How does the brain control lifespan?

There is generally a positive correlation between brain/body size ratio and lifespan, particularly among mammals, suggesting a role for the brain in determining lifespan. Recent studies in diverse organisms including nematodes, flies and rodents have provided evidence that, indeed the brain may control lifespan. Signaling pathways involved in both central nervous system and peripheral stress responses and regulation of energy metabolism may play important roles in lifespan determination. Indeed, genetic and environmental manipulations of these systems can greatly affect lifespan by changing levels of hormones that modulate energy metabolism, stress resistance and regenerative capacity of cells throughout the body. A signal transduction pathway in neurons involving receptors coupled to phosphatidylinositol-3-kinase, Akt and glycogen synthase kinase-3beta appears to play a key role in regulation of longevity by the brain. Mutations in genes that encode proteins in the insulin signaling pathway can increase lifespan in C. elegans and Drosophila, this signaling pathway in neurons in the brain may be particularly important in limiting lifespan. Dietary restriction results in the upregulation of brain-derived neurotrophic factor (BDNF) in the brain, which may increase the resistance of neurons to aging. Interestingly, BDNF signaling in the brain can increase peripheral insulin sensitivity, suggesting a mechanism whereby the brain can control lifespan. We speculate that during evolution the brain took on the task of monitoring and controlling peripheral energy metabolism, and thereby regulating lifespan in the context of food availability. Roles for other evolutionarily conserved brain signaling pathways in lifespan determination are likely to be discovered in the near future.     

Pre-scaled two-parameter Gauss-Newton image reconstruction to reduce property recovery imbalance

Gauss-Newton image reconstruction in microwave imaging can be formulated in terms of a single complex quantity, the wave number squared (k2), with the understanding that the relative permittivity and conductivity images can be extracted afterwards through a simple constitutive relationship. However, this approach ignores the fact that the magnitude of the average real and imaginary components can be considerably out of balance depending on the operating frequency and tissue characteristics which can inadvertently imbalance the process in favour of one parameter over the other. In an effort to achieve property recovery which is balanced, we introduce a pre-scaling procedure at the property update stage of the reconstruction. Utilization of this concept in conjunction with our two-step regularization process for both simulation and phantom experiments demonstrates that the penalty term weighting parameters for the optimal mean-squared property errors for the two recovered distributions (relative permittivity and conductivity) together with that yielding the lowest least-squared electric field error coincide only when the scaling is applied. The scheme provides a means for simultaneous optimization of the two permittivity and conductivity images.     

Secondary microkeratome-induced flap interference with the pathway of the primary flap

PURPOSE: To report a flap-related complication that occurs when a secondary microkeratome pass interferes with the pathway of a complicated first microkeratome pass. DESIGN: Small, retrospective, noncomparative, interventional case series. PARTICIPANTS: Three patients. METHODS: In three cases, each patient experienced a different flap-related complication with the original surgery, followed by interference of a secondary flap with the primary. The first patient experienced a free cap, followed by an interference of the secondary flap at the nasal portion of the free cap. The second patient experienced a buttonhole, followed by secondary flap interference in the superior quadrant adjacent to the buttonhole. The third patient experienced a decentered flap originally, followed by secondary flap interference temporally. MAIN OUTCOME MEASURES: Visual result after secondary microkeratome-induced flap-related complications. RESULTS: All three patients had poor best spectacle-corrected visual acuity on the first postoperative day, with subsequent visual recovery. All three patients had induced flattening on keratometry along the axis where stromal tissue was removed. In addition, two patients required multiple enhancements to achieve desired visual outcomes. CONCLUSIONS: Complications related to the primary microkeratome pass add further risk for complications to arise during a second microkeratome pass. A secondary microkeratome pass should be attempted only if the original flap cannot be identified, if it is the result of primary flap complication, or if the desired treatment zone is notably larger than the diameter of the original flap. Intraoperative pachymetry of the residual stromal bed should be performed routinely. It is important to examine the stromal bed closely for loose or displaced slivers of tissue and to remove them before excimer treatment.     

Laser epithelial keratomileusis: outcome of initial cases performed by an experienced surgeon

PURPOSE: To evaluate refractive outcome and objective clinical data, and determine efficacy, predictability, and safety of laser epithelial keratomileusis (LASEK) for myopic treatments. METHODS: We performed a retrospective non-comparative single-surgeon case series on the first 20 LASEK procedures (Alcon LADARVision 4000 laser). Mean patient age was 41.2 years (range 21 to 60 yr): 13 men and 7 women. Mean preoperative spherical equivalent refraction was -6.47+/-2.78 D. Corneal haze, uncorrected and spectacle-corrected visual acuity and manifest refraction were evaluated. RESULTS: Of 20 eyes studied, 3 were corrected for monovision. In the non-monovision group, 20/40 or better visual acuity was achieved in 94% (16 eyes) at 1 month, 100% (13 eyes) at 3 months, and 91% (10 eyes) at 6 months after LASEK; 20/20 or better was achieved in 12% (2 eyes) at 1 month, 46% (6 eyes) at 3 months, and 45% (5 eyes) at 6 months. Corneal haze at 1 month was grade 0.5 in 35% (7 eyes), 1 in 20% (4 eyes) and 2 in 10% (2 eyes). At 3 months, 62% (12 eyes) had grade 0.5 and 31% (6 eyes) had grade 1. At 6 months, 58% (12 eyes) had grade 0.5, 25% (5 eyes) had grade 1, and 8% (2 eyes) had grade 2. CONCLUSIONS: LASEK is a challenging procedure. Creating the epithelial flap is not simple and may have contributed to the high haze incidence in our study.     

Cyclophosphamide treatment modifies tumor oxygenation and glycolytic rates of RIF-1 tumors: 13C magnetic resonance spectroscopy, Eppendorf electrode, and redox scanning

The effect of cyclophosphamide (Cp) on the glycolytic rate of radiation-induced fibrosarcomas (RIF-1) was measured in vivo in C3H mice by following the production of [3-(13)C]lactate after tail vein infusion of labeled [1-(13)C]glucose. Cp administered i.p. at a dose of 300 mg/kg caused a significant drop in glycolytic rate 24 h after treatment (P < 0.01). This drop was accompanied by an increase in [C-3]/[C-4] glutamate ratio in perchloric acid extracts of the tumors, indicating an increase in the Kreb's cycle activity. Treatment with Cp led to a significant decrease (P < 0.01) in tissue pO(2), measured in vivo with an oxygen Eppendorf electrode. Increases in NADH levels were also observed in rapidly frozen excised tumors examined by three-dimensional optical redox scanning. A significant decrease in tumor pO(2) and an increase in the NADH levels are suggestive of an increase in oxygen consumption by these tumors after Cp treatment. Overall, these data indicate that the reduction in glycolytic rate of Cp-treated RIF-1 tumors is due to an increase in aerobic metabolism.     

Transesophageal Echocardiographic Diagnosis of Coronary Stenosis in a Stroke Patient

This study represents another example of the usefulness of transesophageal echocardiography in the assessment of stenosis involving the proximal, mid, and distal coronary arteries in stroke patients referred for exclusion of a cardiac source of embolism.     

Cutaneous leishmaniasis in Guatemala: comparison of diagnostic methods

A comparison was made of methods used to diagnose suspected cutaneous leishmaniasis in Guatemala. The most sensitive method was a combination of thin smears made from superficial scrapings of the ulcers and inoculation of culture medium with either aspirates or scrapings. The diagnosis was confirmed in 252 (70%) of 362 patients. Ability to cultivate Leishmania was correlated with the concentration of amastigotes seen on thin smears. Leishmania were cultured in 42 (27%) of 153 patients with no amastigotes found in 400 oil-immersion fields and in 174 (83%) of 209 patients with at least 1 amastigote. No difference in diagnostic outcome was found when we compared smears or cultures taken from the center or the border of the ulcer or from an incision made tangential from the ulcer. We found no difference when we compared smears obtained with scalpels, capillary tubes, or dental broaches. The use of scrub brushes soaked in iodine neither decreased the rate of culturing parasites nor decreased contamination rates.