Covalently and ionically, dually crosslinked chitosan nanoparticles block quorum sensing and affect bacterial cell growth on a cell-density dependent manner.

In our efforts to improve the quality and stability of chitosan nanoparticles (NPs), we describe here a new type of chitosan NPs dually crosslinked with genipin and sodium tripolyphosphate (TPP) that display quorum quenching activity. These NPs were created using a simplified and robust procedure that resulted in improved physicochemical properties and enhanced stability. This procedure involves the covalent crosslinking of chitosan with genipin, followed by the formation of chitosan NPs by ionic gelation with TPP. We have optimized the conditions to obtain genipin pre-crosslinked nanoparticles (PC-NPs) with positive ς-potential (~ +30 mV), small diameter (~130 nm), and low size distributions (PdI = 0.1-0.2). PC-NPs present physicochemical properties that are comparable to those of other dually crosslinked chitosan NPs fabricated with different protocols. In contrast to previously characterized NPs, however, we found that PC-NPs strongly reduce the acyl homoserine lactone (AHL)-mediated quorum sensing response of an Escherichia coli fluorescent biosensor. Thus, PC-NPs combine, in a single design, the stability of dually crosslinked chitosan NPs and the quorum quenching activity of ionically crosslinked NPs. Similar to other chitosan NPs, the mode of action of PC-NPs is consistent with the existence of a "stoichiometric ratio" of NP/bacterium, at which the positive charge of the NPs counteracts the negative ς-potential of the bacterial envelope. Notably, we found that the time of the establishment of the "stoichiometric ratio" is a function of the NP concentration, implying that these NPs could be ideal for applications aiming to target of bacterial populations at specific cell densities. We are confident that our PC-NPs are up-and-coming candidates for the design of efficient anti-quorum sensing and a new generation antimicrobial strategies.

Indicators of dysautonomia in severe Guillain-Barré syndrome.

This study sought to establish quantitative criteria for dysautonomia in artificially ventilated patients with Guillain-Barré syndrome (GBS). Such criteria would help to identify patients at risk for cardiovascular complications. This retrospective controlled clinical study compared hourly cardiovascular monitoring data from 36 successive, artificially ventilated GBS patients with that from 11 artificially ventilated control patients with myasthenia. Tolerance limits for daily means, extremes, and variations in heart rate (HR) and blood pressure (BP) were estimated from the most abnormal subgroups of the treatment days of our control patients. These exceeded previously suggested arbitrary cutoff values for dysautonomia. The range in systolic BP was increased in 27 GBS patients, despite an upper limit of normal (85 mmHg) that was double the value suggested in previous work. All 16 patients with mean systolic BP above 165 mmHg also had persistent tachycardia (mean HR > 125 bpm), or were treated with beta-blockers. This pattern of sympathetic hyperactivity was combined with probable vagal hyperactivity (bradycardia < 48 bpm) in 6 patients. Hypotension (minimal systolic BP < 85 mmHg) and unprovoked bradycardia indicated sympathetic hypoactivity in 3 patients. Except in one patient who suffered from asystole on his first day on the ICU, all episodes of bradycardia were preceded by increased daily systolic BP variation (> 85 mmHg), which thus proved to be a sensitive and prognostically valuable indicator of dysautonomia in GBS.

Spectral analysis of heart rate and blood pressure in Guillain-Barré patients with respiratory failure.

The clinical value of heart rate and blood pressure variation (HRV and BPV) spectra was assessed in 11 consecutive patients with Guillain-Barré syndrome (GBS) on artificial ventilation. Their HRV and BPV spectra were compared with those from 28 control intensive care unit (ICU) patients without peripheral nerve disorders. ICU controls had low respiratory HRV during controlled ventilation. If present, it was closely related to, but smaller than BPV, suggesting baroreceptor reflex mediation. Respiratory HRV similar to that of healthy controls was observed only in ICU controls with significant spontaneous ventilation. HRV was prominent in a subgroup of GBS patients who suffered from bradycardia or sinus arrest, whereas GBS patients without episodic bradycardia only exceptionally had respiratory HRV. Interpretation of HRV during artificial ventilation cannot be extrapolated from experience with spontaneously breathing subjects. In contrast to diabetic neuropathy, not loss, but preservation of respiratory HRV was ominous in artificially ventilated GBS patients. A pattern of prominent broad respiratory HRV peaks and narrow BPV peaks occurred only in GBS and forebode sinus arrest.

Residential differences in the incidence of nursing home admissions across a six-year period.

Data from the Longitudinal Study of Aging are used to examine the incidence of nursing home admissions over a six-year period (1984-1990) among older adults (70+ at T1) living in four different residential contexts. Bivariate analysis identified significant differences between residence groups. Elders from less urbanized and thinly populated nonmetropolitan counties had the highest likelihood of admissions, while older residents of large metropolitan areas had the lowest. In multivariate models, differences by residence could not be accounted for by sociodemographic, health, and social support network characteristics that are known to influence admissions. Further research is needed to identify the specific community context factors that account for variation by place of residence in admissions experiences.

Racial differences in the household composition of elders by age, gender, and area of residence.

Using census data and an innovative technique for describing the composition of households from the perspective of elders, this research provides a more detailed description of race differences in living arrangements of older persons than has previously existed. In addition, cross tabulations of race with other factors known to influence household composition (gender, age, and area of residence) are examined. While white women are more likely than black women to live alone, the reverse is true among men. Whites are more likely than blacks to live in married-couple-only households, and blacks are more likely than whites to live in multigenerational households, although these differences decrease with advancing age. Blacks are also more likely than whites to live with collateral kin or non-kin only, although these categories comprise small proportions of the population. Implications of these differences for caregiving and quality of life among older persons are discussed.