Body mass index and infectious disease mortality in midlife in a cohort of 2.3 million adolescents.

BACKGROUND: Obesity was linked to altered immunity, but also to favorable outcomes among patients with infectious disease (ID) in some settings. We assessed the association between adolescent body mass index (BMI) and ID mortality. METHODS: BMI of 2 294 139 Israeli adolescents (60% men; age 17.4±0.3 years) was measured between 1967 and 2010. The outcome, obtained by linkage with official national records, was death due to ID as the underlying cause. Multivariable Cox proportional hazards models were applied. RESULTS: During 42 297 007 person-years of follow-up (median 18.4 years), there were 689 deaths from ID (mean age 44.1±10.5 years). Adjusted hazard ratios (HR) were 1.039 (1.011-1.068) and 1.146 (1.099-1.194) among men and women, respectively, per unit increment in BMI (P for sex interaction=4.4 × 10-5). Adjusted hazard ratios among men were 1.2 (1.0-1.5), 1.9 (1.4-2.5) and 2.5 (1.5-4.2) for those with high-normal BMI (22.0-24.9 kg m-2), overweight and obese, respectively, compared with the 18.5⩽BMI<22 kg m-2 reference group, and 1.7 (1.1-2.6), 2.6 (1.6-4.3) and 6.6 (3.3-13.1) among women, respectively. The increased risk among underweight (<18.5 kg m-2) boys was attenuated when the study sample was restricted to those with unimpaired health at baseline. A multivariable spline model indicated a minimum risk for total ID mortality at 20.7 and 18.0 kg m-2 for men and women, respectively, with significantly increased risk seen above adolescent BMI values of 23.6 and 24.0 kg m-2, respectively. The association with BMI was particularly evident for bacterial infections (predominantly sepsis), airways and central nervous system infections (63% of the ID deaths). CONCLUSIONS: Adolescent overweight and obesity were strongly associated with ID mortality, especially of bacterial origin and among women.

Population-based trends in overweight and obesity: a comparative study of 2,148,342 Israeli male and female adolescents born 1950-1993.

BACKGROUND: The epidemic of obesity has been identified as a major source of morbidity, not just in developed countries but globally, in adults as well as at younger ages. OBJECTIVE: The aims of this study were to describe trends in obesity and overweight in Israeli adolescents and observe temporal changes and association by risk factors. METHODS: The research analyzed records of 2,148,342 Jewish adolescents, over a span of 44 years and included data for individual body measurements, place of residence, area of origin and education levels. Body mass index (BMI) was measured by professionals, calculated and categorized as overweight or obesity according to age- and gender-specific BMI curves established in recent years. We processed the data in multinomial logistic regression model and calculated odds ratios for various risk factors. RESULTS: Obesity and overweight are on the rise for male and female adolescents born from the mid-1960s onwards, and especially for men from the 1980s onwards. Risk factors for male adolescents include lower socioeconomic status, inferior education levels and Western origins (vs. Asian, African or Israeli origins). Risk modifiers for women were similar, except for African origins, which were associated with increased risk rather than decreased risk. Asian and Israeli origins were protective for both genders, and education was more strongly associated with obesity for women. CONCLUSIONS: We recommend stronger preventive efforts directed at adolescents as a whole, and particularly vulnerable groups with lower education levels and poverty, or those with specific geographical origins. Gender disparities are evident and should be considered in these efforts and in further research.

Nitric oxide modulates the transfer function between cones and horizontal cells during changing conditions of ambient illumination.

It has been suggested that nitric oxide (NO) serves as a retinal neuromodulator, adjusting retinal function to changing conditions of adaptation. We tested this hypothesis in the intact turtle retina by recording the photoresponses of L-cones and L1-horizontal cells, while changing retinal NO level and background illumination. Raising the retinal level of NO, by adding an NO donor (sodium nitroprusside) or the precursor for NO synthesis (L-arginine), induced response augmentation in L-cones and L1-horizontal cells. Lowering retinal level of NO by adding L-NAME, an inhibitor of NO synthesis, reduced the amplitudes of the photoresponses in these retinal neurons. The transfer function between L-cones and L1-horizontal cells, constructed from the photoresponses of these cells, was modified by NO and by background lights. The nonlinear transfer function, characteristic of the dark-adapted retina, became linear and of low gain when the retinal NO level was increased or by increasing the level of ambient illumination. In contrast, inhibiting NO synthesis in the light-adapted retina induced nonlinearity in the cone-to-horizontal cell transfer function similar to that seen in the dark-adapted state. NADPH diaphorase histochemistry, conducted on isolated retinal cells, demonstrated activity in cone inner segments and distal process of Müller cells. These findings support the hypothesis that NO synthesis in the distal turtle retina is triggered by background illumination, and that NO acts to adjust the modes of visual information processing in the outer plexiform layer to the conditions required during continuous background illumination.

Spatial-chromatic interactions in C-type horizontal cells of the turtle (Mauremys caspica) retina.

Horizontal cells are second-order retinal neurons that play a key role in spatial information processing. In some cold-blooded vertebrates such as turtles, a subtype of these cells, the chromaticity horizontal cells exhibit color-opponent responses and therefore are considered to be important also for color information processing. To reveal spatial and color interactions, the receptive-field properties of Red/Green and Yellow/Blue chromaticity horizontal cells in the retina of the turtle Mauremys caspica were studied by intracellular recordings from the everted eyecup preparation. We found that the polarity of the photoresponses depended not only upon the wavelength and intensity of the stimulus, but also upon its spatial configuration. Thus, a hyperpolarizing photoresponse that was elicited by full-field stimulation with bright light of wavelength close to the "neutral" one was reversed in polarity to a pure depolarizing one when a small spot or a thin annular pattern were used for stimulation. This finding could not be explained either by different balances between depolarizing and hyperpolarizing inputs to different cells or by stray light that effectively reduced the light intensity in the center of the small spot. Rather, it was found that the depolarizing and hyperpolarizing components were characterized by different receptive-field size and that these differences could account for the dependency of response polarity upon the spatial pattern of the stimulus. These findings indicate that color information processing in turtle C-type horizontal cells is a complex process that depends upon the wavelength and intensity of the light stimulus as well as upon its spatial properties.

Turtle C-type horizontal cells act as push-pull devices.

Chromaticity (C-type) horizontal cells in the retina of cold-blooded vertebrates receive antagonistic inputs from cone photoreceptors of different spectral types leading to color opponency. The relative contribution of each spectral type of cones can be selectively altered by chromatic background illumination. Therefore, the spectral properties of C-type horizontal cells are expected to change when the intensity and color of ambient illumination are altered. In this study, we investigated the effects of chromatic background lights upon color opponency in Red/Green (RGH) and Yellow/Blue (YBH) C-type horizontal cells in the everted eyecup preparation of the turtle Mauremys caspica. Photoresponses were elicited by long-wavelength and short-wavelength light stimuli in the dark-adapted state and under conditions of chromatic background illumination. We found that the total voltage range. within which graded depolarizing and the hyperpolarizing photoresponses could be elicited, either increased or decreased depending upon the color of the background light. However, the maximal and minimal potential levels determined respectively by long-wavelength and short-wavelength light stimuli of supersaturating intensity remained unchanged, regardless of the wavelength and intensity of the background. These findings indicate that turtle C-type horizontal cells operate as push-pull devices. A sufficiently bright short-wavelength stimulus can push them all the way to the maximal hyperpolarizing level while a very bright long-wavelength stimulus can pull them towards the most depolarizing potential.

Dynamic changes in the receptive fields of L1-type horizontal cells in the retina of the turtle Mauremys caspica.

The resistances of the horizontal cell syncytium in the vertebrate retina are modulated in a time-dependent fashion during light stimulation. Therefore, the spatial properties of horizontal cells are expected to change with time after the illumination conditions are altered. This study was designed to investigate time- and intensity-dependent changes in the receptive-field properties of L1-type horizontal cells in the turtle Mauremys caspica. Photoresponses were elicited by monochromatic (650 nm) light stimuli of 2-s duration covering retinal spots of different radii. The length constants were derived from the relationships between amplitude and spot radius that were constructed for different time intervals after onset of the light stimulus. For a given stimulus intensity, the length constant transiently increased to a peak value and then slowly recovered to a plateau level. When the length constant was compared to the amplitude of the response to full-field illumination for the entire duration of the light stimulus, an ellipse-like curve was obtained indicating that for a given membrane potential, two different values of the length constant could be obtained. Dopamine considerably reduced the size of the receptive fields but did not affect the time-dependent changes in the length constant. These results indicate that changes in the membrane resistance underlie short-term modulation of the receptive-field properties of turtle L1-type horizontal cells after onset of a light stimulus.