Development and validation of a real-time PCR assay protocol for the specific detection and quantification of pelagiphages in seawater samples.

Earth is inhabited by numerous adaptations of cellular forms shaped by the persistent scrutiny of natural selection. Thus, as natural selection has fixed beneficial adaptations of functional traits, cellular life has conquered almost all environmental niches on our planet. However, cellular life succumbs in number and genetic diversity to viruses. Among all viruses, phages are highly prevalent in diverse environments, and due to their vast genetic diversity and abundance, their relevant role as significant players in several ecological processes is now fully recognized. Pelagiphages, bacteriophages infecting bacteria of the SAR11 clade, are the most abundant viruses in the oceans. However, the ecological contribution of pelagiphages on populations of Pelagibacterales remains largely underestimated. An essential aspect of estimating the impact of bacteriophages is their absolute and precise quantification, which provides relevant information about the host-virus interactions and the structure of viral assemblages. Consequently, due to its abundance and claimed influence in the biogeochemical cycling of elements, the accurate quantification of pelagiphages results in an essential task. This study describes the development and validation of a sensitive, specific, accurate and reproducible qPCR platform targeting pelagiphages. Moreover, this method allowed the detection and quantification of pelagiphages in the Gulf of California for the first time.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Consumo de riesgo de alcohol y sentido de vida en adolescentes de 18 a 20 años en Tezontepec de Aldama / Risk consumption of alcohol and its impact on the meaning of life in adolescents aged 18 to 20 in Tezontepec de Aldama

Introducción: el consumo de alcohol aumento en los últimos años en adolescentes, la Organización Mundial de la Salud (OMS) indica que América Latina se posiciona en primer lugar de consumo y México ocupa el décimo lugar, en la población adolescente 38.8 % ha consumido alcohol alguna vez en su vida. Objetivo: conocer el nivel de consumo de riesgo de alcohol y el sentido de vida en los adolescentes de 18 a 20 años de edad de la comunidad de Presas, Tezontepec de Aldama, Hidalgo. Material y métodos: de aplicabilidad básica, cuantitativo, con un nivel de alcance descriptivo; diseño metodológico no experimental (observacional), prolectivo, transversal, prospectivo. Resultados: por medio de la escala dimensional del sentido de vida, 34 participantes refieren tener una búsqueda de sentido de vida expresan, experimentar una vida sin propósito y sin sentido, aunque en ocasiones poseen momentos en los que se sienten orientados. En cuanto, al instrumento de medición AUDIT, 10 participantes refieren tener un alto consumo de alcohol. Conclusión: hoy el alcohol sigue siendo un problema en la comunidad adolescente al mismo tiempo impacta de manera negativa en su sentido de vida.

Introduction: adolescent alcohol consumption has increased in recent years. The World Health Organization (WHO) indicates that Latin America is ranked first in this consumption and Mexico's adolescent population occupies tenth place. 38.8% of them have consumed alcohol at some point in their life as much as you have consumed in the last year. Objective: to know the level of risky alcohol consumption and the meaning of life in adolescents between 18 and 20 years of age in the community of Presas, Tezontepec de Aldama. Material and methods: of basic applicability with a quantitative approach and with a descriptive scope level, with a methodological design; non-experimental (observational), prolective, transversal, prospective. Results: 34 participants report having a search for a sense of life, expressing that they are people who experience a life without purpose and meaning, although sometimes they have moments when they feel oriented. Regarding the results of the AUDIT Measurement Instrument, 10 participants report having a high consumption of alcohol, stating that they are personnel who consume alcohol more frequently. Conclusion: alcohol is still a problem in the community today. Adolescent at the same time negatively impacts their sense of life; since young people who are at risk of alcohol have a low meaning of life

Behavioral and Neural Signatures of Working Memory in Childhood.

Working memory function changes across development and varies across individuals. The patterns of behavior and brain function that track individual differences in working memory during human development, however, are not well understood. Here, we establish associations between working memory, other cognitive abilities, and functional MRI (fMRI) activation in data from over 11,500 9- to 10-year-old children (both sexes) enrolled in the Adolescent Brain Cognitive Development (ABCD) Study, an ongoing longitudinal study in the United States. Behavioral analyses reveal robust relationships between working memory, short-term memory, language skills, and fluid intelligence. Analyses relating out-of-scanner working memory performance to memory-related fMRI activation in an emotional n-back task demonstrate that frontoparietal activity during a working memory challenge indexes working memory performance. This relationship is domain specific, such that fMRI activation related to emotion processing during the emotional n-back task, inhibitory control during a stop-signal task (SST), and reward processing during a monetary incentive delay (MID) task does not track memory abilities. Together, these results inform our understanding of individual differences in working memory in childhood and lay the groundwork for characterizing the ways in which they change across adolescence.SIGNIFICANCE STATEMENT Working memory is a foundational cognitive ability that changes over time and varies across individuals. Here, we analyze data from over 11,500 9- to 10-year-olds to establish relationships between working memory, other cognitive abilities, and frontoparietal brain activity during a working memory challenge, but not during other cognitive challenges. Our results lay the groundwork for assessing longitudinal changes in working memory and predicting later academic and other real-world outcomes.

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study.

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data is a resource of unprecedented scale and depth for studying typical and atypical development. The aim of this manuscript is to describe the baseline neuroimaging processing and subject-level analysis methods used by ABCD. Processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI. This manuscript serves as a methodological reference for users of publicly shared neuroimaging data from the ABCD Study.

Neural Signaling of Cortisol, Childhood Emotional Abuse, and Depression-Related Memory Bias.

BACKGROUND: Cortisol has potent effects on learning and neuroplasticity, but little is known about its effects on negative memory biases in depression. Animal models show that aversive caregiving alters effects of glucocorticoids (primarily corticosterone in rodents and cortisol in primates) on learning and neuroplasticity into adulthood. METHODS: We investigated whether history of childhood emotional abuse (EA) moderated effects of cortisol administration (CORT) versus placebo on emotional memory formation in depression. Participants included 75 unmedicated women with varying levels of depression severity and/or EA history. In a double-blind crossover investigation, we used functional magnetic resonance imaging to measure effects of CORT (vs. placebo) on neural function during emotional memory formation. RESULTS: CORT eliminated the well-known relationship between depression severity and negative memory bias, a finding explained by EA severity. For women with a history of severe EA, CORT reduced depression-related negative memory bias and normalized recall for pleasant stimuli. EA severity also moderated CORT effects on neural function: in women with history of severe EA, CORT increased activation in the supplementary motor area during viewing of unpleasant relative to pleasant pictures. Additionally, supplementary motor area activation predicted reduced negative bias for pictures encoded during CORT. CONCLUSIONS: These results suggest that increasing cortisol signaling may be neurocognitively beneficial in depressed women with a history of maltreatment. The findings corroborate prior research suggesting that presence or absence of adverse caregiving is etiologically important in depression. These findings suggest potential neurocognitive mechanisms of therapeutics targeting cortisol signaling, which show promise in treating affective disorders.

The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition across 21 sites.

The ABCD study is recruiting and following the brain development and health of over 10,000 9-10 year olds through adolescence. The imaging component of the study was developed by the ABCD Data Analysis and Informatics Center (DAIC) and the ABCD Imaging Acquisition Workgroup. Imaging methods and assessments were selected, optimized and harmonized across all 21 sites to measure brain structure and function relevant to adolescent development and addiction. This article provides an overview of the imaging procedures of the ABCD study, the basis for their selection and preliminary quality assurance and results that provide evidence for the feasibility and age-appropriateness of procedures and generalizability of findings to the existent literature.

Neural and behavioral correlates of negative self-focused thought associated with depression.

A central feature of major depression (MDD) is heightened negative self-focused thought (negative-SFT). Neuroscientific research has identified abnormalities in a network of brain regions in MDD, including brain areas associated with SFT such as medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). To our knowledge no studies have investigated the behavioral and neural correlates of negative-SFT using a sentence completion task in a sample of individuals with varying depression histories and severities. We test the following hypotheses: (1) negative-SFT will be associated with depression; and (2) depression and negative-SFT will be related to resting-state functional connectivity (rsFC) for brain regions implicated in SFT. Seventy-nine women with varying depression histories and severities completed a sentence completion task and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Standard seed-based voxelwise rsFC was conducted for self-network regions of interest: dorsomedial PFC (dmPFC) and pregenual ACC (pgACC). We performed linear regression analyses to examine the relationships among depression, negative-SFT, and rsFC for the dmPFC and pgACC. Greater negative-SFT was associated with depression history and severity. Greater negative-SFT predicted increased rsFC between dmPFC and pgACC seeds and dorsolateral prefrontal (dlPFC) and parietal regions; depression group was also associated with increased pgACC-dlPFC connectivity. These findings are consistent with previous literature reporting elevated negative-SFT thought in MDD. Our rs-fMRI results provide novel support linking negative-SFT with increased rsFC between self-network and frontoparietal network regions across different levels of depression. Broadly, these findings highlight a dimension of social-affective functioning that may underlie MDD and other psychiatric conditions.

Reduced resting-state thalamostriatal functional connectivity is associated with excessive daytime sleepiness in persons with and without depressive disorders.

BACKGROUND: Excessive daytime sleepiness (EDS) is a common and significant problem encountered in affective illness, however, the biological underpinnings of EDS in persons with psychiatric disorders are not clear. This study evaluated the associations between thalamic connectivity with cortical and subcortical brain regions with EDS in persons with and without depressive disorders (DD). METHODS: Resting-state functional connectivity magnetic resonance imaging scans from 67 unmedicated young to middle-aged women with current DD (n = 30), remitted DD (n = 13), and healthy controls (n = 24) were utilized to examine the associations between thalamic connectivity with cortical/subcortical structures and EDS. RESULTS: After correction for multiple comparisons and adjustment for age, habitual sleep duration, and depressive symptomatology, reduced resting-state connectivity between the bilateral thalamus and left rostral striatum (caudate/putamen) was significantly associated with EDS. LIMITATIONS: Causal inferences between thalamostriatal connectivity and EDS could not be determined. CONCLUSIONS: These results further implicate the role of the striatum and thalamus as central components of the experience of EDS. Further research is indicated to clarify the specific role these structures play in EDS in psychiatric disorders.

Vendaje neuromuscular en músculo tibial anterior durante la marcha en niños con parálisis cerebral tipo hemiparesia espástica: estudio de casos / Kinesiotape in tibialis anterior muscle during gait in children with spastic hemiparetic cerebral palsy: case reports

Introduction: Kinesiotape (Kt) is a therapeutic technique producing somatosensory stimulation when placed on the skin, and has shown improvement in dynamic activities in neuropediatric field; however, there are limited studies on its effect during gait. Objective: To assess the effect of KT in children with spastic hemiparetic cerebral palsy (CP) during gait, when applied on tibialis anterior muscle of the affected side. Method: Study carried out with 9 children with spastic hemiparetic cerebral palsy and Gross Motor Function Classification System (GMFCS) I & II, between 4 and 10 years old, male and female, at Instituto teletón Antofagasta. Gait was recorded in video in 3 instances: before Kt, immediately after application of Kt, and 5 days post application. Recordings were assessed using the Edinburgh Visual Gait Score (EVGS) and range of motion (RoM) of the ankle during gait. Results: None of the subjects showed significant improvement in RoM of the ankle during gait or in the EVGS. Conclusion: Kt did not change ROM of the ankle during gait in the studied cases, nor as an immediate effect or 5 days after application. only 2 out of 9 children showed a 1 point improvement during the swing phase during EVGS. It is suggested to consider other exclusion criteria and extend the duration of Kt therapy.

El vendaje neuromuscular (VN) es una herramienta terapéutica que estimula el nivel somatosensitivo al ubicarlo sobre la piel, que ha demostrado mejoras en actividades dinámicas en el ámbito neuroinfantil; sin embargo, existen escasos estudios sobre su efecto durante la marcha. Objetivo: Evaluar el efecto del VN sobre la marcha de niños con parálisis cerebral (PC) hemiparética espástica, aplicado en músculo tibial anterior del lado afectado. Método: Estudio de 9 niños con PC y Gross Motor Function Classification System (GMFCS) I y II tipo hemiparesia espástica entre 4 y 10 años de edad, de ambos sexos en el Instituto Teletón Antofagasta. Se filmó marcha en 3 instancias: antes del VN, inmediato con VN y a los 5 días post aplicación. Las grabaciones fueron valoradas con la Edinburgh Visual Gait Score (EVGS) y rango de movimiento (RoM) de tobillo durante la marcha. Resultados: Ninguno de los 9 niños presentó mejoría significativa en su ROM del tobillo durante la marcha ni en la EVGS. Conclusión: El vendaje neuromuscular no produjo cambios del RoM del tobillo durante la marcha en los casos presentados, ni como efecto inmediato ni a los 5 días post aplicación. Sólo 2 de 9 mejoraron en 1 punto durante la fase de balanceo en la EVGS. Se sugiere considerar otros criterios de exclusión y ampliar el tiempo de aplicación del VN.

Organ donor management: Eight common recommendations and actions that deserve reflection.

Despite major advances in our understanding of the physiopathology of brain death (BD), there are important controversies as to which protocol is the most appropriate for organ donor management. Many recent reviews on this subject offer recommendations that are sometimes contradictory and in some cases are not applied to other critically ill patients. This article offers a review of the publications (many of them recent) with an impact upon these controversial measures and which can help to confirm, refute or open new areas of research into the most appropriate measures for the management of organ donors in BD, and which should contribute to discard certain established recommendations based on preconceived ideas, that lead to actions lacking a physiopathological basis. Aspects such as catecholamine storm management, use of vasoactive drugs, hemodynamic objectives and monitoring, assessment of the heart for donation, and general care of the donor in BD are reviewed.

The effect of resolution time of acute kidney injury on clinical outcomes.

Acute kidney injury (AKI) is a frequent and complex disease. It is not clearly defined whether its duration is related to adverse outcomes. We determined the effect of AKI resolution time on patient's clinical outcomes. A prospective cohort of hospitalized patients with AKI by AKI network (AKIN) creatinine criteria was included. Variables for prognosis and follow-up were analyzed. One hundred and thirteen patients were included in the study. Seventy-seven (68.1%) were males, mean age 55 years (range, 16-76 years), and 48 (42.5%) were diabetic. The most common cause of AKI was sepsis (31%). AKI resolution time ≤2 days and >2 days was seen in 47 (41.6%) and 66 (58.4%) of the cases, respectively. AKI resolution time >2 days was common in older patients (66.24 ± 17.6 year vs. 47.16 ± 12.32 year, P = 0.004), with the use of mechanical ventilation (27% vs. 4%, P = 0.02) and vasopressors (41% vs. 11%, P ≤ 0.01); it was associated with increased mortality (47% vs. 4%, P ≤ 0.01), and a discharge estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (52% vs. 2%, P = 0.01), than in patients with resolution time ≤2 days. Survival rate was significantly worse in patients with a resolution time >2 days. By multivariate logistic step-wise regression analysis, AKI >2days, vasopressor use, and AKIN stage 2-3 were independently associated with higher mortality. AKI >2 days and vasopressor utilization were independently associated to an eGFR <60 ml/min/1.73 m2 at the time of discharge. We conclude that AKI resolution time >2 days is linked to adverse clinical outcomes.

Evaluación de indicación de linfadenectomía en prostactectomía radical laroscópica según grupo de riesgo y capra -score / Evaluation of indication of lymphadenectomy in radical laparoscopy proststectomy risk gropu and capra-Score

Introducción. El beneficio de la linfadenectomía en el cáncer de próstata sigue siendo controversial. Es el único procedimiento que permite un estadiaje anatomopatológico más preciso. Antiguamente se indicaba en pacientes de riesgo intermedio o mayor. Actualmente utilizamos el Score de CAPRA sobre 2 para indicar el procedimiento con el fin de seleccionar de mejor manera los pacientes que se beneficiarían de este procedimiento. Objetivo. Analizar la utilidad de CAPRA-Score para indicar la linfadenectomía. Pacientes y Métodos. Estudio prospectivo de carácter descriptivo. De un universo de 155 Pacientes sometidos a prostatectomía radical laparoscópica entre 2003-2013 por un único cirujano, se analizaron 34 pacientes a los que se le realizó linfadenectomía . Los datos se recopilaron en el momento de la cirugía y controles postoperatorios. Se agruparon datos: edad, PSA, Estadio Clínico, Gleason y porcentaje de cilindros (+) en biopsia TR. Se agruparon según indicación por Riesgo o CAPRA-S y se compararon los resultados obtenidos en la histología de los ganglios extraídos (linfadenectomías +). Los datos se analizaron considerando p<0,05 estadísticamente significativo según prueba de T de Student. Resultados. Se incluyeron en total 34 pacientes. Hasta el año 2010 un total de 23 linfadenectomía indicadas a grupo de riesgo intermedio-alto, el 78 por ciento (18) indicado por Gleason. Se sacó en promedio 12 ganglios por paciente, 72 por ciento linfadenectomía ampliadas. Ningún paciente tuvo ganglios (+). Desde el año 2011 un total de 11 linfadenectomía por CAPRA-Score >2, sacándose promedio 15 ganglios, 9 fueron linfadenectomías ampliadas. Se obtuvo 18 por ciento linfadenectomías (+) para compromiso metastásico. Conclusiones. De los pacientes previo a CAPRA-Score, un 17 por ciento pacientes estarían sobreindicados según éste y coincide con la negatividad del resultado histológico. Hubo diferencia estadísticamente significativa en la aparición de ganglios (+) en pacientes que se aplicó CAPRA-Score. (P<0.05). Según la serie de pacientes presentados, CAPRA-Score seleccionaría mejor los pacientes que se beneficiarían con una linfadenectomía, sin embargo se requieren estudios de mayor cantidad de pacientes.AU

Introduction. The benefit of lymphadenectomy in prostate cancer remains controversial. It is the only procedure that allows a more accurate anatomopathological staging. It was formerly indicated in patients of intermediate or greater risk. We currently use the CAPRA Score of 2 to indicate the procedure in order to better select patients who would benefit from this procedure. Objective. Analyze the utility of CAPRAScore to indicate lymphadenectomy. Patients and Methods. Prospective descriptive study. From a universe of 155 patients who underwent laparoscopic radical prostatectomy between 2003 and 2013 by a single surgeon, 34 patients who underwent lymphadenectomy were analyzed. Data were collected at the time of surgery and postoperative controls. Data were grouped: age, PSA, Clinical Stage, Gleason and percentage of cylinders (+) in TR biopsy. They were grouped according to indication by Risk or CAPRA-S and the results obtained were compared in the histology of the extracted ganglia (lymphadenectomies +). Data were analyzed considering p <0.05 statistically significant according to Student's T test. Results. A total of 34 patients were included. Until the year 2010 a total of 23 lymphadenectomy Original Works indicated to group of intermediate-high risk, 78% (18) indicated by Gleason. An average of 12 lymph nodes per patient, 72% enlarged lymphadenectomy. No patient had lymph nodes (+). Since 2011 a total of 11 lymphadenectomy for CAPRAScore> 2, with a mean of 15 lymph nodes, 9 were enlarged lymphadenectomies. We obtained 18% lymphadenectomies (+) for metastatic compromise. Conclusions. Of the patients prior to CAPRA-Score, 17% patients would be over-reported according to this and coincides with the negativity of the histological result. There was a statistically significant difference in the appearance of lymph nodes (+) in patients who underwent CAPRA-Score. (P <0.05). According to the series of patients presented, CAPRAScore would better select patients who would benefit from lymphadenectomy, however, more studies are required.AU

Experience-Driven Differences in Childhood Cortisol Predict Affect-Relevant Brain Function and Coping in Adolescent Monozygotic Twins.

Stress and emotion involve diverse developmental and individual differences. Partially attributed to the development of the prefrontal cortex (PFC), the amygdala, and hypothalamic-pituitary-adrenal axis, the precise genetic and experiential contributions remain unknown. In previous work, childhood basal cortisol function predicted adolescent resting-state functional connectivity (rs-FC) and psychopathology. To parse experience-driven (non-genetic) contributions, we investigated these relations with a monozygotic (MZ) twin design. Specifically, we examined whether intrapair differences in childhood afternoon cortisol levels predicted cotwin differences in adolescent brain function and coping. As expected, intrapair differences in childhood cortisol forecast amygdala-perigenual PFC rs-FC (R2 = 0.84, FWE-corrected p = 0.01), and amygdala recovery following unpleasant images (R2 = 0.40, FWE-corrected p < 0.05), such that the cotwin with higher childhood cortisol evinced relatively lower rs-FC and poorer amygdala recovery in adolescence. Cotwin differences in amygdala recovery also predicted coping styles. These data highlight experience-dependent change in childhood and adolescence.

Neuroendocrine Regulation of Metabolism.

Given the current environment in most developed countries, it is a challenge to maintain a good balance between calories consumed and calories burned, although maintenance of metabolic balance is key to good health. Therefore, understanding how metabolic regulation is achieved and how the dysregulation of metabolism affects health is an area of intense research. Most studies focus on the hypothalamus, which is a brain area that acts as a key regulator of metabolism. Among the nuclei that comprise the hypothalamus, the arcuate nucleus is one of the major mediators in the regulation of food intake. The regulation of energy balance is also a key factor ensuring the maintenance of any species as a result of the dependence of reproduction on energy stores. Adequate levels of energy reserves are necessary for the proper functioning of the hypothalamic-pituitary-gonadal axis. This review discusses valuable data presented in the 2015 edition of the International Workshop of Neuroendocrinology concerning the fundamental nature of the hormonal regulation of the hypothalamus and the impact on energy balance and reproduction.

Des-Acyl Ghrelin Directly Targets the Arcuate Nucleus in a Ghrelin-Receptor Independent Manner and Impairs the Orexigenic Effect of Ghrelin.

Ghrelin is a stomach-derived octanoylated peptide hormone that plays a variety of well-established biological roles acting via its specific receptor known as growth hormone secretagogue receptor (GHSR). In plasma, a des-octanoylated form of ghrelin, named des-acyl ghrelin (DAG), also exists. DAG is suggested to be a signalling molecule that has specific targets, including the brain, and regulates some physiological functions. However, no specific receptor for DAG has been reported until now, and, consequently, the potential role of DAG as a hormone has remained a matter of debate. In the present study, we show that DAG specifically binds to and acts on a subset of arcuate nucleus (ARC) cells in a GHSR-independent manner. ARC cells labelled by a DAG fluorescent tracer include the neuropeptide Y (NPY) and non-NPY neurones. Given the well-established role of the ARC in appetite regulation, we tested the effect of centrally administered DAG on food intake. We found that DAG failed to affect dark phase feeding, as well as food intake, after a starvation period; however, it impaired the orexigenic actions of peripherally administered ghrelin. Thus, we conclude that DAG directly targets ARC neurones and antagonises the orexigenic effects of peripherally administered ghrelin.

Effects of general, specific and combined warm-up on explosive muscular performance.

The purpose of this study was to compare the acute effects of general, specific and combined warm-up (WU) on explosive performance. Healthy male (n = 10) subjects participated in six WU protocols in a crossover randomized study design. Protocols were: passive rest (PR; 15 min of passive rest), running (Run; 5 min of running at 70% of maximum heart rate), stretching (STR; 5 min of static stretching exercise), jumping [Jump; 5 min of jumping exercises - 3x8 countermovement jumps (CMJ) and 3x8 drop jumps from 60 cm (DJ60)], and combined (COM; protocols Run+STR+Jump combined). Immediately before and after each WU, subjects were assessed for explosive concentric-only (i.e. squat jump - SJ), slow stretch-shortening cycle (i.e. CMJ), fast stretch-shortening cycle (i.e. DJ60) and contact time (CT) muscle performance. PR significantly reduced SJ performance (p =0.007). Run increased SJ (p =0.0001) and CMJ (p =0.002). STR increased CMJ (p =0.048). Specific WU (i.e. Jump) increased SJ (p =0.001), CMJ (p =0.028) and DJ60 (p =0.006) performance. COM increased CMJ performance (p =0.006). Jump was superior in SJ performance vs. PR (p =0.001). Jump reduced (p =0.03) CT in DJ60. In conclusion, general, specific and combined WU increase slow stretch-shortening cycle (SSC) muscle performance, but only specific WU increases fast SSC muscle performance. Therefore, to increase fast SSC performance, specific fast SSC muscle actions must be included during the WU.

Soluble factors from the notochordal-rich intervertebral disc inhibit endothelial cell invasion and vessel formation in the presence and absence of pro-inflammatory cytokines.

BACKGROUND: Chronic low back pain can be associated with the pathological ingrowth of blood vessels and nerves into intervertebral discs (IVDs). The notochord patterns the IVD during development and is a source of anti-angiogenic soluble factors such as Noggin and Chondroitin sulfate (CS). These factors may form the basis for a new minimally invasive strategy to target angiogenesis in the IVD. OBJECTIVE: To examine the anti-angiogenic potential of soluble factors from notochordal cells (NCs) and candidates Noggin and CS under healthy culture conditions and in the presence of pro-inflammatory mediators. DESIGN: NC conditioned media (NCCM) was generated from porcine NC-rich nucleus pulposus tissue. To assess the effects of NCCM, CS and Noggin on angiogenesis, cell invasion and tubular formation assays were performed using human umbilical vein endothelial cells (HUVECs) ± tumor necrosis factor alpha (TNFα [10 ng/ml]). vascular endothelial growth factor (VEGF)-A, MMP-7, interleukin-6 (IL-6) and IL-8 mRNA levels were assessed using qRT-PCR. RESULTS: NCCM (10 & 100%), CS (10 and 100 µg) and Noggin (10 and 100 ng) significantly decreased cell invasion of HUVECs with and without TNFα. NCCM 10% and Noggin 10 ng inhibited tubular formation with and without TNFα and CS 100 µg inhibited tubules in Basal conditions whereas CS 10 µg inhibited tubules with TNFα. NCCM significantly decreased VEGF-A, MMP-7 and IL-6 mRNA levels in HUVECs with and without TNFα. CS and Noggin had no effects on gene expression. CONCLUSIONS: We provide the first evidence that soluble factors from NCs can inhibit angiogenesis by suppressing VEGF signaling. Notochordal-derived ligands are a promising minimally invasive strategy targeting neurovascular ingrowth and pain in the degenerated IVD.