pyruvate dehydrogenase kinase) interaction are being studied for reversal of Warburg effect. Targeting of the apoptotic regulatory machinery of mitochondria is another potential anticancer field in need of exploration. Additionally, oxidative phosphorylation uncouplers, potassium channel modulators, and mitochondrial redox are under investigation for their anticancer potential. To this end there is an increased demand for agents that specifically hit their target. Delocalized lipophilic cations have shown tremendous potential in delivering anticancer agents selectively to tumor cells. This review provides an overview of the potential anticancer agents that act by targeting cancer cell metabolism and mitochondria, and also brings us face to face with the emerging opportunities in cancer therapy. permeability transition; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 99 m-Tc-MIBI, 99 m-Tc-Sestamibi; MTD, maximum tolerated dose; mTOR, mammalian target of rapamycin; NAD + , nicotinamide adenine dinucleotide (oxidized); NADH, nicotinamide adenine dinucleotide (reduced); NADPH, nicotinamide adenine dinucleotide phosphate (reduced); NCI, National Cancer Institute; NFAT, nuclear factor of activated T cells; NO, nitric oxide; OXPHOS, oxidative phosphorylation; PCD, programmed cell death; PDC, pyruvate dehydrogenase

Exhaust gas recirculation (EGR) strategy has been recently employed in natural gas SI engines as an alternative to lean burn technique in order to satisfy the increasingly stringent emission standards. However, the effect of EGR on some of engine performance parameters compared to lean burn is not yet quite certain. In the current study, the effect of both EGR and lean burn on natural gas SI engine performance was compared at similar operating conditions. This was achieved numerically by developing a computer simulation of the four-stroke spark-ignition natural gas engine. A two-zone combustion model was developed to simulate the in-cylinder conditions during combustion. A kinetic model based on the extended Zeldovich mechanism was also developed in order to predict NO emission. The combustion model was validated using experimental data and a good agreement between the results was found. It was demonstrated that adding EGR to the stoichiometric inlet charge at constant inlet pressure of 130 kPa decreased power more rapidly than excess air; however, the power loss was recovered by increasing the inlet pressure from 130 kPa at zero dilution to 150 kPa at 20% EGR dilution. The engine fuel consumption increased by 10% when 20% EGR dilution was added at inlet pressure of 150 kPa compared to using 20% air dilution at 130 kPa. However, it was found that EGR dilution strategy is capable of producing extremely lower NO emission than lean burn technique. NO emission was reduced by about 70% when the inlet charge was diluted at a rate of 20% using EGR instead of excess air.

Barometric pressure falls with increasing altitude and consequently there is a reduction in the partial pressure of oxygen resulting in a hypoxic challenge to any individual ascending to altitude. A spectrum of high altitude illnesses can occur when the hypoxic stress outstrips the subject's ability to acclimatize. Acute altitude-related problems consist of the common syndrome of acute mountain sickness, which is relatively benign and usually self-limiting, and the rarer, more serious syndromes of high-altitude cerebral edema and high-altitude pulmonary edema. A common feature of acute altitude illness is rapid ascent by otherwise fit individuals to altitudes above 3000 m without sufficient time to acclimatize. The susceptibility of an individual to highaltitude syndromes is variable but generally reproducible. Prevention of altitude-related illness by slow ascent is the best approach, but this is not always practical. The immediate management of serious illness requires oxygen (if available) and descent of more than 300 m as soon as possible. In this article, we describe the setting and clinical features of acute mountain sickness and highaltitude cerebral edema, including an overview of the known pathophysiology, and explain contemporary practices for both prevention and treatment exploring the comprehensive evidence base for the various interventions. (Prog Cardiovasc Dis 2010;52:467-484) An additional clinical assessment scoring is sometimes used. GI indicates gastrointestinal.

Pesticides are widely used in agricultural and other settings, resulting in continued human exposure. Pesticide toxicity has been clearly demonstrated to alter a variety of neurological functions. Particularly, there is strong evidence suggesting that pesticide exposure predisposes to neurodegenerative diseases. Epidemiological data has suggested a relationship between pesticide exposure and brain neurodegeneration. However, an increasing debate has aroused regarding this issue. Paraquat is a highly toxic quaternary nitrogen herbicide which has been largely studied as a model for Parkinson's disease providing valuable insight into the possible mechanisms involved in the toxic effects of pesticides and their role in the progression of neurodegenerative diseases. In this work, we review the molecular mechanisms involved in the neurotoxic actions of pesticides, with a particular emphasis on the mechanisms associated with the induction neuronal cell death by paraquat as a model for Parkinsonian neurodegeneration.

1 de 228 LEY FEDERAL DEL TRABAJO Nueva Ley publicada en el Diario Oficial de la Federación el 1º de abril de 1970 TEXTO VIGENTE Última reforma publicada DOF 09-04-2012 Al margen un sello con el Escudo Nacional, que dice: Estados Unidos Mexicanos.-Presidencia de la República. GUSTAVO DIAZ ORDAZ, Presidente Constitucional de los Estados Unidos Mexicanos, a sus habitantes, sabed: Que el H. Congreso de la Unión se ha servido dirigirme el siguiente D E C R E T O: El Congreso de los Estados Unidos Mexicanos decreta: LEY FEDERAL DEL TRABAJO TITULO PRIMERO Principios Generales Artículo 1o.-La presente Ley es de observancia general en toda la República y rige las relaciones de trabajo comprendidas en el artículo 123, Apartado A, de la Constitución.

The prevalence and severity of obesity, type 2-diabetes, and the resultant metabolic syndrome are rapidly increasing. As successful preventive and therapeutic strategies for these life-threatening health ailments often come with adverse side effects, nutritional elements are widely used in many countries as preventive therapies to prevent or manage metabolic syndrome. Fruits are important dietary components, and contain various bioactive constituents. Many of these constituents have been proven to be useful to manage and treat various chronic diseases such as diabetes, obesity, cancer and cardiovascular diseases. Although exotic fruits are understudied throughout the world due to their limited regional presence, many studies reveal their potent ability to ameliorate metabolic derangements and the resultant conditions i.e. diabetes and obesity. The aim of this article is to review the role of exotic fruits and their constituents in the regulation of metabolic functions, which can beneficially alter diabetes and obesity pathophysiology.

Brain neuronal dysfunction has been implicated in pathogenesis of migraine but direct evidence is lacking. Scintillating scotoma of migraine is generally believed to originate at the visual cortex. While cortical spreading depression is a relatively late physiological alteration in migraine, its protective role in neuronal ischaemia is increasingly being recognized. Atenolol, nadolol, or verapamil prevent migraine but do not readily cross the blood–brain barrier or critically influence any brain or peripheral neuronal function. Typical migraine headache, aura, or scintillating scotoma has not been reported following enucleation or evisceration of the eye. In humans, pain and temperature fibres from only the ophthalmic division of the trigeminal nerve reach the upper cervical spinal segments. Pain in migraine attacks including occipital and nuchal discomfort reflects selective involvement of the ophthalmic nerve. Photophobia is largely a retinal reflex involving the ophthalmic division of the trigeminal nerve. Key clinical features of the migrainous scintillating scotoma are consistent with retinal origin. Spreading depression in the retina is well-established. A subtle regional ocular sympathetic deficit prevails in migraine patients and possibly impairs regulation of intraocular choroidal blood volume and intraocular pressure. Several first-line migraine prophylactic agents lower the intraocular pressure. The neuro-ophthalmological basis for a monocular origin of migrainous scintillating scotomata due to mechanical deformation of the posterior segment of the corneo-scleral envelope consequent to choroidal venous congestion and rise in intraocular pressure is presented. Study of distribution and displaceability of the migrainous scintillating scotoma can settle its site of origin. Headache of migraine possibly arises from a similar mechanical deformation of the anterior eye segment followed by antidromic discharge in the trigeminovascular system. Lateralizing negative deficits such as homonymous hemianopia probably reflect vasospastic complications of migraine. A rational explanation for the most characteristic clinical features of migraine and a new template to elucidate the pharmacological basis of anti-migraine drugs is offered.