A post-market cluster randomized controlled trial of the effect of the TENA SmartCare Change Indicator™ on urinary continence care efficiency and skin health in older nursing home residents.

BACKGROUND: Urinary continence care for residents of nursing homes who are unable to communicate their toileting needs usually involves care aides manually checking continence products (pads) to determine the level of urine saturation prior to changing. The TENA SmartCare Change Indicator is a medical device which estimates urine saturation and notifies caregivers of the optimal time for pad changes. This study will seek to examine the effect of the TENA SmartCare Change Indicator on urinary continence care efficiency and skin health, in comparison to usual care. METHODS: This cluster randomized controlled trial (NCT05247047) involving older nursing home residents with urinary incontinence unable to consistently indicate their toileting needs, and their care aides, will compare technology-based and usual continence care over a period of 8 weeks. Co-primary endpoints of superiority in continence care efficiency and non-inferiority in the maintenance of skin health will be assessed. Secondary outcomes will examine the resident quality of life, sleep quality, responsive behaviours, changes in pad use and leakage episodes outside the pad. Change in care aide work engagement, job satisfaction and rushed tasks will be assessed. Benefits and challenges with the use of the device for continence care will be identified from the perspectives of the care staff. DISCUSSION: Urinary continence assessment and care in nursing homes is reported as suboptimal and threatening to dignity. Data on the utility and effect of technological solutions for improving urinary continence care are few and conflicting. If shown effective, this technological solution has the potential to improve the care for older residents and improve the working lives of caregiving staff who look after this most vulnerable section of the population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05247047. Registration date is Feb 18, 2022.

A Randomized Exploratory Study to Investigate the Inflammatory Response During an Ultraviolet-Radiation-Induced Cold Sore Episode.

INTRODUCTION: Antivirals and occlusive lip patches are key treatments for cold sores. Additional therapeutic options, and validated methods to evaluate these, are needed. METHODS: This exploratory, double-blind, single-center study aimed to evaluate a novel lip patch containing the antiviral aciclovir (ACV) using noninvasive methods for measuring cold sore-associated inflammation. Healthy subjects with ultraviolet radiation (UVR)-induced cold sores were randomized to 10 days' treatment with a lip patch containing ACV (N = 12) or without ACV (N = 13). Outcome measures included blood flux (field laser perfusion imaging, FLPI), skin temperature (thermography), and skin redness (high-resolution color photography, HRCP). RESULTS: Mean blood flux (in perfusion units) and skin temperature (in °C/pixel) were higher for cold sores versus intrasubject control regions. For ACV versus placebo patches, skin temperature was higher for ACV with total day 1-5 mean values of 2.6 versus 0.5 (p = 0.036) and day 1-10 mean values of 3.2 versus 0.8 (p = 0.049). Conversely, mean total episode blood flux values over days 1-5 were lower for ACV versus placebo patch (flux 2227 versus 2939, p = 0.340) and remained lower over days 1-10 (flux ACV 810 versus placebo 961, p = 0.404). HRCP failed to discriminate cold sores from control regions or between treatments. Subject-reported pain/soreness, itching, and burning were generally lower with ACV patch. CONCLUSIONS: FLPI reliably measures cold sore-related inflammation and thermography heat radiating from the skin. HRCP was of little value. TRIAL REGISTRATION: NCT01653509.

The Beauty of Asymmetric Membranes: Reconstitution of the Outer Membrane of Gram-Negative Bacteria.

The architecture of the lipid matrix of the outer membrane of Gram-negative bacteria is extremely asymmetric: Whereas the inner leaflet is composed of a phospholipid mixture, the outer leaflet is built up by glycolipids. For most Gram-negative species, these glycolipids are lipopolysaccharides (LPS), for a few species, however, glycosphingolipids. We demonstrate experimental approaches for the reconstitution of these asymmetric membranes as (i) solid supported membranes prepared by the Langmuir-Blodgett technique, (ii) planar lipid bilayers prepared by the Montal-Mueller technique, and (iii) giant unilamellar vesicles (GUVs) prepared by the phase transfer method. The asymmetric GUVs (aGUVs) composed of LPS on one leaflet are shown for the first time. They are characterized with respect to their phase behavior, flip-flop of lipids and their usability to investigate the interaction with membrane active peptides or proteins. For the antimicrobial peptide LL-32 and for the bacterial porin OmpF the specificity of the interaction with asymmetric membranes is shown. The three reconstitution systems are compared with respect to their usability to investigate domain formation and interactions with peptides and proteins.

Influence of disulfide bonds in human beta defensin-3 on its strain specific activity against Gram-negative bacteria.

Antimicrobial peptides (AMPs) play an important role in the host defense against various microbes. One of the most efficient human AMPs is the human beta defensin-3 (hBD-3) which is produced by, e.g. keratinocytes and lung epithelial cells. However, the structure-function relationship for AMPs and in particular for defensins with their typical three disulfide bonds is still poorly understood. In this study the importance of the three disulfide bonds for the activity of the AMPs is investigated with biological assays and with biophysical experiments utilizing different membrane reconstitution systems. The activities of natural hBD-3, hBD-3-c (cyclic variant with one disulfide bond), and hBD-3-l (linear variant without disulfide bonds) and fragments thereof were tested against specific Gram-negative bacteria. Furthermore, hemolytic and cytotoxic activities were analyzed as well as the potency to neutralize immune cell stimulation of lipopolysaccharide (LPS). Experiments using reconstituted lipid matrices composed of phospholipids or LPS purified from the respective Gram-negative bacteria, showed that the membrane activity of all three hBD-3 peptides is decisive for their capability to kill bacteria and to neutralize LPS. In most of the test systems the linear hBD-3-l showed the highest activity. It was also the only peptide significantly active against polymyxin B-resistant Proteus mirabilis R45. However, the stability of hBD-3 against protease activity decreases with decreasing number of disulfide bonds. This study demonstrates that the refining of AMP structures can generate more active compounds against certain strains.

The combined use of a nonabrasive, activator-containing toothpaste and a light emitting diode device improves the onset time of tooth whitening.

OBJECTIVE: The objective of this randomized clinical study was to assess the onset time of the whitening effect of a combined use of a nonabrasive, activator-containing toothpaste and a light emitting diode (LED) device, compared to that of the toothpaste alone. MATERIALS AND METHODS: A nonabrasive, activator-containing toothpaste was used twice daily alone or combined with an LED device for 15 days. The onset of the tooth whitening effect was evaluated through tooth color (a* b*, CIELAB) and tooth whiteness (WIO) by image analysis of standardized images. Local tolerance was assessed at days 1, 8, and 15. RESULTS: On day 8, a significant (P = 0.003) tooth whitening effect compared to day 1 was observed with the toothpaste and the LED device, sustaining until the end of the study. Whitening using the toothpaste alone was significant compared to day 1 after 15 days, only. One subject reported mild redness, itching, and burning on day 1 on the gum of the lower jaw that was possibly related to with the toothpaste. The subject withdrew from the study. No adverse event was reported in the group using the LED device. CONCLUSION: Both tooth whitening methods had a significant whitening effect after 15 days of use. However, the onset of whitening was significantly faster when using the nonabrasive, activator-containing toothpaste combined with an LED device. The toothpaste and LED device were both safe.

A new topical panthenol-containing emollient: skin-moisturizing effect following single and prolonged usage in healthy adults, and tolerability in healthy infants.

PURPOSE: Two studies were conducted with a new topical panthenol-containing emollient (NTP-CE) to investigate the skin-moisturizing effect in healthy adults and tolerability in healthy infants. METHODS: In Study 1 (N = 44), a single skin application of NTP-CE was performed followed by a 4-week twice-daily application. Skin hydration and stratum corneum (SC) water content change (using Raman spectroscopy) were measured. In the 4-week Study 2 (N = 65, aged 3-25 months), NTP-CE tolerability was assessed using a 5-point scoring system; skin hydration was determined in a subset (N = 21). RESULTS: In Study 1, mean AUC0 - 24 h for skin capacitance change from baseline was 302.03 i.u. with NTP-CE and -15.90 i.u. in control areas (p < .001). With NTP-CE (at 4 h), the water content within the upper SC part was reduced (-45.10 vs. -13.39 g/cm2, p = .013) and the water gradient increased (0.51 vs. 0.11 g/cm4, p = .036), indicating relocation of water into deeper layers. In Study 2, there was no statistically significant change from baseline in mean cutaneous tolerability scores. At days 7, 14, and 28, skin hydration had increased by 42%, 54%, and 49%, respectively (all p < .001). CONCLUSIONS: Single and prolonged NTP-CE usage is associated with sustained and deep skin moisturization. NTP-CE is well tolerated by healthy infants.

A new topical panthenol-containing emollient: Results from two randomized controlled studies assessing its skin moisturization and barrier restoration potential, and the effect on skin microflora.

PURPOSE: Two randomized, intra-individual comparison studies were performed in healthy subjects to evaluate the skin moisturization and barrier restoration potential of a new topical panthenol-containing emollient (NTP-CE) (Study 1), and its effect on skin microflora (Study 2). METHODS: In Study 1 (N = 23), two skin areas, one challenged with 0.5% sodium dodecyl sulfate (SDS) solution and one unchallenged, were treated with NTP-CE for 3 weeks. Transepidermal water loss (TEWL), skin hydration, and intercellular lipid lamellae (ICLL) organization were measured at regular intervals during the study. In Study 2 (N = 20), quantitative bacterial cultures were obtained over 6 h from a skin area undergoing wash stress with 10% SDS with subsequent single application of NTP-CE. RESULTS: In Study 1, mean AUC for TEWL reduction from baseline was more pronounced with NTP-CE compared with control (-168.36 vs. -123.38 g/m2/h, p = 0.023). NTP-CE use was also associated with statistically significant improvements in stratum corneum hydration and an increase in mean ICLL length from baseline (day 22: 120.61 vs. 35.85 nm/1000 nm2, p < 0.001). In Study 2, NTP-CE use had no negative impact on bacterial viability. CONCLUSIONS: NTP-CE use has favorable and lasting effects on barrier function and repair as well as skin hydration without negatively influencing bacterial viability.

Improvement of skin barrier function in atopic dermatitis patients with a new moisturizer containing a ceramide precursor.

BACKGROUND: Atopic dermatitis (AD) is characterized by barrier abnormalities, including insufficient ceramides in the stratum corneum (SC). OBJECTIVE: To measure the effects of a new moisturizer (CRM) containing a ceramide precursor in improving skin barrier function in patients with controlled atopic dermatitis. METHODS: In this randomized, intra-individual comparison, investigator-blinded study, CRM was applied to the test area of one lower leg for 27 days (the other leg remained as untreated control). Evaluations at baseline and day 28 included transepidermal water loss (TEWL), skin hydration by corneometry, dryness severity, Raman spectroscopy, and collection of adverse events. RESULTS: After 4 weeks of treatment, results showed a significantly greater reduction of TEWL and clinical dryness scores, and increased skin hydration (all p < 01) in the CRM-treated than untreated area. A significantly higher level of ceramide (p < 05) and a trend toward increased water content was observed with Raman in the SC for CRM than for the control. There were no related AEs. CONCLUSION: Skin barrier function and hydration were significantly improved after CRM treatment.

Surface acoustic wave biosensor as a tool to study the interaction of antimicrobial peptides with phospholipid and lipopolysaccharide model membranes.

Surface acoustic wave biosensors are a powerful tool for the study of biomolecular interactions. The modulation of a surface-confined acoustic wave is utilized here for the analysis of surface binding. Phase and amplitude of the wave correspond roughly to mass loading and viscoelastic properties of the surface, respectively. We established a procedure to reconstitute phospholipid and lipopolysaccharide bilayers on the surface of a modified gold sensor chip to study the mode of action of membrane-active peptides. The procedure included the formation of a self-assembled monolayer of 11-mercaptoundecanol, covalent coupling of carboxymethyl-dextran, and subsequent coating with a poly- l-lysine layer. The lipid coverage of the surface is highly reproducible and homogeneous as demonstrated in atomic force micrographs. Ethanol/triton treatment removed the lipids completely, which provided the basis for continuous sequences of independent experiments. The setup was applied to investigate the binding of human cathelicidin-derived peptide LL32, as an example for antimicrobial peptides, to immobilized phosphatidylserine membranes. The peptide-membrane interaction results in a positive phase shift and an increase in amplitude, indicating a mass increase along with a loss in viscosity. This suggests that the bilayer becomes more rigid upon interaction with LL32.

Lipid-specific membrane activity of human beta-defensin-3.

Defensins represent a major component of innate host defense against bacteria, fungi, and enveloped viruses. One potent defensin found, e.g., in epithelia, is the polycationic human beta-defensin-3 (hBD3). We investigated the role of the lipid matrix composition, and in particular the presence of negatively charged lipopolysaccharides (LPS) from sensitive (Escherichia coli, Salmonella enterica serovar Minnesota) or resistant (Proteus mirabilis) Gram-negative bacteria or of the zwitterionic phospholipids of human cells, in determining the action of polycationic hBD3 on the different membranes, and related to their biological activity. The main focus was directed on data derived from electrical measurements on a reconstitution system of the OM as a planar asymmetric bilayer composed on one side of LPS and on the other of a phospholipid mixture. Our results demonstrate that the antimicrobial activity and the absence of cytotoxicity can be explained by the lipid-specificity of the peptide. A clear correlation between these aspects of the biological activity of hBD3 and its interaction with lipid matrices could be found. In particular, hBD3 could only induce lesions in those membranes resembling the lipid composition of the OM of sensitive bacterial strains. The permeation through the membrane is a decisive first step for the biological activity of many antimicrobial peptides. Therefore, we propose that the lipid-specificity of hBD3 as well as some other membrane-active antimicrobial peptides is important for their activity against bacteria or mammalian cells.

Lipid-mediated resistance of Gram-negative bacteria against various pore-forming antimicrobial peptides.

Lipopolysaccharides (LPSs) play a dual role as target and as effector molecules. The knowledge of the LPS-induced activation of human immune cells is increasing; however, surprisingly, much less effort seems to be directed towards the understanding of the mechanisms leading to the killing of the bacterial organisms, which eventually results in the release of LPS from the bacterial surface into the blood circulation. We demonstrate mechanisms of interaction of peptides of the innate immune system (e.g. defensins and cathelicidins) as well as of externally administered antibiotics (e.g. Polymyxin B) with Gram-negative bacteria. The main focus is directed on data derived from electrical measurements on a reconstitution system of the outer membrane as an asymmetric bilayer composed on one side of LPS and on the other of phospholipids. All these antimicrobial peptides (AMPs) are membrane-active and induce the permeabilization of the reconstituted membranes by the formation of lesions. We found that differences in the activity of the AMPs against various sensitive and resistant Gram-negative bacteria can be explained solely by variations in the chemical structure of LPS, e.g. in the composition of the sugar head group. A reduction of the net negative charge of LPS is responsible for a reduced interaction with the polycationic AMPs and thus for resistance. A most important side effect of positively charged AMPs is the neutralization of the negatively charged LPS released from the bacterial surface as a consequence of AMP-induced killing.