Mapping epileptic activity: sources or networks for the clinicians?

Epileptic seizures of focal origin are classically considered to arise from a focal epileptogenic zone and then spread to other brain regions. This is a key concept for semiological electro-clinical correlations, localization of relevant structural lesions, and selection of patients for epilepsy surgery. Recent development in neuro-imaging and electro-physiology and combinations, thereof, have been validated as contributory tools for focus localization. In parallel, these techniques have revealed that widespread networks of brain regions, rather than a single epileptogenic region, are implicated in focal epileptic activity. Sophisticated multimodal imaging and analysis strategies of brain connectivity patterns have been developed to characterize the spatio-temporal relationships within these networks by combining the strength of both techniques to optimize spatial and temporal resolution with whole-brain coverage and directional connectivity. In this paper, we review the potential clinical contribution of these functional mapping techniques as well as invasive electrophysiology in human beings and animal models for characterizing network connectivity.

Arthroplasty - current strategies for the management of knee osteoarthritis.

Osteoarthritis of the knee is a major clinical burden. Recent decades have witnessed an improved understanding of knee physiology and kinematics, which has led to the introduction of a wide range of enhanced prosthetic implant designs for a variety of indications. However, the increase in the number of procedures performed annually has led to complications being encountered at higher rates than ever before, requiring the development of optimised therapeutic strategies. The future holds several promising options, primarily in the treatment of early osteoarthritis, biological therapy, surgical navigation and patient-specific implants. This review provides an insight into the current options of knee arthroplasty, with emphasis on available designs, and examines the complications that may be encountered.

Comparison of hepatic adaptation in extreme metabolic phenotypes observed in early lactation dairy cows on-farm

The aim was to study the variation in metabolic responses in early-lactating dairy cows (n = 232) on-farm that were pre-selected for a high milk fat content (>45 g/l) and a high fat/protein ratio in milk (>1.5) in their previous lactation. Blood was assayed for concentrations of metabolites and hormones. Liver was measured for mRNA abundance of 25 candidate genes encoding enzymes and receptors involved in gluconeogenesis (6), fatty acid β-oxidation (6), fatty acid and triglyceride synthesis (5), cholesterol synthesis (4), ketogenesis (2) and the urea cycle (2). Two groups of cows were formed based on the plasma concentrations of glucose, non-esterified fatty acids (NEFA) and β-hydroxybutyric acid (BHBA) (GRP+, high metabolic load; glucose <3.0 mm, NEFA >300 μm and BHBA >1.0 mm, n = 30; GRP-, low metabolic load; glucose >3.0 mm, NEFA <300 μm and BHBA <1.0 mm, n = 30). No differences were found between GRP+ and GRP- for the milk yield at 3 weeks post-partum, but milk fat content was higher (p < 0.01) for GRP+ than for GRP-. In week 8 post-partum, milk yield was higher in GRP+ in relation to GRP- (37.5 vs. 32.5 kg/d; p < 0.01). GRP+ in relation to GRP- had higher (p < 0.001) NEFA and BHBA and lower glucose, insulin, IGF-I, T3 , T4 concentrations (p < 0.01). The mRNA abundance of genes related to gluconeogenesis, fatty acid β-oxidation, fatty acid and triglyceride synthesis, cholesterol synthesis and the urea cycle was different in GRP+ compared to GRP- (p < 0.05), although gene transcripts related to ketogenesis were similar between GRP+ and GRP-. In conclusion, high metabolic load post-partum in dairy cows on-farm corresponds to differences in the liver in relation to dairy cows with low metabolic load, even though all cows were pre-selected for a high milk fat content and fat/protein ratio in milk in their previous lactation.

Monitoring of tumor response to Cisplatin using optical spectroscopy

INTRODUCTION Anatomic imaging alone is often inadequate for tuning systemic treatment for individual tumor response. Optically based techniques could potentially contribute to fast and objective response monitoring in personalized cancer therapy. In the present study, we evaluated the feasibility of dual-modality diffuse reflectance spectroscopy-autofluorescence spectroscopy (DRS-AFS) to monitor the effects of systemic treatment in a mouse model for hereditary breast cancer. METHODS Brca1(-/-); p53(-/-) mammary tumors were grown in 36 mice, half of which were treated with a single dose of cisplatin. Changes in the tumor physiology and morphology were measured for a period of 1 week using dual-modality DRS-AFS. Liver and muscle tissues were also measured to distinguish tumor-specific alterations from systemic changes. Model-based analyses were used to derive different optical parameters like the scattering and absorption coefficients, as well as sources of intrinsic fluorescence. Histopathologic analysis was performed for cross-validation with trends in optically based parameters. RESULTS Treated tumors showed a significant decrease in Mie-scattering slope and Mie-to-total scattering fraction and an increase in both fat volume fraction and tissue oxygenation after 2 days of follow-up. Additionally, significant tumor-specific changes in the fluorescence spectra were seen. These longitudinal trends were consistent with changes observed in the histopathologic analysis, such as vital tumor content and formation of fibrosis. CONCLUSIONS This study demonstrates that dual-modality DRS-AFS provides quantitative functional information that corresponds well with the degree of pathologic response. DRS-AFS, in conjunction with other imaging modalities, could be used to optimize systemic cancer treatment on the basis of early individual tumor response.

The porcine innate immune system: an update.

Over the last few years, we have seen an increasing interest and demand for pigs in biomedical research. Domestic pigs (Sus scrofa domesticus) are closely related to humans in terms of their anatomy, genetics, and physiology, and often are the model of choice for the assessment of novel vaccines and therapeutics in a preclinical stage. However, the pig as a model has much more to offer, and can serve as a model for many biomedical applications including aging research, medical imaging, and pharmaceutical studies to name a few. In this review, we will provide an overview of the innate immune system in pigs, describe its anatomical and physiological key features, and discuss the key players involved. In particular, we compare the porcine innate immune system to that of humans, and emphasize on the importance of the pig as model for human disease.

A survey on the feeding of eventing horses during competition

This study aims at the comparison of the actual feeding of horses with the recommendations from the literature, and it studies the effects of feeding and exercise on several blood metabolic parameters before and after exercise. Blood samples were collected from 25 horses during one-star eventing competitions and evaluated for blood glucose, insulin, lactate, free fatty acids and triglyceride levels. Questionnaires on the feeding practices of the horses were evaluated. The questionnaires revealed that during training, and on tournament days, horses received on average 4.3 kg of concentrate per day (min. 1.54 kg, max. 8 kg). The statistical analysis showed no significant effect of the amount of concentrate fed before exercise on the measured blood values. Oil was supplied as a supplementary energy source to 30% of the horses, but most of them only received very small quantities (0.02–0.4 l/day). Five horses (20%) had no access to salt supplements at all, and eleven horses (45%) had no access to salt on tournament days. Fifteen horses (60%) were supplied with mineral feed. Twenty-one horses (84%) had daily access to pasture during the training period. During competition, 55% of the horses received roughage ad libitum, compared with 37% during training. The majority of the horses received less roughage on days before the cross-country competition. It could not be ascertained whether feeding a large amounts of roughage had a beneficial effect on performance, because only a few horses in this study were fed with very restrictive roughage. Feeding of most of the horses was in agreement with the recommendations from the literature, except the need for sodium and chloride. The sodium and chloride need for sport horses may be overestimated in literature and needs to be re-evaluated.

Relative Age Effect in Young Swiss Alpine Skiers From 2004 to 2011

PURPOSE To verify whether the relative age effects (RAEs) occur among young male and female Swiss alpine skiers of different age groups and performance levels. Additionally, the efficacy of normalizing performance in physical tests to height and body mass to attenuate RAEs eventually present was tested. METHODS The Swiss-Ski Power Test consists of anthropometric measures and physical tests for coordination and speed, endurance and strength and is used since 2004 to evaluate 11- to 19-years old Swiss competitive alpine skiers. We analysed the distribution of 6996 tests performed by 1438 male and 1031 female alpine skiers between 2004 and 2011 according to the athlete's relative age quartile (Q). Differences in anthropometric measures and performance in physical tests according to Q were assessed and the possibility of attenuating eventual RAEs on performance by normalization of results to height and body mass was tested. RESULTS RAEs were found among all female and male age groups, with no differences between age groups. While performance level did not affect RAE for male skiers, it influenced RAE among female skiers. RAEs also influenced results in all physical tests except upper limbs strength. Normalization of results to body mass attenuated most RAEs identified. CONCLUSION small RAEs are present among young Swiss competitive alpine skiers and should be taken into account in training and selection settings, avoiding the waste of possible future talents. When ranking junior athletes according to their performance in physical tests, normalization of results to body mass decreases the bias caused by RAEs.

The great fluid debate: saline or so-called "balanced" salt solutions?

BACKGROUND Intravenous fluids are commonly prescribed in childhood. 0.9 % saline is the most-used fluid in pediatrics as resuscitation or maintenance solution. Experimental studies and observations in adults suggest that 0.9 % saline is a poor candidate for fluid resuscitation. Although anesthesiologists, intensive care specialists, perioperative physicians and nephrologists have been the most active in this debate, this issue deserves some physiopathological considerations also among pediatricians. RESULTS As compared with so-called "balanced" salt crystalloids such as lactated Ringer, administration of large volumes of 0.9 % saline has been associated with following deleterious effects: tendency to hyperchloremic metabolic acidosis (called dilution acidosis); acute kidney injury with reduced urine output and salt retention; damaged vascular permeability and stiffness, increase in proinflammatory mediators; detrimental effect on coagulation with tendency to blood loss; detrimental gastrointestinal perfusion and function; possible uneasiness at the bedside resulting in unnecessary administration of more fluids. Nevertheless, there is no firm evidence that these adverse effects are clinically relevant. CONCLUSIONS Intravenous fluid therapy is a medicine like insulin, chemotherapy or antibiotics. Prescribing fluids should fit the child's history and condition, consider the right dose at the right rate as well as the electrolyte levels and other laboratory variables. It is unlikely that a single type of fluid will be suitable for all pediatric patients. "Balanced" salt crystalloids, although more expensive, should be preferred for volume resuscitation, maintenance and perioperatively. Lactated Ringer appears unsuitable for patients at risk for brain edema and for those with overt or latent chloride-deficiency. Finally, in pediatrics there is a need for new fluids to be developed on the basis of a better understanding of the physiology and to be tested in well-designed trials.

Physiological plasticity to water flow habitat in the damselfish, Acanthochromis polyacanthus: linking phenotype to performance

The relationships among animal form, function and performance are complex, and vary across environments. Therefore, it can be difficult to identify morphological and/or physiological traits responsible for enhancing performance in a given habitat. In fishes, differences in swimming performance across water flow gradients are related to morphological variation among and within species. However, physiological traits related to performance have been less well studied. We experimentally reared juvenile damselfish, Acanthochromis polyacanthus, under different water flow regimes to test 1) whether aspects of swimming physiology and morphology show plastic responses to water flow, 2) whether trait divergence correlates with swimming performance and 3) whether flow environment relates to performance differences observed in wild fish. We found that maximum metabolic rate, aerobic scope and blood haematocrit were higher in wave-reared fish compared to fish reared in low water flow. However, pectoral fin shape, which tends to correlate with sustained swimming performance, did not differ between rearing treatments or collection sites. Maximum metabolic rate was the best overall predictor of individual swimming performance; fin shape and fish total length were 3.3 and 3.7 times less likely than maximum metabolic rate to explain differences in critical swimming speed. Performance differences induced in fish reared in different flow environments were less pronounced than in wild fish but similar in direction. Our results suggest that exposure to water motion induces plastic physiological changes which enhance swimming performance in A. polyacanthus. Thus, functional relationships between fish morphology and performance across flow habitats should also consider differences in physiology.

Changes in miRNA Expression in a Model of Microcephaly

miRNAs function to regulate gene expression through post-transcriptional mechanisms to potentially regulate multiple aspects of physiology and development. Whole transcriptome analysis has been conducted on the citron kinase mutant rat, a mutant that shows decreases in brain growth and development. The resulting differences in RNA between mutant and wild-type controls can be used to identify genetic pathways that may be regulated differentially in normal compared to abnormal neurogenesis. The goal of this thesis was to verify, with quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), changes in miRNA expression in Cit-k mutants and wild types. In addition to confirming miRNA expression changes, bio-informatics software TargetScan 5.1 was used to identify potential mRNA targets of the differentially expressed miRNAs. The miRNAs that were confirmed to change include: rno-miR-466c, mmu-miR-493, mmu-miR-297a, hsa-miR-765, and hsa-miR-1270. The TargetScan analysis revealed 347 potential targets which have known roles in development. A subset of these potential targets include genes involved in the Wnt signaling pathway which is known to be an important regulator of stem cell development.

Biomarker circadian rhythm profiles in critically ill mechanically ventilated patients

Objective: To explore the natural trajectory of core body temperature (CBT) and cortisol (CORT) circadian rhythms in mechanically ventilated intensive care unit (MV ICU) patients. ^ Design: Prospective, observational, time-series pilot study. ^ Setting: Medical-surgical and pulmonary ICUs in a tertiary care hospital. ^ Sample: Nine (F = 3, M = 6) adults who were mechanically ventilated within 12 hrs of ICU admission with mean ± SD age of 65.2 ± 14 years old. ^ Measurements: Core body temperature and environmental measures of light, sound, temperature, and relative humidity were logged in 1-min intervals. Hourly urine specimens and 2-hr interval blood specimens were collected for up to 7 consecutive days for CORT assay. Mechanical ventilation days, ICU length of stay, and ICU mortality were documented. Acute Physiology and Chronic Health Evaluation (APACHE) II scores were computed for each study day. The data of each biologic and environmental variable were analyzed using single cosinor analysis of 24-hr serial segments. One patient did not complete the study because mortality occurred within 8 hrs of enrollment. Nine ICU patients completed the study in 1.6 to 7.0 days. ^ Results: No normal circadian rhythm pattern was found when the cosinor-derived parameters of amplitude (one-half the peak-trough variability) and acrophase (peak time) were compared with cosinor-derived parameter reference ranges of healthy, diurnally active humans, although 83% of patient-day CBT segments showed statistically significant (p ≤ .05) and biologically meaningful (R2≥ 0.30) 24-hr rhythms with abnormal cosinor parameters. Cosinor parameters of the environmental temporal profiles showed 27% of light, 76% of ambient temperature, and 78% of relative humidity serial segments had a significant and meaningful 24-hr diurnal pattern. Average daily light intensity varied from 34 to 187 lx with a maximum light exposure of 1877 lx. No sound measurement segment had a statistically significant cosine pattern, and numerous 1-minute interval peaks ≥ 60 dB occurred around the clock. Average daily ambient temperature and relative humidity varied from 19 to 24°C and from 25% to 61%, respectively. There was no statistically significant association between CBT or clinical outcomes and cosinor-derived parameters of the environmental variables. Circadian rhythms of urine and plasma CORT were deferred for later analysis. ^ Conclusions: The natural trajectory of the CBT circadian rhythm in MV ICU patients demonstrated persistent cosinor parameter alteration, even when a significant and meaningful 24-hr rhythm was present. The ICU environmental measures showed erratic light and sound exposures. Room temperature and relative humidity data produced the highest rate of significant and meaningful diurnal 24-hr patterns. Additional research is needed to clarify relations among the CBT biomarker of the circadian clock and environmental variables of MV ICU patients. ^

Interview with Julie Knobil

An oral interview with Juile (Hotchkiss) Knobil, research professor of physiology and then integrative biology at the Medical School, where she lectured on mammalian physiology and perinatal endocrinology.

Análisis de la mortalidad en la unidad de cuidados intensivos del Hospital Central de Mendoza, Argentina

Objetivo: Analizar la mortalidad en la Unidad de Cuidados Intensivos (UCI) del Hospital Central de Mendoza y evaluar el valor predictivo de la escala APACHE II (Evaluación Fisiológica Aguda y de Salud Crónica). Material y Método: Se realizó un estudio retrospectivo y observacional de los pacientes ingresados a la Unidad de Cuidados Intensivos del Hospital Central de Mendoza, desde el 01/11/06 hasta el 31/03/08. Se calculó la distribución de sexos y de edades de la muestra, la estadía promedio, principales motivos de ingreso a la UCI y la puntuación APACHE II en las primeras 24 horas de internación. Se calculó la mortalidad esperada y la mortalidad obtenida global y se analizó el coeficiente entre ambas mortalidades. Resultados: Se incluyeron 904 pacientes, 61,82% masculinos y 38,18% femeninos, con una edad media 46 años (±19,36). Estadía promedio en la UCI 8,5 días promedio. El principal motivo de internación fueron los Traumatismos Encéfalocraneanos (TEC) con un 27,7% del total (86% asociados a politraumatismo grave). La mortalidad global obtenida fue del 41,48% vs. 24,08% esperable, con un coeficiente de mortalidad de 1,72 (p<0,0001). Conclusiones: La UCI estudiada presenta por las características de la población asistida un elevado índice de mortalidad global. La mortalidad obtenida fue 72% mayor a la mortalidad esperable según la puntuación APACHE II, demostrando esta Escala un bajo valor predictivo en nuestra UCI. La diferencia entre mortalidades podría parcialmente explicarse por la alta prevalencia de entidades con mortalidades subvaloradas por este modelo pronóstico, como pacientes politraumatizados y neurocríticos. En nuestro estudio, la Escala APACHE II presentó una franca subestimación de la mortalidad en ambas patologías. Sugerimos la realización de un estudio de regresión logística local para determinar un factor de corrección y/o adicionar puntos al valor APACHE II según el diagnóstico de ingreso del paciente. Asimismo, proponemos evaluar el empleo de medidas alternativas para predecir mortalidad, como sistemas de tercera generación (por ejemplo: APACHE III, MPM II y SAPS II).

First results of SONNE cruise SO121

The Red Sea is a very young ocean, and is one of the most interesting areas on Earth (ocean in statu nascendi). It is the only ocean where hydrothermal activity associated with ore formation occurs in a sterile environment (anoxic, hot, saline). In addition, its geographical position means that it is predestined to record the monsoonal history of the region in detailed sedimentary sequences. The major aim of the present project is to investigate the dynamics of hydrothermal systems in selected Deeps (Atlantis-II, Discovery, Kebrit, Al Wajh), Additional palaeoceanographic and microbiological questions should also be addressed. Specific aims are: 1. To study the hydrographic changes in individual Deeps (hydrothermal region Atlantis-II) and to investigate the causes of the temperature increase in the last few years (increased heat flow - higher temperature of the brine supply - higher brine flow rates?). 2.a. To document the influence of the hydrothermal systems on the sedimentary organic matter in the Deeps. In particular, the thermogenic production and migration of hydrocarbons in the sediments will be studied. The complex formation mechanisms (bacterial, thermogenic) of short-chain hydrocarbons (trace gases) will also be examined, 2.b. in addition, the polar and macromolecular fraction in samples from the various deeps will be studied in order to elucidate the formation, structure and source of the macromolecular oil fraction. 3. To clarify the palaeoceanographic conditions, sea-level changes and the climatic history (relationship of the circulation system and nutrient supply to the monsoon) of the southern Red Sea. 4. To separate microorganisms from the brines and to characterise them in terms of their metabolic physiology and ecology, and to describe their taxonomy.