46 research outputs found
Extended corresponding-states behavior for particles with variable range attractions
We propose an extension of the law of corresponding states that can be
applied to systems - such as colloidal suspensions - that have widely different
ranges of attractive interactions. We argue that, for such systems, the
``reduced'' second virial coefficient is a convenient parameter to quantify the
effective range of attraction. This procedure allows us to give a simple
definition of the effective range of attraction of potentials with different
functional forms. The advantage of the present approach is that it allows us to
estimate the relative location of the liquid-vapor and solid-fluid coexistence
curves exclusively on basis of the knowledge of the pair-potential.Comment: REVTeX, 5 pages, 2 figure
Lamellar and inverse micellar structures of skin lipids: Effect of templating
The outermost layer of skin, the stratum corneum (SC), comprises rigid
corneocytes in a layered lipid matrix. Using atomistic simulations we find that
the equilibrium phase of the SC lipids is inverse micellar. A model of the
corneocyte is used to demonstrate that lamellar layering is induced by the
patterned corneocyte wall. The inverse micellar phase is consistent with in
vivo observations in the lacunar spaces and at the stratum granulosum - SC
boundary region, and suggests a functional role in the lipid synthesis pathway
in vivo.Comment: pdflatex 5 pages, 10 page supplementary material. Published Physical
Review Letters. Added link to website with animation
Complete structure of an epithelial keratin dimer: implications for intermediate filament assembly
Keratins are cytoskeletal proteins that hierarchically arrange into filaments, starting with the dimer sub-unit. They are integral to the structural support of cells, in skin, hair and nails. In skin, keratin is thought to play a critical role in conferring the barrier properties and elasticity of skin. In general, the keratin dimer is broadly described by a tri-domain structure: a head, a central rod and a tail. As yet, no atomistic-scale picture of the entire dimer structure exists; this information is pivotal for establishing molecular-level connections between structure and function in intermediate filament proteins. The roles of the head and tail domains in facilitating keratin filament assembly and function remain as open questions. To address these, we report results of molecular dynamics simulations of the entire epithelial human K1/K10 keratin dimer. Our findings comprise: (1) the first three-dimensional structural models of the complete dimer unit, comprising of the head, rod and tail domains; (2) new insights into the chirality of the rod-domain twist gained from analysis of the full domain structure; (3) evidence for tri-subdomain partitioning in the head and tail domains; and, (4) identification of the residue characteristics that mediate non-covalent contact between the chains in the dimer. Our findings are immediately applicable to other epithelial keratins, such as K8/K18 and K5/K14, and to intermediate filament proteins in general
Water permeation through stratum corneum lipid bilayers from atomistic simulations
Stratum corneum, the outermost layer of skin, consists of keratin filled
rigid non-viable corneocyte cells surrounded by multilayers of lipids. The
lipid layer is responsible for the barrier properties of the skin. We calculate
the excess chemical potential and diffusivity of water as a function of depth
in lipid bilayers with compositions representative of the stratum corneum using
atomistic molecular dynamics simulations. The maximum in the excess free energy
of water inside the lipid bilayers is found to be twice that of water in
phospholipid bilayers at the same temperature. Permeability, which decreases
exponentially with the free energy barrier, is reduced by several orders of
magnitude as compared to with phospholipid bilayers. The average time it takes
for a water molecule to cross the bilayer is calculated by solving the
Smoluchowski equation in presence of the free energy barrier. For a bilayer
composed of a 2:2:1 molar ratio of ceramide NS 24:0, cholesterol and free fatty
acid 24:0 at 300K, we estimate the permeability P=3.7e-9 cm/s and the average
crossing time \tau_{av}=0.69 ms. The permeability is about 30 times smaller
than existing experimental results on mammalian skin sections.Comment: latex, 8 pages, 6 figure
Effect of monoglycerides and fatty acids on a ceramide bilayer
Monoglycerides and unsaturated fatty acids, naturally present in trace amounts in the stratum corneum (top layer of skin) lipid matrix, are commonly used in pharmaceutical, cosmetic and health care formulations. However, a detailed molecular understanding of how the oil additives get incorporated into the skin lipids from topical application and, once incorporated, how they affect the properties and integrity of the lipid matrix remains unexplored. Using ceramide 2 bilayers as skin lipid surrogates, we use a series of molecular dynamics simulations with six different natural oil ingredients at multiple concentrations to investigate the effect of the oils on the properties and stability of the bilayers. The six oils: monoolein, monostearin, monoelaidin, oleic acid, stearic acid and linoleic acid – all having the same length of the alkyl chain, C18, but a varying degree of saturation, allow us to systematically address the effect of unsaturation in the additives. Our results show that at low oil concentration (∼5%) the mixed bilayers containing any of the oils and ceramide 2 (CER2) become more rigid than pure CER2 bilayers due to more efficient lipid packing. Better packing also results in the formation of larger numbers of hydrogen bonds between the lipids, which occurs at the expense of the hydrogen bonds between lipids and water. The mixed bilayers with saturated or trans-unsaturated oils remain stable over the whole range of oil concentration. In contrast, the presence of the oils with at least one cis-double bond leads to bilayer instability and complete loss of bilayer structure at the oil content of about 50–65%. Two cis-double bonds in the lipid tail induce bilayer disruption at even lower concentration (∼30%). The mixed bilayers remain in the gel phase (without melting to a fluid phase) until the phase transition to a non-bilayer phase occurs. We also demonstrate that the stability of the bilayer strongly correlates with the order parameter of the lipid tails
Fast cholesterol flip-flop and lack of swelling in skin lipid multilayers
Atomistic simulations were performed on hydrated model lipid multilayers that are representative of the lipid matrix in the outer skin (stratum corneum). We find that cholesterol transfers easily between adjacent leaflets belonging to the same bilayer via fast orientational diffusion (tumbling) in the inter-leaflet disordered region, while at the same time there is a large free energy cost against swelling. This fast flip-flop may play an important role in accommodating the variety of curvatures that would be required in the three dimensional arrangement of the lipid multilayers in skin, and for enabling mechanical or hydration induced strains without large curvature elastic costs
The association of indwelling urinary catheter with delirium in hospitalized patients and nursing home residents: an explorative analysis from the "Delirium Day 2015"
Backround: Use of indwelling urinary catheter (IUC) in older adults has negative consequences, including delirium.
Aim: This analysis, from the "Delirium Day 2015", a nationwide multicenter prevalence study, aim to evaluate the association of IUC with delirium in hospitalized and Nursing Homes (NHs) patients.
Methods: Patients underwent a comprehensive geriatric assessment, including the presence of IUC; inclusion criteria were age > 65 years, being Italian speaker and providing informed consent; exclusion criteria were coma, aphasia, end-of-life status. Delirium was assessed using the 4AT test (score ≥ 4: possible delirium; scores 1-3: possible cognitive impairment).
Results: Among 1867 hospitalized patients (mean age 82.0 ± 7.5 years, 58% female), 539 (28.9%) had IUC, 429 (22.9%) delirium and 675 (36.1%) cognitive impairment. IUC was significantly associated with cognitive impairment (OR 1.60, 95% CI 1.19-2.16) and delirium (2.45, 95% CI 1.73-3.47), this latter being significant also in the subset of patients without dementia (OR 2.28, 95% CI 1.52-3.43). Inattention and impaired alertness were also independently associated with IUC. Among 1454 NHs residents (mean age 84.4 ± 7.4 years, 70.% female), 63 (4.3%) had IUC, 535 (36.8%) a 4AT score ≥ 4, and 653 (44.9%) a 4AT score 1-3. The multivariate logistic regression analysis did not show a significant association between 4AT test or its specific items with IUC, neither in the subset of patients without dementia.
Discussion: We confirmed a significant association between IUC and delirium in hospitalized patients but not in NHs residents.
Conclusion: Environmental and clinical factors of acute setting might contribute to IUC-associated delirium occurrence
"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool
Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys