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Toxoplasma gondii inhibits ultraviolet light-induced apoptosis through multiple interactions with the mitochondrion-dependent programmed cell death pathway.

Cells infected with the protozoan parasite Toxoplasma gondii are resistant to diverse apoptotic stimuli. In this study, we perform a detailed analysis of the manipulation of the mitochondrial arm of the apoptotic cascade by the parasite. Apoptosis was induced using irradiation with ultraviolet light (UV), and the kinetics of caspase activation, cytochrome c release and activation of the upstream signalling pathways were examined. The evidence clearly points to T. gondii targeting multiple steps in the transmission [inhibition of c-Jun N-terminal kinase (JNK) activation in response to UV], triggering (inhibition of cytochrome c release by affecting the balance of pro- and anti-apoptotic BCL-2 family members) and execution (inhibition of caspase 9 and caspase 3) phases of the apoptotic cascade. Interestingly, the multilevel pattern of inhibition that emerges suggests that the global inhibition of the mitochondrial arm of apoptosis is not likely to be contributed to by the small subset of mitochondria recruited to the T. gondii parasitophorous vacuole membrane.

Animals↗

Long-term follow-up of patients having infrainguinal bypass performed below stenotic but hemodynamically normal aortoiliac vessels.

Because infrainguinal bypasses performed on the basis of normal papaverine testing in patients with multilevel arterial occlusive disease are done below arteriographically diseased although hemodynamically normal vessels, there is concern about progression of suprainguinal disease compromising long-term success. This study has been done to assess the long-term results of such bypasses. Between 1979 and 1985, infrainguinal bypasses selected by papaverine testing were done on 92 limbs having hemodynamically normal inflow in the presence of arteriographically demonstrable aortoiliac stenoses of 15% to 70%. Long-term hemodynamic and clinical success rates were determined with criteria based on papaverine and noninvasive vascular testing. There was no significant difference in hemodynamic success at 48 months (by life-table analysis) (p = 0.98) when comparing limbs with less than 50% aortoiliac stenoses to limbs having 50% or greater stenoses. The difference between the mean degree of preoperative inflow stenoses for long-term hemodynamic successes (32.5% +/- 1.5%) and failures (34.6% +/- 3.0%) was not significant (p = 0.57). There was no significant difference (p = 0.98) in the number of subsequent inflow procedures required in limbs with preoperative aortoiliac stenoses of less than 50% (13.5%) vs. aortoiliac stenoses of 50% or greater (13.3%). Long-term results of infrainguinal bypass done below stenotic but hemodynamically normal aortoiliac vessels are not related to the amount of angiographically demonstrable inflow stenosis. Selection of patients for infrainguinal bypass on the basis of papaverine testing, irrespective of angiographic findings, eliminates unnecessary inflow procedures without detriment to long-term success.

Aged↗

Evaluation of the school-based smoking-prevention program "BE smokeFREE".

This article examines the impact of the school-based smoking-prevention program "BE smokeFREE" on adolescent smoking. A national representative sample of 99 schools (195 classes, 4,441 students) was used when the intervention started in November 1994. Schools were allocated to one of four groups: a comparison group (A) and three intervention groups (B, C, and D). Group B received the most comprehensive intervention. A baseline (autumn 1994) and three follow-up data collections (1995, 1996, and 1997) were conducted. There were no significant differences in smoking habits among the four groups at baseline. The smoking habits in the group that was involved in the most comprehensive intervention (group B) changed more favourably than those of students in the comparison schools over the three follow-up data collections. At the third follow-up, the proportion of students smoking weekly or more in the comparison group was 29.2%, compared with 19.6% in the model intervention group. The two less comprehensive interventions (no teacher in-service courses in group C, and no involvement of parents in group D) appeared to be less effective than the model intervention. Multilevel multiple logistic regression analyses, comparing changes in smoking habits between students in group B with those among students in the comparison schools, confirm the conclusion that the comprehensive intervention was the most effective. This school-based intervention, based on a social influence approach, proved to be effective at reducing smoking rates among participants.

Adolescent↗

Plaque removal efficacy of a battery-operated power toothbrush compared to two control manual toothbrushes in single use studies.

PURPOSE: Recently, a power toothbrush (Crest SpinBrush) has been reported to remove plaque more effectively than a manual toothbrush (Colgate Navigator). The objective of these studies was to compare the plaque removal efficacy of two control manual toothbrushes (Colgate Wave and Colgate Plus) to an experimental power toothbrush (Crest SpinBrush). The Colgate Plus has an ordinary flat bristle trim design, while the Colgate Wave has an advanced design multilevel bristle trim for greater interproximal penetration. MATERIALS AND METHODS: Each of these two studies were randomized, controlled, examiner-blind, 4-period crossover designs which examined plaque removal with the experimental toothbrush relative to a control manual toothbrush following a single use in 37 and 35 subjects, respectively. Plaque was scored before and after brushing using the Turesky Modification of the Quigley-Hein Index. RESULTS: In the first study, average baseline plaque scores were 2.88 and 2.89 for the experimental toothbrush and advanced designed manual control toothbrush (Colgate Wave) treatment groups, respectively. With respect to all surfaces examined, the experimental toothbrush delivered an adjusted (via analysis of covariance) mean difference between baseline and post-brushing plaque scores of 0.70 while the control toothbrush delivered an adjusted mean difference of 0.59. The difference between the brushes was statistically significant (P < 0.001). The experimental toothbrush removed, on average, 19.9% more plaque than the control toothbrush. In the second study, baseline plaque scores averaged 3.07 and 3.04 for the experimental toothbrush and ordinary flat trim manual control toothbrush (Colgate Plus) treatment groups, respectively. With respect to all surfaces examined, the experimental toothbrush delivered an adjusted (via analysis of covariance) mean difference between baseline and post-brushing plaque scores of 0.87 while the control toothbrush delivered an adjusted mean difference of 0.62. The difference between brushes was statistically significant (P < 0.001). The experimental toothbrush removed, on average, 40.0% more plaque than the control toothbrush.

Adolescent↗

Cytosine methylation does not affect binding of transcription factor Sp1.

DNA methylation may be a component of a multilevel control mechanism that regulates eukaryotic gene expression. We used synthetic oligonucleotides to investigate the effect of cytosine methylation on the binding of the transcription factor Sp1 to its target sequence (a G + C-rich sequence known as a "GC box"). Concatemers of double-stranded 14-mers containing a GC box successfully competed with the human metallothionein IIA promoter for binding to Sp1 in DNase I protection experiments. The presence of 5-methylcytosine in the CpG sequence of the GC box did not influence Sp1 binding. The result was confirmed using double-stranded 20-mers containing 16 base pairs of complementary sequence. Electrophoretic gel retardation analysis of annealed 28-mers containing a GC box incubated with an Sp1-containing HeLa cell nuclear extract demonstrated the formation of DNA-protein complexes; formation of these complexes was not inhibited when an oligomer without a GC box was used as a competitor. Once again, the presence of a 5-methylcytosine residue in the GC box did not influence the binding of the protein to DNA. The results therefore preclude a direct effect of cytosine methylation on Sp1-DNA interactions.

5-Methylcytosine↗

Proposal for an integrated evaluation model for the study of whole systems health care in cancer.

For more than 200 years, biomedicine has approached the treatment of disease by studying disease processes (patho-genesis), inferring causal connections and developing specific approaches for therapeutically interfering with those processes. This pathogenic approach has been highly successful in acute and traumatic disease but less successful in chronic disease, primarily because of the complex, multi-factorial nature of most chronic disease, which does not allow for simple causal inference or for simple therapeutic interventions. This article suggests that chronic disease is best approached by enhancing healing processes (salutogenesis) as a whole system. Because of the nature of complex systems in chronic disease, an evaluation model based on integrative medicine is felt to be more appropriate than a disease model. The authors propose and describe an integrated model for the evaluation of healing (IMEH) that collects multilevel "thick case" observational data in assessing complex practices for chronic disease. If successful, this approach could become a blueprint for studying healing capacity in whole medical systems, including complementary medicine, traditional medicine, and conventional primary care. In addition, streamlining data collection and applying rapid informatics management might allow for such data to be used in guiding clinical practice. The IMEH involves collection, integration, and potentially feedback of relevant variables in the following areas: (1) sociocultural, (2) psychological and behavioral, (3) clinical (diagnosis based), and (4) biological. Evaluation and integration of these components would involve specialized research teams that feed their data into a single data management and information analysis center. These data can then be subjected to descriptive and pathway analysis providing "bench and bedside" information.

Chronic Disease↗

Multilevel genetic analyses of two European supercolonies of the Argentine ant, Linepithema humile.

Some ants have an extraordinary unicolonial social organization, whereby individuals mix freely among physically separated nests. Recently, it was shown that the European population of Linepithema humile consisted of two enormous unicolonial supercolonies. Workers of the same supercolony are never aggressive to each other. In contrast, aggressiveness is invariably high between workers from different supercolonies. Here we investigated whether gene flow occurs between two supercolonies. We identified a contact zone in which we sampled 46 nests. For each nest, aggression tests were conducted against workers from reference nests from both supercolonies. Workers were always very aggressive towards workers of one of the supercolonies but not to workers of the other. Thus, all nests could be clearly assigned to one of the two supercolonies. For 22 of the 46 nests, we genotyped 15-16 workers at five microsatellite loci. A four-level hierarchical analysis of variance revealed very strong genetic differentiation between the two supercolonies (F(SUPERCOLONY-TOTAL) = 0.541) and low differentiation between sectors (i.e. group of nests connected together with trails) within supercolonies (F(SECTOR-SUPERCOLONY) = 0.064). The very high differentiation between the two supercolonies indicates a lack of ongoing gene flow, a conclusion further bolstered by the finding that the two supercolonies share no common alleles at two of the five microsatellite loci. A Bayesian clustering method also revealed the occurrence of two distinct clusters. These clusters exactly match the grouping obtained by aggression tests. None of the 332 genotyped individuals were admixed despite the fact that some nests of the two supercolonies were separated by less than 30 m. These results demonstrate that the two supercolonies have completely separate gene pools.

Aggression↗

Comparative analysis of nodal upstaging between colon and rectal cancers by sentinel lymph node mapping: a prospective trial.

PURPOSE: Sentinel lymph node mapping accurately predicts nodal status in > 90 percent of melanoma and breast and colorectal cancers. However, because of anatomic differences, sentinel lymph node mapping of rectal cancers has been considered inaccurate and difficult relative to colon. A prospective study was undertaken to identify differences in sentinel lymph node mapping between patients with colon cancer and those with rectal cancer. METHODS: At operation 1 to 3 ml of 1 percent isosulfan blue dye was injected subserosally around colon cancers. The first to fourth blue-staining nodes seen within ten minutes of injection were marked as sentinel lymph nodes. For cancer of the mid-rectum to low rectum, the dye was injected submucosally via rigid scope and spinal needle. The mesorectum was dissected ex vivo to identify blue nodes nearest the tumor as sentinel lymph nodes. Multilevel microsections of sentinel lymph nodes were stained with hematoxylin and eosin and immunostained for cytokeratin, and standard examination of the entire specimen was performed. RESULTS: There were 407 consecutive patients (336 with colon and 71 rectum). The sentinel lymph nodes were identified in 99.1 percent of colon and 91.5 percent of rectal patients (P < 0.0001). Skip metastases were found in 3.6 percent of colon vs. 2.8 percent of rectal patients (P = 0.16). Occult micrometastases were found in 13.4 percent of colon vs. 7.0 percent of rectal patients (P = 0.24). Except for success rates, no other parameters were statistically different between colon and rectum. Lower success in sentinel lymph node identification in rectal cancer may have been related to neoadjuvant chemoradiation received in all six of the patients with sentinel lymph node mapping failures. CONCLUSION: Despite higher success rates in sentinel lymph node identification for colon patients, sentinel lymph node mapping was highly successful (91.5 percent) in rectal patients. Nodal upstaging, skip metastases, and occult metastases were similar.

Aged↗

Predictability of a favorable outcome in anorexia nervosa.

OBJECTIVE: In a long-term follow-up of anorexia nervosa (AN) patients, somatic, psychological and social variables at clinical presentation should be investigated using a multilevel approach. METHODS: This study isolated predictors known from the literature over longer time periods and carried out a separate investigation of predictors in a sample of 81 AN patients of the Heidelberg-Mannheim study over a mean period of 12 years (range 9-19 years). Separate hierarchic regression analyses on the basis of the course of the Morgan-Russell categories were calculated for four individually recorded areas: anamnestic, psychological, somatic and social data sets. RESULTS: Age at the onset of the disease, purging behavior, low serum albumin, high glutamic-oxalo acetic transaminase (GOT) psychopathology (ANSS) and social pathology had the highest predictive value qualities. In survival analysis overall assessment of all six main predictors at clinical presentation could differentiate all patients who recovered from those who remained ill (log-rank test P = 0.019). CONCLUSION: A small number of variables were important for detecting a good or poor long-term course of AN. At onset of the disease, it seems necessary to evaluate these psychological, somatic and social predictors.

Adaptation, Psychological↗

Social and emotional impacts of farmwork injuries: an exploratory study.

CONTEXT: The physical hazards of farming have been extensively studied and reported upon. Far less studied are the social and emotional impacts of farmwork injuries and deaths. PURPOSE: To investigate and document broad but targeted issues regarding the impact on individuals, families, and communities of farmwork injuries and fatalities of farmer leaders. METHODS: Ten incidents of farmwork injuries with disabilities or fatalities in Pennsylvania were used for a collective case study. Data were collected through a total of 47 interview sessions with 66 individuals including next of kin, other family members, injured persons, and community members. Thematic analysis was used to identify themes and issues in this descriptive study. FINDINGS: Community members missed the rich, broad, and comprehensive skills, abilities, and perspectives that farmers brought to community service. Participants expressed that the community assistance and support provided to injured persons and families benefited not only the injured persons and their families and farms but also the community members. Participants reported emotional anguish and loss as well as positive transformations and consequences. As expressed by participants, God and religion play an important role in their beliefs regarding the occurrence and outcome of farmwork injury incidents. CONCLUSIONS: Social and emotional impacts on individuals, families, and communities are varied and multileveled. The role that religion and storytelling play in the process of dealing with serious injury incidents raises questions regarding agricultural injury prevention.

Accidents, Occupational↗

Capnocytophaga spp. in periodontitis patients manifesting diabetes mellitus.

BACKGROUND: The subgingival microflora in patients presenting concurrently with periodontitis and diabetes mellitus (DM) are poorly understood. While traditional putative periodontal pathogens are implicated, research involving other oral organisms; e.g., Capnocytophaga spp., is lacking. These organisms produce a range of bacterial enzymes relevant to periodontal breakdown. It is inferred that periodontal bacteria acquire systemic access through the ulcerated periodontal pocket surface; conclusive evidence supporting this notion is limited. The aims of this investigation were to: 1) quantify and identify Capnocytophaga spp. present in healthy and diseased sites in periodontitis patients with and without DM, and 2) isolate periodontal pathogens from these patients' blood. METHODS: Twenty-one DM-periodontitis and 25 periodontitis patients were recruited. Subgingival plaque was collected from three healthy and three diseased sites per subject. Capnocytophaga spp. and total (facultative and obligate) anaerobic counts from each site were estimated. Capnocytophaga spp. were identified using 16S rRNA polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). Statistical analyses were performed using multilevel modeling. Blood samples were subjected to HbA(1c) estimation and bacterial culture. RESULTS: A total of 848 Capnocytophaga spp. were isolated and identified. Significantly higher numbers of Capnocytophaga spp. (P <0.001) and anaerobes (P <0.001) were present in diseased sites in DM-periodontitis subjects compared to healthy sites in non-DM-periodontitis and DM-periodontitis subjects. C. ochracea (and variant) and C. granulosa were the most prevalent species. Blood samples were negative for Capnocytophaga spp. CONCLUSIONS: Total mean counts for Capnocytophaga spp. were significantly higher in DM-periodontitis subjects versus non-DM-periodontitis (P = 0.025) and at diseased sites versus healthy sites (P <0.001). Analysis of individual species revealed that the outcome varied with site status and DM status.

Adult↗

Seizing the moment: California's opportunity to prevent nutrition-related health disparities in low-income Asian American population.

Asian Americans and Pacific Islanders (AAPI) have the fastest growing rate of overweight and obese children. Aggressive programs are urgently needed to prevent unhealthy acculturation-related changes in diet and physical activity and to promote the healthier aspects of traditional lifestyle habits. We conducted focus groups and key informant interviews to explore knowledge, attitudes, dietary practices, and physical activity levels among three low-income Asian American ethnic groups, Chinese, Vietnamese, and Hmong, in California. Content analysis was used to identify similarities and differences among the groups. Several common health beliefs clearly emerged. Participants noted the importance of fresh (not frozen) fruit and vegetable consumption and physical activity for general health. The concept of good health included having a harmonious family, balance, and mental and emotional stability. All groups also expressed the general belief that specific foods have hot or cold properties and are part of the Yin/Yang belief system common to Asian cultures. The lure of fast food, children's adoption of American eating habits, and long work hours were identified as barriers to a healthy, more traditional lifestyle. A California campaign for Asian Americans using multilevel strategies is recommended to counter the alarming rise of obesity among AAPI youth. Strategies directed to individual, community, and policy levels should emphasize maintenance of healthy traditional diets, informed selection of mainstream U.S. foods, and promotion of active lifestyles to prevent an impending burden from cancer and nutrition-related chronic diseases in AAPI populations.

Asian↗

Outpatient treatment of dyslexia through stimulation of the cerebral hemispheres.

Although a number of experimental investigations into the effects of hemisphere stimulation on the reading performance of individuals with dyslexia are currently available, only a few studies have addressed the effects of treatment in the setting of an outpatient clinic. The present study reports on the reading results after a treatment that was based on the balance model and incorporated notions from cognitive psychological origin in 80 children with severe dyslexia who were referred to the outpatient clinic of the Paedological Institute in Amsterdam. Treatment was individually tailored, depending on the type of dyslexia, the phase of the learning-to-read process, and the intermediate results of treatment. Effects on reading performance, measured after preclinical (home-training), clinical, and postclinical intervention periods, were analyzed through multiple time-series and multilevel analyses. Treatment with flash cards, exercising automatic letter-sound conversions, appeared to have a robust and slight effect in the preclinical and clinical phases, respectively, whereas hemisphere stimulation produced robust effects in both the clinical and the postclinical period. The results are discussed in terms of theoretical models, experimental findings of other investigations, intellectual and scholastic characteristics of the subjects, and such treatment factors as compliance (see Note).

Adolescent↗

An assessment of the extent of child maltreatment using administrative databases.

This study examined the extent of violence toward children and factors associated with child maltreatment in Florida using a cohort of children (N=499,330) who were adjudged to be victims of maltreatment between July 1, 1996, and June 30, 2003. To assess the extent of maltreatment, five indicators were proposed and examined. Multivariate analyses found that prior referral, having more than one type of maltreatment during an initial incident, and caregiver absence best predicted the recurrence of maltreatment. Caregivers' alcohol and substance use were strong predictors of neglect and threatened harm but not of abuse. Finally, multilevel analyses found that older, nonminority girls with histories of prior referrals were significantly (psuedo-zs>2.00) more likely to experience high degrees of incident severity. Caregivers' substance use, excluding alcohol, also was significantly linked to incident severity. Implications of the findings are discussed.

Adolescent↗

Anterior cervical fusion: outcome analysis of patients fused with and without anterior cervical plates.

The purpose of this study was to assess the role of the anterior cervical plate in the treatment of cervical spondylosis. Forty-three patients surgically treated for cervical spondylosis were reviewed. The technique for discectomy and fusion was the same for both groups (Smith-Robinson with autologous iliac crest bone graft). Group I consisted of 25 consecutive patients treated with anterior cervical discectomy, autograft fusion, and anterior cervical plate fixation (Morscher titanium hollow screw plate system). Group II consisted of 18 consecutive patients treated without plate fixation. The overall clinical results in this study were not improved with the use of anterior cervical plate fixation (Fisher's exact test, p > 0.05). The fusion rate of one-level cervical fusions was not improved with anterior cervical plate fixation (Fisher's exact test, p > 0.05). The overall graft complication rate (pseudoarthrosis plus delayed union plus graft collapse) in multilevel fusions was decreased with anterior cervical plate fixation (Fisher's exact test, p < 0.01). The cost effectiveness and risk versus benefit of anterior cervical plate fixation in the surgical treatment of cervical spondylosis require further investigation.

Adult↗

Quantitative assessment of changes in patients' constructs of quality of life: an application of multilevel models.

It has often been proposed that quality of life (QL) instruments should account for potentially changing conceptualisations of QL as patients adapt to disease (response-shift). Most instruments do not do this, and some that do are relatively complicated and burdensome for patients. The extent to which patients reconceptualise QL is unknown, and it is unclear whether this additional complication is necessary. This paper reviews existing methods for assessing response-shift and introduces an alternative approach using multilevel models. The method is described using data from a cancer clinical trial, and its performance is evaluated in simulations. The models reveal substantial response-shift in these cancer patients. Simulations under the null hypothesis of zero response-shift confirm that the method performs correctly in terms of its risk of type I error, and further simulations illustrate its statistical power to detect pre-defined levels of response-shift. The method is a relatively simple extension of familiar multiple regression models and yields parameters with a simple interpretation, representing the changes in importance of QL domains over time. It can be applied to existing datasets collected with other analysis strategies in mind and may have application in the investigation of response shifts and other manifestations of adaptation.

Colorectal Neoplasms↗

Migration in Finland, a multi-level system of regions.

A systems approach is applied to the study of migration trends in Finland for the period 1971-1981, with particular attention to the period 1971-1978. The results indicate the existence of six permanent migration regions linked by a multilevel system. "The organization of this system varies from one part of the country to another, the most common modes being hierarchical tree flow networks belonging to a nodal system and polar and dendritic networks associated with a highly polarized system. The nodal system mode is seen to be increasing in currency."

Demography↗

Decision support system for the analysis of hospital operation indicators.

The inauguration of national health insurance (NHI) in many countries and their worsening financial condition has increased the sensitivity to operational cost and efficiency in hospitals. For several years, hospitals have been monitoring their operations by analyzing the financial and operational reports that are provided. Because of the rapidly changing character of the medical industry, statistical data shown on paper are no longer sufficient for decision makers. This paper describes a decision support system (DSS) for hospital administrators to assist in analyzing their operations efficiently and precisely. In hospitals, operational data of outpatients and inpatients are now stored on computers, resulting in much easier and faster data acquisition for administrators. The proposed system makes suggestions to hospital administrators and is able to self-learn to improve its future usefulness. With the dual capabilities of integrating evaluations and data collecting, the system can assist administrators in discovering and resolving problems quickly. The system provides multidimensional and multilevel analyses, by using data warehousing techniques, and generates appropriate advice to users by employing decision-making methodology. The self-learning function of the system makes it work like an expert, continually modifying its content (knowledge) and generating advice that is promptly updated to accord with changes in the medical industry.

Age Distribution↗