Changes In Regional Distribution Research Articles

Adolescent nicotine administration increases nicotinic acetylcholine receptor binding and functional connectivity in specific cortico-striatal-thalamic circuits.

Nicotine exposure is associated with regional changes in brain nicotinic acetylcholine receptors subtype expression patterns as a function of dose and age at the time of exposure. Moreover, nicotine dependence is associated with changes in brain circuit functional connectivity, but the relationship between such connectivity and concomitant regional distribution changes in nicotinic acetylcholine receptor subtypes following nicotine exposure is not understood. Although smoking typically begins in adolescence, developmental changes in brain circuits and nicotinic acetylcholine receptors following chronic nicotine exposure remain minimally investigated. Here, we combined in vitro nicotinic acetylcholine receptor autoradiography with resting state functional magnetic resonance imaging to measure changes in [3H]nicotine binding and α4ß2 subtype nicotinic acetylcholine receptor binding and circuit connectivity across the brain in adolescent (postnatal Day 33) and adult (postnatal Day 68) rats exposed to 6 weeks of nicotine administration (0, 1.2 and 4.8 mg/kg/day). Chronic nicotine exposure increased nicotinic acetylcholine receptor levels and induced discrete, developmental stage changes in regional nicotinic acetylcholine receptor subtype distribution. These effects were most pronounced in striatal, thalamic and cortical regions when nicotine was administered during adolescence but not in adults. Using these regional receptor changes as seeds, resting state functional magnetic resonance imaging identified dysregulations in cortico-striatal-thalamic-cortical circuits that were also dysregulated following adolescent nicotine exposure. Thus, nicotine-induced increases in cortical, striatal and thalamic nicotinic acetylcholine receptors during adolescence modifies processing and brain circuits within cortico-striatal-thalamic-cortical loops, which are known to be crucial for multisensory integration, action selection and motor output, and may alter the developmental trajectory of the adolescent brain. This unique multimodal study significantly advances our understanding of nicotine dependence and its effects on the adolescent brain.

Behavioral and Molecular Consequences of Chronic Sleep Restriction During Development in Fragile X Mice

Sleep is critical for brain development and synaptic plasticity. In male wild-type mice, chronic sleep restriction during development results in long-lasting impairments in behavior including hypoactivity, decreased sociability, and increased repetitive behavior. Disordered sleep is characteristic of many neurodevelopmental disorders. Moreover, the severity of behavioral symptoms is correlated with the degree of disordered sleep. We hypothesized that chronic developmental sleep restriction in a mouse model of fragile X syndrome (FXS) would exacerbate behavioral phenotypes. To test our hypothesis, we sleep-restricted Fmr1 knockout (KO) mice for 3 h per day from P5 to P52 and subjected mice to behavioral tests beginning on P42. Contrary to our expectations, sleep restriction improved the hyperactivity and lack of preference for social novelty phenotypes in Fmr1 KO mice but had no measurable effect on repetitive activity. Sleep restriction also resulted in changes in regional distribution of myelin basic protein, suggesting effects on myelination. These findings have implications for the role of disrupted sleep in the severity of symptoms in FXS.

Diverse Instance-Weighting Ensemble Based on Region Drift Disagreement for Concept Drift Adaptation.

Concept drift refers to changes in the distribution of underlying data and is an inherent property of evolving data streams. Ensemble learning, with dynamic classifiers, has proved to be an efficient method of handling concept drift. However, the best way to create and maintain ensemble diversity with evolving streams is still a challenging problem. In contrast to estimating diversity via inputs, outputs, or classifier parameters, we propose a diversity measurement based on whether the ensemble members agree on the probability of a regional distribution change. In our method, estimations over regional distribution changes are used as instance weights. Constructing different region sets through different schemes will lead to different drift estimation results, thereby creating diversity. The classifiers that disagree the most are selected to maximize diversity. Accordingly, an instance-based ensemble learning algorithm, called the diverse instance-weighting ensemble (DiwE), is developed to address concept drift for data stream classification problems. Evaluations of various synthetic and real-world data stream benchmarks show the effectiveness and advantages of the proposed algorithm.

Estimating the change in regional scale distribution of seagrass and macroalgal beds using discrete local distribution data analyzed from aerial images

AbstractThe sensitivity of vegetated habitats to climate change and catastrophic disturbance, as well as their benefits to human beings, motivate efforts to estimate regional changes in distribution. This study examined the regional changes in the distribution of submerged macrophyte vegetation using aerial and satellite images from before and after the 2011 tsunami disturbance along the Pacific coast of northeastern Japan. We conducted an estimation of the change in the distribution of seagrass and macroalgal beds after the tsunami along the whole coastline (1,635 km). This was based on vegetation change in the 13 local areas (each <40 km) spanning 27% of the coastline and included 28% of the macroalgal area and 59% of the seagrass area documented in satellite imagery before the tsunami, using generalized linear modeling (GLM). We found that in the 13 local areas 716.8 and 1,990.3 ha of macroalgal beds and seagrass beds had disappeared, respectively, suggesting that seagrass beds were more impacted by the tsunami than macroalgal beds. Significant predictors in GLM indicated that more seagrass beds disappeared in geographically complex coastal areas, whereas macroalgal beds were only marginally affected in such areas. It was estimated that the total decline in seagrass beds was at least 76% along the whole coastline, whereas macroalgal beds decreased only by about 20%. The magnitude and predictors of losses in these two vegetated habitats were similar to earlier estimates, suggesting that our simplified method with GLM is sufficient to extrapolate monitoring data to a regional scale.

Comparative Effects of Medical vs. Surgical Weight Loss on Body Composition in a Randomized Trial

Bariatric surgery leads to more rapid and greater weight loss (WL) compared to medical weight loss (MWL), but differences in body composition changes for these methods of WL remain unclear. Due to the known health risks associated with central adiposity, we sought to understand if changes in regional distribution of fat mass (FM) and lean mass (LM) differ by surgical vs. medical WL. This 1:1:1 randomized trial among 15 persons with type 2 diabetes and BMI 30-39.9 kg/m2 compared changes in body composition (measured by dual energy x-ray absorptiometry) at the time of 10% WL (or nine months after intervention) for patients receiving MWL, adjustable gastric banding (AGB), or Roux-en-Y gastric bypass (RYGB). We used non-parametric tests to evaluate differences across all arms and to compare AGB to RYGB. We present results for the 12 participants who received the study intervention and completed follow-up. All participants were women, and 75% were African American. Time to 10% weight loss was shorter for AGB and RYGB. Total FM losses were similar across arms. While differences across arms were not statistically significant, the AGB arm tended to have greater total LM and peripheral FM losses. In conclusion, at similar overall WL, AGB may lead to preferential loss of peripheral FM and total LM. The change in total FM and truncal FM were similar across all three groups. Larger studies are needed to confirm these findings. MWLAGBRYGBPALLPAGB vs. RYGBN444Age (Years, Mean)4654.351.5Mean BMI, Kg/m2Baseline37.135.535Final353231.6Weight, KgBaseline104.796.394.4Final98.286.985.4% Change-6.1-9.8-10.00.0381.0Time to 10% Weight Loss, months7.472.772.510.0380.77Body Composition OutcomesTotal Fat Mass, KgBaseline50.043.044.5Final45.537.738.9% Change-8.5-12.0-12.90.671.0Truncal Fat Mass, KgBaseline24.424.724.2Final21.722.020.4% Change-11.0-10.9-16.30.670. 77Peripheral Fat Mass, KgBaseline24.217.019.2Final22.614.417.3% Change-5.0-15.0-8.70.670.56Lean Mass, KgBaseline53.251.546.9Final50.444.943.3% Change-5.2-12.4-7.30.070.15Abbreviations: MWL: medical weight loss, AGB: adjustable gastric band, RYGB: Roux-en-Y gastric bypass, BMI: body mass indexPALL for comparison across groups using Kruskal-Wallis testPAGB vs RYGB represents comparison of AGB to RYGB group using Wilcoxon-Mann-Whitney test Disclosure S. Varma: None. T. Brown: Advisory Panel; Self; Merck & Co., Inc.. J. Clark: None. N. Maruthur: None. M. Schweitzer: Consultant; Self; Ethicon US, LLC.. T. Magnuson: None. C. Lee: None.

Inequality and change in regional distribution of long-term in-home care institutions

Inequality and change in regional distribution of long-term in-home care institutions

Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease.

Alzheimer's disease is a multifactorial dementia disorder characterized by early amyloid-β, tau deposition, glial activation and neurodegeneration, where the interrelationships between the different pathophysiological events are not yet well characterized. In this study, longitudinal multitracer positron emission tomography imaging of individuals with autosomal dominant or sporadic Alzheimer's disease was used to quantify the changes in regional distribution of brain astrocytosis (tracer (11)C-deuterium-L-deprenyl), fibrillar amyloid-β plaque deposition ((11)C-Pittsburgh compound B), and glucose metabolism ((18)F-fluorodeoxyglucose) from early presymptomatic stages over an extended period to clinical symptoms. The 52 baseline participants comprised autosomal dominant Alzheimer's disease mutation carriers (n = 11; 49.6 ± 10.3 years old) and non-carriers (n = 16; 51.1 ± 14.2 years old; 10 male), and patients with sporadic mild cognitive impairment (n = 17; 61.9 ± 6.4 years old; nine male) and sporadic Alzheimer's disease (n = 8; 63.0 ± 6.5 years old; five male); for confidentiality reasons, the gender of mutation carriers is not revealed. The autosomal dominant Alzheimer's disease participants belonged to families with known mutations in either presenilin 1 (PSEN1) or amyloid precursor protein (APPswe or APParc) genes. Sporadic mild cognitive impairment patients were further divided into (11)C-Pittsburgh compound B-positive (n = 13; 62.0 ± 6.4; seven male) and (11)C-Pittsburgh compound B-negative (n = 4; 61.8 ± 7.5 years old; two male) groups using a neocortical standardized uptake value ratio cut-off value of 1.41, which was calculated with respect to the cerebellar grey matter. All baseline participants underwent multitracer positron emission tomography scans, cerebrospinal fluid biomarker analysis and neuropsychological assessment. Twenty-six of the participants underwent clinical and imaging follow-up examinations after 2.8 ± 0.6 years. By using linear mixed-effects models, fibrillar amyloid-β plaque deposition was first observed in the striatum of presymptomatic autosomal dominant Alzheimer's disease carriers from 17 years before expected symptom onset; at about the same time, astrocytosis was significantly elevated and then steadily declined. Diverging from the astrocytosis pattern, amyloid-β plaque deposition increased with disease progression. Glucose metabolism steadily declined from 10 years after initial amyloid-β plaque deposition. Patients with sporadic mild cognitive impairment who were (11)C-Pittsburgh compound B-positive at baseline showed increasing amyloid-β plaque deposition and decreasing glucose metabolism but, in contrast to autosomal dominant Alzheimer's disease carriers, there was no significant longitudinal decline in astrocytosis over time. The prominent initially high and then declining astrocytosis in autosomal dominant Alzheimer's disease carriers, contrasting with the increasing amyloid-β plaque load during disease progression, suggests astrocyte activation is implicated in the early stages of Alzheimer's disease pathology.

Changing habitat use associated with distributional shifts of wintering raptors

There is widespread evidence that multiple drivers of global change, such as habitat degradation, invasive species, and climate change, are influencing wildlife. Understanding how these drivers interact with and affect species may be difficult because outcomes depend on the magnitude and duration of environmental change and the life history of the organism. In addition, various environmental drivers may be evaluated and managed at different spatial scales. We used a historical dataset from 1991 to 1994 and current information from 2010 to 2012 to examine whether occupancy patterns of wintering raptors were consistent with regional changes in distribution or habitat conditions within a local management unit, the Morley Nelson Snake River Birds of Prey National Conservation Area (NCA). We predicted that if local populations reflected regional shifts, then rates of raptor occupancy within the NCA would be higher compared to historical estimates and birds would use different habitats compared to historical use. Alternatively, if local populations were determined by habitat conditions, then we predicted that occupancy rate of raptors within the NCA would be lower compared to historical estimates and current habitat use would be consistent with historical use. Results support the hypothesis that northward distributional shifts influenced wintering raptor populations in southwest Idaho to a greater extent than local habitat conditions. Wintering raptors had higher occupancy rates in 2010–2012 compared to 1991–1994, whereas invasive grasses have increased and native shrubs have decreased suggesting that habitat suitability for raptors has declined over time. On the species level, changes in habitat use were associated with greater increases in occupancy rates in 2010–2012 compared to 1991–1994. Organisms flexible in their habitat use may be better able to respond to continental forces driving distribution shifts. Conversely, habitat or prey specialists may be poorly equipped to handle such rapid, large-scale global change. Further, Grinnellian niche models predicting species response to change by mapping current habitat use to forecasted vegetation maps should consider plasticity in habitat use and changes in the cost-benefits of life-history strategies. © 2015 The Wildlife Society.

Understanding the contribution of habitats and regional variation to long‐term population trends in tricolored blackbirds

Population trends represent a minimum amount of information required to assess the conservation status of a species. However, understanding and detecting trends can be complicated by variation among habitats and regions, and by dispersal connecting habitats through source-sink dynamics. We analyzed trends in breeding populations between habitats and regions to better understand the overall dynamics of a species' decline. Specifically, we analyzed historical trends in breeding populations of tricolored blackbirds (Agelaius tricolor) using breeding records from 1907 to 2009. The species breeds itinerantly and ephemerally uses multiple habitat types and breeding areas, which make interpretation of trends complex. We found overall abundance declines of 63% between 1935 and 1975. Since 1980 overall declines became nonsignificant and obscure despite large amounts of data from 1980 to 2009. Temporal trends differed between breeding habitat types and were associated with regional differences in population declines. A new habitat, triticale crops (a wheat-rye hybrid grain) produced colonies 40× larger, on average, than other breeding habitats, and contributed to a change in regional distribution since it primarily occurred in a single region. The mechanism for such an effect is not clear, but could represent the local availability of foodstuffs in the landscape rather than something specific to triticale crops. While variation in trends among habitats clearly occurred, they could not easily be ascribed to source-sink dynamics, ecological traps, habitat selection or other detailed ecological mechanisms. Nonetheless, such exchanges provide valuable information to guide management of dynamic systems.

Body fat distribution in relation to smoking and exogenous hormones in British women

Both cigarette smoking and use of exogenous hormones are associated with changes in regional distribution of body fat, but their combined effects are less investigated. We examined the interrelation between smoking, exogenous hormones and fat distribution in premenopausal and postmenopausal women. We used data from 20, 962 women without known cardiovascular disease (CVD) who were employees of a major department store in Britain. They completed a health questionnaire and attended a clinical examination that included waist and hip circumference measurements. The cross-sectional analyses were conducted using linear regression models. Cigarette smoking, particularly smoking ≥20 cigarettes/day, was associated with larger waist circumference and higher waist/hip ratio (WHR) in pre- and postmenopausal women after adjusting for potential confounding factors (all P < 0·001). Premenopausal women using combined oral contraceptive (COC) and postmenopausal women using oestrogen-only hormone replacement therapy (HRT) had lower WHR than non-hormone users in both smokers and nonsmokers. However, smokers had higher WHR than nonsmokers in both groups of hormone users and nonusers. There was no significant interaction between smoking and hormone use in premenopausal and postmenopausal women (P > 0·05). Although exogenous hormones use was related to a more favourable fat distribution in women, smoking was associated with greater abdominal fat accumulation.

Changes in North Sea macrofauna communities and species distribution between 1986 and 2000

The North Sea Benthos Project 2000 was initiated as a follow-up to the 1986 ICES North Sea Benthos Survey with the major aim to identify changes in the macrofauna species distribution and community structure in the North Sea and their likely causes. The results showed that the large-scale spatial distribution of macrofauna communities in the North Sea hardly changed between 1986 and 2000, with the main divisions at the 50 m and 100 m depth contours. Water temperature and salinity as well as wave exposure, tidal stress and primary production were influential environmental factors on a large (North Sea-wide) spatial scale. The increase in abundance and regional changes in distribution of various species with a southern distribution in the North Sea in 2000 were largely associated with an increase in sea surface temperature, primary production and, thus, food supply. This can be most likely related to the North Sea hydro-climate change in the late 1980s influenced by the variability in the North Atlantic Oscillation (NAO). Only one cold-temperate species decreased in abundance in 2000 at most of the stations. Indications for newly established populations of offshore non-native species were not found. Differences in macrofauna community structure on localised spatial scales were predominantly found north of the 50 m depth contour off the British coast along the Flamborough Head Front towards the Dogger Bank, off the coast of Jutland and at the Frisian Front. These changes were most likely attributed to stronger frontal systems in 2000 caused by the increased inflow of Atlantic water masses in relation to the hydro-climate change in the late 1980s.

The influence of methysergide on 5-hydroxytryptamine-induced changes in regional distribution of blood flow.

Systemic and regional haemodynamic variables were measured at the baseline and after saline or 5-HT infusions (5 microgram kg-1 min-1, i.v.) or methysergide injections (0.5 mg kg-1, i.v.). Cardiac output and its complete distribution were measured by the radioactive microsphere (15 micrometer diam) technique. Although 5-HT did not change the systemic variables, methysergide caused a moderate increase in systolic and mean blood pressure and heart rate. 5-HT caused a substantial increase in gastric and a moderate increase in cerebral and myocardial blood flow at the expense of that to the lungs (arteriovenous shunt + bronchial flows), kidneys and skin. While methysergide was able to reduce the vascular responses to 5-HT in stomach, skin, kidneys, heart, lungs and brain, the drug itself, like 5-HT, decreased the number of microspheres reaching the lungs. Since a large number of 15 micron microspheres can escape through the arteriovenous anastomoses to lodge in the lungs it seems likely that both 5-HT and methysergide can reduce the 'non-nutrient' flow through these anastomoses.

No change in the regional distribution of tidal volume during lateral posture in mechanically ventilated patients assessed by electrical impedance tomography

We assessed the distribution of regional lung ventilation during moderate and steep lateral posture using electrical impedance tomography (EIT) in mechanically ventilated patients. Seven patients were placed on a kinetic treatment table. An elastic belt containing 16 electrodes was placed around the chest and was connected to the EIT device. Patients were moved to left and right lateral positions in a stepwise (10°) mode up to 60°. EIT images [arbitrary units (AU)] were generated and scanned for assessment of relative ventilation distribution changes [tidal volume (VT)]. A calibration procedure of arbitrary units (AUs) versus ventilator-derived VT performed in all patients during three predefined positions (supine, 60°-left dependent and 60°-right-dependent) showed a significant correlation between VT in supine, left and right lateral positions with the corresponding AUs (r2 = 0·356, P<0·05). Changes in VT were calculated and compared to supine position, and specific regions of interest (ROIs) were analysed. In our study, in contrast to recent findings, a change in lateral positions did not induce a significant change in regional tidal volume distribution. In right lateral positions, a broader variation of VT with a trend towards an increase in the dependently positioned lung was observed in comparison with supine. Lateral positioning promotes the redistribution of ventilation to the ventral regions of the lung. The use of EIT technology might become a helpful tool for understanding and guiding posture therapy in mechanically ventilated patients.

Changes in regional distribution of lung sounds as a function of positive end-expiratory pressure

IntroductionAutomated mapping of lung sound distribution is a novel area of interest currently investigated in mechanically ventilated, critically ill patients. The objective of the present study was to assess changes in thoracic sound distribution resulting from changes in positive end-expiratory pressure (PEEP). Repeatability of automated lung sound measurements was also evaluated.MethodsRegional lung sound distribution was assessed in 35 mechanically ventilated patients in the intensive care unit (ICU). A total of 201 vibration response imaging (VRI) measurements were collected at different levels of PEEP between 0 and 15 cmH2O. Findings were correlated with tidal volume, oxygen saturation, airway resistance, and dynamic compliance. Eighty-two duplicated readings were performed to evaluate the repeatability of the measurement.ResultsA significant shift in sound distribution from the apical to the diaphragmatic lung areas was recorded when increasing PEEP (paired t-tests, P < 0.05). In patients with unilateral lung pathology, this shift was significant in the diseased lung, but not as pronounced in the other lung. No significant difference in lung sound distribution was encountered based on level of ventilator support needed. Decreased lung sound distribution in the base was correlated with lower dynamic compliance. No significant difference was encountered between repeated measurements.ConclusionsLung sounds shift towards the diaphragmatic lung areas when PEEP increases. Lung sound measurements are highly repeatable in mechanically ventilated patients with various lung pathologies. Further studies are needed in order to fully appreciate the contribution of PEEP increase to diaphragmatic sound redistribution.

Chronic Pain in Canada: Have We Improved Our Management of Chronic Noncancer Pain?

Chronic noncancer pain (CNCP) is a global issue, not only affecting individual suffering, but also impacting the delivery of health care and the strength of local economies. The current study (the Canadian Chronic Pain Study II [CCPSII]) was designed to assess any changes in the prevalence and treatment of CNCP, as well as in attitudes toward the use of strong analgesics, compared with a 2001 study (the CCPSI), and to provide a snapshot of the current standards of care for pain management in Canada. Standard, computer-assisted telephone interview survey methodology was applied in two segments, ie, a general population survey and a survey targeting randomly selected primary care physicians (PCPs) who treat moderate to severe CNCP. The patient-reported prevalence of CNCP within Canada has not markedly changed since 2001 but the duration of suffering has decreased. There have been minor changes in regional distribution and generally more patients receive medical treatment, which includes prescription analgesics. Physicians continue to demonstrate opiophobia in their prescribing practices; however, although this is lessened relating to addiction, abuse remains an important concern to PCPs. Canadian PCPs, in general, are implementing standard assessments, treatment approaches, evaluation of treatment success and tools to prevent abuse and diversion, in accordance with guidelines from the Canadian Pain Society and other pain societies globally, although there remains room for improvement and standardization.

Compensatory alteration of inhibitory synaptic circuits in cerebellum and thalamus of γ‐aminobutyric acid type A receptor α1 subunit knockout mice

Targeted deletion of the alpha1 subunit gene results in a profound loss of gamma-aminobutyric acid type A (GABA(A)) receptors in adult mouse brain but has only moderate behavioral consequences. Mutant mice exhibit several adaptations in GABA(A) receptor subunit expression, as measured by Western blotting. By using immunohistochemistry, we investigated here whether these adaptations serve to replace the missing alpha1 subunit or represent compensatory changes in neurons that normally express these subunits. We focused on cerebellum and thalamus and distinguished postsynaptic GABA(A) receptor clusters by their colocalization with gephyrin. In the molecular layer of the cerebellum, alpha1 subunit clusters colocalized with gephyrin disappeared from Purkinje cell dendrites of mutant mice, whereas alpha3 subunit/gephyrin clusters, presumably located on dendrites of Golgi interneurons, increased sevenfold, suggesting profound network reorganization in the absence of the alpha1 subunit. In thalamus, a prominent increase in alpha3 and alpha4 subunit immunoreactivity was evident, but without change in regional distribution. In the ventrobasal complex, which contains primarily postsynaptic alpha1- and extrasynaptic alpha4-GABA(A) receptors, the loss of alpha1 subunit was accompanied by disruption of gamma2 subunit and gephyrin clustering, in spite of the increased alpha4 subunit expression. However, in the reticular nucleus, which lacks alpha1-GABA(A) receptors in wild-type mice, postsynaptic alpha3/gamma2/gephyrin clusters were unaffected. These results demonstrate that adaptive responses in the brain of alpha1(0/0) mice involve reorganization of GABAergic circuits and not merely replacement of the missing alpha1 subunit by another receptor subtype. In addition, clustering of gephyrin at synaptic sites in cerebellum and thalamus appears to be dependent on expression of a GABA(A) receptor subtype localized postsynaptically.

Body composition and time course changes in regional distribution of fat and lean tissue in unselected cancer patients on palliative care—Correlations with food intake, metabolism, exercise capacity, and hormones

Several investigations that yielded different results in terms of net changes in body composition of weight-losing cancer patients have been reported that employed a variety of methods based on fundamentally different technology. Most of those reports were cross-sectional, whereas to the authors' knowledge there is sparse information available on longitudinal follow-up measurements in relation to other independent methods for the assessment of metabolism and performance. For the current report, the authors evaluated time course changes in body composition (dual-energy X-ray absorptiometry) with measurements of whole body and regional distribution of fat and lean tissue in relation to food and dietary intake, host metabolism (indirect calorimetry), maximum exercise capacity (walking test), and circulating hormones in cancer patients who were receiving palliative care during 4-62 months of follow-up. The entire cohort comprised 311 patients, ages 68 years +/- 3 years who were diagnosed with solid gastrointestinal tumors (84 colorectal tumors, 74 pancreatic tumors, 73 upper gastrointestinal tumors, 51 liver-biliary tumors, 3 breast tumors, 5 melanomas, and 21 other tumor types). Decreased body weight was explained by loss of body fat, preferentially from the trunk, followed by leg tissue and arm tissue, respectively. Lean tissue (fat-free mass) was lost from arm tissue, whereas trunk and leg tissue compartments increased, all concomitant with declines in serum albumin, increased systemic inflammation (C-reactive protein, erythrocyte sedimentation rate), increased serum insulin, and elevated daily caloric intake; whereas serum insulin-like growth factor 1 (IGF-1), resting energy expenditure, and maximum exercise capacity remained unchanged in the same patients. Serum albumin levels (P < 0.001), whole body fat (P < 0.02), and caloric intake (P < 0.001) predicted survival, whereas lean tissue mass did not. Daily intake of fat and carbohydrate was more important for predicting survival than protein intake. Survival also was predicted by serum IGF-1, insulin, leptin, and ghrelin levels (P < 0.02 - P < 0.001). Serum insulin, leptin, and ghrelin (total) levels predicted body fat (P < 0.001), whereas IGF-1 and thyroid hormone levels (T3, free T3) predicted lean tissue mass (P < 0.01). Systemic inflammation primarily explained variation in lean tissue and secondarily explained loss in body fat. Depletion of lean arm tissue was related most to short survival compared with the depletion of lean leg and trunk tissue. The current results demonstrated that body fat was lost more rapidly than lean tissue in progressive cancer cachexia, a phenomenon that was related highly to alterations in the levels of circulating classic hormones and food intake, including both caloric amount and diet composition. The results showed importance in the planning of efficient palliative treatment for cancer patients.

Increased excess deaths in urban areas: quantification of geographical variation in mortality in Japan, 1973–1998

To quantify the magnitude of geographical health inequality by sex and age group, and to observe the change in regional distribution of health disadvantage, this study estimated excess deaths attributable to the mortality variation among municipalities across Japan from 1973 through 1998. The municipalities ( N=3340 in 1995) were divided into quintiles according to standardized mortality ratio (SMR). Using the mortality of the lowest SMR quintile as the standard, the number of excess deaths (ED) and its ratio to observed deaths (EDR) were estimated by sex, age group (total population and under 65-year population) and regional block in 1973–1977, 1978–1982, 1983–1987, 1988–1992 and 1993–1998. Total annual ED in 1993–1998 was estimated as 47,124 for males and 46,562 for females, representing EDR of 9.9 and 11.6%, respectively. The under 65-year population had a higher EDR than the total population. Rural regions showed a marked decrease in EDR in contrast to the increase in urban regions over time. The present study suggests that the reduction of a large number of deaths, especially premature deaths, is expected by elimination of geographical health inequality, and that health policies for urban residents are prioritized.

Picrotoxin-induced generalised convulsive seizure in rat: changes in regional distribution and frequency of the power of electroencephalogram rhythms

Objectives: It is unknown how generalised discharges in primary generalised epilepsy (PGE) develop from background brain electrical activity or how widespread these discharged are throughout the brain. Here we address this by determining which neural structures and rhythms lead to and participate in generalised discharges in the picrotoxin rat model of PGE. Methods: Rats with chronically implanted electrodes were infused with picrotoxin until a seizure occurred. This process we refer to as acute epileptogenesis. The electroencephalogram (EEG) was recorded and spectral analysis applied off-line to determine changes in the spectral power of contributing frequencies in 13 brain regions. Results: Two types of generalised discharge occurred, spindles and seizure, which were present in all brain regions studied. None of the frequencies (1–100 Hz) were significantly increased in background EEG before either spindles or seizure. Within the generalised discharges, power changes revealed significant increases in 6–8 Hz, most powerful in ventrolateral thalamus and neocortex. Gamma frequencies were increased significantly in neocortical structures during spindles with further increases in most structures at seizure onset. 1 Hz was significantly increased in parietal cortex during spindles with differential increases at seizure onset. Conclusions: We conclude that gamma, 1 and 6–8 Hz frequencies do not appear to contribute to picrotoxin epileptogenesis but do play a role in generalised seizures. The distribution of these frequencies during discharges suggests that the spindles are thalamocortical events and that the seizure is a cortical event with downstream effects on other brain regions.

Prostatic ductal system in rats: changes in regional distribution of extracellular matrix proteins during castration-induced regression.

The extracellular matrix (ECM) is an intricate network composed of an array of molecules that play an integral role in the regulation of cell function, differentiation, and tissue-specific gene expression in various epithelia. In the present study, we examined the distribution of collagen type IV and laminin along the rat ventral prostatic duct before and after castration. Mature Sprague-Dawley rats were castrated and their prostates processed for immunocytochemistry of ECM proteins, laminin, and collagen type IV. Tissue sections were also processed for apoptosis staining, using the 3' end-labeling technique. To examine the effect of ECM proteins on epithelial growth, rat ventral epithelial cells were cultured on ECM-coated surfaces. In the intact rat, laminin was localized in the basement membrane along all regions of the ventral prostate ductal system. Collagen type IV was found to be distributed evenly in the basement membrane of the distal and intermediate regions but was absent or poorly organized in the proximal region, where apoptosis in the epithelium occurs at a high rate. In the regressing prostate after castration, there was a shift in apoptosis from the proximal region to the distal intermediate regions of the prostatic duct. Associated with the shift was a remodeling of basement membrane proteins due to the specific loss of collagen type IV in the distal and intermediate regions. Collagen type IV reappeared underneath the epithelium 7 days after castration, when apoptosis in the epithelium stopped. In vitro, collagen type IV enhanced the growth of ventral prostatic epithelial cells, as assessed by cell number. Collagen basement membrane type IV mediates growth of rat ventral prostate epithelium, and its loss during tissue remodeling after castration is associated with cell death.