Viral aetiology influenza like illnesses in Santa Cruz, Bolivia (2010-2012).

BACKGROUND: Acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of Influenza Like Illnesses (ILIs) remain largely unknown in developing countries. This study represents the first attempt to characterise viral aetiologies of ILIs in Bolivia. METHODS: It was performed in Santa Cruz city from January 2010 to September 2012, based on 564 naso-pharyngeal swabs collected in a National Reference Laboratory and real-time PCR techniques, viral cultures and phylogenetic analyses. RESULTS: 50.2% of samples were positive for at least one virus with influenza viruses (Flu A: ~15%; Flu B: ~9%), rhinoviruses (~8%), coronaviruses (~5%) and hRSV (~4%) being the most frequently identified. The pattern of viral infections varied according to age groups. The elucidation rate was the highest (>60%) amongst patients under 10 yo and the lowest (<40%) amongst patients ≥60 yo. Nearly 3% of samples showed dual viral infections. Epidemiological peaks were associated with a predominant virus but generally included 30-50% of infections by different viruses. Unexpectedly, the frequency of influenza in the 0-4 yo population was very low and a complete hRSV eclipse occurred in 2011. Genetic analyses indicated that distinct evolutionary lineages of Flu A(H1N1)pdm2009, Flu A/H3N2 and Flu B have co-circulated in Bolivia in the study period, originating from Central and North America, Europe, Asia and Australia. CONCLUSION: Our results emphasise the requirement for a reinforced epidemiological and genetic follow-up of influenza and other ILIs in Bolivia to further inform the preparation of vaccines used in the region, guide vaccination campaigns and improve the medical management of patients.

Pneumatophore CO2 effluxes decrease with increased salinity in mangrove forests of Yucatan, Mexico.

Although mangrove forests are great carbon sinks, they also release carbon dioxide (CO2) from soil, plants, and water through respiration. Many studies have focused on CO2 effluxes only from soils, but the role of biogenic structures such as pneumatophore roots has been poorly studied. Hence, CO2 effluxes from pneumatophores were quantified at sediment-air (non-flooded sediment) and water-air (flooded sediment) interfaces along a salinity gradient in three mangrove types (fringe, scrub, and basin) dominated by Avicennia germinans during the dry and rainy seasons in Yucatan, Mexico. Pneumatophore abundance explained up to 91% of CO2 effluxes for scrub, 87% for fringe, and 83% for basin mangrove forests at the water-air interface. Overall, CO2 effluxes were inversely correlated with temperature and salinity. The highest CO2 effluxes were in the fringe and the lowest were in the scrub mangrove forests. Flooding decreased CO2 effluxes from the dry to the rainy season in all mangrove forests. These results highlight the contribution of pneumatophores to mangrove respiration, and the need to include them in our current carbon budgets and models, but considering different exchange interfaces, seasons, and mangrove ecotypes.

Online Sexual Abuse and Symptomatology in Chilean Adolescents: The Role of Peer Support.

Several authors are studying sexual abuse via the Internet and its consequences. However, the available studies have not sufficiently detected factors that could help reduce the symptoms that victims may experience. Given the importance of peers during adolescence, especially in the online world, the objective of this study was to evaluate the relationship between online sexual abuse, perceived peer support, and internalizing and externalizing symptomatology. Three hundred and eighty Chilean adolescents (M = 16.12 years, SD = .52, 49.7% girls, 50.3% boys) responded to a set of self-report instruments. The results showed a relationship between online sexual abuse and depressive symptomatology, as well as self-injurious and antisocial behaviors. In turn, peer support was inversely associated with internalizing symptomatology. Results of the study highlight the relevance of peers as factors in intervention programs for adolescents dealing with online sexual abuse.

Improvement in Lactose Tolerance in Hypolactasic Subjects Consuming Ice Creams with High or Low Concentrations of Bifidobacterium bifidum 900791.

Although Bifidobacterium bifidum expresses lactase activity, no clinical trials have determined its impact on lactose-intolerant subjects. This study evaluated whether acute and chronic ingestion of ice creams containing B. bifidum 900791 at high (107 CFU/g) or low (105 CFU/g) concentrations improved lactose tolerance in hypolactasic subjects. Fifty subjects were selected based on a positive lactose (20 g) hydrogen breath test (HBT0) and the presence of digestive symptoms. The recruited subjects were required to perform breath tests after the acute ingestion of: (1) ice cream containing 20 g of lactose without a probiotic (HBT1); (2) the same ice cream, accompanied by a lactase tablet (HBT2); (3) the same ice cream containing the low or high dose of probiotic (HBT3-LD and HBT3-HD); and (4) after the chronic consumption of the ice cream without (placebo) or with the low concentration of probiotic for 1 month (HBT4). Significant decreases in H2 excretion during HBT2 and HBT3-HD as well as digestive symptoms during HBT2, HBT3-HD and HBT3-LD were observed compared to HBT0 and HBT1, while the orocecal transit time increased. Chronic consumption of the probiotic ice cream did not enhance lactose tolerance compared to the placebo. These results suggest that the acute ingestion of ice cream containing high or low concentrations of B. bifidum 900791 improves lactose tolerance in hypolactasic subjects.

Carboxymethyl cellulose coated magnetic nanoparticles transport across a human lung microvascular endothelial cell model of the blood-brain barrier.

Sustained and safe delivery of therapeutic agents across the blood-brain barrier (BBB) is one of the major challenges for the treatment of neurological disorders as this barrier limits the ability of most drug molecules to reach the brain. Targeted delivery of the drugs used to treat these disorders could potentially offer a considerable reduction of the common side effects of their treatment. The preparation and characterization of carboxymethyl cellulose (CMC) coated magnetic nanoparticles (Fe3O4@CMC) is reported as an alternative that meets the need for novel therapies capable of crossing the BBB. In vitro assays were used to evaluate the ability of these polysaccharide coated biocompatible, water-soluble, magnetic nanoparticles to deliver drug therapy across a model of the BBB. As a drug model, dopamine hydrochloride loading and release profiles in physiological solution were determined using UV-Vis spectroscopy. Cell viability tests in Human Lung Microvascular Endothelial (HLMVE) cell cultures showed no significant cell death, morphological changes or alterations in mitochondrial function after 24 and 48 h of exposure to the nanoparticles. Evidence of nanoparticle interactions and nanoparticle uptake by the cell membrane was obtained by electron microscopy (SEM and TEM) analyses. Permeability through a BBB model (the transwell assay) was evaluated to assess the ability of Fe3O4@CMC nanoparticles to be transported across a densely packed HLMVE cell barrier. The results suggest that these nanoparticles can be useful drug transport and release systems for the design of novel pharmaceutical agents for brain therapy.

Redox Signaling, Neuroinflammation, and Neurodegeneration.

SIGNIFICANCE: Production of pro-inflammatory and anti-inflammatory cytokines is part of the defense system that mostly microglia and macrophages display to induce normal signaling to counteract the deleterious actions of invading pathogens in the brain. Also, redox activity in the central nervous system (CNS) constitutes an integral part of the metabolic processes needed by cells to exert their normal molecular and biochemical functions. Under normal conditions, the formation of reactive oxygen and nitrogen species, and the following oxidative activity encounter a healthy balance with immunological responses to preserve cell functions in the brain. However, under different pathological conditions, inflammatory responses recruit pro-oxidant signals and vice versa. The aim of this article is to review the basic concepts about the triggering of inflammatory and oxidative responses in the CNS. Recent Advances: Diverse concurrent toxic pathways are described to provide a solid mechanistic scope for considering intervention at the experimental and clinical levels that are aimed at diminishing the harmful actions of these two contributing factors to nerve cell damage. Critical Issues and Future Directions: The main conclusion supports the existence of a narrow cross-talk between pro-inflammatory and oxidative signals that can lead to neuronal damage and subsequent neurodegeneration. Further investigation about critical pathways crosslinking oxidative stress and inflammation will strength our knowlegde on this topic. Antioxid. Redox Signal. 28, 1626-1651.

The Antiepileptic Drug Levetiracetam Protects Against Quinolinic Acid-Induced Toxicity in the Rat Striatum.

Levetiracetam (LVT) is a relatively novel antiepileptic drug (AED) known to act through binding with the synaptic vesicular 2A (SV2A) protein, thus modulating the presynaptic neurotransmitter release. The tryptophan metabolite quinolinic acid (QUIN) acts as an excitotoxin when its brain concentrations reach toxic levels under pathological conditions. Since increased neuronal excitability induced by QUIN recruits degenerative events in the brain, and novel AED is also expected to exert neuroprotective effects in their pharmacological profiles, in this work the effect of LVT (54 mg/kg, i.p., administered for seven consecutive days) was tested as a pretreatment against the toxicity evoked by the bilateral intrastriatal injection of QUIN (60 nmol/µl) to adult rats. QUIN increased the striatal levels of peroxidized lipids and carbonylated proteins as indexes of oxidative damage 24 h after its infusion. In addition, in synaptosomal fractions isolated from QUIN-lesioned rats 24 h after the toxin infusion, γ-aminobutyric acid (GABA) release was decreased, whereas glutamate (Glu) release was increased. QUIN also decreased motor activity and augmented the rate of cell damage at 7 days post-lesion. All these alterations were significantly prevented by pretreatment of rats with LVT. The results of this study show a neuroprotective role and antioxidant action of LVT against the brain damage induced by excitotoxic events.

Neuroprotective effect of WIN55,212-2 against 3-nitropropionic acid-induced toxicity in the rat brain: involvement of CB1 and NMDA receptors.

The endocannabinoid system (ECS), and agonists acting on cannabinoid receptors (CBr), are known to regulate several physiological events in the brain, including modulatory actions on excitatory events probably through N-methyl-D-aspartate receptor (NMDAr) activity. Actually, CBr agonists can be neuroprotective. The synthetic CBr agonist WIN55,212-2 acts mainly on CB1 receptor. In turn, the mitochondrial toxin 3-nitropropionic acid (3-NP) produces striatal alterations in rats similar to those observed in the brain of Huntington's disease patients. Herein, the effects of WIN55,212-2 were tested on different endpoints of the 3-NP-induced toxicity in rat brain synaptosomes and striatal tissue. Motor activity was also evaluated. The 3-NP (1 mM)-induced mitochondrial dysfunction and lipid peroxidation was attenuated by WIN55,212-2 (1 µM) in synaptosomal fractions. The intrastriatal bilateral injection of 3-NP (500 nmol/µL) to rats increased lipid peroxidation and locomotor activity, augmented the rate of cell damage, and decreased the striatal density of neuronal cells. These alterations were accompanied by transcriptional changes in the NMDA (NR1 subunit) content. The administration of WIN55212-2 (1 mg/kg, i.p.) to rats for six consecutive days, before the 3-NP injection, exerted preventive effects on all alterations elicited by the toxin. The prevention of the 3-NP-induced NR1 transcriptional alterations by the CBr agonist together with the increase of CB1 content suggest an early reduction of the excitotoxic process via CBr activation. Our results demonstrate a protective role of WIN55,212-2 on the 3-NP-induced striatal neurotoxicity that could be partially related to the ECS stimulation and induction of NMDAr hypofunction, representing an effective therapeutic strategy at the experimental level for further studies.

Cannabinoids: Glutamatergic Transmission and Kynurenines.

The endocannabinoid system (ECS) comprises a complex of receptors, enzymes, and endogenous agonists that are widely distributed in the central nervous system of mammals and participates in a considerable number of neuromodulatory functions, including neurotransmission, immunological control, and cell signaling. In turn, the kynurenine pathway (KP) is the most relevant metabolic route for tryptophan degradation to form the metabolic precursor NAD(+). Recent studies demonstrate that the control exerted by the pharmacological manipulation of the ECS on the glutamatergic system in the brain may offer key information not only on the development of psychiatric disorders like psychosis and schizophrenia-like symptoms, but it also may constitute a solid basis for the development of therapeutic strategies to combat excitotoxic events occurring in neurological disorders like Huntington's disease (HD). Part of the evidence pointing to the last approach is based on experimental protocols demonstrating the efficacy of cannabinoids to prevent the deleterious actions of the endogenous neurotoxin and KP metabolite quinolinic acid (QUIN). These findings intuitively raise the question about what is the precise role of the ECS in tryptophan metabolism through KP and vice versa. In this chapter, we will review basic concepts on the physiology of both the ECS and the KP to finally describe those recent findings combining the components of these two systems and hypothesize the future course that the research in this emerging field will take in the next years.

Lesiones acroisquémicas severas en contexto de covid-19: casuística / Severe acroischemic injuries in the context of covid-19: casuistry

RESUMEN Introducción: desde el inicio de la pandemia declarada en marzo del 2020 por la Organización Mundial de la Salud, la piel no se ve excluida de esta afectación, al inicio descripta como hallazgo poco frecuente, actualmente se estima que un 20 % de los pacientes con COVID-19 presentan algún tipo de manifestación dermatológica que se presenta durante la fase aguda de la enfermedad o durante la convalecencia. Las lesiones cutáneas son diversas, entre ellas llama la atención por su importancia y severidad las acroisquémicas. Objetivo: describir las características demográficas, clínicas, laboratoriales y evolutivas de 6 casos de COVID-19 con lesiones acroisquémicas severas. Metodología: estudio retrospectivo, descriptivo y observacional de casos de COVID-19 confirmados por pruebas laboratoriales con lesiones acroisquémicas severas interconsultados en el Servicio de Dermatología del Hospital Nacional o de la consulta privada en el periodo julio 2020 a julio 2021. Resultados: se analizaron 6 casos, 3 mujeres y 3 varones, con promedio de edad de 61.6 años, todos con diagnóstico confirmado de COVID-19. Los patrones clínicos de lesiones acroisquémicas observados fueron 2 isquemias microcirculatorias severas y 4 gangrenas secas. Todos los pacientes presentaron alguna comorbilidad y dímero D elevado. Uno recibió tratamiento ambulatorio, 4 en sala de internados y 1 en unidad de cuidados intensivos. Todos recibieron anticoagulación. La evolución fue satisfactoria en 2 de ellos, en 2 fue necesaria la amputación parcial o total de los miembros afectados y 1 obitó. Conclusión: las lesiones cutáneas acroisquémicas en pacientes que cursan o han cursado con COVID-19 son poco frecuentes, se presentan por lo general en personas mayores y están asociados a un peor pronóstico en cuanto a morbimortalidad.

ABSTRACT Introduction: since the beginning of the pandemic declared in March 2020 by the World Health Organization, the skin is not excluded from this affectation, initially described as a rare finding, currently it is estimated that 20% of patients with COVID-19 present some type of dermatological manifestation that manifests itself during the acute phase of the disease or during convalescence. Skin lesions are diverse, among them acroischemic ones are striking for their importance and severity. Objective: to describe the demographic, clinical, laboratory and evolutionary characteristics of 6 cases of COVID-19 with severe acroischemic lesions. Methodology: Retrospective, descriptive and observational study of COVID-19 cases confirmed by laboratory tests with severe acroischemic lesions consulted in the "Servicio de Dermatología" del "Hospital Nacional" or the private practice in the period July 2020 to July 2021. Results: 6 cases were analyzed, 3 women and 3 men, with an average age of 61.6 years, all with a confirmed diagnosis of COVID-19. The clinical patterns of acroischemic lesions observed were 2 severe microcirculatory ischemia and 4 dry gangrene. All patients had some comorbidity and elevated D-dimer. One received outpatient treatment, 4 in the inpatient ward and 1 in the intensive care unit. All received anticoagulation. The evolution was satisfactory in 2 of them, in 2 it was necessary the partial or total amputation of the affected limbs and 1 died. Conclusion: acroischemic skin lesions in patients with or who have had COVID-19 are rare, generally occur in older people, and are associated with a worse prognosis in terms of morbidity and mortality.

On the Relationship Between the Light/Dark Cycle, Melatonin and Oxidative Stress.

The adaptation of species to the environment in which they live is accomplished by so-called "clocks" that allow the biological, physiological, metabolic and behavioral system to correct any development during the day. The alteration of those 'clocks' (circadian rhythms) shows a strong relationship with organic disorders such as neurodegenerative diseases. Many studies show that oxidative stress combined with pro-inflammatory mechanisms, play a key role in the development of neurodegenerative diseases and psychiatric disorders. Oxidative stress is fought by many antioxidant molecules. Melatonin, a hallmark of circadian rhythm functionality, is a natural antioxidant with a circadian secretion pattern. The mechanisms involved in the antioxidant properties of melatonin are complex but its depletion or lack unequivocally leads to cell damage. This process is also linked to the disruption of the circadian rhythm. A disrupted circadian rhythm followed by oxidative stress and inflammatory processes could be the pathophysiological basis for several disorders of the central nervous system. In the current review we will analyze those interactions. We will focus on the relationship between melatonin and its light/dark rhythms of secretion and how the antioxidant properties of melatonin opens a new therapeutic hope against central nervous system disorders.

Potential Therapeutic Targets of the Endocannabinoid System in Common Neurodegenerative Disorders and Organic Acidemias

Abstract The cannabinoid chemistry is currently being addressed in preclinical approaches as a viable therapeutic alternative for the management of a wide range of signs, symptoms, and some biochemical hallmarks of many neurological pathologies (such as neuroinflammation and neurodegeneration). This clinical orientation is grounded on the consistent promissory profile that cannabinoid compounds have shown, and the great necessity of feasible options to undergo such disorders. Even though at early research stages, metabolic disorders are starting to rise as potential targets of cannabinoid alternatives; approaches in this term could, in turn, aim to modulate the endocannabinoid response for therapeutic purposes. This review recalls the pathologic scenarios endured in the course of neurological diseases of high occurrence and the most typical metabolic disorders, while discussing the neuroprotective mechanisms of cannabinoid agonists in the central nervous system, and the potential targets of the endocannabinoid system and metabolic disorders.