Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type.

Increased peripheral and central nervous system cortisol levels have been reported in Alzheimer's disease (AD) and may reflect dysfunction of cerebral components of the hypothalamic-pituitary-adrenal (HPA) axis. However, brain exposure to high cortisol concentrations may also accelerate disease progression and cognitive decline. The objectives of this study were to investigate whether HPA-axis dysregulation occurs at early clinical stages of AD and whether plasma and CSF cortisol levels are associated with clinical disease progression. Morning plasma and CSF cortisol concentrations were obtained from the subjects with AD dementia, mild cognitive impairment of AD type (MCI-AD), MCI of other type (MCI-O), and controls with normal cognition included in a multicenter study from the German Dementia Competence Network. A clinical and neuropsychological follow-up was performed in a subgroup of participants with MCI-AD, MCI-O, and AD dementia. CSF cortisol concentrations were increased in the subjects with AD dementia or MCI-AD compared with subjects with MCI-O or normal cognition. After controlling for possible confounders including CSF measures of amyloid beta1-42 and total tau, higher baseline CSF cortisol levels were associated with faster clinical worsening and cognitive decline in MCI-AD. The findings suggest that HPA-axis dysregulation occurs at the MCI stage of AD and may accelerate disease progression and cognitive decline.

Micronization of Pharmaceuticals and Food Ingredients using Supercritical Fluid Techniques

Micronization techniques based on supercritical fluids (SCFs) are promising for the production of particles with controlled size and distribution. The interest of the pharmaceutical field in the development of SCF techniques is increasing due to the need for clean processes, reduced consumption of energy, and to their several possible applications. The food field is still far from the application of SCF micronization techniques, but there is increasing interest mainly for the processing of products with high added value. The aim of this study is to use SCF micronization techniques for the production of particles of pharmaceuticals and food ingredients with controlled particle size and morphology, and to look at their production on semi-industrial scale. The results obtained are also used to understand the processes from the perspective of broader application within the pharmaceutical and food industries. Certain pharmaceuticals, a biopolymer and a food ingredient have been tested using supercritical antisolvent micronization (SAS) or supercritical assisted atomization (SAA) techniques. The reproducibility of the SAS technique has been studied using physically different apparatuses and on both laboratory and semi-industrial scale. Moreover, a comparison between semi-continuous and batch mode has been performed. The behaviour of the system during the SAS process has been observed using a windowed precipitation vessel. The micronized powders have been characterized by particle size and distribution, morphology and crystallinity. Several analyses have been performed to verify if the SCF process modified the structure of the compound or caused degradation or contamination of the product. The different powder morphologies obtained have been linked to the position of the process operating point with respect to the vapour-liquid equilibrium (VLE) of the systems studied, that is, mainly to the position of the mixture critical point (MCP) of the mixture. Spherical micro, submicro- and nanoparticles, expanded microparticles (balloons) and crystals were obtained by SAS. The obtained particles were amorphous or with different degrees of crystallinity and, in some cases, had different pseudo-polymorphic or polymorphic forms. A compound that could not be processed using SAS was micronized by SAA, and amorphous particles were obtained, stable in vials at room temperature. The SCF micronization techniques studied proved to be effective and versatile for the production of particles for several uses. Furthermore, the findings of this study and the acquired knowledge of the proposed processes can allow a more conscious application of SCF techniques to obtain products with the desired characteristics and enable the use of their principles for broader applications.

The measurement of ice velocity, mass balance and thinning-rate on Johnsons Glacier, Livingston Island, South Shetland Islands, Antarctica

A network of twenty stakes was set up on Johnsons Glacier in order to determine its dynamics. During the austral summers from 1994-95 to 1997-98, we estimated surface velocities, mass balances and ice thickness variations. Horizontal velocity increased dow nstream from 1 m a- 1 near the ice divides to 40 m a- 1 near the ice terminus. The accumulation zone showed low accumulation rates (maximum of 0,6 m a- 1 (ice)), whereas in the lower part of the glacier, ablation rates were 4,3 m a- 1 (ice). Over the 3-year study period, both in the accumulation and ablation zones, we detected a reduction in the ice surface level ranging from 2 to 10 m from the annual ve rt ical velocities and ice-thinning data, the mass balance was obtained and compared with the mass balance field values, resulting in similar estimates. Flux values were calculated using cross-section data and horizontal velocities, and compared with the results obtained by means of mass balance and ice thinning data using the continuity equation. The two methods gave similar results.

Refractory intraretinal or subretinal fluid in neovascular age-related macular degeneration treated with intravitreal ranizubimab: Functional and Structural Outcome.

PURPOSE: To investigate the visual acuity results of eyes with neovascular age-related macular degeneration and refractory fluid despite monthly treatment with ranibizumab, and to investigate differences between refractory subretinal fluid and intraretinal cystic changes. METHODS: Retrospective chart review of consecutive treatment-refractory neovascular age-related macular degeneration, defined as persistent intraretinal or subretinal fluid despite monthly ranibizumab injections during 12 months or more. Data were evaluated for baseline characteristics, type and location of the refractory fluid, mean visual acuity change, number of injections, and the time point of first complete disappearance of all fluid on spectral domain optical coherence tomography. RESULTS: Seventy-six eyes (74 patients, mean age, 76.8 years) were identified. The mean follow-up was 33.6 months (range, 12-73 months). The mean number of injections was 11.4 in the first year and 27.7 over follow-up. The refractory fluid was located subfoveally in 61.8%. In 27 eyes (35.5%), the fluid resolved after a mean of 21.8 months (range, 13-49 months). Mean visual acuity increased by 9.0, 7.9, and 7.9 letters by Month 12, Month 24, and Month 36, respectively. Subgroup analysis revealed a higher risk for fibrosis (odds ratio, 3.30) or atrophy (odds ratio, 3.34) in patients with refractory cysts as compared with refractory subretinal fluid. Furthermore, refractory cysts showed a higher risk for a 10-letter visual acuity loss (P = 0.018). CONCLUSION: Fluid refractory to monthly treatment with ranibizumab for neovascular age-related macular degeneration still allowed for well-maintained visual improvement, even in subfoveal location. Late fluid resolution may occur. However, refractory cysts were associated with poorer anatomical and functional outcome than subretinal fluid.

Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after Hemodialysis.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with significantly increased cardiovascular morbidity and mortality. Fluid overload may promote obstructive sleep apnea in patients with ESRD through an overnight fluid shift from the legs to the neck soft tissues. Body fluid shift and severity of obstructive sleep apnea before and after hemodialysis were compared in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventeen patients with hemodialysis and moderate to severe obstructive sleep apnea were included. Polysomnographies were performed the night before and after hemodialysis to assess obstructive sleep apnea, and bioimpedance was used to measure fluid overload and leg fluid volume. RESULTS: The mean overnight rostral fluid shift was 1.27±0.41 L prehemodialysis; it correlated positively with fluid overload volume (r=0.39; P=0.02) and was significantly lower posthemodialysis (0.78±0.38 L; P<0.001). There was no significant difference in the mean obstructive apnea-hypopnea index before and after hemodialysis (46.8±22.0 versus 42.1±18.6 per hour; P=0.21), but obstructive apnea-hypopnea index was significantly lower posthemodialysis (-10.1±10.8 per hour) in the group of 12 patients, with a concomitant reduction of fluid overload compared with participants without change in fluid overload (obstructive apnea-hypopnea index +8.2±16.1 per hour; P<0.01). A lower fluid overload after hemodialysis was significantly correlated (r=0.49; P=0.04) with a lower obstructive apnea-hypopnea index. Fluid overload-assessed by bioimpedance-was the best predictor of the change in obstructive apnea-hypopnea index observed after hemodialysis (standardized r=-0.68; P=0.01) in multivariate regression analysis. CONCLUSIONS: Fluid overload influences overnight rostral fluid shift and obstructive sleep apnea severity in patients with ESRD undergoing intermittent hemodialysis. Although no benefit of hemodialysis on obstructive sleep apnea severity was observed in the whole group, the change in obstructive apnea-hypopnea index was significantly correlated with the change in fluid overload after hemodialysis. Moreover, the subgroup with lower fluid overload posthemodialysis showed a significantly lower obstructive sleep apnea severity, which provides a strong incentive to further study whether optimizing fluid status in patients with obstructive sleep apnea and ESRD will improve the obstructive apnea-hypopnea index.

Neonates with Bartter syndrome have enormous fluid and sodium requirements.

AIM: Managing neonatal Bartter syndrome by achieving adequate weight gain is challenging. We assessed the correlation between weight gain in neonatal Bartter syndrome and the introduction of fluid and sodium supplementations and indomethacin during the first 4 weeks of life. METHODS: Daily fluid and electrolytes requirements were analysed using linear regression and Spearman correlation coefficients. The weight gain coefficient was calculated as daily weight gain after physiological neonatal weight loss. RESULTS: We studied seven infants. The highest weight gain coefficients occurred between weeks two and four in the five neonates who either received prompt amounts of fluid (maximum 810 mL/kg/day) and sodium (maximum 70 mmol/kg/day) or were treated with indomethacin. For the two patients with the highest weight gain coefficient, water and sodium supplementations were decreased in weeks two to four leading to a significant negative Spearman correlation between weight gain and fluid supplements (r = -0.55 and -0.68) and weight gain and sodium supplementations (r = -0.96 and -0.72). The two patients with the lowest weight gain coefficient had positive Spearman correlation coefficients between weight gain and fluid and sodium supplementations. CONCLUSION: Infants with neonatal Bartter syndrome required rapid and enormous fluid and sodium supplementations or the early introduction of indomethacin treatment to achieve adequate weight gain during the early postnatal period.

Differential growth responses to water balance of coexisting deciduous tree species are linked to wood density in a Bolivian tropical dry forest

A seasonal period of water deficit characterizes tropical dry forests (TDFs). There, sympatric tree species exhibit a diversity of growth rates, functional traits, and responses to drought, suggesting that each species may possess different strategies to grow under different conditions of water availability. The evaluation of the long-term growth responses to changes in the soil water balance should provide an understanding of how and when coexisting tree species respond to water deficit in TDFs. Furthermore, such differential growth responses may be linked to functional traits related to water storage and conductance. We used dendrochronology and climate data to retrospectively assess how the radial growth of seven coexisting deciduous tree species responded to the seasonal soil water balance in a Bolivian TDF. Linear mixed-effects models were used to quantify the relationships between basal area increment and seasonal water balance. We related these relationships with wood density and sapwood production to assess if they affect the growth responses to climate. The growth of all species responded positively to water balance during the wet season, but such responses differed among species as a function of their wood density. For instance, species with a strong growth response to water availability averaged a low wood density which may facilitate the storage of water in the stem. By contrast, species with very dense wood were those whose growth was less sensitive to water availability. Coexisting tree species thus show differential growth responses to changes in soil water balance during the wet season. Our findings also provide a link between wood density, a trait related to the ability of trees to store water in the stem, and wood formation in response to water availability.

Fluid flow processes at basin scale

S u b s u r face fluid flow plays a significant role in many geologic processes and is increasingly being studied in the scale of sedimentary basins and geologic time perspective. Many economic resources such as petroleum and mineral deposits are products of basin scale fluid flow operating over large periods of time. Such ancient flow systems can be studied through analysis of diagenetic alterations and fluid inclusions to constrain physical and chemical conditions of fluids and rocks during their paleohy d r og e o l ogic evolution. Basin simulation models are useful to complement the paleohy d r og e o l ogic record preserved in the rocks and to derive conceptual models on hydraulic basin evolution and generation of economic resources. Different types of fluid flow regimes may evo l ve during basin evolution. The most important with respect to flow rates and capacity for transport of solutes and thermal energy is gr avitational fluid flow driven by the topographic configuration of a basin. Such flow systems require the basin to be elevated above sea level. Consolidational fluid flow is the principal fluid migration process in basins below sea level, caused by loading of compressible rocks. Flow rates of such systems are several orders of magnitude below topogr a p hy driven flow. Howeve r, consolidation may create significant fluid ove rpressure. Episodic dewatering of ove rpressured compart m e n t s m ay cause sudden fluid release with elevated flow velocities and may cause a transient local thermal and chemical disequilibrium betwe e n fluid and rock. This paper gives an ove rv i ew on subsurface fluid flow processes at basin scale and presents examples related to the Pe n e d è s basin in the central Catalan continental margin including the offshore Barcelona half-graben and the compressive South-Pyrenean basin.

Refractory subretinal fluid in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab: visual acuity outcome.

PURPOSE: To investigate the functional outcome of eyes with neovascular AMD (nAMD) and subretinal fluid (SRF) refractory to treatment with ranibizumab. METHODS: Retrospective chart review of consecutive treatment-refractory SRF in nAMD despite monthly ranibizumab injections during 12 months or more. Data were evaluated for baseline characteristics, location of the refractory SRF, mean visual acuity (VA) change, number of injections, and timepoint of first complete disappearance of SRF. RESULTS: Forty-five eyes in 44 patients (mean age of 76 years) were included. The mean follow-up was 32.4 months (range 12-73 months). The mean number of injections was 11.6 in the first year and 27.5 over follow-up. The refractory SRF was located subfoveally in 66.7 %. In 12 eyes (26.7 %), complete absorption of SRF was found after a mean of 22.6 months (range, 13-41 months). Mean VA increased by 10.4, 8.2, and 8.6 letters by month 12, 24, and 36, respectively. CONCLUSIONS: Neovascular AMD with SRF refractory to monthly retreatment with ranibizumab may still allow good and maintained visual improvement, even if the fluid is located subfoveally. SRF may progressively absorb under continuous monthly treatment. The necessity to treat refractory SRF with monthly injections could be questioned and would need future investigations.

Inflammation in schizophrenia: A question of balance.

In the past decade, there has been renewed interest in immune/inflammatory changes and their associated oxidative/nitrosative consequences as key pathophysiological mechanisms in schizophrenia and related disorders. Both brain cell components (microglia, astrocytes, and neurons) and peripheral immune cells have been implicated in inflammation and the resulting oxidative/nitrosative stress (O&NS) in schizophrenia. Furthermore, down-regulation of endogenous antioxidant and anti-inflammatory mechanisms has been identified in biological samples from patients, although the degree and progression of the inflammatory process and the nature of its self-regulatory mechanisms vary from early onset to full-blown disease. This review focuses on the interactions between inflammation and O&NS, their damaging consequences for brain cells in schizophrenia, the possible origins of inflammation and increased O&NS in the disorder, and current pharmacological strategies to deal with these processes (mainly treatments with anti-inflammatory or antioxidant drugs as add-ons to antipsychotics).

Fluid dynamical prediction of changed v1-flow at energies available at the CERN Large Hadron Collider

Substantial collective flow is observed in collisions between lead nuclei at Large Hadron Collider (LHC) as evidenced by the azimuthal correlations in the transverse momentum distributions of the produced particles. Our calculations indicate that the global v1-flow, which at RHIC peaked at negative rapidities (named third flow component or antiflow), now at LHC is going to turn toward forward rapidities (to the same side and direction as the projectile residue). Potentially this can provide a sensitive barometer to estimate the pressure and transport properties of the quark-gluon plasma. Our calculations also take into account the initial state center-of-mass rapidity fluctuations, and demonstrate that these are crucial for v1 simulations. In order to better study the transverse momentum flow dependence we suggest a new"symmetrized" vS1(pt) function, and we also propose a new method to disentangle global v1 flow from the contribution generated by the random fluctuations in the initial state. This will enhance the possibilities of studying the collective Global v1 flow both at the STAR Beam Energy Scan program and at LHC.