Mean residual life cure models for right-censored data with and without length-biased sampling.

We propose a semiparametric mean residual life mixture cure model for right-censored survival data with a cured fraction. The model employs the proportional mean residual life model to describe the effects of covariates on the mean residual time of uncured subjects and the logistic regression model to describe the effects of covariates on the cure rate. We develop estimating equations to estimate the proposed cure model for the right-censored data with and without length-biased sampling, the latter is often found in prevalent cohort studies. In particular, we propose two estimating equations to estimate the effects of covariates in the cure rate and a method to combine them to improve the estimation efficiency. The consistency and asymptotic normality of the proposed estimates are established. The finite sample performance of the estimates is confirmed with simulations. The proposed estimation methods are applied to a clinical trial study on melanoma and a prevalent cohort study on early-onset type 2 diabetes mellitus.

Benefits of applying virtual reality in pelvic movement training through a Wii Fit: a randomized controlled trial.

BACKGROUND: Pelvic movement training has become compulsory for part of medical students. An increasing amount of research has focused on the influence of virtual reality (VR) on learning effectiveness. However, its application to pelvic floor muscles or pelvic movement training is still in its infancy. We compared the effectiveness of conventional pelvic movement training with or without VR-assisted pelvic movement training for student learning. METHODS: We recruited 44 university students (16 male and 28 female participants; average age = 19.7 ± 0.31 years) who had not previously received pelvic movement education or training. The participants were randomly assigned into traditional and experimental groups to acquire pelvic movements and relevant knowledge. The traditional group received conventional classes (about 15 min), whereas the experimental group received both conventional classes and VR-assisted teaching (additional VR session took approximately 25-45 min depending on the speed of movement of each participant). The participants were asked to control the trajectory of the centre of pressure on the Wii Fit balance board and build-in games to learn pelvic movements. We conducted evaluations before, immediately after, and 2 weeks after the experiment, based on the scores of written and practical examinations. The experimental group was also asked to complete a questionnaire during the posttest. RESULTS: We carried out two-way repeated measures ANOVA and discovered that the written examination scores indicated a significant Time × Group interaction (p=0.015). In each group, the written and practical examinations in the posttest and follow-up test exhibited significantly improved results compared with the baseline value (p <0.001, except for traditional group of written exam in follow up test vs. baseline p=0.001). The written examination in the follow-up test did not decline significantly compared with those in the posttest, but the practical examination in the follow-up test was decline significantly compared with those in the posttest (p=0.033). The experimental group had superior overall performance in the practical examinations than the traditional group (experimental group: mean = 76.27, 95% confidence level [CI] = 70.84-81.71; traditional group: mean = 64.21, 95% CI = 58.78-69.65). No significant difference in the written examination between two groups. The percentage for agreement ratio on the usefulness, ease of use, users' intention to continue using the VR-assisted teaching is high (95.5-100%). CONCLUSIONS: The results of this study suggested that conventional and conventional + VR teaching were both effective. However, the incorporation of VR stimulated learning motivation and facilitated precise performance of pelvic movements. It is recommended that pelvic floor muscles training could be supplemented with VR or games to increase students' motivation and understanding how to perform pelvic movements.

Maximum likelihood estimation for length-biased and interval-censored data with a nonsusceptible fraction.

Left-truncated data are often encountered in epidemiological cohort studies, where individuals are recruited according to a certain cross-sectional sampling criterion. Length-biased data, a special case of left-truncated data, assume that the incidence of the initial event follows a homogeneous Poisson process. In this article, we consider an analysis of length-biased and interval-censored data with a nonsusceptible fraction. We first point out the importance of a well-defined target population, which depends on the prior knowledge for the support of the failure times of susceptible individuals. Given the target population, we proceed with a length-biased sampling and draw valid inferences from a length-biased sample. When there is no covariate, we show that it suffices to consider a discrete version of the survival function for the susceptible individuals with jump points at the left endpoints of the censoring intervals when maximizing the full likelihood function, and propose an EM algorithm to obtain the nonparametric maximum likelihood estimates of nonsusceptible rate and the survival function of the susceptible individuals. We also develop a novel graphical method for assessing the stationarity assumption. When covariates are present, we consider the Cox proportional hazards model for the survival time of the susceptible individuals and the logistic regression model for the probability of being susceptible. We construct the full likelihood function and obtain the nonparametric maximum likelihood estimates of the regression parameters by employing the EM algorithm. The large sample properties of the estimates are established. The performance of the method is assessed by simulations. The proposed model and method are applied to data from an early-onset diabetes mellitus study.

Household structure and concurrent stunting and overweight among young children in Indonesia.

OBJECTIVE: To examine the association of household type and household composition with concurrent stunting and overweight in young children from urban and rural Indonesia. DESIGN: This study is a secondary data analysis using a nationally representative cross-sectional survey. Household structure was analysed as household type, household size, number of working adults, number of dependent adults and children, and household head's gender. We defined 'concurrent stunting and overweight' as height-for-age Z-score <-2 and weight-for-height Z-score >+2 based on WHO growth standards. Multivariable logistic regression to test the aforementioned association was performed separately for urban and rural areas. SETTING: Data were from Indonesia Basic Heath Research 2013. PARTICIPANTS: Children aged 2-5 years (n 45 050). RESULTS: The prevalence of concurrent stunting and overweight children was 5·6 %. In rural areas, this prevalence differed significantly by household types and the highest prevalence was among children in nuclear two-parent households (6·8 %). In rural areas, children in extended households had lower odds of concurrent stunting and overweight than those from nuclear households (OR = 0·73, 95 % CI 0·59, 0·92). In urban areas, household size and number of working adults were significantly associated with the decreased odds of concurrent stunting and overweight in children. CONCLUSIONS: Household structure was associated with children's concurrent stunting and overweight in urban and rural regions of Indonesia. The patterns of the association might differ between urban and rural regions, but no significant interaction term was found.

AimB Is a Small Protein Regulator of Cell Size and MreB Assembly.

The MreB actin-like cytoskeleton assembles into dynamic polymers that coordinate cell shape in many bacteria. In contrast to most other cytoskeleton systems, few MreB-interacting proteins have been well characterized. Here, we identify a small protein from Caulobacter crescentus, an assembly inhibitor of MreB (AimB). AimB overexpression mimics inhibition of MreB polymerization, leading to increased cell width and MreB delocalization. Furthermore, aimB appears to be essential, and its depletion results in decreased cell width and increased resistance to A22, a small-molecule inhibitor of MreB assembly. Molecular dynamics simulations suggest that AimB binds MreB at its monomer-monomer protofilament interaction cleft and that this interaction is favored for C. crescentus MreB over Escherichia coli MreB because of a closer match in the degree of opening with AimB size, suggesting coevolution of AimB with MreB conformational dynamics in C. crescentus. We support this model through functional analysis of point mutants in both AimB and MreB, photo-cross-linking studies with site-specific unnatural amino acids, and species-specific activity of AimB. Together, our findings are consistent with AimB promoting MreB dynamics by inhibiting monomer-monomer assembly interactions, representing a new mechanism for regulating actin-like polymers and the first identification of a non-toxin MreB assembly inhibitor. Because AimB has only 104 amino acids and small proteins are often poorly characterized, our work suggests the possibility of more bacterial cytoskeletal regulators to be found in this class. Thus, like FtsZ and eukaryotic actin, MreB may have a rich repertoire of regulators to tune its precise assembly and dynamics.

Age, period and birth cohort effects on the prevalence of overweight and obesity among Taiwanese adolescents: a national population-based study.

BACKGROUND: The age-period-cohort effects on youth overweight and obesity among junior and senior high school students in Taiwan is not clear. METHODS: We utilized the 2006-14 nationally representative School Physical Fitness Dataset. Based on the International Obesity Task Force cut-off criteria, a log-linear age-period-cohort analysis was performed to determine the influence of age, period and cohort on the trend in being overweight, obese and severely obese for both sexes. RESULTS: The final dataset included 1073173 individuals (n = 520 382 boys and 552 791 girls). For girls, the prevalence of overweight and obesity declined with age, and the prevalence of overweight declined over time. For boys, the prevalence of overweight and obesity declined with age and over time from 2006 to 2014. The prevalence of severe obesity declined over time and increased with age for the boys. The younger birth cohorts had greater odds of being overweight, obese and severely obese than the older birth cohorts. CONCLUSIONS: After differentiating the age-period-cohort effects, the data suggested a decreasing temporal trend in overweight and obesity among adolescents in Taiwan from 2006 to 2014. Among the birth cohorts of the 1990s, the younger cohorts had greater odds of being overweight and obese than the older cohorts when they reached adolescence.

Gender differences and burden of chronic conditions: impact on quality of life among the elderly in Taiwan.

BACKGROUND: Multiple chronic conditions affect people's health-related quality of life (QoL) and the distributions of the conditions may differ between genders. Our goal was to examine gender differences in chronic conditions and QoL among community-living elderly in Taiwan and to examine whether differences in QoL between genders, if present, were attributable to the distribution of chronic conditions. METHODS: We used data from the Nutrition and Health Survey in Taiwan (NAHSIT, 2005-2008), which interviewed a representative sample of the Taiwanese population. The survey questions included the SF-36 questionnaire to assess participants' QoL and items for participants' medical history. We used multiple linear regressions to examine the difference in QoL between genders. RESULTS: We included 1179 elders for our analysis; men accounted for 52% (612/1179). The mean age was 73; women were slightly younger. The mean (standard deviation) of SF-36 physical and mental health component score (PCS and MCS) was 44.5 (11.1) and 55.6 (9.0), respectively, and women reported a significantly lower PCS than men (difference - 4.85, p < 0.001). Urinary incontinence, arthritis, stroke, and kidney disease were associated with a clinically meaningful decrease in PCS (≤ - 6.5 points). The difference in PCS between genders was not attenuated after we accounted for chronic conditions in regression analysis. CONCLUSIONS: Our findings suggest that women tend to report that their physical health-related QoL is poorer than that of men, and such a difference does not seem to be attributable to the distribution of chronic conditions. Elderly men and women may perceive health-related QoL differently.

NASA Mission X Program for Healthy Eating and Active Living among Taiwanese Elementary School Students.

PURPOSE: This study assessed the effects of an intervention program adapted from the NASA Mission X (MX) program on children's Healthy Eating Active Living (HEAL) knowledge and behaviors and anthropometry. METHODS: This clustered randomized control trial recruited 8 elementary schools in remote rural areas of Northern Taiwan. The intervention was the 8-week MX program. All the 3rd and 4th graders were invited to the study (n = 245). Children's weight, height, HEAL knowledge and behaviors were measured pre- and post-intervention. RESULTS: The intervention group had significantly more improvements than control group in physical activity knowledge score (+0.91 vs. +0.25, p = 0.002), diet knowledge score (+0.62 vs. +0.17, p = 0.044), and score of interests in NASA and space exploration (+0.34 vs. -0.07, p < 0.0001). BMI increased from 18.4 to 18.6 (p < 0.05) for the control group but did not change for the intervention group. The changes in BMI between groups did not differ significantly. CONCLUSION AND PRACTICE IMPLICATIONS: This randomized controlled trial showed that the NASA MX program was feasible and acceptable among children in Taiwan, and improved children's HEAL knowledge. (ClinicalTrials.gov registration: NCT03355131).

Structural basis for the geometry-driven localization of a small protein.

In bacteria, certain shape-sensing proteins localize to differently curved membranes. During sporulation in Bacillus subtilis, the only convex (positively curved) surface in the cell is the forespore, an approximately spherical internal organelle. Previously, we demonstrated that SpoVM localizes to the forespore by preferentially adsorbing onto slightly convex membranes. Here, we used NMR and molecular dynamics simulations of SpoVM and a localization mutant (SpoVM(P9A)) to reveal that SpoVM's atypical amphipathic α-helix inserts deeply into the membrane and interacts extensively with acyl chains to sense packing differences in differently curved membranes. Based on binding to spherical supported lipid bilayers and Monte Carlo simulations, we hypothesize that SpoVM's membrane insertion, along with potential cooperative interactions with other SpoVM molecules in the lipid bilayer, drives its preferential localization onto slightly convex membranes. Such a mechanism, which is distinct from that used by high curvature-sensing proteins, may be widely conserved for the localization of proteins onto the surface of cellular organelles.

Employment status and temporal patterns of energy intake: Nutrition and Health Survey in Taiwan, 2005-2008.

OBJECTIVE: To (i) identify the major temporal patterns of energy intake among adults; (ii) examine the association between employment status and the patterns; and (iii) examine the association between dietary quality and the patterns. DESIGN: Secondary analysis based on the cross-sectional population-based nutrition survey in Taiwan, 2005-2008. Based on energy intake levels at six time intervals of a day derived from 24 h recall data, we applied cluster analysis to identify major temporal patterns of energy intake. Self-reported employment status was categorized into six groups: full-time, part-time, no job, student, homemaker and retired. Multinomial logistic regression models were fitted to test the association between temporal patterns of energy intake and employment groups. SETTING: Non-institutionalized community dwellers. SUBJECTS: Non-pregnant adults (≥19 years old) with total energy intake between 2092 and 20920 kJ/d (500 and 5000 kcal/d; n 4508). RESULTS: Five major patterns were identified, which can be seen as the traditional meal pattern and its variants. About 20 % of adults had the traditional pattern. The most prevalent pattern was the delayed morning meal pattern (33 %), which had lower Ca and P intakes than the traditional pattern. About 14 % of adults had the delayed lunchtime pattern, which had lower protein, PUFA, fibre, Ca, P, vitamin D and vitamin E intakes than the traditional. Adjusted prevalence of the delayed lunchtime pattern was highest among full-time students (34 %), followed by part-time workers (24 %), and was lower in retired (8 %), homemakers (11 %) and full-time employed adults (12 %). CONCLUSION: Adults' temporal patterns of energy intake, which varied with their employment status, affected their dietary quality.

Association between obesity with low muscle mass and dialysis mortality.

BACKGROUND/AIM: To examine the association between body composition and dialysis mortality. METHODS: Adult patients who underwent haemodialysis in Taoyuan General Hospital from 2012 to 2016 were enrolled. We reviewed their baseline characteristics and followed up their treatment over 5 years after dialysis. Patients with body mass index >25 kg/m2 were defined as obese. High or low muscle mass were classified by skeletal muscle mass index (SMMI) based on consensus from Chinese population. All age-matched subjects were classified into four groups: (A) optimal; (B) obesity; (C) low muscle mass; and (D) obesity with low muscle mass. Adjusted hazard ratios for mortality and cumulative survival curves were evaluated by Cox proportional hazard model and Kaplan-Meier method. The discriminative power of SMMI was calculated according to the area under the curve and the receiver operating characteristic curve. RESULTS: From a total of 176 age-matched patients, the incidence rates of mortality for different groups were 3.7, 7.8, 10.3 and 16.5 per 1000 person-months. After adjusting for continuous variables, SMMI was independently associated with mortality. The difference between groups A and D was more significant in women than in men after multivariate adjustment (adjusted hazard ratios: 7.465 vs 1.682) (P = 0.035 and 0.553). The discriminative power of SMMI to predict 5-year mortality was 0.700 for men and 0.750 for women, and the best cut-off values were 11.1 and 8.4 kg/m2 CONCLUSIONS: Low muscle mass was associated with dialysis mortality. Obesity with low muscle mass was a predictor for dialysis mortality in women.

Effects of polymerization and nucleotide identity on the conformational dynamics of the bacterial actin homolog MreB.

The assembly of protein filaments drives many cellular processes, from nucleoid segregation, growth, and division in single cells to muscle contraction in animals. In eukaryotes, shape and motility are regulated through cycles of polymerization and depolymerization of actin cytoskeletal networks. In bacteria, the actin homolog MreB forms filaments that coordinate the cell-wall synthesis machinery to regulate rod-shaped growth and contribute to cellular stiffness through unknown mechanisms. Like actin, MreB is an ATPase and requires ATP to polymerize, and polymerization promotes nucleotide hydrolysis. However, it is unclear whether other similarities exist between MreB and actin because the two proteins share low sequence identity and have distinct cellular roles. Here, we use all-atom molecular dynamics simulations to reveal surprising parallels between MreB and actin structural dynamics. We observe that MreB exhibits actin-like polymerization-dependent structural changes, wherein polymerization induces flattening of MreB subunits, which restructures the nucleotide-binding pocket to favor hydrolysis. MreB filaments exhibited nucleotide-dependent intersubunit bending, with hydrolyzed polymers favoring a straighter conformation. We use steered simulations to demonstrate a coupling between intersubunit bending and the degree of flattening of each subunit, suggesting cooperative bending along a filament. Taken together, our results provide molecular-scale insight into the diversity of structural states of MreB and the relationships among polymerization, hydrolysis, and filament properties, which may be applicable to other members of the broad actin family.

A dynamically assembled cell wall synthesis machinery buffers cell growth.

Assembly of protein complexes is a key mechanism for achieving spatial and temporal coordination in processes involving many enzymes. Growth of rod-shaped bacteria is a well-studied example requiring such coordination; expansion of the cell wall is thought to involve coordination of the activity of synthetic enzymes with the cytoskeleton via a stable complex. Here, we use single-molecule tracking to demonstrate that the bacterial actin homolog MreB and the essential cell wall enzyme PBP2 move on timescales orders of magnitude apart, with drastically different characteristic motions. Our observations suggest that PBP2 interacts with the rest of the synthesis machinery through a dynamic cycle of transient association. Consistent with this model, growth is robust to large fluctuations in PBP2 abundance. In contrast to stable complex formation, dynamic association of PBP2 is less dependent on the function of other components of the synthesis machinery, and buffers spatially distributed growth against fluctuations in pathway component concentrations and the presence of defective components. Dynamic association could generally represent an efficient strategy for spatiotemporal coordination of protein activities, especially when excess concentrations of system components are inhibitory to the overall process or deleterious to the cell.

Variations in the binding pocket of an inhibitor of the bacterial division protein FtsZ across genotypes and species.

The recent increase in antibiotic resistance in pathogenic bacteria calls for new approaches to drug-target selection and drug development. Targeting the mechanisms of action of proteins involved in bacterial cell division bypasses problems associated with increasingly ineffective variants of older antibiotics; to this end, the essential bacterial cytoskeletal protein FtsZ is a promising target. Recent work on its allosteric inhibitor, PC190723, revealed in vitro activity on Staphylococcus aureus FtsZ and in vivo antimicrobial activities. However, the mechanism of drug action and its effect on FtsZ in other bacterial species are unclear. Here, we examine the structural environment of the PC190723 binding pocket using PocketFEATURE, a statistical method that scores the similarity between pairs of small-molecule binding sites based on 3D structure information about the local microenvironment, and molecular dynamics (MD) simulations. We observed that species and nucleotide-binding state have significant impacts on the structural properties of the binding site, with substantially disparate microenvironments for bacterial species not from the Staphylococcus genus. Based on PocketFEATURE analysis of MD simulations of S. aureus FtsZ bound to GTP or with mutations that are known to confer PC190723 resistance, we predict that PC190723 strongly prefers to bind Staphylococcus FtsZ in the nucleotide-bound state. Furthermore, MD simulations of an FtsZ dimer indicated that polymerization may enhance PC190723 binding. Taken together, our results demonstrate that a drug-binding pocket can vary significantly across species, genetic perturbations, and in different polymerization states, yielding important information for the further development of FtsZ inhibitors.

Dietary patterns and cognitive decline in Taiwanese aged 65 years and older.

OBJECTIVE: This study examines the association between dietary patterns and cognitive decline in Taiwanese aged 65 years and older. METHODS: Data were from a population-based longitudinal study, the Taiwan Longitudinal Study of Aging, with a nationally representative sample. RESULTS: Nearly 2%, 8%, and 3% of participants had a western, traditional, and healthy dietary pattern, respectively. Western and traditional dietary patterns were negatively associated with subsequent short portable mental state questionnaire score over 4 and/or 8 years (all p < 0.05), whereas a healthy dietary pattern was not. Western dietary patterns significantly increased, by nearly threefold, the risk of subsequent cognitive decline over 8 years (adjusted odds ratio = 4.35, 95% confidence interval = 1.52-12.50, p < 0.05). For elders aged 65-74 years, a western dietary pattern was positively associated with increased, by eightfold, risk of cognitive decline over 8 years (adjusted odds ratio = 9.35, 95% confidence interval = 2.38-36.67, p < 0.05), whereas traditional and healthy dietary patterns were not. For elders aged ≥ 75 years, none of western, traditional, or healthy dietary patterns were associated with cognitive decline over 4 and 8 years. CONCLUSIONS: Dietary patterns correlate with cognitive function in Taiwanese aged 65 years and older and can predict the occurrence of subsequent cognitive decline. Western dietary pattern increases the risk of cognitive decline over 8 years. This study suggests that a diet that involves frequent consumption of meat/poultry and eggs and infrequent consumption of fish, beans/legumes, and vegetables and fruits may adversely affect cognitive function in older Taiwanese.

Nucleotide-dependent conformations of FtsZ dimers and force generation observed through molecular dynamics simulations.

The bacterial cytoskeletal protein FtsZ is a GTPase that is thought to provide mechanical constriction force via an unidentified mechanism. Purified FtsZ polymerizes into filaments with varying structures in vitro: while GTP-bound FtsZ assembles into straight or gently curved filaments, GDP-bound FtsZ forms highly curved filaments, prompting the hypothesis that a difference in the inherent curvature of FtsZ filaments provides mechanical force. However, no nucleotide-dependent structural transition of FtsZ monomers has been observed to support this force generation model. Here, we present a series of all-atom molecular dynamics simulations probing the effects of nucleotide binding on the structure of an FtsZ dimer. We found that the FtsZ-dimer structure is dependent on nucleotide-binding state. While a GTP-bound FtsZ dimer retained a firm monomer-monomer contact, a GDP-bound FtsZ dimer lost some of the monomer-monomer association, leading to a "hinge-opening" event that resulted in a more bent dimer, while leaving each monomer structure largely unaffected. We constructed models of FtsZ filaments and found that a GDP-FtsZ filament is much more curved than a GTP-FtsZ filament, with the degree of curvature matching prior experimental data. FtsZ dynamics were used to estimate the amount of force an FtsZ filament could exert when hydrolysis occurs (20-30 pN per monomer). This magnitude of force is sufficient to direct inward cell-wall growth during division, and to produce the observed degree of membrane pinching in liposomes. Taken together, our data provide molecular-scale insight on the origin of FtsZ-based constriction force, and the mechanism underlying prokaryotic cell division.

Occurrence of triclosan in the tropical rivers receiving the effluents from the hospital wastewater treatment plant.

The objective of this study was to determine the occurrence of triclosan in the tropical rivers where received the effluents from a hospital wastewater treatment plant (HWWTP) in southern Taiwan. Three and ten sampling sites were selected at the Jiaosu River (S0-S2) and Dian-Bao River (S3-S12), respectively. The samples of the HWWTP influent, effluent and receiving river water and sediment were collected and analyzed using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/ MS). Results showed that the triclosan level in surface water of the Jiaosu River and Dian-Bao River ranged from 3 to 68 ng/L and ranged from <2.7 to 51 ng/L, respectively. The hospital did contribute a loading of triclosan to the neighboring river. The mean value of triclosan concentration in the downstream surface water of the Jiaosu River (S1 20.2 ng/L) was approximately three times higher than that of the background level (S0 6.0 ng/L) (p = 0.011). The concentrations of triclosan in two surface water samples were over the predicted no effect concentration (PNEC) of 50 ng/L for algae. In addition, significant seasonal differences of triclosan in surface water of Jiaosu River (p = 0.020) and the HWWTP effluents (p = 0.302) were also observed. The concentrations of triclosan in sediments of these two rivers seemed stable. On average, triclosan was detected in 86 % of the sediment samples with a range from <1.1 to 13 ng/g. Triclosan in surface water and sediments of the tropical rivers might be rapidly photolyzed due to plenty of sunshine. It is worth to further investigate the occurrence and fate of triclosan photoproduct in the aquatic environment of the tropics.

Early inactivation of PKCε associates with late mitochondrial translocation of Bad and apoptosis in ventricle of septic rat.

BACKGROUND: Sepsis is usually accompanied by cardiomyocyte apoptosis and myocardial depression. Protein kinase C (PKC) has been reported to be important in regulating cardiac function and apoptosis; however, which PKC isoform is involved in sepsis-induced myocardial apoptosis remains unknown. MATERIALS AND METHODS: A rat model of sepsis by cecal ligation and puncture was used. Early and late sepsis refers to those rats sacrificed at 9 and 18 h after cecal ligation and puncture, respectively. Ventricular septum (Sep), left ventricle (LV), and right ventricle were fractionated into membrane, mitochondrial, and cytosolic fractions, individually. The protein levels of PKC isoforms (-α, -ß, -δ, -ε, -ζ, -ι, -λ, and -µ) and mitochondrial translocation of Bad were quantified by Western blot analysis. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP in situ nick-end labeling. The morphology of mitochondria was examined by electron microscopy. RESULTS: The membrane/cytosol ratio of PKCε was predominantly higher in the Sep, LV, and right ventricle under physiological conditions. At early sepsis, the membrane/cytosol ratio of PKCε was significantly decreased in Sep and LV. At late sepsis, cardiomyocyte apoptosis associated with severe mitochondrial swelling and crista derangement were observed in Sep and LV at late sepsis. Additionally, mitochondria/cytosol ratio of Bad was significantly increased in Sep and LV. CONCLUSIONS: The early inactivation of PKCε in the ventricle may affect the mitochondrial translocation of Bad and subsequent mitochondrial disruption and apoptosis at late sepsis. This finding opens up the prospect for a potential therapeutic strategy targeting PKCε activation to prevent myocardial depression in septic patients.

The changing food outlet distributions and local contextual factors in the United States.

BACKGROUND: Little is known about the dynamics of the food outlet distributions associated with local contextual factors in the U.S. This study examines the changes in food stores/services at the 5-digit Zip Code Tabulated Area (ZCTA5) level in the U.S., and assesses contextual factors associated with the changes. METHODS: Data from 27,878 ZCTA5s in the contiguous United States without an extreme change in the number of 6 types of food stores/services (supermarkets, small-size grocery stores, convenience stores, fresh/specialty food markets, carry-out restaurants, and full-service restaurants) were used. ZCTA5s' contextual factors were from the 2000 Census. Numbers of food stores/services were derived from the Census Business Pattern databases. Linear regression models assessed contextual factors' influences (racial/ethnic compositions, poverty rate, urbanization level, and foreign-born population%) on 1-year changes in food stores/services during 2000-2001, adjusted for population size, total business change, and census regions. RESULTS: Small-size grocery stores and fresh/specialty food markets increased more and convenience stores decreased more in Hispanic-predominant than other areas. Among supermarket-free places, new supermarkets were less likely to be introduced into black-predominant than white-predominant areas (odds ratio (OR) = 0.52, 95% CI = 0.30-0.92). However, among areas without the following type of store at baseline, supermarket (OR = 0.48 (0.33-0.70)), small-size grocery stores (OR = 1.32 (1.08-1.62)), and fresh/specialty food markets (OR = 0.70 (0.53-0.92)) were less likely to be introduced into areas of low foreign-born population than into areas of high foreign-born population. Higher poverty rate was associated with a greater decrease in supermarket, a less decrease in small-size grocery stores, and a less increase in carry-out restaurants (all p for trends <0.001). Urban areas experienced more increases in full-service and carry-out restaurants than suburban areas. CONCLUSIONS: Local area characteristics affect 1-year changes in food environment in the U.S. Hispanic population was associated with more food stores/services capable of supplying fresh food items. Black-predominant and poverty-afflicted areas had a greater decrease in supermarkets. Full-service and carry-out restaurants increased more in urban than suburban areas. Foreign-born population density was associated with introduction of grocery stores and fresh/specialty food markets into the areas.