The Mediterranean benthic herbivores show diverse responses to extreme storm disturbances

Catastrophic storms have been observed to be one of the major elements in shaping the standing structure of marine benthic ecosystems. Yet, little is known about the effect of catastrophic storms on ecosystem processes. Specifically, herbivory is the main control mechanism of macrophyte communities in the Mediterranean, with two main key herbivores: the sea urchin Paracentrotus lividus and the fish Sarpa salpa. Consequently, the effects of extreme storm events on these two herbivores (at the population level and on their behaviour) may be critical for the functioning of the ecosystem. With the aim of filling this gap, we took advantage of two parallel studies that were conducted before, during and after an unexpected catastrophic storm event. Specifically, fish and sea urchin abundance were assessed before and after the storm in monitored fixed areas (one site for sea urchin assessment and 3 sites for fish visual transects). Additionally, we investigated the behavioural response to the disturbance of S. salpa fishes that had been tagged with acoustic transmitters. Given their low mobility, sea urchins were severely affected by the storm (ca. 50% losses) with higher losses in those patches with a higher density of sea urchins. This may be due to a limited availability of refuges within each patch. In contrast, fish abundance was not affected, as fish were able to move to protected areas (i.e. deeper) as a result of the high mobility of this species. Our results highlight that catastrophic storms differentially affect the two dominant macroherbivores of rocky macroalgal and seagrass systems due to differences in mobility and escaping strategies. This study emphasises that under catastrophic disturbances, the presence of different responses among the key herbivores of the system may be critical for the maintenance of the herbivory function.

Clinico-Pathological discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis

Background Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death. Methods and Findings A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n ¼ 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%). Conclusions Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.

Direct tumor recognition by a human CD4(+) T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses.

Tumor antigen-specific CD4(+) T cells generally orchestrate and regulate immune cells to provide immune surveillance against malignancy. However, activation of antigen-specific CD4(+) T cells is restricted at local tumor sites where antigen-presenting cells (APCs) are frequently dysfunctional, which can cause rapid exhaustion of anti-tumor immune responses. Herein, we characterize anti-tumor effects of a unique human CD4(+) helper T-cell subset that directly recognizes the cytoplasmic tumor antigen, NY-ESO-1, presented by MHC class II on cancer cells. Upon direct recognition of cancer cells, tumor-recognizing CD4(+) T cells (TR-CD4) potently induced IFN-γ-dependent growth arrest in cancer cells. In addition, direct recognition of cancer cells triggers TR-CD4 to provide help to NY-ESO-1-specific CD8(+) T cells by enhancing cytotoxic activity, and improving viability and proliferation in the absence of APCs. Notably, the TR-CD4 either alone or in collaboration with CD8(+) T cells significantly inhibited tumor growth in vivo in a xenograft model. Finally, retroviral gene-engineering with T cell receptor (TCR) derived from TR-CD4 produced large numbers of functional TR-CD4. These observations provide mechanistic insights into the role of TR-CD4 in tumor immunity, and suggest that approaches to utilize TR-CD4 will augment anti-tumor immune responses for durable therapeutic efficacy in cancer patients.

Monitoring Fatigue Status with HRV Measures in Elite Athletes : An Avenue Beyond RMSSD?

Among the tools proposed to assess the athlete's "fatigue," the analysis of heart rate variability (HRV) provides an indirect evaluation of the settings of autonomic control of heart activity. HRV analysis is performed through assessment of time-domain indices, the square root of the mean of the sum of the squares of differences between adjacent normal R-R intervals (RMSSD) measured during short (5 min) recordings in supine position upon awakening in the morning and particularly the logarithm of RMSSD (LnRMSSD) has been proposed as the most useful resting HRV indicator. However, if RMSSD can help the practitioner to identify a global "fatigue" level, it does not allow discriminating different types of fatigue. Recent results using spectral HRV analysis highlighted firstly that HRV profiles assessed in supine and standing positions are independent and complementary; and secondly that using these postural profiles allows the clustering of distinct sub-categories of "fatigue." Since, cardiovascular control settings are different in standing and lying posture, using the HRV figures of both postures to cluster fatigue state embeds information on the dynamics of control responses. Such, HRV spectral analysis appears more sensitive and enlightening than time-domain HRV indices. The wealthier information provided by this spectral analysis should improve the monitoring of the adaptive training-recovery process in athletes.

Las entidades sub-nacionales en Norteamérica y la lucha contra el cambio climático: desarrollo normativo y vinculación de sistemas de comercio de derechos de emisión

[spa] Mientras que en Europa la interdependencia y la dimensión transfronteriza de las cuestiones ligadas al cambio climático ha facilitado una cierta"continentalización" de la gestión de este fenómeno, favorecida por el carácter intergubernamental de las medidas que se adoptan en el marco de la Unión Europea, al otro lado del Atlántico la transversalidad de este mismo fenómeno explica la necesidad de que, ante las limitaciones del marco regional, se pongan en marcha mecanismos que faciliten la intervención no sólo estatal sino también de las entidades sub-nacionales. En este sentido, la ausencia de la acción federal tanto en Estados Unidos como en Canadá ha comportado un mayor desarrollo de la acción de las entidades sub-nacionales, que han tomado el liderazgo en la lucha contra el cambio climático. Son estas medidas las que se han visualizado en el escenario internacional. Ello ha favorecido el establecimiento de mecanismos de coordinación de la acción de estas entidades sub-nacionales en el seno de redes transnacionales, que han ido adquiriendo una mayor relevancia en la implementación del Convenio Marco sobre el Cambio Climático y del Protocolo de Kyoto, particularmente en relación a uno de sus instrumentos, el comercio de los derechos de emisión de gases de efecto invernadero. En este contexto, la futura vinculación de los sistemas de comercio de derechos de emisión de gases de efecto invernadero en Norteamérica con el sistema de la Unión Europea presenta diversos retos de carácter material y formal.

Anomalous sub aortic left brachiocephalic vein: a case report

The left brachiocephalic vein occasionally follows an aberrant course. It is usually associated with congenital cardiac anomaly. We present a case of anomalous left brachiocephalic vein which followed a sub aortic course, with no cardiac abnormality. Multi detector computed tomography is very useful in accurate diagnosis of this condition and prevents any further investigation in cases of isolated abnormalities.

Monitoring Fatigue Status with HRV Measures in Elite Athletes: An Avenue Beyond RMSSD?

Among the tools proposed to assess the athlete's "fatigue," the analysis of heart rate variability (HRV) provides an indirect evaluation of the settings of autonomic control of heart activity. HRV analysis is performed through assessment of time-domain indices, the square root of the mean of the sum of the squares of differences between adjacent normal R-R intervals (RMSSD) measured during short (5 min) recordings in supine position upon awakening in the morning and particularly the logarithm of RMSSD (LnRMSSD) has been proposed as the most useful resting HRV indicator. However, if RMSSD can help the practitioner to identify a global "fatigue" level, it does not allow discriminating different types of fatigue. Recent results using spectral HRV analysis highlighted firstly that HRV profiles assessed in supine and standing positions are independent and complementary; and secondly that using these postural profiles allows the clustering of distinct sub-categories of "fatigue." Since, cardiovascular control settings are different in standing and lying posture, using the HRV figures of both postures to cluster fatigue state embeds information on the dynamics of control responses. Such, HRV spectral analysis appears more sensitive and enlightening than time-domain HRV indices. The wealthier information provided by this spectral analysis should improve the monitoring of the adaptive training-recovery process in athletes.

Comparison of acute non-visual bright light responses in patients with optic nerve disease, glaucoma and healthy controls.

This study examined the effect of optic nerve disease, hence retinal ganglion cell loss, on non-visual functions related to melanopsin signalling. Test subjects were patients with bilateral visual loss and optic atrophy from either hereditary optic neuropathy (n = 11) or glaucoma (n = 11). We measured melatonin suppression, subjective sleepiness and cognitive functions in response to bright light exposure in the evening. We also quantified the post-illumination pupil response to a blue light stimulus. All results were compared to age-matched controls (n = 22). Both groups of patients showed similar melatonin suppression when compared to their controls. Greater melatonin suppression was intra-individually correlated to larger post-illumination pupil response in patients and controls. Only the glaucoma patients demonstrated a relative attenuation of their pupil response. In addition, they were sleepier with slower reaction times during nocturnal light exposure. In conclusion, glaucomatous, but not hereditary, optic neuropathy is associated with reduced acute light effects. At mild to moderate stages of disease, this is detected only in the pupil function and not in responses conveyed via the retinohypothalamic tract such as melatonin suppression.

Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice.

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and the risk of malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas.

Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and ultimately, the rate of malaria related morbidity and mortality. Potential vaccines being designed to complement current intervention efforts therefore need to be evaluated against different malaria endemicity backgrounds. The associations between antibody responses to the chimeric merozoite surface protein 1 block 2 hybrid (MSP1 hybrid), glutamate-rich protein region 2 (GLURP R2) and the peptide AS202.11, and the risk of malaria were assessed in children living in malaria hyperendemic (Burkina Faso, n = 354) and hypo-endemic (Ghana, n = 209) areas. Using the same reagent lots and standardized protocols for both study sites, immunoglobulin (Ig) M, IgG and IgG sub-class levels to each antigen were measured by ELISA in plasma from the children (aged 6-72 months). Associations between antibody levels and risk of malaria were assessed using Cox regression models adjusting for covariates. There was a significant association between GLURP R2 IgG3 and reduced risk of malaria after adjusting age of children in both the Burkinabe (hazard ratio 0.82; 95 % CI 0.74-0.91, p < 0.0001) and the Ghanaian (HR 0.48; 95 % CI 0.25-0.91, p = 0.02) cohorts. MSP1 hybrid IgM was associated (HR 0.85; 95 % CI 0.73-0.98, p = 0.02) with reduced risk of malaria in Burkina Faso cohort while IgG against AS202.11 in the Ghanaian children was associated with increased risk of malaria (HR 1.29; 95 % CI 1.01-1.65, p = 0.04). These findings support further development of GLURP R2 and MSP1 block 2 hybrid, perhaps as a fusion vaccine antigen targeting malaria blood stage that can be deployed in areas of varying transmission intensity.

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates.

The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis.

Clinical and biochemical responses after Gamma Knife surgery for a dopamine-secreting paraganglioma: case report.

The efficacy of Gamma Knife surgery (GKS) in local tumor control of non-secreting paragangliomas (PGLs) has been fully described by previous studies. However, with regard to secreting PGL, only one previous case report exists advocating its efficacy at a biological level. The aims of this study were: 1) to evaluate the safety/efficacy of GKS in a dopamine-secreting PGL; 2) to investigate whether the biological concentrations of free methoxytyramine could be used as a marker of treatment efficacy during the follow-up. We describe the case of a 62-year-old man diagnosed with left PGL. He initially underwent complete surgical excision. Thirty months after, he developed recurrent biological and neuroradiological disease; the most sensitive biomarker for monitoring the disease, concentration of plasma free methoxytyramine, started to increase. GKS was performed at a maximal marginal dose of 16 Gy. During the following 30 months, concentration of free methoxytyramine gradually decreased from 0.14 nmol/l (2*URL) before GKS to 0.09 nmol/l, 6 months after GKS and 0.07 nmol/l at the last follow-up after GKS (1.1*URL), confirming the efficacy of the treatment. Additionally, at 30 months there was approximately 36.6% shrinkage from the initial target volume. The GKS treatment was safe and effective, this being confirmed clinically, neuroradiologically and biologically. The case illustrates the importance of laboratory tests taking into account methoxytyramine when analyzing biological samples to assess the biochemical activity of a PGL. In addition, the identification of methoxytyramine as a unique positive biomarker could designate it for the monitoring of tumor relapse after treatments, including Gamma Knife surgery.

Vulnerability of stream biota to climate change in mediterranean climate regions: a synthesis of ecological responses and conservation challenges

Freshwater species worldwide are experiencing dramatic declines partly attributable to ongoing climate change. It is expected that the future effects of climate change could be particularly severe in mediterranean climate (med-) regions, which host many endemic species already under great stress from the high level of human development. In this article, we review the climate and climate-induced changes in streams of med-regions and the responses of stream biota, focusing on both observed and anticipated ecological responses. We also discuss current knowledge gaps and conservation challenges. Expected climate alterations have already been observed in the last decades, and include: increased annual average air temperatures; decreased annual average precipitation; hydrologic alterations; and an increase in frequency, intensity and duration of extreme events, such as floods, droughts and fires. Recent observations, which are concordant with forecasts built, show stream biota of med-regions when facing climate changes tend to be displaced towards higher elevations and upper latitudes, communities tend to change their composition and homogenize, while some life-history traits seem to provide biota with resilience and resistance to adapt to the new conditions (as being short-lived, small, and resistant to low streamflow and desiccation). Nevertheless, such responses may be insufficient to cope with current and future environmental changes. Accurate forecasts of biotic changes and possible adaptations are difficult to obtain in med-regions mainly because of the difficulty of distinguishing disturbances due to natural variability from the effects of climate change, particularly regarding hydrology. Long-term studies are needed to disentangle such variability and improve knowledge regarding the ecological responses and the detection of early warning signals to climate change. Investments should focus on taxa beyond fish and macroinvertebrates, and in covering the less studied regions of Chile and South Africa. Scientists, policy makers and water managers must be involved in the climate change dialogue because the freshwater conservation concerns are huge.