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Coordination within and between organisms is one of the most complex abilities of living systems, requiring the concerted regulation of many physiological constituents, and this complexity can be particularly difficult to explain by appealing to physics. A valuable framework for understanding biological coordination is the coordinative structure , a self-organized assembly of physiological elements that collectively performs a specific function. Coordinative structures are characterized by three properties: (1) multiple coupled components, (2) soft-assembly, and (3) functional organization. Coordinative structures have been hypothesized to be specific instantiations of dissipative structures, non-equilibrium, self-organized, physical systems exhibiting complex pattern formation in structure and behaviors. We pursued this hypothesis by testing for these three properties of coordinative structures in an electrically-driven dissipative structure. Our system demonstrates dynamic reorganization in response to functional perturbation, a behavior of coordinative structures called reciprocal compensation . Reciprocal compensation is corroborated by a dynamical systems model of the underlying physics. This coordinated activity of the system appears to derive from the system's intrinsic end-directed behavior to maximize the rate of entropy production. The paper includes three primary components: (1) empirical data on emergent coordinated phenomena in a physical system, (2) computational simulations of this physical system, and (3) theoretical evaluation of the empirical and simulated results in the context of physics and the life sciences. This study reveals similarities between an electrically-driven dissipative structure that exhibits end-directed behavior and the goal-oriented behaviors of more complex living systems.

Physical systems open to a flow of energy can exhibit spontaneous symmetry breaking and self-organization. These nonequilibrium self-organized systems are known as dissipative structures. We study the oscillatory mode of an electrically driven dissipative structure. Our system consists of aluminum beads in shallow oil, which, when subjected to a high voltage, self-organize into connected 'tree' structures. The tree structures serve as pathways for the conduction of charge to ground. This system shows a variety of spatio-temporal behaviors, such as oscillating movement of the tree structures. Utilizing a dynamical systems model of the electromagnetic phenomena, we explore a potential mechanism underlying the system's behavior and use the model to make additional empirical predictions. The model reproduces the oscillatory behavior observed in the real system, and the behavior of the real system is consistent with predictions from the model under various constraints. From the empirical results and the mathematical model, we observe a tendency for the system to select modes of behavior with increased dissipation, or higher rates of entropy production, in accord with the proposed Maximum Entropy Production (MEP) Principle., Competing Interests: The authors have declared that no competing interests exist.

Perceptual guidance of movement with simple visual or temporal information can facilitate performance of difficult coordination patterns. Guidance may override coordination constraints that usually limit stability of bimanual coordination to only in-phase and anti-phase. Movement dynamics, however, might not have the same characteristics with and without perceptual guidance. Do visual and auditory guidance produce qualitatively different dynamical organization of movement? An anti-phase wrist flexion and extension coordination task was performed under no specific perceptual guidance, under temporal guidance with a metronome, and under visual guidance with a Lissajous plot. For the time series of amplitudes, periods and relative phases, temporal correlations were measured with Detrended Fluctuation Analysis and complexity levels were measured with multiscale entropy. Temporal correlations of amplitudes and relative phases deviated from the typical 1/f variation towards more random variation under visual guidance. The same was observed for the series of periods under temporal guidance. Complexity levels for all time series were lower in visual guidance, but higher for periods under temporal guidance. Perceptual simplification of the task's goal may produce enhancement of performance, but it is accompanied by changes in the details of movement organization that may be relevant to explain dependence and poor retention after practice under guidance., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This work examines the mechanisms involved in the attenuation of postprandial glycemic and insulinemic responses associated with soluble dietary fibre (SDF) consumption. The effect of SDF, including yellow mustard mucilage, soluble flaxseed gum and fenugreek gum on in vitro amylolysis and maltose transport was studied. Furthermore, a human clinical trial was conducted to investigate the effect of SDF consumption on postprandial glycemic and insulinemic responses and gastric emptying, as estimated based on the absorption of paracetamol. Participants (n = 15) at risk for type II diabetes consumed maltose syrup- and starch-based pudding treatments supplemented with each SDF, each at a concentration to match three times the apparent viscosity (18.54 mPa s at 60 s -1 ) equivalent to the European Food Safety Authority (2011) glycemia control health claim for cereal β-glucan, measured under simulated small intestinal conditions. The presence of each SDF delayed in vitro amylolysis to a similar extent, but had no effect on maltose transport. Generally, all SDF-containing treatments attenuated blood glucose and plasma insulin peak concentrations and plasma paracetamol 1 h incremental area under the curve values to a similar extent, relative to the controls, despite differences in the amounts at which each SDF was used (from 5.9 to 15.5 g). The postprandial attenuations were related to the ability of each SDF to modify digesta viscosity, perhaps through the delay of gastric emptying, as a delay of amylolysis and sugar transport under simulated upper intestinal conditions did not seem to have a substantial effect.

The events we encounter and the emotions we experience are valenced-they are positively or negatively charged. Although these occurrences seem to be distributed irregularly throughout the day, the two experiments presented here reveal systematicity in the temporal dynamics of affective experience using a variety of time-series analyses. In Experiment 1, participants used a portable button to respond to event valence (the positive or negative charge of an event in the environment) or affective valence (one's positive or negative feeling at the time of responding). This methodology yields signed response durations, indexing the valence and intensity of an occurrence, and inter-response intervals, indexing their distribution. These measures revealed that valenced occurrences are correlated with both temporally proximal and remote occurrences. Experiment 2 validated the methodology employed in Experiment 1 using artificial, laboratory-created event structures. Implications of dynamical approaches to understanding emotion are discussed.

Purpose: The results of a study to determine the long-term (up to 14 days) stability of diluted dexmedetomidine kept in polypropylene syringes under typical pharmacy storage conditions are presented., Methods: Four samples of dexmedetomidine injection diluted to 4 μg/mL in 0.9% sodium chloride were prepared and divided into 25-mL portions for storage in syringes at ambient room temperature (20-25 °C) with light exposure or under refrigeration (5 °C) in darkness. At 24 and 48 hours, the percentage of the initial dexmedetomidine concentration remaining in all samples was assessed via high-performance liquid chromatography with diode-array detection; further stability testing of the refrigerated samples was performed on days 7 and 14. At each time point, the test samples were visually inspected for color, clarity, and signs of formation of particulate matter., Results: As determined by chromatographic analyses, the samples of diluted dexmedetomidine stored in syringes at room temperature exhibited a loss of drug concentration of <10% over 48 hours; the refrigerated samples exhibited a loss of drug concentration of <5% over 14 days. All of the syringe-stored samples remained clear and colorless on visual inspection for the duration of the study., Conclusion: Dexmedetomidine diluted to 4 μg/mL in 0.9% sodium chloride injection was stable for at least 48 hours at 20-25 °C and 14 days at 5 °C when stored in polypropylene syringes.

The current research distinguishes two types of attention shifts: those entailed by perceptual learning and those entailed by changing intention. In perceptual learning, participants given feedback have been shown to gradually shift attention toward the optimal (i.e., specifying) information variable for the task. A shift in variable use is also expected when intention changes, because an intention to perceive some property entails attunement to information about that property. We compared the effects of feedback and intention in a dynamic (kinesthetic) touch task by representing both as changes of locus in an information space of inertial variables. Participants wielded variously sized, unseen, rectangular parallelepipeds and made length or width judgments about them. When given feedback, participants made gradual attentional shifts toward the optimal variable, which demonstrates the education of attention. When asked to report a new property, participants made large attentional jumps to the ballpark of the optimal variable for the new property. Exploratory movements were measured on 6 participants and were found to differ as a function of intention and to change with learning.

The variability of coupled rhythmic limb movements is assumed to be a consequence of the strength of a movement's attractor dynamic and a constant stochastic noise process that continuously perturbs the movement system away from this dynamic. Recently, it has been suggested that the nonlinear technique of recurrence analysis can be used to index the effects of noise and attractor strength on movement variability. To test this, three experiments were conducted in which the attractor strength of bimanual wrist-pendulum movements (using coordination mode, movement frequency and detuning), as well as the magnitude of stochastic perturbations affecting the variability of these movements (using a temporally fluctuating visual metronome) was manipulated. The results of these experiments demonstrate that recurrence analysis can index parametric changes in the attractor strength of coupled rhythmic limb movements and the magnitude of metronome induced stochastic perturbations independently. The results of Experiments 1 and 2 also support the claim that differences between the variability of inphase and antiphase coordination, and between slow and fast movement frequencies are due to differences in attractor strength. In contrast to the standard assumption that the noise that characterizes interlimb coordination remains constant for different magnitudes of detuning (Delta omega) the results of Experiment 3 suggest that the magnitude of noise increases with increases in |Delta omega|.

A simple instance of coupling behavior to the environment is oscillating the hands in pace with metronome beats. This environmental coupling can be weaker (1 beat per cycle) or stronger (2 beats per cycle). The authors examined whether strength of environmental coupling enhanced the stability of in-phase bimanual coordination. Detuning by manipulanda that produced different left and right eigenfrequencies shifted the relative phase angle from 0 degrees, with the size of the shift larger for higher movement frequencies. Stronger environmental coupling was found to decrease this relative-phase shift, with accompanying increase and reduction, respectively, in recurrence quantification measures related to coordination stability and coordination noise. Stronger environmental coupling also increased oscillation amplitude. Results are considered from the perspective of parametric stabilization., (Copyright 2006 APA)

We investigate the temporal coordination of human gait and posture and infer the nature of their coupling. Participants viewed a sinusoidally oscillating visual display which induced medial-lateral postural sway during treadmill walking, while display frequency was varied (0.075-1.025 Hz). First, postural responses exhibited the usual low-pass characteristic but with an additional resonance peak near the preferred stride frequency, although shifted downward by 0.12 Hz; this provides evidence of a coupling from gait to posture. Second, the step cycle adapted to mode lock with the visual driver and postural sway, as well as displaying instances of intermittency (slipping in and out of phase) and quasiperiodicity (phase wandering); this provides evidence of a coupling from posture to gait. We observed a spectrum of integer mode locks, including a large 1:1 trapping region about the stride frequency and superharmonic entrainment (stride frequency > driver frequency) at lower driver frequencies. A coupled-oscillator model that incorporates a novel parametric coupling from posture to the gait "stiffness" term reproduces these features of the data, including the resonance peak shift. Biological coordination patterns may thus emerge naturally as properties of a system of appropriately coupled oscillators.

How is human locomotion visually controlled? Fifty years ago, it was proposed that we steer to a goal using optic flow, the pattern of motion at the eye that specifies the direction of locomotion. However, we might also simply walk in the perceived direction of a goal. These two hypotheses normally predict the same behavior, but we tested them in an immersive virtual environment by displacing the optic flow from the direction of walking, violating the laws of optics. We found that people walked in the visual direction of a lone target, but increasingly relied on optic flow as it was added to the display. The visual control law for steering toward a goal is a linear combination of these two variables weighted by the magnitude of flow, thereby allowing humans to have robust locomotor control under varying environmental conditions.

This paper considers interaction of the human arm with "virtual" objects simulated mechanically by a planar robot. Haptic perception of spatial properties of objects is distorted. It is reasonable to expect that it may be distorted in a geometrically consistent way. Three experiments were performed to quantify perceptual distortion of length, angle and orientation. We found that spatial perception is geometrically inconsistent across these perceptual tasks. Given that spatial perception is distorted, it is plausible that motor behavior may be distorted in a way consistent with perceptual distortion. In a fourth experiment, subjects were asked to draw circles. The results were geometrically inconsistent with those of the length perception experiment. Interestingly, although the results were inconsistent (statistically different), this difference was not strong (the relative distortion between the observed distributions was small). Some computational implications of this research for haptic perception and motor planning are discussed.

Three hypotheses have been proposed for the roles of central and peripheral vision in the perception and control of self-motion: (1) peripheral dominance, (2) retinal invariance, and (3) differential sensitivity to radial flow. We investigated postural responses to optic flow patterns presented at different retinal eccentricities during walking in two experiments. Oscillating displays of radial flow (0 degree driver direction), lamellar flow (90 degrees), and intermediate flow (30 degrees, 45 degrees) patterns were presented at retinal eccentricities of 0 degree, 30 degrees, 45 degrees, 60 degrees, or 90 degrees to participants walking on a treadmill, while compensatory body sway was measured. In general, postural responses were directionally specific, of comparable amplitude, and strongly coupled to the display for all flow patterns at all retinal eccentricities. One intermediate flow pattern (45 degrees) yielded a bias in sway direction that was consistent with triangulation errors in locating the focus of expansion from visible flow vectors. The results demonstrate functionally specific postural responses of both central and peripheral vision, contrary to the peripheral dominance and differential sensitivity hypotheses, but consistent with retinal invariance. This finding emphasizes the importance of optic flow structure for postural control regardless of the retinal locus of stimulation.

No past studies of diarrhea in children of the Middle East have examined in detail the phenotypes of enterotoxigenic Escherichia coli (ETEC) strains, which are important pathogens in this setting. During a prospective study conducted from November 1993 to September 1995 with 242 children under 3 years of age with diarrhea living near Alexandria, Egypt, 125 episodes of diarrhea were positive for ETEC. ETEC strains were available for 98 of these episodes, from which 100 ETEC strains were selected and characterized on the basis of enterotoxins, colonization factors (CFs), and O:H serotypes. Of these representative isolates, 57 produced heat-stable toxin (ST) only, 34 produced heat-labile toxin (LT) only, and 9 produced both LT and ST. Twenty-three ETEC strains expressed a CF, with the specific factors being CF antigen IV (CFA/IV; 10 of 23; 43%), CFA/II (5 of 23; 22%), CFA/I (3 of 23; 13%), PCFO166 (3 of 23; 13%), and CS7 (2 of 23; 9%). No ETEC strains appeared to express CFA/III, CS17, or PCFO159. Among the 100 ETEC strains, 47 O groups and 20 H groups were represented, with 59 O:H serotypes. The most common O serogroups were O159 (13 strains) and O43 (10 strains). O148 and O21 were each detected in five individual strains, O7 and O56 were each detected in four individual strains, O73, O20, O86, and O114 were each detected in three individual strains, and O23, O78, O91, O103, O128, and O132 were each detected in two individual strains. The most common H serogroups were H4 (16 strains), 12 of which were of serogroup O159; H2 (9 strains), all of which were O43; H18 (6 strains); H30 (6 strains); and H28 (5 strains); strains of the last three H serogroups were all O148. Cumulatively, our results suggest a high degree of clonal diversity of disease-associated ETEC strains in this region. As a low percentage of these strains expressed a CF, it remains possible that other adhesins for which we either did not assay or that are as yet undiscovered are prevalent in this region. Our findings point out some potential barriers to effective immunization against ETEC diarrhea in this population and emphasize the need to identify additional protective antigens commonly expressed by ETEC for inclusion in future vaccine candidates.

In a population-based study of diarrhea in rural, northern Egypt, 60 Shigella flexneri strains were identified, of which 10 could not be definitively serotyped. Serological analysis with commercial reagents suggested that they were serotype 1, but the strains failed to react with subserotype 1a- or 1b-specific antibodies. All 10 strains reacted with MASF 1c, a monoclonal antibody specific for a provisional S. flexneri subserotype, 1c, first identified in Bangladesh and not previously detected outside of that region. Our results show that S. flexneri subserotype 1c is not unique to Bangladesh and that the inability to detect it may reflect both the limited use of suitable screening methods and the rarity of this subserotype.

Enterotoxigenic Escherichia coli (ETEC) are diverse pathogens that express heat-labile (LT) and/or heat-stable (ST) enterotoxins, yet little is known about whether epidemiologic patterns of pediatric ETEC diarrhea vary by the expressed ETEC toxin phenotype. In total, 242 Egyptian children aged <3 years were prospectively followed in 1993-1995. ETEC episodes were detected during twice-weekly home visits, and asymptomatic ETEC excretion was identified from monthly cross-sectional surveys. ETEC episodes were 0.6 per child-year. ST-only ETEC was 2.6 times (P<.001) more common in warmer than cooler months, while LT-only ETEC showed no seasonal variation. Ownership of a household sanitary latrine, but not breast-feeding, was associated with a lower risk of both enterotoxin phenotypes. Coexpression of a colonization factor by LT- or ST-only ETEC strengthened the association with diarrhea. These findings indicate that the epidemiologic patterns of LT-only and ST-only ETEC are not identical and that disease interventions should include improved household sanitation.

Three experiments tested the hypothesis that postural sway during locomotion is visually regulated by motion parallax as well as optical expansion. Oscillating displays of three-dimensional scenes were presented to participants walking on a treadmill, while postural sway was recorded. Displays simulated: (a) a cloud, in which parallax and expansion are congruent, (b) a hallway, (c) the side walls of the hallway, (d) a ground surface, (e) a wall, (f) the wall with a central hole, (g) a hall farther from the observer, and (h) a wall farther from the observer. In contrast to previous results with a hallway, responses with the cloud were isotropic and directionally specific. The other displays demonstrated that motion parallax was more effective than simple horizontal flow in eliciting lateral sway. These results are consistent with the hypothesis that adaptive control of sway during walking is based on congruent expansion and parallax in natural environments.

Three experiments examined the functional specificity of visually controlled posture during locomotion by presenting large-screen displays to participants walking on a treadmill. Displays simulated locomotion down a stationary hallway, a hallway that traveled with the observer, or a frontal wall that traveled with the observer. A superimposed oscillation specified postural sway in 6 possible directions. With the wall, sway amplitude was isotropic and directionally specific in all conditions. However, with the hallways, sway was anisotropic (lateral > anterior-posterior [AP]), and diagonal responses were flattened into the lateral plane. When the treadmill was turned 90 degrees to the hallway, both the anisotropy and flattening were reversed (AP > lateral), indicating that they are determined by the visual structure of the scene. The results can be explained by postural control laws based on both optical expansion and motion parallax, yielding biases in planar environments that truncate parallax.

To determine the protective efficacy (PE) of three doses of oral B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) vaccines against cholera, a clinical trial was conducted among 62285 children over 2 years and adult women in rural Bangladesh. During 5 years of follow-up, there were 144 cases of cholera in the BS-WC group (PE = 49%; P < 0.001), 150 in the WC group (PE = 47%; P < 0.001), and 283 in the K12 group. Protection by each vaccine was evident only during the first three years of follow-up; long-term protection of young children was observed only against classical but not El Tor cholera; 3-year protection against both cholera biotypes occurred among older persons, but at a higher level against classical cholera.

We outline a theory of infant skill acquisition characterized by an assembly phase, during which a task-specific, low-dimensional action pattern emerges from spontaneous movement in the context of task constraints, and a tuning phase, during which adjustment of the system parameters yields a more energetically efficient and more stable movement. 8 infants were observed longitudinally when bouncing while supported by a harness attached to a spring. We found an initial assembly phase in which kicking was irregular and variable in period, and a tuning phase with more periodic kicking, followed by the sudden appearance of long bouts of sustained bouncing. This "peak" behavior was characterized by oscillation at the resonant frequency of the mass-spring system, an increase in amplitude, and a decrease in period variability. The data are consistent with a forced mass-spring operating at resonance.

The incidence of Plesiomonas shigelloides among diarrhoeal patients attending the Dhaka Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B) from January through December 1987, has been reported. Using bile peptone broth (pH 8.8) as an enrichment medium and Salmonella-Shigella agar to isolate the organism, P. shigelloides was isolated from 838 (6.4%) of 13,142 patients, 523 (4.0%) of whom had no other pathogen isolated. The percentage of isolation was higher from stool (9.2%) than from rectal swab (5.9%) specimens (P < 0.005). The incidence of P. shigelloides was higher among male (64.0%) than female (36.0%) patients (P < 0.005). Isolation was highest among children less than five years. P. shigelloides was isolated most often in March (11.0%) and September (7.7%), indicating two seasonal peaks of incidence before and after the monsoons. All the strains were uniformly sensitive to chloramphenicol, furazolidon, gentamicin and trimethoprim-sulfamethoxazole. Sensitivity of the organism to ampicillin and tetracycline was 27.0% and 89.0%, respectively. This indicates that P. shigelloides may be an important agent of diarrhoea in our patient population.

Escherichia coli isolates from all surveillance patients less than or equal to 20 months of age seen for diarrhoea at the Dhaka Clinical Treatment Facility of the International Centre for Diarrhoeal Disease Research, Bangladesh between March 1 and August 31, 1988, were collected and hybridized with DNA probes to assess the potential importance of diarrhoeagenic E. coli among paediatric patients in Bangladesh. Of 396 patients evaluated, 18% were infected with enteropathogenic E. coli (EPEC) adherence factor (EAF)-positive E. coli, 23% were infected with enterotoxigenic E. coli (ETEC), 9% were infected with Shiga-like toxin-positive E. coli, and 13% were infected with diffuse adhesiveness-positive E. coli. None were infected with enteroinvasive E. coli. Ten percent of patients were colonized with more than one type of potential diarrhoeagenic E. coli. The majority of EAF-positive isolates were of traditional EPEC O:H serotypes. Although this was not a case-control study, the large number of EPEC and ETEC, which are recognized enteric pathogens, suggests these organisms are important causes of diarrhoeal diseases in this pediatric population.

Yersinia enterocolitica was isolated from children in two cohorts in Santiago, Chile. In a cohort containing a cross section of children aged 0 to 4 years, Y. enterocolitica was isolated from stool samples of 1.1% of children with diarrhea and 0.2% of age-matched control children. In a subgroup of this cohort from which weekly stool samples were obtained from all children irrespective of clinical status, 6% of children had asymptomatic Yersinia infections. In a birth cohort (with a greater representation of children less than 1 year of age and a significantly higher rate of diarrhea), Y. enterocolitica was isolated from 1.9% of children with diarrhea and 0.6% of controls (P = 0.05). Biogroup 1A strains (which lacked traditional phenotypic and molecular markers for pathogenicity) were isolated from seven children with diarrhea but from no control children in the birth cohort (P = 0.02). All other isolates, including all isolates from asymptomatic children, were "pathogenic" strains in biogroup 4, serogroup O3; no association between these isolates and occurrence of disease was found. Y. enterocolitica is found among young children in Santiago, with asymptomatic infections not uncommon occurrences. However, questions about the association between previously described virulence factors and diarrheal illness remain.

To test the hypothesis that clinical Vibrio cholerae O1 infections protect against recurrent cholera, treated cholera episodes in a rural Bangladesh population of 188,153 people who were followed between 1985 and 1988 were analysed. Of the 2214 people with initial episodes of cholera, 7 had a second episode. The incidence of cholera was 61% lower in subjects who had had an earlier episode than in those without such an episode. Whereas initial episodes of classical cholera were associated with complete protection against subsequent cholera, initial episodes of El Tor cholera were associated with negligible protection.

This study examined rhythmic finger movements in the steady state and when momentarily perturbed in order to derive their qualitative dynamical properties. Movement frequency, amplitude, and peak velocity were stable under perturbation, signaling the presence of an attractor, and the topological dimensionality of that attractor was approximately equal to one. The strength of the attractor was constant with increasing movement frequency, and the Fourier spectra of the steady-state trials showed an alternating harmonic pattern. These results are consistent with a previously derived nonlinear oscillator model. However, the oscillation was phase advanced by perturbation overall, and a consistent phase-dependent, phase-shift pattern occurred, which is inconsistent with the model. The overall phase advance also shows that any central pattern generator responsible for generating the rhythm must be nontrivially modulated by the limb being controlled.

It has long been suspected that besides their ability to invade enterocytes, enteroinvasive Escherichia coli (EIEC) strains have the ability to elaborate an enterotoxin. We tested 35 EIEC strains for cytotoxins and 9 (1 per serogroup) for enterotoxins. All 35 strains exhibited low levels of Vero cell cytotoxins that are immunologically and genetically distinct from Shiga-like toxin I or II of enterohemorrhagic E. coli. Sterile supernatants and cell lysates of two EIEC strains were tested in rabbit ileal loops, and both stimulated moderate fluid accumulation (circa 0.5 ml/cm) without tissue damage; secretory activity was confirmed in Ussing chambers, where these two strains and the seven others tested significantly increased short circuit current without altering tissue conductance. Curing the 140-MDa invasiveness plasmid from an EIEC strain did not diminish enterotoxin production. Culture in minimal Fe2+ medium is necessary to detect expression of the enterotoxin which is circa 68 to 80 kDa in size and is distinct from the EIEC cytotoxin.

A two-week age-matched case-control survey to detect Clostridium perfringens type C-associated illness was conducted among diarrheal patients hospitalized following the consumption of high protein meals on the occasion of an annual religious festival. From the stool of 33 patients screened, C. perfringens type C was isolated from one patient with bloody diarrhea and from two patients with watery diarrhea. In Bangladesh, C. perfringens type C has been isolated in both bloody and watery diarrhoeal illness and is not necessarily associated with necrotizing enteritis (pigbel).

Trimethoprim-resistance genes of Shigella dysenteriae 1 strains, isolated from a different location of six different countries of Asia over a 5-year period were characterized by using three different dihydrofolate reductase (DHFR) gene probes. The trimethoprim-resistant (TMPR) strains hybridized only with the type I DHFR gene probe by colony hybridization. None of the strains hybridized with types II and III DHFR gene probes. Southern blot experiments using plasmid DNA extracted from these resistant strains indicated that the type I DHFR genes were either on a 20 MDa plasmid or might be located on the chromosome. None of the other plasmids present in S. dysenteriae 1 strains hybridized with the probe. This indicates that the TMP resistance in these S. dysenteriae 1 strains are mediated by type I DHFR enzyme, and there may be transposition of this type I DHFR gene occurs between the 20 MDa plasmid and the chromosome in this serotype of shigella.

In this study, 27 volunteers received one of three non-O group 1 Vibrio cholerae strains in doses as high as 10(9) CFU. Only one strain (strain C) caused diarrhea: this strain was able to colonize the gastrointestinal tract, and produced a heat-stable enterotoxin (NAG-ST). Diarrhea was not seen with a strain (strain A) that colonized the intestine but did not produce NAG-ST, nor with a strain (strain B) that produced NAG-ST but did not colonize. Persons receiving strain C had diarrhea and abdominal cramps. Diarrheal stool volumes ranged from 154 to 5,397 ml; stool samples from the patient having 5,397 ml of diarrhea were tested and found to contain NAG-ST. The median incubation period for illness was 10 h. There was a suggestion that occurrence of diarrhea was dependent on inoculum size. Immune responses to homologous outer membrane proteins, lipopolysaccharide, and whole-cell lysates were demonstrable with all three strains. Our data demonstrate that V. cholerae of O groups other than 1 are able to cause severe diarrheal disease. However, not all strains are pathogenic for humans: virulence of strain C may be dependent on its ability both to colonize the intestine and to produce a toxin such as NAG-ST.

How do space and time relate in rhythmical tasks that require the limbs to move singly or together in various modes of coordination? And what kind of minimal theoretical model could account for the observed data? Earlier findings for human cyclical movements were consistent with a nonlinear, limit cycle oscillator model (Kelso, Holt, Rubin, & Kugler, 1981) although no detailed modeling was performed at that time. In the present study, kinematic data were sampled at 200 samples/second, and a detailed analysis of movement amplitude, frequency, peak velocity, and relative phase (for the bimanual modes, in phase and antiphase) was performed. As frequency was scaled from 1 to 6 Hz (in steps of 1 Hz) using a pacing metronome, amplitude dropped inversely and peak velocity increased. Within a frequency condition, the movement's amplitude scaled directly with its peak velocity. These diverse kinematic behaviors were modeled explicitly in terms of low-dimensional (nonlinear) dissipative dynamics, with linear stiffness as the only control parameter. Data and model are shown to compare favorably. The abstract, dynamical model offers a unified treatment of a number of fundamental aspects of movement coordination and control.

In contrast to social, religious, and economic determinants of acceptance and sustained use of family planning in developing countries, perceived side effects resulting from reproductive tract infections can usually be ameliorated easily and expeditiously. This population-based study examines the magnitude and nature of morbidity due to reproductive tract infections among users of various contraceptive methods and among nonusers in a rural community in Bangladesh. Overall, 22 percent of the 2,929 women surveyed reported symptoms of reproductive tract infection. Of the 472 symptomatic women examined, 68 percent had clinical or laboratory evidence of infection. Users of intrauterine devices and tubectomy were each approximately four times as likely to report symptoms and seven times as likely to have examination-confirmed infection as nonusers. The epidemiology of reproductive tract infections in this population is addressed, and the findings are discussed in terms of their potential programmatic impact.

Antigenic similarity between the oral cholera B subunit-whole cell (BS-WC) and whole-cell only (WC) vaccines and strains of the family Vibrionaceae was studied by crossed immunoelectrophoresis. A reference system consisting of Vibrio cholerae Inaba E1 Tor antigenic extract and homologous rabbit antiserum was applied in the study. The system was represented by 30 anodically migrating antigens forming distinct precipitation bands. Antigenic extracts of other members of the family Vibrionaceae showed the following numbers of cellular antigens shared in common with the reference system: Vibrio cholerae non-01-30, V. mimicus-23, V. fluvialis-15, V. parahaemolyticus-10, Aeromonas hydrophila-7, A. sobria-5, A. caviae-4 and Plesiomonas shigelloides-5 antigens. Homologous rabbit antiserum reacted with 11 antigens of BS-WC vaccine and 10 antigens of WC vaccine. The number of antigens which members of the family Vibrionaceae shared in common with those preserved in the WC component of the vaccines were as follows: Vibrio cholerae non-01, 7; V. mimicus, 5; V. fluvialis, 3; V. parahaemolyticus, 3; Aeromonas hydrophila, 2; A. sobria, 2; and A. caviae, 2; Plesiomonas shigelloides, 1. None of the strains produced an antigen reacting with anti-cholera toxin antibodies. The presence of common antigens in the vaccine and among members of family Vibrionaceae indicates that the oral cholera vaccine could stimulate immunity effectively against other members of the family.

Because of demonstrable cross-reactivity of cellular antigens contained in B subunit-killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines with antigens of various non-cholera species of the family Vibrionaceae (NCV), the protection conferred by the vaccines against diarrhoea associated with NCV was evaluated during a randomized, double-blind field trial in Bangladesh. Children aged 2-15 years and women aged greater than 15 years (62,285 in number) received three doses of BS-WC vaccine, WC-only vaccine, or a placebo consisting of Escherichia coli K12 strain (K12). During 1 year of follow-up, the incidence of treated episodes of diarrhoea associated with non-cholera vibrios known to be enteric pathogens (non-01 Vibrio cholerae, V. fluvialis, V. parahaemolyticus, V. mimicus) in the placebo group was low (1.9 cases per 10,000 recipients) and identical to that for the two vaccine groups combined. The incidence (per 10,000 recipients) of treated diarrhoeal episodes associated with Aeromonas species was considerably higher, but nearly identical in the three groups (26.1 cases for BS-WC, 26.0 cases for WC; 25.9 cases for K12). Pleisiomonas shigelloides was not isolated from any participant. It is concluded that NCV other than Aeromonas were rarely isolated from diarrhoeal patients in our study population and that killed oral vaccines which were effective against cholera exhibited no detectable cross-protection against diarrhoea associated with NCV organisms.

Yersinia enterocolitica was recently reclassified into Yersinia enterocolitica sensu stricto and three additional species. With this new classification, it was of interest to reexamine pathogenicity previously ascribed to Y. enterocolitica. All available clinical isolates of Y. enterocolitica sent to the Centers for Disease Control from 1970 through 1980 were selected for characterization and comparison. One-hundred such strains had been submitted, from 21 states. Most (85%) were biotype 1, and O:8 was the most common of the 24 serotypes encountered. All strains were examined by several virulence assays. Two strains caused conjunctivitis in guinea pigs, 7 were lethal for mice, 54 invaded HEp2 cells, 18 produced a heat-stable enterotoxin, 9 were calcium dependent, 20 autoagglutinated, and 34 had a distinctive colonial morphology at 37 degrees C. Ten isolates of each of the new species that had previously been grouped with Y. enterocolitica (Y. kristensenii, Y. intermedia, and Y. frederiksenii) were characterized and were generally negative in all assays. This study points out pathogenicity differences among Yersinia species, confirms the complex nature of virulence in Y. enterocolitica, and confirms that no single current assay correlates with virulence in Y. enterocolitica.

To evaluate the efficacy of early treatment with erythromycin on the duration of fecal excretion and of diarrhea associated with Campylobacter jejuni, 170 patients, age 3 to 60 months, were randomly assigned in a double-blind fashion to receive either erythromycin ethyl succinate or placebo immediately after being seen at Cayetano Heredia Hospital because of acute dysentery. The groups' pretreatment characteristics were comparable. Of the 30 patients with stools positive for C. jejuni, 12 were in the placebo group and 16 in the treatment group. After 2 days of treatment, none of the patients in the placebo group and 36% of those in the erythromycin group had normal stools (P less than 0.05). After 5 days of treatment, 50% of the patients in the placebo group and 93% of those in the erythromycin group had normal stools (P less than 0.02). Fecal excretion of the organism continued significantly longer in the placebo group (P less than 0.01). There were no treatment failures in the treatment group compared with five (42%) in the placebo group (P less than 0.01). Thus, early administration of erythromycin significantly reduced the duration of both diarrhea and fecal excretion of the organism in infants and children with acute dysentery associated with C. jejuni.

Plasmid profiles and antimicrobial susceptibility patterns of 343 strains of Shigella dysenteriae type 1, obtained from 18 different geographical locations, were analyzed. Three plasmids, with molecular sizes of 140, 6, and 2 megadaltons (MDa), were present in 94, 98, and 96%, respectively, of the 343 strains isolated during either epidemic or nonepidemic periods from 1965 to 1987. In addition to these plasmids, 83% of the strains harbored a 4-MDa plasmid and 25% harbored a 20-MDa plasmid. Various plasmid profiles were observed in which the 140-, 6-, and 2-MDa plasmids occurred commonly, irrespective of the place of isolation and drug resistance pattern of the strains. Certain profiles showed significant association with drug resistance patterns. These findings suggest that three plasmids, of molecular sizes 140, 6, and 2 MDa, are unique to S. dysenteriae type 1 strains and may indicate the global spread of a pathogenic bacterial clone. Additionally, these core plasmids, plus plasmids of various other sizes, could be used to identify emerging subclones which are causing both epidemic and sporadic disease. Thus, plasmid profiles of S. dysenteriae type 1 strains can be used to monitor possible pandemic strains as well as individual epidemic strains.

Isolation rates of Aeromonas hydrophila from stool samples of symptomatic and asymptomatic individuals were examined for several common enteric media. Sheep blood agar with 10 micrograms of ampicillin per ml, preceded by overnight enrichment in alkaline peptone water, yielded 2.6 times the number of isolates as the other media examined and is recommended for the isolation of A. hydrophila from humans.

Bile peptone broth and alkaline peptone water (pH 8.5) were examined as enrichment media for the isolation of Plesiomonas shigelloides from stools, with salmonella-shigella agar as the isolation medium. After 423 parallel examinations in two different experiments, bile peptone broth enrichment for 24 h was observed to be six times more effective (P less than 0.01) than direct plating alone on salmonella-shigella agar. Bile peptone broth was found to be twice as effective as alkaline peptone water for the recovery of P. shigelloides from stools.

The B subunit (BS) of cholera toxin and that of the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) are antigenically similar. We therefore assessed whether a combined cholera toxin BS/whole-cell (BS-WC) oral vaccine against cholera conferred cross-protection against LT-producing ETEC (LT-ETEC) diarrhea in a randomized, double-blind field trial among rural Bangladeshi children and women. The 24,770 persons who ingested two or more doses of BS-WC vaccine were compared with 24,842 controls who took two or more doses of killed whole-cell (WC) oral cholera vaccine. Sixty-seven percent fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term (three-month) follow-up (P less than .01), but no reduction was evident during the ensuing nine months. Short-term protection was particularly notable against LT-ETEC diarrhea causing life-threatening dehydration (protective efficacy, 86%; P less than .05).

Vibrio mimicus has recently been isolated from aquatic environments of Bangladesh. A total of 125 of 300 environmental isolates, representing various biotypes, and 19 human isolates were tested for enteropathogenicity by using several models. Less than 1% of the environmental isolates and slightly more than 10% of the clinical isolates produced cholera toxin-like toxin. A significant percentage of the environmental isolates (25%) and of the human isolates (74%) induced fluid accumulation in ligated rabbit ileal loops. One environmental strain produced heat-stable toxin-like enterotoxin, whereas all of the human isolates did not. V. mimicus strains were divided into the following three groups on the basis of their activity in various toxin assays: (i) organisms which produce a heat-labile enterotoxin immunobiologically similar to cholera toxin, (ii) organisms which produce a heat-stable enterotoxin-like toxin, and (iii) organisms whose whole-cell cultures have some activity characteristic of heat-labile toxin (e.g., fluid accumulation in ligated rabbit ileal loops and positive permeability factor) but are not positive by the GM1 enzyme-linked immunosorbent assay. One isolate from this group was able to elicit these results with cell-free culture filtrates. There was no correlation of biotype with toxic activity of V. mimicus isolates.

In a double-blind, randomized trial, we compared the efficacy of bicarbonate-containing oral rehydration solution vs citrate-containing solution in the treatment of infantile diarrheal dehydration and acidosis. Ninety-seven infants 3 to 24 months of age were entered in the study; 49 received bicarbonate-containing solution and 48 citrate-containing solution. The two groups were similar in all respects at the beginning of the study. Oral rehydration was successful (i.e., no intravenously administered fluids were required) in 85% of study patients; the success rate was similar in both treatment groups. Serum total CO2 concentration increased in a similar fashion in both groups, reaching near normal values at 48 hours after admission. We conclude that sodium citrate can be substituted for sodium bicarbonate in the formulation of the orally administered rehydration solution recommended by the World Health Organization for treatment of diarrheal dehydration in infants.

An adult Bangladeshi woman had persistent bloody diarrhea. Repeated stool cultures yielded Plesiomonas shigelloides in pure growth. Tissue specimens of the colon were consistent with pseudomembranous colitis. Treatment with tetracycline, to which the isolate was susceptible, brought prompt recovery; the stool cultures became negative and the serum antibody titer against P. shigelloides lipopolysaccharide, as measured by hemagglutination inhibition with P. shigelloides lipopolysaccharide-sensitized sheep erythrocytes, declined from 1:160 to 1:40.

We assessed the protective efficacy (PE) of three doses of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral cholera vaccines in a randomized, double-blind trial among 62,285 children and women residing in rural Bangladesh. After one complete year of surveillance, 110 cases of cholera were detected in the placebo group, 52 in the WC group (PE, 53%; P less than .0001), and 41 in the BS-WC group (PE, 62%; P less than .0001). Protection was greater for BS-WC recipients than for WC recipients only during the initial eight months of observation. Both vaccines conferred equivalent protection against cholera associated with life-threatening dehydration and against less severe cholera. High-grade, sustained protection was observed in persons vaccinated when older than five years; in younger persons protection was transient. We conclude that BS-WC and WC vaccines confer significant protection against cholera, particularly in persons vaccinated when older than five years.