Global changes in the hippocampal proteome following exposure to an enriched environment

Exposure to an enriched environment promotes neurochemical, structural and neurophysiological changes in the brain and is associated with enhanced synaptic plasticity and improved hippocampal-dependent learning. Using a global proteomics-based approach we have now been able to reveal the altered expression of a diverse range of hippocampal proteins following exposure to an enriched environment. Male Hooded Lister rats (8 weeks) were subjected to a 6-week regimen in which they were housed in either non-enriched (open field) or enriched conditions (toys, wheels etc.). Whole protein extracts from stratum pyramidale and stratum radiatum of area CA1 were then isolated and subjected to differential gel electrophoresis [McNair K, Davies CH, Cobb SR (2006) Plasticity-related regulation of the hippocampal proteome. Eur J Neurosci 23(2):575-580]. Of the 2469 resolvable protein spots detected in this study, 42 spots (1.7% of the detectable proteome) derived from predominantly somatic fractions and 32 proteins spots from dendritic fractions (1.3% of detectable proteome) were significantly altered in abundance following exposure to an enriched environment (somatic: 14 increased/28 decreased abundance, range -1.5 to +1.4-fold change; dendritic: 16 increased, 16 decreased abundance, range -1.6 to +3.0-fold change). Following in-gel tryptic digestion and Maldi-Tof/Q-star mass spectrometry, database searching revealed the identity of 50 protein spots displaying environmental enrichment-related modulation of expression. Identified proteins belonged to a variety of functional classes with gene ontology analysis revealing the majority (>70%) of regulated proteins to be part of the energy metabolism, cytoplasmic organization/biogenesis and signal transduction processes.     

Guidelines for prevention of hospital acquired infections

These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments.     

Modeling the impact of comorbidity on breast cancer patient outcomes

The objective of this paper is to model the impact of comorbidity on breast cancer patient outcomes (e.g., length of stay and disposition). Previous studies suggest that comorbidities may significantly affect mortality risks for breast cancer patients. The 2006 AHRQ Nationwide Inpatient Sample (NIS) is used to analyze the relationships among comorbidities (e.g., hypertension, diabetes, obesity, and mental disorder), total charges, length of stay, and patient disposition as a function of age and race. A multifaceted approach is used to quantify these relationships. A causal study is performed to explore the effect of various comorbidities on patient outcomes. Least squares regression models are developed to evaluate and compare significant factors that influence total charges and length of stay. Logistic regression is used to study the factors that may cause patient mortality or transferring. In addition, different survival models are developed to study the impact of comorbidity on length of stay with censoring information. This study shows the interactions and relationship among various comorbidities and breast cancer. It shows that certain hypertension may not increase length of stay and total charges; diabetes behaves differently among general population and breast cancer patients; mental disorder has an impact on patient disposition that affects true length of stay and charges, and obesity may have limited effect on patient outcomes. Moreover, this study will help to better understand the expenditure patterns for population subgroups with several chronic conditions and to quantify the impact of comorbidities on patient outcomes. Lastly, it also provides insight for breast cancer patients with comorbidities as a function of age and race.     

Ultrasound-Induced Mild Hyperthermia as a Novel Approach to Increase Drug Uptake in Brain Microvessel Endothelial Cells

Purpose. Drug delivery to the central nervous system (CNS) is limited by the blood-brain barrier (BBB). Thus, a noninvasive and reversible method to enhance BBB permeation of drugs is highly desirable. In the present work, we studied if ultrasound-induced mild hyperthermia (USHT, 0.4 watts (W)/cm² at 41°C) can enhance drug absorption in BBB endothelial cells, and we elucidated the mechanism of USHT on cellular accumulation. Methods. To accomplish these aims, we studied the effects of hyperthermia (41°C), USHT, P-glycoprotein (P-gp) modulator (PSC 833), and combination of USHT and PSC 833 on accumulation of P-gp substrate (R123) and non-P-gp substrates (sucrose, 2-deoxyglucose, and antipyrine) in monolayers of primary bovine brain microvessel endothelial cells (BBMEC). Results. USHT, through its thermal effect, produces a significant (relative to controls; no USHT) and comparable increase in R123 accumulation with PSC 833. We also demonstrate that USHT increases permeability of hydrophobic (R123 and [¹⁴C]-antipyrine) and not hydrophilic molecules ([¹⁴C]-sucrose and 2-[³H]-deoxy-d-glucose). The enhanced permeability is reversible and size dependent, as USHT produces a much larger effect on cellular accumulation of [¹⁴C]-antitpyrine (molecular weight of 188 D) than that of R123 (molecular weight of 380.8 D). Although USHT increases membrane permeability, it did not affect P-gp activity or the activity of glucose transporters. Conclusions. Our results point to the potential use of USHT as a reversible and noninvasive approach to increase BBB permeation of hydrophobic drugs, including P-gp-recognized substrates.     

A TEM/SEM study of the microbial plaque overlying the necrotic gingival papillae of HIV-seropositive,necrotizing ulcerative periodontitis

The purpose of this study was to examine by transmission (TEM) and scanning electron microscopy (SEM) the supragingival microbial plaque overlying the ulcerated gingival papillae of necrotizing ulcerative periodontitis (NUP) lesions in HIV-seropositive patients. The microbiota of NUP and HIV-seropositive patients with periodontitis has been reported to be similar to that of conventional periodontitis in non-infected subjects, although several investigators have also reported high recovery rates of microbes not generally associated with the indigenous oral microbial flora. Light and electron microscopic observations and microbial culture studies indicate a similar high prevalence of spirochetes in both necrotizing ulcerative gingivitis (NUG) and NUP. In addition, several studies have reported more frequent isolation of Candida albicans from diseased periodontal sites in HIV-seropositive patients than from non-diseased sites. Ten male and six female patients, each HIV-seropositive and exhibiting NUP, constituted the study population. Two biopsies of involved gingival papillae from between posterior teeth were obtained from each patient and processed for examination by both TEM and SEM. Microscopic examination revealed a surface biofilm comprised of a mixed microbial flora of various morphotypes in 81.3% of biopsy specimens. The subsurface flora featured dense aggregations of spirochetes in 87.5% of specimens. Zones of aggregated polymorphonuclear leukocytes and necrotic cells were also noted. Yeasts were observed in 65.6% of specimens and herpes-like viruses in 56.5% of the specimens. Collectively, except for the presence of yeast and viruses, the results suggest that the microbial flora and possibly the soft tissue lesions of NUP and necrotizing ulcerative gingivitis are very similar.     

A preliminary study on oxygen saturation levels of patients during periodontal surgery with and without oral conscious sedation using diazepam

BACKGROUND: Stress and anxiety alter respiratory rate and thereby alter oxygen saturation in the blood. Management of psychological stress in the dental office may help maintain blood gas homeostasis. One method of stress management is through the use of preoperative oral sedation. METHODS: The study population consisted of 13 patients scheduled to receive two quadrants of periodontal surgery at two different appointments. A randomized split-mouth crossover design was used with one quadrant of surgery involving preoperative oral sedation (diazepam) and local anesthetic, and the second using local anesthetic only. Oxygen saturation was monitored by pulse oximetry, which recorded the number of times saturation dropped below 95% in a given time period. Data were recorded at 5 time periods: 1) baseline; 2) from time of anesthetic administration to 20 minutes into surgery; 3) 21 to 40 minutes; 4) 41 to 60 minutes; and 5) 61 to 80 minutes into the surgery. Data were analyzed by a two-factor repeated measures ANOVA. The two within-group factors were treatment group and time. RESULTS: Results indicated no significant interaction between time and treatment (P > .05). However, data for groups over time suggested a trend supporting an interaction. The eta2 value of 0.124 suggested a moderate effect favoring the diazepam treatment. No significant difference was noted for the main effect of treatment and time. However, the eta2 value of 0.24 for treatment effect (diazepam versus no diazepam) suggested a meaningful difference between groups. Similarly the eta2 value of 0.135 for time suggested a moderate effect over time within-subjects. CONCLUSIONS: This study indicates that diazepam given orally in adult dosages does not cause significant respiratory depression, and is generally safe for those healthy patients who may require slight to mild sedation during periodontal surgery.     

Qualitative research: what does it have to offer to the gerontologist?

The growing challenges of promoting health and managing illness in an ever-changing health care system require an arsenal of research approaches. Qualitative methods have a long tradition in disciplines such as sociology and anthropology and are being used with greater frequency as interdisciplinary health-related disciplines attempt to understand and explain complex problems. The purpose of this article is to define and describe the main features of qualitative research and to examine ways in which this methodology is relevant and useful in gerontological studies. A concise comparison of quantitative and qualitative methods is made, and suggestions are provided for when qualitative approaches are useful. A review of the three most common approaches is provided. Most important, references are provided for those gerontologists interested in learning more about qualitative research methods.