Physical Activity Is Associated with Slower Cognitive Decline in Older Adults with Type 2 Diabetes.

BACKGROUND: Physical activity is associated with slower cognitive decline in old age. Type 2 diabetes (T2d) is a risk factor for dementia and cognitive decline. Physical activity protects against several T2d complications. Yet, little is known about the contribution of physical activity to cognitive health among the elderly with T2d. OBJECTIVES: To examine the association between physical activity and cognitive decline in older adults with T2d. DESIGN: This is a prospective longitudinal study using data from the Israel Diabetes and Cognitive Decline (IDCD) study. SETTING: ICDC study (N=1,213), is a population-based cohort of adults over the age of 65, diagnosed with type 2 diabetes, who were cognitively normal at baseline and followed up every 18 months. PARTICIPANTS: Participants with at least one follow-up assessment who were in the same physical activity group consistently and had complete demographic data. MEASUREMENTS: Physical activity was measured using Minnesota Leisure Time Activity Questionnaire, cognitive functioning was measured using a broad neuropsychological assessment measuring Executive Functioning, Attention/Working Memory, Semantic Categorization and Episodic Memory. RESULTS: Participants were classified into physical activity groups based on self-reported physical activity at baseline and all follow ups: "active" - participation in recreational physical activity (n=286); "non-active"- the only physical activity was walking from place to place (n=93) and "sedentary" (n=19). Linear mixed effects models were applied to adjust for key demographic and cardiovascular risk factors. Participants were 72.4 (SD 4.6) years old, had 13.3 (SD 3.6) years of education, and 163 (41%) were female. In the fully adjusted model, compared to the non-active group the active group had significantly slower rate of decline in Global Cognition (p=0.005), Executive Functioning (p=.014), and Attention/Working Memory (p=.01). There were no significant group differences for Semantic Categorization (p=.17) and Episodic Memory (p=.88). CONCLUSIONS: Among initially cognitively normal and independent older adults with T2d, a physically active lifestyle was associated with a slower rate of cognitive decline. Future research should examine whether promoting physical activity may prevent or delay onset of dementia in this high-risk population.

ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development.

Epithelial cells of human breast glands are exposed to various mechanical ECM stresses that regulate tissue development and homeostasis. Mechanoadaptation of breast gland tissue to ECM-transmitted shear stress remained poorly investigated due to the lack of valid experimental approaches. Therefore, we created a magnetic shear strain device that enabled, for the first time, to analyze the instant shear strain response of human breast gland cells. MCF10A-derived breast acini with basement membranes (BM) of defined maturation state and basoapical polarization were used to resemble breast gland morphogenesis in vitro. The novel biophysical tool was used to apply cyclic shear strain with defined amplitudes (≤15%, 0.2 Hz) over 22 h on living spheroids embedded in an ultrasoft matrix (<60 Pa). We demonstrated that breast spheroids gain resistance to shear strain, which increased with BM maturation and basoapical polarization. Most intriguingly, poorly developed spheroids were prone to cyclic strain-induced extrusion of apoptotic cells from the spheroid body. In contrast, matured spheroids were insensitive to this mechanoresponse-indicating changing mechanosensing or mechanotransduction mechanisms during breast tissue morphogenesis. Together, we introduced a versatile tool to study cyclic shear stress responses of 3D cell culture models. It can be used to strain, in principle, all kinds of cell clusters, even those that grow only in ultrasoft hydrogels. We believe that this approach opens new doors to gain new insights into dynamic shear strain-induced mechanobiological regulation circuits between cells and their ECM.

Infrared observations of the neptunian system.

The infrared interferometer spectrometer on Voyager 2 obtained thermal emission spectra of Neptune with a spectral resolution of 4.3 cm(-1). Measurements of reflected solar radiation were also obtained with a broadband radiometer sensitive in the visible and near infrared. Analysis of the strong C(2)H(2) emission feature at 729 cm(-1) suggests an acetylene mole fraction in the range between 9 x 10(-8) and 9 x 10(-7). Vertical temperature profiles were derived between 30 and 1000 millibars at 70 degrees and 42 degrees S and 30 degrees N. Temperature maps of the planet between 80 degrees S and 30 degrees N were obtained for two atmospheric layers, one in the lower stratosphere between 30 and 120 millibars and the other in the troposphere between 300 and 1000 millibars. Zonal mean temperatures obtained from these maps and from latitude scans indicate a relatively warm pole and equator with cooler mid-latitudes. This is qualitatively similar to the behavior found on Uranus even though the obliquities and internal heat fluxes of the two planets are markedly different. Comparison of winds derived from images with the vertical wind shear calculated from the temperature field indicates a general decay of wind speed with height, a phenomenon also observed on the other three giant planets. Strong, wavelike longitudinal thermal structure is found, some of which appears to be associated with the Great Dark Spot. An intense, localizd cold region is seen in the lower stratosphere, which does not appear to be correlated with any visible feature. A preliminary estimate of the effective temperature of the planet yields a value of 59.3 +/- 1.0 kelvins. Measurements of Triton provide an estimate of the daytime surface temperature of 38(+3)(-4) kelvins.

Ultraviolet spectrometer observations of uranus.

Data from solar and stellar occultations of Uranus indicate a temperature of about 750 kelvins in the upper levels of the atmosphere (composed mostly of atomic and molecular hydrogen) and define the distributions of methane and acetylene in the lower levels. The ultraviolet spectrum of the sunlit hemisphere is dominated by emissions from atomic and molecular hydrogen, which are kmown as electroglow emissions. The energy source for these emissions is unknown, but the spectrum implies excitation by low-energy electrons (modeled with a 3-electron-volt Maxwellian energy distribution). The major energy sink for the electrons is dissociation of molecular hydrogen, producing hydrogen atoms at a rate of 10(29) per second. Approximately half the atoms have energies higher than the escape energy. The high temperature of the atmosphere, the small size of Uranus, and the number density of hydrogen atoms in the thermosphere imply an extensive thermal hydrogen corona that reduces the orbital lifetime of ring particles and biases the size distribution toward larger particles. This corona is augmented by the nonthermal hydrogen atoms associated with the electroglow. An aurora near the magnetic pole in the dark hemisphere arises from excitation of molecular hydrogen at the level where its vertical column abundance is about 10(20) per square centimeter with input power comparable to that of the sunlit electroglow (approximately 2x10(11) watts). An initial estimate of the acetylene volume mixing ratio, as judged from measurements of the far ultraviolet albedo, is about 2 x 10(-7) at a vertical column abundance of molecular hydrogen of 10(23) per square centimeter (pressure, approximately 0.3 millibar). Carbon emissions from the Uranian atmosphere were also detected.

The influence of PEEP on survival of patients in respiratory failure: a retrospective analysis.

Positive end expiratory pressure breathing (PEEP) is used to decrease morbidity and mortality in patients who are hypoxemic despite breathing oxygen in concentrations potentially toxic to their lungs. We reviewed the hospital course of 78 patients whose arterial oxygen tension (PaO2) was less than 70 torr despite a fraction of inspired oxygen (FiO2) of 1.0. Only 60 per cent of these patients were treated with PEEP and their clinical illnesses and severity of cardiopulmonary dysfunction were similar to those in patients not treated with PEEP. PEEP increased the length of survival from 4.2 to 9.2 days (P less than 0.05) whereas over-all survival, defined as hospital discharge, was similar at 31 per cent with and 26 per cent without PEEP. An improvement in PaO2 and decrease in shunt fraction following a trial of PEEP portends a favorable outcome, but its continued use appears to prolong life for a few days without affecting hospital mortality. Survival appears related more to the maintenance of adequate tissue oxygenation as manifested by a high mixed venous oxygen than to improved gas exchange as reflected by an increase in PaO2.

Synthesis and enzymic activity of some novel xanthine oxidase inhibitors. 3-Substituted 5,7-dihydroxypyrazolo(1,5-alpha)pyrimidines.

A series of 3-substituted 5,7-dihydroxypyrazolo[1,5-alpha]pyrimidines containing various aromatic [phenyl- (3e), 3-pyridyl- (3f), p-bromophenyl- (3g), p-chlorophenyl- (3h), p-acetamidophenyl- (3i), p-tolyl- (3j), m-tolyl- (3k), 3,4-methylenedioxyphenyl- (3m), or naphthyl- (3n)] or nonaromatic [hydrogen- (3a), nitro- (3b), bromo- (3c), or chloro- (3d)] substituents in the 3 position was synthesized and tested as inhibitors of xanthine oxidase. The compounds (3a-m) were synthesized by condensation of the appropriate 3-amino-4-substituted pyrazole with diethyl malonate in alcoholic sodium methoxide and neutralization of the resulting enol sodium salts. As inhibitors of xanthine oxidase, 3e-n greater than 3a,c,d congruent to allopurinol greater than 3b. The 3-aryl-substituted compounds 3e-n were 30-160 times better xanthine oxidase inhibitors than allopurinol using hypoxanthine as substrate and 10-80 times better using xanthine as substrate, as evidenced by a comparison of Ki values. The inhibition by all compounds (3a-n) was totally reversible and of the noncompetitive or mixed type. A study of the pH dependence of xanthine oxidase inhibition by 3a,e,g and allopurinol indicated that the 3-aryl substituents facilitated binding to the enzyme. These and the above results show that the compounds reported here inhibit xanthine oxidase by a mechanism which is significantly different from that of allopurinol.

Synthesis and antitrichomonal activity of certain pyrazolo (1,5-a) pyrimidines.

Several bridgehead nitrogen heterocycles were synthesized to be screened as antimicrobial agents, modeled after nalidixic acid. The activity of these new compounds, all derivatives of 3-nitro-4,6-disubstituted pyrazolo (1,5-a)pyrimidin-7-ones (3,7,8, and 9), however, was found to be highly specific for Trichomonas foetus and completely lacking in activity against bacteria, fungi, and parasites other than Trichomonas. Of the nine componds synthesized, including the intermediate 4,6-disubstituted pyrazolo (1,5-a) pyrimidin-7-ones (2-6) and the 6-substituted or unsubstituted pyrazolo (1,5-a) pyrimidin-7-ones (1 and 4), only 6-carbethoxy-4-ethyl-3-nitropyrazolo(1,5-a)pyrimidin-7-one (7) was found to be a potent antitrichomal agent, being comparable or perhaps better than metronidazole. From a tentative structure-activity relationship study, it was apparent that the combination of the 3-mitro, 4-ethyl, and 6-carbethoxy groups imparted specific activity, wheras other substitutions imparted little or no antitrichomonal activity.

Synthesis and enzymic activity of 6-carbethoxy- and 6-ethoxy-3,7-disubstituted-pyrazolo[1,5-a]pyrimidines and related derivatives as adenosine cyclic 3' ,5'-phosphate phosphodiesterase inhibitors.

A number of 3,7-disubstituted 6-carbethoxypyrazolo [1,5-a] pyrimidines and 3,7-disubstituted 6-ethoxypyrazolo-[1,5-a]pyrimidines have been prepared and evaluated as adenosine cyclic 3',5'-phosphate (cAMP) phosphodiesterase (PDE) inhibitors vs. the low Km enzyme isolated from beef heart, rabbit lung, and kidney preparations. The results were found to be between 0.5 to 13 times as potent as theophylline as inhibitors of PDE, depending on the tissue source. A number of these PDE inhibitors exhibited significant physiological effects in different animal systems, suggesting it should be possible to obtain selective PDE inhibition in various tissues. Several of these heterocycles were found superior to adenosine in inhibiting ADP-induced platelet aggregation in vitro.

2-(Alkylthio)-1,2,4-triazolo[1,5-a]pyrimidines as adenosine cyclic 3',5'-monophosphate phosphodiesterase inhibitors with potential as new cardiovascular agents.

A series of new 2-(alkylthio)-5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines have been prepared as inhibitors of cAMP phosphodiesterase from various tissues. These derivatives were prepared via ring closure of various requisite 3-amino-1,2,4-triazole intermediates. 2-(Benzylthio)-5-methyl-7-(dimethylamino)-1,2,4-triazolo[1,5-a]pyrimidine (15a) is 6.3 times as potent as theophylline in inhibiting cAMP PDE isolated from rabbit heart. Treatment of dogs intravenously with 5 (mg/kg)/h of 15a gave a cardiac output increase of 69%, which was largely sustained for a 2-h period after administration of drug had ceased. There was no significant increase in heart rate upon administration of 15a. Related studies with 5,7-di-n-propyl-2-(benzylthio)-1,2,4-triazolo[1,5-a]pyrimidine (22a) in five dogs showed a 31.5% increase in cardiac output with an increase in stroke volume of 34.4% with no increase in heart rate. The specificity of action of these PDE inhibitors could be due to selective binding at a certain cAMP PDE site in the cardiovascular system. Several of these compounds are candidates for further studies with a view to clinical evaluation.

Effects of changes in arterial carbon dioxide tension on oxygen consumption during cardiopulmonary bypass.

The effects of changes in arterial carbon dioxide tension (PaCO2) on the oxygenation of tissues in 34 patients undergoing surgery for aortocoronary bypass were studied while temperature, systemic blood flow, and the delivery of oxygen to the peripheral tissues remained constant. Mixed venous and superior vena caval oxygen tensions (PvO2 and PsvcO2, respectively) and oxyhemoglobin saturations and the in vivo partial pressure of oxygen at which 50 percent of the hemoglobin is saturated (P50) increased with PaCO2, while peripheral vascular resistance, in vitro P50, the level of 2,3-diphosphoglyceric acid in the red blood cells, and the level of lactate in the blood remained constant. There was a close correlation between increases in PaCO2 and increases in PvO2 (r = 0.912; P less than 0.001) but not increases in PsvcO2 (r = 0.364; not significant). This indicated that the total-body consumption of oxygen diminished with increases in PaCO2 but that some regional redistribution of oxygen consumption occurred between the superior and inferior vena caval vascular beds. Since the level of lactate in the blood remained constant and since signs of metabolism acidosis did not develop, the reduced oxygen consumption due to increases in PaCO2 did not result in detectable increases in anaerobic metabolism.

An epizootiological study of acute death syndrome and leg weakness in broiler chickens in western Canada.

In a survey of 51 broiler chicken flocks, the incidence of chickens dying from acute death syndrome and of those with skeletal deformities varied from 0.71 to 4.07% and from 0.46 to 4.08% among the flocks, respectively. The average incidence of those with skeletal deformities was 1.72%; 1.10% were culled in the field, and 0.62% were condemned or downgraded as carcasses. The major types of skeletal deformities were valgus deformation of the intertarsal joint (70%), varus deformation of the intertarsal joint (9%), tibial rotation (7%), and spondylolisthesis (14%). The strain and source of chickens and the management and nutritional practices were recorded for each flock. Statistical analyses were conducted in an attempt to identify factors that might correlate with the incidence of either chickens dying from acute death syndrome or those with skeletal deformities. Results of these analyses are discussed.

Elevated serum Chlamydia trachomatis IgG antibodies. What do they mean for IVF pregnancy rates and loss?

OBJECTIVE: To evaluate the impact of elevated serum Chlamydia IgG antibodies (Ab) on in vitro fertilization (IVF) outcome in a large infertility population. STUDY DESIGN: One hundred ninety-four women under 40 years of age undergoing a total of 316 IVF cycles were evaluated. All couples with positive serum Chlamydia IgG Ab were pretreated with doxycycline, 100 mg twice daily, for 10 days prior to the first IVF cycle. RESULTS: One hundred seven women (55.2%) had elevated serum Chlamydia IgG Ab. One hundred seventy-two IVF cycles (54.4%) were in patients with elevated Ab as compared to 144 cycles (45.6%) in controls with negative Ab. There were no significant differences in mean age, number of mature oocytes obtained or number of embryos transferred between the two groups. Patients with elevated IgG Ab had on ongoing pregnancy rate of 30.2% (52/172) and implantation rate of 13.5% (101/746) as compared to 34.7% (50/144) and 13.6% (88/649) in the negative Ab group, respectively (P = NS for both). Two ectopic pregnancies occurred in the elevated Ab group (1.2%, 2/172) vs. none in the negative Ab group. The incidence of early pregnancy loss was 8.7% (15/172) and 9.7% (14/144) in the positive and negative Ab groups, respectively (P = NS). CONCLUSION: The prevalence of elevated serum Chlamydia IgG Ab in patients presenting for IVF was higher than in the general population. In the absence of an active genital tract infection, the presence of elevated serum Chlamydia IgG Ab was not associated with a poor IVF outcome when couples were treated with antibiotics prior to stimulation. In addition, there was no correlation between IVF outcome and quantitative IgG Ab titers in women with elevated serum Chlamydia Ab. We recommend that all couples with elevated titers be treated with doxycycline prior to the first IVF attempt to optimize pregnancy rates and minimize infectious complications.

Saline augmentation mammaplasty: nursing implications.

Saline augmentation mammaplasty has dramatically increased in popularity over the past 5 years. Maximizing immediate and long-term results requires skilled perioperative nursing intervention.

The adjustable saline augmentation mammaplasty.

The use of an expander/implant for augmentation mammaplasty allows for increased patient satisfaction in the postoperative period. Surgical time may be shortened as final volume determination is not an intraoperative concern, and secondary surgery for certain complications such as asymmetry, wrinkling, and capsular contracture can often be avoided.