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Estimation of contribution of changes in coronary care to improving survival, event rates, and coronary heart disease mortality across the WHO MONICA Project populations.

BACKGROUND: The revolution in coronary care in the mid-1980s to mid-1990s corresponded with monitoring of coronary heart disease (CHD) in 31 populations of the WHO MONICA Project. We studied the impact of this revolution on coronary endpoints. METHODS: Case fatality, coronary-event rates, and CHD mortality were monitored in men and women aged 35-64 years in two separate 3-4-year periods. In each period, we recorded percentage use of eight treatments: coronary-artery reperfusion before, thrombolytics during, and beta-blockers, antiplatelet drugs, and angiotensin-converting-enzyme (ACE) inhibitors before and during non-fatal myocardial infarction. Values were averaged to produce treatment scores. We correlated changes across populations, and regressed changes in coronary endpoints on changes in treatment scores. FINDINGS: Treatment changes correlated positively with each other but inversely with change in coronary endpoints. By regression, for the common average treatment change of 20, case fatality fell by 19% (95% CI 12-26) in men and 16% (5-27) in women; coronary-event rates fell by 25% (16-35) and 23% (7-39); and CHD mortality rates fell by 42% (31-53) and 34% (17-50). The regression model explained an estimated 61% and 41% of variance for men and women in trends for case fatality, 52% and 30% for coronary-event rates, and 72% and 56% for CHD mortality. INTERPRETATION: Changes in coronary care and secondary prevention were strongly linked with declining coronary endpoints. Scores and benefits followed a geographical east-to-west gradient. The apparent effects of the treatment might be exaggerated by other changes in economically successful populations, so their specificity needs further assessment.

Adult↗

Rhizobium etli CFN42 contains at least three plasmids of the repABC family: a structural and evolutionary analysis.

In this paper, we report the identification of replication/partition regions of plasmid p42a and p42b of Rhizobium etli CFN42. Sequence analysis reveals that both replication/partition regions belong to the repABC family. Phylogenetic analysis of all the complete repABC replication/partition regions reported to date, shows that repABC plasmids coexisting in the same strain arose most likely by lateral transfer instead of by duplication followed by divergence. A model explaining how new incompatibility groups originate, is proposed.

Base Sequence↗

Use of hospital services by AIDS patients with psychiatric illness.

The purpose of this study was to assess the effect of psychiatric illness on length of stay and patterns of admission among AIDS patients hospitalized for medical illnesses. Medical records were abstracted for AIDS patients admitted to hospitals in Washington State from 1990 through 1992. Psychiatric comorbidity was defined by the presence of an International Classification of Disease-9 code reflecting psychiatric illness. Medical morbidity was addressed using CD4 count and AIDS-defining illnesses as markers of disease severity. Of 2834 admissions, 15% included one or more psychiatric diagnoses. Psychiatric illness (F 39.1; df 1,2830; p < 0.001) and discharge disposition (F 81.2; df 2,2830; p < 0.001) contributed significantly to the model, explaining increased length of stay (F 67.2; df 3,2830; p < 0.001). Future research needs to address the possible etiology of psychiatric comorbidity's contribution to length of stay and the effect on quality and cost of care.

AIDS Dementia Complex↗

Contextual fear, gestalt memories, and the hippocampus.

This review examines the relationship between exploration and contextual fear conditioning. The fear acquired to places or contexts associated with aversive events is a form of Pavlovian conditioning. However, an initial period of exploration is necessary to allow the animal to form an integrated memory of the features of the context before conditioning can take place. The hippocampal formation plays a critical role in this process. Cells within the dorsal hippocampus are involved in the formation, storage and consolidation of this integrated representation of context. Projections from the subiculum to the nucleus accumbens regulate the exploration necessary for the acquisition of information about the features of the context. This model explains why electrolytic but not excitotoxic lesions of the dorsal hippocampus cause enhanced exploratory activity but both cause deficits in contextual fear. It also explains why retrograde amnesia of contextual fear is greater than anterograde amnesia.

Animals↗

Effects of hypergravity on the photosynthetic flagellate, Euglena gracilis.

Euglena gracilis, a unicellular, photosynthetic flagellate, orients itself by means of gravi- and phototaxis to reach and stay in regions optimal for survival and growth. An improved version of the slow rotating centrifuge microscope, NIZEMI, was used to test wild type and mutant strains for their responses to hypergravity. Wild type cells could actively move against the acceleration vector up to 8.5 gn and were centrifuged down at higher rates. Even at 10.5 gn, the highest value tested, cells were still negative gravitactically oriented as shown by video images. In contrast, all mutant strains as well as Astasia longa, a close relative of Euglena, could move against the acceleration vector under all conditions tested. With increasing accelerations the mean orientation of the populations shifted according to a vectorial addition of gravity and acceleration. The r-value, a statistical measure of the orientation of a population, increased with moderately increased acceleration rates and decreased at higher values. While wild type Euglena and two of the three mutant strains tested were exclusively negative gravitactically, in the third strain as well as in Astasia longa half of the population reacted negative gravitactically and the other half positive gravitactically. This variation of the wild type behavior was observed at moderate acceleration rates. At high accelerations the cells became exclusively positive gravitactic. The obtained results are discussed on the basis of the current model explaining gravitaxis.

Acceleration↗

Substance use and its relation to sexual activity among inner-city adolescents.

A study of inner-city Black and Caucasian males and females in two junior and two senior high schools provided data on sexual knowledge, attitudes and behaviors, and substance use based on over 2500 anonymous, voluntary self-administered questionnaires. Substance use was high among Caucasians, particularly females. Females smoked more cigarettes than males and men drank more alcohol. Marijuana smoking showed only small racial, age, and gender differences. Compared to Blacks, Caucasians used more hard drugs. Using an index scoring types of substances and frequencies of use, sexually active students were higher than virgins in all subgroups, with those who initiated intercourse early appearing highest on the index. A regression model explaining 21% of the variance in substance use showed independent effects of age, race, gender, and sexual activity. The importance of an index for screening early use is discussed, and research on the relationship of low-level youthful experimentation with future dysfunctional use is proposed.

Adolescent↗

Determinants of condom use intentions of university students in Ghana: an application of the theory of reasoned action.

The study examined the applicability of the Theory of Reasoned Action to the study of condom use intentions of students at a university in southern Ghana. The data supported the model, explaining 33% of the variance in students' condom use intentions. Subjective norms and the perceived disadvantages of condom use were significant determinants of intention, with the former being more important. Respondents who intended to use condoms consistently ("intenders") and those with no such intentions ("non-intenders") were equally motivated to comply with the wishes of their significant referents (sexual partners, close friends, parents and medical doctors). The critical difference was that "intenders" consistently held a stronger belief than "non-intenders" that their significant referents approved of condom use. Significantly, whereas "intenders" believed that their sexual partners would approve of condom use, the "non-intenders" held the contrary belief that their partners would disapprove of such behavior. This suggests that AIDS education interventions targeting a similar audience like the university students in this study should shift their foci away from individuals alone and instead, focus simultaneously on individuals, their sexual partners and their broader social networks in order to enhance perceptions of peer acceptance of condom use.

Acquired Immunodeficiency Syndrome↗

Scanning tunneling microscopy study of cytochrome P450 2B4 incorporated in proteoliposomes.

In the present paper, the application of scanning tunneling microscopy in cytochrome P450s membrane topology is discussed. The method enables visualization of heme location in the lipid-bilayer-incorporated protein. It is supposed that the membrane-bound cytochrome P450 on the tunneling microscope substrate should behave as 'molecular diode'. A model explaining the liposome and the proteoliposome images observed is proposed.

Animals↗

Genesis and role of coordinated firing in a feedforward network: a model study of the enteric nervous system.

The enteric nervous system can generate complex motor patterns independently of the central nervous system. The ascending enteric reflex pathway consists of sensory neurons, long chains of a single class of orally directed interneuron and excitatory motor neurons. Because of the importance of this pathway in peristalsis, it was modelled from the firing of sensory neurons through to muscle membrane activation. The model was anatomically realistic in the number of neurons simulated and in the patterns of connections between neurons. The model was also realistic in the simulation of ligand-gated currents in neuron and muscle membrane, current flow in the muscle syncytium and voltage-dependent currents in muscle. Sensory neurons were activated in a manner consistent with a brief mechanical stimulus. Transmission between sensory neurons and first-order interneurons was by slow excitatory transmission, which caused interneurons to fire continuously for several hundred milliseconds. Interneurons then transmitted to higher order interneurons by fast excitatory postsynaptic potentials, each lasting for around 40 ms. As the activity propagated along the pathway, random firing became progressively more synchronized between neurons, until the network as a whole was firing in a coordinated manner. The coordinated firing was a robust phenomenon over a wide range of network and neuron parameters. It is therefore possible that this is a general property of feedforward networks that receive high levels of sustained input. The smooth muscle model indicated that bursting input to the muscle may increase the likelihood of muscle cells firing action potentials when compared with uniform input. In addition, the syncytium model explains how the predicted muscle excitation might be related to current experimental observations.

Action Potentials↗

Motion sickness and development of synergy within the spatial orientation system. A hypothetical unifying concept.

Adaptation to research paradigms such as rotating rooms and optical alteration of visual feedback during movement results in development of perceptual-motor programs that provide the reflexive assistance that is necessary to skilled control of movement and balance. The discomfort and stomach awareness that occur during the adaptation process has been attributed to conflicting sensory information about the state of motion. Vestibular signals depend on the kinematics of head movements irrespective of the presence or absence of signals from other senses. We propose that sensory conflict when vestibular signals are at least one component of the conflict are innately disturbing and unpleasant. This innate reaction is part of a continuum that operates early in life to prevent development of inefficient perceptual-motor programs. This reaction operates irrespective of and in addition to reward and punishment from parental guidance or goal attainment to yield efficient control of whole body movement in the operating environment of the individual. The same mechanism is involved in adapting the spatial orientation system to strange environments. This conceptual model "explains" why motion sickness is associated with adaptation to novel environments and is in general consistent with motion sickness literature.

Adaptation, Physiological↗

Maintenance of species identity and controlling speciation of bacteria: a new function for restriction/modification systems?

Bacteria frequently exchange DNA among each other by horizontal gene transfer. However, maintenance of species identity and in particular speciation requires a certain barrier against an unregulated uptake of foreign DNA. Here it is suggested that formation of such a barrier is one important biological function of restriction/modification systems, in addition to the classical function of protection of bacteria against bacteriophage infection. This model explains the extreme variability and wide distribution of restriction/modification systems among prokaryotes, the prevalence of RM-systems in pathogenic bacteria and the existence of several RM-systems in single bacterial strains.

Bacteria↗

Application of a factorial design to the study of the flow behavior, spreadability and transparency of a Carbopol ETD 2020 gel. Part II.

A factorial design (2(3)) is applied to study the influence of three of the components of a cosmetic gel (the concentrations of Carbopol ETD 2020, ethanol and glycerine) on flow parameters (Casson's yield value (tau(c)), Casson's viscosity (eta(c)) and apparent viscosity at 125 s-1 (eta(ap.) 125 s-1), spreadability, and transparency. The first-order polynomial equation allowed by the model suitably accounts for the tau(c) and spreadability. Both depend on the concentrations of Carbopol and ethanol, and tau(c) also depends on the ethanol-glycerine interaction. The model explains to a certain extent the complex relationships that are established between the components and that influence eta(c) y eta(ap.) 125 s-1. Transparency is independent of the Carbopol concentration and it is also thought to be independent of the ethanol concentration. In addition, a high linear correlation has been found between the tau(c) and spreadability and other viscoelastic parameters of the gels that were previously determined (Int. J. Pharm. (2001)). The application of the technique of experimental design has been shown to be a very useful tool for formulating gels.

Acrylic Resins↗

Grouping of haemolytic streptococci by monoclonal antibodies: determinant specificity, cross-reactivity and affinity.

Streptococcal group polysaccharide (CHO), A-, A-variant-, B-, C-, D- and G-specific monoclonal antibodies were prepared by the hybridoma technique employing spleen cells of several inbred mouse strains which are either high or low responders to the group A-CHO. The isotypes of these reagents were restricted to the class mu and IgG subclasses gamma 3 and--in small numbers--gamma 1. Two distinct categories of antibodies were identified for all but group D specificity: those which agglutinate suspended bacteria but do not precipitate purified soluble antigen, and those which show both agglutinating and precipitating properties. The group D antibodies described here were only of the latter category. The reactions were inhibitable by haptens in as far as these were known. Cross-reactions were observed in group-A-specific antibodies with E and L polysaccharides. Most G-CHO-specific antibodies cross-reacted with B-CHO. Association constants determined by fluorescence quenching measurements were for binding of complete A and C polysaccharides in the range of 10(6) to greater than 10(8) M-1, and for hapten binding by A-, Av- and C-CHO-specific antibodies in the range of 10(3) to 10(4) M-1. These results support a model of steric arrangements of antigenic determinants on A-variant bacteria and solubilized antigen [42] and allow its extension to streptococcal groups A, B, C and G. This model explains the observed functional differences by postulating single, terminal determinants which interact with the prevailing non-precipitating antibodies and internal repeating determinants which react with precipitins, respectively. No significant differences were found in the reactivity patterns to these streptococcal group antigens between strains of mice in terms of their ability to respond with high or low serum antibody titres to group A-CHO. On the other hand, within high and low responder strains, different kinetics of the optimal timing of fusion after initiation of the secondary immune reaction by boosting was observed. Low responders were most efficiently used for fusion 1.5 days later than high-responder spleen cells. This feature is interpreted to indicate an earlier proliferation of B lymphocytes in high responders, due to either an improved responsiveness to T-lymphocyte help or a reduced reactivity with T suppressor cells in comparison to low-responder B lymphocytes.

Animals↗

Service utilisation and costs of first-contact patients in a community psychiatric service in Italy.

This study describes service utilisation under routine clinical activity and the costs of providing mental health care for 24 months for the whole population of 330 subjects who had first contact with the Magenta Community Mental Health Centre during one year. The mean age of patients was 42.5 years, and 61% were females. According to ICD 10 criteria, 7% were diagnosed as having schizophrenia, 22% mood disorders, 37% neurotic disorders, 15% personality disorders and 19% other diagnoses. The clinical routine activity was monitored for 24 months from the first contact for each patient. The mean cost for a schizophrenic patient is more than double that of other patients. In-patient activity and community services accounted, respectively, for 49.7% and 50.3% of the total costs. Total health care costs per patient differ widely according to whether patients had been hospitalised during the observation period. Patients with a previous psychiatric contact and a longer duration of illness were more costly than the other patients. Multiple regression analysis was used to assess the association between all the individual variables and costs. For the whole population, the model explains 50% of the cost variation. Higher treatment costs were positively associated with the presence of previous psychiatric contacts and referral to the CPS by other sources than a general practitioner, and negatively associated with age.

Adult↗

Regulating the expression and function of homeotic genes.

Research published in the past year has led to plausible molecular models explaining the maintenance of stable patterns of homeotic gene expression through many cell generations. In addition, genes have been identified that modify the functional specificity of homeotic genes without affecting their expression patterns.

Animals↗

Self-polarization and directional motility of cytoplasm.

BACKGROUND: Directional cell motility implies the presence of a steering mechanism and a functional asymmetry between the front and rear of the cell. How this functional asymmetry arises and is maintained during cell locomotion is, however, unclear. Lamellar fragments of fish epidermal keratocytes, which lack nuclei, microtubules and most organelles, present a simplified, perhaps minimal, system for analyzing this problem because they consist of little other than the motile machinery enclosed by a membrane and yet can move with remarkable speed and persistence. RESULTS: We have produced two types of cellular fragments: discoid stationary fragments and polarized fragments undergoing locomotion. The organization and dynamics of the actin-myosin II system were isotropic in stationary fragments and anisotropic in the moving fragments. To investigate whether the creation of asymmetry could result in locomotion, a transient mechanical stimulus was applied to stationary fragments. The stimulus induced localized contraction and the formation of an actin-myosin II bundle at one edge of the fragment. Remarkably, stimulated fragments started to undergo locomotion and the locomotion and associated anisotropic organization of the actin-myosin II system were sustained after withdrawal of the stimulus. CONCLUSIONS: We propose a model in which lamellar cytoplasm is considered a dynamically bistable system capable of existing in a non-polarized or polarized state and interconvertible by mechanical stimulus. The model explains how the anisotropic organization of the lamellum is maintained in the process of locomotion. Polarized locomotion is sustained through a positive-feedback loop intrinsic to the actin-myosin II machinery: anisotropic organization of the machinery drives translocation, which then reinforces the asymmetry of the machinery, favoring further translocation.

Actins↗

Recognition and regulation of metalloproteinase activity in the haemolymph of Galleria mellonella: a new pathway mediating induction of humoral immune responses.

Proteolytic activity released within an organism by wounded tissues or invading pathogens can strongly impair the physiological homeostasis when it remains non-regulated. Thus, an efficient mechanism that enables recognition and inactivation of non-regulated proteolytic activity is essential to limit toxic effects. In larvae of the Greater wax moth Galleria mellonella we discovered that injection of bacterial thermolysin at a sublethal concentration mediates both acquired resistance against a subsequently injected lethal concentration of this metalloproteinase and stimulation of humoral immune response accompanied by the synthesis of an inducible metalloproteinase inhibitor (IMPI) which is released within the haemolymph. In search of a putative mechanism mediating recognition and regulation of released microbial metalloproteinases we determined that thermolysin-mediated hydrolysis of G. mellonella haemolymph proteins in vitro yields small (<3 kDa), heat-stable molecules which were discovered to represent potent elicitors of humoral immune responses when injected into untreated larvae. Obtained results allowed to design a model explaining for the first time regulation of released metalloproteinases within the haemolymph of insects. The determined coherence between regulation of released metalloproteinases by IMPI and the simultaneous induction of antimicrobial proteins provides a new insight into the mechanisms leading to expression of genes in course of humoral immune responses.

Animals↗

Physical and psychological attributes of fatigue in female heart transplant recipients.

BACKGROUND: The attributes of fatigue after orthotopic heart transplantation (OHT) are poorly understood. We conducted this study to assess the prevalence, severity and correlates of fatigue among female OHT survivors. METHODS: Fifty women (age 54.7 +/- 13.0 years) from a single heart transplant center, who underwent OHT 5.1 +/- 4.4 (mean +/- SD) years earlier, completed a battery of questionnaires including the Profile of Mood States-fatigue sub-scale to assess levels of fatigue, the Beck Depression Inventory to measure depression, and the Short Form-36 to measure functional status and mental health. Demographic and clinical data were obtained from self-reports and medical chart reviews. RESULTS: Women reported mean scores of 15.7 +/- 6.8 (range 3 to 27), 13.2 +/- 8.2 (range 0 to 38), 37.2 +/- 10.8 (range 22 to 62) and 41.5 +/- 11.2 (range 17 to 60) for fatigue, depression, functional status and mental health, respectively. Univariate analyses revealed that sociodemographic and clinical variables (e.g., age, employment status, anemia, renal insufficiency) were significantly related to fatigue (p < 0.001). Likewise, depression, functional status and mental health were also significantly related to fatigue (p < 0.001). In a multivariate model, age (adjusted R(2) = 0.23, p < 0.001), anemia (adjusted R(2) = 0.39, p < 0.001), functional status (adjusted R(2) = 0.60, p < 0.001) and depression (adjusted R(2) = 0.69, p < 0.001) were significant predictors of fatigue. The model explained 69% of the variance in fatigue (p < 0.001). CONCLUSIONS: Fatigue is common in women after OHT and is associated with both physiologic and psychologic factors. Clinicians should evaluate all female recipients for symptoms of fatigue, especially those with anemia, renal insufficiency, poor functional status and depression. Other potential mediators of fatigue, such as the denervated donor heart and type of immunosuppressive regimen, may also play a role and require further study.

Adolescent↗