Decreased MT1 melatonin receptor expression in the suprachiasmatic nucleus in aging and Alzheimer's disease

The pineal hormone melatonin is involved in the regulation of circadian rhythms and feeds back to the central biological clock, the hypothalamic suprachiasmatic nucleus (SCN) via melatonin receptors. Supplementary melatonin is considered to be a potential treatment for aging and Alzheimer's disease (AD)-related circadian disorders. Here we investigated by immunocytochemistry the alterations of the MT1 melatonin receptor, the neuropeptides vasopressin (AVP) and vasoactive intestinal peptide (VIP) in the SCN during aging and AD. We found that the number and density of AVP/VIP-expressing neurons in the SCN did not change, but the number and density of MT1-expressing neurons in the SCN were decreased in aged controls compared to young controls. Furthermore, both MT1-expressing neurons and AVP/VIP-expressing neurons were strongly diminished in the last neuropathological stages of AD (Braak stages V-VI), but not in the earliest stages (Braak stages I-II), compared to aged controls (Braak stage 0). Our study suggests that the MT1-mediated effects of melatonin on the SCN are disturbed during aging and even more so in late stage AD, which may contribute to the clinical circadian disorders and to the efficacy of therapeutic melatonin administration under these conditions.     

Calibration and validation of toxicokinetic-toxicodynamic models for three neonicotinoids and some aquatic macroinvertebrates

Ecotoxicology - Exposure patterns in ecotoxicological experiments often do not match the exposure profiles for which a risk assessment needs to be performed. This limitation can be overcome by...     

Use of a matching algorithm to evaluate hospital coronary artery bypass grafting performance as an alternative to conventional risk adjustment

BACKGROUND: Although public reporting of hospital and physician performance is a cornerstone of the effort to improve health care quality, the optimal approach to risk adjustment is unknown. OBJECTIVE: We sought to assess hospital quality using a matching algorithm based on a generalized distance metric and to compare this approach to the more traditional regression-based approach. DESIGN/ DATA SOURCE: This was a retrospective study using the New York State (NYS) Coronary Artery Bypass Surgery Reporting System (CSRS), focusing on all patients undergoing isolated CABG surgery in NYS who were discharged in 1999 (18,116 patients). Patients from specific hospital were matched to a control group using the Mahalanobis distance. The hospitals' expected mortality rate was calculated in 2 ways: (1) as the mortality rate of the control group or (2) as the mortality rate predicted by the NYS CABG model. Hospitals whose observed mortality rate was significantly different from their expected mortality rate (OE difference) were defined as quality outliers. RESULTS: The 2 risk-adjustment methodologies disagreed on the outlier status of 4 of the 33 hospitals. Kappa analysis demonstrated substantial agreement between these 2 methods for identifying quality outliers: kappa = 0.61. There was excellent agreement between the point estimates of the OE difference obtained using these 2 risk adjustment methodologies. CONCLUSION: Basing outcome assessment on either matching or regression modeling yielded similar findings on hospital ranking but only moderate level of agreement on hospital quality. The use of matching may enhance the transparency and acceptance of outcome report cards by hospitals and physicians.     

Oral health status and prosthodontic conditions of Chinese adults: a systematic review

PURPOSE: To assess oral health and prosthodontic conditions of Chinese adults and the changes in these conditions over time. MATERIALS AND METHODS: PubMed was searched by combining the keyword China with dental health survey, oral health, tooth loss, DMFT (decayed/missing/filled teeth), dental prosthesis, or dentures. After selection, 12 studies remained. Data were obtained from these studies on DMFT, DMFT components, and teeth present and were tested against the following independent variables using analysis of variance: age, residence, and year of data collection. RESULTS: DMFT increased with age (P = .0001). Rural subjects presented higher DMFT based on the higher "decayed" component (P = .003), which increased markedly for subjects over 45 years of age. The number of teeth present decreased with increasing age (P = .0002). The results showed that Chinese subjects who are 65 years old have an average of 20 teeth. Urban subjects had more teeth present (P= .05), although no difference was seen for the "missing" component of DMFT. In general, few prosthodontic data could be extracted from the selected studies, and these data were often unspecific or inconclusive. CONCLUSIONS: The "filled" component of DMFT remained consistently low for all ages, indicating limited care. All outcomes were independent from year of data collection, indicating unchanged care. Outcome aggregation on the number of functional teeth and prosthetic care was impossible. For future reports, it is recommended to include additional information about location and function (in terms of occluding pairs) of teeth present when describing oral health status.     

Frontostriatal system in planning complexity: a parametric functional magnetic resonance version of Tower of London task

In the present study, we sought to investigate which brain structures are recruited in planning tasks of increasing complexity. For this purpose, a parametric self-paced pseudo-randomized event-related functional MRI version of the Tower of London task was designed. We tested 22 healthy subjects, enabling assessment of imaging results at a second (random effects) level of analysis. Compared with baseline, planning activity was correlated with increased blood oxygenation level-dependent (BOLD) signal in the dorsolateral prefrontal cortex, striatum, premotor cortex, supplementary motor area, and visuospatial system (precuneus and inferior parietal cortex). Task load was associated with increased activity in these same regions. In addition, increasing task complexity was correlated with activity in the left anterior prefrontal cortex, a region supposed to be specifically involved in third-order higher cognitive functioning.     

Post-surgical pain syndromes: a review for the non-pain specialist

Purpose

This is a selective narrative review of the latest information about the epidemiology, impact, and prevention of chronic post-surgical pain (CPSP), intended primarily for those without a special interest in pain medicine.

Principal findings

Chronic post-surgical pain is an important problem in terms of personal impact. It has staggering economic implications, exerts powerful negative effects on the quality of life of many of those it afflicts, and places a significant burden on chronic pain treatment services in general. It is well known that surgery at certain body sites is apt to cause CPSP, but emerging evidence shows a strong correlation between CPSP and demographic (young age, obesity, and female sex) and psychological characteristics (anxiety, depression, stress, and catastrophizing). Severe acute pain is a strong risk factor for CPSP, and this adds yet more weight to the argument that acute pain should be controlled effectively. In specific circumstances, CPSP can be reduced by regional anesthetic techniques, infiltration of local anesthetic, or preoperative use of gabapentin. The ability of other known interrupters of afferent nociceptive transmission—commonly used to reduce CPSP when administered at the time of surgery—is currently unproven, as is the hypothesis that the use of remifentanil during surgery worsens CPSP.

Conclusions

Reduction of CPSP is a worthy long-term outcome for anesthesia providers to consider as they plan the perioperative care of their patients. More evidence is needed about the effect of currently used analgesics and other perioperative techniques on CPSP.     

Expression of bcr-abl abrogates factor-dependent growth of human hematopoietic M07E cells by an autocrine mechanism

The introduction of a retrovirus vector expressing p210bcr-abl (P210) into the human factor-dependent cell line M07E resulted in the rapid outgrowth of factor-independent cells. Early after infection, four factor-independent clones were isolated and analyzed in greater detail along with mass populations obtained from separate infections. High levels of P210 tyrosine kinase activity were measured in the factor- independent cells. The mass populations and three of the four clones remained responsive to exogenous growth factors. Concentrated conditioned media isolated from the factor-independent populations and from all clones contained biologically active granulocyte-macrophage colony-stimulating factor (GM-CSF); interleukin-3 (IL-3) was detected at low levels in the mass population and in two of the clones. Neutralizing antibodies to IL-3, GM-CSF, and mast cell growth factor inhibited proliferation of the factor responsive clones by 60% to 90%. These results indicate that the growth autonomy of the P210-expressing M07E cells was acquired via an autocrine mechanism. In addition to factor-independent growth, P210-expressing M07E cells readily acquired a more mature megakaryocytic phenotype compared with control M07E cells. These data provide experimental evidence that expression of P210 tyrosine kinase in human hematopoietic cells induced growth factor secretion resulting in a pleiotropic effect on growth factor dependence and differentiation.