Ultrastructural Evidence for a Role of Astrocytes and Glycogen-Derived Lactate in Learning-Dependent Synaptic Stabilization.

Long-term memory formation (LTM) is a process accompanied by energy-demanding structural changes at synapses and increased spine density. Concomitant increases in both spine volume and postsynaptic density (PSD) surface area have been suggested but never quantified in vivo by clear-cut experimental evidence. Using novel object recognition in mice as a learning task followed by 3D electron microscopy analysis, we demonstrate that LTM induced all aforementioned synaptic changes, together with an increase in the size of astrocytic glycogen granules, which are a source of lactate for neurons. The selective inhibition of glycogen metabolism in astrocytes impaired learning, affecting all the related synaptic changes. Intrahippocampal administration of l-lactate rescued the behavioral phenotype, along with spine density within 24 hours. Spine dynamics in hippocampal organotypic slices undergoing theta burst-induced long-term potentiation was similarly affected by inhibition of glycogen metabolism and rescued by l-lactate. These results suggest that learning primes astrocytic energy stores and signaling to sustain synaptic plasticity via l-lactate.

Autonomic dysfunction following mild traumatic brain injury.

PURPOSE OF REVIEW: Between 1.6 and 3.6 million concussions, or mild traumatic brain injuries (mTBI), occur each year, nearly half of which go unreported and untreated. Despite the high incidence, practitioners currently lack both objective gold-standard diagnostic tools and evidence-based treatments to enable optimal care of concussed individuals. RECENT FINDINGS: This article aims to review recent research on the topic, emphasizing the role of the autonomic nervous system (ANS) in concussion. Current data suggests that ANS dysfunction is often evident following mTBI and accounts for many of the symptoms commonly seen in concussed patients. This link suggests several objective biomarkers that could be used to diagnose and monitor recovery following mTBI. Contrary to conventional wisdom, symptoms and biomarkers of ANS function improve when individuals are exposed to a program of graded exercise as treatment within the first week following concussion. SUMMARY: ANS dysfunction contributes to concussion symptomatology, an effect likely mediated through diffuse axonal injury, including brainstem structures and pathways mediating normal cerebrovascular autoregulation. Exercise, which enhances ANS function, is a well tolerated and effective method of treatment for both acute concussion patients and those suffering from postconcussion syndrome (PCS). The relationship between the ANS, exercise, and concussion creates an opportunity for the identification of objective biomarkers that can facilitate the diagnosis and treatment of mTBI.

The myelodysplastic syndromes flow cytometric score: a three-parameter prognostic flow cytometric scoring system.

The prognosis of myelodysplastic syndromes (MDS) is currently estimated by using the revised International Prognostic Scoring System (IPSS-R). Several studies have shown that further refinement of prognostication for MDS can be achieved by adding flow cytometric parameters. However, widespread implementation of flow cytometry for the prognosis of MDS is hampered by complexity of the analysis. Therefore, the aim of this study was to construct a robust and practical flow cytometric score that could be implemented as a routine procedure. To achieve this, bone marrow aspirates of 109 MDS patients were analyzed by flow cytometry. A second cohort consisting of 103 MDS patients was used to validate the MDS flow cytometric score (MFS). The parameters forming the MFS were sideward light scatter and CD117 expression of myeloid progenitor cells and CD13 expression on monocytes. Three MFS risk categories were formed. Patients with MDS and intermediate MFS scores had significantly better overall survival (OS) compared with the patients with high MFS scores. The MFS further refined prognostication within the IPSS-R low-risk category, by identifying patients with worse OS in case of high MFS. In conclusion, a practical three parameter flow cytometric prognostic score was constructed enabling further refinement of prognostication of MDS.

Role and clinical importance of Helicobacter pylori infection in hemodialysis patients.

Dyspepsia is an extrarenal symptom frequently found in hemodialysed patients; it is due to chronic renal failure, and uremic gastritis is a specific associated condition in chronic renal failure (CRF). On the other hand, in the general population, Helicobacter pylori infection is an important dyspepsia-related risk factor; its close connections with gastro-duodenal pathology are already known, above all the peptic disease in a really exclusive way. By observation of a dyalitic group of patients, opportunely matched with a no CRF group, we evaluated CRF-associated uremia and Helicobacter pylori infection which could eventually interact causing symptoms and lesions. A statistical analysis of obtained data allowed us to conclude that, although there is not, from an epidemiological view-point, a larger diffusion of Helicobacter pylori among dyalitic patients compared to general population, moreover the infection is uremia-synergic in causing gastro-duodenal symptoms and lesions. These findings, therefore, suggest systematically investigation a possible Helicobacter pylori infection in CRF patients and its relation to gastritis grading, and searching for probable active peptic lesions.

Heterotrophic bacteria in the northern Adriatic Sea: seasonal changes and ectoenzyme profile.

A seasonal study of the quantitative and qualitative distribution of heterotrophic bacterial community was carried out in the Adriatic Sea between April 1995 and January 1996, in order to evaluate its spatial and temporal variability and metabolic potential in the degradation processes of organic matter. The culturable bacteria (CFU) ranged between 0.1 and 22% of total bacterioplankton with a maximum percentage in surface samples of coastal zones. Their distribution was generally affected by the prevailing hydrological conditions. At the coastal stations about 44-75% of CFU variance could be explained by river runoff. The changes in the composition of heterotrophic bacterial community showed a seasonal succession of main bacterial groups, with a prevalence of Gram negative, non fermenting bacteria in the cold period (April-January) and an increase of Vibrionaccae and pigmented bacteria in summer. The seasonal variations were more important at the stations influenced by rivers than offshore. The bacterial community showed a greater versatility for organic polymers hydrolysis in the offshore station than in the coastal areas. Over 60% of all isolated heterotrophic bacteria expressed peptidase, lipase and phosphatase ectoenzymes activities, in all seasons and showed an increasing trend in warm period (in July October). The alpha- and beta-glucosidase potentials of bacteria were lower (20% on average) and showed different pattern during the year. These results suggest different role of the bacterial community in the decomposition of organic matter in the Adriatic Sea. Since only 20% of bacterial strains expressed glucosidase activity, carbohydrate-rich polymers such as mucilage might accumulate.

Predicting fractures using bone mineral density: a prospective study of long-term care residents.

Bone mineral density (BMD) has been shown to predict fracture risk in community-dwelling older persons; however, no comparable prospective study has been performed in the long-term care setting where the role of BMD testing is uncertain. To determine the ability of a single BMD measurement to predict the risk of subsequent fracture in long-term care residents, we designed a prospective study in a 725-bed long-term care facility. A total of 252 Caucasian nursing home residents (mean age 88 years, 74% women) were recruited between 1992 and 1998. BMD of the hip, radius or both sites was measured using dual-energy X-ray absorptiometry. Participants were followed through September 1999 for the occurrence of fracture. Cox proportional hazards regression models were constructed to determine the relationship between BMD and the risk of fracture controlling for potentially confounding variables. Sixty-three incident osteoporotic fractures occurred during a median follow-up time of 2.3 years. The multivariate-adjusted risk of fracture for each standard deviation decrease in BMD was 2.82 (95% CI 1.81-4.42) at the total hip, 2.79 (95% CI 1.69-4.61) at the femoral neck, 2.26 (95% CI 1.51-3.38) at the trochanter, 1.83 (95% CI 1.14-2.94) at the radial shaft and 1.84 (95% CI 1.21-2.80) at the ultradistal radius. Subjects in the lowest age-specific quartile of femoral neck BMD had over 4 times the incidence of fracture compared with those in the highest quartile. BMD at either hip or radius was a predictor of osteoporotic fracture, although in women, radial BMD did not predict fracture. Knowledge of BMD in long-term care residents provides important information on subsequent fracture risk.

An epidemiologic study of fall-related fractures among institutionalized older people.

OBJECTIVES: The purpose of this study was to assess the incidence of fall-related fractures, and the circumstances surrounding these events, during a 5-year period among all residents of a long-term care facility. PARTICIPANTS: The study group was composed of residents with radiologically confirmed fractures that were the direct result of a fall occurring between the years 1988 and 1992. This group was 82% female and had a mean age of 89 +/- 6 years. DESIGN: The study was designed as a 5-year retrospective cohort study in a long-term care institution where annual incidence rates of fracture were assessed. RESULTS: There were 296 fall-related fractures during the 5-year period. Annual incidence rates remained fairly constant (72, 86, 84, 70, and 94 per 1000 person-years, respectively) despite a 54% decline in the use of physical restraints during the 5-year period. Hip fractures comprised almost 50% of all fractures. Based on incident reports of these fractures, 42% occurred during the day, 55% took place in the bedroom or adjoining bathroom. 67% occurred while the resident was ambulating, and a wet floor was in evidence in 16% of the incidents. CONCLUSION: Fracture incidence in this long-term care facility has remained stable despite reduced restraint use. The incident reporting system may contribute valuable information to the identification of factors that should receive further attention in studies of risk factors for fracture in the long-term care setting.

The effects of analytic software and scan analysis technique on the comparison of dual X-ray absorptiometry with dual photon absorptiometry of the hip in the elderly.

As part of a longitudinal comparison of bone mineral density (BMD) results originally obtained using a Lunar dual photon absorptiometry (DPA) scanner and later, using a Lunar dual X-ray absorptiometry (DXA) scanner, we compared femur results between DPA and DXA according to DXA analytic software (versions 1.3y and 1.4), and according to the method of placement of the femoral neck box (software algorithm or operator placement according to the appearance of the pair of images) in 58 elderly men and women. The mean BMD at each of three femoral sites was higher using DXA version 1.3y than DPA, but the use of software version 1.4 brought the BMD value closer to that of DPA at all sites. Of 58 scans, 12 (21%) were changed by the operator, resulting in an overall reduction in mean percent BMD difference between scan pairs of 79% (from 1.24% to 0.29%). Although the differences between the DPA/DXA software-driven analysis and the DPA/DXA operator-driven analysis appeared small (high r2 values and intra-class correlation coefficients), the increase in sample size that would be required for the same power to detect 2-year changes in BMD if the software-driven analysis was used instead of taking the time to perform the operator-driven analysis was 18%. The findings of this study highlight the need to account for upgrades in analytic software. Furthermore, we present a rational approach for the analysis of serial scans that has face validity and that results in smaller differences between pairs of scans performed on the same individual. The decision to adapt these methods must be based on the relative costs of reducing unwanted scan variability.

Fabrication and characterization of tuned Gaussian mirrors for the visible and the near infrared.

A thin-film technique has been developed for vacuum fabrication of mirrors with Gaussian reflectivity profiles. Samples with diameters from 2 to 8 mm and assigned maximum reflectivities for visible or near-IR wavelengths have been made and their optical properties evaluated. By properly choosing both the geometry of the evaporation source and the masking system, one can obtain quasi-Gaussian or super-Gaussian reflectivity profiles.

Flash evaporation of compounds with a pulsed-discharge CO(2) laser.

Pulsed laser radiation at 10.6 microm has been used to evaporate a number of compounds chosen for their difficulty of evaporation with conventional techniques. An average laser power of 8 W, pulsed at 50 Hz with a 1-msec duration, has been found sufficient to obtain useful evaporation rates for Al(2)O(3) and other highly refractory materials. For easily decomposed materials such as CdS and ZnS, comparison of cw and pulsed evaporation through measurement of optical and photoconductive film properties consistently indicates higher stoichiometry in pulsed evaporation, as well as higher refractive index. The dynamics of film growth during a single laser pulse has been studied by means of a unique thickness monitor.